Ketogenic diet induces p53-dependent cellular senescence in multiple organs.

A ketogenic diet (KD) is a high-fat, low-carbohydrate diet that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different KDs and, at different ages, induce cellular senescence in multiple organs, including the heart and kidney. This effect is mediated through adenosine monophosphate-activated protein kinase (AMPK) and inactivation of mouse double minute 2 (MDM2) by caspase-2, leading to p53 accumulation and p21 induction. This was established using p53 and caspase-2 knockout mice and inhibitors to AMPK, p21, and caspase-2. In addition, senescence-associated secretory phenotype biomarkers were elevated in serum from mice on a KD and in plasma samples from patients on a KD clinical trial. Cellular senescence was eliminated by a senolytic and prevented by an intermittent KD. These results have important clinical implications, suggesting that the effects of a KD are contextual and likely require individual optimization.

Long-Term Results of Cortical Motor Stimulation for Neuropathic Peripheral and Central Pain: Real-World Evidence From Two Independent Centers.

BACKGROUND AND OBJECTIVES: Cortical motor stimulation (CMS) is used to modulate neuropathic pain. The literature supports its use; however, short follow-up studies might overestimate its real effect. This study brings real-world evidence from two independent centers about CMS methodology and its long-term outcomes. METHODS: Patients with chronic refractory neuropathic pain were implanted with CMS. The International Classification of Headache Disorders 3rd Edition was used to classify craniofacial pain and the Douleur Neuropathique en 4 Questions Scale score to explore its neuropathic nature. Demographics and clinical and surgical data were collected. Pain intensity at 6, 12, and 24 months and last follow-up was registered. Numeric rating scale reduction of ≥50% was considered a good response. The Clinical Global Impression of Change scale was used to report patient satisfaction. RESULTS: Twelve males (38.7%) and 19 females (61.3%) with a mean age of 55.8 years (±11.9) were analyzed. Nineteen (61.5%) were diagnosed from painful trigeminal neuropathy (PTN), and seven (22.5%) from central poststroke pain. The mean follow-up was 51 months (±23). At 6 months, 42% (13/31) of the patients were responders, all of them being PTN (13/19; 68.4%). At last follow-up, only 35% (11/31) remained responders (11/19 PTN; 58%). At last follow-up, the global Numeric rating scale reduction was 34% ( P = .0001). The Clinical Global Impression of Change scale punctuated 2.39 (±0.94) after 3 months from the surgery and 2.95 (±1.32) at last follow-up ( P = .0079). Signs of suspicious placebo effect were appreciated in around 40% of the nonresponders. CONCLUSION: CMS might show long-term efficacy for neuropathic pain syndromes, with the effect on PTN being more robust in the long term. Multicentric clinical trials are needed to confirm the efficacy of this therapy for this and other conditions.

Neuromodulation-induced prehabilitation to leverage neuroplasticity before brain tumor surgery: a single-cohort feasibility trial protocol.

Introduction: Neurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy. Methods and analysis: Patients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery. Ethics and dissemination: Ethics approval was obtained from the Research Ethical Committee of Fundació Unió Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses. Clinical trial registration: ClinicalTrials.gov, identifier NCT05844605.

Association of Neutrophil/Lymphocyte Ratio and Neutrophil/Lymphocyte Platelet Ratio With Acute Kidney Injury in Severe COVID-19.

Background Severe disease from COVID-19 was the leading cause of admission to the emergency room and hospitalization during the pandemic in Mexico. Acute kidney injury was one of the most prevalent complications in these patients. The neutrophil/lymphocyte (NL) index and the neutrophil/lymphocyte platelet (NLP) index have previously been described as possible markers associated with complications and mortality in this disease. Objective To determine the association of the NL ratio and the NLP ratio in patients with acute kidney injury secondary to severe COVID-19. Materials and methods This is a case-control study, unpaired, of patients diagnosed with severe COVID-19 who presented or did not present acute kidney injury. On admission to the hospital, the hematological ratios were calculated, and Mann-Whitney U tests and multivariate logistic regression were performed. Results A total of 160 patients were included, and a difference in the NLP ratio (4.2 vs. 3.1, p = 0.001) was observed between patients with and without acute kidney injury. Additionally, the NLP ratio was the main risk variable for acute kidney injury in severe COVID-19, with an odds ratio of 2.5 and a 95% confidence interval of 1.108-5.66. Conclusions The NLP ratio has a moderate association and is a risk factor associated with the presence of acute kidney injury in patients with severe COVID-19.

Genomic methylation patterns in pre-meiotic gynoecia of wild-type and RdDM mutants of Arabidopsis.

Introduction: Although DNA methylation patterns are generally considered to be faithfully inherited in Arabidopsis thaliana (Arabidopsis), there is evidence of reprogramming during both male and female gametogenesis. The gynoecium is the floral reproductive organ from which the ovules develop and generate meiotically derived cells that give rise to the female gametophyte. It is not known whether the gynoecium can condition genomic methylation in the ovule or the developing female gametophyte. Methods: We performed whole genome bisulfite sequencing to characterize the methylation patterns that prevail in the genomic DNA of pre-meiotic gynoecia of wild-type and three mutants defective in genes of the RNA-directed DNA methylation pathway (RdDM): ARGONAUTE4 (AGO4), ARGONAUTE9 (AGO9), and RNA-DEPENDENT RNA POLYMERASE6 (RDR6). Results: By globally analyzing transposable elements (TEs) and genes located across the Arabidopsis genome, we show that DNA methylation levels are similar to those of gametophytic cells rather than those of sporophytic organs such as seedlings and rosette leaves. We show that none of the mutations completely abolishes RdDM, suggesting strong redundancy within the methylation pathways. Among all, ago4 mutation has the strongest effect on RdDM, causing more CHH hypomethylation than ago9 and rdr6. We identify 22 genes whose DNA methylation is significantly reduced in ago4, ago9 and rdr6 mutants, revealing potential targets regulated by the RdDM pathway in premeiotic gyneocia. Discussion: Our results indicate that drastic changes in methylation levels in all three contexts occur in female reproductive organs at the sporophytic level, prior to the alternation of generations within the ovule primordium, offering a possibility to start identifying the function of specific genes acting in the establishment of the female gametophytic phase of the Arabidopsis life cycle.

Phylogeography and transmission of Mycobacterium tuberculosis spanning prisons and surrounding communities in Paraguay.

Recent rises in incident tuberculosis (TB) cases in Paraguay and the increasing concentration of TB within prisons highlight the urgency of targeting strategies to interrupt transmission and prevent new infections. However, whether specific cities or carceral institutions play a disproportionate role in transmission remains unknown. We conducted prospective genomic surveillance, sequencing 471 Mycobacterium tuberculosis complex genomes, from inside and outside prisons in Paraguay's two largest urban areas, Asunción and Ciudad del Este, from 2016 to 2021. We found genomic evidence of frequent recent transmission within prisons and transmission linkages spanning prisons and surrounding populations. We identified a signal of frequent M. tuberculosis spread between urban areas and marked recent population size expansion of the three largest genomic transmission clusters. Together, our findings highlight the urgency of strengthening TB control programs to reduce transmission risk within prisons in Paraguay, where incidence was 70 times that outside prisons in 2021.

Downregulation of miRNA-26 in chronic periodontitis interferes with innate immune responses and cell migration by targeting phospholipase C beta 1.

AIM: To evaluate the potential role of miR-26 family members in periodontal pathogenesis by assessing innate immune responses to periopathic bacteria and regulation of cytoskeletal organization. MATERIALS AND METHODS: Expression of miR-26a-5p and miR-26b-5p was quantified in gingival biopsies derived from healthy and periodontally diseased subjects before and after non-surgical (scaling and root planing) therapy by RT-qPCR. Global pathway analysis and luciferase assays were performed for target identification and validation. Cytokine expression was assessed in miR-26a-5p transfected human oral keratinocytes upon stimulation with either live Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans or Pg lipopolysaccharide (LPS). Wound closure assays were performed in cells transfected with miR-26a-5p, while the impact on cytoskeletal organization was assessed by F-actin staining. RESULTS: miR-26a-5p and miR-26b-5p were downregulated in diseased gingiva and restored 4-6 weeks post-therapy to levels comparable with healthy subjects. Target validation assays identified phospholipase C beta 1 as a bona fide novel target exhibiting antagonistic expression pattern in disease and post-therapy cohorts. miR-26a-5p transfected cells secreted higher levels of cytokine/chemokines upon stimulation with periopathogens and demonstrated impaired cell migration and cytoskeletal rearrangement. CONCLUSIONS: Downregulated miR-26a-5p levels in periodontal inflammation may interfere with key cellular functions that may have significant implications for host defence and wound healing.

Cognitive and quality-of-life related factors of body mass index (BMI) improvement after deep brain stimulation in the subcallosal cingulate and nucleus accumbens in treatment-refractory chronic anorexia nervosa.

BACKGROUND: Up to 20% of the cases of anorexia nervosa (AN) are chronic and treatment-resistant. Recently, the efficacy of deep brain stimulation (DBS) for severe cases of AN has been explored, with studies showing an improvement in body mass index and other psychiatric outcomes. While the effects of DBS on cognitive domains have been studied in patients with other neurological and psychiatric conditions so far, no evidence has been gathered in AN. METHODS: Eight patients with severe, chronic, treatment-resistant AN received DBS either to the nucleus accumbens (NAcc) or subcallosal cingulate (SCC; four subjects on each target). A comprehensive battery of neuropsychological and clinical outcomes was used before and 6-month after surgery. FINDINGS: Although Body Mass Index (BMI) did not normalise, statistically significant improvements in BMI, quality of life, and performance on cognitive flexibility were observed after 6 months of DBS. Changes in BMI were related to a decrease in depressive symptoms and an improvement in memory functioning. INTERPRETATION: These findings, although preliminary, support the use of DBS in AN, pointing to its safety, even for cognitive functioning; improvements of cognitive flexibility are reported. DBS seems to exert changes on cognition and mood that accompany BMI increments. Further studies are needed better to determine the impact of DBS on cognitive functions.

Surgical results and the location of pathological glands in the treatment of primary sporadic hyperparathyroidism with negative preoperative 99mTc-sestamibi scintigraphy.

INTRODUCTION: The primary hyperparathyroidism is a frequent disease whom the surgery is the only curative treatment. The preoperative location imaging techniques could help in the surgical management. Our objective was to analyze surgical results regarding the cure rate, etiology and location of the glands responsible for the primary hyperparathyroidism in patients with negative preoperative 99mTc-sestamibi scintigraphy. METHODS: Observational study in patients with the diagnosis of primary sporadic hyperparathyroidism with negative 99mTc-sestamibi scintigraphy, operated consecutively in an endocrine surgery unit for 18 years. The cure rate, the intraoperatory PTH, the etiology and the pathological glands location were analyzed. RESULTS: In the study were included 120 patients. After surgery 95% of patients (n = 114) presented cure criteria of hyperparathyroidism. 14.1% presented a multigland disease. 69% of the adenomas presented a typical perithyroid location, founding a percentage of 23.9% of ectopic adenomas in cervical location and a 7.1% in mediastinum. CONCLUSIONS: The absence of uptake in the 99mTc-sestamibi scintigraphy should not condition the surgical indication. The success with experienced surgeons is similar to patients with positive results. The surgical indication must be established by clinical and biochemistry criteria.

Palaeoneurology of the early cretaceous iguanodont Proa valdearinnoensis and its bearing on the parallel developments of cognitive abilities in theropod and ornithopod dinosaurs.

Proa valdearinnoensis is a relatively large-headed and stocky iguanodontian dinosaur from the latest Early Cretaceous of Spain. Its braincase is known from three specimens. Similar to that of other dinosaurs, it shows a mosaic ossification pattern in which most of the bones seem to have fused together indistinguishably while a few (frontoparietal, basioccipital) might have remained loosely attached. The endocasts of the three specimens are described based on CT data and digital reconstructions. They show unmistakable morphological similarities with the endocast of closely related taxa, such as Sirindhorna khoratensis (which is close in age but from Thailand). This supports a high conservatism of the endocranial cavity. The issue of volumetric correspondence between endocranial cavity and brain in dinosaurs is analyzed. Although a brain-to-endocranial cavity (BEC) index of 0.50 has been traditionally used, we employ instead 0.73. This is indeed the mid-value between the situation in adults of Alligator mississippiensis and Gallus gallus, which are members of the extant bracketing taxa of dinosaurs (Crocodilia and Aves). We thence gauge the level of encephalization of P. valdearinnoensis through the calculation of the encephalization quotient (EQ), which remains valuable as a metric for assessing the degree of cognitive function in extinct taxa, especially those with fully ossified braincases like dinosaurs and other archosaurs. The EQ obtained for P. valdearinnoensis (3.611) suggests that this species was significantly more encephalized than most if not all extant nonavian, nonmammalian amniotes. Our work adds to the growing body of data concerning theoretical cognitive capabilities in dinosaurs and supports the idea that an increasing encephalization was fostered not only in theropods but also in parallel in the shorter-lived lineage of ornithopods. P. valdearinnoensis was ill-equipped to respond to theropod dinosaurs and possibly lived in groups as a strategy to mitigate the risk of being predated upon. We hypothesize that group-living and protracted caring of juveniles in this and possibly many other iguanodontian ornithopods favored a degree of encephalization that was outstanding by reptile standards.

Surface layer microplastic pollution in four bays of the central Mexican Pacific.

Surface microplastics were sampled monthly in four tropical bays (Manzanillo, Santiago, Navidad and Cuastecomates) of the central Mexican Pacific during March 2017 to February 2018. Microplastic concentrations ranged between 0.01 and 1.05 particles/m2 with a median per bay ranging between 0.26 and 0.40 particles/m2. Raman spectroscopy registered polypropylene (40%), polyethylene (40%) and polyester (20%) polymers. Fibers dominated all samples, except for Manzanillo where fragments numerically dominated during the rainy season (Jun-Oct). Fiber concentration was not significantly different among bays or seasons, likely associated with continuous wastewater discharge. Fragment concentrations were significantly higher in Bahía Manzanillo and Santiago than the other two bays. Non-metric multidimensional scaling showed distinct distribution of Manzanillo samples (which has important port activities) as compared to Santiago, Navidad, Cuastecomates (where tourism economic activities predominate). This first direct comparison of sea surface microplastic concentration among four bays in Mexico provides a baseline to study impacts on marine zooplankton in this tropical ecosystem.

Serie de Casos de Leishmaniasis Detectados en Centros Hospitalarios del Departamento de Caaguazú, Paraguay en 2019

Resumen La leishmaniasis es la tercera de las enfermedades de transmisión vectorial a humanos en importancia por el número de casos y la población en riesgo. En Paraguay la leishmaniasis cutánea es una enfermedad endémica atribuida en casi todos los casos a Leishmania (Viannia) braziliensis. El objetivo del artículo es describir las características demográficas y clínicas de una serie de casos de pacientes con leishmaniasis en el V departamento de Caaguazú y departamentos cercanos, epidemiológicamente endémicos. Se reportan casos diagnosticados en los meses enero a diciembre del año 2019. Los casos se presentaron en el departamento de Caaguazú, abarcando los diferentes distritos que componen y departamentos cercanos como Canindeyú, Alto Paraná y Guaira. De los casos registrados (9 casos) fueron hombres y (6 casos) tuvieron entre 50 a 70 años de edad. La lesión estuvo situada mayormente en el tabique nasal en 8 casos, con una evolución de menos de 10 años (6 casos) y en 4 casos dejo cicatriz. Solo 3 casos completaron su tratamiento. Se sugiere realizar el reporte de casos para tener un panorama de los casos de leishmaniasis en Paraguay como vigilancia sanitaria de la enfermedad y localizar focos de contagio.

Abstract Leishmaniasis is the third most important vector-borne diseases in humans due to the number of cases and the population at risk. In Paraguay, cutaneous leishmaniasis is an endemic disease attributed in almost all cases to Leishmania (Viannia) braziliensis. The objective of the article was to describe the demographic and clinical characteristics of a series of cases of patients with leishmaniasis in the V department of Caaguazú and nearby departments, epidemiologically endemic. Cases diagnosed in the months of January to December of the year 2019 are reported. The cases occurred in the department of Caaguazú, covering the different districts that make up and nearby departments such as Canindeyú, Alto Paraná and Guaira. Of the registered cases (9 cases) were men and (6 cases) were between 50 and 70 years of age. The lesion was located mainly in the nasal septum in 8 cases, with an evolution of less than 10 years (6 cases) and in 4 cases it left a scar. Only 3 cases completed their treatment. It is suggested to carry out the case report to have an overview of Leishmania cases in Paraguay as a health surveillance of the disease and to locate sources of contagion.

In vitro and In vivo Synergistic Interactions of the Flavonoid Rutin with Paracetamol and with Non-Steroidal Anti-Inflammatory Drugs.

AIM/BACKGROUND: The combination of drugs with different mechanisms of action could be more effective due to an enhanced synergistic activity. The pharmacological interactions between rutin and paracetamol, and rutin and non-steroidal anti-inflammatory drugs (NSAIDs), such as naproxen, ketorolac, and diclofenac were investigated using in vitro and in vivo assays. METHODS: Individual and drug combination response curves of rutin-NSAIDs, and rutin-paracetamol (each at 0.001-0.1 mmol for in vitro studies and ranging from 1.25-100 mg/kg p.o. for in vivo studies) were evaluated in RAW 264.7 macrophages [inhibition of nitric oxide (NO) using the Griess reagent] and Balb/c mice (acetic acid-induced writhing test). An isobolographic analysis was used to assess the type of interaction between rutin and NSAIDs and rutin-paracetamol in a proportion of 1:1. RESULTS: Rutin alone and in combination with paracetamol and NSAIDs decreased NO production and the number of writhings in a concentration/dose-dependent manner. The isobolograms showed that all in vitro combinations of rutin-NSAIDs and rutin-paracetamol exerted synergistic effects. The combination rutin-diclofenac showed an interaction index of 0.17. In the in vivo assay, the combinations of rutin-diclofenac (interaction index = 0.195) and rutin-ketorolac (interaction index = 0.408) displayed synergistic effects, and the combination rutin-paracetamol exhibited additive effects. CONCLUSION: Rutin produces synergistic effects with paracetamol and NSAIDs in in vitro and in vivo assays.

[Nutritional screening in hospitalized patients with vascular disease - The relationship of nutritional risk with clinical and economic outcomes in a surgery department]. / Cribado nutricional del paciente con patología vascular hospitalizado: relación del riesgo nutricional con los resultados clínicos y económicos en un servicio quirúrgico.

INTRODUCTION: Introduction: disease-related malnutrition has a negative impact on the outcome in surgical patients. Our objective was to assess the prevalence of nutritional risk in the field of vascular surgery, as well as its consequences on patient outcome and health expenditure. Patients and methods: this is a prospective, observational study conducted during 6 months in a vascular surgery ward at the University Hospital of León, Spain. The Malnutrition Universal Screening Tool was used to obtain data on admission and then every 7 days until hospital discharge. Clinical variables, surgical intervention performed, medical-surgical complications, hospital stay, healthcare costs, and early readmissions were studied. Results: a total of 104 patients, 84.6 % males, with a mean age of 69 (SD: 13) years were enrolled. Of these, 46.2 % were admitted due to peripheral arterial disease; 10.6 % had a positive MUST at the time of admission and 19.2 % at discharge; 100 % of malnourished patients at admission remained in the same situation at discharge. During hospitalization, in 29 patients (27.9 %) the nutritional situation worsened. In all, 81.25 % of patients who experienced worsening of their MUST score had been admitted urgently (p < 0.05). Patients who required urgent surgery significantly worsened in terms of their nutritional status (p < 0.001). Patients with worsening nutritional status obtained higher rates for: surgical reintervention (p < 0.05), pharmaceutical expense (p = 0.017), total hospital expense (€1,000/patient/admission), transfers to chronic care centers (p = 0.0002), and number of early readmissions (p = 0.017). Conclusion: patients with nutritional risk suffered an increase in medical-surgical complications, hospital stay, healthcare costs, and re-admission rates. Therefore, we consider that an implementation of screening procedures and the development of further studies in the vascular surgery setting are necessary.

INTRODUCCIÓN: Introducción y objetivos: la desnutrición relacionada con la enfermedad produce un impacto negativo en la evolución del paciente quirúrgico. Nuestro objetivo es valorar la prevalencia del riesgo nutricional en el ámbito de la cirugía vascular y sus consecuencias en la evolución del paciente y el gasto sanitario. Pacientes y métodos: estudio observacional prospectivo realizado durante 6 meses en la planta de cirugía vascular del Hospital Universitario de León. Se utilizó la herramienta Malnutrition Universal Screening Tool (MUST) para recoger datos al ingreso y cada 7 días hasta el alta hospitalaria. Se estudiaron las variables clínicas, la intervención quirúrgica realizada, las complicaciones médico-quirúrgicas, la estancia hospitalaria, los costes sanitarios y los reingresos precoces. Resultados: el estudio contó con 104 pacientes, de los que el 84,6 % eran varones, cuya media de edad era de 69 años (DE: 13). El 46,2 % habían ingresado por enfermedad arterial periférica. El 10,6 % presentaban un MUST positivo al ingreso y el 19,2 % lo presentaban al alta; el 100 % de los pacientes desnutridos al ingreso permanecían en la misma situación al alta. Durante la hospitalización, en 29 pacientes (27,9 %) empeoró la situación nutricional. El 81,25 % de los pacientes que sufrieron empeoramiento del MUST habían ingresado de forma urgente (p < 0,05). Los pacientes que habían precisado una cirugía urgente empeoraron significativamente en términos de su estado nutricional (p < 0,001). Los pacientes con empeoramiento del estado nutricional obtuvieron mayores porcentajes de: reintervención quirúrgica (p < 0,05), gasto farmacéutico (p = 0,017), gasto hospitalario total (1000 €/paciente/ingreso), traslados a centros de cuidados crónicos (p = 0,0002) y número de reingresos precoces (p = 0,017). Conclusiones: los pacientes en riesgo nutricional se asociaron a un incremento de las complicaciones médico-quirúrgicas, de la estancia hospitalaria, del coste sanitario y de la tasa de reingresos, por lo que consideramos necesaria la implantación de cribados y el desarrollo de estudios en el ámbito de la cirugía vascular.

Implementación de una actividad física en residentes de pediatría y síndrome de Burnout

RESUMEN Introducción: La residencia es un periodo en la formación del médico muy diferente a lo aprendido en la universidad. Objetivo: evaluar el efecto de la actividad física en residentes de pediatría, sobre el Síndrome de Burnout. Materiales y Métodos: Estudio de intervención no aleatorizado controlado. Los residentes de Pediatría fueron asignados a recibir clases de Zumba 2 horas semanales por 10 semanas (grupo estudio) o ninguna intervención (grupo control). Se midió el Síndrome de Burnout utilizando el cuestionario Maslach Burnout Inventory pre y post intervención en ambos grupos. Otras variables estudiadas fueron: edad, género, actividad física y social, estructura familiar y años de residencia. Los datos fueron analizados con SPSS. Se consideró un error alfa inferior al 5%. El protocolo fue aprobado por el comité de ética del hospital, con consentimiento de los participantes. Resultados: Participaron 47 residentes, 23 en el grupo estudio y 24 en el grupo control. El Síndrome de Burnout pre- intervención fue 52,2 % y 37,5 % en el grupo estudio y el grupo control respectivamente p=0,31. Después de la intervención fue de 17,4 % y 45,8% en el grupo estudio y control respectivamente. OR: 0,25 (IC95% 0,65 -0,9) p=0,03. El beneficio absoluto fue del 35% y el número necesario para tratar 2,8. Conclusiones: El ejercicio físico 2 horas semanales mitigó el síndrome de burnout en residentes de Pediatría, con un beneficio absoluto del 35%.

ABSTRACT Introduction: Residency is a period in the training of the doctor very different from what was learned at the university level. Objective: evaluate the effect of physical activity in pediatric residents regarding Burnout Syndrome. Materials and Methods: This was a non-randomized controlled intervention study. Pediatric residents were assigned to receive Zumba classes 2 hours per week for 10 weeks (study group) or no intervention (control group). Burnout Syndrome was measured using the Maslach Burnout Inventory questionnaire pre and post intervention in both groups. Other variables studied were: age, gender, physical and social activity, family structure and years of residence. The data were analyzed with SPSS. An alpha error of less than 5% was considered. The protocol was approved by the ethics committee of the hospital, with participants' consent. Results: 47 residents participated, 23 in the study group and 24 in the control group. Pre-intervention Burnout Syndrome was 52.2% and 37.5% in the study group and the control group, respectively, p = 0.31. After the intervention it was 17.4% and 45.8% in the study and control group respectively. OR: 0.25 (95% CI 0.65 -0.9) p = 0.03. The absolute benefit was 35% and the number needed to treat 2.8. Conclusions: Physical exercise for 2 hours a week alleviated burnout syndrome in Pediatric residents, with an absolute benefit of 35%.

Development of cell-based high throughput luminescence assay for drug discovery in inhibiting OCT4/DNA-PKcs and OCT4-MK2 interactions.

Amplification-independent c-MYC overexpression is suggested in multiple cancers. Targeting c-MYC activity has therapeutic potential, but efforts thus far have been mostly unsuccessful. To find a druggable target to modulate c-MYC activity in cancer, we identified two kinases, MAPKAPK2 (MK2) and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which phosphorylate the Ser111 and the Ser93 residues of OCT4, respectively, to transcriptionally activate c-MYC. Using these observations, we present here a novel cell-based luminescence assay to identify compounds that inhibit the interaction between these kinases and OCT4. After screening approximately 80,000 compounds, we identified 56 compounds ("hits") that inhibited the luminescence reaction between DNA-PKcs and OCT4, and 65 hits inhibiting the MK2-OCT4 interaction. Using custom antibodies specific for pOCT4S93 and pOCT4S111 , the "hits" were validated for their effect on OCT4 phosphorylation and activation. Using a two-step method for validation, we identified two candidate compounds from the DNA-PKcs assay and three from the MK2 assay. All five compounds demonstrate a significant ability to kill cancer cells in the nanomolar range. In conclusion, we developed a cell-based luminescence assay to identify novel inhibitors targeting c-MYC transcriptional activation, and have found five compounds that may function as lead compounds for further development.

Surgical results and the location of pathological glands in the treatment of primary sporadic hyperparathyroidism with negative preoperative 99mTc-sestamibi scintigraphy. / Resultados quirúrgicos y localización de las glándulas patológicas en el tratamiento del hiperparatiroidismo primario esporádico con gammagrafía 99mTc-sestamibi negativa.

INTRODUCTION: The primary hyperparathyroidism is a frequent disease whom the surgery is the only curative treatment. The preoperative location imaging techniques could help in the surgical management. Our objective was to analyze surgical results regarding the cure rate, etiology and location of the glands responsible for the primary hyperparathyroidism in patients with negative preoperative 99mTc-sestamibi scintigraphy. METHODS: Observational study in patients with the diagnosis of primary sporadic hyperparathyroidism with negative 99mTc-sestamibi scintigraphy, operated consecutively in an Endocrine Surgery Unit for 18 years. The cure rate, the intraoperatory parathyroid hormone (PTH), the etiology and the pathological glands location were analyzed. RESULTS: In the study were included 120 patients. After surgery 95% of patients (n = 114) presented cure criteria of hyperparathyroidism. The 14.1% presented a multigland disease; 69% of the adenomas presented a typical perithyroid location, founding a percentage of 23.9% of ectopic adenomas in cervical location and a 7.1% in mediastinum. CONCLUSIONS: The absence of uptake in the 99mTc-sestamibi scintigraphy should not condition the surgical indication. The success with experienced surgeons is similar to patients with positive results. The surgical indication must be established by clinical and biochemistry criteria.

Short- and long-term outcome of patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To describe short-term and 5-year rates of mortality and poor outcome in patients with spontaneous aneurysmal subarachnoid hemorrhage (aSAH) who received repair treatment. METHODS: In this prospective observational study, mortality and poor outcome (modified Rankin Scale score 3-6) were analyzed in 311 patients with aSAH at 3 months, 1 year, and 5 years follow-up. Sensitivity analysis was performed according to treatment modality. In-hospital and 5-year complications were analyzed. RESULTS: Of 476 consecutive patients with spontaneous subarachnoid hemorrhage, 347 patients (72.9%) had aSAH. Of these, 311 (89.6%) were treated (242 endovascular, 69 neurosurgical), with a mean follow-up of 43.4 months (range, 1 to 145). Three-month, 1-year, and 5-year mortality was 18.4%, 22.9%, and 29.0%, and poor outcome was observed in 42.3%, 36.0%, and 36.0%, respectively. Adjusted poor outcome was lower in endovascular than in neurosurgical treatment at 3 months (odds ratio [OR] 0.36 [95% confidence interval [CI] 0.18-0.74]), with an absolute difference of 15.8% (number needed to treat = 6.3), and at 1 year (OR = 0.40 [95% CI 0.20-0.81]), with an absolute difference of 15.9% (number needed to treat = 6.3). Complications did not differ between the 2 procedures. However, mechanical ventilation was less frequent with the endovascular technique (OR 0.67 [95% CI 0.54-0.84]). CONCLUSIONS: Patients with aSAH treated according to current guidelines had a short-term mortality of 18.4% and 5-year mortality of 29%. The majority (64.0%) of patients remained alive without disabilities at 5-year follow-up. Patients prioritized to endovascular treatment had better outcomes than those referred to neurosurgery because endovascular coiling was not feasible.