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University students frequently resort to psychostimulants to enhance their physical and mental performance and manage academic pressures. However, these substances can lead to dependence and other undesired symptoms, and little empirical data are available for relevant stakeholders, raising significant concerns in health care. Therefore, this study aims to characterize neurostimulant use among university students in Rio Grande do Sul, Brazil. We collected from 880 students' data using anonymous self-administration. The questionnaire included consumption patterns of caffeine, nicotine, ecstasy, methamphetamine, "merla" (coca base), methylphenidate, cocaine, crack, and ketamine. Additionally, participants shared information on demographic and socioeconomic factors. Use of at least one neurostimulant was reported by89.2% of the participants. Among nonusers, the most frequently cited reason was "previous information about harmful effects of these drugs." Caffeine, followed by nicotine, ecstasy, and methylphenidate were the most consumed substances, with main reasons being "improving academic performance" and "recreation." Women more often consumed caffeine (72.7%), while other psychostimulants were more consumed by men (42.2%) and individuals of other genders (0.5%). Students who consumed other substances had higher family incomes than that of families of caffeine users. In addition, 60.4% of caffeine users resided with family members, whereas 63.3% of users of other substances did not. Our findings can offer essential data on the reasons and symptoms associated with the use of neurostimulants among university students. This information could aid in raising awareness among students, universities, and health-care agencies about this often-neglected subject.

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Aim: Our objective was to investigate the trypanocidal effect of the chalcone (2E,4E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-5-phenylpenta-2,4-dien-1-one (CPNC). Material & methods: Cytotoxicity toward LLC-MK2 host cells was assessed by MTT assay, and the effect on Trypanosoma cruzi life forms (epimastigotes, trypomastigotes and amastigotes) was evaluated by counting. Flow cytometry analysis was performed to evaluate the possible mechanisms of action. Finally, molecular docking simulations were performed to evaluate interactions between CPNC and T. cruzi enzymes. Results: CPNC showed activity against epimastigote, trypomastigote and amastigote life forms, induced membrane damage, increased cytoplasmic reactive oxygen species and mitochondrial dysfunction on T. cruzi. Regarding molecular docking, CPNC interacted with both trypanothione reductase and TcCr enzymes. Conclusion: CPNC presented a trypanocidal effect, and its effect is related to oxidative stress, mitochondrial impairment and necrosis.

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Chagas disease (CD) is a neglected tropical disease of worldwide health concern, caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi), endemic in Latin America and present in North America and Europe. The WHO recommended drug for CD, benznidazole has low safety profile and several limitations. Therefore, an entity with better therapeutic potential to treat CD is required. Chalcones are an important class of compounds, which have shown antichagasic potential. Thus, the objective of this study was to evaluate the activity of synthetic p-aminochalcones against T. cruzi. Chalcones 1 and 2 were synthesized by Claisen-Schmidt condensation and characterized by both spectroscopic and theoretical methods. Initially, they were submitted to molecular docking simulations using cruzain and trypanothione reductase (TR) enzymes. It was expected to observe the possible interactions of chalcones with the catalytic site and other important regions of these main pharmacological targets of T. cruzi. Their cytotoxicity within host cells were assessed by MTT reduction assay using LLC-MK2 cells, with CC50 = 85.6 ± 9.2 µM and 1115 ± 381.7 µM for chalcones 1 and 2, respectively. These molecules were also tested against epimastigote and trypomastigote life forms of T. cruzi, causing reduction in the number of viable parasites. For the evaluation of the effect on intracellular amastigotes, infected LLC-MK2 cells were incubated with the chalcones for 24 h, causing reduction in the percentage of infected cells and the number of amastigotes/100 cells. Finally, flow cytometry assays were performed for analyzing cell death mechanisms (7-AAD/AxPE labelling), cytoplasmic ROS accumulation (DCFH-DA assay) and mitochondrial transmembrane potential disruption (Rho123 assay). Both chalcones (1 and 2) caused membrane damage, ROS accumulation and mitochondrial depolarization. In conclusion, the synthetic p-aminochalcones presented trypanocidal effect, causing membrane damage and oxidative stress. Their mechanism of action may be related to cruzain and TR inhibition.

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Purpose: To evaluate the effect of MDRO infection on hospital mortality and the risk factors among critically ill patients with sepsis at hospital admission. Patients and Methods: A cross-sectional study was performed between April 2019 and May 2020, followed by a cohort to evaluate hospital mortality that prospectively included all consecutive patients 18 years or older with sepsis admitted within 48 hours of hospital admission to an adult ICU in Brazil. Patients' characteristics, blood samples within one hour of ICU admission, and microbiological results within 48h of hospital admission were collected. In addition, descriptive statistics, binary logistic regression, and propensity score matching were performed. Results: At least one MDRO was isolated in 85 patients (9.8%). The extended-spectrum beta-lactamase-producing Enterobacterales are the most frequent organism (56.1%). Hypoxemic acute respiratory failure (OR 1.87, 95% CI 1.02-3.40, p = 0.04), Glasgow Coma Score below 15 (OR 2.57, 95% CI 1.38-4.80, p < 0.01), neoplasm (OR 2.66, 95% CI 1.04-6.82, p = 0.04) and hemoglobin below 10.0 g/dL (OR 1.82, 95% CI 1.05-3.16, p = 0.03) were associated with increased MDRO. Admission from the Emergency Department (OR 0.25, 95% CI 0.14-0.43, p < 0.01) was associated with decreased MDRO. In the multivariate analysis, MDRO at hospital admission increased hospital mortality (OR 2.80, 95% CI 1.05-7.42, p = 0.04). After propensity score-matching adjusted to age, APACHE II, SOFA, and dementia, MDRO at hospital admission was associated with significantly high hospital mortality (OR 2.80, 95% CI 1.05-7.42, p = 0.04). The E-value of adjusted OR for the effect of MDRO infection on hospital mortality was 3.41, with a 95% CI of 1.31, suggesting that unmeasured confounders were unlikely to explain the entirety of the effect. Conclusion: MDRO infection increased hospital mortality, and MDRO risk factors should be accessed even in patients admitted to ICU within 48 hours of hospital admission.

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Cardiomyopathy is a major cause of death in Chagas disease and early detection of cardiac involvement is essential. Myocardial strain is a reliable technique for assessment of subtle left ventricular (LV) contractility alterations. This study assessed LV global longitudinal strain (GLS) in a large Chagas disease population living in remote areas. Between 2015 and 2016, Chagas disease patients were selected in the northern of the Minas Gerais state. All patients underwent T. cruzi antibodies tests and those who had positive tests were included. A resting 12-lead ECG was recorded and classified using the Minnesota Code criteria. Echocardiography was performed at public health primary care units and speckle-tracking strain was analyzed offline. LV dysfunction was defined as ejection fraction (LVEF < 50%) and reduced GLS was defined as < 16% (absolute value). A total of 1387 patients were included, mean age of 60.0 ± 12.5 years, 68% were women, and 14% had LV dysfunction. Among patients with normal LVEF, 59% had impaired LV GLS. Overall, patients with impaired GLS were older, had more comorbidities and ECG abnormalities than those with normal GLS. The independent factors associated with reduced GLS were ST-T abnormalities (OR 1.954; 95% CI 1.027-3.718), QRS duration (OR 1.009; 95% CI 1.002-1.016), LVEF (OR 0.947; 95% CI 0.923-0.972), and E/e' ratio (OR 1.059; 95% CI 1.009-1.112). In a cohort of Chagas disease from endemic areas, impaired LV GLS was detected in a significant proportion of patients, despite normal ECG and preserved LVEF. The main determinants of reduced LV GLS were ST-T abnormalities, QRS duration, LVEF and E/e' ratio, adjusting for demographical and clinical data.

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Objective: This in vitro study evaluated the effect of neolignan-containing solutions on dentin biomodification previously applied to the bonding procedure in adhesive restorations. Material and Methods: Neolignans, dehydrodieugenol B­CP1 and dehydrodieugenol B methyl ether­CP2, were isolated from Nectandra leucanthaand two aqueous solutions containing 0.13% neolignans, 0.2% propylene glycol and 3.0% ethanol were prepared. Bovine teeth were ground flat to obtain 2-mm thick specimens which received resin composite restorations (N=10). The neolignan solutions were applied before the bonding procedure (60 s). Experimental groups were: control, untreated group, 0.12% chlorhexidine gel, 0.13% CP1 solution, and 0.13% CP2 solution. A push-out bond strength test was conducted (0.5 mm/min). Bovine tooth sections (0.5×1.7×7.0 mm) were also obtained to assess the modulus of elasticity and mass change after treatment (N=15). A three-point bending test evaluated the elastic modulus of fully demineralized dentine beams after immersion in the solutions. The data were statistically analyzed (α = 0.05). Results: The bond strength of the restorations to dentin was significantly improved by the treatment with neolignan-containing solutions, irrespective of the evaluation time (p<0.05). After 6 months, a significant reduction in the bond strength was observed in the groups treated with the solutions (p>0.05), but the means were significantly higher than the control groups (p<0.05). The elastic modulus of demineralized dentin was significantly improved after the treatment with the solutions (p<0.05). All groups lost mass weight. Conclusion: The solutions improved the in vitro longevity of bonded restorations, possibly due to the dentin biomodification effect of the neolignans.(AU)

Objetivo: Este estudo in vitro avaliou o efeito de soluções contendo neolignanas na biomodificação da dentina aplicadas previamente à restaurações adesivas. Material e Métodos: Neolignanas, desidrodieugenol B­CP1 e éter metílico de desidrodieugenol B-CP2, foram isolados da espécie Nectandra leucantha e duas soluções aquosas contendo 0,13% de neolignanos, 0,2% de propilenoglicol e 3,0% de etanol foram preparadas. Dentes bovinos foram lixados para obter espécimes de 2 mm de espessura e preparos cavitários restaurados com resina composta (N=10). As soluções foram aplicadas em dentina antes do procedimento adesivo (60 s). Os grupos experimentais foram: controle, grupo não tratado, gel de clorexidina 0,12%, solução de CP1 a 0,13% e solução de CP2 a 0,13%. Foi realizado o teste de resistência de união push-out (0,5 mm/min). O módulo de elasticidade e a alteração de massa após tratamento da dentina (0,5×1,7×7,0 mm) foram também avaliados em teste de flexão de três pontos (N=15). Os dados foram analisados estatisticamente (α=0,05). Resultados: A resistência de união das restaurações à dentina melhorou significativamente com o tratamento com as soluções, independentemente do tempo de avaliação (p<0,05). Após 6 meses, foi observada redução significativa da resistência de união nos grupos tratados com as soluções (p>0,05), com médias significativamente maiores do que nos grupos controle (p<0,05). O módulo de elasticidade da dentina desmineralizada aumentou significativamente após tratamento com as soluções (p<0,05). Todos os grupos perderam massa, independentemente do tratamento. Conclusão: As soluções melhoraram in vitroa longevidade das restaurações adesivas, possivelmente devido ao efeito biomodificador da dentina das neolignanas(AU)

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BACKGROUND: To evaluate the association of thyroid hormones changes, including increased reverse triiodothyronine (rT3) level, with critically ill clinical patients´ mortality. PATIENTS AND METHODS: This study analyzed the observational data prospectively collected over 8 months (2018) in an adult intensive care unit (ICU) in Brasilia, Brazil. All consecutive ICU-admitted clinical patients were included. Thyroxine (T4), free thyroxine (fT4), triiodothyronine (T3), free triiodothyronine (fT3), rT3, and thyroid-stimulating hormone (TSH) were collected within 48 hours of ICU admission. Patients with hypothyroidism or hyperthyroidism who were previously diagnosed were excluded. RESULTS: Of 353 included patients, age was 68.5 ± 19.0 years, sequential organ failure assessment (SOFA) score was 3.3 ± 2.9, and Acute Physiology and Chronic Health Evaluation II (APACHE II) was 17.1 ± 7.9. ICU mortality was 17.6% (n = 62). Non-survivor patients had a higher incidence of increased rT3 (69.3 vs 59.2%, p = 0.042), lower incidence of low T4 (4.8 vs 9.7%, p = 0.045), and increased age (75.2 ± 16.3 years vs 67.1 ± 19.3 years, p = 0.001), SOFA (3.0 ± 0.4 vs 2.8 ± 2.6, p <0.001), and APACHE II (23.5 ± 7.5 vs 15.7 ± 7.2, p <0.001). Alterations in other thyroid hormones did not show association with mortality. Increased rT3 [odds ratio (OR): 2.436; 95% confidence interval (CI): 1.023-5.800; p = 0.020] and APACHE II (OR: 1.083, 95% CI: 1.012-1.158; p = 0.044) were associated with ICU mortality in the multivariate analysis. CONCLUSION: Increased rT3 was independently associated with increased ICU mortality. In contrast, other thyroid hormone alterations did not show an association with mortality. Determining rT3 levels may be a helpful test to identify an increased risk for ICU mortality in clinical patients. HOW TO CITE THIS ARTICLE: da Silveira CDG, de Vasconcelos FPJ, Moura EB, da Silveira BTG, Amorim FFP, Shintaku LS, et al. Thyroid Function, Reverse Triiodothyronine, and Mortality in Critically Ill Clinical Patients. Indian J Crit Care Med 2021;25(10):1161-1166.

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ABSTRACT: The focus of this prospective cohort study was to evaluate the risk factors of severe acute skin toxicity (grade ≥2) in 100 patients with breast cancer (BC) during radiotherapy (RT).The patients were evaluated weekly during RT and 3 months after treatment. The endpoint included the occurrence of skin toxicity grade ≥2, according to Radiation Therapy Oncology Group (RTOG). Survival analysis was conducted by univariate and multivariate Cox regression analysis.In the multivariate analysis, RT in the afternoon (0-3 pm) (hazard ratios [HR] = 1.566, P = .042) was significantly associated with the early occurrence of skin toxicity, indicating a potential effect of chronotherapy related to this adverse event. In the univariate and multivariate analysis, skin phototype moderate brown (HR = 1.586, P = .042; HR = 1.706, P = .022, respectively) and dark brown or black (HR = 4.517, P < .001; HR = 5.336, P < 0.001, respectively) was significantly associated with the skin toxicity. Tangential field separation >21 cm (HR = 2.550, P = .009, HR = 2.923, P = .003), in women that were submitted to conservative surgery indicates indirectly that large breast size was also significantly associated with skin toxicity.Women with large breasts and dark brown or black skin should be followed more carefully during RT, which should be undergone in the morning, especially when submitted to conventional RT techniques, common in developing countries.

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