Macrophages in Injured Skeletal Muscle: A Perpetuum Mobile Causing and Limiting Fibrosis, Prompting or Restricting Resolution and Regeneration

Macrophages are present in regenerating skeletal muscles and participate in the repair process. This is due to a unique feature of macrophages, i.e., their ability to perceive signals heralding ongoing tissue injury and to broadcast the news to cells suited at regenerating the tissue such as stem and progenitor cells. Macrophages play a complex role in the skeletal muscle, probably conveying information on the pattern of healing which is appropriate to ensure an effective healing of the tissue, yielding novel functional fibers. Conversely, they are likely to be involved in limiting the efficacy of regeneration, with formation of fibrotic scars and fat replacement of the tissue when the original insult persists. In this review we consider the beneficial versus the detrimental actions of macrophages during the response to muscle injury, with attention to the available information on the molecular code macrophages rely on to guide, throughout the various phases of muscle healing, the function of conventional and unconventional stem cells. Decrypting this code would represent a major step forward toward the establishment of novel targeted therapies for muscle diseases

Clinical and experimental evidences on the prothrombotic properties of neutrophils

Epidemiologic studies have shown that the neutrophil count correlates with the risk of myocardial infarction and stroke and identify patients more susceptible to reinfarction and in-hospital death. In particular, neutrophils action was initially associated to blood rheological changes, or to the effect of neutrophil-derived eicosanoids or proteases. Animal models indicate that platelet-leukocyte P-selectin dependent cross-talk contributes to fibrin deposition during in vivo thrombus formation. In fact, platelet P-selectin, through its leukocyte counter-receptor PSGL-1, determines the activation of leukocyte ?2 integrins, the binding of fibrinogen and the expression of tissue factor on leukocyte surface. Monocytes stimulated in vitro with LPS, PMA and P-selectin synthesize and express tissue factor. fMLP, P-selectin, TNFalpha and C5a are effective stimuli that trigger the synthesis and expression of biologically active tissue factor in neutrophils. The experimental evidence well agrees with clinical observations: patients with acute coronary syndromes, acute respiratory distress syndrome, antiphospholipid syndromes, giant cell arteritis and myeloproliferative syndromes have increased the expression of tissue factor on leukocyte surface. Moreover circulating neutrophils express mRNA codifying for fulllength and/or alternatively spliced tissue factor, suggesting a new important link between thrombosis and inflammation. All together, clinical and experimental evidence suggest that the leukocyte thrombogenic profile is a relevant player in patients with a high risk of thromboembolic events and possibly represents a suitable target for molecular intervention

Energy and Seismic Rehabilitation of RC Buildings through an Integrated Approach: An Application Case Study

The high number of existing buildings in Italy without adequate seismic and thermal performances requires the definition of integrated retrofitting techniques in order to improve the seismic performance and to reduce energy losses at the same time. On one hand, an integrated approach appears mandatory considering that improving only the energy efficiency of nonseismic buildings leads to an increase of their exposure and, therefore, of their risk in the case of seismic events. On the other hand, seismic strengthening without an adequate thermal assessment and rehabilitation could compromise living comfort and energy maintenance costs. In this context, an application of integrated approach for the rehabilitation of reinforced concrete (RC) existing buildings has been proposed referring to a case study representative of the Italian building stock. Different configurations of infill panels have been considered in order to analyze both energy and seismic performance. Monthly quasi-steady state and hourly dynamic models have been used for the calculation of the energy need of buildings located in different Italian climate and seismic zones. Seismic performances have been evaluated by means of incremental nonlinear dynamic analysis (IDA). As-built and post-retrofit performances have been compared in order to evaluate the effectiveness of the proposed intervention solutions

General methods for measuring and comparing medical interventions in childbirth: a framework

Abstract Background: The continue increase of interventions during labour in low risk population is a controversial issue of the current obstetric literature, given the lack of evidence demonstrating the benefits of unnecessary interventions for women or infants’ health. This makes it important to have approaches to assess the burden of all medical interventions performed. Methods: Exploiting the nature of childbirth intervention as a staged process, we proposed graphic representations allowing to generate alternative formulas for the simplest measures of the intervention intensity namely, the overall and type-specific treatment ratios. We applied the approach to quantify the change in interventions following a protocol termed Comprehensive Management (CM), using data from Robson classification, collected in a prospective longitudinal cohort study carried out at the Obstetric Unit of the Cà Granda Niguarda Hospital in Milan, Italy. Results: Following CM a substantial reduction was observed in the Overall Treatment Ratio, as well as in the ratios for augmentation (amniotomy and synthetic oxytocin use) and for caesarean section ratio, without any increase in neonatal and maternal adverse outcomes. The key component of this reduction was the dramatic decline in the proportion of women progressing to augmentation, which resulted not only the most practiced intervention, but also the main door towards further treatments. Conclusions: The proposed framework, once combined with Robson Classification, provides useful tools to make medical interventions performed during childbirth quantitatively measurable and comparable. The framework allowed to identifying the key components of interventions reduction following CM. In its turn, CM proved useful to reduce the number of medical interventions carried out during childbirth, without worsening neonatal and maternal outcomes

Endothelin-dependent vasoconstrictor activity in metabolically healthy and unhealthy obese patients

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Quantum linear mutual information and classical correlations in globally pure bipartite systems

We investigate the correlations of initially separable probability distributions in a globally pure bipartite system with two degrees of freedom for classical and quantum systems. A classical version of the quantum linear mutual information is introduced and the two quantities are compared for a system of oscillators coupled with both linear and non-linear interactions. The classical correlations help to understand how much of the quantum loss of purity are due to intrinsic quantum effects and how much is related to the probabilistic character of the initial states, a characteristic shared by both the classical and quantum pictures. Our examples show that, for initially localized Gaussian states, the classical statistical mutual linear entropy follows its quantum counterpart for short times. For non-Gaussian states the behavior of the classical and quantum measures of information are still qualitatively similar, although the fingerprints of the non-classical nature of the initial state can be observed in their different amplitudes of oscillation.Comment: (16 pages, 4 figures

Economic development with deadly communicable diseases and public prevention

Infectious diseases have been a major determinant of human mortality in history and the key regulator of population size, including the first epoch of the Industrial Revolution (until the 1950s) in Western countries and still now in developing countries, especially in Sub-Saharan Africa. In recent times, a new vein of economic research dealing with the interplay between communicable diseases and economic development has grown. However, pioneering previous research (Chakraborty et al., 2010, 2016) has analysed this issue in a framework where prevention decisions were the outcome of private individual rational choices. This assumption neither seems to hold for least-developed countries, primarily due to a lack of resources, nor for developed countries, where prevention policies are mostly planned by the public authority through its (public) health system, as also well documented by the current COVID-19 crisis. Our aim in this article is twofold. First, we pinpoint the properties of Chakraborty et al.'s basic epidemiological equation to fully enlighten its usability in economic-epidemiology modelling. Second, we apply this framework to analyse prevention activities against a range of infectious diseases by endogenous public (rather than private) health expenditures. Our results identify the relationships governing the interplay between -- on one hand -- typical epidemiological phenomena, namely invasion (that is, the tendency of infection to establish in a population) versus endemicity (that is, the tendency of infection to persist in the long term) and -- on the other hand -- economic variables, such as capital accumulation, GDP and taxation. This is done by identifying threshold quantities, depending on both epidemiological and economic parameters, and by bifurcation analysis showing the effects that public intervention can have on previously uncontrolled infectious diseases. Both direct and indirect, that is, partial and general equilibrium, effects of control interventions are identified

Autocrine Nitric Oxide Modulates CD95-induced Apoptosis in γδ T Lymphocytes

Gammadelta T lymphocytes play an important early role in the defense against pathogens. Their function is terminated by acquisition of susceptibility to CD95-triggered apoptosis. Here we show that the regulation of this process depends on the activity of the endothelial NO synthase expressed by gammadelta T lymphocytes, which is modulated in an activation-dependent way. The effects of nitric oxide thus generated, mediated via cGMP generation, are exerted at at least two sites along the CD95 signaling cascade: one at, or upstream, and the other downstream of ceramide generation. At either site, nitric oxide/cGMP action is sufficient for protection from apoptosis. The effect of NO is selective for apoptosis induced by CD95 cross-linking, since it does not affect apoptotic program triggered by other stimuli. The evidence here reported demonstrates a new physiological role for nitric oxide, acting as a survival factor for T lymphocytes

Alcoholic liver cirrhosis, more than a simple hepatic disease – A brief review of the risk factors associated with alcohol abuse

Liver cirrhosis is a significant public health problem, being an important cause of mortality and morbidity, responsible for approximately 1.8% of the total number of deaths in Europe. Chronic alcohol consumption is the most common cause of liver cirrhosis in developed countries. Europe has the highest level of alcohol consumption among all the global World Health Organisation (WHO) regions. In this paper, we briefly review major factors leading to excessive alcohol consumption in order to draw attention to the fact that alcoholic liver cirrhosis is more than a simple liver disease, and if those risk/causal factors can be prevented, the incidence of this disease could be reduced greatly. Although excessive alcohol consumption is regarded as the cause of alcoholic liver cirrhosis, the etiology is complex, involving multiple factors that act in synchrony, and which, if prevented, could greatly reduce the incidence of this disease. Children of addicts are likely to develop an alcohol-related mental disorder; however, there is no “gene for alcoholism”