Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccine in Adults 50-59 Years Compared to ≥60 Years of Age.

BACKGROUND: The adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50-59 years without or with increased risk for RSV disease due to specific chronic medical conditions. METHODS: This observer-blind, phase 3, noninferiority trial included adults aged 50-59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50-59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed. RESULTS: The exposed population included 1152 participants aged 50-59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50-59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups. CONCLUSIONS: RSVPreF3 OA was immunologically noninferior in 50-59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50-59-year-olds was consistent with that in ≥60-year-olds. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05590403.

Computational assessment of lipid production in Rhodosporidium toruloides in two-stage and one-stage batch bioprocesses.

Oleaginous yeasts are promising platforms for microbial lipids production as a renewable and sustainable alternative to vegetable oils in biodiesel production. In this paper, a thorough in silico assessment of lipid production in batch cultivation by Rhodosporidium toruloides was developed. By means of dynamic flux balance analysis, the traditional two-stage bioprocess (TSB) performed by the native strain was contrasted with one-stage bioprocess (OSB) using four designed strains obtained by gene knockout strategies. Lipid titer, yield, content, and productivity were analyzed at different initial C/N ratios as relevant performance indicators used in bioprocesses. By weighting these indicators, a global lipid efficiency metric (GLEM) was defined to consider different scenarios. Under simulated conditions, designed strains for lipid overproduction in OSB outperformed the TSB in terms of lipid title (up to threefold), lipid yield (up to 2.4-fold), lipid content (up to 2.8-fold, with a maximum of 76%), and productivity (up to 1.3-fold), depending on C/N ratios. Using these efficiency parameters and the proposed GLEM, the process of selecting the most suitable candidates for lipid production could be carried out before experimental assays. This methodology holds the potential to be extended to other oleaginous microorganisms and diverse strain design techniques.

[Gastric polyps: experience in Daniel Alcides Carrion Hospital 2014-2016]. / Pólipos gástricos: experiencia en el hospital Daniel Alcides Carrión - Callao 2014-2016.

OBJECTIVE: The purpose of this study was to determine the prevalence of the different types of gastric polyps in the Daniel Alcides Carrión Hospital between the years of 2014 and 2016, and also define the endoscopic and histopathological characteristics of the lesions. MATERIALS AND METHODS: 7559 endoscopic reports were reviewed, in which 148 gastric polyps were found. The patients age and sex as well as the localization, number, size and macroscopic and microscopic aspects of the polyps were recorded. RESULTS: The prevalence of gastric polyps was 1.9%; 74.3% of these were found in women with an average age of 61.5 years. 59.4% of the gastric polyps found were singular, and the majority were located on the body and antrum of the stomach. 74.29% of the polyps were less than 1 cm in diameter and 83.64% of these were sessile when seen macroscopically. According to the histological type, it was found that the majority of gastric polyps were hyperplasic (76.4%), followed by fundic gland polyps (17.5%) and gastric adenomas (6.1%). It was also found that multiple gastric polyps were associated with fundic gland polyps while singular polyps were most likely hyperplastic or adenomas. CONCLUSION: The prevalence of fundic gland polyps has increased, while the other types of polyps have maintained their estimated prevalence.

Survival Analysis of Metastatic Early-Onset Colorectal Cancer Compared to Metastatic Average-Onset Colorectal Cancer: A SEER Database Analysis.

BACKGROUND: Early-onset colorectal cancer (EO-CRC) is defined as colorectal cancer diagnosed before the age of 50 years, and its incidence has been increasing over the last decade, now accounting for 10% of all new CRC diagnoses. Average-onset colorectal cancer (AO-CRC) has shown a steady decline in its incidence and related mortality over the past 20 years. The disparities in outcomes and overall survival (OS) between EO-CRC and AO-CRC are controversial. Our study compared OS and cause-specific survival (CSS) between metastatic EO-CRC (mEO-CRC) and metastatic AO-CRC (mAO-CRC) and identified the associated factors. METHODS: Data on patient characteristics, tumor characteristics, incidence, and mortality were obtained from the SEER database from 2010 to 2020. We identified 23,278 individuals aged > 18 years with a confirmed diagnosis of all histological subtypes of metastatic CRC (M1 on TNM stage) using ICD-O-3 site codes. mEO-CRC and mAO-CRC were compared. OS distributions and CCS were analyzed using the Kaplan-Meier method and log-rank test to assess differences. A Cox regression model was used to assess the associations between variables. RESULTS: mEO-CRC constituted 17.79% of the cases, whereas 82.21% had mAO-CRC. Most patients with mEO-CRC were 45-49 years old (47.66%), male (52.16%) and White (72.57%) and had adenocarcinoma histology (87.30%). Left colon tumors were most prevalent in both groups (40.26%) but were more prevalent in mEO-CRC patients than in mAO-CRC patients (49.63% vs. 38.23%, p < 0.001). Patients with mEO-CRC had higher OS (p < 0.001) and CSS (p < 0.001) than those with mAO-CRC. Patients with mEO-CRC also had significantly better median overall survival (30 months vs. 18 months, p < 0.001). The factors associated with worse OS included mAO-CRC (p < 0.001), mucinous adenocarcinoma (p < 0.001), male sex (p = 0.003), and a lack of surgical intervention (p < 0.001). CONCLUSIONS: Most patients with mEO-CRC fall within the range of 45 to 49 years of age. Patients with mEO-CRC were more likely to receive cancer-directed therapy (including chemotherapy and radiotherapy) and had better OS and CSS than those with mAO-CRC. This is likely attributable to the better performance status, fewer comorbidities, and better tolerance to cancer-directed therapy in mEO-CRC patients. The factors associated with worse OS and CSS were age > 50 years, mucinous adenocarcinoma, male sex, and no surgical treatment.

Survival Analysis, Clinical Characteristics, and Predictors of Cerebral Metastases in Patients with Colorectal Cancer.

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer globally and a leading cause of cancer-related deaths. While liver metastasis is common, brain metastasis (BM) is rare, occurring in 0.1% to 14% of cases. Risk factors for BM include lung metastasis at diagnosis, rectal cancer, and mutations in RAS and KRAS genes. Due to its rarity, guidelines for BM screening and treatment are limited. The aim of this study is to identify the clinical characteristics and predictors of BM at the time of the initial diagnosis of CRC. METHODS: We evaluated patients ≥18 years old with metastatic colorectal cancer and brain metastases at diagnosis from the SEER database (2010-2021). A retrospective cohort study was conducted to analyze overall survival and predictive factors for brain metastasis, utilizing multivariate logistic regression, Kaplan-Meier survival analysis, and the Cox proportional hazards models, with p-values < 0.05 considered significant. RESULTS: Out of 24,703 patients with metastatic colorectal cancer (mCRC), 228 (0.92%) had brain metastasis (BM) at diagnosis. BM was more prevalent in average-onset mCRC (≥50 years) compared to early-onset (<50 years) (1% vs. 0.55%, p = 0.004). Certain factors, such as older age and adenocarcinoma subtype, were associated with BM. Additionally, Asians/Pacific-Islanders (HR 1.83 CI: 1.01-3-33, p = 0.045) and American Indians/Alaska Natives (HR 4.79 CI 1.15-19.97, p = 0.032) had higher mortality rates, while surgical treatment and chemotherapy were linked to decreased mortality. Patients with BM had significantly worse overall survival (6 months vs. 21 months, p < 0.001). CONCLUSION: BM in mCRC is uncommon, but it is associated with significantly worse outcomes, including markedly reduced overall survival. Our study highlights several critical factors associated with the presence of BM, such as older age and specific racial/ethnic groups, which may inform risk stratification and early-detection strategies. Our findings emphasize the need for heightened awareness and screening for BM in high-risk mCRC patients, as well as the inclusion of these patients in clinical trials to explore tailored therapeutic approaches aimed at improving survival and quality of life.

Serological response to SARS-CoV-2 vaccines in patients with multiple sclerosis in Argentina.

INTRODUCTION: The objective was to assess the immunogenicity and effectiveness of vaccines against SARSCoV-2 in multiple sclerosis (MS) patients included in the Argentinean MS registry. METHODS: A prospective cohort study between May and December 2021. The primary outcome was immunogenicity and effectiveness of vaccines during a three-month follow-up. Immunogenicity was evaluated based on detection of total antibodies (Ab) against spike protein and neutralizing Ab in serum 4 weeks after the second vaccine dose. A positive COVID-19 case was defined according to Argentinean Ministry of Health. RESULTS: 94 patients were included, mean age: 41.7 ± 12.1 years. Eighty (85.1%) had relapsing remitting multiple sclerosis (RRMS); 30 (31.9%) were under fingolimod treatment. The Sputnik V vaccine was the first dose in 33 (35.1%), and AstraZeneca in 61 (64.9%). In 60 (63.8%), the vaccine elicited a specific humoral response. Immunological response according to the vaccination schemes showed no qualitative differences (p = 0.45). Stratified analysis according to the MS treatment showed that a significantly smaller number of subjects developed antibodies against spike antigen among those that were on ocrelizumab compared to other groups (p = 0.001), while a reduced number of patients under ocrelizumab where evaluated (n = 7). This was also observed for neutralizing antibodies in the ocrelizumab group (p < 0.001). During the three-month follow-up, two individuals were diagnosed with COVID-19. CONCLUSION: We found that MS patients that received Sputnik V or AstraZeneca vaccines for SARS-CoV-2 developed a serological response with no differences between the vaccines used.

Introducción: El objetivo fue evaluar la inmunogenicidad y efectividad de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple (EM) incluidos en el registro argentino de EM (RelevarEM, NCT03375177). Métodos: Estudio de cohorte prospectivo entre mayo y diciembre 2021. Se evaluó la inmunogenicidad (detección de anticuerpos totales (Ab) contra proteína espiga y anticuerpos neutralizantes en suero) y eficacia (nueva infección por COVID-19) durante seguimiento de tres meses. El momento de detección de anticuerpos fue 4 semanas después de segunda dosis de vacuna. Un caso positivo de COVID-19 se definió de acuerdo con la definición del Ministerio de Salud. Resultados: Se incluyeron 94 pacientes, edad media de 41.7 ± 12.1 años. Ochenta (85.1%) tenían EM remitente-recurrente; 30 (31.9%) en tratamiento con fingolimod. La vacuna Sputnik V fue usada en 33 (35.1%), mientras que AstraZeneca se administró en 61 (64.9%). En 60 pacientes (63.8 %), la vacuna provocó respuesta humoral específica. La respuesta inmunológica según esquemas de vacunación (Sputnik V, Astra Zeneca o esquemas heterólogos) no mostró diferencias cualitativas (p = 0.45). El análisis estratificado según tratamiento recibido para la EM mostró que número significativamente menor de sujetos desarrolló anticuerpos contra el antígeno espiga en los pacientes que recibieron ocrelizumab (p = 0.001), aunque con un número reducido de pacientes evaluados bajo este tratamiento (n = 7). Esto también se observó para anticuerpos neutralizantes en el grupo bajo ocrelizumab (p < 0.001). Durante el seguimiento de tres meses, dos personas fueron diagnosticadas con COVID-19. Conclusión: Encontramos que los pacientes con EM que recibieron vacunas Sputnik V o AstraZeneca para el SARS-CoV-2 desarrollaron respuesta serológica sin diferencias entre las vacunas utilizadas.

Latin American consensus recommendations on the risk of infections in people with multiple sclerosis treated with disease modifying drugs.

INTRODUCTION: The emergence of several therapeutic options in multiple sclerosis (MS), which significantly modify the immune system functioning, has led to the need for the consideration of additional factors, such as risk of infections, in the decision-making process. The aim of these consensus recommendations was to discuss and perform a practical guide to Latin American neurologists on the risk of infections at diagnosis, follow-up and prior to initiation of DMDs. METHODS: A panel of Latin American neurologists, experts in demyelinating diseases and dedicated to management and care of MS patients, gathered during 2021 and 2022 to make consensus recommendations on the risk of infections in PwMS treated with DMDs in Latin America. The RAND/UCLA methodology was developed to synthesize the scientific evidence and expert opinions on health care topics and was used for reaching a formal agreement. RESULTS: Recommendations were established based on relevant published evidence and expert opinion, focusing on: 1- baseline infection disease and vaccination status; 2- opportunistic infections; 3- progressive multifocal leukoencephalopathy; 4- genitourinary system infections; 5- respiratory tract infections; 6- digestive system infections, 7-others local infections and 8- COVID-19. CONCLUSION: The recommendations of this consensus seek to optimize the care, management and treatment of PwMS in Latin America. The standardized evidence-based care of pwMS infections will allow better outcomes.

Extended SEIR Model for Health Policies Assessment Against the COVID-19 Pandemic: the Case of Argentina.

This work presents an extended and age-band compartmentalised SEIR model that allows describing the spread evolution of SARS-CoV-2 and evaluating the effect of different detection rates, vaccination strategies or immunity periods. The model splits up the population into fifteen age groups of 5 years each, linked through a statistical interaction matrix that includes seventeen health states within each age group. An age-dependent transmission rate takes into account infectious between the groups as well the effect of interventions such as quarantines and mobility restrictions. Further, the proposal includes a nonlinear switched controller for model tuning purposes guarantying a simple and fast adjusting process. To illustrate the model potentials, the particular case of COVID-19 evolution in Argentina is analysed by simulation of three scenarios: (i) different detection levels combined with mobility restrictions, (ii) vaccination campaigns with re-opening of activities and (iii) vaccination campaigns with possible reinfections. The results exhibit how the model can aid the authorities in the decision making process.

Ventilator-associated pneumonia in patients on prolonged mechanical ventilation: description, risk factors for mortality, and performance of the SOFA score.

OBJECTIVE: Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation (MV). However, data on VAP in patients on prolonged MV (PMV) are scarce. We aimed to describe the characteristics of VAP patients on PMV and to identify factors associated with mortality. METHODS: This was a retrospective cohort study including VAP patients on PMV. We recorded baseline characteristics, as well as 30-day and 90-day mortality rates. Variables associated with mortality were determined by Kaplan-Meier survival analysis and Cox regression model. RESULTS: We identified 80 episodes of VAP in 62 subjects on PMV. The medians for age, Charlson Comorbidity Index, SOFA score, and days on MV were, respectively, 69.5 years, 5, 4, and 56 days. Episodes of VAP occurred between days 21 and 50 of MV in 28 patients (45.2%) and, by day 90 of MV, in 48 patients (77.4%). The 30-day and 90-day mortality rates were 30.0% and 63.7%, respectively. There were associations of 30-day mortality with the SOFA score (hazard ratio [HR] = 1.30; 95% CI: 1.12-1.52; p < 0.001) and use of vasoactive agents (HR = 4.0; 95% CI: 1.2-12.9; p = 0.02), whereas 90-day mortality was associated with age (HR = 1.03; 95% CI: 1.00-1.05; p = 0.003), SOFA score (HR = 1.20; 95% CI: 1.07-1.34; p = 0.001), use of vasoactive agents (HR = 4.07; 95% CI: 1.93-8.55; p < 0.001), and COPD (HR = 3.35; 95% CI: 1.71-6.60; p < 0.001). CONCLUSIONS: Mortality rates in VAP patients on PMV are considerably high. The onset of VAP can occur various days after MV initiation. The SOFA score is useful for predicting fatal outcomes. The factors associated with mortality could help guide therapeutic decisions and determine prognosis.

Potentials of constrained sliding mode control as an intervention guide to manage COVID19 spread.

This work evaluates the potential of using sliding mode reference conditioning (SMRC) techniques as a guide for non-pharmaceutical intervention (NPI) to control the COVID-19 pandemic. In particular, for the epidemiological problem addressed here, it is used to compute the contact rate reduction requirement in order to limit the infectious population to a given threshold. The SMRC controller allows the desired output variable limit and its approaching rate to be tuned explicitly. Implementation issues are taken into account and a periodically update of the NPI is proposed for the real life application. The strategy is evaluated under different scenarios where its distinctive features are exhibited.

Antibiotic Resistance in Community-Acquired Intra-Abdominal Infections: Diabetes Mellitus as a Risk Factor.

Background: Antimicrobial drug resistance in community-acquired (CA) infections is a growing problem. Knowing the local epidemiology is essential to design empirical antibiotic therapy. Therefore, we conducted this study to evaluate the resistance patterns of microorganisms isolated from surgical samples of community-acquired intra-abdominal infections (IAIs) and to determine the factors associated with resistance. Methods: We analyzed retrospectively the records of patients treated from January 2015 to June 2017 who had IAIs with positives aerobic cultures performed in the first 72 hours after admission. Surgical site infections, abdominal wall procedures, peritoneal dialysis catheters, and patients with admissions in the prior month were excluded. To identify the factors associated with resistance, we considered the resistance to the regimen recommended at our institution, ampicillin/sulbactam (AMS) plus ciprofloxacin (CIP). Results: There were 119 patients with 133 isolates, 59% women, and mean age 54 years. The main sources of infection were appendicitis (38%) and cholecystitis (20%), with 64 patients presenting a complicated IAI (cIAI), defined by the presence of peritonitis (55%). Resistance in Enterobacteriaceae was AMS 32% (6.4% intermediate resistance), CIP 31%, cefotaxime 9%, piperacillin/tazobactam (PTZ) 3%, trimethoprim/sulfamethoxazole 32%, gentamicin 9.5%, and amikacin 2%. Considering all patients, resistance to AMS + CIP was 16.8%. Factors associated with resistant to this regimen was, by univariable and multivariable analysis, the presence of diabetes mellitus (odds ratio [OR] 3.6; 95% confidence interval [CI] 1.1-11.6; p = 0.03). Female gender (OR 2.7; CI 0.9-8.4; p = 0.08) and complicated IAI (OR 2.0; CI 0.7-5.4; p = 0.17) were associated with resistance but did not reach statistical significance. Conclusion: High resistance to CIP and AMS was observed. Although the combination of AMS + CIP offers coverage for 84% of patients, PTZ should be considered as an option for patients with severe infections or diabetes mellitus. Finding factors associated with antibiotic resistance could help to select empirical therapy for CA IAIs better.

Association between serum transaminase levels and insulin resistance in euthyroid and non-diabetic adults.

AIM: To evaluate the association between elevated serum transaminase levels and insulin resistance (IR) in a population of healthy individuals. METHODS: We define IR with a cut-off point of homeostatic model assessment (HOMA-IR) ≥ 3.8. For aspartate aminotransferase (AST), we consider elevated values >30 U/L in women and values >36 U/L in men. For alanine aminotransferase (ALT), we consider elevated values >30 U/L in women and values >40 U/L in men. We performed a crude and adjusted generalized linear model from Poisson family with robust variance, in order to evaluate the association between elevated serum transaminase levels and IR. The associations were presented as prevalence ratio (PR) with their respective 95% confidence intervals (95% CI). RESULTS: We included 261 participants in the study. The median age was 39 years (31-45) and 23.7% of the participants were men. The prevalence of elevated serum transaminase for AST and ALT were, 13.8% and 26.1%, respectively. The prevalence of IR was 34.1%. In the crude analysis we found statistical significance between elevated AST and ALT with IR (PR = 3.18; 95% CI: 2.33-4.34 and PR = 2.44; 95% CI: 1.88-3.30; respectively). However, in the multivariate analysis, the association only remained statistically significance with ALT, but lost its significance with AST, PR = 1.90; CI 95%: 1.31-2.77 and a PR = 1.23; CI 95%: 0.93-1.61; respectively. CONCLUSION: Elevated serum levels of ALT were associated with insulin resistance. ALT could be used in clinical practice as an additional tool to assess IR in apparently healthy people.

Síndrome de burnout en pandemia y satisfacción laboral en médicos serumistas de Ayacucho / Pandemic burnout and job satisfaction among doctors from Ayacucho engaged in the SERUMS program

RESUMEN Objetivo: Evaluar la asociación entre el síndrome de burnout (SB) y la satisfacción laboral (SL) en los médicos serumistas de Ayacucho en el contexto de la pandemia por la COVID-19. Materiales y métodos: Estudio observacional, transversal, que usó un modelo crudo y ajustado para evaluar la asociación entre el SB, valorado por medio del cuestionario Maslach Burnout Inventory (MBI), y la SL, por medio del cuestionario de satisfacción S20/23. Las asociaciones se presentaron como razón de prevalencia (RP) con sus respectivos intervalos de confianza al 95 % (IC al 95 %). Resultados: De los 70 médicos serumistas, se encontró que el 77,14 % tenía entre 18-33 años, el 52,86 % eran hombres, el 51,43 % tenía menos de un año de experiencia laboral y el 88,57 % laboró en un centro de salud del Ministerio de Salud (Minsa). La prevalencia del SB fue de 45,71 %. La prevalencia del SB con insatisfacción fue del 30 %; con satisfacción, 32,86 %, y los indiferentes, 37,14 %. En el análisis crudo encontramos significancia estadística entre el SB y la SL (RP = 13,5; IC del 95 %:3,08-59,24), y en el análisis ajustado por sexo, estado civil y tiempo de experiencia laboral, la asociación entre el SB y la SL permaneció estadísticamente significativa (RP = 14,15; IC del 95 %: 3,02-66,32). Conclusiones: El SB se asocia a la SL de manera negativa, encontrando uno de cada dos médicos con SB. Además, se sugiere que existe mayor probabilidad de insatisfacción laboral en el personal con SB. Ello da a entender que podría usarse como indicador en diferentes áreas de la gestión y ser un punto a evaluar en la toma de decisiones en las directivas de salud. La solución de estos problemas contribuiría a mejorar las condiciones laborales actuales y, por ende, el sistema de salud.

ABSTRACT Objective: To determine the association between psychosocial work factors and symptoms of anxiety or depression among healthcare personnel in the Intensive Care Unit (ICU) at Hospital Regional Eleazar Guzmán Barrón in Nuevo Chimbote. Materials and methods: An observational, cross-sectional study was conducted, using both crude and adjusted models, to determine the association between burnout syndrome (BS), evaluated through the Maslach Burnout Inventory (MBI), and job satisfaction (JS), assessed via the Job Satisfaction Questionnaire S20/23. The associations were expressed as prevalence ratios (PR) with their respective 95 % confidence intervals (95 % CI). Results: Out of the 70 doctors engaged in the SERUMS program, 77.14 % were aged between 18 and 33 years, 52.86 % were males, 51.43 % had less than one year work experience and 88.57 % worked at a health center of the Ministry of Health. The prevalence of BS was 45.71 %. The prevalence of JS was as follows: dissatisfaction 30 %, satisfaction 32.86 % and indifference 37.14 %. In the crude analysis, a statistically significant association between BS and JS was found (PR = 13.5; 95 % CI: 3.08 59.24) and in the analysis adjusted for sex, marital status and length of work experience, the association between BS and JS remained statistically significant (PR = 14.15; 95 % CI: 3.02 66.32). Conclusions: BS is negatively associated with JS, with one in two doctors experiencing BS. Moreover, there appears to be a higher likelihood of job dissatisfaction among personnel with BS. This suggests that BS could serve as an indicator in different management areas and be considered in health management decision-making. Solving these issues could contribute to improving current working conditions and, therefore, the healthcare system.

Comprehensive analysis of a metabolic model for lipid production in Rhodosporidium toruloides.

The yeast Rhodosporidium toruloides has been extensively studied for its application in biolipid production. The knowledge of its metabolism capabilities and the application of constraint-based flux analysis methodology provide useful information for process prediction and optimization. The accuracy of the resulting predictions is highly dependent on metabolic models. A metabolic reconstruction for R. toruloides metabolism has been recently published. On the basis of this model, we developed a curated version that unblocks the central nitrogen metabolism and, in addition, completes charge and mass balances in some reactions neglected in the former model. Then, a comprehensive analysis of network capability was performed with the curated model and compared with the published metabolic reconstruction. The flux distribution obtained by lipid optimization with flux balance analysis was able to replicate the internal biochemical changes that lead to lipogenesis in oleaginous microorganisms. These results motivate the development of a genome-scale model for complete elucidation of R. toruloides metabolism.

Percepción de la accesibilidad de paratletas chilenos rumbo a Santiago 2023 / Percepção dos paratletas chilenos, rumo a Santiago 2023, sobre acessibilidade / Accessibility perception of chilean para-athletes, road to santiago 2023

Resumen El objetivo de esta investigación es triple: 1) comprender las percepciones de los paratletas sobre la accesibilidad respecto a las futuras sedes de los Juegos Parapanamericanos Santiago 2023; 2) establecer diferencias en la percepción debidas al origen de la discapacidad y 3) documentar la percepción de paratletas con grandes necesidades de apoyo (AHSN, por sus siglas en inglés). Esta investigación es cuantitativa transversal que, en su primera etapa, desarrolló el instrumento denominado Encuesta de Percepción de Accesibilidad de Para-atletas (PPA-D, por sus siglas en inglés) y, en una segunda etapa, se aplicó a 96 paratletas chilenos (77.8% hombres, edad promedio = 31.0 ± 11.6 años). Para la prueba, se obtuvo un coeficiente de validación = .96. Respecto a las características de la muestra, 16.6% correspondió a participantes con discapacidad visual; un 35.1% era AHSN; el 51.5% estaba vinculado a la alta competencia y el 59.3% se trasladaba por su cuenta a sus entrenamientos. Se identificó una percepción negativa de la accesibilidad, principalmente en cuanto al transporte en microbús, en los elevadores y en los espacios de baños, afectando principalmente a AHSN con discapacidad visual (F1,101 = 14.01, p = .0003). Se concluye que es importante abordar las brechas de género, origen de discapacidad y AHSN para garantizar una participación equitativa bajo un marco de derecho.

Resumo O objetivo desta pesquisa é triplo: 1) compreender as percepções dos paratletas sobre acessibilidade com relação às futuras sedes dos Jogos Parapan-Americanos de Santiago 2023; 2) estabelecer diferenças de percepção devido à origem da deficiência portada e 3) documentar a percepção de paratletas com altas necessidades de apoio (AHSN, por suas siglas em inglês). Esta pesquisa é quantitativa transversal que, em sua primeira etapa, desenvolveu o instrumento denominado Enquete de Percepção de Acessibilidade de Paratletas (PPA-D, por suas siglas em inglês) e, em uma segunda etapa, foi aplicada a 96 paratletas chilenos (77,8% homens, idade média = 31,0 ± 11,6 anos). Para o teste, obteve-se um coeficiente de validação = 0,96. Em relação às características da amostra, 16,6% corresponderam a participantes com deficiência visual; 35,1% eram AHSN; 51,5% estavam ligados à alta competência e 59,3% se deslocaram por conta própria para o treinamento. Identificou-se uma percepção negativa de acessibilidade, principalmente com relação ao transporte por micro-ônibus, elevadores e banheiros, afetando principalmente os AHSN com deficiência visual (F1.101 = 14,01, p = 0,0003). Conclui-se que é importante abordar as lacunas de gênero, origem da deficiência e AHSN para garantir uma participação equitativa ao abrigo de um quadro jurídico.

Abstract Accessibility perception of chilean para-athletes, road to Santiago 2023. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 20(2), 1-18. The objective of this research is three-fold: 1) to understand Para-athletes' perceptions on accessibility regarding Santiago 2023 Parapan American games' future venues, 2) to establish differences in perception due to the origin of the disability, and 3) document alignment, if any, with athletes with high support needs (AHSN). This research is a two-phased quantitative cross-sectional study, which at the first stage developed the "Para-athletes Perception on Accessibility Survey" (PPA-D) and, at the second stage, the survey was applied to 96 Chilean Para-athletes (77.8% men, mean age = 31.0 ± 11.6 years old). The test obtained a validation coefficient of = 0.96. Regarding the sample characteristics, 16.6% corresponded to participants with visual impairment, 35.1% were AHSN, 51.5% were linked to high-level competition, and 59.3% travelled on their own to their training sessions. A negative perception of accessibility was found, mainly concerning minibuses, elevators, and restroom spaces, affecting mostly AHSN with visual impairment (F1.101 = 14.01, p = .0003). We conclude that it is important to address gender, disability, and AHSN gaps to guarantee equitable participation under a framework of the law and social rights.

Serological response to SARS-COV-2 vaccines in patients with multiple sclerosis in Argentina / Respuesta serológica a vacunas contra SARS-CoV-2 en pacientes con esclerosis múltiple en Argentina

Abstract Introduction : The objective was to assess the im munogenicity and effectiveness of vaccines against SARSCoV-2 in multiple sclerosis (MS) patients included in the Argentinean MS registry. Methods : A prospective cohort study between May and December 2021. The primary outcome was im munogenicity and effectiveness of vaccines during a three-month follow-up. Immunogenicity was evalua ted based on detection of total antibodies (Ab) against spike protein and neutralizing Ab in serum 4 weeks after the second vaccine dose. A positive COVID-19 case was defined according to Argentinean Ministry of Health. Results : 94 patients were included, mean age: 41.7 ± 12.1 years. Eighty (85.1%) had relapsing remitting mul tiple sclerosis (RRMS); 30 (31.9%) were under fingolimod treatment. The Sputnik V vaccine was the first dose in 33 (35.1%), and AstraZeneca in 61 (64.9%). In 60 (63.8%), the vaccine elicited a specific humoral response. Immu nological response according to the vaccination schemes showed no qualitative differences (p = 0.45). Stratified analysis according to the MS treatment showed that a significantly smaller number of subjects developed anti bodies against spike antigen among those that were on ocrelizumab compared to other groups (p ≤ 0.001), while a reduced number of patients under ocrelizumab where evaluated (n = 7). This was also observed for neutralizing antibodies in the ocrelizumab group (p < 0.001). During the three-month follow-up, two individuals were diag nosed with COVID-19. Conclusion: We found that MS patients that recei ved Sputnik V or AstraZeneca vaccines for SARS-CoV-2 developed a serological response with no differences between the vaccines used.

Resumen Introducción : El objetivo fue evaluar la inmunogeni cidad y efectividad de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple (EM) incluidos en el registro argentino de EM (RelevarEM, NCT 03375177). Métodos : Estudio de cohorte prospectivo entre mayo y diciembre 2021. Se evaluó la inmunogenicidad (detec ción de anticuerpos totales (Ab) contra proteína espiga y anticuerpos neutralizantes en suero) y eficacia (nueva infección por COVID-19) durante seguimiento de tres meses. El momento de detección de anticuerpos fue 4 semanas después de segunda dosis de vacuna. Un caso positivo de COVID-19 se definió de acuerdo con la defi nición del Ministerio de Salud. Resultados : Se incluyeron 94 pacientes, edad media de 41.7 ± 12.1 años. Ochenta (85.1%) tenían EM remiten te-recurrente; 30 (31.9%) en tratamiento con fingolimod. La vacuna Sputnik V fue usada en 33 (35.1%), mientras que AstraZeneca se administró en 61 (64.9%). En 60 pa cientes (63.8 %), la vacuna provocó respuesta humoral específica. La respuesta inmunológica según esquemas de vacunación (Sputnik V, Astra Zeneca o esquemas he terólogos) no mostró diferencias cualitativas (p = 0.45). El análisis estratificado según tratamiento recibido para la EM mostró que número significativamente menor de sujetos desarrolló anticuerpos contra el antígeno espiga en los pacientes que recibieron ocrelizumab (p ≤ 0.001), aunque con un número reducido de pacientes evaluados bajo este tratamiento (n = 7). Esto también se observó para anticuerpos neutralizantes en el grupo bajo ocrelizumab (p < 0.001). Durante el seguimiento de tres meses, dos personas fueron diagnosticadas con COVID-19. Conclusión : Encontramos que los pacientes con EM que recibieron vacunas Sputnik V o AstraZeneca para el SARS-CoV-2 desarrollaron respuesta serológica sin diferencias entre las vacunas utilizadas.

Accessibility perception of chilean para-athletes, road to santiago 2023 / Percepción de atletas chilenos, rumbo a Santiago 2023, sobre la accesibilidad

Contreras-Jofré, N. F., Pinochet-Gilli, J. I., Aguayo-Carrasco, E. A., Binimelis-Hermosilla, M., Pérez-Núñez, S. B., Vergara-Ortúzar, R. C. & Muñoz-Hinrichsen, F. (2022). Accessibility perception of chilean para-athletes, road to Santiago 2023. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 20(2), 1-18. The objective of this research is three-fold: 1) to understand Para-athletes' perceptions on accessibility regarding Santiago 2023 Parapan American games' future venues, 2) to establish differences in perception due to the origin of the disability, and 3) document alignment, if any, with athletes with high support needs (AHSN). This research is a two-phased quantitative cross-sectional study, which at the first stage developed the ''Para-athletes Perception on Accessibility Survey" (PPA-D) and, at the second stage, the survey was applied to 96 Chilean Para-athletes (77.8% men, mean age = 31.0 ± 11.6 years old). The test obtained a validation coefficient of = 0.96. Regarding the sample characteristics, 16.6% corresponded to participants with visual impairment, 35.1% were AHSN, 51.5% were linked to high-level competition, and 59.3% travelled on their own to their training sessions. A negative perception of accessibility was found, mainly concerning minibuses, elevators, and restroom spaces, affecting mostly AHSN with visual impairment (F1.101 = 14.01, p = .0003). We conclude that it is important to address gender, disability, and AHSN gaps to guarantee equitable participation under a framework of the law and social rights.

Contreras-Jofré, N. F., Pinochet-Gilli, J. I., Aguayo-Carrasco, E. A., Binimelis-Hermosilla, M., Pérez-Núñez, S. B., Vergara-Ortúzar, R. C. & Muñoz-Hinrichsen, F. (2022). Percepción de para atletas chilenos, rumbo a Santiago 2023, sobre la accesibilidad. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 20(2), 1-18. El objetivo de esta investigación es triple: 1) comprender las percepciones de los paratletas sobre la accesibilidad respecto a las futuras sedes de los Juegos Parapanamericanos Santiago 2023; 2) establecer diferencias en la percepción debidas al origen de la discapacidad y 3) documentar la percepción de paratletas con grandes necesidades de apoyo (AHSN, por sus siglas en inglés). Esta investigación es cuantitativa transversal que, en su primera etapa, desarrolló el instrumento denominado Encuesta de Percepción de Accesibilidad de Para-atletas (PPA-D, por sus siglas en inglés) y, en una segunda etapa, se aplicó a 96 paratletas chilenos (77.8% hombres, edad promedio = 31.0 ± 11.6 años). Para la prueba, se obtuvo un coeficiente de validación = .96. Respecto a las características de la muestra, 16.6% correspondió a participantes con discapacidad visual; un 35.1% era AHSN; el 51.5% estaba vinculado a la alta competencia y el 59.3% se trasladaba por su cuenta a sus entrenamientos. Se identificó una percepción negativa de la accesibilidad, principalmente en cuanto al transporte en microbús, en los elevadores y en los espacios de baños, afectando principalmente a AHSN con discapacidad visual (F1,101 = 14.01, p = .0003). Se concluye que es importante abordar las brechas de género, origen de discapacidad y AHSN para garantizar una participación equitativa bajo un marco de derecho.

Contreras-Jofré, N. F., Pinochet-Gilli, J. I., Aguayo-Carrasco, E. A., Binimelis-Hermosilla, M., Pérez-Núñez, S. B., Vergara-Ortúzar, R. C. & Muñoz-Hinrichsen, F. (2022). Percepção dos paratletas chilenos, rumo a Santiago 2023, sobre acessibilidade. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 20(2), 1-18. O objetivo desta pesquisa é triplo: 1) compreender as percepções dos paratletas sobre acessibilidade com relação às futuras sedes dos Jogos Parapan-Americanos de Santiago 2023; 2) estabelecer diferenças de percepção devido à origem da deficiência portada e 3) documentar a percepção de paratletas com altas necessidades de apoio (AHSN, por suas siglas em inglês). Esta pesquisa é quantitativa transversal que, em sua primeira etapa, desenvolveu o instrumento denominado Enquete de Percepção de Acessibilidade de Paratletas (PPA-D, por suas siglas em inglês) e, em uma segunda etapa, foi aplicada a 96 paratletas chilenos (77,8% homens, idade média = 31,0 ± 11,6 anos). Para o teste, obteve-se um coeficiente de validação = 0,96. Em relação às características da amostra, 16,6% corresponderam a participantes com deficiência visual; 35,1% eram AHSN; 51,5% estavam ligados à alta competência e 59,3% se deslocaram por conta própria para o treinamento. Identificou-se uma percepção negativa de acessibilidade, principalmente com relação ao transporte por micro-ônibus, elevadores e banheiros, afetando principalmente os AHSN com deficiência visual (F1.101 = 14,01, p = 0,0003). Conclui-se que é importante abordar as lacunas de gênero, origem da deficiência e AHSN para garantir uma participação equitativa ao abrigo de um quadro jurídico.

Úlcera solitaria de ciego como etiología poco frecuente de abdomen agudo inflamatorio quirúrgico / Solitary cecal ulcer as a rare cause of acute surgical abdomen

RESUMEN Las úlceras solitarias de ciego (USC) son infrecuentes y no se registran aún en la literatura de la Ar gentina. Existen informes de casos y pequeñas series en otros países. Son de etiología desconocida y diagnóstico diferencial amplio. En este caso se resolvió mediante una hemicolectomía derecha supra selectiva por laparotomía de emergencia.

ABSTRACT Solitary cecal ulcers (SCUs) are rare and no cases have been published in Argentina. Few cases or series have been reported in other countries. The etiology is unknown and many other diseases must be ru led out before making the diagnosis. This case was solved with selective right hemicolectomy through laparotomy in an emergency basis.

Ventilator-associated pneumonia in patients on prolonged mechanical ventilation: description, risk factors for mortality, and performance of the SOFA score / Pneumonia associada à ventilação mecânica em pacientes em ventilação mecânica prolongada: descrição, fatores de risco associados à mortalidade e desempenho do escore SOFA

ABSTRACT Objective: Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation (MV). However, data on VAP in patients on prolonged MV (PMV) are scarce. We aimed to describe the characteristics of VAP patients on PMV and to identify factors associated with mortality. Methods: This was a retrospective cohort study including VAP patients on PMV. We recorded baseline characteristics, as well as 30-day and 90-day mortality rates. Variables associated with mortality were determined by Kaplan-Meier survival analysis and Cox regression model. Results: We identified 80 episodes of VAP in 62 subjects on PMV. The medians for age, Charlson Comorbidity Index, SOFA score, and days on MV were, respectively, 69.5 years, 5, 4, and 56 days. Episodes of VAP occurred between days 21 and 50 of MV in 28 patients (45.2%) and, by day 90 of MV, in 48 patients (77.4%). The 30-day and 90-day mortality rates were 30.0% and 63.7%, respectively. There were associations of 30-day mortality with the SOFA score (hazard ratio [HR] = 1.30; 95% CI: 1.12-1.52; p < 0.001) and use of vasoactive agents (HR = 4.0; 95% CI: 1.2-12.9; p = 0.02), whereas 90-day mortality was associated with age (HR = 1.03; 95% CI: 1.00-1.05; p = 0.003), SOFA score (HR = 1.20; 95% CI: 1.07-1.34; p = 0.001), use of vasoactive agents (HR = 4.07; 95% CI: 1.93-8.55; p < 0.001), and COPD (HR = 3.35; 95% CI: 1.71-6.60; p < 0.001). Conclusions: Mortality rates in VAP patients on PMV are considerably high. The onset of VAP can occur various days after MV initiation. The SOFA score is useful for predicting fatal outcomes. The factors associated with mortality could help guide therapeutic decisions and determine prognosis.

RESUMO Objetivo: A pneumonia associada à ventilação mecânica (PAVM) é uma séria complicação da ventilação mecânica (VM). Entretanto, dados sobre PAVM em pacientes em VM prolongada (VMP) são escassos. Nosso objetivo foi descrever as características de pacientes com PAVM em VMP e identificar fatores associados à mortalidade. Métodos: Estudo de coorte retrospectivo incluindo pacientes com PAVM em VMP. Foram registradas características basais, bem como as taxas de mortalidade em 30 e 90 dias. As variáveis associadas à mortalidade foram determinadas por meio da análise de sobrevida de Kaplan-Meier e do modelo de regressão de Cox. Resultados: Foram identificados 80 episódios de PAVM em 62 indivíduos em VMP. As medianas de idade, índice de comorbidade de Charlson, pontuação no SOFA, e dias em VM foram, respectivamente, de 69,5 anos, 5, 4 e 56 dias. Os episódios de PAVM ocorreram entre o 21º e o 50º dia de VM em 28 pacientes (45,2%) e até o 90º dia de VM em 48 pacientes (77,4%). As taxas de mortalidade em 30 e 90 dias foram de 30,0% e 63,7%, respectivamente. A mortalidade em 30 dias associou-se a pontuação no SOFA (razão de risco [RR] = 1,30; IC95%: 1,12-1,52; p < 0,001) e uso de drogas vasoativas (RR = 4,0; IC95%: 1,2-12,9; p = 0,02), enquanto a mortalidade em 90 dias associou-se a idade (RR = 1,03; IC95%: 1,00-1,05; p = 0,003), pontuação no SOFA (RR = 1,20; IC95%: 1,07-1,34; p = 0,001), uso de drogas vasoativas (RR = 4,07; IC95%: 1,93-8,55; p < 0,001) e DPOC (RR = 3,35; IC95%: 1,71-6,60; p < 0,001). Conclusões: As taxas de mortalidade em pacientes com PAVM em VMP são consideravelmente altas. O início da PAVM pode ocorrer vários dias após a instituição da VM. O escore SOFA é útil para predição de desfechos fatais. Os fatores associados à mortalidade podem ajudar a orientar as decisões terapêuticas e a determinar o prognóstico.

Chemsex y uso de sustancias durante las relaciones sexuales: resultados de una encuesta realizada en Argentina / Chemsex and use of substances during sexual intercourse: results of a survey conducted in Argentina

Introducción: Chemsex está relacionado con el uso de ciertas drogas que facilitan la excitación y el prolongar la duración de los encuentros sexuales.Objetivo: Describir el perfil de consumo de los usuarios de sustancias durante las relaciones sexuales (SRS) y su relación con variables demográficas, de estilo de vida y de salud.Métodos: Estudio descriptivo y transversal realizado a través de una encuesta autoadministrada y anónima en el marco de la plataforma Google Forms® que se transmitió en diferentes redes sociales. Objetivo: describir los aspectos demográficos y de estilo de vida de los encuestados y del subgrupo de usuarios de SRS y chemsex.Resultados: Se recibieron 2924 encuestas; 421 personas (16,9%) refirieron haber consumido al menos una vez uno o más de los siguientes: mefedrona, metanfetamina, crystal meth, GHB/GBL, cocaína, LSD, poppers, ketamina y éxtasis. Chemsex se definió como el consumo de los tres primeros y su prevalencia fue del 1,1%. El perfil de usuario de SRS y chemsex en nuestro estudio fue un hombre de entre 26 y 35 años, HSH y habitante de la Ciudad de Buenos Aires. Hubo mayor proporción de personas con VIH y diagnósticos de ITS en el último año dentro de los usuarios de SRS y chemsex.Conclusiones: Esta es la primera encuesta que trata este tema en nuestro país y en América Latina. Teniendo en cuenta la tendencia a un menor uso de los condones RESUMENARTÍCULO ORIGINALISSN 2314-3193. Actualizaciones en sida e infectología. Buenos Aires. noviembre 2020. volumen 28. número 103: 40-50y a presentar más diagnósticos de ITS y VIH en la población de usuarios de SRS, consideramos de interés conocer la epidemiología en nuestra población

Introduction: Chemsex is related to the use of certain drugs to facilitate sustained arousal and induce a feeling of instant rapport with sexual partners.Aim: To describe the consumption profile of users of substances during sexual intercourse (SSI) and its relationship with demographic, lifestyle and health variables.Methods: Descriptive and cross-sectional study conducted through a self-administered and anonymous survey under the Google Forms platform ® which was broadcasted on different social networks. Main outcome measures: Description on demographic and lifestyle aspects of the respondents and in the subgroup of SSI and chemsex users.Results: 2924 surveys were received; 421 people (16.9%) referred to having consumed at least once one or more of the following: mephedrone, crystal meth, GHB/GBL, cocaine, LSD, poppers, ketamine and ecstasy. Chemsex was defined as the consumption of the first three and its prevalence was 1.1%. A SSI and chemsex user profile in our study was a man between 26 and 35 years, MSM and inhabitant of the city of Buenos Aires. SSI and chemsex users were more likely to and STI in the last year and to have HIV diagnosis.Conclusions: This is the first survey that deals with this issue in our country and in Latin America. Accounting for the tendency to less use of condoms and to present more diagnoses of STIs and HIV in the population of SSI users, we consider it necessary to study this subject in our country as the rising reports in world literature show a boost in substance use.Keywords: Chemsex, Drugs, HIV, VIH, STI, ITS.Chemsex and use of substances during sexual intercourse: results of a survey conducted in Argentina