Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis.

Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10-5) and MSK-IMPACT cohorts (p-value = 3.062 × 10-2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients.

CyberKnife Stereotactic Radiosurgery for Uveal Melanoma: First Case Series in Central America.

Introduction: Uveal melanoma is the most common primary intraocular malignancy in adults, affecting primarily the choroid of the eye. Plaque brachytherapy is the most common procedure for the treatment of small choroidal melanoma, especially in posteriorly located tumors. However, modern radiotherapy techniques, such as CyberKnife or Gamma knife stereotactic radiosurgery (SRS) and proton beam radiotherapy, have shown better results in tumor control and eye retention. Recent studies have indicated that SRS is a promising non-invasive, single-session treatment option, with most studies reporting the best outcomes when using ≥21-22 Gy. However, there is no consistent protocol for managing this pathology using CyberKnife, not only in terms of dose but also fractions. Case Presentations: Here, we report the first case series of patients (n = 4, age range 38-64 years, median age 52.5 years) with choroidal UM in Central America who were treated with CyberKnife SRS (22 Gy in one session). During the follow-up (range 25-29 months, median 27.5 months), a 100% control rate with no systemic metastatic disease has been achieved. We found a statistically significant reduction in the largest basal diameter at 24 months for all tumors. However, visual acuity has progressively decreased in most patients. Notably, two of our patients developed radiation maculopathy, and the other two developed radiation retinopathy after SRS. Conclusions: Our findings suggest that future studies should evaluate the use of different prophylactic therapies to prevent the development of side effects. The clinical management of toxicities presented in our report can serve as a reference in the clinical practice of other centers. Our report supports the growing body of evidence showing that CyberKnife radiosurgery is a safe and effective therapeutic option for the treatment of UM.

A Comprehensive Analysis of the Effect of A>I(G) RNA-Editing Sites on Genotoxic Drug Response and Progression in Breast Cancer.

Dysregulated A>I(G) RNA editing, which is mainly catalyzed by ADAR1 and is a type of post-transcriptional modification, has been linked to cancer. A low response to therapy in breast cancer (BC) is a significant contributor to mortality. However, it remains unclear if there is an association between A>I(G) RNA-edited sites and sensitivity to genotoxic drugs. To address this issue, we employed a stringent bioinformatics approach to identify differentially RNA-edited sites (DESs) associated with low or high sensitivity (FDR 0.1, log2 fold change 2.5) according to the IC50 of PARP inhibitors, anthracyclines, and alkylating agents using WGS/RNA-seq data in BC cell lines. We then validated these findings in patients with basal subtype BC. These DESs are mainly located in non-coding regions, but a lesser proportion in coding regions showed predicted deleterious consequences. Notably, some of these DESs are previously reported as oncogenic variants, and in genes related to DNA damage repair, drug metabolism, gene regulation, the cell cycle, and immune response. In patients with BC, we uncovered DESs predominantly in immune response genes, and a subset with a significant association (log-rank test p < 0.05) between RNA editing level in LSR, SMPDL3B, HTRA4, and LL22NC03-80A10.6 genes, and progression-free survival. Our findings provide a landscape of RNA-edited sites that may be involved in drug response mechanisms, highlighting the value of A>I(G) RNA editing in clinical outcomes for BC.

Dual-Target Radiosurgery for Concomitant Continuous Pain Presentation of Trigeminal Neuralgia: Radiomodulation Effect and Dose.

OBJECTIVES: Patients with trigeminal neuralgia (TN) experience concomitant continuous pain (CCP) that can be difficult to treat. A dual-target approach delivering a high dose of radiation to the nerve and the contralateral thalamus can develop a fast radiomodulation effect on lowering pain. We sought to determine if this effect was dose dependent. METHODS: We retrospectively reviewed 21 patients treated with radiosurgery in CCP and severe TN pain, with a visual analog scale (VAS) score of nine out of 10 at the time of treatment. Ten patients were treated with a high dose (>120 Gy) in the thalamus 90 Gy to the nerve, and the rest with a low dose (<120 Gy) to the thalamus and >90 Gy to the nerve. RESULTS: Of those who received the high dose to the thalamus, six patients (60%) received 140 Gy, and four (40%) received 120 Gy, with a median dose to the trigeminal nerve of 90 and 85 Gy, respectively. The high thalamus dose showed a radiomodulation effect from day 1. The low thalamus dose did not produce radiomodulation on any of the first four days. The percentage of VAS score reduction one month after treatment was higher in the high-thalamus dose group than in the low-thalamus dose group. At three months, VAS score was 2 in the high-dose group and 4 in the low-dose group. CONCLUSIONS: The radiomodulation effect in pain and dual-target radiosurgery is dose dependent in CCP in TN; a high dose can provide a more consistent clinical result than a lower dose.

Selective Concurrence of the Long Non-Coding RNA MALAT1 and the Polycomb Repressive Complex 2 to Promoter Regions of Active Genes in MCF7 Breast Cancer Cells.

In cancer cells, the long non-coding RNA (lncRNA) MALAT1 has arisen as a key partner for the Polycomb Repressive Complex 2 (PRC2), an epigenetic modifier. However, it is unknown whether this partnership occurs genome-wide at the chromatin level, as most of the studies focus on single genes that are usually repressed. Due to the genomic binding properties of both macromolecules, we wondered whether there are binding sites shared by PRC2 and MALAT1. Using public genome-binding datasets for PRC2 and MALAT1 derived from independent ChIP- and CHART-seq experiments performed with the breast cancer cell line MCF7, we searched for regions containing PRC2 and MALAT1 overlapping peaks. Peak calls for each molecule were performed using MACS2 and then overlapping peaks were identified by bedtools intersect. Using this approach, we identified 1293 genomic sites where PRC2 and MALAT1 concur. Interestingly, 54.75% of those sites are within gene promoter regions (<3000 bases from the TSS). These analyses were also linked with the transcription profiles of MCF7 cells, obtained from public RNA-seq data. Hence, it is suggested that MALAT1 and PRC2 can concomitantly bind to promoters of actively-transcribed genes in MCF7 cells. Gene ontology analyses revealed an enrichment of genes related to categories including cancer malignancy and epigenetic regulation. Thus, by re-visiting occupancy and transcriptomic data, we identified a key gene subset controlled by the collaboration of MALAT1 and PRC2.

Caracterización clínica y epidemiológica de pacientes con fractura nasal atendidos en un hospital universitario cubano

Introducción: Las fracturas nasales son las más comunes de la región maxilofacial. Sin embargo, la literatura cubana sobre el tema es escasa y desactualizada, por lo que surgió la motivación para realizar esta investigación. Objetivo: Caracterizar clínica y epidemiológicamente los pacientes con fractura nasal atendidos en un hospital universitario cubano. Métodos: Se realizó un estudio observacional, descriptivo y transversal en pacientes atendidos en el Servicio de Cirugía Maxilofacial del Hospital General Universitario "Carlos Manuel de Céspedes" de Bayamo, provincia Granma, Cuba, en el período comprendido entre el 1 de enero y el 31 de diciembre del 2020. Se estudiaron variables clínicas, epidemiológicas y terapéuticas. Resultados: Se incluyeron 99 pacientes, de los cuales 74 (74,75 por ciento) fueron masculinos. En el 44,44 por ciento de los casos las edades estuvieron comprendidas entre los 21 y 40 años. Cincuenta pacientes (50,51 por ciento) tuvieron fracturas producto de la violencia interpersonal. Noventa y siete pacientes (97,98 por ciento) presentaron epistaxis. Cincuenta y nueve pacientes (59,60 por ciento) recibieron reducción cerrada asociada con taponamiento nasal y fijación externa con yeso. Conclusiones: Predominó el sexo masculino y el grupo de edades de 21 a 40 años. La principal etiología fue la violencia interpersonal. En la mayoría de los casos la epistaxis estuvo presente. Prevalecieron las fracturas cerradas, así como las que tuvieron el dorso desviado lateralmente(AU)

Introduction: Nasal fractures are the most common fractures of the maxillofacial region. However, Cuban literature on the subject is scarce and outdated, so the motivation for this research arose. Objective: To characterize patients with nasal fractures treated in a Cuban university hospital in a clinical and epidemiological manner. Methods: An observational, descriptive and cross-sectional study was carried out in patients treated at the Maxillofacial Surgery Service of the University General Hospital. "Carlos Manuel de Céspedes" of Bayamo, Granma province, Cuba, from January 1 to December 31, 2020. Clinical, epidemiological and therapeutic variables were studied. Results: 99 patients were included, of whom 74 (74.75 percent) were male. In 44.44 percent of the cases the ages were between 21 and 40 years. Fifty patients (50.51 percent) had fractures resulting from interpersonal violence. Ninety-seven patients (97.98 percent) presented epistaxis. Fifty-nine patients (59.60 percent) received closed reduction associated with nasal packing and external fixation with plaster cast. Conclusions: Male gender and age group 21 to 40 years predominated. The main etiology was interpersonal violence. Epistaxis was present in most cases. Closed fractures prevailed, as well as those with laterally deviated dorsum(AU)

A randomised controlled trial testing the rebound-preventing benefit of four days of prednisolone during the induction of oclacitinib therapy in dogs with atopic dermatitis.

BACKGROUND: A rebound of pruritus occasionally occurs after oclacitinib dose reduction in dogs with atopic dermatitis (AD). OBJECTIVES: To determine whether an initial 4-day course of prednisolone decreases the probability of a pruritus rebound after reducing the frequency of oclacitinib administration. ANIMALS: Forty dogs with mild-to-moderate AD lesions and moderate-to-severe pruritus. MATERIALS AND METHODS: Dogs were randomised to receive oclacitinib at 0.4-0.6 mg/kg twice daily for 14 days then once daily, alone or with prednisolone at 0.5 mg/kg, orally, twice daily for the first 4 days. Clinicians graded the Canine Atopic Dermatitis Extent and Severity Index (CADESI)4 and 2D-investigator global assessment (IGA) before and after 28 days; owners assessed the pruritis Visual Analog Scale (PVAS)10 and Owner Global Assessment of Treatment Efficacy (OGATE) on Day (D)0, D4, D14, D21 and D28. We considered a rebound any increase greater than one PVAS10 grade at D21 compared to D14. RESULTS: On D21, there were significantly fewer rebounds in the dogs receiving prednisolone (three of 20, 15%) compared to those given oclacitinib alone (nine of 20, 45%; Fisher's test, p = 0.041). Compared to oclacitinib monotherapy, the concurrent administration of prednisolone for the first 4 days led to significantly lower PVAS10 on D4 and D28, CADESI4 and 2D-IGA on D28, and OGATE on D21 and D28 (Wilcoxon-Mann-Whitney U-tests). Adverse effects of therapy were minor, intermittent and self-resolving. CONCLUSIONS AND CLINICAL RELEVANCE: The initial addition of 4 days of prednisolone significantly decreased the probability of a rebound of pruritus 1 week after oclacitinib dose reduction. This short concomitant glucocorticoid administration led to a higher skin lesion improvement and improved perception of treatment efficacy with minimal adverse effects.

Impact of the COVID-19 on the epidemiology of maxillofacial fractures surgically treated in a Cuban university hospital / Impacto del COVID-19 en la epidemiología de las fracturas maxilofaciales tratadas quirúrgicamente en un hospital universitario cubano

Introduction: COVID-19 pandemic has had a significant impact on people's behavior. Aim: To evaluate the impact of the COVID-19 on the epidemiology of maxillofacial fractures surgically treated in a Cuban university hospital. Methods: This research involved a 4-year descriptive, comparative, retrospective and cross-sectional study. Patients surgically treated between March 1 and December 31, 2020 (COVID-19 period) were compared with those who had undergone surgery between the same date in the years 2017-2019 (non-pandemic period). Age, sex, residence, year, month, alcohol consumption at the time of trauma, etiology, fractures types, and number of fractures per patient were recorded. Results: A decline in patients with maxillofacial fractures in 2020 (n=25) was observed when compared to equivalent periods in the three previous years (2017: n=37; 2018: n=31; 2019: n=41), respectively, with an annual average reduction of 31.19 percent. Interpersonal violence was found to be the paramount etiological factor for maxillofacial fractures during the comparison periods (2017-2019); however, road traffic accident prevailed in the 2020 (n=12; 48 percent). There was a small increase in the number of alcohol-related fractures (56 percent in 2020 vs 46.34 percent, 41.94 percent, and 51.35 percent in 2019, 2018, and 2017, respectively). Conclusion: COVID-19 impacted on the epidemiology maxillofacial fractures surgically treated in this Cuban university hospital (AU)

Introducción: La pandemia de la COVID-19 ha tenido un impacto significativo en el comportamiento de la población. Objetivo: Evaluar el impacto de la COVID-19 en la epidemiología de las fracturas maxilofaciales tratadas quirúrgicamente en un hospital universitario cubano. Métodos: Esta investigación consistió en un estudio descriptivo, comparativo, retrospectivo y transversal de 4 años de duración. Se compararon los pacientes intervenidos quirúrgicamente entre el 1 de marzo y el 31 de diciembre de 2020 (periodo COVID-19) con los intervenidos entre la misma fecha en los años 2017-2019 (periodo no pandémico). Se registraron edad, sexo, residencia, año, mes, consumo de alcohol en el momento del traumatismo, etiología, tipos de fracturas y número de fracturas por paciente. Resultados: Se observó un descenso de pacientes con fracturas maxilofaciales en 2020 (n=25) en comparación con periodos equivalentes de los tres años anteriores (2017: n=37; 2018: n=31; 2019: n=41), respectivamente, con una reducción media anual del 31,19 poe ciento. Se observó que la violencia interpersonal fue el factor etiológico primordial de las fracturas maxilofaciales durante los periodos de comparación (2017-2019); sin embargo, el accidente de tráfico prevaleció en el 2020 (n=12; 48 por ciento). Hubo un pequeño aumento en el número de fracturas relacionadas con el alcohol (56 por ciento en 2020 frente a 46,34 por ciento, 41,94 por ciento y 51,35 por ciento en 2019, 2018 y 2017, respectivamente). Conclusiones: La COVID-19 impactó en la epidemiología de fracturas maxilofaciales atendidas quirúrgicamente en este hospital universitario cubano (AU)

Caracterización de las fracturas nasales atendidas en el servicio de urgencias de cirugía maxilofacial de Bayamo / Characterization of nasal fractures treated in the maxillofacial surgery emergency service of Bayamo / Caracterização de fraturas nasais tratadas no pronto-socorro de cirurgia maxilofacial de Bayamo

RESUMEN La fractura nasal es la más frecuente entre las fracturas de los huesos faciales, pudiendo generar alteraciones estéticas importantes y a su vez determinar cambios en la funcionalidad, tratarlas de forma inmediata evita complicaciones al paciente. Con el objetivo de caracterizar las fracturas nasales atendidas en el servicio de urgencias de cirugía maxilofacial del hospital "Carlos Manuel de Céspedes" se realizó un estudio observacional descriptivo que incluyó todos los pacientes (105) que fueron atendidos ambulatoriamente con diagnóstico de fractura nasal reciente en el servicio de urgencias en el período de enero 2018 a diciembre del 2019. Las variables estudiadas fueron edad, sexo, procedencia, factores etiológicos, signos clínicos, clasificación según desplazamiento, exposición del foco de fractura y dirección del trauma. Se confeccionó una planilla de recolección de datos. Se emplearon números enteros, porcentajes y tablas estadísticas. Se siguieron los principios éticos para la investigación en humanos. La población más afectada se encontró entre los 20 y 29 años de edad, de procedencia urbana y del sexo masculino. Se encontró asociación entre el sexo y los factores etiológicos, predominando las agresiones físicas en hombres y las caídas casuales en mujeres. El principal signo clínico presente en los pacientes fue la epistaxis. Las fracturas nasales desplazadas, con desviaciones laterales y cerradas predominaron en ambos sexos.

ABSTRACT The nasal fracture is the most frequent among the fractures of the facial bones, being able to generate important aesthetic alterations and in turn determine changes in functionality, treating them immediately avoids complications for the patient. In order to characterize the nasal fractures treated in the maxillofacial surgery emergency service of the "Carlos Manuel de Céspedes" hospital, a descriptive observational study was carried out that included all the patients (105) who were seen outpatiently with a diagnosis of recent nasal fracture in the emergency department in the period from January 2018 to December 2019. The variables studied were age, sex, origin, etiological factors, clinical signs, classification according to displacement, exposure of the fracture site and direction of the trauma. A data collection sheet was prepared. Whole numbers, percentages and statistical tables were used. Ethical principles for human research were followed. The most affected population was between 20 and 29 years of age, of urban origin and male. An association was found between sex and etiological factors, predominantly physical aggression in men and accidental falls in women. The main clinical sign present in the patients was epistaxis. Displaced nasal fractures with lateral and closed deviations predominated in both sexes.

RESUMO A fratura nasal é a mais frequente entre as fraturas dos ossos faciais, sendo capaz de gerar alterações estéticas importantes e, por sua vez, determinar alterações na funcionalidade, tratando-as imediatamente evita complicações para o paciente. Com o objetivo de caracterizar as fraturas nasais atendidas no pronto-socorro de cirurgia maxilofacial do hospital Carlos Manuel de Céspedes, foi realizado um estudo observacional descritivo que incluiu todos os pacientes (105) que foram atendidos ambulatorialmente com diagnóstico de fratura nasal recente no pronto-socorro no período de janeiro de 2018 a dezembro de 2019. As variáveis estudadas foram idade, sexo, origem, fatores etiológicos, sinais clínicos, classificação segundo deslocamento, exposição do foco da fratura e direção do trauma. Um formulário de coleta de dados foi preparado. Foram utilizados números completos, percentuais e tabelas estatísticas. Foram seguidos princípios éticos para a pesquisa humana. A população mais afetada foi entre 20 e 29 anos, de origem urbana e do sexo masculino. Foi encontrada associação entre sexo e fatores etiológicos, com aagressão física predominante em homens e quedas casuais nas mulheres. O principal sinal clínico presente nos pacientes foi a epistaxe. Fraturas nasais deslocadas, com desvios laterais e fechados predominaram em ambos os sexos.

Radiomodulation in Mixed, Complex Cancer Pain by Triple Target Irradiation in the Brain: A Preliminary Experience.

Introduction Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach. Methods Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment. A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed. Results Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation. Conclusions In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target "large" dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication.

Características clínicas, epidemiológicas y terapéuticas de pacientes con carcinoma epidermoide de cavidad bucal / Clinical, epidemiological and therapeutic characteristics of patients with oral cavity squamous cell carcinoma

RESUMEN Introducción: La región de la cabeza y el cuello es una de las áreas más complejas del cuerpo y el carcinoma epidermoide es la neoplasia maligna más frecuente en esta localización. Objetivo: Caracterizar, desde el punto de vista clínico, epidemiológico y terapéutico, los pacientes con carcinoma epidermoide de cavidad bucal. Métodos: Estudio observacional, descriptivo y transversal en pacientes tratados en un servicio de cirugía maxilofacial entre el 1 de enero de 2018 y el 31 de diciembre de 2020. Se analizaron variables clínicas, epidemiológicas y terapéuticas. La información se obtuvo mediante la entrevista y el examen clínico. Como medidas de resumen se utilizaron frecuencias absolutas y porcentajes. Resultados: Se estudiaron 29 pacientes, con predominio del sexo masculino (69,0 %). La edad media fue de 60,3 años (rango entre 41 y 80 años). La lengua fue la región anatómica más afectada (34,5 %) y la úlcera hundida o infiltrante la variante clínica de mayor presentación (27,6 %). El 48,3 % de las neoplasias fueron diferenciadas histológicamente. El 65,5 % de los diagnósticos se realizó en estadios avanzados de la enfermedad (etapas III y IV). Los tratamientos más utilizados fueron la cirugía (31,0 %) y la combinación de quimioterapia más radioterapia (27,6 %). Conclusión: Predominan los pacientes masculinos, las lesiones linguales, de aspecto ulcerado y diferenciadas histológicamente. La modalidad terapéutica más utilizada fue la cirugía.

ABSTRACT Introduction: Head and neck region is one of the more complex areas of the body and the squamous cell carcinoma is the most frequent malignant neoplasm in this location. Objective: To characterize, from a clinic, epidemiologic and therapeutic point of view, patients with squamous cell carcinoma of the oral cavity. Methods: Observational, descriptive and cross-sectional study with patients treated in maxillofacial surgery service between January 1, 2018 and December 31, 2020. Clinic, epidemiologic and therapeutic variables were analyzed. The information was obtained through interview and clinical examination. Absolute frequencies and percentages were used as summary measures. Results: Twenty-nine (29) patients, with a predominance of males (69.0 %), were studied. Mean age was 12 years (range between 41 and 80 years). The tongue was the most affected anatomical region (34.5 %) and the sunken or infiltrating ulcer was the most common clinical variant (27.6 %); 48.3 % of the neoplasms were differentiated histologically. 65.5 % of the diagnoses were made in advanced stages of the disease (stages III and IV). The most used treatments were surgery (31.0 %) and the combination of chemotherapy plus radiotherapy (27.6 %). Conclusion: Male patients, lingual lesions, ulcerated appearance and histologically differentiated predominated. The most used therapeutic modality was surgery.

Mortality due to COVID-19 in Spain and its association with environmental factors and determinants of health.

Background: The objective of this study was to identify which air pollutants, atmospheric variables and health determinants could influence COVID-19 mortality in Spain. This study used information from 41 of the 52 provinces in Spain (from Feb. 1, to May 31, 2021). Generalized Linear Models (GLM) with Poisson link were carried out for the provinces, using the Rate of Mortality due to COVID-19 (CM) per 1,000,000 inhabitants as dependent variables, and average daily concentrations of PM10 and NO2 as independent variables. Meteorological variables included maximum daily temperature (Tmax) and average daily absolute humidity (HA). The GLM model controlled for trend, seasonalities and the autoregressive character of the series. Days with lags were established. The relative risk (RR) was calculated by increases of 10 g/m3 in PM10 and NO2 and by 1 â„ƒ in the case of Tmax and 1 g/m3 in the case of HA. Later, a linear regression was carried out that included the social determinants of health. Results: Statistically significant associations were found between PM10, NO2 and the CM. These associations had a positive value. In the case of temperature and humidity, the associations had a negative value. PM10 being the variable that showed greater association, with the CM followed of NO2 in the majority of provinces. Anyone of the health determinants considered, could explain the differential geographic behavior. Conclusions: The role of PM10 is worth highlighting, as the chemical air pollutant for which there was a greater number of provinces in which it was associated with CM. The role of the meteorological variables-temperature and HA-was much less compared to that of the air pollutants. None of the social determinants we proposed could explain the heterogeneous geographical distribution identified in this study. Supplementary Information: The online version contains supplementary material available at 10.1186/s12302-022-00617-z.

Visual Symptoms Outcomes in Cavernous Sinus Radiosurgery and a Systematic Review.

Introduction The complex anatomy of the cavernous sinus confers a true challenge when it comes to safe tumor resection. Due to its non-invasive nature, stereotactic radiosurgery (SRS) is expected to have lower mortality and morbidity rates than microsurgery. The purpose of this study was to evaluate clinical results regarding visual symptoms after SRS for benign tumors invading the cavernous sinus. We also conducted a systematic literature review to provide a robust analysis regarding visual outcomes. Methods The study included 58 patients (43 women and 15 men; mean age: 52 years) with benign tumors invading the cavernous sinus (27 pituitary adenomas and 31 meningiomas) who underwent SRS with different platforms between August 2011 and December 2021. Of these, 26 patients underwent surgery before SRS, and the remaining 32 had SRS as first-line therapy. We identified symptoms involving cranial nerves (CN) II, III, IV, and VI in 38 patients at the time of SRS. We conducted a systematic review to identify all original studies assessing visual outcomes. We searched PubMed, the Latin American and Caribbean Health Sciences Literature index, and Google Scholar using the Medical Subject Heading search terms "radiosurgery" and "cavernous sinus" for valid studies published until January 31, 2022. Results Regarding pituitary adenomas, median tumor volume was 2.05 cc, 3.12 cc, and 2.39 cc for Gamma Knife (GK), CyberKnife (CK), and tomotherapy (Tomo), respectively. Median doses were 14 Gy for GK, 17 Gy for CK, and 15 Gy for Tomo. For meningiomas, median tumor volume was 10.2 cc, 2.62 cc, and 16.3 cc for GK, CK, and Tomo, respectively. The median dose was 14 Gy for GK, 14 Gy for CK, and 14.5 Gy for Tomo. The overall tumor control rate was 100% with a median follow-up of 33 months (range: 6-128 months). A reduction of >30% in total tumor size per the Response Evaluation Criteria in Solid Tumors (RECIST) classification was documented in seven patients (RECIST II; 12.1%), 51 patients (87.9%) had stable disease (RECIST III), and no increase in tumor volume was documented in any patient. Visual symptoms improved in 51.7% of patients. In the systematic review, the mean visual improvement was 36% (range: 25.8-42.5%). Conclusion SRS is an effective treatment for benign tumors invading the cavernous sinus. In this series, patients who underwent SRS as a primary treatment showed improvement in pre-existing cranial neuropathy and visual symptoms. Given the natural history of these tumors, which tend to grow and cause visual alternations, treating asymptomatic patients is a feasible approach worth considering for the appropriate patients.

Short-term influence of environmental factors and social variables COVID-19 disease in Spain during first wave (Feb-May 2020).

This study aims to identify the combined role of environmental pollutants and atmospheric variables at short term on the rate of incidence (TIC) and on the hospital admission rate (TIHC) due to COVID-19 disease in Spain. This study used information from 41 of the 52 provinces of Spain (from Feb. 1, 2021 to May 31, 2021). Using TIC and TIHC as dependent variables, and average daily concentrations of PM10 and NO2 as independent variables. Meteorological variables included maximum daily temperature (Tmax) and average daily absolute humidity (HA). Generalized linear models (GLM) with Poisson link were carried out for each provinces The GLM model controlled for trend, seasonalities, and the autoregressive character of the series. Days with lags were established. The relative risk (RR) was calculated by increases of 10 µg/m3 in PM10 and NO2 and by 1 °C in the case of Tmax and 1 g/m3 in the case of HA. Later, a linear regression was carried out that included the social determinants of health. Statistically significant associations were found between PM10, NO2, and the rate of COVID-19 incidence. NO2 was the variable that showed greater association, both for TIC as well as for TIHC in the majority of provinces. Temperature and HA do not seem to have played an important role. The geographic distribution of RR in the studied provinces was very much heterogeneous. Some of the health determinants considered, including income per capita, presence of airports, average number of diesel cars per inhabitant, average number of nursing personnel, and homes under 30 m2 could explain the differential geographic behavior. As findings indicates, environmental factors only could modulate the incidence and severity of COVID-19. Moreover, the social determinants and public health measures could explain some patterns of geographically distribution founded.

Influence of home/school environments on children's obesity, diet, and physical activity: the SUECO study protocol / Impacto del entorno residencial/escolar en la obesidad, la dieta y la actividad física en población infantil: protocolo del estudio SUECO

Objective: The SUECO study examines the relationship between urban obesogenic environments and health outcomes among school-age children in the city of Madrid, Spain. We will study how features of the urban environment (related to the food- and the physical activity environment) associate with children's anthropometrics, eating habits, and physical activity levels. Method: We describe the study protocol of this multilevel study in a representative sample of school-age children in the city of Madrid (2017; n=5,961 children ages 3-12). Main outcome variables include anthropometrics (body mass index, waist circumference, and body fat), healthy and unhealthy consumption measures, and physical activity measures. The primary explanatory variables are grouped into food environment (e.g., unhealthy food retailers' density) and physical activity environment (e.g., walkability, physical activity opportunities) variable categories. Multilevel models will be used to calculate the associations between each indicator and obesity and physical inactivity. (AU)

Objetivo: El estudio SUECO evaluará la relación entre el entorno urbano obesogénico y los resultados en salud en la población infantil escolarizada en Madrid. El estudio explorará cómo influyen las características del entorno urbano (relacionadas con la alimentación y con la actividad física) en las variables antropométricas, los hábitos alimentarios y la actividad física. Método: Se presenta el protocolo de este estudio multinivel, realizado con una muestra representativa de población infantil escolarizada en la ciudad de Madrid (2017; n=5961 escolares de 3 a 12 años). Las principales variables de resultado incluyen antropometría (índice de masa corporal, circunferencia de cintura y porcentaje de grasa corporal), hábitos alimentarios (saludables y no saludables) y actividad física. Las principales variables independientes son contextuales (del entorno alimentario y del entorno de actividad física). Se utilizarán modelos de regresión multinivel para evaluar las asociaciones entre cada indicador contextual, la obesidad y la inactividad física. (AU)

Inhibition of glutathione reductase uncovers the activation of NADPH-inhibited glucose-6-phosphate dehydrogenase.

Eggleston and Krebs pointed to a paradox in glucose-6-phosphate dehydrogenase (G6PD) regulating process that has not yet been solved, and which originated the term "fine regulation" of G6PD and, therefore, of oxidative phase of pentose phosphate pathway (OPPP). The paradox is that, in basal-like conditions, the activity of G6PD evaluated "in vitro" is very low or nearly null because of the potent inhibiting effect exerted by NADPH, a coenzyme whose concentration in the cell is much higher than that of the substrate NADP+ . However, "in vivo," flow through OPPP occurs in basal conditions. Eggleston and Krebs speculated on the possible existence of a system that would reverse the inhibition by NADPH. Such system would involve oxidized glutathione and exclude the participation of glutathione reductase (GR). The present work confirms the experimental results obtained by Eggleston and Krebs and proves that oxidized glutathione (GSSG) in the absence of NADPH is a direct inhibitor of G6PD. In the presence of GSSG, the G6PD activity recovery system suggested can be observed when GR is previously inhibited by alkylating agents. An unknown element with a molecular weight ranging between 12 and 50 kDa has been found to reverse part of G6PD inhibition by NADPH.

Influence of home/school environments on children's obesity, diet, and physical activity: the SUECO study protocol.

OBJECTIVE: The SUECO study examines the relationship between urban obesogenic environments and health outcomes among school-age children in the city of Madrid, Spain. We will study how features of the urban environment (related to the food- and the physical activity environment) associate with children's anthropometrics, eating habits, and physical activity levels. METHOD: We describe the study protocol of this multilevel study in a representative sample of school-age children in the city of Madrid (2017; n=5,961 children ages 3-12). Main outcome variables include anthropometrics (body mass index, waist circumference, and body fat), healthy and unhealthy consumption measures, and physical activity measures. The primary explanatory variables are grouped into food environment (e.g., unhealthy food retailers' density) and physical activity environment (e.g., walkability, physical activity opportunities) variable categories. Multilevel models will be used to calculate the associations between each indicator and obesity and physical inactivity.

Caracterización de las fracturas nasales atendidas en el servicio de urgencias de cirugía maxilofacial de Bayamo / Characterization of nasal fractures treated in the maxillofacial surgery emergency service of Bayamo

La fractura nasal es la más frecuente entre las fracturas de los huesos faciales, pudiendo generar alteraciones estéticas importantes y a su vez determinar cambios en la funcionalidad, tratarlas de forma inmediata evita complicaciones al paciente. Con el objetivo de caracterizar las fracturas nasales atendidas en el servicio de urgencias de cirugía maxilofacial del Hospital Carlos Manuel de Céspedes se realizó un estudio observacional descriptivo que incluyó todos los pacientes (105) que fueron atendidos ambulatoriamente con diagnóstico de fractura nasal reciente en el servicio de urgencias en el período de enero 2018 a diciembre del 2019. Las variables estudiadas fueron edad, sexo, procedencia, factores etiológicos, signos clínicos, clasificación según desplazamiento, exposición del foco de fractura y dirección del trauma. Se confeccionó una planilla de recolección de datos. Se emplearon números enteros, porcentajes y tablas estadísticas. Se siguieron los principios éticos para la investigación en humanos. La población más afectada se encontró entre los 20 y 29 años de edad, de procedencia urbana y del sexo masculino. Se encontró asociación entre el sexo y los factores etiológicos, predominando las agresiones físicas en hombres y las caídas casuales en mujeres. El principal signo clínico presente en los pacientes fue la epistaxis. Las fracturas nasales desplazadas, con desviaciones laterales y cerradas predominaron en ambos sexos(AU)

The nasal fracture is the most frequent among the fractures of the facial bones, being able to generate important aesthetic alterations and in turn determine changes in functionality, treating them immediately avoids complications for the patient. In order to characterize the nasal fractures treated in the maxillofacial surgery emergency service of the Carlos Manuel de Céspedes hospital, a descriptive observational study was carried out that included all the patients (105) who were seen outpatiently with a diagnosis of recent nasal fracture in the emergency department in the period from January 2018 to December 2019. The variables studied were age, sex, origin, etiological factors, clinical signs, classification according to displacement, exposure ofthe fracture site and direction of the trauma. A data collection sheet was prepared. Whole numbers, percentages and statistical tables were used. Ethical principles for human research were followed. The most affected population was between 20 and 29 years of age, of urban origin and male. An association was found between sex and etiological factors, predominantly physical aggression in men and accidental falls inwomen. The main clinical sign present in the patients was epistaxis. Displaced nasal fractures with lateral and closed deviations predominated in both sexes(EU)