Ritanserin as an adjunct to lithium and haloperidol for the treatment of medication-naive patients with acute mania: a double blind and placebo controlled trial

BACKGROUND: Bipolar disorder is a lifelong episodic condition characterized by mood swings between mania and depression. Several lines of evidence suggest that serotonin is likely to play a pivotal role in the pathophysiology of bipolar disorder. Ritanserin, a 5-HT(2 )receptor antagonist, has been reported to have antipsychotic activity. In this 6-week double blind, placebo controlled study involving moderate to severe manic patients, we assessed the effects of ritanserin plus haloperidol in combination with lithium. METHODS: 45 patients aged between 21–43 were eligible to participate as they met the DSM-IV criteria for a current manic episode, on the basis of a clinical interview by an academician psychiatrist. In addition, a score of at least 20 points on the Young Mania rating Scale was required representing moderate to severe mania. Patients were randomly allocated lithium (1–1.2 mEq/L) + haloperidol (10 mg/day)+ ritanserin (10 mg/day) (Group A) or lithium (1–1.2 mEq/L)+ haloperidol (10 mg/day) + placebo (Group B) for a 6-week, double-blind, placebo-controlled study. Patients were assessed by a third year psychiatry resident at baseline and 3, 7, 14, 21, 28 and 42 days after the medication started. All patients entered the hospital were not previously under any medication. The mean decrease in the Young Mania Rating Scale score from baseline was used as the main outcome measure of response of mania to treatment. The extrapyramidal symptoms were assessed using the Extrapyramidal Symptoms Rating Scale. Side effects were systematically recorded throughout the study and were assessed using a checklist. RESULTS: Young Mania Rating Scale total scores improved with ritanserin. The difference between the two protocols was significant as indicated by the effect of group and the between-subjects factor (F = 5.02, d.f. = 1, P = 0.03). The means Extrapyramidal Symptoms Rating Scale scores for the placebo group were higher than the ritanserin group and the difference was significant in day 42. The difference between the two groups in the frequency of side effects was not significant CONCLUSIONS: The efficacy of ritanserin to obtain a better improvement in patients with mania seems to support the 5-HT hypothesis of bipolar disorder

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Psychological morbidity, sources of stress and coping strategies among undergraduate medical students of Nepal

<p>Abstract</p> <p>Background</p> <p>In recent years there has been a growing appreciation of the issues of quality of life and stresses involved medical training as this may affect their learning and academic performance. However, such studies are lacking in medical schools of Nepal. Therefore, we carried out this study to assess the prevalence of psychological morbidity, sources and severity of stress and coping strategies among medical students in our integrated problem-stimulated undergraduate medical curriculum.</p> <p>Methods</p> <p>A cross-sectional, questionnaire-based survey was carried out among the undergraduate medical students of Manipal College of Medical Sciences, Pokhara, Nepal during the time period August, 2005 to December, 2006. The psychological morbidity was assessed using General Health Questionnaire. A 24-item questionnaire was used to assess sources of stress and their severity. Coping strategies adopted was assessed using brief COPE inventory.</p> <p>Results</p> <p>The overall response rate was 75.8% (407 out of 525 students). The overall prevalence of psychological morbidity was 20.9% and was higher among students of basic sciences, Indian nationality and whose parents were medical doctors. By logistic regression analysis, GHQ-caseness was associated with occurrence of academic and health-related stressors. The most common sources of stress were related to academic and psychosocial concerns. The most important and severe sources of stress were staying in hostel, high parental expectations, vastness of syllabus, tests/exams, lack of time and facilities for entertainment. The students generally used active coping strategies and alcohol/drug was a least used coping strategy. The coping strategies commonly used by students in our institution were positive reframing, planning, acceptance, active coping, self-distraction and emotional support. The coping strategies showed variation by GHQ-caseness, year of study, gender and parents' occupation.</p> <p>Conclusion</p> <p>The higher level of psychological morbidity warrants need for interventions like social and psychological support to improve the quality of life for these medical students. Student advisors and counselors may train students about stress management. There is also need to bring about academic changes in quality of teaching and evaluation system. A prospective study is necessary to study the association of psychological morbidity with demographic variables, sources of stress and coping strategies.</p

N-Myc and GCN5 Regulate Significantly Overlapping Transcriptional Programs in Neural Stem Cells

Here we examine the functions of the Myc cofactor and histone acetyltransferase, GCN5/KAT2A, in neural stem and precursor cells (NSC) using a conditional knockout approach driven by nestin-cre. Mice with GCN5-deficient NSC exhibit a 25% reduction in brain mass with a microcephaly phenotype similar to that observed in nestin-cre driven knockouts of c- or N-myc. In addition, the loss of GCN5 inhibits precursor cell proliferation and reduces their populations in vivo, as does loss of N-myc. Gene expression analysis indicates that about one-sixth of genes whose expression is affected by loss of GCN5 are also affected in the same manner by loss of N-myc. These findings strongly support the notion that GCN5 protein is a key N-Myc transcriptional cofactor in NSC, but are also consistent with recruitment of GCN5 by other transcription factors and the use by N-Myc of other histone acetyltransferases. Putative N-Myc/GCN5 coregulated transcriptional pathways include cell metabolism, cell cycle, chromatin, and neuron projection morphogenesis genes. GCN5 is also required for maintenance of histone acetylation both at its putative specific target genes and at Myc targets. Thus, we have defined an important role for GCN5 in NSC and provided evidence that GCN5 is an important Myc transcriptional cofactor in vivo

Mental health: A cause or consequence of injury? A population-based matched cohort study

BACKGROUND: While a number of studies report high prevalence of mental health problems among injured people, the temporal relationship between injury and mental health service use has not been established. This study aimed to quantify this relationship using 10 years of follow-up on a population-based cohort of hospitalised injured adults. METHODS: The Manitoba Injury Outcome Study is a retrospective population-based matched cohort study that utilised linked administrative data from Manitoba, Canada, to identify an inception cohort (1988–1991) of hospitalised injured cases (ICD-9-CM 800–995) aged 18–64 years (n = 21,032), which was matched to a non-injured population-based comparison group (n = 21,032). Pre-injury comorbidity and post-injury mental health data were obtained from hospital and physician claims records. Negative Binomial regression was used to estimate adjusted rate ratios (RRs) to measure associations between injury and mental health service use. RESULTS: Statistically significant differences in the rates of mental health service use were observed between the injured and non-injured, for the pre-injury year and every year of the follow-up period. The injured cohort had 6.56 times the rate of post-injury mental health hospitalisations (95% CI 5.87, 7.34) and 2.65 times the rate of post-injury mental health physician claims (95% CI 2.53, 2.77). Adjusting for comorbidities and pre-existing mental health service use reduced the hospitalisations RR to 3.24 (95% CI 2.92, 3.60) and the physician claims RR to 1.53 (95% CI 1.47, 1.59). CONCLUSION: These findings indicate the presence of pre-existing mental health conditions is a potential confounder when investigating injury as a risk factor for subsequent mental health problems. Collaboration with mental health professionals is important for injury prevention and care, with ongoing mental health support being a clearly indicated service need by injured people and their families. Public health policy relating to injury prevention and control needs to consider mental health strategies at the primary, secondary and tertiary level

Measures in Visualization Space

Postponed access: the file will be available after 2021-08-12Measurement is an integral part of modern science, providing the fundamental means for evaluation, comparison, and prediction. In the context of visualization, several different types of measures have been proposed, ranging from approaches that evaluate particular aspects of visualization techniques, their perceptual characteristics, and even economic factors. Furthermore, there are approaches that attempt to provide means for measuring general properties of the visualization process as a whole. Measures can be quantitative or qualitative, and one of the primary goals is to provide objective means for reasoning about visualizations and their effectiveness. As such, they play a central role in the development of scientific theories for visualization. In this chapter, we provide an overview of the current state of the art, survey and classify different types of visualization measures, characterize their strengths and drawbacks, and provide an outline of open challenges for future research.acceptedVersio