Transcription Factor 4 (TCF4) has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathological TCF4 mutations affect the human neural tissue is poorly ...understood. Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations in TCF4. We show that neural progenitors bearing these mutations have reduced proliferation and impaired capacity to differentiate into neurons. We identify a mechanism through which TCF4 loss-of-function leads to decreased Wnt signaling and then to diminished expression of SOX genes, culminating in reduced progenitor proliferation in vitro. Moreover, we show reduced cortical neuron content and impaired electrical activity in the patient-derived organoids, phenotypes that were rescued after correction of TCF4 expression or by pharmacological modulation of Wnt signaling. This work delineates pathological mechanisms in neural cells harboring TCF4 mutations and provides a potential target for therapeutic strategies for genetic disorders associated with this gene.
Abstract Scorpionic accidents are a major public health problem due to the high occurrence with potential seriousness. In this manner, the research aimed to analyze the occurrence of scorpionic ...accidents in a municipality in the northeastern of Brazil. An exploratory, descriptive study was made, with a quantitative approach, using secondary data which was gotten from the Notifiable Diseases Information System (SINAN), from 2008 to 2018. Data such as neighborhood, presence of street markets were also used, and the existence of sanitation and climatic data such as temperature and season. Geoprocessing was used to identify possible changes in the environment. In the analyzed period, 9,330 cases of scorpion accidents were recorded, with an average of 848 annual notifications. Scorpionic accidents occurred more frequently in women (5,686; 60.94%). Individuals aged 20 to 29 years (1.727; 18.51%) were more frequent to scorpion stings. Regarding the body parts where the stings were made, the highlights were on the foot (3.515; 37.67%) followed by the hand (2.818; 30.20%). No statistically significant relation was observed between climatic factors and scorpionic accidents. However, the high number of cases of scorpionic accidents was observed in the last 11 years studied. It was evident that during the study period there was no statistical relationship when climatic factors were correlated to scorpionic accidents. On its turn, when it was verified the results of the geoprocessing analysis, it was seen that anthropic factors have been motivating the potentiation of the occurrence of these accidents.
Resumo Os acidentes escorpiônicos apresentam-se como um grande problema de saúde pública em virtude da grande ocorrência com potencial gravidade. Nesse sentido, o trabalho teve como objetivo analisar a ocorrência de acidentes escorpiônicos em um município do nordeste brasileiro. Foi realizado um estudo descritivo, de caráter exploratório, com abordagem quantitativa em que foram utilizados dados secundários obtidos no Sistema de Informação de Agravos de Notificação (SINAN), no período de 2008 a 2018. Também foram utilizados dados como bairro, presença de feiras livres e a existência de saneamento básico e dados climáticos como temperatura e estação do ano. O geoprocessamento foi utilizado para identificar as possíveis alterações no ambiente. No período analisado, foram registrados 9,330 casos de acidentes com escorpião, com média de 848 notificações anuais. Os acidentes escorpiônicos ocorreram com mais frequência em mulheres (5,686; 60,94%). Em indivíduos na faixa etária de 20 a 29 anos (1,727; 18,51%) foram mais frequentes a picada de escorpião. Com relação ao local das picadas destacaram-se o pé (3,515; 37,67%), seguido da mão (2,818; 30,20%). Não foi observada relação estatisticamente significativa entre os fatores clímáticos e os acidentes escorpiônicos. Foi observado elevado número de casos de acidentes escorpiônicos nos últimos 11 anos estudados. Ficou evidente que durante o período de estudo não existiu relação estatística quando se correlacionou fatores climáticos aos acidentes escorpiônicos. Por sua vez, ao verificar os resultados da análise de geoprocessamento foi visto que fatores antrópicos têm sido motivadores da potencialização da ocorrência desses acidentes.
Summary
Assessing the reliability of medical measurements is a crucial step towards the elaboration of an applicable clinical instrument. There are few studies that evaluate the reliability of ...somatosensory assessment and pain modulation of masticatory structures. This study estimated the test–retest reliability, that is over time, of the mechanical somatosensory assessment of anterior temporalis, masseter and temporomandibular joint (TMJ) and the conditioned pain modulation (CPM) using the anterior temporalis as the test site. Twenty healthy women were evaluated in two sessions (1 week apart) by the same examiner. Mechanical detection threshold (MDT), mechanical pain threshold (MPT), wind‐up ratio (WUR) and pressure pain threshold (PPT) were assessed on the skin overlying the anterior temporalis, masseter and TMJ of the dominant side. CPM was tested by comparing PPT before and during the hand immersion in a hot water bath. anova and intra‐class correlation coefficients (ICCs) were applied to the data (α = 5%). The overall ICCs showed acceptable values for the test–retest reliability of mechanical somatosensory assessment of masticatory structures. The ICC values of 75% of all quantitative sensory measurements were considered fair to excellent (fair = 8·4%, good = 33·3% and excellent = 33·3%). However, the CPM paradigm presented poor reliability (ICC = 0·25). The mechanical somatosensory assessment of the masticatory structures, but not the proposed CPM protocol, can be considered sufficiently reliable over time to evaluate the trigeminal sensory function.
The cerebellar floccular and parafloccular lobes are housed in fossae of the periotic region of the skull of different vertebrates. Experimental evidence indicates that the lobes integrate visual and ...vestibular information and control the vestibulo-ocular reflex, vestibulo-collic reflex, smooth pursuit and gaze holding. Multiple paleoneuroanatomy studies have deduced the behaviour of fossil vertebrates by measuring the floccular fossae (FF). These studies assumed that there are correlations between FF volume and behaviour. However, these assumptions have not been fully tested. Here, we used micro-CT scans of extant mammals (47 species) and birds (59 species) to test six possible morphological-functional associations between FF volume and ecological/behavioural traits of extant animals. Behaviour and ecology do not explain FF volume variability in four out of six variables tested. Two variables with significant results require further empirical testing. Cerebellum plasticity may explain the lack of statistical evidence for the hypotheses tested. Therefore, variation in FF volume seems to be better explained by a combination of factors such as anatomical and phylogenetic evolutionary constraints, and further empirical testing is required.
Recent studies have shown that conventional meshes comprising pure titanium and its alloys can be used to assist the recovery of bone fractures in various parts of the human body, such as the face, ...jaw, skull and knee. In anticipation of an improved efficiency for these applications and other applications, this work analyses the thermomechanical behaviour of a type of metallic mesh that is fabricated with NiTi shape memory alloys (SMAs), which are smart metals that exhibit functional properties, such as the shape memory effect (SME) and superelasticity (SE). The development of NiTi SMA meshes with different cell designs, good mechanical strength and recoverable deformation to replace titanium meshes and enhance biomedical applications (as well as applications in other fields) can be considered a current technological challenge. In this framework, this study aims to perform the fabrication and mechanical characterization of NiTi SMA meshes produced by investment casting with three different cell geometries (circular, hexagonal and square) in two states (as cast and heat treated). The obtained results show that the manufactured meshes present functional properties even in the as-cast state, as thermoelastic phase transformation and deformation recovery on the order of 6% is demonstrated. The results show that between the heat treatment and mesh cell geometry, the latter factor is the most influential factor in the mechanical behaviour of the meshes. A brief numerical simulation of the tensile behaviour of the meshes is used to deepen the analysis of the influence of cell geometry on their mechanical behaviour. Overall, as-cast meshes with circular and square cells present a high stiffness under tension and bending. The produced meshes show enough thermomechanical features to enhance biomedical applications. These results support the replacement of conventional titanium alloys, which do not possess functional properties, with NiTi SMAs.
Summary
Lipid bodies (LBs) are intracellular accumulations of neutral lipids surrounded by a single membrane. These organelles are involved in the production of eicosanoids, which modulate immunity ...by either promoting or dampening inflammatory responses. Leishmania infantum, the etiological agent of visceral leishmaniasis in Brazil, is an intracellular parasite that causes disease by suppressing macrophage microbicidal responses. C57BL/6 mouse bone marrow‐derived macrophages infected with L. infantum strain LcJ had higher numbers of LB+ cells (P<.0001) and total LBs than noninfected cultures. Large (>3 μm) LBs were present inside parasitophorous vacuoles (PVs). These results contrast with those of L. infantum‐infected BALB/c macrophages, in which the only LBs are derived from parasite, not macrophage origin. Increased LBs in C57BL/6 macrophages in close association with parasites would position host LBs where they could modulate L. infantum infection. These results imply a potential influence of the host genetics on the role of LBs in host‐pathogen interactions. Overall, our data support a model in which the expression, and the role of LBs upon infection, ultimately depends on the specific combination of host‐pathogen interactions.
Continental-scale assessments of 21st century global impacts of climate change on biodiversity have forecasted range contractions for many species. These coarse resolution studies are, however, of ...limited relevance for projecting risks to biodiversity in mountain systems, where pronounced microclimatic variation could allow species to persist locally, and are ill-suited for assessment of species-specific threat in particular regions. Here, we assess the impacts of climate change on 2632 plant species across all major European mountain ranges, using high-resolution (ca. 100 m) species samples and data expressing four future climate scenarios. Projected habitat loss is greater for species distributed at higher elevations; depending on the climate scenario, we find 36-55% of alpine species, 31-51% of subalpine species and 19-46% of montane species lose more than 80% of their suitable habitat by 2070-2100. While our high-resolution analyses consistently indicate marked levels of threat to cold-adapted mountain florae across Europe, they also reveal unequal distribution of this threat across the various mountain ranges. Impacts on florae from regions projected to undergo increased warming accompanied by decreased precipitation, such as the Pyrenees and the Eastern Austrian Alps, will likely be greater than on florae in regions where the increase in temperature is less pronounced and rainfall increases concomitantly, such as in the Norwegian Scandes and the Scottish Highlands. This suggests that change in precipitation, not only warming, plays an important role in determining the potential impacts of climate change on vegetation.
Abstract Urinary tract infections are responsible for most human infections, these are caused by bacteria, fungi, protozoa and associated microorganisms. The goal of this study was to determine the ...rate of vaginal infection-causing agents in routine cytological exams and also to evaluate the characteristics of positive tested Pap smears. A retrospective documental with descriptive aspect research was performed in a Clinical Pathology laboratory from Maceió-AL. The results of the Pap smears exams for Trichomonas vaginalis, Gardnerella vaginalis, Candida spp and HPV were arranged in a database as well as other data such as bacterial, protozoan, fungal and viral coinfections. The sample was composed by 18.645 women who have undergone Pap smear exams from 2013 to 2017. Of these analyzed exams, 27.4% in 2013, 10.9% in 2014, 10.6% in 2015, 15.2% in 2016 and 13.67% in 2017 were within normal range, however more than half of these exams presented some infections caused by unspecific or microbiological agents. By analyzing all the reports, 4.073 (21.84%) presented inflammations caused by some species of infectious agent with the following rate order: G. vaginalis and T. vaginalis. Furthermore, it was possible to confirm high rates of coinfection by and Candida spp. The rate of genital infections in this study highlights that there is a public health matter that must be controlled, which points a greater need for monitoring, guidance and actions towards greater awareness in order to prevent these problems.
Resumo Infecções do trato urinário são responsáveis pela maior parte das infecções humanas, sendo causadas por bactérias, fungos, protozoários, e por microrganismos associados. O objetivo deste trabalho foi determinar a frequência de agentes causadores de infecções vaginais nos exames citológicos de rotina, bem como avaliar as características dos esfregaços positivos. Foi realizada uma pesquisa do tipo documental retrospectiva de aspecto descritivo, com abordagem quantitativa, em um Laboratório de Patologia Clínica de Maceió-AL. Nesse sentido, os resultados dos exames colpocitológicos para Trichomonas vaginalis, Gardnerella vaginalis, Candida spp e HPV foram organizados em um banco de dados, contendo os resultados para estes agentes, bem como a coinfecção bacteriana, protozoária, fúngica e viral. A amostra foi composta por 18.645 mulheres que realizaram exame colpocitológico, no período de 2013 a 2017. Destes exames analisados 27,4% em 2013, 10,9% em 2014, 10,6% em 2015, 15,2% em 2016 e 13,67% em 2017, estavam dentro do limite da normalidade, porém mais que a metade desses exames analisados apresentou algumas infecções causadas por agentes inespecíficos ou microbiológicos. Do total de laudos analisados, 4.073 (21,84%), apresentaram inflamações causadas por algum tipo de agente infeccioso, com a seguinte ordem de frequência: G. vaginalis, e T. vaginalis. Além disto, foi possível confirmar a elevada frequência de coinfecção entre G. vaginalis e Candida spp. Os índices de infecções genitais nesse trabalho mostram que há um problema de saúde pública que deve ser controlado, apontando uma necessidade maior de acompanhamento, orientações e de ações para uma maior conscientização para prevenir esses problemas.
Osmotic stress induced by high solute concentration can prevent fungal metabolism and growth due to alterations in properties of the cytosol, changes in turgor, and the energy required to synthesize ...and retain compatible solutes. We used germination to quantify tolerance/sensitivity to the osmolyte KCl (0.1–4.5 M, in 0.1 M increments) for 71 strains (40 species) of ecologically diverse fungi. These include 11 saprotrophic species (17 strains, including two xerophilic species), five mycoparasitic species (five strains), six plant-pathogenic species (13 strains), and 19 entomopathogenic species (36 strains). A dendrogram obtained from cluster analyses, based on KCl inhibitory concentrations 50 % and 90 % calculated by Probit Analysis, revealed three groups of fungal isolates accordingly to their osmotolerance. The most-osmotolerant group (Group 3) contained the majority of saprotrophic fungi, and Aspergillus niger (F19) was the most tolerant. The highly xerophilic Aspergillus montevidense and Aspergillus pseudoglaucus were the second- and third-most tolerant species, respectively. All Aspergillus and Cladosporium species belonged to Group 3, followed by the entomopathogens Colletotrichum fioriniae, Simplicillium lanosoniveum, and Trichothecium roseum. Group 2 exhibited a moderate osmotolerance, and included plant-pathogens such as Colletotrichum and Fusarium, mycoparasites such as Clonostachys spp, some saprotrophs such as Mucor and Penicillium spp., and some entomopathogens such as Isaria, Lecanicillium, Mariannaea, Simplicillium, and Torrubiella. Group 1 contained the osmo-sensitive strains: the rest of the entomopathogens and the mycoparasitic Gliocladium and Trichoderma. Although stress tolerance did not correlate with their primary ecological niche, classification of these 71 fungal strains was more closely aligned with their ecology than with their phylogenetic relatedness. We discuss the implications for both microbial ecology and fungal taxonomy.
The mutual effects of water content and carbon black nanoparticle (CBN) concentration on the electrical resistivity and self-sensing properties of mortars are reported in this paper. Previous works ...have focused on moisture effects in CBN-based composites whose conductivity mainly came from direct contact between nanofillers. This study found very distinct behaviors when the CBN concentration was within the percolation zone. Mortars containing different moisture and CBN contents were subjected to direct current (DC) measurements, biphasic DC, and piezoresistivity tests. Effects of water content on the intrinsic capacitance of CBN-based composites were reported. A deep investigation within the percolation zone allowed the design of a promising CBN-based composite whose resistivity and sensing properties are minimally dependent on the water content, because the effects on ionic conduction due to the elimination of pore water were compensated by the effects on contacting conduction due to the elimination of water films on CBN surface. Keywords: capacitive behavior; carbon black nanoparticles; electrical resistivity; piezoresistivity; smart cement-based composites; structural health monitoring; water content.
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