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Studies on the interaction sites of peptide toxins and ion channels typically involve site-directed mutations in toxins. However, natural mutant toxins exist among them, offering insights into how the evolutionary process has conserved crucial sequences for activities and molecular target selection. In this study, we present a comparative investigation using electrophysiological approaches and computational analysis between two alpha toxins from evolutionarily close scorpion species of the genus Tityus, namely, Tst3 and Ts3 from T. stigmurus and T. serrulatus, respectively. These toxins exhibit three natural substitutions near the C-terminal region, which is directly involved in the interaction between alpha toxins and Nav channels. Additionally, we characterized the activity of the Tst3 toxin on Nav1.1-Nav1.7 channels. The three natural changes between the toxins did not alter sensitivity to Nav1.4, maintaining similar intensities regarding their ability to alter opening probabilities, delay fast inactivation, and induce persistent currents. Computational analysis demonstrated a preference for the down conformation of VSD4 and a shift in the conformational equilibrium towards this state. This illustrates that the sequence of these toxins retained the necessary information, even with alterations in the interaction site region. Through electrophysiological and computational analyses, screening of the Tst3 toxin on sodium isoform revealed its classification as a classic α-NaTx with a broad spectrum of activity. It effectively delays fast inactivation across all tested isoforms. Structural analysis of molecular energetics at the interface of the VSD4-Tst3 complex further confirmed this effect.
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Venenos de Escorpião , Escorpiões , Venenos de Escorpião/química , Venenos de Escorpião/genética , Animais , Brasil , Humanos , Xenopus laevis , Ativação do Canal Iônico/efeitos dos fármacos , Sequência de Aminoácidos , Animais PeçonhentosRESUMO
Introduction: The risk of progression to tuberculosis disease is highest within the first year after M. tuberculosis infection (TBI). We hypothesize that people with newly acquired TBI have a unique cytokine/chemokine profile that could be used as a potential biomarker. Methods: We evaluated socio-demographic variables and 18 cytokines/chemokines in plasma samples from a cohort of people deprived of liberty (PDL) in two Colombian prisons: 47 people diagnosed with pulmonary TB, 24 with new TBI, and 47 non-infected individuals. We performed a multinomial regression to identify the immune parameters that differentiate the groups. Results: The concentration of immune parameters changed over time and was affected by the time of incarceration. The concentration of sCD14, IL-18 and IP-10 differed between individuals with new TBI and short and long times of incarceration. Among people with short incarceration, high concentrations of MIP-3α were associated with a higher risk of a new TBI, and higher concentrations of Eotaxin were associated with a lower risk of a new TBI. Higher concentrations of sCD14 and TNF-α were associated with a higher risk of TB disease, and higher concentrations of IL-18 and MCP-1 were associated with a lower risk of TB disease. Conclusions: There were cytokines/chemokines associated with new TBI and TB disease. However, the concentration of immune mediators varies by the time of incarceration among people with new TBI. Further studies should evaluate the changes of these and other cytokines/chemokines over time to understand the immune mechanisms across the spectrum of TB.
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Mycobacterium tuberculosis , Tuberculose , Humanos , Citocinas , Interleucina-18 , Receptores de LipopolissacarídeosRESUMO
Resumen La infección tuberculosa latente (TL) afecta al 23% de la población y constituye un reservorio de tuberculosis (TBC) ya que 10% progresa hacia una TBC. La TL se reconoce por pruebas como la tuberculina (PPD o TST) y los ensayos de liberación de Interferón gama (IGRAs). La sensibilidad de IGRAs (versión Quantiferon TB Gold plus) es 94% y del PPD 77%. La especificidad del Quantiferon TB Gold Plus es 97% y del PPD 68%. El valor predictivo de progresión a TBC activa de estas pruebas es bajo (PPD: 1,5%, IGRAs: 2,7%) pero mejora en personas de alto riesgo de contraer TBC (PPD: 2,4%, IGRAs: 6,8%). Las personas con pruebas negativas que posteriormente presentan viraje (prueba positiva) tienen mayor riesgo de progresión a TBC activa. Estas pruebas son útiles en el seguimiento de contactos intradomiciliarios, extranjeros de países con altas tasas de TBC, inmunosuprimidos, enfermedad renal crónica, diabetes, silicosis y secuelas pulmonares de TBC no tratada. En la terapia de TL se utiliza isoniazida (H) auto-administrada por plazos de 6 a 12 meses con eficacia protectora de 60% y riesgo de toxicidad hepática de 2% pero con baja adherencia (50-70%). La asociación de H con rifapentina en dosis única semanal durante 12 semanas tiene eficacia de 81%, adherencia de 82% y baja toxicidad hepática (0,4%). Nuevos biomarcadores de TL y vacunas que mejoren la inmunidad en TL se encuentran en estudio. El tratamiento de la TL puede reducir la incidencia de TBC a largo plazo.
Latent tuberculosis infection (LT) affects 23% of the population and constitutes a reservoir of tuberculosis (TB) as 10% progresses to TB. LT is recognized by tests such as tuberculin (PPD or TST) and Interferon gamma release assays (IGRAs). The sensitivity of IGRAs (Quantiferon TB Gold plus version) is 94% and PPD 77%. The specificity of Quantiferon TB Gold Plus is 97% and PPD 68%. The predictive value of progression to active TB of these tests is low (PPD: 1.5%, IGRAs: 2.7%) but improves in people at high risk of contracting TB (PPD: 2.4%, IGRAs: 6.8%). People with negative tests who subsequently turn around (positive) have a higher risk of progression to active TB. These tests are useful in the follow-up of intra-household contacts, foreigners from countries with high rates of TB, immunosuppressed, chronic kidney disease, diabetes, silicosis and pulmonary sequelae of untreated TB. In LT therapy, self-administered isoniazid (H) is used for periods from 6 to 12 months with protective efficacy of 60% and risk of liver toxicity of 2%, but with low adherence (50-70%). The association of H with rifapentine in a single weekly dose for 12 weeks has efficacy of 81%, adherence of 82% and low liver toxicity (0.4%). New LT biomarkers and vaccines that improve immunity in LT are under study. Treatment of LT may reduce the incidence of TB in the long term.
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Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/terapia , Teste Tuberculínico , Quimioprevenção , Testes de Liberação de Interferon-gama , Antituberculosos/uso terapêuticoRESUMO
Background: In Brazil, investigation and treatment of tuberculosis infection (TBI) in households contacts (HHC) of TB patients is not a priority. We estimated the cost-effectiveness and budget-impact of scaling-up an enhanced HHC management in Brazil. Methods: We conceptualized a cascade-of-care that captures how HHC of tuberculosis patients are investigated in Brazil (status quo) and two enhanced strategies for management of HHC focusing on: (1) only tuberculosis disease (TBD) detection and, (2) TBD and TBI detection and treatment. Effectiveness was the number of HHC diagnosed with TBD and completing TBI treatment. Proportions in the cascades-of-care were derived from a meta-analysis. Health-system costs (2019 US$) were based on literature and official data from Brazil. The impact of enhanced strategies was extrapolated using reported data from 2019. Findings: With the status quo, 0 (95% uncertainty interval: 0-1) HHC are diagnosed with TBD and 2 (0-16) complete TBI treatment. With strategy(1), an additional 15 (3-45) HHC would be diagnosed with TBD at a cost of US$346 each. With strategy(2), 81 (19-226) additional HHC would complete TBI treatment at a cost of US$84 each. A combined strategy, implemented nationally to enhance TBD detection and TBI treatment would result in an additional 9,711 (845-28,693) TBD being detected, and 51,277 (12,028-143,495) more HHC completing TBI treatment each year, utilizing 10.9% and 11.6% of the annual national tuberculosis program budget, respectively. Interpretation: Enhanced detection and treatment of TBD and TBI among HHC in Brazil can be achieved at a national level using current tools at reasonable cost. Funding: None.
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ABSTRACT Background: Varicose veins appear above and below the dentate line in mixed hemorrhoids, which seriously affects anal function and quality of life. Aim: To propose an improvement in tissue-selecting therapy repair of anal pad combined with complete anal canal epithelial retention comparing with Milligan-Morgan surgery. Methods: A prospective randomized controlled study was designed enrolling 200 patients with grade III and IV hemorrhoids. They were divided into control and observation groups. The control received Milligan-Morgan surgery, and the observation the modified tissue-selecting therapy stapler combined with complete anal canal preservation surgery. All patients were followed for six months to evaluate the treatment differences. Results: In final, control group included 82 and observation 87. The average operation time of the control group was significantly lower than that of the observation, while the bleeding volume was significantly lower in control group. The control group VAS score was 3 (1, 4), and observation 4 (2, 5). There was no significant difference in the incidence of urinary retention, bleeding and wound margin edema after surgery at one month postoperatively. Digital incidence of anal stenosis in the observation group was significantly lower than in control; the same occurred with residual anal margins. The postoperative anal canal diameter was significantly larger than the control group. Wexner anal incontinence score showed that no anal incontinence occurred in both groups, and the control group scored was significantly higher than observation. In final six months follow-up, the observation group did not experience any relapse and four cases were found among controls. The treatment satisfaction of the observation group was better. Conclusions: In grades III and IV hemorrhoids, modified tissue-selecting therapy combined with complete anal canal preservation had better prognosis and treatment satisfaction than Milligan-Morgan procedure, and it is a new surgical method for patients with advanced mixed hemorrhoids.
RESUMO Racional: Veias varicosas aparecem acima e abaixo da linha dentada nas hemorroidas mistas, afetando seriamente a função anal e a qualidade de vida. Objetivo: Propor melhoria na terapia de seleção de tecido de reparo do coxim anal combinado com retenção completa epitelial do canal anal em comparação com a operação de Milligan-Morgan. Métodos: Estudo prospectivo randomizado controlado foi desenhado envolvendo 200 pacientes com hemorroidas graus III e IV. Eles foram divididos em grupos de controle e observação. O controle recebeu operação de Milligan-Morgan, e o de observação procedimento de seleção de tecido modificado combinado com operação completa de preservação do canal anal. Todos os pacientes foram acompanhados por seis meses para avaliar as diferenças de tratamento. Resultados: No final, o grupo controle incluiu 82 e o de observação 87. O tempo médio de operação do grupo controle foi significativamente menor do que o de observação, enquanto o volume de sangramento foi significativamente menor no grupo controle. O escore VAS do grupo controle foi 3 (1, 4) e no de observação 4 (2, 5). Não houve diferença significativa na incidência de retenção urinária, sangramento e edema da margem da ferida no pós-operatório de um mês. A incidência de estenose anal digital no grupo observação foi significativamente menor do que no controle; o mesmo ocorreu com as margens anais residuais. O diâmetro do canal anal pós-operatório foi significativamente maior nele do que o grupo controle. A pontuação de incontinência anal de Wexner mostrou que nenhuma incontinência ocorreu em ambos os grupos, e a pontuação do grupo de controle foi significativamente maior do que no de observação. Nos últimos seis meses de acompanhamento, o grupo observação não teve nenhuma recaída e quatro casos foram encontrados entre os controles. A satisfação com o tratamento do grupo observação foi maior. Conclusões: Nas hemorroidas graus III e IV, o tratamento de seleção de tecido modificado combinado com a preservação completa do canal anal teve melhor prognóstico e satisfação do que com o procedimento de Milligan-Morgan, e é um novo método cirúrgico para pacientes com hemorroidas mistas avançadas.
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Humanos , Hemorroidectomia , Hemorroidas/cirurgia , Canal Anal/cirurgia , Qualidade de Vida , Estudos Prospectivos , Resultado do TratamentoRESUMO
Latent tuberculosis infection (LTBI) is a subclinical mycobacterial infection defined on the basis of cellular immune response to mycobacterial antigens. The tuberculin skin test (TST) and the interferon gamma release assay (IGRA) are currently used to establish the diagnosis of LTB. However, neither TST nor IGRA is useful to discriminate between active and latent tuberculosis. Moreover, these tests cannot be used to predict whether an individual with LTBI will develop active tuberculosis (TB) or whether therapy for LTBI could be effective to decrease the risk of developing active TB. Therefore, in this article, we review current approaches and some efforts to identify an immunological marker that could be useful in distinguishing LTBI from TB and in evaluating the effectiveness of treatment of LTB on the risk of progression to active TB.
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Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/fisiologia , Animais , Biomarcadores/metabolismo , Diagnóstico Diferencial , Progressão da Doença , Humanos , Interferon gama/metabolismo , Risco , Teste TuberculínicoRESUMO
Globally, a quarter of the population is infected with tuberculosis (TB), caused by Mycobacterium tuberculosis. About 5-10% of latent TB infections (LTBI) progress to active disease during the lifetime. Prevention of TB and treating LTBI is a critical component of the World Health Organization's (WHO) End TB Strategy. This study aims to examine the screening practices for prevention and treatment employed by the National Tuberculosis Program of Trinidad and Tobago in comparison to the WHO's standard guidelines. A cross-sectional retrospective study was conducted from the TB registers (2018-2019) for persons aged 18 years and above with recorded tuberculin skin test reactions (TST). Bivariate comparisons for categorical variables were made using Chi-square or Fisher's exact test. Binary logistic regression was used for exploring predictors of TST positivity with adjustment for demographic confounders in multivariable models. Of the total 1972 eligible entries studied, 384 (19.4%) individuals were tested positive with TST. TB contact screening (aOR 2.49; 95% CI 1.65, 3.75) and Bacillus Calmette-Guerin (BCG) vaccination status (aOR 1.66; 95% CI, 1.24 to 2.22) were associated with a positive TST reaction, whereas, preplacement screening failed to show such association when compared to those screened as suspect cases. The findings suggest that TB contact screening and positive BCG vaccination status are associated with TST positivity independent of age and gender.
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The pathogen Xylella fastidiosa belongs to the Xanthomonadaceae family, a large group of Gram-negative bacteria that cause diseases in many economically important crops. A predicted gene, annotated as glutaredoxin-like protein (glp), was found to be highly conserved among the genomes of different genera within this family and highly expressed in X. fastidiosa. Analysis of the GLP protein sequences revealed three protein domains: one similar to monothiol glutaredoxins (Grx), an Fe-S cluster and a thiosulfate sulfurtransferase/rhodanese domain (Tst/Rho), which is generally involved in sulfur metabolism and cyanide detoxification. To characterize the biochemical properties of GLP, we expressed and purified the X. fastidiosa recombinant GLP enzyme. Grx activity and Fe-S cluster formation were not observed, while an evaluation of Tst/Rho enzymatic activity revealed that GLP can detoxify cyanide and transfer inorganic sulfur to acceptor molecules in vitro. The biological activity of GLP relies on the cysteine residues in the Grx and Tst/Rho domains (Cys33 and Cys266, respectively), and structural analysis showed that GLP and GLPC266S were able to form high molecular weight oligomers (> 600 kDa), while replacement of Cys33 with Ser destabilized the quaternary structure. In vivo heterologous enzyme expression experiments in Escherichia coli revealed that GLP can protect bacteria against high concentrations of cyanide and hydrogen peroxide. Finally, phylogenetic analysis showed that homologous glp genes are distributed across Gram-negative bacterial families with conservation of the N- to C-domain order. However, no eukaryotic organism contains this enzyme. Altogether, these results suggest that GLP is an important enzyme with cyanide-decomposing and sulfurtransferase functions in bacteria, whose presence in eukaryotes we could not observe, representing a promising biological target for new pharmaceuticals.
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Cianetos/metabolismo , Glutarredoxinas/metabolismo , Estresse Oxidativo , Sulfurtransferases/metabolismo , Xylella/enzimologia , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Glutarredoxinas/genética , Modelos Moleculares , Filogenia , Conformação Proteica , Sulfurtransferases/genética , Tiossulfato Sulfurtransferase/metabolismoRESUMO
El Boletín Estadístico de la Red Distrital de Sangre del año 2020 conserva el propósito de presentar los principales indicadores relacionados con la promoción de la donación, la captación de donantes, la disponibilidad de hemocomponentes, la gestión de la calidad, hemovigilancia y el uso de los componentes sanguíneos de la ciudad de Bogotá. A su vez, tiene como propósito presentar los resultados obtenidos de las diferentes estrategias realizadas cada año por parte de los actores de la Red Distrital de Sangre, la cual es coordinada por la Secretaría Distrital de Salud de Bogotá, con el fin de garantizar el suministro de componentes sanguíneos de manera oportuna, óptima y segura a todos los habitantes del Distrito Capital.
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Humanos , Estratégias de Saúde , Doações , Segurança do Sangue , Sangue , Saúde , Gestão da Qualidade TotalRESUMO
The Transitivity function, defined in terms of the reciprocal of the apparent activation energy, measures the propensity for a reaction to proceed and can provide a tool for implementing phenomenological kinetic models. Applications to systems which deviate from the Arrhenius law at low temperature encouraged the development of a user-friendly graphical interface for estimating the kinetic and thermodynamic parameters of physical and chemical processes. Here, we document the Transitivity code, written in Python, a free open-source code compatible with Windows, Linux and macOS platforms. Procedures are made available to evaluate the phenomenology of the temperature dependence of rate constants for processes from the Arrhenius and Transitivity plots. Reaction rate constants can be calculated by the traditional Transition-State Theory using a set of one-dimensional tunneling corrections (Bell (1935), Bell (1958), Skodje and Truhlar and, in particular, the deformed ( d -TST) approach). To account for the solvent effect on reaction rate constant, implementation is given of the Kramers and of Collins-Kimball formulations. An input file generator is provided to run various molecular dynamics approaches in CPMD code. Examples are worked out and made available for testing. The novelty of this code is its general scope and particular exploit of d -formulations to cope with non-Arrhenius behavior at low temperatures, a topic which is the focus of recent intense investigations. We expect that this code serves as a quick and practical tool for data documentation from electronic structure calculations: It presents a very intuitive graphical interface which we believe to provide an excellent working tool for researchers and as courseware to teach statistical thermodynamics, thermochemistry, kinetics, and related areas.
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Modelos Químicos , Modelos Teóricos , Algoritmos , CinéticaRESUMO
Control of molecular orientation is emerging as crucial for the characterization of the stereodynamics of kinetics processes beyond structural stereochemistry. The special role played in chiral discrimination phenomena has been particularly emphasized by Aquilanti and collaborators after their extensive probes of experimental control of molecular alignment and orientation. In this work, the manifestation of the Aquilanti mechanism has been demonstrated for the first time in first-principles molecular dynamics simulations: stationary points characterized on potential energy surfaces have been calculated for the study of chemical reactions occurring between the bisulfide anion HS- and oriented prototypical chiral molecules CHFXY (where X = CH3 or CN and Y = Cl or I). The important reaction channels are those corresponding to bimolecular nucleophilic substitution (SN2) and to bimolecular elimination (E2): their relative role has been assessed and alternative pathways due to the mirror forms of the oriented chiral molecule are revealed by the different reactivity of the two enantiomers of CHFCNI in SN2 reaction.
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The activity of 12 thiophenols as primary antioxidants in aqueous solution has been studied using density functional theory. Twelve different substituted thiophenols were tested as peroxyl radicals scavengers. Single electron transfer (SET) and formal hydrogen transfer (FHT) were investigated. The SET mechanism was found to be the main mechanism, with rate constants that are close to the diffusion limit, which means that these thiophenolic compounds have the capacity to scavenge peroxyl radicals before they can damage biomolecules. All 12 thiophenolic compounds react faster with methylperoxyl than with hydroperoxyl radicals. In addition, it was found that pH plays an important role in the reactivity of these compounds. © 2019 Wiley Periodicals, Inc.
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Antioxidantes/química , Peróxidos/química , Fenóis/química , Compostos de Sulfidrila/química , Teoria da Densidade Funcional , Transporte de Elétrons , Cinética , Estrutura Molecular , TermodinâmicaRESUMO
AIMS: To determine the virulence and antimicrobial resistant genes in methicillin resistant Staphylococcus aureus isolates recovered from patients attending two rural health centers in Trinidad and Tobago. SETTINGS AND DESIGN: Cross-sectional observational analysis of patients from two local health centers located in communities in northern region of the country. MATERIALS AND METHODS: Nasal and wound swabs from 300 patients were analyzed using standard and molecular techniques. Multiplex polymerase chain reaction was used to detect 16S rRNA, mec A, Staphylococcal chromosomal cassette SCC mec types, pvl, alpha hemolysin (hla), and Toxic Shock Syndrome Toxin 1 (tst 1) genes. S. aureus ATCC 33591 and Staphylococcus epidermidis ATCC 12228 were used for quality control, respectively. RESULTS: Over a quarter (26.7%, 80/300) of the surveyed patient's samples grew bacterial isolates of which 45% (36/80) were S. aureus and 44.4% (16/36) were mecA-positive. Majority (62.5%, 10/16) possessed the pvl gene, whereas 25% (4/16) possessed the alpha hemolysin (hla) gene. None of the methicillin-resistant Staphylococcus aureus (MRSA) isolates possessed the tst 1 gene. Also, 18.8% (3/16) isolates possessed both virulence genes, pvl and hla. Although the SCCmec types IV and V were detected, but none of the SCCmec I, II, and III were harbored by the isolates. CONCLUSIONS: SCCmec type IV and the pvl genes were common among the MRSA isolates from the community. The hla gene was found infrequently, but none of the isolates possessed the tst 1 gene. Knowledge of this is important for robust surveillance of such cases from the community in the country.
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Antibacterianos/farmacologia , Toxinas Bacterianas/genética , Enterotoxinas/genética , Exotoxinas/genética , Proteínas Hemolisinas/genética , Leucocidinas/genética , Staphylococcus aureus Resistente à Meticilina/genética , Meticilina/farmacologia , Nariz/microbiologia , Superantígenos/genética , Estudos Transversais , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , RNA Ribossômico 16S , População Rural , Staphylococcus aureus , Trinidad e TobagoRESUMO
Although molecular collisions of noble gases (Ng) can be theoretically used to distinguish between the enantiomers of hydrogen peroxide - H2O2 (HP), little is known about the effects of HP-Ng interactions on the chiral rate. In this work, the chiral rate as a function of temperature (CRT) between enantiomeric conformations of HP and Ng (Ng=He, Ne, Ar, Kr, Xe, and Rn) are presented at MP2(full)/aug-cc-pVTZ level of theory through a fully basis set superposition error (BSSE) corrected potential energy surface. The results show that: (a) the CRT is highly affected even at a small decrease in the height of trans-barrier; (b) its smallest values occur with Ne for all temperatures between 100 and 4,000 K; (c) that the decrease of CRT shows an inverse correlation with respect to the average valence electron energy of the Ng and (d) Ne and He may be the noble gases more suitable for study the oriented collision dynamics of HP. In addition to binding energies, the electron density ρ and its Laplacian ∇2 ρ topological analyses were also performed within the atoms in molecules (AIM) theory in order to determine the nature of the HP-Ng interactions. The results of this work provide a more complete foundation on experiments to study HP's chirality using Ng in crossed molecular beams without a light source.
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El Boletín Estadístico de la Red Distrital de Sangre del año 2018 mantiene el propósito de presentar los principales indicadores que dan cuenta de la captación, disponibilidad y uso de la sangre y de sus componentes sanguíneos en la ciudad, y los resultados de los principales procesos realizados cada año por los actores de la Red Distrital de Sangre y Terapia Celular de Bogotá, la cual es coordinada desde la Secretaría Distrital de Salud. Parte de la información que se presenta en este boletín se soporta en los datos suministrados, por medio del aplicativo informático distrital Red Sangre, por los 16 bancos de sangre y 80 servicios de transfusión sanguínea que hicieron parte de la Red durante el 2018.
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Humanos , Sistema Único de Saúde , Bancos de Sangue , Transfusão de Sangue , Sangue , Saúde , Terapia Baseada em Transplante de Células e TecidosRESUMO
BACKGROUND: In household contact investigations of tuberculosis (TB), a second tuberculin skin test (TST) obtained several weeks after a first negative result consistently identifies individuals that undergo TST conversion. It remains unclear whether this delay in M. tuberculosis infection is related to differences in the infectious exposure, TST boosting, partial host resistance, or some other factor. METHODS: We conducted a household contact study Vitória, Brazil. Between 2008 and 2013, we identified culture-positive pulmonary TB patients and evaluated their household contacts with both a TST and interferon gamma release assay (IGRA), and identified TST converters at 8-12 weeks post study enrollment. Contacts were classified as TST-positive (≥10 mm) at baseline, TST converters, or persistently TST-negative. We compared TST converters to TST-positive and to TST-negative contacts separately, using generalized estimating equations. RESULTS: We enrolled 160 index patients and 838 contacts; 523 (62.4%) were TST+, 62 (7.4%) TST converters, and 253 (30.2%) TST-. TST converters were frequently IGRA- at 8-12 weeks. In adjusted analyses, characteristics distinguishing TST converters from TST+ contacts (no contact with another TB patient and residence ownership) were different than those differentiating them from TST- contacts (stronger cough in index patient and contact BCG scar). CONCLUSIONS: The individual risk and timing of M. tuberculosis infection within households is variable and dependent on index patient, contact and environmental factors within the household, and the surrounding community. Our findings suggest a threshold effect in the risk of infection in humans.
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Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Criança , Tosse/microbiologia , Características da Família , Feminino , Humanos , Testes de Liberação de Interferon-gama , Masculino , Mycobacterium tuberculosis/patogenicidade , Teste Tuberculínico , Tuberculose/transmissão , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Adulto JovemRESUMO
APUAMA is a free software designed to determine the reaction rate and thermodynamic properties of chemical species of a reagent system. With data from electronic structure calculations, the APUAMA determine the rate constant with tunneling correction, such as Wigner, Eckart and small curvature, and also, include the rovibrational level of diatomic molecules. The results are presented in the form of Arrhenius-Kooij form, for the reaction rate, and the thermodynamic properties are written down in the polynomial form. The word APUAMA means "fast" in Tupi-Guarani Brazilian language, then the code calculates the reaction rate on a simple and intuitive graphic interface, the form fast and practical. As program output, there are several ASCII files with tabulated information for rate constant, rovibrational levels, energy barriers and enthalpy of reaction, Arrhenius-Kooij coefficient, and also, the option to the User save all graphics in BMP format.
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Bovine colostrum contains compounds, which provide passive immune protection from mother to newborn calves. Little is known about cytokine levels and their role in bovine colostrum. Moreover, the capacity of bovine colostrum cells to mount specific immune responses after natural exposure to bovine tuberculosis (bTB) antigens in dairy herds has not been studied, thus far. The purpose of this study was to identify biomarkers for bTB infection measurable in bovine colostrum. The present study reveals that isolated-immune colostrum cells can mount a specific immune response against bTB antigens, by measuring the novo IFN-γ release in cell culture. We found that IFN-γ levels in the responders (Bov+) to bTB antigen were higher than in non-responders (Bov-). On the other hand, proinflammatory cytokines contained in colostrum's whey were tested in Tuberculin Skin Test (TST) reactor (TST+) and non-reactor (TST-) animals to assess their potential role as biomarker. We observed that IFN-γ levels were lower or undetectable, as opposed to IL4 levels were measurable, the TNF-α level was higher in TST- than TST+, while IL-6 levels showed the opposite reaction and with no statistical significance. Moreover, IL-1α mRNA expression levels were higher in colostrum mononuclear cells (CMC) in Bov+ cattle. Collectively, these data suggest that the differential expression of pro and anti-inflammatory cytokines could have relevant value to diagnose bTB in cattle.
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Biomarcadores , Colostro/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Mycobacterium bovis/imunologia , Tuberculose Bovina/imunologia , Tuberculose Bovina/metabolismo , Animais , Antígenos de Bactérias/imunologia , Bovinos , Citocinas/genética , Feminino , Expressão Gênica , Testes de Liberação de Interferon-gama , Tuberculose Bovina/genéticaRESUMO
El Boletín Estadístico de la Red Distrital de Sangre y Terapia Celular del año 2017 mantiene el propósito de presentar los principales indicadores que dan cuenta de la captación, disponibilidad y uso de la sangre y de sus componentes sanguíneos en la ciudad, así como de los resultados de los principales procesos realizados cada año desde la Secretaría Distrital de Salud relacionados con la captación y uso de la sangre. Parte de la información que se presenta se soporta en los datos suministrados a través del aplicativo informático distrital "Red Sangre" por los 16 bancos de sangre y 85 servicios de transfusión sanguínea que hacen parte de la Red.