Maherpickett4986

In this review I discuss the existing functional evidence for the involvement of ORPs in cancerous growth, discuss the findings in the light of the putative mechanisms outlined above and the possibility of employing ORPs as targets of anti-cancer therapy.Colorectal cancer (CRC) is one of the most malignant cancers in the world. A major cause of death in CRC patients is the limited therapeutic options in its advanced stages. The Farnesoid X receptor (FXR) is a member of the nuclear superfamily, which is effective in slowing the progression of colorectal cancer in addition to its extraordinary role in regulating metabolic disorders. Due to the systemic side-effects caused by non-selective agonists, the intestine-restricted FXR agonists can induce a whole-body benefit without activating the hepatic FXR, suggesting intestinal FXR activation as a potentially safer therapy in the treatment of CRC. This review highlights the effects of FXR on the disturbed bile acid circulation and the carcinogenesis of CRC and with a specific emphasis on listing the functions of several intestinal-restricted FXR agonists.The alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) play critical roles in alcoholism development and alcohol toxicology; however, few studies have focused on the miRNA-mediated mechanisms underlying the expressions of alcohol-metabolizing enzymes. In the present study, we showed the expression changes of each alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver samples of alcoholic hepatitis (AH) patients, and predicted the miRNAs targeting the dysregulated alcohol-metabolizing genes by a systematic in silico analysis. 13 miRNAs were predicted to regulate the expressions of ADH1A, ADH4, and ALDH2, respectively, with hsa-miR-148a-3p (miR-148a) showing the most significant down-regulation in AH patients. Following experimental evidence using HepG2 cells proved that miR-148a promoted ADH4 expression by directly binding to the coding sequence of ADH4 and increasing the mRNA stability via an AGO1-dependent manner. Additional assays showed that secondary structure of ADH4 transcript affected the target accessibility and binding of miR-148a-3p. In sum, our results suggest that the expressions of key alcohol-metabolizing enzymes are repressed in AH patients, and the non-canonical positive regulation of miR-148a on ADH4 reveals a new regulationary mechanism for ADH genes.Keratitis is one of the most prevalent ocular diseases manifested by partial or total loss of vision. Amongst infectious (viz., microbes including bacteria, fungi, amebae, and viruses) and non-infectious (viz., eye trauma, chemical exposure, and ultraviolet exposure, contact lens) risk factors, viral keratitis has been demonstrated as one of the leading causes of corneal opacity. While many viruses have been shown to cause keratitis (such as rhabdoviruses, coxsackieviruses, etc.), herpesviruses are the predominant etiologic agent of viral keratitis. This chapter will summarize current knowledge on the prevalence, diagnosis, and pathobiology of viral keratitis. Virus-mediated immunomodulation of host innate and adaptive immune components is critical for viral persistence, and dysfunctional immune responses may cause destruction of ocular tissues leading to keratitis. Immunosuppressed or immunocompromised individuals may display recurring disease with pronounced severity. Early diagnosis of viral keratitis is beneficial for disease management and response to treatment. Finally, we have discussed current and emerging therapies to treat viral keratitis.

This study aimed to examine the association between physical education classes and PA among adolescents from 50 low- and middle-income countries (LMICs).

A self-reported questionnaire from the Global School-based Student Survey (GSHS) was used to collect information on participation frequency of physical education classes and being physically active over the last week, as well as other control variables (e.g., sex, age, country, sedentary behavior). Multivariable logistic regression and a pooled meta-analysis were performed to explore the association and compared country-wise differences.

Included adolescents aged from 13 to 17 years (n=187,386, %boys=51.7; mean age=14.6 years), the prevalence of sufficient PA (meeting the PA guidelines) was 14.9%. The prevalence of 5 days or more to engage in physical education classes was 16.5%. Compared with adolescents who had 0 days for physical education classes, higher participation frequency was more likely related to sufficient PA (OR 1 day=1.34, 2 days=1.66, 3 days=1.67, 4 days=1.79, 5 days or more=2.46), these findings were also observed in both sexes. A moderate inconsistency on the association across the included countries was found (I

=53%, p<0.01), although the pooled OR was 1.50 (95% CI 1.36-1.65).

Participating in more physical education classes may be an effective approach to increase physical activity levels among adolescents in LMICs. However, promoting physical activity levels among adolescents in LMICs through physical education classes should consider more country-specific factors.

Participating in more physical education classes may be an effective approach to increase physical activity levels among adolescents in LMICs. However, promoting physical activity levels among adolescents in LMICs through physical education classes should consider more country-specific factors.Our first objective was to develop an approach useful for reliable normalization of 2-hydroxyglutarate (2-HG) intracellular levels. The second objective was to use our data normalization strategy to verify previously published report on the higher d-2-HG level in tumors of colorectal cancer (CRC) patients than in normal colon fragments. We examined various methods of 2-HG level normalization in cell/tissue extracts (number of cells, mass of tissue, total protein). In order to solve the problems with reliable normalization of the 2-HG levels in colon fragments, we proposed a strategy based on relating the concentrations of 2-HG isomers to total thymine concentrations measured by ultra-performance liquid chromatography (UPLC) with UV detection in acid hydrolysates of the cell/tissue extracts. We used a common method of derivatization with diacetyl-l-tartaric anhydride (DATAN) to separate l- and d-2-HG enantiomers. DATAN-derivatized 2-HG was quantitated by UPLC with tandem mass spectrometry (MS/MS) in the selected reaction monitoring (SRM) mode. We observed a linear dependence of the total amount of thymine released from lymphocytes, HCT 116, K562, and PC-3 by acid hydrolysis on their number of cells. Our results showed a significantly higher level of l- and d-2-HG in cancer-free colon than in tumor.

The aim was to evaluate patterns of multimorbidity that increase the risk of institutionalization in older persons, also exploring the potential buffering effect of formal and informal care.

Prospective cohort study.

The population-based Swedish National study on Aging and Care in Kungsholmen, Stockholm, Sweden.

In total, 2571 community-dwelling older adults were grouped at baseline according to their underlying multimorbidity patterns, using a fuzzy c-means cluster algorithm, and followed up for 6years to test the association between multimorbidity patterns and institutionalization.

Six patterns of multimorbidity were identified psychiatric diseases; cardiovascular diseases, anemia, and dementia; metabolic and sleep disorders; sensory impairments and cancer; musculoskeletal, respiratory, and gastrointestinal diseases; and an unspecific pattern including diseases of which none were overrepresented. In total, 110 (4.3%) participants were institutionalized during the follow-up, ranging from 1.7% in thential long-term care. Formal and informal care provision may be effective strategies in reducing the risk of institutionalization.

Older persons suffering from specific multimorbidity patterns have a higher risk of institutionalization, especially if they lack formal or informal care. Interventions aimed at preventing the clustering of diseases could reduce the associated burden on residential long-term care. Formal and informal care provision may be effective strategies in reducing the risk of institutionalization.

During the COVID-19 lockdown period from March 17 to May 11, 2020, French authorities in Paris and its suburbs relocated people experiencing recurrent homelessness to emergency shelters, hotels, and large venues. A serological survey was done at some of these locations to assess the COVID-19 exposure prevalence in this group.

We did a cross-sectional seroprevalence study at food distribution sites, emergency shelters, and workers' residences that were provided medical services by Médecins Sans Frontières in Paris and Seine-Saint-Denis in the Ile-de-France region. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seropositivity was detected by Luciferase-Linked Immunosorbent Assay and Pseudo Neutralization Test. Sociodemographic and exposure related information was collected via a verbal questionnaire to analyse risk factors and associations with various COVID-19 symptoms.

Between June 23 and July 2, 2020, 426 (52%) of 818 individuals recruited tested positive in 14 sites. Seroprevale Foundation.

Médecins Sans Frontières, Epicentre, Institut Pasteur's URGENCE nouveau coronavirus fund, Total Foundation.

The objective of this study was to better understand the factors associated with the heterogeneity of in-hospital COVID-19 morbidity and mortality across France, one of the countries most affected by COVID-19 in the early months of the pandemic.

This geo-epidemiological analysis was based on data publicly available on government and administration websites for the 96 administrative departments of metropolitan France between March 19 and May 11, 2020, including Public Health France, the Regional Health Agencies, the French national statistics institute, and the Ministry of Health. Using hierarchical ascendant classification on principal component analysis of multidimensional variables, and multivariate analyses with generalised additive models, we assessed the associations between several factors (spatiotemporal spread of the epidemic between Feb 7 and March 17, 2020, the national lockdown, demographic population structure, baseline intensive care capacities, baseline population health and health-care servOVID-19 incidence or mortality rates.

This ecological study highlights the impact of the epidemic spread, national lockdown, and reactive adaptation of intensive care capacities on the spatial distribution of COVID-19 morbidity and mortality. It provides information for future geo-epidemiological analyses and has implications for preparedness and response policies to current and future epidemic waves in France and elsewhere.

None.

None.

Opinion polls on vaccination intentions suggest that COVID-19 vaccine hesitancy is increasing worldwide; however, the usefulness of opinion polls to prepare mass vaccination campaigns for specific new vaccines and to estimate acceptance in a country's population is limited. H3B-6527 order We therefore aimed to assess the effects of vaccine characteristics, information on herd immunity, and general practitioner (GP) recommendation on vaccine hesitancy in a representative working-age population in France.

In this survey experiment, adults aged 18-64 years residing in France, with no history of SARS-CoV-2 infection, were randomly selected from an online survey research panel in July, 2020, stratified by gender, age, education, household size, and region and area of residence to be representative of the French population. Participants completed an online questionnaire on their background and vaccination behaviour-related variables (including past vaccine compliance, risk factors for severe COVID-19, and COVID-19 perceptions and experience), and were then randomly assigned according to a full factorial design to one of three groups to receive differing information on herd immunity (>50% of adults aged 18-64 years must be immunised [either by vaccination or infection]; >50% of adults must be immunised [either by vaccination or infection]; or no information on herd immunity) and to one of two groups regarding GP recommendation of vaccination (GP recommends vaccination or expresses no opinion).