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0740 nM) than that in tissue (1.29 nM). When scaled up to a human, this model captured the substantial and complex nonlinear pharmacokinetic behavior of linagliptin in human adults that is characterized by less-than dose-proportional increase in plasma exposure, dose-dependent clearance and volume of distribution, as well as long terminal half-life with minimal accumulation after repeated doses. Our modeling work is not only novel but also of high significance as the whole-body PBPK-TMDD model platform developed using linagliptin as the model compound could be applied to other small-molecule compounds exhibiting TMDD to facilitate their optimal dose selection. Graphical abstract.Cancer patients are often not sufficiently oriented to manage side effects at home. Sending text messages with self-care guidelines aimed managing side effects is the main objective of this randomized controlled trial. Patients who started outpatient chemotherapy treatment between March and December 2017 at a hospital in southern Brazil were invited to participate in this study and were allocated to the intervention or control group (ratio 1 1). Each patient in the intervention group received a daily SMS (short message service) with some guidance on management or prevention of side effects. All text messages were sent to the intervention group patients in an automated and tailored way by our app called cHEmotHErApp. Side effects experienced by patients were verified using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30). Results showed intervention group patients experienced fewer side effects compared to the control group in cycle 1 (p  less then  0.05), in general. In addition, intervention group experienced less nausea in relation to the control group, in the cycle 1 and cycle 2 (p  less then  0.05). This study indicate text messaging may be a tool for supporting side effect management in patients receiving chemotherapy. This study was enrolled in ClinicalTrials.gov with the identification number NCT03087422. This research was performed in accordance with the Declaration of Helsinki.<br /><br /> The potential benefits of treating subclinical hypothyroidism (SCH) are unclear and still controversial. Thus, we surgically induced SCH in rats and evaluated the effects of thyroxine (T<br /><br /> ) replacement on the gene expression levels of deiodinases and thyroid hormone (TH) transporters in different tissues.<br /><br /> SCH was induced by hemithyroid electrocauterization. The control animals underwent the same surgical procedure but were not subjected to electrocauterization (sham). After 14days, half of the SCH animals were treated with T<br /><br /> (SCH + T<br /><br /> ). At the end of the experimental protocol, all of the rats were euthanized, serum hormone concentrations were measured, and RNA analyses were performed on different tissues and organs.<br /><br /> Consistent with previous studies, we observed increased TSH levels, normal TH levels, and reduced hypothalamic TRH expression in the SCH group. Additionally, Dio2 mRNA expression was downregulated in the hippocampus and pituitary, and Dio1 was upregulated in the kidney and pituitary of the SCH animals. The changes in Dio3 expression were tissue-specific. [https://www.selleckchem.com/peptide/bulevirtide-myrcludex-b.html find more] Concerning TH transporters, Mct10 expression was upregulated in the pituitary, kidney, hypothalamus, and hippocampus, and Mct8 expression was downregulated in the kidney of the SCH group. Crym expression was upregulated in the kidney and pituitary. Notably, T<br /><br /> replacement significantly attenuated serum TSH levels and reverted Dio1, Dio2, Mct10, and Crym expression in the pituitary, hippocampus, and kidney to levels that were similar to the sham group. Tissue-specific responses were also observed in the liver and hypothalamus.<br /><br /> Our results indicate that treatment of SCH should be considered before the appearance of clinical symptoms of hypothyroidism.<br /><br />Our results indicate that treatment of SCH should be considered before the appearance of clinical symptoms of hypothyroidism.Intimate partner violence (IPV) remains a public health issue plaguing families and communities in the USA. Despite considerable research devoted to individual-level factors affecting IPV and a smaller body of ecological IPV research, few studies explore the interaction between individual-level protective factors and neighborhood- or community-level factors in predicting the incidents of IPV among women. Moreover, most IPV studies utilize a unidimensional approach for social capital, despite strong empirical and theoretical support for a multi-dimensional conceptualization. In a sample of heterosexual women in the USA (N = 1884), we found that concentrated disadvantage, social and physical disorder, and community violence together significantly predicted increased rates of IPV victimization. Concentrated disadvantage and higher scores on the social capital index independently predicted a lower probability of victimization. Moderating effects were found for social capital the protective effects of social capital on the probability of IPV were attenuated for those reporting community violence compared with women who did not report it. These findings enhance the field's understanding of the synergistic relationship between individual- and neighborhood-level factors, providing important implications for community-based IPV interventions.The places that people go and interact with others, along with the characteristics of those places, determine degrees of sexual health risk and concomitant prevention opportunities for gay, bisexual, and other men who have sex with men (MSM). The objective of this paper is to use syndemic theory to guide analyses of 20 in-depth interviews with African American and Hispanic/Latinx MSM living in Los Angeles. We describe the places in which African American and Latinx MSM interviewees live and socialize, and how these places influence sexual behavior, drug use, and access to health care. We find common spatial patterns in mobility, incongruence in residential and sexual places, and differing geographic patterns of sex by men who use geo-social hook-up apps. Significant instability in home life and varying forms of mobility and risk-taking were a response to cumulative disadvantage and intersecting structural forces including poverty, racism, and homophobia. Our results strongly suggest that geographic mobility is a syndemic factor for HIV risk among MSM in Los Angeles, as mobility amplified negative impacts of other syndemic factors.