FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial.

The phase III RV144 HIV-1 vaccine trial estimated vaccine efficacy (VE) to be 31.2%. This trial demonstrated that the presence of HIV-1-specific IgG-binding Abs to envelope (Env) V1V2 inversely correlated with infection risk, while the presence of Env-specific plasma IgA Abs directly correlated with risk of HIV-1 infection.

MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infection with Borrelia burgdorferi.

MicroRNAs have been shown to be important regulators of inflammatory and immune responses and are implicated in several immune disorders including systemic lupus erythematosus and rheumatoid arthritis, but their role in Lyme borreliosis remains unknown. We performed a microarray screen for expression of miRNAs in joint tissue from three mouse strains infected with Borrelia burgdorferi. This screen identified upregulation of miR-146a, a key negative regulator of NF-κB signaling, in all three strains, suggesting it plays an important role in the in vivo response to B.

Detection of primary melanoma in individuals at extreme high risk: a prospective 5-year follow-up study.

Importance: The clinical phenotype and certain predisposing genetic mutations that confer increased melanoma risk are established; however, no consensus exists regarding optimal screening for such individuals. Early identification remains the most important intervention in reducing melanoma mortality.

Objective: To evaluate the impact of full-body examinations every 6 months supported by dermoscopy and total-body photography (TBP) on all patients and sequential digital dermoscopy imaging (SDDI), when indicated, on detecting primary melanoma in an extreme-risk population.

The powdery mildew resistance protein RPW8.2 is carried on VAMP721/722 vesicles to the extrahaustorial membrane of haustorial complexes.

Plants employ multiple cell-autonomous defense mechanisms to impede pathogenesis of microbial intruders. Previously we identified an exocytosis defense mechanism in Arabidopsis against pathogenic powdery mildew fungi. This pre-invasive defense mechanism depends on the formation of ternary protein complexes consisting of the plasma membrane-localized PEN1 syntaxin, the adaptor protein SNAP33 and closely sequence-related vesicle-resident VAMP721 or VAMP722 proteins.

Attitudes of people in the UK with HIV who Are Antiretroviral (ART) Naïve to starting ART at high CD4 counts for potential health benefit or to prevent HIV transmission.

Objective: To assess if a strategy of early ART to prevent HIV transmission is acceptable to ART naïve people with HIV with high CD4 counts.

Design: ASTRA is a UK multicentre, cross sectional study of 3258 HIV outpatients in 2011/12. A self-completed questionnaire collected sociodemographic, behavioral and health data, and attitudes to ART; CD4 count was recorded from clinical records.

Development of the measure of ovarian symptoms and treatment concerns: aiming for optimal measurement of patient-reported symptom benefit with chemotherapy for symptomatic ovarian cancer.

Objective: The aim of this study was to determine the optimal patient-reported outcome measure (PROM) for assessing symptom benefit in trials of palliative chemotherapy for women with symptomatic ovarian cancer.

Methods: Candidate PROMs were EORTC QLQ-C30 plus ovarian-specific QLQ-OV28, Functional Assessment of Cancer Therapy-Ovarian (FACT-O), FACT Ovarian Symptom Index (FOSI), and gynecologic cancer-specific Symptom Representation Questionnaire. Predefined optimality criteria were inclusion of all symptoms necessary for the specified purpose, recall period covering typical length of palliative chemotherapy, numerical item rating scales, and all necessary symptoms included in a single symptom index.

Symptom burden and outcomes of patients with platinum resistant/refractory recurrent ovarian cancer: a reality check: results of stage 1 of the gynecologic cancer intergroup symptom benefit study.

Background: The aim of chemotherapy in patients with platinum resistant ovarian cancer is palliation. Patients' experience of symptoms is not well documented, and the impact of treatment on symptoms has not been evaluated in clinical trials. We report symptom burden and treatment outcomes from stage 1 of the Gynecological Cancer Intergroup (GCIG) Symptom Benefit Study.

Analysis of HLA A*02 association with vaccine efficacy in the RV144 HIV-1 vaccine trial.

Unlabelled: The RV144 HIV-1 vaccine trial demonstrated partial efficacy of 31% against HIV-1 infection. Studies into possible correlates of protection found that antibodies specific to the V1 and V2 (V1/V2) region of envelope correlated inversely with infection risk and that viruses isolated from trial participants contained genetic signatures of vaccine-induced pressure in the V1/V2 region. We explored the hypothesis that the genetic signatures in V1 and V2 could be partly attributed to selection by vaccine-primed T cells.

Test-retest reliability of retinal oxygen saturation measurement.

Purpose: To determine intrasession and intersession repeatability of retinal vessel oxygen saturation from the Oxymap Retinal Oximeter using a whole image-based analysis technique and so determine optimal analysis parameters to reduce variability.

Methods: Ten fundus oximetry images were acquired through dilated pupils from 18 healthy participants (aged 22 to 38) using the Oxymap Retinal Oximeter T1. A further 10 images were obtained 1 to 2 weeks later from each individual.

HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities.

The RV144 ALVAC/AIDSVax HIV-1 vaccine clinical trial showed an estimated vaccine efficacy of 31.2%. Viral genetic analysis identified a vaccine-induced site of immune pressure in the HIV-1 envelope (Env) variable region 2 (V2) focused on residue 169, which is included in the epitope recognized by vaccinee-derived V2 monoclonal antibodies.

HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes.

Objective: Low HDL cholesterol (HDL-C) and small HDL particle size may directly promote hyperglycemia. We evaluated associations of HDL-C, apolipoprotein A-I (apoA-I), and HDL-C/apoA-I with insulin secretion, insulin resistance, HbA1c, and long-term glycemic deterioration, reflected by initiation of pharmacologic glucose control.

Research Design And Methods: The 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study followed 9,795 type 2 diabetic subjects.

HLA class I, KIR, and genome-wide SNP diversity in the RV144 Thai phase 3 HIV vaccine clinical trial.

RV144 is the first phase 3 HIV vaccine clinical trial to demonstrate efficacy. This study consisted of more than 8,000 individuals in each arm of the trial, representing the four major regions of Thailand. Human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptor (KIR) genes, as well as 96 genome-wide ancestry informative markers (AIMs) were genotyped in 450 placebo HIV-1-uninfected individuals to identify the immunogenetic diversity and population structure of this cohort.

Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination.

HIV-1-specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass profiles between different vaccine regimens used in clinical trials with divergent efficacy outcomes can provide information on the quality of the vaccine-induced B cell response.

Transcranial direct current stimulation over right dorsolateral prefrontal cortex enhances error awareness in older age.

The ability to detect errors during cognitive performance is compromised in older age and in a range of clinical populations. This study was designed to assess the effects of transcranial direct current stimulation (tDCS) on error awareness in healthy older human adults. tDCS was applied over DLPFC while subjects performed a computerized test of error awareness.

Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis.

During an infection, the body increases the output of mature immune cells in order to fight off the pathogen. Despite convincing evidence that hematopoietic stem and progenitor cells (HSPCs) can sense pathogens directly, how this contributes to hematopoietic cell output remains unknown. Here, we have combined mouse models with a single-cell proteomics platform to show that, in response to Toll-like receptor stimulation, short-term HSCs and multipotent progenitor cells produce copious amounts of diverse cytokines through nuclear factor κB (NF-κB) signaling.

Syphilis masquerading as focal segmental glomerulosclerosis.

A patient referred to the genitourinary clinic for positive syphilis serology was found to have symptoms and signs of nephrotic syndrome. A renal biopsy showed focal segmental glomerulosclerosis (FSGS). Doxycycline 200 mg twice daily for 28 days coincided with considerable decrease in proteinuria and rise in serum albumin, suggesting a causal relationship.

Pupil diameter covaries with BOLD activity in human locus coeruleus.

The locus coeruleus-noradrenergic (LC-NA) neuromodulatory system has been implicated in a broad array of cognitive processes, yet scope for investigating this system's function in humans is currently limited by an absence of reliable non-invasive measures of LC activity. Although pupil diameter has been employed as a proxy measure of LC activity in numerous studies, empirical evidence for a relationship between the two is lacking. In the present study, we sought to rigorously probe the relationship between pupil diameter and BOLD activity localized to the human LC.

Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.

Unlabelled: In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay.

Dominant frequency increase rate predicts transition from paroxysmal to long-term persistent atrial fibrillation.

Background: Little is known about the mechanisms underlying the transition from paroxysmal to persistent atrial fibrillation (AF). In an ovine model of long-standing persistent AF we tested the hypothesis that the rate of electric and structural remodeling, assessed by dominant frequency (DF) changes, determines the time at which AF becomes persistent.

Methods And Results: Self-sustained AF was induced by atrial tachypacing.

A descriptive survey of the educational preparation and practices of antenatal educators in ireland.

Antenatal education is recommended to prospective parents, yet little is known about the educational preparation of the facilitators of this education, or of the educational practices they use. The aim of this study was to investigate the educational preparation and practices of antenatal educators in Ireland. Data were collected using a questionnaire structured on the three components (abilities, opportunities, and means) of Stamler's theoretical framework of enablement.

Performance of a redesigned HIV Selectest enzyme-linked immunosorbent assay optimized to minimize vaccine-induced seropositivity in HIV vaccine trial participants.

Vaccine-induced seropositivity (VISP) or seroreactivity (VISR), defined as the reaction of antibodies elicited by HIV vaccines with antigens used in HIV diagnostic immunoassays, can result in reactive assay results for vaccinated but uninfected individuals, with subsequent misclassification of their infection status. The eventual licensure of a vaccine will magnify this issue and calls for the development of mitigating solutions in advance. An immunoassay that discriminates between antibodies elicited by vaccine antigens and those elicited by infection has been developed to address this laboratory testing need.

Biomarkers Predict Relapse in Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a small blood vessel vasculitic disorder with a high mortality rate if undiagnosed or treated inadequately. Disease relapse is a key feature of this disease and early identification of relapse episodes is very important in limiting end-organ damage. The advent of indirect immunofluorescence to detect antineutrophil cytoplasmic antibody (ANCA) with specific reactivity against the enzyme proteinase-3 (PR3) has been very useful in the diagnosis of GPA but is less helpful in predicting relapse.

Older adults have diminished awareness of errors in the laboratory and daily life.

Poor recognition of the degree or scope of one's own cognitive deficits is a common feature of many neurological conditions, including diseases of aging, but little is known about the impact the natural aging process has on this aspect of self-awareness (SA). Here, a group of 45 healthy older adults and a comparison group of 45 young adults completed a multidomain assessment of SA. Awareness of daily functioning was evaluated based on discrepancies between self- and informant ratings on questionnaire measures of attentional control, memory functioning, and socioemotional functioning.

Effect of phacoemulsification on trabeculectomy function.

Background: To evaluate the effect of phacoemulsification on trabeculectomy function.

Design: Retrospective case-control study.

Participants: Forty-eight patients who underwent trabeculectomy surgery and had at least 2 years of follow up.

Combat veterans with PTSD after mild TBI exhibit greater ERPs from posterior-medial cortical areas while appraising facial features.

Posttraumatic stress disorder (PTSD) worsens prognosis following mild traumatic brain injury (mTBI). Combat personnel with histories of mTBI exhibit abnormal activation of distributed brain networks-including emotion processing and default mode networks. How developing PTSD further affects these abnormalities has not been directly examined.