The Montreal Cognitive Assessment (MoCA) is a relatively newly designed test that was developed as a tool to screen patients with mild cognitive problems that are not typically detected by the Mini-Mental State Exam (MMSE). While early research suggests that the MoCA is more sensitive to subtle cognitive impairment than the MMSE, there is concern about potential decreased specificity when using the MoCA. The aim of the present study was to examine the comparative utility of using the MoCA and the MMSE to detect subtle cognitive impairment among a group of 82 middle-aged U.
View Article and Find Full Text PDFCyclin dependent kinase (CDK) inhibitors, such as flavopiridol, demonstrate significant single-agent activity in chronic lymphocytic leukemia (CLL), but the mechanism of action in these nonproliferating cells is unclear. Here we demonstrate that CLL cells undergo autophagy after treatment with therapeutic agents, including fludarabine, CAL-101, and flavopiridol as well as the endoplasmic reticulum (ER) stress-inducing agent thapsigargin. The addition of chloroquine or siRNA against autophagy components enhanced the cytotoxic effects of flavopiridol and thapsigargin, but not the other agents.
View Article and Find Full Text PDFThe advent of targeted therapy, specifically to the B-cell receptor (BCR), has changed the convention for the treatment of chronic lymphocytic leukemia (CLL). The phosphoinositide 3-kinase (PI3K) pathway, activated upstream by the BCR, receptor tyrosine kinases, and cytokine receptors, has been a potential target for a multitude of cancers, but until the recent introduction of isoform-specific inhibitors has not been widely used. In this review, we focus on describing the intricate upstream and downstream signaling, leading to cell survival mediated by PI3K in B cells with a specific focus on the impact and importance of the p110δ isoform (which is localized to hematopoietic cells and regulates distinct cellular functions in B cells).
View Article and Find Full Text PDFPurpose: An NINDS-sponsored conference in April of 2011 reviewed issues in epilepsy clinical trials. One goal was to clarify new electronic methods for recording seizure information and other data in clinical trials.
Methods: This selective literature review and compilation of expert opinion considers advantages and limitations of traditional paper-based seizure diaries in comparison to electronic diaries.
Purpose: The main purpose of this study was to investigate whether judo could be practised after joint replacement.
Methods: Two hundred and twelve questionnaires were sent to Judokas licensed at the French Judo Federation, over the age of 60, with at least a black belt 6th Dan. Out of 83 responses, 38 individuals, mean age 72.
Tetraspanins are commonly believed to act only as "molecular facilitators," with no direct role in signal transduction. We herein demonstrate that upon ligation, CD37, a tetraspanin molecule expressed on mature normal and transformed B cells, becomes tyrosine phosphorylated, associates with proximal signaling molecules, and initiates a cascade of events leading to apoptosis. Moreover, we have identified two tyrosine residues with opposing regulatory functions: one lies in the N-terminal domain of CD37 in a predicted "ITIM-like" motif and mediates SHP1-dependent death, whereas the second lies in a predicted "ITAM motif" in the C-terminal domain of CD37 and counteracts death signals by mediating phosphatidylinositol 3-kinase-dependent survival.
View Article and Find Full Text PDFWe describe a family with a history of breast and ovarian cancer in which MLPA analysis of the BRCA1 gene pointed to a deletion including a part of exon 11. Further characterization confirmed a loss of 374 bp in a region completely covered by conventional sequencing which had not revealed the deletion. Because this alteration was only detected serendipitously with an MLPA probe, we calculated the probabilities of detecting medium-sized deletions in large exons by methods including initial PCR amplification.
View Article and Find Full Text PDFWhen testing memory and cognitive abilities, clinicians often administer batteries including multiple tests with similar content. Care must be taken so that such similarities do not unduly impact test performance. This brief report reviews findings from our own clinic, where administration of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in tandem with other screening instruments has led to apparent carry-over at an overall rate of more than one third of cases.
View Article and Find Full Text PDFRegulatory T cells (Treg) with the capacity to suppress T-cell proliferation exert various effects on T cell function. In addition, Treg have been shown to modulate the phenotype and function of antigen-presenting cells (APC) including dendritic cells (DC), B cells and monocytes/macrophages. However, the specific mechanism(s) of how Treg affect APC have not been entirely identified so far.
View Article and Find Full Text PDFEur J Vasc Endovasc Surg
May 2012
Background: Studies of orthostatic changes in cutaneous micro-perfusion have yielded conflicting results, likely from imprecision of legacy equipment.
Methods: Postural flow changes in the femoral vessels and cervical carotids were measured in healthy normal adults using duplex equipment. Nutrient skin flow was measured using Hyperspectral imager (OxyVu-2™), a newer non-touch measurement technology.
In Slovenia, orthopaedics started to develop at the end of WWI, when the number of the handicapped increased. Dr Anton Brecelj, who in 1919 laid the groundwork for the welfare of handicapped and sent a Czech doctor Franc Minař to specialise in orthopaedic surgery. When Minař returned to Ljubljana in 1923, he established an orthopaedic unit within surgery and in 1937 took over its management.
View Article and Find Full Text PDFAgnathia-otocephaly is a rare, often lethal malformation characterized by absence or hypoplasia of the mandible, microstomia, hypoglossia/aglossia, and variable anterior midline fusion of the ears (melotia, synotia). Etiologies have been linked to both genetic and teratogenic factors and to date, a definitive, commonly identifiable cause has not been recognized. Mouse and human genetic studies have implicated OTX2 and PRRX1 as potential candidate genes for agnathia-otocephaly.
View Article and Find Full Text PDFEarly myoclonus in comatose survivors of cardiac arrest, even when it is not myoclonic status epilepticus (MSE), is considered a sign of severe global brain ischemia and has been associated with high rates of mortality and poor neurologic outcomes. We report on three survivors of primary circulatory cardiac arrests who had good neurologic outcomes (two patients with a CPC score=1 and one patient with a CPC score=2) after mild therapeutic hypothermia, despite exhibiting massive myoclonus within the first 4h after return of spontaneous circulation. The concept that early myoclonus heralds a uniformly poor prognosis may need to be reconsidered in the era of post-cardiac arrest mild therapeutic hypothermia.
View Article and Find Full Text PDFObjectives: To study (a) the prevalence of depressive symptoms and (b) the utilization of mental health treatment in an ethnoracially diverse sample consisting primarily of Asian Americans, European Americans, Native Hawaiians, and Pacific Islanders.
Participants: Five hundred eighty-nine college students.
Method: A questionnaire packet that included the Center for Epidemiological Studies Depression Scale (CES-D) was administered to students in introductory psychology courses.
Electroencephalography (EEG) remains central to the investigation of epilepsy. This review discusses two clinical problems at the temporal extremes of neurophysiologic recording: evaluation of the clinical significance of individual spike discharges in benign epilepsy of childhood with centrotemporal spikes (BECTS), and prolonged (several days) continuous EEG monitoring in the ICU. BECTS is misdiagnosed often, and probably mis-treated often as well.
View Article and Find Full Text PDFThe immune balance in patients with rheumatoid arthritis (RA), a disease characterized by TH1 dominance, treated by the preferred combined anti-tumor necrosis factor (anti-TNF) and methotrexate (MTX) therapy was evaluated by assessing the chemokine and cytokine receptors as well as apoptosis induction. A meta-analysis of combined therapy by TNF blockers and MTX in 15 RA patients, MTX monotherapy in 20 RA patients, and 11 diagnosed but untreated RA patients was performed by assessing several immune markers in the whole lymphocyte population, as well as in specific CD4 cells, by both flow cytometry and image analysis. A significant downregulation of CXCR3 and IL-12 receptors (both TH1 markers) and a significant increase in the chemokine receptor CCR4 and, to a lesser extent, IL-4R (both TH2 markers) were found; a particularly marked increase was found in patients treated by combined therapy.
View Article and Find Full Text PDFAutoimmune responses to heterogeneous nuclear ribonucleproteins (hnRNP) occur in many systemic autoimmune diseases, particularly in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus. In RA, humoral and/or cellular autoimmunity to hnRNP-A2/B1 is the most prominent anti-nuclear reactivity, being detectable in more than 50% of patients. However, its pathogenic role has not been fully elucidated yet.
View Article and Find Full Text PDFB-cell receptor (BCR) signaling is aberrantly activated in chronic lymphocytic leukemia (CLL). Bruton tyrosine kinase (BTK) is essential to BCR signaling and in knockout mouse models its mutation has a relatively B cell-specific phenotype. Herein, we demonstrate that BTK protein and mRNA are significantly over expressed in CLL compared with normal B cells.
View Article and Find Full Text PDFIn patients with chronic lymphocytic leukemia (CLL), lenalidomide can promote humoral immune responses but also induces a distinct disease-specific toxicity of tumor flare and cytokine release. These CLL-specific events result from increased expression of costimulatory molecules on B cells. Here we demonstrate that lenalidomide activation of CLL cells depends on the phosphatidylinositol 3-kinase p110δ (PI3K-δ) pathway.
View Article and Find Full Text PDFIn a cross-sectional survey of college students (N = 614) we studied interpersonal violence victimization, perpetration, and mental health outcomes in an ethnoracially diverse rural-based sample of Asian Americans (27%), and Native Hawaiian/Other Pacific Islanders (25%), two groups vastly underrepresented in trauma research. High rates of interpersonal violence (34%), violence perpetration (13%), and probable psychiatric diagnoses (77%), including posttraumatic stress disorder, were found. Exposure to physical violence, sexual violence, and life stress all were predictive of psychopathology.
View Article and Find Full Text PDFJ Am Osteopath Assoc
December 2010
Context: while estimates suggest that between 1.4% and 5.4% of older adults experience abuse, only 1 of 14 cases of elder abuse or neglect is ever reported to authorities.
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