The modified Nice knot has improved mechanical performance compared to the cinch stitch for meniscal root repair.

PURPOSE: According to previous biomechanical studies, the success of meniscus root repair depends on the suture-meniscus interface and optimisation of this procedure seems to be critical. A progressive, reliable and adjustable knot has numerous advantages in meniscal repair since the surgeon can adapt and meticulously tune the final strength of the fixation. We hypothesised that a single passage of one tape at two different points of the posterior meniscal root with a modified Nice knot configuration may allow similar or superior fixation for root repair compared to the cinch stitch suture technique. METHODS: Posterior root repair of medial and lateral meniscus was performed on 26 porcine knees. In group (A), two simple cinch stitches were applied, and in group (B), a modified Nice knot was used in a crossmatch configuration. For both groups, two passages through the meniscus with a 2-mm braided tape were used, and a single transosseous tibial tunnel technique was performed and tested in pull-out conditions. RESULTS: The modified Nice knot showed an improved biomechanical performance considering the maximum failure load for both the medial (600.7 ± 77.5 N) and lateral (686.1 ± 83.5 N) (p = 0.006) posterior root fixation when compared to a double cinch stitch (558.0 ± 123.9 N) and (629.0 ± 110.2 N) (p = 0.178) for medial and lateral fixation, respectively. The maximum stiffness was also higher for the modified Nice knot configuration for both medial (17.1 ± 1.5 vs. 13.3 ± 1.6 N/mm) and lateral meniscus (20.0 ± 2.6 vs. 13.8 ± 2.3 N/mm), being this difference statistically significative (p = 0.001). CONCLUSIONS: The modified Nice knot allowed better adaptation in the pull-out tests and presented higher fixation strength, stiffness and reproducibility, with lower standard deviation, being at the same time economically advantageous, since only one tape is needed. LEVEL OF EVIDENCE: Level III.

Clinical characteristics and outcomes of aortic prosthetic valve endocarditis: comparison between transcatheter and surgical bioprostheses.

PURPOSE: Most data regarding infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) comes from TAVI registries, rather than IE dedicated cohorts. The objective of our study was to compare the clinical and microbiological profile, imaging features and outcomes of patients with IE after SAVR with a biological prosthetic valve (IE-SAVR) and IE after TAVI (IE-TAVI) from 6 centres with an Endocarditis Team (ET) and broad experience in IE. METHODS: Retrospective analysis of prospectively collected data. From the time of first TAVI implantation in each centre to March 2021, all consecutive patients admitted for IE-SAVR or IE-TAVI were prospectively enrolled. Follow-up was monitored during admission and at 12 months after discharge. RESULTS: 169 patients with IE-SAVR and 41 with IE-TAVI were analysed. Early episodes were more frequent among IE-TAVI. Clinical course during hospitalization was similar in both groups, except for a higher incidence of atrioventricular block in IE-SAVR. The most frequently causative microorganisms were S. epidermidis, Enterococcus spp. and S. aureus in both groups. Periannular complications were more frequent in IE-SAVR. Cardiac surgery was performed in 53.6% of IE-SAVR and 7.3% of IE-TAVI (p=0.001), despite up to 54.8% of IE-TAVI patients had an indication. No differences were observed about death during hospitalization (32.7% vs 35.0%), and at 1-year follow-up (41.8% vs 37.5%), regardless of whether the patient underwent surgery or not. CONCLUSION: Patients with IE-TAVI had a higher incidence of early prosthetic valve IE. Compared to IE-SAVR, IE-TAVI patients underwent cardiac surgery much less frequently, despite having surgical indications. However, in-hospital and 1-year mortality rate was similar between both groups.

Effect of temperature on the gas-phase reaction of CH3CN with OH radicals: experimental (T = 11.7-177.5 K) and computational (T = 10-400 K) kinetic study.

Acetonitrile (CH3CN) is present in the interstellar medium (ISM) in a variety of environments. However, at the ultracold temperatures of the ISM, radical-molecule reactions are not widely investigated because of the experimental handicap of getting organic molecules in the gas phase by conventional techniques. The CRESU (French acronym for Reaction Kinetics in a Uniform Supersonic Flow) technique solves this problem. For this reason, we present in this work the kinetic study of the gas-phase reaction of CH3CN with one of the most ubiquitous radicals, the hydroxyl (OH) radical, as a function of temperature (11.7-177.5 K). The kinetic technique employed to investigate the CH3CN + OH reaction was the pulsed laser photolysis-laser induced fluorescence. The rate coefficient for this reaction k(T) has been observed to drastically increase from 177.5 K to 107.0 K (about 2 orders of magnitude), while the increase in k(T) from 107.0 K to 11.7 K was milder (around 4 times). The temperature dependent expressions for k(T) are provided in the two distinct T-ranges, excluding the upper limit obtained for k(177.5 K): In addition, the rate coefficients estimated by the canonical competitive unified statistical (CCUS) theory show a similar behaviour to the experimental results, when evaluated within the high-pressure limit. This is consistent with the experimentally observed independence of k(T) with total gas density at selected temperatures. Astrochemical networks, such as the KIDA database or UMIST, do not include the CH3CN + OH reaction as a potential depletion process for acetonitrile in the ISM because the current studies predict very low rate coefficients at IS temperatures. According to the model (T = 10 K), the impact of the titled reaction on the abundances of CH3CN appears to be negligible in dark molecular clouds of the ISM (∼1% of the total depletion reactions included in UMIST network). With respect to the potential formation of the CH2CN radical in those environments, even in the most favourable scenario, where this radical could be formed in a 100% yield from the CH3CN + OH reaction, this route would only contribute around 2% to the current assumed formation routes by the UMIST network.

Acute complications in open/miss primary and revision thoracolumbar spine surgery: a descriptive study of the most common complications and treatment of choice.

PURPOSE: Main question The aim of this study is to describe and analyze the frequency of acute perioperative (intraoperatively and 30 days after) complications of open/MISS thoracolumbar spine surgery. Secondary questions A) Describe the treatment of choice for every kind of complication mentioned. B) Perform a bibliographic search and compare the complications described and their frequency with those studied in the manuscript. METHODS: A retrospective cohort of 816 patients undergoing spinal surgery over a two year period was analyzed. Acute complications of 59 patients are described whether those with a greater number of levels required longer periods of hospitalization. RESULTS: The frequency of acute complications was 7.2%. The most common was infection (2.7%), followed by dural tear (1.7%), and screw malpositioning (1%), which is consistent with the current literature. No statistically significant results were observed when comparing the mean length of hospital stay among patients operated on a greater number of levels compared to the rest (P: 0.344; 95% CI: -3.88-10.93). CONCLUSIONS: The subsidiary patient of spinal surgery is getting older and has more comorbidities, and therefore, has a higher risk of complications. Although there are models predicting the risk of complications, they are not used in routine clinical practice. It would be necessary to unify the main criteria and establish guidelines for risk detection and therapeutic algorithms based on new high-quality studies.

Social protection in areas vulnerable to tuberculosis: a mixed methods study in São Luís, Maranhão / Protección social en zonas vulnerables a la tuberculosis: un estudio mixto en São Luís, Maranhão / Proteção social em áreas vulneráveis à tuberculose: um estudo misto em São Luís, Maranhão

ABSTRACT Objectives: to analyze the risk areas for tuberculosis and the influences of social protection on the development of treatment for the disease in the municipality of São Luís, Maranhão. Methods: this is explanatory sequential mixed method research. In the quantitative phase, the data were obtained from the Notifiable Diseases Information System from 2010 to 2019, with georeferencing being carried out to identify areas vulnerable to tuberculosis. In the qualitative phase, semi-structured interviews were carried out with individuals who received social benefits. Results: 7,381 cases were geocoded, and, from the purely spatial scanning analysis, it was possible to identify 13 spatial clusters of risk. As for the interviews, there was a positive relationship between patient improvement and receiving benefits. Conclusions: geographic space and social determinants are relevant for reorienting monitoring actions for the conditions that generate the health-disease process.

RESUMEN Objetivos: analizar las áreas de riesgo para la tuberculosis y las influencias de la protección social en el desarrollo del tratamiento de la enfermedad en el municipio de São Luís, Maranhão. Métodos: se trata de una investigación explicativa de método mixto secuencial. En la fase cuantitativa, los datos se obtuvieron del Sistema de Información de Enfermedades de Declaración Obligatoria del 2010 al 2019, realizándose georreferenciación para identificar áreas vulnerables a la tuberculosis. En la fase cualitativa se realizaron entrevistas semiestructuradas a personas que recibían beneficios sociales. Resultados: se geocodificaron 7.381 casos y, a partir del análisis de escaneo puramente espacial, fue posible identificar 13 grupos espaciales de riesgo. En cuanto a las entrevistas, hubo una relación positiva entre la mejora del paciente y la recepción de beneficios. Conclusiones: el espacio geográfico y los determinantes sociales son relevantes para reorientar las acciones de seguimiento de las condiciones que generan el proceso salud-enfermedad.

RESUMO Objetivos: analisar as áreas de risco para a tuberculose e as influências da proteção social no desenvolvimento do tratamento para a doença no município de São Luís, Maranhão. Métodos: trata-se de pesquisa de método misto sequencial explanatório. Na fase quantitativa, os dados foram obtidos do Sistema de Informação de Agravos de Notificação de 2010 a 2019, sendo realizado georreferenciamento para identificação das áreas vulneráveis à tuberculose. Na fase qualitativa, realizaram-se entrevistas semiestruturadas com indivíduos que recebiam benefício social. Resultados: foram geocodificados 7.381 casos, e, a partir da análise de varredura puramente espacial, foi possível identificar 13 aglomerados espaciais de risco. Quanto às entrevistas, verificou-se uma relação positiva entre a melhora dos pacientes e o recebimento de benefícios. Conclusões: o espaço geográfico e os determinantes sociais são relevantes para reorientação das ações de monitoramento das condições geradoras do processo saúde-doença.

HIV and AIDS in the state of Paraná, Brazil, 2007-2022: trends and spatiotemporal distribution / HIV e AIDS no Estado do Paraná, Brasil, 2007-2022: tendência e distribuição espaçotemporal

ABSTRACT Objective: The aim of this study was to analyze the spatiotemporal evolution of the incidence rates of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in the state of Paraná, Brazil. Methods: An ecological study with an analytical component of time series analysis was conducted in the state of Paraná from 2007 to 2022. The data source was the Notifiable Diseases Information System. To study the trend, the Prais-Winsten generalized linear regression model was used by decomposing the time series, and for spatial analysis, the Moran's index was applied. Results: The total sample consisted of 50,676 HIV/AIDS records. The incidence rate showed an increasing trend, with an average growth of 2.14% [95% confidence interval - 95%CI 1.16-3.13] per month. From 2007 to 2014 and from 2015 to 2022, the average number of cases in the state was 105.64 and 159.20 per 100,000 inhabitants, respectively, with significant variation among municipalities. Spatial clusters of high risk persisted in the metropolitan region, the capital, and coastal areas, and a new cluster was observed in the northern region of the state. Conclusion: The incidence rates of HIV/AIDS showed an upward trend over time. The number of cases varied considerably in some municipalities, especially in the coastal region. Spatial analysis revealed geospatial patterns of high risk in the main metropolitan areas of Paraná: Curitiba (including the coastal area), Londrina, and Maringá, which share characteristics such as a high degree of urbanization and ongoing economic development.

RESUMO Objetivo: Este estudo teve como objetivo analisar a evolução espaçotemporal das taxas de incidência do vírus da imunodeficiência humana (HIV) e da síndrome da imunodeficiência adquirida (AIDS) no estado do Paraná, Brasil. Métodos: Foi realizado um estudo ecológico com componente analítico de séries temporais e análise espacial no estado do Paraná, de 2007 a 2022. A fonte de dados foi o Sistema de Informação de Agravos de Notificação. Para estudar a tendência, foi utilizado o modelo de regressão linear generalizada de Prais-Winsten por meio da decomposição de séries temporais e, para a análise espacial, foi aplicado o Índice de Moran. Resultados: A amostra total foi composta de 50.676 registros de HIV/AIDS. A taxa de incidência apresentou tendência crescente, com crescimento médio de 2,14% (intervalo de confiança de 95% — IC95% 1,16-3,13) ao mês. Nos períodos de 2007 a 2014 e 2015 a 2022, a média de casos no estado foi de 105,64 e 159,20 a cada 100 mil habitantes, respectivamente, com importantes variações entre os municípios. Agrupamentos espaciais de alto risco permaneceram na região metropolitana à capital e litoral e um novo agrupamento foi observado à região norte do estado. Conclusão: As taxas de incidência do HIV/AIDS apresentaram tendência temporal crescente. O número de casos variou substancialmente em alguns municípios, principalmente naqueles localizados na região litorânea. A análise espacial revelou padrões geoespaciais de alto risco nas principais regiões metropolitanas do Paraná: Curitiba (abrange o litoral), Londrina e Maringá, as quais compartilham características como elevado grau de urbanização e constante desenvolvimento econômico.

Machine Learning Quantification of Intraepithelial Tumor-Infiltrating Lymphocytes as a Significant Prognostic Factor in High-Grade Serous Ovarian Carcinomas.

The prognostic and predictive role of tumor-infiltrating lymphocytes (TILs) has been demonstrated in various neoplasms. The few publications that have addressed this topic in high-grade serous ovarian carcinoma (HGSOC) have approached TIL quantification from a semiquantitative standpoint. Clinical correlation studies, therefore, need to be conducted based on more accurate TIL quantification. We created a machine learning system based on H&E-stained sections using 76 molecularly and clinically well-characterized advanced HGSOC. This system enabled immune cell classification. These immune parameters were subsequently correlated with overall survival (OS) and progression-free survival (PFI). An intense colonization of the tumor cords by TILs was associated with a better prognosis. Moreover, the multivariate analysis showed that the intraephitelial (ie) TILs concentration was an independent and favorable prognostic factor both for OS (p = 0.02) and PFI (p = 0.001). A synergistic effect between complete surgical cytoreduction and high levels of ieTILs was evidenced, both in terms of OS (p = 0.0005) and PFI (p = 0.0008). We consider that digital analysis with machine learning provided a more accurate TIL quantification in HGSOC. It has been demonstrated that ieTILs quantification in H&E-stained slides is an independent prognostic parameter. It is possible that intraepithelial TIL quantification could help identify candidate patients for immunotherapy.

Case Report: Characterization of known (c.607G>C) and novel (c.416C>G) ELANE mutations in two Mexican families with congenital neutropenia.

The most common causes of congenital neutropenia are mutations in the ELANE (Elastase, Neutrophil Expressed) gene (19p13.3), mostly in exon 5 and the distal portion of exon 4, which result in different clinical phenotypes of neutropenia. Here, we report two pathogenic mutations in ELANE, namely, c.607G>C (p.Gly203Arg) and a novel variant c.416C>G (p.Pro139Arg), found in two Mexican families ascertained via patients with congenital neutropenia who responded positively to the granulocyte colony-stimulating factor (G-CSF) treatment. These findings highlight the usefulness of identifying variants in patients with inborn errors of immunity for early clinical management and the need to rule out mosaicism in noncarrier parents with more than one case in the family.

Digital health for treatment adherence in people with tuberculosis: a systematic review / Saúde digital para a adesão ao tratamento da pessoa com tuberculose: uma revisão sistemática / Salud digital para la adherencia al tratamiento en personas con tuberculosis: una revisión sistemática

Justifications and Objectives: the use of digital health, among people diagnosed with tuberculosis, can be an effective strategy, combined with health services, to increase adherence to treatment and impact the disease's epidemiological data in the country. As this topic has been widely discussed and improved in recent years, it is necessary to further investigate the research available on scientific bases. The objective of this study was to describe the use of digital health technologies to assist with adherence to tuberculosis treatment. Methods: this is a systematic literature review with a rapid review approach, following the PRISMA guidelines and the Cochrane guide. Evidence quality was assessed using the Mixed Methods Appraisal Tool. The studies were identified in PubMed, VHL, CINAHL, Cochrane Trial, SciELO, Scopus and Embase. Experimental, quasi-experimental studies and clinical trials were included, without language restrictions, published between 2020 and 2022. Content: nine studies were selected, which demonstrated that the implementation of digital technologies improved adherence rates to medication treatment and cure rates. Applications use strategies such as synchronous and asynchronous video, voice calls and text messages. Among the studies, only two technology/application names were mentioned. Conclusion: digital technologies have had a positive impact on the treatment of people diagnosed with tuberculosis.(AU)

Justificativas e Objetivos: a utilização da saúde digital, junto às pessoas diagnosticadas com a tuberculose, pode ser uma estratégia eficaz, aliada dos serviços de saúde, para aumentar a adesão ao tratamento e impactar os dados epidemiológicos da doença no país. Como esse tema tem sido amplamente discutido e aprimorado nos últimos anos, é necessário investigar mais a fundo as pesquisas disponíveis nas bases científicas. O objetivo deste estudo foi descrever o uso de tecnologias em saúde digital para auxiliar na adesão ao tratamento da tuberculose. Método: trata-se de revisão sistemática da literatura com abordagem de revisão rápida, seguindo as diretrizes do PRISMA e o guia da Cochrane. A qualidade das evidências foi realizada utilizando a ferramenta Mixed Methods Appraisal Tool. Os estudos foram identificados nas bases de dados PubMed, BVS, CINAHL, Cochrane Trial, SciELO, Scopus e Embase. Foram incluídos estudos experimentais, quase-experimentais e ensaios clínicos, sem restrição de idioma, publicados entre 2020 e 2022. Conteúdo: foram selecionados nove estudos, que demonstraram que a implementação de tecnologias digitais melhorou as taxas de adesão ao tratamento medicamentoso e as taxas de cura. Os aplicativos utilizam estratégias como vídeo síncrono e assíncrono, chamadas de voz e mensagens de texto. Entre os estudos, apenas dois nomes de tecnologia/aplicativo foram mencionados. Conclusão: as tecnologias digitais têm impactado de forma positiva no tratamento das pessoas com diagnóstico de tuberculose.(AU)

Justificaciones y objetivos: el uso de la salud digital entre las personas diagnosticadas con tuberculosis puede ser una estrategia eficaz y aliada de los servicios de salud para aumentar la adherencia al tratamiento e impactar los datos epidemiológicos de la enfermedad en el país. 3. Método: se realizó una revisión sistemática de la literatura con un enfoque de revisión rápida, siguiendo las pautas de PRISMA y la guía de Cochrane. La calidad de la evidencia se evaluó utilizando la herramienta Mixed Methods Appraisal Tool. Los estudios se identificaron en las siguientes bases de datos: PubMed, BVS, CINAHL, Cochrane Trial, SciELO, Scopus y Embase. Se incluyeron estudios experimentales, cuasiexperimentales y ensayos clínicos, sin restricciones de idioma, publicados entre 2020 y 2022. Contenido: se seleccionaron nueve estudios que demostraron que la implementación de tecnologías digitales mejoró las tasas de adherencia al tratamiento con medicamentos y las tasas de curación. Las aplicaciones utilizan estrategias como video sincrónico y asincrónico, llamadas de voz y mensajes de texto. Entre los estudios, sólo se mencionaron dos nombres de tecnologías/aplicaciones. Conclusión: las tecnologías digitales han tenido un impacto positivo en el tratamiento de personas diagnosticadas con tuberculosis.(AU)

HLA-G 14 bp Ins/Del (rs66554220) Variant Is Not Associated with Breast Cancer in Women from Western Mexico.

HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3'UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of endogen cell factors; nevertheless, the reports are discrepant and controversial. Herein, the relationship of the 14-bp Ins/Del variant (rs66554220) with breast cancer (BC) and its clinical characteristics were analyzed in 182 women with non-familial BC and 221 disease-free women as a reference group. Both groups from western Mexico and sex-age-matched (sm-RG). The rs66554220 variant was amplified by SSP-PCR and the fragments were visualized in polyacrylamide gel electrophoresis. The variant rs66554220 was not associated with BC in our population. However, we suggest the Ins allele as a possible risk factor for developing BC at clinical stage IV (OR = 3.05, 95% CI = 1.16-7.96, p = 0.01); nevertheless, given the small stratified sample size (n = 11, statistical power = 41%), this is inconclusive. In conclusion, the 14-bp Ins/Del (rs66554220) variant of HLA-G is not associated with BC in the Mexican population, but might be related to advanced breast tumors. Further studies are required.

Gas-phase formation of glycolonitrile in the interstellar medium.

Our automated reaction discovery program, AutoMeKin, has been utilized to investigate the formation of glycolonitrile (HOCH2CN) in the gas phase under the low temperatures of the interstellar medium (ISM). The feasibility of a proposed pathway depends on the absence of barriers above the energy of reactants and the availability of the suggested precursors in the ISM. Based on these criteria, several radical-radical reactions and a radical-molecule reaction have been identified as viable formation routes in the ISM. Among the radical-radical reactions, OH + CH2CN appears to be the most relevant, considering the energy of the radicals and its ability to produce glycolonitrile in a single step. However, our analysis reveals that this reaction produces hydrogen isocyanide (HNC) and formaldehyde (CH2O), with rate coefficients ranging from (7.3-11.5) × 10-10 cm3 molecule-1 s-1 across the temperature range of 10-150 K. Furthermore, the identification of this remarkably efficient pathway for HNC elimination from glycolonitrile significantly broadens the possibilities for any radical-radical mechanism proposed in our research to be considered as a feasible pathway for the formation of HNC in the ISM. This finding is particularly interesing given the persistently unexplained overabundance of hydrogen isocyanide in the ISM. Among the radical-molecule reactions investigated, the most promising one is OH + CH2CHNH, which forms glycolonitrile and atomic hydrogen with rate coefficients in the range (0.3-6.6) × 10-10 cm3 molecule-1 s-1 within the 10-150 K temperature range. Our calculations indicate that the formation of both hydrogen isocyanide and glycolonitrile is efficient under the harsh conditions of the ISM.

Evaluation of a polymeric topical formulation of Endoxifen in an estrogen receptor positive breast cancer murine model.

Breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer and, in terms of mortality, is the fifth leading cause with 684,996 new deaths (6.7% of all cancer-related deaths) and the highest mortality amongst all cancers (15.5%) in women. Selective estrogen-receptor modulators (SERMs) have been used for the last thirty years for estrogen receptor-positive (ER+) BC prevention and treatment. Tamoxifen (TAM), the most widely used SERM, is orally administered and its long-term oral administration has been associated to toxicity and adverse side effects. Endoxifen (EDX) is one of the known active metabolites of TAM, with an affinity to ERα 100 times higher than TAM. Furthermore, EDX has shown antiproliferative activity against the ER+ BC cell line MCF-7. Alternative administration routes that avoid the metabolic processing of TAM seem an appealing alternative to its oral administration. With this aim, we have prepared a polymeric gel-like solution of Pluronic® F127 as vehicle for topical administration of EDX. In order to shed light on the potential clinical use of this formulation, we have compared it with the standard pharmaceutical form, i.e. orally administered TAM. The biodistribution, antitumor efficacy and toxic effects of topical EDX and oral TAM were evaluated in ER+ tumor xenograft athymic nu/nu mouse models. The results showed a statistically significant antitumor effect and reduced toxicity of topical EDX as compared to oral TAM or empty F127 gel. This novel administration route of SERMs could also have a strong impact in the prevention of BC at early development stages and could help to ameliorate the mortality and morbidity related to this disease.

Lung Cancer Screening in Asia: An Expert Consensus Report.

INTRODUCTION: The incidence and mortality of lung cancer are highest in Asia compared with Europe and USA, with the incidence and mortality rates being 34.4 and 28.1 per 100,000 respectively in East Asia. Diagnosing lung cancer at early stages makes the disease amenable to curative treatment and reduces mortality. In some areas in Asia, limited availability of robust diagnostic tools and treatment modalities, along with variations in specific health care investment and policies, make it necessary to have a more specific approach for screening, early detection, diagnosis, and treatment of patients with lung cancer in Asia compared with the West. METHOD: A group of 19 advisors across different specialties from 11 Asian countries, met on a virtual Steering Committee meeting, to discuss and recommend the most affordable and accessible lung cancer screening modalities and their implementation, for the Asian population. RESULTS: Significant risk factors identified for lung cancer in smokers in Asia include age 50 to 75 years and smoking history of more than or equal to 20 pack-years. Family history is the most common risk factor for nonsmokers. Low-dose computed tomography screening is recommended once a year for patients with screening-detected abnormality and persistent exposure to risk factors. However, for high-risk heavy smokers and nonsmokers with risk factors, reassessment scans are recommended at an initial interval of 6 to 12 months with subsequent lengthening of reassessment intervals, and it should be stopped in patients more than 80 years of age or are unable or unwilling to undergo curative treatment. CONCLUSIONS: Asian countries face several challenges in implementing low-dose computed tomography screening, such as economic limitations, lack of efforts for early detection, and lack of specific government programs. Various strategies are suggested to overcome these challenges in Asia.

Mapping early serum proteome signatures of liver regeneration in living donor liver transplant cases.

The liver is the only solid organ capable of regenerating itself to regain 100% of its mass and function after liver injury and/or partial hepatectomy (PH). This exceptional property represents a therapeutic opportunity for severe liver disease patients. However, liver regeneration (LR) might fail due to poorly understood causes. Here, we have investigated the regulation of liver proteome and phosphoproteome at a short time after PH (9 h), to depict a detailed mechanistic background of the early LR phase. Furthermore, we analyzed the dynamic changes of the serum proteome and metabolome of healthy living donor liver transplant (LDLT) donors at different time points after surgery. The molecular profiles from both analyses were then correlated. Insulin and FXR-FGF15/19 signaling were stimulated in mouse liver after PH, leading to the activation of the main intermediary kinases (AKT and ERK). Besides, inhibition of the hippo pathway led to an increased expression of its target genes and of one of its intermediary proteins (14-3-3 protein), contributing to cell proliferation. In association with these processes, metabolic reprogramming coupled to enhanced mitochondrial activity cope for the energy and biosynthetic requirements of LR. In human serum of LDLT donors, we identified 56 proteins and 13 metabolites statistically differential which recapitulate some of the main cellular processes orchestrating LR in its early phase. These results provide mechanisms and protein mediators of LR that might prove useful for the follow-up of the regenerative process in the liver after PH as well as preventing the occurrence of complications associated with liver resection.

Concordância às medidas de flexibilização durante a pandemia de covid-19 no brasil / Conformidad con las medidas de flexibilización durante la pandemia de covid-19 en brasil / Agreement to the flexibility measures during the covid-19 pandemic in brazil

RESUMO Objetivo: analisar os fatores associados à concordância com a flexibilização das medidas de proteção no Brasil durante a pandemia pela COVID-19. Método: estudo transversal, com dados de uma web survey realizada com adultos residentes no Brasil, entre agosto de 2020 e fevereiro de 2021. Resultados: dos 1.516 respondentes, a maioria possuía idade entre 40 a 59 anos (38,8%), sexo feminino (69,4%), nível de pós-graduação (48%), raça/cor branca (64,2%), separados/solteiros (48,3%). A maioria dos participantes concordou com as medidas de flexibilização (41,1%), todavia consideraram os ambientes nada ou pouco adequados para a retomada das atividades cotidianas (com exceção dos locais abertos para atividades físicas). As medidas implementadas pelo Estado durante a pandemia por COVID-19 também foram tidas como pouco e nada adequadas. Houve mais chance de concordância com as medidas de flexibilização entre as pessoas que moravam/conviviam com trabalhadores expostos ao risco de contrair a COVID-19. Conclusão: de modo geral, houve concordância às medidas de flexibilização no país. Morar/conviver com trabalhadores expostos ao risco de contrair a COVID-19 foi o principal fator associado à maior chance de concordar com as medidas de flexibilização, o que sinaliza a carga biopsicossocial trazida pela doença.

RESUMEN Objetivo: analizar los factores asociados a la conformidad con la flexibilización de las medidas de protección en Brasil durante la pandemia por COVID-19. Método: estudio transversal, con datos de una websurvey realizada con adultos residentes en Brasil, entre agosto de 2020 y febrero de 2021. Resultados: de los 1.516 encuestados, la mayoría poseía edad entre 40 y 59 años (38,8%), sexo femenino (69,4%), nivel de posgrado (48%), raza/color blanco (64,2%), separados/solteros (48,3%). La mayoría de los participantes estuvo de acuerdo con las medidas de flexibilización (41,1%), sin embargo, consideraron los ambientes nada o poco adecuados para la reanudación de las actividades cotidianas (con excepción de los locales abiertos para actividades físicas). Las medidas aplicadas por el Estado durante la pandemia de COVID-19 también fueron consideradas poco y nada adecuadas. La conformidad con las medidas de flexibilización se dio más entre las personas que vivían/convivían con trabajadores expuestos al riesgo de contraer la COVID-19. Conclusión: en general, hubo concordancia con las medidas de flexibilización en el país. Vivir/convivir con trabajadores expuestos al riesgo de contraer la COVID-19 fue el principal factor asociado a la mayor probabilidad de concordar con las medidas de flexibilización, lo que señala la carga biopsicosocial ocasionada por la enfermedad.

ABSTRACT Objective: to analyze the factors associated with agreement with the flexibility of protection measures in Brazil during the COVID-19 pandemic. Method: cross-sectional study with data from a websurvey conducted with adults living in Brazil, between August 2020 and February 2021. Results: of the 1,516 respondents, the majority were aged between 40 and 59 years (38.8%), female (69.4%), graduate level (48%), white race/color (64.2%), separated/single (48.3%). Most participants agreed with the flexibility measures (41.1%), but considered the environments not suitable or inadequate for the resumption of daily activities (except for places open for physical activities). The measures implemented by the State during the COVID-19 pandemic were also seen as nothing and inadequate. There was a greater chance of agreement with the flexibility measures among people who lived with workers exposed to the risk of contracting COVID-19. Conclusion: in general, there was agreement to the flexibility measures in the country. Living/living with workers exposed to the risk of contracting COVID-19 was the main factor associated with the greater chance of agreeing with the flexibility measures, which signals the biopsychosocial burden brought by the disease.

Aglomerados de risco para ocorrência de hanseníase e as incapacidades em menores de 15 anos em Cuiabá: um estudo geoespacial / Clusters of risk for the occurrence of leprosy and disabilities in children under 15 years of age in Cuiabá: a geospatial study

RESUMO Objetivo: Este estudo teve como objetivo analisar a distribuição espacial da hanseníase e as incapacidades em menores de 15 anos de idade em Cuiabá. Métodos: Estudo ecológico realizado na cidade de Cuiabá, Mato Grosso, Brasil. A população do estudo foi composta de casos de hanseníase em menores de 15 anos notificados no Sistema de Informações de Agravos de Notificação, entre os anos de 2008 e 2018. Com base nos endereços residenciais, os casos foram georreferenciados. Na análise da distribuição espacial dos casos, foi utilizada a estimativa da densidade de Kernel e, posteriormente, aplicada a estatística de varredura espacial, espaço-temporal e variação espacial nas tendências temporais. Resultados: Foram notificados 514 casos de hanseníase em menores de 15 anos em Cuiabá, com percentual de 10,1% de casos com grau de incapacidade física 1 e 2,3% com grau de incapacidade física 2 no momento do diagnóstico. Com as técnicas de varredura espacial e espaço-temporal, foram identificados aglomerados de risco para hanseníase nas regiões norte, oeste, leste e sul de Cuiabá, e com a técnica de variação espacial nas tendências temporais foi identificado um aglomerado na região oeste de Cuiabá. Conclusão: Em Cuiabá, os casos de hanseníase em menores de 15 anos com incapacidades estavam distribuídos em toda a extensão urbana da cidade, com maior densidade de casos nas regiões norte e oeste, seguida da região leste. Os aglomerados de maior risco relativo foram identificados nas regiões leste e oeste, caracterizadas por apresentar baixo e médio níveis de renda.

ABSTRACT Objective This study aimed to analyze the spatial distribution of leprosy and disabilities in children under 15 years of age in Cuiabá. Methods Ecological study carried out in the city of Cuiabá, Mato Grosso, Brazil. The study population consisted of leprosy cases in children under 15 years old notified in the Notifiable Diseases Information System, between 2008 and 2018. Based on residential addresses, cases were georeferenced. In the analysis of the spatial distribution of the cases, the estimation of the Kernel density was used and, later, the statistics of spatial, spatio-temporal and Spatial Variation in Temporal Trends were applied. Results 514 cases of leprosy were reported in children under 15 years of age in Cuiabá, with a percentage of 10.1% of cases with degree of physical disability 1 and 2.3% with degree of physical disability 2 at the time of diagnosis. With the techniques of spatial and spatio-temporal scanning, clusters of risk for leprosy were identified in the North, West, East and South regions of Cuiabá, and with the technique of Spatial Variation in Temporal Trends, a cluster was identified in the West region of Cuiabá. Conclusion In Cuiabá, cases of leprosy in children under 15 years of age with disabilities were distributed throughout the urban area of the city, with the highest density of cases in the North and West regions, followed by the East region. The clusters with the highest Relative Risk were identified in the East and West regions, characterized by having low and medium income levels

Sobre "os remédios e medicinas que se haviam dado a negros enfermos": os gastos com a saúde e a morte de escravos do Ofício da Província Jesuítica do Paraguay, 1711-1745 / On "the remedies and medications which were given to ailing negroes: "health and death spending on slaves by the Office of the Jesuit Province of Paraguay, 1711-1745

Neste texto, analisamos o tratamento dispensado aos escravos enfermos do Ofício da Província Jesuítica do Paraguay e da Estância de Santa Catalina entre 1711 e 1745. As fontes analisadas - Libro de cuentas del Ofício, Memoriales e Cartas ânuas - revelam que o adoecimento de escravos do Ofício gerava despesas tanto com a aquisição de medicamentos, roupas e alimentos quanto com mortalhas para seu sepultamento. No caso dos escravos da Estância de Santa Catalina, observou-se que, dependendo da enfermidade, eles eram encaminhados à cidade de Córdoba, onde eram tratados por leigos treinados nas artes de curar, o que implicava despesas de outra natureza também registradas nos relatórios contábeis.

Abstract This text analyzes the way sick slaves were treated at the Office (ofício) of the Jesuit Province of Paraguay and Santa Catalina Farm (estancia) between 1711 and 1745. The sources consulted - Libro de cuentas del Ofício, Memoriales, and Cartas ânuas - reveal that the sickness of the enslaved people generated expenses, not only for medications, clothing, and food, but also for shrouds for their burial. As for the slaves from the Santa Catalina Farm, the sources indicate that depending on the infirmity, they were sometimes sent to Córdoba, where they were treated by laypersons trained in the healing arts, which incurred different expenses, also recorded in the ledgers.

Spatial and temporal analysis of tuberculosis incidence in Guinea-Bissau, 2018 to 2020 / Análisis espacial y temporal de la incidencia de tuberculosis en Guinea-Bissau, 2018 a 2020 / Análise espacial e temporal da incidência da tuberculose em Guiné-Bissau, 2018 a 2020

ABSTRACT Objective: to analyze the epidemiological profile, spatial and temporal distribution of tuberculosis in Guinea-Bissau from 2018 to 2020. Methods: an ecological study, carried out in Guinea-Bissau, considering new cases of tuberculosis. Spatial analysis of areas was used to verify tuberculosis distribution in the country, and time series were used to identify incidence evolution over the years of study. Results: a total of 6,840 new cases of tuberculosis were reported. Tuberculosis incidence rate in the country ranged from 36.8 to 267.7 cases/100,000 inhabitants, with emphasis on the regions of Bissau and Biombo (over 90 cases/100,000). By using time series, it was possible to observe an increase in case incidence over the years of study. Conclusions: the study made it possible to identify the epidemiological profile of tuberculosis in Guinea-Bissau, spatial distribution heterogeneity, in addition to identifying the disease evolution over the years of investigation.

RESUMEN Objetivo: analizar el perfil epidemiológico, distribución espacial y temporal de la tuberculosis en Guinea-Bissau, de 2018 a 2020. Métodos: estudio ecológico, realizado en Guinea-Bissau, considerando nuevos casos de tuberculosis. Se utilizó análisis espacial de áreas para verificar la distribución de la tuberculosis en el país y series de tiempo para identificar la evolución de la incidencia a lo largo de los años de estudio. Resultados: se notificaron 6.840 nuevos casos de tuberculosis. La tasa de incidencia de tuberculosis en el país varió de 36,8 a 267,7 casos/100.000 habitantes, con énfasis en las regiones de Bissau y Biombo (más de 90 casos/100.000). Con el uso de series de tiempo, fue posible observar un aumento en la incidencia de casos a lo largo de los años del estudio. Conclusiones: el estudio permitió identificar el perfil epidemiológico de la tuberculosis en Guinea-Bissau, la heterogeneidad de la distribución espacial, además de identificar la evolución de la enfermedad a lo largo de los años de investigación.

RESUMO Objetivo: analisar o perfil epidemiológico, a distribuição espacial e temporal da tuberculose em Guiné-Bissau, no período de 2018 a 2020. Métodos: estudo ecológico, realizado em Guiné-Bissau, considerando os casos novos de tuberculose. Empregaram-se análise espacial de áreas, para verificar a distribuição da tuberculose no país, e séries temporais, para identificar a evolução da incidência ao longo dos anos de estudo. Resultados: foram notificados 6.840 casos novos de tuberculose. A taxa de incidência da tuberculose no país variou de 36,8 a 267,7 casos/100.000 habitantes, com destaque para as regiões de Bissau e Biombo (superior a 90 casos/100.000). Com o uso de séries temporais, foi possível observar um aumento na incidência dos casos ao longo dos anos do estudo. Conclusões: o estudo permitiu identificar o perfil epidemiológico da tuberculose em Guiné-Bissau, a heterogeneidade da distribuição espacial, além de identificar a evolução da doença ao logo dos anos de investigação.

Acquired and Transmitted Multidrug-Resistant Tuberculosis among the Incarcerated Population and Its Determinants in the State of Paraná-Brazil.

(1) Background: Tuberculosis remains a public health problem in the world. The study analyzed the factors associated with drug-resistant tuberculosis in the prison population of the state of Paraná. (2) Methods: Ecological study of drug-resistant tuberculosis cases registered in the Paraná Information System, Brazil (2008 to 2018). We performed descriptive statistics of quantitative parameters calculated with absolute frequencies. Additionally, we used binary regression logistics, where the odds ratio with its respective confidence interval was calculated. (3) Results: Of the 653 cases registered as cases of tuberculosis in the incarcerated population, 98 were drug-resistant tuberculosis. We observed that educational level of up to 8 to 11 years of schooling, negative bacterial culture (test outcome) and no tobacco use were factors associated with the non-development of drug-resistant tuberculosis, while clinically confirmed pulmonary TB and positive sputum smear microscopy in the fourth month of follow-up showed an association for the development of drug resistance. (4) Conclusions: The study showed that clinically confirmed pulmonary TB and a positive sputum smear microscopy in the fourth month of follow-up were associated with drug-resistant tuberculosis.