Miracle-dz/UniFAR-FTUs huggingface dataset:
N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03

Background:HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that play important roles either in correct folding or in shielding vulnerable viral protein surfaces from antibody recognition. Methods:In our previous work, 25 potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were individually mutated, and the resulting effects on infectivity and antibody-mediated neutralization were evaluated. To further understand the functional role of these PNGS, we generated double and multiple mutants from selected individual PNGS mutants. The effects were then evaluated by examining infectivity and sensitivity to antibody-mediated neutralization by neutralizing monoclonal antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. Results:Infectivity results showed that, among the 12 combined PNGS mutants, only 197M.1 (N197D/N301Q) lost infectivity completely, whereas all others (except for 197M.6) showed reduced viral infectivity. In terms of neutralization sensitivity to known nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing N197D significantly increased neutralization sensitivity to VRC01 and VRC03, suggesting N197 and N463 have a strong synergistic effect in regulating the neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. Structural analysis based on the available structures of gp120 alone and in complex with CD4 and various nMAbs elucidates a molecular rationale for this experimental observation. Conclusions:The data indicate that N463 plays an important role in regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of N197D mutation of gp120, which should provide valuable information for a better understanding of the interplay between HIV-1 and VRC01/03.
Background to the post-acute care trial of community hospital rehabilitation for older people

The post-acute care trial of community hospitals (PATCH) study is a multicentre, randomized controlled trial (RCT) comparing outcomes of rehabilitation for older people provided in five district general hospitals (DGHs) and seven associated community hospitals (CHs) in urban and rural settings. This article describes the background to the PATCH study, compares the characteristics of the participating DGHs and CHs and describes the participating patients. Descriptions of the DGHs and CHs were produced from information obtained from each centre. Recruitment rates, patient characteristics and hospital stays were compared between centres. There was variation in operational policies of the DGHs and in the organizational features of the CHs, such that patient characteristics and lengths of hospital stay differed between centres. Statistical comparisons suggested that these differences were not systematically distributed. This underpinning study to the PATCH RCT suggests that the variation in study sites and pat.
Incidence, characteristics, and economic burden of rotavirus gastroenteritis associated with hospitalization of israeli children <5 years of age, 2007-2008.

BACKGROUND Limited data exist on the epidemiology and burden of rotavirus gastroenteritis in Israel. Objectives. Our objective was to examine the incidence, characteristics, and economic burden of rotavirus gastroenteritis associated with hospitalization of children <5 years of age in Israel. METHODS A prospective study was initiated in pediatric wards at 3 hospitals in northern Israel. Presence of rotavirus in stool specimens was detected by immunochromatography, and G and P genotypes were determined by reverse-transcriptase polymerase chain reaction. Demographic data, clinical manifestations, and expenditures related to a child's illness were studied using parental interviews. RESULTS From November 2007 through October 2008, 472 children hospitalized with gastroenteritis were enrolled in the study. Rotavirus gastroenteritis was diagnosed in 39.1% of children, with a peak identification rate during November 2007-January 2008 (62.5%-71.0%). Most cases of rotavirus gastroenteritis (87.2%) occurred in children <2 years of age. In infections with 1 rotavirus genotype, G1P[8] was the most frequently detected (49.1%), followed by G1P[4] (11.1%) and G9P[8] (9.3%). Mixed rotavirus isolates were identified in 28.9% of the children. The estimated incidence of primary hospitalizations for rotavirus gastroenteritis among children aged 0-5 years was 5.7 hospitalizations per 1000 children per year (95% confidence interval, 5.1-6.3 hospitalizations per 1000 children per year), resulting in an estimate of 4099 annual national hospitalizations (95% confidence interval, 3668-4531 hospitalizations per year). This figure represents approximately 6.5% of the total annual hospitalizations among Israeli children <5 years of age. The annual calculated cost of hospitalizations for rotavirus gastroenteritis was US $7,680,444, including US $4,578,489 (59.6%) in direct costs to the health care system and US $3,101,955 in overall household costs. CONCLUSIONS Our findings are important for decision making regarding implementation and evaluation of a routine immunization program against rotavirus gastroenteritis.
Pegylated interferon and ribavirin promote early evolution of nonstructural 5A protein in individuals with hepatitis C who demonstrate a response to treatment.

BACKGROUND Hepatitis C virus (HCV) quasispecies diversity is more likely to affect early viral decline during treatment of hepatitis C than is having human immunodeficiency virus (HIV) infection. We evaluated the influence of HCV therapy on changes in the nonstructural 5A (NS5A) protein. METHODS Fifteen patients with HCV genotype 1 infection with or without HIV infection were recruited for the present study, and the decrease in the HCV RNA level was measured at early time points. The evolution of HCV NS5A quasispecies within the first week was analyzed by comparing the clones observed at later times in the study with the baseline consensus sequence of individual patients. The response to therapy was defined as an early response (ER; ie, an HCV RNA level <615 IU/mL at week 4) or a slow response (SR; ie, a detectable HCV RNA level at week 4). RESULTS HIV infection did not affect early viral kinetics. At baseline, lower diversity was seen in NS5A and in the amino and carboxyl termini of patients with an ER, compared with those with an SR. Rapid evolution of the NS5A genetic region occurred in patients with an ER (P = .01) but not in those with an SR (P = .73). The evolution was the result of an increase in the number of amino acid substitutions in the carboxyl region (P = .02) in patients with an ER. CONCLUSIONS Selective pressure appears to result in more-marked changes in individuals with an ER than in those with an SR. The carboxyl terminus was subject to the most change and may be an important determinant of phenotypic resistance to interferon-based therapy.
Evaluation of Provider Profiling in Public Sector Substance Abuse Treatment

Few evaluations of provider profiles and performance measurement in publicly funded substance abuse treatment exist. This study examined a 7-year period in which the Connecticut Department of Mental Health and Addiction Services alternately implemented, suspended, and reintroduced profiling of treatment agencies. The profiles contained quarterly statistical reports indicating the agency's performance and peer comparison on percentages of clients connecting to lower levels of care and readmitted to higher levels of care. Neither measure changed during the first profiling period, but both improved during the second. Although adjustment for concurrent initiatives may be incomplete, profiling proved somewhat beneficial.
Clinical and Virologic Outcomes After Changes in First Antiretroviral Regimen at 7 Sites in the Caribbean, Central and South America Network

Background:HIV-infected persons in resource-limited settings may experience high rates of antiretroviral therapy (ART) change, particularly because of toxicity or other nonfailure reasons. Few reports address patient outcomes after these modifications. Methods:HIV-infected adults from the 7 Caribbean, Central and South America network clinical cohorts who modified >1 drug from the first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. We assessed cumulative incidence of, and factors associated with, death, virologic failure (VF), and regimen change after starting ART-2. Results:Five thousand five hundred sixty-five ART-naive highly active ART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 because of toxicity and 11% because of failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4%, and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio = 1.5 vs. failure, 95% confidence interval: 1.0 to 2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at the start of ART-2, and starting ART-2 because of failure (adjusted hazard ratio = 2.1 vs. toxicity, 95% confidence interval: 1.5 to 2.8). Conclusions:Among patients modifying the first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success.
The use of videophones to enhance palliative care outreach nursing in remote areas

Abstract This project explores the use of analogue videophones between rural palliative care nurses and their more remote general nursing colleagues caring for palliative care patients in surrounding communities. The videophones were easily transported and were most often used when the general nurses were visiting patients' homes where they plugged the videophones into the telephone line. This supplemented the specialist palliative care visits. The nurses completed questionnaires to document their experience. The major advantages cited by the palliative care nurses were that vision enhanced their communication with the patients and travelling time was saved, while the remote nurses believed that access to palliative care expertise was improved. The major disadvantages were the limitations of the equipment available and dropout during calls, while technophobic nursing staff and the high turnover of remote staff made it difficult to develop expertise in using these phones. Videophones are useful in extending the outreach of palliative care nurses.
Brief Report: Apparent Antiretroviral Overadherence by Pill Count is Associated With HIV Treatment Failure in Adolescents

Abstract:Pill counts with calculated adherence percentages are used in many settings to monitor adherence, but can be undermined by patients discarding pills to hide nonadherence. Pill counts suggesting that >100% of prescribed doses were taken can signal “pill dumping. ” We defined “overadherence” among a cohort of 300 HIV-infected adolescents as having greater than one-third of pill counts with >100% adherence during a year of follow-up. Apparent overadherence was more common in those with virologic failure than in those with suppressed viral loads (33% vs 13%, &khgr;2 P = 0.001). Pill count adherence repeatedly >100% may identify HIV-infected adolescents at increased risk of treatment failure.
The implementation of social, personal and health education in Irish schools

Purpose – Social, Personal and Health Education (SPHE) is mandated in all Irish schools. This study aims to illuminate the perceived value and quality of SPHE and to document facilitators of successful implementation.Design/methodology/approach – A case study approach was taken, where 713 pupils, 968 parents and 49 teachers and other staff across a stratified random sample of 12 schools completed questionnaires and participated in interviews and focus groups. Data were integrated at the school level and subsequently across schools.Findings – Stakeholders generally agreed on the worth of SPHE. However, its perceived value relative to other areas of the curriculum varied by school context. Facilitators for successful implementation included training for teachers, inclusion of SPHE in school planning and evaluation processes, and organisational support for SPHE via timetabling and resource management within schools.Research limitations/implications – Case studies were useful for investigating implementation .
Postexposure rabies prophylaxis completed in 1 week: preliminary study.

BACKGROUND Patients exposed to a rabid animal often travel long distances to receive postexposure prophylaxis (PEP), which requires 4 or 5 visits. Reducing the number of clinic visits would not only reduce costs for the patient but may also help increase compliance to receive complete PEP. We made an effort to develop PEP completed in 1 week. METHODS We administered the 4-site intradermal injections of 0.1 mL of purified Vero cell rabies vaccine to the deltoids and thighs on days 0, 3, and 7, with and without equine rabies immunoglobulin (40 IU/kg). A control group received the World Health Organization-approved and widely used Thai Red Cross regimen (2-site intradermal injections on days 0, 3, and 7 and 1 injection on days 28 and 90) with equine rabies immunoglobulin. We then determined rabies neutralizing antibody (NAb) up to day 360. RESULTS Geometric mean titers for subjects receiving the 4-site intradermal regimen, with or without equine rabies immunoglobulin, had significantly higher NAb values than did the control group on day 14 and 28 (P<.001). All subjects in all groups had a NAb value > or =0.5 IU/mL on days 14 and 28. The percentages of subjects who had a NAb value > or =0.5 IU/mL from days 0 through 360 were not significantly different among the 3 groups. CONCLUSIONS After any PEP regimen, World Health Organization recommendations require a NAb value > or =0.5 IU/mL on days 14 and 28. The 1-week PEP regimen, therefore, appears promising. It increased immunogenicity over the 2-site intradermal schedule, and it is convenient and can be used in small clinics, because it consumes almost the entire supplied vaccine ampoule volume.
Progressive Patient Care

to expect the reader to believe that every case was either hypochromic or hyperchromic anaemia and that in this practice no case of normochromic anaemia was ever discovered. We are told on page 1733 that "Of 222 cases, 205 (92%) were of iron-deficiency anaemia," yet, if we analyse Table III, 166 are listed as " no obvious cause " and might possibly have been due to simple iron deficiency, while 39 other cases from this 205 showed very obvious reasons for their anaemia other than " iron deficiency," varying from peptic ulcer to neoplasm and chronic nephritis. One must wonder how the replacement of iron in the diet even in heroic quantities would affect their so-called " iron deficiency. " In the management of these cases we have little to quarrel with Dr. Fry about, except perhaps to stress the importance of urine examination for blood chemically and by microscope in children and women, a point not made under "Diagnosis," and to suggest that while access to radiology is available in Crawley we feel that enthusiasm for the radiography of the digestive tract might as easily lead to anaemia as give indications for its cure. Is it not wiser in these days of increasing recognition of the radiation danger to be wary of the routine barium meal and barium enema ? Perhaps it should also be emphasized that there are patients-particularly the elderly living alone and the faddy youngster-when the addition of vitamin C to the therapy helps to improve the hypochromic anaemia. Since the article is aimed at general practitioners throughout the country may we also make the point that the increasing number of coloured people with whom we have to deal-we now have ten such families-means that we must bear in mind the rarer anaemias from the tropics such as hookworm and sickle anaemia. -We are, etc., IVAN CLouT. AuDREY HARDWICK. H. KIRK WATSON.
Brief Report: Recovery of Bone Mineral Density After Discontinuation of Tenofovir-Based HIV Pre-exposure Prophylaxis

Background: Oral tenofovir disoproxil fumarate (TDF) for HIV prevention and treatment is associated with decreases in bone mineral density (BMD). Previous reports suggest that these changes may be reversible after discontinuation of TDF. Setting: A metabolic substudy of 498 participants in a randomized, placebo-controlled HIV prevention trial of oral coformulated TDF with emtricitabine (TDF/FTC, Truvada) for HIV pre-exposure prophylaxis (PrEP) enrolling a global sample of men who have sex with men and trans women. Methods: Participants underwent dual X-ray absorptiometry to quantify bone mineral density (BMD) in the hip and spine during PrEP and at 2 visits after stopping (median of 23 and 79 weeks post-PrEP, respectively). Results are stratified by pharmacologic measure of TDF/FTC adherence. Results: There was no significant difference in change in hip/spine BMD at any time point between placebo and those with low adherence. Adherent participants had a mean (standard error) BMD change at TDF/FTC discontinuation of −1.02% (0.24) in the hip and −1.84% (0.36) in the spine. After stop, annualized BMD increases of 1.13% per year (0.27) in hip and 1.81% per year (0.36) in spine BMD were observed in adherent participants compared with 0.19% (0.16) and 0.74% (0.21) in the placebo group, respectively (P = 0.003, both comparisons). On average, BMD returned to baseline levels by 1 year after PrEP stop. Recovery was consistent across age, baseline BMD z-score, and treatment duration. Conclusions: Mean BMD returns to baseline levels within 12–18 months after TDF-based PrEP discontinuation in both hip and spine with consistency across participant subgroups. Clinical Trials Registration: clinicaltrials.gov NCT00458393.
Investigation of DNA damage in cells exposed to poly (lactic-co-glycolic acid) microspheres.

Poly (lactic-co-glycolic acid) (PLGA)-based materials are widely investigated for drug delivery and tissue engineering applications. Despite their popularity the genotoxic potential of PLGA has not been investigated. In this study, the comet assay, a sensitive assay for DNA damage, was used to evaluate potential genotoxicity in model cell types exposed to PLGA microspheres. Human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) cells were exposed to PLGA microspheres (0.4-6 mg/mL) and DNA damage assessed at 24 h, 4 days, and 7 days. DNA damage was not identified after 24 h. However, after 4 and 7 days of exposure to 2 and 6 mg/mL of PLGA microspheres a significant elevation of DNA damage in both cell types was observed. The PLGA microspheres did not exhibit any cytotoxic effects on the cells under the conditions tested. Our results suggest that PLGA may have a genotoxic effect on cells. A broader investigation of the PLGA genotoxic profile in biological systems is needed. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 284-291, 2017.
Cryotherapy Reduces Progression of Cervical Intraepithelial Neoplasia Grade 1 in South African HIV-Infected Women: A Randomized, Controlled Trial

Background: HIV-infected women are at an increased risk of cervical cancer, especially in resource-limited countries. Cervical cancer prevention strategies focus treating cervical high-grade squamous intraepithelial lesions (HSIL). The management of low-grade squamous intraepithelial lesions (LSIL) in HIV-infected women is unknown. Setting: HIV treatment clinic in Johannesburg, South Africa. Methods: We randomized HIV-infected women with histologic cervical LSIL to cervical cryotherapy vs. no treatment (standard of care). Cervical high-risk human papillomavirus testing (hrHPV) was performed at baseline. All women underwent cervical cytology and colposcopic biopsies 12 months after enrollment. The primary end point was HSIL on histology at month 12. Chi-square was used to compare arms. Results: Overall, 220 HIV-infected women were randomized to cryotherapy (n = 112) or no treatment (n = 108). Median age was 38 years, 94% were receiving antiretroviral therapy; median CD4 was 499 cells per cubic millimeter, and 59% were hrHPV positive. Cryotherapy reduced progression to HSIL: 2/99 (2%) in the cryotherapy arm and 15/103 (15%) in the no treatment arm developed HSIL, 86% reduction (95% confidence interval: 41% to 97%; P = 0.002). Among 17 HSIL end points, 16 were hrHPV+ at baseline. When restricting the analysis to hrHPV+ women, HSIL occurred in 2/61 (3%) in the cryotherapy arm vs. 14/54 (26%) in the no treatment arm, 87% reduction (95% confidence interval: 47% to 97%; P = 0.0004). Participants in the cryotherapy arm experienced greater regression to normal histology and improved cytologic outcomes. Conclusions: Treatment of cervical LSIL with cryotherapy decreased progression to HSIL among HIV-infected women especially if hrHPV positive. These results support treatment of LSIL in human papillomavirus test-and-treat approaches for cervical cancer prevention in resource-constrained settings.
Identification of a Mycoplasma ovis-like organism in a herd of farmed white-tailed deer (Odocoileus virginianus) in rural Indiana.

Mycoplasma ovis is a hemoplasma parasite of sheep, goats, and reindeer; however, natural hemoplasma infection in white-tailed deer has not previously been reported. Subsequent to finding many coccoid, bacillary, and ring-shaped organisms, consistent with hemotropic mycoplasmas, on RBCs from a 72-day-old female white-tailed fawn, we sought to (1) identify the putative hemoplasma observed in blood from the fawn, (2) evaluate others in the herd for hemoplasma infection, and (3) identify clinicopathologic characteristics of hemoplasma-infected white-tailed deer. EDTA-anticoagulated whole blood was collected from the fawn and 8 apparently healthy does in the same herd. CBCs were performed on 7 nonclotted samples from the fawn and 6 does. DNA was extracted from all samples, followed by PCR amplification of bacterial (16S rDNA) and protozoal (18S rDNA) genes. The nearly complete 16S rDNA product from the fawn's sample was directly sequenced and compared with known sequences in the GenBank database. Samples from the fawn and 7 of 8 does were PCR-positive using hemoplasma-specific and M ovis-specific protocols. The fawn was PCR-negative for Anaplasma spp. , Babesia spp. , and Theileria spp. The 16S rDNA sequence from the fawn (GenBank accession number, FJ824847) was most closely related to M ovis (AF338268), having 98.5% sequence identity. The fawn had a mild nonregenerative anemia, a neutrophilic left-shift with toxic change, aspiration bronchopneumonia, and gastrointestinal disease. Hematologic values, including blood film evaluation, in infected does were unremarkable. The M ovis-like organism may have acted as either an opportunistic or primary pathogen in the fawn. The high occurrence of subclinical infections in the does suggests that white-tailed deer may act as wildlife reservoirs for M ovis.