Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of early resistance development at the first failure timepoint in elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate-treated patients.

OBJECTIVES The patterns of emergent HIV-1 drug resistance in patients failing a single-tablet regimen consisting of elvitegravir, boosted by cobicistat, plus emtricitabine and tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) include mutations in HIV-1 reverse transcriptase (RT) and integrase (IN). The order of development of mutations at early virological failure has not been described. The aim of this study was to determine the first resistance mutations to emerge during virological failure on EVG/COBI/FTC/TDF. PATIENTS AND METHODS Population sequencing was conducted at the first virological failure timepoint with HIV-1 RNA ≥400 copies/mL for each of the 18 patients with emergent resistance in the EVG/COBI/FTC/TDF arms of two randomized, double-blind, Phase 3 studies of EVG/COBI/FTC/TDF through Week 144. RESULTS At first failure compared with confirmed virological failure, 4 of the 18 patients had no detectable resistance mutation in their virus and only 51% of the RT and IN mutations were detected overall. M184V/I in RT was the first mutation to appear in many cases (n = 6) and was then followed by additional mutations in RT and IN. No case with development of resistance to the IN strand-transfer inhibitor prior to the development of M184V/I was detected. CONCLUSIONS The analysis of first failure found fewer patients with emergent resistance and fewer resistance mutations than the standard analysis at the later confirmation of virological failure. The early detection of resistance may preserve later treatment options.
Male Partners’ Involvement Towards Prenatal Screening And Diagnostic Testing For Down Syndrome

Introduction: Now, male partners’ involvement in prenatal screening and diagnostic testing for Down syndrome is becoming increasingly recognized as well to ensure that parents are well informed of the risks and benefits of screening. The aim of study was to understand the degree of male partners’ involvement during pregnancy in Singapore population. Methods: A cross-sectional survey of male partners’ attending prenatal counseling was performed. The instrument used to measure the level of involvement is a self-assessment questionnaire that identifies the role of male partners with a Likert scale. Descriptive statistics was used to analyze data gained. Result: A total of 107 participants completed the questionnaire. Sixty-seven percent of male partners were found to have a highlevel of involvement while 32.7% was found to have a medium level of involvement. Most of them stated that women can pursue prenatal testing without their permission. Male partners found it more important for them to accompany their spouse to amniocentesis or CVS than to the Down syndrome screening test. When participants were asked about how much information about Down syndrome they sought prior to the appointment, how much discussion they had with their spouse about Down syndrome testing, and about whether they or their spouse should be the first person to receive test results, most stated that they were undecided. Conclusion: These results revealed that male partners were very well involved in the Down syndrome testing during pregnancy and future studies should assess possible underlying factors that influence male partners’ involvement.
Managing the Iatrogenic Risks of Risk Management

Introduction Risk management aims to protect, but many’s the slip betwixt help and health. Medical care is meant to make people well, but it can harm as it heals. This is the pervasive problem of “iatrogenic” (care-induced) and “nosocomial” (hospital-induced) injury.1 “Most treatments have side effects as well as benefits. ”2 “Medical care is an inherently risky enterprise. ”3 “[M]edical progress has provided physicians with an arsenal of double-edged swords. ”4 The modern medical community appears, more or less, to accept iatrogenesis as a fact of life, and to work diligently to manage the risks of its own risk management measures.5
Risk Assessment of developing type 2 diabetes mellitus in patient on antihypertensive medication

Objective: The purpose of this study was to examine the risk assessment of developing type 2 diabetes mellitus in patient on antihypertensive medication. Material & Method: In the present study total 30 patient with essential hypertension of both sex with mean age (48.6±0.8313) were recruited as per the inclusion criteria. Patients were segregated on the behalf of therapy they were using. 22 patients were on Losartan+HCTZ therapy and 8 patients were on Atenolol therapy. Result: After six month of antihypertensive therapy Atenolol group showing a significant difference in their blood glucose (0.0014) whereas in Losartan+HCTZ group significant difference was not observed (0.1542). Patients of Atenolol group when compared with patient of Losartan+HCTZ group a significant difference was observed in the serum cholesterol level (0.0290). Conclusion: We found that the use of β-blocker was independently associated with increased risk of type 2 diabetes. So increase in blood glucose in the Atenolol group patient revealed a significant association between use of Atenolol therapy and metabolic dysfunction whereas in Losartan+HCTZ group significant increase in blood glucose was not observed and from these we can conclude therapy with Losartan+HCTZ therapy not associated with metabolic dysfunction.
PERCEPTION OF PARAMEDICAL STUDENTS IN A TEACHING INSTITUTE ON BMI, DIET AND SOCIAL HABITS–A CROSS SECTIONAL SURVEY

Objective : The study focuses on young paramedical students’ perception on Body Mass Index (BMI), diet, and social habits. Methods : A total of 232 paramedical (pharmacy, physiotherapy, and nursing) students were enrolled in the study. Information about socio-demographic details was obtained by using a self-administered questionnaire. Body weight and height were taken and BMI was calculated. The questionnaire also assessed the students’ eating habits, social habits, and exercise habits and also their perception towards their social habits like drinking alcohol and smoking cigarettes. Results : The BMI of the female participants were on the upper limits of the normal Body Mass Index range levels. More female participants were found to be in the severely underweight or underweight, overweight, and obese category compared to their male counterparts. The study showed that most of the participants took either coffee or tea daily and a small percentage of students perceived smoking cigarettes and alcohol consumption to be good. Most students eat fewer amounts of fruits or vegetables than the prescribed daily intake and many do not exercise as required. Conclusion : The out comes with paramedical student fraternity caution us to plan changes in practices in teaching facilities to bridge the gap in preaching and following what we preach in reality.
Split‐Ubiquitin System for Identifying Protein‐Protein Interactions in Membrane and Full‐Length Proteins

Protein‐protein interactions play a fundamental role in the regulation of almost all cellular processes. Thus, the identification of interacting proteins can help to elucidate their function. The mating‐based split‐ubiquitin system (mbSUS) uses yeast as a test organism to identify potential interactions between full‐length membrane proteins or between a full‐length membrane protein and a soluble protein. The mbSUS can also be used to provide further evidence for protein‐protein interactions detected with other methods and to map the interaction domains of selected proteins. The mbSUS is optimized for systematic screening approaches employing a mating‐based approach, as typically used to determine protein interactions on a genomic scale. Construction of bait and prey fusions is simplified by adapting two different cloning procedures: (i) in vivo cloning in yeast, and (ii) Gateway cloning in E. coli. Protocols for small‐scale interaction tests, as well as systematic approaches using sorted bait and prey arrays, are described. Curr. Protoc. Neurosci. 41:5.27. 1‐5.27. 41. © 2007 by John Wiley & Sons, Inc.
Characterization of Sarcocystis fayeri's actin‐depolymerizing factor as a toxin that causes diarrhea

Raw horsemeat has the potential to induce food poisoning which often presents with diarrheal symptoms. A sample of horsemeat was found to be infected with Sarcocystis fayeri, and a 15‐kDa protein isolated from the cysts of S. fayeri was found to clearly show its diarrhea‐inducing activity. A nested polymerase chain reaction was used to clone the cDNA of the 15‐kDa protein. The deduced amino acid sequence showed homology to actin‐depolymerizing factor (ADF). A recombinant 15‐kDa protein depolymerized prepolymerized actins in a test tube. The 15‐kDa protein possessed conserved amino acid sequences of ADF of Toxoplasma gondii and Eimeria tenella. These characteristics indicate that the 15‐kDa protein of S. fayeri belongs to the ADF/cofilin protein family. The recombinant 15‐kDa protein evoked fluid accumulation in the looped ileum, resulting in diarrhea, but it did not kill the cultured fibroblast cells, macrophages or intestinal mucosal cells. In addition, the culture supernatant of the macrophages treated with the recombinant 15‐kDa protein killed the fibroblast L929 cells. This fact indicates that ADF of S. fayeri induced cytotoxic substances, such as tumor necrosis factor‐α, according to the published reports. Although further experiments are needed now to elucidate the enterotoxic mechanism of S. fayeri's ADF, our findings may offer new insight into research on parasites and parasite‐instigated food poisoning.
Time to detection in liquid culture of sputum in pulmonary MDR-TB does not predict culture conversion for early discharge.

OBJECTIVES UK guidelines advise that patients with pulmonary MDR-TB are isolated in hospital until the results of sputum cultures are negative (culture conversion), typically after 42 days of incubation with no growth. MDR-TB patients may be isolated ≥42 days longer than is necessary for public safety, which has major implications for patients and hospitals. Our objective was to determine whether analysis of time to detection (TTD) in liquid culture could predict the earliest safe discharge date of MDR-TB patients. PATIENTS AND METHODS Fifteen pulmonary MDR-TB patients were identified retrospectively from the London TB Register and hospital records. We performed linear regression of TTD against days elapsed between admission and sample date. If the regression line crossed the observed culture-conversion date at TTD = 42 days, the data were deemed to give 'precise prediction' of the earliest safe discharge date. RESULTS The median length of stay was 91 days (IQR 79-131 days). Culture conversion occurred at a median of 59 days (IQR 46-86 days). Twelve patients were hospitalized beyond culture conversion, with a median overstay of 52 days (IQR 35-68 days). TTD tended to lengthen until culture conversion and, for nearly half of the patients (7/15, 47%), linear regression of TTD against time from admission gave a good fit to the data (r(2) ≥ 0.6) and supported precise prediction. However, data from the remaining patients showed considerable variation, and linear regression did not support prediction of safe discharge. CONCLUSIONS TTD data from these pulmonary MDR-TB patients did not support a simple clinical prediction tool, but our analysis was limited by the small size of our sample.
Tigecycline resistance in clinical isolates of Enterococcus faecium is mediated by an upregulation of plasmid-encoded tetracycline determinants tet(L) and tet(M).

OBJECTIVES Tigecycline represents one of the last-line therapeutics to combat multidrug-resistant bacterial pathogens, including VRE and MRSA. The German National Reference Centre for Staphylococci and Enterococci has received 73 tigecycline-resistant Enterococcus faecium and Enterococcus faecalis isolates in recent years. The precise mechanism of how enterococci become resistant to tigecycline remains undetermined. This study documents an analysis of the role of efflux pumps in tigecycline resistance in clinical isolates of Enterococcus spp. METHODS Various tigecycline MICs were found for the different isolates analysed. Tigecycline-resistant strains were analysed with respect to genome and transcriptome differences by means of WGS and RT-qPCR. Genes of interest were cloned and expressed in Listeria monocytogenes for verification of their functionality. RESULTS Detailed comparative whole-genome analyses of three isogenic strains, showing different levels of tigecycline resistance, revealed the major facilitator superfamily (MFS) efflux pump TetL and the ribosomal protection protein TetM as possible drug resistance proteins. Subsequent RT-qPCR confirmed up-regulation of the respective genes. A correlation of gene copy number and level of MIC was inferred from further qPCR analyses. Expression of both tet(L) and tet(M) in L. monocytogenes unequivocally demonstrated the potential to increase tigecycline MICs upon acquisition of either locus. CONCLUSIONS Our results indicate that increased expression of two tetracycline resistance determinants, a tet(L)-encoded MFS pump and a tet(M)-encoded ribosomal protection protein, is capable of conferring tigecycline resistance in enterococcal clinical isolates.
The New Potential for Understanding Groundwater Contaminant Transport

The groundwater remediation field has been changing constantly since it first emerged in the 1970s. The remediation field has evolved from a dissolved‐phase centric conceptual model to a DNAPL‐dominated one, which is now being questioned due to a renewed appreciation of matrix diffusion effects on remediation. Detailed observations about contaminant transport have emerged from the remediation field, and challenge the validity of one of the mainstays of the groundwater solute transport modeling world: the concept of mechanical dispersion (Payne et al. 2008). We review and discuss how a new conceptual model of contaminant transport based on diffusion (the usurper) may topple the well‐established position of mechanical dispersion (the status quo) that is commonly used in almost every groundwater contaminant transport model, and evaluate the status of existing models and modeling studies that were conducted using advection‐dispersion models.
Antimicrobial susceptibility testing of Arcobacter butzleri and Arcobacter cryaerophilus strains isolated from Belgian patients.

OBJECTIVES To evaluate the feasibility of different methods for susceptibility testing of human Arcobacter isolates, to assess susceptibility to antibiotics commonly used to treat diarrhoeal illness and to obtain MIC distribution data. METHODS One-hundred-and-six unique Arcobacter strains were collected during an epidemiological study on pathogens in gastroenteritis. Strains were identified by multiplex PCR and PCR-RFLP, and characterized by PFGE. Susceptibility to ampicillin, erythromycin, tetracycline, doxycycline, gentamicin and ciprofloxacin was determined using gradient strip and disc diffusion methodology. Optimal conditions for growth and incubation were tested. Azithromycin was tested with gradient strip diffusion on a subset of 40 strains. Sequence analysis of the quinolone resistance-determining region of gyrA was performed for a subset of 18 strains. RESULTS Based on gradient diffusion results, most Arcobacter strains were susceptible to gentamicin (99%) and tetracycline (89%). Erythromycin (78%), ciprofloxacin (72%) and doxycycline (76%) retained moderate activity against Arcobacter spp. Only 9% of the strains were susceptible to ampicillin. Most Arcobacter butzleri strains were susceptible to ciprofloxacin (87%), whereas half of the Arcobacter cryaerophilus isolates (51%) showed high-level resistance (MIC >32 mg/L). MIC50 values were comparable for both macrolide antibiotics. Ciprofloxacin-resistant strains possessed an identical mutation in gyrA. Overall, categorical agreement between gradient and disc diffusion results was 60%. Gradient diffusion showed superior readability. CONCLUSIONS Gradient diffusion methodology is preferred for routine susceptibility testing. Acquired resistance to fluoroquinolones was observed in A. cryaerophilus. Macrolides are not first-choice empirical antibiotics for Arcobacter infections. Tetracyclines can be suggested for treatment of documented Arcobacter-related gastrointestinal infections.
Thermal stability of exchange bias nanostructures

The thermal stability of an array of square exchange bias nanoelements has been investigated as a function of both the element size and the microstructure of the antiferromagnetic layer. The thermal stability of the nanostructures is measured in terms of their median blocking temperature ⟨TB⟩. It is shown that, generally, ⟨TB⟩ is lower for nanostructures than for the equivalent thin film system. However, the opposite behavior can be observed depending on the measurement conditions, specifically the temperature of measurement and the setting temperature. These results emphasize the importance/limitations of the setting process in exchange bias systems.
Contribution of Indirect Causes to Maternal Mortalities Based on a Methodological Approach to Clinical Epidemiology in Iran

Introduction: Level of mothers’ literacy, pregnancy history of more than four times, residence in villages, lack of receiving intensive care during pregnancy, as well as inaccessibility to obstetric emergency services have been reported, in Iran and the world, as major factors for maternal mortal-ity. Considering significance of identifying indirect causes of maternal mortalities, the present study was aimed to determine the contribution of indirect causes to maternal mortalities in Markazi province, Iran. Methods: This retrospective, descriptive-analytical study analyzes root causes and sentinel events through describing a case of maternal mortality reported in Markazi province. The data were gathered through interviews and documents’ investigation, and Bayesian analysis and calculation of conditional probability in Netica 5.08 software were used. Results: Findings on a 36-year-old mother, in the 37th week of her third pregnancy and suffering from cardiomyopathy, indicated that lack of re-ceiving prenatal care on time, insensitivity of health and medical person-nel to pursuing the patient’s timely referrings according to Ministry of Health and Medical Education guidelines, lack of coordination and mon-itoring on the part of team of specialists responsible for the pregnant mother’s treatment in hospital, and indifference toward appropriate man-agement of treatment were determined as indirect causes of the mother’s death. Conclusion: While cardiomyopathy was registered as direct cause of death, according to root cause analysis indirect causes had a 43% contri-bution to the mother’s death. Thus, planning for determination of major causes and eliminating indirect causes are very important for reducing ma-ternal mortalities.
Review of Quantitative Surveys of the Length and Stability of MTBE, TBA, and Benzene Plumes in Groundwater at UST Sites

Quantitative information regarding the length and stability condition of groundwater plumes of benzene, methyl tert‐butyl ether (MTBE), and tert‐butyl alcohol (TBA) has been compiled from thousands of underground storage tank (UST) sites in the United States where gasoline fuel releases have occurred. This paper presents a review and summary of 13 published scientific surveys, of which 10 address benzene and/or MTBE plumes only, and 3 address benzene, MTBE, and TBA plumes. These data show the observed lengths of benzene and MTBE plumes to be relatively consistent among various regions and hydrogeologic settings, with median lengths at a delineation limit of 10 µg/L falling into relatively narrow ranges from 101 to 185 feet for benzene and 110 to 178 feet for MTBE. The observed statistical distributions of MTBE and benzene plumes show the two plume types to be of comparable lengths, with 90th percentile MTBE plume lengths moderately exceeding benzene plume lengths by 16% at a 10‐µg/L delineation limit (400 feet vs. 345 feet) and 25% at a 5‐µg/L delineation limit (530 feet vs. 425 feet). Stability analyses for benzene and MTBE plumes found 94 and 93% of these plumes, respectively, to be in a nonexpanding condition, and over 91% of individual monitoring wells to exhibit nonincreasing concentration trends. Three published studies addressing TBA found TBA plumes to be of comparable length to MTBE and benzene plumes, with 86% of wells in one study showing nonincreasing concentration trends.
The Role of Groundwater for Lake‐Water Quality and Quantification of N Seepage

The heterogeneous nature of both groundwater discharge to a lake (inflow) and nitrate concentrations in groundwater can lead to significant errors in calculations of nutrient loading. Therefore, an integrated approach, combining groundwater flow and transport modelling with observed nitrate and ammonium groundwater concentrations, was used to estimate nitrate loading from a catchment via groundwater to an oligotrophic flow‐through lake (Lake Hampen, Denmark). The transport model was calibrated against three vertical nitrate profiles from multi‐level wells and 17 shallow wells bordering a crop field near the lake. Nitrate concentrations in groundwater discharging to the lake from the crop field were on average 70 times higher than in groundwater from forested areas. The crop field was responsible for 96% of the total nitrate loading (16.2 t NO3/year) to the lake even though the field only covered 4.5% of the catchment area. Consequently, a small change in land use in the catchment will have a large effect on the lake nutrient balance and possible lake restoration. The study is the first known attempt to estimate the decrease of nitrate loading via groundwater to a seepage lake when an identified catchment source (a crop field) is removed.
Comparative effects of overproducing the AraC-type transcriptional regulators MarA, SoxS, RarA and RamA on antimicrobial drug susceptibility in Klebsiella pneumoniae.

OBJECTIVES In Klebsiella pneumoniae, overproduction of RamA and RarA leads to increased MICs of various antibiotics; MarA and SoxS are predicted to perform a similar function. We have compared the relative effects of overproducing these four AraC-type regulators on envelope permeability (a combination of outer membrane permeability and efflux), efflux pump and porin production, and antibiotic susceptibility in K. pneumoniae. METHODS Regulators were overproduced using a pBAD expression vector. Antibiotic susceptibility was measured using disc testing. Envelope permeability was estimated using a fluorescent dye accumulation assay. Porin and efflux pump production was quantified using proteomics and validated using real-time quantitative RT-PCR. RESULTS Envelope permeability and antibiotic disc inhibition zone diameters both reduced during overproduction of RamA and to a lesser extent RarA or SoxS, but did not change following overproduction of MarA. These effects were associated with overproduction of the efflux pumps AcrAB (for RamA and SoxS) and OqxAB (for RamA and RarA) and the outer membrane protein TolC (for all regulators). Effects on porin production were strain specific. CONCLUSIONS RamA is the most potent regulator of antibiotic permeability in K. pneumoniae, followed by RarA then SoxS, with MarA having very little effect. This observed relative potency correlates well with the frequency at which these regulators are reportedly overproduced in clinical isolates.