Animal medical genetics: a historical perspective on more than 50 years of research into genetic disorders of animals at Massey University.

Over the last 50 years, there have been major advances in knowledge and technology regarding genetic diseases, and the subsequent ability to control them in a cost-effective manner. This review traces these advances through research into genetic diseases of animals at Massey University (Palmerston North, NZ), and briefly discusses the disorders investigated during that time, with additional detail for disorders of major importance such as bovine α-mannosidosis, ovine ceroid-lipofuscinosis, canine mucopolysaccharidosis IIIA and feline hyperchylomicronaemia. The overall research has made a significant contribution to veterinary medicine, has provided new biological knowledge and advanced our understanding of similar disorders in human patients, including testing various specific therapies prior to human clinical trials.

COVID-19: looking beyond the peak. Challenges and tips for radiologists in follow-up of a novel patient cohort.

As the coronavirus pandemic evolves, the focus of radiology departments has begun to change. The acute phase of imaging a new disease entity whilst rationalising radiology services in the face of lockdown has passed. Radiologists are now becoming familiar with the complications of COVID-19, particularly the lung parenchymal and pulmonary vascular sequelae and are considering the impact follow-up imaging may have on departments already struggling with a backlog of suspended imaging in the face of reduced capacity. This review from the British Society of Thoracic Imaging explores both the thoracic and extra-thoracic complications of COVID-19, recognising the importance of a holistic approach to patient follow-up. The British Thoracic Society guidelines for respiratory follow-up of COVID-19 will be discussed, together with newly developed reporting templates, which aim to provide consistency for clinicians as well as an opportunity for longer-term data collection.

Food additives: Assessing the impact of exposure to permitted emulsifiers on bowel and metabolic health - introducing the FADiets study.

Emulsifiers are common components of processed foods consumed as part of a Western diet. Emerging in vitro cell-line culture, mouse model and human intestinal tissue explant studies have all suggested that very low concentrations of the food emulsifier polysorbate 80 may cause bacterial translocation across the intestinal epithelium, intestinal inflammation and metabolic syndrome. This raises the possibility that dietary emulsifiers might be factors in conditions such as coronary artery disease, type 2 diabetes and Crohn's disease. The potential mechanism behind the observed effects of this emulsifier is uncertain but may be mediated via changes in the gut microbiota or by increased bacterial translocation, or both. It is also unknown whether these effects are generalisable across all emulsifiers and detergents, including perhaps the natural emulsifier lecithin or even conjugated bile acids, particularly if the latter escape reabsorption and pass through to the distal ileum or colon. A major objective of the Medical Research Council (MRC)-funded Mechanistic Nutrition in Health (MECNUT) Emulsifier project is therefore to investigate the underlying mechanisms and effects of a range of synthetic and natural emulsifiers and detergents in vitro and in vivo, and to determine the effects of a commonly consumed emulsifier (soya lecithin) on gut and metabolic health through a controlled dietary intervention study in healthy human volunteers - the FADiets study. This report provides an overview of the relevant literature, discussing the impact of emulsifiers and other additives on intestinal and metabolic health, and gives an overview of the studies being undertaken as part of the MECNUT Emulsifier project.

Tibial nailing using a suprapatellar rather than an infrapatellar approach significantly reduces anterior knee pain postoperatively: a multicentre clinical trial.

AIMS: The aim of this study was to compare the incidence of anterior knee pain after antegrade tibial nailing using suprapatellar and infrapatellar surgical approaches. PATIENTS AND METHODS: A total of 95 patients with a tibial fracture requiring an intramedullary nail were randomized to treatment using a supra- or infrapatellar approach. Anterior knee pain was assessed at four and six months, and one year postoperatively, using the Aberdeen Weightbearing Test - Knee (AWT-K) score and a visual analogue scale (VAS) score for pain. The AWT-K is an objective patient-reported outcome measure that uses weight transmitted through the knee when kneeling as a surrogate for anterior knee pain. RESULTS: A total of 53 patients were randomized to a suprapatellar approach and 42 to an infrapatellar approach. AWT-K results showed a greater mean proportion of weight transmitted through the injured leg compared with the uninjured leg when kneeling in the suprapatellar group compared with the infrapatellar group at all timepoints at all follow-up visits. This reached significance at four months for all timepoints except 30 seconds. It also reached significance at six months at 0 seconds, and for one year at 60 seconds. CONCLUSION: The suprapatellar surgical approach for antegrade tibial nailing is associated with less anterior knee pain postoperatively compared with the infrapatellar approach Cite this article: Bone Joint J 2019;101-B:1138-1143.

Dietary carbohydrate rather than protein intake drives colonic microbial fermentation during weight loss.

PURPOSE: High protein weight loss diets are effective in aiding body weight management. However, high protein and low carbohydrate intakes can alter colonic fermentation profiles in humans and may impact on colonic health. This study aims to identify the most important dietary contributors to colonic fermentation during diet-controlled weight loss. METHODS: Overweight or obese male volunteers (n = 18) consumed a body weight maintenance diet (fed at 1.5× basic metabolic rate, BMR) followed by three weight loss diets (fed at 1× BMR) for 10 days each in a cross-over design. Weight loss diets were designed as normal protein (NPWL, 15% of energy from protein, 55% from carbohydrate), normal protein enriched with free amino acids and moderate amounts of carbohydrate (NPAAWL, 15% of energy from protein, 15% from free AA, 40% from carbohydrate) or high protein containing moderate amounts of carbohydrate (HPWL, 30% of energy from protein, 40% from carbohydrate). Faecal samples collected at the end of each diet period were profiled for dietary metabolites using LC-MS/MS. RESULTS: This study shows that the NPWL diet only induced very minor changes in the faecal metabolome, whereas NPAAWL and HPWL diets decreased carbohydrate-related metabolites (butyrate, ferulic acid) and increased protein-related metabolites. Most faecal metabolites were correlated with dietary carbohydrate and not protein intake. CONCLUSION: This study demonstrates that dietary carbohydrate is the main driver of colonic fermentation in humans and that a balance between dietary carbohydrate and protein should be maintained when designing safe, effective and healthy weight loss diets.

Combined Volar and Dorsal Approach for Fixation of Comminuted Intra-Articular Distal Radial Fractures.

Purpose Multifragmentary intra-articular fractures displaced in multiple planes are a challenge. We use a reproducible technique of fracture and articular reduction using an initial volar approach targeting reduction in the volar lunate facet first with plate and unicortical locking screws. This creates a template for reduction in dorsal fragments through a dorsal approach. Our study investigated the radiological, clinical, and functional outcomes of patients treated with this technique. Materials and Methods We reviewed the postoperative radiographs and notes of 18 patients that had this method of fixation between the years 2008 and 2015, the mean age being 43. These patients were reviewed functionally on average 2 years and 3 months following their definitive operation. Results Normal alignment and length to the distal radius were restored with on average a 0.6 mm articular step. The average range of motion was 64% and preservation of grip strength was 71% compared with the uninjured wrist. Functional assessment averages were 29 for both the quick Disabilities of the Arm, Shoulder and Hand (DASH) and for Patient Rated Wrist Evaluation. The modified system of Green and O'Brien had results of good in 10, fair in 7, and poor in 1. With respect to the Gartland and Werley system, three patients had an excellent result, four had a good result, six had a fair result, and five had a poor result. The mean arthritic grading was 1 (grading 0-3) according to Knirk and Jupiter. Conclusion This reproducible technique provides an option for these devastating fractures providing a functioning wrist with all of the patients returning to their original form of employment.

The Big Breakfast Study: Chrono-nutrition influence on energy expenditure and bodyweight.

A growing body of evidence highlights the importance of the biological clock as a modulator of energy balance and metabolism. Recent studies in humans have shown that ingested calories are apparently utilised more efficiently in the morning than in the evening and this is manifest through improved weight loss, even under iso-energetic calorie intake. The mechanisms behind this enhanced morning energy metabolism are not yet clear, although it may result from behavioural adaptations or circadian driven variations in physiology and energy metabolism. A major objective of the newly funded Big Breakfast Study therefore is to investigate the mechanistic basis of this amplified morning thermogenesis leading to enhanced weight loss, by exploring behavioural and physiological adaptations in energy expenditure alongside the underlying circadian biology. This report briefly discusses the current research linking meal timing, circadian rhythms and metabolism; highlights the research gaps; and provides an overview of the studies being undertaken as part of the Medical Research Council-funded Big Breakfast Study.

Protein for Life: Towards a focussed dietary framework for healthy ageing.

'Ageing well' has been highlighted as an important research area by the World Health Organization. In the UK, healthy ageing has been identified as a priority research area by multiple Research Councils and is a key NHS priority. Sarcopaenia, the decline of muscle mass/strength and a key component of healthy ageing, can have a major impact on quality of life and is associated with premature mortality. Increasing protein intake at all stages of the life course may help to reduce the rate of muscle decline and the onset of associated health conditions. However, there is a lack of understanding of the social, demographic and psychological drivers of food choices surrounding protein intake. This report describes the multidisciplinary approach that has been adopted by the Protein for Life project to create a framework for the development of palatable, cost-effective higher-protein foods suitable for an ageing population.

Effects of hunger state on the brain responses to food cues across the life span.

The abundant exposure to food cues in our environment is one of the main drivers of overconsumption. Food evaluation is important for the regulation of food intake by the brain and it's interaction with hunger state. Children are especially susceptible to food cues. Understanding the mechanisms behind this regulation in healthy individuals across the life span can help to elucidate the mechanisms underlying overconsumption and aid the development of future obesity prevention strategies. Few functional neuroimaging studies have been done in children and elderly. Furthermore, it is unknown how hunger state affects neural food cue reactivity in these groups, since this has not been examined consistently. We examined the effects of hunger state and age on the brain responses to low- and high calorie foods. On two mornings, 122 participants (17 children; 38 teens; 36 adults; 31 elderly) performed a food image viewing task while being scanned using fMRI, either fasted or sated. Hunger induced greater activation during high versus low calorie food image viewing than satiety in the bilateral dorsomedial (dmPFC) and in the right dorsolateral prefrontal cortex (dlPFC) across all age groups. There was no significant main effect of age group on high versus low calorie food image viewing and no interaction between age group and hunger state. The greater activation of the dlPFC across all age groups during high calorie food image viewing in a fasted state might reflect increased inhibitory control in response to these foods. This may underlie the ability to resist overconsumption of high calorie foods. Furthermore, increased medial prefrontal cortex activation during hunger might reflect increased reward value of high calorie foods, which declines with satiation. Further studies are needed to better understand these results. Notably, overweight and obese individuals should be included to examine whether these responses are altered by weight status across the life span.

Effects of maternal high-fat diet and sedentary lifestyle on susceptibility of adult offspring to ozone exposure in rats.

Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O3). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O3. Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O3 with responses markedly exacerbated in males. HF diet and O3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O3 in their adult offspring in a sex-specific manner.

The feasibility of contraceptive injections at the community pharmacy.

PURPOSE: The progestogen-only intramuscular injectable Depo-Provera® (depot medroxyprogesterone acetate) is an effective contraceptive method, but users need to attend a clinic every 12-13 weeks for a repeat injection from a doctor/nurse. This limits convenience of the method and may affect continuation rates. We conducted a pilot study to examine the feasibility and acceptability of users receiving the subcutaneous form of the contraception injection from pharmacists in the community pharmacy setting. MATERIALS AND METHODS: Existing users of Depo-Provera®, who wished to switch to the subcutaneous preparation with the same active ingredient (Sayana Press®) were invited to attend 1 of 11 community pharmacies for up to three repeat injections, given by a pharmacist. Evaluation consisted of (i) self-administered questionnaires of women and (ii) interviews with participating pharmacists, at study exit on their respective experiences. RESULTS: Global unavailability of the product during the study adversely affected recruitment and retention. 50 women were recruited. Only 48 injections were delivered at the pharmacy out of a possible 150 (34%). About 26 participants received no injections at the pharmacy and only seven (14%) participants received all three injections at the pharmacy. Participants reported mixed experiences, with some welcoming the intervention but others experiencing difficulty with pharmacist availability. Pharmacists were enthusiastic about this expansion of their role, and did not view their availability as a barrier to service delivery. CONCLUSIONS: Delivery of the subcutaneous contraceptive injectable from a community pharmacy may be feasible but availability of sufficient numbers of pharmacists trained in this technique is necessary for a robust model of service delivery.

An ovine hepatorenal fibrocystic model of a Meckel-like syndrome associated with dysmorphic primary cilia and TMEM67 mutations.

Meckel syndrome (MKS) is an inherited autosomal recessive hepatorenal fibrocystic syndrome, caused by mutations in TMEM67, characterized by occipital encephalocoele, renal cysts, hepatic fibrosis, and polydactyly. Here we describe an ovine model of MKS, with kidney and liver abnormalities, without polydactyly or occipital encephalocoele. Homozygous missense p.(Ile681Asn; Ile687Ser) mutations identified in ovine TMEM67 were pathogenic in zebrafish phenotype rescue assays. Meckelin protein was expressed in affected and unaffected kidney epithelial cells by immunoblotting, and in primary cilia of lamb kidney cyst epithelial cells by immunofluorescence. In contrast to primary cilia of relatively consistent length and morphology in unaffected kidney cells, those of affected cyst-lining cells displayed a range of short and extremely long cilia, as well as abnormal morphologies, such as bulbous regions along the axoneme. Putative cilia fragments were also consistently located within the cyst luminal contents. The abnormal ciliary phenotype was further confirmed in cultured interstitial fibroblasts from affected kidneys. These primary cilia dysmorphologies and length control defects were significantly greater in affected cells compared to unaffected controls. In conclusion, we describe abnormalities involving primary cilia length and morphology in the first reported example of a large animal model of MKS, in which we have identified TMEM67 mutations.

Systemic granulomatous and haemorrhagic syndrome in New Zealand dairy cattle.

CASE HISTORY: Cases were obtained through passive surveillance reporting by veterinary pathologists, via the Ministry for Primary Industries Exotic Pest and Disease Hotline. They included ill or dead cows that had evidence of frank haemorrhage, petechial haemorrhages on mucous membranes, wasting or dermatitis of unknown cause, and were reported between 2009-2014. Affected cows (n=16) were from nine seasonally calving dairy farms, aged ≥3 years, and were predominantly in their mid-to-late non-lactating period. A brassica crop was identified in 15/16 cases as part of the current or recent ration. CLINICAL FINDINGS: Eight cows were found dead or died within 2 days of first signs. In eight cases death or euthanasia took place up to 3 weeks after signs were first observed. Cattle clinically examined prior to death (n=11) were generally inappetant, and recumbent or reluctant to move. Five cases had pale mucous membranes, three had petechiae and two were jaundiced. Rectal temperature was normal to sub-normal in eight cases. Evidence of melena or fresh blood at the anus or mouth was found in five cases. In three cases, alopecia and skin thickening was present, predominantly affecting the head and neck. PATHOLOGICAL FINDINGS: Petechiation of mucosal and internal serosal membranes, myocardium, subcutis and skeletal muscle was found in 10 cases. Frank haemorrhage was present in six cases, including haematomas of the subcutis, skeletal musculature, mesentery or omentum, and lumenal haemorrhage of the abomasum and/or intestine. In five cases pale nodules within myocardium and/or kidney, liver or spleen were present. Histopathologically, these were confirmed as granulomatous inflammatory lesions, which were also present within a wide range of tissues. Granulomatous foci typically comprised aggregates of macrophages, lymphocytes, plasma cells, prominent multinucleated giant cells and eosinophils. DIAGNOSIS: Idiopathic multisystemic granulomatous and haemorrhagic disease, occurring sporadically in dairy cattle, in the absence of feeds or feed additives previously associated with comparable syndromes. CLINICAL RELEVANCE: This is the first description of a novel systemic granulomatous and haemorrhagic syndrome seen in adult dairy cattle most often in their non-lactating period. The presentation can mimic important exotic disease differentials in New Zealand including anthrax, haemorrhagic septicaemia (associated with selected Pasteurella multocida strains) or infection with bovine viral diarrhoea virus type 2.