Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

Potential Determinants of Thyroid Peroxidase Antibodies and Mortality Risk: Results From the ELSA-Brasil Study.

CONTEXT: The presence of thyroid peroxidase antibodies (TPOAbs) may be considered as an indicator of adverse health outcomes. OBJECTIVE: We aimed to investigate the potential determinants of TPOAb levels and to analyze the association between TPOAb titers and the risk of all- and specific-cause mortality. METHODS: Baseline and longitudinal data of 13 187 participants from the ELSA-Brasil Study were analyzed. We investigated the association of TPOAb, detectability, positivity, and persistent positivity with sociodemographic and lifestyle factors using logistic regressions. Cox proportional hazards and Fine-Gray subdistribution hazard regression analyses were used to verify the association of TPOAbs with mortality. RESULTS: The determinants of TPOAb detectability and positivity were younger age, higher body mass index, female sex, and former and current smoking status. Black, mixed, and other self-reported races, intermediate and higher education, and heavy drinking were determinants of detectable and positive TPOAb levels. Female sex, White race, and former smoking were determinants of persistent TPOAb positivity at 2 visits, although only the female sex maintained its association at 3 visits. Moreover, after multivariate adjustment, there were associations between higher levels of TPOAbs and higher risk of cancer-related mortality among men, and TPOAb detectability and mortality by other causes among women. CONCLUSION: Sociodemographic and lifestyle-related factors were determinants of multiple TPOAb categories. TPOAb levels were associated with mortality risk; however, the low mortality rate in this sample might have compromised this finding. We suggest further studies to explore the clinical importance of detectable TPOAb levels, not only its positivity, as a potential marker of inflammation.

NIFTPs may be reclassified not only from FVPTCs but also from follicular adenomas.

Few studies have focused on reclassifying follicular adenomas (FAs) as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), but none have been conducted in America or Europe. The aims of this study were to analyze the prevalence of NIFTP reclassified from follicular variant of papillary thyroid carcinomas (FVPTCs) and FAs before NIFTP was defined in the literature, the rate of NIFTP among PTC (papillary thyroid carcinomas) established in real time between 2017 and 2022, and demographic, ultrasonographic, and cytologic characteristics of NIFTPs compared with FVPTCs and FAs. This was a retrospective cohort study of tumors diagnosed as PTCs (n = 247) and FAs (n = 144) at a Brazilian hospital. Overall, 13.4% of PTCs and 7% of FAs were reclassified as NIFTPs. The rate of real-time diagnosed NIFTPs among PTC was 12.3%. The median tumor size was larger among NIFTPs (3.0 cm) than FVPTCs (1.1 cm; P < 0.01). A high-risk ultrasonographic pattern was rare in NIFTPs (5.6%). The cytologic classifications differed between FVPTCs and NIFTPs (P < 0.01), and the most frequent category among NIFTPs was 'follicular neoplasm' (52.6%). The category 'suspicious for malignancy' was frequent in FVPTCs and rare (5.3%) in NIFTPs. In conclusion, FVPTCs and FAs may be reclassified as NIFTPs. The prevalence of NIFTPs reclassified from FAs was lower in our cohort than in Asian studies. The rate of NIFTPs reclassified from PTC was similar to that of NIFTPs diagnosed in real time and was aligned with rates reported in studies from America and Europe. Preoperative features could not differentiate NIFTPs from FVPTCs or FAs.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

Avaliação da mortalidade associada ao status tireoidiano em uma coorte de pessoas idosas eutireoidianas de ambulatório de geriatria em hospital universitário / Assessment of mortality associated with thyroid status in a cohort of euthyroid older adults from a geriatric outpatient clinic at a university hospital

Resumo Objetivo Avaliar associações entre a média da tireotropina (TSH) e tiroxina livre (T4L) mantida durante follow-up, e mortalidade em pacientes idosos eutireoidianos definidos de acordo com a faixa de referência específica para a idade (FR-e) do TSH. Método Coorte retrospectiva tipo análise de sobrevivência incluindo pacientes idosos eutireoidianos acompanhados no ambulatório de hospital universitário entre 2010 e 2013. Todos os participantes haviam sido avaliados quanto ao risco de incapacidade funcional como critério para admissão nesse ambulatório. As médias dos valores de TSH e T4L foram calculadas através das dosagens obtidas no período de acompanhamento. Cada FR-e de TSH foi dividida em quatro partes iguais, considerando níveis mais baixos como variável de exposição (≤1,75 mUI/L para <80 e ≤2,0 mUI/L para ≥80 anos). Os níveis de T4L foram dicotomizados em duas categorias (< e ≥1,37 ng/dL). O desfecho foi o tempo até a morte. A regressão de risco proporcional de Cox foi empregada para estimar a hazard ratio (HR) e o intervalo de confiança (IC) de 95% Resultados 285 participantes (73% mulheres, idade média =80,4 anos) seguidos pela mediana de 5,7 anos (IQR =3,7-6,4; máximo =7), sendo que 114 faleceram. Após o modelo final ajustado, a mortalidade esteve associada ao TSH no limite inferior (HR=1,7; IC=1,1-2,7; p=0,016) e ao T4L mais elevado. (HR=2,0; IC=1,0-3,8; p=0,052). Conclusão Níveis médios de T4L mais altos e de TSH mais baixos foram associados ao risco de morte em coorte de idosos eutireoidianos usando FR-e de TSH.

Abstract Objective To assess the associations between the mean thyrotropin (TSH) and mean free thyroxine (FT4), detected during follow-up, and mortality in a group of older euthyroid patients according to age-specific reference range (as-RR) for TSH. Method Retrospective survival analysis cohort including euthyroid elderly patients who were being monitored at the outpatient clinic of a university hospital from 2010 to 2013. All participants had been assessed for the risk of functional disability as a criterion for admission to this outpatient clinic. Mean TSH and FT4 values were calculated using hormone dosages obtained during the follow-up period. Each as-RR for TSH was divided into four equal parts, considering the lower levels as the main exposure variable (≤1.75 mlU/L for <80, and ≤2.0 mlU/L for ≥80 years). FT4 levels were explored according to two categories (< e ≥1.37 ng/dL). The outcome was time to death. We used Cox proportional hazard regression to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results 285 participants (73% females, mean age =80.4 years) followed by a median of 5.7 years (IQR =3.7-6.4; maximum =7), of which 114 died. After the adjusted final model, mortality was associated with the lowest mean TSH (HR=1.7; CI=1.1-2.7; p=0.016) and with the upper mean of FT4 (HR=2.0; CI=1.0-3.8; p=0.052). Conclusions Higher FT4 and lower TSH mean levels were associated with risk of death in a cohort of euthyroid older adults using an as-RR of TSH.

Thyroid Volume in Pregnancy is Associated with Parity, Gestational Age, and Body Mass Index in an Iodine-sufficient Area.

OBJECTIVE: We compared thyroid volume (TV) and presence of nodular goiter (NG) in pregnant vs. non-pregnant women in an iodine-sufficient area. We also evaluated the relationship between gestational age, parity, and TV in the pregnant women group, and determined the 2.5th and 97.5th percentiles of normal TV in pregnancy. METHODS: This cross-sectional study included 299 healthy women (216 pregnant) without previous thyroid diseases. Thyroid ultrasounds were performed and compared between pregnant and non-pregnant women. The range of normal distribution of TV (2.5th and 97.5th percentiles) in pregnancy was determined after excluding individuals with positive thyroid antibodies, NG, and/or abnormal serum thyrotropin (TSH) or free thyroxine (FT4). RESULTS: Thyroid volume was larger among pregnant compared to non-pregnant women (8.6 vs 6.1 cm3; p < 0.001) and was positively correlated with gestational age (rs = 0.221; p = 0.001), body mass index (BMI, rs 0.165; p = 0.002), and FT4 levels (rs 0.118 p = 0.021). Nodular goiter frequency did not differ between the two groups. There was a negative correlation between TV and TSH (rs -0.13; p = 0.014). Thyroid volume was lower among primiparous compared to multiparous patients (7.8 vs 8.9; p < 0.001) and was positively correlated with parity (rs 0.161; p = 0.016). The 2.5th and 97.5th percentiles of TV were 4.23 and 16.47 cm3, respectively. CONCLUSION: Thyroid volume was higher in pregnant compared to non-pregnant women and was positively related to parity, BMI, and gestational age in a normal iodine status population. Pregnancy did not interfere with the development of NG.

OBJETIVO: Comparamos o volume tireoidiano (VT) e a presença de bócio nodular (BN) em mulheres grávidas e não grávidas em uma área suficiente em iodo. Também avaliamos a relação entre idade gestacional, paridade e VT no grupo de gestantes e determinamos os percentis 2,5 e 97,5 de VT normal na gestação. MéTODOS: Este estudo transversal incluiu 299 mulheres saudáveis (216 grávidas) sem doenças tireoidianas prévias. Ultrassonografias de tireoide foram realizadas e comparadas entre mulheres grávidas e não grávidas. A faixa de distribuição normal de VT (percentis 2,5 e 97,5) na gestação foi determinada após a exclusão de indivíduos com anticorpos tireoidianos positivos, BN e/ou tireotropina sérica (TSH) ou tiroxina livre (T4L) anormais. RESULTADOS: O VT foi maior entre as gestantes em comparação com as mulheres não grávidas (8,6 vs 6,1 cm3; p < 0,001) e foi positivamente correlacionado com a idade gestacional (rs = 0,221; p = 0,001), índice de massa corporal (IMC, rs 0,165; p = 0,002) e níveis de T4L (rs 0,118 p = 0,021). A frequência de BN não diferiu entre os dois grupos. Houve correlação negativa entre VT e TSH (rs -0,13; p = 0,014). O VT foi menor entre as primíparas em comparação com as multíparas (7,8 vs 8,9; p < 0,001) e foi positivamente correlacionado com a paridade (rs 0,161; p = 0,016). Os percentis 2,5 e 97,5 de VT foram 4,23 e 16,47 cm3, respectivamente. CONCLUSãO: O VT foi maior em gestantes em comparação com mulheres não grávidas e foi positivamente relacionado à paridade, IMC e idade gestacional em uma população com status iódico normal. A gravidez não interferiu no desenvolvimento de BN.

Lyotropic liquid crystalline 2D and 3D mesophases: Advanced materials for multifunctional anticancer nanosystems.

Cancer remains a leading cause of mortality. Despite significant breakthroughs in conventional therapies, treatment is still far from ideal due to high toxicity in normal tissues and therapeutic inefficiency caused by short drug lifetime in the body and resistance mechanisms. Current research moves towards the development of multifunctional nanosystems for delivery of chemotherapeutic drugs, bioactives and/or radionuclides that can be combined with other therapeutic modalities, like gene therapy, or imaging to use in therapeutic screening and diagnosis. The preparation and characterization of Lyotropic Liquid Crystalline (LLC) mesophases self-assembled as 2D and 3D structures are addressed, with an emphasis on the unique properties of these nanoassemblies. A comprehensive review of LLC nanoassemblies is also presented, highlighting the most recent advances and their outstanding advantages as drug delivery systems, including tailoring strategies that can be used to overcome cancer challenges. Therapeutic agents loaded in LLC nanoassemblies offer qualitative and quantitative enhancements that are superior to conventional chemotherapy, particularly in terms of preferential accumulation at tumor sites and promoting enhanced cancer cell uptake, lowering tumor volume and weight, improving survival rates, and increasing the cytotoxicity of their loaded therapeutic agents. In terms of quantitative anticancer efficacy, loaded LLC nanoassemblies reduced the IC50 values from 1.4-fold against lung cancer cells to 125-fold against ovarian cancer cells.

Impact of Bariatric Surgery on Thyroid Morphology and Thyroid Function.

INTRODUCTION: Few studies have evaluated the impact of bariatric surgery (BS) on thyroid function and morphology, and how it correlates to inflammatory and metabolic markers. We aimed to evaluate all those parameters together. METHODS: A longitudinal study included 70 patients with severe obesity. The bariatric group (BG) enrolled 40 patients who underwent BS, and the control group (CG) enrolled 30 patients who did not undergo BS. Both were submitted (pre- and 2nd-year) to thyroid ultrasound and laboratory analyses to determine the levels of thyroid hormones, inflammatory, and metabolic markers. RESULTS: Thyroid volume (TV) decreased after BS (-1.5 cm3), differing significantly from the CG (+0.6 cm3; p = 0.003). ΔTV was independently and positively correlated with ΔHOMA-IR (0.41 (0.11/7.16) p = 0.007) and ΔIL6 (0.02 (0.01/0.3) p = 0.016). A nonsignificant correlation between ΔTV and ΔBMI was detected (0.38 (-0.01/0.09) p = 0.152). We also observed a negative correlation between ΔTV and ΔTSH (-2.03 (-2.87/-1.19) p = 0.000) and ΔT3/T4 ratio (-0.06 (-0.09/-0.02) p = 0.001). TSH had a nonsignificant reduction with BS (-0.3872 vs. -0.2483 p = 0.128). The conversion of T4 to T3 had a significant increase after BS, as demonstrated by the T3/T4 ratio (+5.16 p = 0.01). Despite an increase in the prevalence of thyroid nodules in the BG, it was not statistically significant (p = 0.340). CONCLUSION: BS was associated with a reduction in TV and a nonstatistically significant reduction in TSH. The variations in TV were related to the metabolic markers and inflammatory changes. An increase in the conversion of T4 to T3 with BS was detected, possibly related to inflammatory improvement.

GlycA as a Novel Biomarker of Systemic Inflammation in Hypothyroidism.

Background: GlycA is a novel glycoprotein biomarker of systemic inflammation and cardiovascular risk. Our objective was to assess the levels of GlycA in individuals with hypothyroidism. We also explored whether levothyroxine (LT4)-treated patients had different levels of GlycA, with attention to thyrotropin (TSH) levels. Methods: We performed a cross-sectional analysis, using baseline data from the ELSA-Brasil cohort study. We included only participants with serum TSH and GlycA levels measurements, using magnetic resonance spectroscopy (n = 4745). We excluded individuals with endogenous hyperthyroidism and those using drugs impacting thyroid function. Participants not taking LT4 and whose serum TSH was 0.4-4.0 mIU/L were classified as euthyroid (EU) and those with elevated TSH as undiagnosed hypothyroidism (UH). For those on LT4 (n = 345), adequacy of treatment was defined as TSH within the reference range. Those with TSH <0.4 mIU/L were considered over-treated (OT), and those >4.0 mIU/L, under-treated (UT). Both (UT+OT) were considered inadequately treated (IT). Group comparisons were performed by Kruskal-Wallis, adjusted Chi-square, and the post hoc Dunn test. Additional subgroup analysis were performed in patients with circulating thyroperoxidase antibodies (TPO-Ab+). Respective multivariable analyses were performed to evaluate the relationship between thyroid-related variables and GlycA levels (Generalized Linear Model), as well as an abnormal GlycA (>400 µmol/L; Logistic Binary Regression). Results: The prevalence rate of UH was 9.8% (467/4745) and, among those on LT4, only 61.7% (213/345) were adequately treated (AT). GlycA levels were higher in IT in comparison to EU (429 vs. 410 µmol/L, p < 0.01) but did not differ between UH (413 µmol/L) and euthyroidism. However, the subgroup analysis of those TPO-Ab+ showed that not only those with IT, but also those with UH, had higher levels of GlycA in comparison to euthyroidism (423 and 424 vs. 402 µmol/L, p = 0.04). This association between higher levels of GlycA and IT was maintained even in multivariable analysis (odds ratio 1.53, confidence interval 1.03 to 2.31) Lower levels of GlycA were detected in AT (405 µmol/L,) compared with OT (432 µmol/L, 0.04) and UT (423 µmol/L, p = 0.02). Conclusions: Patients with IT, both OT and UT, had higher GlycA levels, which may be associated with low-grade systemic inflammation and, possibly, increased cardiovascular risk.

Does a three-degree hypoechogenicity grading improve ultrasound thyroid nodule risk stratification and affect the TI-RADS 4 category? A retrospective observational study.

Objective: The aim of this study was to determine whether classifying hypoechogenicity in three degrees (mild, moderate, and marked) could improve the distinction between benign and malignant nodules and whether such an approach could influence Category 4 of the Thyroid Imaging Reporting and Data System (TI-RADS). Materials and methods: In total, 2,574 nodules submitted to fine needle aspiration, classified by the Bethesda System, were retrospectively assessed. Further, a subanalysis considering solid nodules without any additional suspicious findings (n = 565) was performed with the purpose of evaluating mainly TI-RADS 4 nodules. Results: Mild hypoechogenicity was significantly less related to malignancy (odds ratio [OR]: 1.409; CI: 1.086-1.829; p = 0.01), compared to moderate (OR: 4.775; CI: 3.700-6.163; p < 0.001) and marked hypoechogenicity (OR: 8.540; CI: 6.355-11.445; p < 0.001). In addition, mild hypoechogenicity (20.7%) and iso-hyperechogenicity (20.5%) presented a similar rate in the malignant sample. Regarding the subanalysis, no significant association was found between mildly hypoechoic solid nodules and cancer. Conclusion: Stratifying hypoechogenicity into three degrees influences the confidence in the assessment of the rate of malignancy, indicating that mild hypoechogenicity has a unique low-risk biological behavior that resembles iso-hyperechogenicity, but with minor malignant potential when compared to moderate and marked hypoechogenicity, with special influence on the TI-RADS 4 category.

Natural Compounds: Co-Delivery Strategies with Chemotherapeutic Agents or Nucleic Acids Using Lipid-Based Nanocarriers.

Cancer is one of the leading causes of death, and latest predictions indicate that cancer- related deaths will increase over the next few decades. Despite significant advances in conventional therapies, treatments remain far from ideal due to limitations such as lack of selectivity, non-specific distribution, and multidrug resistance. Current research is focusing on the development of several strategies to improve the efficiency of chemotherapeutic agents and, as a result, overcome the challenges associated with conventional therapies. In this regard, combined therapy with natural compounds and other therapeutic agents, such as chemotherapeutics or nucleic acids, has recently emerged as a new strategy for tackling the drawbacks of conventional therapies. Taking this strategy into consideration, the co-delivery of the above-mentioned agents in lipid-based nanocarriers provides some advantages by improving the potential of the therapeutic agents carried. In this review, we present an analysis of the synergistic anticancer outcomes resulting from the combination of natural compounds and chemotherapeutics or nucleic acids. We also emphasize the importance of these co-delivery strategies when reducing multidrug resistance and adverse toxic effects. Furthermore, the review delves into the challenges and opportunities surrounding the application of these co-delivery strategies towards tangible clinical translation for cancer treatment.

Os jovens por eles mesmos: um estudo acerca do fenômeno juvenil na perspectiva de estudantes do Ensino Médio de colégios e unidades sociais no Brasil / The young people self-explained: a study about the youth phenomenon from the perspective of Brazilian High School students from schools and social units

Neste estudo, objetivou-se compreender o ser jovem na contemporaneidade a partir da visão de estudantes do Ensino Médio. Foram utilizados dados de uma pesquisa maior, que contou com dez grupos focais com estudantes brasileiros. Utilizou-se Análise Textual Discursiva para avaliação dos achados. Participaram 80 estudantes oriundos de colégios e unidades sociais de uma rede de ensino privada, habitantes de distintas regiões do país. Os resultados demonstraram que, para a amostra pesquisada, ser jovem era vivenciar pressão por desempenho, por desenvolvimento de um futuro profissional e pela mudança da sociedade. Além disso, envolvia desenvolver autoconhecimento, ser crítico e socialmente responsável, enfrentar riscos e desafios e conquistar autonomia. Os resultados foram discutidos a partir de uma fundamentação gestáltica e fenomenológica. As conclusões apontam para a diversidade e potência das experiências juvenis na contemporaneidade e levantam questionamentos sobre os impactos na clínica psicológica.

The aim of this study was to understand the contemporary young person from the perspective of High School students. We used data from a larger survey, which had ten focus groups of Brazilian students. We used Textual Discourse Analysis to assess the findings. Eighty High School students from schools and social units of a private educational network in different regions of the country participated in the study. The results showed that, for the sample surveyed, being young was to experience pressure for performance, career development, and social change. It also involved developing self-knowledge, being critical and socially responsible, facing risks and challenges and gaining autonomy. The results were discussed using gestalt and phenomenological bases. The conclusions point to the diversity and potential of youth experiences in the contemporaneity and raise questions about their impact on the psychological clinic.

pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance.

Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy.

Os jovens por eles mesmos: um estudo acerca do fenômeno juvenil na perspectiva de estudantes do Ensino Médio de colégios e unidades sociais no Brasil / The young people self-explained: a study about the youth phenomenon from the perspective of Brazilian High School students from schools and social units

Neste estudo, objetivou-se compreender o ser jovem na contemporaneidade a partir da visão de estudantes do Ensino Médio. Foram utilizados dados de uma pesquisa maior, que contou com dez grupos focais com estudantes brasileiros. Utilizou-se Análise Textual Discursiva para avaliação dos achados. Participaram 80 estudantes oriundos de colégios e unidades sociais de uma rede de ensino privada, habitantes de distintas regiões do país. Os resultados demonstraram que, para a amostra pesquisada, ser jovem era vivenciar pressão por desempenho, por desenvolvimento de um futuro profissional e pela mudança da sociedade. Além disso, envolvia desenvolver autoconhecimento, ser crítico e socialmente responsável, enfrentar riscos e desafios e conquistar autonomia. Os resultados foram discutidos a partir de uma fundamentação gestáltica e fenomenológica. As conclusões apontam para a diversidade e potência das experiências juvenis na contemporaneidade e levantam questionamentos sobre os impactos na clínica psicológica. (AU)

The aim of this study was to understand the contemporary young person from the perspective of High School students. We used data from a larger survey, which had ten focus groups of Brazilian students. We used Textual Discourse Analysis to assess the findings. Eighty High School students from schools and social units of a private educational network in different regions of the country participated in the study. The results showed that, for the sample surveyed, being young was to experience pressure for performance, career development, and social change. It also involved developing self-knowledge, being critical and socially responsible, facing risks and challenges and gaining autonomy. The results were discussed using gestalt and phenomenological bases. The conclusions point to the diversity and potential of youth experiences in the contemporaneity and raise questions about their impact on the psychological clinic. (AU)

The effect of probiotics on postsurgical complications in patients with colorectal cancer: a systematic review and meta-analysis.

CONTEXT: Clinical trials have investigated the effect of probiotics on postsurgical complications in colorectal cancer (CRC). However, so far, there are no systematic reviews evaluating the effect of probiotics and synbiotics on the clinical or infectious postsurgical complications of colorectal cancer. OBJECTIVE: The objective of this review was to synthesize the best available evidence on the effects of the use of probiotics or synbiotics on pre-, peri-, and post-operative complications of CRC surgical resection. DATA SOURCES: A search of the PubMed, Embase, LILACS, Scopus, Cochrane, Web of Science, ProQuest, and Google Scholar databases was conducted for clinical trials published up until January 2022. DATA EXTRACTION: The population characteristics, period and protocol of supplementation, and postoperative complications were extracted and reported. A random-effects model was used to estimate the effect of probiotic and synbiotic treatment on these variables. DATA SYNTHESIS: In total, 2518 studies were identified, of which 16 were included in the qualitative synthesis and 13 in the meta-analysis. Overall, probiotic supplementation reduced the incidence of ileus (odds ratio [OR] = .13, 95% confidence interval [CI]: .02, .78), diarrhea (OR = .32, 95% CI: .15, .69), abdominal collection (OR: .35, 95% CI: .13, .92), sepsis (OR = .41, 95% CI: .22, .80), pneumonia (OR = .39, 95% CI: .19, .83), and surgical site infection (OR = .53, 95% CI: .36, .78). The results of the subgroup analysis indicated that lower dose (<109 colony-forming units), higher duration of supplementation (>14 days), and being administrated ≤5 days before and >10 days after surgery was more effective at reducing the incidence of surgical site infection. CONCLUSION: Probiotics and synbiotics seem to be a promising strategy for the prevention of postoperative complications after CRC surgery. Larger, high-quality randomized controlled trials are needed to establish the optimal treatment protocol for the use of probiotics and synbiotics in preventing postoperative complications for CRC surgery.

Thyroid Volume in Pregnancy is Associated with Parity, Gestational Age, and Body Mass Index in an Iodine-sufficient Area / O volume tireoidiano em gestantes está associado à paridade, idade gestacional e índice de massa corporal em uma área suficiente em iodo

Abstract Objective We compared thyroid volume (TV) and presence of nodular goiter (NG) in pregnant vs. non-pregnant women in an iodine-sufficient area. We also evaluated the relationship between gestational age, parity, and TV in the pregnant women group, and determined the 2.5th and 97.5th percentiles of normal TV in pregnancy. Methods This cross-sectional study included 299 healthy women (216 pregnant) without previous thyroid diseases. Thyroid ultrasounds were performed and compared between pregnant and non-pregnant women. The range of normal distribution of TV (2.5th and 97.5th percentiles) in pregnancy was determined after excluding individuals with positive thyroid antibodies, NG, and/or abnormal serum thyrotropin (TSH) or free thyroxine (FT4). Results Thyroid volume was larger among pregnant compared to non-pregnant women (8.6 vs 6.1 cm3; p< 0.001) and was positively correlated with gestational age (rs = 0.221; p= 0.001), body mass index (BMI, rs 0.165; p= 0.002), and FT4 levels (rs 0.118 p= 0.021). Nodular goiter frequency did not differ between the two groups. There was a negative correlation between TV and TSH (rs -0.13; p= 0.014). Thyroid volume was lower among primiparous compared to multiparous patients (7.8 vs 8.9; p< 0.001) and was positively correlated with parity (rs 0.161; p= 0.016). The 2.5th and 97.5th percentiles of TV were 4.23 and 16.47 cm3, respectively. Conclusion Thyroid volume was higher in pregnant compared to non-pregnant women and was positively related to parity, BMI, and gestational age in a normal iodine status population. Pregnancy did not interfere with the development of NG.

Resumo Objetivo Comparamos o volume tireoidiano (VT) e a presença de bócio nodular (BN) em mulheres grávidas e não grávidas em uma área suficiente em iodo. Também avaliamos a relação entre idade gestacional, paridade e VT no grupo de gestantes e determinamos os percentis 2,5 e 97,5 de VT normal na gestação. Métodos Este estudo transversal incluiu 299 mulheres saudáveis (216 grávidas) sem doenças tireoidianas prévias. Ultrassonografias de tireoide foram realizadas e comparadas entre mulheres grávidas e não grávidas. A faixa de distribuição normal de VT (percentis 2,5 e 97,5) na gestação foi determinada após a exclusão de indivíduos com anticorpos tireoidianos positivos, BN e/ou tireotropina sérica (TSH) ou tiroxina livre (T4L) anormais. Resultados O VT foi maior entre as gestantes em comparação com as mulheres não grávidas (8,6 vs 6,1 cm3; p< 0,001) e foi positivamente correlacionado com a idade gestacional (rs = 0,221; p= 0,001), índice de massa corporal (IMC, rs 0,165; p= 0,002) e níveis de T4L (rs 0,118 p= 0,021). A frequência de BN não diferiu entre os dois grupos. Houve correlação negativa entre VT e TSH (rs -0,13; p= 0,014). O VT foi menor entre as primíparas em comparação com as multíparas (7,8 vs 8,9; p< 0,001) e foi positivamente correlacionado com a paridade (rs 0,161; p= 0,016). Os percentis 2,5 e 97,5 de VT foram 4,23 e 16,47 cm3, respectivamente. Conclusão O VT foi maior em gestantes em comparação com mulheres não grávidas e foi positivamente relacionado à paridade, IMC e idade gestacional em uma população com status iódico normal. A gravidez não interferiu no desenvolvimento de BN.

Eficácia do rejuvenescimento da região periorbital com uma sessão de laser fracionado Erbium: YAG 2940nm no modo duplo / Efficacy of periorbital region rejuvenation with a single session of Erbium: YAG 2940nm fractional laser in dual mode

Introdução: rugas e flacidez na região periorbital são queixas frequentes. O laser fracionado ablativo (LFA) CO2 10600nm e o Erbium: YAG 2940nm têm a capacidade de induzir a neocolagênese e a contração das fibras de colágeno. Objetivos: o objetivo do nosso estudo foi observar a eficácia de uma única sessão de laser fracionado Erbium: YAG 2940nm dual mode no tratamento de flacidez, rítides e bolsas de gordura das pálpebras superiores e inferiores. Métodos: 17 pacientes com flacidez, rítides e bolsas de gordura das pálpebras superiores e inferiores foram submetidos a uma sessão de laser fracionado ablativo Erbium: YAG 2940nm da plataforma Etherea em modo duplo. Os registros fotográficos foram realizados no mesmo ambiente antes do tratamento e um mês após o término do protocolo. A avaliação foi realizada objetivamente por cinco dermatologistas e cirurgiões plásticos independentes ao estudo. Resultados: as melhorias na avaliação de rítides, linhas de expressão e flacidez foram clínica e estatisticamente significativas, com poucos efeitos adversos, como edema, eritema e descamação. No entanto, as bolsas de gordura não melhoraram significativamente. Conclusão: uma única sessão com o modo duplo LFA Erbium: YAG 2940nm pode contribuir para uma melhoria significativa de rítides, linhas finas e flacidez da área periorbital.

Background: Wrinkles and flaccidity in the periocular region are frequent complaints. Ablative fractional lasers (AFL) CO2 10600nm and Erbium:YAG 2940nm can induce neocollagenesis and contraction of collagen fibers. Objective: Our study aimed to observe the effectiveness of one session of dual mode Erbium:YAG 2940nm fractional laser to treat sagging, rhytids, and fat bags of the upper and lower eyelids. Methods: Seventeen patients with sagging, rhytids, and fat bags of the upper and lower eyelids underwent one session of Ablative fractional laser (AFL) 2940nm from the Etherea platform in dual mode. Photographic records were taken in the same environment before treatment and one month after the end of the protocol, and five dermatologists and plastic surgeons independent of the study assessed them objectively. Results: The improvements in the evaluation of rhytids, fine lines, and flaccidity were clinically and statistically significant with few adverse events such as edema, erythema, and desquamation. However, eyelid bags did not improve significantly. Conclusion: A single session with the dual mode AFL Erbium:YAG tip 2940 can contribute to a significant improvement in rhytids, fine lines, and flaccidity of the periorbital area.

Does a three-degree hypoechogenicity grading improve ultrasound thyroid nodule risk stratification and affect the TI-RADS 4 category? A retrospective observational study

ABSTRACT Objective: The aim of this study was to determine whether classifying hypoechogenicity in three degrees (mild, moderate, and marked) could improve the distinction between benign and malignant nodules and whether such an approach could influence Category 4 of the Thyroid Imaging Reporting and Data System (TI-RADS). Materials and methods: In total, 2,574 nodules submitted to fine needle aspiration, classified by the Bethesda System, were retrospectively assessed. Further, a subanalysis considering solid nodules without any additional suspicious findings (n = 565) was performed with the purpose of evaluating mainly TI-RADS 4 nodules. Results: Mild hypoechogenicity was significantly less related to malignancy (odds ratio [OR]: 1.409; CI: 1.086-1.829; p = 0.01), compared to moderate (OR: 4.775; CI: 3.700-6.163; p < 0.001) and marked hypoechogenicity (OR: 8.540; CI: 6.355-11.445; p < 0.001). In addition, mild hypoechogenicity (20.7%) and iso-hyperechogenicity (20.5%) presented a similar rate in the malignant sample. Regarding the subanalysis, no significant association was found between mildly hypoechoic solid nodules and cancer. Conclusion: Stratifying hypoechogenicity into three degrees influences the confidence in the assessment of the rate of malignancy, indicating that mild hypoechogenicity has a unique low-risk biological behavior that resembles iso-hyperechogenicity, but with minor malignant potential when compared to moderate and marked hypoechogenicity, with special influence on the TI-RADS 4 category.

Natural Sympathomimetic Drugs: From Pharmacology to Toxicology.

Sympathomimetic agents are a group of chemical compounds that are able to activate the sympathetic nervous system either directly via adrenergic receptors or indirectly by increasing endogenous catecholamine levels or mimicking their intracellular signaling pathways. Compounds from this group, both used therapeutically or abused, comprise endogenous catecholamines (such as adrenaline and noradrenaline), synthetic amines (e.g., isoproterenol and dobutamine), trace amines (e.g., tyramine, tryptamine, histamine and octopamine), illicit drugs (e.g., ephedrine, cathinone, and cocaine), or even caffeine and synephrine. In addition to the effects triggered by stimulation of the sympathetic system, the discovery of trace amine associated receptors (TAARs) in humans brought new insights about their sympathomimetic pharmacology and toxicology. Although synthetic sympathomimetic agents are mostly seen as toxic, natural sympathomimetic agents are considered more complacently in the terms of safety in the vision of the lay public. Here, we aim to discuss the pharmacological and mainly toxicological aspects related to sympathomimetic natural agents, in particular of trace amines, compounds derived from plants like ephedra and khat, and finally cocaine. The main purpose of this review is to give a scientific and updated view of those agents and serve as a reminder on the safety issues of natural sympathomimetic agents most used in the community.

Relationship between Attention to Body Shape, Social Physique Anxiety, and Personal Characteristics of Brazilians: A Structural Equation Model.

People can develop eating disorders due to excessive body image concerns. The primary objective of this study was to examine the relationship between attention to body shape, social physique anxiety, and personal characteristics in a sample of Brazilians. The secondary objective was to evaluate the correlation of the constructs with the participants' body composition. First, 1795 individuals (70% female; Mage = 25.5 ± 6.6 years) completed the Attention to Body Shape Scale, the Social Physique Anxiety Scale, and a sociodemographic questionnaire. Then, 286 participants (58% female; Mage = 25.3 ± 5.7 years) underwent a bioimpedance exam to identify body composition. Structural equation modeling was used to estimate the relationship between the variables. The greater the attention to body shape, the greater the expectations of negative physical evaluation and the less comfort with physical presentation. Younger age, female gender, consumption of supplements/substances for body change, restrictive diets, physical inactivity, poor self-assessment of food quality, and overweight/obesity were related to negative body concerns. An expectation of negative physical evaluation was positively correlated with body fat and negatively with muscle mass. Comfort with physical presentation was negatively correlated with fat and positively with muscle. These results can support preventive strategies aimed at reducing eating disorders resulting from body image concerns.