Ethical regulation of biomedical research in Brazil: a quality improvement initiative.

BACKGROUND: Q-CEP (Qualificação dos Comitês de Ética em Pesquisa que compõem o Sistema CEP/Conep) is a nationwide project resulting from a partnership between the Brazilian National Research Ethics Commission (Conep), the Ministry of Health and Hospital Moinhos de Vento (HMV). It was developed to consolidate policy for ethical review of research with human beings in all members of the CEP/Conep System, Brazil's national system of institutional review boards. The aim of this study was therefore to report on the experience and results of the Q-CEP project. METHODS: An observational, retrospective study includes data from the Q-CEP, obtained from visits to all the institutional research ethics committees (RECs) in the country. The actions implemented by Q-CEP were part of a two-step process: (i) training visits to each REC; (ii) development of distance learning modules on strategic topics pertaining to research ethics evaluation. The data presented herein cover step one (training visits), defined by Q-CEP as the diagnostic stage of the project. For a country with social and economics inequalities such as Brazil, this is a particularly important stage; an accurate picture of reality is needed to inform planning of quality improvement strategies. RESULTS: In 2019-2021, Q-CEP visited 832 RECs and trained 11,197 people. This sample covered almost all active RECs in the country; only 4 (0.5%) were not evaluated. Of the 94 items evaluated, 62% did not reach the target of at least 80% compliance and around 1/4 (26%) were below 50% compliance. The diagnostic stage of the process revealed inadequacies on the part of the RECs in their ethical reviews. The analysis of informed consent forms showed compliance in only 131 RECs (15.74%). The description of pending issues made by RECs in their reports was compliant in 19.33% (n = 161). Administrative and operational aspects were also considered inadequate by more than half of the RECs. CONCLUSIONS: Overall, Brazilian RECs showed poor compliance in several aspects of their operation, both in ethics evaluation and in other processes, which justifies additional training. The Q-CEP project is part of a quality improvement policy promoted by the Brazilian Ministry of Health. The data obtained in the diagnostic step of the project have contributed to the qualification and consolidation of one of the world's largest research ethics evaluation systems.

Exploring the sex-associated differences in molars fused roots.

BACKGROUND: Human sexual dimorphism is associated with many biological characteristics, including dental variables. OBJECTIVES: To investigate if molars fused roots present sex-associated differences. METHODS: Panoramic radiographs were used to investigate the frequency and distribution of permanent molars fused roots. Only patients with all first and second permanent molars were included. Third molars were not investigated. Any molar with roots fused apical to the usual furcal position were considered molar fused roots. Comparisons between males and females were performed using chi-square or Fisher's and Mann-Whitney tests and the established alpha was 5% (p<0.05). Sex-differential liability models were also proposed. RESULTS: A total of 84 males and 86 females were included and 1360 molars were analyzed. Among them, 46 (26.06%) present at least one molar with fused root. Second maxillary molars were the most affected teeth. There was an association between sex and molars with fused roots. Females had a 3.4 higher chance to present fused roots than males (OR=3.4, CI 95% 1.6-6.8; p=0.0008). The female: male ratio of molars with fused roots was 2.5:1. The number of molars with fused roots ranged from 1 to 6 per patient, and the mean number of Females presented more molars with fused roots (mean = 1.01; standard deviation = 1.52) than males (mean = 0.31; standard deviation = 0.85) (p<0.05). CONCLUSIONS: Molar fused root of permanent teeth presents sex-associated differences, in which females are more affected than males. Our results support sex-differential liability models for molars fused roots.

Psoriasis and steatotic liver disease: Are PNPLA3 and TM6SF2 polymorphisms suitable for the hepato-dermal axis hypothesis?

INTRODUCTION AND OBJECTIVES: A high prevalence of steatotic liver disease has been described in psoriasis. However, the influence of genetic polymorphisms has yet to be investigated in this scenario. This study aims to determine the frequency of steatosis, advanced liver fibrosis and PNPLA3/TM6SF2 genotypes in individuals with psoriasis and to evaluate the impact of genetic polymorphisms, metabolic parameters and cumulative methotrexate dose on steatosis and fibrosis. MATERIALS AND METHODS: Cross-sectional study that prospectively included psoriasis outpatients, submitted to clinical and laboratory analysis, transient elastography (FibroScan®, Fr) and PNPLA3/TM6SF2 genotyping. Steatosis was defined by CAP ≥275 dB/m and advanced liver fibrosis as transient elastography ≥10 kPa. Logistic regression analysis evaluated the independent variables related to steatosis and fibrosis; p-value< 0.05 was considered significant. RESULTS: One hundred and ninety-nine patients were enrolled (age 54.6 ± 12.6 years, 57.3% female). Metabolic syndrome (MetS), steatosis and advanced liver fibrosis prevalence were 55.8%, 54.8% and 9%, respectively. PNPLA3 and TM6SF2 genotypes frequencies were CC 42.3%/CG 49.5%/GG 8.2% and CC 88.7%/ CT 11.3%/ TT 0%. MetS (OR3.01 95%CI 1.51-5.98; p = 0.002) and body mass index (OR1.17 95%CI 1.08-1.26; p < 0.01) were independently associated with steatosis. Diabetes Mellitus (T2DM) (OR10.76 95%CI 2.42-47.87; p = 0.002) and harboring at least one PNPLA3 G allele (OR5.66 95%CI 1.08-29.52; p = 0.039) were associated with advanced fibrosis, but not TM6SF2 polymorphism or cumulative MTX dose. CONCLUSIONS: MetS and T2DM confer higher odds for steatosis and advanced fibrosis in individuals with psoriasis. PNPLA3 G allele, but not TM6SF2 polymorphism, impacts a 5-fold odds of advanced liver fibrosis.

Impact of PNPLA3 and TM6SF2 polymorphisms on the prognosis of patients with MASLD and type 2 diabetes mellitus.

BACKGROUND/AIMS: Longitudinal studies assessing the impact of genetic polymorphisms on outcomes in patients with Type 2 Diabetes Mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) are scarce. This study aimed to evaluate the effect of PNPLA3 and TM6SF2 risk alleles on hepatic and extrahepatic outcomes in T2DM-MASLD individuals. METHODS: Patients' polymorphisms were analysed as follows: PNPLA3 CC, CG and GG; TM6SF2 CC and CT + TT; combined comparing no mutant allele, one allele G or T or ≥2 alleles G or T. Hierarchical models were built to assess associations between polymorphisms and outcomes, independently of confounding factors. Multivariate logistic regression was used for cirrhosis and its complications and extrahepatic cancer, and Cox regression for cardiovascular events (CVEs) and all-cause mortality. RESULTS: In total, 407 T2DM-MASLD patients (62.1 ± 10.5 years, 67.6% women) were followed for 11 (6-13) years. Having at least one G or T allele independently increased the risk of cirrhosis in the separate analysis of PNPLA3 and TM6SF2. Combined polymorphism analysis demonstrated an even higher risk of cirrhosis if two or more risk alleles were present (OR 18.48; 95% CI 6.15-55.58; p < .001). Regarding cirrhosis complications, the risk was higher in PNPLA3 GG and TM6SF2 CT + TT, also with an even higher risk when two or more risk alleles were present in the combined evaluation (OR 27.20; 95% CI 5.26-140.62; p < .001). There were no associations with CVEs or mortality outcomes. CONCLUSION: In T2DM, PNPLA3 and TM6SF2 polymorphisms, individually and additively, impact MASLD severity, with an increased risk of cirrhosis and its complications.

Parental History of Type 2 Diabetes Mellitus and PNPLA3 Polymorphism Increase the Risk of Severe Stages of Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: In non-alcoholic fatty liver disease (NAFLD), the influence of parental history of type 2 diabetes (T2D) allied to single nucleotide polymorphisms (SNPs) in the offspring is not known. We aimed to investigate the impact of the parental history of T2D, PNPLA3 and TM6SF2 polymorphisms in liver steatosis and fibrosis. METHODS: This was a case-control study involving the offspring of T2D patients and controls without a parental history of T2D. Participants underwent clinical and laboratory evaluation, transient elastography (TE) by Fibroscan® (Echosens, Fr) and genotyping for PNPLA3 and TM6SF2. Multivariate logistic regression evaluated the influence of parental history of T2D on liver steatosis and fibrosis, controlled for age, gender, metabolic traits and SNPs. RESULTS: 161 T2D offspring and 78 controls, 10-46 years old, were included. The offspring of T2D had higher prevalences of obesity, T2D, arterial hypertension and sedentarism. Parental history of T2D was associated with fibrosis ≥ F2 (OR 8.89, CI 95% 1.09-72.01, p = 0.041) after adjustment for age, gender, metabolic traits and SNPs. PNPLA3 GG genotype was independently associated with steatosis ≥ S1 (OR 8.15, CI 95% 1.93-34.38, p = 0.004) and fibrosis ≥ F2 (OR 4.31, CI 95% 1.11-16.61, p = 0.034). CONCLUSIONS: The offspring of T2D patients present a worse metabolic profile and the parental history of T2D confers an increased likelihood of hepatic fibrosis, independent of metabolic factors. PNPLA3 homozygous GG, but not TM6SF2 genotypes, also impacts on this phenotype.

Real-World Populational-Based Quality of Life and Functional Status After Stroke.

OBJECTIVES: This study aimed to describe health-related quality of life (HRQoL) 3 months and 1 year after stroke, compare HRQoL between dependent (modified Rankin scale [mRS] 3-5) and independent (mRS 0-2) patients, and identify factors predictive of poor HRQoL. METHODS: Patients with a first ischemic stroke or intraparenchymal hemorrhage from the Joinville Stroke Registry were analyzed retrospectively. Using the 5-level version of the EuroQol-5D questionnaire, HRQoL was calculated for all patients 3 months and 1 year after stroke, stratified by mRS score (0-2 or 3-5). One-year HRQoL predictors were examined using univariate and multivariate analyses. RESULTS: Three months after a stroke, data from 884 patients were analyzed; 72.8% were categorized as mRS 0-2 and 27.2% as mRS 3-5, and the mean HRQoL was 0.670 ± 0.256. At 1-year follow-up, 705 patients were evaluated; 75% were classified as mRS 0-2 and 25% as mRS 3-5, and the mean HRQoL was 0.71 ± 0.249. An increase in HRQoL was observed between 3 months and 1 year (mean difference 0.024, P < .0001), both in patients with 3-month mRS 0-2 (0.013, P = .027) and mRS 3-5 (0.052, P < .0001). Increasing age, female sex, hypertension, diabetes, and a high mRS were associated with poor HRQoL at 1 year. CONCLUSIONS: This study described the HRQoL after a stroke in a Brazilian population. This analysis shows that the mRS was highly associated with HRQoL after stroke. Age, sex, diabetes, and hypertension were also associated with HRQoL, although not independently of mRS.

Evaluation of in-vitro susceptibility of ß-lactam-resistant Gram-negative bacilli to ceftazidime-avibactam and ceftolozane-tazobactam from clinical samples of a general hospital in southern Brazil.

BACKGROUND: The spread of carbapenemase- and extended-spectrum ß-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of ß-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance. METHODS: Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The ß-lactamase-encoding genes were investigated using polymerase chain reaction. RESULTS: High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-ß-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common. CONCLUSIONS: C/A and C/T were active against microorganisms with ß-lactam-resistant phenotypes, except when resistance was mediated by metallo-ß-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more ß-lactamase-encoding genes (62.5% and 77.4%, respectively).

Evaluation of in-vitro susceptibility of ß-lactam-resistant Gram-negative bacilli to ceftazidime-avibactam and ceftolozane-tazobactam from clinical samples of a general hospital in southern Brazil

ABSTRACT Background: The spread of carbapenemase- and extended-spectrum β-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of β-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance. Methods: Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The β-lactamase-encoding genes were investigated using polymerase chain reaction. Results: High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-β-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common. Conclusions: C/A and C/T were active against microorganisms with β-lactam-resistant phenotypes, except when resistance was mediated by metallo-β-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more β-lactamase-encoding genes (62.5% and 77.4%, respectively).

Incidência de Injúria Renal Aguda em Pacientes Críticos com COVID-19 e Sobrevida em 90 dias: Coorte Retrospectiva de Uma Unidade de Tratamento Intensivo Pública, Joinville/Brasil / Incidence of acute kidney injury in critically ill patients with COVID-19 and 90-day survival: Retrospective Cohort of a Public Intensive Care Unit, Joinville/Brazil

Cerca de um terço dos pacientes com COVID-19 em unidades de terapia intensiva (UTI) apresentam injúria renal aguda (IRA) dialítica. Poucos estudos têm avaliado a sobrevida de pacientes com IRA em UTI exclusivamente pública. O objetivo do estudo foi avaliar a sobrevida intra-hospitalar em 90 dias de pacientes com e sem IRA dialítica internados com COVID-19 grave. Trata-se de uma coorte histórica de um hospital geral em Joinville, Santa Catarina/Brasil. Foram incluídos todos os pacientes admitidos na UTI entre março e dezembro de 2020 com diagnóstico confirmado de COVID-19. Definiu-se IRA como a presença de alteração de função renal aguda com necessidade de hemodiálise. Utilizou-se modelo multivariado por regressão de Cox para avaliar a sobrevida de pacientes com e sem IRA dialítica. Os resultados do estudo demonstraram que dos 187 pacientes incluídos (55,5% homens) com média de idade de 62,8±13,6 anos, 37,4% apresentaram IRA dialítica. Pacientes com IRA dialítica usaram mais drogas vasoativas, tinham maior gravidade na admissão e maior mortalidade (84,3% vs. 63,2%; p=0,002) em relação àqueles sem IRA. O risco de morte nos pacientes com IRA foi maior (RR bruto= 1,60; IC 95% 1,13-2,26; p= 0,007). Após ajustes para idade, sexo, comorbidades e gravidade clínica, a presença de IRA dialítica se manteve associada a uma frequência maior de mortalidade em 90 dias (RR= 1,49; IC 95% 1,03-2.15; p=0,032). A sobrevida de pacientes com COVID-19 grave e IRA dialítica na amostra estudada foi menor em relação a UTIs privadas no Brasil, o que sugere desigualdades no sistema público.

About one third of patients with COVID-19 in intensive care units (ICU) have acute kidney injury (AKI) requiring dialysis. Few studies have evaluated the survival ratel of patients with AKI in exclusively public ICUs. The aim of this study was to evaluate the 90-day in-hospital survival of patients with and without AKI requiring dialysis hospitalized with severe COVID-19. This is a historical cohort of a general hospital in Joinville, Santa Catarina/Brazil. All patients admitted to the ICU between March and December of 2020 with a confirmed diagnosis of COVID-19 were included. AKI was defined by the presence of acute renal function alteration requiring hemodialysis. A multivariate Cox regression model was used to assess the survival of patients with and without AKI requiring dialysis. The results of the study showed that, of the 187 patients included (55.5% men) with a mean age of 62.8±13.6 years, 37.4% had AKI requiring dialysis. Patients with AKI requiring dialysis used more vasoactive drugs, had greater severity on admission and higher mortality rate (84.3% vs. 63.2%; p=0.002) compared to those without AKI. The risk of death in patients with AKI was higher (crude RR= 1.60; 95% CI 1.13-2.26; p= 0.007). After adjustments for age, sex, comorbidities and clinical severity, the presence of AKI requiring dialysis remained associated with a higher frequency of 90-day mortality (RR= 1.49; 95% CI 1.03-2.15; p=0.032). The survival of patients with severe COVID-19 and AKI requiring dialysis in the studied sample was lower compared to private ICUs in Brazil, which suggests inequalities in the public system.

Oral manifestations and injuries related to covid- 19: an experience report on the role of hospital dentistry / Manifestações orais e lesões relacionadas à covid-19: um relatório de experiência sobre o papel da odontologia hospitalar / Manifestaciones orales y lesiones relacionadas con covid- 19: un informe de experiencia sobre el papel de la odontología hospitalaria

SARS-COV-2 is transmitted among human beings by saliva droplets that come in direct contact with the oral cavity, nose, and eyes. Since the mouth is one of the anatomical sites primarily contaminated, oral manifestations have also been reported beyond the serious consequences inherent to progressive respiratory failure. This study aimed to identify oral manifestations possibly related to the infection by COVID-19 in hospitalized patients. A prospective study was carried out with patients diagnosed with COVID-19 in the period between March and June 2021, admitted to the Moderate COVID-19 Care Unit of the Hans Dieter Schmidt Regional Hospital, by applying a form and performing a clinical exam of the oral cavity. Out of all patients (n=45), 33.3% reported both olfactory (anosmia) and taste dysfunction (dysgeusia), with an average duration of 5.9 ±3.0 days. Regarding other oral manifestations evaluated, two patients reported dry and burning mouth and one patient reported a change in taste associated with plaque-like changes in the tongue. No patients presented ulcers or other lesions in the oral cavity. Olfactory and taste dysfunction were symptoms recognized of the novel coronavirus disease (COVID-19). However, the association with other oral manifestations is still controversy. Unfortunately, dentistry professionals are still not part of most teams in the hospital environment, mostly because of the lack of prioritization of dental care. Working with a multidisciplinary team may avoid possible systemic complications due to poor dental care.

Sars-COV-2 é transmitida entre os seres humanos por gotículas de saliva que entram em contato direto com a cavidade oral, nariz e olhos. Uma vez que a boca é um dos sítios anatômicos principalmente contaminados, as manifestações orais também foram relatadas para além das graves consequências inerentes à insuficiência respiratória progressiva. Este estudo teve como objetivo identificar manifestações orais possivelmente relacionadas à infecção por Covid-19 em pacientes hospitalizados. Foi realizado um estudo prospetivo com pacientes diagnosticados com Covid-19 no período entre março e junho de 2021, internados na Unidade de Atendimento Moderado contra a Covid-19 do Hospital Regional Hans Dieter Schmidt, aplicando um formulário e realizando um exame clínico da cavidade oral. De todos os pacientes (n=45), 33,3% relataram disfunção olfativa (anosmia) e gustativa (disgeusia), com duração média de 5,9 ±3,0 dias. Em relação a outras manifestações orais avaliadas, dois pacientes relataram boca seca e ardente e um paciente relatou alteração no paladar associada a alterações semelhantes a placas na língua. Nenhum paciente apresentou úlceras ou outras lesões na cavidade oral. Disfunção olfativa e gustativa foram sintomas reconhecidos do novo coronavírus (Covid-19). No entanto, a associação com outras manifestações orais ainda é controversa. Infelizmente, os profissionais de odontologia ainda não fazem parte da maioria das equipes do ambiente hospitalar, principalmente por causa da falta de priorização dos cuidados odontológicos. Trabalhar com uma equipe multidisciplinar pode evitar possíveis complicações sistêmicas devido a cuidados odontológicos deficientes.

SARS-COV-2 se transmite entre los seres humanos por las gotitas de saliva que entran en contacto directo con la cavidad oral, la nariz y los ojos. Dado que la boca es uno de los sitios anatómicos principalmente contaminados, también se han informado manifestaciones orales más allá de las consecuencias graves inherentes a la insuficiencia respiratoria progresiva. El objetivo de este estudio fue identificar las manifestaciones bucales posiblemente relacionadas con la infección por COVID-19 en pacientes hospitalizados. Se realizó un estudio prospectivo con pacientes diagnosticados de COVID-19 en el periodo comprendido entre marzo y junio de 2021, ingresados en la Unidad de Cuidados Moderados de COVID-19 del Hospital Regional Hans Dieter Schmidt, mediante la aplicación de un formulario y la realización de un examen clínico de la cavidad oral. De todos los pacientes (n=45), el 33,3% notificó tanto disfunción olfativa (anosmia) como gustativa (disgeusia), con una duración media de 5,9 ±3,0 días. En cuanto a las demás manifestaciones orales evaluadas, dos pacientes notificaron sequedad y ardor de boca y un paciente notificó un cambio en el gusto asociado a cambios en la lengua en forma de placa. Ningún paciente presentó úlceras u otras lesiones en la cavidad oral. La disfunción olfativa y gustativa fueron síntomas reconocidos de la nueva enfermedad por coronavirus (COVID-19). Sin embargo, la asociación con otras manifestaciones orales es aún controvertida. Desafortunadamente, los profesionales de la odontología todavía no son parte de la mayoría de los equipos en el entorno hospitalario, principalmente debido a la falta de priorización de la atención odontológica. Trabajar con un equipo multidisciplinario puede evitar posibles complicaciones sistémicas debido a la mala atención dental.

Urgent vs. planned peritoneal dialysis initiation: complications and outcomes in the first year of therapy / Diálise peritoneal de início urgente versus planejado: complicações e desfechos no primeiro ano de terapia

Abstract Introduction: Urgent-start peritoneal dialysis (US-PD) has been proposed as a safe modality of renal replacement therapy (RRT) for end-stage renal disease (ESRD) patients with an indication for emergency dialysis initiation. We aimed to compare the characteristics, 30-day complications, and clinical outcomes of US-PD and planned peritoneal dialysis (Plan-PD) patients over the first year of therapy. Methods: This was a single-center retrospective study that included incident adult patients followed for up to one year. US-PD was considered when incident patients started therapy within 7 days after Tenckhoff catheter implantation. Plan-PD group consisted of patients who started therapy after the breaking period (15 days). Mechanical and infectious complications were compared 30 days from PD initiation. Hospitalization and technique failure during the first 12 months on PD were assessed by Kaplan-Meier curves and the determinants were calculated by Cox regression models. Results: All patients starting PD between October/2016 and November/2019 who fulfilled the inclusion criteria were analyzed. We evaluated 137 patients (70 in the US-PD x 67 Plan-PD). The main complications in the first 30 days were catheter tip migration (7.5% Plan-PD x 4.3% US-PD - p= 0.49) and leakage (4.5% Plan-PD x 5.7% US-PD - p=0.74). Most catheters were placed using the Seldinger technique. The main cause of dropout was death in US-PD patients (15.7%) and transfer to HD in Plan-PD patients (13.4%). The occurrence of complications in the first 30 days was the only risk factor for dropout (OR = 2.9; 95% CI 1.1-7.5, p = 0.03). Hospitalization rates and technique survival were similar in both groups. Conclusion: The lack of significant differences in patients' outcomes between groups reinforces that PD is a safe and applicable dialysis method in patients who need immediate dialysis.

Resumo Introdução: A diálise peritoneal de início urgente (US-PD) foi proposta como modalidade segura de terapia renal substitutiva (TRS) para pacientes com doença renal em estágio 5 (DRC-5) com indicação de início de diálise de emergência. Buscamos comparar características, complicações em 30 dias e desfechos clínicos de pacientes em US-PD e diálise peritoneal planejada (DP-plan) no primeiro ano de terapia. Métodos: Estudo retrospectivo de centro único, que incluiu pacientes adultos incidentes em DP acompanhados por até um ano. Considerou-se US-PD quando os pacientes iniciaram terapia até 7 dias após implante do cateter Tenckhoff. O grupo DP-plan consistiu de pacientes iniciando terapia após período break-in (15 dias). Compararam-se complicações mecânicas e infecciosas 30 dias após o início da DP. Hospitalização e falha da técnica durante os primeiros 12 meses em terapia foram avaliados por curvas Kaplan-Meier e os seus determinantes foram analisados por modelos de regressão de Cox. Resultados: Analisaram-se todos os pacientes iniciando DP entre Outubro/2016-Novembro/2019 que preencheram os critérios de inclusão. Avaliamos 137 pacientes (70 US-PD x 67 DP-plan). As principais complicações nos primeiros 30 dias foram migração da ponta do cateter (7,5% DP-plan x 4,3% US-PD - p= 0,49) e extravasamento (4,5% DP-plan x 5,7% US-PD - p=0,74). A maioria dos cateteres foi implantada pela técnica de Seldinger. A principal causa de saída da terapia foi óbito em pacientes em US-PD (15,7%) e transferência para HD em pacientes em DP-plan (13,4%). A ocorrência de complicações nos primeiros 30 dias foi o único fator de risco para saída da terapia (OR = 2,9; IC 95% 1,1-7,5, p = 0,03). Taxas de hospitalização e sobrevida da técnica foram similares em ambos os grupos. Conclusão: A ausência de diferenças significativas nos desfechos dos pacientes entre os grupos reforça que DP é um método de diálise seguro e aplicável em pacientes que necessitam diálise imediata.

Phosphate solubilization by Antarctic yeasts isolated from lichens.

Antarctica has a great diversity of microorganisms with biotechnological potential but is not very well Known about yeasts with phosphate solubilization activity. Thus, the aim of this study was to evaluate the ability of yeasts from Antarctica lichens to solubilize phosphate in vitro. In the screening, 147 yeasts were tested and 43 (29%) showed P solubilization in solid NBRIP medium at 15.0 °C, with a higher prevalence of positive genera Vishniacozyma, followed by Cystobasidium. Most of the positive yeasts were isolated from Usnea auratiacoatra, followed by Polycauliona regalis and Lecania brialmontii. Two strains with better activity after screening were selected for the solubilization in the liquid medium, Vishniacozyma victoriae 2.L15 and A.L6 (unidentified). Vishniacozyma victoriae 2.L15 exhibiting activities at 25.0 °C (29.91 mg/L of phosphate and pH 6.85) and at 30.0 °C (619.04 mg/L of phosphate and pH 3.73) and A.L6 strain at 25.0 °C (25.05 mg/L of phosphate and pH 6.69) and at 30.0 °C (31.25 mg/L of phosphate and pH 6.47). Of eight organic acids tested by HPLC, tartaric and acetic acids were detected during phosphate solubilization, with greater release in the period of 144 (2.13 mg/L) and 72 (13.72 mg/L) hours, respectively. Future studies to elucidate the presence of functional genes for P metabolism in lichens, as well as studies in the field of proteomics for the discovery of yeast proteins related to P solubilization are needed. Thus, the high prevalence of lichen-associated yeast communities probably contributed to the high frequency of phosphate-solubilizing isolates in this study.

Incidence, lethality, and post-stroke functional status in different Brazilian macro-regions: The SAMBA study (analysis of stroke in multiple Brazilian areas).

Background: Stroke is the second leading cause of death in Brazil. The social and financial burden of stroke is remarkable; however, the epidemiological profile remains poorly understood. Objective: The aim of this study was to report the incidence, lethality, and functional status at 30 and 90 days post-stroke in the cities of different Brazilian macro-regions. Methods: This is an observational, prospective, and population-based study, led in Canoas (South), Joinville (South, reference center), Sertãozinho (Southeast), and Sobral (Northeast) in Brazil. It was developed according to the three-step criteria recommended by the World Health Organization to conduct population-based studies on stroke. Using different sources, all hospitalized and ambulatory patients with stroke were identified and the same criteria were kept in all cities. All first events were included, regardless of sex, age, or type of stroke. Demographic and risk factor data were collected, followed by biochemical, electrocardiographic, and radiological test results. Functional status and lethality were obtained using the mRankin scale through telephonic interview (validated Brazilian version). Results: In 1 year, 932 stroke cases were registered (784 ischemic stroke, 105 hemorrhagic stroke, and 43 subarachnoid hemorrhage). The incidence rates per 100,000 inhabitants, adjusted for the world population, were 63 in Canoas, 106 in Joinville, 72 in Sertãozinho, and 96 in Sobral. The majority (70.8%) were followed for 90 days. Kaplan-Meier curves showed that 90-day survival was different among cities. Sobral, which has the lowest socioeconomic indexes, revealed the worst results in terms of lethality and functional status. Conclusion: This study expands the knowledge of stroke epidemiology in Brazil, a middle-income country with enormous socioeconomic and cultural diversity. The discrepancy observed regarding the impact of stroke in patients from Joinville and Sobral highlights the need to improve the strategic allocation of resources to meet the health priorities in each location.

Cerebrospinal fluid analysis of pregnant women at early stages of COVID-19.

OBJECTIVE: To determine the presence or absence of SARS-CoV-2 in the cerebrospinal fluid of pregnant women at early stages of COVID-19. MATERIALS AND METHODS: We conducted a prospective observational study with pregnant women undergoing cesarean section and real-time polymerase chain reaction to SARS-CoV-2 was performed in the cerebrospinal fluid in the early stages of COVID-19. RESULTS: Fourteen pregnant women, whose COVID-19 symptoms started between four to 18 days prior to delivery, were included. Eleven of the women reported anosmia, dysgeusia, and headaches and there were two fatal cases. SARS-Cov-2 was not present in the cerebrospinal fluid of these COVID-19 patients with early neurological symptoms, even in severe cases. CONCLUSION: Our study suggests that peripheric cell damage and parainfectious phenomena may predominate over direct central nervous system injury in the pathophysiology of COVID-19 related early neurological symptoms on pregnant women.

Demographic history differences between Hispanics and Brazilians imprint haplotype features.

Admixture is known to greatly impact the genetic landscape of a population and, while genetic variation underlying human phenotypes has been shown to differ among populations, studies on admixed subjects are still scarce. Latin American populations are the result of complex demographic history, such as 2 or 3-way admixing events, bottlenecks and/or expansions, and adaptive events unique to the American continent. To explore the impact of these events on the genetic structure of Latino populations, we evaluated the following haplotype features: linkage disequilibrium, shared identity by descent segments, runs of homozygosity, and extended haplotype homozygosity (integrated haplotype score) in Latinos represented in the 1000 Genome Project along with array data from 171 Brazilians sampled in the South and Southeast regions of Brazil. We found that linkage disequilibrium decay relates to the amount of American and African ancestry. The extent of identity by descent sharing positively correlates with historical effective population sizes, which we found to be steady or growing, except for Puerto Ricans and Colombians. Long runs of homozygosity, a particular instance of autozygosity, was only enriched in Peruvians and Native Americans. We used simulations to account for random sampling and linkage disequilibrium to filter positive selection indexes and found 244 unique markers under selection, 26 of which are common to 2 or more populations. Some markers exhibiting positive selection signals had estimated time to the most recent common ancestor consistent with human adaptation to the American continent. In conclusion, Latino populations present highly divergent haplotype characteristics that impact genetic architecture and underlie complex phenotypes.

Urgent vs. planned peritoneal dialysis initiation: complications and outcomes in the first year of therapy.

INTRODUCTION: Urgent-start peritoneal dialysis (US-PD) has been proposed as a safe modality of renal replacement therapy (RRT) for end-stage renal disease (ESRD) patients with an indication for emergency dialysis initiation. We aimed to compare the characteristics, 30-day complications, and clinical outcomes of US-PD and planned peritoneal dialysis (Plan-PD) patients over the first year of therapy. METHODS: This was a single-center retrospective study that included incident adult patients followed for up to one year. US-PD was considered when incident patients started therapy within 7 days after Tenckhoff catheter implantation. Plan-PD group consisted of patients who started therapy after the breaking period (15 days). Mechanical and infectious complications were compared 30 days from PD initiation. Hospitalization and technique failure during the first 12 months on PD were assessed by Kaplan-Meier curves and the determinants were calculated by Cox regression models. RESULTS: All patients starting PD between October/2016 and November/2019 who fulfilled the inclusion criteria were analyzed. We evaluated 137 patients (70 in the US-PD x 67 Plan-PD). The main complications in the first 30 days were catheter tip migration (7.5% Plan-PD x 4.3% US-PD - p= 0.49) and leakage (4.5% Plan-PD x 5.7% US-PD - p=0.74). Most catheters were placed using the Seldinger technique. The main cause of dropout was death in US-PD patients (15.7%) and transfer to HD in Plan-PD patients (13.4%). The occurrence of complications in the first 30 days was the only risk factor for dropout (OR = 2.9; 95% CI 1.1-7.5, p = 0.03). Hospitalization rates and technique survival were similar in both groups. CONCLUSION: The lack of significant differences in patients' outcomes between groups reinforces that PD is a safe and applicable dialysis method in patients who need immediate dialysis.

Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes.

BACKGROUND: Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used in an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi. OBJECTIVES: Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "inhouse" library of both AGH and TSC derivatives and their structurally-related compounds. METHODS: A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software. RESULTS: The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 µM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms. CONCLUSION: The promising antileishmanial activity of three AGH's and three TSC's was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 µM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are in progress, which will help choose the best hits for in vivo experiments.

Evaluation of TP53 Gene Expression in Patients with Childhood Cancer in Northeast Santa Catarina, Brazil

ABSTRACT Introduction In Brazil, 8,000 new cases of childhood cancer are estimated each year, whose causes are still little known, although some have genetically determined factors. Approximately 70% of human cancers have alterations in the TP53 gene, which encodes the protein responsible for inhibiting the disordered growth of cells exposed to injuries. However, the frequency of alterations in the expression of TP53 in childhood cancers in Brazil remains poorly known. Objective To evaluate the expression of TP53 gene in patients with childhood cancer in northeastern of Santa Catarina, Brazil. Materials and Methods: Retrospectively, 282 patients diagnosed with cancer between 2005 and 2015 in Joinville were included. TP53 expression was evaluated by immunohistochemistry using a score based on the intensity and percentage of stained cells. Results The p53 protein was positive in 25.2% of cases, with no difference between sexes. Considering the five main groups of tumors in the sample, the expression was positive in 31.8%, 27.3%, 20%, 17.2% and 5.9% of lymphomas, nephroblastomas, neuroblastomas, tumors of the Central Nervous System and leukemias, respectively. Conclusion The prevalence of TP53 expression was evaluated in different childhood cancers in the northeastern of Santa Catarina. Positivity was higher among lymphomas and lower in leukemias, but with no significant difference among the five most frequent tumors. Further studies that allow correlation with aggressiveness and disease evolution are required.

ABO blood group system and occurrence of ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a multifactorial disease that presents high rates of morbimortality in Brazil. Several studies proved that there is a link between the ABO blood group system and the occurrence of thrombotic events. Nonetheless, its association with IS is not well established. OBJECTIVE: For that reason, the purpose hereof was to investigate the relation between the ABO blood groups and the occurrence of IS in a Brazilian cohort of cerebrovascular diseases. METHODS: Five hundred and twenty-nine subjects were included over 12 months, from which 275 presented an IS episode and 254 composed the control group. Blood samples were drawn for direct and reverse serotyping. The control and IS groups were compared regarding the traditional risk factors and the distribution of the ABO blood groups. RESULTS: The IS group presented a higher prevalence of systemic arterial hypertension (SAH), diabetes mellitus, smoking habits, family history, cardiopathy, and sedentary lifestyle in comparison with the control group. The AB blood type prevailed among the patients (5.1 vs. 1.6%; p<0.05) and this group had more SAH cases in comparison with the O type group (92.9 vs. 67.3%; p<0.05). CONCLUSIONS: Our results suggest that the occurrence of IS is more frequent among patients of the AB blood type.