The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

HIV-1 pol Diversity among Female Bar and Hotel Workers in Northern Tanzania

A national ART program was launched in Tanzania in October 2004. Due to the existence of multiple HIV-1 subtypes and recombinant viruses co-circulating in Tanzania, it is important to monitor rates of drug resistance. The present study determined the prevalence of HIV-1 drug resistance mutations among ART-naive female bar and hotel workers, a high-risk population for HIV-1 infection in Moshi, Tanzania. A partial HIV-1 pol gene was analyzed by single-genome amplification and sequencing in 45 subjects (622 pol sequences total; median number of sequences per subject, 13; IQR 5–20) in samples collected in 2005. The prevalence of HIV-1 subtypes A1, C, and D, and inter-subtype recombinant viruses, was 36%, 29%, 9% and 27%, respectively. Thirteen different recombination patterns included D/A1/D, C/A1, A1/C/A1, A1/U/A1, C/U/A1, C/A1, U/D/U, D/A1/D, A1/C, A1/C, A2/C/A2, CRF10_CD/C/CRF10_CD and CRF35_AD/A1/CRF35_AD. CRF35_AD was identified in Tanzania for the first time. All recombinant viruses in this study were unique, suggesting ongoing recombination processes among circulating HIV-1 variants. The prevalence of multiple infections in this population was 16% (n = 7). Primary HIV-1 drug resistance mutations to RT inhibitors were identified in three (7%) subjects (K65R plus Y181C; N60D; and V106M). In some subjects, polymorphisms were observed at the RT positions 41, 69, 75, 98, 101, 179, 190, and 215. Secondary mutations associated with NNRTIs were observed at the RT positions 90 (7%) and 138 (6%). In the protease gene, three subjects (7%) had M46I/L mutations. All subjects in this study had HIV-1 subtype-specific natural polymorphisms at positions 36, 69, 89 and 93 that are associated with drug resistance in HIV-1 subtype B. These results suggested that HIV-1 drug resistance mutations and natural polymorphisms existed in this population before the initiation of the national ART program. With increasing use of ARV, these results highlight the importance of drug resistance monitoring in Tanzania

Avaliação terapêutica do praziquantel (Embay 8440) na infecção humana pelo S. mansoni

Foram tratados com praziquantel, dose oral única de 40 ou 50 mg/kg, 200 indivíduos portadores de esquistossomose mansoni, matriculados na Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. As idades dos pacientes variavam de seis a 63 anos, sendo que 33 (16,5%) eram menores de 15 anos. Os principais efeitos colaterais consistiram em tontura 27,5%; sonolência 21,0%; eólica 17,5%; náusea 16,0%; diarréia 9,0%; cefaléia 7,5%; vômito 4,0%; febre 2,0%; disenteria 1,0%; tremor 1,0%; exantema 1,0% e urticaria 0,5%. A toxicidade do medicamento foi investigada mediante a realização, pré e pós-tratamento, de exames hematimétricos, bem como de função renal (uréia e creatinina), hepática (enzimas de liberação hépato-canalicular e bilirrubinas), cardíaca (ECG) e neuropsiquiátrica (EEG). Não foram encontradas nesses controles alterações relevantes que repercutissem clinicamente. O controle de cura verificou-se em 115 indivíduos, através de oito coproscopias, no período de seis meses, subseqüente ao tratamento, utilizando-se duas técnicas (HOFFMAN e KATO/KATZ) para cada amostra de fezes. Dos 82 indivíduos que tiveram as oito coproscopias negativadas, 62 realizaram biópsia retal. Essa mostrou-se positiva em duas oportunidades, indicando um percentual de 3,2% de achados falsos negativos com relação às coproscopias. Os índices de cura variaram de 65,2%, nos pacientes menores de 15 anos, a 75% nos acima dessa idade. Para todas as faixas etárias a eficácia foi de 71,3%. Os resultados obtidos demonstram ter o praziquantel, nas doses empregadas, relativa eficácia no tratamento da esquistossomose mansoni, bem como ser determinante de baixos efeitos tóxico-colaterais

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Avaliação terapêutica do praziquantel (Embay 8440) na infecção humana pelo S. mansoni

Foram tratados com praziquantel, dose oral única de 40 ou 50 mg/kg, 200 indivíduos portadores de esquistossomose mansoni, matriculados na Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. As idades dos pacientes variavam de seis a 63 anos, sendo que 33 (16,5%) eram menores de 15 anos. Os principais efeitos colaterais consistiram em tontura 27,5%; sonolência 21,0%; eólica 17,5%; náusea 16,0%; diarréia 9,0%; cefaléia 7,5%; vômito 4,0%; febre 2,0%; disenteria 1,0%; tremor 1,0%; exantema 1,0% e urticaria 0,5%. A toxicidade do medicamento foi investigada mediante a realização, pré e pós-tratamento, de exames hematimétricos, bem como de função renal (uréia e creatinina), hepática (enzimas de liberação hépato-canalicular e bilirrubinas), cardíaca (ECG) e neuropsiquiátrica (EEG). Não foram encontradas nesses controles alterações relevantes que repercutissem clinicamente. O controle de cura verificou-se em 115 indivíduos, através de oito coproscopias, no período de seis meses, subseqüente ao tratamento, utilizando-se duas técnicas (HOFFMAN e KATO/KATZ) para cada amostra de fezes. Dos 82 indivíduos que tiveram as oito coproscopias negativadas, 62 realizaram biópsia retal. Essa mostrou-se positiva em duas oportunidades, indicando um percentual de 3,2% de achados falsos negativos com relação às coproscopias. Os índices de cura variaram de 65,2%, nos pacientes menores de 15 anos, a 75% nos acima dessa idade. Para todas as faixas etárias a eficácia foi de 71,3%. Os resultados obtidos demonstram ter o praziquantel, nas doses empregadas, relativa eficácia no tratamento da esquistossomose mansoni, bem como ser determinante de baixos efeitos tóxico-colaterais.Two hundred patients with schistosomiasis mansoni, registered in the Infectious and Parasitic Disease Ward, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, were treated with praziquantel, single oral dose of 40 or 50 mg/kg BWT. Their ages ranged from 6 to 63 years and 33 cases (16.5%) were under 15 years old. The main side-effects were: dizziness 27.5%; drowsiness 21.0%; abdominal cramps 17.5%; nausea 16.0%; diarrhea 9.0%; headache 7.5%; vomiting 4.0%; fever 2.0%; dysentery 1.0%; shivers 1.0%; rash 1.0% and urticaria 0.5%. The drug toxicity was evaluated by laboratory workout blood counts, hepatic function tests (serum enzymes and bilirubin), kidney function tests (BUN and creatinine), EKG and EEG performed before as well as after treatment. No relevant abnormality was found leading to clinical manifestations. Success of therapy was assessed in 115 cases through eight consecutive stool examinations performed during the six-month period following the drug administration. Both Hoffman's and Kato-Katz's techniques were used. Rectal biopsy was carried out in 62 patients out of 82 whose stool examinations were negative. Two positive cases were found indicating a 3.2% rate of false-negative results in relation to stool examinations. The cure rates varied from 65.2% in patients under 15 years old to 75.0% in those over this age. The mean rate was 71.3%. These results point out that praziquantel, at the used dose levels, is relatively efficaceous in the treatment of schistosomiasis mansoni and yields a low incidence of side effects and toxic reactions

Avaliação terapêutica do praziquantel (Embay 8440) na infecção humana pelo S. mansoni Therapeutical investigation of praziquantel in human infection due to Schistosoma mansoni

Foram tratados com praziquantel, dose oral única de 40 ou 50 mg/kg, 200 indivíduos portadores de esquistossomose mansoni, matriculados na Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. As idades dos pacientes variavam de seis a 63 anos, sendo que 33 (16,5%) eram menores de 15 anos. Os principais efeitos colaterais consistiram em tontura 27,5%; sonolência 21,0%; eólica 17,5%; náusea 16,0%; diarréia 9,0%; cefaléia 7,5%; vômito 4,0%; febre 2,0%; disenteria 1,0%; tremor 1,0%; exantema 1,0% e urticaria 0,5%. A toxicidade do medicamento foi investigada mediante a realização, pré e pós-tratamento, de exames hematimétricos, bem como de função renal (uréia e creatinina), hepática (enzimas de liberação hépato-canalicular e bilirrubinas), cardíaca (ECG) e neuropsiquiátrica (EEG). Não foram encontradas nesses controles alterações relevantes que repercutissem clinicamente. O controle de cura verificou-se em 115 indivíduos, através de oito coproscopias, no período de seis meses, subseqüente ao tratamento, utilizando-se duas técnicas (HOFFMAN e KATO/KATZ) para cada amostra de fezes. Dos 82 indivíduos que tiveram as oito coproscopias negativadas, 62 realizaram biópsia retal. Essa mostrou-se positiva em duas oportunidades, indicando um percentual de 3,2% de achados falsos negativos com relação às coproscopias. Os índices de cura variaram de 65,2%, nos pacientes menores de 15 anos, a 75% nos acima dessa idade. Para todas as faixas etárias a eficácia foi de 71,3%. Os resultados obtidos demonstram ter o praziquantel, nas doses empregadas, relativa eficácia no tratamento da esquistossomose mansoni, bem como ser determinante de baixos efeitos tóxico-colaterais.<br>Two hundred patients with schistosomiasis mansoni, registered in the Infectious and Parasitic Disease Ward, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, were treated with praziquantel, single oral dose of 40 or 50 mg/kg BWT. Their ages ranged from 6 to 63 years and 33 cases (16.5%) were under 15 years old. The main side-effects were: dizziness 27.5%; drowsiness 21.0%; abdominal cramps 17.5%; nausea 16.0%; diarrhea 9.0%; headache 7.5%; vomiting 4.0%; fever 2.0%; dysentery 1.0%; shivers 1.0%; rash 1.0% and urticaria 0.5%. The drug toxicity was evaluated by laboratory workout — blood counts, hepatic function tests (serum enzymes and bilirubin), kidney function tests (BUN and creatinine), EKG and EEG — performed before as well as after treatment. No relevant abnormality was found leading to clinical manifestations. Success of therapy was assessed in 115 cases through eight consecutive stool examinations performed during the six-month period following the drug administration. Both Hoffman's and Kato-Katz's techniques were used. Rectal biopsy was carried out in 62 patients out of 82 whose stool examinations were negative. Two positive cases were found indicating a 3.2% rate of false-negative results in relation to stool examinations. The cure rates varied from 65.2% in patients under 15 years old to 75.0% in those over this age. The mean rate was 71.3%. These results point out that praziquantel, at the used dose levels, is relatively efficaceous in the treatment of schistosomiasis mansoni and yields a low incidence of side effects and toxic reactions