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During gestation, the developing fetus relies on precise maternal circadian signals for optimal growth and preparation for extrauterine life. These signals regulate the daily delivery of oxygen, nutrients, hormones, and other biophysical factors while synchronizing fetal rhythms with the external photoperiod. However, modern lifestyle factors such as light pollution and shift work can induce gestational chronodisruption, leading to the desynchronization of maternal and fetal circadian rhythms. Such disruptions have been associated with adverse effects on cardiovascular, neurodevelopmental, metabolic, and endocrine functions in the fetus, increasing the susceptibility to noncommunicable diseases (NCDs) in adult life. This aligns with the Developmental Origins of Health and Disease theory, suggesting that early-life exposures can significantly influence health outcomes later in life. The consequences of gestational chronodisruption also extend into adulthood. Environmental factors like diet and stress can exacerbate the adverse effects of these disruptions, underscoring the importance of maintaining a healthy circadian rhythm across the lifespan to prevent NCDs and mitigate the impact of gestational chronodisruption on aging. Research efforts are currently aimed at identifying potential interventions to prevent or mitigate the effects of gestational chronodisruption. Melatonin supplementation during pregnancy emerges as a promising intervention, although further investigation is required to fully understand the precise mechanisms involved and to develop effective strategies for promoting health and preventing NCDs in individuals affected by gestational chronodisruption.

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Background: The endothelium is the most posterior layer of the cornea and is essential for maintaining corneal transparency. Due to variations in corneal endothelial parameters among different species, knowledge of the normal parameters for each species is crucial. Aim: To evaluate the corneal endothelium of bovines using contact specular microscopy. Methods: Twenty eyeballs from 10 male Brangus (Bos taurus) aged 24 months were evaluated. Contact specular microscopy was performed on the central corneal area. The analyzed parameters were endothelial cell density (ECD) and endothelial cell morphology. Results: The ECD in the central area was 1,277 cells/mm2. Regarding the morphology, mainly cells with six (74.3%), five (14.7%) and seven sides (10%) were found. There were no significant differences in ECD and morphology between left and right eyes. Conclusion: Contact specular microscopy facilitated the analysis and measurement of corneal endothelial parameters in bovines. The data obtained will serve as a reference for the analysis of bovine corneal endothelium.

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Introduction: Gestational chronodisruption impact maternal circadian rhythms, inhibiting the nocturnal increase of melatonin, a critical hormone that contributes to maternal changes adaptation, entrains circadian rhythms, and prepares the fetus for birth and successful health in adulthood. In rats, we know that gestational chronodisruption by maternal chronic photoperiod shifting (CPS) impaired maternal melatonin levels and resulted in long-term metabolic and cardiovascular effects in adult male offspring. Here, we investigated the consequences of CPS on mother and adult female offspring and explored the effects of melatonin maternal supplementation. Also, we tested whether maternal melatonin administration during gestational chronodisruption rescues maternal circadian rhythms, pregnancy outcomes, and transcriptional functions in adult female offspring. Methods: Female rats raised and maintained in photoperiod 12:12 light: dark were mated and separated into three groups: (a) Control photoperiod 12:12 (LD); (b) CPS photoperiod; and (c) CPS+Mel mothers supplemented with melatonin in the drinking water throughout gestation. In the mother, we evaluated maternal circadian rhythms by telemetry and pregnancy outcomes, in the long-term, we study adult female offspring by evaluating endocrine and inflammatory markers and the mRNA expression of functional genes involved in adrenal, cardiac, and renal function. Results: In the mothers, CPS disrupted circadian rhythms of locomotor activity, body temperature, and heart rate and increased gestational length by almost 12-h and birth weight by 12%, all of which were rescued by maternal melatonin administration. In the female offspring, we found blunted day/night differences in circulating levels of melatonin and corticosterone, abnormal patterns of pro-inflammatory cytokines Interleukin-1a (IL1a), Interleukin-6 (IL6), and Interleukin-10 (IL10); and differential expression in 18 out of 24 adrenal, cardiac, and renal mRNAs evaluated. Conclusion: Maternal melatonin contributed to maintaining the maternal circadian rhythms in mothers exposed to CPS, and the re-establishing the expression of 60% of the altered mRNAs to control levels in the female offspring. Although we did not analyze the effects on kidney, adrenal, and heart physiology, our results reinforce the idea that altered maternal circadian rhythms, resulting from exposure to light at night, should be a mechanism involved in the programming of Non-Communicable Diseases.

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Synchronization to periodic cues such as food/water availability and light/dark cycles is crucial for living organisms' homeostasis. Both factors have been heavily influenced by human activity, with artificial light at night (ALAN) being an evolutionary challenge imposed over roughly the last century. Evidence from studies in humans and animal models shows that overt circadian misalignment, such as that imposed to about 20% of the workforce by night shift work (NSW), negatively impinges on the internal temporal order of endocrinology, physiology, metabolism, and behavior. Moreover, NSW is often associated to mistimed feeding, with both unnatural behaviors being known to increase the risk of chronic diseases, such as eating disorders, overweight, obesity, cardiovascular, metabolic (particularly type 2 diabetes mellitus) and gastrointestinal disorders, some types of cancer, as well as mental disease including sleep disturbances, cognitive disorders, and depression. Regarding deleterious effects of ALAN on reproduction, increased risk of miscarriage, preterm delivery and low birth weight have been reported in shift-worker women. These mounting lines of evidence prompt further efforts to advance our understanding of the effects of long-term NSW on health. Emerging data suggest that NSW with or without mistimed feeding modify gene expression and functional readouts in different tissues/organs, which seem to translate into persistent cardiometabolic and endocrine dysfunction. However, this research avenue still faces multiple challenges, such as functional characterization of new experimental models more closely resembling human long-term NSW and mistimed feeding in males versus females; studying further target organs; identifying molecular changes by means of deep multi-omics analyses; and exploring biomarkers of NSW with translational medicine potential. Using high-throughput and systems biology is a relatively new approach to study NSW, aimed to generate experiments addressing new biological factors, pathways, and mechanisms, going beyond the boundaries of the circadian clock molecular machinery.

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Compelling evidence in rats support the idea that gestational chronodisruption induces major changes in maternal circadian rhythms and fetal development and that these changes impact adult life at many physiological levels. Using a model of chronic photoperiod shifting throughout gestation (CPS), in which pregnant female rats (Sprague-Dawley strain; n = 16 per group) were exposed to lighting schedule manipulation every 3-4 days reversing the photoperiod completely or light/dark photoperiod (12/12; LD), we explored in the adult rat male offspring body weight gain, glucose homeostasis, adipose tissue content, adipose tissue response to norepinephrine (NE), and adipose tissue proteomic in the basal condition with standard diet (SD) and in response to high-fat diet (HFD). In adult CPS male (100-200 days old; n = 8 per group), we found increasing body weight, under SD and adiposity. Also, we found an increased response to intraperitoneal glucose (IGTT). After 12 weeks of HFD, white adipose tissue depots in CPS offspring were increased further, and higher IGTT and lower intraperitoneal insulin tolerance response were found, despite the lack of changes in food intake. In in vitro experiments, we observed that adipose tissue (WAT and BAT) glycerol response to NE from CPS offspring was decreased, and it was completely abolished by HFD. At the proteomic level, in CPS adipose tissue, 275 proteins displayed differential expression, compared with LD animals fed with a standard diet. Interestingly, CPS offspring and LD fed with HFD showed 20 proteins in common (2 upregulated and 18 downregulated). Based on these common proteins, the IPA analysis found that two functional pathways were significantly altered by CPS: network 1 (AKT/ERK) and network 2 (TNF/IL4; data are available via ProteomeXchange with identifier PXD026315). The present data show that gestational chronodisruption induced deleterious effects in adipose tissue recruitment and function, supporting the idea that adipose tissue function was programmed in utero by gestational chronodisruption, inducing deficient metabolic responses that persist into adulthood.

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INTRODUCTION: Low molecular weight heparin is currently the standard therapy for the primary prevention of thromboembolic disease in cancer patients. The use of direct-acting anticoagulants could be an alternative, but its efficacy and safety profile in these types of patients remains unclear. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple sources of information, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from identified reviews, analyzed data from primary studies, performed a meta-analysis, and prepared a summary table of results using the GRADE method. RESULTS AND CONCLUSIONS: We identified four systematic reviews that together included two primary studies, of which both correspond to trials. We conclude that the use of direct-acting oral anticoagulants probably increases the outcome of major bleeding and likely slightly increases the risk of thromboembolic disease. No studies were found that evaluated the outcome of quality of life or mortality.

INTRODUCCIÓN: El uso de heparina de bajo peso molecular es actualmente la terapia estándar para prevención primaria de enfermedad tromboembólica en pacientes con cáncer. El uso de los anticoagulantes de acción directa podría ser una alternativa pero su perfil de eficacia y seguridad en este tipo de pacientes sigue siendo aún poco claro. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cuatro revisiones sistemáticas que, en conjunto, incluyeron dos estudios primarios, los que corresponden a ensayos. Concluimos que el uso de anticoagulantes orales de acción directa probablemente aumenta el desenlace hemorragia mayor y probablemente aumenta levemente el riesgo de enfermedad tromboembólica. No se encontraron estudios que evaluaran el desenlace calidad de vida ni de mortalidad.

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RESUMEN Objetivos: medir el impacto en la calidad de la prescripción antibiótica empírica en los médicos generales luego de la implementación de un sistema de evaluación y retroalimentación. Métodos: estudio cuasiexperimental con pre y postintervención en una clínica de tercer nivel en Medellín. Se revisó las prescripciones de un grupo de antibióticos por un médico internista, un epidemiólogo y un infectólogo. Se midió el consumo de antibióticos, las retroalimentaciones realizadas, el diagnóstico de la sepsis, tiempo de inicio de los antibióticos en el servicio de urgencias y la prevalencia de Escherichia coli productora de betalactamasa de espectro extendido. Resultados: el número de retroalimentaciones descendió de 10,9 a 2 %. Se redujo el consumo de ceftriaxona (p = 0,04), piperacilina tazobactam (p = 0,01), cefepime (p = 0,04) y ciprofloxacina (p = 0,01). Se evidenció una tendencia a la reducción en la prevalencia de E. coli BLEE (p = 0,3). La intervención no produjo un retraso en el inicio de antibióticos en el servicio de urgencias. Conclusión: una estrategia de auditoría y retroalimentación a los médicos generales, referente a la calidad de la prescripción antibiótica, reduce el consumo de antibióticos sin afectar la oportunidad del diagnóstico de sepsis o el inicio de su tratamiento y puede impactar favorablemente en el perfil de resistencia de la flora microbiana institucional.

SUMMARY Objectives: To measure the impact on the quality of the empirical antibiotic prescription in general practitioners, after the implementation of an evaluation and feedback system. Methods: Quasi-experimental study with pre- and post-intervention in a tertiary care center in Medellín. The prescriptions of a group of antibiotics were reviewed by an internist, an epidemiologist and an infectologist. When failures were found, prescribing doctors were informed. Subsequently, antibiotic consumption, feedbacks, sepsis diagnosis, start time of antibiotics in the emergency department and monthly incidence of Escherichia coli producing extended spectrum betalactamase were measured. Results: The numbers of feedbacks decreased from 10.9% to 2%. Consumption of ceftriaxone (p = 0.04), piperacillin tazobactam (p = 0.01), cefepime (p = 0.04) and ciprofloxacin (p = 0.01) was reduced. There was a tendency to reduce the prevalence of E. coli ESBL. The intervention did not cause a delay in the start of antibiotics in the emergency department. Conclusions: A strategy of continuous feedback to general practitioners regarding the quality of antibiotic prescription reduces consumption of antibiotics without causing changes in diagnosis opportunity or the beginning of antibiotics in sepsis and can impact favorably the resistance profile of the institutional microbial flora.

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INTRODUCTION: Before the start of the GES program in 2002, mortality was 128.2 deaths per million children under 15 years of age (RENCI). This public program managed to ensure the opportunity for diagnosis and treatment in children under 15 years of age and those less than 25 years of age who recur. Objective: To assess how GES has impacted on in-hospital mortality and lethality between1997and 2016. Methods: Retrospective case control study of 28,997 hospital discharges and 12,434 deaths analyzed using Prais-Weinstein time series between the years 1997 to 2016. They prepared contingency tables with data on: hospital discharges, age, sex and forecasts for 2001 and 2016. Fisher's p <0.05 test was used. Results: For the PreGes period an increase of 1.8% in the male crude mortality rate was observed, while for the Post Ges period an increase was observed with a breaking point at the end of 2008, with an increase of 11.04% compared to the PreGes period. An unexpected increase in the female mortality rate was observed. The odd's ratios associated with sex (higher mortality inmen than in women)0.816CI-0.679- 0.982; p <0.05; OR'S age 1,047 (0.981 per year) IC-1.044-1.051; p <0.0001 FORECAST (FONASA-1.942 IC 1.304-2.89 / ISAPRE = 2.186; IC = 1.267-3.773 p <0.005); Hospitalization days = 1.031 confirmed our research hypothesis 1.026-1.035 p <0.0001. Conclusion: This study found that there are statistically significant differences regarding hospital discharges between the public-private system, in relation to mortality andincreasein sustained crudemalemortality between the years1997 to 2016

INTRODUCCIÓN: Antes del inicio del programa GESen2002, la mortalidad era 128,2 muertes por millón de niños menores de 15 años (RENCI). Este programa público logró asegurar la oportunidad de diagnóstico y tratamiento en menores de15 años y aquellos menores de25añosque recidivan. Objetivo: Evaluar cómo el GES ha impactado en la mortalidad y letalidad intrahospitalaria entre1997a2016. Métodos: Estudio retrospectivo de control de casos en 28.997 egresos hospitalarios y 12.434 defunciones analizadas mediante series temporales de Prais-Weinstein entre los años 1997 a 2016. Se prepararon tablas de contingencia con datos sobre: egresos hospitalarios, edad, sexo y previsiones para2001y 2016.Se utilizóla prueba p <0.05de Fisher. Resultados: Se observó para el período PreGES un incremento de 1.8% en la tasa mortalidad cruda masculina, mientras que para el período Post GES se observó un incremento con punto de quiebre a fines del año 2008, con incremento del 11,04% respecto al período PreGES. Se observó incremento no sostenido en la tasa mortalidad femenina. Los odd's ratios asociados al sexo (mayor mortalidad en hombres que en mujeres) 0.816 IC-0.679-0.982; p <0,05; OR'S edad 1,047 (0.981 por año) IC-1.044-1.051; p<0.0001 PREVISIÓN (FONASA-1.942 IC 1.304-2.89 / ISAPRE =2.186; IC= 1,267-3,773 p<0.005); Días de Hospitalización=1,031 confirmó nuestra hipótesis de investigación 1,026-1,035 p<0.0001. Conclusión: Este estudio encontró que hay diferencias estadísticamente significativas respecto egresos hospitalarios entre el sistema público privado, en relación con la mortalidad e incremento en la mortalidad cruda masculina sostenida entre los años 1997 a 2016. acción en la función auditiva mediante audiometría tonal.

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BACKGROUND: The importance of dietary potassium in health and disease has been underestimated compared with that placed on dietary sodium. Larger effort has been made on reduction of sodium intake and less on the adequate dietary potassium intake, although natural food contains much more potassium than sodium. The benefits of a potassium-rich diet are known, however, the mechanism by which it exerts its preventive action, remains to be elucidated. With the hypothesis that dietary potassium reduces renal vasoconstrictor components of the renin-angiotensin system in the long-term, we studied the effect of high potassium diet on angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2. METHODS: Sprague Dawley male rats on a normal sodium diet received normal potassium (0.9%, NK) or high potassium diet (3%, HK) for 4 weeks. Urine was collected in metabolic cages for electrolytes and urinary volume measurement. Renal tissue was used to analyze angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2 expression. Protein abundance analysis was done by Western blot; gene expression by mRNA levels by RT-qPCR. Renal distribution of angiotensin-I converting enzyme and renin was done by immunohistochemistry and morphometric analysis in coded samples. RESULTS: High potassium diet (4 weeks) reduced the levels of renin, angiotensin-I converting enzyme, and angiotensin converting enzyme 2. Angiotensin-I converting enzyme was located in the brush border of proximal tubules and with HK diet decreased the immunostaining intensity (P < 0.05), decreased the mRNA (P < 0.01) and the protein levels (P < 0.01). Renin localization was restricted to granular cells of the afferent arteriole and HK diet decreased the number of renin positive cells (P < 0.01) and renin mRNA levels (P < 0.01). High potassium intake decreased angiotensin converting enzyme 2 gene expression and protein levels (P < 0.01).No morphological abnormalities were observed in renal tissue during high potassium diet.The reduced expression of angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2 during potassium supplementation suggest that high dietary potassium intake could modulate these vasoactive enzymes and this effects can contribute to the preventive and antihypertensive effect of potassium.

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The fibrinolytic system is critical during the onset of fibrinolysis, a fundamental mechanism for fibrin degradation. Both tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) trigger fibrinolysis, leading to proteolytic activation of plasminogen to plasmin and subsequently fibrin proteolysis. This system is regulated by several inhibitors; plasminogen activator inhibitor-1 (PAI-1), the most studied, binds to and inactivates both tPA and uPA. Through the action of plasmin, this system regulates several physiological processes: embryogenesis, activation of inflammatory cells, cell proliferation and death, synaptic plasticity, wound healing, and others. The deregulated intervention of fibrinolysis in the pathophysiology of various diseases has been widely studied; findings of altered functioning have been reported in different chronic non-communicable diseases (NCD), reinforcing its pleiotropic character and the importance of its physiology and regulation. The evidence indicates that fundamental elements of the fibrinolytic system, such as tPA and PAI-1, show a circadian rhythm in their plasmatic levels and their gene expression are regulated by circadian system elements, known as clock genes - Bmal, Clock, Cry-, and accessory clock genes such as Rev-Erb and Ror. The disturbance in the molecular machinery of the clock by exposure to light during the night alters the natural light/dark cycle and causes disruption of the circadian rhythm. Such exposure affects the synchronization and functioning of peripheral clocks responsible for the expression of the components of the fibrinolytic system. So, this circadian disturbance could be critical in the pathophysiology of chronic diseases where this system has been found to be deregulated.