This roadmap reviews CARDIO4Cities, a whole-of-city approach designed to reduce cardiovascular risk and disease at population level. As urbanization accelerates globally - with 68% of the global population projected to live in cities by 2050 - cities across income settings face a growing burden of cardiovascular disease, yet often lack operational models that translate evidence into scalable action. CARDIO4Cities responds to this gap by combining a simple, standardized population-health framework with locally adaptable implementation pathways that can be embedded within existing city systems. The approach is organized around six reinforcing pillars: quality and coordination of Care, Access to early diagnosis and management of cardiovascular risk factors, policy Reform, Data and technology, Intersectoral collaboration, and local Ownership. Rather than relying on new parallel infrastructures, CARDIO4Cities integrates evidence-based interventions into routine health services and leverages non-traditional community and private-sector actors, enabling replication across cities with varying levels of health-system maturity and resources. This document provides city health officials and their partners with a step-by-step implementation pathway, including governance structures, target-setting frameworks, intervention design processes, monitoring systems, and scaling strategies. Evaluations from the first three implementation cities-São Paulo (Brazil), Dakar (Senegal), and Ulaanbaatar (Mongolia)-demonstrated significant improvements in hypertension control and reductions in acute cardiovascular events within one to two years. Modeling projected that, without further CARDIO4Cities interventions, 2.7-7.9% of premature deaths would be averted over the subsequent decade, at costs meeting WHO-CHOICE cost-effectiveness thresholds. These results, achieved in diverse geographic, economic, and health-system contexts, illustrate the transferability of the model across income settings. Since standardization of the approach, CARDIO4Cities has expanded to more than 40 cities worldwide, including major cities in Europe and the Americas, equipping city leaders with operational guidance to implement evidence-based cardiovascular population health programs adapted to local contexts and resources. We position CARDIO4Cities as a replicable and scalable model for improving cardiovascular population health across diverse urban contexts, from resource-constrained cities initiating basic risk-factor detection to data-rich cities advancing toward precision population health.
Motivational interventions have been tested in addition to pulmonary rehabilitation in order to increase and prolong the benefits obtained, however it is not well established. Therefore, the aim of this study was to investigate whether motivational interventions increase the benefits of pulmonary rehabilitation in physical and psychosocial outcomes in patients with chronic obstructive pulmonary disease (COPD). A systematic review of studies comparing pulmonary rehabilitation "with" versus "without" motivational techniques for adults with COPD was registred on PROSPERO (CRD42020162921) and performed in PubMed, Embase, EBSCO, PEDro, LILACS, the Cochrane Central Register of Controlled Trials, and Google Scholar. The outcomes analyzed were PADL, sedentary behavior, psychosocial factors, exacerbation, dyspnea symptoms, and patient self-efficacy after the intervention and after the follow-up period. The methodological quality and certainty of evidence were evaluated by PEDro Scale and GRADE, respectively. The data were meta-analyzed for the pooled studies and motivational technique subgroups. Ten studies with a total of 832 patients with COPD were included. The motivational techniques in trials used were behavioral interventions with and without pedometer-based feedback, and pedometer-based feedback alone. Half of the studies have good methodological quality. With a low to very low certainty of evidence, the meta-analyses showed that the addition of motivational techniques to pulmonary rehabilitation does not increase physical and psychosocial outcomes on the short- or medium to long-term. Despite efforts to incorporate motivational strategies into pulmonary rehabilitation for individuals with COPD to prolong its benefits, current evidence does not support significant improvements in physical or psychosocial outcomes. Among the interventions evaluated separately, only behavioral strategies incorporating pedometer-based feedback demonstrated potential to increase daily step counts in the medium to long term. However, the certainty of the available evidence is still rated as low to very low.
The responses underlying heightened sensitivity of young populations to deoxynivalenol (DON) toxicity remain uncharacterized in translational murine models. This study aimed to fill this gap by providing the first systematic, multi-organ (intestine, liver, and kidney) comparison of DON toxicity, contrasting the responses of prepubertal and adult mice. Prepubertal (21-day-old) and adult (65-day-old) Swiss mice (n = 10/group) were fed control or 10 mg/kg DON-contaminated diets for 15 or 28 days, respectively. Growth performance was monitored, and intestine, liver, and kidney were subsequently collected for histopathological, morphometric, and biochemical analyses. DON induced a severe, acute weight gain reduction (∼59.6%) in prepubertal mice, with no effect on adults or systemic biochemical profiles. DON toxicity was highly organ-specific: the prepubertal intestine mounted an adaptive response, coupling oxidative damage with compensatory antioxidant production and enterocyte hypertrophy, but without structural lesions. In contrast, the liver and kidney sustained direct histopathological damage in both age groups. However, their biochemical responses diverged: the liver showed a young-specific inflammatory signal, whereas the kidney remained biochemically silent despite the damage it sustained. This multi-organ comparison in mice shows that DON toxicity is age- and organ-specific, demonstrating that at the exposure dose used, prepubertal mice exhibit more pronounced toxic responses.
To explore the correlations between endocrine-metabolic characteristics and body fat distribution, appetite, growth, and memory in children with Prader-Willi Syndrome (PWS). Forty-six children with PWS and forty-six with simple obesity were studied, alongside a healthy control group. Researchers measured physical development, hyperphagia, memory, hormone levels, and lipid profiles. They compared endocrine-metabolic differences across groups and examined correlations between these indicators and body fat, appetite, growth, and memory in children with PWS. The PWS group presented overweight, growth retardation, increased body fat, elevated hyperphagia scores and reduced memory scores relative to simple obesity and healthy control groups, with distinct plasma metabolic and endocrine profiles (higher ghrelin, Triglycerides [TG], Total Cholesterol [TC], Low-Density Lipoprotein Cholesterol [LDL-C], Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] and C-peptide; lower Insulin-like Growth Factor-1 [IGF-1], Triiodothyronine [T3], Thyroxine [T4], Thyroid-Stimulating Hormone [TSH] and High-Density Lipoprotein Cholesterol [HDL-C]). Correlation analyses confirmed positive associations of ghrelin, cortisol, and HOMA-IR with Fat Mass Index (FMI); of cortisol and HOMA-IR with hyperphagia score; of TSH, TG, HOMA-IR, and C-peptide with Body Mass Index (BMI); and of IGF-1 and T3 with memory score, as well as negative associations of IGF-1 with FMI and hyperphagia score; of HDL-C with BMI; and of ghrelin with memory score (all p < 0.05). Children with PWS present major endocrine-metabolic abnormalities associated with abnormal body fat, hyperphagia, growth retardation, and memory impairment, which help clarify multisystem damage in hereditary obesity and guide targeted clinical interventions.
Motor overflow, a neuromotor phenomenon characterized by involuntary activation of muscles during voluntary movement, reflects impairments in interhemispheric and intracortical inhibition and is commonly observed in conditions such as stroke, cerebral palsy, dystonia, and Parkinson's disease. Transcranial Magnetic Stimulation (TMS) is a non-invasive neuromodulatory technique with potential to modulate the cortical excitability underlying overflow-related dysfunctions. This systematic review aimed to evaluate the efficacy of TMS in reducing motor overflow across neurological populations. Seven randomized controlled trials (RCTs) were included, encompassing participants with stroke, cerebral palsy, Parkinson's disease, and focal hand dystonia. Protocols varied in frequency (1-10 Hz), target area (M1, SMA, PSC, PMC), and design (e.g., crossover, combined protocols with constraint-induced therapy or cerebellar stimulation; Motor overflow was directly assessed in only two studies, one involving Parkinson's disease and one involving dystonia, thereby limiting cross-study comparisons. Therefore, evidence supporting a direct effect of TMS on motor overflow remains preliminary and condition-specific. In dystonia, high-frequency rTMS (10 Hz) targeting the primary somatosensory cortex led to significant reductions in overflow, demonstrated by handwriting kinematics. In Parkinson's disease, although physiological modulation (reduced IHI) was observed after SMA stimulation, mirror movements remained unchanged. In stroke and cerebral palsy populations, overflow was not directly evaluated, though improvements in motor function, spasticity, and cortical excitability were consistently reported. Risk of bias was low in most included studies, although gaps in allocation reporting and standardization of outcome measures were noted. This review highlights the potential of TMS, particularly high-frequency protocols, to modulate motor overflow in focal dystonia. However, the lack of targeted assessment in other neurological conditions suggests a critical need for future trials with standardized protocols and specific outcome measures focused on overflow to clarify the therapeutic role of TMS in rehabilitation.
Postbiotics, inactivated microorganisms or their components, offer significant health-promoting benefits, in addition to greater stability and a longer shelf life compared to probiotics. However, maximizing their therapeutic efficacy requires preserving their bioaccessibility under rigorous food-processing conditions and during harsh gastrointestinal transit. Typical delivery methods include emulsions, hydrogels, and nanostructures, each offering distinct benefits regarding biocompatibility and food product enhancement. This review aims to investigate innovative approaches and advancements in postbiotic delivery to optimize the therapeutic potential of postbiotics in improving gut health and overall well-being. Furthermore, it evaluates enhancements in bioavailability and functionality by analyzing advancements in emulsions, hydrogels, and nanotechnology-based systems. The findings are expected to identify technological gaps and propose innovations to drive the development of next-generation delivery platforms, ultimately improving postbiotic applications across sectors. The potential of postbiotics to overcome the limitations of probiotics lies in integrating cutting-edge delivery technologies that can notably enhance postbiotic stability and targeted action, thereby overcoming the traditional limitations of viable probiotics. This review highlights the role of emulsions, hydrogels, and nanotechnology in maximizing the therapeutic benefits of postbiotics, positioning them as promising tools for improving gut health and for broader applications in food science and nutrition, and underscoring their potential to enhance consumer health and well-being.
The diagnosis of Sjögren's disease (SD) relies on expert opinion and fulfillment of items in classification criteria sets, together with additional clinical, pathological, and laboratory evaluations. Imaging is not yet part of any criteria set, although sonography has recently demonstrated strong potential for inclusion as an additional item. Besides sonography, some evidence suggests that magnetic resonance (MR) imaging could also be a useful adjunct in diagnosing this disease. We describe and illustrate the findings of SD on conventional pulse sequences and MR sialography, as well as comment on their diagnostic performance. The role of advanced imaging techniques, including diffusion-weighted imaging (DWI) and proton-density fat fraction (PDFF) imaging, and evidence regarding how MR relates to other frequently requested complementary tests are also reviewed. We conclude by presenting several knowledge gaps that, in our opinion, need to be addressed before MR imaging can be included in the diagnostic workup of SD.
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The existing information supports the use of this material as described in this safety assessment. β-Naphthyl isobutyl ether was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Target data and data from read-across analog β-naphthyl methyl ether (CAS # 93-04-9) show that β-naphthyl isobutyl ether is not expected to be genotoxic. Data on β-naphthyl isobutyl ether provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity endpoint. Data on read-across analog β-naphthyl methyl ether (CAS # 93-04-9) provide a calculated MOE >100 for the reproductive toxicity endpoint. Data show that there are no safety concerns for β-naphthyl isobutyl ether for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; β-naphthyl isobutyl ether is not expected to be photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to β-naphthyl isobutyl ether is below the TTC (0.47 mg/day). The environmental endpoints were evaluated; β-naphthyl isobutyl ether was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients (RQs), based on its current volume of use (VoU) in Europe (EU), North America (NA), Asia-Pacific (AP), and South America (SA) (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.
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Changes in energy metabolism are commonly observed in bipolar disorder (BD) and have been linked to a more severe clinical course. 'Metabolic jet lag' (MJL) is a state of shift in circadian patterns of energy homeostasis, expressed through behavioral changes such as irregular meal timing. However, the relationship between MJL and the pathophysiology of BD remains unknown. The objective of this study is to determine the feasibility of an investigation assessing the association between MJL, evaluated through eating rhythm disruption, and markers of illness burden in ten individuals with DSM-5-defined BD type 1. This is a 14-day longitudinal, naturalistic study that used the smartphone application 'RxFood' to elaborate a personalized, time-stamped "feedogram" for each participant. Illness burden and severity parameters were collected at baseline, and the Acceptability E-Scale was administered at the endpoint. Eating rhythm disruption scores were calculated based on a novel analytical approach applied to the "feedogram" data. The use of 'RxFood' demonstrated excellent feasibility and acceptability (94%) in individuals with BD and captured 628 eating occasions over the study period. Eating rhythm disruption scores varied between participants and correlated with the number of manic episodes (r = 0.718, p = 0.019), although the association was not significant after correcting for multiple comparisons. Ecological momentary assessment of eating rhythms is feasible in individuals with BD. Larger investigations evaluating the association between eating rhythm disruption and clinical illness trajectories are needed to delineate the role of MJL in the pathophysiology of BD.
Preeclampsia (PE) is a leading cause of maternal and perinatal morbimortality, particularly in low- and middle-income countries. Despite advances in clinical management, its etiology and pathogenesis remain unclear, and effective predictive biomarkers are lacking. The Brazilian Longitudinal Study for the Investigation of Preeclampsia (ECLIPSE-BRAZIL) is a prospective cohort designed to investigate genetic, immunological, hemostatic, biochemical, and angiogenic profiles in pregnant women at risk for PE, aiming to identify biomarkers that effectively and affordably predict PE risk early in pregnancy. ECLIPSE-BRAZIL follows 500 to 1,000 pregnant women receiving care at the High-Risk Prenatal Care clinics in Belo Horizonte and Divinópolis, Minas Gerais, Brazil. Clinical and laboratory assessments are conducted at four gestational stages and postpartum for PE cases. Clinical data, including sociodemographic, clinical and behavioral factors, and blood and urine samples are systematically collected. Plasma and urine levels of inflammatory markers, angiogenic factors, oxidative stress parameters, extracellular vesicles, microRNAs, endothelial and platelet markers will be analyzed. Participants are stratified by PE development and gestational age at diagnosis. Standardized criteria and data protocols ensure rigor, while quality check and audits enhance data reliability. To minimize follow-up loss, participants are contacted frequently, with flexible sampling and the use of hospital records. ECLIPSE-BRAZIL will provide novel insights into PE pathophysiology, improving disease prediction and management. By studying a diverse population, we will identify biological signatures to inform health innovations: development of cost-effective diagnostic tools, point-of-care tests and simple clinical algorithms to identify women at risk before symptoms become severe. Finally, we will provide a deeper understanding of biological mechanisms driving PE and its subtypes, including endothelial function and immune response, which may lead to the discovery of new therapeutic targets. ECLIPSE-BRAZIL represents a major advancement in PE research, integrating a comprehensive evaluation of clinical, biochemical, and molecular markers throughout pregnancy. Its findings may inform public health policies and improve clinical practices worldwide. Not applicable. This is an observational cohort study approved by the Research Ethics Committees, as documented under the following CAAE numbers: 12471918.0.0000.5149, 12471918.0.3002.5119, 12471918.0.3003.5130, 12471918.0.3006.5545.
To evaluate clinical and immunological characteristics associated with adverse perinatal outcomes among pregnant people living with HIV (PPLH). This retrospective cohort study included singleton pregnancies of PPLH followed between 2006 and 2019 at a Brazilian tertiary referral center for high-risk pregnancies. Clinical and HIV-related data, including viral load (VL), CD4+ cell count, lymphopenia, and opportunistic infections (OI), were obtained from medical records. The primary endpoint was a composite adverse perinatal outcome defined as preterm birth (PTB) and/or low birth weight (LBW). Multivariable logistic regression was performed to identify factors independently associated with adverse outcomes. A total of 167 pregnancies were analyzed. The prevalence of the composite adverse perinatal outcome was 28.1%. Adverse outcomes were associated with previous opportunistic infection (p = 0.049), gestational opportunistic infection (p = 0.019), higher baseline viral load (p = 0.049), baseline lymphopenia (p = 0.002), lower body mass index (p = 0.044), lower CD4 cell count at 34 weeks (p = 0.014), and lack of viral suppression at 34 weeks (p = 0.008). In multivariable analysis, baseline VL (adjusted OR = 1.73, 95% CI = 1.10-2.99) and baseline lymphopenia (adjusted OR = 7.67, 95% CI = 1.37-42.8) remained independently associated with adverse perinatal outcomes. Adverse perinatal outcomes remain frequent among PPLH. Baseline viral load and lymphopenia were independently associated with PTB and/or LBW, highlighting the importance of early viral suppression and immune stabilization during pregnancy.
Hydrocephalus is one of the most common pediatric neurosurgical conditions worldwide, with an incidence of approximately 6000 new cases in infants annually, 50% of which are congenital. While shunt placement remains a standard treatment, endoscopic third ventriculostomy (ETV) combined with choroid plexus cauterization (CPC) has emerged as a less invasive and durable alternative in selected cases. However, ETV-CPC is technically demanding and requires extensive surgical training, especially for pediatric populations. This chapter explores an innovative, mixed-reality simulation model that combines a physical baby simulator with an expert AI-driven avatar to reduce the learning curve for pediatric neuroendoscopy. The training model, designed specifically for use in under-resourced regions such as the Brazilian Amazon region, was evaluated and showed a 41.65% average decrease in surgical errors post-training. This chapter also discusses the global implications of this methodology for neurosurgical training and equitable medical education.
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This study aimed to evaluate the impact of simulated obesity in rats on Receptor Activator of Nuclear Factor κB (RANK), Receptor Activator of Nuclear Factor κB Ligand (RANKL) and Osteoprotegerin (OPG) expression during orthodontic tooth movement (OTM). Forty male Wistar rats 6 weeks old were allocated into non-obese and obese groups. Obesity was simulated by a high-fat diet for 8 weeks. After, the left maxillary first molar was moved by stretched orthodontic nickel-titanium coiled springs. The animals were euthanized after 7 and 14 days of OTM, and the alveolar bone surrounding the roots of the left and right maxillary first molar was dissected to gene expression by qRT-PCR. TaqMan assays for RANK, RANKL, OPG and GAPDH were used, and the values of gene expression were compared by one- and two-way ANOVA with Tukey post-test (alpha = 5%). RANK expression in OTM side at 7 days was statistically different between non- and obese rats (p < 0.01), but not at 14 days (p > 0.05). The RANKL and OPG expression levels on the OTM side did not differ between the groups after 7 or 14 days of OTM. The RANKL and OPG gene expression is not affected by OTM in simulated obese rats. The impact of obesity on RANK gene expression needs to be further studied. Este estudo avaliou o impacto da obesidade induzida em ratos e a expressão gênica de RANK, RANKL e OPG durante a movimentação dentária. Quarenta ratos machos com seis semanas de vida foram alocados em grupos obesos e não obesos. A obesidade foi induzida por dieta hipercalórica durante 8 semanas. Em seguida, foi aplicado força ortodôntica no primeiro molar superior esquerdo com mola de níquel titânio. Os animais foram eutanasiados depois de 7 e 14 dias do início da movimentação dentária e o osso alveolar adjacente às raízes dos primeiros molares superiores direito e esquerdo foram coletadas para análise gênica por qRT‐PCR. Foi usado kit TaqMan para avaliar a expressão gênica de RANK, RANKL e OPG, e comparadas por testes estatístico ANOVA com pós teste de Tukey (alfa = 5%). A expressão de RANK nos sítios de movimentação dentária durante 7 dias foram estatisticamente significantes entre os grupos de ratos obesos e não obesos (p < 0.01), mas não no período de 14 dias (p > 0,05). O nível de RANKL e OPG não apresentou diferença entre os grupos de 7 e 14 dias. A expressão de RANKL e OPG não foi alterada pela movimentação dentária em ratos com obesidade induzida. O impacto da obesidade na expressão gênica de RANK precisa de mais estudos para ser consolidada.
Covalent organic frameworks (COFs) have emerged as promising porous organic semiconductors for chemical sensing, owing to their structurally tunable electronic properties and accessible pores. A key challenge for the rational design of these materials is establishing a clear understanding of how molecular-level functionalization dictates their optoelectronic response. Here, we address this challenge through a computational investigation of TBQP-based COFs, combining density functional theory and molecular dynamics to investigate the impact of edge functionalization on their electronic structure, optical properties, and adsorption reactivity toward Cl2, ClF3, and SO2. Using representative molecular models and fragments derived from the TBQP architecture, our results demonstrate that the Frontier orbital energies and band gap of the extended framework are primarily governed by the electronic character of the constitutive building blocks. This enables systematic property modulation through targeted substituent effects. We establish quantitative correlations between experimental Hammett parameters, DFT-based reactivity indices, and analyte-induced electronic perturbations, providing descriptors that link chemical modification to optoelectronic behavior. Furthermore, we find that analyte adsorption can introduce midgap states, revealing a general electronic sensing mechanism for π-conjugated COFs. These findings not only offer practical guidelines for tailoring the electronic and reactive properties of TBQP frameworks but also underscore the critical role of molecular functionalization in governing the sensing performance of porous organic semiconductors. The identified structure-property relationships provide useful guidelines for the rational design of COF-based sensors.
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The present study evaluates the effect of borax as a cross-linker at different concentrations (0%, 1.32%, 2.61%, and 3.87%w/w) on the physicochemical properties of the films comprised of pectin, glycerol, and borax. The film-forming solutions were made by two distinct preparation methods: i. a heated system, at 85 °C, without stirring (thermal method, TM) and ii. a nonheated high-speed stirring system, 30,000 rpm (agitation method, AM). Films produced by both methods were compared to assess their structural, thermal, mechanical, and antimicrobial properties. Steady-state and real-time infrared spectroscopy (FTIR) indicated the formation of B-O-C moieties, with cross-linking efficiency favored under both higher pH and temperature. SEM images and mechanical analyses revealed that AM gave rise to markedly coherent and continuous films, whereas TM-derived films exhibited surface defects and breakpoints, particularly at higher borax concentrations. Thermal analyses (TGA/DTA) indicated that borax enhances the thermal stability of the films regardless of the preparation method. Increasing borax content, however, generally reduced tensile strength and elongation at break, suggesting a competitive balance between cross-linking and plasticization. The films did not display significant antibacterial effects, likely due to partial solubilization during diffusion-based assays. Overall, the results demonstrate that temperature and borax concentration in the film-forming solution play a key role toward pectin film properties.