Exploring first-degree family history in a cohort of Portuguese Alzheimer's disease patients: population evidence for X-chromosome linked and recessive inheritance of risk factors.

BACKGROUND: Alzheimer's disease (AD) heritability is estimated to be around 70-80%. Yet, much of it remains to be explained. Studying transmission patterns may help in understanding other factors contributing to the development of AD. OBJECTIVE: In this study, we aimed to search for evidence of autosomal recessive or X- and Y-linked inheritance of risk factors in a large cohort of Portuguese AD patients. METHODS: We collected family history from patients with AD and cognitively healthy controls over 75 years of age. We compared the proportions of maternal and paternal history in male and female patients and controls (to search for evidence of X-linked and Y-linked inherited risk factors). We compared the risk of developing AD depending on parents' birthplace (same vs. different), as a proxy of remote consanguinity. We performed linear regressions to study the association of these variables with different endophenotypes. RESULTS: We included 3090 participants, 2183 cognitively healthy controls and 907 patients with AD. Men whose mother had dementia have increased odds of developing AD comparing to women whose mother had dementia. In female patients with a CSF biomarker-supported diagnosis of AD, paternal history of dementia is associated with increased CSF phosphorylated Tau levels. People whose parents are from the same town have higher risk of dementia. In multivariate analysis, this proxy is associated with a lower age of onset and higher CSF phosphorylated tau. CONCLUSIONS: Our study gives evidence supporting an increased risk of developing AD associated with an X-linked inheritance pattern and remote consanguinity.

2D Phase Formation on 3D Perovskite: Insights from Molecular Stiffness.

Several studies have demonstrated that low-dimensional structures (e.g., two-dimensional (2D)) associated with three-dimensional (3D) perovskite films enhance the efficiency and stability of perovskite solar cells. Here, we aim to track the formation sites of the 2D phase on top of the 3D perovskite and to establish correlations between molecular stiffness and steric hindrance of the organic cations and their influence on the formation and crystallization of 2D/3D. Using cathodoluminescence combined with a scanning electron microscopy technique, we verified that the formation of the 2D phase occurs preferentially on the grain boundaries of the 3D perovskite. This helps explain some passivation mechanisms conferred by the 2D phase on 3D perovskite films. Furthermore, by employing in situ grazing-incidence wide-angle X-ray scattering, we monitored the formation and crystallization of the 2D/3D perovskite using three cations with varying molecular stiffness. In this series of molecules, the formation and crystallization of the 2D phase are found to be dependent on both steric hindrance around the ammonium group and molecular stiffness. Finally, we employed a 2D/3D perovskite heterointerface in a solar cell. The presence of the 2D phase, particularly those formed from flexible cations, resulted in a maximum power conversion efficiency of 21.5%. This study provides insight into critical aspects related to how bulky organic cations' stiffness and steric hindrance influence the formation, crystallization, and distribution of 2D perovskite phases.

Rare genetic variants of NLRP12 in Admixed Latino-American Children with SARS-CoV-2-related Multisystem Inflammatory Syndrome.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole-exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on NF-κB signaling. Nine rare, potentially deleterious variants were found in eight of 21 patients, located in IL17RC, IFNA10, or NLRP12 genes. Unlike the wild-type NLRP12 protein, which inhibits NF-κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C.

Acute generalized exanthematous pustulosis triggered by COVID-19.

Acute generalized exanthematous pustulosis is a severe adverse skin reaction, usually caused by drugs, but in rare cases it can be associated with infections. Several cases related to COVID-19 have been reported, however, almost all were drug-related. Here we report a case of acute generalized exanthematous pustulosis associated with COVID-19 in a previously healthy 64-year-old woman, with no culprit drugs.

Fluorogenic RNA-based biomaterials for imaging and tracking the cargo of extracellular vesicles.

Extracellular vesicles (EVs), or exosomes, play important roles in physiological and pathological cellular communication and have gained substantial traction as biological drug carriers. EVs contain both short and long non-coding RNAs that regulate gene expression and epigenetic processes. To fully capitalize on the potential of EVs as drug carriers, it is important to study and understand the intricacies of EV function and EV RNA-based communication. Here we developed a genetically encodable RNA-based biomaterial, termed EXO-Probe, for tracking EV RNAs. The EXO-Probe comprises an EV-loading RNA sequence (EXO-Code), fused to a fluorogenic RNA Mango aptamer for RNA imaging. This fusion construct allowed the visualization and tracking of EV RNA and colocalization with markers of multivesicular bodies; imaging RNA within EVs, and non-destructive quantification of EVs. Overall, the new RNA-based biomaterial provides a useful and versatile means to interrogate the role of EVs in cellular communication via RNA trafficking to EVs and to study cellular sorting decisions. The system will also help lay the foundation to further improve the therapeutic efficacy of EVs as drug carriers.

Arsenic bioaccumulation and biotransformation in different tissues of Nile tilapia (Oreochromis niloticus): A comparative study between As(III) and As(V) exposure and evaluation of antagonistic effects of selenium.

The speciation of arsenic in fish has been widely investigated, but bioaccumulation and biotransformation of inorganic As in different tissues of Nile tilapia (Oreochromis niloticus) are not fully understood. The present study aimed to investigate the bioaccumulation of As in Nile tilapia, as well as to evaluate the distribution of the main arsenic species (As(III), As(V), MMA, DMA, and AsB) in liver, stomach, gill, and muscle, after controlled exposures to As(III) and As(V) at concentrations of 5.0 and 10.0 mg L-1 during periods of 1 and 7 days. Total As was determined by inductively coupled plasma mass spectroscopy (ICP-MS). For both exposures (As(III) and As(V)), the total As levels after 7-day exposure were highest in the liver and lowest in the muscle. Overall, the Nile tilapia exposed to As(III) showed higher tissue levels of As after the treatments, compared to As(V) exposure. Speciation of arsenic present in the tissues employed liquid chromatography coupled to ICP-MS (LC-ICP-MS), revealing that the biotransformation of As included As(V) reduction to As(III), methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and subsequent conversion to nontoxic arsenobetaine (AsB), which was the predominant arsenic form. Finally, the interactions and antagonistic effects of selenium in the bioaccumulation processes were tested by the combined exposure to As(III), the most toxic species of As, together with tetravalent selenium (Se(IV)). The results indicated a 4-6 times reduction of arsenic toxicity in the tilapia.

The Clinical and Economic Impact of Delayed Reperfusion Therapy: Real-World Evidence. / O Impacto Clínico e Econômico do Atraso na Terapia de Reperfusão: Evidências do Mundo Real.

BACKGROUND: Early reperfusion therapy is acknowledged as the most effective approach for reducing case fatality rates in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVE: Estimate the clinical and economic consequences of delaying reperfusion in patients with STEMI. METHODS: This retrospective cohort study evaluated mortality rates and the total expenses incurred by delaying reperfusion therapy among 2622 individuals with STEMI. Costs of in-hospital care and lost productivity due to death or disability were estimated from the perspective of the Brazilian Unified Health System indexed in international dollars (Int$) adjusted by purchase power parity. A p < 0.05 was considered statistically significant. RESULTS: Each additional hour of delay in reperfusion therapy was associated with a 6.2% increase (95% CI: 0.3% to 11.8%, p = 0.032) in the risk of in-hospital mortality. The overall expenses were 45% higher among individuals who received treatment after 9 hours compared to those who were treated within the first 3 hours, primarily driven by in-hospital costs (p = 0.005). A multivariate linear regression model indicated that for every 3-hour delay in thrombolysis, there was an increase in in-hospital costs of Int$497 ± 286 (p = 0.003). CONCLUSIONS: The findings of our study offer further evidence that emphasizes the crucial role of prompt reperfusion therapy in saving lives and preserving public health resources. These results underscore the urgent need for implementing a network to manage STEMI cases.

FUNDAMENTO: A terapia de reperfusão precoce é reconhecida como a abordagem mais eficaz para reduzir as taxas de letalidade de casos em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). OBJETIVO: Estimar as consequências clínicas e econômicas do atraso da reperfusão em pacientes com IAMCSST. MÉTODOS: O presente estudo de coorte retrospectivo avaliou as taxas de mortalidade e as despesas totais decorrentes do atraso na terapia de reperfusão em 2.622 indivíduos com IAMCSST. Os custos de cuidados hospitalares e perda de produtividade por morte ou incapacidade foram estimados sob a perspectiva do Sistema Único de Saúde indexado em dólares internacionais (Int$) ajustados pela paridade do poder de compra. Foi considerado estatisticamente significativo p < 0,05. RESULTADOS: Cada hora adicional de atraso na terapia de reperfusão foi associada a um aumento de 6,2% (intervalo de confiança de 95%: 0,3% a 11,8%, p = 0,032) no risco de mortalidade hospitalar. As despesas gerais foram 45% maiores entre os indivíduos que receberam tratamento após 9 horas em comparação com aqueles que foram tratados nas primeiras 3 horas, impulsionados principalmente pelos custos hospitalares (p = 0,005). Um modelo de regressão linear multivariada indicou que para cada 3 horas de atraso na trombólise, houve um aumento nos custos hospitalares de Int$ 497 ± 286 (p = 0,003). CONCLUSÕES: Os achados do nosso estudo oferecem mais evidências que enfatizam o papel crucial da terapia de reperfusão imediata no salvamento de vidas e na preservação dos recursos de saúde pública. Estes resultados enfatizam a necessidade urgente de implementação de uma rede para gerir casos de IAMCSST.

Application of experimental design as a statistical approach to recover bioactive peptides from different food sources.

Bioactive peptides (BAPs) derived from samples of animals and plants have been widely recommended and consumed for their beneficial properties to human health and to control several diseases. This work presents the applications of experimental designs (DoE) used to perform factor screening and/or optimization focused on finding the ideal hydrolysis condition to obtain BAPs with specific biological activities. The collection and discussion of articles revealed that Box Behnken Desing and Central Composite Design were the most used. The main parameters evaluated were pH, time, temperature and enzyme/substrate ratio. Among vegetable protein sources, soy was the most used in the generation of BAPs, and among animal proteins, milk and shrimp stood out as the most explored sources. The degree of hydrolysis and antioxidant activity were the most investigated responses in obtaining BAPs. This review brings new information that helps researchers apply these DoE to obtain high-quality BAPs with the desired biological activities.

Ruas de Lazer em Pelotas: Modelo lógico e descrição dos processos de planejamento e execução / Open streets in Pelotas: Logical model and description of the planning and execution process

O objetivo do estudo foi desenvolver o modelo lógico do projeto Ruas de Lazer na cidade de Pelotas em 2022, assim como descrever os processos de planejamento, pactuação e execução. Trata-se de um estudo qualitativo, que utilizou a técnica de observação participante e o emprego de modelo lógico. O projeto possui características de gestão compartilhada que demarcam potencial relevante na criação de vínculo entre universidade, gestão pública e população local. Em 2022, sete eventos foram realizados com proposição de atividades culturais com música e dança, atividades físicas e esportivas e de educação em saúde. O projeto está em permanente construção e evolução, apostando na ampliação de investimentos para atingir os objetivos imediatos de oferta de atividades de lazer e de ampliação da democratização de acesso aos espaços públicos para o uso da população.

The aim of this study was to develop a logical model of the Ruas de Lazer project in the city of Pelotas, Rio Grande do Sul, Brazil, in 2022, as well as to describe the processes of planning, agreement, and execution. This is a qualitative study that employed the technique of participant observation and the use of a logical model. The project has characteristics of shared management that mark a relevant potential in creating a bond between the university, public management, and the local population. In 2022, seven events were held, proposing cultural activities with music and dance, physical and sports activities, and health education. The project is in permanent construction and evolution, betting on the expansion of investments to achieve the immediate objectives of offering leisure activities and expanding the democratization of access to public spaces for the use of the population.

Fullerene-C60 and PCBM as interlayers in regular and inverted lead-free PSCs using CH3NH3SnI3: an analysis of device performance and defect density dependence by SCAPS-1D.

One of the challenges hindering the commercialization of perovskite solar cells (PSCs) is the presence of toxic metals such as lead in their composition. Simulation studies using SCAPS-1D have already been conducted on lead-free PSCs to find optimized solar cell parameters, having tin as the primary candidate for replacing lead in perovskites. Here, we used fullerene-C60 and its derivative PCBM as interlayers in a lead-free tin-based PSC between the ETL (ZnO) and the perovskite MASI in both regular and inverted configurations of PSCs using SCAPS-1D software. To the best of our knowledge, this is the first simulation study reporting the impact of using fullerene-C60 and PCBM as interlayers in lead-free PSCs. The defect density (Nt) of the perovskite material is varied, allowing us to observe its influence on the power conversion efficiency (PCE). Using an Nt value of 1017 cm-3 without the interlayer, the PCE was 6.90% and 3.72% for regular and inverted devices. Using PCBM as an interlayer improves the efficiency of both simulated PSCs, achieving a maximum PCE of 8.11% and 5.26% for the regular and inverted configurations, respectively. Decreasing the Nt from 1017 cm-3 to 1016 cm-3 caused a significant increase in efficiency, reaching 13.38% (n-i-p) and 10.00% (p-i-n). Finally, using the optimized parameters and an ideal Nt value (1013 cm-3), both PSCs achieved a PCE close to 30%.

Citizenship status and career self-efficacy: An intersectional study of biomedical trainees in the United States.

This study examines the intersectional role of citizenship and gender with career self-efficacy amongst 10,803 doctoral and postdoctoral trainees in US universities. These biomedical trainees completed surveys administered by 17 US institutions that participated in the National Institutes of Health Broadening Experiences in Scientific Training (NIH BEST) Programs. Findings indicate that career self-efficacy of non-citizen trainees is significantly lower than that of US citizen trainees. While lower career efficacy was observed in women compared with men, it was even lower for non-citizen female trainees. Results suggest that specific career interests may be related to career self-efficacy. Relative to US citizen trainees, both male and female non-citizen trainees showed higher interest in pursuing a career as an academic research investigator. In comparison with non-citizen female trainees and citizen trainees of all genders, non-citizen male trainees expressed the highest interest in research-intensive (and especially principal investigator) careers. The authors discuss potential causes for these results and offer recommendations for increasing trainee career self-efficacy which can be incorporated into graduate and postdoctoral training.

Unlocking the Potential: Increasing Muscle Strength in Lower Limbs of Youth Soccer Players over Five Weeks through Mat Pilates Training-A Pilot Study.

The interest in soccer generally starts during childhood, with children and young people often looking for opportunities in sports. New exercise techniques can be effective in improving training. The aim of this study was to compare the effects on the strength and physical posture of a group practicing Pilates with another not practicing Pilates, both undergoing continuous football training. In this controlled randomized clinical trial, the participants were 15 soccer club members, who had a training frequency of least three times weekly. The sample was divided into a control group (n = 7) of players who did not undergo any therapeutic intervention (only the usual training) and a Pilates group (n = 8) of players who participated in the mat Pilates program. The intervention consisted of fifteen sessions. Postural evaluations were performed using biophotogrammetry and force analysis. Significant improvements were obtained in terms of increased muscle strength (p = 0.001) for the Pilates group, but there were no significant postural alterations when comparing the two groups. Five weeks of mat Pilates was sufficient to increase lower limb muscle strength in young football players. This pilot study indicates that Mat Pilates as a method that could be planned to be included in training.

Evaluation of photobiomodulation therapy (PBMT) on salivary flow and composition in head and neck cancer patients undergoing radiation therapy.

OBJECTIVE: Assess the impact of photobiomodulation therapy (PBMT) on xerostomia, salivary flow rate (SFR) and composition in patients undergoing radiotherapy (RT) for head and neck cancer (HNC). STUDY DESIGN: Thirty patients undergoing RT (65 Gy) for HNC were enrolled. Saliva and xerostomia evaluations collected pre- and post-PBMT-RT. PBMT involved irradiation of extra and intraoral points, 15-20 sessions, 2-3 times/week. SFR, trace elements, total protein, alkaline phosphatase, xerostomia, and pH were analyzed. RESULTS: The average age was 60.7 years. After treatment, there was not a significant reduction in SFR and there was no difference on xerostomia. Significant reductions in Al, Cd, Fe, Ni, P, and Sb concentrations were observed, along with a significant increase in Mg concentration. Sample data were organized into 3 groups based on a self-organizing map. Low concentrations of Al, As, Co, Cr, Cu, Fe, Mn, Mo, S, Sr, and Zn were the primary discriminatory factors for group A, while group B consisted of post-PBMT-RT samples with high concentrations of Ca, K, Mg, Na, and S. CONCLUSIONS: PBMT prevented a significant reduction in SFR and xerostomia induced by radiation therapy. These findings suggest that PBMT prevents salivary gland damage minimizing the decline in salivary flow.

Pain characterization in patients with Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease (PD) often report chronic pain, which is one of the most complex non-motor symptoms. Therefore, this study aims to review the literature on the characteristics of pain in patients with PD. METHODS: A systematic literature review was conducted following MOOSE recommendations. Observational studies reporting pain in patients with PD were included. No time restrictions were applied, but studies in Portuguese, Spanish, and English were considered. The search was performed in PubMed®, LILACS, and SciELO databases. RESULTS: Twenty-six articles of observational studies were identified, reporting an average pain prevalence of 67.36%, emphasizing the significance of this symptom in the PD population. Pain was reported in various body regions, including lower limbs, upper limbs, lumbar spine, cervical spine, and other joints. Pain classification varied, encompassing musculoskeletal pain, PD-related pain, neuropathic pain, and dystonic pain, among others. DISCUSSION: Pain in patients with PD is a prevalent and multifactorial condition, significantly impacting patients' quality of life. CONCLUSION: Heterogeneity in data across included studies was observed, highlighting the need for additional research to elucidate the underlying mechanisms of pain in patients with PD and develop effective therapeutic strategies to address this symptom and improve the quality of life for individuals living with the disease.

Structural characterization of the human DjC20/HscB cochaperone in solution.

J-domain proteins (JDPs) form a very large molecular chaperone family involved in proteostasis processes, such as protein folding, trafficking through membranes and degradation/disaggregation. JDPs are Hsp70 co-chaperones capable of stimulating ATPase activity as well as selecting and presenting client proteins to Hsp70. In mitochondria, human DjC20/HscB (a type III JDP that possesses only the conserved J-domain in some region of the protein) is involved in [FeS] protein biogenesis and assists human mitochondrial Hsp70 (HSPA9). Human DjC20 possesses a zinc-finger domain in its N-terminus, which closely contacts the J-domain and appears to be essential for its function. Here, we investigated the hDjC20 structure in solution as well as the importance of Zn+2 for its stability. The recombinant hDjC20 was pure, folded and capable of stimulating HSPA9 ATPase activity. It behaved as a slightly elongated monomer, as attested by small-angle X-ray scattering and SEC-MALS. The presence of Zn2+ in the hDjC20 samples was verified, a stoichiometry of 1:1 was observed, and its removal by high concentrations of EDTA and DTPA was unfeasible. However, thermal and chemical denaturation in the presence of EDTA led to a reduction in protein stability, suggesting a synergistic action between the chelating agent and denaturators that facilitate protein unfolding depending on metal removal. These data suggest that the affinity of Zn+2 for the protein is very high, evidencing its importance for the hDjC20 structure.

O Impacto Clínico e Econômico do Atraso na Terapia de Reperfusão: Evidências do Mundo Real / The Clinical and Economic Impact of Delayed Reperfusion Therapy: Real-World Evidence

Resumo Fundamento: A terapia de reperfusão precoce é reconhecida como a abordagem mais eficaz para reduzir as taxas de letalidade de casos em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). Objetivo: Estimar as consequências clínicas e econômicas do atraso da reperfusão em pacientes com IAMCSST. Métodos: O presente estudo de coorte retrospectivo avaliou as taxas de mortalidade e as despesas totais decorrentes do atraso na terapia de reperfusão em 2.622 indivíduos com IAMCSST. Os custos de cuidados hospitalares e perda de produtividade por morte ou incapacidade foram estimados sob a perspectiva do Sistema Único de Saúde indexado em dólares internacionais (Int$) ajustados pela paridade do poder de compra. Foi considerado estatisticamente significativo p < 0,05. Resultados: Cada hora adicional de atraso na terapia de reperfusão foi associada a um aumento de 6,2% (intervalo de confiança de 95%: 0,3% a 11,8%, p = 0,032) no risco de mortalidade hospitalar. As despesas gerais foram 45% maiores entre os indivíduos que receberam tratamento após 9 horas em comparação com aqueles que foram tratados nas primeiras 3 horas, impulsionados principalmente pelos custos hospitalares (p = 0,005). Um modelo de regressão linear multivariada indicou que para cada 3 horas de atraso na trombólise, houve um aumento nos custos hospitalares de Int$ 497 ± 286 (p = 0,003). Conclusões: Os achados do nosso estudo oferecem mais evidências que enfatizam o papel crucial da terapia de reperfusão imediata no salvamento de vidas e na preservação dos recursos de saúde pública. Estes resultados enfatizam a necessidade urgente de implementação de uma rede para gerir casos de IAMCSST.

Abstract Background: Early reperfusion therapy is acknowledged as the most effective approach for reducing case fatality rates in patients with ST-segment elevation myocardial infarction (STEMI). Objective: Estimate the clinical and economic consequences of delaying reperfusion in patients with STEMI. Methods: This retrospective cohort study evaluated mortality rates and the total expenses incurred by delaying reperfusion therapy among 2622 individuals with STEMI. Costs of in-hospital care and lost productivity due to death or disability were estimated from the perspective of the Brazilian Unified Health System indexed in international dollars (Int$) adjusted by purchase power parity. A p < 0.05 was considered statistically significant. Results: Each additional hour of delay in reperfusion therapy was associated with a 6.2% increase (95% CI: 0.3% to 11.8%, p = 0.032) in the risk of in-hospital mortality. The overall expenses were 45% higher among individuals who received treatment after 9 hours compared to those who were treated within the first 3 hours, primarily driven by in-hospital costs (p = 0.005). A multivariate linear regression model indicated that for every 3-hour delay in thrombolysis, there was an increase in in-hospital costs of Int$497 ± 286 (p = 0.003). Conclusions: The findings of our study offer further evidence that emphasizes the crucial role of prompt reperfusion therapy in saving lives and preserving public health resources. These results underscore the urgent need for implementing a network to manage STEMI cases.

Comparative cross-sectional study of socio-psychological orthodontic needs and oral habits in Autism Spectrum Disorder.

OBJECTIVE: This cross-sectional study analyzed the socio-psychological need for orthodontic treatment in children and adolescents with and without Autism Spectrum Disorder (ASD) and its association with deleterious oral habits. METHODS: Children/adolescents aged 6-14 years old, with and without ASD, and their respective caregivers were included. Caregivers completed a questionnaire addressing children and adolescents' deleterious oral habits. To assess the socio-psychological need for orthodontic treatment, we utilized the aesthetic component of the Index of Orthodontic Treatment Needs (IOTN). Caregivers and an orthodontist independently used the standardized IOTN aesthetic attractiveness scale containing ten intraoral photographs and compared them with the most similar condition of the child/adolescent. Data collection occurred at two universities in northeastern Brazil and at an ASD referral center. Statistical analyses encompassed descriptive statistics, Shapiro-Wilk, Kruskal-Wallis, Mann-Whitney, and Chi-squared tests with linear trend (α5%). RESULTS: The study involved 144 participants, evenly divided into two groups (ASD and non-ASN). The ASD group showed higher average IOTN-AC scores as evaluated by both professionals (mean score = 4.78 [± 2.34], p = .182) and caregivers (mean score = 4.31 [± 2.71], p = .992). Caregivers reported notably elevated IOTN-AC scores in cases where onychophagy was absent (p = .049). CONCLUSIONS: Patients with ASD are indicated as having a relatively higher socio-psychological need for orthodontic treatment.

Self-assembly of perovskite nanoplates in colloidal suspensions.

In recent years, perovskite nanocrystal superlattices have been reported with collective optical phenomena, offering a promising platform for both fundamental science studies and device engineering. In this same avenue, superlattices of perovskite nanoplates can be easily prepared on different substrates, and they too present an ensemble optical response. However, the self-assembly and optical properties of these aggregates in solvents have not been reported to date. Here, we report on the conditions for this self-assembly to occur and show a simple strategy to induce the formation of these nanoplate stacks in suspension in different organic solvents. We combined wide- and small-angle X-ray scattering and scanning transmission electron microscopy to evaluate CsPbBr3 and CsPbI3 perovskite nanoplates with different thickness distributions. We observed the formation of these stacks by changing the concentration of nanoplates and the viscosity of the colloidal suspensions, without the need for antisolvent addition. We found that, in hexane, the concentration for the formation of the stacks is rather high and approximately 80 mg mL-1. In contrast, in decane, dodecane, and hexadecane, we observe a much easier self-assembly of the nanoplates, presenting a clear correlation between the degree of aggregation and viscosity. We, then, discuss the impact of the self-assembly of perovskite nanoplates on Förster resonant energy transfer. Our predictions suggest an energy transfer efficiency higher than 50% for all the donor-acceptor systems evaluated. In particular, we demonstrate how the aggregation of these particles in hexadecane induces FRET for CsPbBr3 nanowires. For the n = 2 nanowires (donor) to the n = 3 nanowires (acceptor), the FRET rate was found to be 4.1 ns-1, with an efficiency of 56%, in agreement with our own predictions.

Comparative effectiveness and cost-effectiveness of cardioprotective glucose-lowering therapies for type 2 diabetes in Brazil: a Bayesian network model.

BACKGROUND: The escalating prevalence of type 2 diabetes (T2DM) poses an unparalleled economic catastrophe to developing countries. Cardiovascular diseases remain the primary source of costs among individuals with T2DM, incurring expenses for medications, hospitalizations, and surgical interventions. Compelling evidence suggests that the risk of cardiovascular outcomes can be reduced by three classes of glucose-lowering therapies (GLT), including SGLT2i, GLP-1A, and pioglitazone. However, an evidence-based and cost-effective protocol is still unavailable for many countries. The objective of the current study is to compare the effectiveness and cost-effectiveness of GLT in individuals with T2DM in Brazil. METHODS: We employed Bayesian Networks to calculate the incremental cost-effectiveness ratios (ICER), expressed in international dollars (Int$) per disease-adjusted life years [DALYs] averted. To determine the effectiveness of GLT, we conducted a systematic review with network meta-analysis (NMA) to provide insights for our model. Additionally, we obtained cardiovascular outcome incidence data from two real-world cohorts comprising 851 and 1337 patients in primary and secondary prevention, respectively. Our cost analysis took into account the perspective of the Brazilian public health system, and all values were converted to Int$. RESULTS: In the NMA, SGLT2i [HR: 0.81 (95% CI 0.69-0.96)], GLP-1A [HR: 0.79 (95% CI 0.67-0.94)], and pioglitazone [HR: 0.73 (95% CI 0.59-0.91)] demonstrated reduced relative risks of non-fatal cardiovascular events. In the context of primary prevention, pioglitazone yielded 0.2339 DALYs averted, with an ICER of Int$7,082 (95% CI 4,521-10,770) per DALY averted when compared to standard care. SGLT2i and GLP-1A also increased effectiveness, resulting in 0.261 and 0.259 DALYs averted, respectively, but with higher ICERs of Int$12,061 (95% CI: 7,227-18,121) and Int$29,119 (95% CI: 23,811-35,367) per DALY averted. In the secondary prevention scenario, all three classes of treatments were deemed cost-effective at a maximum willingness-to-pay threshold of Int$26,700. Notably, pioglitazone consistently exhibited the highest probability of being cost-effective in both scenarios. CONCLUSIONS: In Brazil, pioglitazone presented a higher probability of being cost-effective both in primary and secondary prevention, followed by SGLT2i and GLP-1A. Our findings support the use of cost-effectiveness models to build optimized and hierarchical therapeutic strategy in the management of T2DM. TRIAL REGISTRATION: CRD42020194415.

Severe KIDAR syndrome caused by deletion in the AP1B1 gene: Report of a teenage patient and systematic review of the literature.

Autosomal recessive keratitis-ichthyosis-deafness syndrome (KIDAR MIM #242150) is a very rare disorder caused by pathogenic loss-of-function variants in the AP1B1 gene. So far, nine patients have been reported in the literature and more clinical descriptions are essential to further delineate the phenotype of KIDAR. Here we report a new patient with KIDAR and compare the clinical findings with those from the other published cases with molecular confirmation. We describe a 14-year-old male born to non-consanguineous parents with unremarkable family history. The patient had fetal ascites, neonatal pancreatic insufficiency with consequent failure to thrive, feeding difficulties, recurrent infections and sepsis. The skin examination was remarkable for an ichthyosis with conspicuous palmoplantar keratoderma, sparse and brittle hair with alopecia on the vertex and slight bilateral ectropion. He had short stature, thin build, frontal bossing, small teeth and prominent abdomen. Additional features were congenital profound bilateral sensorineural deafness, photosensitivity and photophobia. Mild global developmental delay was noted. Persistent mild anemia, neutropenia, thrombocytopenia, and low serum copper, ceruloplasmin and growth hormone were also present. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and thin corpus callosum. Genetic testing revealed a homozygous deletion in the AP1B1 gene, possibly including the same exons as a previously reported deletion. Comparing the phenotypes of all reported individuals, they are highly concordant and major features are enteropathy with feeding difficulties, failure to thrive, ichthyosis, palmoplantar keratoderma, sensorineural deafness and sparse and brittle hair. Here we report other features present in more than one patient that could be part of the phenotypic spectrum and suggest copy number variation analysis to be performed alongside sequencing of the AP1B1 gene in case of suspicion.