Cerebellar Atrophy and Neurocognitive Disorder as Primary Presentation of Antiphospholipid Syndrome in a Young Male

Antiphospholipid syndrome (APS) is a multisystem autoimmunedisorder characterized by arterial or venous thrombosis and pregnancymorbidity in the presence of antiphospholipid antibodies(aPL).1 It can be primary or secondary. Primary antiphospholipid syndromeoccurs in the absence of any other related disease. Secondaryantiphospholipid syndrome occurs with other autoimmune diseases,such as systemic lupus erythematosus.The presence of aPL can be demonstrated in one of three ways:the presence of anticardiolipin antibodies (aCL), β 2-glycoprotein Iantibodies (GPI), or lupus anticoagulant antibodies (LA).1 To meetclassification criteria for antiphospholipid syndrome, patients shouldhave one clinical criterion, either vascular thrombosis (venous orarterial) or pregnancy morbidity (at least one fetal death or pretermdelivery or three or more unexplained, consecutive, spontaneouspregnancy losses) and one laboratory criterion, the presence of aPLantibodies need to be seen twice and at least 12 weeks apart for confirmation.Neurological manifestations are common in APS and areattributed mainly to vascular thrombosis and aPL-induced neuronaltissue injury. The most common neurological presentation is an ischemiccerebrovascular accident (CVA) or transient ischemic attack(TIA). However, clinical presentations including cognitive dysfunction,headaches, seizures, and psychosis may be atypical in some cases,which makes diagnosis more difficult.2In our case, a male patient initially presented with a neurocognitivedisorder, dementia, cerebral atrophy, and seizure of unknown etiology.A diagnosis of APS was made after a brain biopsy revealed microinfarctsand intimal fibrosis and an aPL antibody test was positive

“‘Sink or swim’: buoyancy and coping in the cognitive test anxiety – academic performance relationship”

© 2015 Taylor & Francis This study explores the relationship between students’ self-report levels of cognitive test anxiety (worry), academic buoyancy (withstanding and successfully responding to routine school challenges and setbacks), coping processes and their achieved grades in high-stakes national examinations at the end of compulsory schooling. The sample comprised 325 English students in their final year of secondary school preparing for high-stakes examinations. While controlling for prior attainment and gender, higher worry predicted lower examinations scores. This was partially mediated by less use of effective pre-exam coping strategies. Academic buoyancy moderated the indirect relationship such that the indirect negative relationship from worry to examination performance was stronger when academic buoyancy was lower. The paper concludes that providing in-school training in task-focus and orientation and how to withstand academic pressures may help to ameliorate the influence of performance-interfering worries, and potentially enhance performance among students inclined to worry about examinations

Hydrography, nutrients, and carbon pools in the Pacific sector of the Southern Ocean: Implications for carbon flux

PDF Tools Share Abstract We investigated the hydrography, nutrients, and dissolved and particulate carbon pools in the western Pacific sector of the Antarctic Circumpolar Current (ACC) during austral summer 1996 to assess the region\u27s role in the carbon cycle. Low f CO2 values along two transects indicated that much of the study area was a sink for atmospheric CO2. The f CO2 values were lowest near the Polar Front (PF) and the Subtropical Front (STF), concomitant with maxima of chlorophyll a and particulate and dissolved organic carbon. The largest biomass accumulations did not occur at fronts, which had high surface geostrophic velocities (20–51 cm s−1), but in relatively low velocity regions near fronts or in an eddy. Thus vertical motion and horizontal advection associated with fronts may have replenished nutrients in surface waters but also dispersed phytoplankton. Although surface waters north of the PF have been characterized as a “high nutrient‐low chlorophyll” region, low silicic acid (Si) concentrations (2–4 μM ) may limit production of large diatoms and therefore the potential carbon flux. Low concentrations (4–10 μM Si) at depths of winter mixing constrain the level of Si replenishment to surface waters. It has been suggested that an increase in aeolian iron north of the PF may increase primary productivity and carbon export. Our results, however, indicate that while diatom growth and carbon export may be enhanced, the extent ultimately would be limited by the vertical supply of Si. South of the PF, the primary mechanism by which carbon is exported to deep water appears to be through diatom flux. We suggest that north of the PF, particulate and dissolved carbon may be exported primarily to intermediate depths through subduction and diapycnal mixing associated with Subantarctic Mode Water and Antarctic Intermediate Water formation. These physical‐biological interactions and Si dynamics should be included in future biogeochemical models to provide a more accurate prediction of carbon flux

The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is a complex disease trait where genetic variations and environment interact to determine disease progression. The association of PNPLA3 with advanced disease has been consistently demonstrated but many other modifier genes remain unidentified. In NAFLD, increased fatty acid oxidation produces high levels of reactive oxygen species. Manganese-dependent superoxide dismutase (MnSOD), encoded by the SOD2 gene, plays an important role in protecting cells from oxidative stress. A common non-synonymous polymorphism in SOD2 (C47T; rs4880) is associated with decreased MnSOD mitochondrial targeting and activity making it a good candidate modifier of NAFLD severity. METHODS: The relevance of the SOD2 C47T polymorphism to fibrotic NAFLD was assessed by two complementary approaches: we sought preferential transmission of alleles from parents to affected children in 71 family trios and adopted a case-control approach to compare genotype frequencies in a cohort of 502 European NAFLD patients. RESULTS: In the family study, 55 families were informative. The T allele was transmitted on 47/76 (62%) possible occasions whereas the C allele was transmitted on only 29/76 (38%) occasions, p=0.038. In the case control study, the presence of advanced fibrosis (stage>1) increased with the number of T alleles, p=0.008 for trend. Multivariate analysis showed susceptibility to advanced fibrotic disease was determined by SOD2 genotype (OR 1.56 (95% CI 1.09-2.25), p=0.014), PNPLA3 genotype (p=0.041), type 2 diabetes mellitus (p=0.009) and histological severity of NASH (p=2.0×10(-16)). CONCLUSIONS: Carriage of the SOD2 C47T polymorphism is associated with more advanced fibrosis in NASH

Role of nutrient-sensing taste 1 receptor (T1R) family members in gastrointestinal chemosensing

Luminal nutrient sensing by G-protein-coupled receptors (GPCR) expressed on the apical domain of enteroendocrine cells activates intracellular pathways leading to secretion of gut hormones that control vital physiological processes such as digestion, absorption, food intake and glucose homeostasis. The taste 1 receptor (T1R) family of GPCR consists of three members: T1R1; T1R2; T1R3. Expression of T1R1, T1R2 and T1R3 at mRNA and protein levels has been demonstrated in the intestinal tissue of various species. It has been shown that T1R2-T1R3, in association with G-protein gustducin, is expressed in intestinal K and L endocrine cells, where it acts as the intestinal glucose (sweet) sensor. A number of studies have demonstrated that activation of T1R2-T1R3 by natural sugars and artificial sweeteners leads to secretion of glucagon-like peptides 1&2 (GLP-1 and GLP-2) and glucose dependent insulinotropic peptide (GIP). GLP-1 and GIP enhance insulin secretion; GLP-2 increases intestinal growth and glucose absorption. T1R1-T1R3 combination co-expressed on the apical domain of cholecystokinin (CCK) expressing cells is a luminal sensor for a number of l-amino acids; with amino acid-activation of the receptor eliciting CCK secretion. This article focuses on the role of the gut-expressed T1R1, T1R2 and T1R3 in intestinal sweet and l-amino acid sensing. The impact of exploiting T1R2-T1R3 as a nutritional target for enhancing intestinal glucose absorption and gut structural maturity in young animals is also highlighte

Interacting models may be key to solve the cosmic coincidence problem

It is argued that cosmological models that feature a flow of energy from dark energy to dark matter may solve the coincidence problem of late acceleration (i.e., "why the energy densities of both components are of the same order precisely today?"). However, much refined and abundant observational data of the redshift evolution of the Hubble factor are needed to ascertain whether they can do the job.Comment: 25 pages, 11 figures; accepted for publication in JCA

Hybrid brain-computer interface and functional electrical stimulation for sensorimotor training in participants with tetraplegia: a proof-of-concept study

Background and Purpose: Impaired hand function decreases quality of life in persons with tetraplegia. We tested functional electrical stimulation (FES) controlled by a hybrid brain-computer interface (BCI) for improving hand function in participants with tetraplegia. Methods: Two participants with subacute tetraplegia (participant 1: C5 Brown-Sequard syndrome, participant 2: complete C5 lesion) took part in this proof-of-concept study. The goal was to determine whether the BCI system could drive the FES device by accurately classifying participants' intent (open or close the hand). Participants 1 and 2 received 10 sessions and 4 sessions of BCI-FES, respectively. A novel time-switch BCI strategy based on motor imagery was used to activate the FES. In one session, we tested a hybrid BCI-FES based on 2 spontaneously generated brain rhythms: a sensory-motor rhythm during motor imagery to activate a stimulator and occipital alpha rhythms to deactivate the stimulator. Participants received BCI-FES therapy 2 to 3 times a week in addition to conventional therapy. Imagery ability and muscle strength were measured before and after treatment. Results: Visual feedback was associated with a 4-fold increase of brain response during motor imagery in both participants. For participant 1, classification accuracy (open/closed) for motor imagery-based BCI was 83.5% (left hand) and 83.8% (right hand); participant 2 had a classification accuracy of 83.8% for the right hand. Participant 1 had moderate improvement in muscle strength, while there was no change for participant 2. Discussion and Conclusion: We demonstrated feasibility of BCI-FES, using 2 naturally generated brain rhythms. Studies on a larger number of participants are needed to separate the effects of BCI training from effects of conventional therapy

Development of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves

Members of the voltage-gated K+ channel subfamily (Kv1), involved in regulating transmission between neurons or to muscles, are associated with human diseases and, thus, putative targets for neurotherapeutics. This applies especially to those containing Kv1.1 α subunits which become prevalent in murine demyelinated axons and appear abnormally at inter-nodes, underlying the perturbed propagation of nerve signals. To overcome this dysfunction, akin to the consequential debilitation in multiple sclerosis (MS), small inhibitors were sought that are selective for the culpable hyper-polarising K+ currents. Herein, we report a new semi-podand – compound 3 – that was designed based on the modelling of its interactions with the extracellular pore region in a deduced Kv1.1 channel structure. After synthesis, purification, and structural characterisation, compound 3 was found to potently (IC50 = 8 µM) and selectively block Kv1.1 and 1.6 channels. The tested compound showed no apparent effect on native Nav and Cav channels expressed in F-11 cells. Compound 3 also extensively and selectively inhibited MS-related Kv1.1 homomer but not the brain native Kv1.1- or 1.6-containing channels. These collective findings highlight the therapeutic potential of compound 3 to block currents mediated by Kv1.1 channels enriched in demyelinated central neurons

Is Excess Calcium Harmful to Health?

Most current guidelines recommend that older adults and the elderly strive for a total calcium intake (diet and supplements) of 1,000 to 1,300 mg/day to prevent osteoporosis and fractures. Traditionally, calcium supplements have been considered safe, effective and well tolerated, but their safety has recently been questioned due to potential adverse effects on vascular disease which may increase mortality. For example, the findings from a meta-analysis of randomized controlled trials (currently published in abstract form only) revealed that the use of calcium supplements was associated with an ~30% increased risk of myocardial infarction. If high levels of calcium are harmful to health, this may alter current public health recommendations with regard to the use of calcium supplements for preventing osteoporosis. In this review, we provide an overview of the latest information from human observational and prospective studies, randomized controlled trials and meta-analyses related to the effects of calcium supplementation on vascular disease and related risk factors, including blood pressure, lipid and lipoprotein levels and vascular calcification

Nutrient sensing of gut luminal environment

Sensing of nutrients by chemosensory cells in the gastrointestinal tract plays a key role in transmitting food-related signals, linking information about the composition of ingested foods to digestive processes. In recent years, a number of G protein-coupled receptors (GPCR) responsive to a range of nutrients have been identified. Many are localised to intestinal enteroendocrine (chemosensory) cells, promoting hormonal and neuronal signalling locally, centrally and to the periphery. The field of gut sensory systems is relatively new and still evolving. Despite huge interest in these nutrient-sensing GPCR, both as sensors for nutritional status and targets for preventing the development of metabolic diseases, major challenges remain to be resolved. However, the gut expressed sweet taste receptor, resident in L-enteroendocrine cells and responsive to dietary sweetener additives, has already been successfully explored and utilised as a therapeutic target, treating weaning-related disorders in young animals. In addition to sensing nutrients, many GPCR are targets for drugs used in clinical practice. As such these receptors, in particular those expressed in L-cells, are currently being assessed as potential new pathways for treating diabetes and obesity. Furthermore, growing recognition of gut chemosensing of microbial-produced SCFA acids has led further attention to the association between nutrition and development of chronic disorders focusing on the relationship between nutrients, gut microbiota and health. The central importance of gut nutrient sensing in the control of gastrointestinal physiology, health promotion and gut–brain communication offers promise that further therapeutic successes and nutritional recommendations will arise from research in this area