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Abstract This novel study applies targeted functional proteomics to examine tissues and cells obtained from a cohort of individuals with severe obesity who underwent bariatric surgery (BS), using a Reverse-Phase Protein Array (RPPA). In obese individuals, visceral adipose tissue (VAT), but not subcutaneous adipose tissue (SAT), shows activation of DNA damage response (DDR) markers including ATM, ATR, histone H2AX, KAP1, Chk1, and Chk2, alongside senescence markers p16 and p21. Additionally, stress-responsive metabolic markers, such as survivin, mTOR, and PFKFB3, are specifically elevated in VAT, suggesting both cellular stress and metabolic dysregulation. Conversely, peripheral blood mononuclear cells (PBMCs), while exhibiting elevated mTOR and JNK levels, did not present significant changes in DDR or senescence markers. Following BS, unexpected increases in phosphorylated ATM, ATR, and KAP1 levels, but not in Chk1 and Chk2 nor in senescence markers, were observed. This was accompanied by heightened levels of survivin and mTOR, along with improvement in markers of mitochondrial quality and health. This suggests that, following BS, pro-survival pathways involved in cellular adaptation to various stressors and metabolic alterations are activated in circulating PBMCs. Moreover, our findings demonstrate that the DDR has a dual nature. In the case of VAT from individuals with obesity, chronic DDR proves to be harmful, as it is associated with senescence and chronic inflammation. Conversely, after BS, the activation of DDR proteins in PBMCs is associated with a beneficial survival response. This response is characterized by metabolic redesign and improved mitochondrial biogenesis and functionality. This study reveals physiological changes associated with obesity and BS that may aid theragnostic approaches.

Purpose: To compare the ocular perfusion pressure (OPP) response during physical exercise in individuals with and without a family history (FH+, FH−) of glaucoma. Methods: Thirty-four subjects, divided into FH+ and FH− groups, realized 3 min at rest, 3 min of isometric handgrip exercise at 30% of maximal voluntary contraction, followed by 3 min of recovery. Blood pressure (Dixtal® automatic device) and intraocular pressure (Goldmann applanation tonometer) were measured during rest, exercise, and recovery. The mean OPP (mOPP) was calculated. Results: In the FH+ group (17 subjects), baseline mOPP values were significantly lower than in the FH− group (17 subjects) (right eye: P < 0.001, left eye: P < 0.001, respectively). During exercise, both the FH+ and FH− groups showed a similar increase in mOPP in both eyes (right eye: FH+: 38 ± 4 mmHg vs. 51 ± 7 mmHg, FH−: 48 ± 5 mmHg vs. 57 ± 9 mmHg, P < 0.001; left eye: FH+: 39 ± 3 mmHg vs. 51 ± 7 mmHg; FH−: 46 ± 5 mmHg vs. 58 ± 8 mmHg, P < 0.001, respectively). However, the FH+ group maintained significantly lower mOPP values compared to the FH− group in the right and left eyes (group effect: P = 0.002, P = 0.002, respectively). The percentage of increase in mOPP in the FH+ group was greater compared to the FH− group during exercise (right eye: 34.1% ± 15.9% vs. 22.1% ± 13.2%, respectively; P = 0.025; left eye: 33.2% ± 17.7% vs. 22.4% ± 13.7%, respectively, P = 0.056). Conclusions: mOPP increased during physical exercise in both groups, but the FH+ group had lower absolute values. In addition, the FH+ group appears to demonstrate a higher percentage increase in mOPP compared to the FH− group.

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5 untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.

Resumo Tomando por fonte o relato de uma visita da jornalista belgo-brasileira Yvonne Jean à Escola Regional de Meriti em 1948, o objetivo deste artigo é construir uma compreensão dessa narrativa sobre méritos e deméritos, sucessos e insucessos, inovações e problemas do modelo educacional praticado na escola e tendo em vista os desafios próprios da educação brasileira daqueles tempos. De início, a atenção recai sobre as práticas inovadoras da escola de Meriti conforme a descrição e interpretação de Yvonne Jean; depois, o foco se concentra nas ponderações críticas dela sobre o modelo de escolarização da escola visitada, instituição particular dirigida por uma partidária da Escola Nova e que se destacava no cenário do estado do Rio de Janeiro e da Baixada Fluminense.

Abstract Background This study investigates myocardial structural changes in stable coronary artery disease (CAD) patients with type 2 diabetes (T2D) using cardiac magnetic resonance (CMR) strain and T1 mapping. Methods A total of 155 stable CAD patients underwent CMR examination, including left ventricular (LV) morphology and function assessment, late gadolinium enhancement (LGE), and feature tracking (CMR-FT) for LV global longitudinal, circumferential, and radial strain. T1 mapping with extracellular volume (ECV) evaluation was also performed. Results Among the enrolled patients, 67 had T2D. Diabetic patients exhibited impaired LV strain and higher ECV compared to non-diabetics. Multivariate analysis identified T2D as an independent predictor of increased ECV and decreased strain. Conclusions CMR-based strain and T1 mapping highlighted impaired myocardial contractility, elevated ECV, and potential interstitial fibrosis in diabetic patients with stable CAD. This suggests a significant impact of diabetes on myocardial health beyond CAD, emphasizing the importance of a comprehensive assessment in these individuals. Trial registration http://www.controlled-trials.com/ISRCTN09454308

O governo de Getúlio Vargas formalizou a criação do Departamento Nacional da Criança (DNCr) via Decreto-Lei nº 2.024, publicado em 17 de fevereiro de 1940, documento esse que fixou “[...] as bases da organização da proteção à maternidade, à infância e à adolescência do País” (Decreto-Lei nº 2.024, 1940). Nessa perspectiva, o artigo objetivou analisar a gênese e a atuação do Departamento Nacional da Criança em Cuiabá-MT no período de 1940 a 1948. O trabalho partiu do seguinte questionamento: Como o governo de Mato Grosso se apropriou das orientações dadas pelo DNCr para a educação, assistência e saúde das crianças das camadas populares? O período analisado justifica-se por ser o ano de criação do departamento – 1940, até a sua primeira reorganização pela Lei Federal nº 282 (Lei nº 282, 1948). O referencial teórico metodológico se baseou na pesquisa qualitativa documental e foram utilizados os periódicos em circulação, Boletins do DNCr, legislações; publicações do DNCr, entre outros. Os resultados da pesquisa demonstram as movimentações entre governo federal e estadual para concretizar os propósitos do DNCr, pois este documento apresentou mais como articulador e organizador do que como executor; ou seja, se propôs mais a pensar em ações e soluções. No Estado do Mato Grosso foi possível perceber que as iniciativas assistenciais se centravam, principalmente, nas mãos da primeira-dama do estado, Maria de Arruda Muller, que ocupava a presidência na Sociedade de Proteção à Maternidade e à Infância e da Legião Brasileira da Boa Vontade (LBA). Assim, o estado, contando com a liderança da família Muller, pôde investir no cuidado da criança, subsidiado e acompanhado pelo DNCr e pela LBA.

Background: The approval of ustekinumab (UST) has opened new options for the treatment of Crohn’s disease (CD), but potential markers predicting the efficacy of this interleukin-12/23 inhibitor are lacking. Contrast-enhanced ultrasound (CEUS) is non-invasive alternative to endoscopy, demonstrating early transmural changes after treatment induction. Objectives: We conducted a prospective monocentric study aiming to explore the value of multimodal intestinal ultrasound (IUS) in predicting the response to UST in patients with active CD who have been previously exposed to anti-tumour necrosis factor α (TNFα). Design and methods: Consecutive patients with moderate-to-severe CD involving the terminal ileum who were scheduled to begin UST therapy were enrolled between January 2020 and October 2021 in the inflammatory bowel diseases outpatient centre. A complete IUS evaluation, including B-mode, Doppler, dynamic CEUS and elastography, was performed at the time of induction (T0) and after 8 (T1), 16 (T2), 24 (T3) and 48 (T4) weeks of therapy. Each IUS parameter and their variations from baseline were correlated with endoscopic response and mucosal healing after 1 year. Results: A total of 52 patients were included, 29 (55.8%) of which reached endoscopic response at T4. The univariate analysis revealed that, between T3 and T0, the percentage changes of bowel wall thickness, Limberg score, mean signal intensity, rise time, wash-in rate, C reactive protein and Harvey–Bradshaw Index were associated with long-term therapeutic outcome. Based on the above parameters, we developed an IUS score that showed a good performance in predicting 1 year-endoscopic response (area under the curve: 0.91). Conclusion: Multimodal ultrasound could be helpful to predict long-term therapeutic outcome in patients with CD treated with UST. Registration: NCT05987501.

Da oltre quarant’anni si utilizzano gli ultrasuoni per rilevare una placca carotidea e per seguire nel tempo la sua evoluzione. I protocolli terapeutici hanno ridotto enormemente il suo impatto sulla salute delle persone ma la scelta fra terapia medica e chirurgica si fonda su una valutazione clinica e strumentale che è solo apparentemente semplice. Nei referti di un esame ultrasonografico riportiamo il più delle volte delle percentuali di stenosi, a volte puntuali, a volte in termini di range oppure ci esprimiamo con aggettivi che descrivono la gravità della stenosi ma spesso ci facciamo confondere dai numeri e dalle differenti modalità di calcolo del range di stenosi ed è indubbio che, a volte, le conclusioni risultano ambigue ed estremamente dipendenti dall’interpretazione dell’operatore. Il problema è che l’angiografia digitale, gold standard diagnostico per la stenosi carotidea, adotta delle metriche non del tutto riproducibili con gli ultrasuoni. Con questo documento vogliamo condividere la ricerca di un linguaggio comune, a partire dal referto dei nostri esami. Noi refertiamo così… voi?

Abstract This investigation delves into the complex interaction at metal-semiconductor interfaces, highlighting the magnetic proximity effect in Ni/Si interfaces through systematic X-ray magnetic circular dichroism (XMCD) studies at Ni and Si edges. We analyzed two Ni/Si heterostructures with differing semiconductor doping, uncovering a magnetic proximity effect manifesting as equilibrium magnetization in the semiconductor substrate induced by the adjacent Ni layer. Our results display distinct magnetization signs corresponding to the doping levels: low-doped samples show parallel alignment to the Ni layer, while high-doped samples align antiparallel, indicating a nuanced interplay of underlying magnetization mechanisms. These findings pinpoint the roles of electron tunneling and exchange splitting modification in the magnetization behavior. The study enriches the understanding of ferromagnetic-semiconductor interface behavior, setting a precedent for the design of advanced spintronic devices that leverage the nuanced magnetic properties of these hybrid systems.

The influence of playing formations and team ranking on the physical performance of professional soccer players is an open question that needs to be explored. The present study aimed to investigate the impact of these factors on the physical exertion of Serie A soccer players. We analyzed match data from 375 players, categorizing teams based on their final ranking and comparing performance across different playing formations. The Kruskal–Wallis test and the Dunn test with Bonferroni adjustment revealed that high-ranking (HR) teams exhibited a higher percentage of high-intensity (HI) accelerations compared to mid-ranking teams, suggesting the critical role of HI efforts in achieving favorable match outcomes. Moreover, the 4-3-3 playing formation was associated with greater acceleration demands than other formations, particularly in HR teams. Our study also established benchmarks for various performance metrics, enabling coaches to assess player performance and identify potential signs of overtraining. These findings contribute to a deeper understanding of the physical demands in soccer and offer practical implications for coaches and players in optimizing training and performance strategies.

(1) Background: The objective of this study is to evaluate the predictive value of the Eaton–Littler radiologic classification for thumb carpometacarpal osteoarthritis (CMC OA) relating to intra-articular cartilage damage assessed by the Outerbridge arthroscopic classification. (2) Methods: A total of 51 thumb CMC OA arthroscopies were performed on patients classified as Eaton stages 1, 2, or 3. Post-arthroscopic evaluations of cartilage damage were categorized using the Outerbridge classification. Comparative analyses were conducted between the radiological Eaton stages and the arthroscopic Outerbridge stages. (3) Results: Arthroscopic examination revealed Outerbridge stage 3 and 4 cartilage damage in 26 cases classified as Eaton stage 2 and in 18 cases classified as Eaton stage 3. The detection of severe cartilage damage in patients classified as Eaton stage 2 was unexpected. (4) Conclusions: Arthroscopy demonstrated that many patients with mild radiological degenerative signs exhibited significant cartilage destruction. Although the Eaton classification is widely used for staging thumb CMC OA, it may not accurately reflect the severity of intra-articular damage. The Eaton classification does not reliably predict intra-articular damage in Eaton stage 2 cases.

Em 1918, o mundo foi assolado pela pandemia da Gripe Espanhola e em 2020, pela pandemia da SARS-CoV-19. No Brasil, é possível perceber algumas semelhanças entre esses dois momentos. Este artigo tem por objetivo analisar as alterações ocorridas nos espaços e práticas pedagógicas visando a superação das situações pandêmicas. Optou-se pela abordagem da História Cultural, utilizando as concepções de Norbert Elias. Utilizou-se como fontes documentais oficiais, pronunciamento em mídia social e periódicos. Como resultado observou-se que unindo os esforços para a manutenção da vida, as escolas em alguns momentos serviram de espaços para serviços de internação e enfermaria.

Nocardia is a genus of gram-positive, filamentous, aerobic bacteria that belongs to the Actinomycetales order. With over 50 species, it is ubiquitous in dust, soil, decaying organic matter, and stagnant water. Inhalation of the pathogen often leads to pulmonary nocardiosis, while extrapulmonary nocardiosis can affect the central nervous system, skin, and subcutaneous tissues. Primary cutaneous nocardiosis occurs when the pathogen is introduced through a skin lesion or insect bite, for example, this report presents a case of primary cutaneous nocardiosis in a patient with Minimal Change Glomerulonephritis and iatrogenic immunosuppression. Magnetic resonance imaging revealed extensive involvement of the skin, subcutaneous tissue, and lower limb muscles.

Abstract Human cellular reprogramming to induced pluripotency is still an inefficient process, which has hindered studying the role of critical intermediate stages. Here we take advantage of high efficiency reprogramming in microfluidics and temporal multi-omics to identify and resolve distinct sub-populations and their interactions. We perform secretome analysis and single-cell transcriptomics to show functional extrinsic pathways of protein communication between reprogramming sub-populations and the re-shaping of a permissive extracellular environment. We pinpoint the HGF/MET/STAT3 axis as a potent enhancer of reprogramming, which acts via HGF accumulation within the confined system of microfluidics, and in conventional dishes needs to be supplied exogenously to enhance efficiency. Our data suggest that human cellular reprogramming is a transcription factor-driven process that it is deeply dependent on extracellular context and cell population determinants.

Inflammatory bowel diseases (IBDs) are intricate systemic conditions that can extend beyond the gastrointestinal tract through both direct and indirect mechanisms. Sarcopenia, characterized by a reduction in muscle mass and strength, often emerges as a consequence of the clinical course of IBDs. Indeed, sarcopenia exhibits a high prevalence in Crohn’s disease (52%) and ulcerative colitis (37%). While computed tomography and magnetic resonance imaging remain gold-standard methods for assessing muscle mass, ultrasound is gaining traction as a reliable, cost-effective, and widely available diagnostic method. Muscle strength serves as a key indicator of muscle function, with grip strength test emerging nowadays as the most reliable assessment method. In IBDs, sarcopenia may arise from factors such as inflammation, malnutrition, and gut dysbiosis, leading to the formulation of the ‘gut–muscle axis’ hypothesis. This condition determines an increased need for surgery with poorer post-surgical outcomes and a reduced response to biological treatments. Sarcopenia and its consequences lead to reduced quality of life (QoL), in addition to the already impaired QoL. Of emerging concern is sarcopenic obesity in IBDs, a challenging condition whose pathogenesis and management are still poorly understood. Resistance exercise and nutritional interventions, particularly those aimed at augmenting protein intake, have demonstrated efficacy in addressing sarcopenia in IBDs. Furthermore, anti-TNF biological therapies showed interesting outcomes in managing this condition. This review seeks to furnish a comprehensive overview of sarcopenia in IBDs, elucidating diagnostic methodologies, pathophysiological mechanisms, and clinical implications and management. Attention will also be paid to sarcopenic obesity, exploring the pathophysiology and possible treatment modalities of this condition.