Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid detection and identification of herpes simplex virus in cell culture by a direct immunoperoxidase staining procedure

Cell monolayers were inoculated with 169 fresh and 76 previously frozen clinical specimens and examined for the presence of herpes simplex virus (HSV) by noting the appearance of characteristic cytopathic effect (CPE) and by using direct immunoperoxidase (IP) stain for viral antigen. HSV was detected by IP staining in 40 of 169 (23.7%) monolayers and by CPE in 39 of 169 (23.1%) monolayers inoculated with fresh specimens. All 40 isolates were detected and confirmed by IP staining within 24 h. Although 39 of 40 isolates were detected by CPE, only 9 of 39 (23%) were positive within 24 h. CPE was observed at 2.7 days on the average, but 4 days were required before 90% of the cultures were positive and more than 5 days were required before all HSV isolates were recognized. Similar results were observed for frozen specimens. HSV was detected earlier with IP staining, which demonstrated more extensive infection of cell monolayers inoculated with titrated fresh culture isolates and clinical specimens than did CPE. IP staining reduces the amount of time required for detection and identification of HSV in culture, is readily adaptable for use in the clinical laboratory, and permanent stained preparations can be made.
Programmed cell death 4 (PDCD4): a novel player in ethanol-mediated suppression of protein translation in primary cortical neurons and developing cerebral cortex.

BACKGROUND Prenatal exposure to ethanol (EtOH) elicits a range of neuro-developmental abnormalities, microcephaly to behavioral deficits. Impaired protein synthesis has been connected to pathogenesis of EtOH-induced brain damage and abnormal neuron development. However, mechanisms underlying these impairments of protein synthesis are not known. In this study, we illustrate the effects of EtOH on programmed cell death protein 4 (PDCD4), a tumor and translation repressor. METHODS Primary cortical neurons (PCNs) were treated with 2.5 and 4 mg/ml EtOH for different time points (4 to 24 hours), and PDCD4 expression was detected by Western blotting. Protein synthesis was determined using [(35) S] methionine incorporation assay. Methyl cap pull-down assay was performed to establish the effect of EtOH on association of eukaryotic initiation factor 4A (eIF4A) with capped mRNA. Luciferase assay was performed to determine the in vivo translation. A 2-day acute 5-dose binge model with EtOH (4 g/kg body wt, 25% v/v) was performed in Sprague-Dawley rats at 12-hour intervals and analyzed for PDCD4, eIF4A, and eIF4A-methyl cap association. RESULTS EtOH increased PDCD4 expression in a time- and dose-dependent manner in PCNs, which inhibited the association of eIF4A with methyl cap. EtOH and ectopic PDCD4 expression suppressed in vivo translation in PCNs and RNAi targeting of PDCD4 blocked the inhibitory effect of EtOH on protein synthesis. In utero exposure of pregnant rats to EtOH resulted in a significant increase in PDCD4 in fetal cerebral cortex along with the inhibition of methyl cap-associated eIF4A, compared with isocaloric controls. Increased PDCD4 also occurred in pooled fractions of remaining brain regions. CONCLUSIONS Our data, for the first time, illustrate that PDCD4 mediates inhibitory effects of EtOH on protein synthesis in PCNs and developing brain.
Tissue Penetration and Activity of Camptothecins in Solid Tumor Xenografts

The ability of a panel of camptothecin derivatives to access the tumor compartment was evaluated to determine the mechanisms by which the architecture of solid tumors may act to limit their activity. Microregional localization and activity of members of the camptothecin class of topoisomerase I targeting agents, including topotecan, irinotecan, and irinophore C, a lipid-based nanoparticulate formulation of irinotecan, were evaluated over time in HCT116 and HT29 colorectal tumor xenografts. Using native drug fluorescence, their distributions in tissue cryosections were related to the underlying tumor vasculature, tumor cell proliferation, and apoptosis. Topotecan exhibited a relatively uniform tumor distribution; in tissue 100 μm away from vessels, it reached 94% ± 5% of levels seen around blood vessels, whereas irinotecan and irinophore C were found to reach only 41% ± 10% and 5% ± 2%, respectively. Surprisingly, all three agents were able to initially inhibit proliferation uniformly throughout the tumors, and it was their rate of washout (topotecan > irinotecan > irinophore C) that correlated with activity. To explain this discrepancy, we looked at SN38, the active metabolite of irinotecan, and found it to penetrate tissue similarly to topotecan. Hence, the poor access to the tumor compartment of irinotecan and irinophore C could be offset by their systemic conversion to SN38. It was concluded that all three agents were effective at reaching tumor cells, and that despite the poor access to the extravascular compartment of irinophore C, its extended plasma exposure and systemic conversion to the diffusible metabolite SN38 enabled it to effectively target solid tumors. Mol Cancer Ther; 13(11); 2727–37. ©2014 AACR.
IL-22–producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis

IL-22 plays an important role in mucosal epithelial cell homeostasis. Using a dextran sodium sulfate-induced mouse model of acute colitis, we observed an IL-23–dependent up-regulation of IL-22 in the middle and distal colon at the onset of epithelial cell damage. This heightened IL-22 correlated with an influx of innate immune cells, suggesting an important role in colonic epithelial protection. Freshly isolated colon-infiltrating neutrophils produced IL-22 contingent upon IL-23 signaling, and IL-22 production was augmented by TNF-α. Importantly, the depletion of neutrophils resulted in diminished IL-22 levels in the colon, and the transfer of IL-22–competent neutrophils to Il22a-deficient mice protected the colonic epithelium from dextran sodium sulfate-induced damage. In addition, IL-22–producing neutrophils targeted colonic epithelial cells to up-regulate the antimicrobial peptides, RegIIIβ and S100A8. This study establishes a role for neutrophils in providing IL-22–dependent mucosal epithelial support that contributes to the resolution of colitis.
The effect on patient loyalty of service quality, patient visit experience and perceived switching costs: lessons from one Taiwan university hospital

The reimbursement system changed from fee-for-service to fixed prospective payments in Taiwan, the effect on the physician–patient's relationship is worth being studied. We examined the relationship between patient visit experience, cost perceptions and the two important aspects of quality of care, curing and interpersonal performance, and patients' loyalty to the hospital physicians. A total of 404 patients from an acute care hospital in Taiwan, Kaohsiung Medical University Hospital (KMUH), were investigated using a self-administered mailing survey. All measures including patient loyalty (PL), curing service quality (CSQ), interpersonal service quality (ISQ), visit experience (VE) and perceived switching costs (PSC), were adapted and modified from existing scales. Our results showed that the physician's CSQ and ISQ positively affected patients' loyalty to KMUH. The interaction between the main effects of service quality, patients' VE and three types of switching visit costs, yielded additional insights into the importance of service quality for patient retention. The CSQ of physicians becomes a more important determinant of loyalty than ISQ as patients' VE increases. The importance of CSQ and ISQ increases in relation to PL as the perceived procedural and relational costs of changing care providers increases. Neither CSQ nor ISQ has a reduced relationship with PL as the perceived financial costs of switching hospitals increase. Our study indicates that the impact of CSQ and ISQ on loyalty varies according to the perceived visit costs of changing hospitals and the patients' VE.
Myocardial function and haemodynamics in extensive burn trauma: evaluation by clinical signs, invasive monitoring, echocardiography and cytokine concentrations. A prospective clinical study

Background: The objectives of this study were to (1) describe the haemodynamic profile of patients with extensive burns during the early fluid resuscitation phase, (2) evaluate myocardial performance by invasive monitoring and echocardiography and (3) analyze the relations between serum cytokine (IL‐6, IL‐8, TNF) and natriuretic peptide (ANP, BNP) concentrations and myocardial function in these patients.
Testing under a special form of heteroscedasticity

ABSTRACT In the presence of heteroscedasticity, conventional standard errors (which assume homoscedasticity) can be biased up or down. The most common form of heteroscedasticity leads to conventional standard errors that are too small. In this study, we discuss the conditions under which conventional standard errors are too large. In such settings, standard tests of heteroscedasticity may fail and leave the heteroscedasticity undetected. This is particularly problematic as power gains can be achieved when testing for the causal effect in such settings.
Effects of prebiotics on the immune response to vaccination in the elderly.

BACKGROUND Prebiotics stimulate the growth of bifidogenic bacteria in the gut. The aim of this work was to assess the effects of a prebiotic mixture on the immune response in healthy elderly people. METHODS Healthy free-living elderly people (age, > or = 70 years), receiving a nutritional supplement that provided 1.6 MJ, 15 g of protein, and 50% of vitamin daily reference values per day, were randomly assigned to receive a prebiotic mixture (6 g/d of a 70% raftilose and 30% raftiline mixture) or placebo (6 g of maltodextrin powder) for 28 weeks. At week 2 of the study, all subjects were vaccinated with influenza and pneumococcal vaccines. At weeks 0, 2, and 8 of the study, serum total proteins, albumin, immunoglobulins, saliva secretory immunoglobulin A (IgA), and serum titers of influenza A and B and pneumococcal antibodies were measured. At week 8, cultured peripheral monocyte cell secretion of interleukin-4, interferon-gamma, and lymphocyte proliferation, stimulated with phytohemagglutinin and influenza antigen, were measured. RESULTS Sixty-six subjects were considered eligible for the study, and 43 (20 receiving prebiotics and 23 receiving placebo) were considered for final analyses on a per protocol basis. No changes in serum proteins, albumin, immunoglobulins, and secretory IgA were observed. Antibodies against influenza B and pneumococcus increased significantly from weeks 0 to 8, with no significant differences between groups. Antibodies against influenza A did not increase. No effects of prebiotics on interleukin-4 and interferon-gamma secretion by cultured monocytes were observed. CONCLUSIONS No immunological effects of prebiotics were observed in this study.
Does Tranexamic Acid Reduce Bleeding during Femoral Fracture Operation?

BACKGROUND Proximal Femoral shaft fractures are commonly associated with marked blood loss which can lead to postoperative acute anemia and some other complications. Tranexamic acid (TA) is an antifibrinolytic medication that reduces intra-and postoperative blood loss and transfusion requirements during some elective surgeries. The aim of this study is to evaluate the effect of intravenous Tranexamic acid (TA) on intraoperative blood loss and a subsequent need for transfusion in patients who were undergoing surgery for femoral shaft fractures in trauma setting. METHODS Thirty-eight ASA grade I-II patients undergoing proximal femoral shaft fracture surgery with intra medullary nailing were included in this double blind randomized controlled clinical trial. They were allocated into two groups. Group I, the intervention group with eighteen patients received 15 mg/kg (TA) via intravenous infusion before surgical incision. Patients in the placebo group received an identical volume of normal saline. Hemoglobin level was measured four hours before and after the surgeries. Postoperative blood loss and hemoglobin change as well as transfusion rates and volumes were compared between the two groups. RESULTS Mean Percentage fall in hemoglobin after surgery were 1.75±0.84 and 2.04±1.9 in the study and placebo groups, respectively (P=0.570). Hemoglobin loss was higher in the placebo group. Transfusion rates was lower in TA group (5.6%) compared to the placebo group (30%) (P=0.06). No significant difference in The Allowable Blood Loss during the surgery was found between the two groups (P=0.894). CONCLUSION Preoperative treatment with TA reduces postoperative blood loss and the need for blood transfusion during traumatic femoral fracture operation.
Real-time use of the iPad by third-year medical students for clinical decision support and learning: a mixed methods study

Purpose Despite widespread use of mobile technology in medical education, medical students’ use of mobile technology for clinical decision support and learning is not well understood. Three key questions were explored in this extensive mixed methods study: 1) how medical students used mobile technology in the care of patients, 2) the mobile applications (apps) used and 3) how expertise and time spent changed overtime. Methods This year-long (July 2012–June 2013) mixed methods study explored the use of the iPad, using four data collection instruments: 1) beginning and end-of-year questionnaires, 2) iPad usage logs, 3) weekly rounding observations, and 4) weekly medical student interviews. Descriptive statistics were generated for the questionnaires and apps reported in the usage logs. The iPad usage logs, observation logs, and weekly interviews were analyzed via inductive thematic analysis. Results Students predominantly used mobile technology to obtain real-time patient data via the electronic health record (EHR), to access medical knowledge resources for learning, and to inform patient care. The top four apps used were Epocrates®, PDF Expert®, VisualDx®, and Micromedex®. The majority of students indicated that their use (71%) and expertise (75%) using mobile technology grew overtime. Conclusions This mixed methods study provides substantial evidence that medical students used mobile technology for clinical decision support and learning. Integrating its use into the medical student's daily workflow was essential for achieving these outcomes. Developing expertise in using mobile technology and various apps was critical for effective and efficient support of real-time clinical decisions.
Effect of surfactant HLB and different formulation variables on the properties of poly-D,L-lactide microspheres of naltrexone prepared by double emulsion technique

The aim of this work was to investigate the role of HLB of emulsifier as well as volume of the internal aqueous phase (W1) and presence of salt in the external aqueous phase (W2) on the morphology, size and encapsulation efficiency of poly(D,L-lactide) microspheres containing naltrexone HCl. PLA microparticles containing naltrexone HCl, an effective opiate antagonist, were prepared by a water-in-oil-in-water emulsification–solvent evaporation procedure. One of the five different emulsifiers: span 80, span 20, tween 85, tween 80 and tween 20, with HLB values from 4–17 were added to W1. Presence of emulsifier in W1 resulted in smaller particles with a more dense and uniform internal structure. Incorporation of span 80 (HLB 4.3, suitable for W/O emulsions) yield the highest encapsulation efficiency. Increasing the HLB value to 8 or 11 (span 20 or tween 85) decreased the efficiency of naltrexone HCl-loading. HLB values higher than 15 (tween 80 or tween 20) increased encapsulation efficiency unexpectedly, which could be attributed to migration of these emulsifiers to the O/W2 interface and modifying the surface properties of microparticles. Increasing the internal water phase volume from 0.2–1.8 ml resulted in larger particle size with poor encapsulation efficiency. Addition of 10% w/w NaCl to the W2 changed the surface morphology of microspheres from a porous form to a smooth surface. It was shown that, by selecting the appropriate HLB value of emulsifier in W1, addition of salt to W2 and controlling the volume of W1, one can control the encapsulation efficiency, size and morphology of microspheres.
The polyamine metabolism genes ornithine decarboxylase and antizyme 2 predict aggressive behavior in neuroblastomas with and without MYCN amplification

High polyamine (PA) levels and ornithine decarboxylase (ODC) overexpression are well‐known phenomena in many aggressive cancer types. We analyzed the expression of ODC and ODC‐activity regulating genes antizymes 1‐3 (OAZ1‐3) and antizyme inhibitors 1‐2 (AZ‐IN1‐2) in human neuroblastoma (NB) tumors and correlated these with genetic and clinical features of NB. Since ODC is a known target gene of MYCN, the correlation between ODC and MYCN was of special interest. Data were obtained from Affymetrix micro‐array analysis of 88 NB tumor samples. In addition, mRNA expression levels of ODC, OAZ2 and MYCN in a MYCN‐inducible NB cell line were determined by quantitative real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR). ODC mRNA expression in NB tumors was significantly predictive of decreased overall survival probability and correlated with several unfavorable clinical NB characteristics (all p < 0.005). Interestingly, high ODC mRNA expression also showed significant correlation with poor survival prognosis in Kaplan‐Meier analyses stratified for patients without MYCN amplification, suggesting an additional role for ODC independent of MYCN. Conversely, high OAZ2 mRNA expression correlated with increased survival and with several favorable clinical NB characteristics (all p < 0.003). In addition, we provide first evidence of a role for MYCN‐associated transcription factors MAD2 and MAD7 in ODC regulation. In NB cell cultures, ectopic overexpression of MYCN altered ODC but not OAZ2 mRNA levels. In conclusion, these data suggest that elevated ODC and low OAZ2 mRNA expression levels correlate with several unfavorable genetic and clinical features in NB, offering new insights into PA pathways and PA metabolism‐targeting therapy in NB.
Rapid communication Identification and kainic acid-induced up-regulation of low-affinity p 75 neurotrophin receptor ( p 75 NTR ) in the nigral dopamine neurons of adult rats

Parkinson’s disease is a common and severe debilitating neurological disease that results from massive and progressive degenerative death of dopamine neurons in the substantia nigra, but the mechanisms of neuronal degeneration and disease progression remains largely obscure. We are interested in possible implications of low-affinity p75 neurotrophin receptor (p75NTR), which may mediate neuronal apoptosis in the central nervous system, in triggering cell death of the nigral dopamine neurons. The RTPCR and immunohistochemistry were carried out to detect if p75NTR is expressed in these nigral neurons and up-regulated by kainic acid (KA) insult in adult rats. It revealed p75NTR-positive immunoreactivity in the substantia nigra, and co-localization of p75NTR and tyrosine hydroxylase (TH) was found in a large number of substantia nigra neurons beside confirmation of p75NTR in the choline acetyltransferase (ChAT)-positive forebrain neurons. Cell count data further indicated that about 47–100% of TH-positive nigral neurons and 98–100% of ChAT-positive forebrain neurons express p75NTR. More interestingly, significant increasing in both p75NTR mRNA and p75NTR-positive neurons occurred rapidly following KA insult in the substantia nigra of animal model. The present study has provided first evidence on p75NTR expression and KA-inducing p75NTR upregulation in substantia nigra neurons in rodent animals. Taken together with previous data on p75NTR functions in neuronal apoptosis, this study also suggests that p75NTR may play important roles in neuronal cell survival or excitotoxic degeneration of dopamine neurons in the substantia nigra in pathogenesis of Parkinson’s disease in human beings. 2008 Elsevier Ltd. All rights reserved.
Cystic Fibrosis: Isolation and Physical Properties of a Salivary Cystic Fibrosis Factor

Summary: A ciliostatic factor has been isolated from cystic fibrosis (CF) saliva by dialyzing it from purified α-amylase prepared by a glycogen-complex method. This method of isolating the CF factor is an improvement over the previously employed heparin procedure. The activity of the isolated factor is proportional with concentration using the oyster gill ciliostatic assay and in its inhibition of mammalian glycogen debranching enzyme. The ciliostatic action of the factor can be reversed by heparin under certain conditions. The type of inhibition of the debranching enzyme by the isolated CF factor indicates that its chemical structure is similar to that observed with hydroxyalkylamines and polyamine metabolites. Physical properties of the isolated factor indicate that it is of low molecular weight and is labile as a function of pH and temperature. At neutral pH the conditions under which it is maintained have a direct effect on the length of time that it is stable.Speculation: These studies indicate how the stability of the ciliostatic CF factor isolated from saliva is related to the physical conditions to which it is exposed. This information should be of value in evaluating its activity as well as in investigations into its chemical nature.
Alcohol consumption and work-related injuries among farmers in Heilongjiang Province, People's Republic of China.

BACKGROUND Alcohol consumption has been found to be associated with work-related injuries among workers around the world, but this association has not well been studied among agricultural workers in China. METHODS This population-based survey aimed to study the association between alcohol use and work-related agricultural injury. Farmers in a northeastern province of China were questioned about work-related injury in the past year (May 2007-April 2008), alcohol use, farming practices, and sociodemographic factors. The Chi-square test and logistic regression analyses were used to investigate the role of alcohol drinking in agricultural injuries. RESULTS Among 2,050 farmers who completed the survey, the 12-month prevalence of work-related injury was 12.2%. The leading external cause of injury was exposure to mechanical force. The odds of injury among farmers with past month drinking, who drank distilled spirits, and reported intoxication were respectively 1.77 (95% CI = 1.27-2.47), 1.89 (95% CI = 1.35-2.66), 2.12 (95% CI = 1.42-3.11). The odds of injury also significantly increased with greater average amounts of pure alcohol per day, with increased frequency of drinking per week, and with greater reported years of drinking. Each alcohol use variable was associated with injury in logistic regression models while controlling for sex, age, years of farm work, months of farm work in the past 12 months, driving a motor vehicle, and agricultural machinery use. CONCLUSIONS We found a significant association between alcohol consumption and work-related injuries among farmers. Our findings stress the need for culturally appropriate interventions which affect alcohol use and prevent injuries among Chinese farmers.