Increased Cardiovascular Risk Associated with Chemical Sensitivity to Perfluoro-Octanoic Acid: Role of Impaired Platelet Aggregation

Perfluoro\u2013alkyl substances (PFAS), particularly perfluoro\u2013octanoic acid (PFOA), are persisting environmental chemicals showing bioaccumulation in human tissues. Recently, exposure to PFAS has been associated with increased prevalence of cardiovascular diseases (CVDs). However, a causal role of PFAS in atherosclerosis pathogenesis is under-investigated. Here, we investigated the effect of PFOA exposure on platelets\u2019 function, a key player in atherosclerosis process. PFOA accumulation in platelets was evaluated by liquid chromatography-mass spectrometry. Changes in platelets\u2019 membrane fluidity and activation after dose-dependent exposure to PFOA were evaluated by merocyanine 540 (MC540) and anti P-Selectin immune staining at flow cytometry, respectively. Intracellular calcium trafficking was analyzed with Fluo4M probe, time-lapse live imaging. Platelets\u2019 aggregation state was also evaluated with Multiplate\uae aggregometry analyzer in 48 male subjects living in a specific area of the Veneto region with high PFAS environmental pollution, and compared with 30 low-exposure control subjects. Platelets\u2019 membrane was the major target of PFOA, whose dose-dependent accumulation was associated in turn with increased membrane fluidity, as expected by a computational model; increased activation at resting condition; and both calcium uptake and aggregation upon activation. Finally, exposed subjects had higher serum and platelets levels of PFOA, together with increased aggregation parameters at Multiplate\uae, compared with controls. These data help to explain the emerging association between PFAS exposure and CVD

The missing link in human security research: dialogue and insecurity in Kosovo

The concept of human security continues to defy definitional clarity at the same time as it is being embraced by policymakers. This article proposes a practice-grounded approach that focuses on investigative method as a way of linking conceptual understanding of human security to the research process. Probing the 'actorness' of individuals in volatile contexts, a study of insecurity in Kosovo shows how dialogue can be applied as a research tool to access and assess human security in the field. Dialogue permits recognition of the power of the researched in the construction of knowledge of security, and accordingly reflects the conceptual shift represented by human security from states to communities and individuals. In the Kosovo study, dialogic research captured individual agency in the face of pervasive insecurity and revealed contradictory effects of such agency. This led to the formulation of the idea of the multidirectional security marker as a means of understanding experiences of insecurity in relation to strategies to combat it. Three such markers - self-reliance, informality and community solidarity - emerged and are analysed in the case of Kosovo. Simultaneously denoting restrictions on people's security and possibilities for overcoming those very same limitations, the markers express the agential dimension of human security and show how agency and security interact

Increased Fatigability of the Gastrocnemius Medialis Muscle in Individuals with Intermittent Claudication

AbstractBackgroundWe attempted to identify possible differences in the contractility of the gastrocnemius medialis (GM) muscle between healthy controls and individuals with peripheral arterial disease (PAD) and intermittent lower-limb claudication.MethodsThe GM muscles of 17 PAD patients and 17 healthy controls were examined with tensiomyography. Single or multiple electrical impulses were used to trigger muscle contractions, and the time and amplitude of contractions were measured.ResultsAfter single-impulse stimulation, the GM muscles of PAD patients showed significantly shorter contraction times (P < 0.001) than the GM muscles of controls. During 1 min of repetitive electrical stimulation, the contraction velocity of the controls' GM muscles typically showed a sustained increase throughout the stimulation period, whereas in PAD patients, a significant decrease in contraction velocity was observed after 30 s. The onset of muscle fatigue was unrelated to the ankle brachial index (ABI) of the examined leg. When the legs of PAD patients with higher and lower ABIs were compared to each other, no significant differences were found regarding the time and amplitude of contraction after single-impulse stimulation.ConclusionsThe GM muscles of individuals with intermittent claudication contract more quickly and fatigue earlier than the GM muscles of healthy controls. Because the contraction time, measured with tensiomyography, reflects the individual's muscle fibre composition, our findings may reflect a shift from type I fibres to type II fibres in the GM muscles of PAD patients. Our data support the idea that calf myopathy is present in claudication-prone patients and, in part, determines the clinical manifestations of PAD