Characterization of the interaction between the Sec61 translocon complex and ppαF using optical tweezers.

The Sec61 translocon allows the translocation of secretory preproteins from the cytosol to the endoplasmic reticulum lumen during polypeptide biosynthesis. These proteins possess an N-terminal signal peptide (SP) which docks at the translocon. SP mutations can abolish translocation and cause diseases, suggesting an essential role for this SP/Sec61 interaction. However, a detailed biophysical characterization of this binding is still missing. Here, optical tweezers force spectroscopy was used to characterize the kinetic parameters of the dissociation process between Sec61 and the SP of prepro-alpha-factor. The unbinding parameters including off-rate constant and distance to the transition state were obtained by fitting rupture force data to Dudko-Hummer-Szabo models. Interestingly, the translocation inhibitor mycolactone increases the off-rate and accelerates the SP/Sec61 dissociation, while also weakening the interaction. Whereas the translocation deficient mutant containing a single point mutation in the SP abolished the specificity of the SP/Sec61 binding, resulting in an unstable interaction. In conclusion, we characterize quantitatively the dissociation process between the signal peptide and the translocon, and how the unbinding parameters are modified by a translocation inhibitor.

Women Are Also Disadvantaged in Accessing Transplant Outside the United States: Analysis of the Spanish Liver Transplantation Registry.

Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.

Obesity is an independent risk factor for cancer development following diagnosis of dermatomyositis.

Patients with dermatomyositis (DM) are at an increased risk of cancer development, especially around the time of diagnosis of DM. Obesity is also a risk factor in the general population for cancer development. This study aimed to assess the association between cancer in DM patients with and without obesity as defined by ICD code and BMI data. In this analysis of patients with DM, logistic regression modeling of the odds of cancer outcome was performed for patients with DM and obesity compared to those without obesity, adjusted for age and sex. A total of 12,722 patients with DM were identified, of whom 6,055 had available BMI data. DM patients who were coded obese at any point had significantly higher odds 1.98 (95 % Confidence interval (CI) 1.70, 2.30) of a subsequent cancer diagnosis. This association was also found in the subgroup analysis with available BMI where patients with obesity (BMI ≥30 kg/m2) had an increased odds of cancer 1.23 (1.02, 1.49) when compared to patients with BMI <30 kg/m2 with DM. In time to event analysis any obesity code was associated with a 16 % increased hazard of cancer (adjusted hazard ratio 1.16 [95 % CI 1.02, 1.31]). Overall, the most frequent type of cancer was breast cancer, however patients with DM and obesity had higher frequencies of lymphoma, colorectal, melanoma, uterine, renal cancers compared to patients with DM without obesity.

Salvage of a Fractured Proximal Ulnar Osteoarticular Allograft Using a Medial Femoral Condyle Free Flap: A Case Report.

CASE: We present the case of a 47-year-old paraplegic woman who underwent resection of an intermediate-grade chondrosarcoma in the proximal ulna, which was initially reconstructed with an osteoarticular allograft. However, after more than 25 years without complications, she sustained an intra-articular fracture of the allograft, which was then successfully treated using a vascularized medial femoral condyle (MFC) flap and anterolateral thigh flap. The patient has subsequently recovered her baseline elbow function, has no pain, and can use her wheelchair without restrictions. CONCLUSION: Free MFC flaps are viable options to salvage osteoarticular allografts that are affected by intra-articular fractures.

TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck.

Objectives: The aim of this study was to confirm the efficacy of the ERBITAX scheme (paclitaxel 80 mg/m2 weekly and cetuximab 400 mg/m2 loading dose, and then 250 mg/m2 weekly) as first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) who are medically unfit for cisplatin-based (PT) chemotherapy. Materials and methods: This retrospective, non-interventional study involved 16 centers in Spain. Inclusion criteria were to have started receiving ERBITAX regimen from January 2012 to December 2018; histologically confirmed SCCHN including oral cavity, oropharynx, hypopharynx, and larynx; age ≥18 years; and platinum (PT) chemotherapy ineligibility due to performance status, comorbidities, high accumulated dose of PT, or PT refractoriness. Results: A total of 531 patients from 16 hospitals in Spain were enrolled. The median age was 66 years, 82.7% were male, and 83.5% were current/former smokers. Patients were ineligible to receive PT due to ECOG 2 (50.3%), comorbidities (32%), PT cumulative dose ≥ 225 mg/m2 (10.5%), or PT refractoriness (7.2%). Response rate was 37.7%. Median duration of response was 5.6 months (95% CI: 4.4-6.6). With a median follow-up of 8.7 months (95% CI: 7.7-10.2), median PFS and OS were 4.5 months (95% CI: 3.9-5.0) and 8.9 months (95% CI: 7.8-10.3), respectively. Patients treated with immunotherapy after ERBITAX had better OS with a median of 29.8 months compared to 13.8 months for those who received other treatments. The most common grade ≥ 3 toxicities were acne-like rash in 36 patients (6.8%) and oral mucositis in 8 patients (1.5%). Five (0.9%) patients experienced grade ≥ 3 febrile neutropenia. Conclusion: This study confirms the real-world efficacy and tolerability of ERBITAX as first-line treatment in recurrent/metastatic SCCHN when PT is not feasible. Immunotherapy after treatment with ERBITAX showed remarkable promising survival, despite potential selection bias.

The Slipper Fracture: Revisited.

Objectives The term "slipper fracture" is used to describe a fracture of the radius at the junction of the metaphysis and diaphysis. This fracture has an "evil" reputation because it often angulates in the cast. Historically, there have been differing opinions on the optimal way to cast slipper fractures either with a long arm cast in pronation or a long arm cast in supination to prevent angulation. The purpose of this study is to report the outcomes of "slipper fractures" treated with casting. Methods Sixteen slipper fractures were retrospectively reviewed. Electronic medical records (EMRs) and radiographs were analyzed to gather data on body weight, cast type, cast position, cast index, loss of reduction, cast wedging, repeat reduction, surgery, and amount of remodeling. Results The average age of the patients was eight years old. The average body weight was 30.4 kg. Initial casting included 14 long arm casts in neutral, one short arm cast, and one sugar tong splint. The average cast index was 0.87. Only one cast had a cast index of less than 0.8. This fracture was treated with a long arm cast and did not displace. Of the fractures, 94% lost reduction in the cast and angulated an average of 26 degrees. Two cases were treated with a cast wedge; 13 were observed. Remodeling occurred at an average rate of 2.7 degrees/month. The average remodeling measured at the last follow-up was 15 degrees. Conclusion Slipper fractures are difficult to treat due to the angulation of the fracture in the cast. The current study indicates that a long arm cast, appropriate cast index, and cast position are key to preventing the loss of reduction or angulation of a slipper fracture.

Comparison between Wright and Shukla formulas: which is better for the placement of umbilical catheters in newborns ≤ 1500 g? / Comparación entre las fórmulas de Wright y de Shukla: ¿cuál es mejor para la colocación de catéteres umbilicales en recién nacidos ≤ 1500 g?

Abstract Background: Intravascular venous (VUC) or arterial (AUC) umbilical catheter placement is the most frequent invasive procedure in the neonatal intensive care unit (NICU). Either Wright's or Shukla's formula is used to introduce the catheters. However, Shukla's formula is associated with incorrect insertion, especially for newborns < 1500 g. This study aimed to determine by chest X-ray if Wright's formula is better than Shukla's formula for the correct placement of umbilical catheters in newborns ≤ 1500 g. Methods: We included patients admitted to the NICU of a secondary-level hospital between 2021-2022 who received VUC or AUC through the Wright or Shukla formulas. Results: A total of 129 newborns were included: 78 with VUC and 51 with AUC. In VUC, 50% with Wright and 36.8% with Shukla formulas had the correct location, (p = 0.24). In AUC, 56.6 % with Wright and 52.4% with Shukla formulas were placed correctly placed, (p = 0.76). VUC with weight < 1000 g were correctly placed in 36.4% with Wright and 33.3% with Shukla formulas (p = 0.58). VUC in newborns > 1000 g were correctly placed in 66.6% with Wright and 38.4% with Shukla formulas (p = 0.065). AUC in newborns < 1000 g were correctly placed in 45% using Wright and 42.9% Shukla formulas (p = 0.63). AUC in newborns > 1000 g were correctly placed in 80% using Wright and 57.1% Shukla formulas (p = 0.23). Conclusions: We found 13% more correctly placed VUC using Wright's formula. Moreover, Wright's formula was 29% above Shukla's VUC placement in neonates > 1000 g, although there was no significant difference due to the sample size.

Resumen Introducción: La colocación de catéteres intravasculares venosos umbilicales (CVU) y arteriales (CAU) es el procedimiento invasivo más frecuente en la unidad de cuidados intensivos neonatales (UCIN). Para introducirlos se utilizan las fórmulas de Wright y de Shukla, aunque esta última podría estar asociada con una inserción incorrecta, especialmente en neonatos < 1500 g. El objetivo de este estudio fue determinar mediante radiografía de tórax cuál fórmula es mejor para la correcta colocación de catéteres umbilicales en recién nacidos ≤ 1500 g. Métodos: Se incluyeron los pacientes ingresados en la UCIN de un hospital de segundo nivel entre 2021-2022 que recibieron CVU o CAU mediante las fórmulas de Wrigth o Shukla. Resultados: Se incluyeron en total 129 recién nacidos: 78 CVU y 51 CAU. En CVU, Wright 50% y Shukla 36.8% tuvieron localización correcta, p = 0.24. En las CAU, Wright 56.6% y Shukla 52.4% tenían una ubicación correcta, p = 0.76. En CVU con peso < 1000 g, Wright 36.4% y Shukla 33.3% bien situados, p = 0.58. En CVU > 1000 g, Wright 66.6% y Shukla 38.4% bien situados, p = 0.065. En CAU < 1000 g, Wright 45% y Shukla 42.9%, p = 0.63. En CAU con peso > 1000 g, Wright 80% y Shukla 57.1%, p = 0.23. Conclusiones: La colocación del CVU fue 13% mejor con la fórmula de Wright. La fórmula de Wright superó en el 29% la colocación del CVU en los neonatos > 1000 g en comparación con la de Shukla, aunque no hubo diferencia significativa debido al tamaño de la muestra.

Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical trials because of the theoretical risk of irAEs. This study aimed to evaluate the risk of irAEs in patients with pre-existing rheumatologic diseases on ICIs, impact of anti-rheumatic therapy on irAEs, and malignancy outcomes. METHODS: We performed a retrospective chart review of patients with a pre-existing rheumatologic diagnosis receiving ICIs at the University of North Carolina from 2014 to 2019. Risk differences (RD) and asymptotic 95% confidence intervals (95% CIs) using a continuity correction along with odds ratios (OR) and exact 95% CIs were produced between pre-specified risk factors and flares of the underlying rheumatologic disease and/or irAEs. Kaplan-Meier survival estimates for time to unfavorable cancer response between subsets of patients were compared using the log-rank test. RESULTS: We identified 45 patients receiving an ICI with an underlying rheumatologic diagnosis, including 22 with rheumatoid arthritis (RA). Overall, 13 patients (29%) had a flare of their autoimmune disease, 20 patients (44%) had a new-onset irAE, and 27 (60%) had either a flare or new-onset irAE. Patients with RA had higher risk of flares compared to those with other rheumatologic disorders (45% vs 13%, RD 32%, 95% CI 2.0-56.8); all RA flares were ≤ grade 2 and treated in the outpatient setting. Concurrent treatment of the rheumatologic disease at the start of ICI therapy was not associated with a reduced risk of flare (OR 0.86, 95% CI 0.19-3.76) or new onset irAE (OR 3.21, 95% CI 0.83-13.6) compared to those not on anti-rheumatic medications. Anti-rheumatic therapy did not impact time to unfavorable malignancy outcome (p = 0.52). CONCLUSION: The majority of our study cohort experienced a flare or new onset irAE with ICI treatment. Treatment with anti-rheumatic therapy did not prevent disease flares or new onset irAEs, but did not negatively impact malignancy outcomes. Research is needed to determine safe anti-rheumatic therapy options to prevent flares and irAEs that do not interfere with malignancy outcomes.

Postreperfusion Biopsy as a Predictor of Biliary Complication After Deceased Donor Liver Transplantation. A Retrospective Cohort Study.

BACKGROUND: Ischemia reperfusion injury (IRI) on postreperfusion biopsies is associated with worse outcomes after liver transplantation, although the influence on biliary complications (BC) remains poorly studied. Therefore, the primary aim of our study was to assess the influence of IRI on the incidence of BC. A secondary aim was to assess the influence of steatosis on biliary complications and determine factors that predictor BC. METHODS: We report a retrospective cohort study including patients with liver transplantation and postreperfusion injury. Biopsies were classified as relevant and nonrelevant ischemia reperfusion injury for assessment of BC. BC included anastomotic stricture, ischemic cholangiopathy, leaks, and bilomas. Independent predictive factors of biliary complications were assessed using univariate and multivariate analyses. RESULTS: 302 patients were included, and 125 patients fulfilled the criteria for relevant IRI (41.4%). Worse IRI was not associated with biliary complications (42.5% vs 40.1%; P = .68), nor was liver graft steatosis associated with BC (40.5% vs 41.5%, P = .95). The median time until biliary complications did not differ between the 2 groups (2 months; interquartile range = 1-15 vs 3 months; interquartile range = 1-12.5; P = .18). Hepatic artery thrombosis (odds ratio [OR] = 3.4; 95% confidence interval [CI], 1.4-8.2; P = .004), older donor age (OR = 2.1; 95% CI, 1.1-4.1; P = .024), and prolonged cold ischemia time (OR = 1.9; 95% CI, 1.1-3.2) were independent factors of biliary complications. CONCLUSION: Severe IRI on the postreperfusion injury does not predict development of biliary complications.

Postreperfusion Liver Biopsy as Predictor of Early Graft Dysfunction and Survival After Orthotopic Liver Transplantation.

Background: Postreperfusion liver biopsy (PRB) can assess the degree of ischemia/reperfusion injury (IRI) after orthotopic liver transplantation (OLT). The influence of IRI on graft outcomes and overall survival is controversial. Aim: To determine the correlation between the severity of IRI in PRB and overall graft and patient survival and, secondarily, to identify factors on PRB that predict poor graft outcomes. Methods: This is a retrospective analysis of all patients who underwent OLT using donation after brain death (DBD) with PRB. The severity of IRI in PRB was graded. Predictors of IRI were assessed using univariate and multivariate analysis and the Kaplan-Meier with log rank test for the graft and overall survival, respectively. Results: We included 280 OLTs (64.7%). The histopathological assessment of IRI severity was as follows: no IRI (N = 96, 34.3%), mild IRI (N = 65; 23.2%), moderate IRI (N = 101; 36.1%), and severe IRI (N = 18; 6.4%). The incidence rates of initial good graft function (IGGF), primary nonfunction and early allograft dysfunction (EAD) were 32.5%, 3.9%, and 18.6%, respectively. Severe IRI was associated with a lower incidence of IGGF (OR: 0.34, 95% CI 0.12-0.92; P = 0.03). Patients with severe IRI tended to have a higher incidence of EAD (33.2% vs. 18.6, P = 0.23). The cold ischemia time was an independent predictor of severe IRI on the multivariate analysis. Severe IRI was associated with poor 1- and 5-year overall survival rates (67% and 44%, respectively, compared with 84 and 68% in nonsevere IRI). Patients with severe IRI exhibited worse graft and overall survival. Conclusions: Cold ischemia time predicts the development of severe IRI. Patients with severe IRI show worse graft and overall survival and a lower incidence of IGGF, suggesting that histopathological findings could be useful for identifying patients at high risk of worse outcomes after OLT.

BRCA1 and BRCA2 screening of nine Chilean founder mutations through allelic-discrimination and real-time PCR in breast/ovarian cancer patients.

BACKGROUND: In a previous work, we identified nine founder mutations present in close to 80% of BRCA1 and BRCA2 mutation carriers, and distributed across the country. The presence of founder mutations constitutes a valuable opportunity to develop new strategies for genetic screening. Genetic tests are primarily performed by NGS sequencing, which requires sophisticated and expensive equipment, and it takes 2-3 weeks for the results to be informed to the patient. In addition, genetic tests are not covered by insurance companies in Latin American countries. In this work, we present the standardization and technical validation of a real-time PCR based methodology for allelic discrimination in order to identify the nine Chilean founder mutations in BRCA1 and BRCA2 genes. METHODS AND RESULTS: We designed nine pairs of probes and nine pairs of primers to amplify synchronically nine regions of the BRCA1/BRCA2 genes by real-time PCR, in order to identify the nine founder mutations through allelic discrimination analyses. Technical validation was performed using 90 positive and 90 negative samples for each mutation. The methodology was tested in a second group of 60 patients. Our method correctly classified carriers and non-carriers of one of the nine Chilean founder mutations with a 100% specificity and 100% sensitivity, compared with Sanger sequencing performance. CONCLUSIONS: We develop an inexpensive, simple, and fast mutation detection method that could be implemented locally in Hospitals from the Private to Public health system. This methodology may be useful for the screening of BRCA1 and BRCA2 mutations in other populations.

Mortalidad por sepsis neonatal entre los años 2016 y 2020 en Chile: una mirada nacional / Mortality due to neonatal sepsis between 2016 and 2020 in Chile: a national perspective

Introducción: La sepsis neonatal (SN) es una infección sistémica que ocurre antes de los 90 días de vida y que representa una amenaza potencialmente mortal. Esta investigación busca describir la tendencia de defunción por SN en Chile, durante el periodo 2016-2020. Materiales y métodos: Estudio descriptivo observacional, que incluyó a niños fallecidos por SN (n=249) en el periodo 2016-2020 en Chile según datos del departamento de estadísticas e información de salud de Chile. Las variables estudiadas fueron: año de fallecimiento, grupo etario, sexo, región y agente etiológico. No se requirió comité de ética. Resultados: El 2020 tuvo la menor tasa de mortalidad por SN (0,17) y el 2017 la mayor (0,31). El grupo etario de 0-2 días de nacido tuvo la mayor tasa de mortalidad (0,07), mientras que el grupo de 27-28 días corresponde a la menor (0,00). La región de Antofagasta tuvo la mayor mortalidad (0,44) y la región de Magallanes la menor (0,11). La tasa de mortalidad promedio en hombres corresponde a 0,12 y en mujeres a 0,10. En el 89,16% de los casos no se identificó el agente etiológico. Discusión: La mayor mortalidad en 2017 podría deberse a una proporción más alta de nacimientos pretérmino en dicho año. La mayor cantidad de defunciones a menor edad cronológica estaría relacionada con su inmadurez inmunológica. La no detección del agente etiológico pudo deberse al bajo rendimiento de los hemocultivos. Sin embargo, faltan más investigaciones acerca de la incidencia y mortalidad por sepsis neonatal.

Introduction: Neonatal sepsis (NS) is a systemic infection that occurs before 90 days of life and represents a life-threatening threat. This research seeks to describe the trend of death by NS in Chile, during the period 2016-2020. Materials and methods: Observational descriptive study, which included children who died due to NS (n=249) in the period 2016-2020 in Chile, according to data from the Department of Statistics and Health Information of Chile. The variables studied were: year of death, age group, sex, region and etiological agent. No ethics committee was required. Results: 2020 had the lowest mortality rate due to NS (0.17) and 2017 the highest (0.31). The age group of 0-2 days of birth had the highest mortality rate (0.07), while the group of 27-28 days corresponds to the lowest (0.00). The Antofagasta region had the highest mortality (0.44) and the Magallanes region the lowest (0.11). The average mortality rate in men corresponds to 0.12 and in women to 0.10. In 89.16% of the cases, the etiological agent was not identified. Discussion: The higher mortality in 2017 could be due to a higher proportion of preterm births in that year. The greater number of deaths at a lower chronological age would be related to their immunological immaturity. The non-detection of the etiological agent could be due to the low yield of the blood cultures. However, more research on the incidence and mortality from neonatal sepsis is lacking.

Synergic effects of ultrasound and laser therapies on mesentery for management of obesity and diabetes in rats.

Nowadays, the mesentery as a new organ was discovered. Mesenteric events may play an important role in the pathophysiology of several diseases. The aim of our study was investigate the synergic effects of ultrasound (US) and laser therapies on mesentery in obese-hyperglycemic rats. The 25 male Wistar rats were randomized into five groups. Obese nondiabetic (OND) group: obese rats without diabetes and no treatment conditions; SHAM group: obese-hyperglycemic rats treated with placebo; US group: obese-hyperglycemic rats treated with US; LASER group: obese-hyperglycemic rats treated with laser and; US+LASER group: obese-hyperglycemic rats treated with US plus laser. An animal model of type 2 diabetes based on a hyperlipidemic diet combined with a low dose of streptozotocin was used in this study. Body mass and biochemical measurements were performed. GOT and GPT level showed a significant reduction in the treated groups than SHAM. The total cholesterol, triglycerides and very low-density lipoprotein (VLDL) levels showed significantly lower values for the US+LASER group. There was also reduced risk of cardiovascular diseases evidenced by Castelli index in the treated groups than SHAM. This study showed that the US and laser treatment on mesentery resulted to an improvement in biochemical measurements of the obese-hyperglycemic rats, especially the total cholesterol, triglycerides and VLDL levels.

Cine y resistencia: jóvenes, poderes y contrapoderes en la película La noche de los lápices / Cinema and resistance: Young people, powers and counter-powers in the movie «The Night of the Pencils¼ / Cinema e resistência: Jovens, poderes e contrapoderes no filme A Noite dos Lápis

Resumen (analítico) Las juventudes y movimientos estudiantiles en el mundo, especialmente en América Latina y Francia, retoman disertaciones sobre poder, contrapoder y resistencia desde la reflexión teórica de autores como Niklas Luhmann y Nicos Poulantzas. Aquellos señalan que los fenómenos de protesta y movimientos sociales de jóvenes son recreados con precisión en el cine en películas como La noche de los lápices (Olivera, 1986). Los autores, desde una mirada histórica y cinematográfica, evidencian las particularidades en los ejes detentores del poder (Estado y sociedad civil o jóvenes) que, medidos frente al Estado, experimentan significado, manifestación y abordaje en escenarios que cohabitan con la violencia. El artículo sugiere rutas para indagar el concepto de poder y estudios orientados en el cine sobre movimientos estudiantiles y juveniles en la actualidad.

Abstract (analytical) Youth and student movements around the world, especially in Latin America and France, are the subject of dissertations on power, counterpower and resistance through theoretical reflection by Niklas Luhmann and Nicos Poulantzas. These authors point out that the phenomena of protest and social movements of young people are accurately recreated in cinema in films such as "The Night of the Pencils" (Olivera, 1986). From an historical and cinematographic point of view, the authors highlight the specific depiction of holders of power contained in this film; the State and civil society or young people, and when measured against the State, experience meaning, manifestation and approach in scenarios that coexist with violence. The article ends with suggestions on routes for exploring the concept of power and film-oriented studies in relation to current student and youth movements.

Resumo (analítico) As juventudes e os movimentos estudantis no mundo, especialmente na América Latina e França, retomam dissertações sobre poder, contrapoder e resistência, com base na reflexão teórica de autores como Niklas Luhmann e Nicos Poulantzas que assinalam que os fenômenos de protesto e movimentos sociais de jovens são recriados com precisão no cinema, em filmes como A noite dos lápis (Olivera, 1986). Os autores, a partir de um olhar histórico e cinematográfico, evidenciam as particularidades nos eixos detentores do poder: Estado e sociedade civil ou jovens, que medidos frente ao Estado, experimentam significado, manifestação e abordagem em cenários que coabitam com a violência. O artigo finaliza com sugestões sobre caminhos para questionar o conceito de poder e estudos orientados no cinema sobre movimentos estudantis e juvenis na atualidade.

Association of Lupus Nephritis Histopathologic Classification With Venous Thromboembolism-Modification by Age at Biopsy.

INTRODUCTION: Lupus nephritis (LN) is an independent risk factor for venous thromboembolism (VTE). The risk of VTE has not been analyzed by International Society of Nephrology/Renal Pathology Society or World Health Organization LN class. Study goals were to measure VTE incidence in an LN patient cohort, to evaluate associations between VTE and LN class, and to investigate factors modifying associations between VTE and LN class. METHODS: A retrospective analysis was performed using Glomerular Disease Collaborative Network data. Image-confirmed VTE was compared between patients with any LN class V lesion and patients with only LN class III or IV. Logistic regression was used to calculate odds ratios and 95% confidence intervals. Effect modification was assessed between main effect and covariates. RESULTS: Our cohort consisted of 534 LN patients, 310 (58%) with class III/IV and 224 (42%) with class V with or without class III/IV, including 106 with class V alone. The VTE incidence was 62 of 534 (11.6%). The odds of VTE were not significantly different between patients with class III/IV and class V in adjusted analyses (odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.45-1.48). An age interaction was observed (P = 0.009), with increased odds of VTE with class III/IV diagnosed at a younger age (2.75, 0.90-8.41 estimated at age 16 years) and decreased odds with class III/IV diagnosed at an older age (0.23, 0.07-0.72 estimated at age 46 years), compared to class V. CONCLUSIONS: The VTE incidence was similar among patients with LN classes III/IV and V, suggesting that VTE risk is not limited to class V-related nephrotic syndrome and that age may modulate LN class-specific VTE risk.

Immune Checkpoint Inhibitor-Related Pneumonitis in Lung Cancer: Real-World Incidence, Risk Factors, and Management Practices Across Six Health Care Centers in North Carolina.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are standard treatments for advanced non-small cell lung cancer and have expanded use in small cell lung cancer. Although generally better tolerated than traditional chemotherapy, immune-related adverse events, such as immune checkpoint inhibitor-related pneumonitis (ICI-P), remain poorly understood toxicities that limit ICI treatment and can result in considerable morbidity. In this retrospective case-control study, we assessed a lung cancer cohort to identify ICI-P risk factors. RESEARCH QUESTION: What are the risk factors, clinical presentations, radiographic findings, and outcomes for ICI-P in a real-world lung cancer cohort? Do chronic pulmonary diseases confer increased risk for ICI-P? STUDY DESIGN AND METHODS: Medical records from lung cancer patients receiving nivolumab, pembrolizumab, or combination ipilimumab and nivolumab at six centers in North Carolina were reviewed (January 2004-July 2017). Patients with ICI-P and control participants were characterized, and logistic regression was used to assess for ICI-P risk factors. RESULTS: Three hundred fifteen lung cancer patients who predominantly received nivolumab (76.5%) or pembrolizumab (22%) were included. The incidence of ICI-P was 9.5%, with a median time to diagnosis of 52.5 days. Most patients with ICI-P had cases of high severity, and eight patients (27%) died with ongoing ICI-P treatment. Development of ICI-P was independently associated with the presence of baseline fibrosis on chest CT scan (adjusted OR [aOR], 6.61; 95% CI, 2.48-17.7), a composite measure of obstructive lung disease (aOR, 2.79; 95% CI, 1.07-7.29), and treatment with pembrolizumab (aOR, 2.57; 95% CI, 1.08-6.11). INTERPRETATION: In this cohort, ICI-P was more common and severe than previously reported and carried an unexpectedly high mortality rate. Risk for ICI-P was shown to be independently associated with several chronic pulmonary diseases, which may account for the higher incidence of ICI-P in patients with lung cancer.

Incidence and progression of ankle osteoarthritis: The johnston county osteoarthritis project.

OBJECTIVE: To determine the incidence and progression of ankle osteoarthritis (OA) and associated risk factors in a community-based cohort of African Americans and whites. METHODS: Data were from 541 participants who had standardized lateral and mortise radiography of the ankles in weight bearing at baseline (2013-2015) and follow-up (2017-2018). Incident radiographic ankle OA (rAOA) was defined as a Kellgren-Lawrence grade (KLG) ≥ 1 at follow-up among ankles with baseline KLG < 1; progressive rAOA was a ≥ 1 KLG increase at follow-up among ankles with KLG ≥ 1 at baseline. Symptoms were assessed using self-reported pain, aching, and stiffness (PAS) on most days and the Foot and Ankle Outcome Score (FAOS) symptoms subscale. Ankle-level logistic regression models were used to assess associations of ankle outcomes with covariates (age, sex, race, body mass index [BMI], smoking, number of symptomatic joints, comorbidities, prior ankle injury, and knee or foot OA). RESULTS: Among ankles without rAOA at baseline, 28% developed incident rAOA, 37% had worsening FAOS symptoms, and 7% had worsening PAS. Incident rAOA and worsening ankle symptoms were associated with higher BMI and symptoms in other joints. Among ankles with baseline rAOA, 4% had progressive rAOA, 35% had worsening of FAOS symptoms, and 9% had worsening PAS. rAOA progression was associated with ankle injury and concomitant knee or foot OA; worsening of symptoms was associated with higher BMI and other symptomatic joints. CONCLUSIONS: Not all ankle OA is post-traumatic. Smoking prevention/cessation, a healthy weight, and injury prevention may be methods for reducing the incidence and progression of rAOA.

Infection Control in the Dental Practice with Emphasis on Intraoral Scanners and Semi-Critical Complex Instruments / Control de Infecciones en la Práctica Dental Con Énfasis en Escáneres Intraorales e Instrumentos Complejos Semicríticos

ABSTRACT: We present an integrative review of the literature conducted to find and analyse specific measures for disinfection and/or sterilization of intraoral complex instruments, applicable to intraoral scanners. We performed a two-stage search in the PubMed/MEDLINE, SciELO, REDALYCS, and LILACS databases, and the Google Scholar website, which included full articles in Spanish, Portuguese, and English. The strategy associated the terms 'disinfection', 'biosecurity', 'decontamination', and (a) 'intraoral scanners', and (b) other 'semi-critical' intraoral complex instruments, according to the American Dental Association definition (e.g., 'turbine', etc). Strategy (a) produced just one outcome, whereas (b) produced nine articles, which only suggested low-level disinfectants.The lack of empirically based protocols that allow effective microbiological control makes it necessary to create a new categorization for these instruments when trying to comply with American Dental Association recommendations for dental practice.

RESUMEN: Presentamos una revisión integradora de la literatura realizada para encontrar y analizar medidas específicas de desinfección y / o esterilización de instrumentos complejos intraorales, aplicables a los escáneres intraorales. Realizamos una búsqueda en dos etapas en las bases de datos PubMed / MEDLINE, SciELO, REDALYCS y LILACS, y en el sitio web Google Scholar, que incluía artículos completos en español, portugués e inglés. La estrategia asoció los términos 'desinfección', 'bioseguridad', 'descontaminación' y (a) 'escáneres intraorales', y (b) otros instrumentos complejos intraorales 'semicríticos', según la definición de la Asociación Dental Ameri- cana (p. Ej., 'turbina', etc.). La estrategia (a) produjo un solo resultado, mientras que (b) produjo nueve artículos, que solo sugirieron desinfectantes de bajo nivel. La falta de protocolos de base empírica que permitan un control microbiológico efectivo hace necesario crear una nueva categorización para estos instrumentos, cuando se trata de cumplir con las recomendaciones de la Asociación Dental Americana para la práctica dental.

Mode of Delivery and Maternal Sensitivity: Effects on the Socioemotional Development of Children at One Year of Age / Tipo de parto y sensibilidad materna: Efectos en el desarrollo socioemocional de niños y niñas al año de edad

Abstract Early childhood is a period of high relevance in children's socioemotional development, establishing the basis for future development. Acquisitions during the first year of life are significant predictors of future social and emotional skills. During this period, maternal sensitivity is also essential, and there is evidence regarding its effects on the socioemotional development of the child. Considering the relevance of this competence, together with the global and national increase in cesarean rates and the possible risks associated with the type of delivery experienced, the influence of the type of delivery and the maternal sensitivity in child's socioemotional development at one year of age was analyzed. For this, an intentional non-probabilistic sample of 91 mothers with their respective children of different socioeconomic levels, who attended public or private nurseries in the city of Santiago, Chile, was studied. The instruments used were the Adult Sensitivity Scale (ESA) and the Functional Emotional Assessment Scale (FEAS). The results showed no differences in the children's socioemotional development according to the type of delivery. However, it was possible to observe an association between a higher maternal sensitivity and a more significant socioemotional development on children at one year of age. The implications of promoting maternal sensitivity are discussed to support optimal socioemotional development in infants.

Resumen La infancia temprana es un periodo de gran relevancia en el desarrollo socioemocional infantil; de hecho, es donde se sientan las bases del desarrollo futuro. En este sentido, las adquisiciones durante el primer año de vida son predictores importantes de las habilidades sociales y emocionales futuras, de modo que la sensibilidad materna, según evidencia respecto a sus efectos en el desarrollo socioemocional del niño, ha demostrado ser un aspecto fundamental durante este periodo. Teniendo esto en cuenta, y considerando la relevancia de dicha competencia, así como el alza mundial y nacional en las tasas de cesárea y los posibles riesgos asociados al tipo de parto vivenciado, el presente estudio tuvo como objetivo analizar la influencia de la sensibilidad materna y del tipo de parto en el desarrollo socioemocional infantil al año de edad. Para ello, se estudió una muestra no probabilística intencionada de 91 madres con sus respectivos hijos o hijas -de distinto nivel socioeconómico- que asistían a salas cuna públicas o privadas en la ciudad de Santiago, Chile, por medio de dos instrumentos: la escala de sensibilidad del adulto (ESA) y la functional emotional assessment scale (FEAS). En general, los resultados no mostraron diferencias en el desarrollo socioemocional de los niños según el tipo de parto, aunque sí se pudo apreciar una relación entre una mayor sensibilidad materna y un mayor desarrollo socioemocional de los niños al año de edad. Al final se discuten las implicaciones de promover la sensibilidad materna con el fin de apoyar un óptimo desarrollo socioemocional en los infantes.

Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia.

BACKGROUND: The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. RESULTS: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. CONCLUSIONS: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening.