Single nucleotide polymorphisms (SNPs) near the IL28B gene have been shown to be associated with response to treatment for chronic hepatitis C and also with spontaneous clearance of hepatitis C virus ...(HCV) infection. We analysed the association between IL28B genetic variants and spontaneous clearance of HCV infection in 376 HCV‐infected Chinese paid plasma donors. Genotyping of eight SNPs near the IL28B region was performed by the iPLEX system (MassARRAY® SNP Genotyping; Sequenom) in all donors, and sequencing was performed on all 80 donors who cleared HCV and on 160 of 296 donors who did not clear HCV to validate the genotypes. Eighty (21.3%) donors spontaneously cleared HCV. Four SNPs were significantly associated with spontaneous HCV clearance: rs8099917 TT (vs GT), rs8105790 TT (vs CT), rs12980275 AA (vs AG) and rs10853728 CC (vs CG or GG) with OR (95% CI) 15.27 (2.07–112.50), 14.88 (2.02–109.72), 7.92 (1.88–33.32) and 2.32 (1.22–4.42) respectively. No association between the other four IL28B SNPs including rs12979860 and spontaneous HCV clearance was found. Women had a higher rate of spontaneous HCV clearance than men 56/213 (26.3%) vs 24/163 (14.6%), P = 0.007, and this was true even after stratification for IL28B genotypes with OR of 1.9–2.2 among those with favourable genotypes. Our results confirmed that IL28B polymorphism is associated with spontaneous clearance of HCV in Chinese subjects, but the SNPs that predict HCV clearance in Chinese subjects were different from those reported in Caucasians. Women were more likely to clear HCV infection regardless of IL28B genotypes.
Osteoporosis is a complex multifactorial disease that can lead to an increased risk of fracture. However, selective and effective osteoporosis drugs are still lacking. We showed that Asperosaponin VI ...(AVI) has the implications to be further developed as an alternative supplement for the prevention and treatment of bone loss. AVI has been found to have beneficial effects on metabolic diseases such as bone loss, obesity, and atherosclerosis. Our study was designed to determine the effect and mechanism of action of AVI against bone loss through regulating microbial dysbiosis. A hindlimb unloading mouse model was established to determine the effect of AVI on bone microarchitecture, gut microbiota, and serum metabolites. Eighteen female C57BL/6 J mice were divided into three groups: control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with AVI (HLU-AVI, 200 mg/kg/day). AVI was administrated orally for 4 weeks. The results demonstrated that AVI improved the bone microstructure by reversing the decrease in bone volume fraction and trabecular number, and the increase in trabecular separation and structure model index of cancellous bone in hindlimb suspension mice. The results of 16sRNA gene sequencing suggested that the therapeutic effect of AVI on bone loss may be achieved through it regulating the gut microbiota, especially certain specific microorganisms. Combined with the analysis of ELISA, immunohistochemistry, and serum metabolome results, it could be speculated that AVI played an important role in adjusting the balance of bone metabolism by influencing specific flora such as
Clostridium
and its metabolites to regulate the 5-hydroxytryptophan pathway. The study explored the novel mechanism of AVI against osteoporosis, and has implications for the further development of AVI as an alternative supplement for the prevention and treatment of bone loss.
Graphical Abstract
Abstract
We select the largest sample of Swift gamma-ray bursts (GRBs) so far to reexamine the classification in terms of time duration, hardness ratio, and physical collapse model. To analyze the ...sample selection effect, we divide the observed Swift GRB sample into four subsamples according to signal-to-noise level, spectral quality, and extended emission. First, we find that only the sample of Swift GRBs with well-measured peak energy can be evidently divided into two types at a boundary of ∼1 s, and other data sets are well described by three Gaussian functions. Using Swift GRBs with known redshift, a Kolmogorov–Smirnov test shows the intrinsic duration distributions of five data sets are equally distributed. Second, we ascertain in the plane of hardness ratio versus duration that the hardness ratio of short GRBs is significantly higher than those of middle classes and long GRBs, while the latter two components are the same in statistics, implying the so-called middle class to be artificial. Third, we apply a collapse model to discriminate the boundaries between collapse and noncollapse Swift bursts. It is interesting to find that a significant fraction, ≥30%, of Swift short GRBs could have originated from the collapsing progenitors, while all long GRBs are produced from the collapsars only. Finally, we point out that short GRBs with extended emission are the main contributors to the noncollapsar population with longer duration.
Accessible summary
What is known on the subject?
Suicide is a global mental health issue. Taking care of suicidal individuals is a substantial challenge. Most studies emphasize the suicidal ...individual. Few studies have emphasized the family caregivers of suicidal individuals.
No study has explored the relationship between family caregivers' caring stress with suicidal attitudes and suicide care ability.
What this paper adds to existing knowledge?
The main results indicated that the older family caregivers tended to have a more negative attitude towards suicidal individuals. Female family caregivers' stress was higher than that of male family caregivers.
A mild level of caring stress would help family caregivers have a more positive attitude towards suicidal individuals. Furthermore, a positive attitude would help family caregivers improve their caring ability.
What are the implications for practice?
Mental health nurses could help family caregivers, especially female family caregivers, reduce their holistic caring burden by looking for support resources and enhancing their coping strategies.
Mental health nurses could help family caregivers promote positive attitudes towards suicidal relatives by understanding suicidal individuals' suffering.
Introduction
Suicide is a global mental health issue. Family caregivers play a key role in preventing suicide attempts.
Aims
The aim of this study was to examine the relationship among stress due to the family caregiver's role, suicidal attitude of the family caregiver and suicide care ability among family caregivers. Additionally, instruments of caring stress, attitudes towards suicidal relatives and caring abilities used in the study were tested to measure construct validity.
Methods
A cross‐sectional correlational study was conducted with 164 family caregivers of people who are suicidal. The following three questionnaires were used: the Caring Stress Scale, the Suicidal Attitudes Scale and the Suicidal Caring Ability Scale. Structural equation modelling was performed using SPSS AMOS 19.0 to examine the path relationships among variables.
Results
Bivariate analyses showed that age was negatively correlated with suicidal attitude. In the final path model, caring stress had a positive effect on suicidal attitudes. Suicidal attitude and suicide care ability were highly positively correlated. Gender had a direct effect on caring stress, which indicated that female family caregivers experienced more stress from their role.
Implications for practice:
Mental health nurses could help family caregivers become aware of the emotional pain that suicidal people experience and then promote their positive attitudes towards their suicidal relatives. Furthermore, family caregivers could increase their ability to care for their suicidal relatives, which could reduce the numbers of suicides.
One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of ...brain death resides in the rostral ventrolateral medulla (RVLM). RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α) plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death.
A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1), Ubc9 (the only known conjugating enzyme for the sumoylation pathway) or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase.
We conclude that sumoylation of HIF-1α in RVLM ameliorates brain stem cardiovascular regulatory failure during experimental brain death via upregulation of nitric oxide synthase I/protein kinase G signaling. This information should offer new therapeutic initiatives against this fatal eventuality.
Abstract
SARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults are unclear. Here, we report SARS-CoV-2 specific T cell responses in infected adults ...and children and find that the acute and memory CD4
+
T cell responses to structural SARS-CoV-2 proteins increase with age, whereas CD8
+
T cell responses increase with time post-infection. Infected children have lower CD4
+
and CD8
+
T cell responses to SARS-CoV-2 structural and ORF1ab proteins when compared with infected adults, comparable T cell polyfunctionality and reduced CD4
+
T cell effector memory. Compared with adults, children have lower levels of antibodies to β-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses are increased, whilst monocyte numbers are reduced, indicating rapid adaptive co-ordination of the T and B cell responses and differing levels of inflammation. Therefore, reduced prior β-coronavirus immunity and reduced T cell activation in children might drive milder COVID-19 pathogenesis.
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