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Wnt, PI3K-Akt-mTOR, and NF-κB pathways were reported to be involved in DNA damage repair (DDR). DDR-deficient cancers become critically dependent on backup DNA repair pathways. Neuritin 1 (NRN1) is reported to be involved in PI3K-Akt-mTOR, and its role in DDR remains unclear. Methylation-specific PCR, siRNA, flow cytometry, esophageal cancer cell lines, and xenograft mouse models were used to examine the role of NRN1 in esophageal cancer. The expression of NRN1 is frequently repressed by promoter region methylation in human esophageal cancer cells. NRN1 was methylated in 50.4% (510/1012) of primary esophageal cancer samples. NRN1 methylation is associated significantly with age (P less then .001), tumor size (P less then .01), TNM stage (P less then .001), differentiation (P less then .001) and alcohol consumption (P less then .05). We found that NRN1 methylation is an independent prognostic factor for poor 5-y overall survival (P less then .001). NRN1 inhibits colony formation, cell proliferation, migration, and invasion, and induces apoptosis and G1/S arrest in esophageal cancer cells. NRN1 suppresses KYSE150 and KYSE30 cells xenografts growth in nude mice. PI3K signaling is reported to activate ATR signaling by targeting CHK1, the downstream component of ATR. By analyzing the synthetic efficiency of NVP-BEZ235 (PI3K inhibitor) and VE-822 (an ATR inhibitor), we found that the combination of NVP-BEZ235 and VE-822 increased cytotoxicity in NRN1 methylated esophageal cancer cells, as well as KYSE150 cell xenografts. In conclusion, NRN1 suppresses esophageal cancer growth both in vitro and in vivo by inhibiting PI3K-Akt-mTOR signaling. Methylation of NRN1 is a novel synthetic lethal marker for PI3K-Akt-mTOR and ATR inhibitors in human esophageal cancer.

This study was undertaken to identify clinically meaningful comorbidity patterns and their associations with the demographic/clinical characteristics of people with multiple sclerosis (MS).

We conducted latent class analysis to identify clinically distinct comorbidity patterns in MS using the 15 most common comorbidities among 1518 Australian Multiple Sclerosis Longitudinal Study participants. The associations between demographic/clinical characteristics and comorbidity patterns were examined using log-binomial and multinomial logistic regression.

Five distinct comorbidity patterns were identified "minimally diseased class" (30.8%), consisting of participants with no or one comorbidity; "metabolic class" (22.7%); "mental health-allergy class" (21.7%); "nonmetabolic class" (7.6%); and "severely diseased class" (7.0%), consisting of participants with higher prevalence of these comorbidities. The relative probabilities of being assigned to comorbidity classes compared to the minimally diseased class were sr, people who were obese, and people who had higher disability levels were more likely to be in classes with higher levels of comorbidity. These findings may offer opportunities for designing more personalised approaches to comorbidity prevention and treatment.Beta-lactam (BL) allergy suspicion is common in children and constitutes a major public health problem, with an impact on patient's health and on medical costs. read more However, it has been found that most of these reactions are not confirmed by a complete allergic workup. The diagnostic value of the currently available allergy tests has been investigated intensively recently by different groups throughout the world. This has led to major changes in the management of children with a suspected BL allergy. Particularly, it is now well accepted that skin tests can be skipped before the drug provocation test in children with a benign non-immediate reaction to BL. However, there is still a debate on the optimal allergic workup to perform in children with a benign immediate reaction. In addition, management of children with severe cutaneous adverse drug reactions remains difficult. In this review, based on a selection of the most relevant studies found in the literature, we will review and discuss the diagnosis of different forms of BL allergy in children.Bladder cancer (BLCA) remains the leading cause of cancer-related mortality among genitourinary malignancies worldwide. BLCA metastasis represents the primary reason for its poor prognosis. In this study, we report that decreased expression of partitioning defective 3 (Par3), a polarity protein (encoded by PARD3), is associated with tumor aggressive phenotypes and poor prognosis in BLCA patients. Consistently, ablation of Par3 promotes the metastasis and invasion of BLCA cells in vitro and in vivo. Further studies reveal that zinc finger protein Snail represses the expression of Par3 by binding to E2-box (CAGGTG) of PARD3 promoter-proximal. Inhibition of GSK-3β promotes the expression and nuclear localization of Snail and then reduces the expression of Par3, resulting in the metastasis and invasion of BLCA cells. Moreover, we detected the interaction between Par3 (936-1356 aa) and ZO-1 (1372-1748 aa), which is involved in the maintenance of tight junction. Together, our results demonstrate that the GSK-3β/Snail/Par3/ZO-1 axis regulates BLCA metastasis, and Snail is a major regulator for Par3 protein expression in BLCA.

This study aimed to explore the experiences of individuals discussing sexual well-being with healthcare professions within the context of their cardiac illness to determine their sexual health information needs.

Cardiovascular disease is the leading cause of morbidity and mortality worldwide and known to have a detrimental impact on sexual health. Despite sexual health being recognised as a fundamental component of well-being, it may be a neglected aspect of care within the context of cardiovascular disease.

A qualitative exploratory study conducted in accordance with COREQ guidelines.

We conducted semi-structured interviews with participants (n=13) aged between 30-77years who had been diagnosed with a cardiovascular disease. Data were transcribed and subject to thematic analysis.

Analysis revealed two major themes-Sexual healthcare information and expectations I expect them to tell me and Experiences of sexual adversity it's really scary. Although participants expected and welcomed information in relation to their illness and sexual health, this was rarely received.