Toxicological evaluation of Alpinia oxyphylla-derived molecule (PD-00105): In vitro genotoxicity studies and 90-day oral toxicity study in rats.

PD-00105 corresponds to a compound initially identified in the fruit of Alpinia oxyphylla Miq., obtained by chemical synthesis and proposed to be use in dietary supplements for its potential neuroprotective properties. The aim of this study was to perform a toxicological evaluation of PD-00105 in accordance with the testing strategy recommended by food regulatory authorities. All studies were conducted in accordance with Good Laboratory Practice (GLP), and followed the Organization for Economic Co-operation and Development (OECD) test guidelines for chemicals. Studies included a bacterial reverse mutation test, one in vitro micronucleus test in mammalian cells, and a repeated dose 90-day oral toxicity study. No sign of toxicity was observed in the two genotoxicity tests. The test item induced a significant liver and kidney toxicity at high doses (50 and 100 mg/kg BW/day), highlighted by significant increases in liver and kidney absolute and relative weights, associated with histopathological findings and concomitant changes in hematology and clinical chemistry. Increases in alanine aminotransferase, alkaline phosphatase, total protein, albumin, globulin, cholesterol, LDL, and HDL have been measured in these two groups. However, findings observed in the low-dose group (10 mg/kg BW/day) were considered as minimal and non-adverse, and were limited to an increase in liver weight in males and in kidneys weight in females, without concomitant changes in blood chemistry. The No Observed Adverse Effect Level (NOAEL) of PD-00105 was established as 10 mg/kg BW/day under the conditions of this study. This study substantiates the use of PD-00105 in dietary supplements at doses of 10 mg/day, taking into account a safety margin factor for dose conversion to humans.

Membranous urethral length is the single independent predictor of urinary continence recovery at 12 months following Retzius-sparing robot-assisted radical prostatectomy.

The influence of anatomical parameters on urinary continence (UC) after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) remains uncharted. Our objective was to evaluate their association with UC at 3, 6 and 12 months post-operatively. Data from patients who underwent RS-RARP were prospectively collected. Continence was defined as no pad use. Anatomic variables were measured on preoperative magnetic resonance imaging (MRI). Regression analyses were performed to identify predictors of UC at each time point. We included 158 patients with a median age of 60 years, most of whom had a localized tumor (≤ cT2). On multivariate analyses, at 3 months post-surgery, urinary incontinence (UI) rises with age, odds ratio (OR) 1.07 [95% confidence interval (CI) 1.004-1.142] and with prostate volume (PV), OR 1.029 (95% CI 1.006-1.052); it reduces with longer membranous urethral length (MUL), OR 0.875 (95% CI 0.780-0.983) and with higher membranous urethral volume (MUV), OR 0.299 (95% CI 0.121-0.737). At 6 months, UI rises with PV, OR 1.033 (95% CI 1.011-1.056) and decreases with MUV, OR 0.1504 (95% CI 0.050-0.444). Significantly, at 12 months post-surgery, the only predictor of UI is MUL, OR 0.830 (95% CI 0.706-0.975), establishing a threshold associated with a risk of UI of 5% (MUL > 15 mm) in opposition to a risk of 25% (MUL < 10 mm). This single institutional study requires external validation. To our knowledge, this is the first prospective cohort study supporting MUL as the single independent predictor of UC at 12 months post-surgery. By establishing MUL thresholds, we enable precise patient counseling.

Multidisciplinary Team Care in Pituitary Tumours.

The optimal care for patients with pituitary tumours is best provided in a multidisciplinary and collaborative environment, which requires the contribution of multiple medical specialties working together. The benefits and advantages of the pituitary multidisciplinary team (MDT) are broad, and all relevant international consensus and guidelines in the field recommend that patients with pituitary tumours should always be managed in a MDT. Endocrinologists and neurosurgeons are normally the leading specialties within the pituitary MDT, supported by many other specialties with significant contributions to the diagnosis and management of pituitary tumours, including neuropathology, neuroradiology, neuro-ophthalmology, and otorhinolaryngology, among others. Here, we review the literature concerning the concepts of Pituitary MDT/Pituitary Tumour Centre of Excellence (PTCOE) in terms of their mission, goals, benefits, structure, proposed models of function, and barriers, and we also provide the views of different specialists involved in our Pituitary MDT.

Clinical and functional outcomes associated with pulmonary complications after coronary artery bypass grafting.

INTRODUCTION: Coronary artery bypass grafting(CABG) is a surgical treatment for coronary artery disease aiming at improving symptoms and life expectancy. Despite this, there are pulmonary and functional complications that may arise during the postoperative period due to invasive mechanical ventilation(IMV), cardiopulmonary bypass and immobility, leading to longer hospital stays. OBJECTIVE: To evaluate the clinical and functional outcomes related to pulmonary complications in the postoperative period of CABG. METHODS: Prospective cohort. During the ICU stay the patients were divided into: Non Complicated Group(NCG) who did not present complications and Complicated Group(CG) who presented complication. Functional variables were applied as the six-minute walk test(6MWT), gait speed, sit up and stand up test, Timed Up and Go, peripheral muscle strength, ventilatory, pulmonary function and Functional Independence Measure. These tests were applied preoperatively, at ICU discharge, hospital discharge and six months after surgery. RESULTS: The study evaluated 90 patients, 59 in the NCG and 31 CG. In the 6MWT there was a 2%(p = 0.43) decrease in the NCG, while the decrease was 13%(p < 0.01) in the CG. In the MRC the drop was 2%(p = < 0.01) in the CNG, while in the CG the drop was 14%(p = < 0.01). In MIP the NCG had a 6%(p = 0.67) decrease, while the CG had a 16%(p = < 0.01) decrease. CONCLUSION: Patients with postoperative complications of CABG may have reduced functional performance, muscle strength, and pulmonary function at hospital discharge and after six months.

Comparing the Extraction Performance in Mouse Plasma of Different Biphasic Methods for Polar and Nonpolar Compounds.

Many metabolomic studies are interested in both polar and nonpolar analyses. However, the available sample volume often precludes multiple separate extractions. Therefore, there are major advantages in performing a biphasic extraction and retaining both phases for subsequent separate analyses. To be successful, such approaches require the method to be robust and repeatable for both phases. Hence, we determined the performance of three extraction protocols, plus two variant versions, using 25 µL of commercially available mouse plasma. The preferred option for nonpolar lipids was a modified diluted version of a method employing methyl tert-butyl ether (MTBE) suggested by Matyash and colleagues due to its high repeatability for nonpolar compounds. For polar compounds, the Bligh-Dyer method performs best for sensitivity but with consequentially poorer lipid performance. Overall, the scaled-down version of the MTBE method gave the best overall performance, with high sensitivity for both polar and nonpolar compounds and good repeatability for polar compounds in particular.

Uso do método de Pontos para a Reestruturação de Objetivos Fonéticos e Oro-Musculares (PROMPT) no Transtorno do Espectro Autista: um estudo de caso / Use of the Prompts for Reestructuring Oral Muscular Phonetic Targets (PROMPT) in Autism Spectrum Disorder: a case study

RESUMO O Transtorno do Espectro Autista (TEA) é classificado pelo Manual de Diagnóstico e Estatístico de Transtornos Mentais (DSM-5) como um Transtorno do Neurodesenvolvimento, sendo caracterizado, principalmente, por alterações na comunicação social e pela presença de um repertório restrito de atividades e interesses. Na literatura, há muitos estudos sobre autismo, fala e linguagem, mas poucos correlacionando fala e autismo. Este estudo teve como finalidade realizar um estudo de caso que abordou autismo, fala e PROMPT (Pontos para a Reestruturação de Objetivos Fonéticos e Oro-Musculares) e mensurou a melhora da fala no participante com autismo, utilizando o método. Foram definidas palavras-alvo para toda a intervenção, conforme o Sistema de Observação e Análise (SOA) e Hierarquia Motora de Fala (HMF), que fazem parte da avaliação de PROMPT. Após a avaliação, o participante foi atendido por 16 sessões, uma vez semanalmente. Após análise dos dados, observou-se melhora em todos os aspectos que foram delineados de acordo com a avaliação no pré-tratamento, como controle fonatório, controle mandibular, controle lábio-facial e controle lingual, como também no movimento sequenciado, apesar deste não ser o objetivo traçado na avaliação. Também foi possível mensurar melhora no número de vocábulos adequados, número de fonemas adequados, porcentagens de consoantes corretas - revisado (PCC-R) e inteligibilidade.

ABSTRACT Autism Spectrum Disorder (ASD) is classified by Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a neurodevelopmental disorder, whose characteristics are mainly deficits in social communication and a restricted range of interests. There are several studies about autism, speech, and language in the literature, but few correlate speech and autism. This study aims to carry out a case study that will address autism, speech, and PROMPT (Restructuring Oral Muscular Phonetic Targets) and also to describe the speech improvement in the participant with autism using the method. The target words were defined for the entire intervention according to the System Analysis Observation (SAO) and Motor Speech Hierarchy (MSH), which are parts of the PROMPT evaluation. After the evaluation, the participant was attended for 16 sessions, once weekly, with the objective of improving their speech. After analyzing the data, it was possible to observe improvement in all aspects outlined according to the pre-treatment evaluation of the method such as phonatory control, mandibular control, lip-facial control and lingual control as well as in the sequenced movement although this was not the aim outlined in the evaluation. It was also possible to measure the improvement of an adequate number of words, an adequate number of phonemes, percentages of correct consonants - revised (PCC-R), and intelligibility.

Effect of Mobilization with Movement on Pain, Disability, and Range of Motion in Patients with Shoulder Pain and Movement Impairment: A Systematic Review and Meta-Analysis.

BACKGROUND: Shoulder pain is a disabling musculoskeletal disorder worldwide. Thus, it is important to identify interventions able to improve pain and disability. OBJECTIVE: To investigate the effects of mobilization with movement (MWM) on pain, disability, and range of motion in patients with shoulder pain and movement impairment. METHODS: A systematic search of different databases was performed. The systematic review protocol has been registered in PROSPERO (CRD42023404128). A random-effects model for meta-analysis was used to determine the mean difference (MD), standardized mean differences (SMD), and 95% confidence interval for the outcome of interest. RESULTS: Twenty-six studies were included. Of these, eighteen were included in the meta-analysis. MWM improved pain during movement with a moderate effect SMD of (-0.6; 95% confidence interval, -1.1 to -0.1, I2 = 0%; N = 66;) and shoulder abduction MD of (12.7°; 1.3 to 24.0; I2 = 73%; N = 90) compared to sham MWM in the short term (0-6 weeks). Combined MWM and conventional rehabilitation improved pain at rest, with a MD of (-1.2; -2.2 to -0.2; I2 = 61%; N = 100), and disability SMD of (-1.3; confidence interval -2.2 to -0.4; I2 = 87%; N = 185) compared to conventional rehabilitation alone in the short term. Combined MWM and conventional rehabilitation also resulted in improvement in shoulder abduction and external rotation. Compared to Maitland, MWM resulted in improvement in the shoulder abduction MD (20.4°; confidence interval 4.3 to 36.5; I2 = 89%; N = 130) in the short term. There is no information regarding long-term effects. CONCLUSION: Evidence suggests that MWM may reduce shoulder pain and restore shoulder range of motion and function. Our findings are promising, but the evidence is not strong enough to recommend it pragmatically.

Use of the Prompts for Reestructuring Oral Muscular Phonetic Targets (PROMPT) in Autism Spectrum Disorder: a case study. / Uso do método de Pontos para a Reestruturação de Objetivos Fonéticos e Oro-Musculares (PROMPT) no Transtorno do Espectro Autista: um estudo de caso.

Autism Spectrum Disorder (ASD) is classified by Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a neurodevelopmental disorder, whose characteristics are mainly deficits in social communication and a restricted range of interests. There are several studies about autism, speech, and language in the literature, but few correlate speech and autism. This study aims to carry out a case study that will address autism, speech, and PROMPT (Restructuring Oral Muscular Phonetic Targets) and also to describe the speech improvement in the participant with autism using the method. The target words were defined for the entire intervention according to the System Analysis Observation (SAO) and Motor Speech Hierarchy (MSH), which are parts of the PROMPT evaluation. After the evaluation, the participant was attended for 16 sessions, once weekly, with the objective of improving their speech. After analyzing the data, it was possible to observe improvement in all aspects outlined according to the pre-treatment evaluation of the method such as phonatory control, mandibular control, lip-facial control and lingual control as well as in the sequenced movement although this was not the aim outlined in the evaluation. It was also possible to measure the improvement of an adequate number of words, an adequate number of phonemes, percentages of correct consonants - revised (PCC-R), and intelligibility.

O Transtorno do Espectro Autista (TEA) é classificado pelo Manual de Diagnóstico e Estatístico de Transtornos Mentais (DSM-5) como um Transtorno do Neurodesenvolvimento, sendo caracterizado, principalmente, por alterações na comunicação social e pela presença de um repertório restrito de atividades e interesses. Na literatura, há muitos estudos sobre autismo, fala e linguagem, mas poucos correlacionando fala e autismo. Este estudo teve como finalidade realizar um estudo de caso que abordou autismo, fala e PROMPT (Pontos para a Reestruturação de Objetivos Fonéticos e Oro-Musculares) e mensurou a melhora da fala no participante com autismo, utilizando o método. Foram definidas palavras-alvo para toda a intervenção, conforme o Sistema de Observação e Análise (SOA) e Hierarquia Motora de Fala (HMF), que fazem parte da avaliação de PROMPT. Após a avaliação, o participante foi atendido por 16 sessões, uma vez semanalmente. Após análise dos dados, observou-se melhora em todos os aspectos que foram delineados de acordo com a avaliação no pré-tratamento, como controle fonatório, controle mandibular, controle lábio-facial e controle lingual, como também no movimento sequenciado, apesar deste não ser o objetivo traçado na avaliação. Também foi possível mensurar melhora no número de vocábulos adequados, número de fonemas adequados, porcentagens de consoantes corretas ­ revisado (PCC-R) e inteligibilidade.

Urinary continence recovery after Retzius-sparing robot-assisted radical prostatectomy in relation to surgeon experience.

Urinary incontinence is one of the main concerns for patients after radical prostatectomy. Differences in surgical experience among surgeons could partly explain the wide range of frequencies observed. Our aim was to evaluate the association between the surgeons` experience and center caseload with relation to urinary continence recovery after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). Prospective observational single-center study. Five surgeons consecutively operated 405 patients between July 2017 and February 2022. Continence recovery was evaluated with pad count and by employing the short form of the International Consultation on Incontinence Questionnaire (ICIQ-SF), pre- and postoperatively at 1 year. Non-parametric tests were used. Median age was 63 years, 30% of patients presented with local advanced disease; the positive surgical margin rate (over 3 mm length) was 16%. Complication rate was 1% (Clavien-Dindo > II). One year after surgery, continence was assessed in 282 patients, of whom 87% were pad free and 51% never leaked (ICIQ-SF = 0). With respect to the mean annual number of procedures per surgeon, divided in < 20, 20-39 and ≥ 40, pad-free rates were achieved in 93%, 85%, and 84% and absence of urine leak rates in 47%, 62% and 48% of patients, respectively. Postoperative median ICIQ-SF was five. We acknowledge the limitation of a 12-month follow-up and the fact that we are a medium-volume center. There is no statistically significant association between continence recovery, surgeon's experience and center caseload. Continence recovery at 1 year after surgery is adequate and robust to surgeon's experience.

Differentiated Thyroid Cancer in a Pediatric Population: Estimating the Risk of Recurrence and Evolution Over Time.

Background Differentiated thyroid cancer (DTC) is the most common endocrine cancer during childhood, and the prognosis is usually good. The 2015 American Thyroid Association (ATA) pediatric guidelines for DTC classify patients into three categories (low, intermediate, and high) that represent the risk for persistent/recurrent disease. The "Dynamic Risk Stratification" (DRS) System showed that, in adults, reassessment of disease status during follow-up was a better predictor of disease status at the end of follow-up when compared to ATA risk stratification. This system is still not validated for the pediatric population with DTC. Our aim was to evaluate the usefulness of the DRS system in predicting DTC disease behaviour in this specific population. We also aimed to evaluate potential clinical-pathological factors associated with persistent disease at the end of follow-up. Methods A retrospective analysis of 39 pediatric patients (≤18 years) with DTC was conducted in our institution between 2007 and 2018, including 33 patients who had follow-up ≥ 12 months; these were classified into ATA risk groups and re-stratified according to their response to treatment at 12-24 months of follow-up. The associations between the ordinal variables of the baseline ATA risk group and the disease status re-evaluated 12-24 months after diagnosis (as per the DRS system) and at the end of follow-up were evaluated using a linear-by-linear association test. Gender, age at diagnosis, tumor size, multicentricity, extrathyroid extension, vascular invasion, lymph node metastasis, distant metastasis, and stimulated thyroglobulin (sTg) during the first RAI administration were evaluated as potential factors associated with persistent disease at 27 months after diagnosis using Firth's bias-reduced penalized-likelihood logistic regression. Results In this study, 39 patients were retrospectively analyzed, including 33 patients who had follow-ups ≥ 12 months with a median time of 56 (27-139) months who were classified in ATA risk groups and then re-stratified depending on their response to treatment between 12 and 24 months of follow-up. There was a statistically significant association between ATA risk groups and re-evaluation at 12 and 24 months (p=0.001) and between these two stratifications and the state of disease at final follow-up (p<0.001 for both). Factors with a statistically significant association with persistent disease at 27 months of follow-up were male sex, lymph node metastases at diagnosis, distant metastasis, extrathyroidal extension, and stimulated Tg values. Conclusions The assessment of the response to treatment between 12 and 24 months and at the end of follow-up refines the initial ATA risk stratification, confirming that dynamic risk evaluation is also helpful in the pediatric population.

Strengths and weaknesses in the high-risk baby care network.

OBJECTIVE: To characterize the Stork Network in health care for high-risk babies, pointing out its main challenges. METHOD: questionnaires were applied with those responsible for the babies and with network health professionals. Data were analyzed quantitatively. RESULTS: statistically relevant variables were: link with the Basic Health Unit; individuals' awareness of Family Health Support Center team; awareness of Family Health teams regarding the diagnosis of high-risk pregnancy and compliance with prenatal care; means of communication of individuals' birth; awareness of the need for hospitalization as well as its duration; awareness of follow-up in Secondary Health Care; and its outcome, pointing to a difficulty in the axis of coordination and longitudinality of the services provided in the network. CONCLUSION: the greatest challenges lie in covering the territory by Family Health strategy teams, expanding teams and solidifying partnerships with Higher Education Institutions, guaranteeing a differentiated professional training.

Metastatic follicular thyroid cancer with a longstanding responsiveness to gemcitabine plus oxaliplatin.

Background: Treatment of advanced follicular thyroid carcinoma (FTC) is based primarily on indirect evidence obtained with multikinase inhibitors (MKI) in clinical trials in which papillary carcinomas represent the vast majority of cases. However, it should be noted that MKI have a non-negligible toxicity that may decrease the patient's quality of life. Conventional chemotherapy with GEMOX (gemcitabine plus oxaliplatin) is an off-label therapy, which seems to have some effectiveness in advanced differentiated thyroid carcinomas, with a good safety profile, although further studies are needed. Case report: We report a case of a metastatic FTC, resistant to several lines of therapy. However, with a durable response to GEMOX, the overall survival of our patient appears to have been extended significantly due to this chemotherapy. Conclusion: GEMOX may have a role in patients with thyroid cancer unresponsive to MKI.

Retzius-sparing robot-assisted radical prostatectomy in a medium size oncological center holds adequate oncological and functional outcomes.

Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has emerged as a surgical option for patients with prostatic cancer in high-volume centers. The objective is to assess oncological and functional outcomes when implementing RS-RARP in a medium-volume center without previous experience of robotic surgery. This is a prospective observational single-center study. Patients operated between July 2017 and April 2020 were divided into two consecutive groups, A and B, each with 104 patients. The surgeons had prior experience in laparoscopic surgery and underwent robotic training. Positive surgical margin (PSM) status, urinary continence, and erectile function projected by Kaplan-Meier curves, together with patient reported quality of life outcomes at 12 months post-surgery were documented. Median patient age was 63 years (IQR = 59-67), overall PSM rate were 33%, 28% for pT2 disease. Pre-operative values showed no significant difference between both groups. The rate of urinary continence dropped from 81 to 78% (SE = 5.7) (Group A) and from 90 to 72% (SE = 6.3) (Group B) using the International Consultation on Incontinence Questionnaire-Short Form. Baseline sexual function was regained in 41% (Group A) and 47% (Group B) of patients. The median Expanded Prostate Index Composite-26 total score decreased from 86 to 82. These outcomes relate favorably to prior reports. There was a clinically significant decrease in median operative time in the successive groups with post-operative complications occurring in less than 2% of surgical procedures overall. A 12-month follow-up suggests that RS-RARP may be safely introduced in a medium-volume center without previous experience of robotic surgery.

Strengths and weaknesses in the high-risk baby care network / Fortalezas y debilidades en la red de atención al bebé de alto riesgo / Potencialidades e fragilidades na rede de cuidados do bebê de alto risco

ABSTRACT Objective: To characterize the Stork Network in health care for high-risk babies, pointing out its main challenges. Method: questionnaires were applied with those responsible for the babies and with network health professionals. Data were analyzed quantitatively. Results: statistically relevant variables were: link with the Basic Health Unit; individuals' awareness of Family Health Support Center team; awareness of Family Health teams regarding the diagnosis of high-risk pregnancy and compliance with prenatal care; means of communication of individuals' birth; awareness of the need for hospitalization as well as its duration; awareness of follow-up in Secondary Health Care; and its outcome, pointing to a difficulty in the axis of coordination and longitudinality of the services provided in the network. Conclusion: the greatest challenges lie in covering the territory by Family Health strategy teams, expanding teams and solidifying partnerships with Higher Education Institutions, guaranteeing a differentiated professional training.

RESUMEN Objetivo: caracterizar la Red Cigüeña en la atención a la salud de los bebés de alto riesgo, señalando sus principales desafíos. Método: se aplicaron cuestionarios con los responsables de los bebés y con los profesionales de salud de la red. Los datos se analizaron cuantitativamente. Resultados: las variables estadísticamente relevantes fueron: vinculación con la Unidad Básica de Salud; conocimiento de las personas sobre el equipo de los Centros de Apoyo a la Salud de la Familia; sensibilización de los equipos de Salud de la Familia sobre el diagnóstico del embarazo de alto riesgo y la adherencia al control prenatal; medio de comunicación del nacimiento de las personas; conciencia de la necesidad de hospitalización, así como de su duración; conocimientos sobre seguimiento en Atención Secundaria de Salud; y su resultado, apuntando a una dificultad en el eje de coordinación y longitudinalidad de los servicios prestados en la red. Conclusión: los mayores desafíos están en la cobertura del territorio por los equipos de la estrategia de Salud de la Familia, en la ampliación de los equipos y en la consolidación de alianzas con Instituciones de Educación Superior, garantizando una formación profesional diferenciada.

RESUMO Objetivo: caracterizar a Rede Cegonha na atenção à saúde ao bebê de alto risco, apontando seus principais desafios. Método: questionários foram aplicados com os responsáveis pelos bebês e com os profissionais de saúde da rede. Os dados foram analisados quantitativamente. Resultados: as variáveis estatisticamente relevantes foram: vínculo com a Unidade Básica de Saúde; conhecimento dos indivíduos sobre a equipe Núcleos de Apoio à Saúde da Família; ciência das equipes de Saúde da Família quanto ao diagnóstico de gravidez de risco e adesão ao pré-natal; via de comunicação do nascimento dos indivíduos; ciência quanto à necessidade de internação hospitalar, bem como sua duração; conhecimento sobre acompanhamento na Atenção Secundária à Saúde; e o desfecho do mesmo, apontando para uma dificuldade no eixo da coordenação e longitudinalidade dos serviços prestados na rede. Conclusão os maiores desafios estão na cobertura do território pelas equipes de estratégia de Saúde da Família, na ampliação de equipes e na solidificação das parcerias com as Instituições de Ensino Superior, garantindo uma formação profissional diferenciada.

A Comparison of Solvent-Based Extraction Methods to Assess the Central Carbon Metabolites in Mouse Bone and Muscle.

The identification of endogenous metabolites has great potential for understanding the underlying tissue processes occurring in either a homeostatic or a diseased state. The application of gas chromatography-mass spectrometry (GC-MS)-based metabolomics on musculoskeletal tissue samples has gained traction. However, limited comparison studies exist evaluating the sensitivity, reproducibility, and robustness of the various existing extraction protocols for musculoskeletal tissues. Here, we evaluated polar metabolite extraction from bone and muscle of mouse origin. The extraction methods compared were (1) modified Bligh-Dyer (mBD), (2) low chloroform (CHCl3)-modified Bligh-Dyer (mBD-low), and (3) modified Matyash (mMat). In particular, the central carbon metabolites (CCM) appear to be relevant for musculoskeletal regeneration, given their role in energy metabolism. However, the sensitivity, reproducibility, and robustness of these methods for detecting targeted polar CCM remains unknown. Overall, the extraction of metabolites using the mBD, mBD-low, and mMat methods appears sufficiently robust and reproducible for bone, with the mBD method slightly bettering the mBD-low and mMat methods. Furthermore, mBD, mBD-low, and mMat were sufficiently sensitive in detecting polar metabolites extracted from mouse muscle; however, they lacked repeatability. This study highlights the need for a re-thinking, towards a tissue-specific optimization of methods for metabolite extractions, ensuring sufficient sensitivity, repeatability, and robustness.

Early discharge for patients with benign pleural effusions using a Wayne catheter (pigtail) chest drain - analysis of safety, complications, and quality of life.

OBJECTIVE: to assess safety, efficacy and quality of life in patients with benign pleural effusions undergong pleural drainage with Wayne pleural catheter (DW) in an outpatient setting. METHOD: this is a prospective study, in which 47 patients were evaluated between July 2017 and October 2018. Patients with non-malignant pleural effusions underwent pleural drainage with clinical evolution compatible with outpatient care were included. Patients who underwent drainage due to other conditions and patients were excluded. RESULTS: after catheter placement, the mean length of hospital stay was 3.14 (± 3.85) days, and 21 patients (44.68%) were discharged within 24 hours. The mean time with the catheter was 12.63 (± 7.37) days. The analysis of the pleural fluid was transudate in 87.3% of cases and exudate in 12.3%. The causes of pleural effusion were heart failure (72.3%), renal failure (19.1%), liver failure (6.3%) and pneumonia (8.5%). The quality of life, analyzed according to the parameters of the questionnaire SF 36, showed low average values when compared to other studies. Analyzing each descriptor, the average was greater only in the limitation related to physical aspects. In the other descriptors, the results were similar, but smaller. CONCLUSION: the outpatient use of pleural catheters of the Wayne type (pigtail) proved to be feasible, safe and with a low associated infection rate. This is a viable option for selected patients.

Challenges of Implementing Lung Cancer Screening in a Developing Country: Results of the Second Brazilian Early Lung Cancer Screening Trial (BRELT2).

PURPOSE: This paper aims to present the results of a series of several Brazilian institutions that have been carrying out lung cancer screening (LCS). MATERIALS AND METHODS: This is a retrospective, cohort study, with follow-up of individuals of both sexes, with a heavy smoking history, who participated in LCS programs between December 2013 and January 2021 in six Brazilian institutions located in the states of São Paulo, Rio Grande do Sul, and Bahia. RESULTS: Three thousand four hundred seventy individuals were included, of which 59.8% were male (n = 2,074) and 50.6% were current smokers (n = 1,758), with 60.7 years (standard deviation 8.8 years). Lung-RADS 4 was observed in 233 (6.7%) patients. Biopsy was indicated by minimally invasive methods in 122 patients (3.5%). Two patients who demonstrated false-negative biopsies and lung cancer were diagnosed in follow-up. Diagnosis of lung cancer was observed in 74 patients (prevalence rate of 2.1%), with 52 (70.3%) in stage I or II. Granulomatous disease was found in 20 patients. There were no statistical differences in the incidence of lung cancer, biopsies, granulomatous disease, and Lung-RADS 4 nodules between public and private patients. CONCLUSION: There are still many challenges and obstacles in the implementation of LCS in developing countries; however, our multi-institutional data were possible to obtain satisfactory results in these scenarios and to achieve similar results to the main international studies. Granulomatous diseases did not increase the number of lung biopsies. The authors hope that it could stimulate the creation of organized screening programs in regions still endemic for tuberculosis and other granulomatous diseases.

Early discharge for patients with benign pleural effusions using a Wayne catheter (pigtail) chest drain - analysis of safety, complications, and quality of life / Alta precoce para pacientes com derrames pleurais benignos em uso de dreno pleural de Wayne (pigtail) - análise de segurança, complicações e qualidade de vida

ABSTRACT Objective: to assess safety, efficacy and quality of life in patients with benign pleural effusions undergong pleural drainage with Wayne pleural catheter (DW) in an outpatient setting. Method: this is a prospective study, in which 47 patients were evaluated between July 2017 and October 2018. Patients with non-malignant pleural effusions underwent pleural drainage with clinical evolution compatible with outpatient care were included. Patients who underwent drainage due to other conditions and patients were excluded. Results: after catheter placement, the mean length of hospital stay was 3.14 (± 3.85) days, and 21 patients (44.68%) were discharged within 24 hours. The mean time with the catheter was 12.63 (± 7.37) days. The analysis of the pleural fluid was transudate in 87.3% of cases and exudate in 12.3%. The causes of pleural effusion were heart failure (72.3%), renal failure (19.1%), liver failure (6.3%) and pneumonia (8.5%). The quality of life, analyzed according to the parameters of the questionnaire SF 36, showed low average values when compared to other studies. Analyzing each descriptor, the average was greater only in the limitation related to physical aspects. In the other descriptors, the results were similar, but smaller. Conclusion: the outpatient use of pleural catheters of the Wayne type (pigtail) proved to be feasible, safe and with a low associated infection rate. This is a viable option for selected patients.

RESUMO Objetivo: avaliar a segurança, a eficácia, as complicações e a qualidade de vida da alta precoce e acompanhamento ambulatorial de pacientes com derrames pleurais benignos submetidos à drenagem pleural com dreno de Wayne (DW). Método: estudo prospectivo, em que foram avaliados 47 pacientes entre julho de 2017 e outubro de 2018. Foram incluídos os pacientes com derrames pleurais não malignos, submetidos a drenagem pleural com evolução clínica compatível com o cuidado ambulatorial. Foram excluídos os pacientes submetidos a drenagem por outras afecções. Resultados: após a drenagem, a média do tempo de internação dos pacientes foi de 3,14 (±3,85) dias, sendo que 21 pacientes (44,68%) tiveram alta em até 24 horas após a drenagem. O tempo médio de permanência com o dreno foi de 12,63 (±7,37) dias. A análise do líquido pleural mostrou tratar-se de transudato em 87,3% dos casos e de exsudato em 12,3%. Dentre as causas do derrame pleural, destacaram-se insuficiência cardíaca (72,3%), insuficiência renal (19,1%), hepatopatias (6,3%) e pneumonias (8,5%). A qualidade de vida, analisada segundo os parâmetros do questionário SF 36, teve valores médios baixos, principalmente em relação a outros estudos. Na análise de cada descritor, a média apresentou-se maior somente na limitação por aspectos físicos. Nos demais descritores, os resultados foram semelhantes, mas menores. Conclusão: o uso ambulatorial de cateteres pleurais do tipo Wayne (pigtail) mostrou-se factível, seguro e com baixa taxa de infecções associadas. Trata-se de opção viável para pacientes selecionados.

A pathogenic variant in CHEK2 shows a founder effect in Portuguese Roma patients with thyroid cancer.

PURPOSE: Germline mutations in DNA repair-related genes have been recently reported in cases with familial non-medullary thyroid carcinoma (FNMTC). A Portuguese family from the Roma ethnic group with four members affected with papillary thyroid carcinoma (PTC), and three members with multinodular goiter (MNG) was identified. The aim of this study was to investigate the involvement of DNA repair-related genes in the etiology of FNMTC in this family and in the Roma ethnic group. METHODS: Ninety-four hereditary cancer predisposition genes were analyzed through next-generation sequencing. Sanger sequencing was used for variant confirmation and screening. Twelve polymorphic markers were genotyped for haplotype analysis in the CHEK2 locus. RESULTS: A germline pathogenic frameshift variant in the CHEK2 gene [c.596dupA, p.(Tyr199Ter)] was detected in homozygosity in the proband (PTC) and in his brother (MNG), being heterozygous in his mother (PTC), two sisters (PTC), and one nephew (MNG). This variant was absent in 100 general population controls. The screening of the CHEK2 variant was extended to other Roma individuals, being detected in 2/33 Roma patients with thyroid cancer, and in 1/15 Roma controls. Haplotype segregation analysis identified a common ancestral core haplotype (Hcac), covering 10 Mb in the CHEK2 locus, shared by affected CHEK2 variant carriers. Analysis of 62 individuals CHEK2 wild-type indicated that none presented the Hcac haplotype. The estimated age for this variant suggested that it was transmitted by a relatively recent common ancestor. CONCLUSIONS: We identified a founder CHEK2 pathogenic variant, which is likely to underlie thyroid cancer and other cancer manifestations in the Roma population.

Bats from the Pedra Branca Forest, Rio de Janeiro, Brazil.

The Pedra Branca Forest is located in a highly-urbanised region of the central portion of Rio de Janeiro City, comprises the largest urban forest on the continent and is isolated from other Atlantic Forest remnants. The local flora and fauna are protected by three conservation units (Pedra Branca State Park, Prainha Municipal Natural Park and Guaratiba State Biological Reserve) and one biological station (Fiocruz Atlantic Forest Biological Station-EFMA). Here, we provide an updated list of the bat fauna for the remnant. The results are based on samplings at EFMA and literature data from Pedra Branca State Park and Prainha Natural Park. The three sampling sites combined resulted in 31 species, 23 genera and four families. Phyllostomidae was the richest family with 24 species, followed by Vespertilionidae with five species (3%) and Molossidae and Noctilionidae with one species. The local bat fauna was predominantly composed of species with a broad geographic distribution.