Machine Learning

WHIM (warts, hypogammaglobulinemia, infections, myelokathexis) syndrome is a rare disease characterized by diverse symptoms indicative of aberrantly functioning immunity. It is caused by mutations in the chemokine receptor CXCR4, which impair its intracellular trafficking, leading to increased responsiveness to chemokine ligand and retention of neutrophils in bone marrow. Yet WHIM symptoms related to adaptive immunity, such as delayed IgG switching and impaired memory B-cell function, remain largely unexplained. We hypothesized that the WHIM-associated mutations in CXCR4 may affect the formation of immunologic synapses between T cells and antigen-presenting cells (APCs). We show that, in the presence of competing external chemokine signals, the stability of T-APC conjugates from patients with WHIM-mutant CXCR4 is disrupted as a result of impaired recruitment of the mutant receptor to the immunologic synapse. Using retrogenic mice that develop WHIM-mutant T cells, we show that WHIM-mutant CXCR4 inhibits the formation of long-lasting T-APC interactions in ex vivo lymph node slice time-lapse microscopy. These findings demonstrate that chemokine receptors can affect T-APC synapse stability and allow us to propose a novel mechanism that contributes to the adaptive immune response defects in WHIM patients.

Organization of immune responses requires exchange of information between cells. This is achieved through either direct cell-cell contacts and establishment of temporary synapses or the release of soluble factors, such as cytokines and chemokines. Here we show a novel form of cell-to-cell communication based on adenosine triphosphate (ATP). ATP released by stimulated T cells induces P2X4/P2X7-mediated calcium waves in the neighboring lymphocytes. Our data obtained in lymph node slices suggest that, during T-cell priming, ATP acts as a paracrine messenger to reduce the motility of lymphocytes and that this may be relevant to allow optimal tissue scanning by T cells.

The Turin Astronomical Observatory, Italy, has implemented in ALTEC, Turin, a new Optical Payload Systems (OPSys) facility for testing of contamination sensitive optical space flight instrumentation. The facility is specially tailored for tests on solar instruments like coronagraphs. OPSys comprises an ISO 7 clean room for instrument assembly and a relatively large (4.4 m3) optical test and calibration vacuum chamber:

A cohort study. The causes of the pain can be difficult for clinicians to diagnose due to the complexity of the shoulder anatomy and the wide spectrum of shoulder conditions. The aim of this study was to investigate the clinical usefulness of provocative diagnostic tests, in patients with partial-thickness tears of the supraspinatus (SST) tendon. The partial-thickness tears SST tendon group consisted of 50 patients and 50 subjects with shoulder pain. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios of five physical examination tests were calculated using a 2 × 2 table. All the tests exhibited clinical useful positive LR greater than 2 (all, >7.0). The Yocum, Jobe, and Hawkinse-Kennedy exhibited clinically useful negative LR of less than 0.5. The provocative tests examined were clinically useful in determining the presence or absence of pathology of the supraspinatus tendon. 2b.

... Id: 254192. Autor: Araujo, Elisabeth; Palombini, Bruno; Stolz, Daiana P; Leiria, Tiago Luiz Luz; Richter, Vinícius Torres; Anselmi, Fábio; Pires, Leonardo Martins. Título: Sinuisite fúngica: uma análise clínica em nosso meio / Fungal sinusitis: a clinical analysis in our reality. ...