Streptokinase is ineffective in restoring early myocardial reperfusion in Asian patients with acute myocardial infarction

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Non-ancient solution of the Ricci flow

For any complete noncompact K$\ddot{a}$hler manifold with nonnegative and bounded holomorphic bisectional curvature,we provide the necessary and sufficient condition for non-ancient solution to the Ricci flow in this paper.Comment: seven pages, latex fil

A Qualitative Analysis of Motivators to Participation in Suicide-Focused Research from a Community-Based Australian Sample

Suicide prevention strategies internationally appear to be falling short of making a meaningful impact on global suicide deaths. Increasing the rates of general community participation in suicide research may improve knowledge generalisability as it relates to suicidal behaviour and leads to new suicide prevention approaches. This study aims to explore the motivations of a community-based sample to participate in suicide research. A subsample of the Australian general population took part in an online survey which is part of a multilevel suicide prevention trial. The survey concluded with an optional open-text question asking about peoples’ motivations for participating in the study; 532 participants left a response to this question. These responses were qualitatively analysed using Thematic Network Analysis. Motivations to participate in suicide research were represented by four global themes: altruism, solve systemic problems, lived experience, and personal benefit. Of these themes, three were focused on the benefit of others, while only the final theme articulated motivation to participate that was self-focused. The impact of suicide is felt throughout the wider community. This new understanding of the motivations of community-based samples to participate in suicide research should be used to increase participation rates and reach people who would not normally contribute their voice to suicide researc

Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

BackgroundThe trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. There is critical knowledge gap in understanding how tau is released and transmitted, and how that is dysregulated in diseases. Previously, we reported that lysine acetyltransferase p300/CBP acetylates tau and regulates its degradation and toxicity. However, whether p300/CBP is involved in regulation of tau secretion and propagation is unknown.MethodWe investigated the relationship between p300/CBP activity, the autophagy-lysosomal pathway (ALP) and tau secretion in mouse models of tauopathy and in cultured rodent and human neurons. Through a high-through-put compound screen, we identified a new p300 inhibitor that promotes autophagic flux and reduces tau secretion. Using fibril-induced tau spreading models in vitro and in vivo, we examined how p300/CBP regulates tau propagation.ResultsIncreased p300/CBP activity was associated with aberrant accumulation of ALP markers in a tau transgenic mouse model. p300/CBP hyperactivation blocked autophagic flux and increased tau secretion in neurons. Conversely, inhibiting p300/CBP promoted autophagic flux, reduced tau secretion, and reduced tau propagation in fibril-induced tau spreading models in vitro and in vivo.ConclusionsWe report that p300/CBP, a lysine acetyltransferase aberrantly activated in tauopathies, causes impairment in ALP, leading to excess tau secretion. This effect, together with increased intracellular tau accumulation, contributes to enhanced spreading of tau. Our findings suggest that inhibition of p300/CBP as a novel approach to correct ALP dysfunction and block disease progression in tauopathy

The Microvasculature of Human Oral Mucosa Using Vascular Corrosion Casts and India Ink Injection I. Tongue Papillae

The microvasculature of human tongue papillae originating from 9 males and 6 females, aged 0.5 to 2 years was studied by scanning electron microscopy (SEM) of vascular corrosion casts and by light microscopy (LM) of India ink injected specimens. All papillae showed a microvasculature characterized by primary, secondary and tertiary capillary loops. In the filiform papillae the loops were generally arranged in a corolla-like pattern with the tertiary loops demonstrating a hair-pin shape. The fungiform papillae showed basically a similar architectural pattern although the loops were somewhat more compact and complex in structure. A small, shallow depression of the tertiary loops at the top of these papillae was found to be occupied by a prominent rete ridge of the surface epithelium. There was a gradual transition from filiform to foliate papillae, the latter appearing as rows of coalesced filiform papillae. The circumvallate papillae easily identified by the surrounding furrow showed a rather complex and compact pattern of capillary loops of which typical hair-pin shaped tertiary loops dominated the periphery of the papilla. Small grooves or depressions in the vascular network were found to be occupied by rete ridges of the overlying mucosal epithelium

The K526R substitution in viral protein ​PB2 enhances the effects of E627K on influenza virus replication

Host-adaptive strategies, such as the E627K substitution in the ​PB2 protein, are critical for replication of avian influenza A viruses in mammalian hosts. Here we show that mutation ​PB2-K526R is present in some human H7N9 influenza isolates, in nearly 80% of H5N1 human isolates from Indonesia and, in conjunction with E627K, in almost all seasonal H3N2 viruses since 1970. Polymerase complexes containing ​PB2-526R derived from H7N9, H5N1 or H3N2 viruses exhibit increased polymerase activity. ​PB2-526R also enhances viral transcription and replication in cells. In comparison with viruses carrying 627K, H7N9 viruses carrying both 526R and 627K replicate more efficiently in mammalian (but not avian) cells and in mouse lung tissues, and cause greater body weight loss and mortality in infected mice. ​PB2-K526R interacts with nuclear export protein and our results suggest that it contributes to enhance replication for certain influenza virus subtypes, particularly in combination with 627K.published_or_final_versio

Genetic and polygenic risk score analysis for Alzheimer's disease in the Chinese population

Introduction: Dozens of Alzheimer's disease (AD)-associated loci have been identified in European-descent populations, but their effects have not been thoroughly investigated in the Hong Kong Chinese population. Methods: TaqMan array genotyping was performed for known AD-associated variants in a Hong Kong Chinese cohort. Regression analysis was conducted to study the associations of variants with AD-associated traits and biomarkers. Lasso regression was applied to establish a polygenic risk score (PRS) model for AD risk prediction. Results: SORL1 is associated with AD in the Hong Kong Chinese population. Meta-analysis corroborates the AD-protective effect of the SORL1 rs11218343 C allele. The PRS is developed and associated with AD risk, cognitive status, and AD-related endophenotypes. TREM2 H157Y might influence the amyloid beta 42/40 ratio and levels of immune-associated proteins in plasma. Discussion: SORL1 is associated with AD in the Hong Kong Chinese population. The PRS model can predict AD risk and cognitive status in this population

Frequency and patterns of early recanalization after vasectomy

BACKGROUND: Our understanding of early post-vasectomy recanalization is limited to histopathological studies. The objective of this study was to estimate the frequency and to describe semen analysis patterns of early recanalization after vasectomy. METHODS: Charts displaying serial post-vasectomy semen analyses were created using the semen analysis results from 826 and 389 men participating in a randomized trial of fascial interposition (FI) and an observational study of cautery, respectively. In the FI trial, participants were randomly allocated to vas occlusion by ligation and excision with or without FI. In the cautery study, sites used their usual cautery occlusion technique, two with and two without FI. Presumed early recanalization was based on the assessment of individual semen analysis charts by three independent reviewers. Discrepancies were resolved by consensus. RESULTS: Presumed early recanalization was characterized by a very low sperm concentration within two weeks after vasectomy followed by return to large numbers of sperm over the next few weeks. The overall proportion of men with presumed early recanalization was 13% (95% CI 12%–15%). The risk was highest with ligation and excision without FI (25%) and lowest for thermal cautery with FI (0%). The highest proportion of presumed early recanalization was observed among men classified as vasectomy failures. CONCLUSION: Early recanalization, occurring within the first weeks after vasectomy, is more common than generally recognized. Its frequency depends on the occlusion technique performed

overall survival results of ceritinib in alki naive patients with alk rearranged nsclc ascend 3

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