Gender and non-communicable diseases in Mexico: a political mapping and stakeholder analysis.

BACKGROUND: Mexico and other low- and middle-income countries (LMICs) present a growing burden of non-communicable diseases (NCDs), with gender-differentiated risk factors and access to prevention, diagnosis and care. However, the political agenda in LMICs as it relates to health and gender is primarily focused on sexual and reproductive health rights and preventing violence against women. This research article analyses public policies related to gender and NCDs, identifying political challenges in the current response to women's health needs, and opportunities to promote interventions that recognize the role of gender in NCDs and NCD care in Mexico. METHODS: We carried out a political mapping and stakeholder analysis during July-October of 2022, based on structured desk research and interviews with eighteen key stakeholders related to healthcare, gender and NCDs in Mexico. We used the PolicyMaker V5 software to identify obstacles and opportunities to promote interventions that recognize the role of gender in NCDs and NCD care, from the perspective of the political stakeholders interviewed. RESULTS: We found as a political obstacle that policies and stakeholders addressing NCDs do not take a gender perspective, while policies and stakeholders addressing gender equality do not adequately consider NCDs. The gendered social and economic aspects of the NCD burden are not widely understood, and the multi-sectoral approach needed to address these aspects is lacking. Economic obstacles show that budget cuts exacerbated by the pandemic are a significant obstacle to social protection mechanisms to support those caring for people living with NCDs. CONCLUSIONS: Moving towards an effective, equity-promoting health and social protection system requires the government to adopt an intersectoral, gender-based approach to the prevention and control of NCDs and the burden of NCD care. Despite significant resource constraints, policy innovation may be possible given the willingness among some stakeholders to collaborate, particularly in the labour and legal sectors. However, care will be needed to ensure the implementation of new policies has a positive impact on both gender equity and health outcomes. Research on successful approaches in other contexts can help to identify relevant learnings for Mexico.

Survey on the Situation of Medical Departments in the Pharmaceutical Industry in Spain.

INTRODUCTION: Medical departments have evolved from a position of support to one of strategic leadership. The number of tasks and the complexity of interactions in which they are involved is increasing. However, the spectrum of their activity in the sector differs significantly from one company to another. Therefore, the aim of this study was to describe their situation within the pharmaceutical industry, analyzing the positions, functions, and profiles of their professionals. METHODS: This study consisted of an online survey containing 25 questions grouped into four blocks (structure, medical direction, training, and activities and responsibilities). Medical departments in the Spanish pharmaceutical industry of different sizes and scope were invited to participate. The survey took place in 2021, with a designated response period of three months. It is important to note that all responses collected during this time were treated as anonymous. RESULTS: Thirty companies participated. A total of 93.3% of respondents worked for an international laboratory, with a size of 0-5 or 11-20 people (20.7%). For 27.6% of the companies, the number of medical advisors per medical department was 1 or 4, with varying numbers of medical scientific liaisons (1, 6-10, and > 20). A total of 56.7%, 33.3%, and 6.7% indicated that the country manager, head of regional medical affairs, and head of global medical affairs, respectively, had a solid-line reporting relationship with the medical directorate. Medical directors were mostly graduates in medicine (86.2%) with a doctorate (34.5%), and medical managers were mainly graduates in medicine (77.8%) and pharmacy (66.7%). CONCLUSIONS: This study reveals that respondents predominantly work in internationally focused laboratories, with professionals ranging from experienced medical directors to managers with 6-20 years of experience, each with distinct roles.

[Genetics of ADHD in clinical practice]. / Genética del TDAH en la práctica clínica.

Attention-deficit/hyperactivity disorder (ADHD) is a complex and heterogeneous neurodevelopmental disorder from a causal, clinical and prognostic perspective. Research reflects its multifactorial nature with a prominent role of genetic factors. Population studies have historically pointed to the involvement of numerous genetic variants of small effect size, which hardly by themselves increase the risk of presenting the disorder and hardly justify its high heritability. Many of them are present in more than 60% of the general population, suggesting their modulatory rather than causal role. However, after the irruption of new genetic techniques in the last 15 years, a greater number of cases are being identified with genetic disorders (many of them monogenic), whose genetic variants alone explain the presence of ADHD. A detailed study of the personal and family history, as well as a complete physical examination, can help to identify some of them. The identification of the cause in this group of cases has a crucial value in clinical counseling, genetic-familial counseling and prognostic anticipation, as well as in the performance or avoidance of complementary studies and in the design of the intervention plan.

El trastorno por déficit de atención/hiperactividad (TDAH) es un trastorno del neurodesarrollo complejo y heterogéneo desde una perspectiva causal, clínica y pronóstica. La investigación refleja su carácter multifactorial con un papel destacado de los factores genéticos. Los estudios poblacionales han señalado históricamente la implicación de numerosas variantes genéticas de escaso tamaño de efecto, las cuales por sí mismas apenas incrementan el riesgo de TDAH y difícilmente justifican su elevada heredabilidad. Muchas de ellas están presentes en más del 60% de la población general, lo que sugiere su papel modulador más que causal. No obstante, gracias a la irrupción de nuevas técnicas genéticas en los últimos 15 años, se están identificando un mayor número de casos con trastornos genéticos (muchos de ellos monogénicos), cuyas variantes genéticas explican por sí mismas la presencia del TDAH. El estudio detallado de los antecedentes personales y familiares, así como una exploración física completa, puede ayudar a identificar algunos de ellos. La identificación de la causa en este conjunto de casos tiene un valor crucial en el asesoramiento clínico, el consejo genético-familiar y la anticipación pronóstica, así como en la realización o evitación de estudios complementarios y en el diseño del plan terapéutico.

Prognostic value of neutrophil-to-lymphocyte ratio at diagnosis in colorectal cancer: propensity score analysis.

INTRODUCTION: Baseline neutrophil-to-lymphocyte ratio (NLR) at the time of colorectal cancer (CRC) diagnosis has been proposed as a predictor of long-term survival. The aim of the study was to analyse its usefulness in a homogeneous population with control of the main confounding factors. METHODOLOGY: Observational study of 836 patients operated on for CRC who were divided into two groups: NLR ≤ 3.3 vs NLR > 3.3. To control for confounders, they were matched one-to-one by propensity analysis. A final sample of 526 patients remained for study. RESULTS: The two groups were mismatched in terms of age, comorbidity, tumour stage, rectal location, and neoadjuvant therapy. Once matching was performed, baseline NLR was statistically significantly associated with long-term survival (p < 0.001) and behaved as an independent prognostic factor for survival (p = 0.001; HR: 1,996; 95% CI: 1.32-3.00) when adjusted in a Cox regression model using age (p < 0,001; HR: 1,04; IC95%: 1,02-1,06) and the Charlson Comorbidity Index (p < 0,001; HR: 1,40; IC95%: 1,27-1,55). Neoadjuvant therapy lost its statistical significance (p = 0,137; HR: 1,59; IC95%: 0,86-2,93). CONCLUSIONS: A high baseline NLR (> 3.3) in patients with colorectal cancer at diagnosis represents a poor prognostic factor in terms of survival. Its use in routine practice could intensify therapeutic strategies and follow-up in these patients.

Tatton-Brown-Rahman syndrome: Novel pathogenic variants and new neuroimaging findings.

Tatton-Brown-Rahman syndrome (TBRS) or DNMT3A-overgrowth syndrome is characterized by overgrowth and intellectual disability associated with minor dysmorphic features, obesity, and behavioral problems. It is caused by variants of the DNMT3A gene. We report four patients with this syndrome due to de novo DNMT3A pathogenic variants, contributing to a deeper understanding of the genetic basis and pathophysiology of this autosomal dominant syndrome. Clinical and magnetic resonance imaging assessments were also performed. All patients showed corpus callosum anomalies, small posterior fossa, and a deep left Sylvian fissure; as well as asymmetry of the uncinate and arcuate fascicles and marked increased cortical thickness. These results suggest that structural neuroimaging anomalies have been previously overlooked, where corpus callosum and brain tract alterations might be unrecognized neuroimaging traits of TBRS syndrome caused by DNMT3A variants.

el degeneracionismo al exterminio en la psiquiatría nazi. De Arthur de Gobineau y Benedict Morel a Emil Kraepelin y Ernst Rüdin / From degenerationism to extermination in nazi psychiatry. From Arthur de Gobineau and Benedict Morel to Emil Kraepelin and Ernst Rüdin

Este artículo analiza, a partir el vínculo entre psiquiatría y antropología, cómo se consolidó un discurso organicista capaz de legitimar el exterminio nazi y las políticas eugenésicas en los países democráticos. Partimos del degeneracionismo del siglo XIX y contrastamos la vertiente étnica y racial de Arthur de Gobineau con la vertiente alienista de Benedict Morel, hasta llegar a la síntesis de Cesare Lombroso. Visibilizamos el vínculo que Emil Kraepelin estableció entre la “degeneración” de los individuos y la de las razas, señalando al pueblo judío, como determinante en la consolidación científica de la Rassenhygiene en la que Adolf Hitler fundamentó su Mein Kampf. Destacamos como la justificación para “destruir la vida indigna de ser vivida”, que emergió desde el ensamblaje entre la psiquiatría y la justicia, fue determinante en la transición del III Reich entre la esterilización forzosa y el exterminio. Abordamos el Programa de Eutanasia forzosa a través del importante papel político de Ernst Rüdin, sucesor de Kraepelin y fundador de la psiquiatría genética. Concluimos que el nacionalsocialismo llevó a su máxima expresión la lógica de muerte inscrita en el degeneracionismo. Finalmente, tras una reflexión sobre las reacciones y alternativas de posguerra, destacamos la persistencia contemporánea tanto del determinismo biológico como de la desigualdad legal que marcaron el destino de las primeras víctimas del exterminio nazi.(AU)

This article analyses, from the link between psychiatry and anthropology, how an organicist discourse capable of legitimizing both, nazi extermination and eugenic policies in democratic countries, was consolidated. We depart from 19th century theory of degeneration and contrast the ethnic and racial facet of Arthur de Gobineau with the alienist facet of Benedict Morel, until reaching the synthesis of Cesare Lombroso. We highlight the link that Emil Kraepelin established between the “degeneration” of individuals and that of races, pointing out to the Jews, as determinative in the scientific consolidation of Rassenhygiene in which Adolf Hitler based its Mein Kampf. We stress the justification for “destroying life unworthy of live”, that emerged from the assemblage between psychiatry and justice, as determinant in the Third Reich transition between forced sterilization and extermination. We approach the forced Euthanasia Program through the important political role of Ernst Rüdin, Kraepelin’s successor and founder of genetic psychiatry. We conclude that National Socialism took to its maximum expression the logic of death inscribed in the theory of degeneration. Finally, after a reflection on post-war reactions and alternatives, we highlight the contemporary persistence of both biological determinism and legal inequality that marked the fate of the first victims of nazi extermination.(AU)

Effect of particle size of zeolite clay included in high-energy diets for feedlot lambs: Growth performance, dietary energy, carcass traits, and visceral mass.

Objective: Several reports on the effects of zeolite (ZEO) inclusion in diets for feedlot lamb diets have indicated improvements in dietary energy efficiency and decreases in internal fat. Inclusion levels and the type of zeolite used have been the main focus of those reports. However, the possible effect of the zeolite particle size on the growth performance and carcass characteristics has not yet been investigated. Material and Methods: Forty-eight male intact Pelibuey × Katahdin lambs were fed for 67 days with a high-energy diet supplemented with ZEO as follows: 1) basal diet 0% ZEO (control); 2) basal diet 3% ZEO particle size 250 µM (sieve 60); 3) basal diet 3% ZEO particle size 149 µM (sieve 100); and 4) basal diet 3% ZEO particle size 74 µM (sieve 200). ZEO replaced corn grain and soybean meal in equal parts. At the end of feeding, lambs were slaughtered, and variables such as carcass characteristics and visceral mass were evaluated. Results: Particle size did not affect growth performance, carcass characteristics, or visceral mass. The inclusion of ZEO reduced 3.4% of dietary net energy in diets but did not affect dry matter intake or average daily gain, thus improving (p ≤ 0.05) dietary energy efficiency by 2.9%. Except for an 18.9% reduction (p = 0.02) in visceral mass fat, ZEO did not affect other carcass characteristics or visceral organ mass. Conclusion: The particle size studied in the present experiment has not affected any of the variables of growth performance or carcass characteristics. ZEO inclusion could be a strategy to reduce the visceral fat in finishing lambs.

The natural virome and pandemic potential: Disease X.

Over the last decade, the emergence of several zoonotic viruses has demonstrated that previously unknown or neglected pathogens have the potential to cause epidemics and therefore to pose a threat to global public health. Even more concerning are the estimated 1.7 million still-undiscovered viruses present in the natural environment or 'global virome', with many of these as-yet uncharacterized viruses predicted to be pathogenic for humans. Thus, in order to mitigate disease emergence and prevent future pandemics, it is crucial to identify the global extent of viral threats to which humans may become exposed. This requires cataloguing the viruses that exist in the environment within their various and diverse host species, and also understanding the viral, host, and environmental factors that dictate the circumstances that result in viral spillover into humans. We also address here which strategies can be implemented as countermeasure initiatives to reduce the risk of emergence of new diseases.

Characteristics of digoxin toxicity attended in Spanish emergency departments according to type of poisoning and administration of digoxin antibodies: the DIGITOX study. / Características de las intoxicaciones por digoxina atendidas en diversos servicios de urgencias españoles en función del tipo de intoxicación y de la administración de anticuerpos antidigoxina: estudio DIGITOX.

OBJECTIVES: Digoxin toxicity accounts for a small percentage of poisonings attended by emergency departments. This study aimed to describe differences between acute and chronic digoxin toxicity and assess the use of digoxin-specific antibody fragments (digoxin-Fab) as an antidote. MATERIAL AND METHODS: Retrospective, observational, multicenter study in 15 hospital emergency departments in 8 Spanish autonomous communities in 7 years. We collected patient, clinical and treatment variables, and discharge destination. Patients were classified according to whether toxicity was acute or chronic and whether digoxin-Fab was administered or not. RESULTS: Twenty-seven acute and 631 chronic digoxin poisonings were attended. The mean (SD) patient age was 83.9 (7.9) years, and 76.9% were women. Patients with acute toxicity were younger (80.0 [12] years) than those with chronic toxicity (84.1 [7.7] years) (P .038), and accidental poisoning was less common (in 85.2% vs 100% in chronic toxicity; P .001). Cases of acute toxicity were also more serious (Poison Severity Score (29.6% vs 12.5% in chronic toxicity; P .001). Thirty-four patients were treated with digoxin-Fab (5.4%). These patients were younger (78.7 [11.5] years vs 84.2 (7.6) years), their toxicity was more often acute (in 20.6% vs 3.2% in chronic toxicity), more had attempted suicide (8.8% vs 0.2% with chronic toxicity), and more had severe symptoms (50% vs 11.2%) (P .001, all comparisons). Hospital admission was required for 76.1%. Overall, mortality was 11.4%. CONCLUSION: Chronic toxicity accounts for most digoxin poisoning cases, and most patients are women. Acute toxicity is more serious. Patients who required digoxin-Fab have more severe poisoning. Such patients usually have acute toxicity, and attempted suicide is more often the reason for the emergency.

OBJETIVO: Las intoxicaciones por digoxina representan un pequeño porcentaje de las intoxicaciones atendidas en urgencias. El objetivo de este estudio fue describir las diferencias entre intoxicaciones agudas y crónicas y evaluar la administración de su antídoto específico: los anticuerpos antidigoxina (AcAD). METODO: Estudio retrospectivo, observacional y multicéntrico en 15 servicios de urgencias hospitalarios de 8 comunidades autónomas durante 7 años. Se recogieron datos de filiación, clínica, tratamiento y destino al alta. Los pacientes se dividieron según era la intoxicación aguda o crónica y según recibían o no AcAD. RESULTADOS: Se recogieron 27 intoxicaciones agudas y 631 crónicas. La edad media fue de 83,9 (7,9) años, y el 76,9% eran mujeres. Los pacientes con intoxicación aguda tenían menor edad media (80,0 (12) vs 84,1 (7,7) años; p 0,038), y porcentaje de causa accidental (85,2% vs 100%; p 0,001) y mayor gravedad en la escala Poison Severity Score (29,6% vs 12,5%; p 0,001). Treinta y cuatro pacientes recibieron AcAD (5,4%) y constituyen un grupo de menor edad [78,7 (11,5) vs 84,2 (7,6); p 0,001], con mayor porcentaje de intoxicaciones agudas (20,6% vs 3,2%), intencionalidad suicida (8,8% vs 0,2%) y gravedad (50% vs 11,2%, p 0,001 en todas las comparaciones). El 76,1% precisó ingreso. La mortalidad fue del 11,4%. CONCLUSIONES: Las intoxicaciones por digoxina suelen ser crónicas y predominan en mujeres. Las intoxicaciones agudas son de mayor gravedad. Los pacientes que precisaron administración de AcAD tenían intoxicaciones más graves y mayor porcentaje de intoxicaciones agudas y con intencionalidad suicida.

Asociación entre calidad y cantidad de sueño con índice de masa corporal en adolescentes universitarios: Estudio transversal / Association between sleep quality and quantity and body mass index in college adolescents: A cross-sectional study

Introducción: La modificación en los patrones de sueño incrementa la susceptibilidad para la ganancia de peso. Objetivo: Estimar la asociación entre la calidad y la cantidad de horas de sueño por noche con el Índice de Masa Corporal (IMC) en adolescentes universitarios mexicanos. Materiales y métodos: Estudio transversal en estudiantes de nuevo ingreso de Enfermería en una Universidad Pública de México. Muestreo por conveniencia de n=134 estudiantes (18­19 años), voluntarios y matriculados en la facultad. La calidad y cantidad de sueño se midió con el Índice de Calidad de Sueño de Pittsburgh. El IMC se calculó con la fórmula estándar. El protocolo fue aprobado por el Comité de Ética de la facultad, los participantes firmaron el Consentimiento Informado. Resultados: Edad promedio de 18,21 años (DE= ,42 años), 82,84% mujeres, 45,52% (IC 95%= 35,46 ­ 52,86%) con sobrepeso u obesidad. El 44,02% de los participantes reportó dormir ≤ 6 horas por noche, 50,00% refirió una mala calidad de sueño en las últimas cuatro semanas. Después de ajustar por edad, sexo y ocupación, la calidad del sueño no se asoció con el IMC (OR= 1,01; IC 95%= ,94 ­ 1,08; z= ,31; p= ,75); el incremento en el IMC se asoció con una mayor probabilidad de dormir 6 horas o menos (OR= 1,08; IC 95%= 1,01 ­ 1,16; z= 2,25; p= ,02). Discusión: Las alteraciones hormonales, los factores conductuales y el entorno pudieran explicar la asociación. Conclusiones: Es recomendable implementar estrategias educativas para mejorar la higiene del sueño en esta población.

Introduction: Changes in sleep patterns increase susceptibility to weight gain. Objective: To estimate the association between the quality and quantity of sleep hours per night and Body Mass Index (BMI) in Mexican college adolescents. Materials and methods: Cross-sectional study conducted among incoming nursing students in a public university in Mexico. Convenience sampling was used, involving n=134 students (18-19 years old), volunteers, and enrolled in the nursing program. Sleep quality and quantity were measured through the Pittsburgh Sleep Quality Index (PSQI). BMI was calculated using the standard formula. The protocol was approved by the School of Nursing Ethics Committee, and the participants signed informed consent. Results: Mean age 18.21 years (SD= .42 years), 82.84% female, 45.52% overweight or obese (95% CI= 35.46 - 52.86%). 44.02% of participants reported sleeping ≤ 6 hours per night, and 50.00% reported poor sleep quality in the past four weeks. After adjustment for age, sex, and occupation, sleep quality was not associated with BMI (OR= 1.01; 95% CI= .94 - 1.08; z= .31; p= .75); increased BMI was associated with a greater likelihood of sleeping 6 hours or less (OR= 1.08; 95% CI= 1.01 - 1.16; z= 2.25; p= .02). Discussion: Hormonal changes, behavioral factors, and the environment may explain the association. Conclusions: It is advisable to implement educational strategies to improve sleep hygiene among this population.

Introdução: A modificação nos padrões de sono aumenta a suscetibilidade ao ganho de peso. Objetivo: Estimar a associação entre a qualidade e a quantidade de sono por noite e o índice de massa corporal (IMC) em adolescentes universitários mexicanos. Materiais e métodos: Estudo transversal de estudantes de enfermagem ingressantes em uma universidade pública no México. Amostragem por conveniência de n=134 estudantes (18-19 anos de idade), voluntários e matriculados na faculdade. A qualidade e a quantidade do sono foram medidas com o Índice de Qualidade do Sono de Pittsburgh. O IMC foi calculado com a fórmula padrão. O protocolo foi aprovado pelo Comitê de Ética da faculdade e os participantes assinaram o Termo de Consentimento Livre e Esclarecido. Resultados: Idade média de 18,21 anos (DP= ,42 anos), 82,84% do sexo feminino, 45,52% (IC 95%= 35,46 - 52,86%) com sobrepeso ou obesidade. 44,02% dos participantes relataram dormir ≤ 6 horas por noite, 50,00% relataram qualidade de sono ruim nas últimas quatro semanas. Após o ajuste para idade, sexo e ocupação, a qualidade do sono não foi associada ao IMC (OR= 1,01; IC 95%= ,94 - 1,08; z= ,31; p= ,75); o aumento do IMC foi associado a uma maior probabilidade de dormir 6 horas ou menos (OR= 1,08; IC 95%= 1,01 - 1,16; z= 2,25; p= ,02). Discussão: Alterações hormonais, fatores comportamentais e o ambiente podem explicar a associação. Conclusões: É aconselhável implementar estratégias educacionais para melhorar a higiene do sono nessa população.

Essential Oils Combined with Vitamin D3 or with Probiotic as an Alternative to the Ionophore Monensin Supplemented in High-Energy Diets for Lambs Long-Term Finished under Subtropical Climate.

Supplementation with natural additives such as essential oils (EO) or probiotics has resulted in comparable growth performance to that of supplemental monensin in fattening lambs in hot environments. Supra-supplementation levels of vitamin D3 improved the carcass weight and dressing percentage of steers fattened under tropical conditions. We hypothesized that certain combinations of these natural additives could be complementary. For this reason, a feeding trial was carried out using 48 Pelibuey × Katahdin non-castrated male lambs (107 ± 14 d age; 17.9 ± 2.51 kg LW). Lambs were fed an 88:12 concentrate to forage ratio basal diet supplemented (dry matter basis, DMI) with: (1) no additive (CON); (2) 28 mg monensin/kg diet (MON); (3) 150 mg of essential oils containing a combination of thymol, eugenol, vanillin, guaiac, and limonene plus 0.12 mg vitamin D3 (EO + D3)/kg diet; and (4) 300 mg of essential oils containing a combination of carvacrol and cynamaldehyde plus 2 g probiotic (2.2 × 108 CFU of bacillus subtilis/kg diet, EO + BS). Lambs were grouped by initial weight and assigned within six weight groupings to 24 pens (2 lambs/pen, 6 replicas per treatment) in a randomized complete block design. The experiment lasted 121 days. Daily maximal THI exceeded the 80 "danger or "emergency" range for 119 days of the 121 days of the trial. Lambs supplemented with MON had similar DMI, growth performance, and dietary energetics to those of CON lambs. Lambs supplemented with EO + BS had a greater (9.2%, p ≤ 0.05) average daily gain (ADG) than the CON and MON groups due to enhanced (10.2%, p ≤ 0.05) dry matter intake. Thus, gain efficiency (GF) and estimated dietary energy were similar for CON, MON, and EO + BS. Lambs receiving EO + D3 had similar (0.254 vs. 0.262 kg/d) ADG but a lower DMI (8%, p < 0.05) compared with EO + BS lambs. Consequently, GF and estimated dietary net energy were greater (4.9 and 3.7%, respectively; p ≤ 0.05) for EO + D3 lambs. Even when ambient heat load was elevated, the efficiency of utilization of dietary energy (observed-to-expected dietary net energy) was close to 1.00 (0.992) expected for EO + D3 lambs. In contrast, efficiency of energy utilization was depressed by -4.4% for lambs on the other treatments. Compared with the other treatments, lambs receiving EO + D3 had greater longissimus muscle area (5.6%, p < 0.05) and lower kidney pelvic fat (21.8%, p ≤ 0.05). There were no treatment effects on shoulder tissue composition or whole cuts (expressed as % of cold carcass weight). Compared to CON, lambs that were fed with natural additives showed 3.5% lower (p ≤ 0.05) intestine mass. All supplemental additives decreased visceral fat mass, which was minimal with EO + D3 treatment. Combinations of essential oils with vitamins or probiotics were superior to antibiotic monensin in finishing diets for feedlot lambs. Combining EO with probiotics promoted DM intake and gain but not gain efficiency, while combining EO with vitamin D3 supra-supplementation increased dietary energy efficiency and improved some carcass characteristics in lambs fattening under high ambient heat loads.

Impact of carob (Ceratonia siliqua L.) pulp inclusion and warm season on gastrointestinal morphological parameters, immune-redox defences and coccidiosis in concentrate-fed light lambs.

This study aimed to evaluate the effects of dietary carob (Ceratonia siliqua L.) pulp and warm season on gastrointestinal morphological parameters, immune-redox defences and coccidiosis in concentrate-fed light lambs. Weaned lambs were assigned to one of three concentrate-based diets: C0 (without carob pulp), C15 (150 g/kg of carob pulp) and C30 (300 g/kg of carob pulp) from 40 to 80 days of age in two consecutive cold and warm batches. Blood samples were collected at Day 80 to determine the metabolic status. Rectal faeces were sampled at Days 50, 65 and 80 to determine consistency and oocyst count per gram. Inclusion of carob pulp in lamb diets did not affect lamb growth but reduced coccidia oocyst excretion, improved faecal consistency and gastrointestinal morphological parameters, enhancing the ruminal thickness of the papilla living strata and reducing the darkness of the epithelium colour. Moreover, carob condensed tannins in the lambs' diet enhanced the expression of antioxidant SOD2 in rumen, while down-regulated NRF2, SOD1, CAT and PPARG in ileum. There was no interaction between the treatments and season in the evaluated variables. Lambs from the warm season exhibited reduced growth performance, altered ruminal epithelium, lower circulating iron levels, increased protein concentrations and higher coccidiosis susceptibility. In addition, regulatory immune and antioxidant mechanisms to counterbalance reactive oxygen species production in gastrointestinal tissues were evident. Dietary inclusion of carob pulp (150 and 300 g/kg) in lamb diets improved gastrointestinal health and homeostasis but did not ameliorate the deleterious effects of warm season.

Hospital admissions due to suicide attempts during the COVID-19 pandemic, a 3-year longitudinal study.

The appearance of the SARS CoV-2 virus and the associated COVID-19 pandemic has been associated with the onset of mental disorders in healthy people and the worsening in those with pre-existing mental conditions. One of the areas that has raised the greatest concern is that of suicidality. Most of the published studies have been carried out cross-sectional or with small samples, without stratifying by age and gender. Thus, the aim of this longitudinal research is to study, in a large population sample of around 6,700,000 inhabitants belonging to the entire region of Madrid (Spain), the admissions in psychiatric hospitalization units due to suicidal attempts along 2019, 2020 and 2021. No clear increase in the number of admissions due to suicidality in the total population have been found. In addition, a higher prevalence in admissions among women is verified. Moreover, stratifying by age and gender, a striking and significant increase in hospital admissions due to suicidality has been observed in the group up to 17 years old, from September 2020 until the end of the study. These results highlight the special vulnerability of children and adolescents, specifically girls, and the need for preventive measures in the face of future pandemics.

Immune correlates of protection for SARS-CoV-2, Ebola and Nipah virus infection.

Correlates of protection (CoP) are biological parameters that predict a certain level of protection against an infectious disease. Well-established correlates of protection facilitate the development and licensing of vaccines by assessing protective efficacy without the need to expose clinical trial participants to the infectious agent against which the vaccine aims to protect. Despite the fact that viruses have many features in common, correlates of protection can vary considerably amongst the same virus family and even amongst a same virus depending on the infection phase that is under consideration. Moreover, the complex interplay between the various immune cell populations that interact during infection and the high degree of genetic variation of certain pathogens, renders the identification of immune correlates of protection difficult. Some emerging and re-emerging viruses of high consequence for public health such as SARS-CoV-2, Nipah virus (NiV) and Ebola virus (EBOV) are especially challenging with regards to the identification of CoP since these pathogens have been shown to dysregulate the immune response during infection. Whereas, virus neutralising antibodies and polyfunctional T-cell responses have been shown to correlate with certain levels of protection against SARS-CoV-2, EBOV and NiV, other effector mechanisms of immunity play important roles in shaping the immune response against these pathogens, which in turn might serve as alternative correlates of protection. This review describes the different components of the adaptive and innate immune system that are activated during SARS-CoV-2, EBOV and NiV infections and that may contribute to protection and virus clearance. Overall, we highlight the immune signatures that are associated with protection against these pathogens in humans and could be used as CoP.

Analyzing the role of cancer-associated fibroblast activation on macrophage polarization.

Snail1 is a transcriptional factor required for cancer-associated fibroblast (CAF) activation, and mainly detected in CAFs in human tumors. In the mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT) model of murine mammary gland tumors, Snai1 gene deletion, besides increasing tumor-free lifespan, altered macrophage differentiation, with fewer expressing low levels of MHC class II. Snail1 was not expressed in macrophages, and in vitro polarization with interleukin-4 (IL4) or interferon-γ (IFNγ) was not altered by Snai1 gene depletion. We verified that CAF activation modified polarization of naïve bone-marrow-derived macrophages (BMDMΦs). When BMDMΦs were incubated with Snail1-expressing (active) CAFs or with conditioned medium derived from these cells, they exhibited a lower cytotoxic capability than when incubated with Snail1-deleted (inactive) CAFs. Gene expression analysis of BMDMΦs polarized by conditioned medium from wild-type or Snai1-deleted CAFs revealed that active CAFs differentially stimulated a complex combination of genes comprising genes that are normally induced by IL4, downregulated by IFNγ, or not altered during the two canonical differentiations. Levels of RNAs relating to this CAF-induced alternative polarization were sensitive to inhibitors of factors specifically released by active CAFs, such as prostaglandin E2 and TGFß. Finally, CAF-polarized macrophages promoted the activation of the immunosuppressive regulatory T cells (T-regs). Our results imply that an active CAF-rich tumor microenvironment induces the polarization of macrophages to an immunosuppressive phenotype, preventing the macrophage cytotoxic activity on tumor cells and enhancing the activation of T-reg cells.