A review of atypical subtrochanteric femoral fractures in Northern Ireland between 2010 and 2014.

The term atypical femoral fractures most commonly occur in the subtrochanteric area. Concerns exist regarding the role of bisphosphonate treatment in their aetiology. Which surgical intervention provides the best outcome remains contentious. We reviewed all atypical subtrochanteric femoral fractures treated in Northern Ireland over 5 years, specifically investigating incidence, prodromal symptoms, association with bisphosphonates and optimal fixation methods. All subtrochanteric fractures treated in the region were identified and reviewed for atypical features. Case notes and imaging were then reviewed for each patient. A total of 364 subtrochanteric femoral fractures were identified during the 5-year study period. Twenty-six of these met the criteria for an atypical fracture (7%). Thirteen patients (50%) had presented with prodromal symptoms prior to complete fracture, six of which had radiological evidence of an incomplete fracture of the lateral cortex. Thirteen patients had a history of bisphosphonate treatment. All were treated operatively, with twenty-five cephalomedullary nails and one dynamic hip screw. Twenty-one patients had follow-up for greater than 2 months, nine of which (42.9%) achieved radiological union with a mean time to union of 297 days. Dynamically locked nails had a higher union rate than statically locked (80% versus 33.3%). Four patients required major revision surgery (15.4%). The quality of reduction was statistically significant in predicting need for revision. Atypical fractures often present with prodromal symptoms. Complete fractures are difficult to successfully manage with longer than expected times to union. Treatment with a dynamically locked, cephalomedullary with a good reduction provided the best results.

Milk fatty acid profile is modulated by DGAT1 and SCD1 genotypes in dairy cattle on pasture and strategic supplementation.

Milk fat composition is important to consumer health. During the last decade, some fatty acids (FA) have received attention because of their functional and beneficial effects on human health. The milk FA profile is affected by both diet and genetics. Differences in milk fat composition are based on biochemical pathways, and candidate genes have been proposed to explain FA profile variation. Here, the association between DGAT1 K232A, SCD1 A293V, and LEPR T945M markers with milk fat composition in southern Chile was evaluated. We selected five herds of Holstein-Friesian, Jersey, Frisón Negro, Montbeliarde, and Overo Colorado cows (pasture-grazed) that received strategic supplementation with concentrates and conserved forages. We genotyped the SNPs and calculated allele frequencies and Hardy-Weinberg equilibrium. Milk fat composition was determined for individual milk samples over a year, and associations between genotypes and milk composition were studied. The most frequent variants for DGAT1, SCD1, and LEPR polymorphisms were GC/GC, C, and C, respectively. The DGAT1 GC/GC allele was associated with lower milk fat and protein content, lower saturated fatty acid levels, and higher polyunsaturated FA (PUFA), n-3 and n-6 FA, and a linolenic acid to cholesterolemic FA ratios, which implied a healthier FA profile. The SCD1 CC genotype was associated with a low cholesterolemic FA content, a high ratio of linolenic acid to cholesterolemic FA, and lower conjugated-linolenic acid and PUFA content. These results suggest the possible modulation of milk fat profiles, using specific genotypes, to improve the nutritional quality of dairy products.

Novel KDM6A (UTX) mutations and a clinical and molecular review of the X-linked Kabuki syndrome (KS2).

We describe seven patients with KDM6A (located on Xp11.3 and encodes UTX) mutations, a rare cause of Kabuki syndrome (KS2, MIM 300867) and report, for the first time, germ-line missense and splice-site mutations in the gene. We demonstrate that less than 5% cases of Kabuki syndrome are due to KDM6A mutations. Our work shows that similar to the commoner Type 1 Kabuki syndrome (KS1, MIM 147920) caused by KMT2D (previously called MLL2) mutations, KS2 patients are characterized by hypotonia and feeding difficulties during infancy and poor postnatal growth and short stature. Unlike KS1, developmental delay and learning disability are generally moderate-severe in boys but mild-moderate in girls with KS2. Some girls may have a normal developmental profile. Speech and cognition tend to be more severely affected than motor development. Increased susceptibility to infections, join laxity, heart, dental and ophthalmological anomalies are common. Hypoglycaemia is more common in KS2 than in KS1. Facial dysmorphism with KDM6A mutations is variable and diagnosis on facial gestalt alone may be difficult in some patients. Hypertrichosis, long halluces and large central incisors may be useful clues to an underlying KDM6A mutation in some patients.

Effects of peroxidized corn oil on performance, AMEn, and abdominal fat pad weight in broiler chicks.

There is a trend to use more alternative lipids in poultry diets, either through animal-vegetable blends, distillers corn oil, or yellow grease. This has resulted in the use of lipids in poultry diets with a higher concentration of unsaturated fatty acids, which have a greater potential for peroxidation. The objective of this experiment was to determine the effects of peroxidized corn oil on broiler performance, dietary AMEn, and abdominal fat pad weight. The same refined corn oil sample was divided into 3 subsamples, 2 of which were exposed to different peroxidative processes. The 3 diets contained the unperoxidized corn oil (UO), a slowly peroxidized corn oil (SO; heated for 72 h at 95°C with compressed air flow rate of 12 L/min), or a rapidly peroxidized corn oil (RO; heated for 12 h at 185°C with compressed air flow rate of 12 L/min). Diets were fed from 0 to 14 d of age with each lipid fed at a 5% inclusion rate, continuing on from 15 to 27 d of age with each lipid fed at a 10% inclusion rate. There were 6 Ross 708 broiler chicks per cage with 10 replicates for each of the 3 dietary treatments. Abdominal fat pad and excreta collection was performed on d 27. Body weight gain, feed intake and feed efficiency were measured for the 0 to 14 and 0 to 27 d periods. The increased level of peroxidation reduced AMEn in broiler diets (UO = 3,490 kcal/kg; SO = 3,402 kcal/kg; RO = 3,344 kcal/kg on an as-is basis; SEM = 12.9, P ≤ 0.01). No significant treatment differences were observed among oil supplemented birds for BW gain, feed intake, feed efficiency, or abdominal fat pad weight. In conclusion, corn oil peroxidation status resulted in a decrease in dietary AMEn, but had minimal effects on broiler performance or fat pad weights.

Joint health scores in a haemophilia A cohort from Pakistan with minimal or no access to factor VIII concentrate: correlation with thrombin generation and underlying mutation.

Haemophilia A is associated with recurrent joint bleeding which leads to synovitis and debilitating arthropathy. Coagulation factor VIII level is an important determinant of bleed number and development of arthropathy . The aim of this study was to compare the haemophilia joint health score (HJHS) and Gilbert score with severity, age, thrombin generation (TG) and underlying mutation in a haemophilia A cohort which had minimal access to haemostatic replacement therapy. Ninety-two haemophilia A individuals were recruited from Pakistan. Age, age at first bleed, target joints, haemophilic arthropathy joints, HJHS and Gilbert score were recorded. A strong correlation was found between HJHS and Gilbert score (r = 0.98), both were significantly higher in severe (n = 59) compared with non-severe (n = 29) individuals before the age of 12 years (P ≤ 0.01) but not thereafter. When individuals were divided according to developmental age (<12 years, 12-16 years and >16 years), both HJHS and Gilbert score were significantly lower in the youngest group (P ≤ 0.001), there was no difference between 12-16 years and >16 years. In severe individuals there was no correlation between in vitro TG and joint score, whereas in non-severe individuals there was a weak negative correlation. In the severe group, no significant difference was observed for either joint score according to the underlying mutation type (inversion, missense, nonsense, frameshift). In this cohort of haemophilia A individuals with minimal access to haemostatic treatment, haemophilic arthropathy correlated with severity and age; among severe individuals, joint health scores did not relate to either the underlying mutation or in vitro TG.

Validation of prediction equations for apparent metabolizable energy of corn distillers dried grains with solubles in broiler chicks.

An experiment consisting of 3 nearly identical trials was conducted to determine the AMEn content of distillers dried grains with solubles (DDGS) to validate 4 previously published prediction equations for AMEn of corn DDGS in broilers. In addition, prior research data were used to generate a best-fit equation for AMEn based on proximate analysis. Fifteen samples of DDGS ranging in ether extract (EE) from 4.98 to 14.29% (DM basis) were collected from various dry-grind ethanol plants and were subsequently fed to broiler chicks to determine AMEn content. A corn-soybean meal control diet was formulated to contain 15% dextrose and test diets were created by mixing the control diet with 15% DDGS at the expense of dextrose. In each trial, male Ross × Ross 708 chicks were housed in grower battery cages and received a common starter diet until the experimental period. Each cage was randomly assigned to 1 of the dietary treatments (trial 1 and trial 2: control + 6 test diets, 13 replicates per diet; trial 3: control + 3 test diets, 12 replicates per diet). Experimental diets were fed over a 6-d acclimation period, followed by a 48-h total excreta collection period. On a DM basis, AMEn of the 15 DDGS samples ranged from 1,975 to 3,634 kcal/kg. Analyses were conducted to determine gross energy, CP, EE, DM, starch, total dietary fiber, neutral detergent fiber, crude fiber (CF), acid detergent fiber, and ash content of the DDGS samples. All results were reported on a DM basis. Application of the 4 equations to the validation data resulted in root mean square error (RMSE) values of 335, 381, 488, and 502 kcal/kg, respectively. Least absolute shrinkage and selection operator technique was applied to proximate analysis data for 30 corn coproducts adapted from prior research and resulted in the following best-fit equation: [AMEn (kcal/kg) = 3,673 - (121.35 × CF) + (51.29 × EE) - (121.08 × ash); P < 0.01; R(2) = 0.70; R(2) adj = 0.67; RMSE = 270 kcal/kg]. The RMSE values obtained through validation were not consistent with the expectation of predictive performance based on internal measures of fit for each equation. These results indicated that validation is necessary to quantify the expected error associated with practical application of each individual prediction equation to external data.

A DPP-IV-resistant triple-acting agonist of GIP, GLP-1 and glucagon receptors with potent glucose-lowering and insulinotropic actions in high-fat-fed mice.

AIMS/HYPOTHESIS: We designed a chemically modified, enzyme-resistant peptide with triple-acting properties based on human glucagon with amino acid substitutions aligned to strategic positions in the sequence of glucose-dependent insulinotropic polypeptide (GIP). METHODS: Y(1)-dA(2)-I(12)-N(17)-V(18)-I(27)-G(28,29)-glucagon (termed YAG-glucagon) was incubated with dipeptidylpeptidase IV (DPP-IV) to assess stability, BRIN-BD11 cells to evaluate insulin secretion, and receptor-transfected cells to examine cAMP production. Acute glucose-lowering and insulinotropic properties of YAG-glucagon were assessed in National Institutes of Health (NIH) Swiss mice, while longer-term actions on glucose homeostasis, insulin secretion, food intake and body weight were examined in high-fat-fed mice. RESULTS: YAG-glucagon was resistant to DPP-IV, increased in vitro insulin secretion (1.5-3-fold; p < 0.001) and stimulated cAMP production in GIP receptor-, glucagon-like peptide-1 (GLP-1) receptor- and glucagon receptor-transfected cells. Plasma glucose levels were significantly reduced (by 51%; p < 0.01) and insulin concentrations increased (1.2-fold; p < 0.01) after acute injection of YAG-glucagon in NIH Swiss mice. Acute actions were countered by established GIP, GLP-1 and glucagon antagonists. In high-fat-fed mice, twice-daily administration of YAG-glucagon for 14 days reduced plasma glucose (40% reduction; p < 0.01) and increased plasma insulin concentrations (1.8-fold; p < 0.05). Glycaemic responses were markedly improved (19-48% reduction; p < 0.05) and insulin secretion enhanced (1.5-fold; p < 0.05) after a glucose load, which were independent of changes in insulin sensitivity, food intake and body weight. CONCLUSIONS/INTERPRETATION: YAG-glucagon is a DPP-IV-resistant triple agonist of GIP, GLP-1 and glucagon receptors and exhibits beneficial biological properties suggesting that it may hold promise for treatment of type 2 diabetes.

MLL2 mosaic mutations and intragenic deletion-duplications in patients with Kabuki syndrome.

Kabuki syndrome (KS) is a rare multi-system disorder that can result in a variety of congenital malformations, typical dysmorphism and variable learning disability. It is caused by MLL2 point mutations in the majority of the cases and, rarely by deletions involving KDM6A. Nearly one third of cases remain unsolved. Here, we expand the known genetic basis of KS by presenting five typical patients with the condition, all of whom have novel MLL2 mutation types- two patients with mosaic small deletions, one with a mosaic whole-gene deletion, one with a multi-exon deletion and one with an intragenic multi-exon duplication. We recommend MLL2 dosage studies for all patients with typical KS, where traditional Sanger sequencing fails to identify mutations. The prevalence of such MLL2 mutations in KS may be comparable with deletions involving KDM6A. These findings may be helpful in understanding the mutational mechanism of MLL2 and the disease mechanism of KS.

Apparent metabolizable energy and prediction equations for reduced-oil corn distillers dried grains with solubles in broiler chicks from 10 to 18 days of age.

An experiment consisting of 2 identically designed trials was conducted to determine the nutrient composition and AMEn content of distillers dried grains with solubles (DDGS) to develop prediction equations for AMEn in broilers. Fifteen samples of DDGS ranging in ether extract (EE) from 3.15 to 13.23% (DM basis) were collected from various dry-grind ethanol plants and were subsequently fed to broiler chicks to determine AMEn content. A corn-soybean meal control diet was formulated to contain 15% dextrose, and test diets were created by mixing the control diet with 15% DDGS at the expense of dextrose. In each trial, 672 male Ross × Ross 708 chicks were housed in grower battery cages with 7 birds per cage (0.06 m(2)/bird) and received a common starter diet until 10 d of age. Each cage was randomly assigned to 1 of 16 dietary treatments, with 6 replicate pens per treatment. Experimental diets were fed over a 6-d acclimation period from 10 to 16 d of age, followed by a 48-h total excreta collection period. Gross energy (GE) and CP of the experimental diets and excreta were determined to calculate AMEn for each DDGS sample. On a DM basis, AMEn of the 15 DDGS samples ranged from 1,869 to 2,824 kcal/kg. Analyses were conducted to determine the GE, CP, EE, DM, starch, total dietary fiber (TDF), neutral detergent fiber (NDF), acid detergent fiber (ADF), and ash content of the DDGS samples. Stepwise regression resulted in the following best-fit equation for AMEn (DM basis) based on the adjusted coefficient of determination (R(2)adj), SE, and prediction error sum of squares (PRESS): AMEn, kcal/kg = -12,282 + (2.60 × GE) + (89.75 × CP) + (125.80 × starch) - (40.67 × TDF; R(2)adj = 0.86; SE = 98.76; PRESS = 199,819; P ≤ 0.001). These results indicated that the composition of DDGS with variable EE content may be used to predict AMEn in broiler chicks.

Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal recessive Robinow syndrome.

Robinow syndrome is a short-limbed dwarfism characterized by abnormal morphogenesis of the face and external genitalia, and vertebral segmentation. The recessive form of Robinow syndrome (RRS; OMIM 268310), particularly frequent in Turkey, has a high incidence of abnormalities of the vertebral column such as hemivertebrae and rib fusions, which is not seen in the dominant form. Some patients have cardiac malformations or facial clefting. We have mapped a gene for RRS to 9q21-q23 in 11 families. Haplotype sharing was observed between three families from Turkey, which localized the gene to a 4. 9-cM interval. The gene ROR2, which encodes an orphan membrane-bound tyrosine kinase, maps to this region. Heterozygous (presumed gain of function) mutations in ROR2 were previously shown to cause dominant brachydactyly type B (BDB; ref. 7). In contrast, Ror2-/- mice have a short-limbed phenotype that is more reminiscent of the mesomelic shortening observed in RRS. We detected several homozygous ROR2 mutations in our cohort of RRS patients that are located upstream from those previously found in BDB. The ROR2 mutations present in RRS result in premature stop codons and predict nonfunctional proteins.

Swine diets: Impact of carbohydrate sources on manure characteristics and gas emissions.

Swine growers seeking to lower costs and environmental impact have turned to alternative carbohydrate feed sources. A feeding trial was conducted to determine the effect carbohydrate sources have on manure composition and gas emissions. A total of 48 gilts averaging 138 kg BW were fed diets consisting of (a) low fiber (LF) grain, or (b) high fiber (HF) aro-industrial co-product (AICP). The LF diets included corn and soybean meal (CSBM) and barley soybean meal (BSBM). The HF AICP diets were CSBM based and supplemented with one of the following materials: beet pulp; corn distillers dried grains with solubles; soybean hulls; or wheat bran. Diets were fed for 42 d with an average daily feed intake of 2.71 kg d-1. Feces and urine were collected twice daily and added to manure storage containers in which manure slurries were monitored for gas emissions and chemical properties. Manures of animals fed HF diets had significantly (P < 0.05) more excretion of solids, C, N, and organic N, but less total S compared to pigs fed the LF diets. Animals feed HF diets had significantly (P < 0.05) higher levels of ammonia, sulfide, volatile fatty acids, and phenols in manure compared to pigs fed the LF diets. Manure of animals fed HF diets had 30% (P < 0.05) lower NH3 and 17% lower hydrogen sulfide emissions; however, fiber had no impact on odor emissions. Based on the partitioning of nutrients, animals fed HF fiber diets had increased manure retention for C and N but decreased levels of N gas emissions and manure S. There were little differences in manure and gas emissions for animals fed LF diets, but the source of HF AICP diets had a significant impact on manure composition and gas emissions.

Apparent metabolizable energy of crude glycerin originating from different sources in broiler chickens.

An energy balance experiment was conducted to determine the AME(n) of various crude glycerin samples, and to generate an equation to predict AME(n) of crude glycerin based on its chemical composition. Dietary treatments consisted of a corn-soybean meal basal diet with no added glycerin and a basal diet supplemented with 6% glycerin. Crude glycerin samples were obtained from biodiesel production facilities throughout the United States, which use a variety of lipid products as their initial feedstock. Two identical energy balance trials were conducted. In each trial, 864 male broilers (Ross × Ross 708) were fed a common starter diet until 17 d of age when they were switched to 1 of 12 experimental diets (6 replicates per treatment) from 17 to 22 d of age, with a 48-h collection period on d 21 and 22. Nitrogen-corrected apparent metabolizable energy values of crude glycerin samples were estimated by difference, whereby AME(n) of the basal diet was subtracted from the complete diet containing the test ingredient. The AME(n) of the basal diet and US Pharmacopeia-grade glycerin were determined to be 3,085 and 3,662 kcal/kg, respectively, whereas the AME(n) of the 10 crude glycerin samples ranged from 3,254 to 4,134 kcal/kg. Two crude glycerin samples had high levels of fatty acids compared with the other samples (24 and 35% vs. <0.30%), and even though their AME(n) was higher than that of the other glycerin samples (3,806 vs. 3,611 kcal/kg, P < 0.01, respectively), their AME(n) as a percentage of gross energy (GE) was lower than that of the other samples (65.5% vs. 97.4%, respectively; P < 0.01). Including all of the glycerin samples, the stepwise regression equation to predict AME(n) was determined to be: [AME(n) (kcal/kg) = 1,605 - (19.13 × % methanol) + (39.06 × % fatty acid) + (23.47 × % glycerin)]; (R(2) = 0.25; SE = 379; P ≤ 0.01). These data indicate that glycerin is a good source of energy for broilers, and the AME(n) of glycerin is dependent on fatty acid, methanol, and water contents.

Energy determination of corn co-products fed to broiler chicks from 15 to 24 days of age, and use of composition analysis to predict nitrogen-corrected apparent metabolizable energy.

An experiment (3 trials) was conducted to determine the AME(n) of 15 corn co-products obtained from various wet and dry milling plants, and to develop prediction equations for AME(n) based on chemical composition. Co-products included distillers dried grains with solubles (DDGS, n = 6), high-protein distillers dried grains (n = 2), corn germ (n = 2), corn germ meal, corn bran with solubles, corn gluten meal, corn gluten feed, and dehulled, degermed corn. Treatments (15) consisted of 85% inclusion of the corn-soybean meal basal diet combined with a 15% inclusion of each corn co-product, as well as a control diet containing glucose•H(2)O (15%) at the expense of the co-product. In each trial, Ross × Ross 708 chicks (10 birds per pen) were randomly assigned to 16 dietary treatments (12 replicate pens; 4 replicate pens per trial). After a 7-d diet acclimation period from 15 to 22 d of age, a 48-h total excreta collection was conducted for the determination of AME(n). Co-products were analyzed for gross energy, CP, moisture, crude fat, starch, crude fiber, ash, total dietary fiber, neutral detergent fiber, and acid detergent fiber, and hemicellulose was determined by difference. Stepwise regression resulted in the following equation: AME(n), kcal/kg of DM = 3,517 + (46.02 × % crude fat, DM basis) - (82.47 × % ash, DM basis) - (33.27 × % hemicellulose, DM basis) (R(2) = 0.89; SEM = 191; P ≤ 0.01). Removing hemicellulose from the model resulted in the following equation: AME(n), kcal/kg of DM = (-30.19 × % neutral detergent fiber, DM basis) + (0.81 × gross energy, kcal/kg of DM basis) - (12.26 × % CP, DM basis) (R(2) = 0.87; SEM = 196; P ≤ 0.01). These results indicate that nutrient composition may be used to generate AME(n) prediction equations for corn co-products fed to broiler chicks.

Swine diets impact manure characteristics and gas emissions: Part I protein level.

Crude protein (CP) is a key nutrient in swine diets supplying essential amino acids, N, and S to animals for growth are fed in excess to maximize growth. Swine diets reduced in CP and supplemented with crystalline amino acids have been shown effective at maintaining animal growth while increasing overall CP use efficiency. A feeding trial study was conducted to determine the effects of reduced dietary CP levels on manure slurry chemical properties and gas emissions. A total of 24 gilts averaging 111 kg BW were fed corn and soybean meal diets formulated with 8.7, 14.8, and 17.6% CP using crystalline amino acid supplementation in the 8.7 and 14.8% CP diets, but only intact protein, soybean meal, in the diet containing 17.6% CP. Diets were fed for 45 d with an average daily feed intake (ADFI) of 2.70 kg across all diets. Animals were fed twice daily with both feces and urine collected during each feeding and added to animal-specific manure storage containers. At the end of the study, manure slurries were monitored for gas emissions and chemical properties. Increasing dietary CP levels increased manure pH, total solids, total N, and total S, including increased levels of ammonia (NH3), volatile fatty acids, and phenolic compounds. Pigs fed lower CP diets had lower emissions of NH3, branched chain fatty acids (BCFA), and phenol compounds which translated into lower emissions in total odor. Emissions of NH3 and odor were reduced by 8.9% and 4.2%, respectively, for each unit percent decline in dietary CP. Hydrogen sulfide was the dominate odorant associated with manure odor emissions. Based on nutrient mass balance, animal retention of dietary N and S increased by 7.0% and 2.4%, respectively, for each unit percent drop in crude protein fed animals, while C retention in the animal declined by 2.1%.

Swine diets impact manure characteristics and gas emissions: Part II protein source.

Soybean meal is the dominate protein source for swine diets in the world driven largely by economics, nutritive value, and availability; but conditions can change requiring growers to consider more economical and available protein alternatives. A feeding trial was conducted to determine the impact dietary protein source material on manure slurry chemical properties and manure gas emissions. A total of 32 gilts averaging 130 kg BW were fed either a control diet formulated with soybean meal (SB) or an alternative protein source that included corn gluten meal (CG); canola meal (CM); or poultry meal (PM), with all diets containing 176 g protein kg-1. Diets were fed for 45 d with an average daily feed intake of 2.68 kg/d. Feces and urine were collected twice daily after each feeding and added to animal-specific manure storage containers. At the end of the study, manure slurries were monitored for gas emissions and chemical properties. Dietary protein source had a significant effect (P < 0.05) on manure pH, total solids, total C, protein N, and total S. Pigs fed the diets containing CM had significantly higher levels of sulfide, butanoic acid, and branch chain fatty acids compared to pigs fed SB diets (P < 0.05). Pigs fed CM diets had significantly lower emissions of NH3 compared to pigs fed SB diets (P < 0.05). There were no significant differences in C or S emissions or in odorant emission as affected by source of dietary protein. Hydrogen sulfide was the most dominate odorants for all dietary treatments.

A review of telephone consultations for head and neck cancer follow up: a patient satisfaction survey.

OBJECTIVE: To review patient satisfaction with the change in practice towards telephone consultations during and after the coronavirus disease 2019 pandemic for head and neck cancer follow up. METHOD: A retrospective analysis was conducted of head and neck cancer telephone appointments during a six-month period in a tertiary referral centre. RESULTS: Patients found the telephone consultations beneficial (98 per cent), with 30 per cent stating they were relieved to not have to attend hospital. Patients who travelled further, those with lower stage disease and patients with a greater interval from initial treatment were most satisfied with the telephone consultations. Sixty-eight per cent of patients stated they would be happy to have telephone consultations as part of their regular follow up after the pandemic. CONCLUSION: Patients found the telephone consultations beneficial and 30 per cent considered them preferable to face-to-face appointments. This study demonstrates that telephone consultations can be used as an adjunct to face-to-face appointments in an effort to reduce hospital attendances whilst maintaining close follow up.

Four weeks administration of Liraglutide improves memory and learning as well as glycaemic control in mice with high fat dietary-induced obesity and insulin resistance.

AIM: Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) mimetic which is a treatment option for type 2 diabetes. GLP-1 peptides, including Liraglutide, cross the blood-brain barrier and may additionally act to improve brain function. The present study tested the hypothesis that, in addition to its antihyperglycaemic actions, peripheral administration of Liraglutide exerts positive actions on cognitive function in mice with high fat dietary-induced obesity and insulin resistance. METHODS: Young Swiss TO mice maintained on high fat diet for 20 weeks received twice-daily injections of Liraglutide (200 µg/kg bw; sc) or saline vehicle over 28 days. An additional group of mice on standard diet received twice-daily saline injections. Energy intake, bodyweight, non-fasting plasma glucose and insulin concentrations were monitored at regular intervals. Glucose tolerance, open field assessment, object recognition testing and electrophysiological long-term potentiation (LTP) were performed at termination of the study. RESULTS: Liraglutide treatment resulted in significant time-dependent reduction in bodyweight and energy intake, whilst improving non-fasting glucose and normalizing glucose tolerance. Although Liraglutide did not alter general behaviour, treated mice exhibited marked increase in recognition index (RI) during object recognition testing, indicative of enhanced learning and memory ability. Furthermore, Liraglutide rescued the deleterious effects of high fat diet on hippocampal LTP of neurotransmission following both chronic and direct intracerebroventricular (icv) administration. CONCLUSION: Liraglutide administered peripherally not only improves metabolic parameters but exerts additional beneficial effects on cognitive function and hippocampal synaptic plasticity. Whether therapy with GLP-1 mimetics has similar effects in humans with type 2 diabetes needs to be established.

SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype.

OBJECTIVE: Mutations of the SPRED1 gene, one of a family of Sprouty (Spry)/Spred proteins known to "downregulate" mitogen activated protein kinase (MAPK) signalling, have been identified in patients with a mild neurofibromatosis type 1 (NF1) phenotype with pigmentary changes but no neurofibromas (Legius syndrome).To ascertain the frequency of SPRED1 mutations as a cause of this phenotype and to investigate whether other SPRED/SPRY genes may be causal, a panel of unrelated mild NF1 patients were screened for mutations of the SPRED1-3 and the SPRY1-4 genes. METHODS: 85 patients with a mild NF1 phenotype were screened for SPRED1 mutations. 44 patients negative for both NF1 and SPRED1 mutations were then screened for SPRED2-3 and SPRY1-4 mutations. Complexity analysis was applied to analyse the flanking sequences surrounding the identified SPRED1 mutations for the presence of direct and inverted repeats or symmetric sequence elements in order to infer probable mutational mechanism. RESULTS: SPRED1 mutations were identified in 6 cases; 5 were novel and included 3 nonsense (R16X, E73X, R262X), 2 frameshift (c.1048_c1049 delGG, c.149_1152del 4 bp), and a single missense mutation (V44D). Short direct or inverted repeats detected immediately adjacent to some SPRED1 mutations may have led to the formation of the microdeletions and base pair substitutions. DISCUSSION: The identification of SPRED1 gene mutation in NF1-like patients has major implications for counselling NF1 families.

Changes in bacterial communities from swine feces during continuous culture with starch.

Bacteria from swine feces were grown in continuous culture with starch as the sole carbohydrate in order to monitor changes during fermentation and to determine how similar fermenter communities were to each other. DNA extracted from fermenter samples was analyzed by denaturing gradient gel electrophoresis (DGGE). A significant decrease in diversity was observed, the Shannon-Weaver index dropped from 1.92 to 1.13 after 14 days of fermentation. Likewise, similarity of fermenter communities to those in the fecal inoculum also decreased over time. Both diversity and similarity to the inoculum decreased most rapidly in the first few days of fermentation, reflecting a period of adaptation. Sequencing of DGGE bands indicated that the same species were present in replicate fermenters. Most of these bacteria were placed in the Clostridium coccoides/Eubacterium rectale group (likely saccharolytic butyrate producers), a dominant bacterial group in the intestinal tract of pigs. DGGE proved useful to monitor swine fecal communities in vitro and indicated the selection and maintenance of native swine intestinal bacteria during continuous culture.