Introduction of a hexavalent vaccine containing acellular pertussis into the national immunization program for infants in Peru: a cost-consequence analysis of vaccination coverage.

BACKGROUND: Infant vaccination coverage rates in Peru have declined in recent years, exacerbated by the COVID-19 pandemic. Introduction of the fully-liquid diphtheria, tetanus, and acellular pertussis (DTaP)-inactivated polio vaccine (IPV)-hepatitis B (HB)-Haemophilus influenzae type B (Hib) hexavalent vaccine (DTaP-IPV-HB-Hib) in Peru's infant National Immunization Program may help improve coverage. We evaluated costs and healthcare outcomes, including coverage, of switching from a pentavalent vaccine containing whole-cell pertussis component (DTwP-HB-Hib) plus IPV/oral polio vaccine (IPV/OPV) to the hexavalent vaccine for the primary vaccination scheme (2, 4 and 6 months). METHODS: The analysis was performed over a 5-year period on a cohort of children born in Peru in 2020 (N = 494,595). Four scenarios were considered: the pentavalent plus IPV/OPV scheme (S1); replacing the pentavalent plus IPV/OPV scheme with the hexavalent scheme (S2); expanded delivery of the pentavalent plus IPV/OPV scheme (S3); expanded delivery of the hexavalent scheme (S4). Vaccine coverage and incidence of adverse reactions (ARs) were estimated using Monte Carlo simulations and previous estimates from the literature. Cases of vaccine-preventable diseases were estimated using a Markov model. Logistical and healthcare costs associated with these outcomes were estimated. Impact of key variables (including coverage rates, incidence of ARs and vaccine prices) on costs was evaluated in sensitivity analyses. RESULTS: The overall cost from a public health payer perspective associated with the pentavalent plus IPV/OPV vaccine scheme (S1) was estimated at $56,719,350, increasing to $61,324,263 (+ 8.1%), $59,121,545 (+ 4.2%) and $64,872,734 (+ 14.4%) in scenarios S2, S3 and S4, respectively. Compared with the status quo (S1), coverage rates were estimated to increase by 3.1% points with expanded delivery alone, and by 9.4 and 14.3% points, if the hexavalent vaccine is deployed (S2 and S4, respectively). In both scenarios with the hexavalent vaccine (S2 and S4), pertussis cases would also be 5.7% and 8.7% lower, and AR rates would decrease by 32%. The cost per protected child would be reduced when the hexavalent vaccine scheme. Incidence of ARs was an important driver of cost variability in the sensitivity analysis. CONCLUSIONS: Implementation of the hexavalent vaccine in Peru's National Immunization Program has a positive public health cost consequence.

The Neuroprotective Effect of Erythropoietin on the Optic Nerve and Spinal Cord in Rats with Experimental Autoimmune Encephalomyelitis through the Activation of the Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway.

Experimental autoimmune encephalomyelitis is a demyelinating disease that causes paralysis in laboratory rats. This condition lacks treatment that reverses damage to the myelin sheaths of neuronal cells. Therefore, in this study, treatment with EPO as a neuroprotective effect was established to evaluate the ERK 1/2 signaling pathway and its participation in the EAE model. EPO was administered in 5000 U/Kg Sprague Dawley rats. U0126 was used as an inhibitor of the ERK 1/2 pathway to demonstrate the possible activation of this pathway in the model. Spinal cord and optic nerve tissues were evaluated using staining techniques such as H&E and the Luxol Fast Blue myelin-specific technique, as well as immunohistochemistry of the ERK 1/2 protein. The EPO-treated groups showed a decrease in cellular sampling in the spinal cord tissues but mainly in the optic nerve, as well as an increase in the expression of the ERK 1/2 protein in both tissues. The findings of this study suggest that EPO treatment reduces cellular death in EAE-induced rats by regulating the ERK pathway.

Chloroplast envelope K+/H+ antiporters are involved in cytosol pH regulation.

Variations in light intensity induce cytosol pH changes in photosynthetic tissues, providing a possible signal to adjust a variety of biochemical, physiological and developmental processes to the energy status of the cells. It was shown that these pH changes are partially due to the transport of protons in or out of the thylakoid lumen. However, the ion transporters in the chloroplast that transmit these pH changes to the cytosol are not known. KEA1 and KEA2 are K+/H+ antiporters in the chloroplast inner envelope that adjust stromal pH in light-to-dark transitions. We previously determined that stromal pH is higher in kea1kea2 mutant cells. In this study, we now show that KEA1 and KEA2 are required to attenuate cytosol pH variations upon sudden light intensity changes in leaf mesophyll cells, showing they are important components of the light-modulated pH signalling module. The kea1kea2 mutant mesophyll cells also have a considerably less negative membrane potential. Membrane potential is dependent on the activity of the plasma membrane proton ATPase and is regulated by secondary ion transporters, mainly potassium channels in the plasma membrane. We did not find significant differences in the activity of the plasma membrane proton pump but found a strongly increased membrane permeability to protons, especially potassium, of the double mutant plasma membranes. Our results indicate that chloroplast envelope K+/H+ antiporters not only affect chloroplast pH but also have a strong impact on cellular ion homeostasis and energization of the plasma membrane.

Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease among children in the United States between 2010 and 2019: An indirect cohort study.

BACKGROUND: A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes. METHODS: We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010-2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %). RESULTS: Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4-96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7-93.3 %), 50.2 % (28.4-80.5 %), and 93.8 % (69.8-98.8 %) against serotypes 19A, 3, and 19F, respectively. CONCLUSIONS: At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.

Economic burden of type-2 diabetes in Peru: a cost-of-illness study valuing cost differences associated with the level of glycemic control.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) represents an increasing public health problem in Peru. This study aims to estimate the national economic burden of this disease for the public funder, the social security, and private sector insurers. METHODS: Direct healthcare costs were estimated for a cohort of 45-to-75-year-old adults diagnosed with T2DM in 2019, over a 20-year period. Disease progression was modeled using PROSIT Models and literature, including acute and chronic microvascular and macrovascular complications. Three scenarios of glycemic control were considered: current levels of 35.8% of the population controlled (HbA1c < 7%) (S1); 100% controlled (S2) and; 100% uncontrolled (S3). The impact of diabetes prevalence on overall costs was evaluated in sensitivity analysis. RESULTS: Total national economic burden was estimated at $15,405,448,731; an annual average per patient of $2,158. Total costs would decrease to $12,853,113,596 (-16.6%) in S2 and increase to $16,828,713,495 (+9.2%) in S3. Treating patients with complications and risk factors could cost 6.5 times more, being stroke the complication with the highest impact. Up to a 67.6% increase in total costs was found when increasing T2DM prevalence. CONCLUSIONS: T2DM places a heavy burden on the Peruvian healthcare budget that will be even greater if poor glycemic control is maintained.

Combined PIK3CA and SOX2 Gene Amplification Predicts Laryngeal Cancer Risk beyond Histopathological Grading.

The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading.

Tumor mutational burden predictability in head and neck squamous cell carcinoma patients treated with immunotherapy: systematic review and meta-analysis.

BACKGROUND: Tumor mutational burden (TMB) has been demonstrated to predict the response to immune checkpoint inhibitors (ICIs) in various cancers. However, the role of TMB in head and neck squamous cell carcinoma (HNSCC) has not yet been specifically addressed. Since HNSCC patients exhibit a rather limited response to ICIs, there is an unmet need to develop predictive biomarkers to improve patient selection criteria and the clinical benefit of ICI treatment. METHODS: We conducted a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. HNSCC cohort studies were selected when TMB prior to ICI treatment was evaluated, TMB cutoff value was available, and the prognostic value of TMB was evaluated by time-to-event survival analysis. A total of 11 out of 1960 articles were analyzed, including 1200 HNSCC patients. RESULTS: The results showed that those patients harboring high TMB exhibited a significantly superior overall response rate (OR = 2.62; 95% CI 1.74-3.94; p < 0.0001) and a survival advantage (HR = 0.53; 95% CI 0.39-0.71; p < 0.0001) after ICI treatment. CONCLUSION: This is the first meta-analysis to demonstrate a higher response and clinical benefit from ICI therapy in HNSCC patients with high TMB.

Avian Plasmodium in invasive and native mosquitoes from southern Spain.

BACKGROUND: The emergence of diseases of public health concern is enhanced by factors associated with global change, such as the introduction of invasive species. The Asian tiger mosquito (Aedes albopictus), considered a competent vector of different viruses and parasites, has been successfully introduced into Europe in recent decades. Molecular screening of parasites in mosquitoes (i.e. molecular xenomonitoring) is essential to understand the potential role of different native and invasive mosquito species in the local circulation of vector-borne parasites affecting both humans and wildlife. METHODS: The presence of avian Plasmodium parasites was molecularly tested in mosquitoes trapped in five localities with different environmental characteristics in southern Spain from May to November 2022. The species analyzed included the native Culex pipiens and Culiseta longiareolata and the invasive Ae. albopictus. RESULTS: Avian Plasmodium DNA was only found in Cx. pipiens with 31 positive out of 165 mosquito pools tested. None of the Ae. albopictus or Cs. longiareolata pools were positive for avian malaria parasites. Overall, eight Plasmodium lineages were identified, including a new lineage described here. No significant differences in parasite prevalence were found between localities or sampling sessions. CONCLUSIONS: Unlike the invasive Ae. albopictus, Cx. pipiens plays a key role in the transmission of avian Plasmodium in southern Spain. However, due to the recent establishment of Ae. albopictus in the area, further research on the role of this species in the local transmission of vector-borne pathogens with different reservoirs is required.

Prognostic value of preoperative inflammatory ratios in early glottic cancer treated with transoral laser surgery.

BACKGROUND: There is growing evidence regarding the prognostic utility of ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIII) in head and neck squamous cell carcinoma (HNSCC). However, most studies to date include heterogeneous series with different treatments or tumor subsites. METHODS: We collected data from 201 patients with stage I-II glottic squamous cell carcinoma treated with transoral laser surgery. NLR, PLR, and SIII were calculated from preoperative cell blood count, cut-off points were obtained by ROC curve analysis, and survival rates were calculated. RESULTS: High NLR (p = 0.012) and SIII (p = 0.037), but not PLR (p = 0.48), were associated with worse disease-specific survival (DSS). A similar trend was observed with overall survival (OS), although it did not reach statistical significance. On multivariable analyses, both high NLR (HR = 3.8, 95% CI = 1.5-9.9, p = 0.006) and high SIII (HR = 2.77, 95% CI = 1.1-6.9, p = 0.03) were significantly associated with shortened DSS. CONCLUSIONS: Preoperative NLR and SIII emerge as independent prognostic biomarkers for early-stage surgically treated glottic tumors and could guide individualized follow-up.

Íleo meconial y falsos negativos del resultado de tripsina inmunorreactiva en una niña portadora de fibrosis quística / Meconium Ileus and false negative immunoreactive trypsine results in a cystic fibrosis carrier infant / Íleo meconial e resultados falso-negativos de tripsina imunorreativa em uma menina com fibrose cística

Introducción: la fibrosis quística (FQ) es una enfermedad genética, multisistémica, caracterizada por la disfunción de las glándulas de secreción exocrina secundaria a la mutación de una proteína transmembrana que actúa como canal de cloro. La inclusión de su búsqueda en el Sistema Nacional de Pesquisa Neonatal (SNPN) determinó un gran impacto sobre la morbimortalidad de esta enfermedad, permitiendo un diagnóstico y tratamiento precoz. El íleo meconial (IM) es la manifestación más precoz de la enfermedad, ocurriendo en un 10% a 18% de los pacientes. Objetivo: describir una forma de presentación precoz de FQ con resultado de pesquisa neonatal normal. Caso clínico: 18 meses. Sexo femenino; 33 semanas de edad gestacional. Retraso en la expulsión del meconio. Al tercer día de vida íleo meconial con oclusión intestinal, vólvulo de intestino medio y necrosis intestinal. Se realiza resección quirúrgica. Tripsina inmunorreactiva (TIR) normal a los 7 y 23 días de vida. No se solicita proteína asociada a la pancreatitis (PAP). Desnutrición crónica, bronquiolitis grave a los 3 meses, neumonías virales a los 7 y 11 meses. Ingreso con diagnóstico de neumonía aguda comunitaria con insuficiencia respiratoria. Test del sudor alterado en dos oportunidades. Elastasa pancreática insuficiente. Se aísla Staphylococcus aureus y Pseudomonas aeruginosa en exudado nasal y de secreciones respiratorias. Estudio genético: mutación Delta F508. Con diagnóstico de FQ se inició abordaje multidisciplinario, tratamiento y derivación al centro especializado. Conclusiones: la existencia de IM puede dar falsos negativos en el valor de la TIR, siendo necesaria la dosificación de la PAP. El pronóstico de estos pacientes va a depender de un diagnóstico precoz y el manejo terapéutico oportuno en centros especializados.

Introduction: cystic fibrosis (CF) is a genetic, multisystemic disease, characterized by dysfunction of the exocrine secretion glands secondary to the mutation of a transmembrane protein that acts as a chloride channel. Including its research by the National Neonatal Screening System (SNPN) caused a great impact on the morbidity and mortality of this disease, enabling early diagnosis and treatment. Meconium ileus (MI) is the earliest manifestation of the disease, occurring in 10% to 18% of patients. Objective: to describe a form of early presentation of CF with normal neonatal screening results. Clinical case: 18 months. Female, 33 weeks gestational age. Delay in the expulsion of meconium. On the third day of life, meconium ileus with intestinal obstruction, midgut volvulus and intestinal necrosis. Surgical resection is performed. Trypsin immunoreactive (TIR) normal at 7 and 23 days of age. Pancreatitis-associated protein (PAP) is not requested. Chronic malnutrition, severe bronchiolitis at 3 months, viral pneumonia at 7 and 11 months. Admission with a diagnosis of acute community pneumonia with respiratory failure. Sweat test altered on two occasions. Insufficient pancreatic elastase. Staphylococcus aureus and Pseudomonas aeruginosa were isolated in nasal exudate and respiratory secretions. Genetic study: Delta F508 mutation. With the CF diagnosis, a multidisciplinary approach, treatment and referral to a specialized center began. Conclusions: the existence of MI can provide false negatives in the IRR value, making PAP dosage necessary. The prognosis of these patients will depend on early diagnosis and timely therapeutic management at specialized centers.

Introdução: a fibrose cística (FC) é uma doença genética, multissistêmica, caracterizada pela disfunção das glândulas secretoras exócrinas secundária à mutação de uma proteína transmembrana que age como canal de cloreto. A inclusão da sua pesquisa no Sistema Nacional de Triagem Neonatal (SNPN) determinou grande impacto na morbimortalidade desta doença, permitindo diagnóstico e tratamento precoces. O íleo meconial (IM) é a manifestação mais precoce da doença, ocorrendo em 10 a 18% dos pacientes. Objetivo: descrever uma forma de apresentação precoce da FC com resultados normais de triagem neonatal. Caso clínico: 18 meses. Sexo feminino. 33 semanas de idade gestacional. Atraso na expulsão do mecônio. No terceiro dia de vida, íleo meconial com obstrução intestinal, vólvulo de intestino médio e necrose intestinal. A ressecção cirúrgica é realizada. Imunorreativo à tripsina (TIR) normal aos 7 e 23 dias de vida. A proteína associada à pancreatite (PAP) não é solicitada. Desnutrição crônica, bronquiolite grave aos 3 meses, pneumonia viral aos 7 e11 meses. Internação com diagnóstico de pneumonia comunitária aguda com insuficiência respiratória. Teste do suor alterado em duas ocasiões. Elastase pancreática insuficiente. Staphylococcus aureus e Pseudomonas aeruginosa foram isolados em exsudato nasal e secreções respiratórias. Estudo genético: mutação Delta F508. Com o diagnóstico de FC iniciou-se abordagem multidisciplinar, tratamento e encaminhamento para centro especializado. Conclusões: a existência de IM pode dar falsos negativos no valor da TIR, tornando necessária a dosagem de PAP. O prognóstico destes pacientes dependerá do diagnóstico precoce e do manejo terapêutico oportuno em centros especializados.

Características de los niños y adolescentes con enfermedades pulmonares crónicas derivados para evaluación por equipo de trasplante pulmonar de Uruguay en el período 2003 - 2023 / Characteristics of children and adolescents with chronic lung diseases referred for assessment by the Uruguayan lung transplant team in 2003 - 2023 / Características de crianças e adolescentes com doenças pulmonares crônicas referidas para avaliação pela equipe uruguaia de transplante pulmonar no período 2003 - 2023

Introducción: el trasplante pulmonar se ha consolidado en los últimos años como una opción terapéutica para niños y adolescentes con enfermedad pulmonar grave en la que han fracasado otros tratamientos. Este procedimiento otorga una buena calidad de vida y una supervivencia prolongada, similar a la del trasplante realizado en pacientes adultos. La indicación general para el trasplante pulmonar es la insuficiencia respiratoria progresiva, y potencialmente letal, debida a una enfermedad pulmonar parenquimatosa o vascular. La selección de candidatos a trasplante es compleja, requiriendo condiciones médicas y socioambientales específicas. Objetivos: analizar las características clínicas de los pacientes pediátricos con enfermedades pulmonares crónicas derivados para evaluación por el equipo de trasplante pulmonar de Uruguay. Analizar las características clínicas y sobrevida de los pacientes trasplantados pulmonares pediátricos uruguayos. Material y métodos: estudio descriptivo y retrospectivo de todos los pacientes menores de 19 años derivados al equipo de trasplante pulmonar entre 2003 y 2023. Datos obtenidos de la base del programa y mediante revisión de historias clínicas. Resultados: se incluyeron 30 pacientes (15 de sexo masculino). La media de edad de los pacientes derivados fue de 13,4 ± 3,6 años. Las etiologías de los pacientes derivados fueron 17/30 (56,6%) fibrosis quística, 4/30 (13,3%) bronquiolitis obliterante postrasplante de médula ósea, 4/30 (13,3%) hipertensión pulmonar, 3/30 (10%) bronquiolitis obliterante posinfecciosa y 2/30 (6,6%) enfermedad pulmonar intersticial difusa. Ingresaron en lista de trasplante 14 pacientes, de los cuales 9 se trasplantaron, 1 se mantiene en lista de espera y 4 fallecieron a la espera del trasplante. Del resto de los pacientes derivados para evaluación: 7 pacientes se encuentran aún en evaluación. Fueron excluidos por razones psicosociales o causas médicas 2 pacientes. Dos pacientes tuvieron pérdida de seguimiento y otros 5 fallecieron durante la evaluación. Las etiologías de los pacientes trasplantados pediátricos fueron fibrosis quística (3/9), bronquiolitis obliterante postrasplante de médula ósea (3/9) e hipertensión pulmonar (3/9). De los pacientes trasplantados, 5 fallecieron (2 en el posoperatorio y 3 fallecieron por sepsis entre 1-2 años postrasplante). Los restantes pacientes están en seguimiento postrasplante hace un mes, 2, 7 y 9 años. No se han encontrado diferencias estadísticamente significativas en la sobrevida condicional cuando se compararon pacientes adultos y pediátricos. Conclusiones: los resultados en los pacientes trasplantados en cuanto a características y causas de mortalidad son comparables con los reportados internacionalmente. La mortalidad postrasplante fue algo mayor que en otros estudios, pero creemos que existe sesgo por el bajo número de pacientes. Dados los resultados mencionados, planteamos que el trasplante sigue siendo una alternativa terapéutica válida en nuestro medio. Los desafíos de este tratamiento incluyen la disponibilidad limitada de órganos de donantes adecuados, la toxicidad de los medicamentos inmunosupresores necesarios para prevenir el rechazo, la prevención y el tratamiento de la bronquiolitis obliterante, así como maximizar el crecimiento, el desarrollo y la calidad de vida de los receptores.

Summary: Introduction: lung transplantation has been recently consolidated as a therapeutic option for children and adolescents with severe lung disease when other treatments have failed. This procedure provides a good quality of life and additional survival, similar to that of transplantation in adult patients. The general indication for lung transplantation is progressive, potentially fatal respiratory failure due to parenchymal or vascular lung disease. The selection of transplant candidates is complex, requiring specific medical and socio-environmental conditions. Objectives: to analyze the clinical characteristics of pediatric patients with chronic lung diseases referred for evaluation by the Uruguayan lung transplant team. To analyze the clinical characteristics and survival of Uruguayan pediatric lung transplant patients. Material and methods: descriptive and retrospective study of all patients under 19 years of age referred to the lung transplant team between 2003 and 2023. The data was obtained from the program's database and through medical records' review. Results: 30 patients were included (15 male). The mean age of the referred patients was 13.4 ± 3.6 years. Etiologies were 17/30 (56.6%) cystic fibrosis, 4/30 (13.3%) bronchiolitis obliterans post-bone marrow transplant, 4/30 (13.3%) pulmonary hypertension, 3 /30 (10%) post-infectious bronchiolitis obliterans, and 2/30 (6.6%) diffuse interstitial lung disease. 14 patients were placed on the transplant list, of which 9 were transplanted, 1 remains on the waiting list and 4 died while waiting for the transplant. Of the rest of the patients referred for evaluation: 7 patients are still under evaluation. 2 patients were excluded for psychosocial reasons or medical reasons. 2 patients could not be followed-up and other 5 died during the evaluation. The etiologies of the pediatric transplant patients were cystic fibrosis (3/9), post-bone marrow transplant bronchiolitis obliterans (3/9), and pulmonary hypertension (3/9). Of the transplanted patients, 5 died (two in the post-operative period, and three died from sepsis between 1-2 years post-transplant). The remaining patients are in post-transplant follow-up for 1 month, 2, 7 and 9 years. No statistically significant differences in conditional survival were found when comparing adult and pediatric patients. Conclusions: results in transplanted patients in terms of characteristics and causes of mortality are comparable with those reported internationally. Post-transplant mortality was somewhat higher than in other studies, but we believe that there is bias due to the low number of patients. Given the results above, we propose that transplantation continues to be a valid therapeutic alternative in our country. The challenges of this treatment include the limited availability of suitable donor organs, the toxicity of immunosuppressive medications necessary to prevent rejection, prevention and treatment of bronchiolitis obliterans, as well as maximizing the growth, development and quality of life of the receivers.

Introdução: o transplante pulmonar consolidou-se nos últimos anos como opção terapêutica para crianças e adolescentes com doença pulmonar grave, nas quais outros tratamentos falharam. Esse procedimento proporciona boa qualidade de vida e sobrevida prolongada, semelhante ao transplante realizado em pacientes adultos. A indicação geral para transplante pulmonar é insuficiência respiratória progressiva e potencialmente fatal devido a doença pulmonar parenquimatosa ou vascular. A seleção de candidatos a transplantes é complexa, exigindo condições médicas e socioambientais específicas. Objetivos: analisar as características clínicas de pacientes pediátricos com doenças pulmonares crônicas encaminhados para avaliação pela equipe uruguaia de transplante pulmonar. Analisar as características clínicas e a sobrevida de pacientes pediátricos uruguaios transplantados pulmonares. Material e métodos: estudo descritivo e retrospectivo de todos os pacientes menores de 19 anos encaminhados à equipe de transplante pulmonar entre 2003 e 2023. Os dados foram obtidos no banco de dados do programa e por meio de revisão de prontuários. Foram incluídos 30 pacientes (15 do sexo masculino). A média de idade dos pacientes encaminhados foi de 13,4 ± 3,6 anos. As etiologias dos pacientes encaminhados foram 17/30 (56,6%) fibrose cística, 4/30 (13,3%) bronquiolite obliterante pós-transplante de medula óssea, 4/30 (13,3%) hipertensão pulmonar, 3/30 (10%) pós -bronquiolite obliterante infecciosa e 2/30 (6,6%) doença pulmonar intersticial difusa. Foram colocados na lista de transplante 14 pacientes, dos quais 9 foram transplantados, 1 permanece em lista de espera e 4 faleceram enquanto aguardavam o transplante. Do restante dos pacientes encaminhados para avaliação: 7 pacientes ainda estão em avaliação, 2 pacientes foram excluídos por motivos psicossociais ou médicos. 2 pacientes foram perdidos no acompanhamento e outros 5 faleceram durante a avaliação. As etiologias dos pacientes transplantados pediátricos foram fibrose cística (3/9), bronquiolite obliterante pós-transplante de medula óssea (3/9) e hipertensão pulmonar (3/9). Dos pacientes transplantados, 5 faleceram (dois no pós-operatório e três por sepse entre 1-2 anos pós-transplante). Os demais pacientes estão em acompanhamento pós-transplante por 1 mês, 2, 7 e 9 anos. Não foram encontradas diferenças estatisticamente significativas na sobrevida condicional quando comparamos pacientes adultos e pediátricos. Conclusões: os resultados em pacientes transplantados em termos de características e causas de mortalidade são comparáveis aos relatados internacionalmente. A mortalidade pós-transplante foi um pouco maior do que em outros estudos, mas acreditamos que exista viés devido ao baixo número de pacientes. Diante dos resultados acima mencionados, propomos que o transplante continue sendo uma alternativa terapêutica válida em nosso meio. Os desafios deste tratamento incluem a disponibilidade limitada de órgãos de doadores adequados, a toxicidade dos medicamentos imunossupressores necessários para prevenir a rejeição, prevenção e tratamento da bronquiolite obliterante, bem como maximizar o crescimento, desenvolvimento e qualidade de vida dos receptores.

An Exploration of Sex Trading for Compensation and LGBTQ+ Inclusive Screening Practices: Perspectives of Young People who have Experienced Sex Trading and/or Homelessness.

Young people's perspectives on social and healthcare providers' assessments of sex trading for financial compensation are lacking. This is particularly important for LGBTQ+ youth who experience substantial barriers in navigating health and social services. Further, increased internet access (because of COVID-19 and other factors) has changed the landscape of the sex trades in ways that are not fully understood. Our study aimed to understand (1) how young people trade sex, and (2) provider strategies that increase youths' comfort in disclosing sex trading and related risks. This community-based participatory research study surveyed currently or formerly homeless youth (ages 16-29). We co-created a cross sectional survey that explored youths' perceptions of: (1) sex trading type, compensation, and meaning; and (2) practices to increase youths' comfort in disclosing sex trading. Participants (N = 103; Mage = 22.9 [SD = 3.5]; 34% white, 55% ciswomen/21% trans; 51% queer) reported that "sex trading" signified multiple meanings, ranging from sex work/occupation to exploitation/trafficking, and included diverse in-person and virtual forms for varied compensation types. Youth reported being more comfortable disclosing when the provider indicated they would advocate for them if they are victims of discrimination. Compared to cisgender youth, trans youth reported feeling significantly more comfortable disclosing sexual activity when a service provider used gender/sexuality inclusive practices (e.g., pronoun pins). Findings suggest important implications for gender-inclusive practice strategies to ultimately reduce potential harms of sex trading and multi-item measures to assess the complexity of sex trading.

Melatonina, lactancia materna y sueño: revisión del tema / Melatonin, breastfeeding and sleep: topic review

Se revisa en el binomio madre-recién nacidos o/y lactantes, los diferentes ritmos circadianos, especialmente del sueño, la secreción de melatonina y las características de la leche materna. Se aconseja manejo para evitar la cronodisrupción

It is reviewed in the binomial mother-newborns or/and infants, the different circadian rhythms, especially sleep, melatonin secretion and the characteristics of breast milk. Handling is advised to avoid chrono disruption

El sufrimiento frente a la etapa final de la vida

La complejidad de una enfermedad terminal pone en evidencia la vulnerabilidad del ser humano ante el dolor y el sufrimiento, y acentúa la crisis subjetiva que acompaña no solo al paciente, sino también al médico que lo asiste. Revisamos la propuesta de un estudio posicionado en la ética del cuidado de quienes necesitan atención integral en el final de la vida. Nos referimos a la investigación titulada "Final de vida, cuidados paliativos y empatía. Manejo de la empatía como recurso fundamental frente a la toma de decisiones al final de la vida" 1. Un extracto de dicho trabajo señala la importancia de que los médicos puedan ubicar el sufrimiento del paciente separado de ellos mismos, de manera que sostengan una resonancia empática que los posicione con capacidad para entrar en el mundo del paciente y su enfermedad, con firmeza personal y profesional. Definimos un espacio de reflexión acerca del sentido del sufrimiento, su correlato en la práctica clínica y un argumento fundamental al momento de proponer una legislación vinculada al final de la vida.

The complexity of a terminal illness highlights the vulnerability of the human being to pain and suffering. It accentuates the subjective crisis that accompanies the patient and the doctor who assists him. We reviewed the proposal for a study on the ethics of care of those who need comprehensive care at the end of life. An excerpt from it points out the importance of doctors being able to place the patient's suffering separate from themselves, maintaining an empathic resonance that positions them with the ability to enter the world of the patient and his disease with personal and professional firmness. We defined a space for reflection on the meaning of suffering, its correlation in clinical practice, and a fundamental argument when proposing legislation linked to the end of life.

A complexidade de uma doença terminal evidencia a vulnerabilidade do ser humano diante da dor e do sofrimento, e acentua a crise subjetiva que acompanha não só o paciente, mas também o médico que o assiste. Analisamos a proposta de um estudo posicionado na ética do atendimento àqueles que necessitam de cuidados integrais no final da vida. Referimo-nos à pesquisa intitulada "Fim da vida, cuidados paliativos e empatia. Gestão da empatia como recurso fundamental na tomada de decisões no fim da vida". Um trecho deste trabalho aponta para a importância de os médicos serem capazes de situar o sofrimento do paciente separadamente de si mesmos, de modo a sustentar uma ressonância empática que os posicione com a capacidade de entrar no mundo do paciente e de sua doença, com firmeza pessoal e profissional. Definimos um espaço de reflexão sobre o significado do sofrimento, seu correlato na prática clinica e um argumento fundamental ao propor uma legislação ligada ao fim da vida.

Efecto del Ejercicio en el Medio Acuático sobre la Aptitud Física en Personas con Discapacidad Intelectual: Una Revisión Sistemática / Effect of Exercise in Aquatic Environments on Physical Fitness in People with Intellectual Disabilities: A Systematic Review / Efeito do exercício aquático sobre a aptidão física em pessoas com deficiência intelectual: uma revisão sistemática

Resumen: Los programas de ejercicio en el medio acuático proporcionan un ambiente motivante y divertido, en el cual las personas con discapacidad intelectual pueden realizar actividades deportivas o recreativas de manera accesible, lo que incide positivamente en la condición física. Propósito: El objetivo de la revisión sistemática fue conocer los efectos del ejercicio acuático sobre la aptitud física en personas con discapacidad intelectual. Metodología: Para lograr el propósito del estudio, se llevó a cabo una búsqueda de literatura en las bases de datos Sport Discus, Science Direct, Scopus y PubMed, cuyas publicaciones comprenden del 2009 al 2018; como criterios de inclusión debían especificar el tipo de ejercicio, los componentes de la carga de entrenamiento, el tipo de discapacidad que presentaban los sujetos del estudio y que la duración de la intervención fue mayor a 4 semanas. Resultados: Solamente 5 trabajos cumplieron los criterios de selección. Aquellos en los que aplicaron intervenciones de natación y ejercicio combinado indicaron que se mejoraron elementos de la aptitud física importantes para la salud, así como el desenvolvimiento de actividades de la vida diaria. Se pudo concluir que se requieren investigaciones con mayor rigor metodológico, para clarificar el efecto del ejercicio en el medio acuático sobre los componentes de la aptitud física en personas con discapacidad intelectual.

Abstract: Exercise programs in aquatic environments guarantee a motivating and fun environment in which people with intellectual disabilities can carry out sports or recreational activities in an accessible way, which has a positive effect on their physical condition. Purpose: the objective of the systematic review was to know the effects of aquatic exercise on physical fitness in people with intellectual disabilities. Methodology: To achieve the purpose of the study, a literature search was conducted in the Sport Discus, Science Direct, Scopus, and PubMed databases, whose publications cover from 2009 to 2018. As selection criteria, these publications had to specify the type of exercise, the components of a load of training, the type of disability presented by the study subjects, and the duration of the intervention that should be greater than four weeks. Results: Only five studies met the selection criteria. the studies in which they applied swimming interruption and combined exercise showed that components of physical fitness important for health were improved, as well as the development of activities of daily living. It was concluded that studies with greater methodological rigor are required to clarify the effect of exercise in aquatic environments on the components of physical fitness in people with intellectual disabilities.

Resumo: Os programas de exercícios aquáticos proporcionam um ambiente motivador e divertido no qual pessoas com deficiências intelectuais podem praticar esportes ou atividades recreativas de maneira acessível, o que tem um impacto positivo sobre a condição física. Objetivo: O objetivo da revisão sistemática era descobrir os efeitos do exercício aquático sobre a aptidão física das pessoas com deficiência intelectual. Metodologia: Para atingir o objetivo do estudo, foi feita uma pesquisa bibliográfica nas bases de dados Sport Discus, Science Direct, Scopus e PubMed, cujas publicações foram de 2009 a 2018. Como critérios de seleção, essas publicações tinham que especificar o tipo de exercício, os componentes de uma carga de treinamento, o tipo de deficiência apresentada pelos sujeitos do estudo e a duração da intervenção que devia ser superior a quatro semanas. Resultados: Apenas cinco estudos cumpriram os critérios de seleção. Os estudos nos quais foram aplicados intervenções de natação e exercícios combinados indicaram que os componentes de aptidão física importantes para a saúde, assim como no desempenho das atividades da vida diária, foram melhorados. Concluiu-se que são necessários estudos com maior rigor metodológico para esclarecer o efeito do exercício aquático sobre os componentes da aptidão física das pessoas com deficiência intelectual.

Spinal alarmin HMGB1 and the activation of TLR4 lead to chronic stress-induced nociceptive hypersensitivity in rodents.

Chronic stress affects millions of people around the world, and it can trigger different behavioral disorders like nociceptive hypersensitivity and anxiety, among others. However, the mechanisms underlaying these chronic stress-induced behavioral disorders have not been yet elucidated. This study was designed to understand the role of high-mobility group box-1 (HMGB1) and toll-like receptor 4 (TLR4) in chronic stress-induced nociceptive hypersensitivity. Chronic restraint stress induced bilateral tactile allodynia, anxiety-like behaviors, phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) and activation of spinal microglia. Moreover, chronic stress enhanced HMGB1 and TLR4 protein expression at the dorsal root ganglion, but not at the spinal cord. Intrathecal injection of HMGB1 or TLR4 antagonists reduced tactile allodynia and anxiety-like behaviors induced by chronic stress. Additionally, deletion of TLR4 diminished the establishment of chronic stress-induced tactile allodynia in male and female mice. Lastly, the antiallodynic effect of HMGB1 and TLR4 antagonists were similar in stressed male and female rats and mice. Our results suggest that chronic restraint stress induces nociceptive hypersensitivity, anxiety-like behaviors, and up-regulation of spinal HMGB1 and TLR4 expression. Blockade of HMGB1 and TLR4 reverses chronic restraint stress-induced nociceptive hypersensitivity and anxiety-like behaviors and restores altered HMGB1 and TLR4 expression. The antiallodynic effects of HMGB1 and TLR4 blockers in this model are sex independent. TLR4 could be a potential pharmacological target for the treatment of the nociceptive hypersensitivity associated with widespread chronic pain.

Dissecting the functions of cancer-associated fibroblasts to therapeutically target head and neck cancer microenvironment.

Head and neck cancers (HNC) are a diverse group of aggressive malignancies with high morbidity and mortality, leading to almost half-million deaths annually worldwide. A better understanding of the molecular processes governing tumor formation and progression is crucial to improve current diagnostic and prognostic tools as well as to develop more personalized treatment strategies. Tumors are highly complex and heterogeneous structures in which growth and dissemination is not only governed by the cancer cells intrinsic mechanisms, but also by the surrounding tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) emerge as predominant TME components and key players in the generation of permissive conditions that ultimately impact in tumor progression and metastatic dissemination. Although CAFs were initially considered a consequence of tumor development, it is now well established that they actively contribute to numerous cancer hallmarks i.e., tumor cell growth, migration and invasion, cancer cell stemness, angiogenesis, metabolic reprograming, inflammation, and immune system modulation. In this scenario, therapeutic strategies targeting CAF functions could potentially have a major impact in cancer therapeutics, providing avenues for new treatment options or for improving efficacy in established approaches. This review is focused on thoroughly dissecting existing evidences supporting the contribution of CAFs in HNC biology with an emphasis on current knowledge of the key molecules and pathways involved in CAF-tumor crosstalk, and their potential as novel biomarkers and/or therapeutic targets to effectively interfere the tumor-stroma crosstalk for HNC patients benefit. involved in CAF-tumor crosstalk, and their potential as novel biomarkers and/or therapeutic targets to effec- tively interfere the tumor-stroma crosstalk for HNC patients benefit.

How Do Providers Assess Young People for Risk of Sex Trafficking? Observed Indicators, Follow-Up, and Assessment Questions from a Sample of Social Service Providers.

The extent to which service providers across systems identify and assess potentially sex trafficked youth is understudied. The purpose of this study is to determine whether and how providers observe relevant indicators and assess for sex trafficking risk among minors (ages 12-17), young adults (ages 18-29), and families of minors. A cross-sectional, web-based survey was disseminated to service providers, who represented child welfare, youth justice, and social services (e.g. runaway youth, sexual violence), in a region of a Midwestern state (United States). Participants (N=267) were asked whether they provided direct services to minors (ages 12-17, n=245), adults (ages 18-29, n=148), and/or families/foster families of minors (ages 12-17, n=163), resulting in three respective client groups. Survey items assessed the extent to which providers (1) identified possible sex trafficking indicators across 5 domains; (2) took follow up actions; and (3) asked risk assessment questions. T-tests were conducted to examine differences between those who reported receiving sex trafficking trainings, compared to those who did not. Results suggest that the most commonly identified indicators included depressive symptoms, shame and guilt, lack of social support. Least common indicators included torture, false IDs, hotel involvement. A third of minor-aged providers did not ask sex trafficking risk assessment questions. Providers reported asking fewer clients about online sex trading than in-person forms. There were statistically significant differences among providers who received training. Implications, including provider strategies for assessing online sex trading and organizational protocols to enhance sex trafficking identification, are discussed.

The effect of bariatric surgery on metabolic syndrome: A retrospective cohort study in Colombia.

Introduction and Objective: Metabolic syndrome (MetS) represents a group of metabolic abnormalities. It is currently a pandemic, and its prevalence is on the rise. MetS has a direct relationship with obesity, for this reason, bariatric and metabolic surgery has been proposed as a method to simultaneously control obesity and MetS. However, in Colombia the results of this intervention are unknown. This study aims to compare metabolic syndrome before and after bariatric surgery in a Colombian population. Methods: Retrospective cohort study conducted in a highly complex institution in Colombia, where comparing the prevalence of metabolic syndrome in patients who underwent bariatric surgery during a 1-year follow-up period, between January 2015 and December 2019. Of these patients, 48 underwent Roux-en-Y gastric bypass, and 32 underwent sleeve gastrectomy by laparoscopic technique. Results: A total of 80 patients were included, of which 67.5% were women and the mean age was 42.8 ± 12.9 years. The most frequent preprocedure comorbidities were arterial hypertension (36.2%), dyslipidemia (32.4%), and sleep apnea (20%). After bariatric surgery, the prevalence of metabolic syndrome decreased from 66.2% to 3.7% (p < 0.05). In addition, a reduction in the Homeostatic Model Assessment for Insulin Resistance score from 77.5% to 22.5% was observed during the follow-up period. HbA1c, creatinine, and thyroid-stimulating hormone, were the only parameters without significant changes. Conclusions: Metabolic and bariatric surgery is an effective treatment for weight reduction, with a high impact in reducing the prevalence of metabolic syndrome and insulin resistance in the short and medium term in the Colombian population.