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Sergio L Schmidt,1,2 Michele Santos da Silva,2 Juliana J Schmidt,2 Ana Lucia Novais Carvalho,3 Claudia Cristina Ferreira Vasconcelos,2 Renata Alves Paes,2 Yolanda EM Boechat,4 Rafael Neder,2 Regina P Alvarenga2 1Department of Neurophysiology, State University of Rio de Janeiro, RJ, Brazil; 2Neurology Department, Federal University of the State of Rio de Janeiro, RJ, Brazil; 3Department of Psychology, Fluminense Federal University, Niteroi, Brazil; 4Department of Internal Medicine, Fluminense Federal University, Niteroi, Brazil Background: In the early phases of multiple sclerosis (MS), patients exhibit slight neuropsychiatric deficits that can only be detected using reliable tools. Aim: The present investigation aimed to examine neuropsychological performance in 35 patients with incipient MS. Patients and methods: For the MS group, the inclusion criteria included time of disease

Natural product ring distortion strategies have enabled rapid access to unique libraries of stereochemically complex compounds to explore new chemical space and increase our understanding of biological processes related to human disease. Herein is described the development of a ring-cleavage strategy using the indole alkaloids yohimbine, apovincamine, vinburnine, and reserpine that were reacted with a diversity of chloroformates paired with various alcohol/thiol nucleophiles to enable the rapid synthesis of 47 novel small molecules. Ring cleavage reactions of yohimbine and reserpine produced two diastereomeric products in moderate to excellent yields, whereas apovincamine and vinburnine produced a single diastereomeric product in significantly lower yields. Free energy calculations indicated that diastereoselectivity regarding select ring cleavage reactions from yohimbine and apovincamine is dictated by the geometry and three-dimensional structure of reactive cationic intermediates. These compounds were screened for antiplasmodial activity due to the need for novel antimalarial agents. Reserpine derivative 41 was found to exhibit interesting antiplasmodial activities against Plasmodium falciparum parasites (EC 50 = 0.50 μM against Dd2 cultures), while its diastereomer 40 was found to be three-fold less active (EC 50 = 1.78 μM). Overall, these studies demonstrate that the ring distortion of available indole alkaloids can lead to unique compound collections with re-engineered biological activities for exploring and potentially treating human disease.

Paracoccidioidomycosis is a highly prevalent systemic mycosis in Latin America, caused by fungi of the genus Paracoccidioides. Copper is essential for eukaryotes and bacteria. This micronutrient is used in many vital biochemical processes, although metal excess levels can be toxic for organisms. Pathways underlying copper overload are poorly understood in members of the Paracoccidioides complex. The responses of Paracoccidioides lutzii yeast cells to copper overload were here evaluated. The results showed that under copper overload, cells presented a dark brown pigment, identified as melanin. Proteomic analyses identified mainly the accumulation of proteins related to amino acids metabolism, ergosterol synthesis and melanin production, suggesting that P. lutzii responds to copper overload by changing aspects of its metabolism and also plasma membrane and cell wall remodeling. Proteomic data were confirmed by biochemical analysis., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: Sporotrichosis occurs through contact with contaminated soil and plant. However, the incidence of sporotrichosis as a zoonotic epidemic has increased, particularly in Rio de Janeiro. Aim: In this work, we decided to evaluate some T-cell phenotypes involved in the immune response. Materials & methods: We used flow cytometry to quantify TCD4 + and TCD8 + and Treg from immunocompetent and immunosuppressed mice infected with Sporothrix species with different levels of virulence and pathogenicity. Results: It was demonstrated the predominance of TCD4 + over the TCD8 + cells in both groups, inoculated with all the species, and percentages of Treg observed in infected immunocompetent mice. Conclusion: This regulatory phenotype can be associated with a protective immunity in the initial periods of infection.

Objective Cognitive dysfunction is common in multiple sclerosis. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was developed to assess cognitive functions most-frequently impaired in multiple sclerosis. However, normative values are lacking in Brazil. Therefore, we aimed to provide continuous and discrete normative values for the BRB-N in a Brazilian population sample. Methods We recruited 285 healthy individuals from the community at 10 Brazilian sites and applied the BRB-N version A in 237 participants and version B in 48 participants. Continuous norms were calculated with multiple-regression analysis. Results Mean raw scores and the 5th percentile for each neuropsychological measure are provided, stratified by age and educational level. Healthy participants' raw scores were converted to scaled scores, which were regressed on age, sex and education, yielding equations that can be used to calculate predicted scores. Conclusion Our normative data allow a more widespread use of the BRB-N in clinical practice and research.

Mycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria that form grains in the tissue. The purpose of this study is to describe the epidemiologic, clinic, laboratory, and therapeutic characteristics of patients with mycetoma at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil, between 1991 and 2014. Twenty-one cases of mycetoma were included in the study. There was a predominance of male patients (1.3:1) and the average patient age was 46 years. The majority of the cases were from the Southeast region of Brazil and the feet were the most affected anatomical region (80.95%). Eumycetoma prevailed over actinomycetoma (61.9% and 38.1% respectively). Eumycetoma patients had positive cultures in 8 of 13 cases, with isolation of Scedosporium apiospermum species complex (n = 3), Madurella mycetomatis (n = 2) and Acremonium spp. (n = 1). Two cases presented sterile mycelium and five were negative. Six of 8 actinomycetoma cases had cultures that were identified as Nocardia spp. (n = 3), Nocardia brasiliensis (n = 2), and Nocardia asteroides (n = 1). Imaging tests were performed on all but one patients, and bone destruction was identified in 9 cases (42.68%). All eumycetoma cases were treated with itraconazole monotherapy or combined with fluconazole, terbinafine, or amphotericin B. Actinomycetoma cases were treated with sulfamethoxazole plus trimethoprim or combined with cycles of amikacin sulphate. Surgical procedures were performed in 9 (69.2%) eumycetoma and in 3 (37.5%) actinomycetoma cases, with one amputation case in each group. Clinical cure occurred in 11 cases (7 for eumycetoma and 4 for actinomycetoma), and recurrence was documented in 4 of 21 cases. No deaths were recorded during the study. Despite of the scarcity of mycetoma in our institution the cases presented reflect the wide clinical spectrum and difficulties to take care of this neglected disease.

Eighty-nine patients with clinical suspicion of leishmaniasis were referred for differential diagnosis. Sporothrix schenckii sensu lato was isolated in Novy-MacNeal-Nicolle + Schneider media in 98% of 64 patients with final diagnosis of sporotrichosis. This medium may be suitable for diagnosis of sporotrichosis in areas where cutaneous leishmaniasis is also endemic., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This article describes some prevalent personality dimensions of recently diagnosed multiple sclerosis patients. A sample of 33 female recently diagnosed with relapsing-remitting multiple sclerosis (RRMS) was assessed with the NEO-FFI personality scale. Beck depression (BDI) and anxiety (BAI) scales were also used. No significant levels of anxiety or depression were identified in this group. As for personality factors, conscientiousness was the most common factor found, whereas openness to experience was the least observed. Literature on the relationship between personality and MS is scarce and there are no Brazilian studies on this subject. Some personality traits might complicate or facilitate the experience of living with a chronic, disabling and uncertain neurological condition such as MS.

Objective: To investigate cognitive deficits in patients with primary Sjögren's syndrome (PSS)., Method: Eighteen patients with PSS, aged between 25 and 61 years, were subjected to a short neuropsychological battery and compared with 18 patients with multiple sclerosis and 18 healthy controls., Results: The analysis of variance (ANOVA) revealed that the clinical groups had significantly worse performance than the control group on the Rey Auditory Verbal Learning Test 3; (F(2,53) =3.500, p=0.038) and 7 (F(2,53) =5.068, p=0.010). The clinical groups had elevated levels of depression on the Beck Depression Inventory (BDI); (p=0.003). The analysis of the data from the Trail Making Test B-A revealed a significant difference between the clinical and control groups (p=0.023). The analysis of covariance with BDI score as a covariate, did not change the outcome., Conclusion: Our study revealed cognitive deficits in patients with PSS detectable by a short neuropsychological battery.

Unlabelled: Cognitive impairment is a symptom of multiple sclerosis (MS). Different clinical forms of multiple sclerosis have different cognitive profiles, according to findings of previous studies which used extensive batteries of neuropsychological tests., Objective: To investigate cognitive profiles of Brazilian patients with relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS) by using a brief battery of neuropsychological tests., Method: Sixty-six patients, within 18-65 of age and 3-18 years of education, were paired with healthy control subjects, regarding gender, age, and education level., Results: On Symbol Digit Modalities Test and Hooper Visual Organization Test, cognition was affected in 50% in RRMS and 69% in PPMS. Fluency of "F" was impaired in 24% of RRMS and 81% of PPMS. Immediate recall was affected in 32% of RRMS and in 63% of PPMS; whereas late recall, in 46% of relapsing-remitting and in 69% of primary progressive., Conclusion: Cognitive profiles of relapsing-remitting and primary progressive patients are different.

Background: There is evidence that the nasal mucosa is affected by estrogen influence. Some authors have already detected estrogen receptors (ER) in the nasal mucosa. However, there doesn't seem to be a consensus about the concentration and distribution of the ER or the possible influence of hormonal contraceptives in the nasal mucosa., Objective: The study was conducted to evaluate the influence of oral contraceptives on the distribution and concentration of estrogenic receptors in nasal mucosa., Study Design: Two groups of 32 women with regular menstrual cycles were selected. One group of women was taking oral contraceptives and the other was not. Samples of mucosa of inferior nasal turbinate were analyzed by immunohistochemical staining for alpha and beta ER., Results: The use of oral contraceptives induced a decrease of beta-receptors only in lamina propria cells. In both groups, there was a predominance of beta-receptors., Conclusion: Women who took oral contraceptives showed a decrease of beta-receptors in some cells of the lamina propria. These findings show us the possibility of effects of contraceptive pills on the cells such as fibroblasts, mast cells, plasmocytes, and other inflammatory cells., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Cognitive impairment is a symptom of multiple sclerosis (MS); however, in the primary progressive form of the disease (PPMS), data on the prevalence and type of cognitive impairment are controversial., Aim: To evaluate the frequency of cognitive impairment, according to the diagnostic criteria defined by Thompson, in Brazilian patients with PPMS attending a referral center for the treatment of MS in Rio de Janeiro, Brazil., Subjects and Methods: A battery of neuropsychological tests was used to evaluate the following cognitive functions: screening for dementia, attention/concentration, speed of information processing, verbal fluency, memory and abstract/conceptual thought. The Beck scale was used to evaluate mood disorders. Twenty-six patients with PPMS and 26 controls paired for gender, age and education level were evaluated. Statistical analysis was based on the study performed by Rao., Results: The frequency of cognitive impairment in the PPMS patients in the present study was 50%. The cognitive functions most affected were: recent memory (60%), verbal fluency (40%) and speed of information processing (40%). Depression was more common in the PPMS patients compared to the control group; however, no association was found between cognitive impairment and depression., Conclusion: These results confirm the presence of cognitive impairment in PPMS and emphasize the need for further studies with larger sample sizes.

Objective: Follicular dendritic cells (FDCs) and interdigitating dendritic cells (IDCs) are dendritic cells found in lymphoid follicles, reactive follicles and in lymphomas. The goal of this study was to evaluate the presence and distribution of FDCs and IDCs in oral lymphomas., Material and Methods: Immunohistochemistry reactions were applied to 50 oral lymphomas using the antibodies anti-CD21, anti-CD35 and anti-caldesmon to FDCs, and anti-S100 protein to IDCs. Caldesmon+/FDCs and S100+/IDCs were quantified in Imagelab software., Results: FDCs revealed by CD21 and CD35 were positively stained in two cases of diffuse large B-cell lymphoma, one MALT lymphoma, and in one case of mantle cell lymphoma. FDCs were immunopositive to caldesmon in all cases, as well as IDCs to S100 protein. Burkitt lymphoma presented a lower amount of caldesmon+/FDCs and S100+/IDCs than diffuse large B-cell lymphoma and plasmablastic lymphoma of the oral mucosa type., Conclusions: The microenvironment determined by neoplastic lymphoid cells in oral lymphomas is responsible by the development and expression of dendritic cells types.

Primary Objective: The cognitive profile of patients with Multiple Sclerosis in the Brazilian population is relatively unknown and no cognitive screening instruments have been developed for this population. The purpose of the present study was to develop a neuropsychological screening instrument battery to identify cognitive impairment in epidemiological research protocols in this country., Methods and Procedures: Fifty-four patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and 54 controls matched by sex, age and educational level were evaluated through a long and comprehensive neuropsychological test battery., Main Outcomes and Results: In comparison to the control group, 51.8% of the patients with RRMS presented some form of cognitive impairment. Three neuropsychological tests - Verbal Fluency, Rey Auditory Verbal Learning and Enhanced Cued Recall - presented an 80.6% sensitivity and 97.2% specificity in differentiating RRMS patients with cognitive deficits from paired control subjects., Conclusions: These three tests constitute a Brief Battery that represents a first Brazilian MS cognitive screening instrument. However, further validation study is necessary to achieve better normative scores in a larger sample and to establish feasibility of this battery.

In this retrospective study, we evaluated 53 patients diagnosed with Burkitt's lymphoma (BL). Patients were admitted to the Pediatric Department of Santa Casa de São Paulo, Brazil from August 1988 to September 2006. The male gender was found more frequently in the proportion of three males to one female. At the time of the diagnosis, the mean age was 6 years. The most frequent clinical presentation was abdominal (extra nodal) in 42 (79.2%) cases. The patients were treated with chemotherapy using two different treatment methods, 30 cases until September 1994 with BGLTI -87 and the other 23 until September of 2006 with BGLTI -96. According to Murphy's classification, 90.2% of the patients were diagnosed as stages III and VI showing an advanced disease at time of diagnosis. Using Tissue Microarrays (TMA); we searched for the expression of the Epstein-Barr virus (EBV) RNA in 50 patients. The presence of EBV using in situ hybridization was found in 33/50 (66%) and there was no association between the presence of the virus in the tumor cells or patient age, as well as the survival rate. There was 74.5% global survival rate until September, 2005 of 12 years and 8 months. The disease free survival rate was 86.5%. The frequency of the EBV association with this neoplasia in Brazil is intermediate between the endemic and sporadic forms of disease.

A case of an AIDS patient with positive blood culture for Paracoccidiodes brasiliensis is reported. The patient was a 29-years-old male born in Nova Londrina (Paraná State, Brazil) who presented splenomegaly and fever of unknown origin. Three blood cultures were performed, each one of them for aerobic bacteria, mycobacteria and fungi. Cultures for aerobic bacteria and mycobacteria were negative. However, the yeast phase P. brasiliensis was isolated from two cultures in BHI agar, 20 days after inoculation in Negroni medium. The patient was classified in group V according to the Centers for Disease Control (CDC) criteria for AIDS, due to a Pneumocystis carinii pneumonia. Treatment was discontinued due to an individual decision of the patient on the second dose of amphotericin B. This antibiotic was replaced by ketoconazole in the daily dose of 800 mg. The patient died one year after the isolation of P. brasiliensis on blood culture.

Hamsters (Mesocricetus auratus) were inoculated with L. (L.) chagasi and killed on days 7, 15, 30, 45 and 60 after infection. The lymphoid organs developed initial proliferation of the B lymphocyte zone with recovery by the 60th day group when pyroninophilic cells were prominent. The T lymphocyte area showed a progressive selective decrease of lymphocytes and cellular density with cellular pleomorphism including macrophages, plasma cells and reticular cells. The mean volume of the white pulp increased with the lymphoid follicle hyperplasia but returned to its initial level by day 60. The main red pulp change was marked hyperplasia of the phagocytic mononuclear cells containing parasites from the 30th day of infection onward. These changes are compatible with the humoral and cellular immunoresponse found in patients with visceral leishmaniasis (VL).

Two examples of familial osteochondritis dissecans are described, one affecting a mother and daughter and the other a father and son. The mother and daughter both have genu valgum and are short statured. This combination of features has not been reported previously. Radiographs of lesions affecting knee, elbow, hip and ankle joints demonstrate the wide spectrum of radiological abnormality that can occur in this condition.

A case of total unilateral loss of pulmonary perfusion with almost normal ventilation, in a 21-year-old male patient is described, and the problem of interpretation in an asymptomatic patient is illustrated.

A scheme of management to achieve maximum success in hydrostatic reduction of intussusception is presented. This takes into account patient selection, radiological technique and the follow-up clinical assessment. By standardizing the management we have increased our success rate and avoided laparotomy in 64% of our patients. Most of the patients in whom the technique failed had infarcted bowel which required resection.