Vascular Occlusion Affects Gait Variability Patterns of Healthy Younger and Older Individuals

Insufficient blood flow is one possible mechanism contributing to altered gait patterns in lower extremity peripheral arterial disease (PAD). Previously, our laboratory found that induced occlusion alters gait variability patterns in healthy young individuals. However the effect of age was not explored. The purpose of this study was to account for age by investigating gait variability following induced vascular occlusion in healthy older individuals and to identify amount of change from baseline to post vascular occlusion between younger and older individuals. Thirty healthy younger individuals and 30 healthy older individuals walked on a treadmill during baseline and post vascular occlusion conditions while lower extremity joint kinematics were captured. Vascular occlusion was induced by thigh cuffs inflated bilaterally on the upper thighs. Amount and temporal structure of gait variability was assessed. Older individuals exhibited significantly increased values of temporal structure of variability post vascular occlusion. Post vascular occlusion values were similar between younger and older individuals after adjusting for baseline measurements. Results show blood flow contributes to altered gait variability. However alterations were less severe than previously documented in symptomatic PAD patients, suggesting that neuromuscular problems in the lower extremities of PAD patients also contribute to gait alterations in these patients

Hypothermia in a surgical intensive care unit

BACKGROUND: Inadvertent hypothermia is not uncommon in the immediate postoperative period and it is associated with impairment and abnormalities in various organs and systems that can lead to adverse outcomes. The aim of this study was to estimate the prevalence, the predictive factors and outcome of core hypothermia on admission to a surgical ICU. METHODS: All consecutive 185 adult patients who underwent scheduled or emergency noncardiac surgery admitted to a surgical ICU between April and July 2004 were admitted to the study. Tympanic membrane core temperature (Tc) was measured before surgery, on arrival at ICU and every two hours until 6 hours after admission. The following variables were also recorded: age, sex, body weight and height, ASA physical status, type of surgery, magnitude of surgical procedure, anesthesia technique, amount of intravenous fluids administered during anesthesia, use of temperature monitoring and warming techniques, duration of the anesthesia, ICU length of stay, hospital length of stay and SAPS II score. Patients were classified as either hypothermic (Tc ≤ 35°C) or normothermic (Tc> 35°C). Univariate analysis and multiple regression binary logistic with an odds ratio (OR) and its 95% Confidence Interval (95%CI) were used to compare the two groups of patients and assess the relationship between each clinical predictor and hypothermia. Outcome measured as ICU length of stay and mortality was also assessed. RESULTS: Prevalence of hypothermia on ICU admission was 57.8%. In univariate analysis temperature monitoring, use of warming techniques and higher previous body temperature were significant protective factors against core hypothermia. In this analysis independent predictors of hypothermia on admission to ICU were: magnitude of surgery, use of general anesthesia or combined epidural and general anesthesia, total intravenous crystalloids administrated and total packed erythrocytes administrated, anesthesia longer than 3 hours and SAPS II scores. In multiple logistic regression analysis significant predictors of hypothermia on admission to the ICU were magnitude of surgery (OR 3.9, 95% CI, 1.4–10.6, p = 0.008 for major surgery; OR 3.6, 95% CI, 1.5–9.0, p = 0.005 for medium surgery), intravenous administration of crystalloids (in litres) (OR 1.4, 95% CI, 1.1–1.7, p = 0.012) and SAPS score (OR 1.0, 95% CI 1.0–1.7, p = 0.014); higher previous temperature in ward was a significant protective factor (OR 0.3, 95% CI 0.1–0.7, p = 0.003). Hypothermia was neither a risk factor for hospital mortality nor a predictive factor for staying longer in ICU. CONCLUSION: The prevalence of patient hypothermia on ICU arrival was high. Hypothermia at time of admission to the ICU was not an independent factor for mortality or for staying longer in ICU

Malinvaud on Wicksell’s legacy to capital theory: some critical remarks

This critique of Malinvaud’s article of 2003 on Wicksell’s legacy to capital theory focuses in particular on three points raised there. The first regards the given amount of existing capital that appears in Wicksell’s theory and its connection with his alleged “missing equation”, the second the particular notion of the marginal product of capital adopted by Malinvaud and the meaning of its equality with the rate of interest, and the third the concept of the average period of production taken by Malinvaud from Hicks and its inverse relation to the rate of interest

Src family kinase-mediated vesicle trafficking is critical for neutrophil basement membrane penetration

Leukocyte recruitment into inflamed tissue is highly dependent on the activation and binding of integrins to their respective ligands, followed by the induction of various signaling events within the cell referred to as outside-in signaling. Src family kinases (SFK) are the central players in the outside-in signaling process, assigning them a critical role for proper immune cell function. Our study investigated the role of SFK on neutrophil recruitment in vivo using Hck-/- Fgr-/- Lyn-/- mice, which lack SFK expressed in neutrophils. We show that loss of SFK strongly reduces neutrophil adhesion and post-arrest modifications in a shear force dependent manner. Additionally, we found that in the absence of SFK, neutrophils display impaired Rab27adependent surface mobilization of neutrophil elastase, VLA3 and VLA6 containing vesicles. This results in a defect in neutrophil vascular basement membrane penetration and thus strongly impaired extravasation. Taken together, we demonstrate that SFK play a role in neutrophil post-arrest modifications and extravasation during acute inflammation. These findings may support the current efforts to use SFK-inhibitors in inflammatory diseases with unwanted neutrophil recruitment. ©2020 Ferrata Storti Foundatio

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Application of real-time global media monitoring and ‘derived questions’ for enhancing communication by regulatory bodies:the case of human papillomavirus vaccines

Abstract Background The benefit-risk balance of vaccines is regularly debated by the public, but the utility of media monitoring for regulatory bodies is unclear. A media monitoring study was conducted at the European Medicines Agency (EMA) concerning human papillomavirus (HPV) vaccines during a European Union (EU) referral procedure assessing the potential causality of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) reported to the authorities as suspected adverse reactions. Methods To evaluate the utility of media monitoring in real life, prospective real-time monitoring of worldwide online news was conducted from September to December 2015 with inductive content analysis, generating ‘derived questions’. The evaluation was performed through the validation of the predictive capacity of these questions against journalists’ queries, review of the EMA’s public statement and feedback from EU regulators. Results A total of 4230 news items were identified, containing personal stories, scientific and policy/process-related topics. Explicit and implicit concerns were identified, including those raised due to lack of knowledge or anticipated once more information would be published. Fifty derived questions were generated and categorised into 12 themes. The evaluation demonstrated that providing the media monitoring findings to assessors and communicators resulted in (1) confirming that public concerns regarding CRPS and POTS would be covered by the assessment; (2) meeting specific information needs proactively in the public statement; (3) predicting all queries from journalists; and (4) altering the tone of the public statement with respectful acknowledgement of the health status of patients with CRSP or POTS. Conclusions The study demonstrated the potential utility of media monitoring for regulatory bodies to support communication proactivity and preparedness, intended to support trusted safe and effective vaccine use. Derived questions seem to be a familiar and effective format for presenting media monitoring results in the scientific-regulatory environment. It is suggested that media monitoring could form part of regular surveillance for medicines of high public interest. Future work is recommended to develop efficient monitoring strategies for that purpose

Buffered memory: a hypothesis for the maintenance of functional, virus-specific CD8(+) T cells during cytomegalovirus infection.

Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and both CD4(+) and CD8(+) CMV-specific T cells are essential. These virus-specific T cells persist in exceptionally large numbers during the infection, traffic into peripheral tissues and remain functional, making CMV an attractive vaccine vector for driving CMV-like T cell responses against recombinant antigens of choice. However, the mechanisms by which these T cells persist and differentiate while remaining functional are still poorly understood, and we have no means to promote their development in immune-compromised patients at risk for CMV disease. In this review, I will briefly summarize our current knowledge of CMV-specific CD8(+) T cells and propose a mechanism that may explain their maintenance and preservation of function during chronic infection

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Forest carbon sequestration:the impact of forest management

In this chapter, we describe alternative ways in which forests and forestry can help to mítigate climate change, along with the potential impact of these activities. The three carbon storage compartments should be considered inall impact estimates. Carbon content in living biomass is easily estimated via species-specific equations or by applying factors to oven-dry biomass weights (e.g.,lbañez et al.,2002, Herrero et al.,2011,Castaño and Bravo, 2012).Litter carbon content has been analysed in many studies on primary forest productivity, though information regarding the influence of forest management on litter carbon content is less abundant (Blanco et al., 2006). In the last decade,efforts have been made to assess soil carbon in forests, but studies on the effect of forest management on soils show discrepancies (Lindner and Karjalainen,2007).Hoover (2011), for example,found no difference in forest floor carbon stocks among stands subjected to partial or complete harvest treatments in the United States.Instituto Universitario de Gestión Forestal Sostenibl