Severe acute respiratory syndrome coronavirus 2 did not replicate efficiently in 13 bat cell lines, whereas severe acute respiratory syndrome coronavirus replicated efficiently in kidney cells of its ...ancestral host, the Rhinolophus sinicus bat, suggesting different evolutionary origins. Structural modeling showed that RBD/RsACE2 binding may contribute to the differential cellular tropism.
This study examined the epidemiology of trauma exposure (TE) and posttraumatic stress disorder (PTSD) among community‐dwelling Chinese adults in Hong Kong. Multistage stratification sampling design ...was used, and 5,377 participants were included. In Phase 1, TE, probable PTSD (p‐PTSD), and psychiatric comorbid conditions were examined. In Phase 2, the Structured Clinical Interview for the DSM‐IV (SCID‐I) was used to determine the weighted diagnostic prevalence of lifetime full PTSD. Disability level and health service utilization were studied. The findings showed that the weighted prevalence of TE was 64.8%, and increased to 88.7% when indirect TE types were included, with transportation accidents (50.8%) reported as the most common TE. The prevalence of current p‐PTSD among participants with TE was 2.9%. Results of logistic regression suggested that nine specific trauma types were significantly associated with p‐PTSD; among this group, severe human suffering, sexual assault, unwanted or uncomfortable sexual experience, captivity, and sudden and violent death carried the greatest risks for developing PTSD, odds ratio (OR) = 2.32–2.69. The occurrence of p‐PTSD was associated with more mental health burdens, including (a) sixfold higher rates for any past‐week common mental disorder, OR = 28.4, (b) more mental health service utilization, p < .001, (c) poorer mental health indexes in level of symptomatology, suicide ideation and functioning, p < .001, and (d) more disability, ps < .001–p = .014. The associations found among TE, PTSD, and health service utilization suggest that both TE and PTSD should be considered public health concerns.
Resumen
Spanish s by Asociación Chilena de Estrés Traumático (ACET)
La Encuesta Hong Kong sobre la Epidemiología de las Experiencias Traumáticas y el Trastorno de Estrés Postraumático
ENCUESTA HONG KONG SOBRE EXPERIENCIA TRAUMÁTICA Y TEPT
Este estudio examinó la epidemiología de la experiencia traumática (ET) y el trastorno por estrés postraumático (TEPT) entre adultos chinos que viven en comunidades en Hong Kong. Se utilizó un diseño de muestreo de estratificación multietapa y se incluyeron 5,377 participantes. En la Fase 1, ET, probable TEPT (p‐TEPT) y enfermedades psiquiátricas comórbidas fueron examinadas. En la Fase 2, se utilizó la Entrevista Clínica Estructurada para el DSM‐IV (SCID‐I) para determinar la prevalencia de diagnóstico ponderado de TEPT completo a lo largo de la vida. Se estudiaron el nivel de discapacidad y la utilización de los servicios de salud. Los resultados mostraron que la prevalencia ponderada de ET fue del 64.8% y aumentó al 88.7% cuando se incluyeron tipos indirectos de ET, tales como accidentes de transporte (50.8%), los que fueron reportados como el ET más común. La prevalencia actual de p‐TEPT entre los participantes con ET fue del 2.9%. Los resultados de la regresión logística sugirieron que nueve tipos específicos de trauma fueron significativamente asociados con p‐PTSD; entre este grupo encontramos: sufrimiento humano severo, agresión sexual, experiencia sexual no deseada o incómoda, cautiverio y la muerte inesperada y violenta acarrearon el mayor riesgo para desarrollar TEPT, odds ratio (OR) = 2.32–2.69. La aparición de p‐PTSD fue asociado con más riesgo de problemas de salud mental, que incluyen (a) tasas 6 veces más altas para cualquier trastorno mental común experimentado la última semana, OR = 28.4 (b) más utilización de servicios de salud mental, p <.001, (c) índices de salud mental más pobres a nivel de sintomatología, ideación y funcionamiento suicida, p <.001, y (d) más discapacidad, p <.001 – p = .014. Las asociaciones encontradas entre ET, TEPT, y la utilización de los servicios de salud sugieren que tanto el ET como el TEPT deben considerarse una preocupación de salud pública.
抽象
Traditional and Simplified Chinese s by the Asian Society for Traumatic Stress Studies (AsianSTSS)
簡體及繁體中文撮要由亞洲創傷心理研究學會翻譯
The Hong Kong Survey on the Epidemiology of Traumatic Experience and Posttraumatic Stress Disorder
Traditional Chinese
標題: 香港的創傷經歷及創傷後壓力症流行病學調查
撮要: 本研究檢視在香港居於社區內的中國裔成人, 當中的創傷經歷(TE)及創傷後壓力症(PTSD)的流行病學。我們採用多段分層抽樣法, 檢視5,377名樣本。第一階段檢視TE、很有可能患PTSD的個案(p‐PTSD), 及共病精神狀況。第二階段採用DSM‐IV結構性臨床會談量表(SCID‐I), 來找出終生患完整PTSD的加權診斷普遍率。我們亦檢視殘疾水平及治療服務使用率。結果反映, TE的加權普遍率為64.8%。當我們把間接的TE類別也包含在內時, TE的加權普遍率提升至88.7%, 當中交通意外(50.8%)屬最普遍的TE。有TE的樣本中, 當前有p‐PTSD的普遍率為2.9%。邏輯迴歸分析顯示, 有9種特殊的創傷類別跟p‐PTSD顯著地有關。當中, 嚴重的痛苦、性侵犯、非自願或令人不安的性經驗、被囚禁, 及突然而且暴力的死亡, 有最大的風險導致PTSD產生(勝算比(OR) = 2.32–2.69)。p‐PTSD跟精神健康負擔較大有關, 包括(a) 過去一星期有任何普遍精神疾病的比率高出六倍(OR = 28.4)、(b) 更常使用心理治療服務(p < .001)、(c) 症狀學、自殺意念、功能運作方面的健康指數較差(p < .001)、(d) 較大程度的殘疾(ps < .001–p = .014)。TE、PTSD與治療服務使用的關連反映, TE 與PTSD應視為公眾健康問題。
Simplified Chinese
标题: 香港的创伤经历及创伤后压力症流行病学调查
撮要: 本研究检视在香港居于小区内的中国裔成人, 当中的创伤经历(TE)及创伤后压力症(PTSD)的流行病学。我们采用多段分层抽样法, 检视5,377名样本。第一阶段检视TE、很有可能患PTSD的个案(p‐PTSD), 及共病精神状况。第二阶段采用DSM‐IV结构性临床会谈量表(SCID‐I), 来找出终生患完整PTSD的加权诊断普遍率。我们亦检视残疾水平及治疗服务使用率。结果反映, TE的加权普遍率为64.8%。当我们把间接的TE类别也包含在内时, TE的加权普遍率提升至88.7%, 当中交通意外(50.8%)属最普遍的TE。有TE的样本中, 当前有p‐PTSD的普遍率为2.9%。逻辑回归分析显示, 有9种特殊的创伤类别跟p‐PTSD显著地有关。当中, 严重的痛苦、性侵犯、非自愿或令人不安的性经验、被囚禁, 及突然而且暴力的死亡, 有最大的风险导致PTSD产生(胜算比(OR) = 2.32–2.69)。p‐PTSD跟精神健康负担较大有关, 包括(a) 过去一星期有任何普遍精神疾病的比率高出六倍(OR = 28.4)、(b) 更常使用心理治疗服务(p < .001)、(c) 症状学、自杀意念、功能运作方面的健康指数较差(p < .001)、(d) 较大程度的残疾(ps < .001–p = .014)。TE、PTSD与治疗服务使用的关连反映, TE 与PTSD应视为公众健康问题。
Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are increasing in prevalence but lack targeted therapeutics. Although the pathological ...mechanisms behind these diseases remain unclear, both ALS and FTD are characterized pathologically by aberrant protein aggregation and inclusion formation within neurons, which correlates with neurodegeneration. Notably, aggregation of several key proteins, including TAR DNA binding protein of 43 kDa (TDP-43), superoxide dismutase 1 (SOD1), and tau, have been implicated in these diseases. Proteomics methods are being increasingly applied to better understand disease-related mechanisms and to identify biomarkers of disease, using model systems as well as human samples. Proteomics-based approaches offer unbiased, high-throughput, and quantitative results with numerous applications for investigating proteins of interest. Here, we review recent advances in the understanding of ALS and FTD pathophysiology obtained using proteomics approaches, and we assess technical and experimental limitations. We compare findings from various mass spectrometry (MS) approaches including quantitative proteomics methods such as stable isotope labeling by amino acids in cell culture (SILAC) and tandem mass tagging (TMT) to approaches such as label-free quantitation (LFQ) and sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) in studies of ALS and FTD. Similarly, we describe disease-related protein-protein interaction (PPI) studies using approaches including immunoprecipitation mass spectrometry (IP-MS) and proximity-dependent biotin identification (BioID) and discuss future application of new techniques including proximity-dependent ascorbic acid peroxidase labeling (APEX), and biotinylation by antibody recognition (BAR). Furthermore, we explore the use of MS to detect post-translational modifications (PTMs), such as ubiquitination and phosphorylation, of disease-relevant proteins in ALS and FTD. We also discuss upstream technologies that enable enrichment of proteins of interest, highlighting the contributions of new techniques to isolate disease-relevant protein inclusions including flow cytometric analysis of inclusions and trafficking (FloIT). These recently developed approaches, as well as related advances yet to be applied to studies of these neurodegenerative diseases, offer numerous opportunities for discovery of potential therapeutic targets and biomarkers for ALS and FTD.
Spinocerebellar ataxia type 3 (SCA3, also known as Machado Joseph disease) is a fatal neurodegenerative disease caused by the expansion of the trinucleotide repeat region within the ATXN3/MJD gene. ...Mutation of ATXN3 causes formation of ataxin‐3 protein aggregates, neurodegeneration, and motor deficits. Here we investigated the therapeutic potential and mechanistic activity of sodium butyrate (SB), the sodium salt of butyric acid, a metabolite naturally produced by gut microbiota, on cultured SH‐SY5Y cells and transgenic zebrafish expressing human ataxin‐3 containing 84 glutamine (Q) residues to model SCA3. SCA3 SH‐SY5Y cells were found to contain high molecular weight ataxin‐3 species and detergent‐insoluble protein aggregates. Treatment with SB increased the activity of the autophagy protein quality control pathway in the SCA3 cells, decreased the presence of ataxin‐3 aggregates and presence of high molecular weight ataxin‐3 in an autophagy‐dependent manner. Treatment with SB was also beneficial in vivo, improving swimming performance, increasing activity of the autophagy pathway, and decreasing the presence of insoluble ataxin‐3 protein species in the transgenic SCA3 zebrafish. Co‐treating the SCA3 zebrafish with SB and chloroquine, an autophagy inhibitor, prevented the beneficial effects of SB on zebrafish swimming, indicating that the improved swimming performance was autophagy‐dependent. To understand the mechanism by which SB induces autophagy we performed proteomic analysis of protein lysates from the SB‐treated and untreated SCA3 SH‐SY5Y cells. We found that SB treatment had increased activity of Protein Kinase A and AMPK signaling, with immunoblot analysis confirming that SB treatment had increased levels of AMPK protein and its substrates. Together our findings indicate that treatment with SB can increase activity of the autophagy pathway process and that this has beneficial effects in vitro and in vivo. While our results suggested that this activity may involve activity of a PKA/AMPK‐dependent process, this requires further confirmation. We propose that treatment with sodium butyrate warrants further investigation as a potential treatment for neurodegenerative diseases underpinned by mechanisms relating to protein aggregation including SCA3.
This study demonstrated that sodium butyrate treatment can induce activity of the autophagy protein quality control pathway. Treating transgenic zebrafish or an SH‐SY5Y cell model of spinocerebellar ataxin‐3 with sodium butyrate increased activity of the autophagy pathway, decreased presence of ataxin‐3 aggregates and improved swimming performance in the zebrafish. The study includes proteomic analysis seeking to identify mechanisms of autophagy induction.
Effect of Kt/V on survival and clinical outcome in CAPD patients in a randomized prospective study.
There has been a lack of randomized control study on the effect of Kt/V on patient outcome. This ...interventional study was designed to examine the effect of Kt/V on continuous ambulatory peritoneal dialysis (CAPD) patients' clinical outcome and nutritional status in a randomized prospective manner.
A total of 320 new CAPD patients with baseline renal Kt/V <1.0 were recruited from six centers in Hong Kong and were randomized into three Kt/V targets: group A, 1.5 to 1.7; group B, 1.7 to 2.0; and group C,>2.0. Kt/V and nutritional status were assessed every 6months and dialysis prescription adjusted accordingly. Nutritional assessment included serum albumin and composite nutritional index (CNI). Patients were allowed to withdraw at the discretion of their physicians or themselves.
Total Kt/V were significantly different between groups (P = 0.000) and the difference was contributed by peritoneal Kt/V only. The overall 2-year patient survival was 84.9%. There was no statistical difference in patient survival among the three groups (2-year survival in group A, 87.3%; group B, 86.1%; and group C, 81.5%). However, there were more patients withdrawn by physicians in group A (group A, 16; group B, 7; and group C, 6; P = 0.023). Total Kt/V or Kt did not significantly affect survival after adjustment to age and diabetes. There was no difference in serum albumin, CNI scores, and hospitalization rate, but there were more patients in group A requiring erythropoietin (EPO) treatment after 1year.
Patients with total Kt/V maintained below 1.7 had significantly more clinical problems and severe anemia but there was no difference in outcome demonstrated for patients with Kt/V maintained above 2.0 and between 1.7 and 2.0. We recommended that the minimal target of total Kt/V should be above 1.7.
The past decade has seen a rapid acceleration in the discovery of new genetic causes of ALS, with more than 20 putative ALS-causing genes now cited. These genes encode proteins that cover a diverse ...range of molecular functions, including free radical scavenging (e.g., SOD1), regulation of RNA homeostasis (e.g., TDP-43 and FUS), and protein degradation through the ubiquitin-proteasome system (e.g., ubiquilin-2 and cyclin F) and autophagy (TBK1 and sequestosome-1/p62). It is likely that the various initial triggers of disease (either genetic, environmental and/or gene-environment interaction) must converge upon a common set of molecular pathways that underlie ALS pathogenesis. Given the complexity, it is not surprising that a catalog of molecular pathways and proteostasis dysfunctions have been linked to ALS. One of the challenges in ALS research is determining, at the early stage of discovery, whether a new gene mutation is indeed disease-specific, and if it is linked to signaling pathways that trigger neuronal cell death. We have established a proof-of-concept proteogenomic workflow to assess new gene mutations, using CCNF (cyclin F) as an example, in cell culture models to screen whether potential gene candidates fit the criteria of activating apoptosis. This can provide an informative and time-efficient output that can be extended further for validation in a variety of
and
models and/or for mechanistic studies. As a proof-of-concept, we expressed cyclin F mutations (K97R, S195R, S509P, R574Q, S621G) in HEK293 cells for label-free quantitative proteomics that bioinformatically predicted activation of the neuronal cell death pathways, which was validated by immunoblot analysis. Proteomic analysis of induced pluripotent stem cells (iPSCs) derived from patient fibroblasts bearing the S621G mutation showed the same activation of these pathways providing compelling evidence for these candidate gene mutations to be strong candidates for further validation and mechanistic studies (such as E3 enzymatic activity assays, protein-protein and protein-substrate studies, and neuronal apoptosis and aberrant branching measurements in zebrafish). Our proteogenomics approach has great utility and provides a relatively high-throughput screening platform to explore candidate gene mutations for their propensity to cause neuronal cell death, which will guide a researcher for further experimental studies.
High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We ...estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010.
We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates.
In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1–11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6–7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain.
The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases.
UK Medical Research Council, US National Institutes of Health.
Human movements in the workspace usually have non-negligible relations with air quality parameters (e.g., CO 2 , PM2.5, and PM10). We establish a system to monitor indoor human mobility with air ...quality and assess the interrelationship between these two types of time series data. More specifically, a sensor network was designed in indoor environments to observe air quality parameters continuously. Simultaneously, another sensing module detected participants' movements around the study areas. In this module, modern data analysis and machine learning techniques have been applied to reconstruct the trajectories of participants with relevant sensor information. Finally, a further study revealed the correlation between human indoor mobility patterns and indoor air quality parameters. Our experimental results demonstrate that human movements in different environments can significantly impact air quality during busy hours. With the results, we propose recommendations for future studies.
Cefazolin plus netilmicin versus cefazolin plus ceftazidime for treating CAPD peritonitis: Effect on residual renal function.
The International Society for Peritoneal Dialysis (ISPD) treatment ...guidelines for continuous ambulatory peritoneal dialysis (CAPD) peritonitis 2000 recommended the use of cefazolin plus ceftazidime as the initial empirical therapy in patients with residual renal function (RRF). However, this treatment regimen has not been compared with the conventional regimen of cefazolin plus netilmicin in prospective, randomized controlled trials.
Stable CAPD patients who developed clinical evidence of peritonitis were randomized to receive intraperitoneal (i.p.) cefazolin plus netilmicin or cefazolin plus ceftazidime once daily in the long dwell for 14 days. For patients with RRF (>1 mL/minute) before entry into the study (N = 50), RRF and 24-hour urine volume were measured at days 1, 14, and 42 after commencement of i.p. antibiotic treatment.
One hundred and two patients were recruited into the study. The primary cure rates of i.p. cefazolin plus netilmicin and cefazolin plus ceftazidime were 66.7% and 64.7%, respectively. The overall cure rate for the 2 treatment regimens was 82.3% for both. Seven patients (14%) from each treatment group required removal of the dialysis catheters due to treatment failure. Relapse of peritonitis occurred in 2 patients (4%) in both treatment groups. Thirty-six patients with RRF at baseline achieved primary cure of their peritonitis by the assigned antibiotics. In this subgroup of patients, their RRF and daily urine volume showed significant reduction at day 14 and returned to near baseline values at day 42. The degree of reduction in RRF and urine volume did not differ significantly between the patients treated with cefazolin plus netilmicin and cefazolin plus ceftazidime.
Intraperitoneal cefazolin plus netilmicin and cefazolin plus ceftazidime have similar efficacy as empirical treatment for CAPD peritonitis. In CAPD patients with RRF, significant but reversible reduction in RRF and 24-hour urine volume could occur after an episode of peritonitis, despite successful treatment by i.p. antibiotics. The effect of i.p. cefazolin plus netilmicin, or i.p. cefazolin plus ceftazidime on RRF in CAPD patients with peritonitis does not appear to be different. Our findings do not support the routine use of cefazolin and ceftazidime as the empirical treatment for CAPD peritonitis.
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