Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.

Relationship between primary vaccination coverage and booster coverage against COVID-19, socio-economic indicators, and healthcare structure in Brazil.

OBJECTIVE: To investigate the relationship between vaccination coverage and booster coverage against COVID-19, socio-economic indicators, and healthcare structure in Brazil. STUDY DESIGN: This is a nationwide population-based ecological study. METHODS: We have obtained data on COVID-19 vaccination for each Brazilian state until December 22, 2022. Our outcomes of interest were primary and booster vaccination coverage. The independent variables included: human development index (HDI); Gini index; population density; unemployment rate; percentage of the population covered by primary health care (PHC); percentage of the population covered by community health workers; number of family health teams; and number of public health establishments. Statistics were performed by using a multivariable linear regression model. RESULTS: Lower rates of primary vaccination coverage were found in states with lower HDI (P = 0.048), population covered by PHC (P = 0.006), and number of public health establishments (P = 0.004). Lower rates of booster coverage were also found in states with lower population density (first booster: P = 0.004; second booster: P = 0.022), PHC (first booster: P = 0.033; second booster: P = 0.042), and public health establishments (first booster: P < 0.001; second booster: P = 0.027). CONCLUSION: Our findings showed heterogeneity in access to vaccination against COVID-19 in Brazil, with lower vaccination coverage in localities with the worst socio-economic indicators and limited healthcare resources.

Dimensions of household food waste focused on family and consumers.

Food waste produced in homes represents the largest fraction of food waste generated along the food chain. Therefore, adequate prevention measures based on the quantitative and qualitative dimensions of the problem need to be put in place to reduce waste. The objective of the review was to identify areas of interest in relation to the food waste in households, considering the family unit as a whole as well as individual family members. Quantifying the problem is an important aspect in order to know its scope and dimension, but prevention also involves knowing the causes in a home. This is a complex issue, which, on a family level, is related to socioeconomic status, educational level, composition and number of members of the household as well as culinary and buying food habits. Individual variables such as age, sex, values, awareness, lifestyle and time spent on food preparation were included to characterize consumers. The focus of the problem is also important because most consumers consider food waste from a social perspective, without being aware of the serious environmental and economic problems. Habits and customs of consumers are considered the leading cause of food waste in homes and knowledge of this issue raises consumer awareness as a preventive tool.

Stakeholder engagement in developing a father-inclusive early life obesity prevention intervention: First Heroes.

BACKGROUND: Although paternal involvement in the perinatal period is associated with benefits for maternal-child health and reduced obesity risk, fathers are seldom included in perinatal or obesity prevention efforts. Engaging community leaders and fathers as stakeholders in intervention development is a critical step in designing a father-inclusive intervention that is efficacious and responsive to their needs. METHODS: We conducted a structured engagement study, including community stakeholder engagement and qualitative interviews with new fathers, to inform the development of a prospective randomized controlled trial that includes mothers and fathers as equal partners in infant obesity prevention. We interpreted stakeholder feedback through the Consolidated Framework for Implementation Research (CFIR) framework. RESULTS: Between September 2019 and April 2020, we held a Community Engagement meeting, formed a Community Advisory Board, and conducted 16 qualitative interviews with new fathers. Stakeholder engagement revealed insights across CFIR domains including intervention characteristics (relative advantage, complexity, design quality & packaging), outer setting factors (cosmopolitanism and culture), individual characteristics (including self-efficacy, state of change, identification with the organization) and process (engagement and adaptation). Stakeholders discussed the diverse challenges and rewards of fatherhood, as well as the intrinsic paternal motivation to be a loving, supportive father and partner. Both community leaders and fathers emphasized the importance of tailoring program delivery and content to meet specific parental needs, including a focus on the social-emotional needs of new parents. CONCLUSIONS: A structured process of multidimensional stakeholder engagement was successful in improving the design of a father-inclusive perinatal obesity prevention interventions. Father engagement was instrumental in both reinforcing community ties and increasing our understanding of fathers' needs, resulting in improvements to program values, delivery strategies, personnel, and content. This study provides a practical approach for investigators looking to involve key stakeholders in the pre-implementation phase of intervention development. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04477577 . Registered 20 July 2020.

Bioecological aspects of triatomines and marsupials as wild Trypanosoma cruzi reservoirs in urban, peri-urban and rural areas in the Western Brazilian Amazon.

In the Amazon region, Trypanosoma cruzi transmission cycles involve a great diversity of Triatominae vectors and mammal reservoirs. Some Rhodnius spp. mainly inhabit palm trees that act as microhabitats for hosts and vectors. The current study aimed to describe aspects of the bio-ecology of the vectors and reservoirs of T. cruzi in relation to human populations resident near areas with large quantities of palm trees, in rural, peri-urban and urban collection environments, located in the Western Brazilian Amazon. Rhodnius pictipes and Didelphis marsupialis were respectively the most predominant vector and reservoir, with rates of 71% for R. pictipes and 96.5% for D. marsupialis. The vast majority of T. cruzi isolates clustered with TcI. The most prevalent haplotype was TcI COII1 (69.7%). Mauritia flexuosa and Attalea phalerata were the main ecological indicators of infestation by triatomines. Birds were the most common food source (27,71%). T. cruzi isolated from R. robustus has the haplotype HUM-13, previously detected in a chronic Chagas patient living in the same area. Our results demonstrate the relevance of this study, with the occurrence of elevated infection rates in animals, and suggest the importance of the Amazon zones where there is a risk of infection in humans.

Replacing soybean meal with okara meal: Effects on production, milk fatty acid and plasma amino acid profile, and nutrient utilization in dairy cows.

Okara meal is a byproduct from the production of soymilk and tofu and can potentially replace soybean meal (SBM) in dairy diets due to its high crude protein (CP) concentration and residual fat. The objective of this study was to investigate the effects of replacing SBM with okara meal on feed intake, yields of milk and milk components, milk fatty acid (FA) profile, nutrient utilization, and plasma AA concentration in lactating dairy cows. Twelve multiparous (65 ± 33 d in milk) and 8 primiparous (100 ± 35 d in milk) organically certified Jersey cows were paired by parity or days in milk, and within pair, randomly assigned to treatments in a crossover design with 21-d periods (14 d for diet adaptation and 7 d for data and sample collection). Diets were fed as total mixed ration formulated to be isonitrogenous and isofibrous and contained (dry matter basis) 50% mixed, mostly grass baleage, 2% sugarcane liquid molasses, 2% minerals-vitamins premix, and either (1) 8.1% SBM, 10% soyhulls, and 27.9% ground corn (CTRL); or (2) 15% okara meal, 8% soyhulls, and 23% ground corn (OKR). Dietary CP, ash-free neutral detergent fiber, and total FA averaged 15.4, 35.3, and 3.08% for CTRL and 15.9%, 36.3%, and 3.74% for OKR, respectively. Substitution of SBM with okara meal did not alter dry matter intake but increased intakes of CP and ash-free neutral detergent fiber. Additionally, no significant differences between treatments were observed for yields of milk and milk components, and concentrations of milk fat, lactose, and total solids. However, milk true protein concentration was lower in cows fed OKR (3.76%) versus CTRL (3.81%). Both milk urea N (8.51 vs. 9.47 mg/dL) and plasma urea N (16.9 vs. 17.8 mg/dL) concentrations decreased with OKR relative to the CTRL diet, respectively. Compared with CTRL, feeding OKR lowered the milk proportions of total odd-chain FA, de novo FA, and mixed FA and increased those of preformed FA, total n-6 FA, and total n-3 FA. The milk proportions of trans-10 18:1, trans-11 18:1, and cis-9,trans-11 18:2 were greater with feeding OKR versus the CTRL diet. The apparent total-tract digestibility of nutrients, urinary excretion of total purine derivatives (uric acid plus allantoin), and total N were not affected by treatments. Except for plasma Leu, which was lower in OKR compared with the CTRL diet, no other significant changes in the plasma concentrations of AA were observed. The plasma concentration of carnosine was lowest in cows receiving the OKR diet. Overall, our results revealed that okara meal can completely replace SBM without negatively affecting production and nutrient digestibility in early- to mid-lactation Jersey cows. Further research is needed to assess the economic feasibility of including okara meal in dairy diets, as well as the amount of okara meal that maximizes yields of milk and milk components in dairy cows in different stages of lactation.

First detection of voltage-gated sodium channel mutations in Phlebotomus argentipes collected from Bangladesh.

BACKGROUND & OBJECTIVES: Phlebotomus argentipes is the main vector of visceral leishmaniasis in Bangladesh and is controlled using deltamethrin, a synthetic pyrethroid, through indoor residual spraying (IRS). A mutation at L1014 (leucine at codon 1014) of the voltage-gated sodium channel (VGSC), known as a knockdown resistance (kdr) gene, is thought to be an important pyrethroid resistance mechanism. This study detected mutations at codon 1014, and at codons 1011, 1016, and 1020, which are kdr sites in other insects. The kdr relationship with deltamethrin resistance in P. argentipes from an IRS-targeted site in Bangladesh was also evaluated. METHODS: Sand flies were collected from Magurjora village, Mymensingh district, Bangladesh in November 2012. A WHO cone bioassay test using deltamethrin was conducted and specimens were grouped as 'live' or 'dead'. After morphological identification, genomic DNA was used to genotype a partial VGSC gene from P. argentipes. The kdr/ pyrethroid resistance relationship was evaluated using Fisher's exact test. RESULTS: Targeted codons were genotyped from 8 'live' and 63 'dead' P. argentipes. All 'live' specimens had mutant alleles (L1014F and L1014S) at codon 1014. The mutant allele rate was 94% for 'live' specimens and 55% for 'dead' specimens. The mutant allele survival odds were higher for the wild-type L1014L allele, and L1014F odds were lower for L1014S. There were no mutations at codons 1011, 1016, and 1020. INTERPRETATION & CONCLUSION: The L1014 mutations suggested that pyrethroid resistance had appeared in Bangladesh. Further research on kdr mutations in P. argentipes is important for the appropriate IRS.

Physical properties of new ordered bimetallic phases M0.25Cd0.75PS3 (M = ZnII, NiII, CoII, MnII).

Four bimetallic phases of the thiophosphate family have been synthesized by the cationic exchange reaction using a freshly prepared K0.5Cd0.75PS3 precursor phase and methanolic solutions of nitrates of the divalent cations ZnII, NiII, CoII, and MnII. All the materials were characterized by FTIR, PXRD, SEM-EDXS and (in the case of the diamagnetic compounds) by solid state NMR. For the K0.5Cd0.75PS3 precursor, the X-ray powder diffraction data suggest a modification of the structure, while solid state NMR results confirm that this phase possesses an ordered arrangement of Cd vacancies. The cationic exchange reaction achieves a complete removal of potassium ions (no potassium detected by SEM-EDXS) and re-occupation of the vacancies by divalent cations. Therefore, the obtained compounds have an average composition of M0.25Cd0.75PS3 (M = ZnII, NiII, CoII, MnII) and possess an ordered distribution of the substituent cations. Even with the paramagnetic substitution level of 25%, antiferromagnetic behaviour is present in the phases with MnII, CoII and NiII, as evidenced by dc susceptibility and in the case of the MnII substituted phase by EPR. The cooperative magnetic interactions confirm the conclusion that the paramagnetic ions adopt an ordered arrangement. The analysis by broad band impedance spectroscopy allows to attribute the conductivity in these materials to charge movements in the layers due to the difference in electronegativity of the metal ions. Zn0.25Cd0.75PS3 is the phase that shows the highest conductivity values. Finally, the band gap energies of the bimetallic phases tend to be lower than those of the single-metal phases, probably due to an overlap of the band structures.

Interleukin-27 and interleukin-37 are elevated in sickle cell anemia patients and inhibit in vitro secretion of interleukin-8 in neutrophils and monocytes.

BACKGROUND AND OBJECTIVE: Inflammation is implicated in the pathogenesis of most complications seen in sickle cell anemia (SCA) patients. We aimed to evaluate serum levels of two newly discovered anti-inflammatory cytokines (IL-27 and IL-37), and pro-inflammatory cytokines among Brazilian SCA patients that are not on hydroxyurea therapy (HbSS), compared with hydroxyurea-treated patients (HbSSHU) and healthy controls (HbAA). Furthermore, we demonstrated the effect of IL-27, IL-37, and heme on in vitro secretions of IL-8 in human neutrophils and monocytes. METHODS: A cross-sectional study of 82 consenting SCA (35 HbSS and 47 HbSSHU) patients in steady state and 49 HbAA consenting individuals. Clinical details were obtained from interviews and medical records. Serum levels of IL-27, IL-37, TGF-ß, TNF-α, IL-1ß, IL-6, and IL-8 were quantified by enzyme linked immunosorbent assay (ELISA). Neutrophils and monocytes were isolated from healthy controls, and cultured separately with or without cytokines (IL-27 and IL-37) and heme. Supernatant IL-8 concentration was determined by ELISA. RESULTS: Serum levels of IL-27, IL-37, IL-1ß, IL-6, and IL-8 were significantly elevated in HbSS patients compared to HbAA controls. Serum IL-8 levels were significantly higher in HbSS and HbSSHU patients than in controls. IL-27 and IL-37 were positively correlated in both HbSS and HbSSHU patients. In vitro IL-8 production by IL-27 and IL-37 pre-treated neutrophils and monocytes was significantly inhibited even after heme addition. CONCLUSIONS: Our findings show that IL-27 and IL-37, as well as the pro-inflammatory cytokines, are elevated in HbSS patients compared with controls, suggesting that the secretion of these anti-inflammatory cytokines is driven by the presence of pro-inflammatory cytokines. This role is probably sufficient in preventing further cellular or tissue damage but not potent enough to prevent inflammation. Therefore, IL-27 and IL-37 may be potential immuno-targets for ameliorating complications associated with elevated heme levels seen in SCA and other hemolytic anemias.

Replacing ground corn with incremental amounts of liquid molasses does not change milk enterolactone but decreases production in dairy cows fed flaxseed meal.

We investigated the effects of replacing ground corn (GRC) with incremental amounts of liquid molasses (LM) on milk enterolactone concentration, antioxidant enzymes activity in plasma, production, milk fatty acid (FA) profile, and nutrient utilization in Jersey cows fed flaxseed meal and low-starch diets. Sixteen multiparous organically certified Jersey cows averaging (mean ± standard deviation) 101 ± 45 d in milk, 462 ± 38 kg of body weight, and 19.8 ± 3.90 kg/d of milk in the beginning of the study were randomly assigned to treatment sequences in a replicated 4 × 4 Latin square design, with 14 d for diet adaptation and 7 d for data and sample collection. Diets were fed as total mixed rations consisting (dry matter basis) of 52% grass-legume baleage, 8% grass hay, 8.5% soyhulls, 2.5% roasted soybean, 15% flaxseed meal, and 2% minerals-vitamins premix. The GRC-to-LM dietary ratios (dry matter basis) were 12:0, 8:4, 4:8, and 0:12. Orthogonal polynomials were used to test linear, quadratic, and cubic effects using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC). The milk concentration of enterolactone tended to respond cubically, thus suggesting that replacing GRC with LM did not affect this lignan in milk. The plasma activities of the antioxidant enzymes glutathione peroxidase and catalase did not differ, but superoxide dismutase activity tended to respond cubically with feeding increasing amounts of LM. Dry matter intake and yields of milk and milk fat, true protein, and lactose decreased linearly with substituting GRC for LM. Whereas the concentrations of milk fat and milk true protein did not differ across treatments, milk lactose content decreased linearly. Feeding incremental levels of LM reduced linearly the milk concentration of urea N and the amount of N excreted in urine, and tended to decrease linearly the concentration of plasma urea N. Apparent total-tract digestibilities of dry matter, organic matter, and neutral and acid detergent fiber did not differ across treatments, whereas digestibility of crude protein decreased linearly. Digestibility of starch responded linearly and quadratically, but the actual differences between treatments were too small to be biologically significant. Milk FA profile was substantially changed most notably by linear increases in cis-9,trans-11 18:2, cis-9,cis-12,cis-15 18:3, Σ odd-chain FA, and the trans-11-to-trans-10 ratio, and linear decreases in cis-9 18:1 and cis-9,cis-12 18:2 when replacing GRC by incremental amounts of LM.

Effect of organic solvents and ultrasound on the removal of orthodontic brackets.

OBJECTIVE: To evaluate the effect of organic gel solvents (70% acetone and 90% ethanol) and ultrasound in the removal of metallic brackets. MATERIALS AND METHODS: Metallic brackets were bonded with light-cured orthodontic composite (Transbond XT) in 120 human bicuspids and divided into 6 groups for the enamel etch-and-rinse adhesive system (XT) and 6 groups to self-etching system (SEPT) according to pretreatment to removal test: control, 70% acetone, 90% ethanol, ultrasound, 70% acetone+ultrasound, and 90% ethanol+ultrasound. The brackets were subjected to removal by shear testing and Adhesive Remnant Index (ARI) evaluation. Some specimens were prepared and its adhesive interface and etching ability observed by scanning electron microscopy (SEM). RESULTS: Only the factor 'ultrasound' and its interaction with 'adhesive' were detected as a source of variance, with the SEPT/ultrasound showing the lowest shear strength than the other groups. Regardless the factor 'ultrasound', XT showed a higher ARI than SEPT; however, when the solvents were used, no differences were detected between XT and SEPT. CONCLUSION: The organic solvents were not effective in reducing shear bond strength. The etch-and-rinse adhesive system showed a higher and more favorable ARI score than the self-etching primer. The behavior of the organic solvents on ARI showed to be better when associated with the self-etching primer. The ultrasound was effective in reducing the shear bond strength of the self-etching adhesive system but not in affecting the ARI of the adhesive systems.

Antimicrobial potential of actinobacteria isolated from the rhizosphere of the Caatinga biome plant Caesalpinia pyramidalis Tul.

Actinobacteria are known to produce various secondary metabolites having antibiotic effects. This study assessed the antimicrobial potential of actinobacteria isolated from the rhizosphere of Caesalpinia pyramidalis Tul. from the Caatinga biome. Sixty-eight actinobacteria isolates were evaluated for antimicrobial activity against different microorganisms by disk diffusion and submerged fermentation, using different culture media, followed by determination of minimum inhibitory concentration (MIC) and chemical prospecting of the crude extract. Of the isolates studied, 52.9% of those isolated at 37°C and 47.05% of those isolated at 45°C had activity against Bacillus subtilis, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Fusarium moniliforme, and Candida albicans. When compared with others actinobacteria, the isolate C1.129 stood out with better activity and was identified by 16S rDNA gene analysis as Streptomyces parvulus. The crude ethanol extract showed an MIC of 0.97 µg/mL for MRSA and B. subtilis, while the ethyl acetate extract showed MIC of 3.9 µg/mL for S. aureus and MRSA, showing the greatest potential among the metabolites produced. Chemical prospecting revealed the presence of mono/sesquiterpenes, proanthocyanidin, triterpenes, and steroids in both crude extracts. This study evaluates S. parvulus activity against multi-resistant microorganisms such as MRSA. Thus, it proves that low-fertility soil, as is found in the Caatinga, may contain important microorganisms for the development of new antimicrobial drugs.

Defining the transition from new to normal: a qualitative investigation of the clinical change process.

Background: Understanding how and when a new evidence-based clinical intervention becomes standard practice is crucial to ensure that healthcare is delivered in alignment with the most up-to-date knowledge. However, rigorous methods are needed to determine when a new clinical practice becomes normalized to the standard of care. To address this gap, this study qualitatively explores how, when, and why a clinical practice change becomes normalized within healthcare organizations. Methods: We used purposive sampling to recruit clinical leaders who worked in implementation science across diverse health contexts. Enrolled participants completed semi-structured interviews. Qualitative data analysis was guided by a modified version of the Normalization Process Theory (NPT) framework to identify salient themes. Identified normalization strategies were mapped to the Expert Recommendations for Implementation Change (ERIC) project. Results: A total of 17 individuals were interviewed. Participants described four key signals for identifying when a novel clinical practice becomes the new normal: 1) integration into existing workflows; 2) scaling across the entire organizational unit; 3) staff buy-in and ownership; and 4) sustainment without ongoing monitoring. Participants identified salient strategies to normalize new clinical interventions: 1) taking a patient approach; 2) gaining staff buy-in and ownership; and 3) conducting ongoing measurement of progress towards normalization. Conclusions: The results offer valuable insight into the indicators that signify when a novel clinical practice becomes normalized, and the strategies employed to facilitate this transition. These findings can inform future research to develop instruments that implementation leaders can use to systematically measure the clinical change process.

Effect of agitation on the performance of an anaerobic sequencing batch biofilm reactor in the treatment of dairy effluents.

Agitation rate is an important parameter in the operation of Anaerobic Sequencing Biofilm Batch Reactors (ASBBRs), and a proper agitation rate guarantees good mixing, improves mass transfer, and enhances the solubility of the particulate organic matter. Dairy effluents have a high amount of particulate organic matter, and their anaerobic digestion presents inhibitory intermediates (e.g., long-chain fatty acids). The importance of studying agitation in such batch systems is clear. The present study aimed to evaluate how agitation frequency influences the anaerobic treatment of dairy effluents. The ASBBR was fed with wastewater from milk pasteurisation process and cheese manufacture with no whey segregation. The organic matter concentration, measured as chemical oxygen demand (COD), was maintained at approximately 8,000 mg/L. The reactor was operated with four agitation frequencies: 500 rpm, 350 rpm, 200 rpm, and no agitation. In terms of COD removal efficiency, similar results were observed for 500 rpm and 350 rpm (around 90%) and for 200 rpm and no agitation (around 80%). Increasing the system's agitation thus not only improved the global efficiency of organic matter removal but also influenced volatile acid production and consumption and clearly modified this balance in each experimental condition.

Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation, Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice.

Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson's disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Graphical Abstract MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.

High frequency of lamivudine resistance mutations in Brazilian patients co-infected with HIV and hepatitis B.

This study analyzed the genotype distribution and frequency of lamivudine (LAM) and tenofovir (TDF) resistance mutations in a group of patients co-infected with HIV and hepatitis B virus (HBV). A cross-sectional study of 847 patients with HIV was conducted. Patients provided blood samples for HBsAg detection. The load of HBV was determined using an "in-house" real-time polymerase chain reaction. HBV genotypes/subgenotypes, antiviral resistance, basal core promoter (BCP), and precore mutations were detected by DNA sequencing. Twenty-eight patients with co-infection were identified. The distribution of HBV genotypes among these patients was A (n = 9; 50%), D (n = 4; 22.2%), G (n = 3; 16.7%), and F (n = 2; 11.1%). Eighteen patients were treated with LAM and six patients were treated with LAM plus TDF. The length of exposure to LAM and TDF varied from 4 to 216 months. LAM resistance substitutions (rtL180M + rtM204V) were detected in 10 (50%) of the 20 patients with viremia. This pattern and an accompanying rtV173L mutation was found in four patients. Three patients with the triple polymerase substitution pattern (rtV173L + rtL180M + rtM204V) had associated changes in the envelope gene (sE164D + sI195M). Mutations in the BCP region (A1762T, G1764A) and in the precore region (G1896A, G1899A) were also found. No putative TDF resistance substitution was detected. The data suggest that prolonged LAM use is associated with the emergence of particular changes in the HBV genome, including substitutions that may elicit a vaccine escape phenotype. No putative TDF resistance change was detected after prolonged use of TDF.

Prediction of acidemia at birth by Doppler assessment of fetal cerebral transverse sinus in pregnancies with placental insufficiency.

OBJECTIVES: To evaluate the prediction of acidemia at birth using cerebral transverse sinus (CTS) Doppler velocimetry and to determine the best parameter and cut-off values for its prediction in pregnancies complicated with placental insufficiency. METHODS: This was a prospective cross-sectional study involving 69 pregnant women (26-40 weeks' gestation) with placental insufficiency managed in two Brazilian hospitals. Doppler assessment of the CTS was carried out in the last 24 h before delivery, and the peak ventricular systolic (S-wave) and diastolic (D-wave) velocities as well as the atrial systolic velocity (A-wave) were recorded and the pulsatility index for veins (PIV) was calculated. At birth, arterial and venous umbilical cord blood samples were collected to determine acid-base and pH status. A receiver-operating characteristics (ROC) curve was constructed for each Doppler parameter with birth acidemia as the dependent variable. Sensitivity, specificity, positive and negative predictive values, accuracy and false-positive and false-negative rates were calculated for the parameters considered to be good predictors of acidemia. RESULTS: The S, D and A peak velocities and the S/A ratio were not good predictors of acidemia at birth. The PIV and the (S - A)/S ratio were good predictors of acidemia (area under the ROC curve = 0.698 (P = 0.009) and 0.654 (P = 0.009), respectively). The cut-off values were PIV = 0.855 and (S - A)/S = 0.703). CONCLUSIONS: The PIV and the (S - A)/S ratio of the CTS were good predictors of acidemia at birth in this high-risk population with placental insufficiency.

Synthetic polymeric barrier membrane associated with blood coagulum, human allograft, or bovine bone substitute for ridge preservation: a randomized, controlled, clinical and histological trial.

During the normal healing process, an extraction site may lose significant bone volume, making implant placement problematic. Quantitative evaluations of the amount of bone maintained by socket preservation with various materials are limited. The objective of this study was to evaluate, both clinically and histologically, the extent of alveolar bone preservation by blood coagulum (BC) and the potential additional benefits of bone allograft material (AL) versus the state-of-the-art bovine bone mineral (BB), covered by a polyethylene glycol (PEG) barrier, in extraction socket grafting procedures. Adult patients (n=32) with single-rooted teeth indicated for extraction were treated (45 sites). After atraumatic extraction, the sockets were filled with BC, AL, or BB and covered with a synthetic PEG barrier membrane. Changes in bone height and width were measured clinically and the amount of bone formed and residual graft particles were measured histologically after 6 months. Changes in ridge width at 6 months were -1.5mm for AL versus -2.5mm for BB and -2.3mm for BC. New bone formation amounted to 47.8%, 33.3%, and 28.2% at BC-, AL-, and BB-treated sites, respectively. Using AL with the PEG barrier preserved the ridge width at 6 months better than BB or BC and resulted in similar amounts of bone histologically to BB.

[Functional decline risk in elderly patients not institutionalized]. / Riesgo de declive funcional en pacientes ancianos no institucionalizados.

OBJECTIVE: To assess the risk of functional decline (DF) by using several prediction scales. MATERIAL AND METHODS: A multicentre, observational, cross-sectional study was conducted on a population of 70 years or more in the health area of ??Toledo. Institutionalised, terminal ill, and patients dependent for three or more basic activities of daily life, were excluded. The sample (480 patients) was calculated for an estimated DF prevalence of 15%, accuracy 2%, confidence level 95%, and 10% of estimated losses. Stratified sampling; first by conglomerates (Health Centres) and then systematic sampling (1/15) by list of patients ordered by age. Response rate: 98%. VARIABLES: Sociodemographic, morbidity, questionnaires to assess the functional capacity for basic activities (Katz index), and tools (Lawton-Brody index) of daily life and risk prediction rules of DF (SHERPA, TRST, ISAR-PC and Inouye). Approved by the Clinical Research Ethics Committee of Toledo. RESULTS: The mean age was 77.94 (SD: 6.27), with 54.4% women. Mean number of illnesses: 4.38 (SD: 2.17) and drugs: 5.57 (SD: 3.35). Risk of DF according to the prediction rules: SHERPA: 32.7% (95% CI: 28.52-36.88) (slight risk: 17.2% [95% CI: 13.83-20.57]; moderate: 9.7% [95% CI: 7.06-12.34] and high: 5.8% [95% CI: 3.72-7.88]); TRST: 42% (95% CI: 37.6-46.4); ISAR-PC: 75.4% (95% CI: 71.14-78.86); Inouye: 49.3% (95% CI: 44.84-53.76) (mean risk: 44.5% [95% CI: 40.07-48.93], and high: risk 4.8% [95% CI: 2.89-6.71]). CONCLUSIONS: A significant percentage of patients are at risk of DF, but there is a wide variation between the different rules. In general, the risk is lower than that found in other studies, and it is necessary to validate new rules adapted to our environment.

[Baseline spirometry parameters that can influence the bronchodilation test]. / Parámetros basales de la espirometría que pueden influir en la prueba de broncodilatación.

OBJECTIVE: To determine whether the baseline parameters of forced spirometry can influence the positivity of the bronchodilation test (BDT), and whether this could have an influence in future positivity criteria. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted in a Primary Care setting. It included all patients referred by their family doctor to perform a forced spirometry test due to smoking, respiratory symptoms, or follow-up of respiratory diseases, between the months of June 2015 and February 2017. All of them were subjected to a forced spirometry with a BDT. RESULTS: A total of 295 patients were included, with a mean age 53.4±15.5 years, and 62% were male.An obstructive pattern was obtained in 20% of the spirometries, with 67.5% presenting with a mild obstruction, 18% a moderate, 9.6% moderate to severe, and 4.8% very severe. The BDT was positive in 8.8% of the spirometries, with 11.2% only positive in volume, and 17.6% were only positive in percentage. It was observed that the patients with a BDT positive in percentage had a lower base forced expiry volume in the first second (1.66 L/sec vs. 2.74 L/sec; P<.001), and a lower forced vital capacity (2.85 l vs.3.73 l; P<.001). The patients with a positive BDT in volume had a lower forced expiry volume in the first second (2.59 l/sec vs. 2. 62 l/sec; P<.001), and a higher forced vital capacity (3.89 l vs. 3.58 l; P<.001). CONCLUSIONS: The baseline forced expiry volume in the first second and forced vital capacity have an influence in the positivity of the BDT. This circumstance should be assessed when establishing the positivity of the BDT.