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Dyslipidaemia is a major risk factor for atherosclerosis and cardiovascular diseases. The molecular mechanisms that translate dyslipidaemia into atherogenesis and reliable markers of its progression are yet to be fully elucidated. To address this issue, we conducted a comprehensive metabolomic and proteomic analysis in an experimental model of dyslipidaemia and in patients with familial hypercholesterolemia (FH).

Liquid chromatography/mass spectrometry (LC/MS) and immunoassays were used to find out blood alterations at metabolite and protein levels in dyslipidaemic ApoE

/LDLR

mice and in FH patients to evaluate their human relevance.

We identified 15 metabolites (inhibitors and substrates of nitric oxide synthase (NOS), low-molecular-weight antioxidants (glutamine, taurine), homocysteine, methionine, 1-methylnicotinamide, alanine and hydroxyproline) and 9 proteins (C-reactive protein, proprotein convertase subtilisin/kexin type 9, apolipoprotein C-III, soluble intercellular adhesion molecule-1, angioatherosclerosis. Our study further identified potential biomarkers for an increased risk of atherosclerosis that may aid in clinical diagnosis or in the personalized treatment.

Capacity strengthening of primary health care workers is widely used as a means to strengthen health service delivery, particularly in low- and middle-income countries. Despite the widespread recognition of the importance of capacity strengthening to improve access to quality health care, how the term 'capacity strengthening' is both used and measured varies substantially across the literature. This scoping review sought to identify the most common domains of individual capacity strengthening, as well as their most common forms of measurement, to generate a better understanding of what is meant by the term 'capacity strengthening' for primary health care workers.

Six electronic databases were searched for studies published between January 2000 and October 2020. A total of 4474 articles were screened at title and abstract phase and 323 full-text articles were reviewed. 55 articles were ultimately identified for inclusion, covering various geographic settings and health topics.

Capacity strengthening is pk of individual capacity strengthening across intra-personal, inter-personal, and technical domains is proposed, as an initial step towards building a common consensus of individual capacity strengthening for future work.

Globally, communities are struggling to gain support for harm reduction strategies being implemented to address the impacts of substance use. A key part of this discussion is understanding and engaging with people who use drugs to help shape community harm reduction strategies. This study focused on how an overdose prevention site has influenced the lives of people who use drugs.

A critical narrative method was utilized, centred on photo-narratives. Twenty-seven individuals accessing an overdose prevention site were recruited to participate in preliminary interviews. Sixteen participants subsequently took photographs to describe the impact of the site and participated in a second round of interviews. Through independent coding and several rounds of team analysis, four themes were proposed to constitute a core narrative encompassing the diverse experiences of participants.

A key message shared by participants was the sense that their lives have improved since accessing the site. The core narrative proposn their lives.

Child blood pressure (BP) is predictive of future cardiovascular risk. Prenatal exposure to metals has been associated with higher BP in childhood, but most studies have evaluated elements individually and measured BP at a single time point. We investigated impacts of prenatal metal mixture exposures on longitudinal changes in BP during childhood and elevated BP at 11 years of age.

The current study included 176 mother-child pairs from the Rhea Study in Heraklion, Greece and focused on eight elements (antimony, arsenic, cadmium, cobalt, lead, magnesium, molybdenum, selenium) measured in maternal urine samples collected during pregnancy (median gestational age at collection 12 weeks). BP was measured at approximately 4, 6, and 11 years of age. Covariate-adjusted Bayesian Varying Coefficient Kernel Machine Regression and Bayesian Kernel Machine Regression (BKMR) were used to evaluate metal mixture impacts on baseline and longitudinal changes in BP (from ages 4 to 11) and the development of elevated BP at ag adolescence. Future studies are needed to identify the major sources of molybdenum and lead in this population.

Prenatal exposure to high levels of molybdenum and lead, particularly in combination, may contribute to higher BP at age 4. These early effects appear to persist throughout childhood, contributing to elevated BP in adolescence. Future studies are needed to identify the major sources of molybdenum and lead in this population.

Signal fidelity depends on protein-protein interaction-'hubs' integrating cues from large interactomes. Recently, and based on a common secondary structure motif, the αα-hubswere defined, which are small α-helical domains of large, modular proteins binding intrinsically disordered transcriptional regulators.

Comparative structural biology.

We assign the harmonin-homology-domain (HHD, also named the harmonin N-terminal domain, NTD) present in large proteins suchas harmonin, whirlin, cerebral cavernous malformation 2, and regulator of telomere elongation 1 to the αα-hubs. The new member of the αα-hubs expands functionality to include scaffolding of supra-modular complexes mediating sensory perception, neurovascular integrity and telomere regulation, and reveal novel features of the αα-hubs. As a common trait, the αα-hubs bind intrinsically disordered ligands of similar properties integrating similar cellular cues, but without cross-talk.

The inclusion of the HHD in the αα-hubs has uncovered new featuresnsically disordered proteins in signaling networks. Video Abstract.

Thailand is a rapidly aging society, which places high demand on home health care services for the elderly. RG2833 cell line The shortage of health care workforce in rural areas is a crucial obstacle to the delivery of adequate home health care services. The appropriate skill-mix between multidisciplinary health team and care givers (CGs) is an attractive solution for improving home health care services in rural Thailand. This study assessed the potential of trained CGs to provide home health care services and projected what the optimal mix for a multidisciplinary home health care team in rural Thailand would be in 2030.

Eleven pilot districts in Thailand were recruited for the study. Secondary data were collected along with surveys of home health care providers. A total of 130 care managers (nurses) and 351 care givers (CG) were recruited for the survey. Workload, skill-mix potential, and acceptance of care givers were assessed in the surveys. The results from secondary data and the survey were used to project the health022 physiotherapists and 50,148 CGs will be required in 2030 to meet the needs of the dependent elderly for home health care in rural Thailand.

With the increased need for home health care services in the future, appropriate team work between the members of the multidisciplinary health team and the CGs in the community is the appropriate solution for likely shortages of health professional workforce.

With the increased need for home health care services in the future, appropriate team work between the members of the multidisciplinary health team and the CGs in the community is the appropriate solution for likely shortages of health professional workforce.

Supply driven programs that are not closely connected to community demand and demand-driven programs that fail to ensure supply both risk worsening inequity. Understanding patterns of uptake of behaviors among the poorest under ideal experimental conditions, such as those of an efficacy trial, can help identify strategies that could be strengthened in routine programmatic conditions for more equitable uptake. WASH Benefits Bangladesh was a randomized controlled efficacy trial that provided free-of cost WASH hardware along with behavior change promotion. The current paper aimed to determine the impact of the removal of supply and demand constraints on the uptake of handwashing and sanitation behaviors across wealth and education levels.

The current analysis selected 4 indicators from the WASH Benefits trial- presence of water and soap in household handwashing stations, observed mother's hand cleanliness, observed visible feces on latrine slab or floor and reported last child defecation in potty or toilet. imultaneously addressing supply and demand-constraints among the poorest, we observed substantial overall improvements in equity. Within scaled-up programs, a separate targeted strategy that relaxes constraints for the poorest can improve the equity of a program.

WASH Benefits Bangladesh ClinicalTrials.gov , identifier NCT01590095 . Date of registration April 30, 2012 'Retrospectively registered'.

WASH Benefits Bangladesh ClinicalTrials.gov , identifier NCT01590095 . Date of registration April 30, 2012 'Retrospectively registered'.

FOLFOX is a combinational regimen of folinic acid (FnA, FOL), fluorouracil (5-Fu, F) and oxaliplatin (OxP, OX), and has been long considered as the standard treatment of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Recent developments of nano delivery systems have provided profound promise for improving anticancer efficacy and alleviating side effects of FOLFOX. Previously, a nanoformulation (termed Nano-Folox) containing OxP derivative and FnA was developed in our laboratory using nanoprecipitation technique. Nano-Folox induced OxP-mediated immunogenic cell death (ICD)-associated antitumor immunity, which significantly suppressed tumor growth in the orthotopic CRC mouse model when administrated in combination with free 5-Fu.

A nanoformulation (termed Nano-FdUMP) containing FdUMP (5-Fu active metabolite) was newly developed using nanoprecipitation technique and used in combination with Nano-Folox for CRC and HCC therapies.

Synergistic efficacy was achieved in orthotopic CRC and HCC mouse models. It resulted mainly from the fact that Nano-FdUMP mediated the formation of reactive oxygen species (ROS), which promoted the efficacy of ICD elicited by Nano-Folox. In addition, combination of Nano-Folox/Nano-FdUMP and anti-PD-L1 antibody significantly inhibited CRC liver metastasis, leading to long-term survival in mice.

This study provides proof of concept that combination of two nano delivery systems can result in successful FOLFOX-associated CRC and HCC therapies. Further optimization in terms of dosing and timing will enhance clinical potential of this combination strategy for patients.

This study provides proof of concept that combination of two nano delivery systems can result in successful FOLFOX-associated CRC and HCC therapies. Further optimization in terms of dosing and timing will enhance clinical potential of this combination strategy for patients.

Pediatric Tuina has been widely used in children with acute diarrhea in China. However, due to the lack of high-quality clinical evidence, the benefit of Tuina as a therapy is not clear. We aimed to assess the effect of pediatric Tuina compared with sham Tuina as an add-on therapy in addition to usual care for 0-6-year-old children with acute diarrhea.

Eighty-six participants aged 0-6 years with acute diarrhea were randomized to receive pediatric Tuina plus usual care (n = 43) or sham Tuina plus usual care (n = 43). The primary outcomes were days of diarrhea from baseline and times of diarrhea on day 3. Secondary outcomes included a global change rating (GCR) and the number of days when the stool characteristics returned to normal. Adverse events were assessed.

Pediatric Tuina was associated with a reduction in times of diarrhea on day 3 compared with sham Tuina in both ITT (crude RR, 0.73 [95% CI, 0.59-0.91]) and PP analyses (crude RR, 0.66 [95% CI, 0.53-0.83]). However, the results were not significant when we adjusted for social demographic and clinical characteristics.

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