INFLUENZA DELLA VITAMINA D SUL SISTEMA RENINA-ANGIOTENSINA CIRCOLANTE ED INTRARENALE IN PAZIENTI CON IPERTENSIONE ARTERIOSA ESSENZIALE

L’obiettivo del lavoro è stato quello di valutare gli effetti dell’attivazione dei recettori della vitamina D sul sistema renina-angiotensina (RAS) sistemico e renale in 53 pazienti con ipertensione essenziale ed ipovitaminosi D. Per questo motivo abbiamo utilizzato varie formulazioni di vitamina D, somministrate con dosaggi e per periodi diversi, in presenza ed assenza di terapia interferente sul RAS ed in diverse condizioni di apporto di sodio. I risultati indicano che dosi di colecalciferolo tali da normalizzare i livelli di vitamina D sono in grado di sopprimere il RAS sistemico, ma non renale, in pazienti ipertesi in wash-out farmacologico con controllato apporto di sodio

Cholecalciferol administration blunts the systemic renin–angiotensin system in essential hypertensives with hypovitaminosis D:

Introduction: Vitamin D plasma levels are negatively associated with blood pressure and cardiovascular mortality, and vita- min D supplementation reduces cardiovascular events. Renin-angiotensin system (RAS) suppression may be one of the mechanisms involved. However, there are no interventional prospective studies demonstrating a reduction in circulating RAS components after vitamin D treatment. Methods: Fifteen consecutive drug-free patients with essential hypertension and hypovitaminosis D underwent therapy with an oral dose of 25000 I.U. of cholecalciferol once a week for two months, while maintaining a constant-salt diet. In basal conditions and at the end of the study, RAS activity (plasma angiotensinogen, renin, PRA, angiotensin II, aldosterone and urinary angiotensinogen) was investigated, in addition to blood pressure and plasma vitamin D levels (25(OH)D). Results: After cholecalciferol administration, all patients exhibited normalized plasma 25(OH)D values. At the end of the study, a reduction (p < 0.05) in plasma renin and aldosterone, and a decrement, although not significant, of PRA and angiotensin II, was observed. No difference was found in plasma and urinary angiotensinogen or blood pressure values. Conclusions: Our data indicate that in essential hypertensives with hypovitaminosis D, pharmacological correction of vitamin D levels can blunt systemic RAS activity

Pre-existing mental health disorders and fear of COVID-19 pandemic: Data from a phone survey in community-dwelling older adults recruited in the NutBrain study

Background: COVID-19 has caused a parallel epidemic of fear, anxiety, depression, stress, and frustration, particularly among the most fragile and vulnerable individuals, such as older people and those with previous mental health disorders. The present study aims to investigate the association between pre-existing mental health disorders, particularly depressive symptoms and Mild Cognitive Impairment (MCI), and the fear of COVID-19 and to explore which cognitive domains were involved in coping with fear in older people. Materials and methods: In April 2020, we conducted a phone-interview questionnaire on community-dwelling older adults living in Lombardy Region (Italy) who participated in the NutBrain study. At baseline, socio-demographic characteristics along with lifestyles, and medical history were recorded. Participants underwent a neuropsychological battery exploring the global cognitive function and specific cognitive domains, to detect cases of MCI. The Center for Epidemiologic Studies Depression scale (CES-D) was used for screening depressive symptoms. During the phone survey, respondents were assessed using a structured questionnaire querying about fear of the COVID-19 pandemic. We performed multivariate logistic regression models to study the association between MCI and depressive symptomatology and fear. We also explored which cognitive domains were associated with fear. Odds Ratios (OR) with Confidence Intervals (95%CI) were estimated adjusting for potential confounders. Results: Out of the 351 respondents (mean age 73.5 6.1 years, 59.8% women, 49.1% high education), at baseline, 22.9% had MCI and 18.8% had Frontiers in Psychiatry 01 frontiersin.org Perdixi et al. 10.3389/fpsyt.2022.995308 depressive symptoms. In the multivariate analyses gender, age, and body mass index were significantly associated with the fear score. Considering different domains of fear, MCI was associated with fear of being infected themselves (OR 2.55, 95%CI 1.39–4.70) while depressive symptoms were associated with fear of contagion for family members (OR 2.38, 95%CI 1.25–4.52). Impaired executive cognitive function was positively associated with the highest tertile of the fear score (OR 3.28, 95%CI 1.37–7.74) and with fear of contagion for themselves (OR 3.39, 95%CI 1.61-7.17). Conclusion: Older adults experienced different fear reactions, particularly when suffering from neurocognitive disorders and depressive symptoms; executive dysfunction was associated with increased fear. These results highlighted the need to pay attention to the psychological effects of the outbreak of COVID-19 to target intervention, especially among vulnerable subgroups of individuals

High-energy ball milling and synthesi temperature study to improve superconducting properties of MgB2 ex-situ tapes and wires

MgB2 monofilamentary nickel-sheated tapes and wires were fabricated by means of the ex-situ powder-in-tube method using either high-energy ball milled and low temperature synthesized powders. All sample were sintered at 920 C in Ar flow. The milling time and the revolution speed were tuned in order to maximize the critical current density in field (Jc): the maximum Jc value of 6 x 10e4 A/cm2 at 5 K and 4 T was obtained corresponding to the tape prepared with powders milled for 144h at 180rpm. Vorious synthesis temperature were also investigated (730-900 C) finding a best Jc value for the wire prepared with powders synthesized at 745 C. We speculate that this optimal temperature is due to the fluidifying effect of unreacted magnesium content before the sintering process which could better connect the grains

EU project "Cheap-GSHPs": the geoexchange field laboratory

Abstract The Molinella test site is the open-air laboratory of the EU project entitled "Cheap-GSHPs: Cheap and Efficient Application of Reliable Ground Source Heat Exchangers and Pumps". Here, innovative helical heat baskets and steel coaxial probes are installed next to the traditional double-U. The tests involve the probes design as well as materials and drilling techniques and machines, therefore the newly developed GSHEs can be directly compared with the traditional ones with respect to technical issues and energetic performances. The Molinella test site therefore represents a very extraordinary possibility to improve the knowledge of heat transfer processes in shallow geo-exchange systems

VID22 counteracts G-quadruplex-induced genome instability

Genome instability is a condition characterized by the accumulation of genetic alterations and is a hallmark of cancer cells. To uncover new genes and cellular pathways affecting endogenous DNA damage and genome integrity, we exploited a Synthetic Genetic Array (SGA)-based screen in yeast. Among the positive genes, we identified VID22, reported to be involved in DNA double-strand break repair. vid22Δ cells exhibit increased levels of endogenous DNA damage, chronic DNA damage response activation and accumulate DNA aberrations in sequences displaying high probabilities of forming G-quadruplexes (G4-DNA). If not resolved, these DNA secondary structures can block the progression of both DNA and RNA polymerases and correlate with chromosome fragile sites. Vid22 binds to and protects DNA at G4-containing regions both in vitro and in vivo. Loss of VID22 causes an increase in gross chromosomal rearrangement (GCR) events dependent on G-quadruplex forming sequences. Moreover, the absence of Vid22 causes defects in the correct maintenance of G4-DNA rich elements, such as telomeres and mtDNA, and hypersensitivity to the G4-stabilizing ligand TMPyP4. We thus propose that Vid22 is directly involved in genome integrity maintenance as a novel regulator of G4 metabolism.Associazione Italiana per la Ricerca sul Cancro (AIRC) 15631, 21806MIUR PRIN 2015- 2015SJLMB9, PRIN 2017-2017KSZZJW, PRIN2017-2017Z55KCMinisterio de Economía y Competitividad BFU2016- 75058-PCanadian Institutes of Health Research FDN-15991

Towards a Long-Read Sequencing Approach for the Molecular Diagnosis of RPGRORF15 Genetic Variants

Sequencing of the low-complexity ORF15 exon of RPGR, a gene correlated with retinitis pigmentosa and cone dystrophy, is difficult to achieve with NGS and Sanger sequencing. False results could lead to the inaccurate annotation of genetic variants in dbSNP and ClinVar databases, tools on which HGMD and Ensembl rely, finally resulting in incorrect genetic variants interpretation. This paper aims to propose PacBio sequencing as a feasible method to correctly detect genetic variants in low-complexity regions, such as the ORF15 exon of RPGR, and interpret their pathogenicity by structural studies. Biological samples from 75 patients affected by retinitis pigmentosa or cone dystrophy were analyzed with NGS and repeated with PacBio. The results showed that NGS has a low coverage of the ORF15 region, while PacBio was able to sequence the region of interest and detect eight genetic variants, of which four are likely pathogenic. Furthermore, molecular modeling and dynamics of the RPGR Glu-Gly repeats binding to TTLL5 allowed for the structural evaluation of the variants, providing a way to predict their pathogenicity. Therefore, we propose PacBio sequencing as a standard procedure in diagnostic research for sequencing low-complexity regions such as RPGRORF15, aiding in the correct annotation of genetic variants in online databases

VID22 counteracts G-quadruplex-induced genome instability

Genome instability is a condition characterized by the accumulation of genetic alterations and is a hallmark of cancer cells. To uncover new genes and cellular pathways affecting endogenous DNA damage and genome integrity, we exploited a Synthetic Genetic Array (SGA)-based screen in yeast. Among the positive genes, we identified VID22, reported to be involved in DNA double-strand break repair. vid22Δ cells exhibit increased levels of endogenous DNA damage, chronic DNA damage response activation and accumulate DNA aberrations in sequences displaying high probabilities of forming G-quadruplexes (G4-DNA). If not resolved, these DNA secondary structures can block the progression of both DNA and RNA polymerases and correlate with chromosome fragile sites. Vid22 binds to and protects DNA at G4-containing regions both in vitro and in vivo. Loss of VID22 causes an increase in gross chromosomal rearrangement (GCR) events dependent on G-quadruplex forming sequences. Moreover, the absence of Vid22 causes defects in the correct maintenance of G4-DNA rich elements, such as telomeres and mtDNA, and hypersensitivity to the G4-stabilizing ligand TMPyP4. We thus propose that Vid22 is directly involved in genome integrity maintenance as a novel regulator of G4 metabolism.Associazione Italiana per la Ricerca sul Cancro (AIRC) [15631, 21806 to M.M.F.]; MIUR [PRIN 2015-2015SJLMB9; PRIN 2017-2017KSZZJW to M.M.F.]; Telethon [GGP15227 to M.M.F.]; F.L. was supported by the University of Milano: ‘‘Piano di Sviluppo dell’Ateneo per la Ricerca. Linea B: Supporto per i Giovani Ricercatori’’; M.C.B. was supported by Fondazione Veronesi; Research at the laboratory of A.A. was funded by the Spanish Ministry of Economy and Competitiveness [BFU2016-75058-P]; B.G.G. was funded by the Spanish Association Against Cancer; MIUR [PRIN2017-2017Z55KC to T.B.]; M.C., D.S.H. are supported by MIUR [PRIN 2017] and CNRbiomics [PIR01_00017]; H2020 Projects ELIXIR-EXCELERATE, EOSC-Life, EOSC-Pillar and Elixir-IIB; G.W.B. was supported by the Canadian Institutes of Health Research[FDN-159913]. Funding for open access charge: Associazione Italiana per la Ricerca sul Cancro (AIRC) [21806]