Background Data for Israel from the Rome Foundation Global Epidemiology Study on the disorders of gut‐brain interaction (DGBI) were used to assess the national prevalence of all 22 DGBI, the percentage of respondents meeting diagnostic criteria for at least one DGBI, and the impact on burden of disease in Israel. Methods The survey was conducted through the Internet with multiple built‐in quality‐assurance techniques and included the Rome IV diagnostic questionnaire and an in‐depth supplemental questionnaire. Key Results 2012 Israeli participants completed the survey nationwide: mean age 44.6 ± 16.4 years, 50% females. The national distribution was very close to the latest Israeli census. 36.4% (95% CI 34.3, 38.4) met diagnostic criteria for at least one DGBI, with 4.4% for any esophageal disorder, 6.5% for any gastroduodenal disorder, 30.8% for any bowel disorder, and 5.3% for any anorectal disorder. The rates were higher for women. Having any DGBI was associated negatively with psychosocial variables (including quality of life, somatization, and concern about digestive problems), and healthcare utilization (including doctor visits, use of medications, and abdominal surgeries). Conclusions & Inferences The results of this study provide the first in‐depth assessment of the prevalence and burden of Rome IV DGBI in Israel and facilitate comparisons with other countries. As 36.4% of the 2,012 participants met diagnostic criteria for at least one DGBI, and 23.5% of those met criteria for more than one DGBI, the burden of DGBI in Israel is high, indicating a need to focus on research and training for patient care.

Despite established efficacy in bipolar disorder patients, lithium (Li) therapy has serious side effects, particularly chronic kidney disease. We examined the safety and behavioral effects of combined chronic low-dose aspirin plus low-dose Li in rats to explore the toxicity and therapeutic potential of this treatment. Rats were fed regular or Li-containing food (0.1% [low-dose, LLD-Li] or 0.2% [standard-dose, STD-Li]) for six weeks. Low-dose aspirin (1 mg/kg) was administered alone or together with Li. Renal function and gastric mucosal integrity were assessed. The effects of the combination treatment were evaluated in depression-like and anxiety-like behavioral models. Co-treatment with aspirin did not alter plasma Li levels. Chronic STD-Li treatment resulted in significant polyuria and polydipsia, elevated blood levels of creatinine and cystatin C, and increased levels of kidney nephrin and podocin—all suggestive of impaired renal function. Aspirin co-treatment significantly damped STD-Li-induced impairments in kidney parameters. There were no gastric ulcers or blood loss in any treatment group. Combined aspirin and LLD-Li resulted in a significant increase in sucrose consumption, and in the time spent in the open arms of an elevated plus-maze compared with the LLD-Li only group, suggestive of antidepressant-like and anxiolytic-like effects, respectively. Thus, we demonstrate that low-dose aspirin mitigated the typical renal side effects of STD-Li dose and enhanced the beneficial behavioral effects of LLD-Li therapy without aggravating its toxicity.

It is well recognized that cancer cells subvert the phenotype of stromal naïve fibroblasts and instruct the neighboring cells to sustain their growth agenda. The mechanisms underpinning the switch of fibroblasts to cancer-associated fibroblasts (CAFs) are the focus of intense investigation. One of the most significant hallmarks of the biological identity of CAFs is that their tumor-promoting phenotype is stably maintained during in vitro and ex vivo propagation without the continual interaction with the adjacent cancer cells. In this review, we discuss robust evidence showing that the master cytokine Transforming Growth Factor-β1 (TGFβ-1) is a prime mover in reshaping, via epigenetic switches, the phenotype of stromal fibroblasts to a durable state. We also examine, in detail, the pervasive involvement of TGFβ-1 signaling from both cancer cells and CAFs in fostering cancer development, taking colorectal cancer (CRC) as a paradigm of human neoplasia. Finally, we review the stroma-centric anticancer therapeutic approach focused on CAFs—the most abundant cell population of the tumor microenvironment (TME)—as target cells.