Proteomic Analysis of a Rat Streptozotocin Model Shows Dysregulated Biological Pathways Implicated in Alzheimer's Disease.

Alzheimer's Disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory loss and cognitive impairment, affecting 35 million individuals worldwide. Intracerebroventricular (ICV) injection of low to moderate doses of streptozotocin (STZ) in adult male Wistar rats can reproduce classical physiopathological hallmarks of AD. This biological model is known as ICV-STZ. Most studies are focused on the description of behavioral and morphological aspects of the ICV-STZ model. However, knowledge regarding the molecular aspects of the ICV-STZ model is still incipient. Therefore, this work is a first attempt to provide a wide proteome description of the ICV-STZ model based on mass spectrometry (MS). To achieve that, samples from the pre-frontal cortex (PFC) and hippocampus (HPC) of the ICV-STZ model and control (wild-type) were used. Differential protein abundance, pathway, and network analysis were performed based on the protein identification and quantification of the samples. Our analysis revealed dysregulated biological pathways implicated in the early stages of late-onset Alzheimer's disease (LOAD), based on differentially abundant proteins (DAPs). Some of these DAPs had their mRNA expression further investigated through qRT-PCR. Our results shed light on the AD onset and demonstrate the ICV-STZ as a valid model for LOAD proteome description.

SpliceProt 2.0: A Sequence Repository of Human, Mouse, and Rat Proteoforms.

SpliceProt 2.0 is a public proteogenomics database that aims to list the sequence of known proteins and potential new proteoforms in human, mouse, and rat proteomes. This updated repository provides an even broader range of computationally translated proteins and serves, for example, to aid with proteomic validation of splice variants absent from the reference UniProtKB/SwissProt database. We demonstrate the value of SpliceProt 2.0 to predict orthologous proteins between humans and murines based on transcript reconstruction, sequence annotation and detection at the transcriptome and proteome levels. In this release, the annotation data used in the reconstruction of transcripts based on the methodology of ternary matrices were acquired from new databases such as Ensembl, UniProt, and APPRIS. Another innovation implemented in the pipeline is the exclusion of transcripts predicted to be susceptible to degradation through the NMD pathway. Taken together, our repository and its applications represent a valuable resource for the proteogenomics community.

Effect of antimicrobial photodynamic therapy on the reduction of bacteria and virulence factors in teeth with primary endodontic infection.

OBJECTIVE: To evaluate the effectiveness of supplemental photodynamic therapy for improving the bacterial removal and the levels of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) by conducting a clinical trial. METHODOLOGY: Twenty-four root canals with pulp necrosis and periapical lesion were selected and randomly divided into conventional group using endodontic treatment with chemo-mechanical preparation (CMP) alone (n = 12) and a group using antimicrobial photodynamic therapy (aPDT) after CMP (n = 12). The samples were collected before and after CMP (conventional group) and after photodynamic therapy (aPDT group). A photosensitizer (0.005% methylene blue) was applied to the root canal for 3 minutes after CMP, whereas aPDT was performed by using a red laser with a power of 30Mw and energy density of 9J/cm2 for 90 s per root canal. Culture technique was performed to determine the bacterial colony forming units. LPS and LTA levels were quantified by using limulus amoebocyte lysate (LAL) assay and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: All samples showed growth of viable bacteria on Fastidious Anaerobe Agar (FAA), with an average of 5.19 × 105 CFU/ mL. CMP was effective in decreasing viable bacteria (p < 0.05), whereas there was a significant decrease (p < 0.05) in the samples treated with aPDT compared to those submitted to CMP. LPS and LTA were detected in all initial samples, with mean values of 20.561 EU/mL and 430.91 pg/mL, respectively. Both CMP and aPDT groups significantly decreased the levels of LPS and LTA (p < 0.05), with a statistical difference between the groups regarding aPDT (p < 0.05). CONCLUSION: Photodynamic therapy as an adjunct to CMP proved to be effective in improving root canal disinfection and reducing the LPS and LTA levels in teeth with primary endodontic infection.

Identification of Novel Genes and Proteoforms in Angiostrongylus costaricensis through a Proteogenomic Approach.

RNA sequencing (RNA-Seq) and mass-spectrometry-based proteomics data are often integrated in proteogenomic studies to assist in the prediction of eukaryote genome features, such as genes, splicing, single-nucleotide (SNVs), and single-amino-acid variants (SAAVs). Most genomes of parasite nematodes are draft versions that lack transcript- and protein-level information and whose gene annotations rely only on computational predictions. Angiostrongylus costaricensis is a roundworm species that causes an intestinal inflammatory disease, known as abdominal angiostrongyliasis (AA). Currently, there is no drug available that acts directly on this parasite, mostly due to the sparse understanding of its molecular characteristics. The available genome of A. costaricensis, specific to the Costa Rica strain, is a draft version that is not supported by transcript- or protein-level evidence. This study used RNA-Seq and MS/MS data to perform an in-depth annotation of the A. costaricensis genome. Our prediction improved the reference annotation with (a) novel coding and non-coding genes; (b) pieces of evidence of alternative splicing generating new proteoforms; and (c) a list of SNVs between the Brazilian (Crissiumal) and the Costa Rica strain. To the best of our knowledge, this is the first time that a multi-omics approach has been used to improve the genome annotation of A. costaricensis. We hope this improved genome annotation can assist in the future development of drugs, kits, and vaccines to treat, diagnose, and prevent AA caused by either the Brazil strain (Crissiumal) or the Costa Rica strain.

The effect of photodynamic therapy on postoperative pain in teeth with primary endodontic infection.

INTRODUCTION: The objective of this study was to investigate the action of photodynamic therapy on pain control after endodontic treatment in asymptomatic teeth with a primary infection, within a single visit. METHODS: Sixty (60) single-rooted teeth with pulp necrosis and periapical lesions were selected and randomly divided into two (2) groups (n = 30), according to the protocol; a control group (CG) and a group using photodynamic therapy (aPDT). The canals were instrumented with Reciproc files # 25 up to 40 along the entire length of the canal, using 2% chlorhexidine gel as the auxiliary chemical substance, followed by irrigation with sterile saline. aPDT consited of 0.005% methylene blue as photosensitizer, using AsGaAl diode laser, 660 nm wavelength, 100 mW of power and 9 J of energy, using optical fibers with 365 µm in diameter. The canals were filled with Endomethasone N cement. RESULTS: Pain intensity was assessed at 8, 12, 24, 48, 72 h and 1 week after endodontic treatment using a visual analogue scale. The level of pain was classified as none (0), mild (1-3), moderate (4-7) or severe (8-10). The data were at a significance level of 5%. There was a statistically significant difference (p<0.05) in the periods of 8, 12, 24, 48 and 72 h between the control group and the aPDT group. After 1 week, there was no statistically significant difference. CONCLUSIONS: It is concluded that photodynamic therapy had a significant effect on decreasing post-endodontic treatment pain in teeth with necrotic pulp and asymptomatic periapical lesions.

Proteogenomics Reveals Orthologous Alternatively Spliced Proteoforms in the Same Human and Mouse Brain Regions with Differential Abundance in an Alzheimer's Disease Mouse Model.

Alternative splicing (AS) may increase the number of proteoforms produced by a gene. Alzheimer's disease (AD) is a neurodegenerative disease with well-characterized AS proteoforms. In this study, we used a proteogenomics strategy to build a customized protein sequence database and identify orthologous AS proteoforms between humans and mice on publicly available shotgun proteomics (MS/MS) data of the corpus callosum (CC) and olfactory bulb (OB). Identical proteotypic peptides of six orthologous AS proteoforms were found in both species: PKM1 (gene PKM/Pkm), STXBP1a (gene STXBP1/Stxbp1), Isoform 3 (gene HNRNPK/Hnrnpk), LCRMP-1 (gene CRMP1/Crmp1), SP3 (gene CADM1/Cadm1), and PKCßII (gene PRKCB/Prkcb). These AS variants were also detected at the transcript level by publicly available RNA-Seq data and experimentally validated by RT-qPCR. Additionally, PKM1 and STXBP1a were detected at higher abundances in a publicly available MS/MS dataset of the AD mouse model APP/PS1 than its wild type. These data corroborate other reports, which suggest that PKM1 and STXBP1a AS proteoforms might play a role in amyloid-like aggregate formation. To the best of our knowledge, this report is the first to describe PKM1 and STXBP1a overexpression in the OB of an AD mouse model. We hope that our strategy may be of use in future human neurodegenerative studies using mouse models.

Condutas práticas e efetivas do cirurgião-dentista frente ao paciente em tratamento de câncer de cabeça e pescoço: revisão de literatura / Practical and effective conducts of the dental surgery in front of the patient in treating head and neck cancer: literature review

O objetivo do presente estudo é salientar através de uma revisão de literatura os possíveis cuidados que o cirurgião dentista precisa ter frente aos principais agravos bucais decorrentes do tratamento oncológico. Os trabalhos foram obtidos através dos sistemas de dados PUBMED, MEDLINE, BBO, SCIELO, LILACS, SCIENCE DIRECT, COCHRANE E BBO. A principal estratégia para o combate de tais neoplasias é na forma de prevenção, ainda que o câncer tenha como um dos fatores etiológicos a hereditariedade, a exposição a determinados agentes (fumo, álcool, HPV, etc.) podendo aumentar as chances de sua ocorrência. Os métodos tradicionais de tratamento oncológico são a cirurgia, a radioterapia e a quimioterapia. O tratamento a ser instituído estará na dependência da localização, do grau de malignidade e da condição de saúde do indivíduo. O cuidado dentário antes do tratamento oncológico visa a redução do risco e a gravidade das complicações orais, prevenir, eliminar ou reduzir a dor de origem bucal, preservar ou melhorar a saúde bucal, contribuindo para a melhoria da qualidade de vida. Conclui-se que diante dos efeitos colaterais importantes aos tecidos bucais, é de suma necessidade o conhecimento por parte do cirurgião dentista, para que possa atuar na prevenção e redução de tais danos(AU)

The aim of the present study is to highlight a literature review on the possible treatments that the dental surgeon needs to face the main oral health problems caused by cancer treatment. The work was carried out through the data systems PUBMED, MEDLINE, BBO, SCIELO, LILACS, CIÊNCIA DIRETA, COCHRANE AND BBO. The main strategy to combat these neoplasms is the form of prevention, but cancer has inherited etiological factors, exposure to dangerous agents (smoking, alcohol, HPV, etc.) that can increase the chances of its occurrence. Traditional methods of cancer treatment are surgery, radiation and chemotherapy. Treatment is instituted depending on the individual's location, degree of malignancy and health condition. Dental care before cancer treatment reduces the risk and severity of oral complications, prevents, eliminates or reduces pain of oral origin, preserves or improves oral health, contributes to improving quality of life. It is concluded that in view of the important effects on oral tissues, knowledge or knowledge on the part of the dental surgeon is necessary, so that it can perform the prevention and reduction of such damages(AU)

Optimal Virulence, Diffusion and Tradeoffs.

In this work we propose a variant of a classical SIR epidemiological model where pathogens are characterized by a (phenotypic) mutant trait x. Imposing that the trait x mutates according to a random walk process and that it directly influences the epidemiological components of the pathogen, we studied its evolutionary development by interpreting the tenet of maximizing the basic reproductive number of the pathogen as an optimal control problem. Pontryagin's maximum principle was used to identify the possible optimal evolutionary strategies of the pathogen. Qualitatively, three types of optimal evolutionary routes were identified and interpreted in the context of virulence evolution. Each optimal solution imposes a different tradeoff relation among the epidemiological parameters. The results predict (mostly) two kinds of infections: short-lasting mild infections and long-lasting acute infections.

The Challenge to Search for New Nervous System Disease Biomarker Candidates: the Opportunity to Use the Proteogenomics Approach.

Alzheimer's disease, Parkinson's disease, prion diseases, schizophrenia, and multiple sclerosis are the most common nervous system diseases, affecting millions of people worldwide. The current scientific literature associates these pathological conditions to abnormal expression levels of certain proteins, which in turn improved the knowledge concerning normal and affected brains. However, there is no available cure or preventive therapy for any of these disorders. Proteogenomics is a recent approach defined as the data integration of both nucleotide high-throughput sequencing and protein mass spectrometry technologies. In the last years, proteogenomics studies in distinct diseases have emerged as a strategy for the identification of uncharacterized proteoforms, which are all the different protein forms derived from a single gene. For many of these diseases, at least one protein used as biomarker presents more than one proteoform, which fosters the analysis of publicly available data focusing proteoforms. Given this context, we describe the most important biomarkers for each neurodegenerative disease and how genomics, transcriptomics, and proteomics separately contributed to unveil them. Finally, we present a selection of proteogenomics studies in which the combination of nucleotide and proteome high-throughput data, from cell lines or brain tissue samples, is used to uncover proteoforms not previously described. We believe that this new approach may improve our knowledge about nervous system diseases and brain function and an opportunity to identify new biomarker candidates.

Análise Comparativa da Diversidade de Splicing Alternativo no Proteoma do Cérebro Humano e Murino / Comparative Analysis of the Diversity of Alternative Splicing in the Human and Murine Brain Proteome

Os avanços obtidos em transcriptômica, em função do desenvolvimento de sequenciadores de alta vazão, e na proteômica, por meio dos modernos espectrômetros de massas (MS), resultaram em um grande volume de dados que passou a ser integrado em diversos estudos de Bioinformática, levando ao melhor entendimento sobre a fração dos RNAs mensageiros efetivamente traduzida em proteínas. A proteogenômica é a área de pesquisa que reúne estas tecnologias, atuando na interface entre a genômica e a proteômica para interpretar eventos moleculares, tais como, por exemplo, o splicing alternativo. Este evento molecular é capaz de gerar RNAs mensageiros diferentes a partir de um mesmo gene, podendo alterar a sequência polipeptídica e, consequentemente, gerar proteoformas com funções distintas. Neste sentido, atualmente alguns projetos têm realizado esta análise integrativa com o intuito de comparar os resultados de amostras de ser humano e outros mamíferos, uma vez que alguns destes animais são utilizados como organismos modelo para o estudo dos aspectos moleculares de doenças, como as neurodegenerativas. Desta forma, este projeto teve como objetivo principal analisar o perfil de expressão de variantes de splicing alternativo em dados de espectrometria de massas de proteínas de amostras de tecidos de cérebros sadios de humano e camundongo

Para tal, foram utilizados dados de mRNAs de referência (Refseq), ESTs e sequências da base de dados Uniprot/Swiss-Prot para confecção de repositórios de sequências proteicas personalizados, utilizando uma metodologia desenvolvida pelo nosso grupo de pesquisa denominada matrizes ternárias. O repositório personalizado para humano continha 20.150 sequências canônicas e 204.294 peptídeos não redundantes, totalizando 224.453 sequências. O repositório de camundongo possuía 16.888 sequências canônicas e 156.889 peptídeos não redundantes, totalizando 173.777 sequências. Estes repositórios de sequências proteicas personalizados foram empregados para a análise de dados de espectrometria de massas de três regiões distintas do cérebro de humano e camundongo (corpo caloso, nervo óptico e bulbo olfatório). A partir destas análises, nós inferimos a expressão de um total de 3.289 proteínas canônicas e 23 proteoformas de genes ortólogos entre humano e camundongo. Dentre as proteoformas, seis foram inferidas a partir de peptídeos proteotípicos idênticos identificados em dados de MS de humano e camundongo (PKM, CRMP1, PRKCB, STXBP1, CADM1 e HNRNPK). Portanto, acreditamos que a identificação de peptídeos compartilhados entre humano e camundongo, pertencentes a proteoformas de genes ortólogos, realizada neste projeto, contribuiu para o melhor conhecimento da diversidade de splicing do cérebro de humano e camundongo. (AU)

Physiological and biochemical characterization of Azospirillum brasilense strains commonly used as plant growth-promoting rhizobacteria.

Azospirillum is a plant growth-promoting rhizobacteria (PGPR) genus vastly studied and utilized as agriculture inoculants. Isolation of new strains under different environmental conditions allows the access to the genetic diversity and improves the success of inoculation procedures. Historically, the isolation of this genus has been performed by the use of some traditional culture media. In this work we characterized the physiology and biochemistry of five different A. brasilense strains, commonly used as cereal inoculants. The aim of this work is to contribute to pose into revision some concepts concerning the most used protocols to isolate and characterize this bacterium. We characterized their growth in different traditional and non-traditional culture media, evaluated some PGPR mechanisms and characterized their profiles of fatty acid methyl esters and carbon-source utilization. This work shows, for the first time, differences in both profiles, and ACC deaminase activity of A. brasilense strains. Also, we show unexpected results obtained in some of the evaluated culture media. Results obtained here and an exhaustive knowledge revision revealed that it is not appropriate to conclude about bacterial species without analyzing several strains. Also, it is necessary to continue developing studies and laboratory techniques to improve the isolation and characterization protocols.

HPV infection, cervical abnormalities, and cancer in HIV-infected women in Mumbai, India: 12-month follow-up.

BACKGROUND: HIV-infected women are at a higher risk of cervical intraepithelial neoplasia (CIN) and cancer than women in the general population, partly due to a high prevalence of persistent human papillomavirus (HPV) infection. The aim of the study was to assess the burden of HPV infection, cervical abnormalities, and cervical cancer among a cohort of HIV-infected women as part of a routine screening in an urban overpopulated slum setting in Mumbai, India. METHODS: From May 2010 to October 2010, Médecins Sans Frontières and Tata Memorial Hospital Mumbai offered routine annual Pap smears and HPV DNA testing of women attending an antiretroviral therapy (ART) clinic and a 12-month follow-up. Women with abnormal test results were offered cervical biopsy and treatment, including treatment for sexually transmitted infections (STIs). RESULTS: Ninety-five women were screened. Median age was 38 years (IQR: 33-41); median nadir CD4-count 143 cells/µL (IQR: 79-270); and median time on ART 23 months (IQR:10-41). HPV DNA was detected in 30/94 women (32%), and 18/94 (19%) showed either low-grade or high-grade squamous intraepithelial lesions (LSIL/HSIL) on Pap smear. Overall, >50% had cervical inflammatory reactions including STIs. Of the 43 women with a cervical biopsy, eight (8.4%) had CIN-1, five (5.3%) CIN-2, and two (2.1%) carcinoma in situ. All but one had HPV DNA detected (risk ratio: 11, 95% confidence interval: 3.3-34). By October 2011, 56 women had completed the 12-month follow-up and had been rescreened. No new cases of HPV infection/LSIL/HSIL were detected. CONCLUSION: The high prevalence of HPV infection, STIs, and cervical lesions among women attending an ART clinic demonstrates a need for routine screening. Simple, one-stop screening strategies are needed. The optimal screening interval, especially when resources are limited, needs to be determined.

Prognostic value of stress hyperglycemia for in-hospital outcome in acute coronary artery disease.

BACKGROUND: In acute coronary syndrome (ACS), admission hyperglycemia is associated with adverse cardiovascular events in diabetic and nondiabetic patients. OBJECTIVE: To assess the prognostic value of stress hyperglycemia for the in-hospital outcome of patients admitted due to ACS. METHODS: This study included 152 patients admitted to the chest pain unit of a tertiary hospital diagnosed with ACS, who had admission blood glucose data, from September 2005 to February 2010. Group I comprised patients with stress hyperglycemia, defined as admission blood glucose concentration > 126 mg/dL for nondiabetic individuals and admission blood glucose concentration > 200 mg/dL for diabetic individuals. Group II was formed by patients with admission blood glucose concentration lower than those established. The association of hyperglycemia and in-hospital outcome was assessed. RESULTS: Stress hyperglycemia associated with in-hospital complications, age increase and female sex. On multivariate analysis, only female sex (OR = 2.04; 95% CI: 1.03 - 4.06; p = 0.007) and in-hospital complications (OR = 3.65; 95% CI: 1.62 - 8.19; p = 0.002) associated independently with admission hyperglycemia. CONCLUSIONS: Stress hyperglycemia is an independent predictive factor for in-hospital complications after ACS in diabetic and nondiabetic patients. The results highlight the need to assess admission blood glucose concentration in all patients admitted due to ACS, including nondiabetic ones, aiming at identifying those at higher risk for complications.

Valor prognóstico da hiperglicemia de estresse na evolução intra-hospitalar na coronariopatia aguda / Prognostic value of stress hyperglycemia for in-hospital outcome in acute coronary artery disease

FUNDAMENTO: Na síndrome coronariana aguda (SCA), a hiperglicemia, à admissão hospitalar, está associada à presença de eventos adversos cardiovasculares em pacientes com ou sem diabetes. OBJETIVO: Avaliar o valor prognóstico da hiperglicemia de estresse na evolução intra-hospitalar de pacientes admitidos por SCA. MÉTODOS: Foram incluídos 152 pacientes admitidos, entre setembro de 2005 e fevereiro de 2010, em unidade de dor torácica de hospital terciário com diagnóstico de SCA, que apresentavam valor da glicemia laboratorial na admissão. O grupo I foi formado pelos pacientes com hiperglicemia de estresse, definida por glicemia na admissão > 126 mg/dL em não diabéticos e > 200 mg/dL nos diabéticos, e o grupo II pelos pacientes com níveis glicêmicos inferiores aos níveis estabelecidos. Analisou-se a associação da hiperglicemia e evolução intra-hospitalar. RESULTADOS: A hiperglicemia de estresse associou-se a complicações intra-hospitalares, aumento da idade e gênero feminino. Na análise multivariada, apenas gênero feminino (OR = 2,04; IC95% 1,03 - 4,06, p = 0,007) e complicações intra-hospitalares (OR = 3,65; IC95% 1,62 - 8,19, p = 0,002) se associaram de forma independente à hiperglicemia na admissão. CONCLUSÃO: A hiperglicemia de estresse é fator preditivo independente para complicações intra-hospitalares após SCA em pacientes diabéticos ou não. Os resultados alertam para a necessidade de avaliarmos a glicemia na admissão em todos os pacientes admitidos por SCA, incluindo os não diabéticos, com o intuito de identificarmos os indivíduos com maior risco de complicações.

BACKGROUND: In acute coronary syndrome (ACS), admission hyperglycemia is associated with adverse cardiovascular events in diabetic and nondiabetic patients. OBJECTIVE: To assess the prognostic value of stress hyperglycemia for the in-hospital outcome of patients admitted due to ACS. METHODS: This study included 152 patients admitted to the chest pain unit of a tertiary hospital diagnosed with ACS, who had admission blood glucose data, from September 2005 to February 2010. Group I comprised patients with stress hyperglycemia, defined as admission blood glucose concentration > 126 mg/dL for nondiabetic individuals and admission blood glucose concentration > 200 mg/dL for diabetic individuals. Group II was formed by patients with admission blood glucose concentration lower than those established. The association of hyperglycemia and in-hospital outcome was assessed. RESULTS: Stress hyperglycemia associated with in-hospital complications, age increase and female sex. On multivariate analysis, only female sex (OR = 2.04; 95% CI: 1.03 - 4.06; p = 0.007) and in-hospital complications (OR = 3.65; 95% CI: 1.62 - 8.19; p = 0.002) associated independently with admission hyperglycemia. CONCLUSIONS: Stress hyperglycemia is an independent predictive factor for in-hospital complications after ACS in diabetic and nondiabetic patients. The results highlight the need to assess admission blood glucose concentration in all patients admitted due to ACS, including nondiabetic ones, aiming at identifying those at higher risk for complications.

Adverse events among HIV/MDR-TB co-infected patients receiving antiretroviral and second line anti-TB treatment in Mumbai, India.

BACKGROUND: Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings. METHODS: Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE. RESULTS: Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5-42) and the median duration of anti-TB treatment was 10 months (range 0.5-30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen. CONCLUSIONS: AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment.

Treatment outcomes in a cohort of patients with chronic hepatitis B and human immunodeficiency virus co-infection in Mumbai, India.

Treatment experiences with patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in resource-limited settings remain poorly documented. This study aimed to evaluate the treatment outcomes in a cohort of HIV/HBV co-infected individuals receiving tenofovir/lamivudine (TDF/3TC)-based antiretroviral therapy (ART) in a programmatic setting in Mumbai, India. Additionally, a cross-sectional laboratory study was carried out measuring serologic and virologic parameters. A total of 57 patients who received TDF/3TC were included in the study. Of these, 52 (91%) were male and the mean age was 38.7 years. The median follow-up period was 16.8 months (IQR:7.9-37.9). Forty-three patients were included in the cross-sectional laboratory study, of whom 38 (67%) were HBeAg(+) positive. Four patients had serum HBsAg conversion to negative and had developed anti-HBs-antibodies. HBV-DNA became undetectable (<1.3 log10 copies/ml or <20 IU/ml) in 35.5% and 75% of the HBeAg(+) and HBeAg(-) patients, respectively. Overall, 46.5% of patients had undetectable HBV-DNA and 90.7% had adequately suppressed HBV-DNA (<3.3 log10 copies/ml or <2000 IU/ml). The median reduction in serum HBV-DNA was 6 log10 copies/ml. In 29 patients (63%) HIV viral load was undetectable. Outcomes included seven (12%) deaths, four (7%) lost to follow-up, one (2%) transferred out and 45 (79%) alive and on treatment. In conclusion, good treatment outcomes were achieved in a cohort of HIV/HBV co-infected patients in India. In regions with a high HIV/HBV burden, all HIV-infected individuals should be tested for chronic hepatitis B. A TDF/3TC-backbone could be considered as first-line standardized ART regimen in these settings.

Ambulatory multi-drug resistant tuberculosis treatment outcomes in a cohort of HIV-infected patients in a slum setting in Mumbai, India.

BACKGROUND: India carries one quarter of the global burden of multi-drug resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV. Despite this reality, provision of treatment for MDR-TB is extremely limited, particularly for HIV-infected individuals. Médecins Sans Frontières (MSF) has been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the first report of treatment outcomes among HIV-infected MDR-TB patients in India. METHODS: HIV-infected patients with suspected MDR-TB were referred to the MSF-clinic by public Antiretroviral Therapy (ART) Centers or by a network of community non-governmental organizations. Patients were initiated on either empiric or individualized second-line TB-treatment as per WHO recommendations. MDR-TB treatment was given on an ambulatory basis and under directly observed therapy using a decentralized network of providers. Patients not already receiving ART were started on treatment within two months of initiating MDR-TB treatment. RESULTS: Between May 2007 and May 2011, 71 HIV-infected patients were suspected to have MDR-TB, and 58 were initiated on treatment. MDR-TB was confirmed in 45 (78%), of which 18 (40%) were resistant to ofloxacin. Final treatment outcomes were available for 23 patients; 11 (48%) were successfully treated, 4 (17%) died, 6 (26%) defaulted, and 2 (9%) failed treatment. Overall, among 58 patients on treatment, 13 (22%) were successfully treated, 13 (22%) died, 7 (12%) defaulted, two (3%) failed treatment, and 23 (40%) were alive and still on treatment at the end of the observation period. Twenty-six patients (45%) experienced moderate to severe adverse events, requiring modification of the regimen in 12 (20%). Overall, 20 (28%) of the 71 patients with MDR-TB died, including 7 not initiated on treatment. CONCLUSIONS: Despite high fluoroquinolone resistance and extensive prior second-line treatment, encouraging results are being achieved in an ambulatory MDR-T- program in a slum setting in India. Rapid scale-up of both ART and second-line treatment for MDR-TB is needed to ensure survival of co-infected patients and mitigate this growing epidemic.

Interactions of anionic dyes with silica-aminopropyl 1. A quantitative multivariate analysis of equilibrium adsorption and adsorption Gibbs free energies.

In this work silica-aminopropyl (Sil-NH2) was synthesized and employed to evaluate the quantitative roles of temperature, pH, dye concentration, and Hg(II) or anionic surfactant SDB interferents in the adsorptions of blue and red remazol dyes in aqueous medium using four distinct 2(4) factorial designs. The results were analyzed statistically using multiple regressions, Student's t-test, analysis of variance, and F-test. Polynomial modelings were used to define the most important factors affecting dye adsorption. The results indicate that the principal effects of dye concentration and pH, as well as most of the interactions of all factors, are statistically very important in relation to the equilibrium adsorption quantities. However, the adsorption Gibbs free energies are influenced, in general, only by pH, dye concentration, and some binary interactions. Temperature changes do not affect the deltaG values significantly.