Metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis

Psoriasis in adults is associated with an increased risk of metabolic disease. Various cardiometabolic comorbidities have been reported in childhood psoriasis, but only a few studies have analyzed the prevalence of metabolic syndrome. We performed a single-center prospective study investigating the prevalence of metabolic syndrome and insulin resistance in children with psoriasis. The prevalence of metabolic syndrome was evaluated in 60 pre-pubertal children with psoriasis (age: 3\u201310 years), accordingly to recently established criteria for the diagnosis of metabolic syndrome in children. Insulin resistance was considered altered when the homeostatic model assessment (HOMA-IR) for insulin resistance was 65 90th sex- and age-specific percentile and HOMA 2-IR was > 1.8. Eighteen (30%) children with psoriasis were found to have metabolic syndrome. Sixteen (27%) children were found to have insulin resistance. Conclusion: Our data underline the importance of assessing metabolic syndrome not only in adults and adolescents but also in young children with psoriasis.What is Known:\u2022 Psoriasis in adults is strongly associated with metabolic disease and insulin resistance.\u2022 Very limited data are available on the prevalence of metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis.What is New:\u2022 This study reports that in pre-pubertal children with psoriasis, there is a high prevalence of metabolic syndrome and insulin resistance.\u2022 In children with psoriasis metabolic syndrome risk factors should be assessed

High prevalence of radiological vertebral fractures in adult patients with Ehlers-Danlos syndrome

Previous studies have reported an increased prevalence of osteoporosis in Ehlers–Danlos syndrome (EDS), but these were limited by a small number of patients and lack of information on fragility fractures. In this cross-sectional study, we evaluated the prevalence of radiological vertebral fractures (by quantitative morphometry) and bone mineral density (BMD, at lumbar spine, total hip and femoral neck by dual-energy X-ray absorptiometry) in 52 consecutive patients with EDS (10 males, 42 females; median age 41 years, range: 21–71; 12 with EDS classic type, 37 with EDS hypermobility type, 1 with classic vascular-like EDS, and 2 without specific classification) and 197 control subjects (163 females and 34 males; median age 49 years, range: 26–83) attending an outpatient bone clinic. EDS patients were also evaluated for back pain by numeric pain rating scale (NRS-11).Vertebral fractures were significantly more prevalent in EDS as compared to the control subjects (38.5% vs. 5.1%; p < 0.001) without significant differences in BMD at either skeletal sites. In EDS patients, the prevalence of vertebral fractures was not significantly (p = 0.72) different between classic and hypermobility types. BMD was not significantly different between fractured and non-fractured EDS patients either at lumbar spine (p = 0.14), total hip (p = 0.08), or femoral neck (p = 0.21). Severe back pain (≥ 7 NRS) was more frequent in EDS patients with vertebral fractures as compared to those without fractures (60% vs. 28%; p = 0.04). In conclusion, this is the first study showing high prevalence of vertebral fractures in a relatively large population of EDS patients. Vertebral fractures were associated with more severe back pain suggesting a potential involvement of skeletal fragility in determining poor quality of life. The lack of correlation between vertebral fractures and BMD is consistent with the hypothesis that bone quality may be impaired in EDS

Vitamin d deficiency induces chronic pain and microglial phenotypic changes in mice

The bioactive form of vitamin .D, 1,25‐dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2‐ 3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β‐galactosidase (B‐gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator‐activated‐receptor‐alpha (PPAR‐α), reduced most of these effects. Morphological analysis of ex‐vivo microglia obtained from vitamin‐D‐deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D

Sex and Heart Failure with Preserved Ejection Fraction: From Pathophysiology to Clinical Studies

Heart failure with preserved ejection fraction (HFpEF) represents the most frequent form of heart failure in women, with almost two-fold higher prevalence than in men. Studies have revealed sex-specific HFpEF pathophysiology, and suggested the possibility of a sex-specific therapeutic approach in these patients. Some cardiovascular risk factors, such as arterial hypertension, obesity, diabetes mellitus, coronary artery disease, atrial fibrillation, and race, show specific features that might be responsible for the development of HFpEF in women. These risk factors are related to specific cardiovascular changes—left ventricular diastolic dysfunction and hypertrophy, ventricular–vascular coupling, and impaired functional capacity—that are related to specific cardiac phenotype and HFpEF development. However, there is no agreement regarding outcomes in women with HFpEF. For HFpEF, most studies have found higher hospitalization rates for women than for men. Mortality rates are usually not different. Pharmacological treatment in HFpEF is challenging, along with many unresolved issues and questions raised. Available data on medical therapy in patients with HFpEF show no difference in outcomes between the sexes. Further investigations are necessary to better understand the pathophysiology and mechanisms of HFpEF, as well as to improve and eventually develop sex-specific therapy for HFpEF

Endothelial cells from umbilical cord of women affected by gestational diabetes: A suitable in vitro model to study mechanisms of early vascular senescence in diabetes

Human umbilical cord endothelial cells (HUVECs) obtained from women affected by gestational diabetes (GD-HUVECs) display durable pro-atherogenic modifications and might be considered a valid in vitro model for studying chronic hyperglycemia effects on early endothelial senescence. Here, we demonstrated that GD- compared to C-HUVECs (controls) exhibited oxidative stress, altered both mitochondrial membrane potential and antioxidant response, significant increase of senescent cells characterized by a reduced NAD-dependent deacetylase sirtuin-1 (SIRT1) activity together with an increase in cyclin-dependent kinase inhibitor-2A (P16), cyclin-dependent kinase inhibitor-1 (P21), and tumor protein p53 (P53) acetylation. This was associated with the p300 activation, and its silencing significantly reduced the GD-HUVECs increased protein levels of P300 and Ac-P53 thus indicating a persistent endothelial senescence via SIRT1/P300/P53/P21 pathway. Overall, our data suggest that GD-HUVECs can represent an “endothelial hyperglycemic memory” model to investigate in vitro the early endothelium senescence in cells chronically exposed to hyperglycemia in vivo

Paleoseismic evidence of five magnitude 7 earthquakes on the Norcia fault system in the past 8,000 years (Central Italy)

Many large-magnitude faults (6.5≤ Mw ≤7.2) of the Italian Apennines are characterized by multi-century return times, so historical sources may have missed their last earthquake or other predecessors. Hence, even in Italy, where seismic catalogs are among the most comprehensive and time-extensive worldwide, there is a need for complementary studies that might fill the lack of historical information and enhance the knowledge concerning the recurrence times of destructive earthquakes. As paleoseismology is the discipline that can do this, in this study, we present results collected in five new trenches opened along the 33-km-long Norcia fault system (central Apennines) where, in addition to the historically known 1703 earthquake (Mw 6.9), we uncovered indications of four Holocene predecessor, with a recurrence time of 1,825 ± 420 years. Considering also the paleoseismic results already published on the nearby Mt Vettore fault system (2016 earthquake of Mw 6.6), we guess that now the seismic hazard of this region could be assessed more robustly

Validation of an echo-Doppler decision model to predict left ventricular filling pressure in patients with heart failure independently of ejection fraction

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Transthoracic coronary flow reserve and dobutamine derived myocardial function: a 6-month evaluation after successful coronary angioplasty

After percutaneous transluminal coronary angioplasty (PTCA), stress-echocardiography and gated single photon emission computerized tomography (g-SPECT) are usually performed but both tools have technical limitations. The present study evaluated results of PTCA of left anterior descending artery (LAD) six months after PTCA, by combining transthoracic Doppler coronary flow reserve (CFR) and color Tissue Doppler (C-TD) dobutamine stress. Six months after PTCA of LAD, 24 men, free of angiographic evidence of restenosis, underwent standard Doppler-echocardiography, transthoracic CFR of distal LAD (hyperemic to basal diastolic coronary flow ratio) and C-TD at rest and during dobutamine stress to quantify myocardial systolic (S(m)) and diastolic (E(m )and A(m), E(m)/A(m )ratio) peak velocities in middle posterior septum. Patients with myocardial infarction, coronary stenosis of non-LAD territory and heart failure were excluded. According to dipyridamole g-SPECT, 13 patients had normal perfusion and 11 with perfusion defects. The 2 groups were comparable for age, wall motion score index (WMSI) and C-TD at rest. However, patients with perfusion defects had lower CFR (2.11 ± 0.4 versus 2.87 ± 0.6, p < 0.002) and septal S(m )at high-dose dobutamine (p < 0.01), with higher WMSI (p < 0.05) and stress-echo positivity of LAD territory in 5/11 patients. In the overall population, CFR was related negatively to high-dobutamine WMSI (r = -0.50, p < 0.01) and positively to high-dobutamine S(m )of middle septum (r = 0.55, p < 0.005). In conclusion, even in absence of epicardial coronary restenosis, stress perfusion imaging reflects a physiologic impairment in coronary microcirculation function whose magnitude is associated with the degree of regional functional impairment detectable by C-TD