A Wolbachia symbiont in Aedes aegypti limits infection with dengue, Chikungunya, and Plasmodium.

Wolbachia are maternally inherited intracellular bacterial symbionts that are estimated to infect more than 60% of all insect species. While Wolbachia is commonly found in many mosquitoes it is absent from the species that are considered to be of major importance for the transmission of human pathogens. The successful introduction of a life-shortening strain of Wolbachia into the dengue vector Aedes aegypti that halves adult lifespan has recently been reported. Here we show that this same Wolbachia infection also directly inhibits the ability of a range of pathogens to infect this mosquito species. The effect is Wolbachia strain specific and relates to Wolbachia priming of the mosquito innate immune system and potentially competition for limiting cellular resources required for pathogen replication. We suggest that this Wolbachia-mediated pathogen interference may work synergistically with the life-shortening strategy proposed previously to provide a powerful approach for the control of insect transmitted diseases.

Levels and health risk assessment of twenty-one current-use pesticides in urban and riverside waters of the Brazilian Amazon Basin.

In Brazil, the favorable weather conditions and abundant land contribute to the thriving agricultural production. Brazilian crops extensively employ pesticides due to their high efficacy, cost-effectiveness, and permissive regulatory framework. However, pesticide use also endangers water resources, animal organisms, and human health. Due to the lack of data on pesticide use in the Amazonas forest-based Brazil, the present study aimed to assess the levels of twenty-one current-use pesticides (CUPs) from five different classes in river waters collected from urban and riverside areas in this region. Moreover, the non-carcinogenic risks associated with water consumption were also characterized. Thirteen CUPs were detected in concentrations above the limit of detection (LOD) in at least one of the water samples, and most pesticides were detected in riverside areas. In contrast, only 18% of the analyzed samples were considered "clean," with only one compound detected. Fenitrothion showed the highest concentration, with a mean value of 4.86 ng/mL (0.30-14.3 ng/mL). Up to 33% of the samples showed levels of fipronil above the LOD, an issue of environmental and human health concern, mainly because of the adverse effects observed in honeybees. Despite this, the human health risk assessment showed a target hazard quotient below one (HQ < 1) in adults for all substances, suggesting that pesticide exposure through water consumption should not mean risk for the riverside populations. Taking into account the large extension of Brazil, as well as its different agricultural practices throughout the country, it would be of great importance to conduct extensive research in other areas. It would help to gain knowledge in this field and to promote eco-friendly alternatives to mitigate pesticide use and, consequently, to reduce their potential adverse effects on human health and the ecosystems.

Blood levels of 21 metals and metalloids in riverside villagers of the Brazilian Amazon: A human biomonitoring study with associations with sociodemographic, dietary, and lifestyle factors.

Human biomonitoring of toxic and essential trace elements is critically important for public health protection. Amazonian riverine communities exhibit distinctive dietary patterns, heavily reliant on locally sourced fish, fruits, and vegetables. These habits may result in unique exposure profiles compared to urban populations. However, comprehensive assessments of their exposure to toxic and essential metals are lacking, representing a critical gap in understanding the health risks faced by these communities. This study aimed to establish baseline levels of 21 metals and metalloids in human blood and explore the influence of sociodemographic factors, dietary habits, and lifestyle choices as potential sources of exposure to these elements. A cross-sectional biomonitoring investigation was conducted with 1,024 individuals from 13 communities in the Tapajós and Amazon Basins (Pará, Brazil). Most of the elements in study was determined for the first time in the region. Blood samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The levels of all elements were summarized by quantiles and compared with cutoff values from other Brazilian populations. Multiple linear regression was used to assess possible associations between element concentrations and sociodemographic characteristics, dietary habits, and lifestyle choices. High detection rates (64%-100%) were observed, indicating the widespread presence of these elements. Elevated blood concentrations were found for mercury (median 21.1 µg.L-1, interquartile range: 12-34 µg.L-1), selenium (median 166 µg.L-1, interquartile range: 137-208 µg.L-1), and lead (median 34 µg.L-1, interquartile range: 20.8-64 µg.L-1). Regression analysis revealed a positive association between mercury levels and fish consumption, while manioc flour intake showed no relationship to lead levels. In conclusion, our findings emphasize the need for continued monitoring and public policy development for these vulnerable populations. Further studies should assess long-term trends and investigate the health implications of prolonged exposure to diverse chemicals in Amazonian riverside communities.

Polycyclic aromatic hydrocarbons (PAHs): Updated aspects of their determination, kinetics in the human body, and toxicity.

Polycyclic aromatic hydrocarbons (PAHs) are legacy pollutants of considerable public health concern. Polycyclic aromatic hydrocarbons arise from natural and anthropogenic sources and are ubiquitously present in the environment. Several PAHs are highly toxic to humans with associated carcinogenic and mutagenic properties. Further, more severe harmful effects on human- and environmental health have been attributed to the presence of high molecular weight (HMW) PAHs, that is PAHs with molecular mass greater than 300 Da. However, more research has been conducted using low molecular weight (LMW) PAHs). In addition, no HMW PAHs are on the priority pollutants list of the United States Environmental Protection Agency (US EPA), which is limited to only 16 PAHs. However, limited analytical methodologies for separating and determining HMW PAHs and their potential isomers and lack of readily available commercial standards make research with these compounds challenging. Since most of the PAH kinetic data originate from animal studies, our understanding of the effects of PAHs on humans is still minimal. In addition, current knowledge of toxic effects after exposure to PAHs may be underrepresented since most investigations focused on exposure to a single PAH. Currently, information on PAH mixtures is limited. Thus, this review aims to critically assess the current knowledge of PAH chemical properties, their kinetic disposition, and toxicity to humans. Further, future research needs to improve and provide the missing information and minimize PAH exposure to humans.

Occurrence of trace elements in print paper products: Non-carcinogenic risk assessment through dermal exposure.

Over time, the risk assessment of dermal exposure to pollutants in print paper products has received considerable attention. Most studies have focused on organic pollutants, especially bisphenol A (BPA). However, little is known about the levels of trace elements in print paper products, despite the knowledge that these elements are components of printing inks and toners. This study was aimed at determining the concentrations of trace elements in 5 types of paper products, namely bulletins, magazines, special events program booklets, handbills, and newspapers. The average daily intake (ADI) of each element was subsequently estimated through dermal exposure to the papers. The detection frequency of the elements of interest was high (nearly 100%) in most paper products, with the exception of chromium, whose detection was low. In contrast, Ag was not detected in any sample. The levels of the elements in the paper products were low and comparable to those found in other personal and consumer products with the potential for skin contact. The range values of estimated ADIs were 1.70-3.90E-08, 2.30-18.2E-10, 2.60-16.4E-09, 3.65-5.75E-08, 1.29-4.38E-08, 6.23-15.6E-10, 1.51-2.80E-10, 1.43-9.16E-09, 0.00-9.47E-09, and 4.68-220E-08 mg/kg bw/day for Mn, Co, Ni, Cu, Zn, As, Cd, Pb, Cr and Fe respectively. These values were well below the dermal standard reference doses (RfD) for each element. The present results indicate that dermal exposure to trace elements from print paper products was low and does not pose significant risks for toxic (non-carcinogenic) effects on humans.

Recent trends in pesticides in crops: A critical review of the duality of risks-benefits and the Brazilian legislation issue.

Due to the increasing population worldwide, in recent years, an exponential increase in agricultural practices has occurred in order to attend to the growing demand for food. Unfortunately, this increase is not associated with the supply of foodstuffs free of environmental pollutants. In Brazil, agriculture is one of the most important economic pillars, making the country one of the largest consumers of pesticides around the world. The intense use of pesticides, mainly glyphosate, 2,4-D, and atrazine, constitutes an essential factor in the viability of this great agricultural productivity. Sugarcane, corn, soybean, and citrus crops consume around 66% of the total pesticides worldwide, representing 76% of the planted area. Pesticide residues have been frequently detected in food and the environment, becoming a significant concern for human health. Monitoring programs for pesticide use are essential to reduce the potential negative impacts on the environment and improve the overall efficiency and sustainability of their use. However, in Brazil, the approval status of pesticide-active ingredients is very discrepant compared to other agricultural countries. Moreover, the duality of benefits and risks of pesticide application creates an economic and toxicological conflict. In this paper, we have critically reviewed the duality of risks-benefits of the use of pesticides in agriculture and the current Brazilian legislation issues. We have also compared this flawed legislation with other countries with high economic potential. Due to the negative environmental impacts on soil and water by the high levels of pesticides, remediation techniques, sustainable agriculture, and the development of new technologies can be considered some viable alternatives to reduce the levels in these compartments. Besides, this paper includes some recommendations that can be included in the coming years.

Association between urinary concentrations of toxic metals/metalloids and oxidative stress in Brazilians living in areas affected by the Fundão dam failure.

The Fundão Dam failure has been the most significant environmental disaster in Brazil. The catastrophe released large amounts of mining waste into the environment, including toxic metals/metalloids, which are recognized to induce carcinogenic effects. The urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG), a widely accepted oxidative stress and carcinogenesis biomarker, provide a potential tool for assessing the disaster's health implications. This study investigated the association between urinary levels of some toxic metals/metalloids and 8OHdG in Brazilian individuals living in areas affected by the Fundão dam failure. Urinary concentrations of arsenic (As), cadmium (Cd), mercury (Hg), nickel (Ni), and lead (Pb) were determined using inductively coupled plasma mass spectrometry, while 8OHdG was analyzed by liquid chromatography-tandem mass spectrometry. Non-parametric bootstrap regression was used to estimate the associations between the urinary levels of toxic elements and 8OHdG. The results showed that except for Hg, urinary concentrations of all metals/metalloids analyzed here exceeded the reference ranges for the Brazilian population. The regression analysis revealed that As (0.337; CI 95%: 0.203; 0.474), Cd (0.268; CI 95%: 0.036; 0.520), and Ni (0.296; CI 950.108; 0.469) were positively associated with creatinine-adjusted urinary 8OHdG levels. Associations were not found for Hg (0.0122; CI 95%: -0.155; 0.183) and Pb (0.201; CI 95%: -0.040; 0.498). The current findings suggest that high exposure to toxic metals/metalloids might increase 8OHdG levels with potential adverse health effects. This study is the first one in which the relationship between toxic metals/metalloids and oxidative stress biomarkers is investigated in populations affected by environmental disasters. Further prospective studies are necessary to monitor exposure levels and explore additional health impacts.

Lipidomic profiling of the Brazilian yellow scorpion venom: new insights into inflammatory responses following Tityus serrulatus envenomation.

Due to the high prevalence and clinical relevance, scorpionism is a critical public health issue in several Brazilian regions. Tityus serrulatus, commonly known as the Brazilian yellow scorpion, is the most venomous genus found in Brazilian fauna and associated with severe clinical manifestations such as localized pain, hypertension, sweating, tachycardia and complex hyperinflammatory responses. In general, T. serrulatus venom contains a complex mixture of active compounds, including proteins, peptides, and amino acids. Although knowledge of the protein fractions of scorpion venom is available, venom lipid components are not yet comprehensively known. The aim of the present study was to determine and characterize the lipid constituents/profile of the T. serratus venom utilizing liquid chromatography coupled with high-resolution mass spectrometry. Lipid species (164 in total) belonging to 3 different lipid categories, glycerophospholipids, sphingolipids, and glycerolipids, were identified. A further search on MetaCore/MetaDrug platform, which is based upon a manually curated database of molecular interactions, molecular pathways, gene-disease associations, chemical metabolism, and toxicity information, exhibited several metabolic pathways for 24 of previously identified lipid species, including activation of nuclear factor kappa B and oxidative stress pathways. Further several bioactive compounds, such as plasmalogens, lyso-platelet-activating factors, and sphingomyelins, associated with systemic responses triggered by T. serrulatus envenomation were detected. Finally, lipidomic data presented provide advanced and valuable information to better comprehend the mechanisms underlying the complex pathophysiology induced by T. serrulatus envenomation.

Exercise Oscillatory Ventilation Improves Heart Failure Prognostic Scores.

BACKGROUND: Several heart failure (HF) prognostic risk scores are available to guide the ideal time for listing candidates for a heart transplant (HTx). The detection of exercise oscillatory ventilation (EOV) during cardiopulmonary exercise testing (CPET) is associated with advanced HF and a worse prognosis, and yet it is not accounted for in these risk scores. Therefore, this study aimed to assess whether EOV further adds prognostic value to HF scores. METHODS: A single-centre retrospective cohort study was undertaken of consecutive HF patients with reduced ejection fraction (HFrEF) who underwent CPET from 1996 to 2018. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group In Chronic Heart Failure (MAGGIC), and Metabolic Exercise Cardiac Kidney Index (MECKI) were calculated. The added value of EOV on top of those scores was assessed using a Cox proportional hazard model. The added discriminative power was also assessed by receiver operating characteristic curve comparison. RESULTS: A total of 390 HF patients with a median age of 58 (IQR 50-65) years were investigated, of whom 78% were male and 54% had ischaemic heart disease. The median peak oxygen consumption was 15.7 mL/kg/min (IQR 12.8-20.1). Exercise oscillatory ventilation was detected in 153 (39.2%) patients. Over a median follow-up of 2 years, 61 patients died (49 due to a cardiovascular reason) and 54 had a HTx. Exercise oscillatory ventilation independently predicted the composite outcome of all-cause death and HTx. Furthermore, the presence of this ventilatory pattern significantly improved the prognostic performance of both HFSS and MAGGIC scores. CONCLUSION: Exercise oscillatory ventilation was often found in a cohort of HF patients with reduced LVEF who underwent CPET. It was found that EOV added further prognostic value to contemporary HF scores, suggesting that this easily obtained parameter should be included in future modified HF scores.

Imaging Aspects of the Hippocampus.

The hippocampus is one of the most sophisticated structures in the brain, owing to its complex anatomy, intriguing functions, relationship with other structures, and relevant associated symptoms. Despite being a structure analyzed for centuries, its anatomy and physiology in the human body are still being extensively studied, as well as associated pathologic conditions and potential biomarkers. It can be affected by a broad group of diseases that can be classified as congenital, degenerative, infectious or inflammatory, neoplastic, vascular, or toxic-metabolic disease. The authors present the anatomy and close structures, function, and development of the hippocampus, as well as an original algorithm for imaging diagnosis. The algorithm includes pathologic conditions that typically affect the hippocampus and groups them into nodular (space occupying) and nonnodular pathologic conditions, serving as a guide to narrow the differential diagnosis. MRI is the imaging modality of choice for evaluation of the hippocampus, and CT and nuclear medicine also improve the analysis. The MRI differential diagnosis depends on anatomic recognition and careful characterization of associated imaging findings such as volumetric changes, diffusion restriction, cystic appearance, hyperintensity at T1-weighted imaging, enhancement, or calcification, which play a central role in diagnosis along with clinical findings. Some pathologic conditions arising from surrounding structures such as the amygdala are also important to recognize. Pathologic conditions of the hippocampus can be a challenge to diagnose because they usually manifest as similar clinical syndromes, so the imaging findings play a potential role in guiding the final diagnosis. Online supplemental material is available for this article. ©RSNA, 2022.

Pectoralis major muscle quantification by cardiac MRI is a strong predictor of major events in HF.

Clinical overt cardiac cachexia is a late ominous sign in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The main goal of this study was to assess the feasibility and prognostic significance of muscle mass quantification by cardiac magnetic resonance (CMR) in HF with reduced LVEF. HF patients with LVEF < 40% (HFrEF) referred for CMR were retrospectively identified in a single center. Key exclusion criteria were primary muscle disease, known infiltrative myocardial disease and intracardiac devices. Pectoralis major muscles were measured on standard axial images at the level of the 3rd rib anteriorly. Time to all-cause death or HF hospitalization was the primary endpoint. A total of 298 HF patients were included (mean age 64 ± 12 years; 76% male; mean LVEF 30 ± 8%). During a median follow-up of 22 months (IQR: 12-33), 67 (22.5%) patients met the primary endpoint (33 died and 45 had at least 1 HF hospitalization). In multivariate analysis, LVEF [Hazard Ratio (HR): 0.950; 95% Confidence Interval (CI): 0.917-0.983; p = 0.003), NYHA class I-II vs III-IV (HR: 0.480; CI: 0.272-0.842; p = 0.010), creatinine (HR: 2.653; CI: 1.548-4.545; p < 0.001) and pectoralis major area (HR: 0.873; 95% CI: 0.821-0.929; p < 0.001) were independent predictors of the primary endpoint, when adjusted for gender and NT-pro-BNP levels. Pectoralis major size measured by CMR in HFrEF was independently associated with a higher risk of death or HF hospitalization. Further studies to establish appropriate age and gender-adjusted cut-offs of muscle areas are needed to identify high-risk subgroups.

Sleep-disordered breathing patterns in hospitalized patients with acute heart failure across the entire spectrum of ejection fraction.

BACKGROUND: Sleep-disordered breathing (SDB) is prevalent in heart failure (HF). Yet, scarce data exist on sleep-patterns in acute HF and differences in specific subgroups. Our goal was to assess SDB prevalence in hospitalized patients with decompensated HF across the entire spectrum of left ventricle ejection fraction (LVEF). METHODS: Single-center retrospective study enrolling patients admitted for acute HF between 2013 and 2018. All patients were screened for SDB with an ApneaLink™ Plus device before discharge while euvolemic and receiving oral therapy. Those with a sleep study time < 3 h were excluded. HF with reduced, moderately reduced, and preserved LVEF (HFrEF, HFmrEF, and HFpEF) was defined by a LVEF < 40%, 40-49%, and ≥ 50%, respectively. SDB was defined by an apnea-hypopnea index (AHI) ≥ 5/h. RESULTS: Overall, 221 patients were included (mean age 75 ± 11 years). Seventy-two (33%) had HFrEF, 26 (11%) HFmrEF, and 123 (56%) HFpEF. In total, 176 (80%) met the criteria for mild SDB, while 59% and 38% had an AHI ≥ 15/h or ≥ 30/h, respectively. SDB prevalence was high and similar between HFrEF, HFmrEF, and HFpEF. Yet, SDB was often more severe in HFrEF when compared to HFpEF. HFmrEF had intermediate characteristics, with an AHI closer to HFrEF. CONCLUSION: In a cohort of patients admitted for acute HF, SDB was highly prevalent in all subgroups, including HFmrEF. The pervasiveness and severity of SDB was particularly noted in HFrEF. These findings suggest that routine SDB screening may be warranted following acute HF.

Automated Lung Sound Classification Using a Hybrid CNN-LSTM Network and Focal Loss Function.

Respiratory diseases constitute one of the leading causes of death worldwide and directly affect the patient's quality of life. Early diagnosis and patient monitoring, which conventionally include lung auscultation, are essential for the efficient management of respiratory diseases. Manual lung sound interpretation is a subjective and time-consuming process that requires high medical expertise. The capabilities that deep learning offers could be exploited in order that robust lung sound classification models can be designed. In this paper, we propose a novel hybrid neural model that implements the focal loss (FL) function to deal with training data imbalance. Features initially extracted from short-time Fourier transform (STFT) spectrograms via a convolutional neural network (CNN) are given as input to a long short-term memory (LSTM) network that memorizes the temporal dependencies between data and classifies four types of lung sounds, including normal, crackles, wheezes, and both crackles and wheezes. The model was trained and tested on the ICBHI 2017 Respiratory Sound Database and achieved state-of-the-art results using three different data splitting strategies-namely, sensitivity 47.37%, specificity 82.46%, score 64.92% and accuracy 73.69% for the official 60/40 split, sensitivity 52.78%, specificity 84.26%, score 68.52% and accuracy 76.39% using interpatient 10-fold cross validation, and sensitivity 60.29% and accuracy 74.57% using leave-one-out cross validation.

Enhanced antibacterial activity of the gentamicin against multidrug-resistant strains when complexed with Canavalia ensiformis lectin.

The lectins are carbohydrate-binding proteins that are highly specific to sugar groups associated to other molecules. In addition to interacting with carbohydrates, a number of studies have reported the ability of these proteins to modulate the activity of several antibiotics against multidrug-resistant (MDR) strains. In this study, we report the enhanced antibacterial activity of the gentamicin against MDR strains when complexed with a lectin from Canavalia ensiformis seeds (ConA). Hemagglutination activity test and intrinsic fluorescence spectroscopy revealed that the gentamicin can interact with ConA most likely via the carbohydrate recognition domain (CRD) with binding constant (Kb) value estimated of (0.44 ± 0.04) x 104 M-1. Furthermore, the minimum inhibitory concentrations (MIC) obtained for ConA against all strains studied were not clinically relevant (MIC ≥ 1024 µg/mL). However, when ConA was combined with gentamicin, a significant increase in antibiotic activity was observed against Staphylococcus aureus and Escherichia coli. The present study showed that ConA has an affinity for gentamicin and modulates its activity against MDR strains. These results indicate that ConA improves gentamicin performance and is a promising candidate for structure/function analyses.

Dapagliflozin in a Real-World Chronic Heart Failure Population: How Many Are Actually Eligible?

BACKGROUND: In patients with heart failure (HF) and reduced ejection fraction (HFrEF) with or without type 2 diabetes mellitus, the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin was recently shown to reduce the risk of worsening HF or death from cardiovascular causes in the dapagliflozin in patients with heart failure and reduced ejection fraction (DAPA-HF) trial. Our goal was to investigate how many patients in a real-world setting would be eligible for dapagliflozin according to the DAPA-HF enrolment criteria. METHODS: This is a single-center retrospective study enrolling consecutive, unselected patients followed up in an HF clinic from 2013 to 2019. Key DAPA-HF inclusion criteria (i.e., left ventricular ejection fraction [LVEF] ≤40% and NT-proBNP ≥600 pg/mL [or ≥900 pg/mL if atrial fibrillation]) and exclusion criteria (estimated glomerular filtration rate [eGFR] <30 mL/kg/1.73 m2 and systolic blood pressure [SBP] <95 mm Hg) were considered. RESULTS: Overall, 479 patients (age 76 ± 13 years; 50.5% male; 78.9% hypertensive; 45.1% with an eGFR <60 mL/min/1.73 m2; 36.5% with TD2M; and 33.5% with ischaemic HF) were assessed. The median SBP was 128.5 (112.0-146.0) mm Hg, mean eGFR was 50.8 ± 23.7 mL/min/1.73 m2, and median NT-proBNP was 2,183 (IQR 1,010-5,310) pg/mL. Overall, 155 (32.4%) patients had LVEF ≤40%. According to the DAPA-HF trial key criteria, 90 patients (18.8%) would be eligible for dapagliflozin. The remainder would be excluded due to LVEF >40% (67.6%), eGFR <30 mL/min/1.73 m2 (19.4%), NT-proBNP below the cutoff (16.7%), and/or SBP <95 mm Hg (6.5%). If we center the analysis to those with LVEF ≤40%, 58.1% would be eligible for dapagliflozin. The remainder would be excluded due to an eGFR <30 mL/min/1.73 m2 (20%), NT-proBNP below the cutoff (16.1%), and/or SBP <95 mm Hg (8.4%). CONCLUSION: Roughly half of our real-world HFrEF cohort would be eligible for dapagliflozin according to the key criteria of the DAPA-HF trial. The main reason for non-eligibility was an eGFR <30 mL/min/1.73 m2. However, two-thirds of patients had LVEF >40%. These findings show that dapagliflozin is a promising complementary new drug in the therapeutic armamentarium of most patients with HFrEF, while highlighting the urgent need for disease-modifying drugs in mid-range and preserved LVEF and the need to assess the efficacy and safety of SLGT2i in advanced kidney disease patients. The results of ongoing SGLT2i trials in these LVEF subgroups are eagerly awaited.

High morbidity cutaneous enzootic myiasis by Dermatobia hominis (Diptera: Oestridae) in sambar deer (Rusa unicolor).

This study describes the first known occurrence and treatment of enzootic cutaneous myiasis by Dermatobia hominis in a herd of sambar deer (Rusa unicolor). Sambar deer are clinically affected by enzootic cutaneous myiasis during the spring and summer in Rio de Janeiro, Brazil. Through direct inspection and clinicopathological evaluation in the herd with 80 R. unicolor, it was observed that infestation by D. hominis caused 100% morbidity. At histological exam, skin had eosinophilic and granulomatous chronic active severe necrohemorrhagic dermatitis associated with botfly and moderate surrounding fibroplasia. The systemic treatment with oral ivermectin at 0.08% was effective in 93.7% of deer with enzootic cutaneous myiasis after fourteen days. After treatment, the skin deer had eosinophilic and granulomatous chronic severe dermatitis associated with degenerated botfly and severe fibroplasia. Notable differences in leukocyte profile were observed between groups pre- and post-treatment. Decrease of relative values of neutrophils and eosinophils were significant in the treated deer group. An increase of relative values of monocytes was also confirmed in the treated group. Sambar deer was the only species affected by D. hominis, even though several other wild herbivores were kept in the same area. More studies are needed to elucidate the susceptibility of R. unicolor to D. hominis cutaneous infestations.

Automatic Classification of Adventitious Respiratory Sounds: A (Un)Solved Problem?

(1) Background: Patients with respiratory conditions typically exhibit adventitious respiratory sounds (ARS), such as wheezes and crackles. ARS events have variable duration. In this work we studied the influence of event duration on automatic ARS classification, namely, how the creation of the Other class (negative class) affected the classifiers' performance. (2) Methods: We conducted a set of experiments where we varied the durations of the other events on three tasks: crackle vs. wheeze vs. other (3 Class); crackle vs. other (2 Class Crackles); and wheeze vs. other (2 Class Wheezes). Four classifiers (linear discriminant analysis, support vector machines, boosted trees, and convolutional neural networks) were evaluated on those tasks using an open access respiratory sound database. (3) Results: While on the 3 Class task with fixed durations, the best classifier achieved an accuracy of 96.9%, the same classifier reached an accuracy of 81.8% on the more realistic 3 Class task with variable durations. (4) Conclusion: These results demonstrate the importance of experimental design on the assessment of the performance of automatic ARS classification algorithms. Furthermore, they also indicate, unlike what is stated in the literature, that the automatic classification of ARS is not a solved problem, as the algorithms' performance decreases substantially under complex evaluation scenarios.

A Wearable Stethoscope for Long-Term Ambulatory Respiratory Health Monitoring.

Lung sounds acquired by stethoscopes are extensively used in diagnosing and differentiating respiratory diseases. Although an extensive know-how has been built to interpret these sounds and identify diseases associated with certain patterns, its effective use is limited to individual experience of practitioners. This user-dependency manifests itself as a factor impeding the digital transformation of this valuable diagnostic tool, which can improve patient outcomes by continuous long-term respiratory monitoring under real-life conditions. Particularly patients suffering from respiratory diseases with progressive nature, such as chronic obstructive pulmonary diseases, are expected to benefit from long-term monitoring. Recently, the COVID-19 pandemic has also shown the lack of respiratory monitoring systems which are ready to deploy in operational conditions while requiring minimal patient education. To address particularly the latter subject, in this article, we present a sound acquisition module which can be integrated into a dedicated garment; thus, minimizing the role of the patient for positioning the stethoscope and applying the appropriate pressure. We have implemented a diaphragm-less acousto-electric transducer by stacking a silicone rubber and a piezoelectric film to capture thoracic sounds with minimum attenuation. Furthermore, we benchmarked our device with an electronic stethoscope widely used in clinical practice to quantify its performance.

Parkia platycephala lectin enhances the antibiotic activity against multi-resistant bacterial strains and inhibits the development of Haemonchus contortus.

Lectins have been studied in the past few years as an alternative to inhibit the development of pathogenic bacteria and gastrointestinal nematodes of small ruminants. The development of new antibacterial and anthelmintic compounds is necessary owing to the increase in drug resistance among important pathogens. Therefore, this study aimed to evaluate the capacity of a glucose/mannose-binding lectin from Parkia platycephala seeds (PPL) to inhibit the development of Haemonchus contortus and to modulate antibiotic activity against multi-resistant bacterial strains, thereby confirming its efficacy when used in combination with gentamicin. PPL at the concentration of 1.2 mg/mL did not show inhibitory activity on H. contortus in the egg hatch test or the exsheathment assay. However, it did show significant inhibition of H. contortus larval development with an IC50 of 0.31 mg/mL. The minimum inhibitory concentration (MIC) obtained for PPL against all tested bacterial strains was not clinically relevant (MIC ≥ 1024 µg/mL). However, when PPL was combined with gentamicin, a significant increase in antibiotic activity was observed against S. aureus and E.coli multi-resistant strains. The inhibition of hemagglutinating activity by gentamicin (MIC = 50 mM) revealed that it may be interacting with the carbohydrate-binding site of PPL. It is this interaction between the antibiotic and lectin carbohydrate-binding site that may be responsible for the enhanced activity of gentamicin against multi-resistant strains. It can be concluded that PPL showed selective anthelmintic effect, inhibiting the development of H. contortus larvae and that it increased the effect of the antibiotic gentamicin against multi-resistant bacterial strains, thus constituting a potential therapeutic resource against resistant bacterial strains and H. contortus.

Purification and biophysical characterization of a mannose/N-acetyl-d-glucosamine-specific lectin from Machaerium acutifolium and its effect on inhibition of orofacial pain via TRPV1 receptor.

A new mannose/N-acetyl-dglucosamine-specific lectin, named MaL, was purified from seeds of Machaerium acutifolium by precipitation with ammonium sulfate, followed by affinity and ion-exchange chromatography. MaL haemagglutinates either native rabbit erythrocytes or those treated with proteolytic enzymes. MaL is highly stable by the ability to maintain its haemagglutinating activity after exposure to temperatures up to 50 °C. The lectin haemagglutinating activity was optimum between pH 6.0 and 7.0 and inhibited after incubation with d-mannose and N-acetyl-d-glucosamine and α-methyl-d-mannopyranoside. MaL is a glycoprotein with relative molecular mass of 29 kDa (α-chain), 13 kDa (ß-chain) and 8 kDa (γ-chain) with secondary structure composed of 3% α-helix, 44% ß-sheet, 21% ß-turn, and 32% coil. The orofacial antinociceptive activity of the lectin was also evaluated. MaL (0.03 mg mL-1) reduced orofacial nociception induced by capsaicin, an effect that occurred via carbohydrate recognition domain interaction, suggesting an interaction of MaL with the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor. Our results confirm the potential pharmacological relevance of MaL as an inhibitor of acute orofacial mediated by TRPV1.