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Europe sees constant increase in gonorrhea infections

Europe sees constant increase in gonorrhea infections

Surprisingly, for the first time since ECDC started collecting this data (2010), the number of cases among women was higher than the number of cases among heterosexual men. Since 2008, the overall rate of reported gonorrhea infections has more than doubled across Europe, going up from 8 per 100,000 population to 20 cases per 100,000 persons in 2014. In total, 66 413 gonorrhea cases were reported in 27 countries of the European Union and European Economic Area (EU/EEA) in 2014—which constitutes an increase of 25% compared with 2013. The highest rates were observed in the United Kingdom (60 per 100,000), Ireland (28), Denmark (20) and Latvia (18). The majority of gonorrhea infections were diagnosed among young adults aged 15-24 years who accounted for 38% of cases; followed by the 25-34-year-olds (34%). Looking at ways of transmission, almost half (44%) of the reported gonorrhea diagnoses in the EU/EEA in 2014 were reported to be among men who have sex with men (MSM). This is only slightly lower than the proportion of male and female heterosexuals combined (49%). Rise in gonorrhea cases among women In 2014, for the first time since ECDC started collecting this data (2010), the number of cases among women was higher than the number of cases among heterosexual men. Given the risk of reproductive tract complications, e.g. pelvic inflammatory disease or, if untreated, infertility, as well as possible transmission from mother to child, this trend among women is of particular concern. A threat for treatment success: drug-resistant gonococci The European treatment guidelines for gonorrhea recommend use of two antimicrobials (ceftriaxone or cefixime together with azithromycin). The latest...
Probiotics could be the answer to preventing C. Difficile in hospitals

Probiotics could be the answer to preventing C. Difficile in hospitals

How soon should they be administered and which probiotics were the most effective in preventing C. Difficile in hospitals? Dr. Shen and her colleagues conducted a literature search and identified 19 studies published from 1989 to 2016 (including PLACIDE) that involved 6942 hospitalized adults taking antibiotics and receiving either a probiotic or placebo as prevention for C difficile infection. There was a significant difference in the incidence of infection between the probiotic and placebo groups (incidence, 1.5% vs 3.5%). The pooled results show “robust efficacy” for probiotics in the prevention of C difficile infection (risk ratio, 0.41; 95% confidence interval, 0.30 – 0.57; P < .001). The greatest probiotic efficacy was seen in studies with the highest incidence of infection. So, which probiotics were the most effective, you might be wondering? Among the nine different probiotics used in the studies, several appeared to perform better than others in preventing C. diff, but the differences were not significant enough to recommend using one over the others. Significantly, probiotics given within 2 days of the antibiotic were found to be more effective than those given later. The available evidence strongly suggests the use of probiotics significantly reduces the risk of CDI in hospitalized patients taking antibiotics and that further studies are not needed to establish efficacy. Read more specifics about the study here....

Methylene bisphosphonates as the inhibitors of HIV RT phosphorolytic activity.

Biochimie 2016 5 24() pii 10.1016/j.biochi.2016.05.012 Abstract The structure-function analysis of 36 methylenebisphosphonates (BPs) as inhibitors of the phosphorolytic activity of native and drug-resistant forms of HIV-1 reverse transcriptase (RT) was performed. It was shown that with the increase of the inhibitory potential of BPs towards the phosphorolytic activity raises their ability to inhibit the RT-catalyzed DNA elongation. Herein, we report the impact of the thymidine analog mutations (TAM) on the activity of bisphosphonates, as well as some structural features of the BPs, allowing them to maintain the inhibitory activity on the enzyme resistant to nucleoside analog therapy. We estimated the Mg(2+)-coordinating group structure, the linker and the aromatic pharmacophore influence on the inhibitory potential of the BPs. Based on the 31 BPs SAR, several BPs with improved inhibitory properties were designed and...

Osteocytic signalling pathways as therapeutic targets for bone fragility.

Nature reviews. Endocrinology 2016 5 27() doi 10.1038/nrendo.2016.71 Abstract Osteocytes are differentiated osteoblasts that become surrounded by matrix during the process of bone formation. Acquisition of the osteocyte phenotype is achieved by profound changes in gene expression that facilitate adaptation to the changing cellular environment and constitute the molecular signature of osteocytes. During osteocytogenesis, the expression of genes that are characteristic of the osteoblast are altered and the expression of genes and/or proteins that impart dendritic cellular morphology, regulate matrix mineralization and control the function of cells at the bone surface are ordely modulated. The discovery of mutations in human osteocytic genes has contributed, in a large part, to our understanding of the role of osteocytes in bone homeostasis. Osteocytes are targets of the mechanical force imposed on the skeleton and have a critical role in integrating mechanosensory pathways with the action of hormones, which thereby leads to the orchestrated response of bone to environmental cues. Current, therapeutic approaches harness this accumulating knowledge by targeting osteocytic signalling pathways and messengers to improve skeletal...

Retrospective hepatitis C seroprevalence screening in the antenatal setting-should we be screening antenatal women?

BMJ open 2016 05 266(5) e010661 doi 10.1136/bmjopen-2015-010661 Abstract OBJECTIVES An unlinked anonymous seroprevalence study was conducted to estimate the prevalence of hepatitis C virus (HCV) infection in samples derived from antenatal clinic attendees at 2 East London Hospitals. An unexpectedly high HCV seroprevalence of 2.6% (1.2% viraemic) had been revealed during an unlinked study of the emergency department at 1 of these hospitals. DESIGN 1000 stored residual samples were tested for HCV antibody (anti-HCV) and reactive samples were further tested for HCV RNA. The study was reviewed by the East Midland NRES ethics committee project ID 181154, approval number 15/WS/0125. RESULTS The anti-HCV reactivity rate was 0.5% (5/1000) with 0.1% (1/1000) confirmed viraemic. Prevalence for the other blood-borne viruses was higher: 1% (10/1000) were hepatitis B surface antigen positive and 0.3% were HIV antigen/antibody positive (3/1000). There were no co-infections. CONCLUSIONS More data to establish the prevalence of HCV in the antenatal population is needed. The addition of anti-HCV testing to the well-established antenatal screening programme provides a unique opportunity to impact on the health of pregnant women, their children, partners and future pregnancies in this new era of treatment for hepatitis...

Glycosylphosphatidylinositol-anchor deficiency attenuates the production of infectious HIV-1 and renders virions sensitive to complement attack.

AIDS research and human retroviruses 2016 5 26() Abstract HIV-1 escapes complement-mediated lysis (CML) by incorporating host regulators of complement activation (RCA) into its envelope. CD59, a key member of RCA, is incorporated into HIV-1 virions at levels that protect against CML. Since CD59 is a glycosylphosphatidylinositol-anchored protein (GPI-AP), we used GPI-anchor deficient Jurkat cells (Jurkat-7) that express intracellular CD59, but not surface CD59, to study the molecular mechanisms underlying CD59 incorporation into HIV-1 virions and the role of host proteins in virus replication. Compared to Jurkat cells, Jurkat-7 cells were less supportive to HIV-1 replication and more sensitive to CML. Jurkat-7 cells exhibited similar capacities of HIV-1 binding and entry to Jurkat cells, but were less supportive to viral RNA and DNA biosynthesis, as infected Jurkat-7 cells produced reduced amounts of HIV-1 RNA and DNA. HIV-1 virions produced from Jurkat-7 cells were CD59-negative, suggesting that viral particles acquire CD59, and probably other host proteins, from the cell membrane rather than intracellular compartments. As a result, CD59-negative virions were sensitive to CML. Strikingly, these virions exhibited reduced activity of virus binding and were less infectious, implicating that GPI-APs may be also important in ensuring the integrity of HIV-1 particles. Transient expression of the PIG-A gene restored CD59 expression on the surface of Jurkat-7 cells. After HIV-1 infection, the restored CD59 was colocalized with viral envelope glycoprotein gp120/gp41 within lipid rafts, which is identical to that on infected Jurkat cells. Thus, HIV-1 virions acquire RCA from the cell surface, likely lipid rafts, to escape CML and to ensure viral...

Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya.

Journal of the International AIDS Society 2016 05 2519(1) 20798 doi 10.7448/IAS.19.1.20798 Abstract INTRODUCTION Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya. METHODS We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients’ characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher’s exact tests. RESULTS Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations. CONCLUSIONS In this Kenyan cohort, tenofovir-based first-line ART resulted in...

Clinical Evaluation of Fully Automated Elecsys(®) Syphilis Assay for the Detection of Antibodies of Treponema pallidum.

Journal of clinical laboratory analysis 2016 5 26() doi 10.1002/jcla.21998 Abstract OBJECTIVE The resurgence of syphilis in recent years has become a serious threat to the public health worldwide, and the serological detection of specific antibodies against Treponema pallidum (TP) remains the most reliable method for laboratory diagnosis of syphilis. The performance of the Elecsys(®) Syphilis assay, a brand new electrochemiluminescene immunoassay (ECLIA), was assessed by large amounts of samples in this study. METHODS In comparison with InTec assay, the Elecsys(®) Syphilis assay was evaluated in 146 preselected samples from patients with syphilis, 1803 clinical routine samples, and 175 preselected samples from specific populations with reportedly increased rates of false-positive syphilis test results. Discrepancy samples must be investigated by Mikrogen Syphilis recomline assay. RESULTS There was an overall agreement of 99.58% between two assays (Kappa = 0.975). The sensitivity and specificity of the Elecsys(®) Syphilis assay were 100.0% (95% CI, 96.8-100.0%) and 99.8% (95% CI, 99.5-100.0%), respectively. The Elecsys syphilis assay displays better sensitivity (100%), specificity (99.8%), PPV (98.7%), and NPV (100%) in 2124 samples enrolled, compared with the InTec assay. CONCLUSION Considering the excellent ease of use and automation, high throughput, and its superior sensitivity, especially in primary syphilis, the Elecsys(®) Syphilis assay could represent an outstanding choice for screening of syphilis in high-volume laboratories. However, more attention was still needed, or the results must be confirmed by other treponemal immunoassays. The new Elecsys(®) Syphilis assay is applied to patients with malignant neoplasm or HIV...

Classical Kaposi sarcoma: case reports with unusual presentation on the penis and scrotum.

International journal of dermatology 2016 5 27() doi 10.1111/ijd.13319 Abstract BACKGROUND Kaposi sarcoma (KS) is the most common vascular neoplasm. Any skin area could be involved, including the genitalia. Traditionally, classic KS lesions have a general distribution, often involving skin of the feet and legs, and to a lesser extent, that of the hands, arms, and trunk. KS limited to the external genitalia is extremely rare in HIV seronegative individuals. METHODS We report six patients of classic KS with generalized dermal KS lesions. RESULTS Two of them presenting with unusual KS lesions on the penis and scrotum beside the other dermal lesions. Patients were HIV negative and human herpes virus eight positive. Histological examination showed classical KS. CONCLUSIONS Primary KS of the penis and scrotum is rare but could occur in HIV-negative...

Usefulness of an HIV DNA resistance genotypic test in patients who are candidates for a switch to the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination.

The Journal of antimicrobial chemotherapy 2016 5 26() pii Abstract OBJECTIVES In the context of a rilpivirine/emtricitabine/tenofovir disoproxil fumarate switch in HIV-1-infected patients with at least 1 year of virological success, we determined whether proviral DNA is an alternative to plasma HIV RNA for resistance genotyping. METHODS Resistance-associated mutations (RAMs) in DNA after at least 1 year of virological success [viral load (VL) 50 copies/mL). Kappa’s coefficient was used to measure agreement between the DNA and RNA genotypes. RESULTS In patients without VF (n = 130) and with VF (n = 114), RNA and DNA showed resistance to at least one drug of the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination in 8% and 9% and in 60% and 45%, respectively. For rilpivirine RAMs, correlation between RNA and DNA was higher in patients without VF than in patients with VF (kappa = 0.60 versus 0.19, P = 0.026). Overall, the prevalence of RAMs was lower in DNA than in RNA. CONCLUSIONS Incomplete information provided by the DNA genotypic test is more notable in patients with VF, suggesting that all resistance mutations associated with prior VF have not been archived in the proviral DNA or decreased to a level below the threshold of detection. In the case where no historical plasma genotypic test is available, DNA testing might be useful to rule out switching to rilpivirine/emtricitabine/tenofovir disoproxil...

Complete Genome Sequence of a Reference Stock of Simian Immunodeficiency Virus RNA (SIVmac251/32H/L28) Determined by Deep Sequencing.

Genome announcements 2016 05 264(3) doi 10.1128/genomeA.00344-16 Abstract A reference preparation for simian immunodeficiency virus (SIV) RNA nucleic acid assays was characterized by complete genome deep sequencing. The entire coding sequence and flanking long terminal repeats, including minority species, were determined. This information will inform SIV research investigations and aid evaluation and development of amplification assays for SIV RNA...

Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway.

Viruses 2016 05 248(6) doi 10.3390/v8060152 Abstract The mammalian target of rapamycin (mTOR) is a central regulator of gene expression, translation and various metabolic processes. Multiple extracellular (growth factors) and intracellular (energy status) molecular signals as well as a variety of stressors are integrated into the mTOR pathway. Viral infection is a significant stress that can activate, reduce or even suppress the mTOR signaling pathway. Consequently, viruses have evolved a plethora of different mechanisms to attack and co-opt the mTOR pathway in order to make the host cell a hospitable environment for replication. A more comprehensive knowledge of different viral interactions may provide fruitful targets for new antiviral...

Tuberculosis, before and after Antiretroviral Therapy among HIV-Infected Children in Nigeria: What Are the Risk Factors?

PloS one 2016 5 2711(5) e0156177 doi 10.1371/journal.pone.0156177 Abstract INTRODUCTION In Nigeria, there is a dearth of pediatric data on the risk factors associated with tuberculosis (TB), before and after antiretroviral therapy (ART). METHODOLOGY A retrospective observational cohort study, between October 2010 and December 2013, at the Federal Medical Centre, Makurdi, Nigeria. TB was noted among children less than 15 years of age at ART enrolment (prevalent TB-PrevTB), within 6 months (early incident tuberculosis-EITB) and after 6 months (late incident tuberculosis-LITB) of a 12-month follow-up on ART. Potential risk factors for PrevTB and incident TB were assessed using the multivariate logistic and Cox regression models respectively. RESULTS Among 368 HIV-1 infected children, PrevTB was diagnosed in 73 children (19.8%). Twenty-eight EITB cases were diagnosed among 278 children over 132 person-years (py) with an EITB rate of 21.2/100 py. Twelve LITB cases were seen among 224 children over 221.9 py with a LITB rate of 5.4/100 py. A significant reduction in the incidence rates of TB was found over time (75%, p˂ 0.001). Young age of children (12-35 months, aOR; 24, 95% CI; 4.1-146.6, p ˂ 0.001; 36-59 months, aOR;21, 95%CI;4.0-114.3, p ˂ 0.001); history of TB in children (aOR; 29, 95% CI; 7.3-119.4, P˂ 0.001); severe immunosuppression (aOR;38, 95% CI;12-123.2,p ˂ 0.001); oropharyngeal candidiasis (aOR;3.3, 95% CI; 1.4-8.0, p = 0.009) and sepsis (aOR; 3.2, 95% CI;1.0-9.6, p = 0.043) increased the risk of PrevTB. Urban residency was protective against EITB (aHR; 0.1, 95% CI; 0.0-0.4, p = 0.001). Virological failure (aHR; 4.7, 95% CI; 1.3-16.5, p ˂ 0.001) and sepsis (aHR; 26, 95% CI; 5.3-131.9, p ˂ 0.001)...

Population-Based Assessment of Hypertension Epidemiology and Risk Factors among HIV-Positive and General Populations in Rural Uganda.

PloS one 2016 5 2711(5) e0156309 doi 10.1371/journal.pone.0156309 Abstract BACKGROUND Antiretroviral therapy scale-up in Sub-Saharan Africa has created a growing, aging HIV-positive population at risk for non-communicable diseases such as hypertension. However, the prevalence and risk factors for hypertension in this population remain incompletely understood. METHODS We measured blood pressure and collected demographic data on over 65,000 adults attending multi-disease community health campaigns in 20 rural Ugandan communities (SEARCH Study: NCT01864603). Our objectives were to determine (i) whether HIV is an independent risk factor for hypertension, and (ii) awareness and control of hypertension in HIV-positive adults and the overall population. RESULTS Hypertension prevalence was 14% overall, and 11% among HIV-positive individuals. 79% of patients were previously undiagnosed, 85% were not taking medication, and 50% of patients on medication had uncontrolled blood pressure. Multivariate predictors of hypertension included older age, male gender, higher BMI, lack of education, alcohol use, and residence in Eastern Uganda. HIV-negative status was independently associated with higher odds of hypertension (OR 1.2, 95% CI: 1.1-1.4). Viral suppression of HIV did not significantly predict hypertension among HIV-positives. SIGNIFICANCE The burden of hypertension is substantial and inadequately controlled, both in HIV-positive persons and overall. Universal HIV screening programs could provide counseling, testing, and treatment for hypertension in Sub-Saharan...

Acute lymphoblastic leukemia in a patient with MonoMAC syndrome/GATA2 haploinsufficiency.

Pediatric blood & cancer 2016 5 27() doi 10.1002/pbc.26084 Abstract Patients with GATA2 haploinsufficiency have a significant predisposition to developing cytopenias, unique infectious manifestations, and myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). We report a unique case of a patient who presented with B-cell acute lymphoblastic leukemia (B-ALL) and was subsequently diagnosed with monocytopenia and mycobacterium avium complex (MonoMAC) syndrome/GATA2 haploinsufficiency. The development of MDS/AML in patients with GATA2 haploinsufficiency is well described, however, the development of ALL has not been reported in the literature. ALL may be associated with GATA2 haploinsufficiency. Clinicians should be attuned to the features of the MonoMAC syndrome in patients with ALL that would prompt additional testing and alter...

‘Coming Out’ of Prison: An Exploratory Study of LGBT Elders in the Criminal Justice System.

Journal of homosexuality 2016 5 27() Abstract This two-phase qualitative study explores the experiences of ten formerly incarcerated LGBT elders’ experiences prior to, during, and after release from prison. A core theme of self and the social mirror emerged from the data that represented LGBT elders ongoing coming out process of unearthing their ‘true selves’ despite managing multiple stigmatized identities or social locations, such as being LGBT, elderly, HIV positive, formerly incarcerated, and a racial/ethnic minority. These findings further our awareness of an overlooked population of LGBT who are older and involved in the criminal justice system. Recommendations that incorporate suggestions from formerly incarcerated LGBT elders for services and policy reform are...

Shortening the HIV-1 TAR RNA Bulge by a Single Nucleotide Preserves Motional Modes Over a Broad Range of Timescales.

Biochemistry 2016 5 27() Abstract Helix-junction-helix (HJH) motifs are flexible building blocks of RNA architecture that help define the orientation and dynamics of helical domains. They are also frequently involved in adaptive recognition of proteins and small molecules, and in the formation of tertiary contacts. Here, we use a battery of nuclear magnetic resonance (NMR) techniques to examine how deleting a single bulge residue (C24) from the human immunodeficiency virus type 1 (HIV-1) transactivation response element (TAR) tri-nucleotide bulge (U23-C24-U25) affects dynamics over a broad range of timescales. Shortening the bulge has a similar effect on picosecond-to-nanosecond inter-helical and local bulge dynamics, as increasing the Mg(2+) and Na(+) concentration; whereby a pre-existing two-state equilibrium in TAR is shifted away from a bent flexible conformation towards a coaxial conformation, in which all three bulge residues are flipped out and flexible. Surprisingly, the point deletion minimally affects microsecond-to-millisecond conformational exchange directed toward two low-populated and short-lived excited conformational states that form through reshuffling of bases pairs throughout TAR. The mutant does, however, adopt a slightly different excited conformational state on the millisecond timescale, in which U23 is intra-helical, mimicking the expected conformation of residue C24 in the excited conformational state of wild-type TAR. Thus, minor changes in HJH topology preserve motional modes in RNA occurring over the picosecond-to-millisecond timescales, but alter the relative populations of the sampled states or cause subtle changes in their conformational...

Simtuzumab treatment of advanced liver fibrosis in HIV and HCV-infected adults: Results of a 6-month open-label safety trial.

Liver international : official journal of the International Association for the Study of the Liver 2016 5 27() doi 10.1111/liv.13177 Abstract BACKGROUND Chronic liver injury can result in fibrosis that may progress over years to end-stage liver disease. The most effective anti-fibrotic therapy is treatment of the underlying disease, however when not possible, interventions to reverse or slow fibrosis progression are needed. AIM To study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 (LOXL2) enzyme, in subjects with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or HCV-HIV co-infection and advanced liver disease. METHODS Eighteen subjects with advanced liver fibrosis received simtuzumab 700mg intravenously every 2 weeks for 22 weeks. Transjugular liver biopsies were performed during screening and at the end of treatment to measure hepatic venous pressure gradient (HVPG) and to stage fibrosis. RESULTS Treatment was well-tolerated with no discontinuations due to adverse events. No significant changes were seen in HVPG or liver biopsy fibrosis score after treatment. Exploratory transcriptional and protein profiling using paired pre- and post-treatment liver biopsy and serum samples suggested up-regulation of TGF-β3 and IL-10 pathways with treatment. CONCLUSION In this open-label, pilot clinical trial, simtuzumab treatment was well-tolerated in HCV- and HIV-infected subjects with advanced liver disease. Putative modulation of TGF-β3 and IL-10 pathways during simtuzumab treatment merits investigation in future trials. This article is protected by copyright. All rights...
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