CD5 expression promotes IL-10 production through activation of the MAPK/Erk pathway and upregulation of TRPC1 channels in B lymphocytes.

CD5 is constitutively expressed on T cells and a subset of mature normal and leukemic B cells in patients with chronic lymphocytic leukemia (CLL). Important functional properties are associated with CD5 expression in B cells, including signal transducer and activator of transcription 3 activation, IL-10 production and the promotion of B-lymphocyte survival and transformation. However, the pathway(s) by which CD5 influences the biology of B cells and its dependence on B-cell receptor (BCR) co-signaling remain unknown. In this study, we show that CD5 expression activates a number of important signaling pathways, including Erk1/2, leading to IL-10 production through a novel pathway independent of BCR engagement. This pathway is dependent on extracellular calcium (Ca2+) entry facilitated by upregulation of the transient receptor potential channel 1 (TRPC1) protein. We also show that Erk1/2 activation in a subgroup of CLL patients is associated with TRPC1 overexpression. In this subgroup of CLL patients, small inhibitory RNA (siRNA) for CD5 reduces TRPC1 expression. Furthermore, siRNAs for CD5 or for TRPC1 inhibit IL-10 production. These findings provide new insights into the role of CD5 in B-cell biology in health and disease and could pave the way for new treatment strategies for patients with B-CLL

Linguistic validation, validity and reliability of the British English versions of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and QuickDASH in people with rheumatoid arthritis

Background: Although the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is widely used in the UK, no British English version is available. The aim of this study was to linguistically validate the DASH into British English and then test the reliability and validity of the British English DASH, (including the Work and Sport/Music DASH) and QuickDASH, in people with rheumatoid arthritis (RA). Methods: The DASH was forward translated, reviewed by an expert panel and cognitive debriefing interviews undertaken with 31 people with RA. Content validity was evaluated using the ICF Core Set for RA. Participants with RA (n=340) then completed the DASH, Health Assessment Questionnaire (HAQ), Short Form Health Survey v2 (SF36v2) and Measure of Activity Performance of the Hand (MAPHAND). We examined internal consistency and concurrent validity for the DASH, Work and Sport/Music DASH modules and QuickDASH. Participants repeated the DASH to assess test-retest reliability. Results: Minor wording changes were made as required. The DASH addresses a quarter of Body Function and half of Activities and Participation codes in the ICF RA Core Set. Internal consistency for DASH scales were consistent with individual use (Cronbach’s alpha = 0.94-0.98). Concurrent validity was strong with the HAQ (rs = 0.69-0.91), SF36v2 Physical Function (rs = -0.71 - -0.85), Bodily Pain (rs = -0.71 - -0.74) scales and MAPHAND (rs =0.71-0.93). Test-retest reliability was good (rs = 0.74-0.95). Conclusions: British English versions of the DASH, QuickDASH and Work and Sport/Music modules are now available to evaluate upper limb disabilities in the UK. The DASH, QuickDASH, Work and Sport/Music modules are reliable and valid to use in clinical practice and research with British people with RA

Strain-Dependent Differences in Bone Development, Myeloid Hyperplasia, Morbidity and Mortality in Ptpn2-Deficient Mice

Single nucleotide polymorphisms in the gene encoding the protein tyrosine phosphatase TCPTP (encoded by PTPN2) have been linked with the development of autoimmunity. Here we have used Cre/LoxP recombination to generate Ptpn2ex2−/ex2− mice with a global deficiency in TCPTP on a C57BL/6 background and compared the phenotype of these mice to Ptpn2−/− mice (BALB/c-129SJ) generated previously by homologous recombination and backcrossed onto the BALB/c background. Ptpn2ex2−/ex2− mice exhibited growth retardation and a median survival of 32 days, as compared to 21 days for Ptpn2−/− (BALB/c) mice, but the overt signs of morbidity (hunched posture, piloerection, decreased mobility and diarrhoea) evident in Ptpn2−/− (BALB/c) mice were not detected in Ptpn2ex2−/ex2− mice. At 14 days of age, bone development was delayed in Ptpn2−/− (BALB/c) mice. This was associated with increased trabecular bone mass and decreased bone remodeling, a phenotype that was not evident in Ptpn2ex2−/ex2− mice. Ptpn2ex2−/ex2− mice had defects in erythropoiesis and B cell development as evident in Ptpn2−/− (BALB/c) mice, but not splenomegaly and did not exhibit an accumulation of myeloid cells in the spleen as seen in Ptpn2−/− (BALB/c) mice. Moreover, thymic atrophy, another feature of Ptpn2−/− (BALB/c) mice, was delayed in Ptpn2ex2−/ex2− mice and preceded by an increase in thymocyte positive selection and a concomitant increase in lymph node T cells. Backcrossing Ptpn2−/− (BALB/c) mice onto the C57BL/6 background largely recapitulated the phenotype of Ptpn2ex2−/ex2− mice. Taken together these results reaffirm TCPTP's important role in lymphocyte development and indicate that the effects on morbidity, mortality, bone development and the myeloid compartment are strain-dependent

Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Dusty Punch Cards and an Eternal Enigma: High-Density Lipoproteins and Atherosclerosis

Epidemiological, clinical, and experimental evidence has accumulated during the last decades suggesting that high-density lipoproteins (HDLs) may protect from atherosclerosis and its clinical consequences. However, more than 55 years after the first description of the link between HDL and heart attacks, many facets of the biochemistry, function, and clinical significance of HDL remain enigmatic. This applies particularly to the completely unexpected results that became available from some recent clinical trials of nicotinic acid and of inhibitors of cholesteryl ester transfer protein (CETP). The concept that raising HDL cholesterol by pharmacological means would decrease the risk of vascular disease has therefore been challenged

Bank Risk Literature (1978–2022): A Bibliometric Analysis and Research Front Mapping

This study maps the conceptual structure of the body of knowledge concerning bank risk to understand this research strand better. A bibliometric analysis including 671 publications from January 1978 to October 2022 was conducted to achieve the aim of the study. The analysis of descriptive indicators identifies the main traits of scholars debating bank risk in terms of the annual production of publications; most productive authors, countries, affiliations, and journals; and most cited articles in the dataset. This study performs a co-word analysis by adopting social network analysis tools to analyze the conceptual structure of the dataset. The results highlight growing academic interest in bank risk research topics, especially following the global financial crisis. The bibliometric analysis reveals three main topics concerning the consideration of bank risk: (1) the adoption of risk management and bank risk, (2) the use of bank risk during the financial crisis, and (3) the interrelations between corporate governance and bank risk.</jats:p