Dynamics of genotype-specific HPV clearance and reinfection in rural Ghana may compromise HPV screening approaches

Persistent Human Papillomavirus (HPV) infection is a prerequisite for cervical cancer development. Few studies investigated clearance of high-risk HPV in low-and-middle-income countries. Our study investigated HPV clearance and persistence over four years in women from North Tongu District, Ghana. In 2010/2011, cervical swabs of 500 patients were collected and HPV genotyped (nested multiplex PCR) in Accra, Ghana. In 2014, 104 women who previously tested positive for high-risk HPV and remained untreated were re-tested for HPV. Cytobrush samples were genotyped (GP5+/6+ PCR & Luminex-MPG readout) in Berlin, Germany. Positively tested patients underwent colposcopy and treatment if indicated. Of 104 women, who tested high-risk HPV+ in 2010/2011, seven (6,7%; 95%CI: 2.7-13.4%) had ≥1 persistent high-risk-infection after ~4 years (mean age 39 years). Ninety-seven (93,3%; 95%CI: 86.6-97.3%) had cleared the original infection, while 22 (21.2%; 95%CI: 13.8-30.3%) had acquired new high-risk infections with other genotypes. Persistent types found were HPV 16, 18, 35, 39, 51, 52, 58, and 68. Among those patients, one case of CIN2 (HPV 68) and one micro-invasive cervical cancer (HPV 16) were detected. This longitudinal observational data suggest that single HPV screening rounds may lead to over-referral. Including type-specific HPV re-testing or additional triage methods could help reduce follow-up rates

Predictors of fetal anemia and cord blood malaria parasitemia among newborns of HIV-positive mothers

Background: Malaria and HIV infections during pregnancy can individually or jointly unleash or confound pregnancy outcomes. Two of the probable outcomes are fetal anemia and cord blood malaria parasitemia. We determined clinical and demographic factors associated with fetal anemia and cord blood malaria parasitemia in newborns of HIV-positive women from two districts in Ghana. Results: We enrolled 1,154 antenatal attendees (443 HIV-positive and 711 HIV-negative) of which 66% were prospectively followed up at delivery. Maternal malaria parasitemia, and anemia rates among HIV+ participants at enrolment were 20.3% and 78.7% respectively, and 12.8% and 51.6% among HIV- participants. Multivariate linear and logistic regression models were used to study associations. Prevalence of fetal anemia (cord hemoglobin level < 12.5 g/dL) and cord parasitemia (presence of P. falciparum in cord blood at delivery) were 57.3% and 24.4% respectively. Factors found to be associated with fetal anemia were maternal malaria parasitemia and maternal anemia. Infant cord hemoglobin status at delivery was positively and significantly associated with maternal hemoglobin and gestational age whilst female gender of infant was negatively associated with cord hemoglobin status. Maternal malaria parasitemia status at recruitment and female gender of infant were positively associated with infant cord malaria parasitemia status. Conclusions: Our data show that newborns of women infected with HIV and/or malaria are at increased risk of anemia and also cord blood malaria parasitemia. Prevention of malaria infection during pregnancy may reduce the incidence of both adverse perinatal outcomes. © 2013 Laar et al.; licensee BioMed Central Ltd

Pharmacist services for non-hospitalised patients

We are very grateful to the Chief Scientist Office, Scottish Government, for funding this review (CZH/4/1041). The authors wish to thank the members of Cochrane Effective Practice and Organisation of Care (EPOC) Group who supported this review, particularly Ms Tamara Rader and Mr Paul Miller for conducting the searches, and Ms Julia Worswick for her continued and good‐natured assistance throughout the update. We are very grateful to Dr Imran Omar for providing additional technical support. We thank Ms Caroline Burnett, Ms Andrea Fraser, Mrs Bev Smith and Ms Lynn McKenzie for their administrative and clerical support of this review. We thank the referees whose comments improved the reporting and interpretation of this review. These include: External referees: Yoon K Loke; Newton Opiyo; Internal editor: Carmel Hughes; Statistical editor: Sofia Massa; Contact editor: Gillian Leng; Managing editor: Daniela Gonçalves‐Bradley We also thank National Institute for Health Research, via Cochrane Infrastructure funding to the EPOC Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.Peer reviewedPublisher PD

Elevated rates of horizontal gene transfer in the industrialized human microbiome

Industrialization has impacted the human gut ecosystem, resulting in altered microbiome composition and diversity. Whether bacterial genomes may also adapt to the industrialization of their host populations remains largely unexplored. Here, we investigate the extent to which the rates and targets of horizontal gene transfer (HGT) vary across thousands of bacterial strains from 15 human populations spanning a range of industrialization. We show that HGTs have accumulated in the microbiome over recent host generations and that HGT occurs at high frequency within individuals. Comparison across human populations reveals that industrialized lifestyles are associated with higher HGT rates and that the functions of HGTs are related to the level of host industrialization. Our results suggest that gut bacteria continuously acquire new functionality based on host lifestyle and that high rates of HGT may be a recent development in human history linked to industrialization.Peer reviewe

S-Glutathionylation at Cys328 and Cys542 Impairs STAT3 Phosphorylation.

STAT3 is a latent transcription factor that promotes cell survival and proliferation and is often constitutively active in cancers. Although many reports provide evidence that STAT3 is a direct target of oxidative stress, its redox regulation is poorly understood. Under oxidative conditions STAT3 activity can be modulated by S-glutathionylation, a reversible redox modification of cysteine residues. This suggests the possible cross-talk between phosphorylation and glutathionylation and points out that STAT3 is susceptible to redox regulation. Recently, we reported that decreasing the GSH content in different cell lines induces inhibition of STAT3 activity through the reversible oxidation of thiol groups. In the present work, we demonstrate that GSH/diamide treatment induces S-glutathionylation of STAT3 in the recombinant purified form. This effect was completely reversed by treatment with the reducing agent dithiothreitol, indicating that S-glutathionylation of STAT3 was related to formation of protein-mixed disulfides. Moreover, addition of the bulky negatively charged GSH moiety impairs JAK2-mediated STAT3 phosphorylation, very likely interfering with tyrosine accessibility and thus affecting protein structure and function. Mass mapping analysis identifies two glutathionylated cysteine residues, Cys328 and Cys542, within the DNA-binding domain and the linker domain, respectively. Site direct mutagenesis and in vitro kinase assay confirm the importance of both cysteine residues in the complex redox regulatory mechanism of STAT3. Cells expressing mutant were resistant in this regard. The data presented herein confirmed the occurrence of a redox-dependent regulation of STAT3, identified the more redox-sensitive cysteines within STAT3 structure, and may have important implications for development of new drugs

Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial

People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines' monitoring.Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines' monitoring versus usual care.Five UK private sector care homes.41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.Problems addressed and changes in medicines prescribed.Information was collected from participants' notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57-4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78-8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80-235.90] and 5.12 [1.45-18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15-17.22).The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines.ISRCTN 48133332

Modeling of negative Poisson’s ratio (auxetic) crystalline cellulose Iβ

Energy minimizations for unstretched and stretched cellulose models using an all-atom empirical force field (Molecular Mechanics) have been performed to investigate the mechanism for auxetic (negative Poisson’s ratio) response in crystalline cellulose Iβ from kraft cooked Norway spruce. An initial investigation to identify an appropriate force field led to a study of the structure and elastic constants from models employing the CVFF force field. Negative values of on-axis Poisson’s ratios nu31 and nu13 in the x1-x3 plane containing the chain direction (x3) were realized in energy minimizations employing a stress perpendicular to the hydrogen-bonded cellobiose sheets to simulate swelling in this direction due to the kraft cooking process. Energy minimizations of structural evolution due to stretching along the x3 chain direction of the ‘swollen’ (kraft cooked) model identified chain rotation about the chain axis combined with inextensible secondary bonds as the most likely mechanism for auxetic response