A pre-post quasi-experimental study: effect of an educational intervention on the quality of life, and coping strategies of people living with HIV (PLHIV).

INTRODUCTION: The current study provides people living with human immunodeficiency virus (PLHIV) the support to cope with this disease and to improve their quality of life, since their longevity has significantly increased. AIM: Investigating the effect of an educational intervention on PLHIV's strategies to cope with HIV. METHODOLOGY: Quasi-experimental, before-and-after study type, whose data were collected before and after educational intervention, was carried out with 75 PLHIV at a School Outpatient Clinic. The Brazilian version of the Ways of Coping Scale was herein used. It is a questionnaire comprising 4 disease-coping domains, namely: coping focused on problem, emotion and on seeking social support and religious practices. RESULTS: There was increased use of all coping-strategy domains after the educational intervention, as well as reduced standard deviation, and it pointed out that the recorded values were grouped closer to the mean therefore showing less variability. Coping focused on social support was the strategy mostly used after the educational intervention; it was followed by strategies focused on both emotion and problem. The least used strategy was the one focused on religion/fantasy. DISCUSSION: This study identified the need of introducing a new coping strategy focused on prejudice against patients with HIV.

Spatial analysis of HIV detection rates among Brazilian young men, 2007-2021.

The main goal of this study was to spatially analyze the HIV epidemic scenario in young men in Brazil, 2007-2021. We used secondary data obtained from the Brazilian Information System for Notifiable Diseases. Individuals aged 15-29 years with permanent residence in Brazil who were diagnosed with HIV during the study period were included in the analysis. Municipality HIV age-adjusted detection rates were analyzed through spatial distribution, autocorrelation, and spatiotemporal risk analyses. During the study period, 108,392 HIV cases were reported in young Brazilian men. The HIV epidemic increased territorially in the northern, northeastern, midwestern, and southeastern regions but decreased in the southern region. Although the number of clusters comprising municipalities with high HIV detection rates (hotspots) decreased, new ones appeared, expanded, or stopped changing size. Hotspots and spatio-temporal risk zones (spatial areas with increased HIV detection in a specific period) comprised economically developed municipalities with high demographic density surrounded by less developed municipalities. The period of the spatiotemporal risk zones was between 2008 and 2021. Our study showed that HIV detection rates continue to increase among young Brazilian men, and health authorities should reinforce efforts mainly in capitals and surrounded municipalities in the north, northeast, southeast, and midwest regions.

Patterns of Chlamydia trachomatis and Neisseria gonorrhoeae in different anatomical sites among Pre-Exposure Prophylaxis (PrEP) users in Brazil.

BACKGROUND: The presence of untreated sexually transmitted infections (STIs) significantly increases the chance of acquiring HIV. In Brazil, testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among Pre-Exposure Prophylaxis (PrEP) users is insufficient, and syndromic treatment is a priority in clinical practice. Multi-site testing for CT/NG improves thescreening of asymptomatic cases and ensures timely treatment. Therefore, it is essential for HIV prevention. This study aims to test the importance of two-site testing for better screening of these pathogens and to determine whether the presence of symptoms is an indicator of CT/NG infection. METHODS: This is a cross-sectional study carried out in four public infectious diseases clinics in São Paulo State, Brazil between January of 2022 and March of 2023. All participants had an anal swab and a first-pass or mid-stream urine collected for CT/NG analysis by Polymerase chain reaction (PCR). Data about sociodemographic, sexual behavioural and clinical aspects were collected. Pathway analysis was used to examine the direct and indirect relationships between variables according to the theoretical model. RESULTS: We screened 171 PrEP users which had two samples collected, resulting in 342 samples. Comparing the anatomic sites, the urine samples showed lower sensitivity for CT and NG than anal samples. Gonorrhoea was directly linked to lower age (ß= -0.161, p = 0.001). Time of PrEP use was directly associated with CT infection (ß = 0.202; p = 0.042) and inversely associated with dysuria (ß= -0.121, p = 0.009). Lower occurrence of yellow-green secretion was linked to detection of CT (ß= -0.089, p = 0.005) and NG (ß= -0.048, p = 0.002) infections. Foul-smelling discharge was directly associated with CT (ß = 0.275, p = 0.004) and NG (ß = 0.295, p = 0.037) infection. CONCLUSION: The symptoms are a bad indicator of CT and NG infection, and the screening must be done in more than one site since most of the positive results would be missed if only urines were tested. In the case of testing only one anatomical site, specifically the urethra, the CT/NG incidence and prevalence would be underestimated. The two-sites testing improves detection rates of CT/NG, and PrEP follow-up benefits people offering STI testing.

Human immunodeficiency virus epidemic scenery among brazilian women: a spatial analysis study.

BACKGROUND: Approximately 37.7 million people worldwide are infected with human immunodeficiency virus (HIV). Although HIV detection among women, they still representing 53% of population living with the virus. Spatial analysis techniques are powerful tools for combating HIV allowing the association of the phenomenon with socioeconomic and political factors. Therefore, the main goal of this study was to spatially analyze HIV prevalence among Brazilian women from 2007 to 2020. METHODS: ecological study was conducted using secondary databases of the Notifiable Diseases Information System (SINAN) for HIV and Acquired Immunodeficiency Syndrom (AIDS) in Brazilian women 15 years old and over. Age-adjusted HIV/AIDS incidence rates were analyzed using spatial distribution, autocorrelation, and spatiotemporal risk analysis techniques. RESULTS: During the study period, 119,890 cases of HIV/AIDS were reported among Brazilian women. The southeastern region had a higher age-adjusted HIV/AIDS incidence than other Brazilian regions. Hotspot HIV/AIDS incidence rates decreased in all Brazil. Piauí, Paraná, and Minas Gerais were the only states with an increased number of cold spots. Previous spatiotemporal risk zones were observed in the states of São Paulo, Rio Grande do Sul, and Rio de Janeiro. Belém was a risk zone with a later spatiotemporal risk. CONCLUSIONS: The efficiency of public policies fighting HIV has not been uniform among municipalities, although HIV/AIDS cases have decreased among Brazilian women. The social determinants of health in each municipality should be considered when local health authorities implement policies. Women empowerment should be promoted, and access to preventive, diagnostic, and treatment healthcare places should be expanded and guaranteed.

Chemical composition and biological activities of the essential oils from Lippia alba and Lippia origanoides.

There is an increasing interest in essential oils extracted from Verbenaceae plant species as potential sources of biologically active compounds that could provide a starting point for designing novel phyto-pharmaceuticals in aquaculture. The present study was aimed to investigate the chemical composition, antioxidant activity, acute toxicity and antimicrobial effects against Vibrio parahaemolyticus of essential oils extracted from Lippia alba and L. origanoides. Approximately 23 components were identified and quantified by gas chromatography-mass spectrometry and flame ionization detection in each species' essential oil. The most predominant compounds were geranial (23.0%), limonene (17.0%) and neral (15.5%) in L. alba, and thymol (47.2%), p-cymene (16.0%) and E-caryophyllene (11.3%) in L. origanoides. The essential oils have antibacterial activity against Vibrio parahaemolyticus presenting Minimum Inhibitory Concentration (MIC) and Bactericidal Concentration (MBC) values between 156-625 µg mL-1. The essential oils also show antioxidant potential estimated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assays, presenting IC50 of 60.16 mg mL-1 and 0.22 mg mL-1 for L. alba and L. origanoides EO, respectively. Both oils were classified as toxic to Artemia salina nauplii. Therefore, these essential oils may be useful for controlling pathogenic bacteria important to the aquaculture industry.

Discovery of a new flavin N5-adduct in a tyrosine to phenylalanine variant of d-Arginine dehydrogenase.

d-Arginine dehydrogenase from Pseudomonas aeruginosa (PaDADH) catalyzes the flavin-dependent oxidation of d-arginine and other d-amino acids. Here, we report the crystal structure at 1.29 Å resolution for PaDADH-Y249F expressed and co-crystallized with d-arginine. The overall structure of PaDADH-Y249F resembled PaDADH-WT, but the electron density for the flavin cofactor was ambiguous, suggesting the presence of modified flavins. Electron density maps and mass spectrometric analysis confirmed the presence of both N5-(4-guanidino-oxobutyl)-FAD and 6-OH-FAD in a single crystal of PaDADH-Y249F and helped with the further refinement of the X-ray crystal structure. The versatility of the reduced flavin is apparent in the PaDADH-Y249F structure and is evidenced by the multiple functions it can perform in the same active site.

The Flavonol Quercitrin Hinders GSK3 Activity and Potentiates the Wnt/ß-Catenin Signaling Pathway.

The Wnt/ß-catenin signaling pathway dictates cell proliferation and differentiation during embryonic development and tissue homeostasis. Its deregulation is associated with many pathological conditions, including neurodegenerative disease, frequently downregulated. The lack of efficient treatment for these diseases, including Alzheimer's disease (AD), makes Wnt signaling an attractive target for therapies. Interestingly, novel Wnt signaling activating compounds are less frequently described than inhibitors, turning the quest for novel positive modulators even more appealing. In that sense, natural compounds are an outstanding source of potential drug leads. Here, we combine different experimental models, cell-based approaches, neuronal culture assays, and rodent behavior tests with Xenopus laevis phenotypic analysis to characterize quercitrin, a natural compound, as a novel Wnt signaling potentiator. We find that quercitrin potentiates the signaling in a concentration-dependent manner and increases the occurrence of the Xenopus secondary axis phenotype mediated by Xwnt8 injection. Using a GSK3 biosensor, we describe that quercitrin impairs GSK3 activity and increases phosphorylated GSK3ß S9 levels. Treatment with XAV939, an inhibitor downstream of GSK3, impairs the quercitrin-mediated effect. Next, we show that quercitrin potentiates the Wnt3a-synaptogenic effect in hippocampal neurons in culture, which is blocked by XAV939. Quercitrin treatment also rescues the hippocampal synapse loss induced by intracerebroventricular injection of amyloid-ß oligomers (AßO) in mice. Finally, quercitrin rescues AßO-mediated memory impairment, which is prevented by XAV939. Thus, our study uncovers a novel function for quercitrin as a Wnt/ß-catenin signaling potentiator, describes its mechanism of action, and opens new avenues for AD treatments.

Increased use of psychoactive substances among Brazilian health care professionals during the COVID-19 pandemic.

This study aimed to estimate the prevalence of increased psychoactive substance use (PSU) and associated factors among health care professionals. A cross-sectional and analytical study with 12,086 Brazilian health professionals was undertaken. An online questionnaire was used to gather data concerning sociodemographic factors, increased consumption of alcoholic beverages, tobacco, and hypnotics or sedatives during the COVID-19 pandemic. The prevalence of tobacco, alcoholic beverages, and hypnotic or sedative consumption were 17.8 %, 69.0 % and 17.1 %, respectively. Regression analyses indicated that having no religion and social isolation were associated with increased PASU during the pandemic. COVID-19 pandemic stressors may increase PASU, and increased PASU may increase the risk of substance use disorders and substance use-related chronic diseases, such as cancer.

A Single-Point Mutation in d-Arginine Dehydrogenase Unlocks a Transient Conformational State Resulting in Altered Cofactor Reactivity.

Proteins are inherently dynamic, and proper enzyme function relies on conformational flexibility. In this study, we demonstrated how an active site residue changes an enzyme's reactivity by modulating fluctuations between conformational states. Replacement of tyrosine 249 (Y249) with phenylalanine in the active site of the flavin-dependent d-arginine dehydrogenase yielded an enzyme with both an active yellow FAD (Y249F-y) and an inactive chemically modified green FAD, identified as 6-OH-FAD (Y249F-g) through various spectroscopic techniques. Structural investigation of Y249F-g and Y249F-y variants by comparison to the wild-type enzyme showed no differences in the overall protein structure and fold. A closer observation of the active site of the Y249F-y enzyme revealed an alternative conformation for some active site residues and the flavin cofactor. Molecular dynamics simulations probed the alternate conformations observed in the Y249F-y enzyme structure and showed that the enzyme variant with FAD samples a metastable conformational state, not available to the wild-type enzyme. Hybrid quantum/molecular mechanical calculations identified differences in flavin electronics between the wild type and the alternate conformation of the Y249F-y enzyme. The computational studies further indicated that the alternate conformation in the Y249F-y enzyme is responsible for the higher spin density at the C6 atom of flavin, which is consistent with the formation of 6-OH-FAD in the variant enzyme. The observations in this study are consistent with an alternate conformational space that results in fine-tuning the microenvironment around a versatile cofactor playing a critical role in enzyme function.

New frontiers in flavin-dependent monooxygenases.

Flavin-dependent monooxygenases catalyze a wide variety of redox reactions in important biological processes and are responsible for the synthesis of highly complex natural products. Although much has been learned about FMO chemistry in the last ~80 years of research, several aspects of the reactions catalyzed by these enzymes remain unknown. In this review, we summarize recent advancements in the flavin-dependent monooxygenase field including aspects of flavin dynamics, formation and stabilization of reactive species, and the hydroxylation mechanism. Novel catalysis of flavin-dependent N-oxidases involving consecutive oxidations of amines to generate oximes or nitrones is presented and the biological relevance of the products is discussed. In addition, the activity of some FMOs have been shown to be essential for the virulence of several human pathogens. We also discuss the biomedical relevance of FMOs in antibiotic resistance and the efforts to identify inhibitors against some members of this important and growing family enzymes.

Predictors of HIV Status Disclosure to Sexual Partners Among People Living with HIV in Brazil.

The objective of this study was to identify the factors associated with the non-disclosure of HIV seropositivity among people living with HIV/AIDS undergoing antiretroviral treatment. A cross-sectional study was carried out in five HIV clinics in the interior of the state of São Paulo, Brazil. Logistic regression analysis was used to determine independent predictors of HIV status disclosure. It was found that 68.5% revealed their HIV seropositivity to their most recent sexual partner. The variables "casual partner" [OR 19.08, 95% CI (4.08, 20.23), p = 0.001], "sexual partners with negative HIV or unknown HIV" [OR 4.54, 95% CI (1.58, 1.01), p = 0.005], "multiple sexual partners" [OR = 3.17, 95% CI (1.34, 7.35), p = 0.009], and "lack of communication with the partner on HIV prevention"[OR = 8.3, 95% CI (3.88, 16.61), p = 0.001] were independently associated with non-disclosure of the diagnosis. Future HIV prevention interventions should encourage open communication between sexual partners.

RESUMEN: El objetivo de este estudio fue identificar los factores asociados con la no divulgación de la seropositividad al VIH entre las personas que viven con el VIH / SIDA en tratamiento antirretroviral. Se realizó un estudio transversal en cinco clínicas de VIH en el interior del estado de São Paulo, Brasil. Se utilizó un análisis de regresión logística para determinar predictores independientes de la revelación del estado del VIH. Se encontró que el 68,5% reveló su seropositividad al VIH a su pareja sexual más reciente. Las variables "pareja casual" [OR 19,08, IC 95% (4,08, 20,23), p = 0,001], "parejas sexuales con VIH negativo o VIH desconocido" [OR 4,54,95% IC 95% (1,58, 1,01), p = 0,005], "múltiples parejas sexuales" [OR 3,17, IC del 95% (1,34, 7,35), p = 0,009] y "falta de comunicación con la pareja sobre la prevención del VIH" [OR 8,3, IC 95% (3,88, 16,61), p = 0,001] se asociaron de forma independiente con la no divulgación del diagnóstico. Las futuras intervenciones de prevención del VIH deberían fomentar la comunicación abierta entre las parejas sexuales.

Knowledge of PEP and PrEP among people living with HIV/aids in Brazil.

BACKGROUND: Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP) are key to preventing sexual transmission of HIV, whose sexual partners are at high risk of acquiring HIV. We aimed to determine the factors associated with PrEP and PEP's knowledge as secondary prevention among people living with HIV/AIDS. METHOD: Cross-sectional analytical study carried out among people living with HIV/AIDS treated at five specialized services in the city of Ribeirão Preto, São Paulo, Brazil. Data were collected from July 2016 to July 2017. Individual interviews were conducted. We used multivariable logistic regression to determine factors associated with knowing PrEP and PEP. RESULTS: Of the 397 participants, 140 (35.26%) were heterosexual women aged 40 to 49 years (36.2%).Participants with less than 11 years of study (adjusted odds: 0.29; 95% CI: 0.13-0.60); who did not have a low viral load or did not know their viral load (adjusted odds: 0.29; 95% CI: 0.09-0.83) and those with casual partners (adjusted odds: 0.29; 95% CI: 0.09-0.83) were less likely to know about the PrEP. MSM (adjusted odds: 2.88; 95% CI: 1.59-5.3) and those who used alcohol during sexual intercourse (adjusted odds: 1.7; 95% CI: 1.0-2.8) were more likely to know about the PEP. CONCLUSIONS: The knowledge about PEP and PrEP is low in Brazil. This may undermine secondary prevention efforts. Educational interventions to raise awareness of these prevention methods are needed among people living with HIV and who have HIV-negative sexual partners.

Serodiscordance predictors among couples in the HIV context: implications for health care.

BACKGROUND: After HIV diagnosis, people maintain, reestablish their sexual lives, or build new relationships, often with HIV seronegative partners. Therefore, understanding the factors concerning couple-vulnerability is essential in order to design effective HIV preventive strategies. We examined HIV serodiscordant couples prevalence and their associated factors from a Brazilian city. METHODS: This is a cross-sectional analytical study carried out with people living with HIV (PLHIV) who had an active sex life and were engagement in HIV health care follow-up. Data were collected using a semi-structured questionnaire during individual interviews. We analyzed data using bivariate and multiple logistic regression analyses. RESULTS: There was 72.0% of HIV serodiscordant partnerships. Those who inconsistently used condoms (aOR: 0.3[0.13-0.7]) and/or had HIV detectable viral load (aOR: 0.29 [0.12-0.7]) were less likely to have an HIV serodiscordant sexual partner. On other hand, the lack of HIV transmission counseling by the health service (aOR: 5.08 [2.02-12.76]), or those who had a casual partner (aOR: 8.12 [1.7-38.8]) or a steady and casual one concomitantly (aOR: 24.82 [1.46-420.83]), were more likely to indicate an HIV serodiscordant partnership. CONCLUSION: The findings showed a high prevalence of serodiscordant partnerships in PLHIV. Greater visibility among couples in the health services is needed as well as a reassessment in order to provide PLHIV and their sexual partners with care strategies, by the health professionals.

The HIV epidemic in Colombia: spatial and temporal trends analysis.

BACKGROUND: Colombia has the fourth highest incidence rate of HIV/AIDS among all Latin American countries and it has been increasing since the 1980s. However, the number of studies that addresses this trend is limited. Here, we employed spatial and temporal trend analyses to study the behaviour of the epidemic in the Colombian territory. METHODS: Our sample included 72,994 cases of HIV/AIDS and 21,898 AIDS-related deaths reported to the National Ministry of Health between 2008 and 2016. We employed the joinpoint regression model to analyse the annual HIV/AIDS incidence and AIDS mortality rates. In the spatial analysis, we used univariate autocorrelation techniques and the Kernel density estimator. RESULTS: While the HIV/AIDS incidence had an increasing trend in Colombia, the AIDS mortality rate was stable. HIV/AIDS incidence and AIDS mortality showed a downward trend in the 0-14 age group. An upward trend was observed for HIV/AIDS incidence in people older than 15 years and with the highest trend in the 65 years and above group. AIDS mortality showed an increasing trend among people aged 65 years or older. The comparison between the sexes showed an upward trend of HIV/AIDS incidence in all age groups and AIDS-mortality rates in 65 years and above in men, while in women, the incidence was upward among those aged 45 years and above, and concerning the AIDS-mortality rate in the 45-64 group. The high-high clusters of HIV/AIDS incidence and AIDS mortality were located in the Andean and Caribbean regions. CONCLUSION: Our study found an upward trend in HIV/AIDS incidence and a stable trend in the AIDS mortality rate in Colombia. The downward trend in HIV/AIDS incidence and AIDS mortality rate in the 0-14 age group reflects the downwards mother-to-child HIV transmission. The upward trend in HIV/AIDS incidence in older women and AIDS mortality in younger women rates, compared with men, may be due to late diagnosis and treatment. The Caribbean and the 'coffee belt' regions were the most impacted by the HIV epidemic, most likely due to sexual tourism. Our results provide crucial information that may help Colombian health authorities fight HIV transmission.

The opposing contribution of neurotrophin-3 and nerve growth factor to orofacial heat hyperalgesia in rats.

It has been proposed that neurotrophin-3 acts in a manner that is opposed to nerve growth factor, especially in the modulation of heat hyperalgesia. Injury to the constriction of the infraorbital nerve (CION) is a well-established model of trigeminal neuropathic pain that leads to robust heat, cold, and mechanical hyperalgesia. Here, we assessed the effect of local neurotrophin-3 treatment on CION-induced hyperalgesia, and we examined some mechanisms related to the effect of neurotrophin-3. Neurotrophin-3 (1 µg/50 µl) injected into the upper lip of CION rats caused a significant and long-lasting reduction of CION-induced heat hyperalgesia, but failed to affect cold and mechanical hyperalgesia. Increased levels of neurotrophin-3 were detected in the injured nerve at the time point that represents the peak of heat hyperalgesia. The anti-hyperalgesic effect of neurotrophin-3 was markedly reduced in the presence of an antagonist of TrkA receptors (K-252a, 1 µg/50 µl). Moreover, association of lower doses of neurotrophin-3 with an antibody anti-nerve growth factor resulted in a synergistic anti-hyperalgesic effect in CION rats. Local injection of nerve growth factor (3 µg/50 µl) or the TRPV1 agonist capsaicin (1 µg/50 µl), but not neurotrophin-3 injection (1 µg/50 µl), resulted in long-lasting facial heat hyperalgesia, which was both significantly reduced by previous neurotrophin-3 local treatment. In conclusion, we suggest that neurotrophin-3 is a potent modulator of facial heat hyperalgesia, which may exert an inhibitory influence on the trkA pathway. Neurotrophin-3 treatment may represent a promising approach, especially in pain conditions associated with increased levels of nerve growth factor.

Kinetic Investigation of a Presumed Nitronate Monooxygenase from Pseudomonas aeruginosa PAO1 Establishes a New Class of NAD(P)H:Quinone Reductases.

PA0660 from Pseudomonas aeruginosa PAO1 is currently classified as a hypothetical nitronate monooxygenase (NMO), but no evidence at the transcript or protein level has been presented. In this study, PA0660 was purified and its biochemical and kinetic properties were characterized. Absorption spectroscopy and mass spectrometry demonstrated a tightly, noncovalently bound FMN in the active site of the enzyme. Analytical ultracentrifugation showed that the enzyme exists as a dimer in solution. Despite its annotation, PA0660 did not exhibit nitronate monooxygenase activity. The enzyme could be reduced with NADPH or NADH with a marked preference for NADPH, as indicated by ∼30-fold larger kcat/ Km and kred/ Kd values. Turnover could be sustained with NAD(P)H and quinones, DCPIP, and to a lesser extent molecular oxygen. However, PA0660 did not turn over with methyl red, consistent with a lack of azoreductase activity. The enzyme turned over through a ping-pong bi-bi steady-state kinetic mechanism with NADPH and 1,4-benzoquinone showing a kcat value of 90 s-1. The rate constant for flavin reduction with saturating NADPH was 360 s-1, whereas that for flavin oxidation with 1,4-benzoquinone was 270 s-1, consistent with both hydride transfers from the pyridine nucleotide to the flavin and from the flavin to 1,4-benzoquinone being partially rate-limiting for enzyme turnover. A BlastP search and a multiple-sequence alignment analysis of PA0660 highlighted the presence of six conserved motifs in >1000 open reading frames currently annotated as hypothetical NMOs. Our results suggest that PA0660 should be classified as an NAD(P)H:quinone reductase and serve as a paradigm enzyme for a new class of enzymes.

Chronic neurodegeneration induces type I interferon synthesis via STING, shaping microglial phenotype and accelerating disease progression.

Type I interferons (IFN-I) are the principal antiviral molecules of the innate immune system and can be made by most cell types, including central nervous system cells. IFN-I has been implicated in neuroinflammation during neurodegeneration, but its mechanism of induction and its consequences remain unclear. In the current study, we assessed expression of IFN-I in murine prion disease (ME7) and examined the contribution of the IFN-I receptor IFNAR1 to disease progression. The data indicate a robust IFNß response, specifically in microglia, with evidence of IFN-dependent genes in both microglia and astrocytes. This IFN-I response was absent in stimulator of interferon genes (STING-/- ) mice. Microglia showed increased numbers and activated morphology independent of genotype, but transcriptional signatures indicated an IFNAR1-dependent neuroinflammatory phenotype. Isolation of microglia and astrocytes demonstrated disease-associated microglial induction of Tnfα, Tgfb1, and of phagolysosomal system transcripts including those for cathepsins, Cd68, C1qa, C3, and Trem2, which were diminished in IFNAR1 and STING deficient mice. Microglial increases in activated cathepsin D, and CD68 were significantly reduced in IFNAR1-/- mice, particularly in white matter, and increases in COX-1 expression, and prostaglandin synthesis were significantly mitigated. Disease progressed more slowly in IFNAR1-/- mice, with diminished synaptic and neuronal loss and delayed onset of neurological signs and death but without effect on proteinase K-resistant PrP levels. Therefore, STING-dependent IFN-I influences microglial phenotype and influences neurodegenerative progression despite occurring secondary to initial degenerative changes. These data expand our mechanistic understanding of IFN-I induction and its impact on microglial function during chronic neurodegeneration.

Factors associated with self-reported non-completion of the hepatitis B vaccine series in men who have sex with men in Brazil.

BACKGROUND: The objective of the present study was to analyze the factors associated with non-completion of the hepatitis B vaccine series among men who have sex with men and use geosocial dating apps in Brazil. METHODS: This was a cross-sectional, population survey-based, analytical study, conducted exclusively online in all the regions of Brazil, with a sample of 1855 men who have sex with men. The data was collected between November 2016 and February 2017, using the social networking website Facebook. RESULTS: Univariate, bivariate and multivariate analyses showed that 4.7% of the participants reported receiving one dose of the vaccine, 12.5% two doses, 19.4% three doses, and 45.8% did not know. Multivariate analysis showed that level of education (OR = 0.31; CI 95% 0.14-0.72; p = 0.007), identification as bisexual (OR = 0.6; CI 95% 0.38-0.95; p = 0.030), HIV serological status (OR:2.3; CI 95% 1.58-3.34; p = < 0.001) and frequency of access to health services (OR = 2.38; CI 95% 1.53-3.72; p = < 0.001) were associated with not completing the vaccine series. Low completion of the hepatitis B vaccine series was detected in the population studied. CONCLUSION: Completion of the hepatitis B vaccine series was low among men who have sex with men and use geosocial dating apps in Brazil. The factors associated with non-completion were related to social, individual and healthcare (programmatic) vulnerabilities.

Crystal structure of yeast nitronate monooxygenase from Cyberlindnera saturnus.

Nitronate monooxygenase (NMO) is an FMN-dependent enzyme that oxidizes the neurotoxin propionate 3-nitronate (P3N) and represents the best-known system for P3N detoxification in different organisms. The crystal structure of the first eukaryotic Class I NMO from Cyberlindnera saturnus (CsNMO) has been solved at 1.65 Å resolution and refined to an R-factor of 14.0%. The three-dimensional structures of yeast CsNMO and bacterial PaNMO are highly conserved with the exception of three additional loops on the surface in the CsNMO enzyme and differences in four active sites residues. A PEG molecule was identified in the structure and formed extensive interactions with CsNMO, suggesting a specific binding site; however, 8% PEG showed no significant effect on the enzyme activity. This new crystal structure of a eukaryotic NMO provides insight into the function of this class of enzymes.