Motive and opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements (an LLMPP study).

ABSTRACT: Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements ("double hit"; HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of and mechanisms driving IG vs non-IG MYC rearrangements have not been elucidated. Here, we used custom targeted capture and/or whole-genome sequencing to characterize oncogene rearrangements across 883 mature B-cell lymphomas including Burkitt lymphoma, follicular lymphoma, DLBCL, and HGBCL-DH-BCL2 tumors. We demonstrate that, although BCL2 rearrangement topology is consistent across entities, HGBCL-DH-BCL2 have distinct MYC rearrangement architecture relative to tumors with single MYC rearrangements or with both MYC and BCL6 rearrangements (HGBCL-DH-BCL6), including both a higher frequency of non-IG rearrangements and different architecture of MYC::IGH rearrangements. The distinct MYC rearrangement patterns in HGBCL-DH-BCL2 occur on the background of high levels of somatic hypermutation across MYC partner loci in HGBCL-DH-BCL2, creating more opportunity to form these rearrangements. Furthermore, because 1 IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B-cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.

Genetic subdivisions of follicular lymphoma defined by distinct coding and noncoding mutation patterns.

Follicular lymphoma (FL) accounts for ∼20% of all new lymphoma cases. Increases in cytological grade are a feature of the clinical progression of this malignancy, and eventual histologic transformation (HT) to the aggressive diffuse large B-cell lymphoma (DLBCL) occurs in up to 15% of patients. Clinical or genetic features to predict the risk and timing of HT have not been described comprehensively. In this study, we analyzed whole-genome sequencing data from 423 patients to compare the protein coding and noncoding mutation landscapes of untransformed FL, transformed FL, and de novo DLBCL. This revealed 2 genetically distinct subgroups of FL, which we have named DLBCL-like (dFL) and constrained FL (cFL). Each subgroup has distinguishing mutational patterns, aberrant somatic hypermutation rates, and biological and clinical characteristics. We implemented a machine learning-derived classification approach to stratify patients with FL into cFL and dFL subgroups based on their genomic features. Using separate validation cohorts, we demonstrate that cFL status, whether assigned with this full classifier or a single-gene approximation, is associated with a reduced rate of HT. This implies distinct biological features of cFL that constrain its evolution, and we highlight the potential for this classification to predict HT from genetic features present at diagnosis.

Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma.

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.

Relapse timing is associated with distinct evolutionary dynamics in DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is cured in over 60% of patients, but outcomes are poor for patients with relapsed or refractory disease (rrDLBCL). Here, we performed whole genome/exome sequencing (WGS/WES) on tumors from 73 serially-biopsied patients with rrDLBCL. Based on the observation that outcomes to salvage therapy/autologous stem cell transplantation are related to time-to-relapse, we stratified patients into groups according to relapse timing to explore the relationship to genetic divergence and sensitivity to salvage immunochemotherapy. The degree of mutational divergence increased with time between biopsies, yet tumor pairs were mostly concordant for cell-of-origin, oncogene rearrangement status and genetics-based subgroup. In patients with highly divergent tumors, several genes acquired exclusive mutations independently in each tumor, which, along with concordance of genetics-based subgroups, suggests that the earliest mutations in a shared precursor cell constrain tumor evolution. These results suggest that late relapses commonly represent genetically distinct and chemotherapy-naïve disease.

Relapse Timing Is Associated With Distinct Evolutionary Dynamics in Diffuse Large B-Cell Lymphoma.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is cured in more than 60% of patients, but outcomes remain poor for patients experiencing disease progression or relapse (refractory or relapsed DLBCL [rrDLBCL]), particularly if these events occur early. Although previous studies examining cohorts of rrDLBCL have identified features that are enriched at relapse, few have directly compared serial biopsies to uncover biological and evolutionary dynamics driving rrDLBCL. Here, we sought to confirm the relationship between relapse timing and outcomes after second-line (immuno)chemotherapy and determine the evolutionary dynamics that underpin that relationship. PATIENTS AND METHODS: Outcomes were examined in a population-based cohort of 221 patients with DLBCL who experienced progression/relapse after frontline treatment and were treated with second-line (immuno)chemotherapy with an intention-to-treat with autologous stem-cell transplantation (ASCT). Serial DLBCL biopsies from a partially overlapping cohort of 129 patients underwent molecular characterization, including whole-genome or whole-exome sequencing in 73 patients. RESULTS: Outcomes to second-line therapy and ASCT are superior for late relapse (>2 years postdiagnosis) versus primary refractory (<9 months) or early relapse (9-24 months). Diagnostic and relapse biopsies were mostly concordant for cell-of-origin classification and genetics-based subgroup. Despite this concordance, the number of mutations exclusive to each biopsy increased with time since diagnosis, and late relapses shared few mutations with their diagnostic counterpart, demonstrating a branching evolution pattern. In patients with highly divergent tumors, many of the same genes acquired new mutations independently in each tumor, suggesting that the earliest mutations in a shared precursor cell constrain tumor evolution toward the same genetics-based subgroups at both diagnosis and relapse. CONCLUSION: These results suggest that late relapses commonly represent genetically distinct and chemotherapy-naïve disease and have implications for optimal patient management.

Long-acting insulin in a public health system: analysis of compliance with clinical protocol in public pharmacies.

Diabetes mellitus (DM) is a chronic disease marked by elevated blood glucose levels. Controlling DM involves adequate diet, physical exercises, medicines and monitoring the blood glucose and glycated hemoglobin (HbA1c) levels. This was a retrospective study of the process of dispensing long-acting insulin analogues to users with diabetes (types 1 and 2) who were registered at high-cost public pharmacies in public health system in a southeast state of Brazil, that sought to evaluate the fulfillment of the criteria of all the clinical protocol to provide these analogs. Of the 987 users registered in the health service, 315 met the inclusion criteria for the study. The evaluation of the dispensing processes of the long-acting insulin analogues revealed that the inclusion, exclusion, and suspension criteria of the protocol related with these insulin analogues were in some extend only partially fulfilled. Additionally, there was no difference between the initial and final fasting glycemic and HbA1c levels. It is concluded that the established criteria for dispensing long-acting insulin analogues were partly fulfilled by pharmacies, compromising the rational use of these analogues. It can directly impact the cost of maintaining the public health service and users' health.

Early Identification of IgA Anti-SARSCoV-2 in Milk of Mother With COVID-19 Infection.

INTRODUCTION: Human milk cannot currently be considered a major source of COVID-19 infection. On the other hand, it can contain specific antibodies that could modulate a possible newborn infection by SARS-CoV-2. MAIN ISSUE: A 32-year-old pregnant woman, gestational age 37 and 3/7 weeks, was admitted with a flu-like syndrome caused by COVID-19. The female newborn was appropriate for gestational age, with a birth weight of 2,890 g, length 48 cm, and head circumference 34 cm. MANAGEMENT: The mother-infant dyad remained in the rooming-in unit during hospitalization, exclusively breastfeeding and following World Health Organization recommendations for contact and airway precautions. On the 3rd day after delivery, two mother's milk samples (3 and 5 mL) were collected by hand expression. The samples were centrifuged for 10 min twice consecutively to separate fat, which was removed, and the remaining material was transferred to another tube to determine anti-SARS-CoV-2 Immunoglobulin A and Immunoglobulin G (ELISA, Kit EUROIMMUN AG, Luebeck, Germany). Anti-SARS-CoV-2 Immunoglobulin A was detected in the two samples evaluated, whose values were 2.5 and 1.9, respectively. No anti-SARSCoV-2 immunoglobulin G was detected. The exclusively-breastfed infant remained well through 45 days of age. CONCLUSION: The presence of SARS-CoV-2 Immunoglobulin A in the milk of mothers infected with COVID-19 may be related to protection against the transmission and severity of the disease in their infants.

Mild cognitive impairment in Parkinson's disease: Characterization and impact on quality of life according to subtype.

AIM: Mild cognitive impairment (MCI) was initially described as a risk factor for Alzheimer's disease. Because of differences in baseline cognitive abilities, MCI in Parkinson's disease (PD; PD-MCI) requires distinct neuropsychological criteria for diagnosis and follow up. In addition to representing a risk factor for PD-related dementia, PD-MCI results in higher morbidity, which can be reduced through early detection. The aim of the present study was to gather data regarding MCI subtypes from neuropsychological profiles and clinical features in PD patients, to evaluate its impact on patients' quality of life according to subtype, and to compare the data with a control (Co) group. METHOD: A total of 149 individuals were selected: 81 controls and 60 patients diagnosed with PD according to the United Kingdom Parkinson's Disease Society Brain Bank criteria. All individuals were submitted to neurological and neuropsychological assessments. RESULTS: The amnestic subtype of MCI was the most common in both the PD and Co groups. PD patients showed greater impairment in MCI than the Co group. The amnestic subtype of PD-MCI was associated with a lower quality of life compared with the non-amnestic group. CONCLUSIONS: The PD group showed worse cognitive performance than the Co group. The amnestic subtype of PD-MCI was associated with the greatest impairment of quality of life. Geriatr Gerontol Int 2019; 19: 497-502.

Volumetric brain analysis as a predictor of a worse cognitive outcome in Parkinson's disease.

Cognitive impairment in Parkinson's disease (PD) results in significant morbidity and mortality being early diagnosis essential. Identification of patients who are at higher risk of developing cognitive impairment based only on clinical data is not sufficient. To this end, magnetic resonance imaging (MRI) with automatic segmentation, such as FreeSurfer, could be a useful tool with high accuracy because it has histological validation. OBJECTIVES: The objective of this study was to evaluate clinical, neuropsychological and FreeSurfer variables that may be related to worse cognitive outcomes over 18 months in PD patients compared with controls. METHODS: PD patients were recruited according to established inclusion and exclusion criteria as well individuals without any neurological or psychiatric diagnosis and were submitted to the same protocol: neurological, neuropsychological and neuroimaging evaluations. After 18 months, the study subjects were reassessed by neurological and neuropsychological evaluations. RESULTS: Of 171 individuals selected for first evaluation, 96 concluded the study during 18-month follow-up. The PD group presented worse performance in the neuropsychological assessment during both the initial and final evaluations. The results obtained by FreeSurfer revealed a significant reduction (unilateral or bilateral) in the volume of thalamus, caudate nucleus, putamen, hippocampus, amygdala, accumbens, corpus callosum and cerebral gray matter in the PD group. A worse cognitive outcome was more prevalent in the PD group. CONCLUSIONS: Worse cognitive performance documented by neuropsychological assessment in the PD group was correlated with reduced volume of several structures by FreeSurfer analysis and may be a biomarker of cognitive decline.

Correlation of MRI Visual Scales with Neuropsychological Profile in Mild Cognitive Impairment of Parkinson's Disease.

Few studies have evaluated magnetic resonance imaging (MRI) visual scales in Parkinson's disease-Mild Cognitive Impairment (PD-MCI). We selected 79 PD patients and 92 controls (CO) to perform neurologic and neuropsychological evaluation. Brain MRI was performed to evaluate the following scales: Global Cortical Atrophy (GCA), Fazekas, and medial temporal atrophy (MTA). The analysis revealed that both PD groups (amnestic and nonamnestic) showed worse performance on several tests when compared to CO. Memory, executive function, and attention impairment were more severe in amnestic PD-MCI group. Overall analysis of frequency of MRI visual scales by MCI subtype did not reveal any statistically significant result. Statistically significant inverse correlation was observed between GCA scale and Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), semantic verbal fluency, Stroop test, figure memory test, trail making test (TMT) B, and Rey Auditory Verbal Learning Test (RAVLT). The MTA scale correlated with Stroop test and Fazekas scale with figure memory test, digit span, and Stroop test according to the subgroup evaluated. Visual scales by MRI in MCI should be evaluated by cognitive domain and might be more useful in more severely impaired MCI or dementia patients.

Symptoms of depression in patients with mild cognitive impairment in Parkinson's disease.

OBJECTIVE: To investigate the most frequent depressive symptoms and their association with cognition in Parkinson's disease (PD) patients with mild cognitive impairment (MCI). METHODS: 48 patients with PD and 44 controls (CG), aged between 50 and 80 years and with at least 4 years of formal education, all with MCI and none diagnosed with depression, were assessed. Patients and controls were matched for age, education, and Mini-Mental State Examination (MMSE) score. Participants underwent clinical evaluation with a neurologist followed by neuropsychological assessment employing the instruments: MMSE, Clock Drawing Test, Verbal Fluency Test (semantic and phonemic), Figures Memory Test (FMT), Stroop Test, Trail Making Test, Digit Span (WAIS III), Rey Auditory Verbal Learning Test (RAVLT), Hooper Visual Organization Test, and Beck Depression Inventory (BDI). RESULTS: The most frequent depressive symptoms in the PD group were: difficulty working, fatigue and sleep disorders (the latter also being present in CG). BDI score correlated negatively with learning and recognition memory in both groups. Episodic memory, evaluated by the FMT and RAVLT tests, was the cognitive function showing greatest impairment. CONCLUSION: Some of the depressive symptoms observed in PD patients with MCI seem to be attributable to complications of PD, while others are common to both PD and MCI, making differential diagnoses complex but crucial.

OBJETIVO: Investigar os sintomas depressivos mais frequentes e sua associação com a cognição de indivíduos com doença de Parkinson (DP) e declínio cognitivo leve (DCL). MÉTODOS: Foram avaliados 48 pacientes com DP e 44 Controles (GC), com idade entre 50 e 80 anos e escolaridade superior a 4 anos, todos com DCL e sem diagnóstico de depressão. Pacientes e controles foram pareados quanto à idade, escolaridade e pontuação do Mini Exame do Estado Mental (MEEM). Os participantes foram submetidos à avaliação clínica com neurologista seguida de avaliação neuropsicológica com os instrumentos MEEM, Teste do Desenho do Relógio, Teste de Fluência Verbal Semântica e Fonêmica, Teste de Memória de Figuras (FMT), Teste Stroop de Cores e Palavras, Teste das Trilhas (TMT), Span de Dígitos WAIS III, Teste de Aprendizagem Auditivo-Verbal de Rey (RAVLT), Teste de Organização Visual de Hooper e Inventário de Depressão de Beck (BDI). RESULTADOS: Os sintomas depressivos mais frequentes no grupo DP foram dificuldade para trabalhar, fatigabilidade e distúrbios do sono, sendo este comum ao grupo controle. A pontuação do BDI correlacionou-se negativamente com aprendizagem e memória de reconhecimento em ambos os grupos. Neste estudo, a memória episódica, avaliada pelos testes FMT e RAVLT, apresentou-se como a função cognitiva com maior comprometimento. CONCLUSÃO: Alguns sintomas depressivos prevalentes nos Parkinsonianos com DCL podem ser atribuídos à DP, dificultando o diagnóstico diferencial.

Pharmaceutical services in primary health care: dissatisfaction among users, managers and pharmacists

Abstract To assess the performance indicators for pharmaceutical services (PS) in primary health care (PHC), the level of satisfaction with pharmacy services among users and managers / pharmacists' impressions in relation to the findings were evaluated. The study used mixed methods, including a retrospective and descriptive study of the performance indicators for PS in PHC, an observational study on the level of satisfaction and a qualitative study of users' perception of pharmacy services at Health Units. Managers and pharmacists' impressions of the study results were also collected. Only 44.4% of pharmacies had a full-time pharmacist. From the establishments visited, 5.3% did not have an air-conditioned environment, and only 33.3% of the items essential to the Good Practices of Storage of Medicines and Supplies criteria were fulfilled. Although 77.9% of the prescribed medicines were dispensed, it did not reach the 80% standard. The satisfaction level of users was 3.2±0.6, indicating dissatisfaction with pharmacies' services. By means of an evaluation of each item within the questionnaire, it was possible to observe that variables related to pharmaceutical care presented low scores in relation to other domains, thus evidencing the fragility of the pharmaceutical- patient relationship in users' perception. Managers and pharmacists suggested that these results were related to the inadequate physical infrastructure of pharmacies, work overload, lack of recognition and undervaluation of pharmacists, lack of interaction within the PHC team, high turnover of pharmacists, and lack of PS prioritization by the administration. PS in PHC has structural and organizational weaknesses that require changes. In general, users are dissatisfied with pharmacies' services, especially with pharmaceutical care.

Long-acting insulin in a public health system: analysis of compliance with clinical protocol in public pharmacies / Insulina de ação prolongada no sistema público de saúde: análise da adesão ao protocolo clínico em farmácias públicas

Abstract Diabetes mellitus (DM) is a chronic disease marked by elevated blood glucose levels. Controlling DM involves adequate diet, physical exercises, medicines and monitoring the blood glucose and glycated hemoglobin (HbA1c) levels. This was a retrospective study of the process of dispensing long-acting insulin analogues to users with diabetes (types 1 and 2) who were registered at high-cost public pharmacies in public health system in a southeast state of Brazil, that sought to evaluate the fulfillment of the criteria of all the clinical protocol to provide these analogs. Of the 987 users registered in the health service, 315 met the inclusion criteria for the study. The evaluation of the dispensing processes of the long-acting insulin analogues revealed that the inclusion, exclusion, and suspension criteria of the protocol related with these insulin analogues were in some extend only partially fulfilled. Additionally, there was no difference between the initial and final fasting glycemic and HbA1c levels. It is concluded that the established criteria for dispensing long-acting insulin analogues were partly fulfilled by pharmacies, compromising the rational use of these analogues. It can directly impact the cost of maintaining the public health service and users' health.

Resumo Diabetes mellitus (DM) é uma doença crônica marcada por níveis sanguíneos elevados de glicose. O controle do DM envolve dieta adequada, exercícios físicos, medicamentos e monitoramento dos níveis sanguíneos de glicose e de hemoglobina glicada (HbA1c). Trata-se de um estudo retrospectivo do processo de dispensação de análogos de insulina de ação prolongada a usuários com diabetes (tipos 1 e 2) cadastrados em farmácias públicas de alto custo do sistema público de saúde de um estado do Sudeste do Brasil, que buscou avaliar o cumprimento dos critérios do protocolo clínico para fornecimento desses análogos. Dos 987 usuários cadastrados no serviço de saúde, 315 preencheram os critérios de inclusão. A avaliação dos processos de dispensação dos análogos de insulina de ação prolongada revelou que os critérios de inclusão, exclusão e suspensão do protocolo dos análogos de insulina eram parcialmente cumpridos. Além disso, não houve diferença entre os níveis inicial e final de glicemia em jejum e HbA1c. Conclui-se que os critérios estabelecidos para dispensação de análogos de insulina de ação prolongada foram parcialmente cumpridos pelas farmácias, comprometendo o uso racional dos análogos. Os achados podem impactar diretamente no custo de manutenção do serviço público de saúde e na saúde do usuário.

Obesity induction with high fat sucrose in rats.

BACKGROUND: Although is complex to identify the factors responsible for the important growth in obesity all over the world, the main causes are increased consumption of energy, highly saturated fats and sugars, and reduced physical activity. AIM: To compare rats with normal and supplemented diet with sucrose in relationship to body mass, weight of gonadal and retroperitoneal fat and Lee index. METHODS: Forty rats were divided into two groups: 20 in the control group that received normal chow diet and water for three months, and 20 animals in the experimental group who received the same diet but supplemented with sucrose 300 g/l of water. The animals were weighed once a week during 91 days. At scheduled death, they had measured the naso-anal length, body weight and Lee index. After laparotomy, retroperitoneal and gonadal fat were isolated, dried and the percentage of weight in relation to body weight at the date of death was evaluated. RESULTS: There was a statistic significant difference between the 14th and 78th day favoring the experiment group indicating that sucrose interferes with weight gain in rats. The average weight was higher in the experimental group in all periods in comparison to initial weight. There was also significant difference in the weight of the gonadal and retroperitoneal fat. There was no significant difference comparing the Lee index. CONCLUSION: The body mass index was higher in animals treated with diet supplemented with sucrose and had higher gonadal and retroperitoneal fat, but no difference in the Lee index.

Changes in clinical and laboratory parameters in obese patients with type 2 diabetes mellitus submitted to Roux-en-y gastrojejunal bypass without ring.

OBJECTIVES: 1) To assess the changes in body weight and body mass index in grade 2 and 3 obese patients with type 2 diabetes mellitus, pre and postoperatively; 2) to assess the changes in pre and postoperative fasting blood glucose, postprandial glucose, glycated hemoglobin and insulin. METHODS: A prospective study was undertaken with 40 selected patients with grade 2 and 3 obesity and type 2 diabetes mellitus, all with indication for surgical treatment of obesity. All patients underwent Roux-en-Y gastric bypass without ring. The clinical parameters weight and body mass index were analyzed, as well as the laboratory parameters fasting blood glucose, postprandial glucose, glycated hemoglobin, and insulin. The analyses were carried out in the preoperative period and at 60 days postoperatively. Statistical analysis was conducted with Student's t and the Kolmogorov-Smirnov tests. RESULTS: Mean preoperative weight was 107.3 kg, declining to 89.5 kg postoperatively. Mean initial body mass index was 39.5 kg/m², and 32.9 kg/m² at 60 postoperative days. Preoperative fasting blood glucose was 132 mg/dL, which was reduced to 40.4 mg/dL, on average, postoperatively. Postprandial blood glucose was 172 mg/dL in the preoperative period and 111.6 mg/dL in the postoperative measurement. Initial glycated hemoglobin was 7%, declining to 5.7% postoperatively. Preoperative and postoperative insulin levels were 29.6 µIU/mL and 13.9 µIU/mL, respectively. The level of significance was p<0.001 for all variables. CONCLUSION: There was a statistically significant reduction in body weight and body mass index between the pre and postoperative periods, as well as in fasting blood glucose, postprandial glucose, glycated hemoglobin.

Symptoms of depression in patients with mild cognitive impairment in Parkinson's disease / Sintomas de depressão em pacientes com declínio cognitivo leve na doença de Parkinson

ABSTRACT Objective: To investigate the most frequent depressive symptoms and their association with cognition in Parkinson's disease (PD) patients with mild cognitive impairment (MCI). Methods: 48 patients with PD and 44 controls (CG), aged between 50 and 80 years and with at least 4 years of formal education, all with MCI and none diagnosed with depression, were assessed. Patients and controls were matched for age, education, and Mini-Mental State Examination (MMSE) score. Participants underwent clinical evaluation with a neurologist followed by neuropsychological assessment employing the instruments: MMSE, Clock Drawing Test, Verbal Fluency Test (semantic and phonemic), Figures Memory Test (FMT), Stroop Test, Trail Making Test, Digit Span (WAIS III), Rey Auditory Verbal Learning Test (RAVLT), Hooper Visual Organization Test, and Beck Depression Inventory (BDI). Results: The most frequent depressive symptoms in the PD group were: difficulty working, fatigue and sleep disorders (the latter also being present in CG). BDI score correlated negatively with learning and recognition memory in both groups. Episodic memory, evaluated by the FMT and RAVLT tests, was the cognitive function showing greatest impairment. Conclusion: Some of the depressive symptoms observed in PD patients with MCI seem to be attributable to complications of PD, while others are common to both PD and MCI, making differential diagnoses complex but crucial.

RESUMO Objetivo: Investigar os sintomas depressivos mais frequentes e sua associação com a cognição de indivíduos com doença de Parkinson (DP) e declínio cognitivo leve (DCL) Métodos: Foram avaliados 48 pacientes com DP e 44 Controles (GC), com idade entre 50 e 80 anos e escolaridade superior a 4 anos, todos com DCL e sem diagnóstico de depressão. Pacientes e controles foram pareados quanto à idade, escolaridade e pontuação do Mini Exame do Estado Mental (MEEM). Os participantes foram submetidos à avaliação clínica com neurologista seguida de avaliação neuropsicológica com os instrumentos MEEM, Teste do Desenho do Relógio, Teste de Fluência Verbal Semântica e Fonêmica, Teste de Memória de Figuras (FMT), Teste Stroop de Cores e Palavras, Teste das Trilhas (TMT), Span de Dígitos WAIS III, Teste de Aprendizagem Auditivo-Verbal de Rey (RAVLT), Teste de Organização Visual de Hooper e Inventário de Depressão de Beck (BDI). Resultados: Os sintomas depressivos mais frequentes no grupo DP foram dificuldade para trabalhar, fatigabilidade e distúrbios do sono, sendo este comum ao grupo controle. A pontuação do BDI correlacionou-se negativamente com aprendizagem e memória de reconhecimento em ambos os grupos. Neste estudo, a memória episódica, avaliada pelos testes FMT e RAVLT, apresentou-se como a função cognitiva com maior comprometimento. Conclusão: Alguns sintomas depressivos prevalentes nos Parkinsonianos com DCL podem ser atribuídos à DP, dificultando o diagnóstico diferencial.

Indução de obesidade com sacarose em ratos / Obesity induction with high fat sucrose in rats

RACIONAL: Embora seja muito complexo identificar o que levou ao grande crescimento da obesidade, as causas principais são o aumento do consumo de alimentos energéticos e ricos em gorduras saturadas e açucares, e a redução das atividades físicas. OBJETIVOS: Comparar a massa corpórea, o peso da gordura retroperitoneal e gonadal e o índice de Lee em ratos submetidos à dieta normal e à suplementada com sacarose. MÉTODOS: A amostra foi de 40 animais, divididos em dois grupos: 20 do grupo controle que receberam dieta de ração normal e água por três meses e 20 do grupo experimento que receberam a mesma ração suplementada com sacarose 300 g/l na água. Os animais foram pesados uma vez por semana durante 91 dias. Na data da morte foram aferidos o comprimento nasoanal, peso corporal e foi calculado o índice de Lee. Após, foram submetidos à laparotomia e a gordura retroperitoneal e gonadal foram individualizadas, ressecadas e avaliada a porcentagem do peso dela em relação ao corporal na data da morte. RESULTADOS: Verificou-se diferença estatisticamente significativa entre o 14º até o 78º dia, quando comparados os grupos indicando que a sacarose interfere no ganho de peso dos ratos. A média de peso foi maior no grupo experimento em todos os períodos, tendo como referência o peso inicial. Verificou-se diferença significativa a favor do grupo experimento no peso da gordura gonadal e retroperitoneal. Não houve diferença significativa da comparação do índice de Lee. CONCLUSÃO: A massa corpórea foi maior nos animais submetidos à dieta suplementada, com maior gordura retroperitoneal e gonadal e sem diferença no índice de Lee.

BACKGROUND: Although is complex to identify the factors responsible for the important growth in obesity all over the world, the main causes are increased consumption of energy, highly saturated fats and sugars, and reduced physical activity. AIM: To compare rats with normal and supplemented diet with sucrose in relationship to body mass, weight of gonadal and retroperitoneal fat and Lee index. METHODS: Forty rats were divided into two groups: 20 in the control group that received normal chow diet and water for three months, and 20 animals in the experimental group who received the same diet but supplemented with sucrose 300 g/l of water. The animals were weighed once a week during 91 days. At scheduled death, they had measured the naso-anal length, body weight and Lee index. After laparotomy, retroperitoneal and gonadal fat were isolated, dried and the percentage of weight in relation to body weight at the date of death was evaluated. RESULTS: There was a statistic significant difference between the 14th and 78th day favoring the experiment group indicating that sucrose interferes with weight gain in rats. The average weight was higher in the experimental group in all periods in comparison to initial weight. There was also significant difference in the weight of the gonadal and retroperitoneal fat. There was no significant difference comparing the Lee index. CONCLUSION: The body mass index was higher in animals treated with diet supplemented with sucrose and had higher gonadal and retroperitoneal fat, but no difference in the Lee index.

Alterações dos parâmetros clínicos e laboratoriais em pacientes obesos com diabetes melito tipo 2 submetidos à derivação gastrojejunal em y de Roux sem anel / Changes in clinical and laboratory parameters in obese patients with type 2 diabetes mellitus submitted to Roux-en-y gastrojejunal bypass without ring

OBJETIVOS: Verificar as alterações do peso e índice de massa corporal em pacientes obesos grau II e III com diabete melito tipo 2 nos períodos pré e pós-operatório e as alterações dos parâmetros laboratoriais de glicemia de jejum, glicemia pós-prandial, hemoglobina glicada, insulina nos períodos pré e pós-operatório. MÉTODOS: Realizou-se estudo prospectivo selecionando 40 pacientes com obesidade grau II e III, submetidos à derivação gastrojejunal em Y-de-Roux sem anel. Analisou-se no pré e pós-operatório de 60 dias o peso, índice de massa corporal, glicemia de jejum, glicemia pós-prandial, hemoglobina glicada e insulina. RESULTADOS: O peso médio pré-operatório foi de 107,3Kg diminuindo para 89,5Kg no pós-operatório. O índice de massa corporal médio inicial foi de 39,5Kg/m2 e 32,9Kg/m2 com 60 dias de pós-operatório. A glicemia de jejum no pré-operatório foi de 132 mg/dl e no pós-operatório diminuiu 40,4 mg/dl em média. A glicemia pós-prandial foi de 172 mg/dl no pré-operatório e 111,6 mg/dl no controle pós-operatório. A hemoglobina glicada inicial foi de 7% declinando para 5,7% no pós-operatório. A insulina pré-operatória foi 29,6 uIU/ml e a pós-operatória 13,9 uIU/ml. Todas as variáveis apresentaram significância estatística com p<0,001. CONCLUSÃO: Houve significante diminuição de peso e no índice de massa corporal entre os períodos pré e pós-operatórios e diminuição também significante dos parâmetros laboratoriais de glicemia de jejum, glicemia pós-prandial, hemoglobina glicada, insulina entre os mesmos períodos.

OBJECTIVES: 1) To assess the changes in body weight and body mass index in grade 2 and 3 obese patients with type 2 diabetes mellitus, pre and postoperatively; 2) to assess the changes in pre and postoperative fasting blood glucose, postprandial glucose, glycated hemoglobin and insulin. METHODS: A prospective study was undertaken with 40 selected patients with grade 2 and 3 obesity and type 2 diabetes mellitus, all with indication for surgical treatment of obesity. All patients underwent Roux-en-Y gastric bypass without ring. The clinical parameters weight and body mass index were analyzed, as well as the laboratory parameters fasting blood glucose, postprandial glucose, glycated hemoglobin, and insulin. The analyses were carried out in the preoperative period and at 60 days postoperatively. Statistical analysis was conducted with Student's t and the Kolmogorov-Smirnov tests. RESULTS: Mean preoperative weight was 107.3 kg, declining to 89.5 kg postoperatively. Mean initial body mass index was 39.5 kg/m², and 32.9 kg/m² at 60 postoperative days. Preoperative fasting blood glucose was 132 mg/dL, which was reduced to 40.4 mg/dL, on average, postoperatively. Postprandial blood glucose was 172 mg/dL in the preoperative period and 111.6 mg/dL in the postoperative measurement. Initial glycated hemoglobin was 7%, declining to 5.7% postoperatively. Preoperative and postoperative insulin levels were 29.6 µIU/mL and 13.9 µIU/mL, respectively. The level of significance was p<0.001 for all variables. CONCLUSION: There was a statistically significant reduction in body weight and body mass index between the pre and postoperative periods, as well as in fasting blood glucose, postprandial glucose, glycated hemoglobin.