REHABILITATION OF PATIENTS WITH INTEGRATED JOINT ENDOPROSTHESIS

Trajanje i izdržljivost endoproteza drastično se povećava te ih većina bez problema izdrži preko deset godina. Ipak, četiri glavne grupe uzročnika mogu skratiti vijek trajanja proteza a to su: 1)labavljenje proteze odnosno eng. aseptic loosening, 2) bakterijske infekcije, 3) periprotetička osifikacija, 4) artrofibroza. U svrhu sprječavanja navedenih problema od ključne važnosti je pravilno rehabilitirati bolesnika nakon ugradnje endoproteze te kvalitetno educirati bolesnika o indiciranim i kontraindiciranim elementima rehabilitacijskog programa.Prosthesis durability has drastically increased and today most of them can be used for more than 10 years. However,there are four pathogenetic groups of diseases that can decrease prosthesis durability: (1) periprosthetic aseptic loosening (2) bacterial infection (3) periprosthetic ossification, and (4) arthrofibrosis. In order to avoid stated problems it is essential to properly rehabilitate patients after joint replacement. It is also very important to educate the patient of indicated as well as contraindicated elements of the rehabilitation program

REHABILITATION OF PATIENTS WITH INTEGRATED JOINT ENDOPROSTHESIS

Trajanje i izdržljivost endoproteza drastično se povećava te ih većina bez problema izdrži preko deset godina. Ipak, četiri glavne grupe uzročnika mogu skratiti vijek trajanja proteza a to su: 1)labavljenje proteze odnosno eng. aseptic loosening, 2) bakterijske infekcije, 3) periprotetička osifikacija, 4) artrofibroza. U svrhu sprječavanja navedenih problema od ključne važnosti je pravilno rehabilitirati bolesnika nakon ugradnje endoproteze te kvalitetno educirati bolesnika o indiciranim i kontraindiciranim elementima rehabilitacijskog programa.Prosthesis durability has drastically increased and today most of them can be used for more than 10 years. However,there are four pathogenetic groups of diseases that can decrease prosthesis durability: (1) periprosthetic aseptic loosening (2) bacterial infection (3) periprosthetic ossification, and (4) arthrofibrosis. In order to avoid stated problems it is essential to properly rehabilitate patients after joint replacement. It is also very important to educate the patient of indicated as well as contraindicated elements of the rehabilitation program

“FRECUENCIA Y USO EN DIFERENTES PATOLOGÍAS DE LA TÉCNICA DE FACILITACIÓN NEUROMUSCULAR PROPIOCEPTIVA POR LOS ALUMNOS DE LA LICENCIATURA EN TERAPIA FÍSICA DE LA UNIVERSIDAD AUTÓNOMA DEL ESTADO DE MÉXICO, 2011”

La finalidad de este trabajo es que se reconozca que la técnica de Facilitación Neuromuscular Propioceptiva no se utiliza demasiado en el ámbito de la fisioterapia, a comparación de cómo debería utilizarse, pues se deja un poco de lado esta, ya que se emplean otras técnicas, pero esta no tanto. Debería dársele más importancia a la técnica de Facilitación Neuromuscular Propioceptiva, pues en este trabajo se demostrará que se puede llevar a cabo en distintas patologías, y que es una muy buena opción de tratamiento

Malaria parasite interactions with the human host

The interaction between the malaria parasite and the human host involves a number of interactions that result in the parasite evading the human immune system. Since the stages of the malaria lifecycle are complex, this allows the use of various immune evasion strategies by the malaria parasite and has major implications in the development of a vaccine for malaria endemic areas. The present review highlights key host:parasite interactions. Plasmodia puts selection pressure on human gene frequencies, and studies into host genetic factors such as the Duffy blood group and sickle cell anaemia offer insight into the host- parasite relationship. In addition, parasite interactions with the different effector arms of the immune system can result in altered peptide ligand (APL) antagonism which alters the immune response from a pro- to an anti-inflammatory T cell response. Recent insights into the interaction between professional antigen presenting cells, dendritic cells (DCs), and malaria parasites is discussed in detail

Platelets kill circulating parasites of all major Plasmodium species in human malaria

Platelets are understood to assist host innate immune responses against infection, although direct evidence of this function in any human disease, including malaria, is unknown. Here we characterized platelet–erythrocyte interactions by microscopy and flow cytometry in patients with malaria naturally infected with Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium knowlesi. Blood samples from 376 participants were collected from malaria-endemic areas of Papua, Indonesia, and Sabah, Malaysia. Platelets were observed binding directly with and killing intraerythrocytic parasites of each of the Plasmodium species studied, particularly mature stages, and was greatest in P vivax patients. Platelets preferentially bound to the infected more than to the uninfected erythrocytes in the bloodstream. Analysis of intraerythrocytic parasites indicated the frequent occurrence of platelet-associated parasite killing, characterized by the intraerythrocytic accumulation of platelet factor-4 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling of parasite nuclei (PF4+TUNEL+ parasites). These PF4+TUNEL+ parasites were not associated with measures of systemic platelet activation. Importantly, patient platelet counts, infected erythrocyte-platelet complexes, and platelet-associated parasite killing correlated inversely with patient parasite loads. These relationships, taken together with the frequency of platelet-associated parasite killing observed among the different patients and Plasmodium species, suggest that platelets may control the growth of between 5% and 60% of circulating parasites. Platelet–erythrocyte complexes made up a major proportion of the total platelet pool in patients with malaria and may therefore contribute considerably to malarial thrombocytopenia. Parasite killing was demonstrated to be platelet factor-4-mediated in P knowlesi culture. Collectively, our results indicate that platelets directly contribute to innate control of Plasmodium infection in human malaria.This work was supported by the Australian National Health and Medical Research Council (Grants #1037304, #1045156, #490037, #605524, #1047082, #1047090, and #1066502, and Fellowships to N.M.A. [#1042072, #1135820], B.E.B. [#1088738], and M.J.G. [#1138860]), the Australian Research Council (grant #120100061), the Wellcome Trust (Fellowships to R.N.P. [#200909] and J.R.P. [#099875]), the Singapore National Medical Research Council (Award to T.W.Y. [CSA INV 15nov007]), and the Australian Department of Foreign Affairs and Trade

Transcriptional profiling and immunophenotyping show sustained activation of blood monocyte in subpatent Plasmodium falciparum infection

Objectives Malaria, caused by Plasmodium infection, remains a major global health problem. Monocytes are integral to the immune response, yet their transcriptional and functional responses in primary Plasmodium falciparum infection and in clinical malaria are poorly understood. Methods The transcriptional and functional profiles of monocytes were examined in controlled human malaria infection with P. falciparum blood stages and in children and adults with acute malaria. Monocyte gene expression and functional phenotypes were examined by RNA sequencing and flow cytometry at peak infection and compared to pre‐infection or at convalescence in acute malaria. Results In subpatent primary infection, the monocyte transcriptional profile was dominated by an interferon (IFN) molecular signature. Pathways enriched included type I IFN signalling, innate immune response and cytokine‐mediated signalling. Monocytes increased TNF and IL‐12 production upon in vitro toll‐like receptor stimulation and increased IL‐10 production upon in vitro parasite restimulation. Longitudinal phenotypic analyses revealed sustained significant changes in the composition of monocytes following infection, with increased CD14+CD16− and decreased CD14−CD16+ subsets. In acute malaria, monocyte CD64/FcγRI expression was significantly increased in children and adults, while HLA‐DR remained stable. Although children and adults showed a similar pattern of differentially expressed genes, the number and magnitude of gene expression change were greater in children. Conclusions Monocyte activation during subpatent malaria is driven by an IFN molecular signature with robust activation of genes enriched in pathogen detection, phagocytosis, antimicrobial activity and antigen presentation. The greater magnitude of transcriptional changes in children with acute malaria suggests monocyte phenotypes may change with age or exposure

Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation

Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro. Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR < 0.07). There was no upregulation of co-stimulatory molecules CD86, CD80, CD40, and reduced surface expression of HLA-DR and CD123 (IL-3R-α). pDC loss from the circulation was associated with active caspase-3, suggesting pDC apoptosis during primary infection. pDC remained responsive to TLR stimulation, producing IFN-α and upregulating HLA-DR, CD86, CD123 at peak-infection. In clinical malaria, pDC retained HLA-DR but reduced CD123 expression compared to convalescence. These data demonstrate pDC retain function during a first blood-stage P. falciparum exposure despite sub-microscopic parasitaemia downregulating HLA-DR. The lack of evident pDC activation in both early infection and malaria suggests little response of circulating pDC to infection

Protective Antibody and CD8+ T-Cell Responses to the Plasmodium falciparum Circumsporozoite Protein Induced by a Nanoparticle Vaccine

Background The worldwide burden of malaria remains a major public health problem due, in part, to the lack of an effective vaccine against the Plasmodium falciparum parasite. An effective vaccine will most likely require the induction of antigen specific CD8+ and CD4+ T-cells as well as long-lasting antibody responses all working in concert to eliminate the infection. We report here the effective modification of a self-assembling protein nanoparticle (SAPN) vaccine previously proven effective in control of a P. berghei infection in a rodent model to now present B- and T-cell epitopes of the human malaria parasite P. falciparum in a platform capable of being used in human subjects. Methodology/Principal Findings To establish the basis for a SAPN-based vaccine, B- and CD8+ T-cell epitopes from the P. falciparum circumsporozoite protein (PfCSP) and the universal CD4 T-helper epitope PADRE were engineered into a versatile small protein (∼125 amino acids) that self-assembles into a spherical nanoparticle repetitively displaying the selected epitopes. P. falciparum epitope specific immune responses were evaluated in mice using a transgenic P. berghei malaria parasite of mice expressing the human malaria full-length P. falciparum circumsporozoite protein (Tg-Pb/PfCSP). We show that SAPN constructs, delivered in saline, can induce high-titer, long-lasting (1 year) protective antibody and poly-functional (IFNγ+, IL-2+) long-lived central memory CD8+ T-cells. Furthermore, we demonstrated that these Ab or CD8+ T–cells can independently provide sterile protection against a lethal challenge of the transgenic parasites. Conclusion The SAPN construct induces long-lasting antibody and cellular immune responses to epitope specific sequences of the P. falciparum circumsporozoite protein (PfCSP) and prevents infection in mice by a transgenic P. berghei parasite displaying the full length PfCSP

Regulatory T Cell Induction during Plasmodium chabaudi Infection Modifies the Clinical Course of Experimental Autoimmune Encephalomyelitis

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is used as an animal model for human multiple sclerosis (MS), which is an inflammatory demyelinating autoimmune disease of the central nervous system characterized by activation of Th1 and/or Th17 cells. Human autoimmune diseases can be either exacerbated or suppressed by infectious agents. Recent studies have shown that regulatory T cells play a crucial role in the escape mechanism of Plasmodium spp. both in humans and in experimental models. These cells suppress the Th1 response against the parasite and prevent its elimination. Regulatory T cells have been largely associated with protection or amelioration in several autoimmune diseases, mainly by their capacity to suppress proinflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we verified that CD4(+)CD25(+) regulatory T cells (T regs) generated during malaria infection (6 days after EAE induction) interfere with the evolution of EAE. We observed a positive correlation between the reduction of EAE clinical symptoms and an increase of parasitemia levels. Suppression of the disease was also accompanied by a decrease in the expression of IL-17 and IFN-γ and increases in the expression of IL-10 and TGF-β1 relative to EAE control mice. The adoptive transfer of CD4(+)CD25(+) cells from P. chabaudi-infected mice reduced the clinical evolution of EAE, confirming the role of these T regs. CONCLUSIONS/SIGNIFICANCE: These data corroborate previous findings showing that infections interfere with the prevalence and evolution of autoimmune diseases by inducing regulatory T cells, which regulate EAE in an apparently non-specific manner