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According to the developmental origin of health and disease concept, the risk of many age-related diseases is not only determined by genetic and adult lifestyle factors but also by factors acting during early development. In particular, maternal obesity and neonatal accelerated growth predispose offspring to overweight and type 2 diabetes (T2D) in adulthood. selleck chemicals llc This concept mainly relies on the developmental plasticity of adipose tissue and pancreatic β-cell programming in response to suboptimal milieu during the perinatal period. These changes result in unhealthy hypertrophic adipocytes with decreased capacity to store fat, low-grade inflammation and loss of insulin-producing pancreatic β-cells. Over the past years, many efforts have been made to understand how maternal obesity induces long-lasting adipose tissue and pancreatic β-cell dysfunction in offspring and what are the molecular basis of the transgenerational inheritance of T2D. In particular, rodent studies have shed light on the role of epigenetic mechanisms in linking maternal nutritional manipulations to the risk for T2D in adulthood. In this review, we discuss epigenetic adipocyte and β-cell remodeling during development in the progeny of obese mothers and the persistence of these marks as a basis of obesity and T2D predisposition.During the last two decades, there have been several reports of an increasing incidence of type 2 diabetes mellitus (T2DM) in children and adolescents, especially among those belonging to minority ethnic groups. This trend, which parallels the increases in prevalence and degree of pediatric obesity, has caused great concern, even though T2DM remains a relatively rare disease in children. Youth T2DM differs not only from type 1 diabetes in children, from which it is sometimes difficult to differentiate, but also from T2DM in adults, since it appears to be an aggressive disease with rapidly progressive β-cell decline, high treatment failure rate, and accelerated development of complications. Despite the recent research, many aspects of youth T2DM still remain unknown, regarding both its pathophysiology and risk factor contribution, and its optimal management and prevention. Current management approaches include lifestyle changes, such as improved diet and increased physical activity, together with pharmacological interventions, including metformin, insulin, and the recently approved glucagon-like peptide-1 analog liraglutide. What is more important for everyone to realize though, from patients, families and physicians to schools, health services and policy-makers alike, is that T2DM is a largely preventable disease that will be addressed effectively only if its major contributor (i.e., pediatric obesity) is confronted and prevented at every possible stage of life, from conception until adulthood. Therefore, relevant comprehensive, coordinated, and innovative strategies are urgently needed.This review aims to summarize the health benefits of exposure to hypoxic conditions during exercise in patients with type 2 diabetes mellitus (T2DM). Exposure to hypoxic conditions during exercise training positively changes the physiological response in healthy subjects. Exposure to hypoxic conditions during exercise could markedly increase skeletal muscle glucose uptake compared to that in normoxic conditions. Furthermore, post-exercise insulin sensitivity of T2DM patients increases more when exercising under hypoxic than under normoxic conditions. Regular exercise under short-term hypoxic conditions can improve blood glucose control at lower workloads than in normoxic conditions. Additionally, exercise training under short-term hypoxic conditions can maximize weight loss in overweight and obese patients. Previous studies on healthy subjects have reported that regular exercise under hypoxic conditions had a more positive effect on vascular health than exercising under normoxic conditions. However, currently, evidence indicating that exposure to hypoxic conditions could positively affect T2DM patients in the long-term is lacking. Therefore, further evaluations of the beneficial effects of exercise under hypoxic conditions on the human body, considering different cycle lengths, duration of exposures, sessions per day, and the number of days, are necessary. In this review, we conclude that there is evidence that exercise under hypoxic conditions can yield health benefits, which is potentially valuable in terms of clinical care as a new intervention for T2DM patients.Diabetes is among the top 10 causes of death in adults and caused approximately four million deaths worldwide in 2017. The incidence and prevalence of diabetes is predicted to increase. To alleviate this potentially severe situation, safer and more effective therapeutics are urgently required. Mice have long been the mainstay as preclinical models for basic research on diabetes, although they are not ideally suited for translating basic knowledge into clinical applications. To validate and optimize novel therapeutics for safe application in humans, an appropriate large animal model is needed. Large animals, especially pigs, are well suited for biomedical research and share many similarities with humans, including body size, anatomical features, physiology, and pathophysiology. Moreover, pigs already play an important role in translational studies, including clinical trials for xenotransplantation. Progress in genetic engineering over the past few decades has facilitated the development of transgenic animals, including porcine models of diabetes. This article discusses features that attest to the attractiveness of genetically modified porcine models of diabetes for testing novel treatment strategies using recent technical advances.

Crohn's disease (CD) causes a range of digestive symptoms including recurrent diarrhea, abdominalgia, and flatulence, and severely impacts the quality of life of patients. Infliximab, a monoclonal antibody against tumor necrosis factor alpha, has recently been promoted as a therapeutic treatment for CD, but its safety margins remain uncertain. We report a case of rapidly progressive colorectal cancer that was diagnosed in a patient with CD who had previously been treated with infliximab.

This case report refers to a 40-year-old male with a 6-year history of CD. The patient underwent transverse colostomy because of inflammatory ileus in 2017. He subsequently received infliximab treatment in 2018. Ten months later, worsening contracture of the transverse colostomy was observed. Imaging tests indicated that the patient may have developed colon cancer with extensive peritoneal implantation. At the same time, colonoscopy revealed a rectal mass and pathological examination indicated well-differentiated adenocarcinoma. Palliative ileostomy was performed to improve defecation in 2019. During the operation, a small nodular mass in the mesentery of the small intestine was identified and pathological examination of the mass revealed advanced adenocarcinoma. The patient was diagnosed with advanced colorectal cancer and administered palliative chemotherapy. He died in June 2020.

We stress the importance of recognizing the possible occurrence of malignance in patients with CD receiving infliximab.

We stress the importance of recognizing the possible occurrence of malignance in patients with CD receiving infliximab.

Angiogenesis inhibitors (AIs) combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer (CRC). Aflibercept (AFL) is an option for second-line treatment of CRC, according to the 'VELOUR' trial. Currently, we can choose from three AIs, including bevacizumab, ramucirumab, and AFL. Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action. We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment.

To determine and compare the efficacy and safety profiles of AFL in the second-line and salvage therapy settings.

Clinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan (FOLFIRI) regimen were collected retrospectively from six institutions in Japan, for the period from May 2017 to March 2019. Patient characteristics collected included age, sex, tumor loce 11% and 0%, respectively (

= 0.50), and the disease control rates were 53% and 50%, respectively (

= 1.00). In the second-line and salvage therapy groups, the aTTF (123 d

71 d, respectively), aMST (673 d

396 d, respectively), and incidence of adverse events of grade 3 [8 (36%)

9 (47%)] were not significantly different between the two groups.

AFL can be used to treat advanced CRC patients, with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.

AFL can be used to treat advanced CRC patients, with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.

Major societies provide differing guidance on management of Barrett's esophagus (BE), making standardization challenging.

To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists.

Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis, surveillance and management of BE.

Five hundred sixty-nine of 1016 (56.0%) respondents completed the survey, with most respondents from Japan (

= 310, 54.5%) and China (

= 129, 22.7%). Overall, the preferred endoscopic landmark of the esophagogastric junction was squamo-columnar junction (42.0%). Distal palisade vessels was preferred in Japan (59.0%

10.0%,

< 0.001) while outside Japan, squamo-columnar junction was preferred (59.5%

27.4%,

< 0.001). Only 16.3% of respondents used Prague C and M criteria all the time. It was never used by 46.1% of Japanese, whereas 84.2% outside Japan, endoscopists used it to varying extents (

< 0.001)opists chose squamo-columnar junction to be the landmark for esophagogastric junction, which is incorrect. Most also did not consistently use Prague criteria, and Seattle protocol. Lack of standardization, education and research are possible reasons.

Remnant gastric cancer (RGC) is a carcinoma arising in the stomach remnant after previous gastric resection. It is frequently reported as a tumor with a poor prognosis and distinct biological features from primary gastric cancer (PGC). However, as it is less frequent, its profile regarding the current molecular classifications of gastric cancer has not been evaluated.

To evaluate a cohort of RGC according to molecular subtypes of GC using a panel of immunohistochemistry and

hybridization to determine whether the expression profile is different between PGC and RGC.

Consecutive RGC patients who underwent gastrectomy between 2009 and 2019 were assessed using seven GC panels Epstein-Barr virus

hybridization, immunohistochemistry for mismatch repair proteins (MutL homolog 1, MutS homolog 2, MutS homolog 6, and PMS1 homolog 2), p53 protein, and E-cadherin expression. Clinicopathological characteristics and survival of these patients were compared to 284 PGC patients.

A total of 40 RGC patients were enrolled in this study.