The role of the right inferior frontal gyrus in the pathogenesis of post-stroke psychosis.

Psychotic symptoms have previously been reported following right hemisphere brain injury. We sought to identify the specific neuroanatomical basis of delusions following stroke by studying a series of patients with post-stroke psychosis. Lesion overlap analysis was conducted on three individuals with delusions following right hemisphere stroke. These cases were compared with a control group of patients with similar anatomical damage. The main outcome measures were presence of delusions and presence of behavioural susceptibility. The right inferior frontal gyrus and underlying white matter, including the superior longitudinal fasciculus and anterior corona radiata, were involved in all three cases. All three had a preexisting untreated psychiatric disorder. In contrast, only one of nine control cases with equivalent lesions had evidence of previous psychiatric disorder (p = 0.0182, Fisher’s exact test), and this was being treated at the time of stroke. We provide clinical evidence from patients with structural brain lesions implicating damage to the right inferior frontal lobe in the generation of persistent psychosis following stroke. We suggest that preexisting psychiatric disease provided a behavioural susceptibility to develop delusions in these individuals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00415-014-7242-x) contains supplementary material, which is available to authorized users

A general approach to simultaneous model fitting and variable elimination in response models for biological data with many more variables than observations

<p>Abstract</p> <p>Background</p> <p>With the advent of high throughput biotechnology data acquisition platforms such as micro arrays, SNP chips and mass spectrometers, data sets with many more variables than observations are now routinely being collected. Finding relationships between response variables of interest and variables in such data sets is an important problem akin to finding needles in a haystack. Whilst methods for a number of response types have been developed a general approach has been lacking.</p> <p>Results</p> <p>The major contribution of this paper is to present a unified methodology which allows many common (statistical) response models to be fitted to such data sets. The class of models includes virtually any model with a linear predictor in it, for example (but not limited to), multiclass logistic regression (classification), generalised linear models (regression) and survival models. A fast algorithm for finding sparse well fitting models is presented. The ideas are illustrated on real data sets with numbers of variables ranging from thousands to millions. R code implementing the ideas is available for download.</p> <p>Conclusion</p> <p>The method described in this paper enables existing work on response models when there are less variables than observations to be leveraged to the situation when there are many more variables than observations. It is a powerful approach to finding parsimonious models for such datasets. The method is capable of handling problems with millions of variables and a large variety of response types within the one framework. The method compares favourably to existing methods such as support vector machines and random forests, but has the advantage of not requiring separate variable selection steps. It is also works for data types which these methods were not designed to handle. The method usually produces very sparse models which make biological interpretation simpler and more focused.</p

Efficacy of different treatment regimes against setariosis (Setaria tundra, Nematoda: Filarioidea) and associated peritonitis in reindeer

<p>Abstract</p> <p>Background</p> <p>When a severe peritonitis outbreak in semi-domesticated reindeer was noticed in 2003 in Finland, the concerned industry urged immediate preventive actions in order to avoid detrimental effects of <it>S. tundra </it>and further economical losses. A research programme was swiftly initiated to study <it>S. tundra </it>and its impact on the health and wellbeing of reindeer.</p> <p>Methods</p> <p>The ultimate aim of this study was to test the efficacy of different treatment regimes against <it>S. tundra </it>and associated peritonitis in reindeer. The timing of the trials was planned to be compatible with the annual rhythm of the reindeer management; (1) the treatment of calves in midsummer, during routine calf ear marking, with ivermectin injection prophylaxis and deltamethrin pour-on solution as a repellent against insect vectors, (2) the treatment of infected calves in early autumn with ivermectin injection, and (3) ivermectin treatment of breeding reindeer in winter. The results were assessed using the post mortem inspection data and <it>S. tundra </it>detection. Finally, to evaluate on the population level the influence of the annual (late autumn-winter) ivermectin treatment of breeding reindeer on the transmission dynamics of <it>S. tundra</it>, a questionnaire survey was conducted.</p> <p>Results</p> <p>In autumn, ivermectin treatment was efficient against peritonitis and in midsummer had a slight negative impact on the degree of peritonitis and positive on the fat layer, but deltamethrin had none. Ivermectin was efficient against adult <it>S. tundra </it>and its smf. All the reindeer herding cooperatives answered the questionnaire and it appeared that antiparasitic treatment of reindeer population was intense during the study period, when 64–90% of the animals were treated. In the southern part of the Finnish reindeer husbandry area, oral administration of ivermectin was commonly used.</p> <p>Conclusion</p> <p>Autumn, and to a lesser degree summer, treatment of reindeer calves with injectable ivermectin resulted in decreased severity of peritonitis and perihepatitis in reindeer calves due to setariosis. In the case of necessity for animal welfare reasons, treatment during early autumn round ups should be considered. On the population level, massive and routinely applied antiparasitic treatments can improve the health of breeding reindeer and decrease the mortality and the number of carriers but during the outbreak could not prevent its movement and expansion to the North.</p

Tri-trophic effects of inter- and intra-population variation in defence chemistry of wild cabbage (Brassica oleracea)

The effect of direct chemical defences in plants on the performance of insect herbivores and their natural enemies has received increasing attention over the past 10 years. However, much less is known about the scale at which this variation is generated and maintained, both within and across populations of the same plant species. This study compares growth and development of the large cabbage butterfly, Pieris brassicae, and its gregarious pupal parasitoid, Pteromalus puparum, on three wild populations [Kimmeridge (KIM), Old Harry (OH) and Winspit (WIN)] and two cultivars [Stonehead (ST), and Cyrus (CYR)] of cabbage, Brassica oleracea. The wild populations originate from the coast of Dorset, UK, but grow in close proximity with one another. Insect performance and chemical profiles were made from every plant used in the experiment. Foliar glucosinolates (GS) concentrations were highest in the wild plants in rank order WIN > OH > KIM, with lower levels found in the cultivars. Caterpillar-damaged leaves in the wild cabbages also had higher GS levels than undamaged leaves. Pupal mass in P. brassicae varied significantly among populations of B. oleracea. Moreover, development time in the host and parasitoid were correlated, even though these stages are temporally separated. Parasitoid adult dry mass closely approximated the development of its host. Multivariate statistics revealed a correlation between pupal mass and development time of P. brassicae and foliar GS chemistry, of which levels of neoglucobrassicin appeared to be the most important. Our results show that there is considerable variation in quantitative aspects of defensive chemistry in wild cabbage plants that is maintained at very small spatial scales in nature. Moreover, the performance of the herbivore and its parasitoid were both affected by differences in plant quality

Expression of hormone receptors in oropharyngeal squamous cell carcinoma

Hormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer. This study consists of 199 consecutive oropharyngeal squamous cell carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone receptor (PR) expressions using immunohistochemistry comparing tumor and patient characteristics. AR was expressed in 16%, PR in 27% and ER-beta in 63% of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than their negative counterparts. High PR expression was associated with poor disease-specific and locoregional recurrence-free survival. AR, PR, and ER-beta are expressed in OPSCC, and AR and PR expressions are associated with HPV and p16 status. Furthermore, PR appears to have prognostic significance. This may allow us to investigate the role of anti-hormone receptors in the treatment of OPSCC.Peer reviewe

Emerging common themes in regulation of PIKKs and PI3Ks

Phosphatidylinositol-3 kinase-related kinases (PIKKs) comprise a family of protein kinases that respond to various stresses, including DNA damage, blocks in DNA replication, availability of nutrients and errors in mRNA splicing. PIKKs are characterized by the presence of a conserved kinase domain (KD), whose activity is regulated by two C-terminal regions, referred to as PIKK-regulatory domain (PRD) and FRAP-ATM-TRRAP-C-terminal (FATC), respectively. Here, we review functional and structural data that implicate the PRD and FATC domains in regulation of PIKK activity, drawing parallels to phosphatidylinositol-3 kinases (PI3K), lipid kinases that have sequence similarity to PIKKs. The PI3K C-terminus, which we propose to be equivalent to the PRD and FATC domains of PIKKs, is in close proximity to the activation loop of the KD, suggesting that in PIKKs, the PRD and FATC domains may regulate kinase activity by targeting the activation loop

Fat free mass and obesity in relation to educational level

© 2009 Seppänen-Nuijten et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Aetiology and risk factors of musculoskeletal disorders in physically active conscripts: a follow-up study in the Finnish Defence Forces

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal disorders (MSDs) are the main reason for morbidity during military training. MSDs commonly result in functional impairment leading to premature discharge from military service and disabilities requiring long-term rehabilitation. The purpose of the study was to examine associations between various risk factors and MSDs with special attention to the physical fitness of the conscripts.</p> <p>Methods</p> <p>Two successive cohorts of 18 to 28-year-old male conscripts (<it>N </it>= 944, median age 19) were followed for six months. MSDs, including overuse and acute injuries, treated at the garrison clinic were identified and analysed. Associations between MSDs and risk factors were examined by multivariate Cox's proportional hazard models.</p> <p>Results</p> <p>During the six-month follow-up of two successive cohorts there were 1629 MSDs and 2879 health clinic visits due to MSDs in 944 persons. The event-based incidence rate for MSD was 10.5 (95% confidence interval (CI): 10.0-11.1) per 1000 person-days. Most MSDs were in the lower extremities (65%) followed by the back (18%). The strongest baseline factors associated with MSDs were poor result in the combined outcome of a 12-minute running test and back lift test (hazard ratio (HR) 2.9; 95% CI: 1.9-4.6), high waist circumference (HR 1.7; 95% CI: 1.3-2.2), high body mass index (HR 1.8; 95% CI: 1.3-2.4), poor result in a 12-minute running test (HR 1.6; 95% CI: 1.2-2.2), earlier musculoskeletal symptoms (HR 1.7; 95% CI: 1.3-2.1) and poor school success (educational level and grades combined; HR 2.0; 95% CI: 1.3-3.0). In addition, risk factors of long-term MSDs (≥10 service days lost due to one or several MSDs) were analysed: poor result in a 12-minute running test, earlier musculoskeletal symptoms, high waist circumference, high body mass index, not belonging to a sports club and poor result in the combined outcome of the 12-minute running test and standing long jump test were strongly associated with long-term MSDs.</p> <p>Conclusions</p> <p>The majority of the observed risk factors are modifiable and favourable for future interventions. An appropriate intervention based on the present study would improve both aerobic and muscular fitness prior to conscript training. Attention to appropriate waist circumference and body mass index would strengthen the intervention. Effective results from well-planned randomised controlled studies are needed before initiating large-scale prevention programmes in a military environment.</p

Swimming Exercise Prevents Fibrogenesis in Chronic Kidney Disease by Inhibiting the Myofibroblast Transdifferentiation

BACKGROUND: The renal function of chronic kidney disease (CKD) patients may be improved by a number of rehabilitative mechanisms. Swimming exercise training was supposed to be beneficial to its recovery. METHODOLOGY/PRINCIPAL FINDINGS: Doxorubicin-induced CKD (DRCKD) rat model was performed. Swimming training was programmed three days per week, 30 or 60 min per day for a total period of 11 weeks. Serum biochemical and pathological parameters were examined. In DRCKD, hyperlipidemia was observed. Active mesangial cell activation was evidenced by overexpression of PDGFR, P-PDGFR, MMP-2, MMP-9, α-SMA, and CD34 with a huge amount collagen deposition. Apparent myofibroblast transdifferentiation implicating fibrogenesis in the glomerular mesangium, glomerulonephritis and glomeruloscelorosis was observed with highly elevated proteinuria and urinary BUN excretion. The 60-min swimming exercise but not the 30 min equivalent rescued most of the symptoms. To quantify the effectiveness of exercise training, a physical parameter, i.e. "the strenuosity coefficient" or "the myokine releasing coefficient", was estimated to be 7.154 × 10(-3) pg/mL-J. CONCLUSIONS: The 60-min swimming exercise may ameliorate DRCKD by inhibiting the transdifferentiation of myofibroblasts in the glomerular mesangium. Moreover, rehabilitative exercise training to rescue CKD is a personalized remedy. Benefits depend on the duration and strength of exercise, and more importantly, on the individual physiological condition