387 research outputs found

    Diabetes Causes Bone Marrow Autonomic Neuropathy and Impairs Stem Cell Mobilization via Dysregulated p66Shc and Sirt1

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    Diabetes compromises the bone marrow (BM) microenvironment and reduces circulating CD34 + cells. Diabetic autonomic neuropathy (DAN) may impact the BM, because the sympathetic nervous system (SNS) is prominently involved in BM stem cell trafficking. We hypothesize that neuropathy of the BM affects stem cell mobilization and vascular recovery after ischemia in diabetes. We report that, in patients, cardiovascular DAN was associated with fewer circulating CD34 + cells. Experimental diabetes (STZ and Ob/Ob ) or chemical sympathectomy in mice resulted in BM autonomic neuropathy, impaired Lin - cKit + Sca1 + (LKS) cell and endothelial progenitor cells (EPC, CD34 + Flk1 + ) mobilization and vascular recovery after ischemia. DAN increased expression of p66Shc and reduced expression of Sirt1 in mice and humans. p66Shc KO in diabetic mice prevented DAN in the BM, and rescued defective LKS cell and EPC mobilization. Hematopoietic Sirt1 KO mimicked the diabetic mobilization defect, while hematopoietic Sirt1 overexpression in diabetes rescued defective mobilization and vascular repair. Through p66Shc and Sirt1 , diabetes and sympathectomy elevated the expression of various adhesion molecules, including CD62L . CD62L KO partially rescued the defective stem/progenitor cell mobilization. In conclusion, autonomic neuropathy in the BM impairs stem cell mobilization in diabetes with dysregulation of the lifespan regulators p66Shc and Sirt1

    Maternal Parenting Practices and Psychosocial Adjustment of Primary School Children

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    This study was aimed at evaluating the associations between maternal parenting practices (positive, negative/inconsistent, and punitive), children’s difficulties (such as conduct problems, emotional symptoms, peer problems, and hyperactivity), and prosocial behaviors. Participants were 131 Italian mothers of primary school children; mothers were aged between 26 and 52 years (M = 38.38, SD = 5.46); children (54% girls) were aged between 6 and 10 years (M = 7.15, SD = 0.98). Mothers completed two scales assessing their parenting practices and their children’s psychosocial adjustment. A path analysis was run to test the hypothesized model. The results showed the following: (a) maternal positive parenting was negatively and significantly related to children’s conduct problems and hyperactivity, and positively and significantly to children’s prosocial behavior; (b) maternal negative/inconsistent parenting was positively and significantly related to children’s conduct problems, emotional symptoms, and hyperactivity; (c) maternal punitive parenting was positively and significantly related to children’s conduct problems and emotional symptoms. Moreover, the results showed that, according to the mothers’ perceptions, boys tended to exhibit higher levels of hyperactivity and peer problems and lower levels of prosocial behaviors than girls. Overall, this study highlights the unique role of different maternal parenting practices in the psychosocial adjustment of primary school children

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    Abstract:  Objective: to assess the adjusted Global Antiphospholipid Syndrome Score (aGAPSS) instrument to estimate the risk of vascular thrombosis in primary antiphospholipid syndrome (pAPS). A retrospective study was done between 2013-2020, including patients with pAPS by Sydney criteria. The presence of arterial and venous thrombosis (tAPS), obstetrical comorbidity (oAPS), non-criteria manifestations (NCM), antiphospholipid antibodies (APLA), recurrent thrombosis and mortality were evaluated. Patients were grouped in tAPS, oAPS or both; the last one was used when the stratification was done. In the first visit, aGAPSS was calculated by adding: arterial hypertension: 1, hyperlipidemia: 3, moderate-high titles of anti-cardiolipin antibody (aCL): 5, anti-β2glicoprotein I (aB2GPI): 4 and lupus anticoagulant (LA): 4. aGAPSS ≥ 10 was considered high. Results: 85 patients entered the study, 74,11% completed the follow-up. 87,1% were women, mean age was 36 years (32,75-40,25), illness of 53 months (25-114). 62,35% had oAPS, 24,5% tAPS and 12,94% both. There were 18 arterial thrombosis, 11 venous thrombosis and 3 in both sites. Patients with tAPS had longer illness (p=0,04), higher rates of aB2GP1 (p=<0,001) and triple positivity (p=0,0003). The mean aGAPSS was 9 (5-12); in tAPS the mean value was 9 (8,75-13) and in oAPS 9 (5-9); p=0,008. There was no difference between patients with criteria manifestations and NCM. New trombosis (12,69%) happened in tAPS; the mean time was 26 months (15-49). There were 4 arterial thrombosis, 2 venous thrombosis and 2 in both sites. The mean aGAPSS in patients with recurrence was 13 (9-13), 62,50% had aGAPSS ≥ 10; and 87% had MNC. 4 (6,34%) patients died, all of them with recurrent thrombosis. aGAPSS ≥ 10 predicted new thrombosis (p=0,016). Patients with recurrence had a worse survival curve (p= 0,00000). Conclusion: assessing the risk of thrombosis in APS with aGAPSS could identify individuals at high risk of recurrence, monitor them, and intervene to prevent future events.Resumen:  Objetivo: valorar el instrumento Global Antiphospholipid Sydrome Score ajustado (aGAPSS) para estimar riesgo de trombosis vascular en SAF primario (SAFP). Se realizó un estudio retrospectivo incluyendo pacientes con SAFP (criterios de Sydney) entre 2013 y 2020 de Hospital Materno-neonatal y Córdoba. Se analizaron: trombosis venosa y arterial (SAFT), morbilidad obstétrica (SAFO), manifestaciones no criterio (MNC), anticuerpos antifosfolípidos (AAF), recurrencia de trombosis y mortalidad. Se agruparon en SAFT, SAFO o ambas; el último grupo se utilizó para estratificación del riesgo. En visita basal calculamos aGAPPS sumando: HTA: 1, dislipemia: 3, anticuerpos anticardiolipinas (ACA) IgM/IgG títulos moderados-altos: 5, anticuerpos antibeta2glicoproteína I (ABGPI): 4 y anticoagulante lúpico (AL): 4. Se consideró aGAPSS alto  ≥ 10. Las variables continuas se expresaron como mediana y rango intercuartil; las categóricas como frecuencia y porcentaje. Se utilizó el test de Fisher para variables categóricas y test de Wilcoxon para variables mensurables. p < 0,05 fueron significativos. Aprobado por CIEIS del Adulto. Resultados: Ingresaron 85 pacientes, 74,11% completaron seguimiento. 87,1% mujeres, mediana de edad 36 años (32,75-40,25). 62,35% presentaban SAFO, 24,5% SAFT y 12,94% ambas. Presentaron 18 trombosis arteriales, 11 venosas y 3 en ambos sitios. Pacientes con SAFT tuvieron mayor duración de enfermedad (p=0,04), mayores tasas de ABGP1 (p=<0,001) y triple positividad (p=0,0003). La mediana del aGAPSS fue de 9 (5-12). En SAFT la mediana fue 9 (8,75-13) y en SAFO 9 (5-9); p=0,008. No hubo diferencia entre pacientes con manifestaciones criterio vs MNC. Las nuevas trombosis 12,69% ocurrieron en SAFT; la mediana del tiempo fue 26 meses (15-49). 4 fueron arteriales, 2 venosas y 2 ambas. La mediana de aGAPSS en pacientes con recurrencia fue 13 (9-13), 62,50% con GAPSS ≥ 10; y 87% presentaron MNC. 4 (6,34 %) pacientes fallecieron, todos con retrombosis. aGAPSS ≥ 10 predijo nuevas trombosis (p=0,016). Los pacientes con retrombosis tuvieron peor curva de sobrevida (p= 0,00000). Conclusión: La valoración del riesgo de trombosis en SAF con aGAPSS permitiría identificar individuos con alto riesgo de recurrencia, monitorizarlos e intervenir para prevenir futuros eventos.

    Polineuropatía desmielinizante inflamatoria crónica como forma de presentación de lupus eritematoso sistémico

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    Se describe el caso de una mujer de 35 años que presenta polineuropatía desmielinizante inflamatoria crónica como compromiso neurológico en su diagnóstico inicial de lupus eritematoso sistémico (LES). Si bien el compromiso neurológico es de una prevalencia variable en lupus, la asociación que se describe no es frecuente y tiene importantes connotaciones en el tratamiento

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    Abstract:  Introduction: Psoriatic Arthritis (PsA) is associated with increased risk of Obesity, Insulin Resistance, Metabolic Syndrome (MetS), Arterial Hypertension (AHT), Dyslipidemia, and Cardiovascular Disease compared to the general population.  The lipid profile in these patients has been studied for a long time, however, the results on this association remain controversial.  Objectives: To study the frequency of altered lipid profiles in patients with Psoriatic arthritis (PsA) and its association with disease activity.   Methods: We studied all the patients diagnosed with PsA who consecutively attended to Rheumatology Unit at Cordoba Hospital from July 2018 to December 2019. Psa was diagnosed according to CASPAR criteria.  Clinical, and laboratory data were collected. The activity of the disease was evaluated by PASI, MDA and DAPSA. p < 0.05 was considered statistically significant.  Results: 42 PsA patients were included. Mean age was 56 years old (47,25-62,75) and 54.76% were female (n=23). 92.86% (n =39) of the patients had plaque Psoriasis. The predominant joint involvement was peripheral and polyarticular (87.8%), the median time since diagnosis was 17 months (12-89). Seventy-six percent were receiving methotrexate and 40% biologics. Disease activity measured by DAPSA was predominantly moderate in 17 patients. The median laboratory values found: total cholesterol 194.5 mg/dl (164.8-218.2), triglycerides 139.50 mg/dl (89.25-191.20) and ApoB/ApoA ratio 0.63 (0.42-0.81). Fifty-seven percent of the patients had an altered lipid profile, with hypertriglyceridemia being the most frequent (48%). There was no correlation between Apo B/Apo A Ratio with DAPSA (rho=0.013; p=0.9396) nor with MDA (rho=-0.029; p=0.8671). Conclusion: In spite of the presence of cardiovascular factors in the majority of PsA patients, lipid profile is not associated with disease activity in this population. However, the presence of hypertriglyceridemia was a characteristic finding in these patients.Resumen:  Introducción: La Artritis Psoriásica (APS) se asocia con mayor riesgo de Obesidad, Insulinorresistencia, Síndrome Metabólico (SMet), Hipertensión arterial (HTA),  Dislipemia y Enfermedad Cardiovascular comparado con la población general.  El perfil lipídico en estos pacientes ha sido estudiado durante mucho tiempo, sin embargo, los resultados sobre esta asociación permanecen controversiales.  Objetivo: Evaluar la frecuencia de alteraciones del perfil lipídico en pacientes con APS, y su posible asociación con la actividad de la enfermedad.  Materiales y métodos: Estudio transversal, realizado en una clínica de Espondiloartritis. Se incluyeron pacientes con APS según criterios de CASPAR, evaluados consecutivamente desde Julio a Diciembre del 2019. Se analizaron características demográficas, comorbilidades. Las variables analizadas fueron tratamiento, tiempo evolutivo, compromiso articular, talla, peso, perímetro abdominal e índice de masa corporal (IMC), actividad de la enfermedad por PASI, MDA y DAPSA. Se recolectaron muestras sanguíneas con ayunas de 12 horas para análisis químicos.  Variables cuantitativas expresadas en mediana y 1er y 3er intercuartil; variables cualitativas expresadas en frecuencia y porcentaje. RESULTADOS: 42 pacientes fueron evaluados, con una mediana de edad de 56 años (47,25-62,75), 23 mujeres (54,76%). 39 (92,86%) presentaban Psoriasis en placa. El compromiso articular predominante fue periférico y poliarticular (87,8%), la mediana desde el diagnóstico fue de 17 meses (12-89). El 76% recibían Metotrexato y el 40% biológicos. La comorbilidad más frecuente hallada fue SMet en 64,3%, seguido de obesidad 52,8%.La actividad de la enfermedad medida por DAPSA fue predominantemente moderada en 17 pacientes. Las medianas de valores de laboratorio hallados: colesterol total 194,5 mg/dl (164,8-218,2) , triglicéridos 139,50 mg/dl (89,25-191,20) y cociente ApoB/ApoA 0,63 (0,42-0,81). Un 57% de los pacientes tenían perfil lipídico alterado, siendo la hipertrigliceridemia la más frecuente (48%). No hubo correlación entre el Cociente Apo B/Apo A con DAPSA (rho=0,013; p=0.9396) ni con MDA (rho=-0,029; p=0.8671). Conclusiones: En esta cohorte no se encontró  relación entre el perfil lipídico y la actividad de la Artritis Psoriásica. Sin embargo, la hipertrigliceridemia fue un hallazgo característico de estos pacientes.

    Quantifying n -Photon Indistinguishability with a Cyclic Integrated Interferometer

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    We report on a universal method to measure the genuine indistinguishability of n photons - a crucial parameter that determines the accuracy of optical quantum computing. Our approach relies on a low-depth cyclic multiport interferometer with N=2n modes, leading to a quantum interference fringe whose visibility is a direct measurement of the genuine n-photon indistinguishability. We experimentally demonstrate this technique for an eight-mode integrated interferometer fabricated using femtosecond laser micromachining and four photons from a quantum dot single-photon source. We measure a four-photon indistinguishability up to 0.81±0.03. This value decreases as we intentionally alter the photon pairwise indistinguishability. The low-depth and low-loss multiport interferometer design provides an original path to evaluate the genuine indistinguishability of resource states of increasing photon number

    The Peritoneum as a Natural Scaffold for Vascular Regeneration

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    Objective: The peritoneum has the same developmental origin as blood vessels, is highly reactive and poorly thrombogenic. We hypothesize that parietal peritoneum can sustain development and regeneration of new vessels. Methods and Results: The study comprised two experimental approaches. First, to test surgical feasibility and efficacy of the peritoneal vascular autograft, we set up an autologous transplantation procedure in pigs, where a tubularized parietal peritoneal graft was covered with a metal mesh and anastomosed end-to-end in the infrarenal aorta. Second, to dissect the contribution of graft vs host cells to the newly developed vessel wall, we performed human-to-rat peritoneal patch grafting in the abdominal aorta and examined the origin of endothelial and smooth muscle cells. In pig experiments, the graft remodeled to an apparently normal blood vessel, without thrombosis. Histology confirmed arterialization of the graft with complete endothelial coverage and neointimal hyperplasia in the absence of erosion, inflammation or thrombosis. In rats, immunostaining for human mitochondri revealed that endothelial cells and smooth muscle cells rarely were of human origin. Remodeling of the graft was mainly attributable to local cells with no clear evidence of c-kit+ endothelial progenitor cells or c-kit+ resident perivascular progenitor cells. Conclusions: The parietal peritoneum can be feasibly used as a scaffold to sustain the regeneration of blood vessels, whic

    The Redox Enzyme p66Shc Contributes to Diabetes and Ischemia-Induced Delay in Cutaneous Wound Healing

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    OBJECTIVE: The redox enzyme p66Shc produces hydrogen peroxide and triggers proapoptotic signals. Genetic deletion of p66Shc prolongs life span and protects against oxidative stress. In the present study, we evaluated the role of p66Shc in an animal model of diabetic wound healing. RESEARCH DESIGN AND METHODS: Skin wounds were created in wild-type (WT) and p66Shc(-/-) control and streptozotocin-induced diabetic mice with or without hind limb ischemia. Wounds were assessed for collagen content, thickness and vascularity of granulation tissue, apoptosis, reepithelialization, and expression of c-myc and beta-catenin. Response to hind limb ischemia was also evaluated. RESULTS: Diabetes delayed wound healing in WT mice with reduced granulation tissue thickness and vascularity, increased apoptosis, epithelial expression of c-myc, and nuclear localization of beta-catenin. These nonhealing features were worsened by hind limb ischemia. Diabetes induced p66Shc expression and activation; wound healing was significantly faster in p66Shc(-/-) than in WT diabetic mice, with or without hind limb ischemia, at 1 and 3 months of diabetes duration and in both SV129 and C57BL/6 genetic backgrounds. Deletion of p66Shc reversed nonhealing features, with increased collagen content and granulation tissue thickness, and reduced apoptosis and expression of c-myc and beta-catenin. p66Shc deletion improved response to hind limb ischemia in diabetic mice in terms of tissue damage, capillary density, and perfusion. Migration of p66Shc(-/-) dermal fibroblasts in vitro was significantly faster than WT fibroblasts under both high glucose and hypoxia. CONCLUSIONS: p66Shc is involved in the delayed wound-healing process in the setting of diabetes and ischemia. Thus, p66Shc may represent a potential therapeutic target against this disabling diabetes complication
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