Chronic Exposure to HIV-Derived Protein Tat Impairs Endothelial Function via Indirect Alteration in Fat Mass and Nox1-Mediated Mechanisms in Mice.

People living with human immunodeficiency virus (HIV) (PLWH) have increased risk for atherosclerosis-related cardiovascular disease (CVD), the main cause of death in this population. Notwithstanding, the mechanisms of HIV-associated vascular pathogenesis are not fully elucidated. Therefore, we sought to determine whether HIV-regulatory protein Tat mediates HIV-induced endothelial dysfunction via NADPH oxidase 1 (Nox1)-dependent mechanisms. Body weight, fat mass, leptin levels, expression of reactive oxygen species (ROS)-producing enzymes and vascular function were assessed in C57BL/6 male mice treated with Tat for 3 days and 4 weeks. Aortic rings and human endothelial cells were also treated with Tat for 2-24 h in ex vivo and in vitro settings. Chronic (4 weeks) but not acute (3 days and 2-24 h) treatment with Tat decreased body weight, fat mass, and leptin levels and increased the expression of Nox1 and its coactivator NADPH oxidase Activator 1 (NoxA1). This was associated with impaired endothelium-dependent vasorelaxation. Importantly, specific inhibition of Nox1 with GKT771 and chronic leptin infusion restored endothelial function in Tat-treated mice. These data rule out direct effects of HIV-Tat on endothelial function and imply the contribution of reductions in adipose mass and leptin production which likely explain upregulated expression of Nox1 and NoxA1. The Nox1 and leptin system may provide potential targets to improve vascular function in HIV infection-associated CVD.

Strategies to establish and maintain trust when working in immigrant communities.

The nursing profession has historically advocated a strong commitment to social justice. As immigration issues have become increasingly politicized, nurses are being called upon to integrate principles of social justice when caring for immigrant populations. Nurse researchers have a particular challenge in winning and maintaining trust in immigrant communities. Data from several studies suggest that erosion of trust in the health care system, due to fears of detention and deportation, is resulting in adverse health outcomes among immigrants. The purpose of this article is to discuss a variety of strategies to establish and maintain trust in immigrant communities. These strategies were developed to maintain an academic-community partnership focused around obesity prevention among Mexican immigrant families. Strategies included: (a) Conceptualize trust as a dynamic continuum; (b) recognize the scope and impact of the stressors; (c) separate fact versus fiction; (d) identify deportation-related stressors and community responses; (e) manage trust and mistrust issues; (f) build bridges; and (g) establish a positive presence. Nurses are well poised to intervene to repair the damaged trust between immigrant communities and the health care system, using community-based participatory methods.

Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia.

Platelet counts (PC) estimate bleeding risk in Immune Thrombocytopenia (ITP). We investigated whether measures of thromboelastometry and absolute immature platelet fraction (A-IPF) would correlate better with acute bleeding score (ABS) than PC or mean platelet volume (MPV). Simultaneous determination of ABS, complete blood count and thromboelastometry was performed in 141 ITP patients; 112 underwent A-IPF testing. Subgroup analyses were performed for paediatric subjects, PC <60 × 10(9) /l and <30 × 10(9) /l. PC significantly inversely correlated with ABS in all subjects, PC <30 × 10(9) /l and total paediatric cohort. MPV did not correlate with ABS in any subgroup. Thromboelastometry measures of clot firmness, but not PC, significantly correlated with ABS in all subjects with PC <60 × 10(9) /l, and children with PC <60 × 10(9) /l and <30 × 10(9) /l. A-IPF demonstrated stronger correlation with ABS than did PC among all subjects, those with PC <60 × 10(9) /l, all children and children with PC <30 × 10(9) /l (r = -0·37; r = -0·34; r = -0·44; r = -0·60) versus ABS with PC (r = -0·36; ns; r = -0·32; ns). Stronger correlations of both thromboelastometry measures of clot firmness and A-IPF than PC with ABS suggest factors beyond PC, i.e. related to platelet function, contribute to ITP bleeding pathophysiology. Thromboelastometry, A-IPF and ABS can be incorporated into routine or acute visits.

Swallowing Kinematic Differences Across Frozen, Mixed, and Ultrathin Liquid Boluses in Healthy Adults: Age, Sex, and Normal Variability.

Purpose: The aim of this study was to examine the effects of frozen and mixed-consistency boluses on the swallowing physiology of younger and older adults. We also aimed to quantify factors that lead to increased variability in swallowing outcomes (i.e., age, sex, bolus type). Method: Forty-one healthy adults (18-85 years old) swallowed 5 blocks of 5 different boluses: 10-ml ultrathin liquid, a teaspoon of iced barium, a teaspoon of room-temperature pudding, a teaspoon of frozen pudding, and ultrathin barium with chocolate chips. All data were recorded with videofluoroscopy and underwent detailed timing kinematic measurements. Results: Neither barium ice nor frozen pudding sped up swallow responses. Many healthy adults initiated swallowing with the bolus as deep as the pyriform sinuses. Swallowing temporal kinematics for ultrathin liquid consistencies are most different from all others tested, requiring the best possible physiological swallowing performance in younger and older healthy individuals (i.e., faster reaction times, longer durations) compared with other bolus types tested. In each measure, older adults had significantly longer durations compared with the younger adults. More variability in swallowing kinematics were seen with age and laryngeal vestibule kinematics. Conclusion: This study provides important contributions to the literature by clarifying normal variability within a wide range of swallowing behaviors and by providing normative data from which to compare disordered populations.

The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by regional vasomotor dysregulation.

Fibromyalgia syndrome (FMS) is a condition of chronic muscle pain and fatigue of unknown etiology and pathogenesis. There is limited support for the various hypotheses espoused to account for the manifestations of FMS, including immunogenic, endocrine, and neurological mechanisms. Treatment, partially effective at best, is directed toward symptomatic relief without the benefit of targeting known, underlying pathology. A noteworthy commonality among partially effective therapies is a vasodilatory effect. This is true both of conventional treatments, unconventional treatments such as intravenous micronutrient therapy, and lifestyle treatments, specifically graduated exercise. The pain of fibromyalgia is described in terms suggestive of the pain in muscles following extreme exertion and anaerobic metabolism. Taken together, these characteristics suggest that the pain could be induced by vasomotor dysregulation, and vasoconstriction in muscle, leading to low-level ischemia and its metabolic sequelae. Vasodilatory influences, including physical activity, relieve the pain of FMS by increasing muscle perfusion. There are some preliminary data consistent with this hypothesis, and nothing known about FMS that refutes it. The hypothesis that the downstream cause of FMS symptoms is muscle hypoperfusion due to regional vasomotor dysregulation has clear implications for treatment; is testable with current technology; and should be investigated.

The Relationship Between Submental Surface Electromyography and Hyo-Laryngeal Kinematic Measures of Mendelsohn Maneuver Duration.

PURPOSE: The Mendelsohn Maneuver (MM) is a commonly prescribed technique that is taught to individuals with dysphagia to improve swallowing ability. Due to cost and safety concerns associated with videofluoroscopy (VFS) use, submental surface electromyography (ssEMG) is commonly used in place of VFS to train the MM in clinical and research settings. However, it is unknown whether ssEMG accurately reflects the prolonged hyo-laryngeal movements required for execution of the MM. The primary goal of this study was to examine the relationship among ssEMG duration, duration of laryngeal vestibule closure, and duration of maximum hyoid elevation during MM performance. METHOD: Participants included healthy adults and patients with dysphagia due to stroke. All performed the MM during synchronous ssEMG and VFS recording. RESULTS: Significant correlations between ssEMG duration and VFS measures of hyo-laryngeal kinematic durations during MM performance ranged from very weak to moderate. None of the correlations in the group of stroke patients reached statistical significance. CONCLUSION: Clinicians and researchers should consider that the MM involves novel hyo-laryngeal kinematics that may be only moderately represented with ssEMG. Thus, there is a risk that these target therapeutic movements are not consistently being trained.

Deep vein thrombosis: thrombolysis in the pediatric population.

Improved medical treatment options have advanced pediatric care but often necessitate both invasive vascular procedures and venous access predisposing these patients to venous thrombotic events. Although pediatric deep vein thrombosis (DVT) is an increasingly recognized phenomenon, high-quality evidence for its antithrombotic treatment in general remains limited, and even more so with respect to thrombolytic therapy. Correspondingly, current American College of Chest Physicians guidelines discourage the routine use of thrombolytic therapy for pediatric DVT; by contrast, American Heart Association guidelines suggest consideration for such therapy in young patients in whom the balance of benefit to risk may be most favorable. The developing hemostatic system and relative rarity of thrombotic events have historically posed impediments to the design and conduction of prospective clinical trials of thrombolysis in children. This narrative review summarizes available information regarding thrombolytic therapy for pediatric DVT.

Transmural heterogeneity of calcium activity and mechanical function in the canine left ventricle.

Although electrical heterogeneity within the ventricular myocardium has been the focus of numerous studies, little attention has been directed to the mechanical correlates. This study examines unloaded cell shortening, Ca(2+) transients, and inward L-type Ca(2+) current (I(Ca,L)) characteristics of epicardial, endocardial, and midmyocardial cells isolated from the canine left ventricle. Unloaded cell shortening was recorded using a video edge detector, Ca(2+) transients were measured in cells loaded with 15 microM fluo-3 AM and voltage and current-clamp recordings were obtained using patch-clamp techniques. Time to peak and latency to onset of contraction were shortest in epicardial and longest in endocardial cells; midmyocardial cells displayed an intermediate time to peak. When contraction was elicited using uniform voltage-clamp square waves, epicardial versus endocardial distinctions persisted and midmyocardial cells displayed a time to peak comparable to that of epicardium. The current-voltage relationship for I(Ca,L) and fluorescence-voltage relationship were similar in the three cell types when quantitated using square pulses. However, peak I(Ca,L) and total charge were significantly larger when an epicardial versus endocardial action potential waveform was used to elicit the current under voltage-clamp conditions. Sarcoplasmic reticulum Ca(2+) content, assessed by rapid application of caffeine, was largest in epicardial cells and contributed to a faster time to peak. Our data point to important differences in calcium homeostasis and mechanical function among the three ventricular cell types. These differences serve to synchronize contraction across the ventricular wall. Although these distinctions are conferred in part by differences in electrical characteristics of the three cell types, intrinsic differences in excitation-contraction coupling are evident.