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pubmed_1027_788 | Subunit interactions of the alpha1- and beta1-subunits of the chicken Na,K-ATPase were explored with the yeast two-hybrid system. Gal4-fusion proteins containing domains of the alpha1- and beta1-subunits were designed for examining both intersubunit and intrasubunit protein-protein interactions. Regions of the alpha- and beta-subunits known to be involved in alpha-beta-subunit assembly were positive in two-hybrid assay, supporting the validity of the assays. A library of beta-subunit ectodomains with C-terminal truncations was screened to find the maximal truncation retaining an interaction with the alpha-subunit extracellular H7H8 loop (where H7 refers to the seventh membrane span, and so on). The maximal truncation removed all the cysteines involved in disulfide bridges, leaving only 63 amino acids of the beta-subunit ectodomain. Scanning alanine mutagenesis led to identification of an evolutionarily conserved sequence of four amino acids (SYGQ) in the extracellular H7H8 loop of the alpha-subunit that is crucial to alpha-beta-intersubunit interactions. Oligomerization studies with single domains failed to detect self-association of either of the two large cytosolic loops (H2H3 and H4H5) within the alpha-subunit. However, evidence was found for an interaction between these two cytoplasmic loops. | 10.1074/jbc.272.19.12366 |
pubmed_1040_4461 | Acute ligation of the anterior descending coronary artery in the dog had little immediate effect on heat clearance but immediately lowered heat production, which fell to its minimum level in 1/2 hr, after which it began to recover; recovery was complete in 6 hr. After 1/2 hr heat clearance also began to fall and reached a minimum level in 1 1/2 hr. Ligation increased oxygen extraction but reduced oxygen consumption markedly though temporarily. Complete recovery followed. After 3 months, there was full recovery in flow, oxygen extraction ratio, and oxygen consumption mVO2. In morphological studies using Microfil injections soon after ligation, capillaries failed to fill retrogradely, though network vessels were perfused. After 1 hr of acute artery ligation, capillaries still did not perfuse but by 3 hr there was some reperfusion. After 6 hr there was marked capillary reperfusion. In dogs kept for 3 months after ligation the microcirculation was normal. These studies confirm that immediate circulatory failure occurred in capillaries (probably critical closure) which accounts for the immediate fall in venous outflow, heat production, and mVO2. Flow continued in network vessels which traversed the ischemic zone without perfusing capillaries. These results are contrasted with the findings of some other workers who found a continued functional decline leading to infarction. The present results were accounted for by closure and reopening to capillaries. | 10.1016/0026-2862(85)90014-7 |
pubmed_1054_826 | Pin and disc wear measurements were made on a commercial dental composite over a stress range from 2.5 to 20 MPa. The wear rates were found to increase suddenly during wear at times which tended to decrease with increasing stress. The results are interpreted in terms of wear mode conversion which results from the build-up of subsurface damage during wear. Micrographs showing damaged layers are compared with those from restorations worn in vivo. | 10.1177/00220345820610091101 |
pubmed_263_490 | BACKGROUND
The aim of this study was to determine the prevalence of Human Immune Virus (HIV) related oral lesions and their association with Cluster of Differentiation 4 (CD4+) count among treatment naïve HIV positive patients.
METHODS
This was a descriptive and analytical cross sectional study. Participants were 346 treatment naïve HIV positive adult patients. These were consecutively recruited from Hoima Regional Referral hospital between March and April 2012. Data collection involved interviews, oral examinations and laboratory analysis.
RESULTS
A total of 168(48.6%) participants had oral lesions. The four commonest lesions were oral candidiasis (24.9%, CI = 20.6-29.7%), melanotic hyperpigmentation (17.3%, CI = 13.7-21.7%), kaposi sarcoma (9.3%, CI = 6.6-12.8%) and Oral Hairy Leukoplakia (OHL) (5.5%, CI = 3.5-8.4%). There was significant association between oral candidiasis and immunosuppression measured as CD4+ less than 350 cells/mm3 (OR = 2.69, CI = 1.608-4.502, p < 0.001). Oral candidiasis was the only oral lesion significantly predictive of immunosuppression (OR = 2.56, CI = 1.52-4.30, p < 0.001) with a Positive Predictive Value (PPV) of 48.2%, Negative Predictive Value (NPV) of 74.3%, 38.1% sensitivity and specificity of 81.4%.
CONCLUSION
Oral candidiasis can be considered as a marker for immunesuppression, making routine oral examinations essential in the management of HIV positive patients. | 10.1186/1472-6831-14-143 |
pubmed_509_2049 | RATIONALE
The striatopallidal medium spiny neurons have been viewed as a final common path for drug reward, and the ventral pallidum (VP) as a convergent point for hedonic and motivational signaling. The medium spiny neurons are GABAergic, but they colocalize enkephalin.
OBJECTIVE
The present study investigated the role of the GABAergic mechanisms of the VP in ethanol consumption.
METHODS
The effects of bilateral microinjections of GABA(A) and GABA(B) receptor agonists and antagonists into the VP on voluntary ethanol consumption were monitored in alcohol-preferring Alko alcohol rats given 90 min limited access to ethanol in their home cages every other day. The influences of coadministration of GABA and opioid receptor modulators were also studied.
RESULTS
The GABA(A) receptor agonist muscimol (1-10 ng/site) decreased ethanol intake dose-dependently, while administration of the GABA(A) receptor antagonist bicuculline (10-100 ng) had an opposite effect. The GABA(B) receptor agonist baclofen (3-30 ng) also suppressed ethanol intake, but the GABA(B) receptor antagonist saclofen (0.3-3 μg) failed to modify it. Animals coadministered with bicuculline (30 ng) and baclofen (30 ng) consumed ethanol significantly less than those treated with bicuculline alone. Coadministration of the μ-receptor agonist D-Ala2,N-Me-Phe4,Glyol5-enkephalin (DAMGO, 0.1 μg) with bicuculline counteracted, whereas the μ-receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP, 1 μg) enhanced the bicuculline-induced increase of ethanol intake. When given alone, DAMGO decreased while CTOP increased ethanol intake.
CONCLUSIONS
The study provides evidence for the ventral pallidal GABAergic mechanisms participating in the regulation of ethanol consumption and supports earlier work suggesting a role for pallidal opioidergic transmission in ethanol reward. | 10.1007/s00213-012-2709-x |
pubmed_374_25240 | A novel domino reaction from benzaldehydes and 2-acetylfuran/2-acetylthiophene with sodium sulfide was developed to synthesize a series of tetrahydrothiopyran (THTP) derivatives. The reaction proceeded well to construct a tetrahydrothiopyran ring and five new bonds in one step. A mechanism is proposed, involving a stepwise Aldol/double Michael addition/Aldol (AMMA) reaction cascade. In this transformation, sodium sulfide acts as a nucleophile and base. This method is characterized by transition-metal-free, commercially available starting materials and mild reaction conditions. | 10.1021/acs.joc.0c01006 |
pubmed_984_5974 | Here, we have analysed the H(+)-ATPase-mediated extrusion of protons across the plasma membrane (PM) of rhizodermic cells, a process that is inducible by iron (Fe) deficiency and thought to serve in the mobilization of sparingly soluble Fe sources. The induction and function of Fe-responsive PM H(+)-ATPases in Arabidopsis roots was investigated by gene expression analysis and by using mutants defective in the expression or function of one of the isogenes. In addition, the expression of the most responsive isogenes was investigated in natural Arabidopsis accessions that have been selected for their in vivo proton extrusion activity. Our data suggest that the rhizosphere acidification in response to Fe deficiency is chiefly mediated by AHA2, while AHA1 functions as a housekeeping isoform. The aha7 knock-out mutant plants showed a reduced frequency of root hairs, suggesting an involvement of AHA7 in the differentiation of rhizodermic cells. Acidification capacity varied among Arabidopsis accessions and was associated with a high induction of AHA2 and IRT1, a high relative growth rate and a shoot-root ratio that was unaffected by the external Fe supply. An effective regulation of the Fe-responsive genes and a stable shoot-root ratio may represent important characteristics for the Fe uptake efficiency. | 10.1111/j.1469-8137.2009.02908.x |
pubmed_614_23332 | Traumatic brain injury (TBI) is often a result of traffic accidents, contact sports or battlefield explosions. A mild form of traumatic brain injury (mTBI) is frequently underestimated, as the immediate physical symptoms decrease rapidly and conventional neuroimaging studies often do not show visible evidence of brain lesions. However, cognitive impairments persist for weeks, months or even years after the incident. Endogenous opioids were documented to play a role in thmodulation of mTBI pathology, whereas exogenous opioids were shown to possess neuroprotective properties. In the present study, biphalin, a dimeric enkephalin analog, improved cognitive performance in the Morris Water Maze and Novel Object Recognition tests in a mouse weight-drop model of mTBI. The effect of a single systemic injection of 10 mg/kg biphalin immediately after trauma was reversed by naltrexone, suggesting an opioid receptor-mediated mechanism. Biphalin also reduced cortical and hippocampal neurodegeneration, as shown by silver staining. Our data indicates that opioid receptor activation by biphalin may provide neuroprotection of post-traumatic neurodegeneration processes and may protect against memory impairments. | pubmed_614_23332 |
pubmed_1122_10545 | Theiler's virus persistently infects the white matter of the spinal cord in susceptible strains of mice. This infection is associated with inflammation and primary demyelination and is studied as a model of multiple sclerosis. The H-2D gene is the major gene controlling viral persistence. However, the SJL/J strain is more susceptible than predicted by its H-2(s) haplotype. An (SJL/J x B10. S)F1 x B10.S backcross was analyzed, and one quantitative trait locus (QTL) was located in the telomeric region of chromosome 10 close to the Ifng locus. Another one was tentatively mapped to the telomeric region of chromosome 18, close to the Mbp locus. We now report the study of 14 congenic lines that carry different segments of these two chromosomes. Although the presence of a QTL on chromosome 18 was not confirmed, two loci controlling viral persistence were identified on chromosome 10 and named Tmevp2 and Tmevp3. Furthermore, the Ifng gene was excluded from the regions containing Tmevp2 and Tmevp3. Analysis of the mode of inheritance of Tmevp2 and Tmevp3 identified an effect of sex, with males being more infected than females. | 10.1093/genetics/152.1.385 |
pubmed_320_5994 | Since the discovery of nephrin, the first integral component of the slit diaphragm to be identified, the podocyte slit pore has become a major focus in research concerning the glomerular filtration barrier. Nephrin is a central component of the glomerular ultrafilter, with both structural and signaling functions. The extracellular domain of nephrin and other components of the slit diaphragm seem to form a porous molecular sieve. The intracellular domain of nephrin is associated with linker proteins, such as CD2-associated protein and Nck proteins that can connect nephrin to the actin cytoskeleton. Alterations in nephrin interactions with other proteins during development or injury can lead to complex signaling reactions aimed at establishing or restoring the filter function. | 10.1016/j.molmed.2007.06.006 |
pubmed_64_10568 | We tested whether a psychoeducational course improved well-being in three cohorts. Study 1 found significantly higher mental well-being in first year undergraduates who took the course compared to a waiting-list control. Study 2 revealed that students taking the course when COVID-19 restrictions began did not experience increases in mental well-being but had significantly higher well-being than a third matched group. In Study 3, an online course increased mental well-being in University students and staff during a COVID-19 lockdown. These findings support the claim that psychoeducational courses are beneficial in both live and online formats and in times of collective uncertainty. | 10.1177/2055102921999291 |
pubmed_364_13095 | BACKGROUND
Brown adipose tissue (BAT) is a site of metabolic thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1) and represents a target for a therapeutic intervention in obesity. Cold exposure activates UCP1-mediated thermogenesis in BAT and causes drastic changes in glucose, lipid, and amino acid metabolism; however, the relationship between these metabolic changes and UCP1-mediated thermogenesis is not fully understood.
METHODS
We conducted metabolomic and GeneChip array analyses of BAT after 4-h exposure to cold temperature (10 °C) in wild-type (WT) and UCP1-KO mice.
RESULTS
Cold exposure largely increased metabolites of the glycolysis pathway and lactic acid levels in WT, but not in UCP1-KO, mice, indicating that aerobic glycolysis is enhanced as a consequence of UCP1-mediated thermogenesis. GeneChip array analysis of BAT revealed that there were 2865 genes upregulated by cold exposure in WT mice, and 838 of these were upregulated and 74 were downregulated in UCP1-KO mice. Pathway analysis revealed the enrichment of genes involved in fatty acid (FA) β oxidation and triglyceride (TG) synthesis in both WT and UCP1-KO mice, suggesting that these metabolic pathways were enhanced by cold exposure independently of UCP1-mediated thermogenesis. FA and cholesterol biosynthesis pathways were enhanced only in UCP1-KO mice. Cold exposure also significantly increased the BAT content of proline, tryptophan, and phenylalanine amino acids in both WT and UCP1-KO mice. In WT mice, cold exposure significantly increased glutamine content and enhanced the expression of genes related to glutamine metabolism. Surprisingly, aspartate was almost completely depleted after cold exposure in UCP1-KO mice. Gene expression analysis suggested that aspartate was actively utilized after cold exposure both in WT and UCP1-KO mice, but it was replenished from intracellular N-acetyl-aspartate in WT mice.
CONCLUSIONS
These results revealed that cold exposure induces UCP1-mediated thermogenesis-dependent glucose utilization and UCP1-independent active lipid metabolism in BAT. In addition, cold exposure largely affects amino acid metabolism in BAT, especially UCP1-dependently enhances glutamine utilization. These results contribute a comprehensive understanding of UCP1-mediated thermogenesis-dependent and thermogenesis-independent metabolism in BAT. | 10.1016/j.metabol.2020.154396 |
others_78_3499 | There is a considerable lack of data concerning the diagnostic testing for kidney damage after surgical procedures. In this situation the most important variables should be examined with respect to their clinical informative value, the costs associated with their analysis, and their potential use in routine diagnostic testing. Forty patients in the surgical intensive care unit (ICU) with acute kidney injury (AKI) that developed during their stay of 13-18 (median, 16) days in the ICU were examined daily during their entire ICU admission. The bulk of the laboratory research consisted of the measurement of creatinine, urea, and sodium, as well as clearances rates and diuresis. Various tests for diagnosing regional renal damage (enzymes and proteins) were also carried out. The included photometry, nephelometric analysis, and ELISA (enzyme-linked immunosorbent assay). Five days before an AKI became evident, pathologic levels of urinary α1-microglobulin (tubular parameter) could already be confirmed. Serum creatinine values or creatinine clearance indicated the presence of disease only 1 day before the AKI was seen. Our results show that determination of α1-microglobulin and immunoglobulin G (glomerular parameter) levels, in addition to the level of urea in serum, be recommended for patients in surgical intensive care units who are at risk for AKI. Use of these procedures can achieve early recognition and sufficiently precise localization of renal damage. © 2010 Versita Warsaw and Springer-Verlag Berlin Heidel | 10.2478/s11536-010-0028-3 |
pubmed_483_3317 | Organic photovoltaic devices operate by absorbing light and generating current. These two processes are governed by the optical and transport properties of the organic semiconductor. Despite their common microscopic origin-the electronic structure-disclosing their dynamical interplay is far from trivial. Here we address this issue by time-resolved photoemission to directly investigate the correlation between the optical and transport response in organic materials. We reveal that optical generation of non-interacting excitons in a fullerene film results in a substantial redistribution of all transport levels (within 0.4 eV) of the non-excited molecules. As all observed dynamics evolve on identical timescales, we conclude that optical and transport properties are completely interlinked. This finding paves the way for developing novel concepts for transport level engineering on ultrafast time scales that could lead to novel functional optoelectronic devices. | 10.1038/s41467-019-09136-7 |
pubmed_1018_23263 | During surgical laparoscopy, total hepatic blood flow (THBF) may be modified by CO2 insufflation, changes of tilt, ventilation with high tidal volume, hypercapnia, and anesthesia, but little information is available on the THBF during the procedure. To investigate the changes of hepatic blood flow following the combination of abdominal CO2 insufflation and changes of tilt, we measured mean arterial pressure (MAP), cardiac output, portal vein blood flow (PVBF), and hepatic artery blood flow (HABF) in anesthetized and ventilated pigs. CO2 was insufflated in the abdomen [intra-abdominal pressure (IAP) approximately 15 mmHg], and the hepatic blood flow was measured in various positions (horizontal, 10 degrees and 20 degrees head down, and 10 degrees and 20 degrees head up) before and during CO2 insufflation. CO2 insufflation in the horizontal position did not modify MAP, cardiac output, or PVBF but increased HABF. The head-up tilt decreased MAP, cardiac output, and both hepatic flows in the absence of pneumoperitoneum, but in the presence of abdominal CO2 only cardiac output and PVBF were decreased. The head-down tilt increased MAP and THBF in the absence of pneumoperitoneum, whereas no change was observed in the presence of abdominal CO2. The combination of CO2 insufflation and changes of tilt was not deleterious to hepatic perfusion. These results suggest that hepatic blood flow may be preserved during surgical laparoscopy if the tilt does not exceed 20 degrees and if IAP after CO2 insufflation remains <15 mmHg. | 10.1152/ajpheart.1998.275.3.H900 |
pubmed_1050_24886 | The prevalence of oral squamous cell carcinoma (OSCC) in the elderly is expected to increase by nearly a third in the next decade. Its management in older patients is potentially more challenging due to their pre-existing medical comorbidities, frailty, reduced life expectancy, and social issues. The aim of this retrospective review was to report on treatment given to patients aged 75 years and over, case mix, and survival. All patients aged 75 years and over who were diagnosed with OSCC in Merseyside between 1 January 2007 and 31 December 2016, and treated with either curative or palliative intent, were included. Their hospital notes were reviewed. Fisher's exact test and Kaplan-Meier analysis were used for data analysis. There were 236 patients (median (IQR) age 81 (78-86) years); 67% were treated curatively and 33% palliatively. Factors associated with palliation included older age, advanced tumour stage, cognitive impairment, and residence in a nursing or residential home. Of the 165 patients who were offered curative treatment, six (4%) declined due to personal or family reasons. Overall survival for palliative patients was 12% at one year and 7% at two years, whereas for patients treated curatively it was 74% at one year, 56% at two years, and 34% at five years. Patients over 85 years of age were less likely to have composite free flaps and postoperative radiotherapy. Perioperative mortality was 2.6%. Improvements in surgical techniques and perioperative management have enabled clinicians to offer treatment with curative intent to older frail patients, and with careful case selection outcomes can be very good. | 10.1016/j.bjoms.2020.08.086 |
others_375_17608 | Thirty-three crossbred boars, 47 to 58 days of age, were randomly allocated to receive maize-soya bean meal diets containing 0·05, 0·15 or 0·30 mg selenium per kg. Body weights, testicular widths, and blood samples from vena cava puncture were taken at regular intervals. Libido was subjectively scored upon exposure to ovariectomized-oestrogenized gilts. Seven animals from each group were slaughtered at 9 months of age and selected reproductive structures were retrieved. Analysis of the relationships among body weight, libido and plasma testosterone levels indicated that differences (P < 0·01) existed between treatments, as analyzed over time, but that the overall treatment effect was not significant. Testicular widths were also found to be different (P < 0·05) over time. Values for all four criteria as measured over time were greater for boars fed 0·05 mg selenium per kg than for those fed 0·15 which were in turn greater than those fed 0·30. Post-mortem examination showed no treatment differences (1) in testis weights; (2) spermatozoan concentrations within the capita, corporea or caudae segments of the epididymis and (3) spermatozoan morphology examined within the caudae epididymis. Also testis lengths, weights, circumferences and spermatozoan concentrations were not significantly different between treatments. These results suggest that boars fed selenium at 0·15 or 0·30 mg/kg may exhibit some signs of retarded sexual development for a short period preceding the onset of sexual maturity. © 1983, British Society of Animal Science. All rights reser | 10.1017/S0003356100002014 |
pubmed_878_3989 | The applicability of a HVGGSSV peptide targeted "nanosponge" drug delivery system for sequential administration of a microtubule inhibitor (paclitaxel) and topoisomerase I inhibitor (camptothecin) was investigated in a lung cancer model. Schedule-dependent combination treatment with nanoparticle paclitaxel (NP PTX) and camptothecin (NP CPT) was studied in vitro using flow cytometry and confocal imaging to analyze changes in cell cycle, microtubule morphology, apoptosis, and cell proliferation. Results showed significant G2/M phase cell cycle arrest, changes in microtubule dynamics that produced increased apoptotic cell death and decreased proliferation with initial exposure to NP PTX, followed by NP CPT in lung cancer cells. In vivo molecular imaging and TEM studies validated HVGGSSV-NP tumor binding at 24 h and confirmed the presence of Nanogold labeled HVGGSSV-NPs in tumor microvascular endothelial cells. Therapeutic efficacy studies conducted with sequential HVGGSSV targeted NP PTX and NP CPT showed 2-fold greater tumor growth delay in combination versus monotherapy treated groups, and 4-fold greater delay compared to untargeted and systemic drug controls. Analytical HPLC/MS methods were used to quantify drug content in tumor tissues at various time points, with significant paclitaxel and camptothecin levels in tumors 2 days postinjection and continued presence of both drugs up to 23 days postinjection. The efficacy of the NP delivery system in sequential treatments was corroborated in both in vitro and in vivo lung cancer models showing increased G2/M phase arrest and microtubule disruption, resulting in enhanced apoptotic cell death, decreased cell proliferation and vascular density. | 10.1021/mp400432b |
pubmed_722_17625 | PURPOSE
Previously, we found that gene expression in histologically normal breast epithelium (NlEpi) from women at high breast cancer risk can resemble gene expression in NlEpi from cancer-containing breasts. Therefore, we hypothesized that gene expression characteristic of a cancer subtype might be seen in NlEpi of breasts containing that subtype.
EXPERIMENTAL DESIGN
We examined gene expression in 46 cases of microdissected NlEpi from untreated women undergoing breast cancer surgery. From 30 age-matched cases [15 estrogen receptor (ER)+, 15 ER-] we used Affymetryix U133A arrays. From 16 independent cases (9 ER+, 7 ER-), we validated selected genes using quantitative real-time PCR (qPCR). We then compared gene expression between NlEpi and invasive breast cancer using four publicly available data sets.
RESULTS
We identified 198 genes that are differentially expressed between NlEpi from breasts with ER+ (NlEpiER+) compared with ER- cancers (NlEpiER-). These include genes characteristic of ER+ and ER- cancers (e.g., ESR1, GATA3, and CX3CL1, FABP7). qPCR validated the microarray results in both the 30 original cases and the 16 independent cases. Gene expression in NlEpiER+ and NlEpiER- resembled gene expression in ER+ and ER- cancers, respectively: 25% to 53% of the genes or probes examined in four external data sets overlapped between NlEpi and the corresponding cancer subtype.
CONCLUSIONS
Gene expression differs in NlEpi of breasts containing ER+ compared with ER- breast cancers. These differences echo differences in ER+ and ER- invasive cancers. NlEpi gene expression may help elucidate subtype-specific risk signatures, identify early genomic events in cancer development, and locate targets for prevention and therapy. | 10.1158/1078-0432.CCR-10-1369 |
pubmed_100_19275 | BACKGROUND
Increasing evidence suggests that nutrients from fruits and vegetables have chemoprotective effects on various cancers including hematologic malignancies, but the effects of nutritional supplements are poorly examined.
METHODS
Herein, we prospectively evaluated the association of vitamin, mineral, and specialty supplements with incident hematologic malignancies in 66,227 men and women aged 50 to 76 years from Washington State recruited from year 2000 to 2002 to the VITamins And Lifestyle (VITAL) cohort study. Hematologic malignancies cases (n = 588) were identified through December 2008 by linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry. HRs and 95% CIs associated with supplement use were estimated with Cox proportional hazards models.
RESULTS
After adjustment, high use of garlic supplements [≥4 days per week for ≥3 years; HR = 0.55 (95% CI = 0.34-0.87); P(trend) = 0.028] and ever use of grape seed supplements [HR = 0.57 (95% CI = 0.37-0.88)] were inversely associated with hematologic malignancies in our models. In addition, high use (8-10 pill-years) of multivitamins was suggestive of an inverse association [HR = 0.80 (95% CI = 0.64-1.01)]. In contrast, no associations were observed for the remaining supplements.
CONCLUSIONS
These data indicate that the use of garlic and grape seed may be associated with reduced risk of hematologic malignancies.
IMPACT
This is the first cohort study to suggest a possible role of these supplements in the chemoprevention of hematologic malignancies. | 10.1158/1055-9965.EPI-11-0494 |
pubmed_652_6921 | Cystic fibrosis can affect food digestion and nutrient absorption. The underlying mutation of the cystic fibrosis trans-membrane regulator gene depletes functional cystic fibrosis trans-membrane regulator on the surface of epithelial cells lining the digestive tract and associated organs, where Cl(-) secretion and subsequently secretion of water and other ions are impaired. This alters pH and dehydrates secretions that precipitate and obstruct the lumen, causing inflammation and the eventual degradation of the pancreas, liver, gallbladder and intestine. Associated conditions include exocrine pancreatic insufficiency, impaired bicarbonate and bile acid secretion and aberrant mucus formation, commonly leading to maldigestion and malabsorption, particularly of fat and fat-soluble vitamins. Pancreatic enzyme replacement therapy is used to address this insufficiency. The susceptibility of pancreatic lipase to acidic and enzymatic inactivation and decreased bile availability often impedes its efficacy. Brush border digestive enzyme activity and intestinal uptake of certain disaccharides and amino acids await clarification. Other complications that may contribute to maldigestion/malabsorption include small intestine bacterial overgrowth, enteric circular muscle dysfunction, abnormal intestinal mucus, and intestinal inflammation. However, there is some evidence that gastric digestive enzymes, colonic microflora, correction of fatty acid abnormalities using dietary n-3 polyunsaturated fatty acid supplementation and emerging intestinal biomarkers can complement nutrition management in cystic fibrosis. | pubmed_652_6921 |
pubmed_948_15798 | According to the authors of the present paper, the formation of the MR+ and MR- groups is not explained by the variable degree of acidification, but by the various capacity of realkalinization of cultures. pH increases to values tending to 8 due to the formation of amines, ammonia and other basic products. They are the result of oxidative degradation processes, thus explaining the dependence on oxygen and the strictly aerobic character of the reaction. The acid-alkaline variation is influenced by the different content of peptones in monoaminodicarboacylic (meat-contraindicated) and diaminomenocarvoxylic (casein/soya bean-recommended) acids. The alkaline reversion may be determined in liquid media, having included ab initio either bromthymol blue, or bromcresol purple. The changes in pH may be read directly, colorimetrically, after an 18-20-hour incubation. By changing the interpretation (acid from glucose) and the indicator suggested by Clark and Lubs, the name "methyl red" becomes meaningless. At the same time, the introduction of other biochemical parameters (proteinic catabolism, realkalinization, dependence on oxygen) and the modification of the conditions of methods, justify the suggestion that the process of alkaline reversion, noted by the abbreviation "Reval", should be considered as a "per se" reaction and the laboratory determination should be patented as a routine test for the diagnosis of Enterobacteria. | pubmed_948_15798 |
pubmed_1098_17092 | OBJECTIVES
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with a high case fatality rate. Key gaps remained as to the assessment of the clinical picture in fatal cases.
METHODS
A retrospective study was performed on 496 patients with fatal SFTS. The dynamic pattern of clinical manifestations and laboratory indicators were delineated.
RESULTS
The mean age of the fatal cases was 69.0 years (standard deviation: 9.3), and 52.8% were male. The median clinical course from disease onset to death was 11 (interquartile range: 10-13) days. A total of 11 laboratory indicators (neutrophil %, platelet, aspartate aminotransferase, aspartate aminotransferase/alanine transaminase, lactate dehydrogenase, creatine kinase, cystatin C, D-dimer, activated partial thromboplastin time, thrombin time, glucose) persistently deviated from normality across hospitalization. The critical time points when the rapid worsening of the indicators was at 6-9 days after disease onset. Alanine transaminase, AST, lactate dehydrogenase, total bile acid, gamma-glutamyl transpeptidase, and glucose were all elevated to a more pronounced level in fatal cases of those aged ≤70 years.
CONCLUSION
The fatal outcome was developed in rather a short course after the disease onset of SFTS. High vigilance should be put on the key time points when the severe worsening and severe complications occur. | 10.1016/j.ijid.2022.10.008 |
pubmed_724_16822 | Carrots ( Daucus carota L.) contain phytochemicals including carotenoids, phenolics, polyacetylenes, isocoumarins, and sesquiterpenes. Purple carrots also contain anthocyanins. The anti-inflammatory activity of extracts and phytochemicals from purple carrots was investigated by determining attenuation of the response to lipopolysaccharide (LPS). A bioactive chromatographic fraction (Sephadex LH-20) reduced LPS inflammatory response. There was a dose-dependent reduction in nitric oxide production and mRNA of pro-inflammatory cytokines (IL-6, IL-1beta, TNF-alpha) and iNOS in macrophage cells. Protein secretions of IL-6 and TNF-alpha were reduced 77 and 66% in porcine aortic endothelial cells treated with 6.6 and 13.3 microg/mL of the LH-20 fraction, respectively. Preparative liquid chromatography resulted in a bioactive subfraction enriched in the polyacetylene compounds falcarindiol, falcarindiol 3-acetate, and falcarinol. The polyacetylenes were isolated and reduced nitric oxide production in macrophage cells by as much as 65% without cytotoxicity. These results suggest that polyacetylenes, not anthocyanins, in purple carrots are responsible for anti-inflammatory bioactivity. | 10.1021/jf073494t |
pubmed_175_13628 | The mechanism by which the content of the major groups of seminal plasma proteins in stallion semen changes between the breeding and non-breeding seasons remains unknown. Here, we investigated the proportions of non-heparin-binding, phosphorylcholine-binding, and heparin-binding proteins in seminal plasma with the aim of relating them to sperm quality and testosterone levels in good and bad freezer stallions. Only minor variations in the major protein groups were found between the breeding and non-breeding seasons. In the non-breeding season, a higher content of a subset of non-heparin binding proteins as well as of heparin-binding proteins was found. Analysis of semen characteristics revealed a somewhat contrasting picture. While only minor variations in sperm kinematics and sperm morphology were found between seasons, the flow-cytometric measurements of mitochondrial membrane potential and also, to some extent, reactive oxygen species production indicated lower sperm quality in the breeding season. Chromatin integrity and testosterone levels were unchanged between seasons. The results suggest that stallion ejaculates could be used year-round for freezing, since only minor differences in protein composition exist between the breeding and non-breeding seasons, as well as between good and bad freezers. In addition, sperm quality is not impaired during the non-breeding season. | 10.1262/jrd.2019-072 |
pubmed_878_18199 | Electronic noses have the benefit of obtaining smell information in a simple and objective manner, therefore, many applications have been developed for broad analysis areas such as food, drinks, cosmetics, medicine, and agriculture. However, measurement values from electronic noses have a tendency to vary under humidity or alcohol exposure conditions, since several types of sensors in the devices are affected by such variables. Consequently, we show three techniques for reducing the variation of sensor values: (1) using a trapping system to reduce the infering components; (2) performing statistical standardization (calculation of z-score); and (3) selecting suitable sensors. With these techniques, we discriminated the volatiles of four types of fresh mushrooms: golden needle (Flammulina velutipes), white mushroom (Agaricus bisporus), shiitake (Lentinus edodes), and eryngii (Pleurotus eryngii) among six fresh mushrooms (hen of the woods (Grifola frondosa), shimeji (Hypsizygus marmoreus) plus the above mushrooms). Additionally, we succeeded in discrimination of white mushroom, only comparing with artificial mushroom flavors, such as champignon flavor and truffle flavor. In conclusion, our techniques will expand the options to reduce variations in sensor values. | 10.3390/s131115532 |
pubmed_948_16225 | Several strains of Bacteroides gingivalis had strong activities of superoxide dismutase (SOD) and were markedly tolerant in the presence of oxygen in 13 strains of black-pigmented Bacteroides species tested. Thus, the strains were maintained and incubated in the either anaerobic or aerobic system. It was found that the SOD activity was significantly induced by oxygen, especially in B. gingivalis 381. The SODs, anaero-SOD and aero-SOD from the extracts of B. gingivalis 381 cells, each was purified by hydrophobic chromatography followed by anion exchange chromatography, and then by gel filtration, respectively. Both the purified enzymes having molecular weight of about 46,000 consisted of two subunits of equal sizes. Spectral analysis revealed that anaero-SOD had the characteristic A350 of Fe-SOD, but aero-SOD exhibited A475 of Mn-SOD. Both samples contained three isozymes with identical isoelectric points of 5.25, 5.10 and 5.00. On the basis of inactivation of SOD by H2O2, it was shown that aero-SOD consisted of one Mn-SOD and a small quantity of two Fe-SODs, whereas anaero-SOD contained only Fe-SOD. To ascertain whether or not the apoprotein of aero-SOD is the same as that of anaero-SOD, each apoprotein was prepared by dialysis in guanidinium chloride plus 8-hydroxyquinoline. Only one protein band with the same isoelectric point of 5.30 on an isoelectric focusing gel was obtained in each purified SOD sample. Subsequent reconstitution of both apoenzymes with either Fe (NH4)2 (SO4)2 or MnCl2 significantly restored their activity. These reconstituted SODs showed only one protein band with SOD activity on Native-PAGE. The complete amino acid sequence of anaero-SOD was determined by automated Edman degradation of the protein, Achrombacter protease I, endoproteinase Asp-N and tryptic digestion. The sequence consisted of 191 residues corresponding to a molecular weight of 21,500 per subunit. Furthermore, the first 36 amino acid sequence of aero-SOD was determined following N-terminal analysis. The two enzymes had similar amino acid compositions, and their amino-terminal sequences were identical through the first 36 amino acids in which methionine residue was present at N-terminal. These results suggest the three isozymes of either anaero-SOD or aero-SOD in B. gingivalis 381 may be formed from the same apoprotein. | pubmed_948_16225 |
pubmed_574_7174 | Because aspiration pneumonia contributes significantly to morbidity and mortality in hospitalized patients, this study was undertaken to identify risk factors for morbidity and mortality associated with aspiration pneumonia. Patients with a discharge diagnosis of aspiration pneumonia in 1985 and 1990 were studied. Factors associated with death from aspiration pneumonia were: altered mental status, cerebrovascular accident, endotracheal intubation, tachycardia, and hypoxemia. Fever, cough, and unilateral infiltrates on chest radiograph were associated with survival. Attention to proper positioning of comatose patients, aggressive treatment of gastroesophageal reflux, and strict attention to endotracheal tubes and tracheostomies should decrease the morbidity and mortality associated with aspiration pneumonia. | pubmed_574_7174 |
pubmed_180_3939 | Mycoplasma pneumonia is responsible for multisystemic infection. Pulmonary symptoms are most common in children. We describe herein two unusual severe forms of M. pneumoniae infection without initial pulmonary symptoms. The first case is an 8-month-old boy who was hospitalized in the pediatric intensive care unit with severe sepsis. There were no initial pulmonary symptoms, nor obvious clinical infection. Initial blood tests and x-ray did not aid the diagnosis. The blood tests came back positive for M. pneumonia. Pulmonary symptoms eventually appeared 24h later, and there was a pneumonia outbreak on the chest radiograph. The boy was given josamycin and improved quickly. The second case concerns an 8-year-old child who was hospitalized in the pediatric intensive care unit with toxic shock. No clinical infectious origin was found. A broad-spectrum antibiotic therapy was started with ceftriaxone and josamycin. The M. pneumoniae blood test came back positive, which confirmed the diagnosis of septic shock in M. pneumoniae, requiring adjustment of the antibiotic therapy. Current guidelines for the choice of probabilistic antibiotic therapy in case of severe sepsis do not include the case of M. pneumoniae. The early initiation of antibiotic therapy plays a major role in the prognosis of these patients. It seems useful to search for M. pneumoniae in cases of severe atypical infections, particularly in the absence of pulmonary symptoms. | pubmed_180_3939 |
pubmed_1011_2994 | Testosterone secretion by foetal rat testes (13 1/2-21 1/2 days of gestation) explanted for 3 days in a synthetic medium was measured every 24 h by radioimmunoassay. During the first day of explantation, the foetal testis produced, respectively, 1013 +/- 132, 8734 +/- 1118, 9179 +/- 2185 and 3886 +/- 309 (S.E.M.) pg/testis when explanted at 14 1/2, 16 1/2, 18 1/2 and 21 1/2 days respectively. Testosterone production by 13 1/2-day-old testes was not detectable on the first day of culture, but appeared on subsequent days. Daily testosterone secretion increased on the 2nd and 3rd days of culture in 14 1/2-day-old testes and decreased in older stages. These results suggest that the functional differentiation of the testis is independent of stimulatory factors like gonadotrophins. Dibutyryl cyclic AMP was found to stimulate testosterone production significantly from 14 1/2 days of gestation onwards. | 10.1677/joe.0.0710231 |
pubmed_207_21791 | OBJECTIVE
To determine whether birth weight and gestational age are associated with respiratory illness and lung function in children aged 5-11 years.
DESIGN
Cross sectional analysis of parent reported birth weight, gestational age, and respiratory symptoms; parental smoking and social conditions; forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory rates between 25% and 75% and 75% and 85% (FEF25-75 and FEF75-85), and height.
SETTING
Primary schools in England and Scotland in 1990.
SUBJECTS
5573 children aged 5-11 (63.3% of eligible children) had respiratory symptoms analysed and 2036 children (67.1% of eligible children) had lung function measured.
MAIN OUTCOME MEASURES
Symptoms of asthma, bronchitis, occasional and frequent wheeze, cough first thing in the morning, and cough at any other time and lung function.
RESULTS
Birth weight adjusted for gestational age was significantly associated with all lung function measurements, except FEF25-75. The association remained for FVC (b = 0.475, 95% confidence interval 0.181 to 0.769) and FEV1 (b = 0.502, 0.204 to 0.800) after adjustment for gestational age, parental smoking, and social factors. FEF75-85 was the only lung function related to gestational age. Respiratory symptoms, especially wheeze most days (adjusted odds ratio 0.9, 0.84 to 0.97) were significantly associated with prematurity. Every extra week of gestation reduced the risk of severe wheeze by about 10%.
CONCLUSIONS
Lung function is affected mainly by intrauterine environment while respiratory illness, especially wheezing, in childhood is related to prematurity. | 10.1136/bmj.306.6881.817 |
pubmed_170_18570 | BACKGROUND AND AIM
Earlier research has suggested that local communities develop different sickness absence practices, expressed in variation in the absence figures. This study aimed to test the hypothesis that the work places residing in a locality share similar sickness absence practice.
METHODS
Register data from the major public sector employers and from private industrial employers were used to compare the absence in two localities.
RESULTS
There were significant differences by locality in both branches and both in short and in long sickness absences. Population-level statistics showed a corresponding locality difference in recipients of sickness allowance benefits and in primary healthcare visits, but not in indicators of mortality and morbidity. Social problems were more common in the locality with high rate of absence.
CONCLUSION
Area-specific practice, or habitus, as an independent determinant of sickness absence is discussed and an explicitly sociological context is recommended for debates about ''best sickness absence practices'' and corresponding intervention measures. | 10.1177/1403494809364561 |
pubmed_813_10689 | BACKGROUND AND PURPOSE
Genetic enzyme variation and vitamin intake are important determinants of blood homocyst(e)ine levels. The prevalence of common genetic polymorphisms influencing homocyst(e)ine levels varies by race, and vitamin intake varies by socioeconomic status. Therefore, we examined the effect of vitamin intake, race, and socioeconomic status on the association of homocyst(e)ine with stroke risk.
METHODS
All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. One hundred sixty-seven cases of first ischemic stroke among women aged 15 to 44 years were compared with 328 controls identified by random-digit dialing from the same region. Risk factor data were collected by standardized interview and nonfasting phlebotomy. Plasma homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection.
RESULTS
Blacks and whites did not differ in median homocyst(e)ine levels, nor did race modify the association between homocyst(e)ine and stroke. After adjustment for cigarettes per day, poverty status, and regular vitamin use, a plasma homocyst(e)ine level of >/=7.3 micromol/L was associated with an odds ratio for stroke of 1.6 (95% CI, 1.1 to 2.5).
CONCLUSIONS
The association between elevated homocyst(e)ine and stroke was independent not only of traditional vascular risk factors but also of vitamin use and poverty status. The degree of homocyst(e)ine elevation associated with an increased stroke risk in young women is lower than that previously reported for middle-aged men and the elderly and was highly prevalent, being present in one third of the control group. | 10.1161/01.str.30.8.1554 |
pubmed_625_8725 | Hypereosinophilia (HE) is currently defined by a peripheral blood absolute eosinophil count (AEC) of ≥1,500 cells/microL. Although mild blood eosinophilia (AEC 500-1,500 cells/microL) is observed relatively frequently within the pediatric population, persistent HE is uncommon and should prompt additional clinical evaluation. While the clinical manifestations and underlying etiologies of HE in adults have been well-characterized, there is a paucity of data on HE in children. Limited evidence suggests that many similarities between adult and pediatric HE likely exist, but some important differences remain between these populations. The evaluation of HE in children can be challenging given the broad differential diagnosis, which includes primary hematologic disorders and secondary eosinophilia in which the increased eosinophil levels are propagated by disease states that promote eosinophil production and survival. On the basis of the underlying etiology, clinical manifestations can range from benign, self-resolving elevations in the AEC to life-threatening disorders with the potential for significant end-organ damage. Given the broad differential diagnosis of HE, it remains essential to systematically approach the evaluation of unexplained HE in children. This review will discuss the differential diagnosis for pediatric HE, highlighting etiologies that are more prevalent within the pediatric population. Additionally, a summary of the epidemiology of pediatric HE will be presented, with focus on some of the differences that exist between pediatric and adult HE. Finally, a directed approach to the diagnostic evaluation of children with HE will be discussed. | 10.3389/fimmu.2018.01944 |
pubmed_42_6387 | Keratinocyte growth factor (KGF, FGF-7) is a potent mitogen for epithelial cells. We instilled recombinant human KGF to determine the effects of KGF on alveolar epithelial cells. Left lungs of adult rats were instilled intrabronchially with KGF (5 mg/kg) or normal saline. KGF instillation resulted in epithelial cell hyperplasia, and the alveolar bromodeoxyuridine (BrdU) labeling index peaked at 35% on day 2 after instillation. The mRNA levels for the surfactant proteins (SPs) SP-A, SP-B, and SP-D were increased in whole lung tissue on days 1 and 2 after KGF treatment and then returned to control levels on days 3-7. SP-C mRNA levels were increased on days 2-5 after KGF instillation. However, all surfactant protein mRNAs were reduced in type II cells isolated from rats instilled with KGF 2 or 3 days before isolation. These observations were confirmed by in situ hybridization. Instillation of KGF also increased the amount of SP-A and SP-D in lavage fluid. Transcripts for CC10, the 10-kDa Clara cell protein, were decreased. KGF increases the mRNA for the surfactant proteins per lung because of type II cell hyperplasia, but the mRNA per cell is slightly diminished as measured in isolated cells or estimated by in situ hybridization. | 10.1152/ajplung.2000.279.6.L1146 |
pubmed_111_2939 | The effect of spinal anesthesia, dilatation and curettage plus the first intracavitary radiotherapy or only that of intracavitary radiotherapy on growth hormone (HGH = the response of anterior pituitary) and arginine vasopressin (AVP = the response of posterior pituitary) levels was studied in 10 patients suffering from cervical or endometrial uterine cancer. Differing from earlier animal studies, irradiation had no effect on GH or AVP secretion, nor was there any change in the hormone levels following spinal anesthesia and dilatation and curettage. The neurosecretory response of hypothalamic-hypophyseal axis to spinal anesthesia and minor gynecological surgery appears to be minimal. | pubmed_111_2939 |
pubmed_655_18118 | OBJECTIVES
The aim of this study was to find out whether spot urinary concentrations of type 1 collagen cross-linked N-telopeptides (NTx) and deoxypyridinoline (Pyrilinks-D) can differentiate between active and inactive disease in rheumatoid arthritis (RA) and to investigate the extent to which they correlate with indices of disease activity.
METHODS
Using enzyme-linked immunosorbent assays, the concentrations of NTx and Pyrilinks-D were estimated in spot urine samples from 25 females with active disease, 25 females with inactive disease, and in 25 controls.
RESULTS
In Patients with active disease, urinary concentrations of NTx and Pyrilinks-D were significantly higher (p < 0.01) than in those with inactive disease or in healthy controls. In active disease there were significant positive correlation between urinary NTx and ESR, the swollen joint count, the tender joint count, and the patient's global assessment. | pubmed_655_18118 |
pubmed_1046_10525 | Hoarding disorder is characterized by difficulty parting with possessions and by clutter that impairs the functionality of living spaces. Cognitive behavioral therapy conducted by a therapist (individual or in a group) for hoarding symptoms has shown promise. For those who cannot afford or access the services of a therapist, one alternative is an evidence-based, highly structured, short-term, skills-based group using CBT principles but led by non-professional facilitators (the Buried in Treasures [BIT] Workshop). BIT has achieved improvement rates similar to those of psychologist-led CBT. Regardless of modality, however, clinically relevant symptoms remain after treatment, and new approaches to augment existing treatments are needed. Based on two recent studies - one reporting that personalized care and accountability made treatments more acceptable to individuals with hoarding disorder and another reporting that greater number of home sessions were associated with better clinical outcomes, we tested the feasibility and effectiveness of adding personalized, in-home uncluttering sessions to the final weeks of BIT. Participants (n = 5) had 15 sessions of BIT and up to 20 hours of in-home uncluttering. Reductions in hoarding symptoms, clutter, and impairment of daily activities were observed. Treatment response rate was comparable to rates in other BIT studies, with continued improvement in clutter level after in-home uncluttering sessions. This small study suggests that adding in-home uncluttering sessions to BIT is feasible and effective. | 10.1016/j.jpsychires.2018.10.001 |
pubmed_861_6767 | LC-MS/MS with multiple reaction monitoring (MRM) is a powerful tool for targeted metabolomics analysis including screening and quantification of known metabolites. Given the complexity of biological samples, the difference in ionization efficiency, and signal intensity of each metabolite, isotopically labeled internal standards are often used for accurate quantification. In this chapter, we describe a detailed protocol for the quantitative analysis of polyunsaturated fatty acids (PUFAs) and their oxidized products (oxylipins) by LC-MS/MS-MRM with isotope dilution. PUFAs are very susceptible to oxidation by both enzymatic and nonenzymatic pathways. Free PUFAs and corresponding oxylipins, known as bioactive lipids, are involved in many processes with varying biological functions depending on their chemical structure and concentration. Accurate quantification is thus becoming crucial to understanding the role of these bioactive lipids in health, disease(s), and other settings. | 10.1007/978-1-4939-9236-2_7 |
pubmed_213_9681 | The respiratory properties of mitochondria isolated from the livers of rats infected with the parasite Fasciola hepatica were examined. Oligomycin-sensitive ATPase activity was also examined during the acute stage (2-4 weeks post-infection). At 2,4 and 6 weeks post-infection, mitochondrial respiration in vitro (supported by site I and site II substrates) was completely uncoupled. Limited respiratory control had returned by 11 weeks post-infection, but complete recovery was not observed even at 21 weeks post-infection. At 4 weeks post-infection, uncoupled respiration (from all three energy-conserving sites) was also markedly attenuated (to the greatest extent with NADH-linked substrate). Except for pyruvate-supported respiration, this attenuation was not apparent at any other stage of the infection. The attenuation of pyruvate-supported respiration declined, but was still present, at 6 weeks post-infection. In addition to these perturbations in mitochondrial respiratory properties, mitochondrial ATPase activity at 4 weeks post-infection was insensitive to oligomycin, indicating a change in the structural integrity of the ATPase complex. | 10.1042/bj2600517 |
pubmed_591_1727 | Long noncoding RNAs (lncRNAs) are lengthy noncoding transcripts which are involved in critical signaling pathways including cell cycle and apoptosis so it is not surprising to see their altered expression in human tumors. Colorectal adenocarcinoma is one the most frequent malignancies worldwide. The role of lncRNAs in colorectal adenocarcinoma is not well understood. To study the significance of lncRNAs in colorectal adenocarcinoma, we retrieved 189 approved lncRNAs from HGNC. The genes were imported into the cBioPortal database for transcriptomic analyses. We queried all the samples from TCGA provisional colorectal adenocarcinoma with RNA-seq v2 data in our study and considered RNA dysregulation with Z-score: ±2. The lncRNA which was altered in most of the patients were considered as "significant lncRNA" for further analyses. We considered the association of candidate lncRNAs with clinicopathologic parameters of samples including tumor disease anatomic site, neoplasm histologic types, tumor stage and survival. We also compute the specificity of the significant lncRNAs expression in colorectal adenocarcinoma comparing with other human cancers in cancer portal. Our analysis showed that lncRNAs SNHG6, PVT1 and ZFAS1 allocated the maximum alteration among the colorectal cases. The expression of SNHG6 and ZFAS1 was more in rectal adenocarcinoma than the colon carcinoma while the PVT1 showed the same expression levels in both tissues. However, we found that upregulation of PVT1 has been reduced the overall survival in patients. Altogether these data showed SNHG6, PVT1 and ZFAS1, are promising candidates for experimental research on colorectal adenocarcinoma to discover novel biomarker for this prevalent cancer. | 10.1007/s12253-018-0428-2 |
others_52_14454 | Twenty-five F1 hybrid families of black currants (Ribes nigrum L.) originating from diallel crosses of five cultivars were assessed. Phenotypic correlation coefficient between full-sib family means (rFS), genetic correlation coefficient between full-sib family expected values (rG) and the environmental correlation were estimated on the basis of two years of observations for 12 quantitative characteristics studied. Evident repeatability of correlations in both years was proved. A considerable consistence between the values of genetic and phenotypic correlation coefficients was also observed. Coefficients of phenotypic and environmental correlation were significant for many pairs of traits. Most of the significant environmental correlation coefficients were found for the same pairs of characteristics for which phenotypic correlation coefficients were significant. This shows that genetic and environmental factors affected similar traits. Fruit yield expressed the largest number of significant correlations with other traits. Path coefficient analysis indicated that plant and berry size were the main factors influencing directly fruit yield in both years. It was proved that the number and length of one-year-old shoots via bush size had very large indirect effects on fruit yield per plan | others_52_14454 |
pubmed_537_15016 | AIMS
To examine the frequency of intraocular metastases in patients who had died of cancer, in an eye bank and necropsy population sample.
METHODS
The first group included 302 cancer cases received from the Wisconsin Eye Bank between 1988 and 1993. In the second group, ocular pathology records at the Wilmer Institute from 1976 to 1980 were analysed for ocular metastases in necropsy subjects dying of cancer. Nonocular cancer was the cause of death in 741 cases; among these, 510 were attributed to carcinomas.
RESULTS
In the Wisconsin Eye Bank group, three cases (1%) had gross metastases. Out of 255 carcinoma cases, one (0.4%) had gross metastases. In the Wilmer Institute group, gross metastases were observed in 35 (4.7%) cases. Of the 510 patients dying of carcinomas, six (1.2%) had macroscopic metastases. Ocular metastases were detected histopathologically in 93 of 741 (12.6%) of cases.
CONCLUSION
Even though it is difficult to assess the true frequency of ocular metastases in patients dying of cancer, the answer to this question was attempted by determining the frequency of ocular metastasis in patients who died of cancer and who donated their eyes to the Wisconsin Eye Bank or had postmortem examination at the Johns Hopkins Hospital. Microscopic metastases were found in 12.6% of cases. The frequency of gross metastases has decreased over the past 12 years from 4.7% to 1% (p value = 0.005) owing to improved treatment of leukaemia; however, the frequency of macroscopic metastases due to carcinomas has not changed (p value = 0.38). | 10.1136/bjo.80.2.125 |
pubmed_934_20531 | Objective. The aim of this study was to evaluate the impact of two exercise programs, whole body vibration and resistance training on bone mineral density (BMD) and anthropometry in obese postmenopausal women. Material and Methods. Eighty Egyptian obese postmenopausal women were enrolled in this study; their age ranged from 50 to 68 years. Their body mass index ranged (30-36 kg/m(2)). The exercise prescription consisted of whole body vibration (WBV) and resistance training. Bone mineral density (BMD) and anthropometrical parameters were measured at the beginning and at the end of the study. Changes from baseline to eight months in BMD and anthropometric parameters were investigated. Results. BMD at the greater trochanter, at ward's triangle, and at lumbar spine were significantly higher after physical training, using both WBV and resistive training. Moreover, both exercise programs were effective in BMI and waist to the hip ratio. Simple and multiple regression analyses showed significant associations between physical activity duration and BMD at all sites. The highest values of R (2) were found for the models incorporating WBV plus BMI. Conclusion. The study suggests that both types of exercise modalities had a similar positive effect on BMD at all sites in obese postmenopausal women. Significant association was noted between physical activity and anthropometric variables and BMD measures at all sites. | 10.1155/2014/702589 |
pubmed_898_2575 | BACKGROUND
Because of increased risk of metachronous colorectal cancer (CRC), all patients with Lynch syndrome (LS) are offered a total colectomy. However, because metachronous CRC rate by mismatch repair (MMR) gene is uncertain, and total colectomy negatively impacts quality of life, it remains unclear whether segmental resection is indicated for lower penetrance MMR genes. We evaluated metachronous CRC incidence according to MMR gene in LS patients who underwent a segmental colectomy.
STUDY DESIGN
Single-center, retrospective cohort study in patients with an earlier colectomy for CRC and an MMR germline mutation in MLH1, MSH2, MSH6, or PMS2 followed prospectively in a hereditary CRC family registry. All patients underwent surveillance colonoscopy. Metachronous CRC was defined as one detected more than 1 year after index resection. Primary end point was cumulative incidence of metachronous CRC overall and by MMR gene.
RESULTS
One hundred and ten patients were included: 35 with MLH1 likely pathogenic/pathogenic (LP/P) variants (32%), 42 MSH2 (38%), 20 MSH6 (18%), and 13 PMS2 (12%). Median follow-up 4.26 years (range 0.53 to 19.92 years). Overall, metachronous CRC developed in 22 patients (20%). At 10-year follow-up, incidence was 12% (95% CI 6% to 23%), with no metachronous CRC detected in patients with a PMS2 or MSH6 LP/P variant.
CONCLUSIONS
After index segmental resection, metachronous CRC is less likely to develop in LS patients with MSH6 or PMS2 LP/P variant than in MLH1 or MSH2 carriers. Our data support segmental resection and long-term colonoscopic surveillance rather than total colectomy in carefully selected, well-informed LS patients with MSH6 or PMS2 LP/P variant. | 10.1016/j.jamcollsurg.2020.01.005 |
pubmed_990_11829 | A recurrent craniopharyngioma associated with moyamoya vessels was successfully treated by partial removal of the tumor via the transsphenoidal approach followed by gamma-knife radiosurgery. This 19-year-old man was first treated by partial tumor removal and radiotherapy (54Gy) at the age of 6 years. Growth hormone and human chorionic gonadotropin were given from the ages of 13 to 18 years. At ag 17 years, follow-up magnetic resonance imaging (MRI) revealed regrowth of the tumor. At the age of 19 years, he was readmitted for treatment of the enlarging remnant tumor. Neurological examination revealed bilateral blindness. MRI showed marked suprasellar, sphenoidal and bilateral cavernous sinus extension of the tumor. Angiography revealed stenosis of the right internal carotid artery and the M1 and A1 segments of the right cerebral arteries, as well as occlusion of the C3 segment of the left internal carotid artery. There were vault and ethmoidal moyamoya vessels. The patient underwent tumor removal via the transsphenoidal approach, instead of craniotomy, to avoid injury to the transdural anastomosis. The intrasellar solid tumor was partially removed. The tumor was then irradiated by the gamma knife. MRI 15 months after the treatment showed marked reduction of the tumor. The pathogenesis of the moyamoya phenomenon and the choice of the treatment in this patient are discussed. | pubmed_990_11829 |
pubmed_922_15678 | Over the past decades, the field of in vivo magnetic resonance (MR) has built up an impressive repertoire of data acquisition and analysis technologies for anatomical, functional, physiological, and molecular imaging, the description of which requires many book volumes. As such it is impossible for a few authors to have an authoritative overview of the field and for a brief article to be inclusive. We will therefore focus mainly on data acquisition and attempt to give some insight into the principles underlying current advanced methods in the field and the potential for further innovation. In our view, the foreseeable future is expected to show continued rapid progress, for instance in imaging of microscopic tissue properties in vivo, assessment of functional and anatomical connectivity, higher resolution physiologic and metabolic imaging, and even imaging of receptor binding. In addition, acquisition speed and information content will continue to increase due to the continuous development of approaches for parallel imaging (including simultaneous multi-slice imaging), compressed sensing, and MRI fingerprinting. Finally, artificial intelligence approaches are becoming more realistic and will have a tremendous effect on both acquisition and analysis strategies. Together, these developments will continue to provide opportunity for scientific discovery and, in combination with large data sets from other fields such as genomics, allow the ultimate realization of precision medicine in the clinic. | 10.1016/j.jmr.2019.07.034 |
pubmed_515_9803 | How HIV-1 affects the monocyte proteome is incompletely understood. We posit that one functional consequence of virus-exposure to the monocyte is the facilitation of protein transformation from the cytosol to the plasma membrane (PM). To test this, cell surface labeling with CyDye fluorophores followed by 2 dimensional differential in-gel electrophoresis (2D DIGE) and liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed. Fifty three percent of HIV-1 induced proteins were PM associated. These were linked, in large measure, to cellular activation and oxidative stress. They included, but not limited to, biliverdin reductase, leukotriene hydrolase A(4), heat shock protein 70, and cystatin B. HIV-1 induced PM protein translocation was associated with cathepsin B- and caspase 9, 3-dependent apoptosis. In contrast, PMA-treated monocytes bypassed caspase 3, 9 pathways and lead to cathepsin B-dependent necrosis. These results demonstrate that HIV-1 uniquely affects monocyte activation and oxidative stress. These do not affect viral infection dynamics but are linked to stress-induced cell death. | 10.1016/j.cellimm.2009.03.012 |
pubmed_749_19675 | BACKGROUND
Trauma and depression have each been associated with neurocognitive alterations, but their combined effect on neurocognition is unclear. We investigated the separate and interactive associations of trauma and depression on neurocognition in a sample of ethnically diverse urban dwellers, and explored the impact of age on these effects.
METHODS
284 adults aged 30-89 were divided into groups based on their current depression and trauma history. Individuals meeting DSM-IV criteria for depression were considered Depressed (D+) and individuals rated through diagnostic interview as having trauma history were considered positive for Trauma (T+). Resulting Ns were 73 D+T+, 56 D+T-, 68 D-T+, and 87 D-T-. A principal component analysis of neuropsychological scores resulted in a 3-factor solution representing verbal learning/memory/recognition (VERBAL-LMR), visual learning/memory/recognition, and speeded attention/cognitive flexibility accounting for 70.21% of the variance.
RESULTS
Multivariable linear regressions adjusting for age revealed that Trauma, regardless of Depression, is associated with worse VERBAL-LMR performance. This Trauma association was driven by verbal list and prose passages learning and memory, but not recognition memory. Age-stratified (<60 versus ≥60 years) regressions revealed the Trauma association was only significant for older adults. No main or interactive effects for Depression were observed.
CONCLUSIONS
Trauma, regardless of Depression, is associated with worse verbal learning and memory, but not recognition performance. These results suggest that trauma exposure may negatively impact neurocognition. Clinicians working with adults in urban settings should query for trauma in addition to depression when considering subjective and objective measures of neurocognitive functioning, particularly in older adults. | 10.1016/j.jpsychires.2017.01.008 |
pubmed_173_17281 | BACKGROUND
Data relating to non-fatal cardiovascular events are poor but these data are essential to organize targeted interventions on the territory and to understand their effectiveness.
METHODS
We calculated the rates of morbidity from cardiovascular events covering the period 1998/99-2008/09, in a cohort of 1200 persons (600 men and 600 women) aged 25 to 74 years. Data were standardized using the European standard population.
RESULTS
The incidence of events to ten years of non-fatal myocardial infarc.ion was 2.2% in men and of 1.8% in women. PCI interventions to ten year have been 3.3% in men and 3.4% in women, the interventions of aorto-coronary bypass have been 2.4% and 0.5% for men and women respectively. While all major cardiovascular events have been more frequent in men, in women there was a higher incidence of stroke (1.6% vs 0.9%).
CONCLUSION
Although by comparison with other European countries Italy is among the countries considered at low-risk of coronary heart disease, in Campania cardiovascular diseases reach higher rates than the rest of the country. Our results are in keeping with the literature data and confirm that cardiovascular diseases are a major public health problem. Local analysis are useful in providing additional information for planning prevention interventions targeted to its own territory. | 10.4081/monaldi.2014.62 |
pubmed_692_11427 | Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Only 30%-40% of the patients with HCC are eligible for curative treatments, which include surgical resection as the first option, liver transplantation and percutaneous ablation. Unfortunately, there is a high frequency of tumor recurrence after surgical resection and most HCC seem resistant to conventional chemotherapy and radiotherapy. Sorafenib, a multi-tyrosine kinase inhibitor, is the only chemotherapeutic option for patients with advanced hepatocellular carcinoma. Patients treated with Sorafenib have a significant increase in overall survival of about three months. Therefore, there is an urgent need to develop alternative treatments. Due to its role in cell growth and development, the insulin-like growth factor system is commonly deregulated in many cancers. Indeed, the insulin-like growth factor (IGF) axis has recently emerged as a potential target for hepatocellular carcinoma treatment. To this aim, several inhibitors of the pathway have been developed such as monoclonal antibodies, small molecules, antisense oligonucleotides or small interfering RNAs. However recent studies suggest that, unlike most tumors, HCC development requires increased signaling through insulin growth factor II rather than insulin growth factor I. This may have great implications in the future treatment of HCC. This review summarizes the role of the IGF axis in liver carcinogenesis and the current status of the strategies designed to target the IGF-I signaling pathway for hepatocellular carcinoma treatment. | 10.4254/wjh.v6.i10.716 |
pubmed_164_25037 | Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide, presenting a great challenge to the public health systems due to high morbidity and mortality, because of frequent micro-/macro-vascular complications. Many treatment options are now available, with different efficacy as well as mechanisms of action to improve deranged glucose metabolism. We review some of the available data on derivatives of meglitinide, namely nateglinide and repaglinide. These two compounds increase insulin secretion by a mechanism similar to the one of sulfonylureas, but with a shorter half-life. Nateglinide and repaglinide, derivatives of meglitinides, have characteristic pharmacodynamic and pharmacokinetic properties that, together with their proposed mechanism of action, make them useful for type 2 diabetes mellitus, especially when used in combination therapy. | 10.5114/aoms.2013.34991 |
pubmed_695_23598 | This work describes the development of novel dual-stimuli-responsive nanocomposites based on silica-coated iron oxide/polyaniline (Si-MNPs/PANI) for biomedical applications. Si-MNPs/PANI nanocomposites were developed via chemical oxidative polymerization of aniline in the presence of Si-MNPs (25 and 50 wt%). Si-MNPs/PANI were obtained both in nanotubular (SPNTs) and granular (SGTs) forms by altering the synthesis parameters such as acid concentration and mixing process. The effects of nanocomposite morphology were evaluated by investigating their chemical, physical and biological properties. Material characterization was comparatively carried out via SEM, TEM, FTIR, XRD, TGA, room temperature VSM, and electrical resistivity measurements. Biological properties were evaluated by indirect in vitro cytotoxicity and in vitro hemocompatibility analyses according to ISO standards. Results indicated that Si-MNPs/PANI nanocomposites exhibited both magnetically and electrically-responsive properties. Magnetization values of Si-MNPs/PANI nanocomposites increased with increasing Si-MNPs content. However, electrical conductivity was inversely proportional to Si-MNPs content. In addition, SGTs represented remarkably higher electrical conductivity (1.1 S/cm) than SPNTs (4.8 × 10-2 S/cm), but lower saturation magnetization (21 emu/g) compared to SPNTs (27 emu/g). Furthermore, in vitro cytocompatibility and hemocompatibility of the SGTs and SPNTs varied in a dose-dependent manner, suggesting their use in certain doses for biomedical applications. In conclusion, the developed Si-MNPs/PANI, with magnetic sensitivity and electrical conductivity have potential as nanocomposites for utilization in biomedical applications, e.g. biosensing, controlled-drug delivery, bioelectronic systems, tissue engineering and regenerative medicine as active compound. Besides, the selection of the appropriate synthesis protocol allows Si-MNPs/PANI nanocomposites to exhibit superior properties according to the targeted application area. | 10.1016/j.msec.2020.111600 |
pubmed_828_11712 | INTRODUCTION
Hyperglycaemia at the time of acute myocardial infarction (AMI) is a predictor of survival and is associated with increased mortality and morbidity in patients with or without diabetes mellitus. On the other hand, insulin has been shown to reduce myocardial injury in experimental studies but its benefits have not been confirmed in clinical studies.
METHODS
The isolated perfused heart model was used to examine the direct effect of incremental doses of insulin and varying degrees of hyperglycaemia on infarct size and cardiomyocyte apoptosis in rabbit hearts. The rabbit hearts were subjected to 30-min ischaemia and 2.5-h reperfusion.
RESULTS
Insulin, given alone just before reperfusion, dramatically reduced infarct size in a dose-dependent manner (75-300 μU/ml) during experimental myocardial infarction (46%±2% to 10.9%±3%, P<.001). Acutely elevated glucose levels (33 mmol/L) induced a significantly greater infarct size and cardiomyocyte apoptosis compared to hearts subjected to normal glucose levels. On the other hand, high-dose insulin (300 μU/ml) given 5 min before reperfusion attenuated the extent of infarction and reduced apoptosis in hearts that were exposed to high glucose levels.
CONCLUSION
Acutely elevated levels of glucose induced larger infarct area during ischaemia-reperfusion, and this is mediated through proapoptotic pathways. Insulin, when given just before reperfusion, confers cardioprotection in a dose-dependent manner and reverses the detrimental effect of acute hyperglycaemia. High-dose insulin as well as maintaining normoglycaemia remain important factors that improve outcomes following myocardial infarction. | 10.1016/j.jdiacomp.2010.01.001 |
pubmed_1113_224 | Proteins from halophiles have adapted to challenging environmental conditions and require salt for their structure and function. How halophilic proteins adapted to a hypersaline environment is still an intriguing question. It is important to mimic the physiological conditions of the archae extreme halophiles when characterizing their enzymes, including structural characterization. The NMR derived structure of Haloferax volcanii dihydrofolate reductase in 3.5 M NaCl is presented, and represents the first high salt structure calculated using NMR data. Structure calculations show that this protein has a solution structure which is similar to the previously determined crystal structure with a difference at the N terminus of beta3 and the type of beta-turn connection beta7 and beta8. | 10.1110/ps.072950407 |
pubmed_596_23006 | Huntington's disease (HD) is a devastating and incurable neurodegenerative disorder characterized by progressive cognitive, psychiatric and motor impairments. Although the disease has been seen as a disorder purely of the brain, there is now emerging evidence that abnormalities outside the central nervous system are commonly seen in HD. Indeed, the mutant huntingtin (mHtt) coded for by the abnormal gene in HD is found in every cell type where its presence has been sought. In particular, there are a number of recent observations in HD patients that mHtt interacts with the immune system with accumulating evidence that changes in the immune system may critically contribute to the pathology of HD. However, the nature of this contribution remains unclear, to the extent that it is not even known whether the immune system has a beneficial or detrimental role in HD patients. In this review, we attempt to bring a novel understanding to the interaction of the immune system to HD pathology, thereby shedding light on its potential pathogenic role. As part of this discussion, we revisit the clinical data on the anti-inflammatory drug trials in HD and propose new experimental approaches to interrogate the role of immunity in this currently incurable disorder. | 10.1038/mp.2011.28 |
pubmed_197_5498 | Angiogenesis, the physiological process of sprouting of new blood vessels from pre-existing ones, is a key biological feature of almost all cancers. Among the multitude of factors driving tumor angiogenesis, vascular endothelial growth factor (VEGF) is the most potent, exerting myriad effects on vascular pruning and sprouting, permeability, network formation, proliferation, and cell death. Despite the initial unimpressive clinical performance of anti-VEGF antibody (bevacizumab) as cancer monotherapy, clear improvements in clinical outcomes following combination bevacizumab and chemotherapy regimens and multi-targeted VEGF receptor tyrosine kinase inhibitors (sorafenib and sunitinib) in select tumor types have established VEGF-targeted agents as an effective means of controlling cancer growth. Prolongation of overall survival and cure with these agents, however, remains elusive. Moreover, recent data has revealed key differences in the therapeutic and biological tumor response to antibody versus receptor kinase VEGF inhibitors and suggested, at least pre-clinically, that VEGF blockade in certain circumstances may actually promote more aggressive tumor growth. Given the diverse mechanisms and potentially opposing roles of VEGF neutralization in cancer biology, identification of novel biomarkers predictive of in vivo angiogenic responses may hold the key to optimizing therapeutic outcomes of anti-VEGF therapy in future cancer patients. | 10.1016/j.cyto.2010.06.012 |
pubmed_1089_4607 | Mycosporine-like amino acids (MAAs) are valuable molecules that are the basis for important photoprotective constituents. Here we report molecular analysis of mycosporine-like amino acid biosynthetic genes from the halotolerant cyanobacterium Aphanothece halophytica, which can survive at high salinity and alkaline pH. This extremophile was found to have a unique MAA core (4-deoxygadusol)-synthesizing gene separated from three other genes. In vivo analysis showed accumulation of the mycosporine-2-glycine but not shinorine or mycosporine-glycine. Mycosporine-2-glycine accumulation was stimulated more under the stress condition of high salinity than UV-B radiation. The Aphanothece MAA biosynthetic genes also manifested a strong transcript level response to salt stress. Furthermore, the transformed Escherichia coli and Synechococcus strains expressing four putative Aphanothece MAA genes under the control of a native promoter were found to be capable of synthesizing mycosporine-2-glycine. The accumulation level of mycosporine-2-glycine was again higher under the high-salinity condition. In the transformed E. coli cells, its level was approximately 85.2 ± 0.7 μmol/g (dry weight). Successful production of a large amount of mycosporine in these cells provides a new opportunity in the search for an alternative natural sunscreen compound source. | 10.1128/AEM.03729-13 |
pubmed_861_15351 | INTRODUCTION
Revision knee arthroplasty surgery can range from patella resurfacing or polyethylene exchange, to staged revision and revision to a more constrained implant. Subsequently, the ability to elicit outcomes becomes difficult to obtain and hence information on functional outcome and survivorship for all modes of failure with a single revision system is valuable.
METHODS
We retrospectively assessed 100 consecutive revision knee replacements that were converted from a primary knee replacement to a Triathlon total stabilizer (TS) knee system (Stryker Orthopaedics, Mahwah, NJ). Inclusion criteria included failure of a primary knee replacement of any cause converted to a Stryker TS knee system. Midterm outcome of at least 5 years was required. Implants survivorship, Oxford Knee Score (OKS), Forgotten Joint Score (FJS-12), Short Form (SF-) 12, reported patient satisfaction and radiographic analysis were recorded.
RESULTS
The all-cause survival rate at 5 years was 89.0% [95% confidence interval (CI) 87.3 to 90.7]. The all-cause survival rate was generally static after the first 4 years. The mean OKS was 27 (SD 11.9, range 0 to 46), FJS was 32.3 (SD 30.4, range 0 to 100), SF-12 physical component summary was 40.6 (SD 17.6, range 23.9 to 67.1), and mental component summary was 48.3 (SD 15.5, range 23.9 to 69.1). Reported patient satisfaction in patients who were not re-revised was 82%.
CONCLUSION
The midterm survivorship of cemented Stryker Triathlon TS knee revision for all-cause mode of failure is good to excellent; however, future follow-up is required to ensure this survivorship is observed into the long term. Despite limited functional outcome, overall patient satisfaction rates are high. | 10.1007/s00590-019-02449-9 |
others_30_6699 | The plant response to different stress types can occur through stimulus recognition and the subsequent signal transduction through second messengers that send information to the regulation of metabolism and the expression of defense genes. The phospholipidic signaling pathway forms part of the plant response to several phytoregulators, such as salicylic acid (SA), which has been widely used to stimulate secondary metabolite production in cell cultures. In this work, we studied the effects of SA treatment on [32-P]Pi phospholipid turnover and phospholipase D (PLD) activity using cultured Capsicum chinense cells. In cultured cells, the PIP2 turnover showed changes after SA treatment, while the most abundant phospholipids (PLs), such as phosphatidylcholine (PC), did not show changes during the temporal course. SA treatment significantly increased phosphatidic acid (PA) turnover over time compared to control cells. The PA accumulation in cells treated with 1-butanol showed a decrease in messengers; at the same time, there was a 1.5-fold increase in phosphatidylbutanol. These results suggest that the participation of the PLD pathway is a source of PA production, and the activation of this mechanism may be important in the cell responses to SA treatment. © 2015 Elsevier Masson SAS | 10.1016/j.plaphy.2015.02.022 |
pubmed_659_23544 | The Rh(iii)-catalyzed synthesis of spiroquinoxalinone derivatives from 3-arylquinoxalin-2(1H)-ones and alkynes via a C-H functionalization/[3 + 2] annulation sequence has been developed. This method, featuring low catalyst loading, was amenable to Gram scale synthesis and tolerated a variety of functional groups and substitution patterns on the aryl rings, providing the target products in good to excellent yields. | 10.1039/d0ra03348k |
pubmed_1041_2017 | A multiplex real-time PCR assay for the detection of Mycoplasma pneumoniae (MP181), Chlamydia (Chlamydophila) pneumoniae (CP-Arg), Legionella spp. (Pan-Leg), and the human RNase P (RNase P) gene was developed for rapid testing of atypical bacterial respiratory pathogens in clinical specimens. This method uses 4 distinct hydrolysis probes to detect 3 leading causes of community-acquired pneumonia. The assay was evaluated for specificity and sensitivity by testing against 35 related organisms, a dilution series of each specific target and 197 clinical specimens. Specificity testing demonstrated no cross-reactivity. A comparison to previously validated singleplex real-time PCR assays for each agent was also performed. The analytical sensitivity for specific pathogen targets in both the singleplex and multiplex was identical (50 fg), while efficiencies ranged from 82% to 97% for the singleplex assays and from 90% to 100% for the multiplex assay. The clinical sensitivity of the multiplex assay was improved for the Pan-Leg and CP-Arg targets when compared to the singleplex. The MP181 assay displayed equivalent performance. This multiplex assay provides an overall improvement in the diagnostic capability for these agents by demonstrating a sensitive, high-throughput and rapid method. This procedure may allow for a practical and efficient means to test respiratory clinical specimens for atypical pneumonia agents in health care settings and facilitate an appropriate public health response to outbreaks. | 10.1016/j.diagmicrobio.2010.11.014 |
pubmed_313_10584 | HLA-class I molecules form trimeric complexes (pMHC) of peptides, class I heavy chains, and β2microglobulins (β2m) that regulate immune responses by binding to T cells and other immune receptors. B2m-free class I heavy chains (FHCs) form on cells either as a consequence of the natural turnover of pMHC or, in the case of HLA-F, are expressed without β2m. Distinct characteristics of certain HLA-class I members, such as HLA-B27 and HLA-F, stabilize these forms facilitating interactions with immune receptors. FHC forms of HLA-class I have been shown to bind to killer-cell immunoglobulin-like receptor (KIR) family members. The binding of FHC forms to KIR3DL2 regulates natural killer (NK) and T-cell functiona and promotes lymphocyte survival. KIR3DL2 binding to B27 FHC dimers has been implicated in the pathogenesis of spondyloarthritis (SpA). KIR3DL2 binding FHC forms could also play a role in immune cell recognition of certain tumors and in regulation of immune homeostasis at the maternal-fetal interface. Here, I review the evidence for the functional interaction of cell surface HLA-class I FHCs with KIR family members. I also discuss the relevance of these interactions in immune homeostasis and immune dysfunction in diseases in which FHC-binding KIRs have been implicated. | 10.1615/CritRevImmunol.2016017965 |
pubmed_456_13174 | OBJECTIVES
To estimate the relationship between data breaches and hospital advertising expenditures.
STUDY DESIGN
Observational data on hospital expenditures were analyzed using a propensity score-matched regression. The regression was specified as a generalized linear model using a gamma distribution and log link.
METHODS
The study sample included Medicare hospitals captured by a survey of traditional media outlets. Hospitals included were nonfederal acute care inpatient hospitals from 2011 to 2014. Voicetrak provided data on hospital advertising expenditures. The Healthcare Cost Report Information System provided data on hospital characteristics and financial variables. Study groups were matched using observable characteristics, such as revenue, number of beds, discharges, ownership, and teaching status. The study excluded hospitals in Maryland and the US territories for financial reporting consistency. Data breaches included theft, loss, unauthorized access/disclosure, improper disposal, and hacking. Advertising expenditures were collected from media outlets including television, radio, newspapers and business journals, and local magazines in a city/metropolitan area.
RESULTS
Breached hospitals (n = 72) were more likely to be large, teaching, and urban hospitals relative to the control group (unweighted n = 915). A data breach was associated with a 64% (95% CI, 7.2%-252%; P = .023) increase in annual advertising expenditures, holding observable characteristics constant.
CONCLUSIONS
Breached hospitals were associated with significantly higher advertising expenditures in the 2 years after the breach. Efforts to repair the hospital's image and minimize patient loss to competitors are potential drivers of the increased spending. Advertising costs subsequent to a breach are another cost to the healthcare system that could be avoided with better data security. | pubmed_456_13174 |
pubmed_1118_25820 | BACKGROUND
Transjugular intrahepatic portosystemic shunt (TIPS) is used to treat complications of portal hypertension, such as ascites and variceal bleeding (VB). While liver doppler ultrasound (DUS) is used to assess TIPS patency, trans-shunt venography (TSV) is the gold standard.
AIM
To determine the accuracy of DUS to assess TIPS dysfunction and for need for revision.
METHODS
Retrospective review of patients referred for TIPS revision from 2008-2021. Demographics, DUS parameters at baseline and at the DUS preceding TIPS revision, TSV data were collected. Receiver operating characteristics curves, sensitivity, specificity, performance for doppler to predict need for revision were performed. Univariate and multivariate analyses were used to predict clinical factors associated with need for TIPS revision.
RESULTS
The cohort consisted of 89 patients with cirrhosis (64% men, 76% white, 31% alcohol as etiology); median age 59 years. Indication for initial TIPS were VB (41%), refractory ascites (51%), and other (8%). TIPS was revised in 44%. On univariate analysis, factors associated with need for TIPS revision were male (P = 0.03), initial indication for TIPS (P = 0.05) and indication for revision (P = 0.01). Revision of TIPS was associated with lower mortality (26% vs 46%) and significantly lower rates of transplant (13% vs 24%; P = 0.1). In predicting need for TIPS revision, DUS has a 40% sensitivity, 45% specificity, PPV 78%, and NPV 14%. The most accurate location for shunt velocity measure was distal velocity (Area under the curve: 0.79; P = 0.0007).
CONCLUSION
DUS has poor overall sensitivity and specificity in predicting need for TIPS revision. Non-invasive methods of predicting TIPS dysfunction are needed since those needing TIPS revision had better survival. | 10.4254/wjh.v14.i6.1200 |
pubmed_581_12414 | BACKGROUND
To assess the efficacy of using transcranial direct current stimulation (tDCS) to remediate the deleterious effects of fatigue induced by sleep deprivation and compare these results to caffeine, a commonly used fatigue countermeasure.
OBJECTIVE/HYPOTHESIS
Based on previous research, tDCS of the dorsolateral prefrontal cortex (DLPFC) can modulate attention and arousal. The authors hypothesize that tDCS can be an effective fatigue countermeasure.
METHODS
Five groups of ten participants each received either active tDCS and placebo gum at 1800, caffeine gum with sham tDCS at 1800, active tDCS and placebo gum at 0400, caffeine gum with sham tDCS at 0400, or sham tDCS with placebo gum at 1800 and 0400 during 36-h of sustained wakefulness. Participants completed a vigilance task, working memory task, psychomotor vigilance task (PVT), and a procedural game beginning at 1800 h and continued every two hours throughout the night until 1900 the next day.
RESULTS
tDCS dosed at 1800 provided 6 h of improved attentional accuracy and reaction times compared to the control group. Caffeine did not produce an effect. Both tDCS groups also had an improved effect on mood. Participants receiving tDCS reported feeling more vigor, less fatigue, and less bored throughout the night compared to the control and caffeine groups.
CONCLUSIONS
We believe tDCS could be a powerful fatigue countermeasure. The effects appear to be comparable or possibly more beneficial than caffeine because they are longer lasting and mood remains more positive. | 10.1016/j.brs.2017.08.005 |
pubmed_504_1203 | Objectives Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer health benefits to the host. Probiotics are currently being recommended and considered for many medical conditions. The Asia-Pacific region contributes to more than 40% of the global industry. Quality of commercial probiotics remains a challenge globally and has been a major concern in various countries in Europe, South Africa, Taiwan, India, Pakistan, and the USA. Research from these countries indicate that the contents do not correspond to the label information in terms of identity, viability, number of microorganisms or purity. The objective of this study is to assess the commercial probiotic bacterial contents and their label accuracy in India. No previous research has been done in this area in India, on commercial probiotics that are sold as "pharmaceuticals". Methods A random selection of the most prescribed probiotics for various clinical indications were chosen with a minimum shelf life of 12 months. The probiotics were single and multiple strains and these were evaluated by culture, viable plate count, DNA isolation and targeted metagenomics. Our study is the first step in scrutinizing probiotics in terms of quality and quantity analysis which are used across various age groups for multiple indications. Results Out of the 20 chosen probiotics eight products were single strain and 12 products were multiple strains. These probiotics showed very poor correlation between the declared contents on the pack and lab values in viable cell count colonies, the genus and species strain identification, presence of contaminants and these were confirmed with 16s RNA and next generation sequencing. Conclusion Poor correlation in the quality and quantity of probiotics proves that the label claim and actual claim of these "drugs" show exceptionally poor correlation and raises safety concerns in clinical use, especially in vulnerable age groups such as neonates, children and the elderly. Our study shows that "policing" of these probiotics is essential in protecting these patients who are at risk and ensuring quality control and helping clinicians making the right choice. | 10.7759/cureus.11334 |
pubmed_632_25215 | INTRODUCTION
The aim of this study is to evaluate the outcome of catheter directed thrombolysis (CDT) in acute lower limb ischaemia depending on the underlying etiology.
METHODS
Retrospective single center analysis of electronic clinical data on patients with acute lower limb ischaemia treated with CDT. Between January 2011 and September 2017, 128 procedures in 106 patients were included. The etiology of ischaemia was native artery thrombosis in 39 procedures (30,5%), PTFE graft thrombosis in 56 (43,8%), intra-stent thrombosis in 11 (8,6%), emboly in 9 (7%), popliteal aneurysm thrombosis in 9 (7%), vein graft thrombosis in 2 (1,6%) and popliteal artery entrapment in 2 (1,6%).
RESULTS
Median follow-up time was 14 months [range: 6-31], during which 22% needed further intervention. The need for reintervention was 27,6% in native artery thrombosis group, 65,2% in PTFE graft thrombosis group, 18,2% in intra- stent thrombosis group. No reinterventions occurred neither in popliteal aneurysm group or emboly group. Amputation free survival was 83,3% (SE 4,6%) at 27 months and cumulative incidence of death was 10,1% (SE 5,2%) at 32 months, with no differences between the groups.
CONCLUSION
Intra-arterial thrombolytic therapy achieves good mid-term clinical outcomes, reducing obviating the need to open surgical treatment in many patients. These results support the choice for CDT as a valid option in acute limb ischaemia of several etiologies. | pubmed_632_25215 |
pubmed_110_7085 | To compare two sequences of endurance (E) and high-velocity resistance (HVR) training, sixteen male oarsmen were separated into Group ES which trained endurance prior to strength and Group SE which trained strength prior to endurance. The endurance program consisted of up to 60 min a session, five days a week for five weeks. HVR exercise was conducted on 12 stations of variable resistance hydraulic equipment, four sessions per week for five weeks. Endurance training significantly improved VO2max and submaximal heart rate and blood lactate responses in both groups regardless of the sequence followed. HVR training improved VO2max in group SE only and had no effect on submaximal response to exercise. Peak torque increases for knee extension and flexion with HVR training were greater in group SE than group ES. These results show that organizing strength and endurance training into sequential programs can influence the physiological adaptation to training. | pubmed_110_7085 |
others_148_9662 | Approximately 4-5-fold stimulation of acid phosphatase activity was witnessed in embryo-less half-seeds of wheat in response to gibberellic acid (GA3) (48 h). This enzyme activity was secreted into the incubation medium. The increase in enzyme activity in GA3-treated wheat half-seeds was inhibited significantly by cordycepin, cycloheximide (CHI) and amino acid analogues. This indicated the requirement of fresh transcription and translation for the GA3-regulated acid phosphatase activity. Abscisic acid completely abolished the GA3-induced acid phosphatase activity. Conclusive proof for de novo synthesis of acid phosphatase in GA3-treated half-seeds was achieved by the in vivo labelling of enzyme with [35S]sulphate. The label was recovered in the cysteine residues of the purified enzyme. Acid phosphatase was purified (109-fold) to electrophoretic homogeneity by Con A-agarose affinity chromatography. The molecular weight of the native enzyme is 185 000 as determined by molecular sieve chromatography on Sepharose CL-6B. The Km of the enzyme for p-nitrophenyl phosphate is 5 × 10-4 M. The pH optimum of the purified enzyme was 5.0. The enzyme activity was completely inhibited by NaF (2 mM). Both β-mercapto-ethanol (10 mM) and dithiothreitol (10 mM) brought about a 2.5-3-fold activation of acid phosphatase, thereby indicating the requirement of free sulfhydryl groups for the catalytic efficiency of the enzyme. © 1989 | 10.1016/0168-9452(89)90182-9 |
pubmed_935_2779 | The development of left ventricular contracture and myocardial perfusion defect was studied in isolated rat hearts during global ischaemia of 90 min duration. The left ventricular pressure was measured by a balloon catheter inserted into the ventricle and filled with water. The pressure reached the maximum at 16 min of ischaemia. The left ventricular volume and compliance (passive distensibility) were measured by the same balloon, the former by connecting the balloon to an open catheter and the latter by applying a constant additional volume (0.020 ml) into the balloon. the left ventricular volume and compliance both decreased progressively for 20 min of ischaemia after which they remained low for the rest of the observation period (90 min). The myocardial perfusability was tested by infusing 0.1 per cent sodium fluorescein in isotonic saline into the cannulated aortic root of the isolated heart preparation. The percentage perfused with the fluorescent tracer in horizontal frozen myocardial sections was estimated by point counting from colour photogragraphs taken under ultraviolet light. The proportion of the perfused area decreased gradually from 100% at 0 min of ischaemia to 93, 67, 43 and 37% at 15, 30, 60 and 90 min of ischaemia, respectively. It was concluded that ischaemic contracture of the left ventricle is followed by the development of a myocardial perfusion defect in isolated ischaemic rat heart. | 10.1007/BF00427400 |
pubmed_441_4691 | The acute skin phototoxicity in hairless mice resulting from applications of crude shale oil or natural petroleum oil and exposure to near ultraviolet light has been investigated. In addition, the absorption and excitation-emission spectra of these oils have been described. While the application of crude shale oil alone was shown to elicit acute skin damage, the combination of the crude shale oil and near ultraviolet light induced skin damage much more severe than that produced by either agent alone. In contrast, the application of the natural petroleum oil and near ultraviolet light was less toxic than that of the crude shale oil in the absence of light. These results suggest that a potential health hazard exists from contact with shale oil compounds and exposure to near ultraviolet light from either the sun or artificial sources. | 10.1016/0300-483x(80)90039-6 |
pubmed_982_3315 | The effect of total knee arthroplasty (TKA) on the Insall-Salvati ratio (ISR) and the effect of the ISR on the outcome of TKA have not been clearly established. A retrospective review of 1055 primary TKAs performed in 1997 to 1998 was performed. Radiographic measurements were made preoperatively and postoperatively, and the ISR was calculated. Regression analysis was performed to determine the effects of these variables on range of motion (ROM), Knee Society Score, and stair, function, and pain scores. Total knee arthroplasty resulted in a decrease in the patella tendon length, as measured by the ISR in 50% of cases. Patella infera (ISR less than 0.8) developed postoperatively in 9.8% of TKAs and was twice as likely to occur in women as men. A decrease in the ISR was associated with diminished stair and function scores (P = .0004 and 0.0081, respectively). There was no effect of the ISR upon ROM, Knee Society Score, or pain scores. Optimal outcomes occurred in patients where the ISR was not decreased after TKA, with superior stair and function scores. | 10.1016/j.arth.2006.04.014 |
pubmed_798_5551 | PURPOSE
We investigated whether the one-window method for thoracoscopic operations is possible as an operation for early-stage lung cancer.
DESCRIPTION
The subjects were the 40 patients in whom ND2 lymph node dissection was performed among those with a preoperative diagnosis of stage IA (T1 N0 M0) lung cancer who underwent thoracoscopic operations in our hospital during the 2-year period from January 2001 to December 2002. With the patient in the lateral position, a Thoraco Holder (Fuji Systems Corp, Tokyo, Japan) was inserted between the fourth and fifth intercostal space on the anterior axillary line. The surgeon used it as a port for performing the surgical maneuvers. An access needle was placed in the auscultatory triangle in the fifth intercostal space, and a 3-mm thoracoscope was used. Pulmonary lobectomy and mediastinal dissection were performed in the same manner as the standard thoracoscopic two-windows method.
EVALUATION
The one-window technique was successful in 38 patients, and conversion to the two-windows method occurred in the other 2. Mean operation time was 2 hours 18 minutes. A mean number of 16.5 lymph nodes were removed, and mean blood loss was 22 mL. All 40 patients are alive and free of recurrence at 5 or more years since the operation.
CONCLUSIONS
As a result of mastering the operation and developing improved instruments, pulmonary lobectomies can now be performed by the one-window method. This method is the least invasive method of pulmonary cancer surgery available at the present time. | 10.1016/j.athoracsur.2008.09.080 |
pubmed_963_19446 | Meningiomas are common intracranial tumors, the majority of which are considered benign. However, they sometimes show altered biologic behavior, associated with local aggressiveness and late distant metastasis. We report a patient with a convexity meningioma, which recurred as a malignant transformation 26 years after a total tumor removal. A 75-year-old man was transferred to a local hospital because of general convulsions and left hemiparesis. The patient had had an operation for the total removal of a right frontal convexity meningioma at the age of 46 and had been free of its effects until the age of 72. Brain magnetic resonance imaging (MRI) showed a recurrent tumor located in the anterior area of the previous craniotomy. Over the following two and a half years, MRI revealed rapid enlargement and infiltration of the tumor into the brain parenchyma. The primary tumor was nodular, macroscopically well demarcated from the surrounding brain tissue and, histologically, was a transitional type of meningioma without any atypical features. In contrast, the recurrent tumor, whose border was ill-defined, had invaded the neighboring brain. A histological specimen of the recurrent tumor showed highly malignant features such as necrosis, intracerebral infiltration, dense cellularity, and high proliferating activity as demonstrated by a cell kinetic study using the MIB 1 staining index. We should be mindful that recurrence from common benign type meningiomas may occur as malignant transformations after more than two decades. | pubmed_963_19446 |
pubmed_354_10047 | AIM
Postoperative ascites is one of the most common complications after hepatic resection and is related to liver fibrosis. Mac-2 binding protein glycosylation isomer (M2BPGi) is a reliable and non-invasive marker for assessing liver fibrosis. This study aimed to evaluate whether preoperative M2BPGi level can predict postoperative refractory ascites in patients with curative hepatic resection for hepatocellular carcinoma.
METHODS
The present study retrospectively evaluated 59 patients between January 2016 and June 2018. We assessed the relationship between preoperative M2BPGi levels, expressed as the cut-off index, and postoperative ascites.
RESULTS
The median M2BPGi level was 1.36 (range 0.34-11.56). Postoperative ascites occurred in seven patients (11.9%). Among them, refractory ascites, defined as diuretic-resistant ascites, occurred in four patients (6.8%). Uni- and multivariate analysis showed that preoperative M2BPGi level was the only independent risk factor of postoperative ascites (odds ratio 3.28, P = 0.033). The cut-off values of M2BPGi for postoperative ascites and refractory ascites were 2.41 and 3.10, respectively. Remarkably, there were no patients with postoperative ascites and refractory ascites when the preoperative M2BPGi levels were less than each cut-off value.
CONCLUSION
Our results suggest that M2BPGi level is a reliable and non-invasive surrogate marker for predicting postoperative ascites before curative resection for hepatocellular carcinoma. | 10.1111/hepr.13412 |
pubmed_812_5522 | INTRODUCTION
Organ shortage remains the main limiting factor for expanding liver transplantation (LT) in Saudi Arabia. Therefore, living donor liver transplantation (LDLT) was recently undertaken by our team at King Faisal Specialist Hospital and Research Center (KFSH&RC), in an effort to meet the increasing demand for LT in Saudi Arabia.
OBJECTIVE
Analysis of donors assessed for LDLT at KFSH&RC.
METHODS
Between September 2002 and May 2003, 39 potential donors were assessed for LDLT. First- or second-degree relationship to the recipient was an essential precondition. Assessment included biochemical testing, radiological studies (computed tomography: magnetic resonance angiography, magnetic resonance cholangiography), and thorough psychosocial analysis. Liver biopsy and hepatic angiogram was performed in some but not all donors.
RESULTS
Male:female ratio was 28:11. Median age was 27 (18 to 34). Of 39 potential donors, only three underwent LDLT. The remaining 36 were rejected for different reasons including: psychosocial in 8 (20.5%), fatty liver in 7 (17.9%), recipient issues in 6 (15.4%), refusal after initial approval in 3 (7.7%), unfavorable anatomy in 2 (5.1%), inadequate liver volume in 2 (5.1%), abnormal liver functions in 2 (5.1%), hepatitis C virus in 2 (5.1%), liver pathology in 1 (2.6%), and other medical concerns in remaining 3 donors (7.7%).
CONCLUSION
In Saudi Arabia, donor availability as well as recipient characteristics may limit the value of LDLT in overcoming organ shortage. Therefore, efforts should be directed to improve the number and quality of available cadaveric organs. Until then, LDLT may be the only way forward to save patients from dying on the waiting list. | 10.1016/j.transproceed.2004.08.127 |
pubmed_212_2704 | A new inventory aimed at the assessment of perceived parental rearing practices (EMBU) and an inventory aimed at assessing psychogenic needs (CMPS) were completed by 152 healthy subjects of both sexes (108 males and 44 females). The series was comprised of 73 conscripts, 57 medical students, 15 vocational therapy students and 7 staff personnel who were 17-46 years old. Several significant correlations were found between dimensions of parental rearing behaviour and personality characteristics, most of them being consistent with earlier findings by other authors. Although statistically significant, the correlation coefficients were mostly low, leaving a large amount of unexplained variance. The findings of this study support the general assumption that the perception of parental rearing practices is an important factor in the shaping of personality make-up but that other, still unexplored factors might have an even greater importance in the determination of habitual personality characteristics. | 10.1007/BF00365740 |
pubmed_690_2114 | Selective interruption of cochlear blood flow is possible without operative manipulations in the middle or inner ear. By fitting a magnet into the external auditory canal and injecting iron filings into the cephalic vein is it possible to obtain an impaired inner ear in otherwise healthy experimental animals that can be kept alive for any length of time. The hearing loss induced by the ischemia normally remains unchanged over a period of weeks. The highly vascularised areas of the cochlea, namely the spiral ligament, the vascular stria, the spiral prominence and the root cells in the external spiral sulcus, as well as the spiral limbus were all clearly degenerated, but to different degrees. Pronounced vacuolisation of cells, degeneration of tissue, reduction of cellular elements, stasis in large and small blood vessels and morphological disorganisation were observed. The organ of Corti showed no changes worthy of note. On revascularisation of the spiral ligament and the spiral limbus with resumption of function, the organ of Corti can return to normal activity again. Repeat blood flow disturbances can also lead to recurrent sudden hearing loss and intermittent loss of hearing. | pubmed_690_2114 |
pubmed_1110_5848 | In clinical practice, one subgroup patients of breast cancer might have developed resistance to multi-anti-HER2 targeted drugs(trastuzumab, lapatinib and/or T-DM1) and can not benefit from the anti-HER2 targeted therapy continuously. We attempt to change the next therapic way for these patients. Two patients with metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy were treated with pembrolizumab (2 mg/Kg, day1) plus albumin-bound paclitaxel (125 mg/m2, day1,8) every 3 weeks. CT evaluation and HER2 ECD test were performed every 2 cycles. Both of the two patients achieved remarkable response with Partial Remission (PR), meanwhile serum HER2 ECD levels (the upper normal limit is 15 ng/ml) showed a remarkable decreases(compared to the base line decreases 75% and 60% respectively). The results indicate that regimen of pembrolizumab combination with albumin-bound paclitaxel might produce response in patients with HER2-positive metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy. | 10.1080/15384047.2017.1414761 |
pubmed_345_15656 | BACKGROUND
Secondary failure of oral hypoglycemic agents is common in patients with type 2 diabetes mellitus (T2DM); thus, patients often need insulin therapy. The most common complication of insulin treatment is lipohypertrophy (LH).
OBJECTIVES
This study was conducted to estimate the prevalence of LH among insulin-treated patients with Patients with T2DM, to identify the risk factors for the development of LH, and to examine the association between LH and glycemic control.
PATIENTS AND METHODS
A total of 1090 patients with T2DM aged 20 to 89 years, who attended the diabetes clinics at the National Center for Diabetes, Endocrinology, and Genetics (NCDEG, Amman, Jordan) between October 2011 and January 2012, were enrolled. The presence of LH was examined by inspection and palpation of insulin injection sites at the time of the visit as relevant clinical and laboratory data were obtained. The LH was defined as a local tumor-like swelling of subcutaneous fatty tissue at the site of repeated insulin injections.
RESULTS
The overall prevalence of LH was 37.3% (27.4% grade 1, 9.7% grade 2, and 0.2% grade 3). The LH was significantly associated with the duration of diabetes, needle length, duration of insulin therapy, lack of systematic rotation of insulin injection sites, and poor glycemic control.
CONCLUSIONS
The LH is a common problem in insulin-treated Jordanian patients with T2DM. More efforts are needed to educate patients and health workers on simple interventions such as using shorter needles and frequent rotation of the insulin injection sites to avoid LH and improve glycemic control. | 10.5812/ijem.20776 |
pubmed_1089_322 | OBJECTIVES
We compared the accuracy of a conceptually simple pediatric weight estimation technique, the finger counting method, with other commonly used methods.
METHODS
We prospectively collected cross-sectional data on a convenience sample of 207 children aged 1 to 9 presenting to our pediatric emergency department. Bland-Altman plots were constructed to compare the finger counting method to the Broselow tape method, parental estimate, the Luscombe formula, and the advanced pediatric life support (APLS) formula. Proportions within 10% and 20% of measured weight were compared.
RESULTS
Mean difference and range of agreement in kilograms for Bland-Altman plots were as follows: -1.8 (95% confidence interval [CI], -2.3 to -1.3) and 15.4 (95% CI, 13.6-17.2) for the finger counting method; -1.4 (95% CI, -2.0 to -0.9) and 15.8 (95% CI, 13.9-17.6) for the Broselow method; -0.02 (95% CI, -0.53 to 0.49) and 14.8 (95% CI, 13-16.6) for parental estimate; 0.2 (95% CI, -0.33 to 0.72) and 15.3 (95% CI, 13.5-17.2) for the Luscombe formula; and -3.8 (95% CI, -4.4 to -3.2) and 17.2 (95% CI, 15.2-19.2) for the APLS formula. The finger counting method estimated weights within 10% in 59% of children (95% CI, 52%-65%) and within 20% in 87% of children (95% CI, 81%-91%). Proportions within 10% were similar for all methods, except the APLS method, which was lower.
CONCLUSIONS
The finger counting method is an acceptable alternative to the Broselow method for weight estimation in children aged 1 to 9 years. It outperforms the traditional APLS method but underestimates weights compared with parental estimate and the Luscombe formula. | pubmed_1089_322 |
pubmed_540_21026 | Charge recombination reactions (CRRs) are responsible for the major loss of power conversion efficiency (PCE) in dye-sensitized solar cells (DSSCs). This study tracks the impact of the dielectric constant (ε') of two D-π-A types of triphenylamine-based organic dyes (TpAzo 1 and TpAzo 2) with naphthalene and anthracene π-bridges on CRRs, respectively, and these dyes are sandwiched as dielectric layers of capacitors between Al electrodes via rf-sputtering deposition. The structure and thickness of components of capacitors were considered by applying field emission scanning electron microscopy (FESEM), and ε', ε'', tan δ, ac conductivity (σac) and electric modulus (M*) of capacitors were analyzed by LCRmetry at different frequencies (f: 102-104 Hz) and temperatures (T: 299-390 K). Cyclic voltammetry (CV) and UV-visible spectroscopy analysis of dyes were performed for revealing the optical profiles, highest occupied molecular orbitals (HOMO), lowest unoccupied molecular orbitals (LUMO), and band gap (Eg); the results were found to be highly consistent with density functional theory (DFT) quantum calculation outputs. The f- and T-dependent relationships were detected for ε', ε'', tan δ and σac, which experienced an upward trend and a downward trend with the increase in T and the decrease in f, respectively. The results indicated higher ε', ε'' M' and M'' values for TpAzo 2 than those of TpAzo 1, which from the molecular point of the view could be related to the more extending π-conjugated structure of anthracene in comparison to naphthalene π-bridges that not only provided appropriate dipole moments and exciton binding energy, but also facilitated powerful intramolecular charge transfer (ICT). Therefore, this study proposes ε', ε'', M' and M'' as novel physiochemical characters in dye design, which have been neglected so far and can open a new synthesis paradigm for developing more efficient organic sensitizers for DSSCs. | 10.1039/d2cp02744e |
pubmed_630_7039 | OBJECTIVE
To summary clinical and genetic features of childhood dyskeratosis congenital (DC) patients with bone marrow failure.
METHODS
The clinical data of 8 DC patients with bone marrow failure diagnosed between September 2010 and September 2015 were collected. Whole exons with flanking regions of the 16 telomere-related genes, including DKC1, TERC, TERT, NOP10, NHP2, TINF2 and so on, were analyzed by next generation sequence.
RESULTS
Six males and two females were included, with a median age of 42(15-60) months. The median blood cell count at onset were as follow: WBC 3.99 (1.26-5.44) × 10(9)/L, ANC 1.11 (0.38-2.15) × 10(9)/L, RBC 2.45 (0.37-3.56) × 10(12)/L, HGB 82.5(15-127) g/L, PLT 27 (2-112) ×10(9)/L. Hypoplastic or marked hypoplastic bone marrow were seen in 6 patients. DKC1 mutiaton were indentified in 3 patients: one c.961C>A mutation, and two c.1058C>T mutation. TINF2 mutations were identified in 4 patients: c.849delC, c.844C>T, c.811C>T, c.862T>A combined c.871delA. One patient had TINF2 mutation c.848C>A combined TERT mutation c.1138C>T. DKC1 c.961C>A mutation, TINF2 c.849delC mutation and TINF2 c.871delA mutaion were not reported so far. 5 of 7 patients got better after androgen administration. During follow-up, one patient died of serious infection, the other seven patients continued the treatment.
CONCLUSIONS
TINF2 and DKC1 mutations were the main genetic phenotypes in childhood DC with marrow failure patients. Androgen is effetive in some cases. | 10.3760/cma.j.issn.0253-2727.2016.03.008 |
pubmed_467_5605 | BACKGROUND
Both experimental and clinical studies have shown that electroacupuncture (EA) administration ameliorates chronic inflammatory pain (CIP). However, the multifaceted mechanism underlying the effects of EA on CIP is poorly understood. In this study, the mRNA transcriptome was used to study various therapeutic targets of EA.
METHODS
Using RNA-sequencing, protein-coding mRNA expression profiles of the L4-L5 dorsal root ganglion (DRG) were examined in the control (CN), complete Freund's adjuvant- (CFA-) induced CIP, and EA-treated CIP groups. A series of bioinformatics analyses was performed; "EA-reversed upregulated genes with CIP" (up-DEGs) and "EA-reversed downregulated genes with CIP" (down-DEGs) were identified. Thereafter, based on up-DEGs and down-DEGs, biological functions and signaling pathways were enriched using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses.
RESULTS
In total, 189 DEGs were identified, including 134 up- and 55 down-DEGs, which were enriched in arachidonic acid metabolism (rno00590), glutamatergic synapse (rno04724), serotonergic synapse (rno04726), FoxO signaling pathway (rno04068), insulin signaling pathway (rno04910), amyotrophic lateral sclerosis (rno05014), cholinergic synapse (rno04725), ECM-receptor interaction (rno04512), and choline metabolism in cancer (rno05231).
CONCLUSION
We identified a few GOs, pathways, and genes that could play key roles in the amelioration of CIP by EA. Hence, this study may provide a theoretical basis for CIP amelioration by EA. | 10.1155/2020/7061972 |
pubmed_121_10755 | Biomaterials capable of precisely controlling the delivery of agrochemicals/biologics/drugs/fragrances have significant markets in the agriscience/healthcare industries. Here, we report the development of degradable electroactive polymers and their application for the controlled delivery of a clinically relevant drug (the anti-inflammatory dexamethasone phosphate, DMP). Electroactive copolymers composed of blocks of polycaprolactone (PCL) and naturally occurring electroactive pyrrole oligomers (e.g., bilirubin, biliverdin, and hemin) were prepared and solution-processed to produce films (optionally doped with DMP). A combination of in silico/in vitro/in vivo studies demonstrated the cytocompatibility of the polymers. The release of DMP in response to the application of an electrical stimulus was observed to be enhanced by ca. 10-30% relative to the passive release from nonstimulated samples in vitro. Such stimuli-responsive biomaterials have the potential for integration devices capable of delivering a variety of molecules for technical/medical applications. | 10.1021/acs.biomac.2c00516 |
pubmed_278_16254 | PURPOSE
Advances in the diagnosis and treatment of prostate cancer have increased the patients' stress level and decreased the quality of life. A variety of instruments are currently available to evaluate patients with prostate cancer. However, only a few tools are available to assess Korean patients, and therefore we demonstrated a linguistic validation of Korean Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP).
METHODS
EPIC-CP was translated into Korean and the linguistic validation was evaluated. The evaluation process includes permission for translation, forward translation, reconciliation, backward translation, cognitive debriefing, and proofreading. Two bilingual translators independently translated the original questionnaire, discussed the feasibility and naturalness of initial translation, followed by revision to the reconciled version. Another translator then performed a backward translation into English. Ten patients with prostate cancer completed the translated questionnaire and performed cognitive debriefing.
RESULTS
The original EPIC-CP was translated into 2 Korean versions. The different wording in both versions and the ordinary words in the initial translations were changed considering the nuances and meanings of medical terms. During the backward translation, the panels made slight changes to clarify the meaning and nuances of the translated questionnaire. During cognitive debriefing, 10 patients answered the questionnaire and offered their opinions regarding comprehensibility and naturalness. Most patients agreed that the translation was comprehensible in general.
CONCLUSION
Our study provides a successful linguistic validation of the EPIC-CP questionnaire. The translation is a helpful diagnostic tool to ensure the quality of life of patients with prostate cancer attending crowded clinics. | 10.5213/inj.2040316.158 |
pubmed_183_21869 | Transcriptomes and growth physiologies of the hyperthermophile Thermotoga maritima and an antibiotic-resistant spontaneous mutant were compared prior to and following exposure to chloramphenicol. While the wild-type response was similar to that of mesophilic bacteria, reduced susceptibility of the mutant was attributed to five mutations in 23S rRNA and phenotypic preconditioning to chloramphenicol. | 10.1128/AEM.00453-07 |
pubmed_757_6495 | BACKGROUND & AIM
We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19.
METHODS
From August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates.
RESULTS
The overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT-qPCR were 72% (95%CI 62%-81%), 99% (95% CI95%-100%), 99% (95%CI 93%-100%), and 78% (95%CI 70%-85%), 0.28 (95%CI 0.21-0.39), and 72 (95%CI 10-208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%-99%), TSO > 4 days 100% (95%CI 54%-100%), and asymptomatic 100% (95%CI 78-100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed.
CONCLUSIONS
This study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak. | 10.1371/journal.pone.0257817 |
pubmed_669_9019 | The ability to detect and adapt to different levels of ambient light is critical for animal survival. Light detection is the basis of vision, but light also regulates eye development and drives several non-image-forming functions, including synchronizing circadian rhythms to the daily light/dark cycle, restricting pupils in response to changes in light intensity, and modulating mood in response to light. Until the early 2000s, these functions were thought to be solely mediated by ocular photoreceptors. However, neuropsin (OPN5), a UV-sensitive opsin, has been receiving growing attention, as new methods have revealed previously unappreciated functions of OPN5. In fact, OPN5-mediated extraocular and deep-brain photoreception have recently been described for the first time in mammals. This review aims to synthesize current knowledge of the properties and functions of OPN5 across vertebrates. | 10.1016/j.tins.2021.11.008 |
pubmed_737_17738 | Stem cell-based therapy for liver regeneration has been proposed to overcome the persistent shortage in the supply of suitable donor organs. A requirement for this to succeed is to find a rapid method to detect functional hepatocytes, differentiated from embryonic stem cells. We propose Fourier transform infrared (FTIR) microspectroscopy as a versatile method to identify the early and last stages of the differentiation process leading to the formation of hepatocytes. Using synchrotron-FTIR microspectroscopy, the means of identifying hepatocytes at the single-cell level is possible and explored. Principal component analysis and subsequent partial least-squares (PLS) discriminant analysis is applied to distinguish endoderm induction from hepatic progenitor cells and matured hepatocyte-like cells. The data are well modeled by PLS with endoderm induction, hepatic progenitor cells, and mature hepatocyte-like cells able to be discriminated with very high sensitivity and specificity. This method provides a practical tool to monitor endoderm induction and has the potential to be applied for quality control of cell differentiation leading to hepatocyte formation. | 10.1117/1.3580253 |
pubmed_251_5955 | Apomorphine, 2 mg/kg (s.c.) produced significant contralateral turning in rats with unilateral radiofrequency lesions of the habenula nucleus over a test period of 60 min when tested at post-surgery days 3, 7, and 14. Levels of contralateral circling were not significantly increased when the animals were tested on days 21 and 28, although a contralateral bias was still observed. Rotation induced by apomorphine was completely blocked by the administration of haloperidol (0.3 mg/kg i.p.), and there was no behavioural asymmetry in lesioned animals following administration of saline or a high dose of haloperidol (2 mg/kg i.p.). These results indicate that unilateral habenula lesions lead to imbalance of dopaminergic activity, which is expressed as contralateral circling when the animal is challenged with apomorphine. | 10.1007/BF00228622 |
pubmed_774_8950 | PURPOSE
Early integration of outpatient palliative care (OPC) benefits patients with advanced cancer and also the health care systems in which these patients are seen. Successful development and implementation of models of OPC require attention to the needs and values of both the patients being served and the institution providing service.
SUMMARY
In the 2016 clinical guideline, ASCO recommended integrating palliative care early in the disease trajectory alongside cancer-directed treatment. Despite strong endorsement and robust evidence of benefit, many patients with cancer lack access to OPC. Here we define different models of care delivery in four successful palliative care clinics in four distinct health care settings: an academic medical center, a safety net hospital, a community health system, and a hospice-staffed clinic embedded in a community cancer center. The description of each clinic includes details on setting, staffing, volume, policies, and processes.
CONCLUSION
The development of robust and capable OPC clinics is necessary to meet the growing demand for these services among patients with advanced cancer. This summary of key aspects of functional OPC clinics will enable health care institutions to evaluate their specific needs and develop programs that will be successful within the environment of an individual institution. | 10.1200/JOP.18.00634 |
pubmed_489_14044 | Although individual phlorotannins contained in the edible brown algae have been reported to possess strong anti-inflammatory activity, the responsible components of Eisenia bicyclis have yet to be fully studied. Thus, we evaluated their anti-inflammatory activity via inhibition against production of lipopolysaccharide (LPS)-induced nitric oxide (NO) and tert-butylhydroperoxide (t-BHP)-induced reactive oxygen species (ROS), along with suppression against expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), in RAW 264.7 cells. The anti-inflammatory activity potential of the methanolic extract and its fractions of E. bicyclis was in the order of dichloromethane>methanol>ethyl acetate>n-butanol. The strong anti-inflammatory dichloromethane fraction was further purified to yield fucosterol. From the ethyl acetate fraction, six known phlorotannins were isolated: phloroglucinol, eckol, dieckol, 7-phloroeckol, phlorofucofuroeckol A and dioxinodehydroeckol. We found that these compounds, at non-toxic concentrations, dose-dependently inhibited LPS-induced NO production. Fucosterol also inhibited t-BHP-induced ROS generation and suppressed the expression of iNOS and COX-2. These results indicate that E. bicyclis and its constituents exhibited anti-inflammatory activity which might attribute to inhibition of NO and ROS generation and suppression of the NF-κB pathway and can therefore be considered as a useful therapeutic and preventive approach to various inflammatory and oxidative stress-related diseases. | pubmed_489_14044 |
pubmed_456_2943 | The present study investigated the association between the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway with tumor progression and prognosis of colon cancer. A total of 62 patients with colon cancer were selected as the colon cancer group, and 40 patients with colon lesions were selected as the benign colon lesion group. Immunohistochemistry was used to detect the expression levels of JAK-1 and STAT-3 proteins in colon tissues. The association of JAK-1 and STAT-3 proteins with the pathological parameters and prognosis of colon cancer were analyzed. The total positive rates of JAK-1 and STAT-3 proteins in lesions of patients in the colon cancer group were significantly higher compared with those in the benign colon lesion group (P<0.05). The positive expression of JAK-1 and STAT-3 proteins in patients with colon cancer were not significantly associated with sex, age, tumor differentiation degree and neurovascular invasion (P>0.05), but significantly associated with the clinical stage of colon cancer, tumor infiltration depth and lymph node metastasis (P<0.05). The survival time of patients with colon cancer with positively-expressed JAK-1 and STAT-3 proteins was significantly shorter compared with that of patients with negatively-expressed JAK-1 and STAT-3 proteins (P<0.05). tumor-node-metastasis (TNM) stage, lymph node metastasis and the expression of JAK-1 and STAT-3 proteins in the tumor were associated with the prognosis of patients with colon cancer (P<0.05). TNM stage and the expression levels of JAK-1 and STAT-3 proteins were independent risk factors influencing the prognosis of colon cancer (P<0.05). The JAK/STAT signal may be used as a novel tumor marker and prognostic factor for the diagnosis, assessment and prognosis of colon cancer. | 10.3892/ol.2018.9569 |
pubmed_743_19426 | BACKGROUND
The establishment of a risk-appropriate care approach for pregnant women and newborn infants under the COVID-19 pneumonia is vital to prevent the main pregnancy complications.
OBJECTIVES AND DESIGN
This study reviewed the vertical transmission (VT) potential of COVID-19 pneumonia in pregnant women. Key-related symptoms and adverse clinical outcomes for mothers and infants before and after childbirth were summarized. Some practical therapies and preventive health solutions were also proposed.
RESULTS
There was a high susceptibility in pregnant women to COVID-19 infection, especially in the third trimester of pregnancy. The most common symptoms in 22-40-year-old patients infected with COVID-19 were fever (87.6%), cough (52.3%), dyspnea (27.6%), fatigue (22.4%), sore throat (13.5%), malaise (9.4%), and diarrhea (3.4%), respectively. The viral infection led to an increase in preterm labor and cesarean delivery without any intrauterine infection and severe neonatal asphyxia. No infection in the newborn infants was reported despite a high risk of the VT phenomenon. The most important therapies were the reception of antiviral and antibiotic drugs, oxygenation therapy, psychological interventions, and food supplements with health-promoting effects. The best proposed medical strategies to control the COVID-19 infection were bi-monthly screening and following-up the mothers' and fetuses' health, not using the potent broad-spectrum antibiotics and corticosteroids, providing the delivery room with negative pressure for emergency cesarean section, and the immediate isolation of newborns after childbirth without direct breastfeeding.
CONCLUSION
Babies with respiratory problems may be born to some mothers with COVID-19, who have weak immune systems. Thus, the virus transmission cycle should be disrupted to prevent adverse maternal and fetal outcomes by integrating individual health guidelines, efficient medical care therapies, and hospital preventive practices. | 10.1007/s00404-021-06325-y |
pubmed_496_1008 | CD4CD25(+) regulatory T cells are fundamental to the maintenance of peripheral tolerance and have great therapeutic potential. However, efforts in this regard have been hampered by limiting cell numbers in vivo, an anergic phenotype in vitro, and a rudimentary understanding of the molecular basis for the functional state of CD4CD25(+) regulatory T cells (Treg cells). Here we show heterogeneity of suppressor activity among activated CD4CD25(+) Treg cells and that, within this population, the functionally active, hyaluronan-binding form of CD44 (CD44(act)) is strikingly correlated with superior suppressor activity. Within 16 hours after in vitro activation, CD44(act) can discriminate enhanced suppressive function in in vitro proliferation assays and in an in vivo bone marrow engraftment model. The expression of other surface markers and that of Foxp3 are similar irrespective of hyaluronan binding and associated degree of suppressor potency. Furthermore, CD44(act) is induced on resting CD4CD25(+) cells in vivo by allogeneic stimulation, with similar functional consequences. These results reveal a cell-surface marker that delineates functional activity within a population of activated CD4CD25(+) regulatory T cells, thereby providing a potential tool for identifying regulatory activity and enriching for maximal suppressor potency. | 10.1182/blood-2005-06-2277 |
pubmed_496_16426 | OBJECTIVE
To develop a preliminary epidemiological description of a men who have sex with men (MSM) "POZ Party," an emerging sex environment for HIV+ MSM.
METHODS
As part of a pilot study in New York City in 2003, data were collected using a brief, behavioural intercept survey at entry to POZ Party events. Domains include demographic characteristics, history of HIV infection, motivations for attending POZ parties, lifetime and recent exposure to drugs (including use during POZ Party events), and recent sexual practices (both within both POZ Party venues as well as in non-POZ Party venues).
RESULTS
Predominantly white and over the age of 30, subjects in the sample include a broad range of years living with HIV infection. Motivations for using a POZ Party venue for sexual partnering include relief from burdens for serostatus disclosure, an interest in not infecting others, and opportunities for unprotected sexual exchange. High rates of unprotected sex with multiple partners are prevalent in the venue. Although the sample evidences high rates of lifetime exposure to illicit drugs, relatively little drug use was reported in these sexual environments. These reports are consistent with evidence from direct observation at the venues themselves, in which no drug use was apparent.
CONCLUSION
Serosorting among HIV+ MSM may reduce new HIV infections, a stated interest of both POZ Party organisers and participants alike. However, high rates of unprotected anal intercourse within these venues signal continued risk for STIs. Additionally, unprotected sexual contact with HIV partners and status unknown partners outside POZ Party venues heightens concern for diffusion of HIV superinfection. | 10.1136/sti.2005.014894 |
pubmed_94_10350 | Human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). Novel strategies to combat this pandemic include the discovery of cellular proteins targeting distinct steps of the HIV replication cycle. Here, we summarize our current knowledge on antiviral proteins interfering with the infectivity of released HIV particles. | 10.1016/j.micinf.2020.05.009 |
pubmed_968_15528 | Transcription factor 4 (TCF4) is a basic helix-loop-helix transcription factor essential for neurocognitive development. The aberrations in TCF4 are associated with neurodevelopmental disorders including schizophrenia, intellectual disability, and Pitt-Hopkins syndrome, an autism-spectrum disorder characterized by developmental delay. Several disease-associated missense mutations in TCF4 have been shown to interfere with TCF4 function, but for many mutations, the impact remains undefined. Here, we tested the effects of 12 functionally uncharacterized disease-associated missense mutations and variations in TCF4 using transient expression in mammalian cells, confocal imaging, in vitro DNA-binding assays, and reporter assays. We show that Pitt-Hopkins syndrome-associated missense mutations within the basic helix-loop-helix domain of TCF4 and a Rett-like syndrome-associated mutation in a transcription activation domain result in altered DNA-binding and transcriptional activity of the protein. Some of the missense variations found in schizophrenia patients slightly increase TCF4 transcriptional activity, whereas no effects were detected for missense mutations linked to mild intellectual disability. We in addition find that the outcomes of several disease-related mutations are affected by cell type, TCF4 isoform, and dimerization partner, suggesting that the effects of TCF4 mutations are context-dependent. Together with previous work, this study provides a basis for the interpretation of the functional consequences of TCF4 missense variants. | 10.1016/j.jbc.2021.101381 |
Subsets and Splits