Neurotoxic effects of androgens in spinal and bulbar muscular atrophy.

AbstractExpansion of polyglutamine tracts in nine different genes causes selective neuronal degeneration through unknown mechanisms. Expansion of polyglutamine in the androgen receptor is responsible for spinal and bulbar muscular atrophy (SBMA), a neuromuscular disorder characterized by the loss of lower motor neurons in the brainstem and spinal cord. A unique feature of SBMA in the family of polyglutamine diseases is sex specificity. SBMA fully manifests only in males. SBMA is a disease triggered by the binding of polyglutamine androgen receptor to its natural ligand testosterone. Recent evidence has emerged showing that the expanded polyglutamine tract itself is not the only determinant of disease pathogenesis. There is evidence that both the native structure and function of the disease protein strongly influence the pathogenicity of mutant protein. Here, we review recent progress in the understanding of disease pathogenesis and advancements towards development of potential therapeutic strategies for SBMA

Corneal Pachymetry and Endothelial Microscopy by Slit-Lamp

A slit-lamp biomicroscope Visionix VX75 has been equipped with a high-resolution digital sensor. A specular reflection technique at an angular magnification of 36× performed by the slit-lamp biomicroscope is used to develop a procedure to (i) measure the thickness of the human cornea by measuring the distance between the two reflections of its anterior and posterior surfaces and (ii) capture suitable images for morphometric analyses of the corneal endothelium’s cell mosaic. The examples of morphometric analysis of these images are reported. The biases due to the dioptric power of the anterior surface of the cornea, the oblique observation, and the asymmetry of the digital biomicroscope are discussed. These biases can be corrected by a specific calibration

Use of uteroglobin for the engineering of polyvalent, polyspecific fusion proteins

We report a novel strategy to engineer and express stable and soluble human recombinant polyvalent/polyspecific fusion proteins. The procedure is based on the use of a central skeleton of uteroglobin, a small and very soluble covalently linked homodimeric protein that is very resistant to proteolytic enzymes and to pH variations. Using a human recombinant antibody (scFv) specific for the angiogenesis marker domain B of fibronectin, interleukin 2, and an scFv able to neutralize tumor necrosis factor-α, we expressed various biologically active uteroglobin fusion proteins. The results demonstrate the possibility to generate monospecific divalent and tetravalent antibodies, immunocytokines, and dual specificity tetravalent antibodies. Furthermore, compared with similar fusion proteins in which uteroglobin was not used, the use of uteroglobin improved properties of solubility and stability. Indeed, in the reported cases it was possible to vacuum dry and reconstitute the proteins without any aggregation or loss in protein and biological activity

Endoscopic management of gastric, duodenal and rectal NETs: Position paper from the Italian Association for Neuroendocrine Tumors (Itanet), Italian Society of Gastroenterology (SIGE), Italian Society of Digestive Endoscopy (SIED)

The present paper reflects the position of the Italian Association for Neuroendocrine Tumors (Itanet), the Italian Society of Gastroenterology (SIGE), and the Italian Society of Digestive Endoscopy (SIED) regarding the management of patients affected by gastric, duodenal, and rectal neuroendocrine neoplasms (NENs) amenable to endoscopic treatment. The key questions discussed in this paper are summarized in Table 1. Data were extracted from the MEDLINE database through searches; expert opinions and recommendations are provided in accordance with the available scientific evidence and the authors' expertise. Recommendations are presented alongside a level of evidence and grade of recommendation based on the GRADE system. This paper specifically focuses on subgroups of NENs considered suitable for endoscopic management according to current international guidelines: i. well-differentiated gastric neuroendocrine tumors (gNET) type 1 < 2 cm and selected cases of type 3; ii. well-differentiated duodenal, non-functioning, non-ampullary NET with size < 2 cm; and well-differentiated rectal NET with size < 2 cm

Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes

The predominant mechanism by which adipose mesenchymal stem cells (AMSCs) participate to tissue repair is through a paracrine activity and their communication with the inflammatory microenvironment is essential part of this process. This hypothesis has been strengthened by the recent discovery that stem cells release not only soluble factors but also extracellular vesicles, which elicit similar biological activity to the stem cells themselves. We demonstrated that the treatment with inflammatory cytokines increases the immunosuppressive and anti-inflammatory potential of AMSCs-derived exosomes, which acquire the ability to shift macrophages from M1 to M2 phenotype by shuttling miRNA regulating macrophages polarization. This suggests that the immunomodulatory properties of AMSCs-derived exosomes may be not constitutive, but are instead induced by the inflammatory microenvironment

The sustainable transformation of the Colombian cattle sector: Assessing its circularity

Circular food systems are increasingly acknowledged for their potential to contribute to the transition towards sustainable futures. In a circular food system, the use of finite and limited resources is minimized, and nutrients in residual streams and inedible biomass for humans are reused as inputs in the bioeconomy. Livestock has become relevant in this narrative for upcycling nutrients contained in food by-products and grass resources into nutritious food for humans without using human-edible resources. Evaluating on-going national sustainability initiatives in the livestock sector is key to determine if circularity elements are already represented and to identify new opportunities and pathways for the future. In this paper we synthetize the environmental actions promoted by different initiatives driving the sustainable transformation of Colombian cattle production systems and assess the inclusion of circularity elements in these actions. The proposed environmental actions were concentrated in the conservation of remaining natural ecosystems, zero-deforestation and the sustainable intensification of cattle production through silvopastoral and paddock rotational systems. Circularity was addressed by some initiatives via the use organic fertilizers and the use of manure as fertilizers or feedstock for bioenergy generation. However, given that cattle farming is often practiced in low-input systems where the collection of by-products for reutilization (e.g., manure) is not always feasible, these actions are expected to have limited impact in the sector. Silvopastoral systems can positively promote circularity by creating the conditions for internal nutrient recycling via litterfall, biological nitrogen fixation, phosphorus solubilization, and presence of beneficial insects. However, to avoid food-feed competition and to remain circular, these should only be installed in agricultural areas unsuitable for crop production. In areas where crops can grow, other production systems that prioritize the production of plant biomass for human consumption (i.e., agrosilvopastoral systems, mixed crop-livestock systems or forms of crop intercropping) should be considered

Divergent Effects of Cyclophilin-D Inhibition on the Female Rat Heart: Acute Versus Chronic Post-Myocardial Infarction

Background/Aims: The mitochondrial permeability transition pore opening plays a critical role in the pathogenesis of myocardial infarction. Inhibition of cyclophilin-D (CyP-D), a key regulator of the mitochondrial permeability transition pore, has been shown to exert cardioprotective effects against ischemia-reperfusion injury on various animal models, mostly in males. However, failure of recent clinical trials requires a detailed elucidation of the cardioprotective efficacy of CyP-D inhibition. The aim of this study was to examine whether cardioprotective effects of sanglifehrin A, a potent inhibitor of CyP-D, on post-infarcted hearts depends on reperfusion. Methods: Acute or chronic myocardial infarction was induced by coronary artery ligation with/without subsequent reperfusion for 2 and 28 days in female Sprague-Dawley rats. Cardiac function was estimated by echocardiography. Oxygen consumption rates, ROS production, permeability transition pore opening, protein carbonylation and respiratory supercomplexes were analyzed in isolated cardiac mitochondria. Results: Sanglifehrin A significantly improved cardiac function of reperfused hearts at 2 days but failed to protect after 28 days. No protection was observed in non-reperfused post-infarcted hearts. The respiratory control index of mitochondria was significantly reduced in reperfused infarcted hearts at 2-days with no effect at 28-days post-infarction on reperfused and non-reperfused hearts. Likewise, only a minor increase in reactive oxygen species production was observed at 2-days in non-reperfused post-infarcted hearts. Conclusion: This study demonstrates that CyP-D inhibition exerts cardioprotective effects in reperfused but not in non-reperfused infarcted hearts of female rats, and the effects are observed only during acute post-infarction injury

The vulnerable coronary plaque: update on imaging technologies.?

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Estudio de seroprevalencia en personal de salud: Relación de la vacunación con la presencia de infección previa por SARS-COV-2 en el contexto de la campaña nacional de vacunación para coronavirus luego de la primer dosis Gam-COVID-VAc (Sputnik-V)

In the context of the vaccination campaign for health personnel at high risk of exposure to SARS-COV-2 with the Sputnik-V vaccine, a study of seroprevalence of antibodies is proposed through the lateral flow test (Test of IgM and IgG antibodies of lateral flow type. COVID19 IgG / IgM Rapid Test from Orient Gene Biotech) in individuals who have or have not received the Sputnik-V vaccine. During the months of January to March 2021 in all health personnel who voluntarily give their consent, after at least 21 days after the first dose of the vaccine and in personnel who have not been vaccinated, the detection will be carried out qualitative antibody test with the lateral flow test (COVID19 IgG / IgM Rapid Test from Orient Gene Biotech), also recording previous RT-PCR, previous serology with IgG with a similar method, vaccination and seroconversion attributable to the first vaccination dose. Episodes of new infection will also be recorded in the period from 7 days after vaccination and during the follow-up period. The main objective of this work is to detect the prevalence of antibodies to SARS-COV-2 in health personnel with high exposure after the first dose of the Sputnik-V vaccine, as well as in unvaccinated personnel and its relationship with a previous confirmed infection for SARS -COV-2.En el contexto de la campaña de vacunación del personal de salud con alto riesgo de exposición para SARS-COV-2 con la vacuna Sputnik 5, se plantea la realización de un estudio de seroprevalencia de anticuerpos a través del test de flujo lateral (Test de anticuerpos IgM e IgG de tipo flujo lateral. COVID19 IgG/IgM Rapid Test from Orient Gene Biotech) en individuos que haya o no recibido la vacuna Sputnik 5. Durante los meses de Enero a Marzo del 2021 en todo el personal de salud que preste en forma voluntaria su consentimiento, luego de al menos 21 días luego de la primera dosis de la vacuna y en personal que no haya sido vacunado, se realizará la detección cualitativa de anticuerpos con el test de flujo lateral (COVID19 IgG/IgM Rapid Test from Orient Gene Biotech) consignándose además PCR-RT previa, serología previa con IgG con método similar, vacunación y seroconversión atribuible a la primera dosis de vacunación. También se consignará episodios de infección nueva en el período que va desde 7 días luego de la vacunación y durante el período de seguimiento.  El objetivo principal de este trabajo es detectar la prevalencia de anticuerpos para SARS-COV-2 en personal de salud de alta exposición luego de la primera dosis de la vacuna Sputnik 5 además en personal no vacunado y su relación con infección previa confirmada para SARS-COV-2