Acetylcholinesterase Inhibitors (AChEI's) for the treatment of visual hallucinations in schizophrenia: a case report

Background: Visual hallucinations are commonly seen in various neurological and psychiatric disorders including schizophrenia. Current models of visual processing and studies in diseases including Parkinsons Disease and Lewy Body Dementia propose that Acetylcholine (Ach) plays a pivotal role in our ability to accurately interpret visual stimuli. Depletion of Ach is thought to be associated with visual hallucination generation. AchEI’s have been used in the targeted treatment of visual hallucinations in dementia and Parkinson’s Disease patients. In Schizophrenia, it is thought that a similar Ach depletion leads to visual hallucinations and may provide a target for drug treatment Case Presentation: We present a case of a patient with Schizophrenia presenting with treatment resistant and significantly distressing visual hallucinations. After optimising treatment for schizophrenia we used Rivastigmine, an AchEI, as an adjunct to treat her symptoms successfully. Conclusions: This case is the first to illustrate this novel use of an AchEI in the targeted treatment of visual hallucinations in a patient with Schizophrenia. Targeted therapy of this kind can be considered in challenging cases although more evidence is required in this field. Background Visual hallucinations occur in a variety of neurologica

Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment-related aspects of apathy from depression in neurocognitive disorders

Objectives: This narrative review describes the clinical features of apathy and depression in individuals with neurocognitive disorders (NCDs), with the goal of differentiating the two syndromes on the basis of clinical presentation, diagnostic criteria, neuropathological features, and contrasting responses to treatments. Methods: Literature was identified using PubMed, with search terms to capture medical conditions of interest; additional references were also included based on our collective experience and knowledge of the literature. Results: Evidence from current literature supports the distinction between the two disorders; apathy and depression occur with varying prevalence in individuals with NCDs, pose different risks of progression to dementia, and have distinct, if overlapping, neurobiological underpinnings. Although apathy is a distinct neuropsychiatric syndrome, distinguishing apathy from depression can be challenging, as both conditions may occur concurrently and share several overlapping features. Apathy is associated with unfavorable outcomes, especially those with neurodegenerative etiologies (e.g., Alzheimer's disease) and is associated with an increased burden for both patients and caregivers. Diagnosing apathy is important not only to serve as the basis for appropriate treatment, but also for the development of novel targeted interventions for this condition. Although there are currently no approved pharmacologic treatments for apathy, the research described in this review supports apathy as a distinct neuropsychiatric condition that warrants specific treatments aimed at alleviating patient disability. Conclusions: Despite differences between these disorders, both apathy and depression pose significant challenges to patients, their families, and caregivers; better diagnostics are needed to develop more tailored treatment and support

Phenotypic and Genetic Divergence among Poison Frog Populations in a Mimetic Radiation

The evolution of Müllerian mimicry is, paradoxically, associated with high levels of diversity in color and pattern. In a mimetic radiation, different populations of a species evolve to resemble different models, which can lead to speciation. Yet there are circumstances under which initial selection for divergence under mimicry may be reversed. Here we provide evidence for the evolution of extensive phenotypic divergence in a mimetic radiation in Ranitomeya imitator, the mimic poison frog, in Peru. Analyses of color hue (spectral reflectance) and pattern reveal substantial divergence between morphs. However, we also report that there is a “transition-zone� with mixed phenotypes. Analyses of genetic structure using microsatellite variation reveals some differentiation between populations, but this does not strictly correspond to color pattern divergence. Analyses of gene flow between populations suggest that, while historical levels of gene flow were low, recent levels are high in some cases, including substantial gene flow between some color pattern morphs. We discuss possible explanations for these observations

Acupuncture Point Localization Varies Among Acupuncturists

Background: Studies assessing the point-specific effect of acupuncture or the characteristics of acupuncture points (APs) tend to yield inconclusive results. In order to identify a possible confounding factor, we aimed to examine the variability in AP localization by means of a survey. Material and Methods: Attendees of the 14th ICMART (International Council of Medical Acupuncture and Related Techniques) congress as well as DAGfA (German Medical Society of Acupuncture) lecturers and students were asked to locate and mark the APs LI 10 and TH 5 on a research assistant's arm. Identified points were transferred into a coordinate system, and the respective bivariate distribution function was calculated. Additionally, participants filled out a questionnaire about their acupuncture education and experience, the acupuncture style and point localization techniques used most frequently, and their estimation of the size of an AP. Results: The areas of the ellipses, theoretically containing 95% of AP localizations, varied between 44.49 and 5.18 cm(2). The largest distance between 2 identified points was 8.45 cm for LI 10 and 5.3 cm for TH 5. Apart from being trained at the same school, no other factor could be identified that determined the variability in AP localization. Conclusion: Our results indicate that congruity of AP localization among experienced acupuncturists might be low. Although there are some limitations to our results, this possible bias should be taken into account when conducting acupuncture trials and interpreting results of previous acupuncture studies

Pilot case-control investigation of risk factors for hip fractures in the urban Indian population

<p>Abstract</p> <p>Background</p> <p>Despite the reported high prevalence of osteoporosis in India, there have been no previous studies examining the risk factors for hip fracture in the Indian population.</p> <p>Methods</p> <p>We carried out a case control investigation comprising 100 case subjects (57 women and 43 men) admitted with a first hip fracture into one of three hospitals across New Delhi. The 100 controls were age and sex matched subjects who were either healthy visitors not related to the case patients or hospital staff. Information from all subjects was obtained through a questionnaire based interview.</p> <p>Results</p> <p>There was a significant increase in the number of cases of hip fracture with increasing age. There were significantly more women (57%) than men (43%). Univariate analysis identified protective effects for increased activity, exercise, calcium and vitamin supplements, almonds, fish, paneer (cottage cheese), curd (plain yogurt), and milk. However, tea and other caffeinated beverages were significant risk factors. In women, hormone/estrogen therapy appeared to have a marginal protective effect. For all cases, decreased agility, visual impairment, long term medications, chronic illnesses increased the risk of hip fracture. The multivariate analysis confirmed a protective effect of increased activity and also showed a decrease in hip fracture risk with increasing body mass index (odds ratio (OR) 0.024, 95% confidence interval (CI) 0.006-0.10 & OR 0.81, 95% CI 0.68-0.97 respectively). Individuals who take calcium supplements have a decreased risk of hip fracture (OR 0.076; CI 0.017-0.340), as do individuals who eat fish (OR 0.094; CI 0.020-0.431), and those who eat paneer (OR 0.152; 0.031-0.741). Tea drinkers have a higher risk of hip fracture (OR 22.8; 95% CI 3.73-139.43). Difficulty in getting up from a chair also appears to be an important risk factor for hip fractures (OR 14.53; 95% CI 3.86-54.23).</p> <p>Conclusions</p> <p>In the urban Indian population, dietary calcium, vitamin D, increased body mass index, and higher activity levels have a significant protective effect on hip fracture. On the other hand, caffeine intake and decreased agility increase the risk of hip fracture. Future studies should be done in order to direct primary preventive programs for hip fracture in India.</p

Looking inside the black box : a theory-based process evaluation alongside a randomised controlled trial of printed educational materials (the Ontario printed educational message, OPEM) to improve referral and prescribing practices in primary care in Ontario, Canada

Background: Randomised controlled trials of implementation strategies tell us whether (or not) an intervention results in changes in professional behaviour but little about the causal mechanisms that produce any change. Theory-based process evaluations collect data on theoretical constructs alongside randomised trials to explore possible causal mechanisms and effect modifiers. This is similar to measuring intermediate endpoints in clinical trials to further understand the biological basis of any observed effects (for example, measuring lipid profiles alongside trials of lipid lowering drugs where the primary endpoint could be reduction in vascular related deaths). This study protocol describes a theory-based process evaluation alongside the Ontario Printed Educational Message (OPEM) trial. We hypothesize that the OPEM interventions are most likely to operate through changes in physicians' behavioural intentions due to improved attitudes or subjective norms with little or no change in perceived behavioural control. We will test this hypothesis using a well-validated social cognition model, the theory of planned behaviour (TPB) that incorporates these constructs. Methods/design: We will develop theory-based surveys using standard methods based upon the TPB for the second and third replications, and survey a subsample of Ontario family physicians from each arm of the trial two months before and six months after the dissemination of the index edition of informed, the evidence based newsletter used for the interventions. In the third replication, our study will converge with the "TRY-ME" protocol (a second study conducted alongside the OPEM trial), in which the content of educational messages was constructed using both standard methods and methods informed by psychological theory. We will modify Dillman's total design method to maximise response rates. Preliminary analyses will initially assess the internal reliability of the measures and use regression to explore the relationships between predictor and dependent variable (intention to advise diabetic patients to have annual retinopathy screening and to prescribe thiazide diuretics for first line treatment of uncomplicated hypertension). We will then compare groups using methods appropriate for comparing independent samples to determine whether there have been changes in the predicted constructs (attitudes, subjective norms, or intentions) across the study groups as hypothesised, and will assess the convergence between the process evaluation results and the main trial results.The OPEM trial and OPEM process evaluation are funded by the Canadian Institute of Health Research (CIHR). The OPEM process evaluation study was developed as part of the CIHR funded interdisciplinary capacity enhancement team KT-ICEBeRG. Gaston Godin, Jeremy Grimshaw and France Légaré hold Canada Research Chairs. Louise Lemyre holds an R.S. McLaughlin Research Chair

The Amyloid-beta Pathway in Alzheimer's Disease

Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer’s disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-temporal dynamics leading to synaptic failure, neurodegeneration, and clinical onset are still under intense investigation, the established biochemical alterations of the Aβ cycle remain the core biological hallmark of AD and are promising targets for the development of disease-modifying therapies. Here, we systematically review and update the vast state-of-the-art literature of Aβ science with evidence from basic research studies to human genetic and multi-modal biomarker investigations, which supports a crucial role of Aβ pathway dyshomeostasis in AD pathophysiological dynamics. We discuss the evidence highlighting a differentiated interaction of distinct Aβ species with other AD-related biological mechanisms, such as tau-mediated, neuroimmune and inflammatory changes, as well as a neurochemical imbalance. Through the lens of the latest development of multimodal in vivo biomarkers of AD, this cross-disciplinary review examines the compelling hypothesis- and data-driven rationale for Aβ-targeting therapeutic strategies in development for the early treatment of AD