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.     

Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

Magnesium lithospermate B acts against dextran sodiumsulfate-induced ulcerative colitis by inhibiting activation of the NRLP3/ASC/Caspase-1 pathway

This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway.     

杜长海名老中医应用药对治疗功能性便秘的临床经验探析

功能性便秘的发生严重困扰着现代人群,进而影响人们的生活质量。杜长海名老中医认为功能性便秘究其内因为大肠传导失常,外因乃现代人的生活方式、紧张的生活氛围等等,因此杜老结合自己数十年的临床经验,根据中医辨证总结出临床常用药对,对有效治疗功能性便秘进行了经验总结。     

Characterization of membrane occupation and recognition nexus repeat containing 3, meiosis expressed gene 1 binding partner,in mouse male germ cells

Mammalian spermatogenesis is a well-organized process of cell development and differentiation. Meiosis expressed gene 1 (MEIG1) plays an essential role in the regulation of spermiogenesis. To explore potential mechanisms of MEIG1''s action, a yeast two-hybrid screen was conducted, and several potential binding partners were identified; one of them was membrane occupation and recognition nexus repeat containing 3 (MORN3). MORN3 mRNA is only abundant in mouse testis. In the testis, Morn3 mRNA is highly expressed in the spermiogenesis stage. Specific anti-MORN3 polyclonal antibody was generated against N-terminus of the full-length MORN3 protein, and MORN3 expression and localization was examined in vitro and in vivo. In transfected Chinese hamster ovary cells, the antibody specifically crossed-reacted the full-length MORN3 protein, and immunofluorescence staining revealed that MORN3 was localized throughout the cytoplasm. Among multiple mouse tissues, about 25 kDa protein, was identified only in the testis. The protein was highly expressed after day 20 of birth. Immunofluorescence staining on mixed testicular cells isolated from adult wild-type mice demonstrated that MORN3 was expressed in the acrosome in germ cells throughout spermiogenesis. The protein was also present in the manchette of elongating spermatids. The total MORN3 expression and acrosome localization were not changed in the Meig 1-deficient mice. However, its expression in manchette was dramatically reduced in the mutant mice. Our studies suggest that MORN3 is another regulator for spermatogenesis, probably together with MEIG1.     

Predictors of condom use behaviour among male street labourers in urban Vietnam using a modified Information-Motivation-Behavioral Skills (IMB) model

HIV risk in vulnerable groups such as itinerant male street labourers is often examined via a focus on individual determinants. This study provides a test of a modified Information-Motivation-Behavioral Skills (IMB) model to predict condom use behaviour among male street workers in urban Vietnam. In a cross-sectional survey using a social mapping technique, 450 male street labourers from 13 districts of Hanoi, Vietnam were recruited and interviewed. Collected data were first examined for completeness; structural equation modelling was then employed to test the model fit. Condoms were used inconsistently by many of these men, and usage varied in relation to a number of factors. A modified IMB model had a better fit than the original IMB model in predicting condom use behaviour. This modified model accounted for 49% of the variance, versus 10% by the original version. In the modified model, the influence of psychosocial factors was moderately high, whilst the influence of HIV prevention information, motivation and perceived behavioural skills was moderately low, explaining in part the limited level of condom use behaviour. This study provides insights into social factors that should be taken into account in public health planning to promote safer sexual behaviour among Asian male street labourers.     

Eating sweets without the wrapper: perceptions of HIV and sexually transmitted infections among street youth in western Kenya

Street-connected youth in Kenya are a population potentially at risk of HIV transmission, yet little is known about their perceptions and experiences of sexually transmitted infections (STIs), despite their living in an HIV endemic region. We sought to elucidate the language and sociocultural factors rooted in street life that impact on street-connected young people’s knowledge of and perceptions about the prevention and transmission of STIs, and their diagnosis and treatment, using qualitative methods in western Kenya. We conducted a total of 25 in-depth interviews and 5 focus-group discussions with 65 participants aged 11–24 years in Eldoret, Kenya. Thematic analysis was conducted and data were coded according to themes and patterns emergent until saturation was reached. In general, street-connected young people knew of STIs and some of the common symptoms associated with these infections. However, there were many misconceptions regarding transmission and prevention. Gender inequities were prominent, as the majority of men described women as individuals who spread STIs due to unhygienic practices, urination and multiple partners. Due to misconceptions, gender inequity and lack of access to youth-friendly healthcare there is an urgent need for community-based organisations and healthcare facilities to introduce or augment their adolescent sexual and reproductive health programmes for vulnerable young people.     

Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

Efficacy and safety of herbal medicines for idiopathic Parkinson's disease: a systematic review.

The objective of this study is to assess the efficacy and safety of herbal medicines (HMs), as a monotherapy or adjunct therapy, compared to placebo or conventional approaches in the treatment of idiopathic Parkinson's disease (PD). We conducted a systematic review of randomized controlled trials from both conventional and alternative medicine sources. Outcome measures were overall improvement, quality of life, reduction of levodopa dose, and adverse events. Nine studies were included, each testing a different HM. Six of the trials had limited internal validity due to major flaws in design, including the lack of proper randomization; insufficient blinding; unclear inclusive criteria in terms of diagnostic criteria, baseline staging, and duration of disease; lack of proper sample size calculation; and insufficient data analysis. Imbalances in gender and ethnicity among the patients in the included trials were observed. No major adverse events emerged, and no specific pattern was detected from the trials describing such data. In addition to major methodological defects, heterogeneity in (1) HM tested, (2) control treatment, and (3) outcome measure hindered in-depth data analysis and synthesis. Current evidence is insufficient to evaluate the efficacy and safety of various HMs. Further studies with improved trial design and reporting, with assessment on cost-effectiveness, quality of life, and qualitative data are warranted.