Antifungal susceptibility and multilocus sequence typing (MLST) of Cryptococcus neoformans complex from HIV-associated cryptococcal meningitis patients in Manaus, Amazonas, Brazil.

Cryptococcus neoformans is primarily responsible for cases of cryptococcal meningitis in individuals with HIV/AIDS. This study evaluated the susceptibility of C. neoformans obtained from individuals with cryptococcal meningitis associated with HIV/AIDS in Manaus, Amazonas, Brazil, against the action of the antifungals amphotericin B, flucytosine, fluconazole, itraconazole and posaconazole and analyzed it using Multilocus Sequence Typing (MLST) in order to identify the Sequence Types (STs). We analyzed 30 isolates of C. neoformans, from 24 HIV/AIDS patients diagnosed with cryptococcosis from 2017 to 2019 in a reference hospital, in addition to 3 environmental isolates: 1 isolate obtained in the home of a patient and 2 isolates obtained from neighboring homes of patients. 86.6% (n = 26/30) of the clinical isolates were identified as C. neoformans VNI ST93, 6.6% (n = 2/30) as C. neoformans VNI ST5, 3.3% (n = 1/30) as C. neoformans VNI ST32 and 3.3% (n = 1/30) as C. neoformans VNB ST232. The environmental isolates were identified as C. neoformans VNI ST93 (n = 3/3). 96.6% (n = 29/30) isolates were sensitive to amphotericin B, though there was variation in the MIC. 60% (n = 18/30) presented a MIC above the proposed epidemiological cutoff values for one or more antifungals. All environmental isolates were sensitive to the tested antifungals. The MLST showed that there is an important relationship between C. neoformans VNI ST93 and individuals with HIV/AIDS, including in the environmental isolates analyzed. C. neoformans VNB ST232 was observed for the first time in Amazonas. Amphotericin B was proven to be the best drug, but fluconazole and posaconazole also showed relevant action.

Adapted Sequential Extraction Protocol to Study Mercury Speciation in Gold Mining Tailings: Implications for Environmental Contamination in the Amazon.

Artisanal small-scale gold mining (ASGM), an increasingly prevalent activity in South America, generates mercury-contaminated tailings that are often disposed of in the environment, leading to the introduction of mercury into ecosystems and the food web, where it bioaccumulates. Therefore, studying the geochemical processes involved in the desorption and dissolution of mercury in these tailings is essential for critical risk evaluations in the short and long term. For this purpose, sequential extraction procedures (SEPs) can be useful because they help to identify the phases to which Hg is associated, although they also have limitations such as a lack of selectivity and specificity. In this work, we propose a modified four-step SEP: exchangeable mercury (F1), oxidizable mercury (F2), mercury bound to Fe oxides (F3), and strongly bound mercury (F4). To test this adapted sequential extraction method, we evaluated the Hg contamination in mercury-contaminated tailings of the Amazon basin. The results revealed a total mercury concentration of 103 ± 16 mg·kg-1 in the tailings, with a significant portion in F1 (28% of the total), where Hg was bioavailable. The large Hg concentration in F3 (36%) suggested that Fe oxides likely contribute to mercury retention. Together, the SEP results emphasize the urgent need for improved surveillance of gold mining activities and responsible tailings management practices to mitigate environmental contamination and safeguard the health of the Amazon ecosystem.

Impact of the COVID-19 pandemic on perinatal care and outcomes: A retrospective study in a tertiary hospital in Northern Ghana.

BACKGROUND: Perinatal mortality remains a global challenge. This challenge may be worsened by the negative effects of the COVID-19 pandemic on maternal and child health. OBJECTIVES: Examine the impact of the COVID-19 pandemic on perinatal care and outcomes in the Tamale Teaching Hospital in northern Ghana. METHODS: A hospital-based retrospective study was conducted in the Tamale Teaching Hospital. We compared antenatal care attendance, total deliveries, cesarean sections, and perinatal mortality before the COVID-19 pandemic (March 1, 2019 to February 28, 2020) and during the COVID-19 pandemic (March 1, 2020 to February 28, 2021). Interrupted time series analyses was performed to evaluate the impact of the COVID-19 pandemic on perinatal care and outcomes at TTH. RESULTS: A total number of 35,350 antenatal visits and 16,786 deliveries were registered at TTH from March 2019 to February 2021. Antenatal care, early neonatal death, and emergency cesarean section showed a rapid decline after the onset of the pandemic, with a progressive recovery over the following months. The total number of deliveries and fresh stillbirths showed a step change with a marked decrease during the pandemic, while the macerated stillbirths showed a pulse change, a temporary marked decrease with a quick recovery over time. CONCLUSION: The COVID-19 pandemic had a negative impact on perinatal care and outcomes in our facility. Pregnancy monitoring through antenatal care should be encouraged and continued even as countries tackle the pandemic.

Asthma in the Brazilian Unified Health Care System: an epidemiological analysis from 2008 to 2021.

OBJECTIVE: To analyze the number of hospitalizations, the length of hospital stay, and mortality due to asthma, as well as the costs to the Unified Health Care System in Brazil between 2008 and 2021. METHODS: This was a cross-sectional epidemiological study using data from the Information Technology Department of the Brazilian Unified Health Care System. Proportional hospitalization and death rates were estimated per 100,000 population by age, microregion, and year. RESULTS: The number of hospitalizations and deaths due to asthma decreased from 2008 to 2021 (205,392 vs. 55,009 and 822 vs. 327, respectively). In addition, a between-sex difference was observed in asthma-related hospitalizations in 2008, and more men were hospitalized in 2021 (51.8%). Asthma mortality rates were similar for both sexes (50.0% each) in 2008, and a slight increase was observed in women's deaths in 2021 (52.9%). Even so, approximately one death/day and more than 55,000 hospitalizations were observed yearly, with a mean length of hospital stay of three days. Additionally, the Southeast region allocated more financial resources to asthma-related hospitalizations. CONCLUSIONS: Our results showed that the number of deaths and hospitalizations due to asthma substantially declined during the study period.

Immediate effect of extracorporeal shockwave therapy in patients with chronic non-specific low back pain: A randomised placebo-controlled triple-blind trial.

OBJECTIVE: To compare the immediate effects of shockwave therapy using two different tips in patients with chronic non-specific low back pain. DESIGN: Randomised placebo-controlled study with three intervention groups. SETTING: The patients recruited for this study were sent for physiotherapy treatment at primary care between May and July 2022. PARTICIPANTS: Eighty-one patients with chronic non-specific low back pain aged 18-80 years with pain for ≥3 months and pain intensity ≥3 were randomly recruited for the study. INTERVENTION: The patients received a single intervention of radial shockwave therapy with 2000 discharges at 100 mJ energy and 5 Hz frequency using concave or convex tips or placebo treatment. MAIN MEASURES: The primary outcome was pain intensity immediately post-intervention. The secondary outcomes were pressure pain threshold, temporal summation of pain, and functional performance. Data were collected at baseline and post-intervention. RESULTS: The post-intervention pain intensity in the concave tip group is an average of two points lower (95% CI = -3.6, -0.4; p < 0.01) than that in the placebo group. The post-intervention pressure pain threshold for the concave tip group was an average of 62.8 kPa higher (95% CI = 0.4, 125.1; p < 0.05) than for the convex tip group and 76.4 kPa higher (95% CI = 14, 138.7; p < 0.01) than in the placebo group. CONCLUSION: The concave tip shockwave therapy is effective in reducing pain and local hyperalgesia in patients with chronic non-specific low back pain.

Cultivable Fungi from Amazon River Dolphins Engaged in Wildlife Ecotourism in the Anavilhanas National Park, Brazil.

Amazon River dolphins are an important flagship species in the Anavilhanas National Park, Brazil, where they interact with visitors. This study aimed to quantify and identify fungi isolated from dolphin skin and oral samples and their surrounding environment in this unique ecosystem. Samples were collected from three dolphins and water samples from Flutuante dos Botos and the Novo Airão city harbor. Fungi were isolated using culture media and identified through micromorphology assays and ITS region sequencing. Oral swab samples resulted in culture of Trichosporon montevideense and Exophiala dermatitidis. Skin samples from one dolphin revealed Toxicocladosporium irritans and Diaporthe lithocarpus. Water samples exhibited higher fungal counts and diversity, with Rhodotorula mucilaginosa, Exophiala dermatitidis, Penicillium citrinum, Fomitopsis meliae, and Nectria pseudotrichia identified at the collection site and Candida spencermartinsiae and Penicillium chermesinum at the city harbor. This study provides important insights into the fungal diversity associated with Amazon River dolphins and their environment, enhancing our understanding of the public health and ecological dynamics in the Anavilhanas National Park.

Analysis of learning curves in predictive modeling using exponential curve fitting with an asymptotic approach.

The existence of large volumes of data has considerably alleviated concerns regarding the availability of sufficient data instances for machine learning experiments. Nevertheless, in certain contexts, addressing limited data availability may demand distinct strategies and efforts. Analyzing COVID-19 predictions at pandemic beginning emerged a question: how much data is needed to make reliable predictions? When does the volume of data provide a better understanding of the disease's evolution and, in turn, offer reliable forecasts? Given these questions, the objective of this study is to analyze learning curves obtained from predicting the incidence of COVID-19 in Brazilian States using ARIMA models with limited available data. To fulfill the objective, a retrospective exploration of COVID-19 incidence across the Brazilian States was performed. After the data acquisition and modeling, the model errors were assessed by employing a learning curve analysis. The asymptotic exponential curve fitting enabled the evaluation of the errors in different points, reflecting the increased available data over time. For a comprehensive understanding of the results at distinct stages of the time evolution, the average derivative of the curves and the equilibrium points were calculated, aimed to identify the convergence of the ARIMA models to a stable pattern. We observed differences in average derivatives and equilibrium values among the multiple samples. While both metrics ultimately confirmed the convergence to stability, the equilibrium points were more sensitive to changes in the models' accuracy and provided a better indication of the learning progress. The proposed method for constructing learning curves enabled consistent monitoring of prediction results, providing evidence-based understandings required for informed decision-making.

Exploring the mechanism of the reductive amination of acetophenones via the Borch approach: the role of the acid catalyst.

The energetic viability of several mechanistic variations of the reductive amination of acetophenones via the Borch approach was re-examined through density functional theory calculations. The crucial involvement of the acid catalyst is evident not only in the elimination of water, but also in the initial nucleophilic step. This role increases with the electron-donating capability of the substituent positioned at the para-position of acetophenone.

Comparison of self-etching and conventional bifunctional coupling agent in lithium disilicate ceramic: A systematic review and meta-analysis.

Background: The aim of this systematic review is to determine the effectiveness of self-etching primers in comparison to the conventional protocol with hydrofluoric acid and silane treatment for bonding lithium disilicate ceramics. Material and Methods: The formulated PICO question for this research was: "Does self-etching silane primer surface treatment in lithium disilicate ceramics present a similar bond strength value compared to conventional hydrofluoric acid and silane treatment?". Combinations of words and appropriate truncations were adapted for each database. For the selection, duplicate articles were systematically eliminated using Mendeley software. The Cohen's Kappa statistic was then computed, RoBDEMAT questions were addressed, and the meta-analyses were conducted using RevMan 5.4, at a significance level of 5%. Results: Two independent reviewers conducted a blind and independent analysis of 190219 articles from PubMed, Scopus, Web of Science, and OpenGrey. Subsequently, they extracted data from 21 studies for the systematic review and in 16 the meta-analysis. In all in vitro studies, the most frequently cited concentration of hydrofluoric acid was 5%. In the meta-analysis, no statistical differences were observed between the two treatments concerning bond strength. Conclusions: Self-etching silane primers demonstrate promising results in lithium disilicate bonding, suggesting their potential as an alternative surface treatment to hydrofluoric acids + silane. Key words:Lithium disilicate, Hydrofluoric acid, Dental Porcelain, Ceramics, Silanes.

Applicability of machine learning algorithm to predict the therapeutic intervention success in Brazilian smokers.

Smoking cessation is an important public health policy worldwide. However, as far as we know, there is a lack of screening of variables related to the success of therapeutic intervention (STI) in Brazilian smokers by machine learning (ML) algorithms. To address this gap in the literature, we evaluated the ability of eight ML algorithms to correctly predict the STI in Brazilian smokers who were treated at a smoking cessation program in Brazil between 2006 and 2017. The dataset was composed of 12 variables and the efficacies of the algorithms were measured by accuracy, sensitivity, specificity, positive predictive value (PPV) and area under the receiver operating characteristic curve. We plotted a decision tree flowchart and also measured the odds ratio (OR) between each independent variable and the outcome, and the importance of the variable for the best model based on PPV. The mean global values for the metrics described above were, respectively, 0.675±0.028, 0.803±0.078, 0.485±0.146, 0.705±0.035 and 0.680±0.033. Supporting vector machines performed the best algorithm with a PPV of 0.726±0.031. Smoking cessation drug use was the roof of decision tree with OR of 4.42 and importance of variable of 100.00. Increase in the number of relapses also promoted a positive outcome, while higher consumption of cigarettes resulted in the opposite. In summary, the best model predicted 72.6% of positive outcomes correctly. Smoking cessation drug use and higher number of relapses contributed to quit smoking, while higher consumption of cigarettes showed the opposite effect. There are important strategies to reduce the number of smokers and increase STI by increasing services and drug treatment for smokers.

Peri-implantitis: Knowledge and attitudes of implantology clinicians regarding the disease management: Peri-implantitis knowledge.

OBJECTIVES: Since peri-implantitis is an increasing and prevalent concern in clinical practice and there is no consensus regarding the best therapeutic protocol, this study evaluated the knowledge and behaviours of dentists working in Implantology regarding implant-related infections modulating factors and therapeutic protocols used in the management of peri-implantitis. METHODS: Cross-sectional study was conducted with 86 Brazilian Implantology clinicians. Data were collected using a structured and online questionnaire evaluating socioeconomic characteristics, education, work/clinical practice, knowledge and attitudes regarding the risk factors and management of peri-implantitis. The reliability of the questionnaire was evaluated by test-retest technique. The questionnaire was developed based on the last consensus on peri-implant diseases (2018) and the current evidence related to implant-related infections. Descriptive, bivariate and logistic regression analyses were conducted adopting a significance level of 5%. RESULTS: In this study, 89.5% of included dentists reported that already treated patients with peri-implantitis. Approximately 80% of dentists use antibiotics and mouth rinses during the treatment, and surgical procedures seem the main choice to treat peri-implantitis (91.8%) by dentists. As a preventive approach, 94.2% of dentists reported that routinely assessed biofilm accumulation in the follow-up visits after implant placement. Logistic regression showed that the self-reported ability to treat peri-implantitis was statistically (p < 0.05) higher among dentists who reported abilities to diagnose the disease and use laser for peri-implantitis treatment. CONCLUSION: Dentists working in Implantology have a good level of knowledge and behaviors in the management of peri-implantitis. However, the lack of consensus regarding the best treatment protocols may reflect dentist's behaviours because different treatment protocols have been used by evaluated clinicians.

Predicting functional decline in aging and Alzheimer's disease with PET-based Braak staging.

The progression of PET-based Braak stages correlates with cognitive deterioration in aging and Alzheimer's disease. Here, we investigate the association between PET-based Braak stages and functional impairment and assess whether PET-based Braak staging predicts a longitudinal decline in the performance of activities of daily living. In this cohort study, we evaluated cognitively unimpaired individuals and individuals with mild cognitive impairment or Alzheimer's disease dementia. Participants underwent [18F]MK6240 tau-PET, were assigned a PET-based Braak stage at baseline and were followed for a mean (SD) of 1.97 (0.66) years. Functional performance was evaluated with the Functional Activities Questionnaire, Everyday Cognition and functional Clinical Dementia Rating sum of boxes. Multiple linear regressions assessed the association of PET-based Braak stages with baseline functionality and with the longitudinal rate of change in functional scores, adjusting for age, sex and amyloid-ß load. We employed voxel-based regression models to investigate the association between functionality and tau-PET signal and assessed the voxel overlap with Braak regions of interest. We included 291 individuals (181 cognitively unimpaired, 56 amyloid-ß+ mild cognitive impairment and 54 amyloid-ß+ Alzheimer's disease) aged 70.60 (7.48) years. At baseline, PET-based Braak stages III-IV (ß = 0.43, P = 0.03) and V-VI (ß = 1.20, P < 0.0001) showed associations with poorer Functional Activities Questionnaire scores. Similarly, stages III-IV (ß = 0.43, P = 0.02) and V-VI (ß = 1.15, P < 0.0001) were associated with worse Everyday Cognition scores. Only stages V-VI were associated with higher functional Clinical Dementia Rating sum of boxes (ß = 1.17, P < 0.0001) scores. Increased tau-PET signals in all Braak regions of interest were linked to worse performance in all tools. The voxelwise analysis showed widespread cortical associations between functional impairment and tau-PET and high voxel overlap with Braak regions of interest. Baseline PET-based Braak stages V-VI predicted significant longitudinal functional decline as assessed by the Functional Activities Questionnaire (ß = 1.69, P < 0.0001), the Everyday Cognition (ß = 1.05, P = 0.001) and the functional Clinical Dementia Rating sum of boxes (ß = 1.29, P < 0.0001). Our results suggest that functional impairment increases with the severity of tau accumulation. These findings also indicate that PET-based Braak staging is a good predictor of functional impairment in the Alzheimer's disease continuum. Finally, our study provides evidence for the clinical significance of the PET-based Braak staging framework.

Antimicrobial activity of carvacrol and its derivatives on Mycobacterium spp.: systematic review of preclinical studies.

Background: The scope of the study was to analyze original preclinical studies on the antimicrobial effects of carvacrol and derivatives on the Mycobacterium genus. Materials & methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, four databases (PubMed, Web of Science, SCOPUS and EMBASE) were searched. Results: The search retrieved 392 records, of which 11 papers were selected. Heterogeneity in the techniques and mycobacterial targets was observed. Carvacrol demonstrated synergistic antimycobacterial activity with rifampicin against multidrug-resistant Mycobacterium tuberculosis on membranes and biofilms. In silico approaches showed specific targets in mycobacteria, by inhibition and molecular docking assays, on the enzyme chorismate mutase and the heat shock protein 16.3. Conclusion: Carvacrol has been shown to be a scaffold candidate for future molecules with activity against mycobacteria.

Histoplasmosis in HIV/AIDS patients in Amazonas, Northern Brazil.

Histoplasmosis is commonly observed in AIDS patients as a neglected opportunistic disease that has an important relationship with environmental factors. The present study described the clinical characteristics of HIV/AIDS patients diagnosed with disseminated histoplasmosis in a tertiary healthcare facility in Manaus, Amazonas, Brazil, and evaluated the patients' homes and urban environmental samples as a source of exposure to Histoplasma capsulatum. A review of medical records from 2017 to 2019 of patients with HIV/AIDS associated with histoplasmosis was carried out, as well as the collection of environmental samples in the homes of these patients. These samples were subjected to DNA extraction and then subjected to qPCR. A total of 62 patients diagnosed with HIV/AIDS and histoplasmosis were identified, which corresponds to 4.5% (n = 62/1372) of the HIV/AIDS cases detected in the period. Of these, 68% (n = 42/62) were male, with a mean age of 36 years and low education. In 47% (n = 29/62) of the cases, the diagnosis of HIV/AIDS and histoplasmosis occurred simultaneously. Mortality was 45% (n = 28/62), and 68% (n = 42/62) of these patients did not regularly use highly active antiretroviral therapy. The main symptoms found were respiratory, gastrointestinal, and weight loss, and in 81% (n = 50/62), the place of residence was in an urban area. A total of 57 environmental samples were analyzed, and the presence of Histoplasma capsulatum was not detected in any of the analyzed samples. There was a high mortality rate in the studied group of patients with AIDS and histoplasmosis. Most patients reported residing in urban areas of Manaus, with no history of travel to other areas previously known as being high risk for histoplasmosis.

Vulnerabilities and reparative strategies during pregnancy, childbirth, and the postpartum period: moving from rhetoric to action.

Maternal outcomes throughout pregnancy, childbirth, and the postnatal period are influenced by interlinked and interdependent vulnerabilities. A comprehensive understanding of how various threats and barriers affect maternal and perinatal health is critical to plan, evaluate and improve maternal health programmes. This paper builds on the introductory paper of the Series on the determinants of maternal health by assessing vulnerabilities during pregnancy, childbirth, and the postnatal period. We synthesise and present the concept of vulnerability in pregnancy and childbirth, and map vulnerability attributes and their dynamic influence on maternal outcomes in early and late pregnancy and during childbirth and the postnatal period, with a particular focus on low-income and middle-income countries (LMICs). We summarise existing literature and present the evidence on the effects of various reparative strategies to improve pregnancy and childbirth outcomes. Lastly, we discuss the implications of the identified vulnerability attributes and reparative strategies for the efforts of policymakers, healthcare professionals, and researchers working towards improving outcomes for women and birthing people in LMICs.

Aetiology and use of antibiotics in pregnancy-related infections: results of the WHO Global Maternal Sepsis Study (GLOSS), 1-week inception cohort.

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.

Deciphering the Absolute Configuration of Murgantiol Isomers in the Pheromone Blend of the Rice Stink Bug, Mormidea v-luteum (Hemiptera, Pentatomidae).

The males-produced pheromone blend of the Mormidea v-luteum (Hemiptera, Pentatomidae) consists in two isomers of zingiberenol (1) and three of murgantiol (2). While the absolute configuration of the zingiberenol isomers has been described, the configurations of the murgantiol isomers remained unexplored. So, our objective was to identify the absolute configuration of the murgantiol isomers (2 a-c) in the pheromone blend. To achieve this, we initially performed dehydration of the natural extract followed by enantiomeric resolution and, as a result, the three isomers was identified as (4R,1'S)-murgantiol. By leveraging the fixed cis and trans relationships among all pheromone components, we established the configuration at C-1 for isomers 2 a and 2 b is S, while that of 2 c is R. Finally, employing microchemical Sharples asymmetric dihydroxylation and epoxide ring closure, we determined the absolute configuration of the epoxide ring. Consequently, the natural isomers 2 a, 2 b, and 2 c were identified as (1S,4R,1'S,4'R)-, (1S,4R,1'S,4'S)-, and (1R,4R,1'S,4'S)-murgantiol, respectively.

Characterisation of an area of coexistent visceral and cutaneous leishmaniasis transmission in the State of Piauí, Brazil.

BACKGROUND: In Brazil, transmission of visceral and cutaneous leishmaniasis has expanded geographically over the last decades, with both clinical forms occurring simultaneously in the same area. OBJECTIVES: This study characterised the clinical, spatial, and temporal distribution, and performed entomological surveillance and natural infection analysis of a leishmaniasis-endemic area. METHODS: In order to characterise the risk of leishmaniasis transmission in Altos, Piauí, we described the clinical and socio-demographic variables and the spatial and temporal distribution of cases of American visceral leishmaniasis (AVL) and American cutaneous leishmaniasis (ACL) cases and identified potential phlebotomine vectors. FINDINGS: The urban area concentrated almost 54% of ACL and 86.8% of AVL cases. The temporal and spatial distribution of AVL and ACL cases in Altos show a reduction in the number of risk areas, but the presence of permanent disease transmission foci is observed especially in the urban area. 3,808 phlebotomine specimens were captured, with Lutzomyia longipalpis as the most frequent species (98.45%). Of the 35 females assessed for natural infection, one specimen of Lu. longipalpis tested positive for the presence of Leishmania infantum and Leishmania braziliensis DNA. MAIN CONCLUSION: Our results indicate the presence of risk areas for ACL and AVL in the municipality of Altos and highlight the importance of entomological surveillance to further understand a possible role of Lu. longipalpis in ACL transmission.

The glutamatergic system in Alzheimer's disease: a systematic review with meta-analysis.

Glutamatergic neurotransmission system dysregulation may play an important role in the pathophysiology of Alzheimer's disease (AD). However, reported results on glutamatergic components across brain regions are contradictory. Here, we conducted a systematic review with meta-analysis to examine whether there are consistent glutamatergic abnormalities in the human AD brain. We searched PubMed and Web of Science (database origin-October 2023) reports evaluating glutamate, glutamine, glutaminase, glutamine synthetase, glutamate reuptake, aspartate, excitatory amino acid transporters, vesicular glutamate transporters, glycine, D-serine, metabotropic and ionotropic glutamate receptors in the AD human brain (PROSPERO #CDRD42022299518). The studies were synthesized by outcome and brain region. We included cortical regions, the whole brain (cortical and subcortical regions combined), the entorhinal cortex and the hippocampus. Pooled effect sizes were determined with standardized mean differences (SMD), random effects adjusted by false discovery rate, and heterogeneity was examined by I2 statistics. The search retrieved 6 936 articles, 63 meeting the inclusion criteria (N = 709CN/786AD; mean age 75/79). We showed that the brain of AD individuals presents decreased glutamate (SMD = -0.82; I2 = 74.54%; P < 0.001) and aspartate levels (SMD = -0.64; I2 = 89.71%; P = 0.006), and reuptake (SMD = -0.75; I2 = 83.04%; P < 0.001. We also found reduced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR)-GluA2/3 levels (SMD = -0.63; I2 = 95.55%; P = 0.046), hypofunctional N-methyl-D-aspartate receptor (NMDAR) (SMD = -0.60; I2 = 91.47%; P < 0.001) and selective reduction of NMDAR-GluN2B subunit levels (SMD = -1.07; I2 = 41.81%; P < 0.001). Regional differences include lower glutamate levels in cortical areas and aspartate levels in cortical areas and in the hippocampus, reduced glutamate reuptake, reduced AMPAR-GluA2/3 in the entorhinal cortex, hypofunction of NMDAR in cortical areas, and a decrease in NMDAR-GluN2B subunit levels in the entorhinal cortex and hippocampus. Other parameters studied were not altered. Our findings show depletion of the glutamatergic system and emphasize the importance of understanding glutamate-mediated neurotoxicity in AD. This study has implications for the development of therapies and biomarkers in AD.