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Marijuana and opioid addictions have increased alarmingly in recent decades, especially in the United States, posing threats to society. When the drug user is a pregnant mother, there is a serious risk to the developing baby. Congenital anomalies are associated with prenatal exposure to marijuana and opioids. Here, we summarize the current data on the prevalence of marijuana and opioid use among the people of the United States, particularly pregnant mothers. We also summarize the current zebrafish studies used to model and understand the effects of these drug exposures during development and to understand the behavioral changes after exposure. Zebrafish experiments recapitulate the drug effects seen in human addicts and the birth defects seen in human babies prenatally exposed to marijuana and opioids. Zebrafish show great potential as an easy and inexpensive model for screening compounds for their ability to mitigate the drug effects, which could lead to new therapeutics.Inflammatory bowel disease is a common name for Crohn's disease and ulcerative colitis. These inflammatory states cause damage in the sidewalls of the gastrointestinal tract, resulting in malabsorption of food and vitamins. Folic acid (Vitamin B9) is often associated with inflammatory bowel diseases since reduced overall folate concentration in the human body may lead to the development of colorectal cancer and megaloblastic anaemia. However, its deficiency is easily compensated by taking an additional folic acid pill during regular therapy. At the moment, there are no studies that have examined the compatibility of folic acid with 5-aminosalicylate drugs used in the treatment of inflammatory bowel diseases. In this work, differential scanning calorimetry, forced degradation studies, isothermal stress testing and dissolution stability testing were used to determine the stability of folic acid and one of the most commonly used 5-aminosalicylates, mesalazine, when present in the same solution or blend. To monitor the assay of folic acid, mesalazine and nine of its related impurities, a single HPLC method was developed. Results of compatibility studies showed that no physicochemical interaction between mesalazine and folic acid occurs when combined, opening the path to the development of new formulations, such as a mesalazine/folic acid fixed-dose combination.Melanoma is one of the most aggressive and highly resistant tumors. Cell plasticity in melanoma is one of the main culprits behind its metastatic capabilities. The detailed molecular mechanisms controlling melanoma plasticity are still not completely understood. Here we combine mathematical models of phenotypic switching with experiments on IgR39 human melanoma cells to identify possible key targets to impair phenotypic switching. Our mathematical model shows that a cancer stem cell subpopulation within the tumor prevents phenotypic switching of the other cancer cells. Experiments reveal that hsa-mir-222 is a key factor enabling this process. Our results shed new light on melanoma plasticity, providing a potential target and guidance for therapeutic studies.Planning is paramount in sport. Among different philosophical approaches to planning, periodization is a highly popular concept that refers to structured training periods with ensuing programs encompassing moments of progressively-loaded training, followed by recovery; it is normally deemed paramount to optimize adaptations and performance. While planning provides generic guidelines, periodization refers to the sequencing/ordering of training periods to enforce a given plan, therefore referring to longer temporal scales, and programming refers to more micro-scale aspects. In fact, similar periodization schemes may implement distinct programming strategies. Literature on the topic has used the linear and nonlinear terms to describe the content of periodized programs. However, these concepts have not been clearly defined in the literature, which may lead to inaccurate and misleading interpretations. Moreover, nonlinear periodization is usually using nonlinear programming, but with pre-stipulated sequencing of the training periods. Finally, it can be argued that nonlinearity has been an integral part of periodization since its inception, at least theoretically. Tofacitinib mouse In this essay, the literature was critically reviewed to better understand the validity of the linearity and nonlinearity concepts as applied in currently proposed periodization models. In addition, a novel approach for a de facto nonlinear periodization is presented.Grape stem is rich in phenolic compounds, especially stilbenes. These antioxidants can be degraded during the storage of grape stem extracts for long periods of time. The aim of this work was to analyze the stability of Mazuelo stem extracts during storage at 25 and 40 °C, in two different light conditions (amber and transparent vials). The stability of the antioxidants was studied after 2, 4 and 6 months of conservation. Gallic acid and the quercetin derivative concentration were stable throughout the storage period. In contrast, catechin disappeared from all the extracts in just two months of storage. Anthocyanins were significantly affected by temperature, and light enhanced their degradation when the extracts were kept at 40 °C. Resveratrol and viniferin showed a similar behavior. Their concentration decreased from the beginning of storage, and in both cases, they were significantly affected by both temperature and light.The compound 62 chlorinated polyfluorinated ether sulfonate (F-53B), a replacement for perfluorooctanesulfonate (PFOS) in the electroplating industry, has been widely detected in numerous environmental matrices, human sera, and organisms. Due to regulations that limit PFOS use, F-53B use is expected to increase. Therefore, in this study, we performed a subchronic oral toxicity study of F-53B in Sprague Dawley (SD) rats. F-53B was administered orally once daily to male and female rats for 28 days at doses of 5, 20, and 100 mg/kg/day. There were no toxicologically significant changes in F-53B-treated rats, except in the thyroid gland. However, F-53B slightly reduced the serum concentrations of thyroid hormones, including triiodothyronine and thyroxine, compared with their concentrations in the vehicle group. F-53B also induced follicular hyperplasia and was associated with increased thyroid hormone biosynthesis-associated protein expression. These results demonstrate that F-53B is a strong regulator of thyroid hormones in SD rats as it disrupts thyroid function.
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