Pancreatic cancer (PC) is a highly lethal malignancy with rising incidence and mortality rates, although its burden remains poorly investigated in Brazil. Understanding its regional and sex-specific trends is critical for tailoring public health interventions and mitigating the disease's impact in the Brazilian population. This study aimed to evaluate the temporal trends in PC mortality among Brazilian individuals between 1980 and 2023 and its alignment with the global projections. This retrospective, population-based ecological study analyzed PC mortality data using the Sistema de Informação de Mortalidade (SIM) and demographic data from the Instituto Brasileiro de Geografia e Estatística (IBGE). Annual Percent Change (APC) calculations were performed to assess temporal trends by Brazilian geographic regions and sex, accounting for demographic shifts over time. A total of 257,671 PC-related deaths occurred during the study period, averaging 5,856 deaths per year. The overall mortality trend for PC in Brazil showed a continuous increase of (APC: 1.23; 95%CI: 1.16-1.32; P-value <0.01). Regional analyses revealed significant increases in the North (APC: 2.32), South (APC: 0.59), and Midwest (APC: 1.45) regions. Sex-specific trends indicated a steady increase for women throughout the period, while men experienced alternating phases of rising and stationary trends. PC mortality in Brazil has risen significantly over the past four decades, with marked regional and sex-specific disparities, aligning with global perspectives. These findings highlight the need for targeted PC prevention, early detection, and equitable access to high-quality cancer care, particularly in vulnerable regions and populations. O câncer de pâncreas (CP) é uma neoplasia altamente letal, com incidência e mortalidade crescentes em todo o mundo. Apesar de seu impacto significativo, a carga da doença permanece pouco investigada no Brasil, especialmente quanto às diferenças regionais e entre sexos, aspectos fundamentais para orientar estratégias de saúde pública. Avaliar as tendências temporais da mortalidade por câncer de pâncreas no Brasil entre 1980 e 2023 e verificar seu alinhamento com as projeções epidemiológicas globais. Estudo ecológico retrospectivo de base populacional utilizando dados de mortalidade do Sistema de Informação sobre Mortalidade (SIM) e estimativas populacionais do Instituto Brasileiro de Geografia e Estatística (IBGE). Os óbitos por câncer de pâncreas foram identificados pelos códigos ‘157 da CID-9 e C25 da CID-10. As tendências temporais foram avaliadas por meio do cálculo da Variação Percentual Anual (Annual Percent Change - APC) utilizando análise de joinpoint, estratificada por sexo e regiões geográficas do Brasil. Entre 1980 e 2023 foram registrados 257.671 óbitos por câncer de pâncreas no Brasil, com média anual de 5.856 mortes. Observou-se tendência global crescente de mortalidade ao longo de todo o período analisado (APC: 1,23; IC95%: 1,16-1,32; p<0,01). Nas análises regionais, foram identificadas tendências significativas de aumento nas regiões Norte (APC: 2,32), Sul (APC: 0,59) e Centro-Oeste (APC: 1,45). Entre os sexos, as mulheres apresentaram aumento contínuo da mortalidade ao longo de todo o período, enquanto os homens apresentaram fases alternadas de crescimento e estabilidade nas taxas de mortalidade. A mortalidade por câncer de pâncreas no Brasil aumentou significativamente nas últimas quatro décadas, com importantes disparidades regionais e diferenças entre os sexos. Esses achados acompanham as tendências observadas globalmente e destacam a necessidade de estratégias direcionadas de prevenção, diagnóstico precoce e ampliação do acesso equitativo ao cuidado oncológico, especialmente em regiões e populações mais vulneráveis.
Understanding how phenotypic plasticity arises in sensory traits is a key challenge in evolutionary and developmental biology. Eusocial insects offer a useful model for exploring it, because their castes perform distinct tasks and occupy different light environments. We examined morphological variation and scaling in the visual systems of female castes of Protopolybia sedula, a neotropical wasp with simultaneous polygyny. Although queens are larger than workers, both castes showed similar eye area, ommatidial diameter, and ommatidia number. However, queens showed greater variability in ommatidial diameter, while workers varied more in eye area and ommatidia number. Allometric patterns also diverged: queen eye area scaled hypoallometrically and ommatidial diameter hyperallometrically with body size, whereas workers displayed isometric scaling for both traits. Analysis of ommatidia size and number indicates workers allocate more resources to increasing ommatidia number, while queens emphasize enlarging ommatidia. These differences highlight distinct developmental and scaling strategies that generate caste-specific visual adaptations. Additional language abstract Compreender como a plasticidade fenotípica em características sensoriais surge é um desafio fundamental na biologia evolutiva e do desenvolvimento. Insetos eussociais oferecem um modelo útil para explorá-la, pois suas castas desempenham tarefas distintas e ocupam diferentes ambientes luminosos. Examinamos a variação morfológica e a escala nos sistemas visuais de castas femininas de Protopolybia sedula, uma vespa neotropical com poliginia simultânea. Embora as rainhas sejam maiores que as operárias, ambas as castas apresentaram área do olho, diâmetro dos omatídios e número de omatídios semelhantes. No entanto, as rainhas mostraram maior variabilidade no diâmetro dos omatídios, enquanto as operárias variaram mais na área do olho e no número de omatídios. Os padrões alométricos também divergiram: a área dos olhos das rainhas apresentou escala hipoalométrica e o diâmetro dos omatídios hiperalométrica com o tamanho do corpo, enquanto as operárias exibiram escala isométrica para ambas as características. A análise do tamanho e do número de omatídios indica que as operárias alocam mais recursos para aumentar o número de omatídios, enquanto as rainhas priorizam o aumento do tamanho dos omatídios. Essas diferenças destacam estratégias distintas de desenvolvimento e escalonamento que geram adaptações visuais específicas para cada casta.
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant myocardial disorder affecting 0·2% of the global population and a leading cause of sudden cardiac death in young individuals and athletes. Current guidelines recommend periodic clinical screening of first-degree relatives for early diagnosis and risk stratification. Genetic testing identifies at-risk individuals while exempting genotype-negative relatives from lifelong surveillance. However, it remains unavailable in Brazil's public health system (Sistema Único de Saúde, SUS). This study aimed to evaluate the cost-utility of genetic testing for HCM cascade screening in Brazil. A cost-utility analysis was conducted from the SUS perspective, using a hybrid decision tree and Markov model to project lifetime costs and health outcomes. Inputs were derived from literature and validated by a multidisciplinary expert panel. Genetic testing costs were micro-costed; other costs were obtained from Brazil's national reimbursement database (SIGTAP). Effectiveness was measured in quality-adjusted life-years (QALYs). Deterministic and probabilistic analyses assessed model robustness. Genetic testing was cost-effective (incremental cost-effectiveness ratio: US$1411 per QALY), yielding an incremental gain of 0·06 QALYs per relative at an additional cost of $87 per relative. Utility values had the greatest influence on cost-utility outcomes. In probabilistic analysis, genetic testing was cost-effective in 99·4% of simulations at the Brazilian willingness-to-pay threshold of $7421 per QALY. In the base-case hypothetical cohort of 1000 relatives (250 probands with four first-degree relatives each), 205 (20·5%) of 1000 relatives were exempted from lifelong surveillance, reducing screening visits by 18·6% per tested individual. Genetic testing is a cost-effective strategy for HCM cascade screening in Brazil's public health system. By exempting genotype-negative relatives from lifelong surveillance, it optimises resource allocation, reduces unnecessary follow-ups and psychological burden, and supports informed family planning. These findings provide an economic evidence base for integrating genetic testing into SUS clinical practice guidelines. Programa Nacional de Genômica e Saúde de Precisão (Genomas Brasil) of the Brazilian Ministry of Health and Conselho Nacional de Desenvolvimento Científico e Tecnológico.
Biodiversity offsetting aims to compensate for ecological losses from development through conservation and restoration. However, its long-term outcomes under repeated impact-offset cycles remain uncertain. Using a conceptual forest succession model, we evaluated how offset outcomes are affected by interactions among compensation scale, duration of protection, habitat conversion rate, and land availability constraints. Additionally, we considered that these outcomes may differ across biodiversity components, including habitat maturity associated with successional habitat-forming species and metapopulation dynamics of persistent colonizers and successional specialists. We showed that effective offsetting requires restoring areas larger than those impacted and maintaining protection over timescales aligned with ecological recovery, particularly where ongoing habitat conversion reshapes landscape structure. High rates of habitat conversion consistently reduced offsetting success, particularly for colonizing species reliant on habitat quality and long-term protection. Our results further showed that delayed ecological responses and cumulative impacts can undermine offsetting efforts that appear effective in the short term. Robust offset design must therefore explicitly account for temporal lags, dynamic landscape trajectories, adequate spatial compensation, and multiple biodiversity indicators to avoid the ecological fallacy that short-term restoration success equates to long-term biodiversity and ecosystem integrity. Optimización de la compensación de la biodiversidad para la sucesión de hábitats y la dinámica de colonización Resumen La compensación de la biodiversidad tiene como objetivo compensar las pérdidas ecológicas derivadas del desarrollo mediante la conservación y la restauración. Sin embargo, los resultados a largo plazo en el marco de ciclos repetidos de impacto y compensación siguen siendo inciertos. Utilizamos un modelo conceptual de sucesión forestal para evaluar cómo los resultados de la compensación se ven afectados por las interacciones entre la escala de compensación, la duración de la protección, la tasa de conversión del hábitat y las restricciones de disponibilidad de suelo. También consideramos que estos resultados pueden variar según los componentes de la biodiversidad, incluyendo la madurez del hábitat asociada a especies de sucesión formadoras de hábitat y la dinámica de metapoblaciones de colonizadores persistentes y especialistas de sucesión. Demostramos que una compensación efectiva requiere restaurar áreas más extensas que las afectadas y mantener la protección durante periodos de tiempo acordes con la recuperación ecológica, especialmente cuando la conversión continua del hábitat remodela la estructura del paisaje. Las altas tasas de conversión del hábitat redujeron de forma sistemática el éxito de la compensación, en particular para las especies colonizadoras que dependen de la calidad del hábitat y de una protección a largo plazo. Nuestros resultados demostraron además que las respuestas ecológicas retardadas y los impactos acumulativos pueden socavar los esfuerzos de compensación que parecen eficaces a corto plazo. Por lo tanto, un diseño sólido de las medidas de compensación debe tener en cuenta explícitamente los retrasos temporales, las trayectorias dinámicas del paisaje, una compensación espacial adecuada y múltiples indicadores de biodiversidad, a fin de evitar la falacia ecológica según la cual el éxito de la restauración a corto plazo equivale a la biodiversidad y la integridad de los ecosistemas a largo plazo.
This study analyses how LGBTQ+ healthcare users and healthcare professionals navigate and reconfigure access to healthcare within Brazil's Sistema Único de Saúde (Unified Health System) in contexts shaped by institutional LGBTQ-phobia. The study employed a qualitative intervention-research design informed by cartography. Fieldwork was conducted in a family health clinic in northeastern Brazil and combined participant observation with semi-structured interviews with LGBTQ+ healthcare users and healthcare professionals. The analysis conceptualises access not as a linear process but as a set of negotiated pathways, mapped as five routes of access to healthcare: facilitated access; access 'by force'; unnoticed access; access through detours; and access through support networks. These routes reveal how access is continuously produced through relational practices, micropolitical negotiations and collective arrangements that both reproduce and disrupt institutional norms. The findings position agency as a central analytical axis, demonstrating how subjects and professionals actively invent alternative forms of care in response to institutional violence and exclusion.
The Brazilian Health Reform Movement succeeded in enshrining health as a constitutional social right, resulting in the creation of the Unified Health System (Sistema Único de Saúde, or SUS), based on the principles of universality, comprehensive care, equity, and democratized participation of users and workers in system management. However, the SUS faces a process of privatization by private Social Health Organizations (Organizações Sociais de Saúde, or OSS). This article reports part of a study involving researchers, including public mental health service workers. The methodological strategy explored narratives related to episodes of care in workplaces. The results revealed what we termed the 'enterprise-mode,' impacting both workers and the care provided in services managed by OSS. SUS health care workers on the shop floor face the challenge of commercial privatizing forces acting against the foundational principles of democratic management inscribed in the Brazilian Psychiatric Reform law enacted in 2001. A relationship is imposed that corrodes interactions within the team and between the team and service users, attempting to silence those who defend the SUS. However, the narratives also reveal sparks of resistance and insubordination emerging in the daily lives of SUS shop floor workers that can strengthen resistance movements for social health rights.
Brazil's Unified Health System (Sistema Único de Saúde, SUS) represents one of the world's largest universal health systems and provides a unique real-world platform for integrating prevention, diagnosis, treatment, and survivorship across the cancer continuum. While One Health frameworks have traditionally focused on infectious diseases, environmental exposures, and planetary health, their application to surgical oncology and health-system innovation remains insufficiently explored. This article proposes that the SUS offers a valuable model for operationalizing One Health and population health principles in prostate cancer care by connecting environmental, social, biological, and healthcare system determinants across the patient journey. The recent incorporation of robot-assisted radical prostatectomy (RARP) into the SUS represents a critical milestone in this evolution. Beyond the adoption of an advanced surgical technology, this initiative illustrates the capacity of a universal health system to evaluate, implement, and monitor complex innovations while balancing effectiveness, equity, sustainability, and population-level impact. The Brazilian experience highlights the emergence of a learning health system in which real-world evidence, implementation science, surgical quality assessment, and health policy interact to guide innovation at the national scale. In this context, RARP serves as a case study of how technological advances can be integrated into publicly funded healthcare while generating evidence relevant to diverse populations and healthcare settings. By bridging concepts from Surgical Public Health, population health, health-systems science, implementation science, and One Health, the SUS provides a distinctive framework for understanding how surgical innovation can contribute to resilient and equitable cancer care. As translational oncology increasingly incorporates environmental, societal, and biological determinants of disease, Brazil offers important lessons on the governance, evaluation, and dissemination of high-complexity surgical technologies within universal health systems. The insights emerging from this experience may help inform future strategies to optimize prostate cancer care and strengthen health-system resilience globally.
Although ovarian cancer is the most lethal among gynecological cancers, access to massive BRCA testing is still limited. Its cost-effectiveness is still a topic of discussion in several countries. In Brazil, olaparib was recently incorporated into the public health system, access to BRCA testing is still limited. In this article, we aim to review the cost-effectiveness of offering BRCA testing to the at-risk population. A working group composed of 14 specialists in surgical oncology and cancer genetics was established to discuss the cost-effectiveness of population-based BRCA testing for ovarian cancer. The project was divided into five main areas, each with subtopics assigned among the 14 participants. They were: the existing clinical testing guidelines, the current healthcare infrastructure in the Brazilian public health system, cost-effectiveness analysis, challenges in implementing prophylactic surgeries, and family counseling and risk communication. A comprehensive literature review was conducted, followed by a series of meetings among the article's contributors to reach consensus on unresolved issues. These discussions aimed to build recommendations based on the best available scientific evidence. Using as a basis the current structure already existing within the Brazilian public health service (SUS [Sistema Único de Saude]), and based on the testing of the at-risk population chosen by our experts, we estimated savings. The net savings for a population of 100 000 women would range from BRL 7030.30 (US$1255.41) to BRL 1853.92 (US$331.05). And these costs could have an even greater impact when public service PARP inhibitors are incorporated. The working group of the Brazilian Society of Surgical Oncology understands that large-scale BRCA testing is cost-effective, especially when risk-reducing surgery is implemented. Other measures are important, such as training teams of non-specialists to recognize the population at risk, in addition to creating an entire line of care for patients with ovarian cancer in the SUS.
Epidemiology has been fundamental for analyzing health problems and supporting decision-making in healthcare systems and public health. However, traditional epidemiological methods, designed fundamentally to identify causal associations at the population level through aggregate data measures, present inherent limitations in capturing individual heterogeneity in response to specific exposures. This population-based approach hinders personalized prediction of outcomes in a particular individual whose risk factors may manifest differently from the group average, particularly when multiple contextual variables and unique biological profiles are involved. Advances in artificial intelligence have generated tools capable of integrating large volumes of information, identifying complex patterns in specific subgroups, and producing more personalized estimates, transitioning from a reactive approach based on population averages toward predictive models centered on individual trajectories. However, these developments do not replace the methodological foundations of epidemiology, as the identification of exposures, outcomes, and causal relationships continues to depend on the epidemiological conceptual framework. From this perspective, current tensions do not represent a disciplinary crisis, but rather a transition toward broader approaches that combine population-based analyses with advanced predictive tools. This integration is particularly relevant for large-scale healthcare institutions and national health systems, which require models capable of leveraging diverse data to improve understanding of health processes and support clinical and operational decisions. La epidemiología ha sido fundamental para el análisis de los problemas de salud y para la toma de decisiones en los sistemas sanitarios y la salud pública. No obstante, los métodos tradicionales de la epidemiología, diseñados fundamentalmente para identificar asociaciones causales a nivel poblacional mediante medidas de datos agrupados, presentan limitaciones inherentes para capturar la heterogeneidad individual en la respuesta ante exposiciones específicas. Esta aproximación poblacional dificulta la predicción personalizada del desenlace en un individuo particular, cuyos factores de riesgo pueden manifestarse de forma distinta al promedio grupal, particularmente cuando intervienen múltiples variables contextuales y perfiles biológicos únicos. Los avances en inteligencia artificial han generado herramientas capaces de integrar grandes volúmenes de información, identificar patrones complejos en subgrupos específicos y elaborar estimaciones más personalizadas, transicionando desde un enfoque reactivo basado en promedios poblacionales hacia modelos predictivos centrados en trayectorias individuales. Sin embargo, estos desarrollos no sustituyen los fundamentos metodológicos de la epidemiología, ya que la identificación de exposiciones, desenlaces y relaciones causales continúa dependiendo del marco conceptual epidemiológico. Bajo esta perspectiva, las tensiones actuales no representan una crisis disciplinaria, sino una transición hacia enfoques más amplios que combinan análisis poblacionales con herramientas predictivas avanzadas. Esta integración resulta especialmente relevante para instituciones de gran escala, como las de seguridad social, que requieren modelos capaces de aprovechar datos diversos para mejorar la comprensión de los procesos de salud y apoyar decisiones clínicas y operativas.
In this study, the valorization of poly(lactic acid) (PLA) waste as well as rice husk into sustainable materials was explored. To simulate the industrial valorization of defective PLA parts, scraps and burrs, PLA was reprocessed (rPLA) by melt extrusion and further plasticized with 15 wt.% of acetyl tributyl citrate (ATBC) and reinforced with rice husk (RH) or rice husk biochar (RHB) in 1 or 3 wt.%. The melt flow index was determined to assess the effect of reprocessing and the addition of RH or RHB on the material degradation. The obtained films were characterized in terms of their structural, mechanical, and thermal behavior. The water-related behavior of the materials was evaluated by measuring the static water contact angle and the water vapor transmission rate (WVTR). Compostability was proposed as an end-of-life option, therefore disintegration under composting conditions was assessed. Reprocessing increased the MFI and slightly reduced the strength and the modulus, consistent with chain scission. ATBC facilitated the processability, improved the particles' dispersion and provided ductility to the final materials. RH and RHB acted mainly as nucleating agents and strongly modified the surface wettability. A low RHB loading improved the WVTR, whereas a higher filler content and ATBC generally increased the WVTR. All the films were completely disintegrated within 18 to 21 days. These results show practical valorization routes to obtain rPLA films with tunable properties and to preserve the inherent composting disintegration of PLA.
Coxiella burnetii is a globally distributed zoonotic bacterium responsible for Q fever in humans, with domestic ruminants serving as primary reservoirs. In Colombia, while livestock production is a vital economic sector, the dynamics of C. burnetii circulation among ticks and domestic animal hosts remain poorly understood. This study aimed to identify C. burnetii in hosts and ticks from two cattle farms in the Magdalena Medio region. Ticks were collected directly from domestic animal hosts through physical inspections and the use of the dragging technique on pasture vegetation and identified via morphological keys and COI barcoding as Rhipicephalus microplus s.l., predominating on cattle, Dermacentor nitens on equines, and Rhipicephalus sanguineus s.l. on dogs. Blood-meal analysis using PCR-HRM and sequencing identified feeding sources in equines, bovines, and humans, with human DNA detected in all larval pools. Following tick characterization, Coxiella spp. were screened by qPCR targeting the IS1111 insertion sequence, revealing a frequency of 10.5% in domestic animal hosts and 1.36% in ticks. Finally, phylogenetic analysis of 16S rRNA and rpoB genes confirmed the coexistence of C. burnetii (Clade A) in hosts and ticks, alongside Coxiella-like endosymbionts (Clade C), primarily in R. microplus s.l. These findings reveal complex tick-host interactions and confirm the molecular circulation of Coxiella spp. in tropical livestock systems. The results underscore the need to use multigene markers to differentiate pathogens from endosymbionts and suggest a potential human exposure risk, highlighting the importance of One Health surveillance in these agroecosystems.
Climate change is expected to increase temperatures in agricultural producing regions, potentially affecting fruit development and quality. To date, the molecular responses of raspberry fruits to moderate warming under field conditions have not been explored. In this paper, raspberry plants (Rubus idaeus L. cv. Heritage) growing in two contrasting agroclimatic regions of Chile were exposed to a moderate increase in temperature during fruit development. Fruit phenotyping, histological analyses, and RNA sequencing were used to evaluate physiological and transcriptomic responses to warming. Elevated temperature increased fruit weight and fruit dimensions in both orchards and was associated with larger drupelet and cell areas, which was accompanied by reduced cell density. Moreover, transcriptomic analyses revealed marked differences in gene expression responses between raspberries fruits from different locations with only a small number of heat-responsive genes shared across locations. Nevertheless, the common enrichment of oxylipin-related processes was observed, suggesting a conserved response. In addition, a combined treatment model identified the enrichment of processes like ribosome biogenesis, RNA metabolism, cell cycle regulation, cytokinesis, and structural cellular remodeling. These transcriptional changes were consistent with the cellular phenotypes observed in heat-treated fruits. Overall, our results show that moderate warming promotes larger raspberry fruits through changes in cellular organization, while the underlying molecular responses are strongly influenced by agroclimatic context.
Ficus carica L. is traditionally used for diabetes management. This study evaluated the antihyperglycemic activity, safety, possible mechanisms, and phytochemical composition of its aqueous leaf extract (EAcFc). EAcFC activity was evaluated in streptozotocin-nicotinamide-induced type 2 diabetic (ST2D) mice under acute and subchronic conditions. EAcFc showed low acute toxicity (LD50 > 3000 mg/kg). Acute and subchronic oral administration of EAcFc (300 mg/kg) significantly reduced blood glucose levels in ST2D mice. Although sustained HbA1c reduction was not observed, EAcFc improved lipid profiles, notably reducing triglyceride concentrations in ST2D males (from 156 ± 19.4 to 89.7 ± 3.3 mg/dL at week 4) and females (from 138 ± 2.0 to 77 ± 16.0 mg/dL at week 4). In oral sucrose and lactose tolerance tests (3 g/kg load), EAcFc (300 mg/kg) significantly attenuated postprandial hyperglycemia at 30, 60, and 120 min, an effect comparable to acarbose (50 mg/kg). No significant activity was observed during the oral glucose tolerance test (1.5 mg/kg load), suggesting the effect is not mediated by SGLT-1 inhibition. Preparative TLC and NMR analysis identified narcissin, nicotiflorin, and β-sitosterol. Thus, EAcFc possesses antihyperglycemic and lipid-modulating properties partially associated with α-glucosidase inhibition and bioactive flavonoids and phytosterol.
Sustained profitability in dairy production requires continuous improvements in milk yield and composition, traits that are strongly influenced by underlying genetic factors. Polymorphisms in the milk protein genes β-lactoglobulin (β-Lg) and κ-casein (κ-Cn) have been associated with variation in milk production, composition, and technological properties across dairy breeds. This study applied polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to characterize β‑Lg and κ‑Cn gene variants in Jersey (JE), crossbred (XX), and Creole (CR) dairy cattle in Panama. Genotypic and allelic variation was evaluated using a convenience sample of 351 blood samples collected between 2014 and 2015 (JE, n = 230; XX, n = 90; CR, n = 26). Although the sampling strategy does not support population‑level inference, it is suitable for assessing the feasibility of PCR‑RFLP and conducting an exploratory characterization of genetic variability. Amplification success was 98.6% for β‑Lg and 76.6% for κ‑Cn. At the β‑Lg locus, allele A predominated in JE (0.55) and CR (0.52) cattle, whereas allele B was more frequent in XX cattle (0.73). At the κ‑Cn locus, allele B predominated across all groups. Overall, PCR‑RFLP proved to be a practical and accessible method for detecting variations in milk protein genes, supporting its application in future population‑based studies under Panamanian production conditions. A rentabilidade sustentável da produção leiteira requer melhorias contínuas na produção e na composição do leite, características fortemente influenciadas por fatores genéticos subjacentes. Polimorfismos nos genes das proteínas do leite β-lactoglobulina (β-Lg) e κ-caseína (κ-Cn) têm sido associados a variações na produção, na composição e nas propriedades tecnológicas do leite em diferentes raças leiteiras. Este estudo aplicou a técnica de reação em cadeia da polimerase seguida de análise de polimorfismo de comprimento de fragmentos de restrição (PCR-RFLP) para caracterizar variantes dos genes β-Lg e κ-Cn em bovinos leiteiros das raças Jersey (JE), mestiços (XX) e Crioulos (CR) no Panamá. A variação genotípica e alélica foi avaliada utilizando uma amostra de conveniência composta por 351 amostras de sangue coletadas entre 2014 e 2015 (JE, n = 230; XX, n = 90; CR, n = 26). Embora a estratégia de amostragem não permita inferências em nível populacional, ela é adequada para avaliar a viabilidade da técnica PCR-RFLP e realizar uma caracterização exploratória da variabilidade genética. O sucesso de amplificação foi de 98,6% para β-Lg e de 76,6% para κ-Cn. No locus β-Lg, o alelo A predominou nos animais JE (0,55) e CR (0,52), enquanto o alelo B foi mais frequente nos animais XX (0,73). No locus κ-Cn, o alelo B predominou em todos os grupos avaliados. De modo geral, a técnica PCR-RFLP mostrou-se um método prático e acessível para a detecção de variações em genes de proteínas do leite, apoiando sua aplicação em futuros estudos populacionais conduzidos sob as condições de produção do Panamá.
Developmental Dysplasia of the Hip (DDH) is the most common human congenital malformation. When diagnosed and treated before five months of age, it has a high cure rate. If not, surgical management is required with high economic costs, a great impact on morbidity and sequelae that can generate permanent disability. To design and validate an instrument to timely detect DDH. An instrument developed from a literature review on the timely diagnosis of DDC, using the PRISMA methodology. To validate it, an expert panel was formed comprising specialists from different healthcare institutions. All participants in the expert panel agreed that DDH is a public health problem. They consider that there are many patients with late diagnosis and sequelae due to a lack of timely treatment. There was consensus on the feasibility of implementing the proposal. The expressed need to update the current regulations regarding diagnostic means was identified. It is necessary to promote epidemiology, risk factors, correct physical examination, ideal imaging methods according to the patient's age, and timely referral pathways for patients. Add our DDH instrument to the section to the healthy child card. This should include risk factors: pelvic presentation, female sex, and family history of DDH. As well as the marking of a normal vs abnormal physical examination. la displasia del desarrollo de la cadera (DDC) es la malformación congénita más común en humanos. Si se diagnostica y trata antes de los cinco meses de edad presenta una alta tasa de curación; si no, requiere tratamiento quirúrgico con altos costos económicos, gran impacto en la morbilidad y secuelas que pueden generar discapacidad permanente. diseñar y validar un instrumento para detectar tempranamente la DDC. instrumento elaborado a partir de una revisión de la literatura sobre el diagnóstico oportuno de DDC, utilizando la metodología PRISMA. Para validarlo se conformó un panel de expertos con especialistas de diferentes instituciones de salud. todos los participantes del panel de expertos coincidieron en que la DDC es un problema de salud pública. Consideran que existen muchos pacientes con diagnóstico tardío y secuelas debido a la falta de tratamiento oportuno. Hubo consenso sobre la viabilidad de implementar la propuesta. Se identificó la necesidad de actualizar la normativa vigente en materia de medios de diagnóstico. es necesario promover la exploración física correcta, los métodos de imagen ideales según la edad del paciente y las vías de derivación oportunas. Incluir nuestro instrumento de DDC en la sección de la tarjeta del niño sano. Se deben incluir factores de riesgo: presentación pélvica, sexo femenino y antecedentes familiares de DDC. Además, se debe marcar una exploración física normal frente a anormal.
Bixa orellana L. is the primary source of the apocarotenoid bixin, whose biosynthesis is predicted to be initiated by carotenoid cleavage dioxygenases (CCDs). A genome-wide analysis was conducted to identify nonredundant CCD genes in B. orellana, classifying them into subfamilies. Gene structure, codon-based Ka/Ks divergence, conserved domains and motifs, subcellular localization, chromosomal distribution, paralog pairs, synteny, phylogenetic relationships (including reference orthologs from A. thaliana and T. cacao), transcriptomic expression patterns, and promoter cis-regulatory elements were all analyzed. These analyses identified 28 nonredundant CCD genes in B. orellana, classified into the CCD1, CCD4, CCD7, CCD8, NCED, and LCO subfamilies. Gene structure fell into three classes: intronless/single-exon genes (likely retrotransposition-derived), genes with intermediate 2-8 exon organizations, and complex genes with 10-15 exons (264 bp-6,254 bp genomic length). Ka/Ks analysis showed heterogeneous synonymous divergence (Ks: 0.367-1.449). Ten conserved sequence motifs were identified across all 28 proteins, including a broadly conserved NDH-type catalytic motif in 20 of 28 proteins spanning multiple subfamilies; full-length CCD1, CCD4, and NCED members harbored the complete motif set. Subcellular localization was predominantly cytoplasmic for CCD1 and core CCD4 members, with CCD1_copy3/4/5 predicted in peroxisomes and BoCCD4_chl isoforms in chloroplasts. Chromosomal mapping revealed two major hotspots: a CCD1 tandem array on scaffold 4 and a CCD4 cluster on scaffold 9, accounting for 59.4% of all CCD genes. Paralog analysis identified 39 tandem duplication candidate pairs (distance < 200 kb, Ks < 1.0), supported by synteny analysis showing partial flanking gene conservation (CCD1, CCD7, CCD8, NCED) and lineage-specific reorganization of the scaffold 9 CCD4 cluster. Phylogenetic analysis confirmed expansion of the CCD1 and CCD4 subfamilies, particularly CCD4-2 copies on scaffold 9. Transcriptomic data showed elevated seed expression of CCD1_copy5, CCD4-1, CCD4-3, and several CCD4-2 variants. Promoter analysis predicted abundant light-responsive elements, followed by hormone- and stress-responsive elements. These findings provide quantitative evidence that tandem duplication is the primary driver of CCD family expansion in B. orellana. The elevated seed expression of specific CCD1 and CCD4 copy variants is consistent with predicted roles in bixin biosynthesis, while the distinct subcellular localization patterns and abundant light-, hormone-, and stress-responsive promoter elements suggest functional diversification and regulatory complexity within the CCD gene family that may underlie pathway-specific apocarotenoid production.
Live-attenuated vaccines can replicate for a transient period post-vaccination and may be associated with symptoms resembling natural infection. The tetravalent dengue vaccine, TAK-003, has undergone extensive preclinical assessment to investigate vaccine RNAemia, viremia, genetic stability, and transmissibility. Here, we investigated the presence of vaccine RNAemia, attenuation loci reversions, and their association with viral-syndrome-like adverse events (AEs) in participants throughout the clinical development program. TAK-003 RNA positive serum samples were evaluated for viral replication and sequenced for reversions. Safety data (solicited AEs within 7/14 days; unsolicited AEs within 28 days) were assessed from a pooled phase 1/2 trial analysis. Participants who experienced febrile illness within 30 days post vaccination in the pivotal phase 3 DEN-301 trial and the phase 2 DEN-313 trial were tested for RNAemia and evaluated for AEs. TAK-003 RNAemia was detected in 441/805 (54.8%) of vaccinees (seronegative: 67.0%; seropositive: 33.0%) in the pooled analysis and in 39 participants with febrile illness from the DEN-301/DEN-313 trials (from 1022 febrile illnesses investigated). RNAemia peaked during the second week post-vaccination and mostly occurred after first dose. Although all four dengue virus (DENV) components were detected, RNAemia was most commonly due to DENV-2. 69 single locus reversions were detected; AEs reported in participants with reversions were generally non-serious, and not indicative of increased symptom severity. Pain at injection site (without RNAemia = 42.0%; RNAemia = 46.8%) and headache (without RNAemia = 36.6%; RNAemia = 37.6%) were the most frequently reported solicited AEs. Incidences of pain, erythema, rash, arthralgia, and fatigue were higher in participants with RNAemia. The incidence of unsolicited AEs was higher in participants with RNAemia (62.4%) than without (52.0%). In the DEN-301/DEN-313 analysis, participants with febrile illness showed a similar pattern of symptoms with and without RNAemia. The presence of RNAemia was associated with transient, mild-to-moderate symptoms, resembling natural infection, which were also observed in the absence of RNAemia.
Whole Genome Sequencing (WGS) enables detailed characterization of circulating and emerging bacterial strains. Although tens of thousands of Salmonella genomes have been acquired over the years, analyses of the genomic differences between strains of different phage types are scarce. We compared two Salmonella enterica subsp. enterica serovar Enteritidis (SEn) phage types, namely phage types 1 and 4 from available databases, using bioinformatic tools and nanopore sequencing of a Chilean PT1 strain. Comparisons between the two phage types show very low genomic divergence and high genomic sequence similarity. Single nucleotide polymorphism (SNP) searches identified SNPs specific to each phage type. Although a translocated region was identified in the Chilean PT1 strain analyzed in this study when compared to the genome of a PT4 strain, this was not present in the genomes of other PT1 strains, suggesting a local strain-specific rearrangement. Further analyses yielded no differences in the CRISPR-Cas locus, but a slight difference was observed in Gifsy-2 prophage detection and DNA modification systems between PT1 and PT4 strains. Our findings provide insights into the genomic differences between SEn strains of two different phage types, serving as a basis for future genomic studies, yet further analyses with more diverse geographical locations collected over a longer time span are essential to validate these differences with the potential to establish molecular markers for strain identification and characterization in the context of epidemiological surveillance as a complement to WGS when this technique is not available.
Individuals with psychosis face persistent barriers to care. Peru's recent mental health reform expanded services nationwide but coincided with the COVID-19 pandemic. We hypothesized that service utilization among individuals with psychosis would increase between 2018 and 2024, particularly in underserved regions. We analyzed outpatient morbidity data from the Peruvian National Superintendence of Health (2018-2024). Sex was available as binary male/female coding; gender identity and race/ethnicity data were not available. Service utilization was compared across three groups: psychosis, non-psychotic mental disorders, and general medical conditions. We examined changes in access (rate ratios, rate differences), the impact of the pandemic (interrupted time series), and decentralization trends (Poisson regression), separately for each disorder group. In 2024 compared with 2018, monthly service utilization per 100,000 declined for psychosis (28.2 in 2018-19.2 in 2024; rate ratio 0.68), rose for non-psychotic mental disorders (225.2 in 2018-304.6 in 2024; 1.35), and slightly fell for general medical conditions (12,688.1 in 2018-12,370.4 in 2024; 0.97). The pandemic caused a comparable immediate drop in service utilization, with rates falling to 37.9%, 37.0%, and 35.3% of expected levels for the three groups in March 2020, followed by gradual monthly increases (psychosis 1.3%, non-psychotic mental disorders 2.6%, general medical conditions 2.2%). A shift from tertiary to primary and regional facilities was seen for both mental disorder groups, but greater utilization in underserved regions was observed only for non-psychotic mental disorders. Despite nationwide expansion of mental health services, individuals with psychosis did not experience higher service use. The pandemic's impact was acute and enduring for this group. Findings underscore the need to examine reasons for this stagnation in service utilization and evaluate the acceptability and appropriateness of Peru's current service model for psychosis. Canadian Institutes of Health Research, Canada Research Chairs program. Las personas con psicosis enfrentan barreras para acceder a la atención en salud. La reforma de salud mental en Perú incrementó los servicios de salud mental a nivel nacional, pero coincidió con la pandemia de COVID-19. Hipotetizamos que la utilización de servicios de salud por personas con psicosis podría aumentar entre el 2018 y el 2024, particularmente en regiones desatendidas. Analizamos datos de morbilidad ambulatoria de la Superintendencia Nacional de Salud del Perú (2018–2024). La variable sexo fue categorizada de forma binaria (hombre/mujer); no se contó con información sobre identidad de género ni raza/etnicidad. La utilización de servicios de salud se comparó entre tres grupos diagnósticos: psicosis, trastornos mentales no psicóticos y condiciones médicas generales. Examinamos cambios en el acceso (razones de tasas, diferencias de tasas), el impacto de la pandemia (series de tiempo interrumpidas) y las tendencias de descentralización (regresión de Poisson), por separado para cada grupo diagnóstico. En el 2024, en comparación con el 2018, la utilización mensual de servicios de salud por cada 100,000 habitantes disminuyó para psicosis (28.2 en 2018-19.2 en 2024; razón de tasas 0.68), aumentó para trastornos mentales no psicóticos (225.2 en 2018-304.6 en 2024; 1.35) y disminuyó ligeramente en condiciones médicas generales (12,688.1 en 2018-12,370.4 en 2024; 0.97). La pandemia causó una caída inmediata similar en la utilización de servicios de salud para los tres grupos en marzo de 2020, con tasas que descendieron al 37.9%, 37.0% y 35.3% de los niveles esperados, seguida de aumentos mensuales graduales en la utilización de servicios (psicosis 1.3%, trastornos mentales no psicóticos 2.6%, condiciones médicas generales 2.2%). Se observó un desplazamiento desde establecimientos terciarios hacia la atención primaria y regional en ambos grupos de trastornos mentales, pero el incremento en regiones desatendidas solo se evidenció para los trastornos mentales no psicóticos. A pesar de la expansión de los servicios de salud mental a nivel nacional, las personas con psicosis no tuvieron una mayor utilización de servicios. El impacto de la pandemia fue agudo y persistente para este grupo. Los hallazgos subrayan la necesidad de examinar las razones de este estancamiento en la utilización de servicios y de evaluar la aceptabilidad y adecuación del modelo actual de atención para los trastornos psicóticos en Perú. Institutos Canadienses de Investigación en Salud, Programa de Cátedras de Investigación de Canadá. Trastornos psicóticos; esquizofrenia; servicios de salud mental, servicios comunitarios de salud mental, macrodatos, Perú.
Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major global health challenge due to its high prevalence and association with chronic complications, highlighting the need for reliable predictive tools to support clinical decision-making. Methods: This study proposes a two-stage hierarchical prediction system based on a Random Forest (RF) classifier. In Stage 1, the model performs multiclass classification into healthy (H), T2DM without complications (D), and T2DM with complications (C). In Stage 2, patients classified as C are further stratified into microvascular or macrovascular complications. The dataset included 31 biochemical, molecular, inflammatory, and oxidative stress variables from Mexican and Spanish cohorts. Feature selection was performed using Pearson correlation, and feature relevance was further assessed using RF importance measures. Model training used stratified cross-validation, with additional evaluation on a hold-out set to approximate real-world performance. Results: The optimized RF achieved an accuracy of 92% and a macro F1-score of 0.92, outperforming baseline models, with an AUC-ROC of 0.89 for complication prediction. Key predictive features included IL-18, miR-126, duration of T2DM, HbA1c, and IL-10. Conclusions: The novelty of this study lies in integrating heterogeneous biomarkers within a hierarchical predictive framework, rather than in the machine learning algorithm itself. This multimodal approach, combined with interpretable machine learning techniques, is designed to deliver clinically meaningful insights for patient stratification and personalized management in T2DM.