Cardiovascular and Thromboembolic Events in Patients With Localized Prostate Cancer Receiving Intensified Neoadjuvant Androgen Deprivation: A Systematic Review and Meta-Analysis.

Several phase II trials have investigated neoadjuvant novel androgen receptor signaling inhibitors (ARSIs) in combination with androgen deprivation therapy (ADT) followed by radical prostatectomy (RP) in prostate cancer (PC) patients. However, data regarding complications of intense hormone therapy and surgical complications are scarce. Our objective was to evaluate the occurrence of cardiovascular (CV) and thromboembolic (TE) adverse events (AE) in patients with localized PC who have received intense neoadjuvant ADT followed by prostatectomy. A comprehensive search in MEDLINE, Embase, Scopus and conference abstracts was performed. The strategies were developed and applied for each electronic database on March 7th, 2023. Eligible studies included randomized and single-arm trials testing ARSIs prior to prostatectomy that adequately reported safety data regarding CV and TE AE, peri-operative complications, and mortality during therapy. Pooled incidence (PI) of AE with 95% confidence interval (95% CI) was estimated using a random effects model. Quality assessment and reporting followed Cochrane Collaboration Handbook and PRISMA guidelines. PROSPERO: CRD42022344104. Nine randomized controlled trials and three single-arm phase II trials were included, comprising 702 patients (702 patients for CV AE and 522 for perioperative complications). The neoadjuvant regimen was classified as monotherapy with ARSI (100 patients), combination therapy with ADT + ARSI (383 patients), or ADT + ARSI + ARSI (219 patients). The PI of TE within the perioperative interval was 4.2% (95% CI = 2.6%-6.6%, I2 = 0.0%, P = .65), and the PI for CV AE was 4.6% (95% CI = 3.1%-6.7%, I2 = 0.0%, P = .71). Seven deaths were reported, resulting in a PI of 2.2% (95% CI = 1.3%-3.8%, I2 = 0.0%, P = .99), of which two were considered treatment-related and occurred within the perioperative period. The PI of hypertension grade 3-5 was 7.3% (95% CI = 4.8%-11.0%, I2 = 38.8%, P = .04). CV and TE AE associated with intense neoadjuvant hormone therapy in patients with localized PC can occur in up to 4.6% of cases. Our data warns for further assessment of thrombotic risk and prophylactic anticoagulation in this setting.

Structural analysis of the Trypanosoma brucei EIF4E6/EIF4G5 complex reveals details of the interaction between unusual eIF4F subunits.

Recognition of the mRNA 5' end is a critical step needed for translation initiation. This step is performed by the cap binding protein eIF4E, which joins the larger eIF4G subunit to form the eIF4F complex. Trypanosomatids have a minimum of five different eIF4F-like complexes formed through specific but not well-defined interactions between four different eIF4E and five eIF4G homologues. The EIF4E6/EIF4G5 complex has been linked with the stage-specific translation of mRNAs encoding the major Trypanosoma brucei virulence factors. Here, to better define the molecular basis for the TbEIF4E6/TbEIF4G5 interaction, we describe the identification of the peptide interacting with TbEIF4E6 in the region comprising residues 79-166 of TbEIF4G5. The TbEIF4E6-TbEIF4G5_79-116 complex reconstituted with recombinant proteins is highly stable even in the absence of cap-4. The crystal structure of the complex was subsequently solved, revealing extensive interacting surfaces. Comparative analyses highlight the conservation of the overall structural arrangement of different eIF4E/eIF4G complexes. However, highly different interacting surfaces are formed with distinct binding contacts occurring both in the canonical and noncanonical elements within eIF4G and the respective eIF4E counterpart. These specific pairs of complementary interacting surfaces are likely responsible for the selective association needed for the formation of distinct eIF4F complexes in trypanosomatids.

Primary Peritoneal Carcinosarcoma in a Breast Cancer Patient Harboring a Germline BRCA2 Pathogenic Variant: Case Report.

Malignant mixed müllerian tumor (MMMT) is a rare neoplasm, consisting of carcinomatous (epithelial) and sarcomatous (mesenchymal) components that most commonly arise in the endometrium and more infrequently in the ovaries, fallopian tube, cervix, and vagina. Primary peritoneal carcinosarcoma (PPCS) is an extremely rare extragenital presentation of MMMT. Although the occurrence of breast cancer and epithelial ovarian carcinoma in association with BRCA pathogenic variants is firmly established, the etiologic role of these genes in the development of other tumor types is less well known. Here, we present a rare case of PPCS in a 42-year-old Brazilian woman with a BRCA2 pathogenic variant, c.2808_2811del (NM_000059.3). The patient developed metastatic breast cancer at the age of 37 and underwent a risk-reducing bilateral salpingo-oophorectomy 2 years later. She was then diagnosed with PPCS 3 years after the risk-reducing surgery. She underwent treatment with surgery, chemotherapy, and targeted therapy but passed away almost 5 years after the second primary tumor diagnosis. To our knowledge, this is the first case of peritoneal carcinosarcoma described in a BRCA2 pathogenic variant carrier, and its report leads to a better understanding of the disease's molecular features and possible therapeutic approaches.

Impact of preoperative body composition in patients with renal cell carcinoma submitted to surgical treatment / Impacto da composição corporal pré-operatória em pacientes com carcinoma de células renais submetidos a tratamento cirúrgico

Abstract Objective: To evaluate the impact of preoperative body composition in patients with renal cell carcinoma (RCC) undergoing surgical treatment. Materials and Methods: This was a retrospective study of 52 patients with RCC undergoing total or partial nephrectomy. Body composition assessment was performed using the body mass index, together with computed tomography analysis at the level of the third lumbar vertebra to measure the area of visceral adipose tissue, as well as the area and density of skeletal muscle mass. Results: Malnutrition, obesity and inadequate skeletal muscle gauge (SMG) were associated with higher hospital length of stay (p = 0.028, p = 0.02 and p = 0.012, respectively). Although the rates of postoperative symptoms and readmissions were low, survival was better among the patients with an adequate SMG than among those with an inadequate SMG (p = 0.003). Conclusion: Among patients with RCC undergoing surgical treatment, preoperative body composition does not seem to be associated with the rates of perioperative complications, although an inadequate SMG seems to be associated with worse overall survival.

Resumo Objetivo Avaliar o impacto da composição corporal pré-operatória em pacientes portadores de carcinoma de células renais (CCR) submetidos a tratamento cirúrgico. Materiais e Métodos: Foi realizado estudo retrospectivo de 52 pacientes portadores de CCR submetidos a tratamento cirúrgico. A avaliação da composição corporal foi realizada por meio do índice de massa corporal e análise da L3 obtida pela tomografia computadorizada para mensurar a área do tecido adiposo visceral, área e densidade da massa muscular esquelética. Resultados: Os pacientes desnutridos, obesos e que apresentaram produto muscular esquelético (PME) inadequado permaneceram mais tempo internados (p = 0,028, p = 0,02 e p = 0,012, respectivamente). As taxas de sintomas e reinternações no pósoperatório foram baixas em toda a amostra, no entanto, observou-se que pacientes com PME inadequado apresentaram uma pior sobrevida em relação aos pacientes com PME adequado (p = 0,003). Conclusão: A análise da composição corporal pré-operatória não mostrou associação com as taxas de complicações periope-ratórias em pacientes portadores de CCR submetidos a nefrectomia total ou parcial, no entanto, a inadequação do PME está associada a uma pior sobrevida.

Survival and Response Outcomes for Gastrointestinal Neuroendocrine Tumor (GEP-NETs) Patients Treated with Lutetium-177-DOTATATE in a Brazilian Reference Center: A Six-Year Follow-Up Experience.

BACKGROUND: PRRT can be an option for all-grade GEP-NETs, but selecting patients is challenging. In this scenario, clinical-pathological and radiological characteristics, such as pre-treatment Ga-68 DOTA PET/CT, might have the potential to help. METHODS: A retrospective chart review was conducted on advanced GEP-NETs treated with at least one PRRT dose. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Krenning Score (KS), and the maximum standardized uptake value (SUVmax) were derived from the pre-treatment scans. A maximally selected rank statistics test was used for SUVmax simple cut point estimate. RESULTS: Among 36 patients, 19 had primary pancreatic tumors. The numbers of G1, G2, and G3 tumors were 10, 18, and 7, respectively. During a median follow-up of 90.5 months, 4 patients died. Median OS was not reached for G1 and G2 tumors, and it was 30 months for G3 (p = 0.001). Median PFS was 23 months, with G3 showing lower PFS compared to G1 [7 versus 30 months; HR 8.41 (95%CI 2.2-31.0; p = 0.001)]. CONCLUSIONS: PRRT provides long-term PFS in patients with G1/G2 GEP-NETs independent of clinical characteristics and primary site. G3 has worse survival, but selected patients may experience long OS after PRRT treatment.

Suspected Germline TP53 Variants and Clonal Hematopoiesis of Indeterminate Potential: Lessons Learned From a Molecular Tumor Board.

OBJECTIVE: Li-Fraumeni syndrome (LFS) is a pan-cancer predisposition syndrome caused by germline pathogenic variants in the gene TP53. The interpretation of TP53 variants in clinical scenarios outside the classic LFS criteria may be challenging. Here, we report a patient affected by 2 primary cancers at later ages, who harbored a likely pathogenic TP53 at low allele frequency detected in a blood sample. METHODS: The Molecular Tumor Board committee at our institution revisited the case of a patient who was enrolled in a research protocol for the investigation of genetic conditions associated with neuroendocrine tumors. Clinical, familial, and molecular data were reviewed. The patient received germline testing using a next generation sequencing multi-gene panel and was incidentally found to harbor a TP53 likely pathogenic variant, with 22% of variant allele fraction. Additional samples, including a second blood sample, oral swab, and saliva, were collected for DNA analysis. A new TP53 sequencing round was performed with the attempt to distinguish between a true constitutional germline variant and a somatically acquired variant due to aberrant clonal expansion of bone marrow precursors. RESULTS: Patient's personal and familial history of cancer did not meet classic nor Chompret LFS criteria. Environmental risk factors for cancer were identified, such as alcohol abuse and tobacco exposure. The TP53 variant initially found in the next-generation sequencing was confirmed by Sanger sequencing in the previous DNA sample extracted from blood for the first analysis and in a second blood sample collected 6 years later. The TP53 variant was not detected in the DNA extracted from the oral swab and saliva samples. CONCLUSION: Considering the low TP53 variant allele fraction in blood, absence of variant detection in oral swab and saliva samples, the lack of LFS clinical criteria, and history of exposure to environmental risk factors for cancer, the main hypothesis for this case was aberrant clonal expansion due to clonal hematopoiesis. Oncologists should interpret TP53 findings during germline testing with caution.

Impact of preoperative body composition in patients with renal cell carcinoma submitted to surgical treatment.

Objective: To evaluate the impact of preoperative body composition in patients with renal cell carcinoma (RCC) undergoing surgical treatment. Materials and Methods: This was a retrospective study of 52 patients with RCC undergoing total or partial nephrectomy. Body composition assessment was performed using the body mass index, together with computed tomography analysis at the level of the third lumbar vertebra to measure the area of visceral adipose tissue, as well as the area and density of skeletal muscle mass. Results: Malnutrition, obesity and inadequate skeletal muscle gauge (SMG) were associated with higher hospital length of stay (p = 0.028, p = 0.02 and p = 0.012, respectively). Although the rates of postoperative symptoms and readmissions were low, survival was better among the patients with an adequate SMG than among those with an inadequate SMG (p = 0.003). Conclusion: Among patients with RCC undergoing surgical treatment, preoperative body composition does not seem to be associated with the rates of perioperative complications, although an inadequate SMG seems to be associated with worse overall survival.

Objetivo: Avaliar o impacto da composição corporal pré-operatória em pacientes portadores de carcinoma de células renais (CCR) submetidos a tratamento cirúrgico. Materiais e Métodos: Foi realizado estudo retrospectivo de 52 pacientes portadores de CCR submetidos a tratamento cirúrgico. A avaliação da composição corporal foi realizada por meio do índice de massa corporal e análise da L3 obtida pela tomografia computadorizada para mensurar a área do tecido adiposo visceral, área e densidade da massa muscular esquelética. Resultados: Os pacientes desnutridos, obesos e que apresentaram produto muscular esquelético (PME) inadequado permaneceram mais tempo internados (p = 0,028, p = 0,02 e p = 0,012, respectivamente). As taxas de sintomas e reinternações no pósoperatório foram baixas em toda a amostra, no entanto, observou-se que pacientes com PME inadequado apresentaram uma pior sobrevida em relação aos pacientes com PME adequado (p = 0,003). Conclusão: A análise da composição corporal pré-operatória não mostrou associação com as taxas de complicações periope-ratórias em pacientes portadores de CCR submetidos a nefrectomia total ou parcial, no entanto, a inadequação do PME está associada a uma pior sobrevida.

Interplay between Tumor Mutational Burden and Mutational Profile and Its Effect on Overall Survival: A Pilot Study of Metastatic Patients Treated with Immune Checkpoint Inhibitors.

Purpose: Solid tumors harboring tumor mutational burden (TMB) ≥10 mutations per megabase (mut/Mb) received agnostic approval for pembrolizumab. This work aims to analyze the somatic mutational profile's influence on the outcomes of patients with TMB-high tumors treated with immune checkpoint inhibitors (ICIs). Methods: This post-hoc analysis evaluated clinical and molecular features of patients with solid tumors treated with ICIs that could be either monoclonal antibody directed against programmed cell death protein-1 or monoclonal antibody directed against programmed cell death ligand 1 (anti-PD-1/anti-PD-L1), monoclonal antibody directed against cytotoxic T lymphocyte-associated antigen (anti-CTLA-4) or a combined treatment regimen including one anti-PD-1/anti-PD-L1 and one anti-CTLA-4 (ICIs combination). We performed OS analysis for TMB thresholds of ≥10, ≥20, and <10 mut/Mb. We assessed OS according to the mutational profile for a TMB ≥ 10 mut/Mb cutoff. For genes correlated with OS at the univariate assessment, we conducted a Cox multivariate analysis adjusted by median TMB, sex, age, microsatellite instability (MSI), and histology. Results: A total of 1661 patients were investigated; 488 with a TMB ≥10 mut/Mb (29.4%). The median OS was 42 months for TMB ≥10 or 20 mut/Mb, and 15 months for TMB <10 mut/Mb (p < 0.005). Among TMB ≥10 mut/Mb patients, mutations in E2F3 or STK11 correlated with worse OS, and mutations in NTRK3, PTPRD, RNF43, TENT5C, TET1, or ZFHX3 with better OS. These associations were confirmed with univariate and multivariate analyses (p < 0.05). Melanoma histology and TMB above the median endowed patients with better OS (p < 0.05), while MSI status, age, and gender did not have a statistically significant effect on OS. Conclusion: Combining TMB and mutation profiles in key cancer genes can better qualify patients for ICI treatment and predict their OS.

Evaluation of a multi-species Protein A-ELISA assay for plague serologic diagnosis in humans and other mammal hosts.

BACKGROUND: The Hemagglutination assay (HA) is widely used in plague diagnosis, however, it has a subjective interpretation and demands high amounts of antigen and other immunobiological supplies. On the other hand, the conventional Anti-IgG ELISA is limited by the need of specific conjugates for multiple plague hosts, which leaves a gap for new diagnostic methods able to cover both the diagnosis of human cases and the epidemiological surveillance of multiple sentinel species. METHODS: We developed an ELISA Protein A-peroxidase method to detect anti-F1 antibodies across several species, including humans. To determine the cut-off and performance rates, HA results from 288 samples (81 rabbits, 64 humans, 66 rodents and 77 dogs) were used as reference. Next, we evaluated the agreement between Protein A-ELISA and Anti-IgG ELISA in an expanded sample set (n = 487). RESULTS: Optimal conditions were found with 250ng/well of F1 and 1:500 serum dilution. Protein A-ELISA showed high repeatability and reproducibility. We observed good correlation rates between the Protein A and IgG ELISAs optical densities and a higher positive/negative OD ratio for the Protein A-ELISA method. The overall sensitivity, specificity and area under the curve for Protein A-ELISA were 94%, 99% and 0.99, respectively. Similar results were observed for each species separately. In the analysis of the expanded sample set, there was a strong agreement between Protein A and IgG assays (kappa = 0.97). Furthermore, there was no cross-reaction with other common infectious diseases, such as dengue, Zika, Chagas disease, tuberculosis (humans) and ehrlichiosis, anaplasmosis and leishmaniasis (dogs). CONCLUSIONS: Altogether, the Protein A-ELISA showed high performance when compared both to HA and Anti-IgG ELISA, with a polyvalent single protocol that requires reduced amounts of antigen and can be employed to any plague hosts.

Cardiovascular toxicity following immune checkpoint inhibitors: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors may be associated with multiple immune-related toxicities. Cardiovascular adverse effects are underreported in clinical trials. METHODS: We conducted a systematic review and meta-analysis to evaluate cardiovascular adverse effects incidence among patients with solid tumors receiving immune checkpoint inhibitors in randomized clinical trials and the relative risk of presenting these effects compared to placebo or best supportive care. The search was conducted through MEDLINE, Embase, and Scopus databases from January 1st, 2010 until July 1st, 2020. Outcomes were reported following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: 57 randomized clinical trials including 12,118 patients were included. All grade CV AEs incidence rate was 8.32% (95% CI = 6.35%-10.53%). When only grade 3-5 CV AEs were considered, ICIs were significantly associated with increased risk than placebo or BSC (RR = 1.36; 95% CI = 1.06-1.73; p = 0.01). CONCLUSION: This meta-analysis corroborates the hypothesis of increased CV risk related to immune checkpoint inhibitors.

Introduction of nickel titanium rotary instruments to undergraduate students: afour-yearclinical experience / Introdução de instrumentos rotários de níquel titânio para alunos de graduação: quatro anos de experiência clínica

Many studies address the quality of root canal treatments, but few refer to endodontics usingrotatory techniques performed by noviceoperators. This study evaluatedthe performance of undergraduates in their first contact with rotary root canal instrumentation concerningthe findings of the final periapical radiograph, and thepostendodontic treatment pain.A longitudinal observational studywas performed on periapical radiographs of 491teethfrom 450 patientssubmitted toroot canal treatmentby undergraduate students from 2015 to 2018. The analysis of the length of root canal filling followed the criteria: (i) acceptable, ifperiapical radiograph presentsroot filling ending 0 -1 mm short of radiographic apex; (ii) over, if periapical radiograph presentsroot filling ending beyond the radiographic apex; and (iii) under, ifperiapical radiograph presentsroot filling ending > 1 mm short of radiographic apex. Evaluation of postendodontic treatment painwas categorized into either absence or presenceof pain. Adequate length root canal filling was observed in 65.9% of the cases (324 teeth). Periapical lesions presenceand dimensions did not interfere to the obturation quality.Statistical relation was found between the pulp condition and postendodontic treatment pain. Thepresence of pain was observed in 4.7% of the vital teeth and 0.3% of non-vital teeth. The presence of periapical lesion did not influence postoperative pain.AdequatelengthrootcanalfillingwasobservedinmostcasesandNitTi rotary instrumentation hadapplicability in undergraduate programs, even with novice operators. Besides that, pulp condition had an effect on post endodontic pain (AU).

Muitos estudos abordam a qualidade dos tratamentos de canal radicular, mas poucos se referem à endodontia por meio de técnicas rotatórias realizada por operadores novatos. Este estudo avaliou o desempenho de graduandos no primeiro contato com a instrumentação endodôntica em relação aos achados da radiografia periapical final e à dor pós-tratamento endodôntico. Um estudo observacional longitudinal foi realizado em radiografias periapicais de 491 dentes de 450pacientes submetidos a tratamento endodôntico por estudantes de graduação no período de 2015 a 2018. A análise do comprimento da obturação de canais radiculares obedeceu aos critérios: (i) aceitável, se a radiografia periapical apresentasse término de obturação 0 -1 mm aquém do ápice radiográfico; (ii) acima, se a radiografia periapical apresentasse obturação que termina além do ápice radiográfico; e (iii) abaixo, se a radiografia periapicalapresentasse obturação, terminando > 1 mm aquém do ápice radiográfico. A avaliação da dor pós-operatória foi categorizada em ausência ou presença de dor. A obturação de canais radiculares de comprimento adequado foi observada em 65,9% dos casos (324 dentes). A presença e as dimensões das lesões periapicais não interferiram na qualidade da obturação. Foi encontrada relação estatística entre a condição pulpar e a dor pós-tratamento endodôntico. Presença de dor foi observada em 4,7% dos dentes vitais e 0,3% dos não vitais. A presença de lesão periapical não influenciou na dor pós-operatória. O comprimento de trabalho adequado foi observado na maioria dos casos e a instrumentação rotatória NitTi teve aplicabilidade em programas de graduação, mesmo com operadores iniciantes. Além disso, a condição pulpar afetou a dor pós-operatória (AU).

Trametinib and Hydroxychloroquine (HCQ) Combination Treatment in KRAS-Mutated Advanced Pancreatic Adenocarcinoma: Detailed Description of Two Cases.

PURPOSE: Over the last decades, cytotoxic chemotherapy has been the cornerstone of metastatic pancreatic adenocarcinoma treatment. In late-stage disease, a range of treatment regimens still offers minor benefits. Molecular profiling studies have shown that pancreatic adenocarcinoma (PDAC) is a mutation-driven tumor type, with KRAS mutations found in approximately 90% of cases, which could partially explain the resistance to chemotherapy. Preclinical data on selective targeting of a downstream point of the RAF-MEK-ERK pathway with a MEK inhibitor along with the concurrent use of an autophagy inhibitor such as hydroxychloroquine appears to be one alternative approach to overcome resistance and inhibit cell proliferation. METHODS: We herein aim to investigate the rationale of autophagy inhibitors use and describe the outcomes of patients who received this experimental treatment. RESULTS: Two patients have received this experimental regimen from January 2020 to the present date, achieving disease stabilization that is clinically meaningful, considering the chemoresistance scenario of the included patients. CONCLUSIONS: Our real-life data regarding KRAS-mutated PDAC patients who received treatment with the MEK inhibitor trametinib combined with hydroxychloroquine after experiencing disease progression are consistent with the preclinical data, pointing to the clinical benefits of this regimen.

Aderência ao autocuidado em indivíduos diabéticos / Adherence to self-care in diabetic individuals

O autocuidado possui papel fundamental no tratamento do diabete e prevenção de suas complicações. Entre os fatores que apresentam associação com a adesão ao autocuidado está o conhecimento do paciente sobre a doença. O presente trabalho possui como objetivo avaliar o conhecimento sobre diabete melito tipo 2 e adesão ao autocuidado. Estudo analítico, observacional, transversal, descritivo. O conhecimento sobre o autocuidado foi feito através de dois questionários validados para a população brasileira: Diabetes Knowlege Scale (DKN-A) e Questionário de Atividade de Autocuidado (QAD). Participaram 61 pacientes. No QAD, observou-se baixa adesão às práticas diárias de autocuidado, sendo que o domínio da atividade física foi a que obteve menor adesão, seguida pela monitorização da glicemia. Quanto aos resultados obtidos no DKN-A, nota-se que a maioria atingiu pontuação igual ou superior a 8, sugerindo conhecimento satisfatório acerca da doença. Em conclusão, observou-se que a maioria atingiu pontuação igual ou superior a 8, sugerindo conhecimento satisfatório. Apesar disso, também a maioria apresentou baixa adesão frente às modificações esperadas no estilo de vida e autocuidado. Sendo assim, o conhecimento sobre a doença não é o único preditor para que isso ocorra.

Self-care has a fundamental role in the treatment of diabetes and prevention of its complications. Among the factors that are associated with adherence to self-care is the patient's knowledge about the disease. This study aims to assess knowledge about type 2 diabetes mellitus and adherence to self-care. It is analytical, observational, crosssectional, descriptive study. Knowledge about self-care was obtained through two questionnaires validated for the Brazilian population: Diabetes Knowlege Scale (DKN-A) and Self-Care Activity Questionnaire (QAD). 61 patients participated in the study. In the QAD, low adherence to daily self-care practices was observed, and the domain of physical activity was the one with the lowest adherence, followed by blood glucose monitoring. As for the results obtained in the DKN-A, it is noted that the majority reached a score equal to or greater than 8, suggesting satisfactory knowledge about the disease. In conclusion, it is observed that the majority reached a score equal to or greater than 8, suggesting satisfactory knowledge. Despite this, most also showed low adherence to the expected changes in lifestyle and self-care. Therefore, knowledge about the disease is not the only predictor for this to occur.

A new recombinant F1 antigen as a cost and time-effective tool for plague diagnosis.

The Yersinia pestis capsular antigen F1 is widely used in plague laboratory diagnosis. Here, we describe the production of an F1 recombinant protein within reduced time and biosafety requirements. Its evaluation in hemagglutination tests indicated that the recombinant F1 can replace the conventional F1 protein for plague diagnosis.

Daily and social activities influence the quality of life of renal chronic patients in hemodialysis / Atividades diárias e sociais influenciam a qualidade de vida de pacientes renais crônicos em hemodiálise

Objective: This study aimed to evaluate the physical and social factors that influence the quality of life of patients with chronic kidney disease (CKD) on hemodialysis (HD). Study Design: Descriptive and cross-sectional. Methods: There were 149 patients with CKD routinely submitted to HD that answered a questionnaire adapted (Medical Results Survey; SF-36) about the presence of symptoms during and after the HD sessions, main diseases concomitant, and the presence of factors that influence the quality of life. Results: According to the multivariate analysis, the presence of symptoms after the HD contributes to a decrease in the quality of life (p=0.04). However, emotional well-being was positively associated with social activities (p=0.01). The daily activities and the absence of concomitant diseases are associated with good health and, therefore, a better quality of life for patients with CKD (p<0.05). Patients with chronic diseases such as hypertension and diabetes should be better observed, since such illnesses are always associated with renal dysfunction. Conclusion: The results of the present study demonstrate that the chronic renal patients should be inserted into social environments and should perform daily activities despite the limitations of the treatment since an active lifestyle contributes positively to their well-being and quality of life (AU)

Objetivo: O objetivo deste estudo foi avaliar os fatores físicos e sociais que influenciam a qualidade de vida de pacientes com doença renal crônica (DRC) em hemodiálise (HD). Modelo de estudo: Descritivo e transversal. Métodos: Foram incluídos 149 pacientes com DRC rotineiramente submetidos a HD que responderam ao questionário adaptado (Medical Results Survey; SF-36) sobre a presença de sintomas durante e após as sessões de HD, principais doenças concomitantes e presença de fatores que influenciam a qualidade de vida. Resultados: De acordo com a análise multivariada, a presença de sintomas após a HD contribui para uma diminuição da qualidade de vida (p=0,04). Entretanto, o bem-estar emocional foi positivamente relacionado com as atividades sociais (p=0,01). As atividades diárias e a ausência de doenças concomitantes estão associadas com uma boa saúde e assim, a uma melhor qualidade de vida dos pacientes com DRC (p<0,05). Pacientes com doenças crônicas como hipertensão e diabetes devem ser melhor acompanhados, uma vez que, estas doenças estão constantemente associadas a disfunção renal. Conclusão: Os resultados do presente estudo demonstram que os pacientes crônicos renais devem ser inseridos no ambiente social e devem realizar atividades cotidianas, apesar das limitações do tratamento, uma vez que um estilo de vida ativo contribui positivamente para a melhora da qualidade de vida. (AU)

Phosphorylation and interactions associated with the control of the Leishmania Poly-A Binding Protein 1 (PABP1) function during translation initiation.

The Poly-A Binding Protein (PABP) is a conserved eukaryotic polypeptide involved in many aspects of mRNA metabolism. During translation initiation, PABP interacts with the translation initiation complex eIF4F and enhances the translation of polyadenylated mRNAs. Schematically, most PABPs can be divided into an N-terminal RNA-binding region, a non-conserved linker segment and the C-terminal MLLE domain. In pathogenic Leishmania protozoans, three PABP homologues have been identified, with the first one (PABP1) targeted by phosphorylation and shown to co-immunoprecipitate with an eIF4F-like complex (EIF4E4/EIF4G3) implicated in translation initiation. Here, PABP1 phosphorylation was shown to be linked to logarithmic cell growth, reminiscent of EIF4E4 phosphorylation, and coincides with polysomal association. Phosphorylation targets multiple serine-proline (SP) or threonine-proline (TP) residues within the PABP1 linker region. This is an essential protein, but phosphorylation is not needed for its association with polysomes or cell viability. Mutations which do impair PABP1 polysomal association and are required for viability do not prevent phosphorylation, although further mutations lead to a presumed inactive protein largely lacking phosphorylated isoforms. Co-immunoprecipitation experiments were carried out to investigate PABP1 function further, identifying several novel protein partners and the EIF4E4/EIF4G3 complex, but no other eIF4F-like complex or subunit. A novel, direct interaction between PABP1 and EIF4E4 was also investigated and found to be mediated by the PABP1 MLLE binding to PABP Interacting Motifs (PAM2) within the EIF4E4 N-terminus. The results shown here are consistent with phosphorylation of PABP1 being part of a novel pathway controlling its function and possibly translation in Leishmania.

Trypanosoma brucei EIF4E2 cap-binding protein binds a homolog of the histone-mRNA stem-loop-binding protein.

Trypanosomatids are parasitic protozoans characterized by several unique structural and metabolic processes that include exquisite mechanisms associated with gene expression and regulation. During the initiation of protein synthesis, for instance, mRNA selection for translation seems to be mediated by different eIF4F-like complexes, which may play a significant role in parasite adaptation to different hosts. In eukaryotes, the heterotrimeric eIF4F complex (formed by eIF4E, eIF4G, and eIF4A) mediates mRNA recognition and ribosome binding and participates in various translation regulatory events. Six eIF4Es and five eIF4Gs have been described in trypanosomatids with several of these forming different eIF4F-like complexes. This has raised questions about their role in differential mRNA translation. Here we have studied further TbEIF4E2, the least known eIF4E homologue from Trypanosoma brucei, and found that it is not associated with an eIF4G homolog. It is, however, associated with mature mRNAs and binds to a histone mRNA stem-loop-binding protein (SLBP), one of two Trypanosoma SLBP homologs (TbSLBP1 and TbSLBP2). TbSLBP1 is more similar to the mammalian counterpart while TbSLBP2 is exclusive to trypanosomatids and related organisms. TbSLBP2 binds to TbEIF4E2 through a conserved central region missing in other SLBP homologs. Both SLBPs, as well as TbEIF4E2, were found to localize to the cytoplasm. TbEIF4E2 and TbSLBP2 are differentially expressed during cell culture, being more abundant in early-log phase, with TbSLBP2 also showing cell-cycle dependent expression. The new data reinforce unique aspects of the trypanosomatid eIF4Es, with the TbEIF4E2-TbSLBP complex possibly having a role in differential selection of mRNAs containing stem-loop structures.

Effect of A One-Week Balanced Diet on Expression of Genes Related to Zinc Metabolism and Inflammation in Type 2 Diabetic Patients.

To evaluate the effect of diet on metabolic control and zinc metabolism in patients with type 2 diabetes mellitus (T2DM). One-week balanced diet was provided to 10 Brazilians patients with T2DM. Nutritional assessment, laboratorial parameters and expression of zinc transporter and inflammatory genes in peripheral blood mononuclear cells (PBMC) were performed. Healthy non-diabetic subjects of the same demographic were recruited to provide baseline data. Diabetic patients had higher body mass index and greater fasting plasma glucose, plasma tumor necrosis factor α (TNFα) and plasma interleukin 6 (IL6) levels compared with healthy subjects. In addition, the expression of transporters 4 (ZnT4) mRNA was lower and IL6 mRNA was higher in PBMC of these diabetic patients than in healthy subject. One week after a balanced diet was provided, fasting plasma glucose decreased significantly as did TNFα, IL6 and Metallothionein 1 (MT1) mRNAs. No change was observed in zinc transporter expression in PBMC after the dietary intervention. A healthy eating pattern maintained for one week was able to improve metabolic control of diabetic patients by lowering fasting plasma glucose. This metabolic control may be related to down-regulation of zinc-related transcripts from PBMCs, as TNFα, IL6 and MT1 mRNA.