Improved accuracy in pentraxin-3 quantification assisted by aqueous biphasic systems as serum pretreatment strategies.

Although pentraxin-3 holds promise as a diagnosis/prognosis biomarker of microbial infections and lung cancer, its analysis in human serum can be constrained by matrix effects caused by high abundance proteins - human serum albumin and immunoglobulin G. Aqueous biphasic systems composed of polymers and citrate buffer are here proposed as a serum pretreatment step to improve the accuracy of pentraxin-3 analysis. Binodal curves were determined to identify the compositions required to form two phases and to correlate the polymers' properties and performance in serum pretreatment and biomarker extraction. Aqueous biphasic systems were evaluated regarding their ability to deplete human serum albumin and immunoglobulin G at the interphase. Polymers of relatively high to intermediate hydrophobicity were unveiled as efficient components to deplete high abundance serum proteins. Considering the possibility to extract pentraxin-3 from human serum into the polymer-rich phase, the system composed of polyethylene glycol with a molecular weight of 1000 g·mol-1 simultaneously achieved >93 % of human serum albumin and immunoglobulin G depletion and complete biomarker extraction. The accuracy of analysis of pretreated human serum by enzyme-linked immunosorbent assays outperformed that of a non-pretreated sample, with a relative error of 0.8 % compared to 14.6 %, contributing to boost pentraxin-3 usefulness as a biomarker.

Prevalence and Predictors of COVID-19 Long-Term Symptoms: A Cohort Study from the Amazon Basin.

It remains unclear whether a previous history of tropical infectious diseases and a second SARS-COV-2 infection may influence the likelihood of later symptoms. In this prospective cohort study, individuals infected with SARS-CoV-2 were followed up by telephone shortly after diagnosis of COVID-19 and again 12 months later. Poisson regression was used to identify the predictors of the highest number of symptoms in the post-COVID-19 syndrome. A total of 1,371 patients with COVID-19, with a mean age of 39.7 ± 11.7 years and 50% female, were followed for 12 months. Reinfection was found in 32 (2.3%) participants, and 806 (58.8%) individuals reported a previous history of dengue, malaria, Zika, chikungunya, leprosy, and visceral leishmaniasis. Eight hundred seventy-seven (63.9%) participants reported late symptoms related to COVID-19. After adjusting for multiple factors, female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection were independent predictors of higher number of symptoms in post-COVID-19 syndrome. Female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection, but not previous endemic tropical diseases, were associated with long-term symptoms.

Deep Eutectic Solvent Formulations and Alginate-Based Hydrogels as a New Partnership for the Transdermal Administration of Anti-Inflammatory Drugs.

The transdermal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is a valuable and safer alternative to their oral intake. However, most of these drugs display low water solubility, which makes their incorporation into hydrophilic biopolymeric drug-delivery systems difficult. To overcome this drawback, aqueous solutions of bio-based deep eutectic solvents (DES) were investigated to enhance the solubility of ibuprofen, a widely used NSAID, leading to an increase in its solubility of up to 7917-fold when compared to its water solubility. These DES solutions were shown to be non-toxic to macrophages with cell viabilities of 97.4% (at ibuprofen concentrations of 0.25 mM), while preserving the anti-inflammatory action of the drug. Their incorporation into alginate-based hydrogels resulted in materials with a regular structure and higher flexibility. These hydrogels present a sustained release of the drug, which is able, when containing the DES aqueous solution comprising ibuprofen, to deliver 93.5% of the drug after 8 h in PBS. Furthermore, these hydrogels were able to improve the drug permeation across human skin by 8.5-fold in comparison with the hydrogel counterpart containing only ibuprofen. This work highlights the possibility to remarkably improve the transdermal administration of NSAIDs by combining new drug formulations based on DES and biopolymeric drug delivery systems.

Using infrared thermography to detect subclinical mastitis in dairy cows in compost barn systems.

This study aimed to evaluate the use of thermal imaging obtained by infrared thermography (IRT) to detect cases of subclinical mastitis in dairy cows under commercial conditions of compost barn systems in a region of Brazil with a semiarid climate. Twenty-eight crossbred cows were evaluated twice a day for one week using IRT. Three thermal images were obtained for each cow, referring to the anatomical regions of the right and left fore udder and rear udder. A computer program was used to analyze the images and obtain the right fore udder temperature (RFUT, °C), left fore udder temperature (LFUT, °C), rear udder temperature (RUT, °C), and average udder temperature (AUT, °C). In addition, samples of milk from each quarter of the udder were collected for somatic cell count (SCC) to correlate the diseases observed on the thermal image with any infection in the udder region. The results obtained using IRT were subjected to regression and correlation analyses. It was observed that LFUT, RAQT, RUT, and AUT were adjusted in quadratic polynomial models with good prediction of SCC (i.e., infection) with R2 = 0.92, 0.97, 0.86, and 0.94, respectively. The region of the anterior quarters of the udder was the most promising for imaging, stronger correlations were obtained between LFUT and RFUT with SCC (r = 0.87 and 0.88, respectively). The IRT is a practical technology capable of detecting cases of mastitis in dairy cows with good precision, especially with thermal images from the anatomical region of the front quarters of the udder. However, more detailed studies are needed to make thermal imaging processing a more useful method for routine activities on farms in compost barn systems.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: rationale and design of the RIVER trial

Background The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. Design RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. Summary RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Pathological, microbiological and immunohistochemical characterization of avian colibacillosis in broiler chickens of Mozambique

ABSTRACT: Avian colibacillosis is an acute and globally occurring infectious disease of domestic and wild birds caused by Escherichia coli, and it is associated with considerable economic losses mainly due to the morbidity and mortality associated. The present study aimed to describe the pathological, bacteriological and immunohistochemical aspects of avian colibacillosis in broiler chickens of Mozambique. Forty-nine broiler chicken presented anorexia, decreased weight gain, ataxia, diarrhea, dyspnea, and death in a clinical course of 3-5 days. The birds were raised in five farms (small, medium and large farms) with manual and automatic breeding system, with flocks ranging from 100 to 20,000 birds. At the necropsy, all birds had poor body condition, and the pericardium and the Glissons capsule of all avian exhibited different degrees of adherence often associated with severe fibrin deposition. The thoracic and abdominal air sacs were thickened and adhered to the costal wall. Mild, moderate or marked hepatomegaly associated with white pinpoint multifocal areas (100%, 49/49) and mild to moderate splenomegaly in 75.5% (37/49) with a mottled surface were observed. The lungs and kidney were enlarged and reddish. Histologically, a multiorgan fibrinoheterophilic polyserositis was observed in 75.5% of the cases (37/49), which were characterized by inflammatory infiltrates composed mainly of degenerative heterophils, macrophages and plasma cells, associated with fibrin deposits and intermixed by coccobacillary bacterial basophilic aggregates. These affected mainly the pericardium (28.6%, 14/49), the pleura (18.4%, 9/49), the Glissons capsule (10.2%, 5/49), the ventriculus (10.2, 5/33), and the proventriculus (8.2%, 4/49) serosa. Multifocal to coalescing areas of coagulative necrosis associated with similar inflammatory cells were observed mainly in the spleen (28.6%, 14/49), liver (24.5%, 12/49), and intestines (22.4%, 11/49). A similar infiltrate was also observed affecting the the lungs (16.3%, 8/49), the kidney (16.3%, 8/49) and the myocardium (14.3%, 7/49). Isolation and identification of E. coli was obtained in 12 cases through bacterial culture. Some organs (2 cases of each farms) were selected and submitted to immunohistochemistry anti-E. coli, and a positive stain was observed in all tested cases in liver (3/3), heart (4/4), spleen (1/1), lungs (4/4), intestines (4/4), bursa of Fabricius (1/1), ventriculus (1/1), and proventriculus (1/1) tissue sections. These results demonstrate that E. coli was the cause of mortality in these birds. Therefore, biosecurity and management measures should be employed to prevent and control the disease occurrence in Mozambiques poultry farming.

RESUMO: A colibacilose aviária é uma doença aguda de ocorrência mundial que acomete aves domésticas e silvestres, causada por Escherichia coli e resulta em perdas econômicas consideráveis devido à elevada morbidade e mortalidade das aves. O presente estudo teve o objetivo de descrever os aspectos patológicos, bacteriológicos e imuno-histoquímicos de colibacilose aviária em frangos de corte de Moçambique. Um total de 49 frangos de corte apresentaram anorexia, baixo ganho de peso, ataxia, diarreia, dispneia e morte em um curso clínico de 3 a 5 dias. As aves eram provenientes de 5 granjas (pequenas, média e grandes), com sistema de criação manual e automático, com rebanhos que variavam de 100 a 20.000 aves. À necropsia, todas as aves exibiam condição corporal ruim a caquética, além de pericárdio e cápsula de Glisson de todas aves (100%; n=49) com diferentes graus de aderência e deposição de fibrina de forma difusa acentuada. Os sacos aéreos torácicos e abdominais estavam espessados e aderidos à parede costal. Foi observado ainda hepatomegalia discreta, moderada a severa frequentemente associada com áreas multifocais puntiformes brancacentas (100%; 49/49), e esplenomegalia discreta a moderada, associado a áreas multifocais moteadas (75,5%; 37/49). Os pulmões e rins estavam aumentados e com coloração avermelhada. Histologicamente, observou-se majoritariamente serosite fibrinoheterofílica em 75,5% dos casos (37/49), caracterizadas por infiltrado inflamatório composto por heterófilos degenerados, macrófagos, linfócitos e plasmócitos, com deposição de fibrina entremeada por uma miríade de estruturas bacterianas cocobacilares. Esta lesão foi observada principalmente em pericárdio (28,6%; 14/49), pleura (18,4%; 9/49), cápsula de Glisson (10,2%; 5/49), ventrículo (10,2; 5/33) e em proventrículo (8,2%; 4/49). Áreas multifocais a coalescentes de necrose de coagulação associada a infiltrado inflamatório semelhante ao descrito foi observado principalmente no baço (28,6%; 14/49), fígado (24.5%; 12/49), e intestinos (8,2%; 4/49). Um infiltrado inflamatório semelhante também foi visualizado em pulmões (16,3%; 8/49), rins (16,3%; 8/49) e miocárdio (14,3%; 7/49), Colônias puras de E. coli foram identificadas e isoladas em 12 casos. Alguns órgãos (2 de cada granja) foram submetidos ao exame imuno-histoquímico anti-E. coli e marcação positiva foi visualizada em todos casos testados, como em fígado (3/3), coração (4/4), baço (1/1), pulmão (4/4), intestinos (4/4), bursa de Fabricius (1/1), rim (1/1), ventrículo (1/1) e proventrículo (1/1). Estes resultados demonstram que E. coli foi a causa de morte destas aves. Sendo assim, a adoção de boas medidas de biosseguridade e de manejo são indispensáveis para a prevenção e controle da ocorrência da doença nas granjas de frango de corte de Moçambique.

Pathological, microbiological and immunohistochemical characterization of avian colibacillosis in broiler chickens of Mozambique / Caracterização patológica, microbiológica e imuno-histoquímica de colibacilose em frangos de corte de Moçambique

Avian colibacillosis is an acute and globally occurring infectious disease of domestic and wild birds caused by Escherichia coli, and it is associated with considerable economic losses mainly due to the morbidity and mortality associated. The present study aimed to describe the pathological, bacteriological and immunohistochemical aspects of avian colibacillosis in broiler chickens of Mozambique. Forty-nine broiler chicken presented anorexia, decreased weight gain, ataxia, diarrhea, dyspnea, and death in a clinical course of 3-5 days. The birds were raised in five farms (small, medium and large farms) with manual and automatic breeding system, with flocks ranging from 100 to 20,000 birds. At the necropsy, all birds had poor body condition, and the pericardium and the Glisson's capsule of all avian exhibited different degrees of adherence often associated with severe fibrin deposition. The thoracic and abdominal air sacs were thickened and adhered to the costal wall. Mild, moderate or marked hepatomegaly associated with white pinpoint multifocal areas (100%, 49/49) and mild to moderate splenomegaly in 75.5% (37/49) with a mottled surface were observed. The lungs and kidney were enlarged and reddish. Histologically, a multiorgan fibrinoheterophilic polyserositis was observed in 75.5% of the cases (37/49), which were characterized by inflammatory infiltrates composed mainly of degenerative heterophils, macrophages and plasma cells, associated with fibrin deposits and intermixed by coccobacillary bacterial basophilic aggregates. These affected mainly the pericardium (28.6%, 14/49), the pleura (18.4%, 9/49), the Glisson's capsule (10.2%, 5/49), the ventriculus (10.2, 5/33), and the proventriculus (8.2%, 4/49) serosa. Multifocal to coalescing areas of coagulative necrosis associated with similar inflammatory cells were observed mainly in the spleen (28.6%, 14/49), liver (24.5%, 12/49), and intestines (22.4%, 11/49). A similar infiltrate was also observed affecting the the lungs (16.3%, 8/49), the kidney (16.3%, 8/49) and the myocardium (14.3%, 7/49). Isolation and identification of E. coli was obtained in 12 cases through bacterial culture. Some organs (2 cases of each farms) were selected and submitted to immunohistochemistry anti-E. coli, and a positive stain was observed in all tested cases in liver (3/3), heart (4/4), spleen (1/1), lungs (4/4), intestines (4/4), bursa of Fabricius (1/1), ventriculus (1/1), and proventriculus (1/1) tissue sections. These results demonstrate that E. coli was the cause of mortality in these birds. Therefore, biosecurity and management measures should be employed to prevent and control the disease occurrence in Mozambique's poultry farming.(AU)

A colibacilose aviária é uma doença aguda de ocorrência mundial que acomete aves domésticas e silvestres, causada por Escherichia coli e resulta em perdas econômicas consideráveis devido à elevada morbidade e mortalidade das aves. O presente estudo teve o objetivo de descrever os aspectos patológicos, bacteriológicos e imuno-histoquímicos de colibacilose aviária em frangos de corte de Moçambique. Um total de 49 frangos de corte apresentaram anorexia, baixo ganho de peso, ataxia, diarreia, dispneia e morte em um curso clínico de 3 a 5 dias. As aves eram provenientes de 5 granjas (pequenas, média e grandes), com sistema de criação manual e automático, com rebanhos que variavam de 100 a 20.000 aves. À necropsia, todas as aves exibiam condição corporal ruim a caquética, além de pericárdio e cápsula de Glisson de todas aves (100%; n=49) com diferentes graus de aderência e deposição de fibrina de forma difusa acentuada. Os sacos aéreos torácicos e abdominais estavam espessados e aderidos à parede costal. Foi observado ainda hepatomegalia discreta, moderada a severa frequentemente associada com áreas multifocais puntiformes brancacentas (100%; 49/49), e esplenomegalia discreta a moderada, associado a áreas multifocais moteadas (75,5%; 37/49). Os pulmões e rins estavam aumentados e com coloração avermelhada. Histologicamente, observou-se majoritariamente serosite fibrinoheterofílica em 75,5% dos casos (37/49), caracterizadas por infiltrado inflamatório composto por heterófilos degenerados, macrófagos, linfócitos e plasmócitos, com deposição de fibrina entremeada por uma miríade de estruturas bacterianas cocobacilares. Esta lesão foi observada principalmente em pericárdio (28,6%; 14/49), pleura (18,4%; 9/49), cápsula de Glisson (10,2%; 5/49), ventrículo (10,2; 5/33) e em proventrículo (8,2%; 4/49). Áreas multifocais a coalescentes de necrose de coagulação associada a infiltrado inflamatório semelhante ao descrito foi observado principalmente no baço (28,6%; 14/49), fígado (24.5%; 12/49), e intestinos (8,2%; 4/49). Um infiltrado inflamatório semelhante também foi visualizado em pulmões (16,3%; 8/49), rins (16,3%; 8/49) e miocárdio (14,3%; 7/49), Colônias puras de E. coli foram identificadas e isoladas em 12 casos. Alguns órgãos (2 de cada granja) foram submetidos ao exame imuno-histoquímico anti-E. coli e marcação positiva foi visualizada em todos casos testados, como em fígado (3/3), coração (4/4), baço (1/1), pulmão (4/4), intestinos (4/4), bursa de Fabricius (1/1), rim (1/1), ventrículo (1/1) e proventrículo (1/1). Estes resultados demonstram que E. coli foi a causa de morte destas aves. Sendo assim, a adoção de boas medidas de biosseguridade e de manejo são indispensáveis para a prevenção e controle da ocorrência da doença nas granjas de frango de corte de Moçambique.(AU)

Molecular profile of mannan-binding lectin in hepatitis C patients with MBL gene polymorphisms by a modified mannan-coated nitrocellulose assay.

The aim of this study was to develop an assay to analyze the serum profile of Mannose-binding lectin (MBL) through a simple and "in-house" method (called "dot-N-man"). Furthermore, the study attempted to associate molecular masses of MBL to the profile of MBL gene polymorphisms in patients with hepatitis C. Heterogeneity in molecular masses of MBL is due to the impairment of oligomers formation, which is linked to genetic polymorphisms in the MBL gene. Individuals with AA genotype (wild-type) produce high-molecular-mass proteins, whereas AO and OO individuals produce intermediate and low-molecular-mass proteins, respectively. Sera of thirty patients carrying the hepatitis C virus (HCV) were investigated using MBL binding assay with mannan-coated nitrocellulose (dot-N-man). Purified MBL was evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Dot-N-Man assay yielded MBL with molecular masses ranging between 55 and 320 kDa, comparable to low and high molecular mass forms of MBL. Nonreducing SDS-PAGE showed high molecular mass bands in all AA individuals while bands of 270 and 205 kDa were observed in sera for a number of patients with AO and OO genotypes, respectively. Immunoblotting confirmed the MBL samples obtained from the dot-N-man. These results provide new insights to understand the MBL molecular forms profile in patients infected with HCV- which could be useful in future investigations on the influence of the MBL structure/genotype on both the progression of infection and the response to hepatitis C therapy.

A Review of Three Commonly Used Herbs Which Enhance Memory and New Evidences Which Show Their Combination Could Improve Memory in Young Animals.

BACKGROUND: This review looks into the herbs Gingko biloba, Polygala tenuifolia, and Lycii fructus for their widely studied neuroprotective properties. In particular, we investigated memory enhancing effect of these herbs, and their potential synergetic effect on memory with new data. Sixmonth treated mice demonstrated shorter escape latency in water maze and shorter arrival time in a consolidated memory task. Immunochemistry showed evident increase in superoxide dismutase activities in the prefrontal cortex, implying protection against free radicals during aging. Discrete increase of catecholaminergic neurons was found in the prefrontal cortex, hippocampus, corpus striatum, and midbrain, suggesting better memory and better control on mood and behavior. Necrotic cells in the brain decreased as indicated by immunocytochemistry of lactic dehydrogenase. Terminal deoxynucleotidyl transferase dUTP nick end labeling showed no apoptotic cells in most brain areas in high dose group. Biochemistry revealed increase of dopaminergic cells in treatment groups at prefrontal cortex, and in the hippocampus and cerebellum of the high dose group. Most 6-month groups showed increase of serotonin in all three areas. For the high dose group, GABA increased in the hippocampus but not prefrontal cortex, which would help induce sleep at night. Protein kinase C increased in most groups at prefrontal cortex, hippocampus and cerebellum, signifying increase of possible signal transduction pathways for memory or other nervous activations. CONCLUSION: Our results intimate that the interaction of the three herbs exerts beneficial effects on memory, associated cognitive function, and necrosis. Future investigations based on the present data shall aid development of clinically relevant medication.

Role of Interleukin-22 in chronic liver injury.

Liver fibrosis is the result of an exacerbated wound-healing response associated with chronic liver injury. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and frequently requires liver transplantation. The host immune response has an important role driving fibrosis deposition by activating hepatic stellate cells (HSCs). Interleukin-22 (IL-22) is a cytokine that plays a key role in promoting antimicrobial immunity and tissue repair at barrier surfaces. Data from literature suggest that IL-22 has a protective role in the liver by reducing fibrosis in some pathological conditions, however the results are contradictory. This review highlights current knowledge of IL-22' role in chronic liver injury, as well as its therapeutic potential for the treatment of chronic liver injury.

Association of Catalase and Glutathione Peroxidase 1 Polymorphisms with Chronic Hepatitis C Outcome.

The hepatic damage caused by hepatitis C virus (HCV) infection is associated with the host immune response and viral regulatory factors. Catalase (CAT) and glutathione peroxidase 1 (GPX1) are antioxidant enzymes located in the peroxisomes and mitochondria, respectively, and are responsible for the control of intracellular hydrogen peroxide levels. Polymorphisms in CAT (C-262T) and GPX1 (Pro198Leu) are correlated with serum levels and enzyme activity. This study aimed to investigate the association of genetic polymorphisms of CAT C-262T (rs1001179) and GPX1 Pro198Leu (rs1050450) with different stages of liver fibrosis and development of hepatocellular carcinoma (HCC). This study included 445 patients with chronic hepatitis C, of whom 139 patients had mild fibrosis (F0-F1), 200 had moderate/severe fibrosis (F2-F4), and 106 had HCC. Genotyping of SNPs was performed by real-time PCR using TaqMan probes. The Pro/Pro genotype of GPX1 was significantly associated with fibrosis severity, HCC, Child Pugh score, and BCLC staging. Additionally, patients carrying both CT+TT genotypes in the CAT gene and the Pro/Pro genotype in the GPX1 gene had higher risk for developing moderate/severe fibrosis or HCC (p = 0.009, OR 2.40 and p = 0.002, OR 3.56, respectively). CAT and GPX1 polymorphisms may be implicated in the severity of liver fibrosis and HCC caused by HCV.

Prenatal Transmission of Syphilis and Human Immunodeficiency Virus in Brazil: Achieving Regional Targets for Elimination.

Background. The Pan-American Health Organization has called for reducing (1) human immunodeficiency virus (HIV) mother-to-child transmission (MTCT) to ≤0.30 infections/1000 live births (LB), (2) HIV MTCT risk to ≤2.0%, and (3) congenital syphilis (CS) incidence to ≤0.50/1000 LB in the Americas by 2015. Methods. Using published Brazilian data in a mathematical model, we simulated a cohort of pregnant women from antenatal care (ANC) through birth. We investigated 2 scenarios: "current access" (89.1% receive one ANC syphilis test and 41.1% receive 2; 81.7% receive one ANC HIV test and 18.9% receive birth testing; if diagnosed, 81.0% are treated for syphilis and 87.5% are treated for HIV) and "ideal access" (95% of women undergo 2 HIV and syphilis screenings; 95% receive appropriate treatment). We conducted univariate and multivariate sensitivity analyses on key inputs. Results. With current access, we projected 2.95 CS cases/1000 LB, 0.29 HIV infections/1000 LB, 7.1% HIV MTCT risk, and 11.11 intrauterine fetal demises (IUFD)/1000 pregnancies, with significant regional variation. With ideal access, we projected improved outcomes: 1.00 CS cases/1000 LB, 0.10 HIV infections/1000 LB, HIV MTCT risk of 2.4%, and 10.65 IUFD/1000 pregnancies. Increased testing drove the greatest improvements. Even with ideal access, only HIV infections/1000 LB met elimination goals. Achieving all targets required testing and treatment >95% and reductions in prevalence and incidence of HIV and syphilis. Conclusions. Increasing access to care and HIV and syphilis antenatal testing will substantially reduce HIV and syphilis MTCT in Brazil. In addition, regionally tailored interventions reducing syphilis incidence and prevalence and supporting HIV treatment adherence are necessary to completely meet elimination goals.

Novel partial duplication of EYA1 causes branchiootic syndrome in a large Brazilian family.

OBJECTIVE: To identify novel genetic causes of syndromic hearing loss in Brazil. DESIGN: To map a candidate chromosomal region through linkage studies in an extensive Brazilian family and identify novel pathogenic variants using sequencing and array-CGH. STUDY SAMPLE: Brazilian pedigree with individuals affected by BO syndrome characterized by deafness and malformations of outer, middle and inner ear, auricular and cervical fistulae, but no renal abnormalities. RESULTS: Whole genome microarray-SNP scanning on samples of 11 affected individuals detected a multipoint Lod score of 2.6 in the EYA1 gene region (chromosome 8). Sequencing of EYA1 in affected patients did not reveal pathogenic mutations. However, oligonucleotide-array-CGH detected a duplication of 71.8Kb involving exons 4 to 10 of EYA1 (heterozygous state). Real-time-PCR confirmed the duplication in fourteen of fifteen affected individuals and absence in 13 unaffected individuals. The exception involved a consanguineous parentage and was assumed to involve a different genetic mechanism. CONCLUSIONS: Our findings implicate this EYA1 partial duplication segregating with BO phenotype in a Brazilian pedigree and is the first description of a large duplication leading to the BOR/BO syndrome.

Adenoma pleomórfico em mucosa jugal: relato de caso / Pleomorphic adenoma on the buccal mucosa: a case report

O adenoma pleomórfico, que é uma neoplasia mista de glândula salivar, é uma morbidade relativamente comum. Apresenta prevalência dominante como neoplasia em glândula parótida, podendo acometer também glândulas salivares menores. É derivado de uma mistura de elementos ductais e mioepiteliais. O tumor geralmente é solitário e apresenta umcrescimento lento e indolor, como massa nodular única, independentedo sítio de origem. Quando intraoral é mais comum em palato duro e lábio superior, sendo relativamente incomum em mucosa jugal. Nesse trabalho, relata-se um caso clínico de adenoma pleomórfico em mucosa jugal, apresentando sete anos de evolução, com completa resolução após o tratamento cirúrgico conservador.

The pleomorphic adenoma, which is a mixed salivary gland neoplasm, is a relatively common disease. It has dominant prevalence such as neoplasm on parotid gland may also affect the minor salivary glands. It is derived from a mixture of ductal and myoepithelial elements. The tumor is usually solitary and presents a slow and pain less growth, being a single mass, independent of site of origin. When intraoral, it is more common onthe hard palate and upper lip. It is relatively uncommon on the buccal mucosa. In this paper, we report a case of pleomorphic adenoma in the buccal mucosa, with seven years of evolution, with complete resolution after conservatory surgical treatment.

Patterns of cortical activation following motor tasks and psychological-inducing movie cues in heroin users: an fMRI study.

OBJECTIVE: Drug abuse and addiction are worldwide health problems. However, few studies have used fMRI to investigate the effect of chronic heroin use on brain activation. This is a study along this line. METHOD: fMRI positive sites in the brain were recorded during different motor and sensory activities. RESULTS: Following motor activities, heroin users had more sites globally activated in the brain than in normal volunteers, with ex-heroin users being least reactive. Conversely, a "heroin puffing" movie produced more activation in ongoing-heroin and ex-heroin users than in the normal individuals, whereas a movie with explicit sexual content was less stimulatory in both groups of heroin users compared to normal individuals. CONCLUSIONS: These significant findings relative to the function of specific brain nuclei are discussed.

Effects of double ligation of Stensen's duct on the rabbit parotid gland.

Salivary gland duct ligation is an alternative to gland excision for treating sialorrhea or reducing salivary gland size prior to tumor excision. Duct ligation also is used as an approach to study salivary gland aging, regeneration, radiotherapy, sialolithiasis and sialadenitis. Reports conflict about the contribution of each salivary cell population to gland size reduction after ductal ligation. Certain cell populations, especially acini, reportedly undergo atrophy, apoptosis and proliferation during reduction of gland size. Acini also have been reported to de-differentiate into ducts. These contradictory results have been attributed to different animal or salivary gland models, or to methods of ligation. We report here a bilateral double ligature technique for rabbit parotid glands with histologic observations at 1, 7, 14, 30, 60 days after ligation. A large battery of special stains and immunohistochemical procedures was employed to define the cell populations. Four stages with overlapping features were observed that led to progressive shutdown of gland activities: 1) marked atrophy of the acinar cells occurred by 14 days, 2) response to and removal of the secretory material trapped in the acinar and ductal lumens mainly between 30 and 60 days, 3) reduction in the number of parenchymal (mostly acinar) cells by apoptosis that occurred mainly between 14-30 days, and 4) maintenance of steady-state at 60 days with a low rate of fluid, protein, and glycoprotein secretion, which greatly decreased the number of leukocytes engaged in the removal of the luminal contents. The main post- ligation characteristics were dilation of ductal and acinar lumens, massive transient infiltration of mostly heterophils (rabbit polymorphonuclear leukocytes), acinar atrophy, and apoptosis of both acinar and ductal cells. Proliferation was uncommon except in the larger ducts. By 30 days, the distribution of myoepithelial cells had spread from exclusively investing the intercalated ducts pre-ligation to surrounding a majority of the residual duct-like structures, many of which clearly were atrophic acini. Thus, both atrophy and apoptosis made major contributions to the post-ligation reduction in gland size. Structures also occurred with both ductal and acinar markers that suggested acini differentiating into ducts. Overall, the reaction to duct ligation proceeded at a considerably slower pace in the rabbit parotid glands than has been reported for the salivary glands of the rat.

Chronic ketamine administration modulates midbrain dopamine system in mice.

Ketamine is an anesthetic and a popular abusive drug. As an anesthetic, effects of ketamine on glutamate and GABA transmission have been well documented but little is known about its long-term effects on the dopamine system. In the present study, the effects of ketamine on dopamine were studied in vitro and in vivo. In pheochromocytoma (PC 12) cells and NGF differentiated-PC 12 cells, ketamine decreased the cell viability while increasing dopamine (DA) concentrations in a dose-related manner. However, ketamine did not affect the expression of genes involved in DA synthesis. In the long-term (3 months) ketamine treated mice, significant increases of DA contents were found in the midbrain. Increased DA concentrations were further supported by up-regulation of tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine synthesis. Activation of midbrain dopaminergic neurons could be related to ketamine modulated cortical-subcortical glutamate connections. Using western blotting, significant increases in BDNF protein levels were found in the midbrain, suggesting that perhaps BDNF pathways in the cortical-subcortical connections might contribute to the long-term ketamine induced TH upregulation. These data suggest that long-term ketamine abuse caused a delayed and persistent upregulation of subcortical DA systems, which may contribute to the altered mental status in ketamine abusers.

DL-3-n-Butylphthalide, an anti-oxidant agent, prevents neurological deficits and cerebral injury following stroke per functional analysis, magnetic resonance imaging and histological assessment.

DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide which was isolated from seeds of Apium graveolens. The present study aims at evaluating the outcome of NBP given prior to and after the onset of ischemic stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two months prior to MCAO. For post-treatment, NBP was given daily for seven consecutive days after MCAO. Seven days post-surgery, rats were tested for the presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to calculate the infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra area were examined microscopically for pathological changes. In SHR, NBP pre- and post-treatment significantly lowered neurological deficit scores, reduced infarct volume, and minimized pathological changes in the penumbra area when compared to oil-vehicle treated controls. In WKY, these beneficial effects were observed only in the post-treatment group. The beneficial effects of NBP post-treatment were greater in WKY than in SHR. Results indicated that NBP could exert both preventive and therapeutic effects on ischemic stroke in SHR, but only exerted therapeutic effect in WKY.

Effects of DL-3-n-butylphthalide on vascular dementia and angiogenesis.

3-n-Butylphthalide (NBP) is a compound extracted from Chinese celery and is used as an anti-hypertensive herbal medicine for treating stroke patients. The aim of this study is to demonstrate the effects and mechanisms of this compound through in vitro and in vivo experiments. Culture experiments were performed by adding hydrogen peroxide (H(2)O(2)) to SH-SY5Y cells. From the MTT assay result, enhanced cell survival was observed with DL-NBP treatment, regardless of whether they are added before, simultaneously with or after the addition of H(2)O(2). For the in vivo experiment, Spontaneously Hypertensive rats and Wistar Kyoto control rats with chronic cerebral ischemia, which were induced by bilateral transection of the common carotid arteries, were given DL-NBP. Their performances in the place navigation test and spatial probe test in the Morris Water Maze have significantly improved compared with the DL-NBP untreated animals, indicating an improvement in spatial learning and memory in the ischemic-animals. In addition, in the chick embryonic chorioallantoic membrane assay, angiogenesis was more vigorous under the effects of DL-NBP, together with increased expression of growth factors, VEGF, VEGF-receptor and bFGF. All these suggested that one of the mechanisms of DL-NBP might be ameliorating vascular dementia and promoting angiogenesis.