Limitations in the field of vision of young operators of utility all-terrain vehicles.

PROBLEM: All-Terrain Vehicles (ATVs) cause a distressing number of fatalities and injuries among farm youth in the United States. The number of severe injuries caused by ATV crashes on farms, which stood at 25 children in 2019, is expected to rise due to increased ATV sales during the COVID-19 pandemic. Existing research into children's injuries has explored physical capabilities like anthropometry, strength, and visual acuity. Yet, studies assessing youths' physical ability to operate ATVs remain limited. This study tests the hypothesis that diminished vision field in young ATV operators raises crash risks. METHODS: This study used SAMMIECAD digital human modeling system to simulate and compare the field of vision of youth and adult ATV operators. The simulations incorporated 3-D mockups of ATVs, humans, sprayer tanks, windshields, and obstacles. Ten utility ATVs and children of both genders across nine ages (8-16) and three height percentiles (5th, 50th, 95th) were evaluated. RESULTS: Simulations showed that young ATV operators generally have a more restricted field of vision than adults, particularly those aged 6-11 years. DISCUSSION: Visual limitations hinder riders' ability to see ATV controls, potentially leading to vehicle control loss. Moreover, they impair environmental perception during riding, compromising youths' ATV operation abilities and increasing crash risks. PRACTICAL APPLICATIONS: These findings offer crucial data in support of modifying ATV safety guidelines. Additionally, they can guide youth occupational health professionals in preventing ATV-related incidents in agricultural settings.

Bipolar Resistive Switching in 2D MoSe2 Grown by Atmospheric Pressure Chemical Vapor Deposition.

Two-dimensional (2D) transition metal dichalcogenides (TMDCs) are highly promising nanomaterials for various electronic devices such as field-effect transistors, junction diodes, tunneling devices, and, more recently, memristors. 2D MoSe2 stands out for having high electrical conductivity, charge carrier mobility, and melting point. While these features make it particularly appropriate as a switching layer in memristive devices, reliable and scalable production of large-area 2D MoSe2 still represents a challenge. In this study, we manufacture 2D MoSe2 films by atmospheric-pressure chemical vapor deposition and investigate them on the atomic scale. We selected and transferred MoSe2 bilayer to serve as a switching layer between asymmetric Au-Cu electrodes in miniaturized crossbar vertical memristors. The electrochemical metallization devices showed forming-free, bipolar resistive switching at low voltages, with clearly identifiable nonvolatile states. Other than low-power neuromorphic computing, low switching voltages approaching the range of biological action potentials could unlock hybrid biological interfaces.

Ability of youth operators to reach agricultural all-terrain vehicles controls.

PROBLEM: Utility All-Terrain Vehicles (ATVs) are one major cause of youth injuries and fatalities on farms. Utility ATVs have heavy weights and fast speeds that require complex maneuvering. Youth's physical capabilities may not be sufficient to perform those complex maneuvers correctly. Therefore, it is hypothesized that most youth engage in ATV-related incidents because they ride vehicles unfit for them. There is a need to assess ATV-youth fit based on youth anthropometry. METHOD: This study focused on evaluating potential inconsistencies between the operational requirements of utility ATVs and the anthropometric measures of youth through virtual simulations. Virtual simulations were performed to assess 11 youth-ATV fit guidelines proposed by several ATV safety advocacy organizations (National 4-H council, CPSC, IPCH, and FReSH). In total, 17 utility ATVs along with male-and-female-youth of nine ages (8 to 16 years old) and three height percentiles (5th, 50th, and 95th) were evaluated. RESULTS: The results demonstrated a physical mismatch between ATVs' operational requirements and youth's anthropometry. For example, male-youth aged 16 of the 95th height percentile failed to pass at least 1 out of the 11 fit guidelines for 35 % of all vehicles evaluated. The results were even more concerning for females. Female youth 10 years old and younger (from all height percentiles) failed to pass at least one fit guideline for all ATVs evaluated. DISCUSSION: Youth are not recommended to ride utility ATVs. PRACTICAL APPLICATIONS: This study provides quantitative and systematic evidence to modify current ATV safety guidelines. Furthermore, youth occupational health professionals could use the present findings to prevent ATV-related incidents in agricultural settings.

Lyotropic liquid crystal mesophases as transdermal delivery systems for lipophilic drugs: A comparative study.

The present work aimed to evaluate different Liquid Crystal Mesophases (LCM) as transdermal drug delivery systems (TDDS) for nifedipine (NFD), a lipophilic drug model. The formulations composed of water, Citrus sinensis essential oil (CSEO), PPG-5-CETETH-20, and Olive oil ester PEG-7 were obtained and characterized by polarized light microscopy (PLM), rheology, small-angle x-ray scattering (SAXS), Fourier transform infrared coupled with an attenuated total reflection accessory (FTIR-ATR) and in vitro assays: bioadhesion, drug release, skin permeation, and retention tests. As a result, changes in component proportions led to several transparent viscous systems with an anisotropic profile. PLM and SAXS proved the presence of lamellar (S1), hexagonal (S3), and lamellar + hexagonal (S2) LCM, and rheology showed a high viscoelasticity profile. LCMs were able to adhere to the skin, and S2 achieved higher adhesion strength. NFD (5 mg/mL) has not modified the organization of LCMs. Results also showed that S3 promoted higher permeation and retention and higher disorganization of stratum corneum lipids, which is the main permeation-enhancing mechanism. Thus, the formulations obtained can carry and improve drug delivery through the skin and are promising TDDS for lipophilic drug administration, such as NFD.

A Systematic Review of Youth and All-Terrain Vehicles Safety in Agriculture.

All-terrain vehicle (ATV) incidents are one of the leading causes of injuries and fatalities among youth in the agricultural industry. It has been hypothesized that many youth-related ATV incidents occur because children ride ATVs that do not fit their capabilities and are not following basic safe riding practices. In addition, various ATV safety guidelines regarding youth (e.g., CPSC, ANSI/SVIA, ASI) are inconsistent and may not align with state or local laws. To the best of our knowledge, no comprehensive studies have compared the physical and mental requirements for riding ATVs and the youth's capabilities to ride ATVs safely. Consequently, there are no scientific-based recommendations for age limitation, physical and mental capabilities, and safety requirements for youth to ride ATVs safely. Thus, there is a need to review the available sources related to youth safety and ATVs in the agricultural industry, identify the research voids, and recommend modifications to current ATV guidelines. This study conducted a systematic review of available ATV-related studies, standards, guidelines, and laws to establish better-informed minimum age, physical and mental capabilities, and safety requirements for youths to ride ATVs on the farm.

Cerebral cryptococcoma successfully treated by isavuconazole in an immunocompetent patient: A case report.

Cryptococcosis has been recognized as an increasing cause of severe systemic mycosis in immunocompetent patients in the last few years. Cerebral cryptococcomas are a more uncommon manifestation of cryptococcal meningitis, which are not usually included in the differential of brain masses. We report a case of a young, immunocompetent woman that rapidly developed severe neurological deficits. She was ultimately diagnosed with cerebral cryptococcoma caused by both Cryptococcus neoformans and Cryptococcus gattii, and was treated with amphotericin B and isavuconazole. After several complications during hospitalization, including hydrocephalus and cerebellitis, she was discharged home on isavuconazole. On follow-up, she only complained of anosmia. We review the clinical and radiological findings of similar cases. It is the first time that this form of cryptococcal meningitis is favorably treated with isavuconazole and is caused by 2 species of Cryptococcus. We emphasize that cerebral cryptococcomas should be suspected in immunocompetent patients that present with brain masses.

Forces required to operate controls on agricultural all-terrain vehicles: implications for youth.

All-terrain vehicle (ATV) crashes are among the leading causes of injury and death among youth in the agriculture industry. It is hypothesised that youth are involved in ATV-related incidents because they cannot effectively activate the vehicle's controls. This study evaluated potential discrepancies between the required activation forces of the controls of fifty-four utility ATVs and the strength of male-and-female youth of varying ages (6-20 years old) and strength percentiles (5th, 50th, and 95th). The activation forces of the ATVs' controls were measured experimentally, while the youth's corresponding strength was retrieved from the literature. The results of this study demonstrated a physical mismatch between the forces required to operate ATV controls and youth's strength. Turning the handlebar, pressing the footbrake, and pushing the ATV off are the most difficult tasks for ATV operation. These discrepancies compromise the youth's ability to ride ATVs, increasing their risk of crashes. Practitioner summary: Previous studies indicate that some youth engage in ATV incidents because they cannot activate the vehicle's controls. We measured the forces required to operate eight ATV controls and compared them with the youth's corresponding strength. Our results demonstrated physical mismatches between the forces required to operate ATV controls and the youth's strength.

Metástase iridociliar presumida de carcinoma mamário: relato de caso / Presumed iridociliary metastasis of breast carcinoma: case report

RESUMO A metástase ocular é uma patologia incomum, principalmente quando se considera a íris como sítio da metástase. Apesar de incomum, a metástase ocular possui o câncer de mama como um de seus principais sítios primários. Ocasionalmente, a manifestação oftalmológica pode ser primária a qualquer outra clínica. Este artigo relata o caso de uma paciente com carcinoma de mama ductal invasivo com presumida metástase em corpo ciliar e íris em olho direito. O diagnóstico precoce interfere de forma significativa na evolução do quadro, sendo necessário o acompanhamento oftalmológico.

ABSTRACT Ocular metastasis is an uncommon pathology, especially when considering the iris as the site of metastasis. Although uncommon, eye metastasis has breast cancer as one of its main primary sites. Occasionally, the ophthalmologic manifestation may be primary to any other clinical manifestation. This article reports the case of a patient with invasive ductal breast carcinoma with presumed metastasis in the ciliary body and iris in the right eye. Early diagnosis significantly affects the evolution of the condition, requiring ophthalmologic follow-up.

Chitosan-functionalized nanostructured lipid carriers containing chloroaluminum phthalocyanine for photodynamic therapy of skin cancer.

The objective of this study was to obtain optimized nanostructured lipid carriers (NLC) functionalized with chitosan containing chloroaluminum phthalocyanine (ClAlPc) as a photosensitizer. Initially, the optimization of the preparation method of the NLC was performed, where the influence of different surfactants such as PVA and Tween 80, as well as different solid lipids such as stearic acid and Glycerol Monostearate (GM) was evaluated. The formulation containing GM and PVA (NLC10) was considered promising. Following, by the adsorption method (NLC10q), the formulation was functionalized with chitosan and characterized. NLC10 and NLC10q presented sizes of 131.5 and 231.5 nm, and ZP of -24.30 and + 19.96 mV, respectively. The encapsulation efficiency of NLC10q was 96 %, higher than NLC10 (79 %). The formulations were able to promote significant cutaneous retention of ClAlPc, after 2 h and 4 h of the study, and showed to be non-toxic to fibroblasts (biocompatible). PDT in BF16-F10 melanoma resulted in reduced cell viability to 70 % and 50 % for NLC10 and NLCq, respectively. In view of the results obtained, NLC showed to be promising in the treatment of skin cancer through PDT. NLC10q showed higher encapsulation efficiency and stability than NLC10, but, contrary to what was expected, it presented lower photodynamic efficiency.

Hesperetin-Based Hydrogels Protect the Skin against UV Radiation-Induced Damage.

UV radiation can cause damages, such as erythema, skin photoaging, and carcinogenesis. The adoption of protective measures against sun exposure is essential to prevent these damages, and the interest in using natural substances as an alternative for photoprotection is growing. Thus, hesperetin with antioxidant, anti-inflammatory, and anticancer properties is a promising substance to be used with photochemopreventive action and to protect the skin from damage induced by UV radiation. Therefore, the present study aimed to develop a topical formulation based on AAMVPC gel containing hesperetin and evaluate its photoprotective effect on the skin of rats exposed to UVA-UVB radiation. The animals were submitted to the irradiation protocol UVA-UVB, and at the end, erythema, lipid peroxidation, and activity of the antioxidant enzyme catalase and superoxide dismutase were evaluated. Additionally, it evaluated the activity of myeloperoxidase and histological changes. The formulation presented a rheological and spreadability profile suitable for cutaneous application. In vivo results demonstrated that the topical formulation of AAMVPC gel containing hesperetin at a concentration of 10% protected the skin from damage induced by UVA-UVB radiation, with the absence of erythema, lipid lipoperoxidation, and inflammation (low myeloperoxidase activity), and increased catalase and superoxide dismutase activities. The morphology and architecture of the dermo-epidermal tissue of these animals were like those observed under normal conditions (non-irradiated animals). Thus, the results showed that hesperetin was able to protect the animals' skin against UV radiation-induced skin damage and the protection mechanisms may be related to the antioxidant and anti-inflammatory properties of this natural product.

PipeCoV: a pipeline for SARS-CoV-2 genome assembly, annotation and variant identification.

Motivation: Since the identification of the novel coronavirus (SARS-CoV-2), the scientific community has made a huge effort to understand the virus biology and to develop vaccines. Next-generation sequencing strategies have been successful in understanding the evolution of infectious diseases as well as facilitating the development of molecular diagnostics and treatments. Thousands of genomes are being generated weekly to understand the genetic characteristics of this virus. Efficient pipelines are needed to analyze the vast amount of data generated. Here we present a new pipeline designed for genomic analysis and variant identification of the SARS-CoV-2 virus. Results: PipeCoV shows better performance when compared to well-established SARS-CoV-2 pipelines, with a lower content of Ns and higher genome coverage when compared to the Wuhan reference. It also provides a variant report not offered by other tested pipelines. Availability: https://github.com/alvesrco/pipecov.

Microemulsions formed by PPG-5-CETETH-20 at low concentrations for transdermal delivery of nifedipine: Structural and in vitro study.

Nifedipine is a potent anti-hypertensive, which is poorly orally bioavailable on account of first-pass metabolism, short half-life, and low water solubility. This study aimed to develop a microemulsified system with low surfactant concentration and to evaluate the influence of microemulsion (ME) phase behavior on skin permeation of nifedipine, as drug model. Thereafter, MEs were obtained using PPG-5-CETETH-20, oleic acid, and phosphate buffer at pH 5.0. The selected MEs were isotropic, with droplet diameters less than 10 nm, polydispersity index < 0.25, and pH between 5.0 and 5.2. MEs presented low viscosity and Newtonian behavior. SAXS results confirmed bicontinuous and oil-in-water (o/w) MEs formation. The presence of the drug promoted only very slight modifications in the ME structure. The MEs presented ability to deliver nifedipine via the transdermal route when in comparison with the control. Nevertheless, the skin permeated and retained amounts from the o/w and bicontinuous formulations did not differ significantly. The ATR-FTIR demonstrated that both formulations promoted fluidization and disorganization of lipids and increased the drug diffusion and partition coefficients in the skin. In conclusion, PPG-5-CETETH-20 MEs obtained proved to be effective skin permeation enhancers, acting by rising the coefficients of partition and diffusion of the nifedipine in the skin.

Avaliação do emprego da imunoglobulina humana endovenosa sobre a densidade de infecções em pacientes com mieloma múltiplo / Evaluation of the use of human intravenous immunoglobulin on the incidence density of infections in patients with multiple myeloma

Introdução: O mieloma múltiplo (MM) é uma neoplasia hematológica que cursa com hipogamaglobulinemia e consequente imunodeficiência secundária. Uma das principais causas de morbimortalidade desses pacientes são infecções. Objetivou-se com esse estudo avaliar o impacto da reposição de imunoglobulina endovenosa (IgIV) na taxa de infecções em pacientes portadores de MM. Métodos: Trata-se de um estudo de análise documental, com variáveis qualitativas e quantitativas, com objetivo de realizar análise retrospectiva dos prontuários de pacientes com MM que receberam tratamento com imunoglobulina humana endovenosa em um hospital privado na cidade de Patos de Minas, MG, Brasil, no período de 01/05/2016 a 31/12/2020. Foram coletados dados epidemiológicos, resultados de exames, episódios de infecções, eventos adversos da medicação e desfecho dos pacientes nos prontuários analisados. Resultados: Foram identificados 10 pacientes com diagnóstico de MM, todos receberam IgIV na dose de 300 a 400 mg/kg/mês. Nenhuma reação adversa relacionada ao uso da IgIV foi registrada nos prontuários. Foram identificados seis quadros infecciosos que ocorreram em quatro pacientes. Nenhum diagnóstico de sepse foi registrado. A densidade de incidência de infecções foi de 0,28 episódios/pacientes-ano. Conclusão: A densidade de incidência de infecções observada no presente estudo foi significativamente menor em comparação ao que se tem registro na literatura, sugerindo importante papel da IgIV na prevenção de infecções em pacientes com MM.

Introduction: Multiple myeloma (MM) is a hematologic malignancy that leads to hypogammaglobulinemia and consequent secondary immunodeficiency. Infections are a major cause of morbidity and mortality in these patients. The objective of this study was to evaluate the impact of intravenous immunoglobulin (IVIg) replacement on the rate of infections in patients with MM. Methods: This document analysis study used qualitative and quantitative variables to perform a retrospective analysis of the medical records of patients with MM who were treated with human IVIg in a private hospital in the city of Patos de Minas, MG, Brazil, from May 1, 2016 to December 31, 2020. Epidemiological data, test results, episodes of infections, adverse medication events, and patient outcomes were collected from the medical records. Results: Ten patients diagnosed with MM were identified, and they all received IVIg at a dose of 300 to 400 mg/kg/month. No adverse reactions related to the use of IVIg were recorded. Six infections that occurred in 4 patients were identified. No diagnosis of sepsis was recorded. The incidence density of infections was 0.28 episodes/patient-years. Conclusion: The incidence density of infections was significantly smaller in this study in comparison with previous literature findings, which suggests a significant role of IVIg in the prevention of infections in patients with MM.

Listeriose em pacientes nefropatas imunossuprimidos - relato de dois casos / Listeriosis in patients immunosuppressed nephropaths - report of two cases

Contexto: A Listeria monocytogenes é um bacilo gram-positivo de baixa patogenicidade na população geral, mas importante causa de mortalidade por sepse e meningite em pacientes imunocomprometidos. Receptores de órgãos sólidos e candidatos em tratamento de dessensibilização são suscetíveis à infecção pela Listeria monocytogenes, embora sua apresentação clínica seja pouco reconhecida. Descrição dos casos: Paciente do sexo masculino, 43 anos, internado devido a rejeição aguda de enxerto pós-transplante renal, apresenta pico febril matutino e cefaleia. Paciente do sexo feminino, 59 anos, com doença renal crônica e em terapia de dessensibilização devido reatividade a painel antígeno leucocitário humano, busca pronto-socorro com febre, cefaleia e diarreia. A infecção por Listeria monocytogenes foi confirmada por hemocultura em ambos os casos. Discussão: A ocorrência de listeriose é esporádica e associada ao consumo de alimentos altamente contaminados, como laticínios, produtos frescos e carnes processadas. A redução da imunocompetência é o principal fator de risco para o desenvolvimento da doença em não gestantes, bem como para o aumento da mortalidade. O diagnóstico é estabelecido majoritariamente por hemocultura e o exame do líquido cefalorraquidiano é imprescindível para acessar o acometimento do sistema nervoso central, uma vez que os sinais meníngeos podem estar ausentes. O tratamento é realizado com beta-lactâmicos ou aminoglicosídeos. A ampicilina foi utilizada nos casos relatados e promoveu boa resposta clínica. Conclusão: Os profissionais devem atentar para a gravidade da infecção por Listeria monocytogenes e considerar sua ocorrência em pacientes imunocomprometidos, fornecendo orientações profiláticas a todos os candidatos a transplante de órgãos sólidos e tratamento empírico nos casos suspeitos.

The Shared Use of Extended Phenotypes Increases the Fitness of Simulated Populations.

Extended phenotypes are manifestations of genes that occur outside of the organism that possess those genes. In spite of their widespread occurrence, the role of extended phenotypes in evolutionary biology is still a matter of debate. Here, we explore the indirect effects of extended phenotypes, especially their shared use, in the fitness of simulated individuals and populations. A computer simulation platform was developed in which different populations were compared regarding their ability to produce, use, and share extended phenotypes. Our results show that populations that produce and share extended phenotypes outrun populations that only produce them. A specific parameter in the simulations, a bonus for sharing extended phenotypes among conspecifics, has a more significant impact in defining which population will prevail. All these findings strongly support the view, postulated by the extended fitness hypothesis (EFH) that extended phenotypes play a significant role at the population level and their shared use increases population fitness. Our simulation platform is available at https://github.com/guilherme-araujo/gsop-dist.

Microemulsion systems to enhance the transdermal permeation of ivermectin in dogs: A preliminary in vitro study.

This study aims to evaluate the influence of the phase behavior of microemulsions in the transdermal administration ("spot-on") of ivermectin, an antiparasitic drug widely used in the treatment of endoparasites and ectoparasites in dogs. In this regard, pseudoternary phase diagrams composed of water (aqueous phase), isopropyl myristate (oil phase), tween 80 (surfactant) and labrasol (cosurfactant) were obtained in a different surfactant: cosurfactant (S:CS) ratios. S:CS in 1:3 ratio presented a larger region of microemulsion formation and three microemulsions were selected from it and characterized. Subsequently, in vitro permeation and retention studies were conducted using canine skin as membrane. SAXS, rheology and conductivity data were employed to confirm the phase behavior of the microemulsions (w/o, bicontinuous or o/w). The cutaneous permeation and retention tests showed that the w/o microemulsion, followed by bicontinuous microemulsion, resulted in a higher amount of drug permeated through canine skin, suggesting better transdermal permeation. On the other hand, o/w microemulsion resulted in a higher amount of drug accumulated into the skin, suggesting better topical activity. Thus, it can be concluded that phase behavior of microemulsions influenced the drug permeation in the canine skin differently from other animal models. Microemulsions, especially w/o and bicontinuous, can be promising vehicles regarding the transdermal delivery of ivermectin.

Anicteric Leptospirosis-Associated Meningitis in a Tropical Urban Environment, Brazil.

While studying aseptic meningitis in Salvador, Brazil, we diagnosed anicteric leptospirosis in 1.7% (5/295) of patients hospitalized for aseptic meningitis. Leptospirosis-associated meningitis patients had lower mean cerebrospinal fluid cell counts and protein than other-cause aseptic meningitis (p<0.05). Clinicians must consider leptospirosis-associated meningitis in appropriate clinical-epidemiologic contexts.

In situ microemulsion-gel obtained from bioadhesive hydroxypropyl methylcellulose films for transdermal administration of zidovudine.

This study aims to develop in situ microemulsion-gel (ME-Gel) obtained from hydroxypropyl methylcellulose (HPMC) films for transdermal administration of Zidovudine (AZT). Firstly, HPMC films containing propylene glycol (PG) and eucalyptus oil (EO) were obtained and characterized. Later, a pseudo-ternary phase diagram composed of water, EO, tween 80 and PG was obtained and one microemulsion (ME) with a similar proportion of the film components was obtained. ME was transformed in ME-Gel by the incorporation of HPMC. Finally, HPMC films were hydrated with Tween 80 solution to yield in situ ME-Gel and its effect on AZT skin permeation was compared with HPMC film hydrated with water (F5hyd). The results showed that the ME and ME-Gel presented a droplet size of 16.79 and 122.13 µm, respectively, polydispersity index (PDI) < 0.39 and pH between 5.10 and 5.40. The incorporation of HPMC resulted in viscosity about 2 times higher than the use of ME. The presence of AZT did not alter the formulation properties. The in situ ME-Gel promoted a two-fold increase in the permeated amount of AZT compared to F5hyd. The results suggest that it was possible to obtain an ME-Gel in situ from HPMC films and that its effect on transdermal permeation of AZT was significant.

Isolados: uma interpretação fotográfica do isolamento social / Isolateds: a photographic interpretation of social isolation

Este ensaio trata do processo de criação do livro Isolados, o qual, tem a proposta de trazer uma interpretação fotográfica das medidas de prevenção e de controle da Doença do Coronavírus-19 (COVID-19), isolamento social (separação dos casos de COVID-19, suspeitos ou confirmados, dos outros indivíduos, para evitar a transmissão da doença) e distanciamento social (diminuição de interação entre as pessoas para reduzir a velocidade de disseminação do SARS-CoV-2). As fotografias produzidas pelos nove fotógrafos que subscrevem a obra revelam aspectos profundos desse episódio singular de continência, em que as atividades cotidianas são reduzidas ao necessário para a sobrevivência. A produção se ancora na capacidade de a linguagem fotográfica propiciar uma chave de interpretação da realidade que se desata diante das lentes. A compreensão da realidade social, entretanto, não é considerada factível a partir do ponto de vista isolado de um operação que fragmenta a realidade ­ a fotografia ­ mas pela composição das propostas fotográficas que proporcionam um aprofundamento da análise. Assim, a fragmentação, que é própria da câmera ao enquadrar seu objeto, só pode ser superado pela composição das imagens registradas.

Elevated Activation of Neutrophil Toll-Like Receptors in Patients with Acute Severe Leptospirosis: An Observational Study.

Leptospirosis is the leading cause of zoonotic morbidity and mortality globally, yet little is known about the immune mechanisms that may contribute to pathogenesis and severe disease. Although neutrophils are a key component of early immune responses to infection, they have been associated with tissue damage and inflammation in some febrile infections. To assess whether neutrophils contribute to the pathogenesis observed in severe leptospirosis, we quantitated levels of neutrophil activation markers in patients with varying disease severities. Hospitalized leptospirosis patients had significantly higher levels of toll-like receptors 2 and 4 (TLR2 and TLR4, respectively) on peripheral neutrophils than healthy controls, with the highest levels detected in patients with organ dysfunction. We observed no significant differences in other neutrophil baseline activation markers (CD62L and CD11b) or activation capacity (CD62L and CD11b levels following stimulation), regardless of disease severity. Our results provide preliminary evidence supporting the hypothesis that higher initial bacterial loads or inadequate or delayed neutrophil responses, rather than TLR-driven inflammation, may drive severe disease outcomes.