Contribution of telomerase RNA retrotranscription to DNA double-strand break repair during mammalian genome evolution

A comparative analysis of two primate and two rodent genomes suggests that telomerase was utilized, in some instances, for the repair of DNA double-strand breaks during mammalian evolution

Cardiovascular abnormalities and impaired exercise performance in adolescents with congenital adrenal hyperplasia

Context: Patients with classic Congenital Adrenal Hyperplasia (CAH) are treated with lifelong glucocorticoids (GCS). Cardiovascular (CV) and metabolic effects of such therapy in adolescents have never been quantified. Objective: To investigate left ventricular (LV) morphology, function and exercise performance in adolescents with CAH. Design and Setting: cross-sectional and controlled study conducted at a tertiary referral centre. Patients: Twenty patients with classic CAH (10 females) aged 13.6±2.5 years and 20 healthy controls comparable for sex and pubertal status were enrolled in the study and compared to a group of 18 patients without CAH receiving a similar dose of GCS for Juvenile Idiopathic Arthritis (JIA). Main Outcomes Measures: Echocardiographic assessment and symptom-limited exercise testing were performed. Anthropometric, hormonal and biochemical parameters were also measured. Results: Compared to healthy controls, patients with CAH exhibited an increased BMI (p<0.001), waist-to-height ratio (p<0.001), percentage of body fat (p<0.001) as well as higher insulin concentrations and HOMA index even after adjustment for BMI (p=0.03 and p=0.05, respectively). Moreover, CAH patients exhibited an impaired exercise capacity as shown by reduced peak workload (99±27 vs 126±27 W, p<0.01) and higher systolic blood pressure response at peak (156±18 vs 132±11 mmHg, p<0.01; Δ=45±24 vs 22±10 mmHg, p=0.05) with respect to healthy controls. CAH males displayed mild LV diastolic dysfunction as documented by significant prolongation of both isovolumic relaxation time (IRT) (118±18 vs 98±11ms, p<0.05) and mitral deceleration time (MDT) (138±25 vs 111±15 ms, p<0.01). No significant differences in CV function were found between CAH and JIA patients. Conclusion: Adolescents with CAH exhibit impaired exercise performance and enhanced systolic blood pressure response during exercise. In our population, such abnormalities appear related to GCS therapy rather than CAH per se. CAH males, but no females, present mild LV diastolic dysfunction that correlates with testosterone concentrations suggesting a sex hormone related difference

The impact of gender in cardiovascular medicine: Lessons from the gender/sex-issue in heart failure

Heart Failure (HF) is a major healthcare issue, given its high prevalence and incidence, the rate of comorbidities, the related high health-care costs and its poor outcome. In the last years mounting evidence revealed several differences between men and women affected by this clinical condition. Apart from the well-known difference in phenotype (HF with reduced ejection fraction (HFrEF) occurs more commonly in men, and HF with preserved ejection fraction (HFpEF) is more frequent in women) other relevant sex-related issues dwell upon epidemiology, presentation, risk stratification and management. These differences shed new lights on the possibility to consider HF as a prototype of the impact of gender/sex issue in cardiovascular medicine. A call for action and future strategies might help in the achievement of a cleaver patient-care

Biomarkers in Heart Failure and Associated Diseases

Biomarkers in heart failure and associated disease

Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system. This review summaries the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population. Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS

Laparoscopic bariatric surgery is safe during phase 2-3 of COVID-19 pandemic in Italy: A multicenter, prospective, observational study

Background: Sars-Cov-2 epidemic in Italy caused one of the greatest 2020 European outbreaks, with suspension of elective bariatric/metabolic surgery (BMS). From May 2020 a significant decline of the epidemic has been observed (phase 2); National Health Service protocols permitted elective BMS' resumption. A new, more severe COVID-19 surge, the "second wave", started on October 2020 (phase 3).Aim: The primary end point was to analyze the outcomes of any Sars-Cov-2 infection and related morbidity/mortality within 30 POD after laparoscopic BMS during phase 2-3; secondary end points were readmission and reoperation rates.Methods: Study design prospective, multicenter, observational.Setting: Eight Italian high-volume bariatric centers. All patients undergoing BMS from July 2020 through January 2021 were enrolled according to the following criteria: no Sars-Cov-2 infection; primary procedures; no concomitant procedure; age &gt; 18 &lt; 60 years; compensated comorbidities; informed consent including COVID-19 addendum; adherence to specific admission, in-hospital and follow-up protocols. Data were collected in a prospective database. Patients undergone BMS during July-December 2019 were considered a control group.Results: 1258 patients were enrolled and compared with 1451 operated on in 2019, with no differences for demographics, complications, readmission, and reintervention rates. Eight patients (0.6%) tested positive for Sars-Cov-2 infection after discharge, as well as and 15 healthcare professionals, with no related complications or mortality.Conclusions: Introduction of strict COVID-19 protocols concerning the protection of patients and health-care professionals guaranteed a safe resumption of elective BMS in Italy. The safety profile was, also, maintained during the second wave of outbreak, thus allowing access to a cure for the obese population. (C) 2021 Elsevier B.V. All rights reserved

Estudos epidemiológicos entre populações indígenas da Amazônia. II. Prevalências da microfilaremia de Mansonella ozzardi: comparação de dois métodos de diagnóstico ()

The prevalence of microfilaremia among a representative sample of the adolescents and adults in 13 Brazilian Amazon Indian villages was determined for July-August, 1976. With Giemsa-stained peripheral blood smears, preparations from peripheral blood lymphocyte cultures, or both, 533 persons aged 10 years and older and 68 children below age 10 were tested. Mansonella ozzardi was the only blood-borne microfilarial species found. Prevalence was highly village-specific. In four of 13 villages persons tested had no detectable microfilaremia by the methods used. In four other villages the overall prevalences for residents aged 10 years and older were in excess of 60% by one of the methods used. In villages where microfilaremia was documented only five (13%) of the total 38 children tested were positive. There was a general trend for prevalence to rise with increasing age. The ratio of the prevalence of microfilaremia among males to that among females was approximately 1.4:1 with peripheral blood smear test results but exactly 1:1 with the other method. In each of the five microfilaremia-positive villages tested using both methods, we detected a higher prevalence of microfilaremia with the preparations made from the lymphocyte culture studies.Foi determinada a prevalência de microfilaremia em uma amostra representativa de adolescentes e adultos, em 13 aldeias, de índios amazônicos brasileiros em julho-agosto de 1976. Através de esfregaço de sangue periférico corados com Giemsa e de preparações de culturas de linfócitos de sangue periférico, ou ambas, foram testadas 533 pessoas com idade acima de 10 anos e 68 crianças com menos de 10 anos. A Mansonella ozzardi foi a única espécie de microfilária encontrada. A prevalência foi altamente aldeia-específica. Em quatro (4) das 13 aldeias, houve casos de não detecção de microfilaremia pelos métodos usados. Em quatro (4) outras aldeias, as prevalências encontradas para os residentes de 10 anos e mais velhos foram em excesso de 60% para cada método utilizado. Em aldeias onde a microfilaremia foi documentada, apenas cinco (13%) do total de 38 crianças testadas foram positivas. Houve uma tendência geral da prevalência aumentar com o aumento da idade, A razão de prevalência de microfilaremia entre homens e mulheres foi de aproximadamente 1,4:1 para o teste de esfregaço de sangue periférico e exatamente 1:1 para o outro. Em cada 5 aldeões com microfilaremia-positiva testados com ambos os métodos, detectamos uma mais alta prevalência da microfilaremia com as preparações feitas de cultura de linfócitos

Apolipoprotein B signal peptide polymorphism distribution among South Amerindian populations

This is the published version, also available here: http://www.jstor.org/stable/41465798

Rationale and protocol of a double-blind, randomized, placebo-controlled trial to test the efficacy, safety, and tolerability of dimethyl fumarate in Friedreich Ataxia (DMF-FA-201)

IntroductionFriedreich Ataxia (FRDA) is an autosomal recessive neurodegenerative disorder that causes gait and limb ataxia, dysarthria, and impaired vibratory sense, with cardiomyopathy being the predominant cause of death. There is no approved therapy, which results in the use of symptomatic treatments and the chronic support of physiotherapy. Dimethyl fumarate (DMF) is a fumaric acid ester used for the treatment of psoriasis and Multiple Sclerosis (MS). It induces Nrf2 in vitro and in vivo, and it increases frataxin in FRDA patient lymphoblasts, in mouse models, and in MS treated patients.MethodsThe aim of our study is to investigate if DMF can increase the expression of the FXN gene and frataxin protein and ameliorate in-vivo detectable measures of mitochondrial dysfunction in FRDA. The study is composed of a screening visit and two sequential 12-week phases: a core phase and an extension phase. During the first phase (core), patients will be randomly assigned to either the DMF or a placebo group in a 1:1 ratio. During the first week, patients will receive a total daily dose of 240 mg of DMF or placebo; from the second week of treatment, the dose will be increased to two 120 mg tablets BID for a total daily dose of 480 mg. During the second phase (extension), all patients will be treated with DMF. EudraCT number 2021-006274-23.EndpointsThe primary endpoint will be a change in FXN gene expression level after 12 weeks of treatment. Secondary endpoints will be frataxin protein level, cardiopulmonary exercise test outputs, echocardiographic measures, Nrf2 pathway and mitochondrial biogenesis gene expression, safety, clinical scales, and quality of life scales.ConclusionsThis is the first study aimed at exploring the ability of DMF, an already available treatment for MS and psoriasis, to correct the biological deficits of FRDA and potentially improve mitochondrial respiration in-vivo

The tosca registry: an ongoing, observational, multicenter registry for chronic heart failure

The ageing of the population in western countries, the continuous increase of the prevalence of chronic diseases, the frequent coexistence of several morbid conditions (comorbidity) requires health professionals and Institutions to face difficult challenges, including increasing costs, need for more effective and sustainable therapies, and organizational issues. The European Innovation Partnership on Active and Healthy Ageing aims at enabling European citizens to lead healthy, active and independent lives while ageing. We herein discuss some key concepts bearing a special significance in the light of the Partnership aims, and present research and educational projects active in our local environment. Among these, the multicentre project TOSCA (Trattamento Ormonale nello Scompenso CArdiaco) that, although primarily focused on the understanding of the interactions between hormones and chronic heart failure (CHF), is also aimed at developing more effective models of clinical care. We provide the scientific background and current stage of the project. In the context of a growing complexity of the patients’ clinical management, the polipharmacy is a new arising challenge for clinicians, bearing direct economic, organizational and clinical implications. A better understanding, characterization and management of this issue represent an additional target of the TOSCA network