Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Occupational therapy workforce needs: a model for demand-based studies.

PURPOSE: To provide a model for assessing occupational therapy workforce needs by using a demand-based approach to determine current workforce status in the Northwest region. Regional information may have implications for addressing national occupational therapy service needs. METHOD: A questionnaire was sent to a proportional random sample of 234 facilities that hire occupational therapy practitioners. Data were collected in July-August 2003 using structured mailing and follow-up procedures. RESULTS: Response rate was 79%. Twenty-four percent reported occupational therapy vacancies and 11% occupational therapy assistant vacancies; 48% predicted an increase in occupational therapy positions in the next 2 years and 41% an increase in occupational therapy assistant positions. Sixty-three percent of respondents reported difficulty in hiring. DISCUSSION: This study identifies an occupational therapy workforce shortage in the Northwest. Management of a shortage is critical, for even short-term adjustments could lead to permanent changes in service provision. This study demonstrates the importance of current information on the status of the national workforce and serves as a model for future studies.     

High-resolution imaging of progressive articular cartilage degeneration.

The objective of this study was to develop and verify a new technique for monitoring the progression of osteoarthritis (OA) by combining a rat model with the imaging modality optical coherence tomography (OCT). Time-sequential, in vivo, OCT imaging was performed on the left femoral condyles of 12 Wistar rats following sodium-iodoacetic acid-induced OA progression. The right femoral condyles (untreated) were also imaged and served as controls. Imaging was performed on days 0, 10, 20, 30, and 60 with an OCT system capable of acquiring images at four frames per second and an axial resolution of 5 microm. Progressive changes were analyzed using an OA scoring system. OCT successfully identified progressive cartilage degeneration as well as alteration of the cartilage/bone interface. Significant changes to both of these structures were observed in the sodium-iodoacetic acid-injected condyles. Structural changes detected with OCT were confirmed histologically. OCT in combination with a well-known model used in arthritis research represents a powerful tool for following degenerative joint disease progression in a given animal by detecting changes to the cartilage/bone interface and articular cartilage.     

Cross-cultural validation of the Japanese version of the lung cancer subscale on the functional assessment of cancer therapy-lung.

BACKGROUND: The Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, which consists of a core questionnaire (the General Measure of FACT [FACT-G]) and a 9-item Additional Concerns comprised of a 7-item Lung Cancer Subscale (LCS), was developed in an English-speaking culture. The validation of the Japanese FACT-G was reported previously, and this report describes the cross-cultural validation of the LCS. METHODS: The Japanese version of the LCS was developed through an iterative forward-backward translation sequence used throughout the FACT Multilingual Translation Project. In evaluating psychometric performance, its construct validity was investigated with Cronbach's alpha coefficient and factor analysis. Clinical validities of a known-groups comparison and longitudinal validity were also investigated. RESULTS: The FACT-L was administered twice to 180 patients with lung cancer within 2 weeks. The Japanese LCS had borderline values for Cronbachs alpha coefficients (0.62-0.67). Factor analysis indicated that the LCS had the three dimensions of respiratory symptoms, appetite plus body weight, and clear thinking. For clinical validity, a known-groups comparison showed that the LCS could differentiate patients according to truth disclosure, as Japanese doctors sometimes do not fully inform terminally ill patients. However, responsiveness was not proved when performance status was used as an anchor, probably owing to the short interval between the administration of the two measures. CONCLUSION: The Japanese version of the LCS asked questions about multiple symptoms of patients with lung cancer, as did the original English LCS. The longitudinal clinical validity of the Japanese version should be investigated in future clinical trials.     

Role of aminophylline and allopurinol in the reformation of peritoneal adhesions

The role of aminophylline in the re-formation of peritoneal adhesions was considered in 23 rats. Since the adhesions were obtained, the animals were subsequently divided into three groups, the first one containing seven units, the others containing eight animals each. During the four days prior the surgery, allopurinol at the dose of 50 mg/kg/die was added to the regular ground laboratory chow in the animals of the second group; aminophylline at the dose of 40 mg/kg/die was administered four hours and immediately prior the surgery, to the animals of the third group. The adhesions that we observed, were graded and evaluated assigning them a score. At the moment of the lysis of adhesions, we observed the score of 2.71 +/- 1.11 in the first group, 3.12 +/- 1.13 in the second group, and 2.75 +/- 1.03 in the third one. Matching each group one another no statistically significant difference was found. At the end the experiment, we observed a score of 3.71 +/- 0.49 for the adhesions in the first group, 2 +/- 0.75 in the second group, and 3.87 +/- 0.35 in the third one. Matching these scores with those observed at the moment of their lysis, they appeared significantly higher in the animals of the first group (p less than 0.02) and of the third group (p less than 0.05), but they were lower in the second group (p less than 0.05). Such results indicate that the re-formation of peritoneal adhesions following their lysis is constant, that allopurinol decreases the intensity of the process, while aminophylline increases it.     

Preselection Thymocytes Are More Sensitive to T Cell Receptor Stimulation Than Mature T Cells

During T cell development, thymocytes which are tolerant to self-peptides but reactive to foreign peptides are selected. The current model for thymocyte selection proposes that self-peptide–major histocompatibility complex (MHC) complexes that bind the T cell receptor with low affinity will promote positive selection while those with high affinity will result in negative selection. Upon thymocyte maturation, such low affinity self-peptide–MHC ligands no longer provoke a response, but foreign peptides can incidentally be high affinity ligands and can therefore stimulate T cells. For this model to work, thymocytes must be more sensitive to ligand than mature T cells. Contrary to this expectation, several groups have shown that thymocytes are less responsive than mature T cells to anti-T cell receptor for antigen (TCR)/CD3 mAb stimulation. Additionally, the lower TCR levels on thymocytes, compared with T cells, would potentially correlate with decreased thymocyte sensitivity. Here we compared preselection thymocytes and mature T cells for early activation events in response to peptide–MHC ligands. Remarkably, the preselection thymocytes were more responsive than mature T cells when stimulated with low affinity peptide variants, while both populations responded equally well to the antigenic peptide. This directly demonstrates the increased sensitivity of thymocytes compared with T cells for TCR engagement by peptide–MHC complexes.     

Follicular dendritic cells (FDC) in retroviral infection: host/pathogen perspectives

Summary: Follicular dendritic cells (FDC) are found in the follicles of virtually all secondary lymphoid tissues. In health, these cells trap and retain antigens (Ag) in the form of immune complexes and preserve them for months in their native conformation. FDC thus serve as a long-term repository of extracellular Ag important for induction and maintenance of memory responses. In retroviral infection. FDC trap and retain large numbers of retroviral particles with profound effects on FDC. FDC-trapped retrovirus induces follicular hyperplasia, and conventional Ag trapped prior to infection are lost and new Ag cannot be trapped. Concomitantly, antibody-forming cells (AFC) specific for Ag lost from FDC decrease follow I by loss of specific serum antibody (Ab). Eventually, FDC die and follicular lysis occurs. From the pathogen perspective, binding to FDC is remarkably beneficial, bringing together virus and activated target cells that are highly susceptible to infection. Furthermore, FDC permit HIV to infect surrounding cells even in the presence of a vast excess of neutralizing Ab. Preliminary data suggest that FDC maintain virus infectivity - even when the virus cannot replicate. Thus retrovirus infection monopolizes FDC networks, thereby transforming the FDC Ag repository into a highly infectious retroviral reservoir.