Evaluation of a multidisciplinary Tier 3 weight management service for adults with morbid obesity, or obesity and comorbidities, based in primary care

A multidisciplinary Tier 3 weight management service in primary care recruited patients with a body mass index ≥40 kg·m−2, or 30 kg·m−2 with obesity-related co-morbidity to a 1-year programme. A cohort of 230 participants was recruited and evaluated using the National Obesity Observatory Standard Evaluation Framework. The primary outcome was weight loss of at least 5% of baseline weight at 12 months. Diet was assessed using the two-item food frequency questionnaire, activity using the General Practice Physical Activity questionnaire and quality of life using the EuroQol-5D-5L questionnaire. A focus group explored the participants' experiences. Baseline mean weight was 124.4 kg and mean body mass index was 44.1 kg·m−2. A total of 102 participants achieved 5% weight loss at 12 months. The mean weight loss was 10.2 kg among the 117 participants who completed the 12-month programme. Baseline observation carried forward analysis gave a mean weight loss of 5.9 kg at 12 months. Fruit and vegetable intake, activity level and quality of life all improved. The dropout rate was 14.3% at 6 months and 45.1% at 1 year. Focus group participants described high levels of satisfaction. It was possible to deliver a Tier 3 weight management service for obese patients with complex co-morbidity in a primary care setting with a full multidisciplinary team, which obtained good health outcomes compared with existing services

Cholesterol regulates volumesensitive osmolyte efflux from human SH-SY5Y neuroblastoma cells following receptor activation

ABSTRACT The ability of cholesterol to modulate receptor-mediated increases in the volume-dependent release of the organic osmolyte, taurine, has been examined. Depletion of cholesterol from SH-SY5Y neuroblastoma by preincubation of the cells with 5 mM methyl-␤-cyclodextrin (CD) for 10 min resulted in a 40 to 50% reduction in cholesterol and an enhancement of the ability of proteinase-activated receptor (PAR) 1, muscarinic cholinergic receptor (mAChR), and sphingosine 1-phosphate receptor to stimulate taurine efflux, when monitored under hypoosmotic conditions. Basal (swelling-induced) release of taurine was also enhanced by cholesterol depletion, but less markedly. Both basaland receptor-mediated increases in taurine efflux were mediated via a volume-sensitive organic osmolyte and anion channel in control and cholesterol-depleted cells. Studies with the PAR-1 and mAChR receptor subtypes indicated that the stimulatory effect of CD pretreatment could be reversed by incubation of the cells with either CD/cholesterol or CD/5-cholesten-3␣-ol donor complexes and that cholesterol depletion increased agonist efficacy, but not potency. The ability of cholesterol depletion to promote the PAR-1 receptor-mediated stimulation of osmolyte release was most pronounced under conditions of isotonicity or mild hypotonicity. In contrast to CD pretreatment, preincubation of the cells with cholesterol oxidase, a condition under which lipid microdomains are also disrupted, had no effect on either basal-or receptor-stimulated taurine efflux. Taken together, the results suggest that cholesterol regulates receptor-mediated osmolyte release via its effects on the biophysical properties of the plasma membrane, rather than its presence in lipid microdomains

The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic 3D renal tumouroids

Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia, while the more ‘resistant’ CAKI-2 tumouroids showed no decrease in viability, 786-O tumouroids required higher Pazopanib concentrations to induce cell death. In complex tumouroids, Pazopanib exposure led to a reduction in the overall cell viability (p < 0.0001), disruption of endothelial networks and direct killing of renal cell carcinoma cells. We report a biomimetic multicellular tumouroid for drug testing, suitable for agents whose primary target is not confined to cancer cells

Characterization of tissue inhibitor metalloproteinases in semen and their relationship with vital sperm function tests vis-à-vis fertility of breeding buffalo bulls

The present study was undertaken to separate and compare the tissue inhibitor metalloproteinases (TIMP) of seminal plasma and frozen-thawed sperm extracts from 30 buffalo bulls by immunoblotting and determine a relationship between various TIMP with post-thaw sperm function tests vis-à-vis bull fertility. Seven immunoreactive bands in seminal plasma (65, 55, 48, 33, 31, 24 and 11 kDa) and 5 in frozen-thawed spermatozoa (75, 65, 55, 24 and 16 kDa) were detected in Western blots following incubation (TIMP–140) and subsequent washing in vitro, indicating that TIMP is bound to sperm membranes. The frozen-thawed semen was evaluated for first service conception rate (FSCR), per cent HOST, acrosome reaction, viability, DNA integrity and total motility and linked to TIMP. In seminal plasma, the bulls positive for 48, 33 and 24 kDa TIMP had significantly higher FSCR (57.0 ± 2.6 vs 27.0 ± 2.4%, 55.7 ± 3.0 vs 31.3 ± 3.2% and 45.0 ± 3.8 vs 32.8 ± 4.7%, respectively) as compared to their negative counterparts. Except per cent viability, almost all seminal parameters (acrosome reaction, per cent HOST, DNA integrity and total motility) were significantly higher in bulls positive for TIMP of 48, 33, 31 and 24 kDa than in their negative contemporary mates. In frozen-thawed sperm extracts, the bulls positive for TIMP–24 had significantly higher FSCR (51.7 ± 3.7 vs 27.2 ± 3.0%), higher percentage of acrosome-reacted (55.9 ± 2.8 vs 48.9 ± 2.2%) and HOS-positive (69.2 ± 1.5 vs 65.3 ± 1.9%) spermatozoa in comparison to their negative herd mates. These results suggested that TIMP influences semen quality and subsequent fertility of buffalo bulls through inhibition of metalloprotease activity in semen

Determining the impact regions of competing options in preference space

2017 ACM SIGMOD International Conference on Management of Data, SIGMOD 2017, Chicago, Illinois, USA, 14-19 May 2017In rank-aware processing, user preferences are typically represented by a numeric weight per data attribute, collectively forming a weight vector. The score of an option (data record) is defined as the weighted sum of its individual attributes. The highest-scoring options across a set of alternatives (dataset) are shortlisted for the user as the recommended ones. In that setting, the user input is a vector (equivalently, a point) in a d-dimensional preference space, where d is the number of data attributes. In this paper we study the problem of determining in which regions of the preference space the weight vector should lie so that a given option (focal record) is among the top-k score-wise. In effect, these regions capture all possible user profiles for which the focal record is highly preferable, and are therefore essential in market impact analysis, potential customer identification, profile-based marketing, targeted advertising, etc. We refer to our problem as k-Shortlist Preference Region identification (kSPR), and exploit its computational geometric nature to develop a framework for its efficient (and exact) processing. Using real and synthetic benchmarks, we show that our most optimized algorithm outperforms by three orders of magnitude a competitor we constructed from previous work on a different problem.Department of Computing2016-2017 > Academic research: refereed > Refereed conference paperbcw

A CO Funnel in the Galactic Centre: Molecular Counterpart of the Northern Galactic Chimney?

We report the discovery of a velocity coherent, funnel shaped ^13CO emission feature in the Galactic centre (GC) using data from the SEDIGISM survey. The molecular cloud appears as a low velocity structure (V_LSR=[-3.5, +3.5] km/s) with an angular extent of 0.95{\deg} x 1{\deg}, extending toward positive Galactic latitudes. The structure is offset from Sgr A* toward negative Galactic longitudes and spatially and morphologically correlates well with the northern lobe of the 430 pc radio bubble, believed to be the radio counterpart of the multiwavelength GC chimney. Spectral line observations in the frequency range of 85-116 GHz have been carried out using the IRAM 30 metre telescope toward 12 positions along the funnel-shaped emission. We examine the ^12C/^13C isotopic ratios using various molecules and their isotopologues. The mean ^12C/^13C isotope ratio (30.6+-2.9) is consistent with the structure located within inner 3 kpc of the Galaxy and possibly in the GC. The velocity of the molecular funnel is consistent with previous radio recombination line measurements of the northern lobe of radio bubble. Our multiwavelength analysis suggests that the funnel shaped structure extending over 100 pc above the Galactic plane is the molecular counterpart of the northern GC chimney.Comment: Accepted for publication in A&A Letter

Association of statin pretreatment with collateral circulation and final infarct volume in acute ischemic stroke patients: A meta-analysis

Statin pretreatment (SP) is associated with improved outcomes in acute ischemic stroke (AIS) patients. Collateral circulation status and final infarct volume (FIV) are independent predictors of functional outcome in AIS.info:eu-repo/semantics/publishedVersio

An occasional diagnosis of myasthenia gravis - a focus on thymus during cardiac surgery: a case report

<p>Abstract</p> <p>Background</p> <p>Myasthenia gravis, an uncommon autoimmune syndrome, is commonly associated with thymus abnormalities. Thymomatous myasthenia gravis is considered to have worst prognosis and thymectomy can reverse symptoms if precociously performed.</p> <p>Case report</p> <p>We describe a case of a patient who underwent mitral valve repair and was found to have an occasional thymomatous mass during the surgery. A total thymectomy was performed concomitantly to the mitral valve repair.</p> <p>Conclusion</p> <p>The diagnosis of thymomatous myasthenia gravis was confirmed postoperatively. Following the surgery this patient was strictly monitored and at 1-year follow-up a complete stable remission had been successfully achieved.</p