Impact of Blood Pressure Variability on Cardiac and Cerebrovascular Complications in Hypertension

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Exposure to novel coronavirus in patients on renal replacement therapy during the exponential phase of COVID-19 pandemic: survey of the Italian Society of Nephrology

Background: Between February and April 2020, Italy experienced an overwhelming growth of the COVID-19 pandemic. Little is known, at the country level, where and how patients on renal replacement therapy (RRT) have been mostly affected. Methods: Survey of the network of Nephrology centers using a simplified 17 items electronic questionnaire designed by Italian Society of Nephrology COVID-19 Research Group. We used spatial epidemiology and geographical information systems to map SARS-CoV-2 spread among RRT patients in Italy. Results: On April 9th 2020, all nephrology centers (n = 454) listed in the DialMap database were invited to complete the electronic questionnaire. Within 11 days on average, 365 centers responded (80.4% response rate; 2.3% margin of error) totaling 60,441 RRT patients. The surveyed RRT population included 30,821 hemodialysis (HD), 4139 peritoneal dialysis (PD), and 25,481 transplanted (Tx) patients respectively. The proportion of SARS-CoV-2 positive RRT patients in Italy was 2.26% (95% CI 2.14\u20132.39) with significant differences according to treatment modality (p < 0.001). The proportion of patients positive for SARS-CoV-2 was significantly higher in HD (3.55% [95% CI 3.34\u20133.76]) than PD (1.38% [95% CI 1.04\u20131.78] and Tx (0.86% [95% CI 0.75\u20130.98]) (p < 0.001), with substantial heterogeneity across regions and along the latitude gradient (p < 0.001). In RRT patients the highest rate was in the north-west (4.39% [95% CI 4.11\u20134.68], followed by the north-east (IR 2.06% [1.79\u20132.36]), the center (0.91% [0.75\u20131.09]), the main islands (0.67% [0.47\u20130.93]), and the south (0.59% [0.45\u20130.75]. During the COVID-19 pandemic, among SARS-Cov-2 positive RRT patients the fatality rate was 32.8%, as compared to 13.3% observed in the Italian population as of April 23rd. Conclusions: A substantial proportion of the 60,441 surveyed RRT patients in Italy were SARS-Cov-2 positive and subsequently died during the exponential phase of COVID-19 pandemic. Infection risk and rates seems to differ substantially across regions, along geographical latitude, and by treatment modality

A case study of green design in electrical engineering: an integrated LCA/LCC analysis of an Italian manufactured HV/MV power transformer

The aim of this study is to present an experience of the application of the Sustainability Assessment Methodology to a traditional private business. It deals about a significant case study in which CESI S.p.A. applied an integrated LCA/LCC analysis to a 250 MVA HV/MV power transformer produced from the Italian Tamini Trasformatori S.r.l. and remanufactured from the traditional design- according to an innovative environmentally sustainable vision – changing the insulation material from mineral to ester oil. The study was the starting point to realize an Environmental Product Declaration and the preceding Product Category Rules, currently underway. Such an innovative and green product development tries to anticipate market demands, to improve the environmental performance and benefits of the energy transformation process, to increase the migration to bio and renewable sources solutions

Epidermal Notch1 recruits RORγ+ group 3 innate lymphoid cells to orchestrate normal skin repair

Notch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal. Epidermal Notch induces recruitment of immune cell subsets including RORγ + ILC3s into wounded dermis; RORγ + ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for RORγ + ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNFα and the ILC3 recruitment chemokines CCL20 and CXCL13. TNFα, as a Notch1 effector, directs ILC3 localization and rates of wound healing. Altogether these findings suggest that Notch is a key stress/injury signal in skin epithelium driving innate immune cell recruitment and normal skin tissue repair

Clathrin light chains' role in selective endocytosis influences antibody isotype switching

Clathrin, a cytosolic protein composed of heavy and light chain subunits, assembles into a vesicle coat, controlling receptor-mediated endocytosis. To establish clathrin light chain (CLC) function in vivo, we engineered mice lacking CLCa, the major CLC isoform in B lymphocytes, generating animals with CLC-deficient B cells. In CLCa-null mice, the germinal centers have fewer B cells, and they are enriched for IgA-producing cells. This enhanced switch to IgA production in the absence of CLCa was attributable to increased transforming growth factor β receptor 2 (TGFβR2) signaling resulting from defective endocytosis. Internalization of C-X-C chemokine receptor 4 (CXCR4), but not CXCR5, was affected in CLCa-null B cells, and CLC depletion from cell lines affected endocytosis of the δ-opioid receptor, but not the β2-adrenergic receptor, defining a role for CLCs in the uptake of a subset of signaling receptors. This instance of clathrin subunit deletion in vertebrates demonstrates that CLCs contribute to clathrin’s role in vivo by influencing cargo selectivity, a function previously assigned exclusively to adaptor molecules

Magnetic Resonance Imaging to Assess Blood–Brain Barrier Damage in Murine Trypanosomiasis

The ability of trypanosomes to invade the brain and induce an inflammatory reaction is well-recognized. This study uses magnetic resonance imaging (MRI) in conjunction with a murine model of central nervous system (CNS) stage trypanosomiasis to investigate this phenomenon at the level of the blood–brain barrier (BBB). Mice were scanned before and after administration of the contrast agent. Signal enhancement maps were generated, and the percentage signal change was calculated. The severity of the neuroinflammation was also assessed. Statistical analysis of the signal change data revealed a significantly (P = 0.028) higher signal enhancement in mice at 28 days post-infection (least squares mean = 26.709) compared with uninfected animals (6.298), indicating the presence of BBB impairment. Leukocytes were found in the meninges and perivascular space of some blood vessels in the infected mice. This study shows that the integrity of the BBB is compromised during CNS stage trypanosomiasis and that the impairment does not correlate with inflammatory cell infiltration

Ret/PTC activation does not influence clinical and pathological features of adult papillary thyroid carcinomas

OBJECTIVE: RET proto-oncogene rearrangements (ret/PTCs) represent the most common genetic alterations found in papillary thyroid carcinomas (PTCs). Correlation of ret/PTC expression with clinical outcome is controversial. The aim of the present study was to analyze the frequency of RET rearrangements in adult PTCs, and to investigate if ret/PTCs influence biological behavior and clinical features of the cancers. DESIGN: Ret/PTC rearrangements were looked for in tIssue samples of 48 PTCs collected at our institution. Data about clinical and pathological features of the tumors were also reviewed. Three separate association analyses were carried out on the cohort evaluating the effects of, respectively, ret/PTC positivity, preferential RET tyrosine kinase domain (RET-TK) expression, and ret/PTC plus RET-TK positivity, on age, sex, tumor size, staging, number of neoplastic foci, and histological subtype. METHODS: The genetic study was conducted with the RT-PCR-Southern blot technique. Standard Student's t-test and Fisher exact test were applied for the association analyses. RESULTS: The molecular genetic study demonstrated the positivity of ret/PTC1 and ret/PTC3 in 13 of 48 tumors (27.1%), and an exclusive or preferential RET-TK expression in 17 cases (35.4%). None of the three genetico-clinical analyses showed any significant association between ret/PTC expression and the clinical and pathological features of the cancers. CONCLUSIONS: These data indicate that RET rearrangements may not play any distinctive role in driving histotype development and cancer progression in these neoplasms. Moreover, they weaken the possibility of using ret/PTC as a prognostic marker for papillary thyroid carcinomas

Serum uric acid / serum creatinine ratio as a predictor of cardiovascular events. Detection of prognostic cardiovascular cut-off values

Objective: In the frame of the Uric Acid Right for Heart Health (URRAH) study, a nationwide multicenter study involving adult participants recruited on a regional community basis from all the territory of Italy under the patronage of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, we searched for the cut-off values of the ratio between serum uric acid (SUA) and serum creatinine (sCr) able to predict cardiovascular (CV) events. Methods: Among 20 724 participants followed-up for 126 ± 64 months, after detecting cut-off by the receiver operating characteristic curves, we calculated by Cox models adjusted for confounders having CV events as dependent variable the hazard ratio (HR) of SUA/sCr > cut-off. We also verified if the role of cut-off varied with increasing SUA/sCr. Results: A plausible prognostic cut-off of SUA/sCr was found and was the same in the whole database, in men and in women (>5.35). The HR of SUA/sCr > cut-off was 1.159 (95% confidence interval [CI] 1.092-1.131, P < 0.03) in all, 1.161 (95% CI 1.021-1.335, P < 0.02) in men, and 1.444 (95% CI 1.012-1.113, P < 0.03) in women. In increasing quintiles of SUA/sCr the cut-offs were >3.08, >4.87, >5.35, >6.22 and >7.58, respectively. The HRs significantly increased from the 3rd to the 5th quintile (1.21, 95% CI 1.032-1.467, P = 0.018; 1.294, 95% CI 1.101-1.521, P = 0.002; and 1.642, 95% CI 1.405-1.919, P < 0.0001; respectively), that is, over 5.35, whereas the 2nd quintile was not significantly different from the 1st (reference). Conclusion: Having SUA/sCr >5.35 is an independent CV risk indicator both in men and women. The cut-off is dynamic and significantly increases with increasing SUA/sCr

Serum Uric Acid Predicts All-Cause and Cardiovascular Mortality Independently of Hypertriglyceridemia in Cardiometabolic Patients without Established CV Disease: A Sub-Analysis of the URic acid Right for heArt Health (URRAH) Study

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan-Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (≥4.7 mg/dL) and CVM (≥5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12-1.40], p < 0.001) and CVM (1.31 [1.11-1.74], p < 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12-1.43], p < 0.001) and hypertriglyceridemia (1.31 [1.02-1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23-1.73], p < 0.001) and hypertriglyceridemia (HR 1.31 [0.99-1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels

Panethnic Differences in Blood Pressure in Europe: A Systematic Review and Meta-Analysis

BACKGROUND: People of Sub Saharan Africa (SSA) and South Asians(SA) ethnic minorities living in Europe have higher risk of stroke than native Europeans(EU). Study objective is to provide an assessment of gender specific absolute differences in office systolic(SBP) and diastolic(DBP) blood pressure(BP) levels between SSA, SA, and EU. METHODS AND FINDINGS: We performed a systematic review and meta-analysis of observational studies conducted in Europe that examined BP in non-selected adult SSA, SA and EU subjects. Medline, PubMed, Embase, Web of Science, and Scopus were searched from their inception through January 31st 2015, for relevant articles. Outcome measures were mean SBP and DBP differences between minorities and EU, using a random effects model and tested for heterogeneity. Twenty-one studies involving 9,070 SSA, 18,421 SA, and 130,380 EU were included. Compared with EU, SSA had higher values of both SBP (3.38 mmHg, 95% CI 1.28 to 5.48 mmHg; and 6.00 mmHg, 95% CI 2.22 to 9.78 in men and women respectively) and DBP (3.29 mmHg, 95% CI 1.80 to 4.78; 5.35 mmHg, 95% CI 3.04 to 7.66). SA had lower SBP than EU(-4.57 mmHg, 95% CI -6.20 to -2.93; -2.97 mmHg, 95% CI -5.45 to -0.49) but similar DBP values. Meta-analysis by subgroup showed that SA originating from countries where Islam is the main religion had lower SBP and DBP values than EU. In multivariate meta-regression analyses, SBP difference between minorities and EU populations, was influenced by panethnicity and diabetes prevalence. CONCLUSIONS: 1) The higher BP in SSA is maintained over decades, suggesting limited efficacy of prevention strategies in such group in Europe;2) The lower BP in Muslim populations suggests that yet untapped lifestyle and behavioral habits may reveal advantages towards the development of hypertension;3) The additive effect of diabetes, emphasizes the need of new strategies for the control of hypertension in groups at high prevalence of diabetes