Fungicides as a risk factor for the development of neurological diseases and disorders in humans: a systematic review.

Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As fungicides are used widely in Brazil, it is necessary to gather evidence to support actions aimed at safely using of these chemicals. We investigated through a systematic review of publications on the use of fungicides and consequences of exposure related to nervous system diseases or neurological disorders in humans. The protocol review was registered on PROSPERO and followed the guidelines of the PRISMA-Statement. As far as it is known, there is no apparent systematic review in the literature on this topic. The search was comprised of the following databases: PubMed; Web of Science; Scopus and EMBASE, using groups of Mesh terms and strategies specific to each database. Thirteen articles were selected for this review. Regarding the substances analyzed in the studies, some reported the use of fungicides in general, without separating them by type, while others summarized the categories of all pesticides by their function (insecticides, herbicides, fungicides, etc.) or chemical class (dithiocarbamate, dicarboximide, inorganic, etc.). However, most of the articles referred to fungicides that contain the metal manganese (Mn) in their composition. As for neurological disorders, articles addressed Parkinson's disease (PD), neurodevelopmental outcomes, extrapyramidal syndrome resembling PD, cognitive disorders, depression, neural tube defects, motor neurone disease, and amyotrophic lateral sclerosis. Most investigations pointed to exposure to fungicides, mainly maneb and mancozeb, leading to the development of at least one neurological disease, which suggests the need for further multicentric clinical trials and prospective studies for greater clarity of the research problem.

Combination of Conventional Drugs with Biocompounds Derived from Cinnamic Acid: A Promising Option for Breast Cancer Therapy.

Despite the options available for breast cancer (BC) therapy, several adverse effects and resistance limit the success of the treatment. Furthermore, the use of a single drug is associated with a high failure rate. We investigated through a systematic review the in vitro effects of the combination between conventional drugs and bioactive compounds derived from cinnamic acid in BC treatment. The information was acquired from the following databases: PubMed, Web of Science, Embase, Scopus, Lilacs and Cochrane library. We focused on "Cinnamates", "Drug Combinations" and "Breast neoplasms" for publications dating between January 2012 and December 2022, based on the PRISMA statement. The references of the articles were carefully reviewed. Finally, nine eligible studies were included. The majority of these studies were performed using MCF-7, MDA-MB-231, MDA-MB-468 and BT-20 cell lines and the combination between cisplatin, paclitaxel, doxorubicin, tamoxifen, dactolisib and veliparib, with caffeic acid phenethyl ester, eugenol, 3-caffeoylquinic acid, salvianolic acid A, ferulic acid, caffeic acid, rosmarinic acid and ursolic acid. The combination improved overall conventional drug effects, with increased cytotoxicity, antimigratory effect and reversing resistance. Combining conventional drugs with bioactive compounds derived from cinnamic acid could emerge as a privileged scaffold for establishing new treatment options for different BC types.

Plants of the Phytolaccaceae family with antimicrobial activity: A systematic review.

Phytolaccaceae is a plant family of the order Caryophyllales, which includes species used in traditional medicine to treat diseases. The purpose of this study was to investigate Phytolaccaceae family plants with potential antimicrobial action, through a systematic review. The study was conducted following the criteria of PRISMA protocol. The search was performed in the electronic databases PubMed, Web of Science, Scopus, and LILACS, in March 2021. The search strategy used free descriptors and terms, limiting articles to the English language, regardless of publication year. The risk of bias and the quality of publications were based on the CONSORT checklist, modified for in vitro studies and SYRCLE's RoB tool for in vivo study. Five independent judges performed quality assessments of publications and risk of bias analysis. Ninety-five publications were retrieved from the databases and, after screening and eligibility criteria, 22 articles remained, from 1998 to 2019. In the selected studies, the plants were obtained from eight countries. In vivo and in vitro studies of extracts from the Phytolaccaceae family plants, evaluating antibacterial (8 publications), antifungal (8), anti-Trypanosoma (2), anti-Leishmania (2), antiviral (1), and antiamoebic (1) activities, are included. The plant species identified belong to genera Petiveria, Phytolacca, Gallesia, Trichostigma, and Seguieria. The risk of bias in the 22 publications both in vitro and in vitro was suboptimal. The evidence obtained showed that the Phytolaccaceae family, a source of plants with antimicrobial action, can serve as a basis for the creation of new herbal medicines, expanding the possibility of treatment for infectious diseases and stimulating their preservation and biodiversity. However, more high-quality studies are needed to establish the clinical efficacy of the plant.

Systematic review of disulfiram as an antibacterial agent: what is the evidence?

The objective of this systematic review was to retrieve and examine published studies related to in vitro and in vivo evaluation of disulfiram for the treatment of bacterial infections. Five scientific databases (PubMed, Embase, Scopus, Web of Science, and Latin American and Caribbean Health Sciences Literature) were searched to retrieve the maximum literature regarding the study's aim. The search strategy retrieved a total of 870 studies, of which 31 were included and 19 approached disulfiram as the primary aim and 12 included it as a secondary finding from other investigational objectives. The evidence pointed out five main aspects of pre-clinical testing regarding disulfiram antibacterial activity, namely spectrum of antimicrobial action, drug combinations, intracellular studies, animal studies and bacterial targets. Findings to emerge from this study are the observed potential of disulfiram as a non-antibiotic drug being proposed as a potential drug to contribute to the treatment of bacterial diseases usually with few treatment alternatives in the context of drug resistance. We evaluated the potency and selectivity of disulfiram, which indeed until now shows potential to be explored for use as an adjunctive chemical to antimicrobial ones. Even with the level of evidence being reserved, the potential of combining disulfiram with other drugs, already used or new to be used for the treatment of mycobacterial diseases, as well as its likely immunomodulatory effect, deserve to be further investigated. Furthermore, the copper-dependent mode of action in Gram-positive bacteria is an alternative to be explored in drug design or repurposing of chemicals.

Asymptomatic Neurosyphilis in HIV infected patients at a Brazilian HIV and AIDS specialized service: a cross sectional study.

BACKGROUND: Many human immunodeficiency virus (HIV) and syphilis co-infected patients are not diagnosed, which may evolve into asymptomatic neurosyphilis (ANS). We studied the occurrence of ANS an HIV-infected population. METHODS: This was a cross-sectional study of cerebrospinal fluid (CSF) samples collected from patients co-infected with HIV and Treponema pallidum. Social-demographic and clinical-laboratory characteristics were studied. RESULTS: Of the 348 patients infected with HIV, 33 (9.5%) had reagent treponemic and non-treponemic tests. CSF was collected from 19 asymptomatic patients. Of these, 8 (42.1%) presented with laboratory alterations suggestive of ANS. CONCLUSION: Social-demographic and clinical-laboratory variables should be considered for the indication of CSF collection.

The anti-Leishmania potential of bioactive compounds derived from naphthoquinones and their possible applications. A systematic review of animal studies.

Leishmaniasis affects millions of people worldwide, and available treatments have severe limitations. Natural and derivative products are significant sources of innovative therapeutic agents. Naphthoquinones are natural or synthetic chemical compounds with broad biological activity. This systematic review aimed to evaluate the potential anti-Leishmania activity of bioactive compounds derived from naphthoquinones in animal models. Conducted in accordance with PRISMA guidelines, two blocks of MeSH terms were assembled: group I, Leishmania OR Leishmaniasis; group II, Atovaquone OR Lapachol OR Beta lapachone OR Naphthoquinones. The search was performed on PubMed, Web of Science, SCOPUS, EMBASE, and Lilacs databases. Twenty-four articles were retrieved and submitted for quality assessment using the SYRCLE critical appraisal tool. The in vivo anti-Leishmania potential of naphthoquinones was evaluated in visceral and cutaneous leishmaniasis using several measurement parameters. Analyzed compounds varied in structure, association with reference drugs, and encapsulation using a drug delivery system. The study design, including treatment protocol, differed between studies. The findings of the studies in this systematic review indicate the anti-Leishmania potential of naphthoquinones in vivo, with different treatment regimens directed against different Leishmania species. The employed drug delivery systems improve the results concerning selectivity, distribution, and required therapeutic dose. The immunomodulatory action was shown to be beneficial to the host, favoring an adequate immune response against infection by Leishmania parasites since it favored Th1 responses. All studies presented a moderate to high risk of bias. These findings suggest that more studies are needed to assess the overall effectiveness and safety of these treatments.

Asymptomatic Neurosyphilis in HIV infected patients at a Brazilian HIV and AIDS specialized service: a cross sectional study

ABSTRACT Background: Many human immunodeficiency virus (HIV) and syphilis co-infected patients are not diagnosed, which may evolve into asymptomatic neurosyphilis (ANS). We studied the occurrence of ANS an HIV-infected population. Methods: This was a cross-sectional study of cerebrospinal fluid (CSF) samples collected from patients co-infected with HIV and Treponema pallidum. Social-demographic and clinical-laboratory characteristics were studied. Results: Of the 348 patients infected with HIV, 33 (9.5%) had reagent treponemic and non-treponemic tests. CSF was collected from 19 asymptomatic patients. Of these, 8 (42.1%) presented with laboratory alterations suggestive of ANS. Conclusion: Social-demographic and clinical-laboratory variables should be considered for the indication of CSF collection.

Prevalência e características do consumo de álcool entre universitários / Prevalence and characteristics of alcohol consumption among university students

O objetivo desta pesquisa foi conhecer o consumo de álcool entre estudantes de uma universidade no sul do Brasil. Realizou-se estudo transversal, quantitativo, com acadêmicos de Biomedicina (n=134) por meio do instrumento Alcohol Use Disorders Identification Test, versão traduzida. Utilizou-se teste estatístico para verificar associação entre variáveis categóricas. Houve predomínio de mulheres, de 18 a 21 anos. Verificou-se início precoce de consumo de álcool, anterior à chegada à universidade, vinculado a festas e companhia de amigos. Após ingressar no curso, 41,04% disseram ter aumentado a ingestão (p=0,0001). Quanto ao risco, 72,38% foram classificados como consumidores de baixo risco, 19,39% como de risco, 5,98% de alto risco e 2,25% dependentes. Ser acadêmico da área da saúde e conhecer os prejuízos associados ao consumo do álcool não favorece a adoção de um estilo de vida saudável. Evidencia-se que o uso de álcool não é exclusivamente influenciado pelo conhecimento dos riscos.

This research aimed to know about alcohol consumption among students at a university in southern Brazil. A cross-sectional, quantitative study was carried out with Biomedicine students (n = 134) using the Alcohol Use Disorders Identification Test, translated version. Statistical tests were used to verify the association between categorical variables. There was a predominance of women, aged 18 to 21 years. There was an early onset of alcohol consumption, prior to arrival at the university, linked to parties and the company of friends. After entering the course, 41.04% said they had increased their intake (p = 0.0001). As for risk, 72.38% were classified as low risk consumers, 19.39% as risk consumers, 5.98% high risk and 2.25% dependent. Being a health academic and knowing the losses associated with alcohol consumption does not favor the adoption of a healthy lifestyle. It is evident that the use of alcohol is not exclusively influenced by the knowledge of the risks.

Correlation between serology and nucleic acid amplification test in blood donors who are reactive for hepatitis B virus, hepatitis C and human immunodeficiency virus and evaluation of the epidemiological profile of infected people in blood centers in the State of Paraná.

OBJECTIVES: To compare the results of conventional serological tests and molecular technology (NAT, Nucleic Acid Amplification Test), identify donors in the diagnostic window period, and determine the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) among the samples of blood donors blocked by serological screening. METHODS: A retrospective cross-sectional study was carried out by analyzing blood donor information contained in the database of 20 blood centers in Paraná, from January 2018 to December 2019. RESULTS: A total of 1,496 blood bags were reactive for HBV, HCV, or HIV in serological and/or NAT tests. The 20th Regional Health (RH) Unit had the greatest number of unfit individuals with altered screening for the three infections, with a prevalence of 0.70%. The lowest number of blocked blood donors occurred in the 15th RH, with a prevalence of 0.08%. The highest prevalence of HBV occurred in the 8th RH, with a reagent serology of 0.34% and a positive NAT of 0.17%. For HCV, the prevalence for reagent serology was 0.28%, while that for NAT was 0.02%, which occurred in the 20th RH. For HIV and for NAT, the prevalence of blood donors with positive serology occurred in the 20th RH, at 0.25% and 0.04%, retrospectively. The 13th RH had the highest prevalence of HIV in relation to NAT, that is, conventional serology in concomitance with NAT technology, at 0.07%. During the 2-year period, only 1 reactive donor in the 9th was found for NAT (HBV), in a diagnostic window. CONCLUSION: In Paraná's blood centers, the inability to donate due to HBV, HCV, and HIV, occurred mainly in initial donors, men, those with >8 years of education, aged 16-45 years, married, and O positive. The most affected regions were located in the west and northwest of Paraná. Most of the results showed a discrepancy between the methodologies used.

Genetic variations in the human immune system influence susceptibility to tegumentary leishmaniasis: a systematic review and meta-analysis.

OBJECTIVES: The outcomes of tegumentary leishmaniasis (TL) rely on a complex interaction between the host immune system and the parasite. This study assessed the influence of polymorphisms in immune-related genes on TL. METHODS: Web of Science, Scopus, PubMed, and Embase databases were searched systemically. The meta-analysis used a retrospective model in examining alleles, heterozygotes, and homozygotes. A quality assessment and an analysis of cumulative evidence were performed. RESULTS: A total of 29 genes (encoding for cytokines, chemokines, and other immune receptors) and 84 polymorphisms were analyzed. The IL-1ß_rs16944 (OR = 1.341, p = 0.003), TNF-α_rs1800629 (OR = 3.804, p = 0.004), MIF_rs755622 (OR = 3.357, p = 0.001), and INF- γ_rs243056 (OR = 1.670, p = 0.028) polymorphisms were speculated as risk factor for TL. They decrease the expression of the corresponding genes crucial for TL control. The quality assessment score was approximately 50%, suggesting the need for a clear method and polymorphism characterization for further comparison. The relevant risk of bias and other considerations resulted in low and moderate cumulative evidence confidence. CONCLUSIONS: IL-1ß_rs16944, TNF-α_rs1800629, MIF_rs755622, and INF-γ_rs2430561 polymorphisms were speculated as risk factor for TL, corroborating that IL-1ß, TNF-α, INF-γ, and MIF are involved in the TL pathogenesis.

Padrão prescritivo de medicamentos para hipertensão arterial sistêmica na atenção primária em saúde: revisão sistemática e meta-análise / Pattern prescription drugs for systemic hypertension in primary health care: systematic review and meta-analysis

Investigamos publicações científicas sobre o padrão prescritivo de medicamentos para hipertensão arterial sistêmica e uso de diretrizes na atenção primária em saúde por revisão sistemática e meta-análise. Os artigos foram selecionados nas bases de dados PubMed, Web of Science e LILACS, de acordo com as declarações PRISMA, de 2004 a 2020. A revisão sistemática mostrou um padrão de prescrição superior para terapia combinada (52,9%). A metanálise confirmou a superioridade para a terapia combinada (OR 1,76; IC 1,29 - 2,41). Foi observada maior prevalência de monoterapia no estudo Sueco (98%) e terapia combinada no Nigeriano (98%). Maior frequência prescritiva de inibidores da enzima de conversão da angiotensina em Trinidade (64%); diuréticos (64%), betabloqueadores (63%) e bloqueadores dos canais de cálcio (53%) na Nigéria; e bloqueadores dos receptores da angiotensina (43%) em Portugal. Quanto ao uso das diretrizes, 53% dos estudos relataram a sua utilização na prescrição de anti-hipertensivos na atenção primária em saúde.

We investigated scientific publications on the prescription pattern of systemic hypertension drugs and use of guidelines in primary health care by systematic review and meta-analysis. Articles were selected in the PubMed, Web of Science and LILACS databases, according to the PRISMA statements, from 2004 to 2020. The systematic review showed a higher prescription pattern for combination therapy (52,9%). The meta-analysis confirmed the superiority of prescription for combination therapy (OR 1.76, CI 1.29 - 2.41). Was observed higher monotherapy prevalence in the Swedish study (98%) and combined therapy in Nigerian (98%). Higher frequency prescriptive of angiotensin-converting enzyme inhibitors in Trinidad (64%); diuretics (64%), beta blockers (63%), and calcium channel blockers (53%) in Nigeria; and angiotensin-receptor blockers (43%) in Portugal. Regarding the use of guidelines, 50% the studies reported their use for the prescription of antihypertensive in primary health care.

Effect of essential oils on Leishmania amazonensis: a systematic review.

This systematic review investigated the evidence for the therapeutic potential of essential oils (EOs) against Leishmania amazonensis. We searched available scientific publications from 2005 to 2019 in the PubMed and Web of Science electronic databases, according to PRISMA statement. The search strategy utilized descriptors and free terms. The EOs effect of 35 species of plants identified in this systematic review study, 45.7% had half of the maximal inhibitory concentration (IC50) 10 < IC50 ⩽ 50 µg mL-1 and 14.3% had a 10 < IC50µg mL-1 for promastigote forms of L. amazonensis. EOs from Cymbopogon citratus species had the lowest IC50 (1.7 µg mL-1). Among the plant species analyzed for activity against intracellular amastigote forms of L. amazonensis, 39.4% had an IC50 10 < IC50 ⩽ 50 µg mL-1, and 33.3% had an IC50 10 < IC50µg mL-1. Aloysia gratissima EO showed the lowest IC50 (0.16 µg mL-1) for intracellular amastigotes. EOs of Chenopodium ambrosioides, Copaifera martii and Carapa guianensis, administered by the oral route, were effective in reducing parasitic load and lesion volume in L. amazonensis-infected BALB/c mice. EOs of Bixa orellana and C. ambrosioides were effective when administered intraperitoneally. Most of the studies analyzed in vitro and in vivo for the risk of bias showed moderate methodological quality. These results indicate a stimulus for the development of new phytotherapy drugs for leishmaniasis treatment.

Effects of Highly Diluted Drugs on Experimental Infection with Trypanosoma cruzi In Vivo: Systematic Review.

Objective: To investigate, through a systematic review, the effects of the use of highly diluted drugs in the treatment of experimental infection with Trypanosoma cruzi. Design: The authors searched for scientific publications in the databases PubMed, Web of Science, SCOPUS, LILACS, and the Google Scholar search system, from 2000 to 2018, following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. According to the criteria established, a total of 22 studies were included. Settings/Location: The study took place at the State University of Maringá, Maringá, PR, Brazil. Subjects: Male mice (Mus musculus) or rats (Rattus norvegicus). Interventions: Highly diluted drugs. Outcome measures: The parameters evaluated in the studies were parasitological, clinical, immunological, histopathological and hematological. Results: The studies demonstrated that the effects of highly diluted drugs are related to their dynamizations, treatment regimen, and host susceptibility to T. cruzi infection, and depend on the initial information transmitted to the treated organism, making this information the "model" of how the treated organism will react. Regardless of the mechanism of action, these drugs provide a decrease in inflammation, which is one of the central phenomena of the pathogenesis of T. cruzi infection. Conclusions: This systematic review brings out the importance of the T. cruzi infection model as a reliable and valid model for studying different effects produced by highly diluted drugs. Considering the findings and in a broader perspective, this study contributes to considering these drugs as a possible way of dealing with "treatment" in general, presents the need to reexamine the biochemical model and develop a model for the effect of high dilutions in general, as well as for the treatment of parasitic infections.

Minimum Bactericidal Concentration Techniques in Mycobacterium tuberculosis: A Systematic Review.

Minimum bactericidal concentration (MBC) assay is an accepted parameter for evaluating new antimicrobial agents, and it is frequently used as a research tool to provide a prediction of bacterial eradication. To the best of our knowledge, there is no standardization among researchers regarding the technique used to detect a drug's MBC in Mycobacterium tuberculosis. Thus, the aim of this systematic review is to discuss the available literature in determining a drug's MBC in M. tuberculosis, to find the most commonly used technique and standardize the process. A broad and rigorous literature search of three electronic databases (PubMed, Web of Knowledge, and LILACS) was performed according to the PRISMA statement. We considered studies that were published from January 1, 1990 to February 19, 2019. Google Scholar was also searched to increase the number of publications. We searched for articles using the MeSH terms "microbiological techniques," "Mycobacterium," "antibacterial agents." In addition, free terms were used in the search. The search yielded 6,674 publications. After filter application, 5,348 publications remained. Of these, we evaluated the full text of 187 publications. By applying the inclusion criteria, 69 studies were included in the present systematic review. In the literature analyzed, a great variety in the techniques used to determine a drug's MBC in M. tuberculosis was observed. The most common variability is related to the culture media used, culture incubation time, and the percentage of bacterial death for the drug to be considered as bactericidal. The most commonly used technique for drug's MBC determination was carried out using the drug's minimum inhibitory concentration (MIC) assay. Aliquots from prior MIC values were subcultured in Middlebrook agar and incubated for 4 weeks at 35°C for determining the colony forming unit (CFU) with relevance to detect 99.9% bacilli killed or reduction in 3 log10 viable bacilli.

PROFILE OF HCV GENOTYPES AND HIV-SUBTYPES AMONG HIV-COINFECTED PATIENTS IN SOUTHERN BRAZIL.

BACKGROUND: Hepatitis B and C virus (HBV and HCV) are the two most common infections among human immunodeficiency virus (HIV)-infected patients. OBJECTIVE: To identify the frequency of HIV subtypes and HCV genotypes in HIV-coinfected patients. METHODS: A cross-sectional and retrospective study was carried out into two reference centers in Southern Brazil between January 1, 2002 and June 30, 2016. The Abbott Real Time HCV Genotype II system was used for routine diagnostics to determine the HCV genotype based on dual-target real-time PCR. Proviral HIV-1 RNA was extracted from serum samples and fragments of the pol gene were generated by PCR. The HIV-1 PT and RT gene sequences were submitted to Maximum Likelihood Phylogenetic analysis by collecting reference sequences from the HIV-1 group M subtype of the Los Alamos database. RESULTS: During the study period, 3340 patients with HIV were diagnosed at both referral centers, of which 4.97% (166/3340) had HBV and/or HCV coinfection. Seroprevalence of HIV-HBV, HIV-HCV and HIV-HBV-HCV was 37.4%, 58.4%, and 4.2%, respectively. HIV-HCV-coinfected patients had a lower median nadir CD4+ T-cell count when compared to HIV-HBV-coinfected patients (P=0.01). Among those coinfected with HCV, HCV-1 (HCV-1) and HCV-3 (HCV-3) genotypes were the most prevalent, being detected in 73.8% and 21.4%, respectively. Among the HCV-1 coinfected patients, 79.3% and 20.1% had subtypes 1a and 1b, respectively. HIV subtype B was the most prevalent in HIV-coinfected patients. There was no significant difference regarding nadir CD4+ T-cell count and HIV viral load when compared to coinfected with HCV-1 with HCV-3, as well as those co-infected with HCV-1a with HCV-1b. CONCLUSION: In the present study, a higher frequency of subtype B of HIV and HCV-1 were found in HIV-coinfected patients. Further larger-scale and long-term studies are needed to better understand the effect of HCV genotypes in HIV-infected patients.

PCR primers designed for new world Leishmania: A systematic review.

Studies of the primers that were designed to detect New World Leishmania were systematically reviewed to report the characteristics of each target, detection limit, specificity of the primers designed and diagnostic sensibility. The papers identified in the databases PubMed and Web of Science involved 50 studies. Minicircle is the most applied target in molecular research for diagnosis, due to its high sensitivity in detecting Leishmania in different clinical samples, a characteristic that can be partially attributed to the higher number of copies of the minicircle per cell. The other molecular targets shown in this review were less sensitive to diagnostic use because of the lower number of copies of the target gene per cell, but more specific for identification of the subgenus and/or species. The choice of the best target is an important step towards the result of the research. The target allows the design of primers that are specific to the genus, subgenus or a particular species and also imparts sensitivity to the method for diagnosis. The findings of this systematic review provide the advantages and disadvantages of the main molecular targets and primers designed for New World Leishmania, offering information so that the researcher can choose the PCR system best suited to their research need. This is a timely and extremely thorough review of the primers designed for New World Leishmania.

Perfil dos genótipos do HCV e subtipos de HIV em pacientes coinfectados no Sul do Brasil / Profile of hcv genotypes and hiv-subtypes among hiv-coinfected patients in southern brazil

ABSTRACT BACKGROUND: Hepatitis B and C virus (HBV and HCV) are the two most common infections among human immunodeficiency virus (HIV)-infected patients. OBJECTIVE: To identify the frequency of HIV subtypes and HCV genotypes in HIV-coinfected patients. METHODS: A cross-sectional and retrospective study was carried out into two reference centers in Southern Brazil between January 1, 2002 and June 30, 2016. The Abbott Real Time HCV Genotype II system was used for routine diagnostics to determine the HCV genotype based on dual-target real-time PCR. Proviral HIV-1 RNA was extracted from serum samples and fragments of the pol gene were generated by PCR. The HIV-1 PT and RT gene sequences were submitted to Maximum Likelihood Phylogenetic analysis by collecting reference sequences from the HIV-1 group M subtype of the Los Alamos database. RESULTS: During the study period, 3340 patients with HIV were diagnosed at both referral centers, of which 4.97% (166/3340) had HBV and/or HCV coinfection. Seroprevalence of HIV-HBV, HIV-HCV and HIV-HBV-HCV was 37.4%, 58.4%, and 4.2%, respectively. HIV-HCV-coinfected patients had a lower median nadir CD4+ T-cell count when compared to HIV-HBV-coinfected patients (P=0.01). Among those coinfected with HCV, HCV-1 (HCV-1) and HCV-3 (HCV-3) genotypes were the most prevalent, being detected in 73.8% and 21.4%, respectively. Among the HCV-1 coinfected patients, 79.3% and 20.1% had subtypes 1a and 1b, respectively. HIV subtype B was the most prevalent in HIV-coinfected patients. There was no significant difference regarding nadir CD4+ T-cell count and HIV viral load when compared to coinfected with HCV-1 with HCV-3, as well as those co-infected with HCV-1a with HCV-1b. CONCLUSION: In the present study, a higher frequency of subtype B of HIV and HCV-1 were found in HIV-coinfected patients. Further larger-scale and long-term studies are needed to better understand the effect of HCV genotypes in HIV-infected patients.

RESUMO CONTEXTO: Os vírus das hepatites B e C (VHB e VHC) são os causadores das duas infecções mais comuns entre os pacientes infectados pelo vírus da imunodeficiência humana (HIV). OBJETIVO: Identificar a frequência dos subtipos do HIV e genótipos de VHC em pacientes coinfectados com HIV. MÉTODOS: Estudo transversal e retrospectivo realizado em dois centros de referência do Sul do Brasil, entre 1º de janeiro de 2002 e 30 de junho de 2016. O sistema Abbott Real Time HCV Genótipo II foi utilizado para diagnósticos de rotina para determinar o genótipo do HCV com base na PCR em tempo real de duplo alvo. O RNA viral do HIV-1 foi extraído de amostras de soro e fragmentos do gene pol foram obtidos por PCR. As sequências do gene PT e RT do HIV-1 foram submetidas à análise filogenética por máxima verossimilhança através da coleta de sequências de referência do subtipo M do grupo HIV-1 da base de dados Los Alamos. RESULTADOS: Durante o período do estudo, 3340 pacientes foram diagnosticados com HIV em ambos os centros de referência, dos quais 4,97% (166/3340) possuíam coinfecção com HBV e/ou HCV. A soroprevalência de HIV-HBV, HIV-HCV e HIV-HBV-HCV foi de 37,4%, 58,4% e 4,2%, respectivamente. Pacientes HIV-VHC possuíam menor nadir de células T CD4+ quando comparados aos pacientes HIV-VHB (P=0,01). Entre os pacientes HIV-VHC, os genótipos VHC-1 e VHC-3 foram os mais prevalentes, sendo encontrados em 73,8% e 21,4%, respectivamente. Entre os coinfectados com VHC-1, 79,3% e 20,1% tinham subtipos 1a e 1b, respectivamente. O subtipo B do HIV foi o mais prevalente em pacientes coinfectados. Não houve diferença significativa em relação nadir de células T CD4+ e carga viral do HIV quando comparadas os coinfectados com o VHC-1 com o VHC-3, assim como, os coinfectados com HCV-1a quando comparados com o HCV-1b. CONCLUSÃO: No presente estudo, uma maior frequência do subtipo B do HIV e do VHC-1 foram encontrados em pacientes coinfectados com HIV. Outros estudos em larga escala e a longo prazo são necessários para entender melhor o efeito dos genótipos do HCV em pacientes infectados pelo HIV.

The impact of KIR/HLA genes on the risk of developing multibacillary leprosy.

BACKGROUND: Killer-cell immunoglobulin-like receptors (KIRs) are a group of regulatory molecules able to activate or inhibit natural killer cells upon interaction with human leukocyte antigen (HLA) class I molecules. Combinations of KIR and HLA may contribute to the occurrence of different immunological and clinical responses to infectious diseases. Leprosy is a chronic neglected disease, both disabling and disfiguring, caused mainly by Mycobacterium leprae. In this case-control study, we examined the influence of KIRs and HLA ligands on the development of multibacillary leprosy. METHODOLOGY/PRINCIPAL FINDINGS: Genotyping of KIR and HLA genes was performed in 264 multibacillary leprosy patients and 518 healthy unrelated controls (238 healthy household contacts and 280 healthy subjects). These are unprecedented results in which KIR2DL2/KIR2DL2/C1/C2 and KIR2DL3/2DL3/C1/C1 indicated a risk for developing lepromatous and borderline leprosy, respectively. Concerning to 3DL2/A3/A11+, our study demonstrated that independent of control group (contacts or healthy subjects), this KIR receptor and its ligand act as a risk factor for the borderline clinical form. CONCLUSIONS/SIGNIFICANCE: Our finding suggests that synergetic associations of activating and inhibitory KIR genes may alter the balance between these receptors and thus interfere in the progression of multibacillary leprosy.

Laringotraqueoscopia flexível na decanulação de pacientes traqueostomizados: otimização de segurança para o paciente / Flexible laringotracheoscopy in de-cannulation of tracheostomized patients: safety improvements for the patient

Avaliar a decanulação utilizando a laringotraqueoscopia flexível visando o reconhecimento das lesões laringotraqueais não diagnosticadas quando utilizados somente critérios clínicos. Participaram do estudo 100 pacientes, com idade entre 18 e 80 anos, traqueostomizados, com indicação de decanulação que foram submetidos à oclusão da cânula por 03 minutos para avaliar fonação e ventilação seguido da realização do exame. Foi comparada a indicação de decanulação por critérios clínicos com o diagnóstico de lesões laringotraqueais reconhecidas após o término da laringotraqueoscopia flexível. Os critérios de Myer-Cotton foram utilizados como referencial para classificação de doença laringotraqueal. Resultados: 62 (62%) pacientes apresentaram critérios clínicos para decanulação, porém, com doença laringotraqueal identificada pela laringotraqueoscopia flexível. Dentre estes, oito (8%) considerados aptos à decanulação baseados nos critérios clínicos apresentaram contraindicação à retirada da cânula. Apenas 26 (26%) pacientes não apresentaram doença laringotraqueal; 11 (11%) não foram decanulados por não preencherem critérios clínicos e endoscópicos. A laringotraqueoscopia flexível reconheceu doença laringotraqueal nos pacientes que preenchiam critérios clínicos para retirada da cânula traqueal. Este exame como rotina na avaliação de pacientes preenchendo critérios de decanulação mostrou-se útil e seguro.

To evaluate de-cannulation by flexible laringeotracheoscopy for laringeotracheal lesions which are not diagnosed by clinical criteria. One hundred tracheostomized patients, aged between 18 and 80 years old, with indication of de-cannulation submitted to occlusion of the cannula during three minutes to evaluate fonation and ventilation, followed by tests. De-cannulation by clinical criteria was compared with diagnosis of larigeotracheal lesions after the end of flexible laringeotracheoscopy. Myer-Cotton criteria were employed, a referential for the classification of laringeotracheal diseases. Sixty-two (62%) patients had clinical criteria for de-cannulation but with laringeotracheal disease identified by flexible largineotracheoscopy. Eight (8%) could be de-cannulated, based on clinical criteria which counterindicated the removal of the cannula. Only twenty-six (26%) did not present a laringeotracheal disease. Eleven (11%) were not de-cannulated since they did not comply with clinical and endoscopy criteria. Flexible laringeotracheoscopy acknowledged the laringeotracheal disease in patients who complied with clinical criteria for the removal of tracheal cannula. The test, as a routine in patients´ evaluation complying with de-cannulation criteria, was useful and safe.

Hepatitis B prophylaxis in newborns: A cross-sectional study of 7-year attendance in a public hospital of Brazil.

BACKGROUND: Children with vertically transmitted hepatitis B virus develop chronic infection up to 90% of the time. This study aimed to verify the prevalence of hepatitis B surface antigen (HBsAg) in pregnant patients treated in a Brazilian public hospital and analyze the prophylactic measures in newborns. METHODS: A cross-sectional study was conducted by collcting data in the electronic charts of patients who attended the obstetric and maternity departments, from January 1, 2010, to December 31, 2016, and evaluating the results of pregnant women's HBsAg, prophylaxis in newborns, and clinical follow-up. The data were tabulated and analyzed using Microsoft Excel software. RESULTS: Among the 7,763 participating patients, 109 were reactive to HBsAg, and 3 were indeterminate. However, only 28 had correct information on HBV prophylaxis with the parturient and newborn in the chart, and only 16 completed the follow-up. CONCLUSIONS: Most of the HBsAg-positive pregnant women (75%) did not have prophylactic information in the charts, and almost 50% of the pregnant women and newborns who had appropriate prophylaxis did not return for medical follow-up. Failure of prophylaxis can promote vertical/perinatal transmission of hepatitis B virus in newborns of mothers who are HBsAg positive.