Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to highdose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.stem cells | DNA damage | chemotherapy | fasting C ancer patients undergoing chemotherapy experience high rates of morbidity, despite regimens that attempt to balance timing and dose intensity to mitigate off-target effects and doselimiting toxicities (1-3). Interestingly, fasting has been shown to provide host-protective effects against high-dose chemotherapyinduced toxicity in preclinical and clinical studies. For example, etoposide, which forms a ternary complex with DNA and topoisomerase II causing DNA double-strand breaks (DSBs), is far less toxic if mice are fasted before treatment (4). Fasting has also been shown to protect normal, but not cancer cells, from the toxicity of chemotherapy, thereby extending the lifespan of tumorbearing mice (4-8).Because of the rapid rate of epithelial cell proliferation in the small intestine (SI), gastrointestinal (GI) toxicity is one of the most common complications for a variety of chemotherapeutic treatments (9). Therefore, we investigated if fasting was capable of mitigating the GI toxicity normally associated with high-dose chemotherapy. Herein, we demonstrate that mice allowed to feed ad libitum before receiving high-dose chemotherapy showed marked histological changes to SI epithelium before death. These histological changes reflected loss of regenerative capacity as a result of stem cell depletion as well as structural damage from inflammatory cell infiltrates, similar to the SI response to high-dose ionizing radiation (10). In contrast, SI homeostasis was preserved in fasted mice by protection of stem cell viability and prevention of proinflammatory cell infiltrates. These results indicate that fasting mitigates GI side effects associated with chemotherapy by activating pathways that preserve SI stem cell integrity and by maintaining barrier function.

BackgroundThe last 5 years’ studies using next-generation sequencing provided evidences that many types of solid tumors present spatial and temporal genetic heterogeneity and are composed of multiple populations of genetically distinct subclones that evolve over time following a pattern of branched evolution. The evolutionary nature of cancer has been proposed as the major contributor to drug resistance and treatment failure. In this review, we present the current state of knowledge about the clonal evolution of high-grade serous ovarian cancer and discuss the challenge that clonal evolution poses for efforts to achieve an optimal cancer control.MethodsA systemic search of peer-reviewed articles published between August 2007 and October 2016 was performed using PUBMED and Google Scholar database.Results and conclusionsRecent studies using next-generation sequencing have allowed us to look inside the evolutionary nature of high-grade serous ovarian cancer, which in the light of current evidence can explain the relapsing course of the disease frequently observed in the clinical practice. Since only minimal improvement in the survival of patients treated with standard therapy has been observed in the last decade, novel molecular targeted therapies are of great interest in high-grade serous ovarian cancer. However, both spatial and temporal intratumoral genetic heterogeneity is a major challenge for personalized medicine, and greater knowledge of the molecular rules that drive tumor evolution through space and time is required to achieve a long-term clinical benefit from personalized therapy.

Introduction: The menopause transition is associated with decreased health functioning. About 80-90% of women experience mild to severe physical or physiological menopause-related complaints per year when approaching menopause. Physical activity may reduce some climacteric symptoms and improve the quality of life.Aim of the study was to investigate the influence of a 12-week training programme on the quality of life (QoL) in menopausal-aged women living in a rural area.Material and methods: Participants were 80 women aged 40-65 years and divided into two randomly selected groups in training sessions (exercising group, n = 40 and control group, n = 40). SF36 was used to assess the quality of life in both groups before and after 12 weeks. Exercising women participated in training session 3 times a week. Each 60-minute exercise session included warming-up exercises, walking, stretching, strengthening exercises with an elastic band and cooling down exercises.Results: A non-significant positive difference in all SF36 domains in the exercising group was observed. The results of the study showed a statistically significant higher QoL in the exercising group compared to the control group after 12-week training in two domains: vitality and mental health. The improvement in the quality of life in the study group was 0.19 points (role limits -physical domain, least change) and 4.96 (vitality domain, most change).Conclusions: Controlled and regular exercise for 12 weeks was significantly correlated with a positive change in vitality and mental health. Sedentary women should consider modification of their lifestyle to include physical activity as it leads to improvement of their quality of life.

Introduction: Hormone-related changes in menopause may negatively affect sexual function.Aim: The primary aim of this study was to evaluate sexual functioning in Polish women with the Female Sexual Function Index (FSFI). The secondary aim was to evaluate the major factors affecting sexual functions in middleaged Polish women. Methods: The Menopause Rating Scale was used to assess the menopausal symptoms. The Polish translation of the FSFI was used to assess sexual function. Outcomes: 69.73% of respondents had sexual dysfunction according to FSFI (FSFI score 26.55). Results: 80.61% of women experienced menopausal symptoms during the 4-week period of study. Psychological and urogenital symptoms were the most frequently reported among all the women enrolled in the study (78.23% and 77.21%). Sexual problems were observed in women who did not use hormone therapy (b ¼ 0.09, t ¼ À1.97, P ¼ .048) and showed no somatic symptoms (b ¼ 0.03, t ¼ 2.95, P ¼ .002). Clinical Implications: It is important for health care providers to ask women about this problem and understand the factors that may influence sexual problems in menopause. Strengths & Limitations:A validated survey tool was used. The limitation was selection of participants in the clinical setting and sample population size. Conclusion: Sexual problems were much more common in women who did not use hormone therapy and showed no somatic symptoms. Dąbrowska-Galas M, Dąbrowska J, Michalski B. Prevalence and Associated

BACKGROUND Vulvar cancers, although rare, are becoming an increasingly serious threat to women's health. Cancer of the vulva accounted for 0.3% of all new cancers in the United States in 2019, with 6,070 newly diagnosed cases. This review details the epidemiology, pathogenesis, diagnosis, staging, and treatment of vulvar malignancies. OBJECTIVE To review cancer entities of the vulva, including vulvar intraepithelial neoplasms, squamous cell carcinoma (SCC), malignant melanoma, basal cell carcinoma, neuroendocrine tumors, and adenocarcinomas. MATERIALS AND METHODS Literature review using PubMed search for articles related to cancer of the vulva. RESULTS Vulvar intraepithelial neoplasms represent premalignant precursors to SCC of the vulva. There are several different histopathologic subtypes of SCC, and treatment is dependent on characteristics of primary tumor and lymph node involvement. Melanoma is the second most common cancer to affect the vulva, and staging is based on tumor, node, and metastatic spread. CONCLUSION Vulvar malignancies are rare, and diagnosis is dependent on biopsy and pathologic evaluation. Treatment for vulvar malignancies depends on histopathologic diagnosis but ranges from wide local excision with or without lymph node biopsy or dissection to radiation therapy with chemo- or immunotherapy. Overall survival varies by diagnosis.