The genome sequence analysis of H5N1 avian influenza A virus isolated from the outbreak among poultry populations in Thailand

In this report, the genome of the Thai avian influenza virus A (H5N1); A/Chicken/Nakorn-Pathom/Thailand/CU-K2/04, isolated from the Thai avian influenza A (AI) epidemic during the early of 2004 was sequenced. Phylogenetic analyses were performed in comparison to AI viruses from Hong Kong 1997 outbreaks and other AI (H5N1) isolates reported during 2001-2004. Molecular characterization of the Thai AI (H5N1) HA gene revealed a common characteristic of a highly pathogenic AI (HPAI), a 20-codon deletion in the neuraminidase gene, a 5-codon deletion in the NS gene and polymorphisms of the M2 and PB2 genes. Moreover, the HA and NA genes of the Thai AI displayed high similarity to those of the AI viruses isolated from human cases during the same epidemic. Finally, our results demonstrated that the Thai AI emerged as a member of 2000's AI lineage with most of the genetic sequences closely related to the Influenza A/Duck/China/E319.2/03 (H5N1).     

Interventions to Increase Multivitamin Use Among Women in the Interconception Period: An IMPLICIT Network Study

Maternal and Child Health Journal - Each year, 3% of infants in the Unites States (US) are born with congenital anomalies, including 3000 with neural tube defects. Multivitamins (MVIs) including...     

Effects of intradialytic cycling exercise on daily physical activity,physical fitness,body composition,and clinical parameters in high-volume online hemodiafiltration patients: a pilot randomized-controlled trial

Purpose

The mortality of dialysis patients treated with high-volume online hemodiafiltration (OL-HDF) is better than hemodialysis, but is still higher than healthy population. Low daily physical activity increases cardiovascular mortality. Addition of intradialytic exercise (IDX) program might improve physical activity and health status in OL-HDF patients. This pilot open-labeled randomized-controlled trial was conducted to evaluate the effects of IDX on physical activity and other clinical parameters in OL-HDF patients.

Methods

Twelve OL-HDF patients were randomized into control (n?=?6) or IDX (n?=?6) groups. The subjects in IDX group were trained to exercise using a cycle ergometer for 60 min during each OL-HDF session. Physical activity measured as daily step count using a wrist-worn triaxial accelerometer, physical fitness, or cardiorespiratory fitness assessed by VO₂max and other physical performance tests, lean body mass determined by the Dual-energy X-ray absorptiometry (DXA), quality of life (QOL), and various parameters were compared between baseline and 6 months.

Results

The baseline physical activity status was comparable. Following 6-month IDX, the physical activity was significantly improved in IDX group [+?1048.79 (+?741.50,?+?2792.54) vs. ? 362.06 (? 1626.82, ? 167.47) steps/day, p?=?0.01], while physical fitness and QOL were unchanged. The lean body mass parameters were preserved in the IDX group while seemed to decrease in the control group. Serum albumin was significantly increased in the IDX group (p?=?0.01). The hemoglobin changes were significantly better (p?=?0.01) and the erythropoietin resistance index was significantly lower in the IDX group (p?=?0.03). Phosphate reduction was significantly greater in the IDX group (p?=?0.04).

Conclusions

IDX could improve physical activity and other metabolic parameters in OL-HDF patients and these might contribute to further improvement in clinical and survival outcomes.

Trial registration

ClinicalTrials.gov Registration: NCT03353844.

     

Helicobacter pylori Infection Impairs the Mucin Production Rate and Turnover in the Murine Gastric Mucosa

To protect the surface of the stomach, the epithelial cells secrete a mucus layer, which is mainly comprised of the MUC5AC mucin. Further protection is provided by a thick glycocalyx on the apical surface of the epithelial cell, with the cell surface mucin MUC1 as a major component. Here, we investigate the production rate and turnover of newly synthesized mucin in mice and analyze the effects of early colonization and chronic infection with H. pylori. Metabolic incorporation of an azido GalNAc analog (GalNAz) was used as a nonradioactive method to perform pulse experiments in the whole animal. First, the subcellular movement of newly synthesized mucin and mucin turnover was determined in uninfected mice. Based on the time line for mucin transport and dissemination, 2, 6, and 12 h after GalNAz injection was selected to collect the stomachs from mice infected with H. pylori strain SS1 during early colonization (7 days) and chronic infection (90 days). The results demonstrated that the speed from the start of glycosylation to the final destination is faster for the membrane-bound mucin to reach the glycocalyx (2 h) than for the secretory mucins to become secreted into the mucus layer (5 h). Furthermore, infection with H. pylori reduces the rate of mucin turnover and decreases the levels of Muc1. Since H. pylori colonizes this mucus niche, the decreased turnover rate indicates that H. pylori creates a more stable and favorable environment for itself by impairing the defense mechanism for clearing the mucosal surface of pathogens by mucus flow.     

The matricellular protein CCN3 regulates NOTCH1 signalling in chronic myeloid leukaemia

Deregulated NOTCH1 has been reported in lymphoid leukaemia, although its role in chronic myeloid leukaemia (CML) is not well established. We previously reported BCR‐ABL down‐regulation of a novel haematopoietic regulator, CCN3, in CML; CCN3 is a non‐canonical NOTCH1 ligand. This study characterizes the NOTCH1–CCN3 signalling axis in CML. In K562 cells, BCR‐ABL silencing reduced full‐length NOTCH1 (NOTCH1‐FL) and inhibited the cleavage of NOTCH1 intracellular domain (NOTCH1‐ICD), resulting in decreased expression of the NOTCH1 targets c‐MYC and HES1. K562 cells stably overexpressing CCN3 (K562/CCN3) or treated with recombinant CCN3 (rCCN3) showed a significant reduction in NOTCH1 signalling (> 50% reduction in NOTCH1‐ICD, p < 0.05). Gamma secretase inhibitor (GSI), which blocks NOTCH1 signalling, reduced K562/CCN3 colony formation but increased that of K562/control cells. GSI combined with either rCCN3 or imatinib reduced K562 colony formation with enhanced reduction of NOTCH1 signalling observed with combination treatments. We demonstrate an oncogenic role for NOTCH1 in CML and suggest that BCR‐ABL disruption of NOTCH1–CCN3 signalling contributes to the pathogenesis of CML. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Histological observations on the anterior olfactory nucleus in human

Aim: Localization of isolated clusters of anterior olfactory nucleus (AON) in a human olfactory bulb and tract. Materials and methods: This investigation was done on human olfactory bulbs and their tracts, collected from the freshly donated cadavers, before embalming, in the Department of Anatomy, IPGMER, Kolkata. H&E stained histological slides were prepared along the whole length of specimens and examined under a Leica DM 2000 microscope and with a Leica Quin image analyzer. Results: The anterior olfactory nucleus was detected in the form of a major cluster and in two smaller clusters of neurons. The major cluster was located at the caudal pole of the bulb and was composed of medium-sized triangular cells which had an average diameter of 13.92 ± 3.43 μm. Out of the two minor clusters, one was detected at the beginning and another at the middle of the olfactory tract. Here neurons were little larger in size and their diameter ranged approximately 15–17 μm. Olfactory striae also accommodated some neurons in a scattered manner. Conclusion: This observation will be helpful in exploration of the complex role of AON in the organization and function of the olfactory system and its clinical significance in human.     

Recent progress in therapeutic strategies for microglia-mediated neuroinflammation in neuropathologies

Introduction: Chronic activation of microglia is the hallmark of numerous neuropathologies such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. The activated microglia perpetuate inflammation by releasing an array of pro-inflammatory and neurotoxic factors, which eventually exacerbate neurotoxicity and neurodegeneration upon chronic activation of these cells. However, under acute conditions, activated microglia elicit pro-inflammatory as well as anti-inflammatory responses that are associated with neuroprotection. Given the role of microglia in neuroinflammation, recent studies have attempted to unravel the mechanisms that aid to establish microglial cell-based therapy.

Areas covered: While total suppression of microglial activation may compromise its beneficial role in tissue repair in the aftermath of an insult, the benefits of modulating microglial activation and promoting microglia polarization to a neuroprotective phenotype have been highlighted recently.

Expert opinion: So far, the therapeutic strategy focussed on neutralizing microglia-mediated neuroinflammation using drugs that block the release of pro-inflammatory mediators has limitations, such as unwarranted side effects. Recent advances reveal several alternative molecular targets and potential epi-drugs that are capable of modulating microglial function and promoting neuroprotection. This review discusses the recent progress made in understanding the mechanisms of microglia-mediated neuroinflammation in various neuropathologies, and the emerging anti-inflammatory therapeutic strategies in this field.     

Immune checkpoint blockade and biomarkers of clinical response in non–small cell lung cancer

Immunotherapy with PD-1 and PD-L1 inhibitors has revolutionized the treatment for patients with NSCLC the last years with increased overall survival and in particular increased number of long-time survivors in patients with metastatic disease. It is now a treatment of choice for patients with distant metastases (stage IV) and in conjunction with chemoradiotherapy for patients with limited spread confined to the chest (stage III). PD-1 inhibition has been proven to be superior to standard chemotherapy, both as a single treatment and when combined with either chemotherapy or CTLA-4 inhibition. Despite the success of immunotherapy, the majority of patients do not respond or relapse within a short time frame. Biomarkers that would help to properly select patients with a high likelihood of clinical response to PD-1 and PD-L1 inhibitors are scarce and far from optimal, and only one (PD-L1 expression) has reached clinical practice. Thus for immunotherapy to be effective, the discovery and validation of additional biomarkers is critical for patient selection and prediction of clinical response. In this mini-review, we give an overview of current clinical management of NSCLC including treatment landscape with regard to immunotherapy, as well as discuss the current genetic and immune cell biomarker studies and their potential for introduction into clinical practice.     

Targeted specific inhibition of bacterial and Candida species by mesoporous Ag/Sn–SnO2 composite nanoparticles: in silico and in vitro investigation

Invasive bacterial and fungal infections have notably increased the burden on the health care system and especially in immune compromised patients. These invasive bacterial and fungal species mimic and interact with the host extracellular matrix and increase the adhesion and internalization into the host system. Further, increased resistance of traditional antibiotics/antifungal drugs led to the demand for other therapeutics and preventive measures. Presently, metallic nanoparticles have wide applications in health care sectors. The present study has been designed to evaluate the advantage of Ag/Sn–SnO₂ composite nanoparticles over the single oxide/metallic nanoparticles. By using in silico molecular docking approaches, herein we have evaluated the effects of Ag/Sn–SnO₂ nanoparticles on adhesion and invasion responsible molecular targets such as LpfD (E. coli), Als3 (C. albicans) and on virulence/resistance causing PqsR (P. aeruginosa), RstA (Bmfr) (A. baumannii), FoxA (K. pneumonia), Hsp90 and Cyp51 (C. albicans). These Ag/Sn–SnO₂ nanoparticles exhibited higher antimicrobial activities, especially against the C. albicans, which are the highest ever reported results. Further, Ag/Sn–SnO₂ NPs exhibited interaction with the heme proionate residues such as Lys143, His468, Tyr132, Arg381, Phe105, Gly465, Gly464, Ile471 and Ile304 by forming hydrogen bonds with the Arg 381 residue of lanosterol 1 4α-demethylase and increased the inhibition of the Candida strains. Additionally, the Ag/Sn–SnO₂ nanoparticles exhibited extraordinary inhibitory properties by targeting different proteins of bacteria and Candida species followed by several molecular pathways which indicated that it can be used to eliminate the resistance to traditional antibiotics.

Mesoporous Ag/Sn–SnO₂ composite nanoparticles exhibits extraordinary inhibitory properties by targeting different proteins of bacteria and Candida species which can be used to eliminate the resistance of traditional antibiotics.