The Effect of Claw Lesions and Claw Infections on Lameness in Loose Housing of Pregnant Sows

During a 12-month period lameness, claw lesions and claw infections were studied in 15 herds with loose housing of pregnant sows on partly slatted concrete floors. Of these herds, 12 herds had concrete slats and 3 herds had plastic slats. The mean prevalence proportion of lame sows in the herds was 13.1%. The risk of lameness increased with increasing claw lesion score and with the presence of claw infections. In the herds with concrete slats, the relative risk of lame sows was 2.4 times higher than in the herds with plastic slats. In the herds with poor floor hygiene, the relative risk of lameness was 2.8 times higher than in the herds with dry and clean floors. The mean prevalence proportion of sows with claw infections at the 3 separate examinations in the 15 herds was 3.8%. Claw infections were more prevalent in herds with dirty floors and in herds with little space per animal (<2m2). In the herds with concrete slats, the relative risk of claw infections was 2 times higher than in the herds with plastic slats.     

Symptoms Associated with Victimization in Patients with Schizophrenia and Related Disorders

Background

Patients with psychoses have an increased risk of becoming victims of violence. Previous studies have suggested that higher symptom levels are associated with a raised risk of becoming a victim of physical violence. There has been, however, no evidence on the type of symptoms that are linked with an increased risk of recent victimization.

Methods

Data was taken from two studies on involuntarily admitted patients, one national study in England and an international one in six other European countries. In the week following admission, trained interviewers asked patients whether they had been victims of physical violence in the year prior to admission, and assessed symptoms on the Brief Psychiatric Rating Scale (BPRS). Only patients with a diagnosis of schizophrenia or related disorders (ICD-10 F20–29) were included in the analysis which was conducted separately for the two samples. Symptom levels assessed on the BPRS subscales were tested as predictors of victimization. Univariable and multivariable logistic regression models were fitted to estimate adjusted odds ratios.

Results

Data from 383 patients in the English sample and 543 patients in the European sample was analysed. Rates of victimization were 37.8% and 28.0% respectively. In multivariable models, the BPRS manic subscale was significantly associated with victimization in both samples.

Conclusions

Higher levels of manic symptoms indicate a raised risk of being a victim of violence in involuntary patients with schizophrenia and related disorders. This might be explained by higher activity levels, impaired judgement or poorer self-control in patients with manic symptoms. Such symptoms should be specifically considered in risk assessments.     

Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic Disorders

Objective

Evidence points to a founder of the multifunctional CCN family, NOV/CCN3, as a circulating molecule involved in cardiac development, vascular homeostasis and inflammation. No data are available on the relationship between plasma NOV/CCN3 levels and cardiovascular risk factors in humans. This study investigated the possible relationship between plasma NOV levels and cardiovascular risk factors in humans.

Methods

NOV levels were measured in the plasma from 594 adults with a hyperlipidemia history and/or with lipid-lowering therapy and/or a body mass index (BMI) >30 kg/m². Correlations were measured between NOV plasma levels and various parameters, including BMI, fat mass, and plasma triglycerides, cholesterol, glucose, and C-reactive protein. NOV expression was also evaluated in adipose tissue from obese patients and rodents and in primary cultures of adipocytes and macrophages.

Results

After full multivariate adjustment, we detected a strong positive correlation between plasma NOV and BMI (r = 0.36 p<0.0001) and fat mass (r = 0.33 p<0.0005). According to quintiles, this relationship appeared to be linear. NOV levels were also positively correlated with C-reactive protein but not with total cholesterol, LDL-C or blood glucose. In patients with drastic weight loss induced by Roux-en-Y bariatric surgery, circulating NOV levels decreased by 28% (p<0.02) and 48% (p<0.0001) after 3 and 6 months, respectively, following surgery. In adipose tissue from obese patients, and in human primary cultures NOV protein was detected in adipocytes and macrophages. In mice fed a high fat diet NOV plasma levels and its expression in adipose tissue were also significantly increased compared to controls fed a standard diet.

Conclusion

Our results strongly suggest that in obese humans and mice plasma NOV levels positively correlated with NOV expression in adipose tissue, and support a possible contribution of NOV to obesity-related inflammation.     

Increased Plin2 Expression in Human Skeletal Muscle Is Associated with Sarcopenia and Muscle Weakness

Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG) deposition in lipid droplets, which are associated with perilipin proteins, such as Perilipin2 (Plin2). It is not known whether Plin2 expression changes with age and if this has consequences on muscle mass and strength. We studied the expression of Plin2 in the vastus lateralis (VL) muscle of both healthy subjects and patients affected by lower limb mobility limitation of different age. We found that Plin2 expression increases with age, this phenomenon being particularly evident in patients. Moreover, Plin2 expression is inversely correlated with quadriceps strength and VL thickness. To investigate the molecular mechanisms underpinning this phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in muscle physiology. We found that Plin2 expression strongly correlates with increased p53 activation and reduced IGF-1 expression. To confirm these observations made on humans, we studied mice overexpressing muscle-specific IGF-1, which are protected from sarcopenia. These mice resulted almost negative for the expression of Plin2 and p53 at two years of age. We conclude that fat deposition within skeletal muscle in form of Plin2-coated lipid droplets increases with age and is associated with decreased muscle strength and thickness, likely through an IGF-1- and p53-dependent mechanism. The data also suggest that excessive intramuscular fat accumulation could be the initial trigger for p53 activation and consequent loss of muscle mass and strength.     

Synaptic Dysfunction in Neurodevelopmental Disorders Associated with Autism and Intellectual Disabilities

The discovery of the genetic causes of syndromic autism spectrum disorders and intellectual disabilities has greatly informed our understanding of the molecular pathways critical for normal synaptic function. The top-down approaches using human phenotypes and genetics helped identify causative genes and uncovered the broad spectrum of neuropsychiatric features that can result from various mutations in the same gene. Importantly, the human studies unveiled the exquisite sensitivity of cognitive function to precise levels of many diverse proteins. Bottom-up approaches applying molecular, biochemical, and neurophysiological studies to genetic models of these disorders revealed unsuspected pathogenic mechanisms and identified potential therapeutic targets. Moreover, studies in model organisms showed that symptoms of these devastating disorders can be reversed, which brings hope that affected individuals might benefit from interventions even after symptoms set in. Scientists predict that insights gained from studying these rare syndromic disorders will have an impact on the more common nonsyndromic autism and mild cognitive deficits.It is estimated that ∼1% of the human population has an autism spectrum disorder (ASD). ASD has widely varied behavioral manifestations, severity, and comorbid conditions (hence the term “spectrum”), but those diagnosed with autism are characterized by impaired communication and reciprocal social interactions, and restricted and repetitive patterns of activities and interests (Baird et al. 2006). Approximately 70% of those diagnosed with autism also have intellectual disability (ID), and 25% have a seizure disorder (Tuchman and Rapin 2002). There is a strong genetic basis for autism, but the risk architecture is highly heterogeneous, and a large number of genes have been implicated (Abrahams and Geschwind 2008). This daunting phenotypic and etiologic complexity, shared by other major psychiatric illnesses, has slowed progress toward developing new therapies.However, autism researchers are optimistic that the possibility of substantial progress may soon be realized (Krueger and Bear 2011). First, the genes have been discovered for numerous syndromic disorders that prominently feature ASD and ID. Second, these gene mutations have been reproduced in animal models that allow detailed examination of the underlying brain pathophysiology. Third, animal research has converged on altered synaptic function as a likely basis for impaired cognition and possibly ASD. Fourth, insights gained on how synapses function differently in the face of these mutations have suggested novel therapeutic interventions validated in preclinical models and that have shown promise in preliminary human clinical trials. Fifth, the fact that ASD and ID can be diagnosed in early childhood maximizes potential benefits of therapy because it can be started at a time when the brain is most plastic. Finally, animal studies using gene reactivation or pharmacological interventions suggest that substantial improvements can be seen even when treatments begin in adulthood (Ehninger et al. 2008b). Thus, a genetic diagnosis of a developmental brain disorder need not be a “life sentence” of permanent and inexorable mental disability.The path from gene discovery to novel treatment is outlined in Figure 1. This process often begins with astute clinical observations that some patients can be distinguished by a common set of phenotypic traits, thus defining a syndrome. Molecular genetic studies can then be undertaken to test the hypothesis that the syndrome has a genetic cause. In the event that disruption of a single gene or DNA segment causes the disease (i.e., a “highly penetrant” mutation), then it is possible to create an animal model (usually a mouse) that carries the same genetic disruption. Although the effects of the genetic lesion will likely manifest differently at the behavioral level in animals and humans because of differences in the complexity of the brains, it is reasonable to postulate that disruptions in elementary neuronal functions are likely to be shared. Understanding this neuronal pathophysiology is critical for identifying potential therapeutic targets. If these targets can be validated in the animal models, then chemistry ensues to generate molecules that can engage the target and satisfy the pharmacodynamic and pharmacokinetic drug requirements. If they are shown to be safe, drug candidates may then advance to human clinical trials. There are currently clinical trials ongoing in several single-gene syndromic disorders associated with ASD and ID. Most of these target alterations in synaptic signaling.Open in a separate windowFigure 1.The promise of molecular medicine in genetically defined disorders of brain development.The notion that some ASD and associated ID represent “synapsopathies” (or “synaptopathies”) is supported by the preponderance of penetrant mutations in genes associated with synaptic structure and function. The most common single-gene mutations in ASD with ID are associated with fragile X syndrome (FMR1), tuberous sclerosis (TSC1, TSC2), neurofibromatosis (NF1), Angelman syndrome (UBE3A), Rett syndrome (MECP2), the PTEN hamartoma tumor syndrome, and Phelan-McDermid syndrome (SHANK3) (for review, see Betancur 2011). Rare mutations in the neuroligin (NLGN3, NLGN2) and neurexin (NRXN1) genes also cause autism (Jamain et al. 2003). Although this is by no means an exhaustive list of genes implicated in autism (and many await discovery), it is notable nonetheless that these highly penetrant mutations occur in genes that are critical regulators of synaptic function, and further, illuminate biochemical pathways that might be pathogenic in ASD and ID (Fig. 2).Open in a separate windowFigure 2.(A) Schematic of a neuron and axonal-dendritic synapse that depict examples of cellular localization of the various types of defects in ASD/ID. (B) A signaling pathway at the excitatory synapses that couples activity as registered by the release of glutamate to local control of protein synthesis. Disruption of the gene products indicated in the colored boxes greatly increases the risk of ASD/ID. Syndromic disorders with increased prevalence of ASD include Phelan-McDermid Syndrome (SHANK3); Noonan syndrome (RAF1, MEK1); Neurofibromatosis type 1 (NF1); Costello syndrome (H-Ras, MEK1); Cowden syndrome (PTEN); Cardio-facio-cutaneous (CFC) syndrome (MEK1/2); Tuberous sclerosis complex (TSC1/2); Fragile X syndrome (FMRP); Angelman syndrome (AS UBE3a); Rett syndrome (RTT–MeCP2); and Rubinstein-Taybi syndrome (RTS–CREB binding protein, p300). Rare, nonsyndromic ASDs include NLGN3/4 and NRXN1; ID/ASD: SHANK2.In this article, we focus on a few syndromic disorders associated with ASD and ID that are characterized by penetrant mutations in genes that have been shown in animal models to disrupt synaptic function. Our goal is to highlight the similarities and differences in these syndromes and their underlying synaptic pathophysiology. Optimal synaptic function occurs within a narrow dynamic range along many dimensions, and it is not surprising that pathophysiology occurs at the edges of these spectra. What has come as a surprise, however, is that ASD and ID appear to be common consequences of disruptive mutations that cause synaptic pathophysiology at both ends of a spectrum. In other words, both “gain-of-function” and “loss-of-function” mutations can manifest in similar ways. Insights into the pathophysiology of ASD and ID have raised the possibility of therapeutic interventions to bring synapses into a normal operating range.     

Osteochondrosis and Arthrosis in Pigs

Eight feeding experiments, each comprising 48 boars or gilts, were carried out. The factors feed level, Ca, P and protein levels were varied within practical physiological limits. The animals were slaughtered at close to 100 kg live weight. Lesions in joints and bones were of a noninfectious, non-rachitic nature and of the osteochondrosis and arthrosis type. Ten to 12 g Ca and approx. 10 g P/kg ration gave histomorphologically seemingly more optimum structure of the spongious bone tissue and a higher ash percentage in bones than 7 g Ca and 6 g P, or unbalanced mineral levels in the ration. However, there was no significant difference in degree or incidence of joint and bone lesions between mineral groups. Neither were there such differences present between feed level groups or protein level groups. This may for the feed level groups be partly due to the low feed level pigs having a longer period of time during which they were highly susceptible to the development of lesions. The low feed level animals had longer long bones at 100 kg live weight than the high feed level animals. The length of the vertebral column was, however, approximately similar in the 2 feed level groups. The angles of the condyles and head of the femur according to the length axis were influenced by feed level or growth rate, most probably by an effect on the endochondral ossification.     

OAS Gene Family Expression Is Associated with HIV-Related Neurocognitive Disorders

HIV-associated neurocognitive disorders are common in HIV-infected individuals, even in the combination antiretroviral therapy (c-ART) era. Several mechanisms are involved in neuronal damage, including chronic inflammation immune activation. Mammalian 2′-5′-oligoadenylate synthetase (OAS) genes are produced in response to interferon (IFN), mainly by monocytes, and exert their antiviral functions by activation of RNase L that degrades viral and cellular RNAs. In this study, we aimed at exploring OAS gene family RNA expression in simian immunodeficiency virus encephalitis (SIVE), in HIV-associated neurocognitive disorders (HAND), and in HIV-associate dementia (HAD). We analyzed three microarray datasets obtained from the NCBI in order to assess the expression levels of OAS gene family network in brain biopsies of macaques with SIVE vs uninfected animals, as well as post-mortem brain of individuals with HAND (on or off ART) vs uninfected controls and three brain regions of HIV-infected individuals with both neurocognitive impairment (HAD) and encephalitis (HIVE). All OAS genes were upregulated both in SIVE and in HAND. OAS expression was significantly higher in high-viremic individuals; increased expression levels persisted in cART subjects when compared to healthy controls. OAS gene network analysis showed that several genes belonging to the type I IFN pathway, especially CXCL10 and IFIT3, were similarly upregulated in SIVE/HAND. Furthermore, we identified a significant upregulation of OAS gene family RNA expression in basal ganglia, white matter, and frontal cortex of HIV-1, HAD, and HAD/HIVE patients compared to healthy subjects. OAS gene family expression is increased in brain sections from individuals with HAND, HAD, and HIVE as well as macaques with SIVE. OAS family expression is likely to be induced by IFN as a consequence of viral replication in the CNS. Its long-term upregulation may contribute to the chronic inflammatory status and neurocognitive impairment we still observe in virologically suppressed individuals on c-ART.     

Muscular Weakness in Individuals with HIV Associated with a Disorganization of the Cortico-Spinal Tract: A Multi-Modal MRI Investigation

Motor impairment is highly prevalent in HIV-infected patients. Here, we assess associations between peripheral muscular deficits as evaluated by the 5 sit-to-stand test (5STS) and structural integrity of the motor system at a central level. Eighty-six HIV-infected patients receiving combination antiretroviral therapy and with no major cerebral events, underwent an MRI scan and the 5STS. Out of 86 participants, forty presented a score greater than two standard deviations above mean normative scores calculated for the 5STS and were therefore considered as motor-impaired. MRI-structural cerebral parameters were compared to the unimpaired participants. Fractional Anisotropy (FA), Axial Diffusivity (AD) and Radial Diffusivity (RD), reflecting microstructural integrity, were extracted from Diffusion-Tensor MRI. Global and regional cerebral volumes or thicknesses were extracted from 3D-T1 morphological MRI. Whereas the two groups did not differ for any HIV variables, voxel-wise analysis revealed that motor-impaired participants present low FA values in various cortico-motor tracts and low AD in left cortico-spinal tract. However, they did not present reduced volumes or thicknesses of the precentral cortices compared to unimpaired participants. The absence of alterations in cortical regions holding motor-neurons might argue against neurodegenerative process as an explanation of White Matter (WM) disorganization.     

Combined Healthy Lifestyle Is Inversely Associated with Psychological Disorders among Adults

Background and Aims

Joint association of lifestyle-related factors and mental health has been less studied in earlier studies, especially in Middle Eastern countries. This study aimed to examine how combinations of several lifestyle-related factors related to depression and anxiety in a large group of middle-age Iranian population.

Methods

In a cross-sectional study on 3363 Iranian adults, a healthy lifestyle score was constructed by the use of data from dietary intakes, physical activity, smoking status, psychological distress and obesity. A dish-based 106-item semi-quantitative validated food frequency questionnaire (FFQ), General Practice Physical Activity Questionnaire (GPPAQ), General Health Questionnaire (GHQ) and other pre-tested questionnaires were used to assess the components of healthy lifestyle score. The Hospital Anxiety and Depression Scale (HADS) was applied to screen for anxiety and depression.

Results

After adjustment for potential confounders, we found that individuals with the highest score of healthy lifestyle were 95% less likely to be anxious (OR: 0.05; 95% CI: 0.01–0.27) and 96% less likely to be depressed (OR: 0.04; 95% CI: 0.01–0.15), compared with those with the lowest score. In addition, non-smokers had lower odds of anxiety (OR: 0.64; 95% CI: 0.47–0.88) and depression (OR: 0.62; 95% CI: 0.48–0.81) compared with smokers. Individuals with low levels of psychological distress had expectedly lower odds of anxiety (OR: 0.13; 95% CI: 0.10–0.16) and depression (OR: 0.10; 95% CI: 0.08–0.12) than those with high levels. Individuals with a healthy diet had 29% lower odds of depression (OR: 0.71; 95% CI: 0.59–0.87) than those with a non-healthy diet.

Conclusion

We found evidence indicating that healthy lifestyle score was associated with lower odds of anxiety and depression in this group of Iranian adults. Healthy diet, psychological distress, and smoking status were independent predictors of mental disorders.     

Wal Mutant Mice Have a Mutation Associated with Autism Spectrum Disorders

Doklady Biological Sciences - The waved alopecia (wal) mutation arose spontaneously in mice. Phenotypically, the wal mutation in a homozygous recessive state is manifested by a wavy coat. Over...     

Pain Threshold Analysis in Patients with Osteoarthrosis of Hip

The pain threshold was measured in patients with osteoarthrosis of the hip. The pain threshold was significantly lower in patients who required surgery than in controls. After successful surgery the threshold rose to normal levels. In patients with few or no symptoms from their osteoarthritic hips the pain threshold was high. Insensitivity to pain does not predispose towards osteoarthrosis of the hip. Indeed, the severity of symptoms can be directly related to an increased sensitivity to pain in osteoarthritic subjects.     

Plasma Amino Acids in Dogs with Osteochondrosis or Hip Dysplasia

Radiography of the hip joints of mature dogs has shown that hip dysplasia is quite common in many middle and large size breeds in Norway. The heritability of hip dysplasia has been estimated in several studies to be between 0.2 and 0.6 (Hedhammar et al 1979). This indicates that environmental factors are important for development and severity of hip dysplasia.