SNOWFALL ANALYSIS OVER PENINSULAR ITALY IN RELATIONSHIP TO THE DIFFERENT TYPES OF SYNOPTIC CIRCULATION: FIRST RESULTS

The time series of snow data for a sample of Italian meteorological stations have been analyzed taking into account, for the time series, an acceptable continuity and quality of meteorological data. The data set is that of the Italian Meteorological Service (UGM), and refer to the period 1982–2004. The Slovenian station of Kredarica, located in the Julian Alps, has been added for convenience. The study is composed of two different parts: - Climatologic analysis of the snow parameters during the last 20 years. In particular, the height of the fresh snow and the number of days with permanence of snow at the ground have been analyzed. - Evidence of the synoptic situations in which snowfalls are observed with at least a thickness of 10 cm in at least a third of the total number of analyzed stations in Central, Southern and insular Ital

THE ROLE OF IMMUNITY SUPPRESSION IN TREATMENT OF MYOCARDITIS

Regardless the common consensus on the benefits of immunity suppression in eosinophilic, granulomatous, giant cell and lymphocyte myocarditis, associated with systemic connective tissue diseases, and in rejection of transplanted heart, role of immune suppression therapy (IST) in treatment of lymphocyte inflammatory cardiomyopathy remains controversial. Previous retrospective studies revealed clinical improvement in 90% of patients with virus-negative inflammatory cardiomyopathy and absence of response or worsening of heart function in 85% of virus-positive inflammatory cardiomyopathy after immunity suppression. Other studies identified the enhanced expression of HLA in cardiomyocytes as an additional indicator of sensitivity of inflammatory cardiomyopathy to IST. Recently, the singlecenter randomized study was performed with double blind application of prednisone and azatioprin as addition to maintenance therapy in 85 patients with virus-negative inflammatory cardiomyopathy. The results of the study showed significant improvement of the left ventricle ejection fraction and decrease of the left ventricle dimensions in 88% patients among 43 of treated comparing to 42 patients on placebo demonstrated worsening of cardiac functioning in 83% cases (the TIMIC study). This data confirms the efficacy of immunity suppression in virus-negative inflammatory cardiomyopathy. Insufficiency of response in 12% cases undermines existence of non-revealed viruses and mechanisms of damage and inflammation, non-sensitive to immunity suppression. Restoring of cardiac function in patients actively responded to immunity suppression, was determined by inhibition of cardiomyocytes death and increase of cells proliferation with ad novo synthesized contractile material

Myocarditis and intramural coronary vasculitis in polyarteritis nodosa: an unusual treatable form of heart failure

We describe an uncommon cardiac presentation of polyarteritis nodosa. A 68-year-old woman, with a history of fatigue, weight loss, and myalgia of the lower extremities, was admitted for congestive heart failure. Coronary arteries were normal. Endomyocardial biopsy showed active lymphocytic myocarditis with associated intramural small vessels necrotizing vasculitis. The overexpression of TLR-4 and the negativity for myocardial viruses suggested an immune mediated mechanism of cardiac damage. These histologic findings associated to weight loss >4 kg not due to dieting or other factors, myalgias, and polyneuropathy, were consistent with the diagnosis of polyarteritis nodosa. Immunosuppressive treatment, consisting of cyclophosphamide and prednisolone, led to a significant improvement of cardiac function. Polyarteritis nodosa can be the cause of unexplained heart failure due to myocarditis and intramural vessels vasculitis. Its recognition is crucial to obtain a cardiac recovery with a tailored immunosuppressive treatment

The Culture Environment Influences Both Gene Regulation and Phenotypic Heterogeneity in Escherichia coli

This is the final version of the article. Available from Frontiers Media via the DOI in this record.Microorganisms shape the composition of the medium they are growing in, which in turn has profound consequences on the reprogramming of the population gene-expression profile. In this paper, we investigate the progressive changes in pH and sugar availability in the medium of a growing Escherichia coli (E. coli) culture. We show how these changes have an effect on both the cellular heterogeneity within the microbial community and the gene-expression profile of the microbial population. We measure the changes in gene-expression as E. coli moves from lag, to exponential, and finally into stationary phase. We found that pathways linked to the changes in the medium composition such as ribosomal, tricarboxylic acid cycle (TCA), transport, and metabolism pathways are strongly regulated during the different growth phases. In order to quantify the corresponding temporal changes in the population heterogeneity, we measure the fraction of E. coli persisters surviving different antibiotic treatments during the various phases of growth. We show that the composition of the medium in which β-lactams or quinolones, but not aminoglycosides, are dissolved strongly affects the measured phenotypic heterogeneity within the culture. Our findings contribute to a better understanding on how the composition of the culture medium influences both the reprogramming in the population gene-expression and the emergence of phenotypic variants.This work was supported by a Royal Society Research Grant (RG140203), a Wellcome Trust Strategic Seed Corn Fund (WT097835/Z/11/Z), and a start up Grant from the University of Exeter awarded to SP. AS acknowledges support from the BBSRC through a SWBio-DTP studentship (BB/M009122/1). KP, KM, and PO would like to acknowledge support from the following awards: Wellcome Trust Institutional Strategic Support Fund (WT097835MF), Wellcome Trust Multi User Equipment Award (WT101650MA), and Medical Research Council Clinical Infrastructure Funding (MR/M008924/1). This work was partly supported by BBSRC award BB/1024631/1 to RT

Prelamin A mediates myocardial inflammation in dilated and HIV-associated cardiomyopathies

Cardiomyopathies are complex heart muscle diseases that can be inherited or acquired. Dilated cardiomyopathy can result from mutations in LMNA, encoding the nuclear intermediate filament proteins lamin A/C. Some LMNA mutations lead to accumulation of the lamin A precursor, prelamin A, which is disease causing in a number of tissues, yet its impact upon the heart is unknown. Here, we discovered myocardial prelamin A accumulation occurred in a case of dilated cardiomyopathy, and we show that a potentially novel mouse model of cardiac-specific prelamin A accumulation exhibited a phenotype consistent with inflammatory cardiomyopathy, which we observed to be similar to HIV-associated cardiomyopathy, an acquired disease state. Numerous HIV protease therapies are known to inhibit ZMPSTE24, the enzyme responsible for prelamin A processing, and we confirmed that accumulation of prelamin A occurred in HIV+ patient cardiac biopsies. These findings (a) confirm a unifying pathological role for prelamin A common to genetic and acquired cardiomyopathies; (b) have implications for the management of HIV patients with cardiac disease, suggesting protease inhibitors should be replaced with alternative therapies (i.e., nonnucleoside reverse transcriptase inhibitors); and (c) suggest that targeting inflammation may be a useful treatment strategy for certain forms of inherited cardiomyopathy

Prelamin A mediates inflammation in dilated and HIV associated cardiomyopathies

Cardiomyopathies are complex heart muscle diseases that can be inherited or acquired. Dilated cardiomyopathy can result from mutations in LMNA, encoding the nuclear intermediate filament proteins lamin A/C. Some LMNA mutations lead to accumulation of the lamin A precursor, prelamin A, which is disease causing in a number of tissues yet its impact upon the heart is unknown. Here we discovered myocardial prelamin A accumulation occurred in a case of dilated cardiomyopathy and show that a novel mouse model of cardiac specific prelamin A accumulation exhibited a phenotype consistent with ‘inflammatory cardiomyopathy’ which we observed to be similar to HIV associated cardiomyopathy, an acquired disease state. Numerous HIV protease therapies are known to inhibit ZMPSTE24, the enzyme responsible for prelamin A processing, and we confirmed that accumulation of prelamin A occurred in HIV+ patient cardiac biopsies. These findings: (1) confirm a unifying pathological role for prelamin A common to genetic and acquired cardiomyopathies; (2) have implications for the management of HIV patients with cardiac disease suggesting protease inhibitors should be replaced with alternative therapies i.e. non-nucleoside reverse transcriptase inhibitors; and (3) suggest that targeting inflammation may be a useful treatment strategy for certain forms of inherited cardiomyopathy

Myocarditis following COVID-19 vaccine: incidence, presentation, diagnosis, pathophysiology, therapy, and outcomes put into perspective. A clinical consensus document supported by the Heart Failure Association of the European Society of Cardiology (ESC) and the ESC Working Group on Myocardial and Pericardial Diseases

Over 10 million doses of COVID-19 vaccines based on RNA technology, viral vectors, recombinant protein, and inactivated virus have been administered worldwide. Although generally very safe, post-vaccine myocarditis can result from adaptive humoral and cellular, cardiac-specific inflammation within days and weeks of vaccination. Rates of vaccine-associated myocarditis vary by age and sex with the highest rates in males between 12 and 39 years. The clinical course is generally mild with rare cases of left ventricular dysfunction, heart failure and arrhythmias. Mild cases are likely underdiagnosed as cardiac magnetic resonance imaging (CMR) is not commonly performed even in suspected cases and not at all in asymptomatic and mildly symptomatic patients. Hospitalization of symptomatic patients with electrocardiographic changes and increased plasma troponin levels is considered necessary in the acute phase to monitor for arrhythmias and potential decline in left ventricular function. In addition to evaluation for symptoms, electrocardiographic changes and elevated troponin levels, CMR is the best non-invasive diagnostic tool with endomyocardial biopsy being restricted to severe cases with heart failure and/or arrhythmias. The management beyond. guideline-directed treatment of heart failure and arrhythmias includes non-specific measures to control pain. Anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs, and corticosteroids have been used in more severe cases, with only anecdotal evidence for their effectiveness. In all age groups studied, the overall risks of SARS-CoV-2 infection-related hospitalization and death are hugely greater than the risks from post-vaccine myocarditis. This consensus statement serves as a practical resource for physicians in their clinical practice, to understand, diagnose, and manage affected patients. Furthermore, it is intended to stimulate research in this area