Circulating human group A rotavirus genotypes in Malaysia

This study examined the temporal distribution of rotavirus genotypes in Malaysia. Rotaviruses from children with diarrhea admitted to hospitals in 1996 (n = 93) and 2007 (n = 12) in two different regions of Peninsular (West) Malaysia were analyzed for their G and P genotypes using a hemi‐nested RT‐PCR assay. In the 2007 samples, the dominant strain was G9P[8]. It was identified in 42% of the samples. Different strains all possessing the G1 genotype were identified in the rest of the samples. In contrast, 81% of the samples collected in 1996 were the G1P[8] strain. No strains with G9 genotype were detected in samples collected in 1996. J. Med. Virol. 82:707–711, 2010. © 2010 Wiley‐Liss, Inc.     

Genetic variation of NSP1 and NSP4 genes among serotype G9 rotaviruses causing hospitalization of children in Melbourne, Australia, 1997-2002

Serotype G9 rotaviruses have emerged as one of the leading causes of gastroenteritis in children worldwide. We examined 29 representative G9 rotavirus isolates from a 6-year collection (1997-2002) and determined the level of variation in genes encoding non-structural proteins, NSP1 and NSP4. Northern hybridization analysis with a whole genome probe derived from the prototype G9 strain, F45, revealed that the NSP1 gene (gene 5) of two isolates (R1 and R14) did not exhibit significant homology. Complementary DNA probes of R1 and R14 genes 5 were used in Northern blot hybridization and indicated the presence of at least two gene 5 alleles among Melbourne G9 rotaviruses. Nucleotide sequence analysis revealed that isolates carrying the R14 gene 5 shared 94-98% sequence identities with one another, while sequence identity to R1 was 78%. Surprisingly, R1 displayed 96% nucleotide identity with the prototype serotype G1 strain, Wa. The detection of different alleles of NSP1 genes prompted us to investigate the level of variation in another non-structural protein, NSP4, a multifunctional protein and the first viral-encoded enterotoxin. Phylogenetic analysis indicated that while all isolates clustered into one group containing the Wa NSP4 allele (genotype 1), isolate R1 was most closely related to Wa. This study reveals new information about the diversity of non-structural proteins of G9 rotaviruses.     

MKK3/6-p38 MAPK signaling is required for IL-1beta and TNF-alpha-induced RANKL expression in bone marrow stromal cells.

Coupled bone turnover is directed by the expression of receptor-activated NF-kappaB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Proinflammatory cytokines, such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) induce RANKL expression in bone marrow stromal cells. Here, we report that IL-1beta and TNF-alpha-induced RANKL requires p38 mitogen-activating protein kinase (MAPK) pathway activation for maximal expression. Real-time PCR was used to assess the p38 contribution toward IL-1beta and TNF-alpha-induced RANKL mRNA expression. Steady-state RANKL RNA levels were increased approximately 17-fold by IL-1beta treatment and subsequently reduced approximately 70%-90% when p38 MAPK was inhibited with SB203580. RANKL mRNA stability data indicated that p38 MAPK did not alter the rate of mRNA decay in IL-1beta-induced cells. Using a RANKL-luciferase cell line receptor containing a 120-kB segment of the 5' flanking region of the RANKL gene, reporter expression was stimulated 4-5-fold by IL-1beta or TNF-alpha treatment. IL-1beta-induced RANKL reporter expression was completely blocked with specific p38 inhibitors as well as dominant negative mutant constructs of MAPK kinase-3 and -6. In addition, blocking p38 signaling in bone marrow stromal cells partially inhibited IL-1beta and TNF-alpha-induced osteoclastogenesis in vitro. Results from these studies indicate that p38 MAPK is a major signaling pathway involved in IL-1beta and TNF-alpha-induced RANKL expression in bone marrow stromal cells.     

A randomised controlled pilot and feasibility study of music therapy for improving the quality of life of hospice inpatients

Background

Evidence about the effectiveness of music therapy for improving the quality of life of palliative care patients is positive but weak in terms of risk of bias.

Methods

This study aimed to determine the feasibility of a randomised controlled trial to evaluate the effectiveness of music therapy for improving the quality of life of hospice inpatients, as measured by the McGill Quality of Life questionnaire. Objectives included recruitment of 52 participants over 12?months and provision of data to support the calculation of the required sample size for a definitive randomised trial, taking into account the retention rates of recruited participants; and evaluation of the viability of the intervention and the acceptability of the assessment tool. The design was a single-centre, researcher-blinded randomised pilot and feasibility study involving two parallel groups. Participants were recruited from one inpatient hospice unit in Northern Ireland. Eligibility criteria were an Eastern Cooperative Oncology Group performance status of two or lower and an Abbreviated Mental Test score of seven or more. Consenting patients were randomly allocated to the intervention or control group using a 1:1 allocation ratio. The intervention group received up to six individual music therapy sessions over 3 weeks in addition to usual care. The control group received usual care only.

Results

Fifty one participants were recruited over 12?months. Twenty five were allocated to the intervention group and 26 to the control group. Seventy one percent of participants were lost to follow up by week 3, the proposed primary endpoint. The primary endpoint was moved from week 3, when 71% were lost to follow up to week 1, when 33% were lost. The McGill Quality of Life questionnaire was generally acceptable to participants. In order to detect a small to moderate effect size of 0.3, a fully powered study would require the recruitment of 698 participants.

Conclusions

A Phase III randomised controlled trial to evaluate the effectiveness of music therapy in improving the quality of life of hospice inpatients is feasible.

Trial registration

ClinicalTrials.gov: NCT02791048. Registered 6 June 2016.

     

Xenophagy in Helicobacter pylori‐ and Epstein–Barr virus‐induced gastric cancer

Helicobacter pylori and Epstein–Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double‐membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori‐ and EBV‐induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal–lysosomal pathway for degradation. In this connection, H. pylori or EBV‐induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori‐ and EBV‐induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents. Published by John Wiley & Sons, Ltd     

Intestinal Protein Characterisation of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2 in Inflammatory Bowel Disease (IBD) and Fatal COVID-19 Infection

Inflammation - The coronavirus SARS-CoV-2 contributes to morbidity and mortality mainly as a result of immune-pathology in the lungs. Recent data has shown multi-system involvement with widespread...     

Recommendations for the classification of group A rotaviruses using all 11 genomic RNA segments

Recently, a classification system was proposed for rotaviruses in which all the 11 genomic RNA segments are used (Matthijnssens et al. in J Virol 82:3204-3219, 2008). Based on nucleotide identity cut-off percentages, different genotypes were defined for each genome segment. A nomenclature for the comparison of complete rotavirus genomes was considered in which the notations Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx are used for the VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 encoding genes, respectively. This classification system is an extension of the previously applied genotype-based system which made use of the rotavirus gene segments encoding VP4, VP7, VP6, and NSP4. In order to assign rotavirus strains to one of the established genotypes or a new genotype, a standard procedure is proposed in this report. As more human and animal rotavirus genomes will be completely sequenced, new genotypes for each of the 11 gene segments may be identified. A Rotavirus Classification Working Group (RCWG) including specialists in molecular virology, infectious diseases, epidemiology, and public health was formed, which can assist in the appropriate delineation of new genotypes, thus avoiding duplications and helping minimize errors. Scientists discovering a potentially new rotavirus genotype for any of the 11 gene segments are invited to send the novel sequence to the RCWG, where the sequence will be analyzed, and a new nomenclature will be advised as appropriate. The RCWG will update the list of classified strains regularly and make this accessible on a website. Close collaboration with the Study Group Reoviridae of the International Committee on the Taxonomy of Viruses will be maintained.