Morbidity burden and community-based palliative care are associated with rates of hospital use by people with schizophrenia in the last year of life: A population-based matched cohort study

Objective: People with schizophrenia face an increased risk of premature death from chronic diseases and injury. This study describes the trajectory of acute care health service use in the last year of life for people with schizophrenia and how this varied with receipt of community based specialist palliative care and morbidity burden. Method: A population-based retrospective matched cohort study of people who died from 01/01/ 2009 to 31/12/2013 with and without schizophrenia in Western Australia. Hospital inpatient, emergency department, death and community-based care data collections were linked at the person level. Rates of emergency department presentations and hospital admissions over the last year of life were estimated. Results: Of the 63508 decedents, 1196 (1.9%) had a lifetime history of schizophrenia. After adjusting for confounders and averaging over the last year of life there was no difference in the overall rate of ED presentation between decedents with schizophrenia and the matched cohort (HR 1.09; 95%CI 0.99–1.19). However, amongst the subset of decedents with cancer, choking or intentional self-harm recorded on their death certificate, those with schizophrenia presented to ED more often. Males with schizophrenia had the highest rates of emergency department use in the last year of life. Rates of hospital admission for decedents with schizophrenia were on average half (HR 0.53, 95%CI 0.44–0.65) that of the matched cohort although this varied by cause of death. Of all decedents with cancer, 27.5% of people with schizophrenia accessed community-based specialist palliative care compared to 40.4% of the matched cohort (p\u3c0.001). Rates of hospital admissions for decedents with schizophrenia increased 50% (95% CI: 10%-110%) when enrolled in specialist palliative care. Conclusion: In the last year of life, people with schizophrenia were less likely to be admitted to hospital and access community-based speciality palliative care, but more likely to attend emergency departments if male. Community-based specialist palliative care was associated with increased rates of hospital admissions

Improving efficiency in meat production

Selective breeding and improved nutritional management over the past 20–30 years has resulted in dramatic improvements in growth efficiency for pigs and poultry, particularly lean tissue growth. However, this has been achieved using high-quality feed ingredients, such as wheat and soya that are also used for human consumption and more recently biofuels production. Ruminants on the other hand are less efficient, but are normally fed poorer quality ingredients that cannot be digested by human subjects, such as grass or silage. The challenges therefore are to: (i) maintain the current efficiency of growth of pigs and poultry, but using more ingredients not needed to feed the increasing human population or for the production of biofuels; (ii) improve the efficiency of growth in ruminants; (iii) at the same time produce animal products (meat, milk and eggs) of equal or improved quality. This review will describe the use of: (a) enzyme additives for animal feeds, to improve feed digestibility;(b) known growth promoting agents, such as growth hormone, β-agonists and anabolic steroids, currently banned in the European Union but used in other parts of the world; (c) recent transcriptomic studies into molecular mechanisms for improved growth efficiency via low residual feed intake. In doing so, the use of genetic manipulation in animals will also be discussed

Effects of insulin like growth factors on early embryonic chick limb myogenesis

Limb muscles derive from pax3 expressing precursor cells that migrate from the hypaxial somite into the developing limb bud. Once there they begin to differentiate and express muscle determination genes such as MyoD. This process is regulated by a combination of inductive or inhibitory signals including Fgf18, retinoic acid, HGF, Notch and IGFs. IGFs are well known to affect late stages of muscle development and to promote both proliferation and differentiation. We examined their roles in early stage limb bud myogenesis using chicken embryos as an experimental model. Grafting beads soaked in purified recombinant IGF-I, IGF-II or small molecule inhibitors of specific signaling pathways into developing chick embryo limbs showed that both IGF-I and IGF-II induce expression of the early stage myogenic markers pax3 and MyoD as well as myogenin. Their effects on pax3 and MyoD expression were blocked by inhibitors of both the IGF type I receptor (picropodophyllotoxin, PPP) and MEK (U0126). The PI3K inhibitor LY294002 blocked IGF-II, but not IGF-I, induction of pax3 mRNA as well as the IGF-I, but not IGF-II, induction of MyoD mRNA. In addition SU5402, an FGFR/ VEGFR inhibitor, blocked the induction of MyoD by both IGFs but had no effect on pax3 induction, suggesting a role for FGF or VEGF signaling in their induction of MyoD. This was confirmed by in situ hybridization showing that FGF18, a known regulator of MyoD in limb myoblasts, was induced by IGF-I. In addition to their well-known effects on later stages of myogenesis via their induction of myogenin expression, both IGF-I and IGF-II induced pax3 and MyoD expression in developing chick embryos, indicating that they also regulate early stages of myogenesis. The data suggests that the IGFs may have slightly different effects on IGF1R signal transduction via PI3K and that their stimulatory effects on MyoD expression may be indirect, possibly via induction of FGF18 expression

The impact of first and second eye cataract surgeries on falls: a prospective cohort study

Purpose: The purpose of this study was to investigate the impact of the first and second eye cataract surgeries on the risk of falls in participants with bilateral cataract and to determine which changes in visual measures are associated with changes in the number of falls throughout the cataract surgery process. Patients and methods: Fifty-five older adults with bilateral cataract aged 55+ years were assessed at three time points during the cataract surgery process, and they completed a falls diary. Two separate generalized estimating equation–negative binomial models were undertaken to assess changes in the number of falls before first eye cataract surgery, between first and second eye surgeries, and after second eye cataract surgery and which changes in visual measures were associated with changes in the number of falls. Results: After adjusting for potential confounding factors, the risk of falls decreased by 54% (incidence rate ratio (IRR) =0.458, 95% CI=0.215–0.974, p=0.04) after first eye cataract surgery only, compared with the period before first eye surgery. The risk of falls decreased by 73% (IRR =0.268, 95% CI =0.114–0.628, p=0.002) after second eye cataract surgery, compared with the period before first eye surgery. Improved binocular visual acuity (IRR =5.488, 95% CI =1.191–25.282, p=0.029) and contrast sensitivity (IRR =0.257, 95% CI =0.070–0.939, p=0.040) were associated with a decrease in the number of falls. Conclusion: The study found that first and second eye cataract surgeries reduced the risk of falls among a cohort of bilateral cataract patients with relatively good baseline vision. This suggests that timely first and second eye cataract surgeries could play an important role in reducing the burden due to falls among older adults with cataract

Differential effects of short-term β agonist and growth hormone treatments on expression of myosin heavy chain IIB and associated metabolic genes in sheep muscle

Growth hormone (GH) and β agonists increase muscle mass, but the mechanisms for this response are unclear and the magnitude of response is thought to vary with age of animal. To investigate the mechanisms driving the muscle response to these agents, we examined the effects of short-term (6 day) administration of GH or cimaterol (a β2-adrenergic agonist, BA) on skeletal muscle phenotype in both young (day 60) and mature (day 120) lambs. Expression of myosin heavy chain (MyHC) isoforms were measured in Longissimus dorsi (LD), Semitendinosus (ST) and Supraspinatus (SS) muscles as markers of fibre type and metabolic enzyme activities were measured in LD. To investigate potential mechanisms regulating the changes in fibre type/metabolism, expression or activity of a number of signalling molecules were examined in LD. There were no effects of GH administration on MyHC isoform expression at either the mRNA or protein level in any of the muscles. However, BA treatment induced a proportional change in MyHC mRNA expression at both ages, with the %MyHCI and/or IIA mRNA being significantly decreased in all three muscles and % MyHCIIX/IIB mRNA significantly increased in the LD and ST. BA treatment induced de novo expression of MyHCIIB mRNA in LD, the fastest isoform not normally expressed in sheep LD, as well as increasing expression in the other two muscles. In the LD, the increased expression of the fastest MyHC isoforms (IIX and IIB) was associated with a decrease in isocitrate dehydrogenase activity, but no change in lactate dehydrogenase activity, indicating a reduced capacity for oxidative metabolism. In both young and mature lambs, changes in expression of metabolic regulatory factors were observed that might induce these changes in muscle metabolism/fibre type. In particular, BA treatment decreased PPAR-γ coactivator-1β mRNA and increased receptor-interacting protein 140 mRNA. The results suggest that the two agents work via different mechanisms or over different timescales, with only BA inducing changes in muscle mass and transitions to a faster, less oxidative fibre type after a 6-day treatment

Gene expression of inflammatory markers in adipose tissue between obese women with polycystic ovary and normal obese women

OBJECTIVE: The pathogenesis of polycystic ovary syndrome (PCOS), a common endocrine disease and metabolic disturbance, is still unknown. The aim of the study was to investigate whether patients with PCOS display increased expression of inflammatory markers in adipose tissue. PATIENTS AND METHODS: Two groups of women were investigated, those diagnosed with PCOS (n = 8) and age and BMI-matched normal women (n = 12). Their age was between 20-45 years and all subjects were apparently healthy and did not take any medications. Adipose tissue levels of mRNA of inflammatory markers were determined by use of real-time PCR. RESULTS: There were no differences between obese patients and obese PCOS in levels of adipocytokines. CONCLUSIONS: There were no effects of PCOS on the expression of any of the adipocytokines genes measured in subcutaneous adipose tissue

The Western Australian Family Connections Genealogical Project: Detection of familial occurrences of single gene and chromosomal disorders

Aim: To investigate using a Western Australian (WA) genealogical database for the identification of single gene and chromosome disorders among families. Method: Hospital admissions for single gene and chromosome disorders recorded during 2000–2006 were identified from the WA Hospital Morbidity Data System. The proportion of these conditions occurring in family groups was then identified using genealogical links created through the WA Family Connections Genealogical Project. Results: There were 216 family clusters among 11,303 people who were recorded as having a genetic or chromosomal disorder on their hospital admission record. The most common single gene conditions found to occur in multiple family members included blood clotting disorders such as Factor VIII deficiency and Von Willebrand’s disease, followed by cystic fibrosis, myotonic dystrophies, neurofibromatosis, tuberous sclerosis, and osteogenesis imperfecta. Discussion: Single gene disorders most commonly occurring in multiple family members have been identified using the WA Family Connections Genealogical Project. These disorders reflect the most common single gene disorders requiring hospital admission, but which are not fatal before reproductive age and do not result in a loss of fertility. They are also restricted to disorders with earlier onset, as the WA Family Connections Genealogical Project currently covers 2–3 of the most recent generations. This study demonstrates the utility of record linkage genealogies to identify kindred with genetic disorders, offering a rich resource of information for focused genetic epidemiological research

Thyroid hormone and vitamin D regulate VGF expression and promoter activity

The Siberian hamster (Phodopus sungorus) survives winter by decreasing food intake and catabolizing abdominal fat reserves, resulting in a sustained, profound loss of body weight. Hypothalamic tanycytes are pivotal for this process. In these cells, short-winter photoperiods upregulate deiodinase 3, an enzyme that regulates thyroid hormone availability, and downregulate genes encoding components of retinoic acid (RA) uptake and signaling. The aim of the current studies was to identify mechanisms by which seasonal changes in thyroid hormone and RA signaling from tanycytes might ultimately regulate appetite and energy expenditure. proVGF is one of the most abundant peptides in the mammalian brain, and studies have suggested a role for VGF-derived peptides in the photoperiodic regulation of body weight in the Siberian hamster. In silico studies identified possible thyroid and vitamin D response elements in the VGF promoter. Using the human neuroblastoma SH-SY5Y cell line, we demonstrate that RA increases endogenous VG expression (P!0.05) and VGF promoter activity (P!0.0001). Similarly, treatment with 1,25-ihydroxyvitamin D3 increased endogenous VGF mRNA expression (P!0.05) and VGF promoter activity (P!0.0001),whereas triiodothyronine (T3) decreased both (P!0.01 and P!0.0001). Finally, intrahypothalamic administration of T3 blocked the short day-induced increase in VGF expression in the dorsomedial posterior arcuate nucleus of Siberian hamsters. Thus, we conclude that VGF expression is a likely target of photoperiod-induced changes in tanycyte-derived signals and is potentially a regulator of seasonal changes in appetite and energy expenditure