Allergic Dermatitis in Pêga Breed Donkeys (Equus asinus) Caused by Culicoides Bites in the Amazon Biome, Pará, Brazil.

An allergy to bites from Culicoides (Diptera: Ceratopogonidae) occurs because of a hypersensitivity reaction caused by the inoculation of insect salivary antigens during the bite, resulting in immune-mediated dermatitis. To the best of our knowledge, no previous studies have focused on allergic dermatitis in donkeys in Brazil. Therefore, this study aimed to describe the epidemiological, clinicopathological, and therapeutic aspects of allergic dermatitis in donkeys and to identify the insects involved in its epidemiology. This study reported the occurrence of dermatitis in 17 animals. The clinical signs were restlessness and severe itching. Skin lesions were found on the head, depigmented areas of the muzzle and cheeks, flanks, pelvic and thoracic limbs, and the scrotal sac. The lesions were characterized by areas of alopecia with crusts accompanied by serosanguineous exudates. Histologically, the lesions were characterized as moderate superficial dermatitis with irregular epidermal acanthosis and pronounced diffuse orthokeratotic hyperkeratosis. In total, 378 Culicoides specimens were collected, with Culicoides ocumarensis Ortiz being the most abundant species. The combined application of copaiba oil and a multivitamin emulsion exhibited potential for topical treatment of allergic dermatitis caused by insect bites in donkeys. Our study revealed an association between allergic dermatitis in donkeys and Culicoides.

A Solution to Prevent and Minimize the Consequences of Accidents with Farm Tractors in the Context of Mountainous Regions with Low Population Density.

Farm tractors have become a key part of daily routine agriculture, converting complex and time-consuming tasks into tasks that are easier to perform and less dependent on human labor, contributing directly to increasing the economic value generated by this activity sector, either by increasing the productivity or by making certain agricultural crops viable, which otherwise would not be sustainable. However, despite all the advantages, accidents with this type of equipment are common, often with critical and sometimes fatal consequences. The evolution of safety requirements of these machines has occurred at a good level; however, a significant part of the agricultural tractors in use are older models that do not have such solutions. Even in the new models, which contain such solutions, these are not always correctly used, and it is even common that they are turned off or simply not used at all. It is therefore natural that accidents continue to occur, a situation that is aggravated by other factors. Lack of situational awareness of the operators, which can result from advanced age, inadequate training, reduced sensitivity/respect for safety rules, or working on irregular terrain like mountainous areas, contribute to high-risk contexts that end in the loss of human life. The consequences of such accidents are clearly aggravated by the time it takes to assist the victims-either because accidents are simply not identified/reported immediately, or by the time it takes to locate and provide help to the victims. This is a scenario that is more common in mountainous regions and regions with low population density. The current paper, using NB-IoT, a set of sensors, and a web application, presents a conceptual toolset conceived to prevent accidents and minimize consequences (human and material) that can be applied to old and new farm tractors. The development was carried out taking the characterization of the farmers and the land in the region in which the authors' research institution is located into account, which has the highest rate of fatal accidents with agricultural tractors in the country; it is a region of mountainous with a very low population density.

Temporal Trends in Mortality from Alzheimer's Disease in Federal District, Brazil: An Ecological Study (2010-2018).

INTRODUCTION: Neuropsychiatric diseases, particularly dementias, has become more prominent with a great impact on the quality of life of the elderly population. OBJECTIVE: To verify the rate of increase in mortality due to Alzheimer's disease in the Federal District, Brazil from 2010 to 2018. METHOD: An ecological study was conducted, with a time series, about the evolution of the mortality coefficient in the Federal District, Brazil carried out at the Federal District State Department of Health. Mortality rates were defined as the dependent variable and years evaluated as the independent variable-from 2010 to 2018. For temporal trend analysis, the Prais-Winsten linear regression model was used and the increment rate with the respective 95% confidence interval was estimated. RESULTS: From 2010 to 2018, 1665 deaths which had Alzheimer's disease as the underlying cause were recorded in the Mortality Information System. The results showed an overall mortality rate of 6.55 deaths per 100,000 inhabitants, with a higher predominance in females, non-Black people, and those aged 80 years or older. There was an increase in the annual trend of the overall mortality coefficient in both sexes. CONCLUSION: The findings demonstrated a significant increase in the temporal evolution of mortality due to Alzheimer's disease in the Federal District, Brazil. It was recommended to conduct original studies to evaluate the factors that can cause the disease in order to collaborate in the process of formulating policies in the area of public health and improvements in clinical practice.

Molecular survey of potentially pathogenic microorganisms in ticks collected from coatis (Nasua nasua) in Iguaçu National Park, Atlantic Forest biome, southern Brazil.

Human contact with wild animals in synanthropic habits is often mediated by arthropod vectors such as ticks. This is an important method of spreading infectious agents that pose a risk to human health. Thus, this study aimed to molecularly detect Ehrlichia spp., Anaplasma spp., Borrelia spp., and protozoa of the order Piroplasmida in ticks collected from coatis of Iguaçu National Park (PNI), Paraná, Brazil. This study involved 553 ticks DNA, including Amblyomma spp. larvae, Haemaphysalis juxtakochi nymphs, Amblyomma brasiliense, Amblyomma coelebs, and adults of Amblyomma ovale. The DNA extracted from each sample was subjected to polymerase chain reaction (PCR) targeting the genes 23S rRNA for the Anaplasmataceae family, 16S rRNA for Anaplasma spp., dsb for Ehrlichia spp., flaB, 16S rRNA, hpt, and glpQ for Borrelia spp., and 18S rRNA for Piroplasmid protozoans. DNA from Anaplasma sp. was detected in ticks of the species A. coelebs (4/553); Borrelia sp. DNA was detected in A. coelebs (3/553), A. ovale (1/553), and Amblyomma larvae (1/553); and Theileria sp. was detected in A. coelebs (2/553). All tested samples were negative for Ehrlichia spp. Our study constitutes the newest report in South America of these microorganisms, which remain poorly studied.

DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway.

DIS3L2 degrades different types of RNAs in an exosome-independent manner including mRNAs and several types of non-coding RNAs. DIS3L2-mediated degradation is preceded by the addition of nontemplated uridines at the 3'end of its targets by the terminal uridylyl transferases 4 and 7. Most of the literature that concerns DIS3L2 characterizes its involvement in several RNA degradation pathways, however, there is some evidence that its dysregulated activity may contribute to cancer development. In the present study, we characterize the role of DIS3L2 in human colorectal cancer (CRC). Using the public RNA datasets from The Cancer Genome Atlas (TCGA), we found higher DIS3L2 mRNA levels in CRC tissues versus normal colonic samples as well as worse prognosis in patients with high DIS3L2 expression. In addition, our RNA deep-sequencing data revealed that knockdown (KD) of DIS3L2 induces a strong transcriptomic disturbance in SW480 CRC cells. Moreover, gene ontology (GO) analysis of significant upregulated transcripts displays enrichment in mRNAs encoding proteins involved in cell cycle regulation and cancer-related pathways, which guided us to evaluate which specific hallmarks of cancer are differentially regulated by DIS3L2. To do so, we employed four CRC cell lines (HCT116, SW480, Caco-2 and HT-29) differing in their mutational background and oncogenicity. We demonstrate that depletion of DIS3L2 results in reduced cell viability of highly oncogenic SW480 and HCT116 CRC cells, but had little or no impact in the more differentiated Caco-2 and HT-29 cells. Remarkably, the mTOR signaling pathway, crucial for cell survival and growth, is downregulated after DIS3L2 KD, whereas AZGP1, an mTOR pathway inhibitor, is upregulated. Furthermore, our results indicate that depletion of DIS3L2 disturbs metastasis-associated properties, such as cell migration and invasion, only in highly oncogenic CRC cells. Our work reveals for the first time a role for DIS3L2 in sustaining CRC cell proliferation and provides evidence that this ribonuclease is required to support the viability and invasive behavior of dedifferentiated CRC cells.

YES1 Kinase Mediates the Membrane Removal of Rescued F508del-CFTR in Airway Cells by Promoting MAPK Pathway Activation via SHC1.

Recent developments in CFTR modulator drugs have had a significant transformational effect on the treatment of individuals with Cystic Fibrosis (CF) who carry the most frequent F508del-CFTR mutation in at least one allele. However, the clinical effects of these revolutionary drugs remain limited by their inability to fully restore the plasma membrane (PM) stability of the rescued mutant channels. Here, we shed new light on the molecular mechanisms behind the reduced half-life of rescued F508del-CFTR at the PM of airway cells. We describe that YES1 protein kinase is enriched in F508del-CFTR protein PM complexes, and that its interaction with rescued channels is mediated and dependent on the adaptor protein YAP1. Moreover, we show that interference with this complex, either by depletion of one of these components or inhibiting YES1 activity, is sufficient to significantly improve the abundance and stability of modulator-rescued F508del-CFTR at the surface of airway cells. In addition, we found that this effect was mediated by a decreased phosphorylation of the scaffold protein SHC1, a key regulator of MAPK pathway activity. In fact, we showed that depletion of SHC1 or inhibition of MAPK pathway signaling was sufficient to improve rescued F508del-CFTR surface levels, whereas an ectopic increase in pathway activation downstream of SHC1, through the use of a constitutively active H-RAS protein, abrogated the stabilizing effect of YES1 inhibition on rescued F508del-CFTR. Taken together, our findings not only provide new mechanistic insights into the regulation of modulator-rescued F508del-CFTR membrane stability, but also open exciting new avenues to be further explored in CF research and treatment.

Exploring the Efficacy of a Set of Smart Devices for Postural Awareness for Workers in an Industrial Context: Protocol for a Single-Subject Experimental Design.

BACKGROUND: In manufacturing industries, tasks requiring poor posture, high repetition, and long duration commonly induce fatigue and lead to an increased risk of work-related musculoskeletal disorders. Smart devices assessing biomechanics and providing feedback to the worker for correction may be a successful way to increase postural awareness, reducing fatigue, and work-related musculoskeletal disorders. However, evidence in industrial settings is lacking. OBJECTIVE: This study protocol aims to explore the efficacy of a set of smart devices to detect malposture and increase postural awareness, reducing fatigue, and musculoskeletal disorders. METHODS: A longitudinal single-subject experimental design following the ABAB sequence will be developed in a manufacturing industry real context with 5 workers. A repetitive task of screw tightening of 5 screws in a standing position into a piece placed horizontally was selected. Workers will be assessed in 4 moments per shift (10 minutes after the beginning of the shift, 10 minutes before and after the break, and 10 minutes before the end of the shift) in 5 nonconsecutive days. The primary outcomes are fatigue, assessed by electromyography, and musculoskeletal symptoms assessed by the Nordic Musculoskeletal Questionnaire. Secondary outcomes include perceived effort (Borg perceived exertion scale); range of motion of the main joints in the upper body, speed, acceleration, and deceleration assessed by motion analysis; risk stratification of range of motion; and cycle duration in minutes. Structured visual analysis techniques will be conducted to observe the effects of the intervention. Results for each variable of interest will be compared among the different time points of the work shift and longitudinally considering each assessment day as a time point. RESULTS: Enrollment for the study will start in April 2023. Results are expected to be available still in the first semester of 2023. It is expected that the use of the smart system will reduce malposture, fatigue, and consequently, work-related musculoskeletal pain and disorders. CONCLUSIONS: This proposed study will explore a strategy to increase postural awareness in industrial manufacturing workers who do repetitive tasks, using smart wearables that provide real-time feedback about biomechanics. Results would showcase a novel approach for improving self-awareness of risk for work-related musculoskeletal disorders for these workers providing an evidence base support for the use of such devices. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/43637.

Social and health indicators in an academic community: enteroparasites, nutritional, allergic and clinical aspects / Indicadores sociais e de saúde em uma comunidade acadêmica: enteroparasitos, aspectos nutricionais, alérgicos e clínicos

Objective: this study aimed to associate enteroparasitic infection with nutritional, allergic, and clinical repercussions and the sociodemographic aspects in an academic community in Santo Antônio de Jesus, Bahia, Brazil. Methods: the cross-sectional research was carried out between February 2018 and March 2020, with 121 participants. Spontaneous sedimentation and Rugai techniques were used for the parasitological diagnosis of fecal samples. Allergies and clinical issues and the sociodemographic aspects were studied via a questionnaire, and the nutritional status was obtained from the assessment of body mass index and arm and abdominal circumferences. Results: there was 38.2% positivity for intestinal parasites; 65.9% for female participants; with the majority of eutrophic, between 18-27 years old; heteronormative, and single. Besides, the Endolimax nana (78.7%) and Giardia duodenalis (21.3%) were the predominant species. Statistical significance was found between obesity rates and the presence of intestinal parasites and those with allergic aspects. Nervousness, headache, and back and abdominal pains were the most common symptoms. Conclusions: this study contributes to obtaining data on epidemiological and public health surveys in the Bahian territory, providing a reference for other researchers. The statistical association of these with nutritional and allergic aspects can support future research on this population.

Objetivo: este estudo teve como objetivo associar a infecção enteroparasitária com aspectos nutricionais, alérgicos, clínicos e sociodemográficos em uma comunidade acadêmica do município de Santo Antônio de Jesus, Bahia, Brasil. Método: a pesquisa transversal foi realizada entre fevereiro de 2018 e março de 2020, com 121 participantes. As técnicas de sedimentação espontânea e Rugai foram utilizadas para o diagnóstico parasitológico de amostras fecais. Alergias, questões clínicas e aspectos sociodemográficos foram estudados por meio de um questionário, e o estado nutricional foi obtido por meio da avaliação do índice de massa corporal e das circunferências braquial e abdominal. Resultados: houve 38,2% de positividade para parasitos intestinais; 65,9% para participantes do sexo feminino; com a maioria eutrófica, entre 18-27 anos; heteronormativa e sigle. Além disso, Endolimax nana (78,7%) e Giardia duodenalis (21,3%) foram as espécies predominantes. Foi encontrada significância estatística entre as taxas de obesidade e presença de parasitos intestinais e com aspectos alérgicos. Nervosismo, dor de cabeça, dores nas costas e abdominais foram os sintomas mais comuns. Conclusões: este estudo contribui para a obtenção de dados sobre inquéritos epidemiológicos e de saúde pública no território baiano, servindo de referência para outras pesquisas. A associação estatística destes com aspectos nutricionais e alérgicos pode subsidiar futuras pesquisas nesta população.

Factors Associated with Cocaine Consumption among Suicide Victim.

Cocaine use is an increasingly frequent event, especially in young people, and can cause irreversible consequences, such as suicide. To evaluate the factors associated with cocaine use in the moments preceding to suicide. This is a population-based, cross-sectional, and analytical study conducted in the Brazilian Federal District by researchers from the Department of Health and the Civil Police Institute of Criminalistics. All people who died due to suicide in 2018 were included in the survey. Cocaine use was considered the dependent variable, and robust Poisson regression was performed to estimate the crude and adjusted prevalence ratios and their respective population confidence intervals. In 2018, 12,157 deaths were recorded, of which suicide accounted for 1.56% of all deaths. It was observed that being between 25 and 44 years old, male, and under the influence of alcohol or cannabis, had a strong positive association with cocaine consumption among suicide victims. Males, people with black skin, with lower level of education, with employment, and who were under the effect of the use of cannabis and/or alcohol in the previous hours of death had a higher propensity to consume cocaine immediately before suicide, with a moderate to strong magnitude of prevalence ratio. The findings of this research indicated the need for monitoring, by health services, of people most vulnerable to suicide through the consumption of psychoactive substances.

Evaluating the Feasibility of Using Brick Powder and Clay Powder in Cement Replacement.

The cement industry generates very large amounts of CO2 into the atmosphere. In recent years, there has been a search for alternative cementitious materials and micro-fillers that could partially or fully replace cement in cement composites without compromising their durability. This paper investigates the possibility of using brick powder (BP) and clay powder (CP) as a partial replacement for cement (up to 20% by weight) in cement paste. The raw materials were characterized, and the physical and mechanical properties of the modified cement pastes were studied, as well as their resistance to a short-term thermal shock at 250 °C. The study was supplemented by intelligent modelling of compressive strength using the support vector machine (SVM) algorithms. The results indicated a significant increase in tensile strength (up to 100%) and an increase in thermal resistance of cement pastes modified with BP and CP. The proposed SVM model had high accuracy (R2 = 0.90), indicating its suitability to predict the compressive strength of the modified cement matrix. This study complements the knowledge in the field of inter alia, the effect of a short-term thermal shock at elevated temperature on the properties of BP and CP modified cement paste, and the effect of BP, which, due to its grain size, plays more the role of a microfiller than a pozzolanic additive.

Adherens Junction Integrity Is a Critical Determinant of Sodium Iodide Symporter Residency at the Plasma Membrane of Thyroid Cells.

While most cases of differentiated thyroid carcinoma (DTC) are associated with a good prognosis, a significant number progress to advanced disease exhibiting aggressive clinical characteristics and often becoming refractory to radioactive iodine (RAI) treatment, the current gold-standard therapeutic option for metastatic disease. RAI-refractoriness is caused by defective functional expression of the sodium-iodide symporter (NIS), which is responsible for the active transport of iodide across the plasma membrane (PM) into thyroid follicles. NIS deficiency in these tumors often reflects a transcriptional impairment, but also its defective targeting and retention at the cells' PM. Using proteomics, we previously characterized an intracellular signaling pathway derived from SRC kinase that acts through the small GTPase RAC1 to recruit and bind the actin-anchoring adaptor EZRIN to NIS, regulating its retention at the PM of both non-transformed and cancer thyroid cells. Here, we describe how by reanalyzing the proteomics data, we identified cell-cell adhesion as the molecular event upstream the pathway involved in the anchoring and retention at the PM. We show that by interacting with NIS at the PM, adherens junction (AJ)-associated P120-catenin recruits and is phosphorylated by SRC, allowing it to recruit RAC1 to the complex. This enables SRC-phosphorylated VAV2 exchange factor to activate RAC1 GTPase, inducing NIS retention at the PM, thus increasing its abundance and function at the surface of thyroid cells. Our findings indicate that the loss of epithelial cell-cell adhesion may contribute to RAI refractoriness, indicating that in addition to stimulating NIS expression, successful resensitization therapies might require the employment of agents that improve cell-cell adhesion and NIS PM retention in refractory TC cells.

Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles-A Systematic Review.

Titanium dioxide nanoparticles (TiO2-NPs) are widely used, and humans are exposed through food (E171), cosmetics (e.g., toothpaste), and pharmaceuticals. The oral and gastrointestinal (GIT) tract are the first contact sites, but it may be systemically distributed. However, a robust adverse outcome pathway (AOP) has not been developed upon GIT exposure to TiO2-NPs. The aim of this review was to provide an integrative analysis of the published data on cellular and molecular mechanisms triggered after the ingestion of TiO2-NPs, proposing plausible AOPs that may drive policy decisions. A systematic review according to Prisma Methodology was performed in three databases of peer-reviewed literature: Pubmed, Scopus, and Web of Science. A total of 787 records were identified, screened in title/abstract, being 185 used for data extraction. The main endpoints identified were oxidative stress, cytotoxicity/apoptosis/cell death, inflammation, cellular and systemic uptake, genotoxicity, and carcinogenicity. From the results, AOPs were proposed where colorectal cancer, liver injury, reproductive toxicity, cardiac and kidney damage, as well as hematological effects stand out as possible adverse outcomes. The recent transgenerational studies also point to concerns with regard to population effects. Overall, the findings further support a limitation of the use of TiO2-NPs in food, announced by the European Food Safety Authority (EFSA).

Recycled Aggregate: A Viable Solution for Sustainable Concrete Production.

Construction and demolition activities consume large amounts of natural resources, generating 4.5 bi tons of solid waste/year, called construction and demolition waste (C&DW) and other wastes, such as ceramic, polyethylene terephthalate (PET), glass, and slag. Furthermore, around 32 bi tons of natural aggregate (NA) are extracted annually. In this scenario, replacing NA with recycled aggregate (RA) from C&DW and other wastes can mitigate environmental problems. We review the use of RA for concrete production and draw the main challenges and outlook. RA reduces concrete's fresh and hardened performance compared to NA, but these reductions are often negligible when the replacement levels are kept up to 30%. Furthermore, we point out efficient strategies to mitigate these performance reductions. Efforts must be spent on improving the efficiency of RA processing and the international standardization of RA.

Effect of TiO2 Nanoparticles on the Fresh Performance of 3D-Printed Cementitious Materials.

3D printing (3DP) of cementitious materials shows several advantages compared to conventional construction methods, but it requires specific fresh-state properties. Nanomaterials have been used in cement-based materials to achieve specific fresh and hardened properties, being potential candidates for 3DP applications. However, there are no reports on using TiO2 nanoparticles (nano-TiO2) in 3DP cementitious composites. Thus, the current work aims to assess the effect of nano-TiO2 on the fresh performance of 3DP cementitious materials. For this purpose, nano-TiO2 was incorporated in pastes and mortars from 0 to 1.5 wt.%. Time-resolved hydration (in situ XRD) and rheological and printing-related properties (buildability and printability) were evaluated. Results showed that nano-TiO2 particles enhanced the cement hydration kinetics, leading to further ettringite formation up to 140 min compared to plain cement paste. Rheological measurements showed that the nano-TiO2 incorporation progressively increased the static and dynamic stress, viscosity, and structuration rate of pastes. Furthermore, nano-TiO2 improved the buildability of the composites, progressively increasing the maximum number of successive layers printed before failure from 11 (0 wt.% TiO2) to 64 (1.5 wt.% TiO2). By contrast, the nano-TiO2 addition reduced the printability (i.e., the printable period during which the sample was able to be molded by the 3D-printing process) from 140 min (0% TiO2) to 90 min (1.5% TiO2). Thus, incorporating "high" nano-TiO2 contents (e.g., >1 wt.%) was beneficial for buildability but would require a quicker 3DP process. The adoption of nano-TiO2 contents of around 0.75−1.00% may be an interesting choice since it reduced the printability of paste by 30 min compared with the control mix but allowed for printing 24 layers (118% higher than plain mortar).

Targeting Cancer by Using Nanoparticles to Modulate RHO GTPase Signaling.

Functionalized nanomaterials have recently been introduced as efficient vehicles for targeted delivery of drugs and other tailored molecules to cancer cells. They emerge as new opportunities for addressing particular challenging targets such as RHO guanosine triphosphatases (GTPases), a group of signaling molecules involved in the progression of a variety of tumor types. RHO GTPases comprise a subfamily of the Ras superfamily of small GTPases. They are best known for their role in cell migration through the remodeling of the actin cytoskeleton. However, they are also key regulators of a broad number of cellular functions, ranging from proliferation to cell adhesion and differentiation. Not surprisingly, their dysregulation has been implicated in the development and progression of many types of cancer. The RHO GTPase subfamily includes 20 members that can be further separated into typical and atypical RHO GTPases. The typical RHO family members include the classical RHOA, RAC1 and CDC42 proteins, which cycle between an active GTP-bound and inactive GDP-bound conformation, under the coordinated action of three types of regulators: GEFs, GAPs and GDIs. Atypical RHO family members have small changes in key residues that alter their regulatory mechanisms. Nevertheless, both typical and atypical RHO GTPases contribute to cancer progression but, in contrast to Ras proteins, very few mutations have been found in tumors. In most cancers, it is the expression level and/or activity of RHO GTPases that is dysregulated. RHO GTPase signaling has thus long been seen as an attractive target for cancer treatment but their ubiquity and the lack of isoform-specific drugs have posed significant obstacles to the development of viable therapeutic strategies. Based on the success of recent nanomedicine approaches, this chapter reviews representative studies of how functionalized nanoparticles can be designed to target tumor-specific molecules and directly or indirectly modulate the expression and/or activity of particular RHO GTPases in cancer cells.