Alemtuzumab use in neuromyelitis optica spectrum disorders: a brief case series.

Alemtuzumab is an anti-CD52 monoclonal antibody recently licensed for use in relapsing-remitting multiple sclerosis. Here, we report our experience of its use in neuromyelitis optica (NMO) spectrum disorders. A retrospective case review of patients treated with alemtuzumab in Cambridge, UK, was conducted to identify those who fulfil the criteria for NMO spectrum disorder. Three cases were identified. Case 1, 9-year-old female, presented with transverse myelitis and bilateral optic neuritis,with one lower medullary and several longitudinally extensive cord lesions. Despite immunosuppression including two courses of alemtuzumab, she continued to relapse, was wheelchair bound and registered blind by age 12, and died at age 18. Case 2, 41-year-old female, presented with bilateral optic neuritis and transverse myelitis with longitudinally extensive cervical cord lesions. Despite three courses of alemtuzumab, she had five relapses with visual impairment and new cord lesions. She later developed tumefactive white matter lesions and died aged 51.Case 3, 31-year-old female, presented with transverse myelitis with longitudinally extensive cervical cord lesions and positive aquaporin-4 antibody. After one course of alemtuzumab, she relapsed with 4 episodes of myelitis with new enhancing lesions and accumulating disability. She became relapse free after rituximab and mycophenolate mofetil. From this case series, we conclude that alemtuzumab failed to prevent disabling relapses and poor outcome in NMO. We hypothesise that rituximab is more effective, as in case 3, because it causes much more prolonged B lymphocyte depletion than alemtuzumab. We therefore caution against the use of alemtuzumab in NMO.Clinical work is performed at the Wellcome Clinical Research Facility. JLJ and AJC are supported by the Cambridge Biomedical Research Centre of the National Institute for Health Research

The use of serious gaming for Open Learning environments

The extensive growth of Open Learning has been facilitated through technological innovation and continuous examination of the global Open Education development. With the introduction of compulsory computing subjects being incorporated into the UK school system in September 2014, the challenge of harnessing and integrating technological advances to aid children's learning is becoming increasingly important, referring to £1.1 million being invested to offer training programs for teachers to become knowledgeable and experienced in computing. From the age of 5, children will be taught detailed computing knowledge and skills such as; algorithms, how to store digital content, to write and test simple programs. Simultaneously, as the Internet and technology are improving, parents and teachers are looking at the incorporation of game based learning to aid children’s learning processes in more exciting and engaging ways. The purpose of game-based learning is to provide a better engagement, and in turn, an anticipated improvement in learning ability. This paper presents a research based on the investigation of properly combining the advantages of serious games and Open Learning to enhance the learning abilities of primary school children. The case study and the adequate evaluation address a learning environment in support of a history subject matter

Skin- and gut-homing molecules on human circulating gamma delta T cells and their dysregulation in inflammatory bowel disease

Changes in phenotype and function of γδ T cells have been reported in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Dysregulation of lymphocyte migration plays a key role in IBD pathogenesis; however, data on migratory properties of γδ T cells are scarce. Human circulating γδ T cells from healthy controls (n = 27), patients with active CD (n = 15), active UC (n = 14) or cutaneous manifestations of IBD (n = 2) were characterized by flow cytometry. Circulating γδ T cells in healthy controls were CD3(hi) and expressed CD45RO. They expressed gut-homing molecule β7 but not gut-homing molecule corresponding chemokine receptors (CCR)9, or skin-homing molecules cutaneous lymphocyte-associated antigen (CLA) and CCR4, despite conventional T cells containing populations expressing these molecules. CCR9 expression was increased on γδ T cells in CD and UC, while skin-homing CLA was expressed aberrantly on γδ T cells in patients with cutaneous manifestations of IBD. Lower levels of CD3 expression were found on γδ T cells in CD but not in UC, and a lower proportion of γδ T cells expressed CD45RO in CD and UC. Enhanced expression of gut-homing molecules on circulating γδ T cells in IBD and skin-homing molecules in cutaneous manifestations of IBD may be of clinical relevance

Prevalence and causes of failure of receiving thrombolytic therapy in patients with acute ST-segment elevation myocardial infarction

AbstractBackgroundMissing thrombolytic therapy in patients with acute ST-elevation myocardial infarction (STEMI) can have dire consequences. We studied the prevalence and causes of failure of receiving thrombolytic therapy in patients with STEMI and its impact on the clinical outcome during hospitalization.Patients and methodsThis was an observational, analytic, cross sectional study carried out in the CCU and emergency departments of three public hospitals in Port Said, Egypt. We interrogated all patients admitted within 72h of possible acute coronary syndrome and only patients proved to have STEMI as defined by the updated ACC criteria were analyzed for receiving thrombolytic therapy or not. All STEMI patients were subjected to: medical history taking, thorough clinical examination, 12-leads surface electrocardiography, cardiac biomarkers (troponin I), and predischarge trans-thoracic echocardiography.ResultsOf 6522 patients screened, only 288 patients had STEMI. The prevalence of missed thrombolysis in these patients was 45%. Delayed presentation after the onset of symptoms represented the most common cause for failure to receive thrombolysis (54% of the cases), while misdiagnosis at the emergency department represented 35% of the cases. Female gender, diabetes mellitus and inferior location of myocardial infarction were independent predictors of missed thrombolytic therapy. Cardiac death, clinical heart failure and significant cardiac dysrhythmias were higher in patients who missed thrombolysis than in those who received it.ConclusionIn this study, up to 45% of patients with STEMI missed the opportunity to receive thrombolysis, most likely due to delayed presentation or misdiagnosis at the emergency department. Patients with missed thrombolysis were at higher risk of cardiac death, clinical heart failure, and hemodynamically significant cardiac dysrhythmias

Decadal changes of the Western Arabian sea ecosystem

Historical data from oceanographic expeditions and remotely sensed data on outgoing longwave radiation, temperature, wind speed and ocean color in the western Arabian Sea (1950–2010) were used to investigate decadal trends in the physical and biochemical properties of the upper 300 m. 72 % of the 29,043 vertical profiles retrieved originated from USA and UK expeditions. Increasing outgoing longwave radiation, surface air temperatures and sea surface temperature were identified on decadal timescales. These were well correlated with decreasing wind speeds associated with a reduced Siberian High atmospheric anomaly. Shoaling of the oxycline and nitracline was observed as well as acidification of the upper 300 m. These physical and chemical changes were accompanied by declining chlorophyll-a concentrations, vertical macrofaunal habitat compression, declining sardine landings and an increase of fish kill incidents along the Omani coast

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

The burden of diabetes mellitus during pregnancy in low- and middle-income countries : a systematic review

Peer reviewedPublisher PD

Enhancing the dissolution of phenylbutazone using Syloid® based mesoporous silicas for oral equine applications

Three mesoporous silica excipients (Syloid® silicas AL-1 FP, XDP 3050 and XDP 3150) were formulated with a model drug known for its poor aqueous solubility, namely phenylbutazone, in an attempt to enhance the extent and rate of drug dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid® silica based excipients and more interestingly, with phenylbutazone, is unknown. This work reports a significant enhancement for both the extent, and rate, of drug release for all three forms of Syloid® silica at a 1:1 drug:silica ratio over a period of 30 minutes. An explanation for this increase was determined to be conversion to the amorphous form and an enhanced drug loading ability within the pores. Differences between the release profiles of the three silicas was concluded to be a consequence of the physicochemical differences between the three forms. Overall, this study confirms that Syloid® silica based excipients can be used to enhance dissolution, and potentially therefore bioavailability, for compounds with poor aqueous solubility, such as phenylbutazone. In addition, it has been confirmed that drug release can be carefully tailored based on the choice of Syloid® silica and desired release profile

When Broadway Was A Pasture

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