Disability and Physical Therapy Services in Rural Nicaragua: A Pilot Study

The World Health Organization (WHO) estimates that 15% of the world’s population is living with disability, a large majority of which can be found in developing nations. Previous studies in Nicaragua have investigated the perceptions of disability among caregivers and noted limited access to rehabilitative services. However, the general knowledge and perceptions of physical therapy services in Nicaragua remains unclear. As a result, this pilot study sought to explore the local knowledge and perceptions of disability and physical therapy services and to characterize the sample from a remote area of northwestern Nicaragua. Participants were recruited using convenience sampling during multidisciplinary medical outreach clinics with OneWorld Health. A nine-question, face-to-face questionnaire was administered using local Nicaraguan translators certified in medical Spanish. A total of 101 participants [16 (15.8%) male, 85 (84.2%) female] were surveyed. A total of 70 (69.3%) report having no knowledge of physical therapy, 79 (78.2%) report no knowledge of anyone who has received physical therapy, and 89 (88.1%) were unaware of any physical therapy services available to them. A total of 94 (93.1%) report having musculoskeletal pain, and 89 (88.2%) report that medications are better at treating their pain. Our results describe the general perception and background knowledge of physical therapy in a unique region of Nicaragua. A very high burden of musculoskeletal complaints, especially neck, low back, and elbow/wrist/hand pain was noted. In large part, it appears that participants from this region have little knowledge of physical therapy and how these services may help them. This study demonstrates that there may be underlying contextual factors, still yet to be uncovered, that influence this communities’ knowledge, perception, and utilization of physical therapy services for physical disability

Hepatitis C virus production requires apolipoprotein A-I and affects its association with nascent low-density lipoproteins

Background/aims The life cycle of hepatitis C virus (HCV) is intimately linked to the lipid metabolism of the host. In particular, HCV exploits the metabolic machinery of the lipoproteins in several steps of its life cycle such as circulation in the bloodstream, cell attachment and entry, assembly and release of viral particles. However, the details of how HCV interacts with and influences the metabolism of the host lipoproteins are not well understood. A study was undertaken to investigate whether HCV directly affects the protein composition of host circulating lipoproteins. Methods A proteomic analysis of circulating very low-, low- and high-density lipoproteins (VLDL, LDL and HDL), isolated from either in-treatment naive HCV-infected patients or healthy donors (HD), was performed using two-dimensional gel electrophoresis and tandem mass spectrometry (MALDI-TOF/TOF). The results obtained were further investigated using in vitro models of HCV infection and replication. Results A decreased level of apolipoprotein A-I (apoA-I) was found in the LDL fractions of HCV-infected patients. This result was confirmed by western blot and ELISA analysis. HCV cellular models (JFH1 HCV cell culture system (HCVcc) and HCV subgenomic replicons) showed that the decreased apoA-I/LDL association originates from hepatic biogenesis rather than lipoprotein catabolism occurring in the circulation, and is not due to a downregulation of the apoA-I protein concentration. The sole non-structural viral proteins were sufficient to impair the apoA-I/LDL association. Functional evidence was obtained for involvement of apoA-I in the viral life cycle such as RNA replication and virion production. The specific siRNA-mediated downregulation of apoA-I led to a reduction in both HCV RNA and viral particle levels in culture. Conclusions This study shows that HCV induces lipoprotein structural modification and that its replication and production are linked to the host lipoprotein metabolism, suggesting apoA-I as a new possible target for antiviral therapy

Lymphocyte distribution and intrahepatic compartmentalization during HCV infection: a main role for MHC-unrestricted T cells

Hepatitis C virus (HCV) infection induces an acute and chronic liver inflammation through an immune-mediated pathway that may lead to cirrhosis and liver failure. Indeed, HCV-related hepatitis is characterized by a dramatic lymphocyte infiltrate into the liver which is mainly composed by HCV non-specific cells. Several data indicated that interferon (IFN)-gamma secretion by intrahepatic lymphocytes (IHL) may drive non-specific cell homing to the liver, inducing interferon inducible protein-10 (IP-10) production. An interesting hallmark of these IHL is the recruitment of lymphocytes associated with mechanisms of innate immunity, such as natural killer (NK), natural killer T (NKT) and gamma delta T lymphocytes. CD81 triggering on NK cell surface by the HCV envelope glycoprotein E2 was recently shown to inhibit NK cell function in the liver of HCV-infected persons, resulting in a possible mechanism contributing to the lack of virus clearance and to the establishment of chronic infection. In contrast, intrahepatic NKT cells restricted to CD1d molecules expressed on the hepatocyte surface may contribute to a large extent to liver damage. Finally, an increased frequency of T cells expressing the gamma delta T cell receptor (TCR) was observed in HCV-infected liver and recent observations indicate that intrahepatic gamma delta T cell activation could be directly induced by the HCV/E2 particle through CD81 triggering. These cells are not HCV specific, are able to kill target cells including primary hepatocytes and their ability to produce T helper (Th)1 cytokines is associated with a higher degree of liver disease. Together, CD1d/NKT and/or E2/CD81 interactions may play a major role in the establishment of HCV immunopathogenesis. In the absence of virus clearance, the chemokine-driven recruitment of lymphocytes with an innate cytotoxic behavior in the liver of HCV-infected patients may boost itself, leading to necroinflammatory and fibrotic liver disease

Experimental and numerical study on the fatigue behaviour of the shot-earth 772

The present research work is devoted to the mechanical, fracture and fatigue experimental characterization of the shot-earth 772, with a particular attention to its fatigue behaviour. To such an aim, an extensive experimental program has been carried out, consisting of: (i) flexural and compression tests, (ii) three-point bending fracture tests, and (iii) bending and compression cyclic tests. Moreover, a FE numerical model is employed to simulate both the above bending and compression cyclic tests, after the input data validation performed by simulating the above fracture tests. The numerical fatigue lifetimes are compared with the corresponding experimental ones for both pulsating bending and compression, highlighting the model accuracy. Finally, the contours of both the damage parameter and the reduced Young modulus are plotted showing the evolution of fatigue damage

Global Health and Disability: A Review and Call to Action for All Rehabilitation Professions

The World Health Organization estimates 15% of the world’s population is living with disability and anticipates an increase as the population ages. Disability is a growing healthcare concern and presents a tremendous burden to all nations. The world will soon need to provide health and rehabilitative care for an enormous number of persons with disability. The purpose of this article is to provide a brief narrative review pertaining to global health and rehabilitation, and to motivate the rehabilitation professions in taking immediate action through further investment in global health initiatives to manage both the current and projected burden of disability. A deficient level of research exists in global health by the rehabilitation professions and there is significant lag in their efforts when compared to other healthcare professions. The World Health Organization’s World Report on Disability (2011), Global Disability Action Plan 2014-2021, and the Global Burden of Disease study are pivotal bodies of work in this field. They serve as both a model and a challenge to affect large-scale global change among the rehabilitation professions. Collectively, an immediate effort is needed to bolster disability and rehabilitation research in developing nations, global rehabilitative outreach programs, and improve access to rehabilitative healthcare to persons with disability in order to fully address the magnitude of this matter

Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation

The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell-derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17-producing T cells (Th17). In vivo analysis of lymph nodes hosting T-cell priming in experimental autoimmune encephalomyelitis revealed activated MCs, Tregs, and Th17 cells displaying tight spatial interactions, further supporting the occurrence of an MC-mediated inhibition of Treg suppression in the establishment of Th17-mediated inflammatory responses. © 2009 by The American Society of Hematology

C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function

We describe a novel localization of C7 as a membrane-bound molecule on endothelial cells (ECs). Data obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis, Northern blot analysis, and mass spectrometry revealed that membrane- associated C7 (mC7) was indistinguish-able from soluble C7 and was associated with vimentin on the cell surface. mC7 interacted with the other late complement components to form membrane-bound TCC (mTCC). Unlike the soluble SC5b-9, mTCC failed to stimulate ECs to express adhesion molecules, to secrete IL-8, and to induce albumin leakage through a monolayer of ECs, and more importantly protected ECs from the proinflammatory effect of SC5b-9. Our data disclose the possibility of a novel role of mC7 that acts as a trap for the late complement components to control excessive inflammation induced by SC5b-9. \ua9 2009 by The American Society of Hematology