Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

Impact of a web-based personally tailored physical activity intervention on depression,anxiety, stress and quality of life: Secondary outcomes from a randomized controlled trial

BackgroundFew studies have investigated the impact of web-based physical activity interventions on mental health outcomes. Therefore, this study examined the impact of a web-based personally tailored physical activity intervention on depression, anxiety, stress and quality of life.Methods501 participants were randomised into either a control group or a pooled intervention condition who received a 3-month web-based personally tailored physical activity intervention. Previously, this intervention has demonstrated to improve self-reported physical activity, but not device-measured physical activity. At baseline, 3- and 9-months, depression, anxiety and stress were assessed using the DASS21, and quality of life was assessed using the SF-12V2. General linear mixed models examined differences between groups over time.ResultsMost participants (>80%) reported normal levels of depression, anxiety or stress. Relative to baseline levels, significant reductions of depression, anxiety, stress and the SF12 mental health component were observed in the pooled intervention group at 3 and 9 months. Relative to the control group, significant reductions were observed in the pooled intervention group for depression and stress (3-months only) and anxiety (3- and 9-months), but not quality of life.ConclusionA web-based physical activity intervention can result in positive mental health outcomes, even in the absence of device-measured physical activity improvements. However, these findings need to be confirmed in future studies.Trial registration numberACTRN12615000057583.     

沉默TRIM23基因抑制骨肉瘤细胞的增殖

目的 探讨TRIM23基因对骨肉瘤细胞增殖能力的影响.方法 应用Western blot实验检测TRIM23基因在骨肉瘤细胞中的表达;应用shRNA质粒转染骨肉瘤细胞系U2OS,通过MTT与平板克隆形成实验评估细胞增殖能力;应用Westernblot实验检测U2OS细胞Akt/P53/P21通路的表达改变.结果 TRIM23蛋白在骨肉瘤细胞中的表达高于成骨细胞;沉默TRIM23基因可以抑制骨肉瘤细胞的增殖能力;沉默TRIM23基因下调P-Akt表达,但总Akt的表达无明显改变,上调P53与P21的表达.结论 TRIM23在骨肉瘤细胞中表达升高,TRIM23能通过调节Akt/P53/P21通路影响骨肉瘤细胞的增殖.     

粪便SEPT-9和miRNA-34b/c基因甲基化检测在大肠肿瘤筛查中的临床应用

目的 评估检测大肠肿瘤患者粪便中SEPT-9和微RNA（miRNA）-34b/c基因甲基化对大肠肿瘤筛查的临床性能。方法 采用病例对照研究方法,使用甲基化敏感性高分辨率熔解曲线法检测大肠肿瘤患者（大肠癌组35例、大肠腺瘤组47例）和正常对照人群（正常对照组52名）粪便中SEPT-9和miRNA-34b/c基因是否存在甲基化,来评估其筛查大肠肿瘤的性能。结果 大肠癌组SEPT-9和miRNA-34b/c基因的甲基化阳性率分别为68.6%、71.4%,大肠腺瘤组分别为57.4%、63.8%,正常对照组分别为9.6%、11.5%。3组的SEPT-9、miRNA-34b/c基因甲基化阳性率比较差异均有统计学意义（²_SEPT-9 = 37.185,²_miRNA-34b/c = 40.040,P均< 0.001）,利用Bonferroni法进行两两比较,大肠癌组和大肠腺瘤组的甲基化阳性率比较差异无统计学意义,两者与正常对照组比较差异均有统计学意义（P均< 0.001）。3组联合检测SEPT-9和miRNA-34b/c基因的甲基化阳性率为88.6%、76.6%、13.5%,大肠癌组和大肠腺瘤组联合检测的甲基化阳性率均高于SEPT-9单基因检测和miRNA-34b/c单基因检测（P均< 0.05）。结论 检测粪便中SEPT-9和miRNA-34b/c基因甲基化具有效好的大肠肿瘤筛查性能,或许可作为大规模人群筛查大肠肿瘤新的生物标志物组合;多基因甲基化联合检测筛查的性能优于单基因。     

An extensive pattern of atypical neural speech-sound discrimination in newborns at risk of dyslexia

ObjectiveIdentifying early signs of developmental dyslexia, associated with deficient speech-sound processing, is paramount to establish early interventions. We aimed to find early speech-sound processing deficiencies in dyslexia, expecting diminished and atypically lateralized event-related potentials (ERP) and mismatch responses (MMR) in newborns at dyslexia risk.MethodsERPs were recorded to a pseudoword and its variants (vowel-duration, vowel-identity, and syllable-frequency changes) from 88 newborns at high or no familial risk. The response significance was tested, and group, laterality, and frontality effects were assessed with repeated-measures ANOVA.ResultsAn early positive and right-lateralized ERP component was elicited by standard pseudowords in both groups, the response amplitude not differing between groups. Early negative MMRs were absent in the at-risk group, and MMRs to duration changes diminished compared to controls. MMRs to vowel changes had significant laterality × group interactions resulting from right-lateralized MMRs in controls.ConclusionsThe MMRs of high-risk infants were absent or diminished, and morphologically atypical, suggesting atypical neural speech-sound discrimination.SignificanceThis atypical neural basis for speech discrimination may contribute to impaired language development, potentially leading to future reading problems.     

Prothymosin‐α enhances phosphatase and tensin homolog expression and binds with tripartite motif‐containing protein 21 to regulate Kelch‐like ECH‐associated protein 1/nuclear factor erythroid 2‐related factor 2 signaling in human bladder cancer

Prothymosin‐α (PTMA) is a small, acidic protein that is usually transported into the nucleus and involves many cellular and immunological functions. Previous studies demonstrated that aberrant location of PTMA expression exists in human bladder cancer, but the role of PTMA protein expression remains elusive. In this study, we created ectopic nuclear or cytoplasmic PTMA expression in human bladder cancer cells by infecting lentiviruses carrying wild type or deleted nuclear localization signal of the PTMA gene. The in vivo tumorigenesis assay showed PTMA protein with deleted nuclear localization signal promotes J82 xenograft tumor growth in mice and shortens their survival more so than the wild type. Chromatin immunoprecipitation showed that wild‐type PTMA protein binds to the PTEN promoter and enhances phosphatase and tensin homolog (PTEN) expression. Through immunoblot proteomics and in vivo ubiquitination studies, PTMA protein can bind with tripartite motif‐containing protein 21 (TRIM21) and block its ubiquitination. Also, TRIM21 can downregulate both forms of PTMA protein. In human bladder tumors, loss of nuclear PTMA expression was an unfavorable prognostic indicator for shorter disease‐free survival (hazard ratio, 1.54; P = 0.009). Our data support that nuclear PTMA protein serves as a tumor suppressor in bladder cancer through upregulating PTEN and orchestrating TRIM21 for the regulation of Nrf2 signaling.