Ticks (Acari: Ixodidae) and rickettsiae associated with wild boars in a rural area of Minas Gerais, Brazil.

Wild boars or feral pigs are classified by the Brazilian Institute for the Environment and Renewable Resources (IBAMA) in "Category I of invasive exotic species". They cause economic losses, harm the environment, serve as hosts and reservoirs for several zoonotic disease agents, and provide a blood meal for tick species that act as vectors for zoonotic diseases. The objective of this study was to identify tick species on wild boars, assess host-seeking ticks in the related environment, and identify other potential tick hosts coexisting with wild boars on a farm located in the state of Minas Gerais, southeastern Brazil. Additionally, the study aimed to determine the presence of rickettsiae in these arthropods and assess the exposure of wild boars to rickettsiae species from the Spotted Fever Group and Rickettsia bellii through serology. A total of 3585 host-seeking ticks from three species (Amblyomma sculptum - 41.58%; Amblyomma dubitatum - 0.39% and Rhipicephalus microplus - 0.05%) were collected in the environment and A. sculptum was the most abundant species. Thirty-one wild boars were evaluated, resulting in the collection of 415 ticks, all of which were A. sculptum. Rickettsia DNA was not detected in samples of A. sculptum and R. microplus from the environment or in A. sculptum ticks from wild boars. However, all A. dubitatum ticks (n = 14) had Rickettsia bellii DNA confirmed by the species-specific PCR protocol. Out of the 31 serum samples from wild boars, 24 reacted with at least one Rickettsia antigen. Among these, seven individuals exhibited a reaction to a probable homologous antigen (PHA) of three rickettsiae species: R. rickettsii (n = 3), R. amblyommatis (n = 3) and R. rhipicephali (n = 1). Despite the high prevalence of seroreactivity, titers were low, indicating limited exposure to Rickettsia spp. Camera traps generated 874 animal records, capturing a total of 1688 individuals. At least 11 species of birds and 14 species of mammals (12 wild and two domestic) shared the environment with wild boars and potentially shared ticks with them. These findings provide baseline information for understanding the sharing of ticks and tick-borne pathogens between wild boars and other animals within the Cerrado biome. Further studies are necessary to monitor the potential and actual risk of wild boars to harbor infected ticks and their role in the transmission and maintenance cycle of Rickettsia spp.

Density and behavior of capybara (Hydrochoerus hydrochaeris) ticks (Acari: Ixodidae) Amblyomma sculptum and Amblyomma dubitatum with notes on Rickettsia bellii infection: Assessing human exposure risk.

In several urban and peri­urban areas of Brazil, populations of Amblyomma sculptum and Amblyomma dubitatum ticks are maintained by capybaras (Hydrochoerus hydrochaeris). In some of these areas, this host and these tick species are associated with Brazilian spotted fever (BSF), a lethal human disease caused by the bacterium Rickettsia rickettsii. In this work, we evaluated the risk of human exposure to these tick species using four collection techniques to discern host-seeking behavior. The study was carried out in 10 urban sites inhabited by capybaras in Uberlândia, a BSF-free municipality in southeastern Brazil. Ticks were collected in areas of 400 m2 at each site and at three seasons. Within the same municipality, the distance and speed of A. sculptum nymphs moving towards the CO2 traps were evaluated. In a sample of ticks Rickettsia DNA was investigated. During the study period, 52,953 ticks were collected. Among these, 83.4 % were A. sculptum (1,523 adults, 10,545 nymphs and 32,104 larvae) and 16.6 % were A. dubitatum (464 adults, 2,153 nymphs and 6,164 larvae). An average annual questing tick density of 4.4/m² was observed, with the highest density recorded at one site in autumn (31.8/m²) and the lowest in summer at another site (0.03/m²). The visual search yielded the highest proportion of A. sculptum larvae, constituting 47 % of the total and 63.6 % of all A. sculptum larvae. In contrast, CO2 traps collected a greater proportion of nymphs and adults of A. sculptum ticks. In the case of A. dubitatum, the CO2 trap was the most efficient technique with 57.7 % of captures of this species, especially of nymphs (94.5 % of captures) and adults (97.8 % of captures). Ticks' ambush height on vegetation (9 to 77 cm), observed by visual search 30 times, yielded a total of 20,771 ticks. Of these, 28 (93 %) were A. sculptum ticks, with only two (7 %) identified as A. dubitatum ticks. Among A. sculptum ticks, the nymph was the most attracted stage to humans and larva in the case of A. dubitatum. Amblyomma sculptum adults and nymphs were significantly more attracted to humans than those of A. dubitatum, but A. dubitatum larvae were significantly more attracted than the same stage of A. sculptum. The maximum distance and speed of horizontal displacement for A. sculptum nymphs were five meters and 2.0 m/h, respectively. The only species of Rickettsia detected in ticks, exclusively in A. dubitatum, was R. bellii. Importantly, it was observed that the higher the proportion of A. sculptum in the community of ticks, the lower the rate of infection of A. dubitatum by R. bellii. In conclusion, host-seeking behavior differed between the two tick species, as well as between stages of the same species. A greater restriction of A. dubitatum ticks to the soil was observed, while larvae and nymphs of A. sculptum dispersed higher in the vegetation. The behavior presented by A. sculptum provides greater opportunities for contact with the hosts, while A. dubitatum depends more on an active search for a host, the hunter behavior. Taken together, these observations show that a human being crossing an area infested with A. sculptum and A. dubitatum ticks will have almost exclusive contact with A. sculptum larvae and/or nymphs. Humans in a stationary position (sitting, lying or immobile) are exposed to both tick species, but they are more attractive to adults and mainly nymphs of A. sculptum compared to the corresponding stages of the tick A. dubitatum. The negative effect of A. sculptum on A. dubitatum infection by R. bellii deserves further studies.

EMG-Informed Neuromusculoskeletal Modelling Estimates Muscle Forces and Joint Moments During Electrical Stimulation.

This study implemented an electromyogram (EMG)-informed neuromusculoskeletal (NMS) model evaluating the volitional contributions to muscle forces and joint moments during functional electrical stimulation (FES). The NMS model was calibrated using motion and EMG (biceps brachii and triceps brachii) data recorded from able-bodied participants (n=3) performing weighted elbow flexion and extension cycling movements while equipped with an EMG-controlled closed-loop FES system. Models were executed using three computational approaches (i) EMG-driven, (ii) EMG-hybrid and (iii) EMG-assisted to estimate muscle forces and joint moments. Both EMG-hybrid and EMG-assisted modes were able estimate the elbow moment (root mean squared error and coefficient of determination), but the EMG-hybrid method also enabled quantifying the volitional contributions to muscle forces and elbow moments during FES. The proposed modelling method allows for assessing volitional contributions of patients to muscle force during FES rehabilitation, and could be used as biomarkers of recovery, biofeedback, and for real-time control of combined FES and robotic systems.

Illustrated keys and a DNA barcode reference library of the amphibians and terrestrial reptiles (Amphibia, Reptilia) of São Tomé and Príncipe (Gulf of Guinea, West Africa).

The herpetofauna of São Tomé and Príncipe consists of nine species of amphibians, all endemic, and 21 species of terrestrial reptiles, of which 17 are endemic. Our current knowledge regarding its natural history, ecology, and distribution is limited. Here two important tools are provided to support researchers, conservationists, and local authorities in the identification of the country's herpetofauna: an illustrated key to the herpetofauna of the two islands and surroundings islets and a DNA barcode reference library. The keys allow a rapid and unambiguous morphological identification of all occurring species. The DNA barcodes for the entire herpetofauna of the country were produced from 79 specimens, all of which are deposited in museum collections. The barcodes generated are available in online repositories and can be used to provide unambiguous molecular identification of most of the species. Future applications and use of these tools are briefly discussed.

DOPE/CHEMS-Based EGFR-Targeted Immunoliposomes for Docetaxel Delivery: Formulation Development, Physicochemical Characterization and Biological Evaluation on Prostate Cancer Cells.

Docetaxel (DTX) is a non-selective antineoplastic agent with low solubility and a series of side effects. The technology of pH-sensitive and anti-epidermal growth factor receptor (anti-EGFR) immunoliposomes aims to increase the selective delivery of the drug in the acidic tumor environment to cells with EFGR overexpression. Thus, the study aimed to develop pH-sensitive liposomes based on DOPE (dioleoylphosphatidylethanolamine) and CHEMS (cholesteryl hemisuccinate), using a Box-Behnken factorial design. Furthermore, we aimed to conjugate the monoclonal antibody cetuximab onto liposomal surface, as well as to thoroughly characterize the nanosystems and evaluate them on prostate cancer cells. The liposomes prepared by hydration of the lipid film and optimized by the Box-Behnken factorial design showed a particle size of 107.2 ± 2.9 nm, a PDI of 0.213 ± 0.005, zeta potential of -21.9 ± 1.8 mV and an encapsulation efficiency of 88.65 ± 20.3%. Together, FTIR, DSC and DRX characterization demonstrated that the drug was properly encapsulated, with reduced drug crystallinity. Drug release was higher in acidic pH. The liposome conjugation with the anti-EGFR antibody cetuximab preserved the physicochemical characteristics and was successful. The liposome containing DTX reached an IC50 at a concentration of 65.74 nM in the PC3 cell line and 28.28 nM in the DU145 cell line. Immunoliposome, in turn, for PC3 cells reached an IC50 of 152.1 nM, and for the DU145 cell line, 12.60 nM, a considerable enhancement of cytotoxicity for the EGFR-positive cell line. Finally, the immunoliposome internalization was faster and greater than that of liposome in the DU145 cell line, with a higher EGFR overexpression. Thus, based on these results, it was possible to obtain a formulation with adequate characteristics of nanometric size, a high encapsulation of DTX and liposomes and particularly immunoliposomes containing DTX, which caused, as expected, a reduction in the viability of prostate cells, with high cellular internalization in EGFR overexpressing cells.

HbA1c and physical performance in older adults from different aging epidemiological contexts: Longitudinal findings of the International Mobility in Aging Study (IMIAS).

OBJECTIVE: This study aimed to assess the longitudinal predictions between glycated hemoglobin A1c (HbA1c) and physical performance scores in different epidemiological contexts of aging. MATERIAL AND METHODS: Longitudinal data of 1,337 older people from three countries (Canada, Brazil and Colombia) of the International Mobility in Aging Study (IMIAS) were used to assess the relationship between HbA1c and Short Physical Performance Battery (SPPB) scores between 2012 and 2016. Linear Mixed Models grouped by sex and adjusted by Age, Study site, Chronic Conditions, Anthropometric Measures, and Inflammatory Level were used to estimate the influence of HbA1c and covariates on SPPB scores. RESULTS: At the IMIAS baseline, Latin American (LA) cities had higher HbA1c averages compared to Canadian cities, with Natal (Brazil) being the city with the highest HbA1c averages in men and women (6.32 ± 1.49; 6,56 ± 1.70 respectively). SPPB scores were significantly lower in LA cities, and older people in Natal had lower SPPB averages in men (9.67 ± 2.38; p-value < 0.05) and women (8.52 ± 2.33; p-value <0.05). In the multivariate mixed linear models of longitudinal analyses, HbA1c was significantly associated with lower SPPB scores in men (ß = -0.25, 95% CI: -0.39 to -0.12, p-value = 0.02) but not in women. CONCLUSION: High HbA1c levels at baseline were longitudinally associated in older adults from different countries, and this association was observed only in men and not in women. This study highlights a possible influence of gender on this relationship.

All in all its just another branch in the tree: A new species of Acanthocercus Fitzinger, 1843 (Squamata: Agamidae), from Angola.

Recent integrative taxonomic studies of the agamid genus Acanthocercus Fitzinger, 1843 have shown that Angola harbors three different taxa, all within the Acanthocercus atricollis (Smith, 1849) species complexA. cyanocephalus (Falk, 1925) in the northeastern parts of the country, A. margaritae Wagner et al. 2021 in the southern regions, and an unnamed species in the central and northwestern parts of Angola. Using the previously published molecular data as evidence of phylogenetic support and newly collected morphological, meristic and coloration data, we here describe this unnamed lineage as a new species. The new species is morphologically very similar to A. cyanocephalus, but it can easily be differentiated from the latter by the coloration pattern of displaying males, with a blue coloration restricted to the head region, and by its inferior scale counts compared to other species of the A. atricollis complex group. As reported in other studies in this group, male breeding coloration is an effective trait for diagnosing these morphologically conserved species. This description raises the number of Acanthocercus species recognized to 15 and is another contribution revealing the rich but still incompletely described herpetological diversity of Angola.

Influence of spatial variability of soil chemical attributes on the nutritional status and growth of the rubber tree

The productive potential of the rubber tree (Hevea brasiliensis) is dependent on its genetic composition, in addition to edaphoclimatic factors and management practices. However, as soil properties are not homogenous, knowing the spatial variability of soil attributes would be important to increase productivity and reduce production costs. In this context, the objective of this study was to determine the spatial variability of chemical attributes of the soil and its influence on the nutritional status and growth of rubber tree clones. Clones FX 3864, FDR 5788, CDC 312, and RRIM 600 were planted at Jaturnaíba Farm, in the municipality of Silva Jardim, Rio de Janeiro State, Brazil. The sampling sites were distributed at a spacing of 20 × 20 m on the northern and southern sides of the relief. The chemical attributes of the soil (pH, Ca2+, Mg2+, K+, P, Al3+, H+Al, sum of bases, cation exchange capacity, and base saturation) were evaluated at a depth of 0­20 cm in the different clone plantations. Additionally, the N, P, K, Ca, and Mg content as well as trunk circumference and total plant height, were also evaluated. Geostatistics was used to determine the spatial variability of the soil and clone attributes, while Ordinary Kriging was used to draw variability maps of the variables. A difference in the distribution of the variables, which was dependent on the slope of the relief, was detected through the maps. The southern side presented better conditions as some degradation was observed on the northern side. Certain soil characteristics influenced the distribution of the attributes of the planted clones; for example, the low concentration of Ca2+ in the soil caused Ca deficiency in the FX clone on the southern slope, indicating that liming did not supply enough nutrients for this clone. Our results showed that the variability in soil attributes influenced the nutritional status and growth of the rubber tree clones, indicating that variability maps can guide the planting and management of the rubber tree, providing more efficient management.

Cuidado à mulher em situação de violência por parceiro íntimo na atenção primária à saúde / Care for women in situations of intimate partner violence in primary health care

A Violência por Parceiro Íntimo (VPI) é uma das principais formas de agressão contra mulheres em todo o mundo. Dados da OMS sugerem que 1 a cada 3 mulheres é vítima de algum tipo de violência perpetrada por seu parceiro. A Atenção Primária à Saúde (APS) é a principal porta de entrada dos serviços de saúde e, por isso mesmo, figura como elemento importante para o reconhecimento e intervenção precoce dos casos de violência contra a mulher. Objetivos: Para isso é necessário conhecer o perfil das mulheres vítimas de tal agravo e as barreiras enfrentadas pelos profissionais de saúde que impedem o cuidado adequado a esta situação. Métodos: Trata-se de uma revisão de literatura a partir de artigos publicados na Biblioteca Virtual de Saúde (BVS) relativos ao tema Violência por Parceiro íntimo. Conclusão: Este trabalho propõe um maior aprofundamento sobre o assunto pelos profissionais de saúde, principalmente aqueles inseridos na APS

Perfil sociodemográfico, de saúde e hábitos de vida de idosos na Atenção Primária à Saúde / Sociodemographic profile, health and life habits of older adults in Primary Health Care / Hábitos sociodemográficos, de salud y de estilo de vida del adulto mayor en Atención Primaria de Salud

O envelhecimento populacional é considerado uma importante conquista da humanidade, no entanto, tem representado um desafio para os países em desenvolvimento, como o Brasil. Assim, conhecer o perfil da população idosa é relevante para o desenvolvimento de ações específicas e para nortear políticas de saúde. Este estudo teve como objetivo caracterizar o perfil sociodemográfico, os hábitos de vida e os aspectos de saúde dos idosos cadastrados em unidades básicas de saúde de um município localizado no interior do Nordeste. Para isso, foi realizada uma pesquisa epidemiológica, observacional e transversal, no ano de 2018. Foram avaliados 109 idosos, a maioria do sexo feminino (77,1%), faixa etária de 65 a 69 anos (45,9%), casados (47,7%), brancos (46,8%), com ensino fundamental incompleto (64,2%). Com relação aos hábitos de vida, a maior parte relatou não fumar (92,7%), não beber álcool (91,7%) e ter comportamento sedentário (60,6%). Quanto às condições de saúde, a maioria apresentou comorbidades (57,8%), sem sintomatologia depressiva (80,7%), além de relatar satisfação com os serviços de saúde. Assim, conclui-se que os resultados obtidos neste estudo podem contribuir para nortear possíveis ações a serem realizadas na Atenção Primária à Saúde e auxiliar no desenvolvimento das políticas de saúde voltadas para a população idosa.

Population aging is an important achievement of humanity; however, it has represented a challenge for developing countries, such as Brazil. Thus, knowing the profile of the aging population is relevant for developing specific actions and guiding health policies. This epidemiological, observational, and cross-sectional study, conducted in 2018, sought to characterize the sociodemographic profile, life habits and health aspects of older adults registered in basic health units in a Northeastern municipality. Total sample evaluated consisted of 109 older adults, mostly female (77.1%), age range 65 to 69 years old (45.9%), married (47.7%), white (46.8%), with incomplete primary education (64.2%). Regarding lifestyle habits, most reported not smoking (92.7%), not drinking alcohol (91.7%), and having sedentary behavior (60.6%). As for health conditions, most participants had comorbidities (57.8%), no depressive symptoms (80.7%), and reported satisfaction with health services. In conclusion, the results obtained in this study can contribute to guide possible Primary Health Care actions and assist in developing health policies aimed at older adults.

El envejecimiento de la población es considerado como un logro importante de la humanidad, sin embargo, ha representado un desafío para los países en desarrollo, como Brasil. Así, conocer el perfil de la población anciana es importante para el desarrollo de acciones específicas y para orientar las políticas de salud. Este estudio tuvo como objetivo caracterizar el perfil sociodemográfico, los hábitos de vida y los aspectos de salud de los ancianos registrados en unidades básicas de salud de un municipio ubicado en el interior del Nordeste (Brasil). Para ello, se realizó una encuesta epidemiológica, observacional y transversal en 2018. Se evaluaron a 109 adultos mayores, la mayoría del sexo femenino (77,1%), con edad entre 65 y 69 años (45,9%), casados ??(47,7%), blancos (46,8%) y con primaria incompleta (64,2%). En cuanto a los hábitos de vida, la mayoría refirió no fumar (92,7%), no consumir alcohol (91,7%) y tener una conducta sedentaria (60,6%). Respecto a las condiciones de salud, la mayoría tenía comorbilidades (57,8%) y sin síntomas depresivos (80,7%); además, reportaron satisfacción con los servicios de salud. Por lo tanto, se concluye que los resultados obtenidos en este estudio pueden contribuir a orientar posibles acciones futuras en la Atención Primaria de Salud y a auxiliar en el desarrollo de políticas de salud dirigidas a la población anciana.

THC shows activity against cultured Plasmodium falciparum.

The FDA approved drug Dronabinol was identified in a previous study applying virtual screening using the haemozoin crystal as a target against malaria parasites. The active ingredient of dronabinol is synthetic tetrahydrocannabinol (THC), which is one of the major cannabinoids from Cannabis sativa. Traditional use of cannabis for malaria fever was reported in the world's oldest pharmacopoeia, dating to around 5000 years ago. In this research we report that THC inhibits ß-haematin (synthetic haemozoin) and malaria parasite growth. Due the psychoactivity of THC, CBD, the other major naturally occurring cannabinoid that lacks the off-target psychoactive effects of THC, was also tested and inhibited ß-haematin but showed only a mild antimalarial activity. To evaluate whether THC inhibit haemozoin formation, we performed a cellular haem fractionation assay that indicated that is not the likely mechanism of action. For the first time, the cannabinoid chemical structure is raised as a new chemical class to be further studied for malaria treatment, aiming to overcome the undesirable psychoactive effects of THC and optimize the antimalarial effects.

Association of Soy and Exclusive Breastfeeding With Central Precocious Puberty: A Case-Control Study.

Introduction: While soy is suggested as a possible risk factor, exclusive breastfeeding (EBF) has a likely protective effect in precocious puberty. Our aim was to evaluate the association between both of these variables with central precocious puberty (CPP). Methods: We performed a retrospective, case-control study. A total of 161 girls were divided into two groups: 84 patients diagnosed with CPP composed the case group and 77 patients without the diagnosis of CPP (had gone through normal onset of puberty) were the control group. Results: Our control group had a higher presence of EBF >6 months, which was an important protective factor for CPP (OR: 0.5; IC 95%: 0.3-0.9, p = 0.05) and also correlated negatively with the presence of it (r = -0.2; p < 0.05). Oppositely, the use of soy was significantly higher in the CPP group, (OR: 3.8; IC 95%: 1.5-6, p < 0.05) and positively correlating (r = 0.2; p < 0.01) with the presence of CPP. Duration of soy intake (years) correlated with bone age (r = 0.415; p < 0.05). A logistic regression was performed to evaluate the effects of EBF duration and soy on CPP. The model was significant (x² (2) = 20,715, p = <0.001) and explained 12.2% (Nagelkerke R2) of the variance, correctly classifying 62.5% of cases. EBF was associated with a reduction of likelihood of having CPP [OR = 0,187 (CI = 0.055-0,635); Wald = 7,222, p = 0.007], while soy intake increased the risk [OR = 3.505 (CI) = 1,688-7,279, Wald = 11,319, p = 0.001]. Conclusion: Our data found the use of soy was associated with CPP. Additionally, EBF was pointed as a protective factor. However, future prospective studies are needed to clarify this issue.

Factors associated with medical students' quality of life in a Brazilian northeast countryside university / Fatores associados à qualidade de vida dos estudantes de medicina no interior do Nordeste brasileiro

Abstract: Introduction: The current policy of interiorization of medical education worldwide and the application of active methods, as well as the lack of consensus regarding the factors associated with medical students' quality of life are topics of discussion in the medical literature. Objective: In view of the scarcity of analyses on the subject, this study aimed to evaluate the topictopic at a medical school in a Brazilian northeast countryside university. Method: Cross-sectional study, developed from March to May of 2018. The questionnaire WHOQOL-bref was used to evaluate the quality of life and the data were related to: sociodemographic characteristics, anthropometric data and lifestyle. Data analysis was performed using descriptive statistics; then, a bivariate analysis was performed with a test for comparison of mean scores aimed to identify possible variables associated with the investigated domains. Binary logistic regression was performed to identify possible factors associated with poor quality of life in the investigated domains. The statistical analysis estimated 95% CI and p-value <0.05. Results: The present study characterized the students' quality of life and identified the following factors as being associated with poor quality of life: female gender, attending preclinical years, being a smoker, having normal weight classified according to the body mass index, having a negative assessment of their own health and quality of life. The results also showed that most students had a negative evaluation regarding the physical, psychological and environmental domains; in contrast to the social relationships domain, in which most reported a positive assessment. Conclusion: The findings allow discussions about measures aimed at dealing with factors that affect the quality of life of medical students attending medical schools located in remote and rural regions.

Resumo: Introdução: A atual política de interiorização da educação médica mundial e a aplicação de métodos ativos, bem como a falta de consenso sobre os fatores associados à qualidade de vida dos estudantes de Medicina, são conhecidos temas de discussão na literatura médica. Objetivo: Tendo em vista a escassez de análise sobre o assunto, este estudo teve como objetivo avaliar a qualidade de vida entre os estudantes de Medicina de uma universidade do interior do Nordeste brasileiro. Método: Trata-se de um estudo transversal, desenvolvido de março a maio de 2018. Utilizou-se o questionário WHOQOL-bref para avaliar a qualidade de vida, e os dados foram relacionados a características sociodemográficas, dados antropométricos e estilo de vida. Analisaram-se os dados por meio de estatística descritiva, e, em seguida, fez-se a análise bivariada com teste para comparação das médias dos escores, a fim de identificar possíveis variáveis associadas aos domínios investigados. Realizou-se regressão logística binária para identificar possíveis fatores associados à pior qualidade de vida nos domínios investigados. A análise estatística estimou IC 95% e valor de p < 0,05. Resultado: O presente estudo caracterizou a qualidade de vida dos estudantes de Medicina e identificou como principais fatores associados à má qualidade de vida: ser do sexo feminino, cursar anos pré-clínicos, ser fumante, ter peso normal classificado pelo índice de massa corporal e apresentar uma avaliação negativa da própria saúde e da qualidade de vida. Os resultados também evidenciaram que a maioria dos estudantes apresentou uma avaliação negativa nos domínios físico, psicológico e meio ambiente, em contraste com o domínio relações sociais, ao qual a maioria atribuiu uma avaliação positiva. Conclusão: Os achados permitem discutir acerca de medidas voltadas a lidar com fatores que prejudicam a qualidade de vida de alunos de escolas de Medicina em regiões remotas e rurais.

Comparing Spatially Distributed and Single Electrode Stimulation on Individuals with Spinal Cord Injury.

It is still a challenge to delay the onset of fatigue on muscle contraction induced by Functional Electrical Stimulation (FES). We explored the use of two stimulation methods with the same total area, single electrode stimulation (SES), and spatially distributed electrical stimulation (SDSS) during isometric knee extension with spinal cord injured (SCI) volunteers. We applied stimulation on the left and right quadriceps of two SCI participants with both methods and recorded isometric force and evoked electromyography (eEMG). We calculated the force-time integral (FTI) and eEMG-time integral (eTI) for each stimulation series and used a linear regression as a measure of decay ratio. Moreover, we also estimated the contribution from each channel from eEMG.

Identification of 2,4-Disubstituted Imidazopyridines as Hemozoin Formation Inhibitors with Fast-Killing Kinetics and In Vivo Efficacy in the Plasmodium falciparum NSG Mouse Model.

A series of 2,4-disubstituted imidazopyridines, originating from a SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity. During lead optimization, several issues were flagged such as cross-resistance against the multidrug-resistant K1 strain, in vitro cytotoxicity, and cardiotoxicity and were addressed through structure-activity and structure-property relationship studies. Pharmacokinetic properties were assessed in mice for compounds showing desirable in vitro activity, a selectivity window over cytotoxicity, and microsomal metabolic stability. Frontrunner compound 37 showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated into in vivo efficacy in the P. falciparum NOD-scid IL-2Rγnull (NSG) mouse model. Preliminary mechanistic studies suggest inhibition of hemozoin formation as a contributing mode of action.

Urticárias crônicas induzidas: atualização do tema / Chronic inducible urticaria: topic update

A urticária é uma doença comum, determinada pela ativação de mastócitos que se apresenta por urticas, angioedema, ou ambos. Convencionou-se classificar a urticária, quanto a sua duração, em duas formas: aguda (UA) e crônica (UC). A urticária é definida como crônica quando persiste por 6 semanas ou mais. A urticária crônica compreende urticária crônica espontânea (UCE) e urticárias crônicas induzidas (UCInd), que incluem as urticárias físicas e não físicas. Estudos sugerem que a presença de UCInd associada a UCE está ligada a um pior prognóstico e duração da doença. Essa revisão tem por objetivo atualizar as informações disponíveis sobre a prevalência, quadros clínicos, métodos diagnósticos e tratamentos das UCInd por estímulos físicos ou não.

Urticaria is a common disease determined by the activation of mast cells that presents with urticaria, angioedema, or both. According to its duration, urticaria is classified into two forms: acute (AU) and chronic (CU). Urticaria is defined as CU when it persists for 6 weeks or more. CU consists of chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), which includes physical and nonphysical urticarias. Studies suggest that the presence of both CIndU and CSU is linked to worse prognosis and longer duration of these diseases. This review aims to update available information on the prevalence, clinical manifestations, diagnostic methods, and treatments of CIndU by physical or nonphysical stimuli.

Naphthylisoquinoline alkaloids, validated as hit multistage antiplasmodial natural products.

The discovery and development of multistage antimalarial drugs targeting intra-erythrocytic asexual and sexual Plasmodium falciparum parasites is of utmost importance to achieve the ambitious goal of malaria elimination. Here, we report the validation of naphthylisoquinoline (NIQ) alkaloids and their synthetic analogues as multistage active antimalarial drug candidates. A total of 30 compounds were tested, of which 17 exhibited IC50 values <1 µM against drug-sensitive P. falciparum parasites (NF54 strain); 15 of these retained activity against a panel of drug-resistant strains. These compounds showed low in vitro cytotoxicity against HepG2 cells, with selectivity indices of >10. The tested compounds showed activity in vitro against both early- and late-stage P. falciparum gametocytes while blocking male gamete formation (>70% inhibition of exflagellation at 2 µM). Additionally, five selected compounds were found to have good solubility (≥170 µM in PBS at pH 6.5), while metabolic stability towards human, mouse, and rat microsomes ranged from >90% to >7% after 30 min. Dioncophylline C (2a) emerged as a front runner from the study, displaying activity against both asexual parasites and gametocytes, a lack of cross-resistance to chloroquine, good solubility, and microsomal stability. Overall, this is the first report on the multistage activity of NIQs and their synthetic analogues including gametocytocidal and gametocidal effects induced by this class of compounds.

Lapatinib, Nilotinib and Lomitapide Inhibit Haemozoin Formation in Malaria Parasites.

With the continued loss of antimalarials to resistance, drug repositioning may have a role in maximising efficiency and accelerating the discovery of new antimalarial drugs. Bayesian statistics was previously used as a tool to virtually screen USFDA approved drugs for predicted ß-haematin (synthetic haemozoin) inhibition and in vitro antimalarial activity. Here, we report the experimental evaluation of nine of the highest ranked drugs, confirming the accuracy of the model by showing an overall 93% hit rate. Lapatinib, nilotinib, and lomitapide showed the best activity for inhibition of ß-haematin formation and parasite growth and were found to inhibit haemozoin formation in the parasite, providing mechanistic insights into their mode of antimalarial action. We then screened the USFDA approved drugs for binding to the ß-haematin crystal, applying a docking method in order to evaluate its performance. The docking method correctly identified imatinib, lapatinib, nilotinib, and lomitapide. Experimental evaluation of 22 of the highest ranked purchasable drugs showed a 24% hit rate. Lapatinib and nilotinib were chosen as templates for shape and electrostatic similarity screening for lead hopping using the in-stock ChemDiv compound catalogue. The actives were novel structures worthy of future investigation. This study presents a comparison of different in silico methods to identify new haemozoin-inhibiting chemotherapeutic alternatives for malaria that proved to be useful in different ways when taking into consideration their strengths and limitations.