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BackgroundLow-and middle-income countries mostly have ageing populations with many unmet economic, social, or health-related needs, Vietnam being an example. Community-based support in Vietnam, organized as Intergenerational Self-Help Clubs (ISHCs) based on the Older People Associations (OPA) model, can help to meet these needs by the provision of services for various aspects of life. This study aims to assess the implementation of the ISHCs and whether successful implementation is associated with more member-reported positive health.MethodsWe used the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to evaluate the implementation using multiple data sources: ISHC board surveys (n = 97), ISHC member surveys (n = 5,080 in 2019 and n = 5,555 in 2020), focus group discussions (6; n = 44), and interviews with members and board leaders (n = 4).ResultsReach ranged between 46 and 83% of ISHCs reaching target groups, with a majority of women and older people participating. Regarding Effectiveness, members indicated high satisfaction with the ISHCs. Adoption scores were high, with 74%–99% for healthcare and community support activities, and in 2019, higher adoption scores were associated with more members reporting good positive health. In 2020, reported positive health slightly decreased, probably due to the influence of the COVID-19 pandemic. A total of 61 ISHCs had consistent or improving Implementation from 2019 to 2020, and confidence in Maintenance was high.ConclusionThe implementation of the OPA model in Vietnam is promising regarding its promotion of health and may help to tackle the needs of an ageing population. This study further shows that the RE-AIM framework helps to assess community health promotion approaches.

Clear cell ovarian carcinoma (CCOC) is an aggressive malignancy affecting younger women. Despite ovarian cancer subtypes having diverse molecular and clinical characteristics, the mainstay of treatment for advanced stage disease remains cytotoxic chemotherapy. Late stage CCOC is resistant to conventional chemotherapy, which means a suboptimal outcome for patients affected. Despite detailed genomic, epigenomic, transcriptomic, and proteomic characterisation, subtype‐specific treatment for CCOC has shown little progress. The unique glycogen accumulation defining CCOC suggests altered metabolic pathway activity and dependency. This study presents the first metabolomic landscape of ovarian cancer subtypes, including 42 CCOC, 20 high‐grade serous and 21 endometrioid ovarian carcinomas, together comprising the three most common ovarian carcinoma subtypes. We describe a distinct metabolomic landscape of CCOC compared with other ovarian cancer subtypes, including alterations in energy utilisation and cysteine metabolism. In addition, we identify CCOC‐specific alterations in metabolic pathways including serine biosynthesis and ROS‐associated pathways that could serve as potential therapeutic targets. Our study provides the first in‐depth study into the metabolome of ovarian cancers and a rich resource to support ongoing research efforts to identify subtype‐specific therapeutic targets that could improve the dismal outcome for patients with this devastating malignancy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

AimsDedifferentiated endometrial carcinoma (DDEC) is defined by the presence of an undifferentiated carcinoma together with an endometrioid carcinoma. Inactivation of SMARCA4 (BRG1) and inactivation of SMARCB1 (INI1) were recently described as potential mechanisms underlying the histological dedifferentiation. The aim of this study was to characterize the immunophenotypic features of DDECs, particularly in cases with prototypical histological and molecular features (BRG1/INI1 deficiency).Methods and resultsWe evaluated PAX8, oestrogen receptor (ER) and p53 immunostaining in the endometrioid and the undifferentiated components of 20 BRG1/INI1-deficient DDECs and 15 BRG1/INI1-intact DDECs, and compared the results with those of 23 grade 3 endometrioid carcinomas. The differentiated endometrioid component was positive for PAX8 and/or ER in 19 of 20 BRG1/INI1-deficient DDECs, whereas the corresponding undifferentiated component of all 20 tumours showed a complete absence of PAX8 and ER staining. All except one of the BRG1/INI1-deficient tumours showed a wild-type p53 staining pattern. PAX8 and ER expression in the undifferentiated component was absent in 67% and 80% of BRG1/INI1-intact DDECs, respectively, whereas 47% of the BRG1/INI1-intact DDECs showed a mutated p53 staining pattern. In comparison, absent PAX8 expression and absent ER expression were each observed in the more solid area of 48% and 48% of grade 3 endometrioid carcinomas.ConclusionsThe consistent absence of PAX8 and ER expression in molecularly defined (BRG1/INI1-deficient) DDECs suggests that the loss of PAX8 and ER expression is a fundamental feature of dedifferentiation. The frequent findings of a mutated p53 staining pattern in BRG1/INI1-intact DDECs indicate that BRG1/INI1-intact DDECs may be biologically different from BRG1/INI1-deficient tumours.

Dedifferentiated endometrial carcinoma is an aggressive type of endometrial cancer that contains a mix of low-grade endometrioid and undifferentiated carcinoma components. We performed targeted sequencing of eight dedifferentiated carcinomas and identified somatic frameshift/nonsense mutations in SMARCA4, a core ATPase of the switch/sucrose non-fermenting (SWI/SNF) complex, in the undifferentiated components of four tumors. Immunohistochemical analysis confirmed the loss of SMARCA4 in the undifferentiated component of these four SMARCA4-mutated cases, whereas the corresponding low-grade endometrioid component showed retained SMARCA4 expression. An expanded survey of other members of the SWI/SNF complex showed SMARCB1 loss in the undifferentiated component of two SMARCA4-intact tumors, and all SMARCA4- or SMARCB1-deficient tumors showed concomitant loss of expression of SMARCA2. We subsequently examined the expression of SMARCA2, SMARCA4, and SMARCB1 in an additional set of 22 centrally reviewed dedifferentiated carcinomas and 31 grade 3 endometrioid carcinomas. Combining the results from the index and the expansion set, 15 of 30 (50%) of the dedifferentiated carcinomas examined showed either concurrent SMARCA4 and SMARCA2 loss (37%) or concurrent SMARCB1 and SMARCA2 loss (13%) in the undifferentiated component. The loss of SMARCA4 or SMARCB1 was mutually exclusive. All 31 grade 3 endometrioid carcinomas showed intact expression of these core SWI/SNF proteins. The majority (73%) of the SMARCA4/SMARCA2-deficient and half of SMARCB1/SMARCA2-deficient undifferentiated component developed in a mismatch repair-deficient molecular context. The observed spatial association between SWI/SNF protein loss and histologic dedifferentiation suggests that inactivation of these core SWI/SNF proteins may contribute to the development of dedifferentiated endometrial carcinoma.

Abstract Uterine carcinosarcomas (UCSs) are highly aggressive malignancies associated with poor prognoses and limited treatment options. These tumors are hypothesized to develop from the endometrial adenocarcinoma (EAC) through epithelial-mesenchymal transition (EMT). We test this long-standing hypothesis by depleting miR-200, a family of microRNAs critical for EMT, in EAC cell lines. Our data suggest that UCSs do not develop from EACs via EMT. Clinically more relevant, we show that miR-200 expression in UCS cells induces a robust mesenchymal-epithelial transition (MET). Using in vitro and murine xenograft models, we demonstrate decreased growth and aggressiveness of miR-200-overexpressing UCS cell lines. Whole transcriptome analysis confirmed changes consistent with an MET and also revealed changes in angiogenic genes expression. Finally, by treatment of UCS-xenografted mice with miR-200c incorporated in DOPC nanoliposomes, we demonstrate anti-tumor activities. These findings suggest that ectopic miR-200 expression using advanced microRNA therapeutics may be a potential treatment approach for patients with UCS.

A 57-year-old woman who had a history of osteoarthritis presented with a nonpruritic rash associated with paresthesia, myalgia, and worsening joint pain. The rash began on the soles of her feet and ascended toward her trunk. Her symptoms began 48 hours after starting atorvastatin and empagliflozin (Jardiance) for metabolic syndrome. [ABSTRACT FROM AUTHOR]

Preventing smoking initiation among adolescents of lower socio-economic groups is crucial for the reduction of socio-economic inequalities in health. The aim of the present study was to examine whether effective smoking prevention interventions in Europe are equally effective among adolescents of low- and high-socio-economic status (SES). As part of the European Union-funded TEENAGE project, three school-based smoking prevention intervention studies in Europe were selected for secondary analyses: (i) a Dutch class competition intervention, (ii) the European Smoking Prevention Framework (ESFA) study and (iii) the A Stop Smoking in Schools Trial (ASSIST) intervention. All three studies differed in effectiveness by SES. The Dutch class competition study only had a significant effect among higher SES adolescents. The results for the ESFA study and ASSIST study were mixed and depended on which SES indicator was used. The conclusion of the study is that stratified analyses provide important insights in differential intervention effects for higher and lower socio-economic groups. Although findings from the different studies were mixed, interventions that use a social network approach in which youngsters are allowed to deliver the intervention themselves may be a successful strategy in targeting adolescents from lower socio-economic groups.

The aim was to study whether physical activity (PA) interventions in European teenagers are equally effective in adolescents of low versus high socio-economic status (SES). Based on a systematic review (Project TEENAGE), three school-based studies for secondary analyses were selected. SES stratified analyses were run in: (i) a Belgian multi-component intervention, (ii) a French multi-component intervention and (iii) a Belgian computer-tailored education trial. Results of the secondary analyses showed that no overall significant differences between low and high SES groups were found, but some interesting specific effects were revealed. Results from the first study showed an increase in objective PA in the low SES group (P = 0.015) compared with no significant effects in the high SES group. In the second study, larger effects were found in adolescents of high SES (increase of 11 min day[superscript -1] P less than 0.001), compared with adolescents of lower SES (increase of 7 min day[superscript -1], P = 0.02) at the longer term. The third study showed a positive effect on school-related PA in adolescents of high SES (P less than 0.05) and on leisure time transportation in adolescents of low SES (P less than 0.05). To conclude, we were not able to show a significant widening or narrowing of inequalities in European adolescents. (Contains 3 tables.)

Endolichenic fungi are considered a promising source of new materials. For further evaluation of some biological activities of the Trichoderma strains isolated from lichens Dirinaria spp. and Cryptothecia spp., their antifungal and antibacterial activities were screened by the methods of dual culture and environmental toxicity. Substrate degradation was evaluated using the qualitative enzyme assays. Fourteen strains of Trichoderma spp. were isolated from 60 lichen samples. All the isolates were able to inhibit the radial growth of tested fungal strains (Bipolaris spp., Colletotrichum spp., Corynespora cassiicola, and Fusarium spp.). Otherwise, only 12/14 isolates were found capable of competing for substrates with Ralstonia solanacearum. The cell-free supernatant obtained from the cultures possessed both antifungal and antibacterial activities. The antagonistic activity of the isolates was selective. Most of the isolates were able to degrade at least one of the investigated substrates, namely cellulose, pectin, and starch. All strains could produce peroxidase; none of the isolates possessed laccase and tyrosinase. A potential antagonistic fungal strain VDT6 has been identified as Trichoderma harzianum. The assessment results indicated that the Trichoderma isolates could be used in agriculture as biological control agents. [ABSTRACT FROM AUTHOR]