Validation of fitness tracker for sleep measures in women with asthma

Objective: Nighttime wakening with asthma symptoms is a key to assessment and therapy decisions, with no gold standard objective measure. The study aims were to (1) determine the feasibility, (2) explore equivalence, and (3) test concordance of a consumer-based accelerometer with standard actigraphy for measurement of sleep patterns in women with asthma as an adjunct to self-report. Methods: Panel study design of women with poorly controlled asthma from a university-affiliated primary care clinic system was used. We assessed sensitivity and specificity, equivalence and concordance of sleep time, sleep efficiency, and wake counts between the consumer-based accelerometer Fitbit Charge? and Actigraph wGT3X+. We linked data between devices for comparison both automatically by 24-hour period and manually by sleep segment. Results: Analysis included 424 938?minutes, 738 nights, and 833 unique sleep segments from 47 women. The fitness tracker demonstrated 97% sensitivity and 40% specificity to identify sleep. Between device equivalence for total sleep time (15 and 42-minute threshold) was demonstrated by sleep segment. Concordance improved for wake counts and sleep efficiency when adjusting for a linear trend. Conclusions: There were important differences in total sleep time, efficiency, and wake count measures when comparing individual sleep segments versus 24-hour measures of sleep. Fitbit overestimates sleep efficiency and underestimates wake counts in this population compared to actigraphy. Low levels of systematic bias indicate the potential for raw measurements from the devices to achieve equivalence and concordance with additional processing, algorithm modification, and modeling. Fitness trackers offer an accessible and inexpensive method to quantify sleep patterns in the home environment as an adjunct to subjective reports, and require further informatics development.     

From the Cover: Leukocyte immunoglobulin-like receptor B1 is critical for antibody-dependent dengue

Viruses must evade the host innate defenses for replication and dengue is no exception. During secondary infection with a heterologous dengue virus (DENV) serotype, DENV is opsonized with sub- or nonneutralizing antibodies that enhance infection of monocytes, macrophages, and dendritic cells via the Fc-gamma receptor (FcγR), a process termed antibody-dependent enhancement of DENV infection. However, this enhancement of DENV infection is curious as cross-linking of activating FcγRs signals an early antiviral response by inducing the type-I IFN-stimulated genes (ISGs). Entry through activating FcγR would thus place DENV in an intracellular environment unfavorable for enhanced replication. Here we demonstrate that, to escape this antiviral response, antibody-opsonized DENV coligates leukocyte Ig-like receptor-B1 (LILRB1) to inhibit FcγR signaling for ISG expression. This immunoreceptor tyrosine-based inhibition motif-bearing receptor recruits Src homology phosphatase-1 to dephosphorylate spleen tyrosine kinase (Syk). As Syk is a key intermediate of FcγR signaling, LILRB1 coligation resulted in reduced ISG expression for enhanced DENV replication. Our findings suggest a unique mechanism for DENV to evade an early antiviral response for enhanced infection.Despite long-lived serotype-specific immunity upon initial infection, predicted global prevalence of dengue now surpasses World Health Organization estimates by more than threefold with 390 million cases annually (1). Furthermore, the risk of severe disease is augmented by cross-reactive or subneutralizing levels of antibody (2, 3), which opsonize dengue virus (DENV) to ligate Fc-gamma receptor (FcγR) for entry into monocytes, macrophages, and dendritic cells, a phenomenon known as antibody-dependent enhancement (ADE) of DENV infection (4, 5). The resultant greater viral burden leads to increased systemic inflammation that precipitates plasma leakage, a hallmark of dengue hemorrhagic fever (6). However, ligation of the activating FcγRs by immune complexes has been shown to induce type-I IFN stimulated genes (ISGs), independent of autocrine or paracrine IFN activity, unless the inhibitory FcγRIIB is coligated (7). We and others reported recently that coligation of FcγRIIB by DENV immune complexes requires high antibody concentration, and such coligation inhibited the entry of DENV immune complexes into monocytes (8, 9). At low antibody concentrations where ADE occurs, the inhibitory FcγRIIB is not coligated (9). Ligation of the activating FcγRs by DENV opsonized with subneutralizing levels of antibody would thus induce the expression of ISGs and hinder DENV replication (10). Here, we demonstrate that DENV employs a unique evasive mechanism by coligating LILRB1 to down-regulate the early antiviral responses triggered by activating FcγRs for ADE.     

Mortality in children with juvenile dermatomyositis: two decades of experience from a single tertiary care centre in North India

Survival and outcomes have improved considerably among patients with juvenile dermatomyositis (JDM) in the west. However, mortality continues to be high in the developing world. There is paucity of literature on this aspect of JDM from developing countries. We reviewed case files of all patients with JDM registered in the Pediatric Rheumatology Clinic, Advanced Pediatrics Centre at the Post Graduate Institute of Medical Education and Research, Chandigarh, during the period 1993–2013. Seventy-six children were diagnosed to have inflammatory myopathy during this period. Of these, 63 had JDM, 3 had polymyositis while 10 had an overlap syndrome. We had reported 2 deaths out of 33 (8.3 %) patients with JDM in 2004, and over the last 9 years, we have encountered five more deaths in this group, thereby accounting for a mortality rate of 11.1 % (7/63) over two decades of follow-up. In these five children now being described, the mean duration between onset of symptoms and institution of appropriate therapy was 9.2 months. Four children (80 %) had severe muscle weakness needing nasogastric tubes at the onset, three (60 %) had cutaneous ulcers and three (60 %) had superadded infections. Two children (40 %) had gastrointestinal vasculitis and one of these developed an intestinal perforation. Three patients (60 %) had progressive pulmonary disease and air leak was identified in two of them. Although the prognosis for survival in JDM has steadily improved, in our experience the disease remains a serious illness and still carries significant mortality in the context of a developing country.     

Molecular docking,pharmacophore based virtual screening and molecular dynamics studies towards the identification of potential leads for the management of H. pylori

The enzyme pantothenate synthetase panC is one of the potential new antimicrobial drug targets, but it is poorly characterized in H. pylori. H. pylori infection can cause gastric cancer and the management of H. pylori infection is crucial in various gastric ulcers and gastric cancer. The current study describes the use of innovative drug discovery and design approaches like comparative metabolic pathway analysis (Metacyc), exploration of database of essential genes (DEG), homology modelling, pharmacophore based virtual screening, ADMET studies and molecular dynamics simulations in identifying potential lead compounds for the H. pylori specific panC. The top ranked virtual hits STOCK1N-60270, STOCK1N-63040, STOCK1N-44424 and STOCK1N-63231 can act as templates for synthesis of new H. pylori inhibitors and they hold a promise in the management of gastric cancers caused by H. pylori.

Computational approaches such as pharmacophore modeling, virtual screening and MD simulations were explored to find the potential hits as H. pylori specific panC inhibitors for the management of gastric ulcers and gastric cancers.     

Maximizing the benefits of antiretroviral therapy for key affected populations

Introduction

Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services.

Discussion

Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed.

Conclusions

Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm reduction and other prevention interventions tailored to meet the needs of key populations. An end to AIDS is only possible if we overcome the barriers of criminalization, stigma and discrimination that remain key drivers of the HIV epidemics among key populations.     

Round Pendant Around the Neck–Thyroid. A Review

The rare situation of thyroid stone is discussed with literature review and case report. A case of isolated solitary stone of the thyroid is documented here. There are incidences of calcification in the thyroid gland commonly associated with carcinoma thyroid and multinodular goiter. But solitary stone of thyroid is reported rarely and one such case is reported from India. The possibility of malignancy is high, in case of calcification of thyroid swellings. Hence, isolated calcification should be surgically treated even if fine needle aspiration cytology is negative for malignancy.