NUM-score: A clinical-analytical model for personalised imaging after urinary tract infections.

AIM: To identify predictive variables and construct a predictive model along with a decision algorithm to identify nephrourological malformations (NUM) in children with febrile urinary tract infections (fUTI), enhancing the efficiency of imaging diagnostics. METHODS: We performed a retrospective study of patients aged <16 years with fUTI at the Emergency Department with subsequent microbiological confirmation between 2014 and 2020. The follow-up period was at least 2 years. Patients were categorised into two groups: 'NUM' with previously known nephrourological anomalies or those diagnosed during the follow-up and 'Non-NUM' group. RESULTS: Out of 836 eligible patients, 26.8% had underlying NUMs. The study identified six key risk factors: recurrent UTIs, non-Escherichia coli infection, moderate acute kidney injury, procalcitonin levels >2 µg/L, age <3 months at the first UTI and fUTIs beyond 24 months. These risk factors were used to develop a predictive model with an 80.7% accuracy rate and elaborate a NUM-score classifying patients into low, moderate and high-risk groups, with a 10%, 35% and 93% prevalence of NUM. We propose an algorithm for approaching imaging tests following a fUTI. CONCLUSION: Our predictive score may help physicians decide about imaging tests. However, prospective validation of the model will be necessary before its application in daily clinical practice.

Loss of GIPR in LEPR cells impairs glucose control by GIP and GIP:GLP-1 co-agonism without affecting body weight and food intake in mice.

OBJECTIVE: The glucose-dependent insulinotropic polypeptide (GIP) decreases body weight via central GIP receptor (GIPR) signaling, but the underlying mechanisms remain largely unknown. Here, we assessed whether GIP regulates body weight and glucose control via GIPR signaling in cells that express the leptin receptor (Lepr). METHODS: Hypothalamic, hindbrain, and pancreatic co-expression of Gipr and Lepr was assessed using single cell RNAseq analysis. Mice with deletion of Gipr in Lepr cells were generated and metabolically characterized for alterations in diet-induced obesity (DIO), glucose control and leptin sensitivity. Long-acting single- and dual-agonists at GIPR and GLP-1R were further used to assess drug effects on energy and glucose metabolism in DIO wildtype (WT) and Lepr-Gipr knock-out (KO) mice. RESULTS: Gipr and Lepr show strong co-expression in the pancreas, but not in the hypothalamus and hindbrain. DIO Lepr-Gipr KO mice are indistinguishable from WT controls related to body weight, food intake and diet-induced leptin resistance. Acyl-GIP and the GIPR:GLP-1R co-agonist MAR709 remain fully efficacious to decrease body weight and food intake in DIO Lepr-Gipr KO mice. Consistent with the demonstration that Gipr and Lepr highly co-localize in the endocrine pancreas, including the ß-cells, we find the superior glycemic effect of GIPR:GLP-1R co-agonism over single GLP-1R agonism to vanish in Lepr-Gipr KO mice. CONCLUSIONS: GIPR signaling in cells/neurons that express the leptin receptor is not implicated in the control of body weight or food intake, but is of crucial importance for the superior glycemic effects of GIPR:GLP-1R co-agonism relative to single GLP-1R agonism.

Global, neuronal or ß cell-specific deletion of inceptor improves glucose homeostasis in male mice with diet-induced obesity.

Insulin resistance is an early complication of diet-induced obesity (DIO)1, potentially leading to hyperglycaemia and hyperinsulinaemia, accompanied by adaptive ß cell hypertrophy and development of type 2 diabetes2. Insulin not only signals via the insulin receptor (INSR), but also promotes ß cell survival, growth and function via the insulin-like growth factor 1 receptor (IGF1R)3-6. We recently identified the insulin inhibitory receptor (inceptor) as the key mediator of IGF1R and INSR desensitization7. But, although ß cell-specific loss of inceptor improves ß cell function in lean mice7, it warrants clarification whether inceptor signal inhibition also improves glycaemia under conditions of obesity. We assessed the glucometabolic effects of targeted inceptor deletion in either the brain or the pancreatic ß cells under conditions of DIO in male mice. In the present study, we show that global and neuronal deletion of inceptor, as well as its adult-onset deletion in the ß cells, improves glucose homeostasis by enhancing ß cell health and function. Moreover, we demonstrate that inceptor-mediated improvement in glucose control does not depend on inceptor function in agouti-related protein-expressing or pro-opiomelanocortin neurons. Our data demonstrate that inceptor inhibition improves glucose homeostasis in mice with DIO, hence corroborating that inceptor is a crucial regulator of INSR and IGF1R signalling.

Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner.

Mammalian circadian clocks respond to feeding and light cues, adjusting internal rhythms with day/night cycles. Astrocytes serve as circadian timekeepers, driving daily physiological rhythms; however, it's unknown how they ensure precise cycle-to-cycle rhythmicity. This is critical for understanding why mistimed or erratic feeding, as in shift work, disrupts circadian physiology- a condition linked to type 2 diabetes and obesity. Here, we show that astrocytic insulin signaling sets the free-running period of locomotor activity in female mice and food entrainment in male mice. Additionally, ablating the insulin receptor in hypothalamic astrocytes alters cyclic energy homeostasis differently in male and female mice. Remarkably, the mutants exhibit altered dopamine metabolism, and the pharmacological modulation of dopaminergic signaling partially restores distinct circadian traits in both male and female mutant mice. Our findings highlight the role of astrocytic insulin-dopaminergic signaling in conveying time-of-feeding or lighting cues to the astrocyte clock, thus governing circadian behavior in a sex-specific manner.

High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-brain satiation pathway via κ-opioid signaling.

Oxytocin-expressing paraventricular hypothalamic neurons (PVNOT neurons) integrate afferent signals from the gut, including cholecystokinin (CCK), to adjust whole-body energy homeostasis. However, the molecular underpinnings by which PVNOT neurons orchestrate gut-to-brain feeding control remain unclear. Here, we show that mice undergoing selective ablation of PVNOT neurons fail to reduce food intake in response to CCK and develop hyperphagic obesity on a chow diet. Notably, exposing wild-type mice to a high-fat/high-sugar (HFHS) diet recapitulates this insensitivity toward CCK, which is linked to diet-induced transcriptional and electrophysiological aberrations specifically in PVNOT neurons. Restoring OT pathways in diet-induced obese (DIO) mice via chemogenetics or polypharmacology sufficiently re-establishes CCK's anorexigenic effects. Last, by single-cell profiling, we identify a specialized PVNOT neuronal subpopulation with increased κ-opioid signaling under an HFHS diet, which restrains their CCK-evoked activation. In sum, we document a (patho)mechanism by which PVNOT signaling uncouples a gut-brain satiation pathway under obesogenic conditions.

ST-Segment Elevation Acute Myocardial Infarction Associated to Covid-19 Vaccination in A Healthy Young Adult with Normal Coronary Arteries.

Despite the beneficial effects of anti-COVID-19 vaccination, monitoring its safety has identified potential cardiac adverse events, mainly myocarditis and pericarditis. The case of a healthy 32-year-old male patient who developed acute myocardial infarction (AMI) 48 hours after the second dose of anti-COVID-19 mRNA vaccine (BNT162b2) is reported. This is the first reported case in the literature of an AMI associated to post-COVID-19 vaccination with mRNA vaccine (BNT162b2) in a healthy young adult without coronary risk factors and normal coronary arteries. Despite this adverse event, the continuation of the anti-COVID-19 vaccination campaign is encouraged due to the benefits it brings.

The obesity-linked human lncRNA AATBC stimulates mitochondrial function in adipocytes.

Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, thermogenic adipocytes are linked to cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this plasticity could help improving metabolism. Here, we show that the lncRNA Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Comparing transcriptional profiles of human adipose tissues and cultured adipocytes we discovered that AATBC was enriched in thermogenic conditions. Using primary and immortalized human adipocytes we found that AATBC enhanced the thermogenic phenotype, which was linked to increased respiration and a more fragmented mitochondrial network. Expression of AATBC in adipose tissue of mice led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, BMI, and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.

Role of the Electrocardiographic MVP Risk Score (Morphology-Voltage-P Wave Duration) in Predicting the Development of Atrial Fibrillation in Patients With Systemic Arterial Hypertension.

BACKGROUND: There is a global tendency to emphasize the prevention and early diagnosis of diseases that have a great impact on public health. Atrial fibrillation (AF) has a prevalence affecting 1.5-2% of the general population. Certain variables of the P wave allow us to identify and stratify patients at risk of developing AF. MATERIALS AND METHODS: This is an observational, descriptive, and longitudinal study to determine the applicability of the electrocardiographic (ECG) morphology, voltage, and P wave duration (MVP) risk score to predict the development of AF in consecutive patients with systemic hypertension (SH) in an initial follow-up of 12 months. RESULTS: Initially, 104 patients were included, of whom 12 died during follow-up and 17 did not attend subsequent checkups during the COVID-19 pandemic; therefore, they were excluded. The study patients were 75, of whom AF was detected in 25 patients (33%). The average duration of the P wave was 120 ± 26 ms, the average voltage was 0.1 ± 0.5 Mv. The high-risk MVP ECG score had an [area under the curve, 0.69; 95% confidence intervals (CI), 0.59-0.79] and demonstrated a specificity and a positive predictive value of 100%, a negative predictive value of 76%, and a sensitivity of 40% for predicting the development of AF. CONCLUSIONS: The present study establishes for the first time that SH patients who possess a high-risk MVP ECG score have a significantly higher incidence of developing AF. The high-risk MVP Score has a specificity and a positive predictive value of 100% and a high negative predictive value with a moderate sensitivity for the prediction of the development of AF in SH patients.

An Adolescent Female With Acute Abdominal Pain: A Rare Case in Pediatrics.

We present the case of a 13-year-old female with a 48-hour history of diffuse abdominal pain, fever, nausea, and vomiting, with worsening in the last few hours. On examination, she had signs of acute abdomen, and laboratory tests showed elevated acute phase reactants (APR). Abdominal ultrasound excluded acute appendicitis. A history of risky sexual behavior was reported, so pelvic inflammatory disease (PID) was considered. Although appendicitis is the most common cause of acute abdomen in adolescents, PID should be suspected in adolescents with risk factors. Prompt treatment is necessary to avoid possible complications and sequelae.

The dietary sweetener sucralose is a negative modulator of T cell-mediated responses.

Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years1. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners2-5. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation. Mechanistically, sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signalling and intracellular calcium mobilization. Mice given sucralose show decreased CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, and reduced T cell function in models of T cell-mediated autoimmunity. Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders.

Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1.

Until menopause, women have a lower propensity to develop metabolic diseases than men, suggestive of a protective role for sex hormones. Although a functional synergy between central actions of estrogens and leptin has been demonstrated to protect against metabolic disturbances, the underlying cellular and molecular mechanisms mediating this crosstalk have remained elusive. By using a series of embryonic, adult-onset, and tissue/cell-specific loss-of-function mouse models, we document an unprecedented role of hypothalamic Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1 (Cited1) in mediating estradiol (E2)-dependent leptin actions that control feeding specifically in pro-opiomelanocortin (Pomc) neurons. We reveal that within arcuate Pomc neurons, Cited1 drives leptin's anorectic effects by acting as a co-factor converging E2 and leptin signaling via direct Cited1-ERα-Stat3 interactions. Together, these results provide new insights on how melanocortin neurons integrate endocrine inputs from gonadal and adipose axes via Cited1, thereby contributing to the sexual dimorphism in diet-induced obesity.

Relationship of the T-wave Tpeak-Tend interval with conduction system disorders in arterial hypertension / Relación del intervalo Tpico-Tfinal de la onda T con trastornos del sistema de conducción en hipertensión arterial

Abstract Purpose: The Tpeak-Tend interval of the T wave has emerged as a new electrocardiographic marker of increased transmural dispersion of ventricular repolarization. We aimed to determine the presence of cardiac conduction system disorders in patients with systemic arterial hypertension (SAH) who have altered Tpeak-Tend interval of the T wave. Methods: The 67 patients with SAH were divided into two groups. Those with prolonged (≥ 77 ms) Tpeak-Tend intervals, 21 (31%) patients were in the study group. Those with normal (< 77 ms) Tpeak-Tend intervals, 46 (69%) patients were in the control group. Alteration of ventricular repolarization manifested as a prolongation of the Tpeak-Tend interval was detected by computerized electrocardiographic analysis tools. Results: The median value of QRS complex duration was significantly wider in the study group as compared to the control group (110 ± 12 ms vs. 94 ± 8 ms p < 0.001). There was a significantly greater incidence of left anterior hemiblock in the study group (14% vs. 0% p < 0.04). The median value of the QTc interval was significantly greater in the study group (440 ± 26 vs. 422 ± 15 p < 0.01). There was a significantly greater incidence of patients with prolonged QTc interval in the study group (33% vs. 11% p < 0.02). The median value of the Tpeak-Tend interval was significantly greater in the study group (84 ± 5 ms vs. 65 ± 4 ms p < 0.001), as well as, the Tpeak-Tend/QTc ratio in the study group (0.19 ± 0.1 vs. 0.16 ± 0.1 p < 0.001). Conclusion: There is a significantly greater ventricular repolarization disorders and abnormalities of the cardiac conduction system in SAH patients who possess altered Tpeak-Tend interval of the T wave.

Resumen Objetivo: El intervalo Tpico-Tfinal de la onda T es un marcador electrocardiográfico de la dispersión transmural aumentada de la repolarización ventricular. Investigamos la presencia de trastornos del sistema de conducción cardíaca en pacientes con hipertensión arterial sistémica (HA) que poseen alterado el intervalo Tpico-Tfinal de la onda T. Métodos: Los 67 pacientes con HA fueron divididos en dos grupos. Aquellos con intervalos de Tpico-Tfinal prolongados (≥ 77 ms), 21 (31%) pacientes (grupo de estudio). Aquellos con intervalos normales (< 77 ms) Tpico-Tfinal, 46 (69%) pacientes (grupo control). Los intervalos Tpico-Tfinal fueron medidos por herramientas de análisis electrocardiográfico computarizado. Resultados: El valor mediano de la duración del complejo QRS fue significativamente más amplio en el grupo de estudio (110 ± 12 ms vs. 94 ± 8 ms p < 0.001). Hubo una incidencia significativamente mayor de hemibloqueo anterior izquierdo en el grupo de estudio (14% vs. 0% p < 0.04). El valor mediano del intervalo QTc fue significativamente mayor en el grupo de estudio (440 ± 26 vs. 422 ± 15 p < 0.01). Hubo una incidencia significativamente mayor de pacientes con intervalo QTc prolongado en el grupo de estudio (33% vs. 11% p < 0.02). El valor mediano del intervalo Tpico-Tfinal fue significativamente mayor en el grupo de estudio (84 ± 5 ms vs. 65 ± 4 ms p < 0.001), así como el cociente Tpico-Tfinal/QTc (0.19 ± 0.1 vs. 0.16 ± 0.1 p < 0.001). Conclusión: Existe una alteración de la repolarización ventricular significativamente mayor y anomalías del sistema de conducción cardíaca en pacientes con HA que poseen alteración del intervalo Tpico-Tfinal de la onda T.

Relationship of the T-wave Tpeak-Tend interval with conduction system disorders in arterial hypertension.

PURPOSE: The Tpeak-Tend interval of the T wave has emerged as a new electrocardiographic marker of increased transmural dispersion of ventricular repolarization. We aimed to determine the presence of cardiac conduction system disorders in patients with systemic arterial hypertension (SAH) who have altered Tpeak-Tend interval of the T wave. METHODS: The 67 patients with SAH were divided into two groups. Those with prolonged (≥ 77 ms) Tpeak-Tend intervals, 21 (31%) patients were in the study group. Those with normal (< 77 ms) Tpeak-Tend intervals, 46 (69%) patients were in the control group. Alteration of ventricular repolarization manifested as a prolongation of the Tpeak-Tend interval was detected by computerized electrocardiographic analysis tools. RESULTS: The median value of QRS complex duration was significantly wider in the study group as compared to the control group (110 ± 12 ms vs. 94 ± 8 ms p < 0.001). There was a significantly greater incidence of left anterior hemiblock in the study group (14% vs. 0% p < 0.04). The median value of the QTc interval was significantly greater in the study group (440 ± 26 vs. 422 ± 15 p < 0.01). There was a significantly greater incidence of patients with prolonged QTc interval in the study group (33% vs. 11% p < 0.02). The median value of the Tpeak-Tend interval was significantly greater in the study group (84 ± 5 ms vs. 65 ± 4 ms p < 0.001), as well as, the Tpeak-Tend/QTc ratio in the study group (0.19 ± 0.1 vs. 0.16 ± 0.1 p < 0.001). CONCLUSION: There is a significantly greater ventricular repolarization disorders and abnormalities of the cardiac conduction system in SAH patients who possess altered Tpeak-Tend interval of the T wave.

OBJETIVO: El intervalo Tpico-Tfinal de la onda T es un marcador electrocardiográfico de la dispersión transmural aumentada de la repolarización ventricular. Investigamos la presencia de trastornos del sistema de conducción cardíaca en pacientes con hipertensión arterial sistémica (HA) que poseen alterado el intervalo Tpico-Tfinal de la onda T. MÉTODOS: Los 67 pacientes con HA fueron divididos en dos grupos. Aquellos con intervalos de Tpico-Tfinal prolongados (≥ 77 ms), 21 (31%) pacientes (grupo de estudio). Aquellos con intervalos normales (< 77 ms) Tpico-Tfinal, 46 (69%) pacientes (grupo control). Los intervalos Tpico-Tfinal fueron medidos por herramientas de análisis electrocardiográfico computarizado. RESULTADOS: El valor mediano de la duración del complejo QRS fue significativamente más amplio en el grupo de estudio (110 ± 12 ms vs. 94 ± 8 ms p < 0.001). Hubo una incidencia significativamente mayor de hemibloqueo anterior izquierdo en el grupo de estudio (14% vs. 0% p < 0.04). El valor mediano del intervalo QTc fue significativamente mayor en el grupo de estudio (440 ± 26 vs. 422 ± 15 p < 0.01). Hubo una incidencia significativamente mayor de pacientes con intervalo QTc prolongado en el grupo de estudio (33% vs. 11% p < 0.02). El valor mediano del intervalo Tpico-Tfinal fue significativamente mayor en el grupo de estudio (84 ± 5 ms vs. 65 ± 4 ms p < 0.001), así como el cociente Tpico-Tfinal/QTc (0.19 ± 0.1 vs. 0.16 ± 0.1 p < 0.001). CONCLUSIÓN: Existe una alteración de la repolarización ventricular significativamente mayor y anomalías del sistema de conducción cardíaca en pacientes con HA que poseen alteración del intervalo Tpico-Tfinal de la onda T.

Amoxicillin overdose in the pediatric emergency department: A descriptive study.

OBJECTIVE: To describe the characteristics of pediatric patients treated in the  emergency department due to amoxicillin overdosing. METHOD: A retrospective single-center observational study was conducted on  patients aged 0 to 16 years treated in a pediatric emergency department due  to amoxicillin overdosing between 2011 and 2021. Epidemiological and  anthropometric data was collected as well as information on the circumstances  of overdosing, clinical manifestations, emergency department management,  and discharge destination. RESULTS: The study comprised 15 patients, 66.6% of them male, with a median age of 3.8 years (interquartile range: 1.9). The most frequent cause  of overdosing was accidental ingestion (8/15; 53.3%). Amoxicillin was mainly ingested in liquid form, except for one case with autolytic attempt,  where it was ingested in the form of tablets. Eighty percent of subjects (12/15) received a single dose of the drug. The median time to presentation to  emergency department was 2.1 hours from ingestion (interquartile range: 2.7) and the median dose of amoxicillin was 219 mg/kg/dose (interquartile range:  148). All patients were asymptomatic, with a normal physical examination.  Blood tests were performed in 7 patients (46.6%) and urinary sediment  analysis in 2 (13.3%), all of them without alterations. Activated charcoal was  administered to 5 (33.3%), patients with a median time to administration of  one hour (interquartile range: 1.2). All patients were discharged to their  homes. Eleven cases (73.3%) required withdrawal of amoxicillin. CONCLUSIONS: Amoxicillin overdosing in this study did not appear to result in  adverse effects, despite the fact that the recommended doses were  significantly exceeded.

OBJETIVO: Describir las características de los pacientes pediátricos atendidos en urgencias por sobreingesta de amoxicilina.Método: Estudio unicéntrico observacional, retrospectivo, en pacientes de 0- 16 años atendidos en urgencias pediátricas por sobreingesta de amoxicilina  entre 2011 y 2021. Se analizaron datos epidemiológicos, antropométricos,  circunstancias de la sobreingesta, síntomas, manejo y destino. RESULTADOS: Se incluyeron 15 pacientes, 66,6% varones, mediana de edad de  3,8 años (rango intercuartílico 1,9). La causa más frecuente de sobreingesta  fue la ingesta accidental por el paciente (8/15; 53,3%). Fue administrada en  forma de suspensión en todos los casos, excepto en un paciente con intención  autolítica (comprimidos). El 80% (12/15) recibieron una única dosis. La  mediana de tiempo de llegada a urgencias desde la sobreingesta fue de 2,1  horas (rango intercuartílico 2,7) y la mediana de dosis de 219 mg/kg/dosis  (rango intercuartílico 148). Todos estaban asintomáticos con exploración  normal. Se realizó analítica sanguínea en 7 (46,6%) y sedimento urinario en 2 (13,3%), sin alteraciones. Cinco (33,3%) recibieron carbón activado, con una mediana de tiempo hasta la administración de 1 hora (rango intercuartílico  1,2). Todos fueron dados de alta, suspendiendo el tratamiento 11 (73,3%). CONCLUSIONES: En este estudio, la sobredosificación de amoxicilina no se  relacionó con efectos adversos, a pesar de exceder las dosis recomendadas.

Sobredosificación por amoxicilina en urgencias pediátricas: Estudio descriptivo / Amoxicillin overdose in the pediatric emergency department: A descriptive study

Objetivo: Describir las características de los pacientes pediátricos atendidos en urgencias por sobreingesta de amoxicilina.Método: Estudio unicéntrico observacional, retrospectivo, en pacientesde 0-16 años atendidos en urgencias pediátricas por sobreingesta deamoxicilina entre 2011 y 2021. Se analizaron datos epidemiológicos,antropométricos, circunstancias de la sobreingesta, síntomas, manejo ydestino.Resultados: Se incluyeron 15 pacientes, 66,6% varones, medianade edad de 3,8 años (rango intercuartílico 1,9). La causa más frecuente de sobreingesta fue la ingesta accidental por el paciente (8/15;53,3%). Fue administrada en forma de suspensión en todos los casos,excepto en un paciente con intención autolítica (comprimidos). El 80%(12/15) recibieron una única dosis. La mediana de tiempo de llegadaa urgencias desde la sobreingesta fue de 2,1 horas (rango intercuartílico 2,7) y la mediana de dosis de 219 mg/kg/dosis (rango intercuartílico 148). Todos estaban asintomáticos con exploración normal. Serealizó analítica sanguínea en 7 (46,6%) y sedimento urinario en 2(13,3%), sin alteraciones. Cinco (33,3%) recibieron carbón activado,con una mediana de tiempo hasta la administración de 1 hora (rangointercuartílico 1,2). Todos fueron dados de alta, suspendiendo el tratamiento 11 (73,3%). (AU)

Objective: To describe the characteristics of pediatric patients treated inthe emergency department due to amoxicillin overdosing.Method: A retrospective single-center observational study was conducted on patients aged 0 to 16 years treated in a pediatric emergencydepartment due to amoxicillin overdosing between 2011 and 2021. Epidemiological and anthropometric data was collected as well as information on the circumstances of overdosing, clinical manifestations, emergency department management, and discharge destination.Results: The study comprised 15 patients, 66.6% of them male, with amedian age of 3.8 years (interquartile range: 1.9). The most frequent cause ofoverdosing was accidental ingestion (8/15; 53.3%). Amoxicillin was mainlyingested in liquid form, except for one case with autolytic attempt, where itwas ingested in the form of tablets. Eighty percent of subjects (12/15) received a single dose of the drug. The median time to presentation to emergencydepartment was 2.1 hours from ingestion (interquartile range: 2.7) and themedian dose of amoxicillin was 219 mg/kg/dose (interquartile range: 148).All patients were asymptomatic, with a normal physical examination. Bloodtests were performed in 7 patients (46.6%) and urinary sediment analysis in2 (13.3%), all of them without alterations. Activated charcoal was administered to 5 (33.3%), patients with a median time to administration of one hour(interquartile range: 1.2). All patients were discharged to their homes. Elevencases (73.3%) required withdrawal of amoxicillin. (AU)

Hypothalamic astrocytes control systemic glucose metabolism and energy balance.

The hypothalamus is key in the control of energy balance. However, strategies targeting hypothalamic neurons have failed to provide viable options to treat most metabolic diseases. Conversely, the role of astrocytes in systemic metabolic control has remained largely unexplored. Here, we show that obesity promotes anatomically restricted remodeling of hypothalamic astrocyte activity. In the paraventricular nucleus (PVN) of the hypothalamus, chemogenetic manipulation of astrocytes results in bidirectional control of neighboring neuron activity, autonomic outflow, glucose metabolism, and energy balance. This process recruits a mechanism involving the astrocytic control of ambient glutamate levels, which becomes defective in obesity. Positive or negative chemogenetic manipulation of PVN astrocyte Ca2+ signals, respectively, worsens or improves metabolic status of diet-induced obese mice. Collectively, these findings highlight a yet unappreciated role for astrocytes in the direct control of systemic metabolism and suggest potential targets for anti-obesity strategy.

Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome.

OBJECTIVE: The Allan-Herndon-Dudley syndrome (AHDS) is a severe disease caused by dysfunctional central thyroid hormone transport due to functional loss of the monocarboxylate transporter 8 (MCT8). In this study, we assessed whether mice with concomitant deletion of the thyroid hormone transporters Mct8 and the organic anion transporting polypeptide (Oatp1c1) represent a valid preclinical model organism for the AHDS. METHODS: We generated and metabolically characterized a new CRISPR/Cas9 generated Mct8/Oatp1c1 double-knockout (dKO) mouse line for the clinical features observed in patients with AHDS. RESULTS: We show that Mct8/Oatp1c1 dKO mice mimic key hallmarks of the AHDS, including decreased life expectancy, central hypothyroidism, peripheral hyperthyroidism, impaired neuronal myelination, impaired motor abilities and enhanced peripheral thyroid hormone action in the liver, adipose tissue, skeletal muscle and bone. CONCLUSIONS: We conclude that Mct8/Oatp1c1 dKO mice are a valuable model organism for the preclinical evaluation of drugs designed to treat the AHDS.

Miositis aguda infantil en urgencias pediátricas / Acute myositis in the paediatric emergency department

Introducción: la miositis aguda benigna de la infancia (MAB) es una enfermedad benigna y autolimitada, considerada en la actualidad como una secuela de enfermedades víricas. Su manifestación clínica típica son las mialgias en las extremidades inferiores acompañadas de rechazo a caminar. Pacientes y métodos: realizamos una revisión retrospectiva de los casos de MAB atendidos en nuestro servicio de urgencias pediátricas durante un periodo de 25 años. Obtuvimos datos demográficos, clínicos y de laboratorio a través de la revisión sistemática de historias clínicas. Se elaboraron estadísticas descriptivas y se efectuaron comparaciones entre grupos a través del test U de Mann-Whitney. Las correlaciones entre variables cuantitativas se realizaron mediante el análisis de rangos de Spearman. Resultados: se identificaron 139 casos de MAB (74,8% varones). La mayor incidencia se produjo en los meses de invierno y en niños de 4-8 años. Las mialgias bilaterales en miembros inferiores fueron el principal motivo de consulta. El 86,3% referían fiebre acompañada de síntomas respiratorios (88,5%), confirmándose en urgencias la infección por virus influenza en 37 casos (75,6% del serotipo B). En el momento del diagnóstico, la mediana de creatincinasa (CK) fue 1794 U/l, no existiendo diferencias significativas en función del sexo (p = 0,687). La función renal fue normal en todos los pacientes, ninguno necesitó hospitalización. Conclusiones: la MAB es una entidad fácilmente reconocible teniendo en cuenta sus manifestaciones clínicas y analíticas. A pesar de las masivas elevaciones de CK, sus complicaciones son excepcionales y la mayoría de los pacientes pueden ser dados de alta con tratamiento conservador (AU)

Introduction: benign acute childhood myositis (BACM) is a benign, self-limiting disease currently believed to be a sequela of viral infections. The typical clinical presentation is myalgia in the lower extremities accompanied by refusal to walk.Patients and methods: we did a retrospective review of all the cases of BACM managed in our paediatric emergency department over a 25-year period. We collected data on demographic, clinical and laboratory variables through the systematic review of health records. We performed a descriptive statistical analysis, followed by comparison of groups with the Mann-Whitney U test. The correlation between quantitative variables was assessed by means of the Spearman rank coefficient.Results: we identified 139 cases of BACM (74.8% in male patients). The highest incidence corresponded to children aged 4 to 8 years and the winter months. Bilateral lower limb myalgia was the most frequent presenting complaint. Fever was reported in 86.3% of cases, accompanied by respiratory symptoms (88.5%); influenza virus infection was confirmed in 37 cases (75.6% serotype B). At diagnosis, the median creatine kinase (CK) level was 1794 U/l, with no significant differences between the sexes (p=0.687). All patients had normal renal function, and none required hospitalization.Conclusions: based on its clinical and analytical manifestations, BACM is easy to recognise. Although massive elevation of CK is common, complications are rare, and most patients can be discharged with conservative treatment. (AU)

Gemelos con convulsiones febriles: coincidencia en tiempo y etiología / Febrile seizures in siblings: coincidence in timing and aetiology

Las convulsiones febriles tienen alta prevalencia en la infancia y son un motivo de consulta frecuente en Urgencias, generando gran ansiedad en los cuidadores. La etiología es multifactorial y se ha descrito una agregación familiar (hasta el 25-40% de los niños con crisis febriles presentan antecedentes familiares de estas). Sin embargo, esta es la primera vez que se describen convulsiones febriles en hermanos al mismo tiempo y con el mismo hallazgo microbiológico. Presentamos dos parejas de hermanos gemelos de 23 y 33 meses, valorados en Urgencias por crisis febriles al mismo tiempo que su respectivo gemelo. La exploración física y el examen neurológico fueron normales en todos ellos. La PCR para enterovirus recogida en faringe y/o recto fue positiva. En todos los casos la recuperación fue completa, permitiendo el alta sin requerir otros estudios. En los últimos años, las infecciones por enterovirus están adquiriendo importancia creciente en el papel de las convulsiones. Ante casos de hermanos con crisis febriles al mismo tiempo debería tenerse en cuenta la posible infección por este agente. Establecer una etiología podría ser tranquilizador para los padres (AU)

The prevalence of febrile seizures is high in the paediatric population, and seizures are a frequent reason for emergency department (ED) visits, and a significant source of anxiety in caregivers. Their aetiology is multifactorial, and family aggregation has been described (as many as 25-40% of children with febrile seizures have a positive family history). However, this is the first time that febrile seizures have been described as occurring in siblings at the same time with identification of the same etiological agent.We present the cases of 2 pairs of twins, aged 23 months and 33 months, respectively, who presented at the ED with simple febrile seizures in both twins at the same time. The physical and neurological examination were normal in all of them. Polymerase chain reaction tests for enterovirus in pharyngeal and/or rectal swabs were positive. All of the patients recovered fully and were discharged home without requiring further diagnostic tests.In recent years, there has been a growing awareness of the important role of enterovirus infection in seizures. Therefore, enterovirus infection should be considered in the case of siblings presenting with febrile seizures at the same time. Establishing the aetiology of seizures may be reassuring to parents. (AU)