Dopamine Agonists and Pathologic Behaviors

The dopamine agonists ropinirole and pramipexole exhibit highly specific affinity for the cerebral dopamine D3 receptor. Use of these medications in Parkinson's disease has been complicated by the emergence of pathologic behavioral patterns such as hypersexuality, pathologic gambling, excessive hobbying, and other circumscribed obsessive-compulsive disorders of impulse control in people having no history of such disorders. These behavioral changes typically remit following discontinuation of the medication, further demonstrating a causal relationship. Expression of the D3 receptor is particularly rich within the limbic system, where it plays an important role in modulating the physiologic and emotional experience of novelty, reward, and risk assessment. Converging neuroanatomical, physiological, and behavioral science data suggest the high D3 affinity of these medications as the basis for these behavioral changes. These observations suggest the D3 receptor as a therapeutic target for obsessive-compulsive disorder and substance abuse, and improved understanding of D3 receptor function may aid drug design of future atypical antipsychotics

Adoption of Plantain within New Zealand Farming Systems

In New Zealand, plantain has been incorporated into the pasture forage base in three ways: as a short-term pure crop; as a major component in “herb mixes” that include clovers and chicory; and as a minor component in perennial grass-based swards. All types are typically grazed in-situ. Given the incentive to optimise the plantain proportion in livestock diet to mitigate nitrogen losses and the observed lack of persistence in grass-dominant pasture over time, there is a need to use various pasture types strategically across a farm system to ensure a long-term sustainable contribution of plantain to feed intake. The inclusion of plantain in the forage base should be relatively straightforward since farmers are already familiar with establishing and managing forage crops and mixed-species pastures. However, there are still technical questions to answer and incentives to implement before we can achieve the region-wide adoption necessary to result in a measurable impact on water quality. The Tararua District, on the east coast of the North Island of New Zealand, represents a useful case study of adoption in a strong dairy farming region. Some underpinning elements for successful adoption were in place: 1) national agronomic experience in using a plantain cultivar released in 1996; and 2) regulatory push in terms of reducing N leaching losses on farms. However, other initiatives were required to see meaningful progress: provision of data from local dairy farm systems, focused on the impact on forage supply/quality; a targeted extension program by a trusted sector leader agency (DairyNZ); individual farmer risk-taking and leadership in establishing and managing new crops and pastures. After three years, awareness is well embedded in the rural community and approximately 30% of dairy farms within the district have started to use plantain

Ultra-High-Resolution Optical Coherence Tomographic Findings in Commotio Retinae

Commotio retinae is a self-limited opacification of the retina secondary to direct blunt ocular trauma. Histologic studies of monkeys and humans relate this clinical observation to damaged photoreceptor outer segments and receptor cell bodies.[superscript 1 - 3] Reports using time-domain optical coherence tomography (OCT) and spectral-domain OCT support the involvement of the photoreceptor layer, but these techniques lack the resolution necessary to confirm results of histologic analysis.[superscript 4 - 6] Prototype high-speed ultra–high-resolution OCT (hs-UHR-OCT) images demonstrate these anatomical changes in a patient with acute commotio retinae.National Institutes of Health (U.S.) (Contract Number RO1-EY11289-23)National Institutes of Health (U.S.) (Contract Number R01-EY13178-07)United States. Air Force Office of Scientific Research (Grant Number FA9550-07-1-0101)United States. Air Force Office of Scientific Research (Grant Number FA9550-07-1-0014

Landscape Diversity Related to Buruli Ulcer Disease in Côte d'Ivoire

Buruli ulcer (BU) is one of the most neglected but treatable tropical diseases. The causative organism, Mycobacterium ulcerans, is from the family of bacteria that causes tuberculosis and leprosy. This severe skin disease leads to long-term functional disability if not treated. BU has been reported in over 30 countries mainly with tropical and subtropical climates, but Côte d'Ivoire is one of the most affected countries. M. ulcerans is an environmental bacterium and its mode of transmission to humans is still unclear, such that the disease is often referred to as the “mysterious disease” or the “new leprosy”. Here, we explored the relationship between environmental and socioeconomic factors and BU cases on a nationwide scale. We found that irrigated rice field cultures areas, and, to a lesser extent, banana fields as well as areas in the vicinity of dams used for irrigation and aquaculture purposes, represent high risk zones for the human population to contract BU in Côte d'Ivoire. This work identifies high-risk areas for BU in Côte d'Ivoire and deserves to be extended to different countries. We need now to obtain a global vision and understanding of the route of transmission of M. ulcerans to humans in order to better implement control strategies

Bradykinesia in Neurodegenerative Disorders: A Blinded Video Analysis of Pathology-Proven Cases

Background: Bradykinesia is a cardinal feature in parkinsonisms. No study has assessed the differential features of bradykinesia in patients with pathology-proven synucleinopathies and tauopathies. Objective: We examined whether bradykinesia features (speed, amplitude, rhythm, and sequence effect) may differ between pathology-proven synucleinopathies and tauopathies. Methods: Forty-two cases who underwent autopsy were included and divided into synucleinopathies (Parkinson's disease and dementia with Lewy bodies) and tauopathies (progressive supranuclear palsy). Two raters blinded to the diagnosis retrospectively scored the Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III and Modified Bradykinesia Rating Scale on standardized videotaped neurological examinations. Bradykinesia scores were compared using the Mann-Whitney test and logistic regression models to adjust for disease duration. Results: Demographic and clinical parameters were similar between synucleinopathies and tauopathies. There were no differences between speed, amplitude, rhythm, and sequence effect in synucleinopathies and tauopathies in unadjusted comparisons and adjusted models (all P > 0.05). Conclusions: Clinical bradykinesia features do not distinguish the underlying neuropathology in neurodegenerative parkinsonisms

Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis

Correction to Martin et al. available at: Genes & Development 30 (19): 2158 (http://genesdev.cshlp.org/content/31/9/953.full.pdf+html).Compaction of chromosomes is essential for accurate segregation of the genome duringmitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here,we report that biallelic mutations inNCAPD2,NCAPH, orNCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish “condensinopathies” as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.This work was supported by funding from the Medical Research Council, the Lister Institute for Preventative Medicine, and the European Research Council (ERC; 281847 to A.P.J.); a Biotechnology and Biological Sciences Research Council grant (BB/ K017632/1 to P.V); a Sir Henry Dale Fellowship (grant 102560/ Z/13/Z to A.J.W.); Medical Research Scotland (to L.S.B.); the Potentials Foundation (to C.A.W.); and the Indian Council of Medical Research (BMS 54/2/2013 to S.R.P). The Deciphering Developmental Disorders Study presents independent research commissioned by the Health Innovation Challenge Fund (grant no. HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant no. WT098051). The views expressed here are those of the authors and not necessarily those of the Wellcome Trust or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83) granted by the Cambridge South Research Ethics Committee, and GEN/ 284/12 granted by the Republic of Ireland. We acknowledge the support of the National Institute for Health Research through the Comprehensive Clinical Research Network

Understanding perceptions on 'Buruli' in northwestern Uganda: A biosocial investigation.

BACKGROUND: An understudied disease, little research thus far has explored responses to Buruli ulcer and quests for therapy from biosocial perspective, despite reports that people seek biomedical treatment too late. METHODS AND FINDINGS: Taking an inductive approach and drawing on long-term ethnographic fieldwork in 2013-14, this article presents perspectives on this affliction of people living and working along the River Nile in northwest Uganda. Little is known biomedically about its presence, yet 'Buruli', as it is known locally, was and is a significant affliction in this region. Establishing a biosocial history of 'Buruli', largely obscured from biomedical perspectives, offers explanations for contemporary understandings, perceptions and practices. CONCLUSIONS/SIGNIFICANCE: We must move beyond over-simplifying and problematising 'late presentation for treatment' in public health, rather, develop biosocial approaches to understanding quests for therapy that take into account historical and contemporary contexts of health, healing and illness. Seeking to understand the context in which healthcare decisions are made, a biosocial approach enables greater depth and breadth of insight into the complexities of global and local public health priorities such as Buruli ulcer

Chronic recurrent Gorham-Stout syndrome with cutaneous involvement

Type IV osteolysis or Gorham-Stout syndrome is a rare condition characterized by recurrent vascular tumors that disrupt normal anatomical architecture. Gorham-Stout syndrome is most commonly associated with the skeletal system with resulting replacement of bone with scar tissue following tumor regression. The loss of entire bones has given Gorham-Stout syndrome the moniker vanishing bone disease. Natural progression of Gorham-Stout syndrome is characterized by spontaneous disease resolution. However, rare variants of recurrent, progressive, and/or systemic disease have been reported. We present a patient with a history of recurrent Gorham- Stout disease refractory to all treatment options considered. In addition to skeletal disease, our patient had soft tissue and cutaneous involvement, thus reflecting the more aggressive disease variant. Previous surgical attempts to control disease had been ineffective and the patient was referred to us for radiation therapy. Treatment with external beam radiation therapy resulted in good local control and symptom palliation, but full disease resolution was never accomplished. In addition to presentation of this patient, a review of the literature on etiological hypotheses and past/future treatment options was conducted and is included