Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy.

Under resting conditions, the failing heart shifts fuel use toward greater glucose and lower free fatty acid (FFA) oxidation. We hypothesized that chronic metabolic abnormalities in patients with dilated cardiomyopathy (DCM) are associated with the absence of the normal increase in myocardial glucose uptake and maintenance of cardiac mechanical efficiency in response to pacing stress. In 10 DCM patients and 6 control subjects, we measured coronary flow by intravascular ultrasonometry and sampled arterial and coronary sinus blood. Myocardial metabolism was determined at baseline, during atrial pacing at 130 beats/min, and at 15 min of recovery by infusion of [(3)H]oleate and [(13)C]lactate and measurement of transmyocardial arteriovenous differences of oxygen and metabolites. At baseline, DCM patients showed depressed coronary flow, reduced uptake and oxidation of FFA, and preferential utilization of carbohydrates. During pacing, glucose uptake increased by 106% in control subjects but did not change from baseline in DCM patients. Lactate release increased by 122% in DCM patients but not in control subjects. Cardiac mechanical efficiency in DCM patients was not different compared with control subjects at baseline but was 34% lower during stress. Fatty acid uptake and oxidation did not change with pacing in either group. Our results show that in DCM there is preferential utilization of carbohydrates, which is associated with reduced flow and oxygen consumption at rest and an impaired ability to increase glucose uptake during stress. These metabolic abnormalities might contribute to progressive cardiac deterioration and represent a target for therapeutic strategies aimed at modulating cardiac substrate utilization

Covid-19 patient management in outpatient setting: A population-based study from southern italy

Evidence on treatments for early-stage COVID-19 in outpatient setting is sparse. We explored the pattern of use of drugs prescribed for COVID-19 outpatients’ management in Southern Italy in the period February 2020–January 2021. This population-based cohort study was conducted using COVID-19 surveillance registry from Caserta Local Health Unit, which was linked to claims databases from the same catchment area. The date of SARS-CoV-2 infection diagnosis was the index date (ID). We evaluated demographic and clinical characteristics of the study drug users and the pattern of use of drugs prescribed for outpatient COVID-19 management. Overall, 40,030 patients were included in the analyses, with a median (IQR) age of 44 (27–58) years. More than half of the included patients were asymptomatic at the ID. Overall, during the study period, 720 (1.8%) patients died due to COVID-19. Azithromycin and glucocorticoids were the most frequently prescribed drugs, while oxygen was the less frequently prescribed therapy. The cumulative rate of recovery from COVID-19 was 84.2% at 30 days from ID and it was lower among older patients. In this study we documented that the drug prescribing patterns for COVID-19 treatment in an outpatient setting from Southern Italy was not supported from current evidence on beneficial therapies for early treatment of COVID-19, thus highlighting the need to implement strategies for improving appropriate drug prescribing in general practice

Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer

The mechanism for generating double minutes chromosomes (dmin) and homogeneously staining regions (hsr) in cancer is still poorly understood. Through an integrated approach combining next-generation sequencing, single nucleotide polymorphism array, fluorescent in situ hybridization and polymerase chain reaction-based techniques, we inferred the fine structure of MYC-containing dmin/hsr amplicons harboring sequences from several different chromosomes in seven tumor cell lines, and characterized an unprecedented number of hsr insertion sites. Local chromosome shattering involving a single-step catastrophic event (chromothripsis) was recently proposed to explain clustered chromosomal rearrangements and genomic amplifications in cancer. Our bioinformatics analyses based on the listed criteria to define chromothripsis led us to exclude it as the driving force underlying amplicon genesis in our samples. Instead, the finding of coexisting heterogeneous amplicons, differing in their complexity and chromosome content, in cell lines derived from the same tumor indicated the occurrence of a multi-step evolutionary process in the genesis of dmin/hsr. Our integrated approach allowed us to gather a complete view of the complex chromosome rearrangements occurring within MYC amplicons, suggesting that more than one model may be invoked to explain the origin of dmin/hsr in cancer. Finally, we identified PVT1 as a target of fusion events, confirming its role as breakpoint hotspot in MYC amplification

A GNR e as Operações de Apoio à Paz: Legitimidade e limites de actuação

O presente trabalho de investigação aplicada está subordinado ao tema: ―A GNR e as Operações de Apoio à Paz: Legitimidade e Limites de Actuação‖. As operações de apoio à paz são uma realidade do mundo actual e a participação da GNR nestas operações tem sido uma constante. Neste sentido, a legitimidade desta participação tem sido ao longo dos anos questionada, tese esta que é debatida neste trabalho. Para além da legitimidade, são também aqui debatidos quais são os limites de actuação desta força militar em operações deste tipo. Neste contexto, desenvolve-se um estudo através da pergunta de partida: "De que forma a participação nas OAP é importante para a GNR? E para o País?." Os principais objectivos do trabalho são responder às perguntas supra mencionadas, verificar a legitimidade da participação da GNR neste tipo de operações, compreender o conceito das regras de empenhamento e a sua criação e, finalmente , identificar a importância destas regras para a decisão de um comandante. O trabalho iniciou-se com uma fase exploratória, procedendo-se em seguida à pesquisa com particular incidência em livros, legislação e textos relacionados com o tema, tendo sido tam bém utilizada a internet como fontes de informação sobre as operações de apoio à paz. A investigação de campo baseou-se na análise de conteúdo das entrevistas efectuadas, o que permitiu responder às perguntas de investigação através da verificação das hipó teses formuladas. Após a análise dos dados, conclui-se que a GNR tem legitimidade para participar nestas operações, o que está contemplado na sua lei orgânica, e que, em simultâneo, estas participações revelam elevada importância não só para a GNR como para o País. No entanto, para que exista uma melhor preparação das forças que executam estas missões será necessário que o novo Centro de Treino e Aprontamento para Forças de Missões Internacionais entre em funcionamento com uma estrutura diferente da planeada. O presente trabalho foi realizado entre Janeiro e Março de 2009.Abstract This investigation project was developed under the theme: ―The GNR (Portuguese Republican National Guard) and the Peace Operations: Legitimacy and Action Limits. The peace-support operations are a reality in our contemporary world and the GNR's participation in these operations has been a constant. Considering this, the legitimacy of such participations has been questioned over the years, fact that led to the thesis discussed along this work. In addition to legitimacy, the limits of military force in such operations are also debated. In this context, this project was based on two former question s: "What is the meaning of the GNR participation in the peace operations? And for the country?". The main goals of the project are answering the questions above, confirming the legitimacy of GNR's participation in such operations, understanding the rules of engagement and its creation and, at last, identifying the rules importance for a commander’s decision. The project began with an exploratory phase, followed by a research work supported by books, legislation and texts on the subject as well as the Internet as sources of information on peace-support operations. The field research was developed by analysing the conducted interviews, which allowed the research to answer the questions while checking the assumptions previously made. After analyzing the data, it is concluded that the GNR is entitled to participate in these operations, which is included in its organic law, and, simultaneously, these actions reveal high importance not only for the GNR but for the country also. Nevertheless, in order to get a better preparation of the forces that will carry out these missions, changes in structure and functioning of the new Training Centre are needed. This work was developed from January to March 2009

Musculoskeletal complaints among Italian X-ray technology students: a cross-sectional questionnaire survey

<p>Abstract</p> <p>Background</p> <p>There is a high prevalence of musculoskeletal disorders among healthcare professional students. Although recent studies show musculoskeletal disorders are a common problem among X-ray technologists, there are no data on these disorders among students of this healthcare profession. We have therefore estimated the prevalence of musculoskeletal complaints among a group of X-ray technology students.</p> <p>Methods</p> <p>The students (n = 109) currently attending the 3-year X-ray technologist school at a large University in the Apulia region of Southern Italy were recruited for the study, with a 100% participation rate. A questionnaire collected data concerning personal characteristics, physical exposure during training activities, and the presence of musculoskeletal symptoms in the neck, shoulders, low back, hand/wrist and legs.</p> <p>Results</p> <p>The prevalence of complaints in any body site over the previous 12 months was 37%. Low back pain was the most frequently reported symptom (27%), followed by neck (16%), shoulder (11%), leg (8%) and hand/wrist (5%) pain. Poor physical activity was associated with the complaints.</p> <p>Conclusions</p> <p>Our study showed prevalence rates of musculoskeletal complaints among X-ray technology students to be somewhat high, representing about half of those found in Italian technologists. The most common musculoskeletal problem was low back pain, which had also been found in research conducted among nursing students. Our research also showed a significant association between poor physical activity and the presence of musculoskeletal disorders in young university students.</p