Strength and muscle mass development after a resistance-training period at terrestrial and normobaric intermittent hypoxia.

This study investigated the effect of a resistance training (RT) period at terrestrial (HH) and normobaric hypoxia (NH) on both muscle hypertrophy and maximal strength development with respect to the same training in normoxia (N). Thirty-three strength-trained males were assigned to N (FiO2 = 20.9%), HH (2,320 m asl) or NH (FiO2 = 15.9%). The participants completed an 8-week RT program (3 sessions/week) of a full body routine. Muscle thickness of the lower limb and 1RM in back squat were assessed before and after the training program. Blood markers of stress, inflammation (IL-6) and muscle growth (% active mTOR, myostatin and miRNA-206) were measured before and after the first and last session of the program. Findings revealed all groups improved 1RM, though this was most enhanced by RT in NH (p = 0.026). According to the moderate to large excess of the exercise-induced stress response (lactate and Ca2+) in HH and N, results only displayed increases in muscle thickness in these two conditions over NH (ES > 1.22). Compared with the rest of the environmental conditions, small to large increments in % active mTOR were only found in HH, and IL-6, myostatin and miR-206 in NH throughout the training period. In conclusion, the results do not support the expected additional benefit of RT under hypoxia compared to N on muscle growth, although it seems to favour gains in strength. The greater muscle growth achieved in HH over NH confirms the impact of the type of hypoxia on the outcomes.

Trapping Microparticles in a Structured Dark Focus.

We experimentally demonstrate stable trapping and controlled manipulation of silica microspheres in a structured optical beam consisting of a dark focus surrounded by light in all directions-the dark focus tweezer. Results from power spectrum and potential analysis demonstrate the nonharmonicity of the trapping potential landscape, which is reconstructed from experimental data in agreement to Lorentz-Mie numerical simulations. Applications of the dark tweezer in levitated optomechanics and biophysics are discussed.

Influence of breed and parasite challenge on the immune response to naturally acquired intestinal nematode infection in sheep.

Natural infection by intestinal nematodes was assessed in Santa Ines and Ile de France sheep breeds, over a five-month grazing period, with emphasis on the development of the immune response in lambs under two anthelmintic treatment regimens. Nineteen Santa Ines and 19 Ile de France male lambs were allocated into two treatment groups: animals under suppressive treatment with anthelmintics; and animals under targeted selective treatment (TST). The nematodes Trichostrongylus colubriformis and Strongyloides papillosus showed the highest infection intensity in the TST animals in both breeds. Parasite-specific immunoglobulin G levels were significantly higher and more rapidly induced in Santa Ines lambs. Additionally, these lambs had higher levels of parasite-specific immunoglobulin A in intestinal mucus. Animals under TST had higher means of mast cells and globule leukocytes in the intestinal mucosa due to longer and greater parasite challenge in comparison with the suppressive group. A breed effect (P < 0.05) was recorded for mast cells, with Santa Ines lambs presenting the highest counts. Although Santa Ines lambs had lower intestinal nematode counts than Ile de France lambs, they had shown a large variation in T. colubriformis burden, with most of them presenting a marked worm burden, despite showing an earlier and more intense immune response to intestinal nematode infection.

Asc-Seurat: analytical single-cell Seurat-based web application.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of transcriptomes, arising as a powerful tool for discovering and characterizing cell types and their developmental trajectories. However, scRNA-seq analysis is complex, requiring a continuous, iterative process to refine the data and uncover relevant biological information. A diversity of tools has been developed to address the multiple aspects of scRNA-seq data analysis. However, an easy-to-use web application capable of conducting all critical steps of scRNA-seq data analysis is still lacking. We present Asc-Seurat, a feature-rich workbench, providing an user-friendly and easy-to-install web application encapsulating tools for an all-encompassing and fluid scRNA-seq data analysis. Asc-Seurat implements functions from the Seurat package for quality control, clustering, and genes differential expression. In addition, Asc-Seurat provides a pseudotime module containing dozens of models for the trajectory inference and a functional annotation module that allows recovering gene annotation and detecting gene ontology enriched terms. We showcase Asc-Seurat's capabilities by analyzing a peripheral blood mononuclear cell dataset. CONCLUSIONS: Asc-Seurat is a comprehensive workbench providing an accessible graphical interface for scRNA-seq analysis by biologists. Asc-Seurat significantly reduces the time and effort required to analyze and interpret the information in scRNA-seq datasets.

Exploring Ubiquinone Biosynthesis Inhibition as a Strategy for Improving Atovaquone Efficacy in Malaria.

Atovaquone (AV) acts on the malaria parasite by competing with ubiquinol (UQH2) for its union to the mitochondrial bc1 complex, preventing the ubiquinone-8 and ubiquinone-9 (UQ-8 and UQ-9) redox recycling, which is a necessary step in pyrimidine biosynthesis. This study focused on UQ biosynthesis in Plasmodium falciparum and adopted proof-of-concept research to better elucidate the mechanism of action of AV and improve its efficacy. Initially, UQ biosynthesis was evaluated using several radioactive precursors and chromatographic techniques. This methodology was suitable for studying the biosynthesis of both UQ homologs and its redox state. Additionally, the composition of UQ was investigated in parasites cultivated at different oxygen saturations or in the presence of AV. AV affected the redox states of both UQ-8 and UQ-9 homologs by increasing the levels of the respective reduced forms. Conversely, low-oxygen environments specifically inhibited UQ-9 biosynthesis and increased the antimalarial efficacy of AV. These findings encouraged us to investigate the biological importance and the potential of UQ biosynthesis as a drug target based on its inhibition by 4-nitrobenzoate (4-NB), a 4-hydroxybenzoate (4-HB) analog. 4-NB effectively inhibits UQ biosynthesis and enhances the effects of AV on parasitic growth and respiration rate. Although 4-NB itself exhibits poor antimalarial activity, its 50% inhibitory concentration (IC50) value increased significantly in the presence of a soluble UQ analog, p-aminobenzoic acid (pABA), or 4-HB. These results indicate the potential of AV combined with 4-NB as a novel therapy for malaria and other diseases caused by AV-sensitive pathogens.

Neurocognitive evaluation using the International HIV Dementia Scale (IHDS) and Montreal Cognitive Assessment Test (MoCA) in an HIV-2 population.

OBJECTIVES: We aimed to characterize neurocognitive impairment (NI) in an HIV-2 population using an observational cross-sectional study in four Portuguese hospitals. METHODS: Adult HIV-2-infected patients were included. Montreal Cognitive Assessment Test (MoCA) and International HIV Dementia Scale (IHDS) scales were applied for screening of NI. Patient Health Questionnaire-9 (PHQ-9) and Instrumental Activities of Daily Living (IADL) scales were used for assessment of depression and functionality. A multivariate analysis was performed to assess for risk factors for NI. RESULTS: Eighty-one patients were included, 50.6% of African origin (n = 41) and 49.4% of Portuguese origin (n = 40). The MoCA scale showed alterations in 81.5% of patients (100% of migrants vs. 62.5% of non-migrants, P < 0.001) and the IHDS scale showed alterations in 42%. Both scales were altered simultaneously in 35.8%. Variables independently associated with NI were age [odds ratio (OR) = 0.885] and migrant status (OR = 9.150). CONCLUSIONS: Neurocognitive impairment (both scales altered) was present in 35.8%, which is comparable to what is described for HIV-1. The MoCA performed worse in the migrant population and might not be applicable in this setting.

Tooth survival following root canal treatment by general dental practitioners in a Swedish county - a 10-year follow-up study of a historical cohort.

AIM: To evaluate the 10-year survival rate of root filled teeth treated by general dental practitioners (GDPs), and to identify possible prognostic factors. METHODOLOGY: In 2006, 3676 individuals had at least one tooth root filled by a GDP within the Norrbotten Public Dental Service, Sweden. Over the next 10 years, 331 individuals died and were excluded. A random sample of 302 of the remaining individuals was included in the study, of whom 280 (n = 280 teeth) were included in the analysis. Dental records were reviewed retrospectively by a calibrated researcher to collect predetermined data regarding individual, pre-operative, intra-operative and post-operative factors. The outcome measure was tooth extraction over time, and cases with no events were censored, regardless of apical status or symptoms, until last known date of tooth survival. In case of missing data, individuals were recalled for a control visit. Kaplan-Meier survival tables and Cox regression models were used for analysis. P < 0.05 was considered statistically significant. RESULTS: The cumulative 10-year survival was 81.7% (standard error: 2.6%), and the mean incidence of tooth extraction during the 10 years was 1.8% per year. The univariate analysis identified three possible prognostic factors (P < 0.05) that were associated with extraction: molars, two or more emergency inter-appointment visits during the treatment, and root canal treatments consisting of five or more separate sessions. A multivariate regression analysis revealed no significant relationships for the variables gender, tooth type, number of contacts, any emergency visits during endodontic treatment, number of sessions to complete endodontic treatment, pulp diagnosis, or type of permanent restoration and extraction. CONCLUSIONS: The mean incidence of tooth loss over the first 10 years after completion of root canal treatment performed by a GDP was approximately 2% per year. No prognostic factors could be identified.

A subpopulation of human Adark spermatogonia behaves as the reserve stem cell.

Human spermatogonial stem cells (SSCs) are an essential source to maintain spermatogenesis as an efficient process for daily sperm production with high self-renewal capacity along adulthood. However, the phenotype and the subpopulation that represent the real reserve SSC for the human testis remain unknown. Moreover, although SSC markers have been described for undifferentiated spermatogonia (Adark and Apale), the existence of a specific subtype that could be identified as the actual/true SSC has not yet been fully determined. Herein we evaluated spermatogonial morphology, kinetics, positioning regarding blood vasculature in relation to protein expression (UTF1, GFRA1, and KIT) as well as proliferative activity (MCM7) and identified a small subpopulation of Adark with nuclear rarefaction zone (AdVac) that behaves as the human reserve SSC. We show that AdVac is the smallest human spermatogonial population (10%), staying quiescent (89%) and positioned close to blood vessels throughout most of the stages of the seminiferous epithelium cycle (SEC) and divides only at stages I and II. Within this AdVac population, we found a smaller pool (2% of A undifferentiated spermatogonia) of entirely quiescent cells exhibiting a high expression of UTF1 and lacking GFRA1. This finding suggests them as the real human reserve SSC (AdVac UTF1+/GFRA1-/MCM7-). Additionally, Adark without nuclear vacuole (AdNoVac) and Apale have similar kinetic and high proliferative capacity throughout the SEC (47%), indicating that they are actively dividing undifferentiated spermatogonia. Identification of human stem cells with evident reserve SSC functionality may help further studies intending to sort SSCs to treat male diseases and infertility.

Spermatogonial asynchrony in Tex14 mutant mice lacking intercellular bridges.

The existence of cytoplasmic passages between germ cells and their potential function in the control of the spermatogenic process has long been an intriguing question. Evidence of the important role of such structures, known as intercellular bridges (ICB), in spermatogenesis has been implicated by the failure of spermatogenesis in testis-expressed gene 14 (Tex14) mutant mice, which lack the ICBs, to progress past the pachytene spermatocyte stage. Using these Tex14 mutants, the present study evaluated, for the first time, the behavior and synchrony of the spermatogonial lineage in the absence of ICBs. Our data suggest that the absence of these cytoplasmic connections between cells affects the expansion of the undifferentiated type A (Aundiff) spermatogonia compartment and their transition to A1, resulting in a significant numerical reduction of differentiating A1 spermatogonia, but did not interfere with cell amplification during subsequent mitotic steps of differentiating spermatogonia from A1 through intermediate (In). However, beginning at the type B spermatogonia, the synchrony of differentiation was impaired as some cells showed delayed differentiation compared to their behavior in a normal seminiferous epithelium cycle. Thus although spermatogonial development is able to proceed, in the absence of ICBs in Tex14-/- mutants, the yield of cells, specific steps of differentiation, the synchrony of the cell kinetics, and the subsequent progression in meiosis are quantitatively lower than normal.

Could land cover influence Aedes aegypti mosquito populations?

Aedes aegypti is mainly found in urban environments, where human activity guarantees the permanent availability of potential larval habitats. The present study aimed to test for a possible association between Ae. aegypti infestation and land cover classes. From 23 February to 22 May 2015, immature mosquitoes (except eggs) were sampled in artificial containers identified in dwellings in Córdoba city, Argentina. The proportion of each land cover class was determined by SPOT-5 (Satellites Pour 1'Observation de la Terre or Earth-observing Satellites) image classification. Generalized linear models were developed to assess a suite of predetermined hypotheses and identified cover class variables associated with Ae. aegypti infestation. Arboreal vegetation was identified as the land cover with the greatest relative importance, negatively associated with Ae. aegypti mosquitoes. More infestation was find in areas with less arboreal vegetation, which corresponds to more urbanized areas.

Eosinophilic dermatosis of hematologic malignancy: a case report.

Eosinophilic dermatosis of hematologic malignancy (EDHM) is a dermatosis characterized by tissue eosinophilia that has been previously reported as insect bite-like reaction. It is a rare condition with a wide variety of clinical presentations ranging from papules, nodules, or blisters that simulate arthropod bites, to the formation of plaques of differing sizes. We report a case of eosinophilic dermatosis of hematologic malignancy in a patient with a hematoproliferative disorder.

Is the inferior occlusal plane a reliable anatomic landmark for inferior alveolar nerve block? A study on dry mandibles of Brazilian adults.

PURPOSE: To investigate the relationship between the mandibular foramen (MF) and the inferior occlusal plane (IOP) of anatomic specimens, in order to guide clinicians in the inferior alveolar nerve block (IANB). METHOD: Eighty-two dry mandibles (totally or partially toothed) of Brazilian adults were selected, totalizing 66 left and 66 right antimeres. A flat plate of rigid PVC plastic was placed on the occlusal surfaces of posterior teeth and pressure was then manually applied to simulate the IOP. Following, the perpendicular distance from the IOP to the lowest point of the MF was measured by the use of a digital caliper, adopting negative values inferiorly and positive values superiorly. RESULTS: Regarding the antimeres, the majority of the lowest limits of the MF was below the IOP (right: 86.4%, left: 81.8%) with a mean of -4.2mm (±4.8) in the right and -4.1mm (±4.8) in the left ones, without any statistical significance. Considering both sexes, no statistically significant difference was obtained between them. CONCLUSION: The IOP seems not to be a good anatomical landmark to localize the MF and, its turn, to guide clinicians during the IANB for Brazilian adults, given the marked topographic variations.

'Seeing is believing': a qualitative approach to studying the use of cone beam computed tomography in endodontics in Sweden.

AIM: To gain insight into the decision processes of dentists when requesting a cone beam computed tomography (CBCT) examination in endodontic settings. METHODOLOGY: Fourteen dentists (eight female) 33-58 years of age (mean = 44) practising in Sweden were interviewed. Ten of the dentists were specialists in Endodontics. The absolute inclusion criterion was experience of referring patients for CBCT for endodontic reasons. The included dentists comprised a strategically selected diverse sample in terms of gender, age, work experience, educational background, location of practice, service affiliation and accessibility to CBCT. Data were obtained through semistructured interviews exposing the context of their last three self-reported referrals. Dentists were encouraged to describe their experiences of the circumstances in their own words, aided by the interviewer's open-ended questions. The interviews were audio-recorded and transcribed verbatim. The text was analysed by qualitative content analysis. RESULTS: The manifest content was organized into three categories that were defined as visualization as a desire, facilitating tough decisions and allocating responsibility. CONCLUSION: An overall theme (covering the latent content) was identified: A balance between clinical common sense and a 'better safe than sorry' attitude guides the use of CBCT in endodontic settings. Informants had high clinical standards, knowledge concerning radiation risks and good sense, which could compensate for their lack of knowledge of guidelines. The national radiation regulatory system was perceived to work as a slightly porous gatekeeper for over-usage.

Spermatogonial behavior in marmoset: a new generation, their kinetics and niche.

STUDY QUESTION: Could a more detailed evaluation of marmoset spermatogonial morphology, kinetics and niches using high-resolution light microscopy (HRLM) lead to new findings? SUMMARY ANSWER: Three subtypes of marmoset undifferentiated spermatogonia, which were not evenly distributed in terms of number and position along the basal membrane, and an extra premeiotic cell division not present in humans were identified using HRLM. WHAT IS KNOWN ALREADY: The seminiferous epithelium cycle (SEC) of marmosets is divided into nine stages when based on the acrosome system, and several spermatogenic stages can usually be recognized within the same tubular cross-section. Three spermatogonial generations have been previously described in marmosets: types Adark, Apale and B spermatogonia. STUDY DESIGN, SIZE, DURATION: Testes from five adult Callithrix penicillata were fixed by glutaraldehyde perfusion via the cardiac route and embedded in Araldite plastic resin for HRLM evaluation. Semi-thin sections (1 µm) were analyzed morphologically and morphometrically to evaluate spermatogonial morphology and kinetics (number, mitosis and apoptosis), spermatogenesis efficiency and the spermatogonial niche. PARTICIPANTS/MATERIALS, SETTING, METHODS: Shape and nuclear diameter, the presence and distribution of heterochromatin, the granularity of the euchromatin, as well as the number, morphology and degree of nucleolar compaction were observed for morphological characterization. Kinetics analyses were performed for all spermatogonial subtypes and preleptotene spermatocytes, and their mitosis and apoptosis indexes determined across all SEC stages. Spermatogenesis parameters (mitotic, meiotic, Sertoli cell workload and general spermatogenesis efficiency) were determined through the counting of Adark and Apale spermatogonia, preleptotene and pachytene primary spermatocytes, round spermatids, and Sertoli cells at stage IV of the SEC. MAIN RESULTS AND THE ROLE OF CHANCE: This is the first time that a study in marmosets demonstrates: the existence of a new spermatogonial generation (B2); the presence of two subtypes of Adark spermatogonia with (AdVac) and without (AdNoVac) nuclear rarefaction zones; the peculiar behavior of AdVac spermatogonia across the stages of the SEC, suggesting that they are quiescent stem spermatogonia; and that AdVac spermatogonia are located close to areas in which blood vessels, Leydig cells and macrophages are concentrated, suggesting a niche area for these cells. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: The C. penicillata spermatogonial kinetics evaluated here consider spermatogonial number across the SEC and their mitotic and apoptotic figures identified in HRLM sections. Therefore, caution is required when comparing absolute values between species. Although morphometric evaluation has suggested that AdVac spermatogonia are stem cells, a functional proof of this is still missing. It is known that parameters of the spermatogenic process in C. penicillata have similarities with those of the common marmoset C. jacchus, however, a detailed study of spermatogonial morphology, kinetics and niche has not yet been performed in C. jacchus, and a full comparison of the two species is not possible. WIDER IMPLICATIONS OF THE FINDINGS: Our findings in C. penicillata contribute to a better understanding of the spermatogonial behavior and spermatogenesis efficiency in non-human primates. Given the phylogenetic closeness of the marmoset to the human species, similar processes might occur in humans. Therefore, marmosets may be an excellent model for studies regarding human testicular biology, fertility and related disorders. STUDY FUNDING/COMPETING INTEREST(S): Experiments were partially supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq). The authors declare that there are no conflicts of interest.

Modelling the distribution of the vector Aedes aegypti in a central Argentine city.

Aedes aegypti (Diptera: Culicidae) is an urban mosquito involved in the transmission of numerous viruses, including dengue, chikungunya and Zika. In Argentina, Ae. aegypti is the main vector of dengue virus and has been involved in several outbreaks in regions ranging from northern to central Argentina since 2009. In order to evaluate areas of potential vector-borne disease transmission in the city of Córdoba, Argentina, the present study aimed to identify the environmental, socioeconomic and demographic factors driving the distribution of Ae. aegypti larvae through spatial analysis in the form of species distribution models (SDMs). These models elucidate relationships between known occurrences of a species and environmental data in order to identify areas with suitable habitats for that species and the consequent risk for disease transmission. The maximum entropy species distribution model was able to fit the training data well, with an average area under the receiver operating characteristic curve (AUC) of > 0.8, and produced models with fair extrapolation capacity (average test AUC: > 0.75). Human population density, distance to vegetation and water channels were the main variables predictive of the vector suitability of an area. The results of this work will be used to target surveillance and prevention measures, as well as in mosquito management.

Spectral refractive index technique for monitoring the beer mashing process.

During beer production, the mashing process is fundamental for extraction of the main sugars from the starch. The quantification of these fermentable sugars during the process provides a measure of the alcoholic content of the final beer. Therefore, monitoring of the sugar composition during beer production is very important for obtaining a quality product. This paper demonstrates the potential of white light interferometry (WLI) for monitoring the extraction of sugars in different mashing processes, by observing the refractive index of the mixture. All the mashings presented linear increases of the refractive index during the temperature steps, which were influenced by the concentrations of sugars produced in each step. Cauchy parameters obtained by refractive index interpretation showed the influence of carbohydrates on absorption in the infrared region, and amino acids on absorption in the ultraviolet region. Strong correlation was obtained between the refractive index and °Bx values, indicating that the WLI technique is a potential analytical method for monitoring the mashing process during beer production.

The role of interleukins in vitiligo: a systematic review.

Vitiligo is a disorder of the skin that causes depigmentation and asymptomatic macules whose exact cause is still unclear. Although its aetiology is not fully elucidated, the main theory of its pathomechanism is that it is associated with the autoimmune process. There is few summarized information about the role of inflammatory mediators, as interleukins, in vitiligo, so our aim was to present a systematic review of the role of interleukins in vitiligo, focusing on interleukins. In this review, we included all studies assessing interleukin levels in vitiligo patients conducted up to June 2017. Quality assessment of these studies was performed using the Newcastle-Ottawa Scale (NOS). The interleukins mainly involved were IL-2, IL-4, IL-6, IL-10 and IL-17. The studies highlight the crucial role of IL-17 in the onset and progression of the disease, and its synergistic action with IL-2, IL-6 and IL-33. Dysregulated levels of the interleukins were also correlated with the stage of disease, the affected skin surface area, and indicated as the main factor for lymphocyte infiltration found in depigmented regions. These findings illustrate the growing need for new therapies targeting vitiligo and further research into the role of interleukins as an area of particular interest.

Digital Image Analysis to Estimate the Minimum Number of Eurytrema Coelomaticum Eggs in the Uterus of Adult Specimens.

This study was carried out to estimate the minimal number of eggs present in adult E. coelomaticum uterus. Samples were collected during post-mortem inspection and were submitted to light microscopy (bright field). The length, width, the total area of the parasite, uterus, and eggs were measured. The ImageJ software was used to calculate the area of the different parameters analyzed in this study. It was possible to observe that the uterus corresponds on average to 51.9 % of the total area of the parasite (ranging from 45 to 64 %). The number of eggs present in the uterus of parasites ranged from 5,946 to 15,813. To estimate the number of eggs three scenarios were considered, where the first taken into account the number of whole eggs observed in the image. In the second way to estimate the number of eggs, all the structures were considered (whole eggs and fractions that could be delimited) and compared with manual counting. Finally, in the last scenario, was considered an occupancy rate of 100 % of the uterine area per eggs, since there are overlapping eggs and these cannot be correctly delimited and accounted for. This study describes an important tool for quantifying eggs in a nondestructive manner and aggregate information until then is not explained by other works.