The predominance and continual emergence of new variants in GII-4 noroviruses (NVs) in recent years have raised questions about the role of host immunity and histo-blood group antigens (HBGAs) in NV evolution. To address these questions, we performed a genetic and phenotypic characterization of GII-4 variants circulating in the past decade (1998 to 2008). Ninety-three GII-4 sequences were analyzed, and of them, 16 strains representing 6 genetic clusters were selected for further characterization. The HBGA binding properties were determined by both saliva-and oligosaccharide-binding assays using P particles as a model of NV capsid. The antigenic properties were also examined by enzyme immunoassay (EIA), Western blot analysis, and receptor blocking assay, using P-particle-specific antibodies from immunized mice and GII-4 virus-infected patients. Our results showed that 15 of the 16 GII-4 viruses bound to saliva of all A, B, and O secretors. Oligosaccharide binding assays yielded largely consistent results, although the binding affinities to some oligosaccharides varied among some strains. The only nonbinder had a mutation in the binding site. While antigenic variations were detected among the 16 strains, significant cross-blocking on the HBGA binding was also noted. Sequence alignment revealed high conservation of HBGA binding interfaces with some variations in adjacent regions. Taken together, our data suggested that the ability of GII-4 to recognize different secretor HBGAs persisted over the past decade, which may explain the predominance of GII-4 over other genotypes. Our data also indicated that both the host immunity and HBGAs play a role in NV evolution. While host immunity may continue driving NV for antigenic change, the functional selection by the HBGAs tends to lock the architecture of the capsid/HBGA interfaces and allows only limited variations outside the HBGA binding sites. A potential outcome of such counterselection between theses two factors in NV evolution is discussed.Noroviruses (NVs) have been recognized as the most important cause of nonbacterial acute gastroenteritis in both developed and developing countries, affecting people of all ages (13,35,39,44,48,56). They are single-stranded positive-sense RNA viruses belonging to the family Caliciviridae. NVs are highly contagious, spreading by a fecal/oral pathway through person-to-person contact and by contaminated food and/or water and usually causing large outbreaks within closed communities in a variety of settings, such as hospitals, nursing homes, schools, childcare centers, restaurants, cruise ships, and the military (11, 63). Human NVs have been difficult to study due to diverse members and the lack of an efficient cell culture and animal model for human NVs. The cloning of the NV genomes (33,36,73) and subsequent expression of the viral capsid proteins in baculovirus and other expression systems (3, 31, 32) have greatly advanced the research of NVs, including host-virus interaction, immunology, diagnosis, molecular virology, and epidemio...

Background:Probiotics supplements provide a new nonpharmacological alternative to reduce cardiovascular risk factors. The impact of probiotics on the reduction of total cholesterol (TC) remains controversial. We conducted a meta-analysis to showcase the most updated and comprehensive evaluation of the studies.Methods:Randomized controlled trials (RCTs) were searched from electronic databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang database dating from January 2007 to January 2017. The curative effects of probiotics on the reduction of TC were assessed using mean difference (MD), as well as their 95% confidence interval (CI). RevMan software (version 5.3) was used to carry out this meta-analysis.Results:Thirty-two RCTs including 1971 patients met the inclusion criteria. Results of this analysis showed that compared with the control group serum TC was significantly reduced in probiotics group [MD = −13.27, 95% CI (−16.74 to 9.80), P < .05]. In addition, specific strains also significantly reduced serum TC, L acidophilus and B lactis [MD = −8.30, 95% CI (−10.44, −6.15), P < .05]; VSL#3 [MD = −11.04, 95% CI (−19.61, −2.48), P < .05]; L plantarum t ≤ 6 weeks: [MD = −1.56, 95% CI (−6.97, −3.86), P < .05] or t > 6 weeks: [MD = −22.18, 95% CI (−28.73, −15.63), P < .05]. Subgroup analysis indicated that the difference of baseline TC, probiotics forms and intervention duration might have a significant impact on the results. However, strains and doses of probiotics had no significant influence on curative effects.Conclusion:Available evidence indicates that probiotics supplements can significantly reduce serum TC. Furthermore, higher baseline TC, longer intervention time, and probiotics in capsules form might contribute to a better curative effect.

Hypothyroidism is resulting from a deficiency of thyroid hormones, which is common condition with potentially devastating health consequences that affect all populations worldwide. 1 Thyroid hormones are essential for growth, neuronal development, reproduction and the regulation of energy metabolism. The prevalence of hypothyroidism varies considerably across the general population, ranging between 0.2% and 5.3% in Europe, 2 0.3% and 3.7% in the USA, 3 11% in India 4 and 17.8% in China (overt hypothyroidism: 1.1%; subclinical hypothyroidism: 16.7%). 5 Longitudinal studies from large UK cohorts report an incidence rate of spontaneous hypothyroidism of 3.5-5.0 per 1000 and 0.6-1.0 per 1000 in women and men, respectively. 6The clinical presentation of hypothyroidism is nonspecific and variable. Therefore, the diagnosis of hypothyroidism is based primarily on biochemical abnormalities. The pituitary hormone thyrotropin (TSH) has a complex inverse relationship with the thyroid hormones thyroxine (T4) and triiodothyronine (T3). 7 Accordingly, overt hypothyroidism is defined as serum TSH concentrations above the reference range with low free T4 (FT4) levels, while subclinical hypothyroidism is diagnosed when TSH levels are high and circulating Abstract Purpose: To compare the effects of l-thyroxine (L-T4) administration before breakfast and administration at bedtime on hypothyroidism. Methods: The PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing L-T4 administration before breakfast to the administration at bedtime in patients with hypothyroidism were included in the analysis. Results: Initially, 2884 articles were retrieved from the databases, and 10 articles were included in the quantitative analysis. The effect of L-T4 administration before breakfast compared with administration at bedtime had no statistically significant association with hormone thyrotropin (TSH) (Standardized mean differences [SMD] = 0.09, 95% confidence intervals (CI): −0.12, 0.30; P = .39), or free triiodothyronine (FT3) (SMD=−0.19, 95% CI: −0.53, 0.15; P = .28) in patients with hypothyroidism. However, the result of FT4 level was favourable for L-T4 bedtime administration group (SMD=−0.27, 95% CI: −0.52, −0.02; P = .03). Conclusion:Our meta-analysis revealed that L-T4 administration at bedtime is as effective as administration before breakfast for patients with hypothyroidism. Taking L-T4 at bedtime may be an attractive option for patients with hypothyroidism. K E Y W O R D Sadministration timing, hypothyroidism, l-thyroxine, meta-analysis How to cite this article: Pang X, Pu T, Xu L, Sun R. Effect of l-thyroxine administration before breakfast vs at bedtime on hypothyroidism: A meta-analysis. Clin Endocrinol (Oxf).

Quantitative microbial risk assessment (QMRA) identifies human enteric viruses in municipal wastewater as the pathogen group requiring the highest log reductions for various reuse applications. However, the performance of methods for estimating virus concentration is not well understood, and without performance assessment, actual risks are likely severely underestimated. To evaluate the efficiency of virus recovery from water, a water sample is often spiked with “known” amounts of virus, and the virus is then recovered after a series of analytical procedures. Yet for water matrices such as wastewater, due to the unknown background concentrations of targeted viruses in the matrix and the variable recovery efficiency between individual processes, only an approximation of the recovery efficiency may be obtained from such spike-and-recovery experiments. In this study, we demonstrated theoretically that for two widely used approximations, the error in estimating virus recovery should be less than the ratio of the amount of target virus in the background sample to that in the spike. Furthermore, we developed an applicable method, based on this new understanding, for deciding on the amount of virus for spiking before conducting a spike-and-recovery experiment, so that the approximation error is restricted to an acceptable level for each individual process. Finally, we applied the method to a set of experimental data for viruses in wastewater, demonstrating its utility and noting its general applicability to other pathogens or water matrices. IMPORTANCE The performance of procedures for pathogen log reduction is at the heart of new risk-based guidance/regulation globally, yet the methods for undertaking assessments of pathogen recovery are not standardized despite their fundamental impacts on assessing log reductions. Here we describe the level of spiking agent(s) that is necessary to correctly assess spiked pathogen/surrogate recovery with whatever method is deployed. The significance of our research lies in identifying the importance of the amount of spiking agents for reducing uncertainty in recovery estimates, which will allow the development of a recommendation for spiking experiments, proactively applying this understanding.