3,792 research outputs found

    A switch from high-fat to normal diet does not restore sperm quality but prevents metabolic syndrome

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    In recent decades, the prevalence of metabolic diseases has concomitantly increased with a decline on fertility rates and sperm quality. High-fat diets (HFD) are seldom considered part of the problem, but the molecular mechanisms underlying its effects on male fertility remain poorly understood. Herein we postulated that HFD alter sperm quality. We evaluated the effects of switching from a HFD to a normal diet in early adulthood on metabolic disease onset, testicular metabolism and sperm quality. Thirty-six male C57BL6/J mice were divided in: a control group fed with standard chow; a group fed with HFD for 200 days; and a group fed with HFD for 60 days and then with standard chow (HFDt). Biometric data and whole-body metabolism were assessed. Epididymal sperm was studied for concentration, motility, viability and morphology. 1H-NMR metabolomics approach was performed on testicular extracts to trace the metabolic changes. Diet switch reduced body weight and fat mass, preventing metabolic syndrome onset. However, sperm viability, motility and morphology were deteriorated by HFD consumption and not restored by diet switch. HFD induced irreversible changes in pyruvate and glutamate metabolism, ethanol degradation and ammonia recycling in testis. Furthermore, HFDt changed purine and cysteine metabolism, urea cycle, and glutathione content. Overall, HFD caused irreversible changes in testicular metabolism even after switching to normal diet. HFD feeding until early adulthood decreases sperm quality, which cannot be restored by diet switch or weight loss, even when development of metabolic syndrome is avoided

    In vitro and in vivo performance of methacrylated gellan gum hydrogel formulations for cartilage repair

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    Methacrylated gellan gum (GGMA) formulation is proposed as a second‐generation hydrogel for controlled delivery of cartilage‐forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof‐of‐concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non‐treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non‐treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno‐free biomaterial to be used with chondrogenic cells for a cost‐effective treatment of focal chondral lesions

    Visceral Adipose Tissue Bioenergetics Varies According to Individuals' Obesity Class

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    Obesity is associated with complex adipose tissue energy metabolism remodeling. Whether AT metabolic reprogramming differs according to body mass index (BMI) and across different obesity classes is unknown. This study's purpose was to evaluate and compare bioenergetics and energy substrate preference of visceral adipose tissue (VAT) pertaining to individuals with obesity class 2 and class 3. VAT obtained from patients with obesity (n = 15) class 2 (n = 7; BMI 37.53 +/- 0.58 kg/m(2)) or class 3 (n = 8; BMI 47.79 +/- 1.52 kg/m(2)) was used to assess oxygen consumption rate (OCR) bioenergetics and mitochondrial substrate preferences. VAT of patients with obesity class 3 presented significantly higher non-mitochondrial oxygen consumption (p < 0.05). In VAT of patients with obesity class 2, inhibition of pyruvate and glutamine metabolism significantly decreased maximal respiration and spare respiratory capacity (p < 0.05), while pyruvate and fatty acid metabolism inhibition, which renders glutamine the only available substrate, increased the proton leak with a protective role against oxidative stress (p < 0.05). In conclusion, VAT bioenergetics of patients with obesity class 2 depicts a greater dependence on glucose/pyruvate and glutamine metabolism, suggesting that patients within this BMI range are more likely to be responsive to interventions based on energetic substrate modulation for obesity treatment

    Diet during early life defines testicular lipid content and sperm quality in adulthood

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    Childhood obesity is a serious concern associated with ill health later in life. Emerging data suggest that obesity has long-term adverse effects upon male sexual and reproductive health but few studies addressed this issue. We hypothesized that exposure to high-fat diet during early life alters testicular lipid content and metabolism leading to permanent damage to sperm parameters. After weaning (day 21 after birth), 36 male mice were randomly divided into 3 groups and fed with different diet regimen for 200 days: CTRL-standard chow; HFD-high-fat diet (Carbohydrate: 35.7%, Protein: 20.5%, Fat: 36.0%); HFDt-high-fat diet for 60 days then replaced by standard chow. Biometric and metabolic data were monitored. Animals were then sacrificed, and tissues collected. Epididymal sperm parameters and endocrine parameters were evaluated. Testicular metabolites were extracted and characterized by 1H-NMR and GC-MS. Testicular mitochondrial and antioxidant activity were evaluated. Our results show that mice fed with high-fat diet, even if only until early adulthood, had lower sperm viability and motility, and higher incidence of head and tail defects. Although diet reversion with weight loss during adulthood prevents the progression of metabolic syndrome, testicular content in fatty acids is irreversibly affected. Excessive fat intake promoted an over-accumulation of pro-inflammatory n-6 polyunsaturated fatty acids in testis, which are strongly correlated with negative effects upon sperm quality. Therefore, the adoption of high-fat diets during early life correlates to irreversible changes in testicular lipid content and metabolism, which are related to permanent damage to sperm quality later in life

    Mycobacterium bovis: polymerase chain reaction identification in bovine Lymphonode biopsies and genotyping in isolates from Southeast Brazil by spolygotyping and restriction fragment length polymorphism

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    Diagnosis of the Mycobacterium tuberculosis complex by direct PCR of mediastinal lymphnode DNA and microbiological tests were compared in cattle suspicious of bearing tuberculous-like lesions detected during slaughter. The PCR procedure applied on DNA samples (n=54) obtained by adding alpha -casein into the thiocyanate extraction mix was positive in 70% of the samples. PCR confirmed the identification of 23 samples (100%) that grew in culture, 9 samples (60%) that failed to grow in culture, plus 6 (37.5%) samples that resulted in growth of bacterial contaminants. Genotyping by IS6110-RFLP and DR-spoligotyping analysis of seven samples revealed the presence of several polimorphisms. Seven of the isolates contained multiple copies of IS6110, thus defining the existence of five singular genotypes.ICB Departamento de BioquĂ­mica e Imunologia LaboratĂłrio de Biologia Molecular de Produtos NaturaisUniversidade Federal de Minas Gerais ICB Escola de VeterinĂĄriaUniversidade Federal de Minas Gerais ICB Departamento de FarmacologiaEscola Paulista de Medicina Departamento de Microbiologia e ParasitologiaLaboratĂłrio Central do Estado do EspĂ­rito SantoInstituto BiolĂłgico de SĂŁo PauloCentro de InvestigaciĂłn en Ciencias Veterinarias Instituto de BiotecnologiaUNIFESP, EPM, Depto. de Microbiologia e ParasitologiaSciEL

    The VMC survey – XXXIX: Mapping metallicity trends in the Small Magellanic Cloud using near-infrared passbands

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    We have derived high spatial resolution metallicity maps covering ∌42 deg2 across the Small Magellanic Cloud (SMC) in an attempt to understand its metallicity distribution and gradients up to a radius of ∌ 4○. Using the near-infrared VISTA Survey of the Magellanic Clouds, our data cover a thrice larger area compared with previous studies. We identify red giant branch (RGB) stars in spatially distinct Y, (Y − Ks) colour–magnitude diagrams. In any of our selected subregions, the RGB slope is used as an indicator of the average metallicity, based on calibration to metallicity using spectroscopic data. The metallicity distribution across the SMC is unimodal and can be fitted by a Gaussian distribution with a peak at [Fe/H] = −0.97 dex (σ[Fe/H] = 0.05 dex). We find evidence of a shallow gradient in metallicity (−0.031 ± 0.005 dex deg−1) from the galactic centre to radii of 2○–2.5○, followed by a flat metallicity trend from ∌ 3.5○ to 4○. We find that the SMCĂąs metallicity gradient is radially asymmetric. It is flatter towards the East than to the West, hinting at mixing and/or distortion of the spatial metallicity distribution (within the inner 3○), presumably caused by tidal interactions between the Magellanic Clouds

    The Silences Framework: A Method for researching sensitive themes and marginalized health perspectives (English version)

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    Objective: To describe the experience of applying of The Silences Framework to underpin health research investigating Tuberculosis/HIV/AIDS coinfection . Method: The Silences Framework originally developed following a study exploring the decisions and silences surrounding black Caribbean men living in England, discussing the themes 'sexual health' and 'ethnicity'. Following this study a conceptual a theory for research on sensitive issues and health care of marginalized populations was developed called 'Screaming Silences' which forms the foundation of The Silences Framework. Screaming Silences define research areas and experiences that are poorly studied, little understood or silenced. Results: The Silences Framework supports researchers in revealing "silences" in the subjects they study - as such results may reflect how beliefs, values, and experiences of some groups influence their health. This framework provides the application of four complementary stages: working the silences, hearing silences, voicing silences and working with the silences. The analysis occurs cyclically and can be repeated as long as the silences inherent in a study are not revealed. Conclusion: this article presents The Silences Framework and the application of the notion of "sounds of silence", mapping an antiessentialist theoretical framework for its use in sensitive research in health and nursing areas, being a reference for other researchers in studies involving marginalized populations. KEYWORDS: Inequalities in health. Methods. Nursing. Coinfection. Research. Tuberculosis. Acquired immunodeficiency syndrome

    The VMC Survey. XXIX. Turbulence-controlled Hierarchical Star Formation in the Small Magellanic Cloud

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    In this paper we report a clustering analysis of upper main-sequence stars in the Small Magellanic Cloud, using data from the VMC survey (the VISTA near-infrared YJK s survey of the Magellanic system). Young stellar structures are identified as surface overdensities on a range of significance levels. They are found to be organized in a hierarchical pattern, such that larger structures at lower significance levels contain smaller ones at higher significance levels. They have very irregular morphologies, with a perimeter–area dimension of 1.44 ± 0.02 for their projected boundaries. They have a power-law mass–size relation, power-law size/mass distributions, and a log-normal surface density distribution. We derive a projected fractal dimension of 1.48 ± 0.03 from the mass–size relation, or of 1.4 ± 0.1 from the size distribution, reflecting significant lumpiness of the young stellar structures. These properties are remarkably similar to those of a turbulent interstellar medium, supporting a scenario of hierarchical star formation regulated by supersonic turbulence

    Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8âș T cells in human cutaneous leishmaniasis

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    Cytotoxic activity mediated by CD8+ T cells is the main signature of the immunopathogenesis of cutaneous leishmaniasis (CL). Here, we performed a broad evaluation of natural killer (NK) cell phenotypic and functional features during cutaneous leishmaniasis. We demonstrate for the first time that CL patients present the accumulation of circulating NK cells with multiple features of replicative senescence including low proliferative capacity and shorter telomeres, elevated expression of CD57, KLRG1 but diminished CD27 stimulatory receptor expression. Moreover, they exhibited higher cytotoxic and inflammatory potential than age‐matched controls. The accumulation of circulating senescent NK cells (CD56dim CD57bright) correlated positively with skin lesion size in the same patients, suggesting that they, like circulating senescent CD8+ T cells, may contribute to the immunopathology of CL. However, this senescent population had lower cutaneous lymphocyte antigen expression and so had diminished skin‐homing potential compared with total or senescent CD8+ T cells. This was confirmed in CL skin lesions where we found a predominance of CD8+ T cells (both senescent and non‐senescent) that correlated with the severity of the disease. Although there was also a correlation between the proportions of senescent NK cells (CD56+ CD57+) in the skin and lesion size, this was less evident. Collectively our results demonstrate first‐hand that senescent cytotoxic cells may mediate skin pathology during human cutaneous leishmaniasis. However, as senescent cytotoxic CD8+ T cells predominate in the skin lesions, they may have a greater role than NK cells in mediating the non‐specific skin damage in CL
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