Recently, a consensus process specified a core outcome set (COS) of domains to be assessed in each comparative effectiveness research and clinical practice related to acute postoperative pain. ...Physical function (PF) was one of these domains. The aim of this review was to investigate which patient-reported outcome measures (PROMs) are used to assess PF after total knee arthroplasty (TKA) in clinical trials and if they fulfil basic requirements for a COS of PROMs based on their psychometric properties.
A systematic review of randomized controlled trials and observational studies based on a search in MEDLINE, EMBASE and CENTRAL was undertaken. PROMs and performance measures were extracted and investigated, including evaluation of psychometric properties of PROMs based on COSMIN recommendations.
From initially 2896 identified records, 479 studies were included in the qualitative synthesis. Only 87 of these trials (18%) assessed PF using PROMs, whereas especially performance outcome measures were used in 470 studies (98%). Application of the 'COSMIN Risk-of-Bias-Box 1' to 13 of the 14 identified PROMs resulted in insufficient content validity of the included PROMs regarding the target population based on the inauguration or development articles.
Our data indicate that a patient-centred postoperative assessment of PF in pain-related clinical trials early after TKA is not common, even though patient-reported assessment is widely recommended. In addition, none of the applied PROMs shows content validity based on their inauguration or development articles for the assessment of postoperative pain-related PF after TKA.
A systematic search for patient-reported outcome measures assessing postoperative, pain-related physical function after total knee arthroplasty in clinical trials and assessment of their content validity revealed none that fulfilled requirements based on COSMIN recommendations.
Certain cationic antimicrobial peptides block the binding of LPS to LPS-binding protein and reduce the ability of LPS to induce the production of inflammatory mediators by macrophages. To gain a more ...complete understanding of how LPS activates macrophages and how cationic peptides influence this process, we have used gene array technology to profile gene expression patterns in macrophages treated with LPS in the presence or the absence of the insect-derived cationic antimicrobial peptide CEMA (cecropin-melittin hybrid). We found that CEMA selectively blocked LPS-induced gene expression in the RAW 264.7 macrophage cell line. The ability of LPS to induce the expression of >40 genes was strongly inhibited by CEMA, while LPS-induced expression of another 16 genes was relatively unaffected. In addition, CEMA itself induced the expression of a distinct set of 35 genes, including genes involved in cell adhesion and apoptosis. Thus, CEMA, a synthetic alpha-helical peptide, selectively modulates the transcriptional response of macrophages to LPS and can alter gene expression in macrophages.
Aim
In the present study, we aimed to elucidate the effects of chronic vasopressin administration on renal medullary oxygen levels.
Methods
Adult Sprague Dawley or vasopressin‐deficient Brattleboro ...rats were treated with the vasopressin V2 receptor agonist, desmopressin (5 ng/h; 3d), or its vehicle via osmotic minipumps. Immunostaining for pimonidazole and the transcription factor HIF‐1α (hypoxia‐inducible factor‐1α) were used to identify hypoxic areas. Activation of HIF‐target gene expression following desmopressin treatment was studied by microarray analysis.
Results
Pimonidazole staining was detected in the outer and inner medulla of desmopressin‐treated rats, whereas staining in control animals was weak or absent. HIF‐1α immunostaining demonstrated nuclear accumulation in the papilla of desmopressin‐treated animals, whereas no staining was observed in the controls. Gene expression analysis revealed significant enrichment of HIF‐target genes in the group of desmopressin‐regulated gene products (P = 2.6*10−21). Regulated products included insulin‐like growth factor binding proteins 1 and 3, angiopoietin 2, fibronectin, cathepsin D, hexokinase 2 and cyclooxygenase 2.
Conclusion
Our results demonstrate that an activation of the renal urine concentrating mechanism by desmopressin causes renal medullary hypoxia and an upregulation of hypoxia‐inducible gene expression.
The activating cytotoxicity receptor NKG2D binds to stress‐regulated molecules encoded by the major histocompatibility complex class I chain‐related (MIC) and UL‐16‐binding protein (ULBP)/retinoic ...acid early transcript (RAET) gene family. To assess whether acute allograft rejection leads to an induction of these inducible ligands and their receptor NKG2D, we examined the mRNA profiles in kidney transplant biopsies. Expression levels were correlated with the incidence of acute rejection (aRx) episodes and chronic allograft nephropathy (CAN) proven by histology. Whereas MICA, ULBP1/3 and RAET1‐E did not display heightened gene expression, elevated levels of NKG2D mRNA could be associated with aRx (p < 0.001). Immunohistology of kidney biopsies diagnosed with aRx revealed NKG2D+ cells in tubulointerstitial areas positive for CD8+ cells. Most importantly, elevated levels of NKG2D mRNA were associated with restricted long‐term graft function assessed by the glomerular filtration rate at 6, 12 and 18 months posttransplantation. Induced NKG2D mRNA expression was still observable in biopsies diagnosed with CAN (p < 0.001), demonstrating a higher sensitivity and specificity compared to CD3, granzyme B and granulysin mRNA measurement. Significant elevated levels of NKG2D mRNA could be further detected in urine sediment prior to aRx, suggesting this receptor as a new candidate marker for the diagnosis of acute and chronic allograft rejection.
The activating natural cytotoxicity receptor NKG2D could be detected at both mRNA and protein level in biopsies diagnosed with acute and chronic nephropathy.
In cancer patients, pain is one of the main symptoms and especially in the late stages of disease, these symptoms can be associated with considerable suffering. In psycho-oncology, preliminary ...psychological therapies targeting cancer pain have been tested; however, a systematic review of available interventions is lacking, especially considering their dissemination, evidence base, study quality, and the comparison with established treatments. Therefore, the aim of the current study is to systematically review the current research on psychological treatments for pain in cancer patients.
During May 2014, MEDLINE, PsycINFO, PSYNDEX, and CENTRAL databases were searched. Psychological treatments for pain in adult cancer patients studied in randomized, controlled trials (RCTs) and referring to pain as primary or secondary outcome were included. After examination for inclusion, structured data extraction and assessment followed. Data were synthesized narratively.
In the review, 32 RCTs were included. Studies mainly referred to patients with breast cancer or patients in earlier stages of the disease. The methodological quality of included studies was heterogeneous. Most commonly, short interventions were delivered by nurses in out-patient settings. Interventions including education and relaxation techniques were utilized most often, followed by interventions with behavioral or cognitive components.
A need for research persists regarding efficacy of current psychotherapeutic interventions, or the role of mediator variables (e. g., coping) on pain perception in cancer patients. Studies with high methodological quality which comprehensively and transparently report on interventions and designs are lacking.
The route of initial entry influences how host cells respond to intracellular pathogens. Recent studies have demonstrated that a wide variety of pathogens target lipid microdomains in host cell ...membranes, known as lipid rafts, to enter host cells as an infectious strategy.
Host responses during the later stages of Salmonella- macrophage interactions are critical to controlling infection but have not been well characterized. After 24 h of infection, nearly half of ...interferon-γ-primed murine RAW 264.7 macrophage-like cells infected by Salmonella enterica serovar Typhimurium contained filamentous bacteria. Bacterial filamentation indicates a defect in completing replication and has been previously observed in bacteria responding to a variety of stresses. To understand whether macrophage gene expression was responsible for this effect on Salmonella Typhimurium replication, we used gene arrays to profile interferon-γ-primed RAW 264.7 cell gene expression following infection. We observed an increase in MEK1 kinase mRNA at 8 h, an increase in MEK protein at 24 h, and measured phosphorylation of MEK's downstream target kinase, ERK1/2, throughout the 24-h infection period. Treatment of cells with MEK kinase inhibitors significantly reduced numbers of filamentous bacteria observed within macrophages after 24 h and increased the number of intracellular colony-forming units. Phagocyte NADPH oxidase inhibitors and antioxidants also significantly reduced bacterial filamentation. Either MEK kinase or phagocyte oxidase inhibitors could be added 4–8 h after infection and still significantly decrease bacterial filamentation. Oxidase activity appears to mediate bacterial filamentation in parallel to MEK kinase signaling, while inducible nitric-oxide synthase inhibitors had no significant effect on bacterial morphology. In summary, Salmonella Typhimurium infection of interferon-γ-primed macrophages triggers a MEK kinase cascade at later infection times, and both MEK kinase and phagocyte NADPH oxidase activity impair bacterial replication. These two signaling pathways mediate a host bacteriostatic pathway and may play an important role in innate host defense against intracellular pathogens.
Changes in macrophage phenotype induced during infection result from the recognition of bacterial products as well as the action of bacterial virulence factors. We used the unprecedented opportunity ...provided by gene arrays to simultaneously study the expression of hundreds of genes during Salmonella typhimurium infection of macrophages and to assess the contribution of the bacterial virulence factor, LPS, in initiating the host responses to Salmonella. We found that S. typhimurium infection caused significant changes in the expression of numerous genes encoding chemokines, cell surface receptors, signaling molecules, and transcriptional activators at 4 h postinfection of the RAW 264.7 murine macrophage cell line. Our results revealed changes in the expression of several genes that had not been previously implicated in the host responses to S. typhimurium infection, as well as changes in the expression of several genes previously shown to be regulated by S. typhimurium infection. An overlapping spectrum of genes was expressed in response to virulent S. typhimurium and purified S. typhimurium LPS, reinforcing the major role of this surface molecule in stimulating the early response of macrophages to bacterial infection. The macrophage gene expression profile was further altered by activation with IFN-gamma, indicating that host cell responses depend on the activation state of the cell.
: Kaposi's sarcoma (KS) is a vascular neoplasm typically observed in the immunocompromised patient populations, such as acquired immunodeficiency syndrome or transplant patients. KS can appear ...simultaneously at multiple sites as red to purple, maculo‐papular or nodular cutaneous lesions sometimes showing a visceral extension. Sirolimus, an immunosuppressive agent with potent antitumor activity, has been effective in combating post‐transplant KS. However, an aggressive regimen of immunosuppression for therapy of severe acute rejection episodes may abolish the antitumor effects of sirolimus. The following is a description of KS development under immunosuppressive therapy with sirolimus, and the successful treatment of KS lesions utilizing the topical application of imiquimod 5% cream, an immune response modifier.
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