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.     

Profilin 1, negatively regulated by microRNA-19a-3p,serves as a tumor suppressor in human hepatocellular carcinoma

Profilin 1 (PFN1) is a critical actin-regulatory protein; however, its functional role in hepatocellular carcinoma (HCC) progression remains to be further elucidated. In the present study, we observed that the expression levels of PFN1 were significantly decreased in HCC tissues and cell lines. Low PFN1 expression was significantly correlated with aggressive clinicopathological characteristics and poor prognosis of HCC patients. Further in vitro experiments demonstrated that overexpression of PFN1 remarkably inhibited the proliferation, migration, invasion and EMT of HCC cells. Moreover, we also found that PFN1 was a direct target gene of miR-19a-3p, and in HCC tissues, and there was a significantly inverse correlation between PFN1 mRNA and miR-19a-3p expression. Collectively, our results showed that PFN1 functions as a tumor suppressor in HCC, and might serve as a diagnostic and therapeutic target for HCC patients.     

Liver-specific knockout of histone methyltransferase G9a impairs liver maturation and dysregulates inflammatory,cytoprotective, and drug-processing genes

1. Methyltransferase G9a is essential for a key gene silencing mark, histone H3 dimethylation at lysine-9 (H3K9me2). Hepatic G9a expression is down-regulated by xenobiotics and diabetes. However, little is known about the role of G9a in liver. Thus, we generated mice with liver-specific knockout (Liv-KO) of G9a.

2. Adult G9a Liv-KO mice had marked loss of H3K9me2 proteins in liver, without overt liver injury or infiltration of inflammatory cells. However, G9a-null livers had ectopic induction of certain genes normally expressed in neural and immune systems. Additionally, G9a-null livers had moderate down-regulation of cytoprotective genes, markedly altered expression of certain important drug-processing genes, elevated endogenous reactive oxygen species, induction of ER stress marker Chop, but decreased glutathione and nuclear Nrf2. microRNA-383, a negative regulator of the PI3K/Akt pathway, was strongly induced in G9a Liv-KO mice. After LPS treatment, G9a Liv-KO mice had aggravated lipid peroxidation and proinflammatory response.

3. Taken together, the present study demonstrates that G9a regulates liver maturation by silencing neural and proinflammatory genes but maintaining/activating cytoprotective and drug-processing genes, in which the G9a/miR-383/PI3K/Akt/Nrf2?(Chop) pathways may play important roles. G9a deficiency due to genetic polymorphism and/or environmental exposure may alter xenobiotic metabolism and aggravate inflammation and liver dysfunction.

     

Long-term changes in dietary intake and its association with eating-related problems after gastric bypass in adolescents

BackgroundRoux-en-Y gastric bypass (RYGB) surgery is an established, effective treatment for severe adolescent obesity. Long-term dietary intake and the relationship to eating-related problems are scarcely evaluated in this population.ObjectivesAssess changes in dietary intake in adolescents after RYGB and explore associations between dietary intake and eating-related problems.Setting: Multicenter study in Swedish university hospitals.MethodDiet history, binge eating scale (BES), and Three-Factor Eating Questionnaire were assessed preoperatively and 1, 2, and 5 years after RYGB in 85 adolescents (67% female) aged 16.5 ± 1.2 years with a body mass index (BMI) of 45.5 ± 6.0 kg/m² and compared with control individuals at 5 years.ResultsFive-year BMI change was –28.6% ± 12.7% versus +9.9% ± 18.9% in RYGB patients versus control individuals (P < .001). Through 5 years, RYGB adolescents reported reduced energy intake, portion size of cooked meals at dinner, and milk/yoghurt consumption (P < .01). The BES scores were 9.3 ± 8.3 versus 13.4 ± 10.5 in RYGB patients versus control individuals (P = .04). Association between BES score and energy intake was stronger in control individuals (r = .27 versus r = .62 in RYGB patients versus control individuals, P < .001). At 5 years, lower energy intake was associated with greater BMI loss in all adolescents (r = .33, P < .001). Higher scores in BES and uncontrolled and emotional eating were associated with higher energy intake, cooked meals, candies/chocolates, cakes/cookies, desserts, and sugary drinks (r > .23, P < .04) and lower intake of fruits/berries (r = –.32, P = .044). A higher score in cognitive restraint was associated with a higher intake of cereals and fruits/berries (r > .22, P < .05) and a lower intake of sugary drinks (r = –.24, P < .03).ConclusionTo support optimization of long-term outcomes in adolescent RYGB patients, it is important to provide management strategies to reduce energy intake. Monitoring eating-related problems could identify potential individuals at risk of poor weight loss and to initiate treatment interventions.     

Characterization of Moyamoya and Middle Cerebral Artery Diseases by Carotid Canal Diameter and RNF213 p.R4810K Genotype

ObjectivesIt is sometimes difficult to differentiate middle cerebral artery disease from moyamoya disease because the two can present similarly yet have different treatment strategies. We investigated whether the presence of a narrow carotid canal and the RNF213 mutation can help differentiate between the two phenotypes.Population and MethodsWe analyzed 78 patients with moyamoya disease, 27 patients with middle cerebral artery disease, and 79 controls from 2 facilities. The carotid canal diameter was measured using computed tomography. The p.R4810K mutation was genotyped by TaqMan assay. A receiver operating characteristics analysis was performed to assess the significance of the carotid canal diameter for the accurate diagnosis of moyamoya disease.ResultsThe carotid canal diameter was significantly narrower in patients with moyamoya disease than in controls. The optimal cutoff values were 5.0 mm for adult males and 4.5 mm for adult females and children (sensitivity: 0.82; specificity: 0.92). Among the patients with middle cerebral artery disease, 18.5% and 25.0% of the affected hemispheres had the p.R4810K mutation and narrow canal (i.e., below the cutoff), respectively, whereas only 3.1% of those had both. Contrastingly, 68.8% of the affected hemispheres in patients with moyamoya disease had both these characteristics. Among the patients with moyamoya disease, those with the p.R4810K mutation tended to have narrower carotid canals.ConclusionsAlthough the presence of a narrow carotid canal or the p.R4810K mutation alone could not be used to distinguish those with moyamoya disease from those with middle cerebral artery disease, the combination of these factors could better characterize the two phenotypes.