PSYCHIATRIC ASPECTS OF HUNTINGTON DISEASE – CASE REPORTS

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Mirela Batta

2004-04-01

Full Text Available Background. Huntington disease occurrs rarely, it can be encountered not only by neurologists and psychiatrists but also by other medical practitioners. Its characteristic features are involuntary movements, cognitive disorders and gradual development of dementia. Diagnosis is given on the basis of these clinical features, positive familial anamnesis, with the laboratory exclusion of other neuropsychiatric diseases and with the help of neuroimaging methods (in particular NMR. The disease can be only confirmed by means of genetic analysis.Patients and methods. In this article, four cases of patients with Huntington disease and diverse psychiatric disorders that were hospitalised at the psychiatric department of the Maribor General Hospital between October 2002 and March 2003 are described. All the patients fulfilled the valid criteria for the diagnosis of Huntington disease. However, they differed according to their accompanying psychiatric psychopathology, age and social problems.Conclusions. The purpose of this article is to draw attention to different psychiatric symptoms and clinical manifestations of Huntington disease that are often misleading in the diagnostic process. In addition, exigency of early diagnostics, guidelines for referrals to genetic testing and psychiatric monitoring of these patients are emphasised.

Semantic, phonologic, and verb fluency in Huntington's disease

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Mariana Jardim Azambuja

Full Text Available Abstract Verbal fluency tasks have been identified as important indicators of executive functioning impairment in patients with frontal lobe dysfunction. Although the usual evaluation of this ability considers phonologic and semantic criteria, there is some evidence that fluency of verbs would be more sensitive in disclosing frontostriatal physiopathology since frontal regions primarily mediate retrieval of verbs. Huntington's disease usually affects these circuitries. Objective: To compare three types of verbal fluency task in the assessment of frontal-striatal dysfunction in HD subjects. Methods: We studied 26 Huntington's disease subjects, divided into two subgroups: mild (11 and moderate (15 along with 26 normal volunteers matched for age, gender and schooling, for three types of verbal fluency: phonologic fluency (F-A-S, semantic fluency and fluency of verbs. Results: Huntington's disease subjects showed a significant reduction in the number of words correctly generated in the three tasks when compared to the normal group. Both controls and Huntington's disease subjects showed a similar pattern of decreasing task performance with the greatest number of words being generated by semantic elicitation followed by verbs and lastly phonologic criteria. We did not find greater production of verbs compared with F-A-S and semantic conditions. Moreover, the fluency of verbs distinguished only the moderate group from controls. Conclusion: Our results indicated that phonologic and semantic fluency can be used to evaluate executive functioning, proving more sensitive than verb fluency. However, it is important to point out that the diverse presentations of Huntington's disease means that an extended sample is necessary for more consistent analysis of this issue.

Major Superficial White Matter Abnormalities in Huntington's Disease

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Phillips, Owen R.; Joshi, Shantanu H.; Squitieri, Ferdinando; Sanchez-Castaneda, Cristina; Narr, Katherine; Shattuck, David W.; Caltagirone, Carlo; Sabatini, Umberto; Di Paola, Margherita

2016-01-01

Background: The late myelinating superficial white matter at the juncture of the cortical gray and white matter comprising the intracortical myelin and short-range association fibers has not received attention in Huntington's disease. It is an area of the brain that is late myelinating and is sensitive to both normal aging and neurodegenerative disease effects. Therefore, it may be sensitive to Huntington's disease processes. Methods: Structural MRI data from 25 Pre-symptomatic subjects, 24 Huntington's disease patients and 49 healthy controls was run through a cortical pattern-matching program. The surface corresponding to the white matter directly below the cortical gray matter was then extracted. Individual subject's Diffusion Tensor Imaging (DTI) data was aligned to their structural MRI data. Diffusivity values along the white matter surface were then sampled at each vertex point. DTI measures with high spatial resolution across the superficial white matter surface were then analyzed with the General Linear Model to test for the effects of disease. Results: There was an overall increase in the axial and radial diffusivity across much of the superficial white matter (p < 0.001) in Pre-symptomatic subjects compared to controls. In Huntington's disease patients increased diffusivity covered essentially the whole brain (p < 0.001). Changes are correlated with genotype (CAG repeat number) and disease burden (p < 0.001). Conclusions: This study showed broad abnormalities in superficial white matter even before symptoms are present in Huntington's disease. Since, the superficial white matter has a unique microstructure and function these abnormalities suggest it plays an important role in the disease. PMID:27242403

Did the "Woman in the Attic" in Jane Eyre Have Huntington Disease?

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Coon, Elizabeth A; Hassan, Anhar

2015-01-01

References to neurologic disorders are frequently found in fictional literature and may precede description in the medical literature. Our aim was to compare Charlotte Brontë's depiction of Bertha Mason in Jane Eyre to the tenets set forth in George Huntington's original essay "On chorea" with the hypothesis that Mason was displaying features of Huntington disease. Charlotte Brontë's 1847 Victorian novel Jane Eyre features the character Bertha Mason, who is portrayed with a progressive psychiatric illness, violent movements, and possible cognitive decline. Similar to Huntington's tenets, Mason has a disorder with a strong family history suggestive of autosomal dominant inheritance with onset in adulthood, and culminating in suicide. Brontë's character had features of Huntington disease as originally described by Huntington. Brontë's keen characterization may have increased awareness of treatment of neuropsychiatric patients in the Victorian era.

Discrepancies in reporting the CAG repeat lengths for Huntington's disease

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Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty

2011-01-01

Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

aliving with Huntington´s disease in the Czech Republic

Czech Academy of Sciences Publication Activity Database

Baxa, Monika

2015-01-01

Roč. 78, Suppl 2 (2015), s. 6-6 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] Institutional support: RVO:67985904 Keywords : Czech Huntington Association * life with Huntington ´ disease Subject RIV: FH - Neurology

Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.

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Novak, Marianne J U; Warren, Jason D; Henley, Susie M D; Draganski, Bogdan; Frackowiak, Richard S; Tabrizi, Sarah J

2012-04-01

Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena

Psychiatric symptoms and CAG expansion in Huntington`s disease

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Weber, M.W.; Schmid, W.; Spiegel, R. [Univ. of Zuerich (Switzerland)

1996-02-16

The mutation responsible for Huntington`s disease (HD) is an elongated CAG repeat in the coding region of the IT15 gene. A PCR-based test with high sensitivity and accuracy is now available to identify asymptomatic gene carriers and patients. An inverse correlation between CAG copy number and age at disease onset has been found in a large number of affected individuals. The influence of the CAG repeat expansion on other phenotypic manifestations, especially specific psychiatric symptoms has not been studied intensively. In order to elucidate this situation we investigated the relation between CAG copy number and distinct psychiatric phenotypes found in 79 HD-patients. None of the four differentiated categories (personality change, psychosis, depression, and nonspecific alterations) showed significant differences in respect to size of the CAG expansion. In addition, no influence of individual sex on psychiatric presentation could be found. On the other hand in patients with personality changes maternal transmission was significantly more frequent compared with all other groups. Therefore we suggest that clinical severity of psychiatric features in HD is not directly dependent on the size of the dynamic mutation involved. The complex pathogenetic mechanisms leading to psychiatric alterations are still unknown and thus genotyping does not provide information about expected psychiatric symptoms in HD gene carriers. 40 refs., 1 fig., 2 tabs.

Clinical and genetic data of Huntington disease in Moroccan patients

African Journals Online (AJOL)

Background: Huntington's disease (HD) occurs worldwide with prevalence varying from 0.1 to 10 /100,000 depending of the ethnic origin. Since no data is available in the Maghreb population, the aim of this study is to describe clinical and genetic characteristics of Huntington patients of Moroccan origin. Methods: Clinical ...

75 FR 13454 - Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY

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2010-03-22

...-AA08 Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY AGENCY: Coast... navigable waters of Huntington Bay, New York due to the annual Fran Schnarr Open Water Championships. The..., ``Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY'' (Docket number USCG...

75 FR 38710 - Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY

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2010-07-06

...-AA08 Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY AGENCY: Coast... Regulation on the navigable waters of Huntington Bay, New York due to the annual Fran Schnarr Open Water... ``Special Local Regulation, Fran Schnarr Open Water Championships, Huntington Bay, NY'' in the Federal...

Earliest functional declines in Huntington disease

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Beglinger, Leigh J.; O'Rourke, Justin J.F.; Wang, Chiachi; Langbehn, Douglas R.; Duff, Kevin; Paulsen, Jane S.

2013-01-01

We examined the gold standard for Huntington disease (HD) functional assessment, the Unified Huntington's Disease Rating Scale (UHDRS), in a group of at-risk participants not yet diagnosed but who later phenoconverted to manifest HD. We also sought to determine which skill domains first weaken and the clinical correlates of declines. Using the UHDRS Total Functional Capacity (TFC) and Functional Assessment Scale (FAS), we examined participants from Huntington Study Group clinics who were not diagnosed at their baseline visit but were diagnosed at a later visit (N = 265). Occupational decline was the most common with 65.1% (TFC) and 55.6% (FAS) reporting some loss of ability to engage in their typical work. Inability to manage finances independently (TFC 49.2%, FAS 35.1%) and drive safely (FAS 33.5%) were also found. Functional decline was significantly predicted by motor, cognitive, and depressive symptoms. The UHDRS captured early functional losses in individuals with HD prior to formal diagnosis, however, fruitful areas for expanded assessment of early functional changes are performance at work, ability to manage finances, and driving. These are also important areas for clinical monitoring and treatment planning as up to 65% experienced loss in at least one area prior to diagnosis. PMID:20471695

The Addenbrooke's Cognitive Examination-Revised accurately detects cognitive decline in Huntington's disease.

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Begeti, Faye; Tan, Adrian Y K; Cummins, Gemma A; Collins, Lucy M; Guzman, Natalie Valle; Mason, Sarah L; Barker, Roger A

2013-11-01

Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington's disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical way to monitor cognition using the Addenbrooke's Cognitive Examination-Revised (ACE-R) in 126 manifest Huntington's disease patients, 28 premanifest gene carriers and 21 controls. Using this test, we demonstrated a selective decrease in phonemic, but not semantic, fluency in premanifest participants Cognitive decline in manifest Huntington's disease varied according to disease severity with extensive cognitive decline observed in early-stage Huntington's disease patients, indicating that this would be an optimal stage for interventions designed to halt cognitive decline, and lesser changes in the advanced cases. We next examined cognitive performance in patients prescribed antidopaminergic drugs as these drugs are known to decrease cognition when administered to healthy volunteers. We paradoxically found that these drugs may be beneficial, as early-stage Huntington's disease participants in receipt of them had improved attention and Mini-Mental State Examination scores. In conclusion, this is the first study to test the usefulness of the ACE-R in a Huntington's disease population and demonstrates that this is a brief, inexpensive and practical way to measure global cognitive performance in clinical practice with potential use in clinical trials.

Suggestions for Local School District Compliance with Title IX Rules and Regulations.

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Arizona State Dept. of Education, Phoenix.

This guidebook is designed to help local districts determine how well they comply with the spirit of the Title IX requirements against sex discrimination, which in turn could aid in compliance with the letter of the law. The document's first section presents samples of required antidiscrimination policy statements issued by two districts. The…

Xeroderma pigmentosum is a definite cause of Huntington's disease-like syndrome.

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Garcia-Moreno, Hector; Fassihi, Hiva; Sarkany, Robert P E; Phukan, Julie; Warner, Thomas; Lehmann, Alan R; Giunti, Paola

2018-01-01

Xeroderma pigmentosum is characterized by cutaneous, ophthalmological, and neurological features. Although it is typical of childhood, late presentations can mimic different neurodegenerative conditions. We report two families presenting as Huntington's disease-like syndromes. The first case (group G) presented with neuropsychiatric features, cognitive decline and chorea. Typical lentigines were only noticed after the neurological disease started. The second case (group B) presented adult-onset chorea and neuropsychiatric symptoms after an aggressive ocular melanoma. Xeroderma pigmentosum can manifest as a Huntington's Disease-like syndrome. Classic dermatological and oncological features have to be investigated in choreic patients with negative genetic tests for Huntington's disease-like phenotypes.

Music therapy in Huntington's disease

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Bruggen-Rufi, van C.H.M.

2018-01-01

The thesis reports about the effects of music therapy with patients in the late stage of Huntington's disease. A literature review, a focus group study, a randomized controlled trial, an evaluation for complex interventions and a case report study are integrated in the thesis. The beneficial

The Wilson films--Huntington's chorea.

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Klein, Christine

2011-12-01

Wilson's Queen Square Case 9 with Huntington's chorea shows a 68-year-old man with mild to moderate generalized chorea, impaired fixation, and probable cognitive decline in keeping with a diagnosis of Huntington's disease (HD). An age of onset in the late sixties and a negative family history suggest a relatively small expanded trinucleotide repeat in the HTT gene in the patient and reduced penetrance of an even shorter repeat allele in one of his parents. A highly sensitive and specific gene test has been offered worldwide for diagnostic testing of HD for almost two decades. This test, obviously unavailable at Wilson's times, became the historic frontrunner for guidelines of symptomatic, presymptomatic, and prenatal testing for an adult-onset neurodegenerative disorder. Regarding treatment of HD, however, we are still awaiting the successful translation of research results into the development of effective cause-directed, neuropreventive and neurorestaurative therapies. Copyright © 2011 Movement Disorder Society.

The use of olanzapine in Huntington disease accompanied by psychotic symptoms

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Cafer Alhan

2014-06-01

Full Text Available Huntington's disease is an autosomal dominant neurodegenerative disease. The disease begins between the ages of 30-50, including motor symptoms, psychiatric symptoms and is characterized by progressive dementia. Common psychiatric disorders of Huntington’s disease include mood and anxiety disorders, behavior and personality changes. Psychosis is relatively rare. Here, a patient is present, who has Huntington’s disease, which is associated with psychotic symptoms. 61-year-old male patient who were followed for Huntington disease for 25 years was admitted for complaints of thinking of poisoning and refuse to eat something. Patient was started on olanzapine at dose of 5 mg/day. In follow up psychotic symptoms disappeared. Emerging psychotic symptoms in Huntington disease is created a need for antipsychotic treatment. Atypical antipsychotic agents should be preferred in the treatment and as in the case olanzapine may be used as a treatment option should be kept in mind to control both involuntary movements and psychotic symptoms in Huntington's disease with psychotic features. J Clin Exp Invest 2014; 5 (2: 326-328

Kas Huntington oli prohvet? / Priit Simson

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Simson Priit, 1977-

2008-01-01

Autor käsitleb Samuel Huntingtoni teese ning leiab, et tegelikult Huntington ei pakkunud õigustust islamiriikide ründamisele, vaid pigem hoiatas tsivilisatsioonide siseasjusse sekkumise, tekkida võiva ahelreaktsiooni eest, kus üks tsivilisatsiooni liige tõmbab sõtta ka teise

The emotional experiences of family carers in Huntington disease.

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Williams, Janet K; Skirton, Heather; Paulsen, Jane S; Tripp-Reimer, Toni; Jarmon, Lori; McGonigal Kenney, Meghan; Birrer, Emily; Hennig, Bonnie L; Honeyford, Joann

2009-04-01

This paper is a report of a study conducted to examine the emotional experience of caregiving by family carers of people with Huntington disease and to describe strategies they used to deal with that experience. Huntington disease, commonly diagnosed in young to middle adulthood, is an inherited single gene disorder involving loss of cognitive, motor and neuropsychiatric function. Many family members become caregivers as well as continuing as parents and wage earners. The emotional aspects of caregiving contribute to mental health risks for family members. Focus groups were conducted with 42 adult carers of people with Huntington disease in four United States and two Canadian Huntington disease centers between 2001 and 2005. Data were analyzed through descriptive coding and thematic analysis. All participants reported multiple aspects of emotional distress. Being a carer was described as experiencing disintegration of one's life. Carers attempted to cope by seeking comfort from selected family members, anticipating the time when the care recipient had died and/or using prescription medications. Spousal carers were distressed by the loss of their relationship with their spouse and dealt with this by no longer regarding the person as an intimate partner. Carers were concerned about the disease risk for children in their families and hoped for a cure. Emotional distress can compromise the well-being of family carers, who attempt to maintain multiple roles. Nurses should monitor carer mental health, identify sources of emotional distress and support effective strategies used by carers to mediate distress.

Américo Negrette and Huntington's disease

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Mariana Moscovich

2011-08-01

Full Text Available The authors present a historical review of the seminal clinical contribution of Professor Américo Negrette, a Venezuelan neurologist, to the evolution of scientific knowledge about Huntington's disease.

Clinical and genetic study of a juvenile-onset Huntington disease

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HAO Ying

2012-06-01

Full Text Available Background Huntington's disease (HD is an autosomal dominant hereditary progressive neurodegenerative disorder with a distinct phenotype characterized by chorea, dementia, cognitive and affective impairment. There are selective neural cell loss and atrophy in the caudate and putamen. Dr. George Huntington firstly described the disease accurately and insightfully, which led to a widespread recognition of the inherited chorea that now bears his name. Huntington disease gene (IT15 locus on chromosome 4p16.3, and encompasses 67 exons with a trinucleotide repeat (CAG in the first exon. The CAG repeat length is highly polymorphic in the population and expanded on at least one chromosome of individuals with HD. Clinically, patient with HD are often onset in adulthood. Juvenile-onset HD is relatively rare. Adult-onset HD patients usually have a CAG expansion from 40 to 55 whereas those with juvenile-onset greater than 60 which are often inherited from the father. We investigated the clinical features of a juvenile-onset case with Huntington disease and dynamic mutation of his family. Methods The CAG repeats of IT15 gene were detected using polymerase chain reaction and capillary electrophoresis in 115 individuals with preliminary diagnosis as Huntington disease. The repeat numbers of some samples carried expanded or intermediate alleles were verified by the pMD18-T vector clone sequencing. Results Fragment analysis showed that one juvenile-onset case presenting with cognitive dysfunction and hypokinesis carried 15/68 CAG repeats of IT15. His father carried 17/37 and mother carried 15/17. Conclusion 1 The juvenile-onset case of HD presented with different clinical features compared with adult-onset cases. The typical signs of adult-onset cases include progressive chorea, rigidity and dementia. The most common sign of juvenile-onset Huntington disease is cognitive decline. 2 The dynamic mutation of IT15 gene expansion of the CAG repeats in the

Testing Students with Disabilities: Practical Strategies for Complying with District and State Requirements. Second Edition.

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Thurlow, Martha L.; Elliott, Judy L.; Ysseldyke, James E.

This book is intended to facilitate the meaningful inclusion of students with disabilities in district and state assessments as required by the 1997 amendments to the Individuals with Disabilities Education Act. First, an introductory chapter offers reasons for including students with disabilities in district and statewide accountability systems.…

A 24-Hour Study of the Hypothalamo-Pituitary Axes in Huntington's Disease.

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Eirini Kalliolia

Full Text Available Huntington's disease is an inherited neurodegenerative disorder characterised by motor, cognitive and psychiatric disturbances. Patients exhibit other symptoms including sleep and mood disturbances, muscle atrophy and weight loss which may be linked to hypothalamic pathology and dysfunction of hypothalamo-pituitary axes.We studied neuroendocrine profiles of corticotropic, somatotropic and gonadotropic hypothalamo-pituitary axes hormones over a 24-hour period in controlled environment in 15 healthy controls, 14 premanifest and 13 stage II/III Huntington's disease subjects. We also quantified fasting levels of vasopressin, oestradiol, testosterone, dehydroepiandrosterone sulphate, thyroid stimulating hormone, free triiodothyronine, free total thyroxine, prolactin, adrenaline and noradrenaline. Somatotropic axis hormones, growth hormone releasing hormone, insulin-like growth factor-1 and insulin-like factor binding protein-3 were quantified at 06:00 (fasting, 15:00 and 23:00. A battery of clinical tests, including neurological rating and function scales were performed.24-hour concentrations of adrenocorticotropic hormone, cortisol, luteinizing hormone and follicle-stimulating hormone did not differ significantly between the Huntington's disease group and controls. Daytime growth hormone secretion was similar in control and Huntington's disease subjects. Stage II/III Huntington's disease subjects had lower concentration of post-sleep growth hormone pulse and higher insulin-like growth factor-1:growth hormone ratio which did not reach significance. In Huntington's disease subjects, baseline levels of hypothalamo-pituitary axis hormones measured did not significantly differ from those of healthy controls.The relatively small subject group means that the study may not detect subtle perturbations in hormone concentrations. A targeted study of the somatotropic axis in larger cohorts may be warranted. However, the lack of significant results despite many

The role of tau in the pathological process and clinical expression of Huntington's disease

DEFF Research Database (Denmark)

Vuono, Romina; Winder-Rhodes, Sophie; de Silva, Rohan

2015-01-01

and progression of Huntington's disease, the exact molecular mechanisms driving its pathogenic cascade and clinical features, especially the dementia, are not fully understood. Recently the microtubule associated protein tau, MAPT, which is associated with several neurodegenerative disorders, has been implicated......-mortem brain samples from patients with Huntington's disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype-phenotype analysis of a large cohort of patients with Huntington's disease (n = 960) with a particular focus on cognitive decline. We report...... not only on the tau pathology in the Huntington's disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some...

The Huntington disease locus is most likely within 325 kilobases of the chromosome 4p telomere

International Nuclear Information System (INIS)

Doggett, N.A.; Cheng, J.F.; Smith, C.L.; Cantor, C.R.

1989-01-01

The genetic defect responsible for Huntington disease was originally localized near the tip of the short arm of chromosome 4 by genetic linkage to the locus D4S10. Several markers closer to Huntington disease have since been isolated, but these all appear to be proximal to the defect. A physical map that extends from the most distal of these loci, D4S90, to the telomere of chromosome 4 was constructed. This map identifies at least two CpG islands as markers for Huntington disease candidate genes and places the most likely location of the Huntington disease defect remarkably close (within 325 kilobases) to the telomere

[The life as a caregiver of a person affected by Chorea Huntington: multiple case study].

Science.gov (United States)

Winkler, Evi; Ausserhofer, Dietmar; Mantovan, Franco

2012-10-01

Chorea Huntington is an autosomal dominantly inherited, neurodegenerative brain disorder that leads to involuntary hyperkinesia, psychotic symptoms and dementia. The illness not only changes the life of the person itself but also the world of the caregivers. The challenges in the care of a person which is affected by Chorea Huntington have an effect on the daily living as an assemblage of natural and social conditions. a multiple case study was conducted. It included semi-structured interviews with three caregivers of people with Chorea Huntington in South Tyrol. The qualitative data was analyzed using the qualitative structured analysis of Mayring (2007). The objective of this study was to describe the phenomenon of change of life from family members that care people affected by Chorea Huntington in a specific cultural setting (South Tyrol, Italy). The caregivers reported that the diagnosis of Chorea Huntington leads to negative changes in "relationship and family". Particularly, frustration, aggression, impatience and apathy were perceived as stressful. At the same time they highlight the positive changes through home care. They report that the relationship became more intimate and integral and it was characterized by more cohesion. Family caregivers get valuable support from the home care service, however, they complain that there is no facility in South Tyrol, which is specialized to care people with Chorea Huntington. Therefore, the caregivers have to "give up a lot" and don't have any personal desires, dreams and expectations for the future. The caregivers have learned independently to deal with their changed life step by step, and to see also the positive effects of the caring role. The life of family caregivers of a person which is affected by Chorea Huntington is characterized by abandonment. A continuous and professional care would be important for the affected and his caregiver. A continuous and professional care is important for both, addressing the

An image-based model of brain volume biomarker changes in Huntington's disease.

Science.gov (United States)

Wijeratne, Peter A; Young, Alexandra L; Oxtoby, Neil P; Marinescu, Razvan V; Firth, Nicholas C; Johnson, Eileanoir B; Mohan, Amrita; Sampaio, Cristina; Scahill, Rachael I; Tabrizi, Sarah J; Alexander, Daniel C

2018-05-01

Determining the sequence in which Huntington's disease biomarkers become abnormal can provide important insights into the disease progression and a quantitative tool for patient stratification. Here, we construct and present a uniquely fine-grained model of temporal progression of Huntington's disease from premanifest through to manifest stages. We employ a probabilistic event-based model to determine the sequence of appearance of atrophy in brain volumes, learned from structural MRI in the Track-HD study, as well as to estimate the uncertainty in the ordering. We use longitudinal and phenotypic data to demonstrate the utility of the patient staging system that the resulting model provides. The model recovers the following order of detectable changes in brain region volumes: putamen, caudate, pallidum, insula white matter, nonventricular cerebrospinal fluid, amygdala, optic chiasm, third ventricle, posterior insula, and basal forebrain. This ordering is mostly preserved even under cross-validation of the uncertainty in the event sequence. Longitudinal analysis performed using 6 years of follow-up data from baseline confirms efficacy of the model, as subjects consistently move to later stages with time, and significant correlations are observed between the estimated stages and nonimaging phenotypic markers. We used a data-driven method to provide new insight into Huntington's disease progression as well as new power to stage and predict conversion. Our results highlight the potential of disease progression models, such as the event-based model, to provide new insight into Huntington's disease progression and to support fine-grained patient stratification for future precision medicine in Huntington's disease.

Destination and source memory in Huntington's disease

NARCIS (Netherlands)

El Haj, M.; Caillaud, M.; Verny, C.; Fasotti, L.; Allain, P.

2016-01-01

Destination memory refers to the recall of the destination of previously relayed information, and source memory refers to the recollection of the origin of received information. We compared both memory systems in Huntington's disease (HD) participants. For this, HD participants and healthy adults

Perceptions of genetic discrimination among people at risk for Huntington's disease: a cross sectional survey.

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Bombard, Yvonne; Veenstra, Gerry; Friedman, Jan M; Creighton, Susan; Currie, Lauren; Paulsen, Jane S; Bottorff, Joan L; Hayden, Michael R

2009-06-09

To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington's disease who had undergone genetic testing or remained untested. Cross sectional, self reported survey. Seven genetics and movement disorders clinics servicing rural and urban communities in Canada. 233 genetically tested and untested asymptomatic people at risk for Huntington's disease (response rate 80%): 167 underwent testing (83 had the Huntington's disease mutation, 84 did not) and 66 chose not to be tested. Self reported experiences of genetic discrimination and related psychological distress based on family history or genetic test results. Discrimination was reported by 93 respondents (39.9%). Reported experiences occurred most often in insurance (29.2%), family (15.5%), and social (12.4%) settings. There were few reports of discrimination in employment (6.9%), health care (8.6%), or public sector settings (3.9%). Although respondents who were aware that they carried the Huntington's disease mutation reported the highest levels of discrimination, participation in genetic testing was not associated with increased levels of genetic discrimination. Family history of Huntington's disease, rather than the result of genetic testing, was the main reason given for experiences of genetic discrimination. Psychological distress was associated with genetic discrimination (PGenetic discrimination was commonly reported by people at risk for Huntington's disease and was a source of psychological distress. Family history, and not genetic testing, was the major reason for genetic discrimination.

A randomized, double-blind, placebo-controlled study of latrepirdine in patients with mild to moderate Huntington disease

DEFF Research Database (Denmark)

Hjermind, Lena Elisabeth

2013-01-01

BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect of latrepir......BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect...... of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Sixty-four research centers in Australia, Europe, and North America. PATIENTS Four hundred three patients with mild to moderate Huntington...... between those randomized to latrepirdine (68.5%) and placebo (68.0%). CONCLUSION In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months was safe and well tolerated but did not improve cognition or global function relative to placebo. TRIAL...

An improved assay for the determination of Huntington`s disease allele size

Energy Technology Data Exchange (ETDEWEB)

Reeves, C.; Klinger, K.; Miller, G. [Intergrated Genetics, Framingham, MA (United States)

1994-09-01

The hallmark of Huntington`s disease (HD) is the expansion of a polymorphic (CAG)n repeat. Several methods have been published describing PCR amplification of this region. Most of these assays require a complex PCR reaction mixture to amplify this GC-rich region. A consistent problem with trinucleotide repeat PCR amplification is the presence of a number of {open_quotes}stutter bands{close_quotes} which may be caused by primer or amplicon slippage during amplification or insufficient polymerase processivity. Most assays for HD arbitrarily select a particular band for diagnostic purposes. Without a clear choice for band selection such an arbitrary selection may result in inconsistent intra- or inter-laboratory findings. We present an improved protocol for the amplification of the HD trinucleotide repeat region. This method simplifies the PCR reaction buffer and results in a set of easily identifiable bands from which to determine allele size. HD alleles were identified by selecting bands of clearly greater signal intensity. Stutter banding was much reduced thus permitting easy identification of the most relevant PCR product. A second set of primers internal to the CCG polymorphism was used in selected samples to confirm allele size. The mechanism of action of N,N,N trimethylglycine in the PCR reaction is not clear. It may be possible that the minimal isostabilizing effect of N,N,N trimethylglycine at 2.5 M is significant enough to affect primer specificity. The use of N,N,N trimethylglycine in the PCR reaction facilitated identification of HD alleles and may be appropriate for use in other assays of this type.

Music therapy in Huntington's disease: a protocol for a multi-center randomized controlled trial.

Science.gov (United States)

van Bruggen-Rufi, Monique; Vink, Annemieke; Achterberg, Wilco; Roos, Raymund

2016-07-26

Huntington's disease is a progressive, neurodegenerative disease with autosomal dominant inheritance, characterized by motor disturbances, cognitive decline and behavioral and psychological symptoms. Since there is no cure, all treatment is aimed at improving quality of life. Music therapy is a non-pharmacological intervention, aiming to improve the quality of life, but its use and efficacy in patients with Huntington's disease has hardly been studied. In this article, a protocol is described to study the effects of music therapy in comparison with a control intervention to improve quality of life through stimulating expressive and communicative skills. By targeting these skills we assume that the social-cognitive functioning will improve, leading to a reduction in behavioral problems, resulting in an overall improvement of the quality of life in patients with Huntington's disease. The study is designed as a multi-center single-blind randomised controlled intervention trial. Sixty patients will be randomised using centre-stratified block-permuted randomisation. Patients will be recruited from four long-term care facilities specialized in Huntington's disease-care in The Netherlands. The outcome measure to assess changes in expressive and communication skills is the Behaviour Observation Scale Huntington and changes in behavior will be assessed by the Problem Behaviour Assesment-short version and by the BOSH. Measurements take place at baseline, then 8, 16 (end of intervention) and 12 weeks after the last intervention (follow-up). This randomized controlled study will provide greater insight into the effectiveness of music therapy on activities of daily living, social-cognitive functioning and behavior problems by improving expressive and communication skills, thus leading to a better quality of life for patients with Huntington's disease. Netherlands Trial Register: NTR4904 , registration date Nov. 15, 2014.

Caregiver roles in families affected by Huntington's disease

DEFF Research Database (Denmark)

Røthing, Merete; Malterud, Kirsti; Frich, Jan C

2013-01-01

AIM: The objective of this study was to explore family caregivers' experiences with the impact of Huntington's disease (HD) on the family structure and roles in the family. METHODOLOGY: We interviewed 15 family caregivers in families affected by HD, based on a semi-structured interview guide...... for impairments by taking on adult responsibilities, and in some families, a child had the role as main caregiver. The increasing need for care could cause conflicts between the role as family member and family caregiver. The burden of care within the family could fragment and isolate the family. CONCLUSIONS......: Huntington's disease has a major impact on family systems. Caregiver roles are shaped by impairments in the affected family member and corresponding dynamic adoption and change in roles within the family. Making assessments of the family structure and roles, professionals may understand more about how...

77 FR 71636 - Huntington Foam LLC, Fort Smith, AR; Notice of Revised Determination on Reconsideration

Science.gov (United States)

2012-12-03

... Smith, AR; Notice of Revised Determination on Reconsideration On August 8, 2012, the Department of Labor... workers and former workers of Huntington Foam LLC, Fort Smith, Arkansas (subject firm). The workers are... reconsideration investigation, I determine that workers of Huntington Foam LLC, Fort Smith, Arkansas, who were...

Unravelling and Exploiting Astrocyte Dysfunction in Huntington's Disease

DEFF Research Database (Denmark)

Khakh, Baljit S.; Beaumont, Vahri; Cachope, Roger

2017-01-01

Astrocytes are abundant within mature neural circuits and are involved in brain disorders. Here, we summarize our current understanding of astrocytes and Huntington's disease (HD), with a focus on correlative and causative dysfunctions of ion homeostasis, calcium signaling, and neurotransmitter...

[Sporadic juvenile forms of Huntington's chorea].

Science.gov (United States)

Zinchenko, A P; Goncharov, V D; Burtianskii, D L; Zakhar'ev, Iu M

1980-01-01

Six patients with Huntington's chorea in the age of 15-24 years old, suffered from diffusive choreic hyperkynesis with slowly progressive dementia. The development of this disease in childhood and adolescence was atypical, as nobody in the family and in kin sufferred from it and it was difficult to diagnose the disease. Recognition of the disease was promoted by pneumoencephalography, electromyography and memory investigation.

Did the "Woman in the Attic" in Jane Eyre Have Huntington Disease?

Directory of Open Access Journals (Sweden)

Elizabeth A. Coon

2015-07-01

Full Text Available Background: References to neurologic disorders are frequently found in fictional literature and may precede description in the medical literature. Aim: Our aim was to compare Charlotte Brontë’s depiction of Bertha Mason in Jane Eyre to the tenets set forth in George Huntington’s original essay “On chorea” with the hypothesis that Mason was displaying features of Huntington disease. Results: Charlotte Brontë’s 1847 Victorian novel Jane Eyre features the character Bertha Mason, who is portrayed with a progressive psychiatric illness, violent movements, and possible cognitive decline. Similar to Huntington’s tenets, Mason has a disorder with a strong family history suggestive of autosomal dominant inheritance with onset in adulthood, and culminating in suicide. Conclusion: Brontë’s character had features of Huntington disease as originally described by Huntington. Brontë’s keen characterization may have increased awareness of treatment of neuropsychiatric patients in the Victorian era.

Motor cortex synchronization influences the rhythm of motor performance in premanifest huntington's disease.

Science.gov (United States)

Casula, Elias P; Mayer, Isabella M S; Desikan, Mahalekshmi; Tabrizi, Sarah J; Rothwell, John C; Orth, Michael

2018-03-01

In Huntington's disease there is evidence of structural damage in the motor system, but it is still unclear how to link this to the behavioral disorder of movement. One feature of choreic movement is variable timing and coordination between sequences of actions. We postulate this results from desynchronization of neural activity in cortical motor areas. The objective of this study was to explore the ability to synchronize activity in a motor network using transcranial magnetic stimulation and to relate this to timing of motor performance. We examined synchronization in oscillatory activity of cortical motor areas in response to an external input produced by a pulse of transcranial magnetic stimulation. We combined this with EEG to compare the response of 16 presymptomatic Huntington's disease participants with 16 age-matched healthy volunteers to test whether the strength of synchronization relates to the variability of motor performance at the following 2 tasks: a grip force task and a speeded-tapping task. Phase synchronization in response to M1 stimulation was lower in Huntington's disease than healthy volunteers (P synchronization (r = -0.356; P synchronization and desynchronization could be a physiological basis for some key clinical features of Huntington's disease. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Network topology and functional connectivity disturbances precede the onset of Huntington's disease.

Science.gov (United States)

Harrington, Deborah L; Rubinov, Mikail; Durgerian, Sally; Mourany, Lyla; Reece, Christine; Koenig, Katherine; Bullmore, Ed; Long, Jeffrey D; Paulsen, Jane S; Rao, Stephen M

2015-08-01

Cognitive, motor and psychiatric changes in prodromal Huntington's disease have nurtured the emergent need for early interventions. Preventive clinical trials for Huntington's disease, however, are limited by a shortage of suitable measures that could serve as surrogate outcomes. Measures of intrinsic functional connectivity from resting-state functional magnetic resonance imaging are of keen interest. Yet recent studies suggest circumscribed abnormalities in resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease, despite the spectrum of behavioural changes preceding a manifest diagnosis. The present study used two complementary analytical approaches to examine whole-brain resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease. Network topology was studied using graph theory and simple functional connectivity amongst brain regions was explored using the network-based statistic. Participants consisted of gene-negative controls (n = 16) and prodromal Huntington's disease individuals (n = 48) with various stages of disease progression to examine the influence of disease burden on intrinsic connectivity. Graph theory analyses showed that global network interconnectivity approximated a random network topology as proximity to diagnosis neared and this was associated with decreased connectivity amongst highly-connected rich-club network hubs, which integrate processing from diverse brain regions. However, functional segregation within the global network (average clustering) was preserved. Functional segregation was also largely maintained at the local level, except for the notable decrease in the diversity of anterior insula intermodular-interconnections (participation coefficient), irrespective of disease burden. In contrast, network-based statistic analyses revealed patterns of weakened frontostriatal connections and strengthened frontal-posterior connections that evolved as disease

Mental Symptoms in Huntington's Disease and a Possible Primary Aminergic Neuron Lesion

Science.gov (United States)

Mann, J. John; Stanley, Michael; Gershon, Samuel; Rossor, M.

1980-12-01

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.

Beautiful Science: The Public and Private History of Astronomy at the Huntington Library

Science.gov (United States)

Lewis, Daniel

2009-05-01

The history of astronomy has a long tradition within research libraries. The rare collections at the Huntington Library (encompassing American and British history from around 1000 CE to the present, in many different subject areas) are among the most heavily-used in the United States, The history of astronomy holdings are a cornerstone within the library's history of science holdings. This talk will present the two faces of the history of astronomy holdings at the Huntington Library. The first of these is the research end of operations: what the collections consist of, how the scholarly public uses the collections, and what the implications are for modern astronomical practice. The second element concerns the public exhibit face of the history of astronomy holdings at The Huntington. Of the 600,000 people who visit the Huntington each year, the majority visit public displays and rare book and manuscript exhibits. "Beautiful Science: Ideas That Changed the World” is a new permanent history of science exhibit. One quarter of the exhibit relates to the history of astronomy. Public exhibits require a particular kind of planning and bring a specific set of values to the history of astronomy. Public exhibits also have their own concerns, and this talk will cover a number of those issues as well as the research issues.

JUNCTOPHILIN 3 (JPH3) EXPANSION MUTATIONS CAUSING HUNTINGTON DISEASE LIKE 2 (HDL2) ARE COMMON IN SOUTH AFRICAN PATIENTS WITH AFRICAN ANCESTRY AND A HUNTINGTON DISEASE PHENOTYPE

Science.gov (United States)

Krause, A; Mitchell, CL; Essop, F; Tager, S; Temlett, J; Stevanin, G; Ross, CA; Rudnicki, DD; Margolis, RL

2015-01-01

Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. PMID:26079385

Clinical neurogenetics: huntington disease.

Science.gov (United States)

Bordelon, Yvette M

2013-11-01

Huntington disease (HD) is an autosomal dominant, adult-onset, progressive neurodegenerative disease characterized by the triad of abnormal movements (typically chorea), cognitive impairment, and psychiatric problems. It is caused by an expanded CAG repeat in the gene encoding the protein huntingtin on chromosome 4 and causes progressive atrophy of the striatum as well as cortical and other extrastriatal structures. Genetic testing has been available since 1993 to confirm diagnosis in affected adults and for presymptomatic testing in at-risk individuals. This review covers HD signs, symptoms, and pathophysiology; current genetic testing issues; and current and future treatment strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

Reduction in mitochondrial DNA copy number in peripheral leukocytes after onset of Huntington's disease

DEFF Research Database (Denmark)

Petersen, Maria Hvidberg; Budtz-Jørgensen, Esben; Sørensen, Sven Asger

2014-01-01

Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by movement disorder, cognitive symptoms and psychiatric symptoms with predominantly adult-onset. The mutant huntingtin protein leads to mitochondrial dysfunction in blood leukocytes. This discovery led to the inve......Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by movement disorder, cognitive symptoms and psychiatric symptoms with predominantly adult-onset. The mutant huntingtin protein leads to mitochondrial dysfunction in blood leukocytes. This discovery led...

Ethical issues and Huntington's disease | Kromberg | South African ...

African Journals Online (AJOL)

The practice of genetic counselling gives rise to many ethical dilemmas, and counsellors need to be familiar with the principles of biomedical ethics. The primary principles include respect for autonomy, beneficence, non-maleficence and justice. A case of identical twins at 50% risk for Huntington's disease, in which only one ...

Characterisation of aggression in Huntington's disease: rates, types and antecedents in an inpatient rehabilitation setting.

Science.gov (United States)

Brown, Anahita; Sewell, Katherine; Fisher, Caroline A

2017-10-01

To systematically review aggression in an inpatient Huntington's cohort examining rates, types and antecedents. Although the prevalence of aggression in Huntington's disease is high, research into this problematic behaviour has been limited. Few studies have investigated the nature of aggressive behaviour in Huntington's disease or antecedents that contribute to its occurrence. A systematic, double-coded, electronic medical file audit. The electronic hospital medical records of 10 people with Huntington's disease admitted to a brain disorders unit were audited for a 90-day period using the Overt Aggression Scale-Modified for Neurorehabilitation framework, yielding 900 days of clinical data. Nine of 10 clients exhibited aggression during the audit period. Both verbal (37·1%) aggression and physical aggression were common (33·8%), along with episodes of mixed verbal and physical aggression (15·2%), while aggression to objects/furniture was less prevalent (5·5%). The most common antecedent was physical guidance with personal care, far exceeding any other documented antecedents, and acting as the most common trigger for four of the nine clients who exhibited aggression. For the remaining five clients, there was intraindividual heterogeneity in susceptibility to specific antecedents. In Huntington's sufferers at mid- to late stages following disease onset, particular care should be made with personal care assistance due to the propensity for these procedures to elicit an episode of aggression. However, given the degree of intraindividual heterogeneity in susceptibility to specific antecedents observed in the present study, individualised behaviour support plans and sensory modulation interventions may be the most useful in identifying triggers and managing aggressive episodes. Rates of aggression in Huntington's disease inpatients can be high. Knowledge of potential triggers, such as personal care, is important for nursing and care staff, so that attempts can be

Family caregivers' views on coordination of care in Huntington's disease

DEFF Research Database (Denmark)

Røthing, Merete; Malterud, Kirsti; Frich, Jan C

2015-01-01

BACKGROUND: Collaboration between family caregivers and health professionals in specialised hospitals or community-based primary healthcare systems can be challenging. During the course of severe chronic disease, several health professionals might be involved at a given time, and the patient......'s illness may be unpredictable or not well understood by some of those involved in the treatment and care. AIM: The aim of this study was to explore the experiences and expectations of family caregivers for persons with Huntington's disease concerning collaboration with healthcare professionals. METHODS......: To shed light on collaboration from the perspectives of family caregivers, we conducted an explorative, qualitative interview study with 15 adult participants experienced from caring for family members in all stages of Huntington's disease. Data were analysed with systematic text condensation, a cross...

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

OpenAIRE

Hensman Moss, Davina J; Pardinas, Antonio; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J; Coleman, A; Santos, R Dar; Decolongon, J; Sturrock, A

2017-01-01

Background\\ud \\ud Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure.\\ud \\ud Methods\\ud \\ud We generated a progression score on the basis of principal ...

Palliative Care in Huntington Disease: Personal Reflections and a Review of the Literature

Directory of Open Access Journals (Sweden)

Christopher G. Tarolli

2017-04-01

Full Text Available Background Huntington disease is a fatal, autosomal dominant, neurodegenerative disorder manifest by the triad of a movement disorder, behavioral disturbances, and dementia. At present, no curative or disease modifying therapies exist for the condition and current treatments are symptomatic. Palliative care is an approach to care that focuses on symptom relief, patient and caregiver support, and end of life care. There is increasing evidence of the benefit of palliative care throughout the course of neurodegenerative conditions including Parkinson disease and amyotrophic lateral sclerosis. However, beyond its application at the end of life, little is known about the role of palliative care in Huntington disease.Methods In this article, we discuss what is known about palliative care in Huntington disease, specifically related to early disease burden, caregiver burnout, advance care planning, and end of life care.Results We provide a review of the current literature and discuss our own care practices.Discussion We conclude by discussing questions that remain unanswered and positing ideas for future work in the field.

Huntington Revisited: Is Conservative Realism Still Essential for the Military Ethic

National Research Council Canada - National Science Library

Mahoney-Norris, Kathleen A

2001-01-01

...). Furthermore, Huntington has developed what appears to be a powerful argument as to why conservative realism should be considered a fundamental component of the professional ethic of the military officer...

The use of stem cells in regenerative medicine for Parkinson's and Huntington's Diseases.

Science.gov (United States)

Lescaudron, L; Naveilhan, P; Neveu, I

2012-01-01

Cell transplantation has been proposed as a means of replacing specific cell populations lost through neurodegenerative processes such as that seen in Parkinson's or Huntington's diseases. Improvement of the clinical symptoms has been observed in a number of Parkinson and Huntington's patients transplanted with freshly isolated fetal brain tissue but such restorative approach is greatly hampered by logistic and ethical concerns relative to the use of fetal tissue, in addition to potential side effects that remain to be controlled. In this context, stem cells that are capable of self-renewal and can differentiate into neurons, have received a great deal of interest, as demonstrated by the numerous studies based on the transplantation of neural stem/progenitor cells, embryonic stem cells or mesenchymal stem cells into animal models of Parkinson's or Huntington's diseases. More recently, the induction of pluripotent stem cells from somatic adult cells has raised a new hope for the treatment of neurodegenerative diseases. In the present article, we review the main experimental approaches to assess the efficiency of cell-based therapy for Parkinson's or Huntington's diseases, and discuss the recent advances in using stem cells to replace lost dopaminergic mesencephalic or striatal neurons. Characteristics of the different stem cells are extensively examined with a special attention to their ability of producing neurotrophic or immunosuppressive factors, as these may provide a favourable environment for brain tissue repair and long-term survival of transplanted cells in the central nervous system. Thus, stem cell therapy can be a valuable tool in regenerative medicine.

Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease

DEFF Research Database (Denmark)

Aziz, N A; Jurgens, C K; Landwehrmeyer, G B

2009-01-01

OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). We aimed to assess whether interaction between CAG repeat sizes in the mutant and normal allele could affect disease severity and progression. METHODS: Using...... with less severe symptoms and pathology. CONCLUSIONS: Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease. The underlying mechanism may involve interaction of the polyglutamine domains of normal...

Hypocretin and melanin-concentrating hormone in patients with Huntington disease.

NARCIS (Netherlands)

Aziz, A.; Fronczek, R.; Maat-Schieman, M.L.; Unmehopa, U.A.; Roelandse, F.W.; Overeem, S.; Duinen, S.G. van; Lammers, G.J.; Swaab, D.F.; Roos, R.A.C.

2008-01-01

To evaluate whether hypocretin-1 (orexin-A) and melanin-concentrating hormone (MCH) neurotransmission are affected in patients with Huntington disease (HD), we immunohistochemically stained hypocretin and MCH neurons and estimated their total numbers in the lateral hypothalamus of both HD patients

Presence of tau pathology within foetal neural allografts in patients with Huntington's and Parkinson's disease.

Science.gov (United States)

Cisbani, Giulia; Maxan, Alexander; Kordower, Jeffrey H; Planel, Emmanuel; Freeman, Thomas B; Cicchetti, Francesca

2017-11-01

Cell replacement has been explored as a therapeutic strategy to repair the brain in patients with Huntington's and Parkinson's disease. Post-mortem evaluations of healthy grafted tissue in such cases have revealed the development of Huntington- or Parkinson-like pathology including mutant huntingtin aggregates and Lewy bodies. An outstanding question remains if tau pathology can also be seen in patients with Huntington's and Parkinson's disease who had received foetal neural allografts. This was addressed by immunohistochemical/immunofluorescent stainings performed on grafted tissue of two Huntington's disease patients, who came to autopsy 9 and 12 years post-transplantation, and two patients with Parkinson's disease who came to autopsy 18 months and 16 years post-transplantation. We show that grafts also contain tau pathology in both types of transplanted patients. In two patients with Huntington's disease, the grafted tissue showed the presence of hyperphosphorylated tau [both AT8 (phospho-tau Ser202 and Thr205) and CP13 (pSer202) immunohistochemical stainings] pathological inclusions, neurofibrillary tangles and neuropil threads. In patients with Parkinson's disease, the grafted tissue was characterized by hyperphosphorylated tau (AT8; immunofluorescent staining) pathological inclusions, neurofibrillary tangles and neuropil threads but only in the patient who came to autopsy 16 years post-transplantation. Abundant tau-related pathology was observed in the cortex and striatum of all cases studied. While the striatum of the grafted Huntington's disease patient revealed an equal amount of 3-repeat and 4-repeat isoforms of tau, the grafted tissue showed elevated 4-repeat isoforms by western blot. This suggests that transplants may have acquired tau pathology from the host brain, although another possibility is that this was due to acceleration of ageing. This finding not only adds to the recent reports that tau pathology is a feature of these neurodegenerative

Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: the TREND-HD study.

Science.gov (United States)

2008-12-01

To determine whether ethyl-eicosapentaenoic acid (ethyl-EPA), an omega-3 fatty acid, improves the motor features of Huntington disease. Six-month multicenter, randomized, double-blind, placebo-controlled trial followed by a 6-month open-label phase without disclosing initial treatment assignments. Forty-one research sites in the United States and Canada. Three hundred sixteen adults with Huntington disease, enriched for a population with shorter trinucleotide (cytosine-adenine-guanine) repeat length expansions. Random assignment to placebo or ethyl-EPA, 1 g twice a day, followed by open-label treatment with ethyl-EPA. Six-month change in the Total Motor Score 4 component of the Unified Huntington's Disease Rating Scale analyzed for all research participants and those with shorter cytosine-adenine-guanine repeat length expansions (<45). At 6 months, the Total Motor Score 4 point change for patients receiving ethyl-EPA did not differ from that for those receiving placebo. No differences were found in measures of function, cognition, or global impression. Before public disclosure of the 6-month placebo-controlled results, 192 individuals completed the open-label phase. The Total Motor Score 4 change did not worsen for those who received active treatment for 12 continuous months compared with those who received active treatment for only 6 months (2.0-point worsening; P=.02). Ethyl-EPA was not beneficial in patients with Huntington disease during 6 months of placebo-controlled evaluation. Clinical Trial Registry clinicaltrials.gov Identifier: NCT00146211.

Remifentanil in a patient with Huntington's chorea - case report ...

African Journals Online (AJOL)

Relatively few published case reports related to the anaesthetic management of Huntington's chorea (HC) exist. At the time of surgery no publications were found related to remifentanil's use in patients with HC. This case report describes the management of a confirmed HC patient requiring urgent decompression of a spinal ...

High Protein Diet and Huntington's Disease.

Directory of Open Access Journals (Sweden)

Chiung-Mei Chen

Full Text Available Huntington's disease (HD is a neurodegenerative disorder caused by the huntingtin (HTT gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT exists in the liver and causes urea cycle deficiency. A low protein diet (17% restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories than in mice (~22%. We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein for 5 days, followed by a high protein diet (HPD, 26.3% protein for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington's Disease Rating Scale (UHDRS. The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378 in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression.

Psychodynamic theory and counseling in predictive testing for Huntington's disease.

Science.gov (United States)

Tassicker, Roslyn J

2005-04-01

This paper revisits psychodynamic theory, which can be applied in predictive testing counseling for Huntington's Disease (HD). Psychodynamic theory has developed from the work of Freud and places importance on early parent-child experiences. The nature of these relationships, or attachments are reflected in adult expectations and relationships. Two significant concepts, identification and fear of abandonment, have been developed and expounded by the psychodynamic theorist, Melanie Klein. The processes of identification and fear of abandonment can become evident in predictive testing counseling and are colored by the client's experience of growing up with a parent affected by Huntington's Disease. In reflecting on family-of-origin experiences, clients can also express implied expectations of the future, and future relationships. Case examples are given to illustrate the dynamic processes of identification and fear of abandonment which may present in the clinical setting. Counselor recognition of these processes can illuminate and inform counseling practice.

A genome-scale RNA-interference screen identifies RRAS signaling as a pathologic feature of Huntington's disease.

Directory of Open Access Journals (Sweden)

John P Miller

Full Text Available A genome-scale RNAi screen was performed in a mammalian cell-based assay to identify modifiers of mutant huntingtin toxicity. Ontology analysis of suppressor data identified processes previously implicated in Huntington's disease, including proteolysis, glutamate excitotoxicity, and mitochondrial dysfunction. In addition to established mechanisms, the screen identified multiple components of the RRAS signaling pathway as loss-of-function suppressors of mutant huntingtin toxicity in human and mouse cell models. Loss-of-function in orthologous RRAS pathway members also suppressed motor dysfunction in a Drosophila model of Huntington's disease. Abnormal activation of RRAS and a down-stream effector, RAF1, was observed in cellular models and a mouse model of Huntington's disease. We also observe co-localization of RRAS and mutant huntingtin in cells and in mouse striatum, suggesting that activation of R-Ras may occur through protein interaction. These data indicate that mutant huntingtin exerts a pathogenic effect on this pathway that can be corrected at multiple intervention points including RRAS, FNTA/B, PIN1, and PLK1. Consistent with these results, chemical inhibition of farnesyltransferase can also suppress mutant huntingtin toxicity. These data suggest that pharmacological inhibition of RRAS signaling may confer therapeutic benefit in Huntington's disease.

Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder.

Science.gov (United States)

Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S; Lee, Jong-Min; Alonso, Isabel; Gusella, James F; Smoller, Jordan W; Sklar, Pamela; MacDonald, Marcy E; Perlis, Roy H

2015-06-01

Huntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTT CAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease. We assessed the distribution of HTT CAG repeat alleles in a cohort of individuals with bipolar disorder. HTT CAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts. We found that HTT CAG repeat alleles > 35 units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects. These findings do not support an association between bipolar disorder and Huntington's disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Effect of Music Therapy in Patients with Huntington's Disease: A Randomized Controlled Trial.

Science.gov (United States)

van Bruggen-Rufi, Monique C H; Vink, Annemieke C; Wolterbeek, Ron; Achterberg, Wilco P; Roos, Raymund A C

2017-01-01

Music therapy may have beneficial effects on improving communication and expressive skills in patients with Huntington's disease (HD). Most studies are, however, small observational studies and methodologically limited. Therefore we conducted a multi-center randomized controlled trial. To determine the efficacy of music therapy in comparison with recreational therapy in improving quality of life of patients with advanced Huntington's disease by means of improving communication. Sixty-three HD-patients with a Total Functional Capacity (TFC) score of ≤7, admitted to four long-term care facilities in The Netherlands, were randomized to receive either group music therapy or group recreational therapy in 16 weekly sessions. They were assessed at baseline, after 8, 16 and 28 weeks using the Behaviour Observation Scale for Huntington (BOSH) and the Problem Behaviour Assessment-short version (PBA-s). A linear mixed model with repeated measures was used to compare the scores between the two groups. Group music therapy offered once weekly for 16 weeks to patients with Huntington's disease had no additional beneficial effect on communication or behavior compared to group recreational therapy. This was the first study to assess the effect of group music therapy on HD patients in the advanced stages of the disease. The beneficial effects of music therapy, recorded in many, mainly qualitative case reports and studies, could not be confirmed with the design (i.e. group therapy vs individual therapy) and outcome measures that have been used in the present study. A comprehensive process-evaluation alongside the present effect evaluation is therefore performed.

Functional Compensation of Motor Function in Pre-Symptomatic Huntington's Disease

Science.gov (United States)

Kloppel, Stefan; Draganski, Bogdan; Siebner, Hartwig R.; Tabrizi, Sarah J.; Weiller, Cornelius; Frackowiak, Richard S. J.

2009-01-01

Involuntary choreiform movements are a clinical hallmark of Huntington's disease. Studies in clinically affected patients suggest a shift of motor activations to parietal cortices in response to progressive neurodegeneration. Here, we studied pre-symptomatic gene carriers to examine the compensatory mechanisms that underlie the phenomenon of…

Challenges of Huntington's disease and quest for therapeutic biomarkers

Czech Academy of Sciences Publication Activity Database

Kotrčová, Eva; Jarkovská, Karla; Valeková, Ivona; Žižková, Martina; Motlík, Jan; Gadher, S. J.; Kovářová, Hana

2015-01-01

Roč. 9, 1-2 (2015), s. 147-158 ISSN 1862-8346 R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR(CZ) TA01011466 Institutional support: RVO:67985904 Keywords : HD biomarkers * Huntington´s disease * Huntingtin neurotoxicity * Huntingtin pathogenesis Subject RIV: FH - Neurology Impact factor: 2.959, year: 2015

Vertraagde diagnose van de ziekte van Huntington in een psychiatrische setting

NARCIS (Netherlands)

Tak, L M; Sizoo, B; de Stegge, B M Aan; Adema, S; van Duijn, E; Kremer, B

2017-01-01

Huntington's disease (hd) is characterised by a triad of neuropsychiatric symptoms, motor disturbances and cognitive decline. If initial symptoms are of neuropsychiatric nature they maybe misinterpreted, which can lead to delayed diagnosis. Three examples of delayed hd diagnosis in a psychiatric

Survival End Points for Huntington Disease Trials Prior to a Motor Diagnosis.

Science.gov (United States)

Long, Jeffrey D; Mills, James A; Leavitt, Blair R; Durr, Alexandra; Roos, Raymund A; Stout, Julie C; Reilmann, Ralf; Landwehrmeyer, Bernhard; Gregory, Sarah; Scahill, Rachael I; Langbehn, Douglas R; Tabrizi, Sarah J

2017-11-01

Predictive genetic testing in Huntington disease (HD) enables therapeutic trials in HTT gene expansion mutation carriers prior to a motor diagnosis. Progression-free survival (PFS) is the composite of a motor diagnosis or a progression event, whichever comes first. To determine if PFS provides feasible sample sizes for trials with mutation carriers who have not yet received a motor diagnosis. This study uses data from the 2-phase, longitudinal cohort studies called Track and from a longitudinal cohort study called the Cooperative Huntington Observational Research Trial (COHORT). Track had 167 prediagnosis mutation carriers and 156 noncarriers, whereas COHORT had 366 prediagnosis mutation carriers and noncarriers. Track studies were conducted at 4 sites in 4 countries (Canada, France, England, and the Netherlands) from which data were collected from January 17, 2008, through November 17, 2014. The COHORT was conducted at 38 sites in 3 countries (Australia, Canada, and the United States) from which data were collected from February 14, 2006, through December 31, 2009. Results from the Track data were externally validated with data from the COHORT. The required sample size was estimated for a 2-arm prediagnosis clinical trial. Data analysis took place from May 1, 2016, to June 10, 2017. The primary end point is PFS. Huntington disease progression events are defined for the Unified Huntington's Disease Rating Scale total motor score, total functional capacity, symbol digit modalities test, and Stroop word test. Of Track's 167 prediagnosis mutation carriers, 93 (55.6%) were women, and the mean (SD) age was 40.06 (8.92) years; of the 156 noncarriers, 87 (55.7%) were women, and the mean (SD) age was 45.58 (10.30) years. Of the 366 COHORT participants, 229 (62.5%) were women and the mean (SD) age was 42.21 (12.48) years. The PFS curves of the Track mutation carriers showed good external validity with the COHORT mutation carriers after adjusting for initial progression. For

First molecular modeling report on novel arylpyrimidine kynurenine monooxygenase inhibitors through multi-QSAR analysis against Huntington's disease: A proposal to chemists!

Science.gov (United States)

Amin, Sk Abdul; Adhikari, Nilanjan; Jha, Tarun; Gayen, Shovanlal

2016-12-01

Huntington's disease (HD) is caused by mutation of huntingtin protein (mHtt) leading to neuronal cell death. The mHtt induced toxicity can be rescued by inhibiting the kynurenine monooxygenase (KMO) enzyme. Therefore, KMO is a promising drug target to address the neurodegenerative disorders such as Huntington's diseases. Fiftysix arylpyrimidine KMO inhibitors are structurally explored through regression and classification based multi-QSAR modeling, pharmacophore mapping and molecular docking approaches. Moreover, ten new compounds are proposed and validated through the modeling that may be effective in accelerating Huntington's disease drug discovery efforts. Copyright © 2016 Elsevier Ltd. All rights reserved.

District health information system assessment: a case study in iran.

Science.gov (United States)

Raeisi, Ahmad Reza; Saghaeiannejad, Sakineh; Karimi, Saeed; Ehteshami, Asghar; Kasaei, Mahtab

2013-03-01

Health care managers and personnel should be aware and literate of health information system in order to increase the efficiency and effectiveness in their organization. Since accurate, appropriate, precise, timely, valid information and interpretation of information is required and is the basis for policy planning and decision making in various levels of the organization. This study was conducted to assess the district health information system evolution in Iran according to WHO framework. This research is an applied, descriptive cross sectional study, in which a total of twelve urban and eight rural facilities, and the district health center at Falavarjan region were surveyed by using a questionnaire with 334 items. Content and constructive validity and reliability of the questionnaire were confirmed with correlation coefficient of 0.99. Obtained data were analyzed with SPSS 16 software and descriptive statistics were used to examine measures of WHO compliance. The analysis of data revealed that the mean score of compliance of district health information system framework was 35.75 percent. The maximum score of compliance with district health information system belonged to the data collection process (70 percent). The minimum score of compliance with district health information system belonged to information based decision making process with a score of 10 percent. District Health Information System Criteria in Isfahan province do not completely comply with WHO framework. Consequently, it seems that health system managers engaged with underlying policy and decision making processes at district health level should try to restructure and decentralize district health information system and develop training management programs for their managers.

Huntington's Disease in a Patient Misdiagnosed as Conversion Disorder.

Science.gov (United States)

Nogueira, João Machado; Franco, Ana Margarida; Mendes, Susana; Valadas, Anabela; Semedo, Cristina; Jesus, Gustavo

2018-01-01

Huntington's disease (HD) is an inherited, progressive, and neurodegenerative neuropsychiatric disorder caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide in Interested Transcript (IT) 15 gene on chromosome 4. This pathology typically presents in individuals aged between 30 and 50 years and the age of onset is inversely correlated with the length of the CAG repeat expansion. It is characterized by chorea, cognitive deficits, and psychiatric symptoms. Usually the psychiatric disorders precede motor and cognitive impairment, Major Depressive Disorder and anxiety disorders being the most common presentations. We present a clinical case of a 65-year-old woman admitted to our Psychiatric Acute Unit. During the 6 years preceding the admission, the patient had clinical assessments made several times by different specialties that focused only on isolated symptoms, disregarding the syndrome as a whole. In the course of her last admission, the patient was referred to our Neuropsychiatric Team, which made the provisional diagnosis of late-onset Huntington's disease, later confirmed by genetic testing. This clinical vignette highlights the importance of a multidisciplinary approach to atypical clinical presentations and raises awareness for the relevance of investigating carefully motor symptoms in psychiatric patients.

Personality Traits in Huntington's Disease

DEFF Research Database (Denmark)

Larsen, Ida Unmack; Mortensen, Erik Lykke; Vinther-Jensen, Tua

2016-01-01

Huntington's disease (HD) is associated with risk for developing psychiatric symptoms. Vulnerability or resilience to psychiatric symptoms may be associated with personality traits. This exploratory study, aimed to investigate personality traits in a large cohort of HD carriers and at risk gene......-expansion negative individuals (HD non-carriers), exploring whether carrying the HD gene or growing up in an HD family influences personality traits. Forty-seven HD carriers, Thirty-nine HD non-carriers, and 121 healthy controls answered the Danish version of the revised NEO personality inventory. Comparisons...... symptoms. Our findings suggest that, there is no direct effect of the HD gene on personality traits, but that personality assessment may be relevant to use when identifying individuals from HD families who are vulnerable to develop psychiatric symptoms....

Why comply with a code of ethics?

Science.gov (United States)

Spielthenner, Georg

2015-05-01

A growing number of professional associations and occupational groups are creating codes of ethics with the goal of guiding their members, protecting service users, and safeguarding the reputation of the profession. There is a great deal of literature dealing with the question to what extent ethical codes can achieve their desired objectives. The present paper does not contribute to this debate. Its aim is rather to investigate how rational it is to comply with codes of conduct. It is natural and virtually inevitable for a reflective person to ask why one should pay any attention to ethical codes, in particular if following a code is not in one's own interest. In order to achieve the aim of this paper, I shall (in "Quasi-reasons for complying with an ethical code" section) discuss reasons that only appear to be reasons for complying with a code. In "Code-independent reasons" section, I shall present genuine practical reasons that, however, turn out to be reasons of the wrong kind. In "Code-dependent reasons" section finally presents the most important reasons for complying with ethical codes. The paper argues that while ethical codes do not necessarily yield reasons for action, professionals can have genuine reasons for complying with a code, which may, however, be rather weak and easily overridden by reasons for deviating from the code.

Current status of PET imaging in Huntington's disease

International Nuclear Information System (INIS)

Pagano, Gennaro; Niccolini, Flavia; Politis, Marios

2016-01-01

To review the developments of recent decades and the current status of PET molecular imaging in Huntington's disease (HD). A systematic review of PET studies in HD was performed. The MEDLINE, Web of Science, Cochrane and Scopus databases were searched for articles in all languages published up to 19 August 2015 using the major medical subject heading ''Huntington Disease'' combined with text and key words ''Huntington Disease'', ''Neuroimaging'' and ''PET''. Only peer-reviewed, primary research studies in HD patients and premanifest HD carriers, and studies in which clinical features were described in association with PET neuroimaging results, were included in this review. Reviews, case reports and nonhuman studies were excluded. A total of 54 PET studies were identified and analysed in this review. Brain metabolism ([ 18 F]FDG and [ 15 O]H 2 O), presynaptic ([ 18 F]fluorodopa, [ 11 C]β-CIT and [ 11 C]DTBZ) and postsynaptic ([ 11 C]SCH22390, [ 11 C]FLB457 and [ 11 C]raclopride) dopaminergic function, phosphodiesterases ([ 18 F]JNJ42259152, [ 18 F]MNI-659 and [ 11 C]IMA107), and adenosine ([ 18 F]CPFPX), cannabinoid ([ 18 F]MK-9470), opioid ([ 11 C]diprenorphine) and GABA ([ 11 C]flumazenil) receptors were evaluated as potential biomarkers for monitoring disease progression and for assessing the development and efficacy of novel disease-modifying drugs in premanifest HD carriers and HD patients. PET studies evaluating brain restoration and neuroprotection were also identified and described in detail. Brain metabolism, postsynaptic dopaminergic function and phosphodiesterase 10A levels were proven to be powerful in assessing disease progression. However, no single technique may be currently considered an optimal biomarker and an integrative multimodal imaging approach combining different techniques should be developed for monitoring potential neuroprotective and preventive treatment

3-NP-induced neurodegeneration studies in experimental models of Huntington's disease.

NARCIS (Netherlands)

Vis, J.C.

2005-01-01

This thesis investigates the possible role of apoptosis, or programmed cell death, in Huntington's disease (HD). HD is caused by an expanded CAG repeat in the N-terminal region of the huntingtin protein leading to specific neostriatal neurodegeneration. The sequence of events that leads to this

Electronic Transport in Single-Stranded DNA Molecule Related to Huntington's Disease

Science.gov (United States)

Sarmento, R. G.; Silva, R. N. O.; Madeira, M. P.; Frazão, N. F.; Sousa, J. O.; Macedo-Filho, A.

2018-04-01

We report a numerical analysis of the electronic transport in single chain DNA molecule consisting of 182 nucleotides. The DNA chains studied were extracted from a segment of the human chromosome 4p16.3, which were modified by expansion of CAG (cytosine-adenine-guanine) triplet repeats to mimics Huntington's disease. The mutated DNA chains were connected between two platinum electrodes to analyze the relationship between charge propagation in the molecule and Huntington's disease. The computations were performed within a tight-binding model, together with a transfer matrix technique, to investigate the current-voltage (I-V) of 23 types of DNA sequence and compare them with the distributions of the related CAG repeat numbers with the disease. All DNA sequences studied have a characteristic behavior of a semiconductor. In addition, the results showed a direct correlation between the current-voltage curves and the distributions of the CAG repeat numbers, suggesting possible applications in the development of DNA-based biosensors for molecular diagnostics.

Huntington's disease does not appear to increase the risk of diabetes mellitus

DEFF Research Database (Denmark)

Boesgaard, T W; Nielsen, Troels Tolstrup; Josefsen, Knud Elnegaard

2009-01-01

Huntington's disease (HD) is an autosomal, dominantly inherited, neurodegenerative disorder characterised by neurological, cognitive and psychiatric symptoms. HD has been associated with diabetes mellitus, which is, to some extent, supported by studies in transgenic HD mice. In transgenic mice...

77 FR 22616 - Huntington Asset Advisors, Inc., et al.; Notice of Application

Science.gov (United States)

2012-04-16

...''), Huntington Strategy Shares (``Trust''), and SEI Investments Distribution Co. Summary of Application.... \\14\\ If Shares are listed on The NASDAQ Stock Market LLC (``Nasdaq'') or a similar electronic Listing... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 30032; 812-13785...

Selected CSF biomarkers indicate no evidence of early neuroinflammation in Huntington disease

DEFF Research Database (Denmark)

Vinther-Jensen, Tua; Börnsen, Lars Svend; Budtz-Jorgensen, Esben

2016-01-01

Objective: To investigate CSF biomarkers of neuroinflammation and neurodegeneration in Huntington disease (HD) gene-expansion carriers compared to controls and to investigate these biomarkers in association with clinical HD rating scales and disease burden score. Methods: We collected CSF from 32...

7 CFR 718.304 - Failure to fully comply.

Science.gov (United States)

2010-01-01

... authorized in accordance with § 718.305 if the participant made a good faith effort to comply fully with the... FSA approval official to have made a good faith effort to comply fully with the terms and conditions...

Motor outcome measures in Huntington disease clinical trials.

Science.gov (United States)

Reilmann, Ralf; Schubert, Robin

2017-01-01

Deficits in motor function are a hallmark of Huntington disease (HD). The Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) is a categoric clinical rating scale assessing multiple domains of motor disability in HD. The UHDRS-TMS or subsets of its items have served as primary or secondary endpoints in numerous clinical trials. In spite of a well-established video-based annual online certification system, intra- and interrater variability, subjective error, and rater-induced placebo effects remain a concern. In addition, the UHDRS-TMS was designed to primarily assess motor symptoms in manifest HD. Recently, advancement of technology resulted in the introduction of the objective Q-Motor (i.e., Quantitative-Motor) assessments in biomarker studies and clinical trials in HD. Q-Motor measures detected motor signs in blinded cross-sectional and longitudinal analyses of manifest, prodromal, and premanifest HD cohorts up to two decades before clinical diagnosis. In a multicenter clinical trial in HD, Q-Motor measures were more sensitive than the UHDRS-TMS and exhibited no placebo effects. Thus, Q-Motor measures are currently explored in several multicenter trials targeting both symptomatic and disease-modifying mechanisms. They may supplement the UHDRS-TMS, increase the sensitivity and reliability in proof-of-concept studies, and open the door for phenotype assessments in clinical trials in prodromal and premanifest HD. Copyright © 2017 Elsevier B.V. All rights reserved.

Huntington's disease: a clinical review

Directory of Open Access Journals (Sweden)

Roos Raymund AC

2010-12-01

Full Text Available Abstract Huntington disease (HD is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD. The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which

Huntington disease: Experimental models and therapeutic perspectives

International Nuclear Information System (INIS)

Serrano Sanchez, Teresa; Blanco Lezcano, Lisette; Garcia Minet, Rocio; Alberti Amador, Esteban; Diaz Armesto, Ivan and others

2011-01-01

Huntington's disease (HD) is a degenerative dysfunction of hereditary origin. Up to date there is not, an effective treatment to the disease which having lapsed 15 or 20 years advances inexorably, in a slow form, toward the total inability or death. This paper reviews the clinical and morphological characteristics of Huntington's disease as well as the experimental models more commonly used to study this disease, having as source the articles indexed in Medline data base, published in the last 20 years. Advantages and disadvantages of all experimental models to reproduce the disease as well as the perspectives to therapeutic assay have been also considered. the consent of outline reported about the toxic models, those induced by neurotoxins such as quinolinic acid, appears to be the most appropriate to reproduce the neuropathologic characteristic of the disease, an genetic models contributing with more evidence to the knowledge of the disease etiology. Numerous treatments ameliorate clinical manifestations, but none of them has been able to stop or diminish the affectations derived from neuronal loss. At present time it is possible to reproduce, at least partially, the characteristics of the disease in experimentation animals that allow therapy evaluation in HD. from the treatment view point, the more promissory seems to be transplantation of no neuronal cells, taking into account ethical issues and factibility. On the other hand the new technology of interference RNA emerges as a potential therapeutic tool for treatment in HD, and to respond basic questions on the development of the disease.

Preliminary business plan: Plzen district heating system upgrade

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-06-01

The district heating system of the City of Plzen, Czech Republic, needs to have physical upgrades to replace aging equipment and to comply with upcoming environmental regulations. Also, its ownership and management are being changed as a result of privatization. As majority owner, the City has the primary goal of ensuring that the heating needs of its customers are met as reliably and cost-effectively as possible. This preliminary business plan is part of the detailed analysis (5 reports in all) done to assist the City in deciding the issues. Preparation included investigation of ownership, management, and technology alternatives; estimation of market value of assets and investment requirements; and forecasting of future cash flow. The district heating system consists of the Central Plzen cogeneration plant, two interconnected heating plants [one supplying both hot water and steam], three satellite heating plants, and cooperative agreements with three industrial facilities generating steam and hot water. Most of the plants are coal-fired, with some peaking units fired by fuel oil.

Apolipoprotein E and presenilin-1 genotypes in Huntington's disease.

Science.gov (United States)

Panas, M; Avramopoulos, D; Karadima, G; Petersen, M B; Vassilopoulos, D

1999-07-01

Huntington's disease (HD) is an autosomal dominant degenerative disease of the central nervous system manifested by involuntary movements (chorea), psychiatric manifestations, and cognitive impairment with a variable age at onset. This variability is mainly attributed to genetic factors. The so-called aging genes [e.g., those for apolipoprotein E (APOE) and presenilin-1 (PS-1) have been implicated in determining the age at onset of Alzheimer's disease, a disease sharing common clinical features with HD. In 60 unrelated patients suffering from HD (mean age at onset 40.1 years, range 20-65) we determined number of CAG repeats and the distribution of the APOE alleles (epsilon2, epsilon3, epsilon4) and PS-1 alleles. The results showed that: (a) The age at onset was higher in the group of patients with the epsilon4 allele (51.6 vs. 38.0 P<0.002), (b) The correlation between the age at onset and the number of CAG repeats was strong in patients with the epsilon3/epsilon3 genotype while it was not detected in patients with epsilon3/epsilon4 genotype. (c) No correlation was found between age at onset and PS-1 alleles. In conclusion, APOE seems to be a significant factor influencing the age at onset of Huntington's disease.

Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease

NARCIS (Netherlands)

van Oostrom, JCH; Maguire, RP; Verschuuren-Bemelmans, CC; van der Duin, LV; Pruim, J; Roos, RAC; Leenders, KL

2005-01-01

Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the

49 CFR 230.12 - Movement of non-complying steam locomotives.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Movement of non-complying steam locomotives. 230... General General Inspection Requirements § 230.12 Movement of non-complying steam locomotives. (a) General limitations on movement. A steam locomotive with one or more non-complying conditions may be moved only as a...

Short G-rich oligonucleotides as a potential therapeutic for Huntington's Disease

Directory of Open Access Journals (Sweden)

Parekh-Olmedo Hetal

2006-10-01

Full Text Available Abstract Background Huntington's Disease (HD is an inherited autosomal dominant genetic disorder in which neuronal tissue degenerates. The pathogenesis of the disease appears to center on the development of protein aggregates that arise initially from the misfolding of the mutant HD protein. Mutant huntingtin (Htt is produced by HD genes that contain an increased number of glutamine codons within the first exon and this expansion leads to the production of a protein that misfolds. Recent studies suggest that mutant Htt can nucleate protein aggregation and interfere with a multitude of normal cellular functions. Results As such, efforts to find a therapy for HD have focused on agents that disrupt or block the mutant Htt aggregation pathway. Here, we report that short guanosine monotonic oligonucleotides capable of adopting a G-quartet structure, are effective inhibitors of aggregation. By utilizing a biochemical/immunoblotting assay as an initial screen, we identified a 20-mer, all G-oligonucleotide (HDG as an active molecule. Subsequent testing in a cell-based assay revealed that HDG was an effective inhibitor of aggregation of a fusion protein, comprised of a mutant Htt fragment and green fluorescent protein (eGFP. Taken together, our results suggest that a monotonic G-oligonucleotide, capable of adopting a G-quartet conformation is an effective inhibitor of aggregation. This oligonucleotide can also enable cell survival in PC12 cells overexpressing a mutant Htt fragment fusion gene. Conclusion Single-stranded DNA oligonucleotides capable of forming stable G-quartets can inhibit aggregation of the mutant Htt fragment protein. This activity maybe an important part of the pathogenecity of Huntington's Disease. Our results reveal a new class of agents that could be developed as a therapeutic approach for Huntington's Disease.

Continuous deep sedation, physician-assisted suicide, and euthanasia in Huntington's disorder.

Science.gov (United States)

Lindblad, Anna; Juth, Niklas; Fürst, Carl Johan; Lynöe, Niels

2010-11-01

To investigate the attitudes among Swedish physicians and the general public towards continuous deep sedation (CDS) as an alternative treatment for a competent, not imminently dying patient with Huntington's disorder requesting physician-assisted suicide (PAS) and euthanasia. A questionnaire was distributed to 1200 physicians in Sweden and 1201 individuals in Stockholm. It consisted of three parts: 1) A vignette about a competent patient with Huntington's disease requesting PAS. When no longer competent, relatives request euthanasia on behalf of the patient. Responders were asked about their attitudes towards these requests and whether CDS would be an acceptable alternative. 2) General questions about PAS and euthanasia. 3) Background variables. The response rate was 56% (physicians) and 52% (general public). The majority of the general public and a fairly large proportion of physicians reported more liberal views on CDS than are expressed in current Swedish and international recommendations. In light of the results, we suggest that there is a need for a broader discussion about the recommendations for CDS, with a special focus on the needs of patients with progressive neurodegenerative disorders.

Adenyl cyclase activator forskolin protects against Huntington's disease-like neurodegenerative disorders

Directory of Open Access Journals (Sweden)

Sidharth Mehan

2017-01-01

Full Text Available Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington's disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a specific phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination (grip strength, beam crossing task, locomotor activity, resulted in learning and memory deficits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus. Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-dependently reversed these behavioral, biochemical and pathological changes caused by 3-nitropropionic acid. These results suggest that forskolin exhibits neuroprotective effects on 3-nitropropionic acid-induced Huntington's disease-like neurodegeneration.

LeBreton Flats district heating: Institutional issues

Energy Technology Data Exchange (ETDEWEB)

Gerow, L.B.; Bernstein, H.

1981-12-01

Despite the growing popularity in Europe of district heating as an alternative to conventional systems, a number of institutional barriers blocked the road to its successful implementation in Canada. These hurdles include questions of ownership, operation/administration, consumer accountability, financial arrangements, and general consumer acceptance of a new technology. In deciding on ownership, the major issues were legal. Provincial laws to be complied with included The Municipal Franchises Act, The Public Utilities Act, The Municipal Act and The Ontario Municipal Board Act. The operation and administration of the project were also beset with legal complications. The relevant laws were The Boilers and Pressure Vessels Act, and The Environmental Assessment Act. How to charge individual users (consumer accountability) raised a number of technical problems including metering and rate-setting for hot water distribution, and heat borrowing between units. The report recommends that groups planning to implement district heating are advised to allow plenty of lead time for obtaining approvals and franchising arrangements so as not to jeopardize construction schedules. 3 refs.

Double strand DNA breaks response in Huntington´s disease

Czech Academy of Sciences Publication Activity Database

Šolc, Petr; Valášek, Jan; Rausová, Petra; Juhásová, Jana; Juhás, Štefan; Motlík, Jan

2015-01-01

Roč. 78, Suppl 2 (2015), s. 15-15 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * DNA damage * double strand DNA breaks Subject RIV: FH - Neurology

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

Directory of Open Access Journals (Sweden)

Erik Karl Håkan Clemensson

Full Text Available The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

Science.gov (United States)

Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

2017-01-01

The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

Current status of PET imaging in Huntington's disease

Energy Technology Data Exchange (ETDEWEB)

Pagano, Gennaro; Niccolini, Flavia; Politis, Marios [King' s College London, Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Camberwell, London (United Kingdom)

2016-06-15

To review the developments of recent decades and the current status of PET molecular imaging in Huntington's disease (HD). A systematic review of PET studies in HD was performed. The MEDLINE, Web of Science, Cochrane and Scopus databases were searched for articles in all languages published up to 19 August 2015 using the major medical subject heading ''Huntington Disease'' combined with text and key words ''Huntington Disease'', ''Neuroimaging'' and ''PET''. Only peer-reviewed, primary research studies in HD patients and premanifest HD carriers, and studies in which clinical features were described in association with PET neuroimaging results, were included in this review. Reviews, case reports and nonhuman studies were excluded. A total of 54 PET studies were identified and analysed in this review. Brain metabolism ([{sup 18}F]FDG and [{sup 15}O]H{sub 2}O), presynaptic ([{sup 18}F]fluorodopa, [{sup 11}C]β-CIT and [{sup 11}C]DTBZ) and postsynaptic ([{sup 11}C]SCH22390, [{sup 11}C]FLB457 and [{sup 11}C]raclopride) dopaminergic function, phosphodiesterases ([{sup 18}F]JNJ42259152, [{sup 18}F]MNI-659 and [{sup 11}C]IMA107), and adenosine ([{sup 18}F]CPFPX), cannabinoid ([{sup 18}F]MK-9470), opioid ([{sup 11}C]diprenorphine) and GABA ([{sup 11}C]flumazenil) receptors were evaluated as potential biomarkers for monitoring disease progression and for assessing the development and efficacy of novel disease-modifying drugs in premanifest HD carriers and HD patients. PET studies evaluating brain restoration and neuroprotection were also identified and described in detail. Brain metabolism, postsynaptic dopaminergic function and phosphodiesterase 10A levels were proven to be powerful in assessing disease progression. However, no single technique may be currently considered an optimal biomarker and an integrative multimodal imaging approach combining different techniques should be developed

Transgenic miniature pig as a model for the study of Huntington´s Disease

Czech Academy of Sciences Publication Activity Database

Baxa, Monika

2012-01-01

Roč. 22, č. 2 (2012), s. 23-25 ISSN 1210-1737 Institutional support: RVO:67985904 Keywords : transgenic pig * Huntington ´s disease * large animal model * neurodegenerative disease Subject RIV: EB - Genetics ; Molecular Biology

4p16.3 haplotype modifying age at onset of Huntington disease

DEFF Research Database (Denmark)

Nørremølle, A; Budtz-Jørgensen, E; Fenger, K

2009-01-01

Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is, ...

Juvenile Huntington's disease confirmed by genetic examination in twins Doença de Huntington juvenil confirmada por exame genético em gêmeas

Directory of Open Access Journals (Sweden)

GILBERTO LEVY

1999-09-01

Full Text Available Early-onset Huntington's disease (HD occurs in approximately 10% of HD's cases. We report juvenile HD in phenotypically identical twins, evaluated by history, clinical and neurologic examination, mini-mental state examination, blood laboratory exams, cerebrospinal fluid examination, skull computed tomography, and genetic examination for HD. Patients had the akinetic-rigid variety (Westphal variant of the disease and paternal inheritance. The laboratory workup confirmed the clinical diagnosis of HD, which adds this report to the rare cases of HD in twins reported in the literature.Doença de Huntington (DH de início precoce ocorre em aproximadamente 10% dos casos de DH. Relatamos DH juvenil em gêmeas fenotipicamente idênticas, avaliadas por história, exames clínico e neurológico, mini-exame do estado mental, exames de sangue, exame do líquido cefalorraquidiano, tomografia computadorizada de crânio e exame genético para DH. As pacientes apresentavam a variedade rígido-acinética (variante de Westphal da doença e herança paterna. A avaliação laboratorial confirmou o diagnóstico clínico de DH, acrescentando-se este relato aos raros casos de DH em gêmeos relatados na literatura.

DOTS Compliance by Tuberculosis Patients in District Raipur (Chhattisgarh

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Teeku Sinha

2010-10-01

Full Text Available Background: Compliance to therapy is one of the important factors that affect the outcome. Non-compliance to self administered multi drug tuberculosis treatment regimens is an important cause of failure of initial therapy and relapse as well as acquired drug resistance, requiring more prolonged and expensive therapy. Objective: To know the compliance of DOTS therapy in TB patients in District Raipur and to find out the reasons of non-compliance of DOTS therapy among the patients. Study Design: Cross sectional observational community based study. Study Setting: Microscopic Centers in District Raipur. Participants: 695 patients of Tuberculosis. Result: Study revealed that 65.93% patients had complied with the DOTS therapy and 33.38% were non compliant. Conclusion: Most of the reasons of non-Compliance can be averted by proper counseling of target group. Hence to achieve the goal of RNTCP, proper counseling of target group must be given top priority.

Striatal grafts in a rat model of Huntington's disease

DEFF Research Database (Denmark)

Guzman, R; Meyer, M; Lövblad, K O

1999-01-01

Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... time-points graft location could not be further verified. Measures for graft size and ventricle size obtained from MR images highly correlated with measures obtained from histologically processed sections (R = 0.8, P fetal rat lateral ganglionic...

Radiation sensitivity of fibroblast strains from patients with Usher's syndrome, Duchenne muscular dystrophy, and Huntington's disease

International Nuclear Information System (INIS)

Nove, J.; Little, J.B.; Tarone, R.E.; Robbins, J.H.

1987-01-01

The colony-forming ability of 10 normal human fibroblast cell strains and of 10 strains representing 3 degenerative diseases of either nerve or muscle cells was determined after exposure of the cells to X-rays or β-particles from tritiated water. Both methods of irradiation yielded similar comparative results. The fibroblast strains from the 5 Usher's syndrome patients and from 1 of the 2 Huntington's disease patients were hypersensitive to radiation, while those from the 3 Duchenne muscular dystrophy patients and the second Huntington's disease patient had normal sensitivity to radiation. These results indicate both disease-specific and strain-specific differences in the survival of fibroblasts after exposure to ionizing radiation. 38 refs.; 2 figs.; 3 tabs

A new mutation for Huntington disease following maternal transmission of an intermediate allele

NARCIS (Netherlands)

Semaka, Alicia; Kay, Chris; Belfroid, René D. M.; Bijlsma, Emilia K.; Losekoot, Monique; van Langen, Irene M.; van Maarle, Merel C.; Oosterloo, Mayke; Hayden, Michael R.; van Belzen, Martine J.

2015-01-01

New mutations for Huntington disease (HD) originate from CAG repeat expansion of intermediate alleles (27-35 CAG). Expansions of such alleles into the pathological range (≥ 36 CAG) have been exclusively observed in paternal transmission. We report the occurrence of a new mutation that defies the

Digital bedrock geologic map of parts of the Huntington, Richmond, Bolton and Waterbury quadrangles, Vermont

Data.gov (United States)

Vermont Center for Geographic Information — Digital Data from VG95-9A Thompson, PJ�and Thompson, TB, 1995, Digital bedrock geologic map of parts of the Huntington, Richmond, Bolton and Waterbury quadrangles,...

Magnetic biomineralisation in Huntington's disease transgenic mice

International Nuclear Information System (INIS)

Beyhum, W; Hautot, D; Dobson, J; Pankhurst, Q A

2005-01-01

The concentration levels of biogenic magnetite nanoparticles in transgenic R6/2 Huntington's disease (HD) mice have been investigated, using seven control and seven HD mice each from an 8 week-old litter and from a 12 week-old litter. Hysteresis and isothermal remnant magnetisation data were collected on a SQUID magnetometer, and analysed using a model comprising dia/paramagnetic, ferrimagnetic and superparamagnetic contributions, to extract the magnetite and ferritin concentrations present. It was found that magnetite was present in both superparamagnetic and blocked states. A larger spread and higher concentration of magnetite levels was found in the diseased mice for both the 8 week-old and 12 week-old batches, compared to the controls

42 CFR 431.712 - Failure to comply with standards.

Science.gov (United States)

2010-10-01

... Programs for Licensing Nursing Home Administrators § 431.712 Failure to comply with standards. The agency... 42 Public Health 4 2010-10-01 2010-10-01 false Failure to comply with standards. 431.712 Section 431.712 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN...

Evidence for Deficits on Different Components of Theory of Mind in Huntington's Disease

NARCIS (Netherlands)

Allain, P.; Havel-Thomassin, V.; Verny, C.; Gohier, B.; Lancelot, C.; Besnard, J.; Fasotti, L.; Le Gall, D.

2011-01-01

Objective: The main aim of this study was to investigate the effects of Huntington's disease (HD) on cognitive and affective Theory of Mind (ToM) abilities. The relation of ToM performance and executive functions was also examined. Method: Eighteen HD patients, early in the course of the disease,

Behavioral testing of minipigs transgenic for the Huntington gene-A three-year observational study

Czech Academy of Sciences Publication Activity Database

Schuldenzucker, V.; Schubert, R.; Muratori, L. M.; Freisfeld, F.; Rieke, L.; Matheis, T.; Schramke, S.; Motlík, Jan; Kemper, N.; Radespiel, U.; Reilmann, R.

2017-01-01

Roč. 12, č. 10 (2017), č. článku e0185970. E-ISSN 1932-6203 Institutional support: RVO:67985904 Keywords : Huntington´s disease * minipigs Subject RIV: EG - Zoology OBOR OECD: Behavioral sciences biology Impact factor: 2.806, year: 2016

Motor, emotional and cognitive deficits in adult BACHD mice : A model for Huntington's disease

NARCIS (Netherlands)

Abada, Yah-se K.; Schreiber, Rudy; Ellenbroek, Bart

2013-01-01

Rationale: Huntington's disease (HD) is characterized by progressive motor dysfunction, emotional disturbances and cognitive deficits. It is a genetic disease caused by an elongation of the polyglutamine repeats in the huntingtin gene. Whereas HD is a complex disorder, previous studies in mice

Reversal learning and associative memory impairments in a BACHD rat model for Huntington disease

NARCIS (Netherlands)

Abada, Yah-se K.; Nguyen, Huu Phuc; Ellenbroek, Bart; Schreiber, Rudy

2013-01-01

Chorea and psychiatric symptoms are hallmarks of Huntington disease (HD), a neurodegenerative disorder, genetically characterized by the presence of expanded CAG repeats (>35) in the HUNTINGTIN (HTT) gene. HD patients present psychiatric symptoms prior to the onset of motor symptoms and we recently

19 CFR 181.13 - Failure to comply with requirements.

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2010-04-01

... warrant where an exporter or a producer in the United States fails to comply with any requirement of this... 19 Customs Duties 2 2010-04-01 2010-04-01 false Failure to comply with requirements. 181.13 Section 181.13 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY...

The adjustment of γ-aminobutyric acidA tonic subunits in Huntington's disease: from transcription to translation to synaptic levels into the neostriatum

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Abraham Rosas-Arellano

2018-01-01

Full Text Available γ-Aminobutyric acid (GABA, plays a key role in all stages of life, also is considered the main inhibitory neurotransmitter. GABA activates two kind of membrane receptors known as GABAA and GABAB, the first one is responsible to render tonic inhibition by pentameric receptors containing α4−6, β3, δ, or ρ1−3 subunits, they are located at perisynaptic and/or in extrasynaptic regions. The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation. On this basis, GABAA tonic inhibition has been proposed as a potential target for therapeutic intervention of Huntington's disease. Huntington's disease is a neurodegenerative disorder caused by a genetic mutation of the huntingtin protein. For experimental studies of Huntington's disease mouse models have been developed, such as R6/1, R6/2, HdhQ92, HdhQ150, as well as YAC128. In all of them, some key experimental reports are focused on neostriatum. The neostriatum is considered as the most important connection between cerebral cortex and basal ganglia structures, its cytology display two pathways called direct and indirect constituted by medium sized spiny neurons expressing dopamine D1 and D2 receptors respectively, they display strong expression of many types of GABAA receptors, including tonic subunits. The studies about of GABAA tonic subunits and Huntington's disease into the neostriatum are rising in recent years, suggesting interesting changes in their expression and localization which can be used as a strategy to delay the cellular damage caused by the imbalance between excitation and inhibition, a hallmark of Huntington's disease.

[Predictors of mental and physical quality of life in Huntington's disease].

Science.gov (United States)

Brugger, F; Hepperger, C; Hametner, E-M; Holl, A K; Painold, A; Schusterschitz, C; Bonelli, R; Holas, C; Wenning, G K; Poewe, W; Seppi, K

2015-02-01

The assessment of health-related quality of life (hrQoL) is an important tool in therapy studies and in the treatment of patients with Huntington's disease (HD). In the absence of causal interventions, HD therapy targets the alleviation of symptoms aiming to improve impaired hrQoL. The aim of this study was to determine the impact of disease characteristics on hrQoL in HD. A total of 80 genetically confirmed HD patients underwent an assessment using the Unified Huntington's Disease Rating Scale, the Beck Depression Inventory, the Hamilton Rating Scale and the SF-36, a scale for the assessment of physical and mental QoL. Multiple regression analysis revealed that health-related physical and mental QoL was considerably influenced by the functional capacity. The mental QoL also correlated with the degree of depressive symptoms, age and the number of CAG repeats. However, there was no statistical relation between QoL and motor and cognitive abilities. This study underlines the relationship between function capacity and depressive symptoms with mental and physical QoL. This is the first time that hrQoL has been investigated in a German speaking cohort. The results are in accordance with previous studies of hrQoL in HD.

Sensory modulation intervention and behaviour support modification for the treatment of severe aggression in Huntington's disease. A single case experimental design.

Science.gov (United States)

Fisher, Caroline A; Brown, Anahita

2017-09-01

Aggression is common in Huntington's disease. However, at present there are no standard guidelines for managing aggression in Huntington's sufferers due to a lack of empirical research. This paper presents a case study of the treatment of very high levels of aggression with sensory modulation and behaviour support intervention in a Huntington's sufferer. The client exhibited a range of aggressive behaviours, including physical aggression to people, furniture and objects, and verbal aggression. Following an eight week baseline phase, five weeks of sensory modulation intervention were employed. A behaviour support plan was then implemented as an adjunct to the sensory intervention, with aggressive behaviour systematically audited for a further 11 weeks. The results indicate a significant reduction in reported levels of aggression during the combined sensory modulation and behaviour support phase, compared to both the baseline and the sensory modulation therapy alone phases. This case study highlights the efficacy non-pharmacological interventions may have for reducing aggression in HD.

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

DEFF Research Database (Denmark)

Metzger, Silke; Walter, Carolin; Riess, Olaf

2013-01-01

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently......, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second...... independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing...

Huntington's disease predictive testing: the case for an assessment approach to requests from adolescents.

Science.gov (United States)

Binedell, J; Soldan, J R; Scourfield, J; Harper, P S

1996-01-01

Adolescents who are actively requesting Huntington's predictive testing of their own accord pose a dilemma to those providing testing. In the absence of empirical evidence as regards the impact of genetic testing on minors, current policy and guidelines, based on the ethical principles of non-maleficence and respect for individual autonomy and confidentiality, generally exclude the testing of minors. It is argued that adherence to an age based exclusion criterion in Huntington's disease predictive testing protocols is out of step with trends in UK case law concerning minors' consent to medical treatment. Furthermore, contributions from developmental psychology and research into adolescents' decision making competence suggest that adolescents can make informed choices about their health and personal lives. Criteria for developing an assessment approach to such requests are put forward and the implications of a case by case evaluation of competence to consent in terms of clinicians' tolerance for uncertainty are discussed. PMID:8950670

77 FR 51064 - Huntington Foam LLC, Fort Smith, AR; Notice of Affirmative Determination Regarding Application...

Science.gov (United States)

2012-08-23

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,475] Huntington Foam LLC, Fort Smith, AR; Notice of Affirmative Determination Regarding Application for Reconsideration By application dated May 21, 2012, the State Workforce Office requested administrative reconsideration of the negative...

Polysomnographic Findings and Clinical Correlates in Huntington Disease: A Cross-Sectional Cohort Study

Science.gov (United States)

Piano, Carla; Losurdo, Anna; Della Marca, Giacomo; Solito, Marcella; Calandra-Buonaura, Giovanna; Provini, Federica; Bentivoglio, Anna Rita; Cortelli, Pietro

2015-01-01

Study Objectives: To evaluate the sleep pattern and the motor activity during sleep in a cohort of patients affected by Huntington disease (HD). Design: Cross-sectional cohort study. Setting: Sleep laboratory. Patients: Thirty HD patients, 16 women and 14 men (mean age 57.3 ± 12.2 y); 30 matched healthy controls (mean age 56.5 ± 11.8 y). Interventions: Subjective sleep evaluation: Epworth Sleepiness Scale (ESS); Berlin's Questionnaire, interview for restless legs syndrome (RLS), questionnaire for REM sleep behavior disorder (RBD). Clinical evaluation: disease duration, clinical severity (unified Huntington disease motor rating scale [UHDMRS]), genetic tests. Laboratory-based full-night attended video-polysomnography (V-PSG). Measurements and Results: The duration of the disease was 9.4 ± 4.4 y, UHMDRS score was 55.5 ± 23.4, CAG repeats were 44.3 ± 4.1. Body mass index was 21.9 ± 4.0 kg/m2. No patients or caregivers reported poor sleep quality. Two patients reported symptoms of RLS. Eight patients had an ESS score ≥ 9. Eight patients had high risk of obstructive sleep apnea. At the RBD questionnaire, two patients had a pathological score. HD patients, compared to controls, showed shorter sleep, reduced sleep efficiency index, and increased arousals and awakenings. Four patients presented with sleep disordered breathing (SDB). Periodic limb movements (PLMs) during wake and sleep were observed in all patients. No episode of RBD was observed in the V-PSG recordings, and no patients showed rapid eye movement (REM) sleep without atonia. The disease duration correlated with ESS score (P Marca G, Solito M, Calandra-Buonaura G, Provini F, Bentivoglio AR, Cortelli P. Polysomnographic findings and clinical correlates in Huntington disease: a cross-sectional cohort study. SLEEP 2015;38(9):1489–1495. PMID:25845698

Radiosensitivity in Huntington's disease: implications for pathogenesis and presymptomatic diagnosis

International Nuclear Information System (INIS)

Moshell, A.N.; Tarone, R.E.; Barrett, S.F.; Robbins, J.H.

1980-01-01

Huntington's disease (HD) is a dominantly inherited fatal disorder characterised by premature death of nerve cells. Cultured lymphocyte lines from four patients with HD were abnormally sensitive to the lethal effects of X rays, as were lines from two of five subjects at risk for HD. The hypersensitivity is specific for ionising radiation, since HD lines had normal survival after exposure to ultraviolet radiation. The hypersensitivity, which may reflect an inherited defect in DNA repair, provides the basis for a presymptomatic diagnostic test for the disease. (author)

Reduced gluconeogenesis and lactate clearance in Huntington's disease

DEFF Research Database (Denmark)

Josefsen, Knud; Nielsen, Signe M B; Campos, André

2010-01-01

We studied systemic and brain glucose and lactate metabolism in Huntington's disease (HD) patients in response to ergometer cycling. Following termination of exercise, blood glucose increased abruptly in control subjects, but no peak was seen in any of the HD patients (2.0 ± 0.5 vs. 0.0 ± 0.2mM, P...... HD mouse model R6/2 following a lactate challenge, combined with reduced phosphoenolpyruvate carboxykinase and increased pyruvate kinase activity in the mouse liver suggest a reduced capacity...... for gluconeogenesis in HD, possibly contributing to the clinical symptoms of HD. We propose that blood glucose concentration in the recovery from exercise can be applied as a liver function test in HD patients....

40 CFR 63.2495 - How do I comply with the pollution prevention standard?

Science.gov (United States)

2010-07-01

... Manufacturing Alternative Means of Compliance § 63.2495 How do I comply with the pollution prevention standard? (a) You may elect to comply with the pollution prevention alternative requirements specified in... comply by using the pollution prevention alternative must begin with the same starting material(s) and...

Minipig Model of Huntington's Disease: H-1 Magnetic Resonance Spectroscopy of the Brain

Czech Academy of Sciences Publication Activity Database

Jozefovičová, M.; Herynek, V.; Jírů, F.; Dezortová, M.; Juhásová, Jana; Juhás, Štefan; Motlík, Jan; Hájek, M.

2016-01-01

Roč. 65, č. 1 (2016), s. 155-163 ISSN 0862-8408 R&D Projects: GA TA ČR(CZ) TA01011466; GA MŠk(CZ) 7F14308; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington´s disease * minipigs * magnetic resonance spectroscopy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.461, year: 2016

CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

DEFF Research Database (Denmark)

Lee, J-M; Ramos, E M; Lee, J-H

2012-01-01

Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound...

Contribution of Neuroepigenetics to Huntington's Disease.

Science.gov (United States)

Francelle, Laetitia; Lotz, Caroline; Outeiro, Tiago; Brouillet, Emmanuel; Merienne, Karine

2017-01-01

Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington's disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the relationship between epigenetic regulations, gene expression and neuronal activity in normal and diseased neurons, including HD neurons. We propose that cell-type specific techniques and 3D-based methods will advance knowledge of epigenome in the context of brain region vulnerability in neurodegenerative diseases. A better understanding of the mechanisms underlying epigenetic changes and of their consequences in neurodegenerative diseases is required to design therapeutic strategies more effective than current strategies based on histone deacetylase (HDAC) inhibitors. Researches in HD may play a driving role in this process.

75 FR 11939 - Fisher & Paykel Appliances, Inc., Huntington Beach, CA; Notice of Termination of Investigation

Science.gov (United States)

2010-03-12

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-71,749] Fisher & Paykel Appliances, Inc., Huntington Beach, CA; Notice of Termination of Investigation Pursuant to Section 221 of the Trade Act of 1974, as amended, an investigation was initiated in response to a petition filed on July 21...

Dynamics of the connectome in Huntington's disease: A longitudinal diffusion MRI study

OpenAIRE

Odish, Omar F.F.; Caeyenberghs, Karen; Hosseini, Hadi; van den Bogaard, Simon J.A.; Roos, Raymund A.C.; Leemans, Alexander

2015-01-01

Abstract Objectives To longitudinally investigate the connectome in different stages of Huntington's disease (HD) by applying graph theoretical analysis to diffusion MRI data. Experimental design We constructed weighted structural networks and calculated their topological properties. Twenty-two premanifest (preHD), 10 early manifest HD and 24 healthy controls completed baseline and 2 year follow-up scans. We stratified the preHD group based on their predicted years to disease onset into a far...

29 CFR 1977.22 - Employee refusal to comply with safety rules.

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2010-07-01

... WILLIAMS-STEIGER OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Some Specific Subjects § 1977.22 Employee refusal to comply with safety rules. Employees who refuse to comply with occupational safety and health... Section 1977.22 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH...

Structural imaging in premanifest and manifest Huntington disease.

Science.gov (United States)

Scahill, Rachael I; Andre, Ralph; Tabrizi, Sarah J; Aylward, Elizabeth H

2017-01-01

Huntington disease (HD) neuropathology has a devastating effect on brain structure and consequently brain function; neuroimaging provides a means to assess these effects in gene carriers. In this chapter we first outline the unique utility of structural imaging in understanding HD and discuss some of the acquisition and analysis techniques currently available. We review the existing literature to summarize what we know so far about structural brain changes across the spectrum of disease from premanifest through to manifest disease. We then consider how these neuroimaging findings relate to patient function and nonimaging biomarkers, and can be used to predict disease onset. Finally we review the utility of imaging measures for assessment of treatment efficacy in clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Nucleic Acid-Based Therapy Approaches for Huntington's Disease

Directory of Open Access Journals (Sweden)

Tatyana Vagner

2012-01-01

Full Text Available Huntington's disease (HD is caused by a dominant mutation that results in an unstable expansion of a CAG repeat in the huntingtin gene leading to a toxic gain of function in huntingtin protein which causes massive neurodegeneration mainly in the striatum and clinical symptoms associated with the disease. Since the mutation has multiple effects in the cell and the precise mechanism of the disease remains to be elucidated, gene therapy approaches have been developed that intervene in different aspects of the condition. These approaches include increasing expression of growth factors, decreasing levels of mutant huntingtin, and restoring cell metabolism and transcriptional balance. The aim of this paper is to outline the nucleic acid-based therapeutic strategies that have been tested to date.

Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice

Energy Technology Data Exchange (ETDEWEB)

Li, Xueyi, E-mail: xli12@partners.org [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B. [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); DiFiglia, Marian, E-mail: difiglia@helix.mgh.harvard.edu [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States)

2012-05-18

Highlights: Black-Right-Pointing-Pointer Primary Huntington's disease neurons are impaired in taking up glucose. Black-Right-Pointing-Pointer Rab11 modulates glucose uptake in neurons. Black-Right-Pointing-Pointer Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. Black-Right-Pointing-Pointer We provide a novel mechanism for glucose hypometabolism in Huntington's disease. -- Abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD{sup 140Q/140Q}). Primary HD{sup 140Q/140Q} cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD{sup 140Q/140Q} neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD{sup 140Q/140Q} neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

Periodontitis determining the onset and progression of Huntington's disease: review of the literature

Directory of Open Access Journals (Sweden)

María Lourdes Rodríguez Coyago

2015-10-01

Full Text Available La enfermedad de Hungtinton es un trastorno neurodegenerativo, causado por la expansión de un triplete de citosina, adenina, guanina en el gen de la huntingtina. Se manifiesta con un deterioro físico, cognitivo y psiquiátrico a distintas edades en el adulto, con un pronóstico fatal. Además del número de repeticiones del triplete, existirían otros factores que explicarían el inicio de esta enfermedad a más temprana edad. Se sabe que la neuroinflamación es un protagonista en los trastornos neurodegenerativos, no siendo la enfermedad de Huntington una excepción. La neuroinflamación exacerba el daño neuronal producido por la mutación, al existir activación aberrante de la célula microglía, disfunción de astrocitos y células dendríticas; compromiso de la barrera hematoencefálica y activación de complemento, todas ellas como efecto directo e indirecto de la mutante y otros estímulos como infecciones crónicas. Es el interés del presente trabajo analizar la periodontitis, como modelo de infección bucodental crónica y fuente de inflamación sistémica. Hipotetizamos que el potencial rol de la periodontitis en la enfermedad de Huntington y los mecanismos por los cuales contribuiría a la manifestación temprana y progreso de dicha enfermedad, para lo cual se consideraron revisiones sistemáticas, metanálisis y estudios experimentales publicados tanto en español como en inglés obtenidos del PubMed y SciELO. Son diversos los mecanismos que generan inflamación en el cerebro de estos pacientes, adquiriendo especial protagonismo los mecanismos de la inmunidad innata. Las infecciones buco dentarias crónicas, como la enfermedad periodontal, pueden constituir un factor exacerbante de la neuroinflamación que per se asocia la enfermedad de Huntington.

Patient satisfaction at accredited antiretroviral treatment sites in the Gert Sibande District

Directory of Open Access Journals (Sweden)

Selente Bezuidenhout

2014-11-01

Aim: This study sought to explore and describe the general satisfaction or dissatisfaction of patients with accredited ART hospital sites at public health facilities in the Gert Sibande District, Mpumalanga and to identify factors contributing to either satisfaction or dissatisfaction. Setting: Six hospitals that initiated ART in the district, participated in the study. Method: The study was conducted using a sample of 300 patients. Proportional random sampling was used in selecting the number of patients from each facility. A structured interview with each participating patient was conducted using a standardised structured questionnaire. The first available required number of patients that complied with requirements from each of the six hospitals was selected for the interview. Descriptive statistics were used to analyse data and data with qualitative aspects were captured and categorised manually. Results: The major factors contributing to satisfaction included the availability of medicines and knowledge regarding how to take medication. Factors contributing to dissatisfaction on the part of the patients included confidentiality issues, long waiting periods, shortage of staff and dirty toilets. Conclusion: This study indicated general satisfaction with the ART-related services at the accredited ART hospital sites in the Gert Sibande District. Regular monitoring and evaluation are recommended.

Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model

DEFF Research Database (Denmark)

Aidt, Frederik Heurlin; Nielsen, Signe Marie Borch; Kanters, Jørgen

2013-01-01

Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of complexes II, III and IV of the electron transport system...

40 CFR 63.2500 - How do I comply with emissions averaging?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true How do I comply with emissions averaging? 63.2500 Section 63.2500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Alternative Means of Compliance § 63.2500 How do I comply with emissions averaging? (a) For an existing source...

49 CFR 1112.3 - Default for failure to comply with schedule; effect of default.

Science.gov (United States)

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Default for failure to comply with schedule; effect of default. 1112.3 Section 1112.3 Transportation Other Regulations Relating to Transportation... § 1112.3 Default for failure to comply with schedule; effect of default. If a party fails to comply with...

Nonparametric estimation for censored mixture data with application to the Cooperative Huntington's Observational Research Trial.

Science.gov (United States)

Wang, Yuanjia; Garcia, Tanya P; Ma, Yanyuan

2012-01-01

This work presents methods for estimating genotype-specific distributions from genetic epidemiology studies where the event times are subject to right censoring, the genotypes are not directly observed, and the data arise from a mixture of scientifically meaningful subpopulations. Examples of such studies include kin-cohort studies and quantitative trait locus (QTL) studies. Current methods for analyzing censored mixture data include two types of nonparametric maximum likelihood estimators (NPMLEs) which do not make parametric assumptions on the genotype-specific density functions. Although both NPMLEs are commonly used, we show that one is inefficient and the other inconsistent. To overcome these deficiencies, we propose three classes of consistent nonparametric estimators which do not assume parametric density models and are easy to implement. They are based on the inverse probability weighting (IPW), augmented IPW (AIPW), and nonparametric imputation (IMP). The AIPW achieves the efficiency bound without additional modeling assumptions. Extensive simulation experiments demonstrate satisfactory performance of these estimators even when the data are heavily censored. We apply these estimators to the Cooperative Huntington's Observational Research Trial (COHORT), and provide age-specific estimates of the effect of mutation in the Huntington gene on mortality using a sample of family members. The close approximation of the estimated non-carrier survival rates to that of the U.S. population indicates small ascertainment bias in the COHORT family sample. Our analyses underscore an elevated risk of death in Huntington gene mutation carriers compared to non-carriers for a wide age range, and suggest that the mutation equally affects survival rates in both genders. The estimated survival rates are useful in genetic counseling for providing guidelines on interpreting the risk of death associated with a positive genetic testing, and in facilitating future subjects at risk

Alpha-7 nicotinic acetylcholine receptor agonist treatment in a rat model of Huntington's disease and involvement of heme oxygenase-1

Directory of Open Access Journals (Sweden)

Laura Foucault-Fruchard

2018-01-01

Full Text Available Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases. We recently reported that repeated alpha-7 nicotinic acetylcholine receptor (α7nAChR activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons. To further investigate the underlying mechanism, we established rat models of early-stage Huntington's disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water, twice a day during 4 days. Western blot assay results showed that the expression of heme oxygenase-1 (HO-1, the key component of the cholinergic anti-inflammatory pathway, in the right striatum of rat models of Huntington's disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water, and that the increase in HO-1 expression was independent of change in α7nAChR expression. These findings suggest that HO-1 expression is unrelated to α7nAChR density and the increase in HO-1 expression likely contributes to α7nAChR activation-related neuroprotective effect in early-stage Huntington's disease.

Insights into gait disorders: walking variability using phase plot analysis, Huntington's disease.

Science.gov (United States)

Collett, Johnny; Esser, Patrick; Khalil, Hanan; Busse, Monica; Quinn, Lori; DeBono, Katy; Rosser, Anne; Nemeth, Andrea H; Dawes, Helen

2014-09-01

Huntington's disease (HD) is a progressive inherited neurodegenerative disorder. Identifying sensitive methodologies to quantitatively measure early motor changes have been difficult to develop. This exploratory observational study investigated gait variability and symmetry in HD using phase plot analysis. We measured the walking of 22 controls and 35 HD gene carriers (7 premanifest (PreHD)), 16 early/mid (HD1) and 12 late stage (HD2) in Oxford and Cardiff, UK. The unified Huntington's disease rating scale-total motor scores (UHDRS-TMS) and disease burden scores (DBS) were used to quantify disease severity. Data was collected during a clinical walk test (8.8 or 10 m) using an inertial measurement unit attached to the trunk. The 6 middle strides were used to calculate gait variability determined by spatiotemporal parameters (co-efficient of variation (CoV)) and phase plot analysis. Phase plots considered the variability in consecutive wave forms from vertical movement and were quantified by SDA (spatiotemporal variability), SDB (temporal variability), ratio ∀ (ratio SDA:SDB) and Δangleβ (symmetry). Step time CoV was greater in manifest HD (p0.05). Phase plot analysis identified differences between manifest HD and controls for SDB, Ratio ∀ and Δangle (all pplot analysis may be a sensitive method of detecting gait changes in HD and can be performed quickly during clinical walking tests. Copyright © 2014 Elsevier B.V. All rights reserved.

47 CFR 90.1420 - Failure to comply with the NSA or the Commission's rules.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Failure to comply with the NSA or the... § 90.1420 Failure to comply with the NSA or the Commission's rules. (a) Failure to comply with the Commission's rules or the terms of the NSA may warrant cancelling the Public Safety Broadband License. The...

Firm Performance and Comply or Explain Disclosure in Corporate Governance

DEFF Research Database (Denmark)

Rose, Caspar

2016-01-01

This study investigates the degree of Danish firm adherence to the Danish Code of Corporate Governance and analyzes if a higher degree of comply or explain disclosure is related to firm performance. This article formulates a methodology for quantifying the degree of comply or explain disclosure...... there is no impact on performance when increasing compliance with the recommendations on risk management and internal controls. This article demonstrates that these three areas are the ones where Danish firms show the lowest degree of comply or explain disclosure, although the overall adherence to the Danish code...... that soft law may be an efficient way of increasing the quality of corporate governance among listed firms. However, in order to strengthen investor confidence, national code authorities/committees should be more active in penalizing poor explanations as well as cases where firms wrongfully state...

47 CFR 27.1320 - Failure to comply with the NSA or the Commission's rules.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Failure to comply with the NSA or the... § 27.1320 Failure to comply with the NSA or the Commission's rules. (a) Failure to comply with the Commission's rules or the terms of the NSA may warrant cancelling the Upper 700 MHz D Block license and...

The roles of family members, health care workers, and others in decision-making processes about genetic testing among individuals at risk for Huntington disease.

Science.gov (United States)

Klitzman, Robert; Thorne, Deborah; Williamson, Jennifer; Marder, Karen

2007-06-01

To understand how individuals at risk for Huntington disease view the roles of others, e.g., family members and health care workers, in decision making about genetic testing. Twenty-one individuals (eight mutation-positive, four mutation-negative, and nine not tested) were interviewed for approximately 2 hours each. Interviewees illuminated several key aspects of the roles of family members and health care workers (in genetics and other fields) in decision making about testing that have been underexplored. Family members often felt strongly about whether an individual should get tested. Health care workers provided information and assistance with decision making and mental health referrals that were often helpful. Yet health care workers varied in knowledge and sensitivity regarding testing issues, and the quality of counseling and testing experiences can range widely. At times, health care workers without specialized knowledge of Huntington disease offered opinions of whether to test. Input from families and health care workers could also conflict with each other and with an individual's own preferences. Larger institutional and geographic contexts shaped decisions as well. Decision-making theories applied to Huntington disease testing have frequently drawn on psychological models, yet the current data highlight the importance of social contexts and relationships in testing decisions. This report, the first to our knowledge to explore individuals' perceptions of social factors (particularly family and health care worker involvement) in Huntington disease testing decisions, has critical implications for practice, education, research, and policy.

Rhes deletion is neuroprotective in the 3-nitropropionic acid model of Huntington's disease

OpenAIRE

Mealer, Robert G.; Subramaniam, Srinivasa; Snyder, Solomon H.

2013-01-01

Although the mutated protein causing Huntington's disease (HD) is expressed throughout the body, the major pathology of HD is localized to the striatum of the brain. We previously reported that the striatal-enriched protein Rhes binds the mutated huntingtin protein and enhances its cytotoxicity. We now demonstrate that Rhes-deleted mice are dramatically protected from neurotoxicity and motor dysfunction in a striatal-specific model of HD elicited by 3-nitropropionic acid. This finding suggest...

Destination and source memory in Huntington's disease.

Science.gov (United States)

El Haj, Mohamad; Caillaud, Marie; Verny, Christophe; Fasotti, Luciano; Allain, Philippe

2016-03-01

Destination memory refers to the recall of the destination of previously relayed information, and source memory refers to the recollection of the origin of received information. We compared both memory systems in Huntington's disease (HD) participants. For this, HD participants and healthy adults had to put 12 items in a black or a white box (destination task), and to extract another 12 items from a blue or a red box (source task). Afterwards, they had to decide in which box each item had previously been deposited (destination memory), and from which box each item had previously been extracted (source memory). HD participants showed poorer source as well as destination recall performance than healthy adults in the proposed tasks. Correlation analysis showed that destination recall was significantly correlated with episodic recall in HD participants. Destination memory impairment in HD participants seems to be considerably influenced by their episodic memory performance. © 2014 The British Psychological Society.

Assessing Impairment of Executive Function and Psychomotor Speed in Premanifest and Manifest Huntington's Disease Gene-expansion Carriers

DEFF Research Database (Denmark)

Unmack Larsen, Ida; Vinther-Jensen, Tua; Gade, Anders

2015-01-01

Executive functions (EF) and psychomotor speed (PMS) has been widely studied in Huntington's disease (HD). Most studies have focused on finding markers of disease progression by comparing group means at different disease stages. Our aim was to investigate performances on nine measures of EF and PMS...

Sodium phenylbutyrate in Huntington's disease: a dose-finding study.

Science.gov (United States)

Hogarth, Penelope; Lovrecic, Luca; Krainc, Dimitri

2007-10-15

Transcriptional dysregulation in Huntington's disease (HD) is mediated in part by aberrant patterns of histone acetylation. We performed a dose-finding study in human HD of sodium phenylbutyrate (SPB), a histone deacetylase inhibitor that ameliorates the HD phenotype in animal models. We used a dose-escalation/de-escalation design, using prespecified toxicity criteria and standard clinical and laboratory safety measures. The maximum tolerated dose was 15 g/day. At higher doses, toxicity included vomiting, lightheadedness, confusion, and gait instability. We saw no significant laboratory or electrocardiographic abnormalities. Gene expression changes in blood suggested an inverse dose-response. In conclusion, SPB at 12 to 15 g/day appears to be safe and well-tolerated in human HD. 2007 Movement Disorder Society

[Speed of ocular saccades in Huntington disease. Prospective study].

Science.gov (United States)

García Ruiz, P J; Cenjor, C; Ulmer, E; Hernández, J; Cantarero, S; Fanjul, S; García de Yébenes, J

2001-02-01

Oculomotor abnormalities, especially slow saccades, have long been recognized in Huntington's disease (HD). To study prospectively horizontal saccade velocity by videonystagmography in 21 patients with genetically confirmed HD. The study included a baseline analysis and a second evaluation after 18.8 +/- 7.1 months. We included a control group of 15 subjects. HD group exhibited decreased saccade velocity when compared with that from a control group (for predictive and unpredictive target). HD patients showed decreased saccade velocity with the passage of time (for predictive target, p < 0.01). Finally we found statistical significant correlation between saccade velocity and triplet length. The measurement of saccade velocity might be an objective method to study the natural evolution of HD, and thus evaluate the effectiveness of future therapies.

Study of protein O-GlcNAcylation in the brain tissue in Huntington´s disease

Czech Academy of Sciences Publication Activity Database

Ondrušková, N.; Rodinová, M.; Kratochvílová, H.; Klempíř, J.; Roth, J.; Motlík, Jan; Radoslav, M.; Zeman, J.; Hansíková, H.

2015-01-01

Roč. 78, Suppl 2 (2015), s. 20-20 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk(CZ) 7F14308; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * glycosylation * N-acetylglucosamine Subject RIV: FH - Neurology

Grunting in genetically modified minipig animal model for Huntington ´s disease - a pilot experiment

Czech Academy of Sciences Publication Activity Database

Tykalová, T.; Hlavnička, J.; Mačáková, Monika; Baxa, Monika; Cmejla, R.; Motlík, Jan; Klempíř, J.; Rusz, J.

2015-01-01

Roč. 78, Suppl 2 (2015), s. 12-13 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * mitochondria * DNA damage Subject RIV: FH - Neurology

Pre-clinical evaluation of AAV5-miHTT gene therapy of Huntington´s disease

Czech Academy of Sciences Publication Activity Database

Konstantinová, P.; Miniarikova, J.; Blits, B.; Zimmer, V.; Spoerl, A.; Southwell, A.; Hayden, M.; van Deventer, S.; Deglon, N.; Motlík, Jan; Juhás, Štefan; Juhásová, Jana; Richard, Ch.; Petry, H.

2015-01-01

Roč. 78, Supl 2 (2015), s. 8-8 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * gene therapy * AAV5-miHTT Subject RIV: EB - Genetics ; Molecular Biology

El papel de la terapia ocupacional en la enfermedad de Huntington

OpenAIRE

Hernández Lozano, David; Fernández Hawrylak, María; Grau Rubio, Claudia

2014-01-01

se analiza el papel del terapeuta ocupacional en el trabajo con las personas afectadas por la enfermedad de Huntington. se realizó una investigación por objetivos a través del diseño y puesta en práctica de un programa de intervención encaminado a mitigar el deterioro producido por la enfermedad mediante el entrenamiento en actividades de la vida diaria y de estimulación cognitiva, y a desarrollar competencias en la familia. la investigación se desarrolló en la Asociación de corea de Huntingt...

Internal consistency of a Brazilian version of the unified Huntington's disease rating scale Consistência interna da versão brasileira da escala unificada para avaliação da doença da Huntington

Directory of Open Access Journals (Sweden)

Vitor Tumas

2004-12-01

Full Text Available We evaluated the reliability of a translated Brazilian version of the Unified Huntington's Disease Rating Scale (UHDRS to establish the reproducibility of the scale in a population that differs substantially from that on which the scale was originally validated. After a training period with the video and guidelines requested from the Huntington Study Group, we applied the UHDRS, except for the cognitive tests, to a group of 21 Brazilian patients with a molecular diagnosis of Huntington's disease (HD. We found a high degree of internal consistency of the motor section of the UHDRS (Cronbach's alpha= 0.841. There was a negative correlation between the total motor score and the functional assessment, the independence scale and the functional capacity. There was a positive correlation between these 3 scales of functional evaluation and a negative correlation between the age of onset of the disease and the number of CAG repeats. The behavioral scale and disease duration were not correlated with any factor. The clinical characteristics of this sample of patients as described by the UHDRS were roughly similar to those reported in the original validation studies and the correlations described were similar to those reported previously. We conclude that the Brazilian version of the UHDRS is reliable and valid to study patients with HD in the Brazilian setting, that this sample of Brazilian patients had clinical characteristics similar to those observed in other world regions, as expected, and that the clinical training method used for the application of the UHDRS was effective to insure a high degree of clinical reproducibility.Nosso estudo avaliou a confiabilidade da versão brasileira da escala unificada para avaliação da doença de Huntington (UHDRS com o objetivo de estabelecer a reprodutibilidade dessa escala em uma população que difere significativamente daquela em que foi originalmente validada. Após um período de treinamento com um v

Does level of specificity affect measures of motivation to comply? A randomized evaluation.

Science.gov (United States)

Branscum, Paul; Senkowski, Valerie

2018-05-30

The theory of planned behavior (TPB) is a popular value-expectancy model in social and behavioral health. Motivation to comply, one of the theory's constructs, has not been well operationalized and measured in the past, and to date, there has been no assessment of whether level of specificity affects the measurement of the construct. The purpose of this study was to measure the motivation to comply construct across four domains (from general to TACT-behavior specific) and evaluate the potential impact the differences have when identifying determinants of generalized injunctive norms. Students (n = 234) attending a large southwestern university completed a TPB survey related to sleep and physical activity, and were randomized to one of four domains that measured motivation to comply (General domain, n = 58; Health domain, n = 60; Behavioral domain, n = 56; and TACT domain, n = 60). Across both behaviors, motivation to comply measurements did not appear to be affected by changing the level of specificity. Referents for sleep and physical activity were mostly significant, but the effects were small to medium. Future researchers should consider removing motivation to comply measures from TPB surveys to reduce respondent burden or find alternative ways of measuring the construct.

Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

Directory of Open Access Journals (Sweden)

Carmela Giampà

2010-10-01

Full Text Available Huntington's disease is a devastating neurodegenerative condition for which there is no therapy to slow disease progression. The particular vulnerability of striatal medium spiny neurons to Huntington's pathology is hypothesized to result from transcriptional dysregulation within the cAMP and CREB signaling cascades in these neurons. To test this hypothesis, and a potential therapeutic approach, we investigated whether inhibition of the striatal-specific cyclic nucleotide phosphodiesterase PDE10A would alleviate neurological deficits and brain pathology in a highly utilized model system, the R6/2 mouse.R6/2 mice were treated with the highly selective PDE10A inhibitor TP-10 from 4 weeks of age until euthanasia. TP-10 treatment significantly reduced and delayed the development of the hind paw clasping response during tail suspension, deficits in rotarod performance, and decrease in locomotor activity in an open field. Treatment prolonged time to loss of righting reflex. These effects of PDE10A inhibition on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal and cortical cell loss, the formation of striatal neuronal intranuclear inclusions, and the degree of microglial activation that occurs in response to the mutant huntingtin-induced brain damage. Striatal and cortical levels of phosphorylated CREB and BDNF were significantly elevated.Our findings provide experimental support for targeting the cAMP and CREB signaling pathways and more broadly transcriptional dysregulation as a therapeutic approach to Huntington's disease. It is noteworthy that PDE10A inhibition in the R6/2 mice reduces striatal pathology, consistent with the localization of the enzyme in medium spiny neurons, and also cortical pathology and the formation of neuronal nuclear inclusions. These latter findings suggest that striatal pathology may be a primary driver of these secondary pathological events. More

Neurotensin receptor binding levels in basal ganglia are not altered in Huntington's chorea or schizophrenia

International Nuclear Information System (INIS)

Palacios, J.M.; Chinaglia, G.; Rigo, M.; Ulrich, J.; Probst, A.

1991-01-01

Autoradiographic techniques were used to examine the distribution and levels of neurotensin receptor binding sites in the basal ganglia and related regions of the human brain. Monoiodo ( 125 I-Tyr3)neurotensin was used as a ligand. High amounts of neurotensin receptor binding sites were found in the substantia nigra pars compacta. Lower but significant quantities of neurotensin receptor binding sites characterized the caudate, putamen, and nucleus accumbens, while very low quantities were seen in both medial and lateral segments of the globus pallidus. In Huntington's chorea, the levels of neurotensin receptor binding sites were found to be comparable to those of control cases. Only slight but not statistically significant decreases in amounts of receptor binding sites were detected in the dorsal part of the head and in the body of caudate nucleus. No alterations in the levels of neurotensin receptor binding sites were observed in the substantia nigra pars compacta and reticulata. These results suggest that a large proportion of neurotensin receptor binding sites in the basal ganglia are located on intrinsic neurons and on extrinsic afferent fibers that do not degenerate in Huntington's disease

EMQN/CMGS best practice guidelines for the molecular genetic testing of Huntington disease

OpenAIRE

Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E

2012-01-01

Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these ...

Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline.

Directory of Open Access Journals (Sweden)

Liliana B Menalled

2010-03-01

Full Text Available Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington's disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington's disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition.

Time perception impairment in early-to-moderate stages of Huntington's disease is related to memory deficits.

Science.gov (United States)

Righi, Stefania; Galli, Luca; Paganini, Marco; Bertini, Elisabetta; Viggiano, Maria Pia; Piacentini, Silvia

2016-01-01

Huntington's disease (HD) primarily affects striatum and prefrontal dopaminergic circuits which are fundamental neural correlates of the timekeeping mechanism. The few studies on HD mainly investigated motor timing performance in second durations. The present work explored time perception in early-to-moderate symptomatic HD patients for seconds and milliseconds with the aim to clarify which component of the scalar expectancy theory (SET) is mainly responsible for HD timing defect. Eleven HD patients were compared to 11 controls employing two separate temporal bisection tasks in second and millisecond ranges. Our results revealed the same time perception deficits for seconds and milliseconds in HD patients. Time perception impairment in early-to-moderate stages of Huntington's disease is related to memory deficits. Furthermore, both the non-systematical defect of temporal sensitivity and the main impairment of timing performance in the extreme value of the psychophysical curves suggested an HD deficit in the memory component of the SET. This result was further confirmed by the significant correlations between time perception performance and long-term memory test scores. Our findings added important preliminary data for both a deeper comprehension of HD time-keeping deficits and possible implications on neuro-rehabilitation practices.

Derivation of Huntington Disease affected Genea046 human embryonic stem cell line

Directory of Open Access Journals (Sweden)

Biljana Dumevska

2016-03-01

Full Text Available The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1–60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

Nonparametric modeling and analysis of association between Huntington's disease onset and CAG repeats.

Science.gov (United States)

Ma, Yanyuan; Wang, Yuanjia

2014-04-15

Huntington's disease (HD) is a neurodegenerative disorder with a dominant genetic mode of inheritance caused by an expansion of CAG repeats on chromosome 4. Typically, a longer sequence of CAG repeat length is associated with increased risk of experiencing earlier onset of HD. Previous studies of the association between HD onset age and CAG length have favored a logistic model, where the CAG repeat length enters the mean and variance components of the logistic model in a complex exponential-linear form. To relax the parametric assumption of the exponential-linear association to the true HD onset distribution, we propose to leave both mean and variance functions of the CAG repeat length unspecified and perform semiparametric estimation in this context through a local kernel and backfitting procedure. Motivated by including family history of HD information available in the family members of participants in the Cooperative Huntington's Observational Research Trial (COHORT), we develop the methodology in the context of mixture data, where some subjects have a positive probability of being risk free. We also allow censoring on the age at onset of disease and accommodate covariates other than the CAG length. We study the theoretical properties of the proposed estimator and derive its asymptotic distribution. Finally, we apply the proposed methods to the COHORT data to estimate the HD onset distribution using a group of study participants and the disease family history information available on their family members. Copyright © 2013 John Wiley & Sons, Ltd.

The story of George Huntington and his disease

Directory of Open Access Journals (Sweden)

Kalyan B Bhattacharyya

2016-01-01

Full Text Available George Huntington described some families with choreiform movements in 1872 in the United States of America and since then many such families have been described in other parts of the world and works on the genetics of the disease have brought new vistas in the understanding of the disease. In 1958, Americo Negrette, a young Venezuelan physician observed similar subjects in the vicinity of Lake Maracaibo which was presented by his co-worker, Ramon Avilla Giron at New York in 1972 when United States of America had been commemorating the centenary year of Huntington′s disease. Nancy Wexler, a psychoanalyst, whose mother had been suffering from the disease attended the meeting and organized a research team to Venezuela and they systematically studied more than 18,000 individuals in order to work out a common pedigree. They identified the genetic locus of the disease in the short arm of chromosome 4 and observed that it was a trinucleotide repeat disorder.

Making a measurable difference in advanced Huntington disease care.

Science.gov (United States)

Moskowitz, Carol Brown; Rao, Ashwini K

2017-01-01

Neurologists' role in the care of people with advanced Huntington disease (HD) (total functional capacity speech and language pathology), behavioral and psychiatric professionals for problem-solving strategies, which must be reviewed with direct care staff before implementation; (3) encourage and support qualitative and quantitative interdisciplinary research studies, and randomized controlled studies of nonpharmacologic interventions; and (4) assist in the development of meaningful measures to further document what works to provide a good quality of life for the patient and family and a comfortable thoughtful approach to a good death. Collaborative models of care depend on: (1) clear communication; (2) ongoing education and support programs; with (3) pharmacologic and rehabilitation interventions, always in the context of respect for the person with HD, a preservation of the individuals' dignity, autonomy, and individual preferences. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain atrophy in Huntington's disease: A CT-scan study

International Nuclear Information System (INIS)

Starkstein, S.E.; Folstein, S.E.; Brandt, J.; McDonnell, A.; Folstein, M.

1989-01-01

CT-scan measurements of cortical and subcortical atrophy were carried out in 34 patients with Huntington's disease (HD). While a significant correlation was observed between parameters of subcortical atrophy (bicaudate ratio, bifrontal ratio and third ventricular ratio) and duration of the disease, there was no significant correlation between these parameters and age. On the other hand, measurements of cortical atrophy (frontal fissure ratio and cortical sulci ratio) correlated significantly with age but not with duration of the disease. When a group of 24 HD patients were compared on CT-scan measurements with a group of 24 age-matched normal controls, significant differences were obtained for all the variables examined, but the bicaudate ratio showed the highest sensitivity and specificity. Even mildly affected patients, with duration of motor symptoms less than 3 years had higher bicaudate ratios than age-matched controls. (orig.)

Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure?

Science.gov (United States)

Morea, Veronica; Bidollari, Eris; Colotti, Gianni; Fiorillo, Annarita; Rosati, Jessica; De Filippis, Lidia; Squitieri, Ferdinando; Ilari, Andrea

2017-07-01

Huntington's disease (HD) or Huntington's chorea is the most common inherited, dominantly transmitted, neurodegenerative disorder. It is caused by increased CAG repeats number in the gene coding for huntingtin (Htt) and characterized by motor, behaviour and psychiatric symptoms, ultimately leading to death. HD patients also exhibit alterations in glucose and energetic metabolism, which result in pronounced weight loss despite sustained calorie intake. Glucose metabolism decreases in the striatum of all the subjects with mutated Htt, but affects symptom presentation only when it drops below a specific threshold. Recent evidence points at defects in glucose uptake by the brain, and especially by neurons, as a relevant component of central glucose hypometabolism in HD patients. Here we review the main features of glucose metabolism and transport in the brain in physiological conditions and how these processes are impaired in HD, and discuss the potential ability of strategies aimed at increasing intracellular energy levels to counteract neurological and motor degeneration in HD patients.

Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington's disease

OpenAIRE

Keene, C. Dirk; Rodrigues, Cecilia M. P.; Eich, Tacjana; Chhabra, Manik S.; Steer, Clifford J.; Low, Walter C.

2002-01-01

Huntington's disease (HD) is an untreatable neurological disorder caused by selective and progressive degeneration of the caudate nucleus and putamen of the basal ganglia. Although the etiology of HD pathology is not fully understood, the observed loss of neuronal cells is thought to occur primarily through apoptosis. Furthermore, there is evidence in HD that cell death is mediated through mitochondrial pathways, and mitochondrial deficits are commonly associated with HD. We have previously r...

Human glia can both induce and rescue aspects of disease phenotype in Huntington disease

DEFF Research Database (Denmark)

Benraiss, Abdellatif; Wang, Su; Herrlinger, Stephanie

2016-01-01

The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells...... chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends...

Using the Theory of Planned Behavior to predict intention to comply with a food recall message.

Science.gov (United States)

Freberg, Karen

2013-01-01

The Theory of Planned Behavior (TPB) has provided considerable insight into the public's intention to comply with many different health-related messages, but has not been applied previously to intention to comply with food safety recommendations and recalls ( Hallman & Cuite, 2010 ). Because food recalls can differ from other health messages in their urgency, timing, and cessation, the applicability of the TPB in this domain is unknown. The research reported here attempted to address this gap using a nationally representative consumer panel. Results showed that, consistent with the theory's predictions, attitudes and subjective norms were predictive of the intention to comply with a food recall message, with attitudes having a much greater impact on intent to comply than subjective norms. Perceived behavioral control failed to predict intention to comply. Implications of these results for health public relations and crisis communications and recommendations for future research were discussed.

Suicidal ideation and suicidal behavior according to the C-SSRS in a European cohort of Huntington's disease gene expansion carriers.

Science.gov (United States)

van Duijn, Erik; Vrijmoeth, Eslie M; Giltay, Erik J; Bernhard Landwehrmeyer, G

2018-03-01

Huntington's disease (HD) gene expansion carriers are at an increased risk of suicide, but so far, no studies have investigated the full spectrum of suicidality, including suicidal ideation, suicidal behavior and self-injurious behavior. We included 1451 HD gene expansion carriers (age 48.4 years (SD 14.0), 54.8% female) of the REGISTRY study of the European Huntington's Disease Network. Lifetime suicidal ideation and suicidal behavior were assessed with the Columbia-Suicidal Severity Rating Scale. Motor symptoms and disease stage were assessed using subscales of the Unified Huntington's Disease Rating Scale, and depressed mood and irritability were assessed by the Problem Behaviors Assessment. Lifetime passive suicidal ideation was reported by 21.2%. Participants in stage II showed the highest prevalence rate of suicidal ideation, while participants in stage IV/V showed the highest prevalence of suicidal behavior. A lifetime suicide attempt was reported by 6.5% of the HD gene expansion carriers. In multivariate regression analyses, both suicidal ideation and suicidal behavior were associated with a depressed mood, and to a lesser extend to irritability. Results may have been affected by denial or recall bias and no conclusions can be made about the temporal and causal relationships with depressed mood and irritability because of the cross-sectional analyses. Given the high prevalence of suicidal ideation and suicidal behavior in all stages of HD, it is important to screen HD gene expansion carriers for suicidal ideation and suicidal behavior on a regular basis in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.

Science.gov (United States)

Latimer, Caitlin S; Flanagan, Margaret E; Cimino, Patrick J; Jayadev, Suman; Davis, Marie; Hoffer, Zachary S; Montine, Thomas J; Gonzalez-Cuyar, Luis F; Bird, Thomas D; Keene, C Dirk

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington's disease (JHD), defined as HD arising before age 20, accounts for 5-10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington's disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. The neuropathologic changes of AOHD are well characterized, but there are fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy's clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD.

Orphan drugs in development for Huntington's disease: challenges and progress

Directory of Open Access Journals (Sweden)

Burgunder JM

2015-02-01

advanced strategies to develop novel treatments in Huntington's disease are examined. Keywords: Huntington's disease, symptomatic treatment, disease-modifying therapy

A Case of Juvenile Huntington Disease in a 6-Year-Old Boy

Directory of Open Access Journals (Sweden)

Jun-Sang Sunwoo

2010-10-01

Full Text Available Huntington disease is a neurodegenerative disorder distinguished by the triad of dominant inheritance, choreoathetosis and dementia, usually with onset in the fourth and fifth decades. It is caused by an unstable cytosine-adenine-guanine (CAG trinucleotide repeat expansion in the gene IT15 in locus 4p16.3. Juvenile HD that constitutes about 3% to 10% of all patients is clinically different from adult-onset form and characterized by a larger number of CAG repeats typically exceeding 60. We report a case of a 6-year-old boy with myoclonic seizure and 140 CAG repeats confirmed by molecular genetic analysis.

A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease

DEFF Research Database (Denmark)

Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J

2015-01-01

Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset....

Assessment of motor function, sensory motor gating and recognition memory in a novel BACHD transgenic rat model for Huntington disease

NARCIS (Netherlands)

Abada, Yah-se K.; Nguyen, Huu Phuc; Schreiber, Rudy; Ellenbroek, Bart

2013-01-01

Rationale: Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97

Willingness to Comply with Corporate Law: An Interdisciplinary Teaching Method in Higher Education

Directory of Open Access Journals (Sweden)

Rafael Robina Ramirez

2018-06-01

Full Text Available Using an innovation training project, an interdisciplinary cross-sectional teaching strategy was developed to enhance students’ willingness to comply with the law. Thirty-five business, finance and accounting teachers examined the effects of ethical education on 484 university students’ willingness to comply with corporate law. Ethical education was based on building students’ ethical decisions on three court judgments in the new Spanish Corporate Governance Code. The ethical training was carried out by developing and applying social justice counter arguments. This perspective allowed students to imagine what decisions other person could have taken if they had managed the company ethically. The results suggest that ethics education in higher education can improve the willingness to comply the law. This methodology can be applied to interdisciplinary departments teaching ethics in business, finance and accounting.

Council Districts

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Town of Cary, North Carolina — View the location of the Town of Cary’s four Town Council districts.Please note that one district, District A, is split into two geo-spatial areas. One area is in...

Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin

DEFF Research Database (Denmark)

Carroll, Jeffrey B; Warby, Simon C; Southwell, Amber L

2011-01-01

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild...

Sertraline and venlafaxine improves motor performance and neurobehavioral deficit in quinolinic acid induced Huntington's like symptoms in rats: Possible neurotransmitters modulation.

Science.gov (United States)

Gill, Jaskamal Singh; Jamwal, Sumit; Kumar, Puneet; Deshmukh, Rahul

2017-04-01

Huntington Disease is autosomal, fatal and progressive neurodegenerative disorder for which clinically available drugs offer only symptomatic relief. Emerging strides have indicated that antidepressants improve motor performance, restore neurotransmitters level, ameliorates striatal atrophy, increases BDNF level and may enhance neurogenesis. Therefore, we investigated sertraline and venlafaxine, clinically available drugs for depression with numerous neuroprotective properties, for their beneficial effects, if any, in quinolinic acid induced Huntington's like symptoms in rats. Rats were administered quinolinic acid (QA) (200 nmol/2μl saline) intrastriatal bilaterally on 0day. Sertraline and venlafaxine (10 and 20mg/kg, po) each were administered for 21days once a day. Motor performance was assessed using rotarod test, grip strength test, narrow beam walk test on weekly basis. On day 22, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH and Nitrite), neuroinflammation (TNF-α, IL-1β and IL-6) and neurochemical analysis (GABA, glutamate, norepinephrine, dopamine, serotonin, DOPAC, HVA and 5-HIAA). QA treatment significantly altered body weight, motor performance, oxidative defense (increased LPO, nitrite and decreased GSH), pro-inflammatory cytokines levels (TNF-α, IL-6 and IL-1β), neurochemical level (GABA, glutamate, nor-epinephrine, dopamine, serotonin, HVA, DOPAC, 5-HIAA). Sertraline and venlafaxine at selected doses significantly attenuated QA induced alterations in striatum. The present study suggests that modulation of monoamines level, normalization of GABA and glutamatergic signaling, anti-oxidant and anti-inflammatory properties could underlie the neuroprotective effect of sertraline and venlafaxine in QA induced Huntington's like symptoms. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Therapeutic strategies for circadian rhythm and sleep disturbances in Huntington disease.

Science.gov (United States)

van Wamelen, Daniel J; Roos, Raymund Ac; Aziz, Nasir A

2015-12-01

Aside from the well-known motor, cognitive and psychiatric signs and symptoms, Huntington disease (HD) is also frequently complicated by circadian rhythm and sleep disturbances. Despite the observation that these disturbances often precede motor onset and have a high prevalence, no studies are available in HD patients which assess potential treatments. In this review, we will briefly outline the nature of circadian rhythm and sleep disturbances in HD and subsequently focus on potential treatments based on findings in other neurodegenerative diseases with similarities to HD, such as Parkinson and Alzheimer disease. The most promising treatment options to date for circadian rhythm and sleep disruption in HD include melatonin (agonists) and bright light therapy, although further corroboration in clinical trials is warranted.

Controlled clinical trial of cannabidiol in Huntington's disease.

Science.gov (United States)

Consroe, P; Laguna, J; Allender, J; Snider, S; Stern, L; Sandyk, R; Kennedy, K; Schram, K

1991-11-01

Based on encouraging preliminary findings, cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease (HD). The effects of oral CBD (10 mg/kg/day for 6 weeks) and placebo (sesame oil for 6 weeks) were ascertained weekly under a double-blind, randomized cross-over design. A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant (p greater than 0.05) or clinically important differences. Correspondingly, plasma levels of CBD were assayed by GC/MS, and the weekly levels (mean range of 5.9 to 11.2 ng/ml) did not differ significantly over the 6 weeks of CBD administration. In summary, CBD, at an average daily dose of about 700 mg/day for 6 weeks, was neither symptomatically effective nor toxic, relative to placebo, in neuroleptic-free patients with HD.

7 CFR 635.4 - Failure to fully comply.

Science.gov (United States)

2010-01-01

... to participants who are determined by the Chief to have made a good faith effort to comply fully with... whether a participant acted in good faith and rendered substantial performance under paragraph (b) of this..., the Chief, or designee, may grant relief in accordance with § 635.5 if the participant made a good...

Swallowing endoscopy findings in Huntington's disease: a case report.

Science.gov (United States)

Alves, Thaís Coelho; Cola, Paula Cristina; Santos, Rarissa Rúbia Dallaqua Dos; Motonaga, Suely Mayumi; Silva, Roberta Gonçalves da

2016-01-01

Huntington's disease (HD) is a degenerative genetic disorder with autosomal-dominant transmission. The triad of symptoms of this disease consists of psychiatric disorders, jerky movements, and dementia. Oropharyngeal dysphagia, which is more evident with disease progression, is also present. Few studies have addressed the swallowing characteristics using objective analysis in this population. The purpose of this research was to describe the swallowing endoscopic findings of the pharyngeal phase in HD. This is a cross-sectional study addressing a clinical case which included two individuals of the same family, male, 32 and 63 years old, designated as individual A and individual B, with progression of the disease for five and 13 years, respectively. Consistent liquid, nectar, and puree were offered during the evaluation. There was presence of posterior oral spillage in liquid and nectar, small amount of pharyngeal residues, and no laryngeal penetration or aspiration in the individuals with HD in this study.

49 CFR 40.341 - Must service agents comply with DOT drug and alcohol testing requirements?

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2010-10-01

... Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Roles and Responsibilities of Service Agents § 40.341 Must service agents comply with DOT drug and alcohol testing... requirements of this part and the DOT agency drug and alcohol testing regulations. (b) If you do not comply...

15 CFR 700.73 - Notification of failure to comply.

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2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Notification of failure to comply. 700.73 Section 700.73 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE...

Altered selenium status in Huntington's disease: neuroprotection by selenite in the N171-82Q mouse model.

Science.gov (United States)

Lu, Zhen; Marks, Eileen; Chen, Jianfang; Moline, Jenna; Barrows, Lorraine; Raisbeck, Merl; Volitakis, Irene; Cherny, Robert A; Chopra, Vanita; Bush, Ashley I; Hersch, Steven; Fox, Jonathan H

2014-11-01

Disruption of redox homeostasis is a prominent feature in the pathogenesis of Huntington's disease (HD). Selenium an essential element nutrient that modulates redox pathways and has been reported to provide protection against both acute neurotoxicity (e.g. methamphetamine) and chronic neurodegeneration (e.g. tauopathy) in mice. The objective of our study was to investigate the effect of sodium selenite, an inorganic form of selenium, on behavioral, brain degeneration and biochemical outcomes in the N171-82Q Huntington's disease mouse model. HD mice, which were supplemented with sodium selenite from 6 to 14 weeks of age, demonstrated increased motor endurance, decreased loss of brain weight, decreased mutant huntingtin aggregate burden and decreased brain oxidized glutathione levels. Biochemical studies revealed that selenite treatment reverted HD-associated changes in liver selenium and plasma glutathione in N171-82Q mice and had effects on brain selenoprotein transcript expression. Further, we found decreased brain selenium content in human autopsy brain. Taken together, we demonstrate a decreased selenium phenotype in human and mouse HD and additionally show some protective effects of selenite in N171-82Q HD mice. Modification of selenium metabolism results in beneficial effects in mouse HD and thus may represent a therapeutic strategy. Copyright © 2014 Elsevier Inc. All rights reserved.

The role of the amygdala during emotional processing in Huntington's disease: from pre-manifest to late stage disease.

Science.gov (United States)

Mason, Sarah L; Zhang, Jiaxiang; Begeti, Faye; Guzman, Natalie Valle; Lazar, Alpar S; Rowe, James B; Barker, Roger A; Hampshire, Adam

2015-04-01

Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis. We investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntington's disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: "the Reading the Mind in the Eyes Test" which has been previously been shown to be amygdala dependent. Psychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, pneural networks underlying social cognition and emotional processing can be detected prior to clinical diagnosis in Huntington's disease. Connectivity between the amygdala and other brain regions is impacted by the disease process in pre-manifest HD and may therefore be a useful way of identifying participants who are approaching a clinical diagnosis

Mitochondrial Metabolism in a Large-Animal Model of Huntington Disease: The Hunt for Biomarkers in the Spermatozoa of Presymptomatic Minipigs

Czech Academy of Sciences Publication Activity Database

Křížová, J.; Štufková, H.; Rodinová, M.; Mačáková, Monika; Bohuslavová, Božena; Vidinská, Daniela; Klíma, Jiří; Ellederová, Zdeňka; Pavlok, Antonín; Howland, D. S.; Zeman, J.; Motlík, Jan; Hansíková, H.

2017-01-01

Roč. 17, 4-5 (2017), s. 213-226 ISSN 1660-2854 R&D Projects: GA MŠk 7F14308; GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : Huntington disease * large animal model * mutant huntingtin Subject RIV: EA - Cell Biology OBOR OECD: Cell biology Impact factor: 2.842, year: 2016

Transgenic Rat Model of Huntington's Disease: A Histopathological Study and Correlations with Neurodegenerative Process in the Brain of HD Patients.

Czech Academy of Sciences Publication Activity Database

Mazurová, Y.; Anděrová, Miroslava; Němečková, I.; Bezrouk, A.

2014-01-01

Roč. 2014, Aug 03 (2014), s. 291531 ISSN 2314-6133 R&D Projects: GA ČR(CZ) GBP304/12/G069 Grant - others:GA MŠk(CZ) Prvouk P37 Institutional support: RVO:68378041 Keywords : Huntington's Disease * neurodegenerative process in the brain Subject RIV: FH - Neurology Impact factor: 1.579, year: 2014

19 CFR 10.431 - Failure to comply with requirements.

Science.gov (United States)

2010-04-01

... United States fails to comply with any requirement of this part. Such measures may include the imposition... Section 10.431 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. United States-Chile...

Assessing and Modulating Kynurenine Pathway Dynamics in Huntington's Disease: Focus on Kynurenine 3-Monooxygenase.

Science.gov (United States)

Sathyasaikumar, Korrapati V; Breda, Carlo; Schwarcz, Robert; Giorgini, Flaviano

2018-01-01

The link between disturbances in kynurenine pathway (KP) metabolism and Huntington's disease (HD) pathogenesis has been explored for a number of years. Several novel genetic and pharmacological tools have recently been developed to modulate key regulatory steps in the KP such as the reaction catalyzed by the enzyme kynurenine 3-monooxygenase (KMO). This insight has offered new options for exploring the mechanistic link between this metabolic pathway and HD, and provided novel opportunities for the development of candidate drug-like compounds. Here, we present an overview of the field, focusing on some novel approaches for interrogating the pathway experimentally.

Decreased mitochondrial density and ultrastructural changes of mitochondria in cultivated skin fibroblasts of patients with Huntington´s disease

Czech Academy of Sciences Publication Activity Database

Rodinová, M.; Marková, M.; Kratochvílová, H.; Kučerová, I.; Tesařová, M.; Lišková, Irena; Klempíř, J.; Roth, J.; Zeman, J.; Hansíková, H.

2015-01-01

Roč. 78, Suppl 2 (2015), s. 20-21 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * fibroblasts * mitochondrial ultrastructure Subject RIV: FH - Neurology

40 CFR 267.90 - Who must comply with this section?

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2010-07-01

... PERMIT Releases from Solid Waste Management Units § 267.90 Who must comply with this section? This subpart applies to you if you own or operate a facility that treats or stores hazardous waste under a 40...

12 CFR 714.10 - What other laws must you comply with when engaged in leasing?

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2010-01-01

..., or provide the member with greater protections or benefits than the Consumer Leasing Act. You are... leasing? You must comply with the Consumer Leasing Act, 15 U.S.C. 1667-67f, and its implementing regulation, Regulation M, 12 CFR part 213. You must comply with state laws on consumer leasing, but only to...

23 CFR 661.3 - Who must comply with this regulation?

Science.gov (United States)

2010-04-01

... authorities must comply to participate in the IRRBP by applying for preliminary engineering (PE), construction, and construction engineering (CE) activities for the replacement or rehabilitation of structurally....3 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC...

49 CFR 229.9 - Movement of non-complying locomotives.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Movement of non-complying locomotives. 229.9... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS General § 229.9 Movement of non... restrictions necessary for safely conducting the movement; (2)(i) The engineer in charge of the movement of the...

Haplotype-based stratification of Huntington's disease.

Science.gov (United States)

Chao, Michael J; Gillis, Tammy; Atwal, Ranjit S; Mysore, Jayalakshmi Srinidhi; Arjomand, Jamshid; Harold, Denise; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F; Lee, Jong-Min

2017-11-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat in HTT, resulting in an extended polyglutamine tract in huntingtin. We and others have previously determined that the HD-causing expansion occurs on multiple different haplotype backbones, reflecting more than one ancestral origin of the same type of mutation. In view of the therapeutic potential of mutant allele-specific gene silencing, we have compared and integrated two major systems of HTT haplotype definition, combining data from 74 sequence variants to identify the most frequent disease-associated and control chromosome backbones and revealing that there is potential for additional resolution of HD haplotypes. We have used the large collection of 4078 heterozygous HD subjects analyzed in our recent genome-wide association study of HD age at onset to estimate the frequency of these haplotypes in European subjects, finding that common genetic variation at HTT can distinguish the normal and CAG-expanded chromosomes for more than 95% of European HD individuals. As a resource for the HD research community, we have also determined the haplotypes present in a series of publicly available HD subject-derived fibroblasts, induced pluripotent cells, and embryonic stem cells in order to facilitate efforts to develop inclusive methods of allele-specific HTT silencing applicable to most HD patients. Our data providing genetic guidance for therapeutic gene-based targeting will significantly contribute to the developments of rational treatments and implementation of precision medicine in HD.

Huntington Disease - principles and practice of nutritional management.

Science.gov (United States)

Zukiewicz-Sobczak, Wioletta; Król, Renata; Wróblewska, Paula; Piątek, Jacek; Gibas-Dorna, Magdalena

2014-01-01

Huntington disease (HD) is a degenerative brain disease clinically manifested by the characteristic triad: physical symptoms including involuntary movements and poor coordination, cognitive changes with less ability to organize routine tasks, and some emotional and behavioral disturbances. For patients with HD, feeding is one of the problems they have to face. People with HD often have lower than average body weight and struggle with malnutrition. As a part of therapy, good nutrition is an intervention maintaining health and functional ability for maximally prolonged time. In the early stages of HD, small amounts of blenderized foods given orally are recommended. In more advanced stages, enteral nutrition is essential using gastric, or jejunal tubes for short term. Most severe cases require gastrostomy or gastrojejunostomy. Although enteral feeding is well tolerated by most of the patients, a number of complications may occur, including damage to the nose, pharynx, or esophagus, aspiration pneumonia, sinusitis, metabolic imbalances due to improper nutrient and fluid supply, adverse effects affecting gastrointestinal system, and refeeding syndrome. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

District heating in Switzerland

International Nuclear Information System (INIS)

Herzog, F.

1991-01-01

District heating has been used in Switzerland for more than 50 years. Its share of the heat market is less than 3% today. An analysis of the use of district heating in various European countries shows that a high share of district heating in the heat market is always dependent on ideal conditions for its use. Market prospects and possible future developments in the use of district heating in Switzerland are described in this paper. The main Swiss producers and distributors of district heating are members of the Association of District Heating Producers and Distributors. This association supports the installation of district heating facilities where ecological, energetical and economic aspects indicate that district heating would be a good solution. (author) 2 tabs., 6 refs

Exploring Genetic Factors Involved in Huntington Disease Age of Onset

DEFF Research Database (Denmark)

Valcárcel-Ocete, Leire; Alkorta-Aranburu, Gorka; Iriondo, Mikel

2015-01-01

age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample......Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim...... of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms...

Stimulating neural plasticity with real-time fMRI neurofeedback in Huntington's disease: A proof of concept study.

Science.gov (United States)

Papoutsi, Marina; Weiskopf, Nikolaus; Langbehn, Douglas; Reilmann, Ralf; Rees, Geraint; Tabrizi, Sarah J

2018-03-01

Novel methods that stimulate neuroplasticity are increasingly being studied to treat neurological and psychiatric conditions. We sought to determine whether real-time fMRI neurofeedback training is feasible in Huntington's disease (HD), and assess any factors that contribute to its effectiveness. In this proof-of-concept study, we used this technique to train 10 patients with HD to volitionally regulate the activity of their supplementary motor area (SMA). We collected detailed behavioral and neuroimaging data before and after training to examine changes of brain function and structure, and cognitive and motor performance. We found that patients overall learned to increase activity of the target region during training with variable effects on cognitive and motor behavior. Improved cognitive and motor performance after training predicted increases in pre-SMA grey matter volume, fMRI activity in the left putamen, and increased SMA-left putamen functional connectivity. Although we did not directly target the putamen and corticostriatal connectivity during neurofeedback training, our results suggest that training the SMA can lead to regulation of associated networks with beneficial effects in behavior. We conclude that neurofeedback training can induce plasticity in patients with Huntington's disease despite the presence of neurodegeneration, and the effects of training a single region may engage other regions and circuits implicated in disease pathology. © 2017 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

Cognitive change in patients with Huntington disease on the Repeatable Battery for the Assessment of Neuropsychological Status.

Science.gov (United States)

Beglinger, Leigh J; Duff, Kevin; Allison, Jessica; Theriault, Danielle; O'Rourke, Justin J F; Leserman, Anne; Paulsen, Jane S

2010-07-01

Huntington disease (HD) is a neurodegenerative disease associated with cognitive, motor, and psychiatric deterioration over time. Although there is currently no cure for HD, there has been a surge of clinical trials available to patients with HD over the past 5 years. However, cognitive measures have generally been lacking from these trials. A brief, repeatable neuropsychological battery is needed to assess cognitive endpoints. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) may be useful for assessing change in interventional studies or for clinical monitoring. A total of 38 patients with HD were assessed using the RBANS, other cognitive tests, and the standardized HD battery (Unified Huntington's Disease Rating Scale, UHDRS) at two clinic visits approximately 16 months apart. The RBANS Attention Index, as well as individual subtest scores on Coding, Digit Span, List Recognition, Figure Copy, and Figure Recall all declined significantly over this interval. Performance on the UHDRS cognitive tests (Symbol Digit Modalities; Stroop Color, and Stroop Word) also declined, as did functional capacity. Results suggest that cognitive changes were detected both on established cognitive tasks used in HD research and on the RBANS in patients with measurable functional decline. The RBANS provided additional information about other cognitive domains affected (e.g., memory) and may be a useful measure for tracking longitudinal change.

The functional implications of motor, cognitive, psychiatric, and social problem-solving states in Huntington's disease.

Science.gov (United States)

Van Liew, Charles; Gluhm, Shea; Goldstein, Jody; Cronan, Terry A; Corey-Bloom, Jody

2013-01-01

Huntington's disease (HD) is a genetic, neurodegenerative disorder characterized by motor, cognitive, and psychiatric dysfunction. In HD, the inability to solve problems successfully affects not only disease coping, but also interpersonal relationships, judgment, and independent living. The aim of the present study was to examine social problem-solving (SPS) in well-characterized HD and at-risk (AR) individuals and to examine its unique and conjoint effects with motor, cognitive, and psychiatric states on functional ratings. Sixty-three participants, 31 HD and 32 gene-positive AR, were included in the study. Participants completed the Social Problem-Solving Inventory-Revised: Long (SPSI-R:L), a 52-item, reliable, standardized measure of SPS. Items are aggregated under five scales (Positive, Negative, and Rational Problem-Solving; Impulsivity/Carelessness and Avoidance Styles). Participants also completed the Unified Huntington's Disease Rating Scale functional, behavioral, and cognitive assessments, as well as additional neuropsychological examinations and the Symptom Checklist-90-Revised (SCL-90R). A structural equation model was used to examine the effects of motor, cognitive, psychiatric, and SPS states on functionality. The multifactor structural model fit well descriptively. Cognitive and motor states uniquely and significantly predicted function in HD; however, neither psychiatric nor SPS states did. SPS was, however, significantly related to motor, cognitive, and psychiatric states, suggesting that it may bridge the correlative gap between psychiatric and cognitive states in HD. SPS may be worth assessing in conjunction with the standard gamut of clinical assessments in HD. Suggestions for future research and implications for patients, families, caregivers, and clinicians are discussed.

20 CFR 416.1326 - Suspension for failure to comply with treatment for drug addiction or alcoholism.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Suspension for failure to comply with treatment for drug addiction or alcoholism. 416.1326 Section 416.1326 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Suspensions and Terminations § 416.1326 Suspension for failure to comply...

Health-related quality of life and unmet healthcare needs in Huntington's disease.

Science.gov (United States)

van Walsem, Marleen R; Howe, Emilie I; Ruud, Gunvor A; Frich, Jan C; Andelic, Nada

2017-01-07

Huntington's disease (HD) is a rare neurodegenerative disorder with a prevalence of 6 per 100.000. Despite increasing research activity on HD, evidence on healthcare utilization, patients' needs for healthcare services and Health-Related Quality of Life (HRQoL) is still sparse. The present study describes HRQoL in a Norwegian cohort of HD patients, and assesses associations between unmet healthcare and social support service needs and HRQoL. In this cross-sectional population-based study, 84 patients with a clinical diagnosis of HD living in the South-East of Norway completed the HRQoL questionnaire EuroQol, EQ-5D-3L. Unmet needs for healthcare and social support services were assessed by the Needs and Provision Complexity Scale (NPCS). Furthermore, functional ability was determined using the Unified Huntington's Disease Rating Scale (UHDRS) Functional assessment scales. Socio-demographics (age, gender, marital status, occupation, residence, housing situation) and clinical characteristics (disease duration, total functional capacity, comorbidity) were also recorded. Descriptive statistics were used to describe the patients' HRQoL. Regression analyses were conducted in order to investigate the relationship between unmet healthcare needs and self-reported HRQoL. The patients were divided across five disease stages as follows: Stage I: n = 12 (14%), Stage II: n = 22 (27%), Stage III: n = 19 (23%), Stage IV: n = 14 (16%), and Stage V: n = 17 (20%). Overall HRQoL was lowest in patients with advanced disease (Stages IV and V), while patients in the middle phase (Stage III) showed the most varied health profile for the five EQ-5D-3L dimensions. The regression model including level of unmet needs, clinical characteristics and demographics (age and education) accounted for 42% of variance in HRQoL. A higher level of unmet needs was associated with lower HRQoL (β value - 0.228; p = 0.018) whereas a better total functional capacity corresponded to

Hyperfine structure studies with the COMPLIS facility

CERN Document Server

Crawford, J E; Le Blanc, F; Lunney, M D; Obert, J; Oms, J; Putaux, J C; Roussière, B; Sauvage, J; Zemlyanoi, S G; Verney, D; Pinard, J; Cabaret, L A; Duong, H T; Huber, G; Krieg, M; Sebastian, V; Girod, M; Peru, S; Genevey, J; Ibrahim, F; Lettry, Jacques

1998-01-01

COMPLIS is an experimental facility designed to carry out spectroscopic studies on radioisotopes produced by disintegration of elements available at CERN's Booster-ISOLDE on-line isotope separator. During recent series of experimental runs, hyperfine structure measurements have yielded information on nuclear moments and deformations of platinum and iridium isotopes, For the first time, population by alpha -decay from Hg was exploited to investigate /sup 178/-/sup 181/Pt-the most neutron-deficient Pt isotopes yet studied. Successful measurements have recently been carried out on /sup 182-189/Ir. (10 refs).

Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington's Disease Mouse Model R6/2.

Science.gov (United States)

Nielsen, Signe Marie Borch; Hasholt, Lis; Nørremølle, Anne; Josefsen, Knud

2015-04-20

Huntington's disease (HD) is a neurodegenerative illness, where selective neuronal loss in the brain caused by expression of mutant huntingtin protein leads to motor dysfunction and cognitive decline in addition to peripheral metabolic changes. In this study we confirm our previous observation of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indicating a potential to explore this defect in a biomarker context. Moreover, R6/2 animals displayed lower blood glucose levels during prolonged fasting compared to wild type animals.

Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes

DEFF Research Database (Denmark)

Vinther-Jensen, T; Nielsen, Troels Tolstrup; Budtz-Jørgensen, E

2016-01-01

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has......-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance...

Association Between Motor Symptoms and Brain Metabolism in Early Huntington Disease.

Science.gov (United States)

Gaura, Véronique; Lavisse, Sonia; Payoux, Pierre; Goldman, Serge; Verny, Christophe; Krystkowiak, Pierre; Damier, Philippe; Supiot, Frédéric; Bachoud-Levi, Anne-Catherine; Remy, Philippe

2017-09-01

Brain hypometabolism is associated with the clinical consequences of the degenerative process, but little is known about regional hypermetabolism, sometimes observed in the brain of patients with clinically manifest Huntington disease (HD). Studying the role of regional hypermetabolism is needed to better understand its interaction with the motor symptoms of the disease. To investigate the association between brain hypometabolism and hypermetabolism with motor scores of patients with early HD. This study started in 2001, and analysis was completed in 2016. Sixty symptomatic patients with HD and 15 healthy age-matched control individuals underwent positron emission tomography to measure cerebral metabolism in this cross-sectional study. They also underwent the Unified Huntington's Disease Rating Scale motor test, and 2 subscores were extracted: (1) a hyperkinetic score, combining dystonia and chorea, and (2) a hypokinetic score, combining bradykinesia and rigidity. Statistical parametric mapping software (SPM5) was used to identify all hypo- and hypermetabolic regions in patients with HD relative to control individuals. Correlation analyses (P motor subscores and brain metabolic values were performed for regions with significant hypometabolism and hypermetabolism. Among 60 patients with HD, 22 were women (36.7%), and the mean (SD) age was 44.6 (7.6) years. Of the 15 control individuals, 7 were women (46.7%), and the mean (SD) age was 42.2 (7.3) years. In statistical parametric mapping, striatal hypometabolism was significantly correlated with the severity of all motor scores. Hypermetabolism was negatively correlated only with hypokinetic scores in the cuneus (z score = 3.95, P motor scores were associated with higher metabolic values in the inferior parietal lobule, anterior cingulate, inferior temporal lobule, the dentate nucleus, and the cerebellar lobules IV/V, VI, and VIII bilaterally corresponding to the motor regions of the cerebellum (z score = 3

Striatal hypometabolism in premanifest and manifest Huntington's disease patients

Energy Technology Data Exchange (ETDEWEB)

Lopez-Mora, Diego Alfonso; Camacho, Valle; Fernandez, Alejandro; Montes, Alberto; Carrio, Ignasi [Autonomous University of Barcelona, Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Perez-Perez, Jesus; Martinez-Horta, Sauel; Kulisevsky, Jaime [Autonomous University of Barcelona, Movement Disorders Unit, Neurology Department, Hospital Sant Pau, Barcelona (Spain); Sampedro, Frederic [University of Barcelona, Barcelona (Spain); Lozano-Martinez, Gloria Andrea; Gomez-Anson, Beatriz [Autonomous University of Barcelona, Neuroradiology, Radiology Department, Hospital Sant Pau, Barcelona (Spain)

2016-11-15

To assess metabolic changes in cerebral {sup 18}F-FDG PET/CT in premanifest and manifest Huntington's disease (HD) subjects compared to a control group and to correlate {sup 18}F-FDG uptake patterns with different disease stages. Thirty-three gene-expanded carriers (Eight males; mean age: 43 y/o; CAG > 39) were prospectively included. Based on the Unified Huntington's Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain {sup 18}F-FDG PET/CT and MRI. {sup 18}F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox. Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of {sup 18}F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50 voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50 voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50 voxels). {sup 18}F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. {sup 18}F-FDG PET/CT appears as a

Empowerment Zones and Enterprise Districts - MDC_CommunityDevelopmentDistrict

Data.gov (United States)

NSGIC Local Govt | GIS Inventory — Community Development Districts (CDDs) are special taxing districts or local units of special-purpose government. A CDD may charge separate non-ad valorem special...

District nurse training

OpenAIRE

Elliott, Arnold; Freeling, Paul; Owen, John

1980-01-01

Training for district nursing is being reviewed. By 1981 district nurses will have a new administrative structure, a new curriculum, and a new examination. Training for nursing, like that for general practice, is to become mandatory. The history of the development of district nurse training is briefly described.

46 CFR 308.516 - Failure to comply with Clause 21.

Science.gov (United States)

2010-10-01

....516 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.516 Failure to comply with Clause 21. (a) If the assured willfully fails to maintain a collateral deposit fund or a surety bond in...

Assessing Banks’ Cost of Complying with Basel II

OpenAIRE

David VanHoose

2007-01-01

This policy brief assesses the implications of Basel II for bank regulatory compliance costs. In spite of widespread complaints by bankers about the costs of complying with Basel II rules, the academic literature has given surprisingly little attention to quantifying these costs. The brief discusses estimates of Basel II compliance costs based on commonly utilized rules of thumb and on survey data collected by the Office of the Comptroller of the Currency (OCC). In addition, it utilizes OCC b...

40 CFR 63.8055 - How do I comply with a weight percent HAP limit in coating products?

Science.gov (United States)

2010-07-01

... HAP limit in coating products? 63.8055 Section 63.8055 Protection of Environment ENVIRONMENTAL...: Miscellaneous Coating Manufacturing Alternative Means of Compliance § 63.8055 How do I comply with a weight percent HAP limit in coating products? (a) As an alternative to complying with the requirements in Table 1...

Neuropsychological correlates of brain atrophy in Huntington's disease: a magnetic resonance imaging study

International Nuclear Information System (INIS)

Starkstein, S.E.; Brandt, J.; Bylsma, F.; Peyser, C.; Folstein, M.; Folstein, S.E.

1992-01-01

Magnetic resonance imaging and a comprehensive cognitive evaluation were carried out in a series of 29 patients with mild to moderate Huntington's disease (HD). A factor analysis of the neuropsychological test scores provided three factors: A memory/speed-of-processing factor, a 'frontal' factor, and a response inhibition factor. The memory/speed factor correlated significantly with measures of caudate atrophy, frontal atrophy, and atrophy of the left (but not the right) sylvian cistern. There were no significant correlations between the 'frontal' or response inhibition factors and measures of cortical or subcortical brain atrophy. Our findings confirm that subcortical atrophy is significantly correlated with specific cognitive deficits in HD, and demonstrate that cortical atrophy also has important association with the cognitive deficits of patients with HD. (orig.)

Social Cognition, Executive Functions and Self-Report of Psychological Distress in Huntington's Disease

DEFF Research Database (Denmark)

Larsen, Ida Unmack; Vinther-Jensen, Tua; Nielsen, Jørgen Erik

2016-01-01

OBJECTIVE: Huntington's disease (HD) is characterized by motor symptoms, psychiatric symptoms and cognitive impairment in, inter alia, executive functions and social cognition. The aim of this study was to investigate the relationship between subjective feeling of psychological distress using...... a self-report questionnaire and performances on tests of executive functions and social cognition in a large consecutive cohort of HD patients. METHOD: 50 manifest HD patients were tested in social cognition and executive functions and each answered a self-report questionnaire about current status...... psychological distress was significantly associated with worse performances on social cognitive tests (mean absolute correlation .34) and that there were no significant correlations between perceived psychological distress and performance on tests of executive functions. The correlations between perceived...

Medical management of motor manifestations of Huntington disease.

Science.gov (United States)

McCusker, Elizabeth A; Loy, Clement T

2017-01-01

The motor and movement disorders of Huntington disease (HD) are managed in the context of the other disease features. Chorea and dystonia are the most common HD-associated movement disorders, and they can be assessed on research rating scales. However other motor manifestations have a significant impact. In particular, dysphagia influences choice and tolerance of treatment for the movement disorder, as will comorbidities, patient awareness, and distress related to the motor feature or movement. Treatment for other disease features may aggravate the motor disorder, e.g., increased swallowing difficulty associated with antipsychotic agents. Basic principles in deciding to institute a treatment are outlined as well as treatment of specific motor manifestations and movements. There is a paucity of evidence to support the treatments available for the motor disorder, with only one agent with class 1 evidence, tetrabenazine, for chorea. There are, however, treatments informed by expert opinion which reflect the management of a wider HD phenotype than that represented in clinical trials. Some treatments are based on evidence from use in other conditions. Medical management is usually undertaken later in the disease with concurrent nonmedical interventions after multidisciplinary assessments. Medication review with HD progression is essential. Copyright © 2017 Elsevier B.V. All rights reserved.

R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

Science.gov (United States)

Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

2012-05-09

A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

Oxidative Stress and Huntington's Disease: The Good, The Bad, and The Ugly.

Science.gov (United States)

Kumar, Amit; Ratan, Rajiv R

2016-10-01

Redox homeostasis is crucial for proper cellular functions, including receptor tyrosine kinase signaling, protein folding, and xenobiotic detoxification. Under basal conditions, there is a balance between oxidants and antioxidants. This balance facilitates the ability of oxidants, such as reactive oxygen species, to play critical regulatory functions through a direct modification of a small number of amino acids (e.g. cysteine) on signaling proteins. These signaling functions leverage tight spatial, amplitude, and temporal control of oxidant concentrations. However, when oxidants overwhelm the antioxidant capacity, they lead to a harmful condition of oxidative stress. Oxidative stress has long been held to be one of the key players in disease progression for Huntington's disease (HD). In this review, we will critically review this evidence, drawing some intermediate conclusions, and ultimately provide a framework for thinking about the role of oxidative stress in the pathophysiology of HD.

Cognitive and behavioral changes in Huntington disease before diagnosis.

Science.gov (United States)

Paulsen, Jane S; Miller, Amanda C; Hayes, Terry; Shaw, Emily

2017-01-01

Phenotypic manifestations of Huntington disease (HD) can be detected at least 15 years prior to the time when a motor diagnosis is given. Advances in clinical care and future research will require consistent use of HD definitions and HD premanifest (prodromal) stages being used across clinics, sites, and countries. Cognitive and behavioral (psychiatric) changes in HD are summarized and implications for ongoing advancement in our knowledge of prodromal HD are suggested. The earliest detected cognitive changes are observed in the Symbol Digit Modalities Test, Stroop Interference, Stroop Color and Word Test-interference condition, and Trail Making Test. Cognitive changes in the middle and near motor diagnostic stages of prodromal HD involve nearly every cognitive test administered and the greatest changes over time (i.e., slopes) are found in those prodromal HD participants who are nearest to motor diagnosis. Psychiatric changes demonstrate significant worsening over time and remain elevated compared with healthy controls throughout the prodromal disease course. Psychiatric and behavior changes in prodromal HD are much lower than that obtained using cognitive assessment, although the psychiatric and behavioral changes represent symptoms most debilitating to independent capacity and wellness. Copyright © 2017 Elsevier B.V. All rights reserved.

45 CFR 1201.9 - Considerations in determining whether the Corporation will comply with a demand or request.

Science.gov (United States)

2010-10-01

... determining whether the Corporation will comply with a demand or request. (a) In deciding whether to comply... discovery or the rules of procedure governing the case or matter in which the demand arose; (2) Whether... conduct of official business; (5) The need to avoid spending the time and money of the United States for...

7 CFR 917.14 - District.

Science.gov (United States)

2010-01-01

... District. (g) Contra Costa District includes and consists of Contra Costa County. (h) Santa Clara District... Ventura County. (l) Stockton District includes and consists of San Joaquin County, Amador County...

Care of patients with Huntington's disease in South America: a survey

Directory of Open Access Journals (Sweden)

Ricardo Oliveira Horta Maciel

2013-06-01

Full Text Available Huntington's disease (HD is a rare neurodegenerative disease with a multitude of symptoms, which requires access to specialized multidisciplinary care for adequate management. The aim of this study was to survey the characteristics of care in various HD centers in South America (SA. Methods A questionnaire was sent to 24 centers involved in the care for HD patients in SA. Results Of the total 24 centers, 19 (79.2% are academic units. The majority of centers (62.5% are general movement disorders clinics. Multidisciplinary care is available in 19 (79.2% centers and in 20 (83.3% care is provided free of charge. Genetic testing and counseling are available in 25 and 66.6% of centers, respectively. The majority of centers (83.3% have no institutional support for end-stage care. Conclusions Although HD centers in SA are committed to providing multidisciplinary care, access to genetic counseling and end-stage care are lacking in most centers.

Is gardening a stimulating activity for people with advanced Huntington's disease?

Science.gov (United States)

Spring, Josephine A; Viera, Marc; Bowen, Ceri; Marsh, Nicola

2014-11-01

This study evaluated adapted gardening as an activity for people with advanced Huntington's disease (HD) and explored its therapeutic aspects. Visitors and staff completed a questionnaire and participated in structured interviews to capture further information, whereas a pictorial questionnaire was designed for residents with communication difficulties. Staff reported that gardening was a constructive, outdoor activity that promoted social interaction, physical activity including functional movement and posed cognitive challenges. Half the staff thought the activity was problem free and a third used the garden for therapy. Visitors used the garden to meet with residents socially. Despite their disabilities, HD clients enjoyed growing flourishing flowers and vegetables, labelling plants, being outside in the sun and the quiet of the garden. The garden is valued by all three groups. The study demonstrates the adapted method of gardening is a stimulating and enjoyable activity for people with advanced HD. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Gardening with Huntington's disease clients--creating a programme of winter activities.

Science.gov (United States)

Spring, Josephine Anne; Baker, Mark; Dauya, Loreane; Ewemade, Ivie; Marsh, Nicola; Patel, Prina; Scott, Adrienne; Stoy, Nicholas; Turner, Hannah; Viera, Marc; Will, Diana

2011-01-01

A programme of garden-related indoor activities was developed to sustain a gardening group for people with mid to late stage Huntington's disease during the winter. The activities were devised by the horticulturist, working empirically, involving the services occupational therapist, physiotherapist, occupational therapy art technician, computer room, recreation and leisure staff. The programme was strongly supported by the nursing and care staff. Feedback on the effectiveness of the activities was sought from the clients, team members and unit staff. The clients' interest in gardening was sustained by a multidisciplinary programme of indoor growing and using plant products in creative activities, computing and group projects. The clients enjoyed all activities except one that they said lacked contact with plants. The inexpensive programme of activities enabled creativity and self-expression, stimulated social contact and helped with therapeutic goals of the clients. In addition, it engaged the multi-disciplinary team and the unit staff, was practical and enhanced the environment.

Legislative Districts, Four layers - One State Assembly district, one State Senate district, one US House of Rep district, and one US Senate district showing the locations in the County of Polk, WI., Published in 2007, 1:24000 (1in=2000ft) scale, Polk County Government.

Data.gov (United States)

NSGIC Local Govt | GIS Inventory — Legislative Districts dataset current as of 2007. Four layers - One State Assembly district, one State Senate district, one US House of Rep district, and one US...

State and district policy influences on district-wide elementary and middle school physical education practices.

Science.gov (United States)

Chriqui, Jamie F; Eyler, Amy; Carnoske, Cheryl; Slater, Sandy

2013-01-01

To examine the influence of state laws and district policies on district-wide elementary school and middle school practices related to physical education (PE) time and the percentage of moderate-to-vigorous physical activity (MVPA) time during PE. Multivariate, cross-sectional analysis of state laws, district wellness and PE policies, and district PE practices for school year 2010-2011 controlling for district-level urbanicity, region, size, race/ethnicity of students, and socioeconomic status and clustered on state. One hundred ninety-five public school districts located in 42 states. District-level PE coordinators for the included districts who responded to an online survey. Minutes and days of PE per week and percent time spent in MVPA during PE time. District PE coordinators reported significantly less PE time than national standards-82.9 and 189.6 minutes at the elementary school and middle school levels, respectively. Physical education was provided an average of 2.5 and 3.7 days per week, respectively; and the percentage of MVPA time in PE was 64.4% and 65.7%, respectively. At the elementary school level, districts in either states with laws governing PE time or in a state and district with a law/policy reported significantly more days of PE (0.63 and 0.67 additional days, respectively), and districts in states with PE time laws reported 18 more minutes of PE per week. At the middle school level, state laws were associated with 0.73 more days of PE per week. Neither state laws nor district policies were positively associated with percent MVPA time in PE. State laws and district policies can influence district-level PE practices-particularly those governing the frequency and duration of PE-although opportunities exist to strengthen PE-related laws, policies, and practices.

A Working Model for Complying with Accessibility Guidelines for Online Learning

Science.gov (United States)

Cifuentes, Lauren; Janney, Alexandra; Guerra, Lauran; Weir, Jennifer

2016-01-01

We describe our activities that emerged in the context of an Office of Distance Education and Learning Technologies' efforts to systematically and systemically address accessibility for online learning in order to comply with ethical principles, best practices, and laws. The activities include three overarching continuous tasks: strategically…

California Political Districts

Data.gov (United States)

California Natural Resource Agency — This is a series of district layers pertaining to California'spolitical districts, that are derived from the California State Senateand State Assembly information....

District nursing in Dominica

NARCIS (Netherlands)

Kolkman, PME; Luteijn, AJ; Nasiiro, RS; Bruney, [No Value; Smith, RJA; Meyboom-de Jong, B

1998-01-01

District nurses constitute the basis of the primary health care services in Dominica. All encounters of three district nurses were registered using the international classification of primary care. Information on other aspects of district nursing was collected by participating observation and the

Private Water Districts

Data.gov (United States)

California Natural Resource Agency — Private Water District boundaries are areas where private contracts provide water to the district in California. This database is designed as a regions polygon...

State Water Districts

Data.gov (United States)

California Natural Resource Agency — State Water Project District boundaries are areas where state contracts provide water to the district in California. This database is designed as a regions polygon...

Huntington's disease-like and ataxia syndromes: identification of a family with a de novo SCA17/TBP mutation

DEFF Research Database (Denmark)

Bech, Sara; Petersen, Thor; Nørremølle, Anne

2010-01-01

The autosomal dominant spinocerebellar ataxias, commonly referred to as SCAs, are clinically and genetically heterogeneous neurodegenerative disorders. Twenty-eight genetic subtypes have been identified, of which 7 are caused by expansion of a CAG trinucleotide repeat that encodes a polyglutamine....... The patient's mother and father both carried normal range repeats, 38/38 and 33/39 respectively. Analysis of the repeat structures revealed that the expansion had occurred upon expansion of the longer paternal allele. We conclude that, however rare, SCA17 must be considered as a cause of Huntington's disease...

Características del habla, el lenguaje y la deglución en la enfermedad de Huntington

OpenAIRE

Camargo-Mendoza, Maryluz; Castillo-Triana, Nicolás; Fandiño-Cardona, Juan Miguel; Mateus-Moreno, Angélica; Moreno-Martínez, Mariana

2017-01-01

Resumen La enfermedad de Huntington (EH) ha sido descrita como una afección de causa genética producida por una mutación en la repetición de la secuencia de nucleótidos CAG (citosina-adenina-guanina). Según el estadio que curse la enfermedad, las personas pueden presentar dificultades en el habla, el lenguaje y la deglución. El propósito de este artículo es exponer con detalle dichas dificultades, así como su tratamiento fonoaudiológico. Se destaca que en el habla se encuentran característica...

Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease.

Science.gov (United States)

Koga, Hiroshi; Martinez-Vicente, Marta; Arias, Esperanza; Kaushik, Susmita; Sulzer, David; Cuervo, Ana Maria

2011-12-14

Autophagy contributes to the removal of prone-to-aggregate proteins, but in several instances these pathogenic proteins have been shown to interfere with autophagic activity. In the case of Huntington's disease (HD), a congenital neurodegenerative disorder resulting from mutation in the huntingtin protein, we have previously described that the mutant protein interferes with the ability of autophagic vacuoles to recognize cytosolic cargo. Growing evidence supports the existence of cross talk among autophagic pathways, suggesting the possibility of functional compensation when one of them is compromised. In this study, we have identified a compensatory upregulation of chaperone-mediated autophagy (CMA) in different cellular and mouse models of HD. Components of CMA, namely the lysosome-associated membrane protein type 2A (LAMP-2A) and lysosomal-hsc70, are markedly increased in HD models. The increase in LAMP-2A is achieved through both an increase in the stability of this protein at the lysosomal membrane and transcriptional upregulation of this splice variant of the lamp-2 gene. We propose that CMA activity increases in response to macroautophagic dysfunction in the early stages of HD, but that the efficiency of this compensatory mechanism may decrease with age and so contribute to cellular failure and the onset of pathological manifestations.

Huntington's disease in Greece: the experience of 14 years.

Science.gov (United States)

Panas, M; Karadima, G; Vassos, E; Kalfakis, N; Kladi, A; Christodoulou, K; Vassilopoulos, D

2011-12-01

A large scale genetic and epidemiological study of Huntington's disease (HD) was carried out in Greece from January 1995 to December 2008. Diagnostic testing was carried out in 461 symptomatic individuals, while 256 were tested for presymptomatic purposes. The diagnosis of HD with a CAG expansion ≥ 36 was confirmed in 278 symptomatic individuals. The prevalence of HD in Greece was estimated at approximately 2.5 to 5.4:100,000, while the mean minimum incidence was estimated at 2.2 to 4.4 per million per year. The molecular diagnosis of HD was confirmed in the majority of patients (84.4%) sent for confirmation. The false-positive cases 15.6% were characterized by the absence of a family history of HD and the presence of an atypical clinical picture. The uptake of predictive testing for HD was 8.6%. A prenatal test was requested in six pregnancies. The findings of our study do not differ significantly from those of similar studies from other European countries despite the relative genetic isolation of Greece. Of interest is the identification of clusters of HD in Greece. The presence or absence of a family history of HD should be interpreted cautiously, during the diagnostic process. © 2010 John Wiley & Sons A/S.

Reduction of IFNα and IL-10 in central nervous system and increase in peripheral IL-8 in transgenic porcine Huntington´s disease model

Czech Academy of Sciences Publication Activity Database

Kovářová, Hana; Valeková, Ivona; Jarkovská, Karla; Kotrčová, Eva; Motlík, Jan; Gadher, S. J.

2015-01-01

Roč. 78, Suppl 2 (2015), s. 10-11 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : porcine Huntington ´s disease model * IFNα * IL-10 Subject RIV: EB - Genetics ; Molecular Biology

Zero Energy Districts

Energy Technology Data Exchange (ETDEWEB)

Polly, Benjamin J [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

2018-05-04

This presentation shows how NREL is approaching Zero Energy Districts, including key opportunities, design strategies, and master planning concepts. The presentation also covers URBANopt, an advanced analytical platform for district that is being developed by NREL.

Care of patients with Huntington's disease in South America: a survey Cuidado de pacientes com doença de Huntington na América do Sul: um inquérito

Directory of Open Access Journals (Sweden)

Ricardo Oliveira Horta Maciel

2013-06-01

Full Text Available Huntington's disease (HD is a rare neurodegenerative disease with a multitude of symptoms, which requires access to specialized multidisciplinary care for adequate management. The aim of this study was to survey the characteristics of care in various HD centers in South America (SA. Methods A questionnaire was sent to 24 centers involved in the care for HD patients in SA. Results Of the total 24 centers, 19 (79.2% are academic units. The majority of centers (62.5% are general movement disorders clinics. Multidisciplinary care is available in 19 (79.2% centers and in 20 (83.3% care is provided free of charge. Genetic testing and counseling are available in 25 and 66.6% of centers, respectively. The majority of centers (83.3% have no institutional support for end-stage care. Conclusions Although HD centers in SA are committed to providing multidisciplinary care, access to genetic counseling and end-stage care are lacking in most centers. A doença de Huntington (DH é uma doença neurodegenerativa rara que requer tratamento multidisciplinar especializado para manejo adequado. O objetivo do presente trabalho foi pesquisar as características da assistência à saúde em centros de DH na América do Sul (AS. Métodos Um questionário foi enviado para 24 centros envolvidos no cuidado de pacientes com DH na AS. Resultados Dos 24 centros, 19 (79,2% são unidades acadêmicas. A maioria (62,5% são clínicas de distúrbios dos movimentos. Cuidado multidisciplinar é disponível em 19 (79,2% dos centros e em 20 (83,3%, o tratamento é gratuito. O teste e o aconselhamento genético estão disponíveis em 25 e 66,6% dos centros, respectivamente. Não há suporte institucional para cuidado terminal em 83,3% dos centros. Conclusões Apesar dos centros de DH na AS terem compromisso com o provimento de cuidados multidisciplinares, o acesso a aconselhamento genético e a tratamento na fase terminal são falhos na maioria dos centros.

Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting

DEFF Research Database (Denmark)

Nielsen, Signe Marie Borch; Vinther-Jensen, Tua; Nielsen, Jørgen E.

2016-01-01

dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest......Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- A nd cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular...... and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity...

Early grey matter changes in structural covariance networks in Huntington's disease.

Science.gov (United States)

Coppen, Emma M; van der Grond, Jeroen; Hafkemeijer, Anne; Rombouts, Serge A R B; Roos, Raymund A C

2016-01-01

Progressive subcortical changes are known to occur in Huntington's disease (HD), a hereditary neurodegenerative disorder. Less is known about the occurrence and cohesion of whole brain grey matter changes in HD. We aimed to detect network integrity changes in grey matter structural covariance networks and examined relationships with clinical assessments. Structural magnetic resonance imaging data of premanifest HD ( n  = 30), HD patients (n = 30) and controls (n = 30) was used to identify ten structural covariance networks based on a novel technique using the co-variation of grey matter with independent component analysis in FSL. Group differences were studied controlling for age and gender. To explore whether our approach is effective in examining grey matter changes, regional voxel-based analysis was additionally performed. Premanifest HD and HD patients showed decreased network integrity in two networks compared to controls. One network included the caudate nucleus, precuneous and anterior cingulate cortex (in HD p  covariance might be a sensitive approach to reveal early grey matter changes, especially for premanifest HD.

Future Services for District Heating Solutions in Residential Districts

Directory of Open Access Journals (Sweden)

Hannele Ahvenniemi

2014-06-01

Full Text Available The underlying assumption of this study is that in order to retain the competitiveness while reaching for the EU targets regarding low-energy construction, district heating companies need to develop new business and service models. How district heating companies could broaden their perspective and switch to a more service-oriented way of thinking is a key interest of our research. The used methods in our study are house builder interviews and a questionnaire. With the help of these methods we discussed the potential interest in heating related services acquiring a comprehensive understanding of the customer needs. The results indicate the importance of certain criteria when choosing the heating system in households: easiness, comfort and affordability seem to dominate the house builders’ preferences. Also environmental awareness seems to be for many an important factor when making a decision about the heating of the house. Altogether, based on the results of this study, we suggest that the prospects of district heating could benefit from highlighting certain aspects and strengths in the future. District heating companies need to increase flexibility, readiness to adopt new services, to invest in new marketing strategies and improving the communication skills.

Perturbations in the p53/miR-34a/SIRT1 pathway in the R6/2 Huntington's disease model

DEFF Research Database (Denmark)

Reynolds, Regina Hertfelder; Petersen, Maria Hvidberg; Willert, Cecilie Wennemoes

2018-01-01

The three factors, p53, the microRNA-34 family and Sirtuin 1 (SIRT1), interact in a positive feedback loop involved in cell cycle progression, cellular senescence and apoptosis. Each factor in this triad has roles in metabolic regulation, maintenance of mitochondrial function, and regulation...... of brain-derived neurotrophic factor (BDNF). Thus, this regulatory network holds potential importance for the pathophysiology of Huntington's disease (HD), an inherited neurodegenerative disorder in which both mitochondrial dysfunction and impaired neurotrophic signalling are observed. We investigated...

Nankana West District of Ghana

African Journals Online (AJOL)

Agribotix GCS 077

Local governments in Ghana play very important roles with actors in the ... Metropolitan, Municipal and District Chief Executives (MMDCEs), the .... District Budget Officer, District Finance Officer, Presiding Member, members of the Works Sub-.

Total recognition discriminability in Huntington's and Alzheimer's disease.

Science.gov (United States)

Graves, Lisa V; Holden, Heather M; Delano-Wood, Lisa; Bondi, Mark W; Woods, Steven Paul; Corey-Bloom, Jody; Salmon, David P; Delis, Dean C; Gilbert, Paul E

2017-03-01

Both the original and second editions of the California Verbal Learning Test (CVLT) provide an index of total recognition discriminability (TRD) but respectively utilize nonparametric and parametric formulas to compute the index. However, the degree to which population differences in TRD may vary across applications of these nonparametric and parametric formulas has not been explored. We evaluated individuals with Huntington's disease (HD), individuals with Alzheimer's disease (AD), healthy middle-aged adults, and healthy older adults who were administered the CVLT-II. Yes/no recognition memory indices were generated, including raw nonparametric TRD scores (as used in CVLT-I) and raw and standardized parametric TRD scores (as used in CVLT-II), as well as false positive (FP) rates. Overall, the patient groups had significantly lower TRD scores than their comparison groups. The application of nonparametric and parametric formulas resulted in comparable effect sizes for all group comparisons on raw TRD scores. Relative to the HD group, the AD group showed comparable standardized parametric TRD scores (despite lower raw nonparametric and parametric TRD scores), whereas the previous CVLT literature has shown that standardized TRD scores are lower in AD than in HD. Possible explanations for the similarity in standardized parametric TRD scores in the HD and AD groups in the present study are discussed, with an emphasis on the importance of evaluating TRD scores in the context of other indices such as FP rates in an effort to fully capture recognition memory function using the CVLT-II.

Plasma homovanillic acid and prolactin in Huntington's disease.

Science.gov (United States)

Markianos, Manolis; Panas, Marios; Kalfakis, Nikos; Vassilopoulos, Dimitrios

2009-05-01

Dopaminergic activity is expected to be altered in patients with Huntington's disease (HD) and be related to factors like duration and severity of illness or patients' specific symptomatology like dementia, depression, or psychotic features. We assessed plasma homovanillic acid (pHVA) and plasma prolactin (pPRL), two correlates of dopaminergic activity, in 116 subjects with CAG repeats expansion in the HD gene, 26 presymptomatic (18 females) and 90 with overt symptomatology (43 females). Patients were evaluated using the Unified HD Rating Scale and the Total Functional Capacity Scale. Presence of dementia, depression, and psychotic features were also assessed. The age range of the patients was 22-83 years, duration of illness from 0.5 to 27 years, and CAG repeat number from 34 to 66. A group of 60 age and sex matched healthy subjects served as control group. Plasma PRL in subjects at risk and in neuroleptic-free patients, evaluated separately for males and females, did not differ from controls. Plasma HVA levels did not differ from controls in the group of presymptomatic subjects, but were significantly higher in the patients group. This increase was positively associated mainly with severity of illness and functional capacity of the patients, and not with presence of depression or dementia. Plasma HVA levels may be proven to be a peripheral index of disease progression. Reducing dopaminergic activity may have not only symptomatic, but also neuroprotective effects in HD.

Somatostatin receptor 1 and 5 double knockout mice mimic neurochemical changes of Huntington's disease transgenic mice.

Directory of Open Access Journals (Sweden)

Padmesh S Rajput

Full Text Available Selective degeneration of medium spiny neurons and preservation of medium sized aspiny interneurons in striatum has been implicated in excitotoxicity and pathophysiology of Huntington's disease (HD. However, the molecular mechanism for the selective sparing of medium sized aspiny neurons and vulnerability of projection neurons is still elusive. The pathological characteristic of HD is an extensive reduction of the striatal mass, affecting caudate putamen. Somatostatin (SST positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimic the model of HD. SST plays neuroprotective role in excitotoxicity and the biological effects of SST are mediated by five somatostatin receptor subtypes (SSTR1-5.To delineate subtype selective biological responses we have here investigated changes in SSTR1 and 5 double knockout mice brain and compared with HD transgenic mouse model (R6/2. Our study revealed significant loss of dopamine and cAMP regulated phosphoprotein of 32 kDa (DARPP-32 and comparable changes in SST, N-methyl-D-aspartic acid receptors subtypes, calbindin and brain nitric oxide synthase expression as well as in key signaling proteins including calpain, phospho-extracellular-signal-regulated kinases1/2, synapsin-IIa, protein kinase C-α and calcineurin in SSTR1/5(-/- and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidylinositol 3-kinases were strain specific. SSTR1/5 appears to be important in regulating NMDARs, DARPP-32 and signaling molecules in similar fashion as seen in HD transgenic mice.This is the first comprehensive description of disease related changes upon ablation of G- protein coupled receptor gene. Our results indicate that SST and SSTRs might play an important role in regulation of neurodegeneration and targeting this pathway can provide a novel insight in understanding the pathophysiology of Huntington's disease.

Map showing selected surface-water data for the Huntington 30 x 60-minute quadrangle, Utah

Science.gov (United States)

Price, Don

1984-01-01

This is one of a series of maps that describe the geology and related natural resources of the Huntington 30 x 60-minute quadrangle, Utah. Streamflow records used to compile this map were collected by the U.S. Geological Survey in cooperation with the Utah Department of Natural Resources, Division of Water Rights, and the Utah Department of Transportation. The principal runoff-producing area shown on the map was delineated from a work map (scale 1:250,000) compiled to estimate water yields in Utah (Bagley and others, 1964). Sources of information about recorded floods resulting from cloudbursts included Woolley (1946) and Butler and Marsell (1972); sources of information about the chemical quality of streamflow included Mundorff (1972) and Mundorff and Thompson (1982).

Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes

Directory of Open Access Journals (Sweden)

Dorra Hmida-Ben Brahim

2014-01-01

Full Text Available Huntington’s disease (HD is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population.

Aerial gamma ray and magnetic survey, Huntington quadrangle: Ohio, West Virginia and Kentucky. Final report

International Nuclear Information System (INIS)

1981-04-01

The Huntington quadrangle of Kentucky, Ohio, and West Virginia covers 7250 square miles of the easternmost Midwestern Physiographic Province. Paleozoic exposures dominate the surface. These Paleozoics deepen toward the east from approximately 500 feet to a maximum depth of 8000 feet. Precambrian basement is thought to underlie the entire area. No known uranium deposits exist in the area. One hundred anomalies were found using the standard statistical analysis. Some high uranium concentration anomalies that may overlie the stratigraphic equivalent of the Devonian-Mississippian New Albany or Chattanooga Shales may represent significant levels of naturally occurring uranium. Future studies should concentrate on this unit. Magnetic data are largely in concurrence with existing structural interpretations but suggest some complexities in the underlying Precambrian

Universal precautions--do Irish anaesthetists comply?

LENUS (Irish Health Repository)

O'Rourke, N

2012-02-03

BACKGROUND: Anaesthetists are at high risk from blood-borne pathogens. Universal Precautions (UP) include the routine use of appropriate barrier precautions and techniques to reduce the likelihood of exposure to blood, body fluids and tissues that may contain pathogens. The compliance of Irish anaesthetists with these precautions has not been studied. AIM: To study the attitudes of Irish anaesthetists to Universal Precautions. METHOD: A postal questionnaire was sent to 210 anaesthetists currently practising in Ireland. The questionnaire was based on a model used in Australia and New Zealand. RESULTS: There was a 50% response rate to the survey. Only 15% of respondents had taken a risk history from a patient in the preceding four weeks. Resheathing of needles was commonplace. The effectiveness of hepatitis B immunisation was rarely checked and only 66% of respondents believe implementation of Universal Precautions to be practical. CONCLUSION: Irish anaesthetists comply poorly with Universal Precautions.

Projected configuration of a coal-fired district heating source on the basis of comparative technical-economical optimization analysis

Directory of Open Access Journals (Sweden)

Tańczuk Mariusz

2017-01-01

Full Text Available District heating technologies should be efficient, effective and environmentally friendly. The majority of the communal heating systems in Poland produce district hot water in coal-fired boilers. A large number of them are considerably worn out, low-efficient in the summer time and will not comply with forthcoming regulations. One of the possible solution for such plants is repowering with new CHP systems or new boilers fuelled with fuels alternative to coal. Optimisation analysis of the target configuration of municipal heat generating plant is analysed in the paper. The work concerns repowering the existing conventional heat generating plant according to eight different scenarios of the plant configuration meeting technical and environmental requirements forecasted for the year of 2035. The maximum demand for heat of the system supplied by the plant is 185 MW. Taking into account different technical configurations on one side, and different energy and fuel prices on the other side, the comparative cost-benefits analysis of the assumed scenarios has been made. The basic economical index NPV (net present value has been derived for each analysed scenario and the results have been compared and discussed. It was also claimed that the scenario with CHP based on ICE engines is optimal.

Projected configuration of a coal-fired district heating source on the basis of comparative technical-economical optimization analysis

Science.gov (United States)

Tańczuk, Mariusz; Radziewicz, Wojciech; Olszewski, Eligiusz; Skorek, Janusz

2017-10-01

District heating technologies should be efficient, effective and environmentally friendly. The majority of the communal heating systems in Poland produce district hot water in coal-fired boilers. A large number of them are considerably worn out, low-efficient in the summer time and will not comply with forthcoming regulations. One of the possible solution for such plants is repowering with new CHP systems or new boilers fuelled with fuels alternative to coal. Optimisation analysis of the target configuration of municipal heat generating plant is analysed in the paper. The work concerns repowering the existing conventional heat generating plant according to eight different scenarios of the plant configuration meeting technical and environmental requirements forecasted for the year of 2035. The maximum demand for heat of the system supplied by the plant is 185 MW. Taking into account different technical configurations on one side, and different energy and fuel prices on the other side, the comparative cost-benefits analysis of the assumed scenarios has been made. The basic economical index NPV (net present value) has been derived for each analysed scenario and the results have been compared and discussed. It was also claimed that the scenario with CHP based on ICE engines is optimal.

Understandings of psychological difficulties in people with the Huntington's disease gene and their expectations of psychological therapy.

Science.gov (United States)

Theed, Rachael; Eccles, Fiona J R; Simpson, Jane

2018-06-01

This study sought to investigate how people who had tested positive for the Huntington's disease (HD) gene mutation understood and experienced psychological distress and their expectations of psychological therapy. A qualitative methodology was adopted involving semi-structured interviews and interpretative phenomenological analysis (IPA). A total of nine participants (five women and four men) who had opted to engage in psychological therapy were recruited and interviewed prior to the start of this particular psychological therapeutic intervention. Interviews were transcribed verbatim and analysed using IPA whereby themes were analysed within and across transcripts and classified into superordinate themes. Three superordinate themes were developed: Attributing psychological distress to HD: 'you're blaming everything on that now'; Changes in attributions of distress over time: 'in the past you'd just get on with it'; and Approaching therapy with an open mind, commitment, and hope: 'a light at the end of the tunnel'. Understandings of psychological distress in HD included biological and psychological explanations, with both often being accepted simultaneously by the same individual but with biomedical accounts generally dominating. Individual experience seemed to reflect a dynamic process whereby people's understanding and experience of their distress changed over time. Psychological therapy was accepted as a positive alternative to medication, providing people with HD with hope that their psychological well-being could be enhanced. People with the Huntington's disease gene mutation have largely biomedical understandings of their psychological distress. This largely biomedical understanding does not, however, preclude them for being interested in the potential gains resulting from psychological therapy. The mechanisms of psychological therapy should be explained in detail before therapy and explored along with current attributions of distress. © 2017 The British

Revelation of the IFN alpha, IL-10, IL-8 and IL-1 beta as promising biomarkers reflecting immuno-pathological mechanisms in porcine Huntington's disease model

Czech Academy of Sciences Publication Activity Database

Valeková, Ivona; Jarkovská, Karla; Kotrčová, Eva; Bucci, J.; Ellederová, Zdeňka; Juhás, Štefan; Motlík, Jan; Gadher, S. J.; Kovářová, Hana

2016-01-01

Roč. 293, č. 2 (2016), s. 71-81 ISSN 0165-5728 R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : porcine Huntington´s disease * immune response * cytokines * central nervous system * serum * biomarkers Subject RIV: FH - Neurology Impact factor: 2.720, year: 2016

Detection of early behavioral markers of Huntington's disease in R6/2 mice employing an automated social home cage

DEFF Research Database (Denmark)

Rudenko, Olga; Tkach, Vadim; Berezin, Vladimir

2009-01-01

developed behavior screening system, the IntelliCage, allows automated testing of mouse behavior in the home cage employing individual recognition of animals living in social groups. The present study validates the ability of the IntelliCage system to detect behavioral and cognitive dysfunction in R6/2 mice......Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder, for which no known cure or effective treatment exists. To facilitate the search for new potential treatments of HD, an automated system for analyzing the behavior of transgenic HD mice is urgently needed. A recently...

District Energy Windsor

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-07-01

This paper presents a summary of how District Energy Windsor operates. It includes a system site map and reasons why it is advantageous to get connected to a district heating system. District Energy Windsor is a division of the Windsor Utilities Commission. It was developed in 1996 and was the first in North America to supply both heating and cooling requirements. It supplies nearly 2 million square feet of heating and cooling for Windsor's city centre. The district energy system produces hot water or chilled water at a central plant. Energy is then piped out to buildings in the area, including the Art Gallery of Windsor, the Royal Bank Business Centre, the Windsor Justice Facility, the Windsor Casino, and Northwind Windsor. The energy, which is transferred through heat exchangers, is used for space heating, domestic hot water heating, and air conditioning. The 8 reasons for getting connected are: (1) less management costs, (2) lower energy costs, (3) lower level of risk management, (4) stable energy rates, (5) better use of building space, (6) reliable service, (7) reduced expansion costs, and (8) a cleaner environment. District heating improves air quality through reduced carbon dioxide and nitrogen oxide emissions. In addition, fuel delivery and storage are eliminated. figs.

Dose-Dependent Lowering of Mutant Huntingtin Using Antisense Oligonucleotides in Huntington Disease Patients.

Science.gov (United States)

van Roon-Mom, Willeke M C; Roos, Raymund A C; de Bot, Susanne T

2018-04-01

On December 11 of 2017, Ionis Pharmaceuticals published a press release announcing dose-dependent reductions of mutant huntingtin protein in their HTTRx Phase 1/2a study in Huntington disease (HD) patients. The results from this Ionis trial have gained much attention from the patient community and the oligonucleotide therapeutics field, since it is the first trial targeting the cause of HD, namely the mutant huntingtin protein, using antisense oligonucleotides (ASOs). The press release also states that the primary endpoints of the study (safety and tolerability) were met, but does not contain data. This news follows the approval of another therapeutic ASO nusinersen (trade name Spinraza) for a neurological disease, spinal muscular atrophy, by the U.S. Food and Drug Administration and European Medicines Agency, in 2016 and 2017, respectively. Combined, this offers hope for the development of the HTTRx therapy for HD patients.

Revisiting "Rodriguez v. Los Angeles Unified School District": A Case of Intra-District Inequities

Science.gov (United States)

Espinosa, Ruben W.

2010-01-01

The educational community and the courts continue to struggle with the challenges of intra-district resource inequality revealed by the California Supreme Court landmark case "Rodriguez v. Los Angeles Unified School District" (1992). Intra-district school resource inequality is one of the remaining bastions of major inequalities in the…

VII international district heating conference

International Nuclear Information System (INIS)

1988-01-01

The proceedings of the 7th International District Heating Conference contain the full texts of the 89 presented papers of which 11 fall under the INIS Subject Scope. The conference met in seven sessions and dealt with the following problem areas: design and optimization of systems of district heating, integration of the power system and the district heating systems, cooperation of nuclear and fossil burning sources in district heating systems, the use of specific nuclear power plants for heating purposes, questions of the control of systems of district heating, the development of components of heating networks, the reliability and design of heat supply pipes. (Z.M.)

District heating in Italy

International Nuclear Information System (INIS)

Sacchi, E.

1998-01-01

The legislative act establishing the electric monopoly virtually shut out the district heating associated with electricity cogeneration, while other laws, issued to counteract the effects of oil shocks, allowed municipal utilities to do so. Thus, district heating has experienced some development, though well below its possibilities. The article analyses the reasons for this lagging, reports district heating data and projects its forecasts against the Kyoto Protocol objectives [it

VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington's disease.

Science.gov (United States)

Díaz-Alonso, Javier; Paraíso-Luna, Juan; Navarrete, Carmen; Del Río, Carmen; Cantarero, Irene; Palomares, Belén; Aguareles, José; Fernández-Ruiz, Javier; Bellido, María Luz; Pollastro, Federica; Appendino, Giovanni; Calzado, Marco A; Galve-Roperh, Ismael; Muñoz, Eduardo

2016-07-19

Cannabinoids have shown to exert neuroprotective actions in animal models by acting at different targets including canonical cannabinoid receptors and PPARγ. We previously showed that VCE-003, a cannabigerol (CBG) quinone derivative, is a novel neuroprotective and anti-inflammatory cannabinoid acting through PPARγ. We have now generated a non-thiophilic VCE-003 derivative named VCE-003.2 that preserves the ability to activate PPARγ and analyzed its neuroprotective activity. This compound exerted a prosurvival action in progenitor cells during neuronal differentiation, which was prevented by a PPARγ antagonist, without affecting neural progenitor cell proliferation. In addition, VCE-003.2 attenuated quinolinic acid (QA)-induced cell death and caspase-3 activation and also reduced mutant huntingtin aggregates in striatal cells. The neuroprotective profile of VCE-003.2 was analyzed using in vivo models of striatal neurodegeneration induced by QA and 3-nitropropionic acid (3NP) administration. VCE-003.2 prevented medium spiny DARPP32(+) neuronal loss in these Huntington's-like disease mice models improving motor deficits, reactive astrogliosis and microglial activation. In the 3NP model VCE-003.2 inhibited the upregulation of proinflammatory markers and improved antioxidant defenses in the brain. These data lead us to consider VCE-003.2 to have high potential for the treatment of Huntington's disease (HD) and other neurodegenerative diseases with neuroinflammatory traits.

7 CFR 958.27 - Districts.

Science.gov (United States)

2010-01-01

...; (2) changes in the relative position of existing districts with respect to onion production; (3) the... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ONIONS GROWN IN CERTAIN DESIGNATED... Districts. (a) For the purpose of selecting committee members, the following districts of the production...

Intra-District Disparities in Primary Education: A Case Study of Bankura District, West Bengal

Directory of Open Access Journals (Sweden)

Krishnendu Maji

2017-03-01

Full Text Available The level of education and its response to different educational opportunities vary from one spatial unit to another depending on various factors like social, economic, cultural, and institutional. It is understood that certain regions acquire relative advancements over others in terms of human resource development and human capital formation. The key purpose of this research is to examine the intra-district disparities in primary education in Bankura District one of the districts of West Bengal. It ranks 11thamong the 19 districts of West Bengal (Human Development Report, 2007.  Overall literacy rate of the district stands at 70.26% but the district scores low in terms of female literacy rates, which is 60.05%,whereas the male literacy rate is 80.05%, which is a huge gender literacy gap of 20%. There are also regional inequalities existing at block level. Kotulpur ranks first with a literacy rate of 78.01% while Saltora occupies the bottom position with literacy rate of just 61.45% (Census of India, 2011. The level of educational development is dependent on several factors—enrolment ratio, dropout and repetition rates, pupil-teacher ratio, habitations covered by educational institutions, space-student ratio, drinking water and sanitation facilities in school, etc. In this context, the present study aims at examining the issues of intra-district disparities in educational attainment with regard to various educational amenities of Bankura district, West Bengal. Ten attributes have been selected to examine the level of development in primary education. It is clear from the study that the level of development in eastern part of the district is relatively better in comparison to other regions. Economic backwardness and physical bottlenecks continue to be major issues in western blocks.

Lieutenant Chief Warden Districts

Data.gov (United States)

Vermont Center for Geographic Information — This dataset is a representation overlay of Lieutenant Chief Warden Districts (areas of responsibility). The Vermont Lieutenant Chief Warden Districts layer is part...

State-Level Guidance and District-Level Policies and Practices for Food Marketing in US School Districts.

Science.gov (United States)

Merlo, Caitlin L; Michael, Shannon; Brener, Nancy D; Blanck, Heidi

2018-06-07

State agencies play a critical role in providing school districts with guidance and technical assistance on school nutrition issues, including food and beverage marketing practices. We examined associations between state-level guidance and the policies and practices in school districts regarding food and beverage marketing and promotion. State policy guidance was positively associated with districts prohibiting advertisements for junk food or fast food restaurants on school property. Technical assistance from states was negatively associated with 2 district practices to restrict marketing of unhealthy foods and beverages, but positively associated with 1 practice to promote healthy options. These findings may help inform the guidance that states provide to school districts and help identify which districts may need additional assistance to address marketing and promotion practices.

36 CFR 1251.6 - How does the General Counsel determine whether to comply with a demand for records or testimony?

Science.gov (United States)

2010-07-01

... determine whether to comply with a demand for records or testimony? 1251.6 Section 1251.6 Parks, Forests... § 1251.6 How does the General Counsel determine whether to comply with a demand for records or testimony? The General Counsel may consider the following factors in determining whether or not to grant an...

77 FR 63326 - Huron Wetland Management District, Madison Wetland Management District, and Sand Lake Wetland...

Science.gov (United States)

2012-10-16

..., consistent with sound principles of fish and wildlife management, conservation, legal mandates, and our... FXRS1265066CCP0] Huron Wetland Management District, Madison Wetland Management District, and Sand Lake Wetland Management District, SD; Final Comprehensive Conservation Plan and Finding of No Significant Impact for...

Embodied emotion impairment in Huntington's Disease.

Science.gov (United States)

Trinkler, Iris; Devignevielle, Sévérine; Achaibou, Amal; Ligneul, Romain V; Brugières, Pierre; Cleret de Langavant, Laurent; De Gelder, Beatrice; Scahill, Rachael; Schwartz, Sophie; Bachoud-Lévi, Anne-Catherine

2017-07-01

Theories of embodied cognition suggest that perceiving an emotion involves somatovisceral and motoric re-experiencing. Here we suggest taking such an embodied stance when looking at emotion processing deficits in patients with Huntington's Disease (HD), a neurodegenerative motor disorder. The literature on these patients' emotion recognition deficit has recently been enriched by some reports of impaired emotion expression. The goal of the study was to find out if expression deficits might be linked to a more motoric level of impairment. We used electromyography (EMG) to compare voluntary emotion expression from words to emotion imitation from static face images, and spontaneous emotion mimicry in 28 HD patients and 24 matched controls. For the latter two imitation conditions, an underlying emotion understanding is not imperative (even though performance might be helped by it). EMG measures were compared to emotion recognition and to the capacity to identify and describe emotions using alexithymia questionnaires. Alexithymia questionnaires tap into the more somato-visceral or interoceptive aspects of emotion perception. Furthermore, we correlated patients' expression and recognition scores to cerebral grey matter volume using voxel-based morphometry (VBM). EMG results replicated impaired voluntary emotion expression in HD. Critically, voluntary imitation and spontaneous mimicry were equally impaired and correlated with impaired recognition. By contrast, alexithymia scores were normal, suggesting that emotion representations on the level of internal experience might be spared. Recognition correlated with brain volume in the caudate as well as in areas previously associated with shared action representations, namely somatosensory, posterior parietal, posterior superior temporal sulcus (pSTS) and subcentral sulcus. Together, these findings indicate that in these patients emotion deficits might be tied to the "motoric level" of emotion expression. Such a double

VT Data - Overlay District 20170419, Colchester

Data.gov (United States)

Vermont Center for Geographic Information — The following Overlay Districts are included in the data:General Development Four Commercial DistrictGeneral Development Four Openspace DistrictShoreland...

Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16

Science.gov (United States)

Djoussé, Luc; Knowlton, Beth; Hayden, Michael R.; Almqvist, Elisabeth W.; Brinkman, Ryan R.; Ross, Christopher A.; Margolis, Russel L.; Rosenblatt, Adam; Durr, Alexandra; Dode, Catherine; Morrison, Patrick J.; Novelletto, Andrea; Frontali, Marina; Trent, Ronald J. A.; McCusker, Elizabeth; Gómez-Tortosa, Estrella; Mayo Cabrero, David; Jones, Randi; Zanko, Andrea; Nance, Martha; Abramson, Ruth K.; Suchowersky, Oksana; Paulsen, Jane S.; Harrison, Madaline B.; Yang, Qiong; Cupples, L. Adrienne; Mysore, Jayalakshmi; Gusella, James F.; MacDonald, Marcy E.

2007-01-01

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Δ2642 (within the HD coding sequence), and BJ56 (D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Δ2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker. PMID:15029481

Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington's disease.

Science.gov (United States)

Valenza, M; Marullo, M; Di Paolo, E; Cesana, E; Zuccato, C; Biella, G; Cattaneo, E

2015-04-01

In the adult brain, neurons require local cholesterol production, which is supplied by astrocytes through apoE-containing lipoproteins. In Huntington's disease (HD), such cholesterol biosynthesis in the brain is severely reduced. Here we show that this defect, occurring in astrocytes, is detrimental for HD neurons. Astrocytes bearing the huntingtin protein containing increasing CAG repeats secreted less apoE-lipoprotein-bound cholesterol in the medium. Conditioned media from HD astrocytes and lipoprotein-depleted conditioned media from wild-type (wt) astrocytes were equally detrimental in a neurite outgrowth assay and did not support synaptic activity in HD neurons, compared with conditions of cholesterol supplementation or conditioned media from wt astrocytes. Molecular perturbation of cholesterol biosynthesis and efflux in astrocytes caused similarly altered astrocyte-neuron cross talk, whereas enhancement of glial SREBP2 and ABCA1 function reversed the aspects of neuronal dysfunction in HD. These findings indicate that astrocyte-mediated cholesterol homeostasis could be a potential therapeutic target to ameliorate neuronal dysfunction in HD.

Reinstating district nursing: A UK perspective.

Science.gov (United States)

Morris, Hannah

2017-09-01

As policy directives gather pace for service provision to be delivered in primary care, district nursing has not been recognised as a valuable asset to facilitate this agenda. Investment in district nursing and specialist district nursing education has fallen. This is concurrent with an ageing district nursing workforce, a lack of recruitment and growing caseloads, as district nursing adapts to meet the challenges of the complexities of contemporary healthcare in the community. The district nurse role is complex and multifaceted and includes working collaboratively and creatively to coordinate care. Redressing the shortages of specialist district nurse practitioners with increased numbers of health care support workers will not replace the skill, knowledge, experience required to meet the complex care needs of today's society. District nursing needs to be reinstated as the valuable asset it is, through renewed investment in the service, research development and in specialist practice education. To prevent extinction district nurses need to be able to demonstrate and articulate the complexities and dynamisms of the role to reinstate themselves to their commissioners as a valuable asset for contemporary practice that can meet current health and social care needs effectively. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

District Consolidation: Rivals Coming Together

Science.gov (United States)

Mart, Dan

2011-01-01

District consolidation is a highly emotional process. One key to success is sticking to the facts. In Iowa, school districts facing financial difficulties or enrollment concerns do not have to move directly to consolidation. In many cases, districts begin by developing sharing agreements. These sharing agreements may start with simple sharing of…

D-β-hydroxybutyrate is protective in mouse models of Huntington's disease.

Directory of Open Access Journals (Sweden)

Soyeon Lim

Full Text Available Abnormalities in mitochondrial function and epigenetic regulation are thought to be instrumental in Huntington's disease (HD, a fatal genetic disorder caused by an expanded polyglutamine track in the protein huntingtin. Given the lack of effective therapies for HD, we sought to assess the neuroprotective properties of the mitochondrial energizing ketone body, D-β-hydroxybutyrate (DβHB, in the 3-nitropropionic acid (3-NP toxic and the R6/2 genetic model of HD. In mice treated with 3-NP, a complex II inhibitor, infusion of DβHB attenuates motor deficits, striatal lesions, and microgliosis in this model of toxin induced-striatal neurodegeneration. In transgenic R6/2 mice, infusion of DβHB extends life span, attenuates motor deficits, and prevents striatal histone deacetylation. In PC12 cells with inducible expression of mutant huntingtin protein, we further demonstrate that DβHB prevents histone deacetylation via a mechanism independent of its mitochondrial effects and independent of histone deacetylase inhibition. These pre-clinical findings suggest that by simultaneously targeting the mitochondrial and the epigenetic abnormalities associated with mutant huntingtin, DβHB may be a valuable therapeutic agent for HD.

33 CFR 3.25-1 - Fifth district.

Science.gov (United States)

2010-07-01

... District § 3.25-1 Fifth district. (a) The District Office is in Portsmouth, Va. (b) The Fifth Coast Guard District is comprised of: North Carolina; Virginia; District of Columbia; Maryland; Delaware; that part of... boundary at the shoreline at the North Carolina-South Carolina border, point located at approximately 30°55...

Diffusion tensor imaging of brain white matter in Huntington gene mutation individuals

Directory of Open Access Journals (Sweden)

Roberta Arb Saba

Full Text Available ABSTRACT Objective To evaluate the role of the involvement of white matter tracts in huntingtin gene mutation patients as a potential biomarker of the progression of the disease. Methods We evaluated 34 participants (11 symptomatic huntingtin gene mutation, 12 presymptomatic huntingtin gene mutation, and 11 controls. We performed brain magnetic resonance imaging to assess white matter integrity using diffusion tensor imaging, with measurement of fractional anisotropy. Results We observed a significant decrease of fractional anisotropy in the cortical spinal tracts, corona radiate, corpus callosum, external capsule, thalamic radiations, superior and inferior longitudinal fasciculus, and inferior frontal-occipital fasciculus in the Huntington disease group compared to the control and presymptomatic groups. Reduction of fractional anisotropy is indicative of a degenerative process and axonal loss. There was no statistically significant difference between the presymptomatic and control groups. Conclusion White matter integrity is affected in huntingtin gene mutation symptomatic individuals, but other studies with larger samples are required to assess its usefulness in the progression of the neurodegenerative process.

National Register Historic Districts

Data.gov (United States)

Iowa State University GIS Support and Research Facility — The National Register Historic District layer is a shape file showing the boundaries of Historic Districts that are listed on the National Register of Historic Places.

Stroke prevention--a population screening day in district XII of Budapest.

Science.gov (United States)

Folyovich, András; Bakos, Mária; Kántor, Zita; Hertelendy, Anna; Horváth, Eszter; Zsiga, Katalin; Lakatos, Henriette; Vadasdi, Károly

2012-03-30

Along with advances in the treatment of acute stroke, new efforts have been made to enhance efficiency of the prevention of cerebrovascular diseases. Population screening is a way to contact high-risk patients, and there is an increasing international and national experience with the procedure. However, efforts are associated with high costs, so an efficient method, complying with local features, should be selected from the various methods. A stroke prevention day was organized in Szent János Hospital, localized in district XII, and data were analyzed. Taking advantage of the potentials of a large hospital, a comprehensive risk assessment - within the capacity of health care workers - was performed. Program and contact information of the screening day was published in the local newspaper of the district. Data of 48 residents of the district were analyzed. In addition to neurologists, a radiologist, a cardiologist and an ophtalmologist, as well as health care workers were involved in the project. A data sheet was filled in for all participants, including known risk factors, BMI, blood pressure and serum cholesterol levels. All participants had duplex sonography of the cervical vessels, cardiac evaluation and ophtalmic examination. Data were analyzed anonymously, and - if participants approved - postcode and educational level were also recorded. Among the 48 individuals screened, 35 were female and 13 were male. Average age was 62.86 (+/- 8.57) years, and participants were typically of higher educational level. 5 individuals had no known risk factors, most of them had 2-3 risk factors, and multiple risk factors were not uncommon. Individuals with six and seven risk factors were also found. 20 of 27 patients with known hypertension had target blood pressure levels. By duplex sonography, 36 individuals had mild, 4 had significant atherosclerosis. There was no significant carotid stenosis or occlusion. Based on ophtalmic evaluation, 26 patients had signs of vascular

The Partnership Pact: Fulfilling School Districts' Research Needs with University-District Partnerships

Science.gov (United States)

Ralston, Nicole; Weitzel, Bruce; Waggoner, Jacqueline; Naegele, Zulema; Smith, Rebecca

2016-01-01

There has been a recent shift in university-district partnership models from traditional transactional partnerships, which lack a shared purpose, to transformational partnerships that are mutually beneficial to both universities and school districts. These transformational research-practice partnerships have gained popularity in the United States…

PPARGC1A/PGC-1α, TFEB and enhanced proteostasis in Huntington disease: Defining regulatory linkages between energy production and protein–organelle quality control

OpenAIRE

La Spada, Albert R.

2012-01-01

Huntington disease (HD) results from CAG repeats that encode expanded polyglutamine tracts in the HTT/huntingtin protein. HD belongs to a large category of inherited and sporadic neurodegenerative disorders in which production of a misfolded protein initiates the pathogenic cascade. Previous studies have shown that misfolded proteins become resistant to cellular protein turnover pathways by eluding and disabling the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway. Based upon ...

19 CFR 12.108 - Detention of articles; time in which to comply.

Science.gov (United States)

2010-04-01

... Sculpture and Murals § 12.108 Detention of articles; time in which to comply. If the importer cannot produce... take the sculpture or mural into Customs custody and send it to a bonded warehouse or public store to... sculpture or mural is taken into Customs custody, or such longer period as may be allowed by the port...

[Risk of certain obstetric pathologies in women employed in working conditions non-complying with the current legal status on work load and working conditions appropriate for pregnant women].

Science.gov (United States)

Makowiec-Dabrowska, Teresa; Hanke, Wojciech; Sobala, Wojciech; Radwan-Włodarczyk, Zyta; Koszada-Włodarczyk, Wiesława

2003-01-01

The aim of the study was to define the incidence of prematurity and small-for-gestational age (SGA) infants in occupationally involved pregnant women, and to find out how far working conditions departing from binding regulations contribute to the risk of the development of these pathologies. The study was carried out on a representative sample of 3050 women employed for longer than one week during pregnancy in the Łódź district. An interview conducted with the subjects few days after delivery was the source of information about working conditions. The obtained information was compared with the real situation in about 10% of randomly selected workposts. A high level of consistence was observed. The study revealed that almost 60% of women work in conditions, which do not comply with the Labor Code provisions setting working conditions permissible for pregnant women. In the study group, 4.68% of prematurity and 6.15% of SGA were recorded. A 66% excess in the risk of delivering SGA infants in case of at least one factor not complying with regulations was revealed. The excess was growing with the increased number of departures from regulations and continuation of employment during pregnancy. It was estimated that the number of SGA cases would decrease by 28% if the working conditions would have met the requirements. A prolonged time of work, local vibration for > 4h/shift, forced work pace, excessive effort and forced body position during the work performance contributed mostly to the risk of pathology. Interestingly, the risk of premature delivery was lower by about 40% in women working in unsatisfactory conditions, which is attributed to termination of work immediately after the occurrence of pregnancy-threatening symptoms. Only those women whose pregnancy was not threatened with pathology could continue their work. The study revealed a quite large number of workplaces not complying with regulations on working conditions permissible for pregnant women. Therefore

District Fiscal Policy and Student Achievement

Directory of Open Access Journals (Sweden)

Gary G. Huang

2002-09-01

Full Text Available School restructuring raises questions about the role of school districts in improving student learning. Centralization by state governments and decentralization to individual schools as proposed in systemic reform leave districts' role unsettled. Empirical research on the district role in the context of ongoing reform is inadequate. This analysis of combined data from the NAEP and the Common Core of Data (CCD was intended to address the issue. We analyzed 1990, 1992, and 1996 NAEP 8th grade mathematics national assessment data in combination with CCD data of corresponding years to examine the extent to which student achievement was related to districts' control over instructional expenditure, adjusting for relevant key factors at both district and student levels. Upon sample modification, we used hierarchical linear modeling (HLM to estimate the relationships of student achievement to two district fiscal policy indictors, current expenditure per pupil (CEPP and districts' discretionary rates for instructional expenditure (DDR. Net of relevant district factors, DDR was found unrelated to districts' average 8th grade math performance. The null effect was consistent in the analysis of the combined NAEP-CCD data for 1990, 1992, and 1996. In contrast, CEPP was found related to higher math performance in a modest yet fairly consistent way. Future research may be productive to separately study individual states and integrate the findings onto the national level.

Age at onset in Huntington's disease: replication study on the association of HAP1.

Science.gov (United States)

Karadima, Georgia; Dimovasili, Christina; Koutsis, Georgios; Vassilopoulos, Demetris; Panas, Marios

2012-11-01

In recent years two association studies investigating the HAP1 T441M (rs4523977) polymorphism as a potential modifying factor of the age at onset (AAO) of Huntington's disease (HD), have been reported. Initially evidence for association was found between the M441 risk allele and the AAO. Subsequently, a second study, although failing to replicate these findings, found evidence for association between the same risk allele and AAO of motor symptoms (mAAO). In the present study, the role of the HAP1 T441M polymorphism as a modifier of the AAO in HD was investigated in a cohort of 298 Greek HD patients. In this cohort the CAG repeat number accounted for 55% of the variance in AAO. No association was found between the HAP1 T441M polymorphism and the AAO of HD. © 2012 Elsevier Ltd. All rights reserved.

Compliance with referral of sick children: a survey in five districts of Afghanistan

Directory of Open Access Journals (Sweden)

Newbrander William

2012-04-01

Full Text Available Abstract Background Recognition and referral of sick children to a facility where they can obtain appropriate treatment is critical for helping reduce child mortality. A well-functioning referral system and compliance by caretakers with referrals are essential. This paper examines referral patterns for sick children, and factors that influence caretakers’ compliance with referral of sick children to higher-level health facilities in Afghanistan. Methods The study was conducted in 5 rural districts of 5 Afghan provinces using interviews with parents or caretakers in 492 randomly selected households with a child from 0 to 2 years old who had been sick within the previous 2 weeks with diarrhea, acute respiratory infection (ARI, or fever. Data collectors from local nongovernmental organizations used a questionnaire to assess compliance with a referral recommendation and identify barriers to compliance. Results The number of referrals, 99 out of 492 cases, was reasonable. We found a high number of referrals by community health workers (CHWs, especially for ARI. Caretakers were more likely to comply with referral recommendations from community members (relative, friend, CHW, traditional healer than with recommendations from health workers (at public clinics and hospitals or private clinics and pharmacies. Distance and transportation costs did not create barriers for most families of referred sick children. Although the average cost of transportation in a subsample of 75 cases was relatively high (US$11.28, most families (63% who went to the referral site walked and hence paid nothing. Most caretakers (75% complied with referral advice. Use of referral slips by health care providers was higher for urgent referrals, and receiving a referral slip significantly increased caretakers’ compliance with referral. Conclusions Use of referral slips is important to increase compliance with referral recommendations in rural Afghanistan.

Compliance with referral of sick children: a survey in five districts of Afghanistan.

Science.gov (United States)

Newbrander, William; Ickx, Paul; Werner, Robert; Mujadidi, Farooq

2012-04-27

Recognition and referral of sick children to a facility where they can obtain appropriate treatment is critical for helping reduce child mortality. A well-functioning referral system and compliance by caretakers with referrals are essential. This paper examines referral patterns for sick children, and factors that influence caretakers' compliance with referral of sick children to higher-level health facilities in Afghanistan. The study was conducted in 5 rural districts of 5 Afghan provinces using interviews with parents or caretakers in 492 randomly selected households with a child from 0 to 2 years old who had been sick within the previous 2 weeks with diarrhea, acute respiratory infection (ARI), or fever. Data collectors from local nongovernmental organizations used a questionnaire to assess compliance with a referral recommendation and identify barriers to compliance. The number of referrals, 99 out of 492 cases, was reasonable. We found a high number of referrals by community health workers (CHWs), especially for ARI. Caretakers were more likely to comply with referral recommendations from community members (relative, friend, CHW, traditional healer) than with recommendations from health workers (at public clinics and hospitals or private clinics and pharmacies). Distance and transportation costs did not create barriers for most families of referred sick children. Although the average cost of transportation in a subsample of 75 cases was relatively high (US$11.28), most families (63%) who went to the referral site walked and hence paid nothing. Most caretakers (75%) complied with referral advice. Use of referral slips by health care providers was higher for urgent referrals, and receiving a referral slip significantly increased caretakers' compliance with referral. Use of referral slips is important to increase compliance with referral recommendations in rural Afghanistan.

Transparency

Science.gov (United States)

LaFee, Scott

2009-01-01

Citizens now expect access to information, particularly from public institutions like local school districts. They demand input and accountability. Cultural and technological changes, such as the Internet, make it possible for districts to comply. Yet transparency--the easily seen and understood actions of a school district and the thinking behind…

District Governance and Student Learning in Indonesia

OpenAIRE

Pradhan, Menno; de Ree, Joppe

2014-01-01

We document the likely importance of district governance and teacher management policies in relation to student learning in Indonesian primary schools. As the responsibility to deliver primary education has been decentralized to district governments, we expect district specific variations in teacher management policies. Consequently, we also expect variations in learning trajectories across districts. We document substantial heterogeneity in learning gains across districts. Furthermore, we sh...

Procedures for selecting and buying district heating equipment. Sofia district heating. Final report

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-11-01

The aim of this Final Report, prepared for the project `Procedures for Selecting and Buying DistRict Heating Equipment - Sofia District Heating Company`, is to establish an overview of the activities accomplished, the outputs delivered and the general experience gained as a result of the project. The main objective of the project is to enable Sofia District Heating Company to prepare specifications and tender documents, identify possible suppliers, evaluate offers, etc. in connection with purchase of district heating equipment. This objective has been reached by using rehabilitation of sub-stations as an example requested by Sofia DH. The project was originally planned to be finalized end of 1995, but due to the extensions of the scope of work, the project has been prolonged until end 1997. The following main activities were accomplished: Preparation of a detailed work plan; Collection of background information; Discussion and advice about technical specifications and tender documents for sub-station rehabilitation; Input to terms of reference for a master plan study; Input to technical specification for heat meters; Collection of ideas for topics and examples related to dissemination of information to consumers about matters related to district heating consumption. (EG)

Bradykinesia in Huntington's disease. A prospective, follow-up study.

Science.gov (United States)

García Ruiz, Pedro J; Hernández, Jaime; Cantarero, Susana; Bartolomé, Manuel; Sánchez Bernardos, Vicenta; García de Yébenez, Justo

2002-04-01

Bradykinesia is a frequent finding in Huntington's disease (HD), but some aspects are presently unknown; including the natural evolution of bradykinesia over time and the correlation between bradykinesia and functional capacity. We studied the motor performance of 20 genetically confirmed patients with HD (age: 40+/-10.8 years; age at onset 33.6+/-11 years; total functional capacity (TFC): 9.57+/-3; UHDRS total motor scale: 31.4+/-13, triplet length (CAG)n: 46.7+/-4 triplets). These patients were studied in baseline conditions and after 18.7+/-6 months of follow-up. In addition, HD patients were compared with 20 age-matched normal controls. Motor study included the four CAPIT timed tests commonly used for Parkinson's disease: pronation-supination (PS), finger dexterity (FD), movement between two points (MTP) and walking test (WT). HD patients were significantly slower than controls in all motor tasks. A significant deterioration occurred over time in three of the four motor tasks (especially FD and WT). A significant correlation between timed tests and TFC score was found (for MTP, r: -0.845; p < 0,0001). In addition a significant correlation between timed tests and the UHDRDS total motor scale was also found (for MTP, r: 0.864; p < 0.0001). In conclusion, simple timed motor tests can detect a deterioration of motor activity over time in HD. Timed tests might be useful to follow the natural evolution of HD and to assess the efficacy of new therapies.

Therapeutic approaches to preventing cell death in Huntington disease.

Science.gov (United States)

Kaplan, Anna; Stockwell, Brent R

2012-12-01

Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors-fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Community Development Agency in Developing Village in The Lamongan District

Directory of Open Access Journals (Sweden)

Abid Muhtarom

2017-03-01

Privileges Institute for Community Empowerment  In Development In Rural System In the Village Administration is (1 Plan development by consensus, (2 Mobilize and increase community participation in the implementation of development, (3 Cultivate dynamic condition of society and increase resilience in the district that studied to perform the function and role in the development of the Institute for Community Empowerment must comply with the rules villages and villages that have been made. However, there are some good functions to be executed to enhance the development of the Institute for Community Empowerment, namely (1 As a means of community participation in planning and implementing development; (2 Cultivating understanding and appreciation and awareness of the Pancasila; (3 Digging, harness, potential and mobilize self-help mutual aid societies to develop; (4 As a means of communication between the Government and the community and between citizens themselves; (5 Improving the knowledge and skills of the community; (6 To foster and mobilize the potential of the youth in development; (7 Fostering cooperation between institutions in society for development; (8 Implementation of other tasks in order to help the village government to build resilience established. Keywords: Role of the Institute of Community and Rural Development.

40 CFR 63.3350 - If I use a control device to comply with the emission standards, what monitoring must I do?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true If I use a control device to comply with the emission standards, what monitoring must I do? 63.3350 Section 63.3350 Protection of... for Monitoring and Performance Tests § 63.3350 If I use a control device to comply with the emission...

Estudio de los procesos activadores de la patologia en la enfermedad de Huntington: Alteraciones en la plasticidad sinaptica y perspectivas terapeuticas

OpenAIRE

Giralt Torroella, Albert

2010-01-01

[spa] La presente tesis posee una introducción donde se plantea y explica la sintomatología, genética y fisiopatología de la enfermedad de Huntington (EH). También explicamos los distintos modelos animales usados para el estudio de la enfermedad y resaltamos su relevancia para propuestas terapéuticas. Seguidamente introducimos lo que son las ideas principales de la tesis. Estas son, el interés por el estudio de los procesos fisiopatológicos de aparición más temprana para la planificación tera...

30 CFR 285.611 - What information must I submit with my SAP to assist MMS in complying with NEPA and other...

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What information must I submit with my SAP to... Assessment Plan § 285.611 What information must I submit with my SAP to assist MMS in complying with NEPA and other relevant laws? (a) You must submit with your SAP detailed information to assist MMS in complying...

Characteristics of uranium districts of the Russian Federation

International Nuclear Information System (INIS)

Boitsov, A.V.; Nikolsky, A.L.

2001-01-01

Uranium deposits are discovered in 15 ore districts of the Russian Federation. They are subdivided into four groups: Streltsovsky district with existing production centre, Stavropolsky district with depleted deposits, three prospective districts and ten reserve districts. The overview of new data on these districts is presented. Streltsovsky district with Priargunsky Production Centre include 19 molybdenum-uranium deposits of structure-bound volcanic type in caldera. The main activities in Stavropolsky district with two depleted uranium deposits are connected with restoration works and wastes rehabilitation. Except Streltsovsky district there are no more deposits in the Russian Federation prepared for uranium production. At the same time some uranium deposits of Vitimsky, Zauralsky, and West-Siberian districts are prospective for new development of production centres. They belong to the sandstone type, related to paleovalley or basal channel, and are suitable for ISL operation. The deposits of the other districts are considered to be reserve and considered unprofitable for uranium production at present and in the nearest future. The biggest of them is Aldansky district with gold-uranium deposits in potassium metasomatites in areas of Mesozoic activation of Archean cratons. Central Transbaikalsky, Yeniseisky, Yergeninsky, Onezhsky, Ladozhsky, Bureinsky, Khankaisky, Volgo-Uralsky reserve districts include mainly small-size deposits of vein, volcanic, surficial and metasomatite types with low uranium grades. (author)

Identification of extreme motor phenotypes in Huntington's disease.

Science.gov (United States)

Braisch, Ulrike; Hay, Birgit; Muche, Rainer; Rothenbacher, Dietrich; Landwehrmeyer, G Bernhard; Long, Jeffrey D; Orth, Michael

2017-04-01

The manifestation of motor signs in Huntington's disease (HD) has a well-known inverse relationship with HTT CAG repeat length, but the prediction is far from perfect. The probability of finding disease modifiers is enhanced in individuals with extreme HD phenotypes. We aimed to identify extreme HD motor phenotypes conditional on CAG and age, such as patients with very early or very late onset of motor manifestation. Retrospective data were available from 1,218 healthy controls and 9,743 HD participants with CAG repeats ≥40, and a total of about 30,000 visits. Boundaries (2.5% and 97.5% quantiles) for extreme motor phenotypes (UHDRS total motor score (TMS) and motor age-at-onset) were estimated using quantile regression for longitudinal data. More than 15% of HD participants had an extreme TMS phenotype for at least one visit. In contrast, only about 4% of participants were consistent TMS extremes at two or more visits. Data from healthy controls revealed an upper cut-off of 13 for the TMS representing the extreme of motor ratings for a normal aging population. In HD, boundaries of motor age-at-onset based on diagnostic confidence or derived from the TMS data cut-off in controls were similar. In summary, a UHDRS TMS of more than 13 in an individual carrying the HD mutation indicates a high likelihood of motor manifestations of HD irrespective of CAG repeat length or age. The identification of motor phenotype extremes can be useful in the search for disease modifiers, for example, genetic or environmental such as medication. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Brain imaging and cognitive dysfunctions in Huntington's disease

Science.gov (United States)

Montoya, Alonso; Price, Bruce H.; Menear, Matthew; Lepage, Martin

2006-01-01

Recent decades have seen tremendous growth in our understanding of the cognitive dysfunctions observed in Huntington's disease (HD). Advances in neuroimaging have contributed greatly to this growth. We reviewed the role that structural and functional neuroimaging techniques have played in elucidating the cerebral bases of the cognitive deficits associated with HD. We conducted a computer-based search using PubMed and PsycINFO databases to retrieve studies of patients with HD published between 1965 and December 2004 that reported measures on cognitive tasks and used neuroimaging techniques. Structural neuroimaging has provided important evidence of morphological brain changes in HD. Striatal and cortical atrophy are the most common findings, and they correlate with cognitive deficits in attention, working memory and executive functions. Functional studies have also demonstrated correlations between striatal dysfunction and cognitive performance. Striatal hypoperfusion and decreased glucose utilization correlate with executive dysfunction. Hypometabolism also occurs throughout the cerebral cortex and correlates with performance on recognition memory, language and perceptual tests. Measures of presynaptic and postsynaptic dopamine biochemistry have also correlated with measurements of episodic memory, speed of processing and executive functioning. Aided by the results of numerous neuroimaging studies, it is becoming increasingly clear that cognitive deficits in HD involve abnormal connectivity between the basal ganglia and cortical areas. In the future, neuroimaging techniques may shed the most light on the pathophysiology of HD by defining neurodegenerative disease phenotypes as a valuable tool for knowing when patients become “symptomatic,” having been in a gene-positive presymptomatic state, and as a biomarker in following the disease, thereby providing a prospect for improved patient care. PMID:16496032

Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

Energy Technology Data Exchange (ETDEWEB)

Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana [IRCCS Neuromed, Neurogenetics Unit and Centre for Rare Disease, Pozzilli (Italy); Romanelli, Pantaleo [IRCCS Neuromed, Department of Neurosurgery, Pozzilli (Italy); Giovacchini, Giampiero; Ciarmiello, Andrea [S. Andrea Hospital, Unit of Nuclear Medicine, La Spezia (Italy); Frati, Luigi [University ' ' Sapienza' ' , Department of Experimental Medicine, Rome (Italy); Mansi, Luigi [Second University of Naples, Department of Nuclear Medicine, Naples (Italy)

2009-07-15

Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and {sup 18}F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

International Nuclear Information System (INIS)

Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana; Romanelli, Pantaleo; Giovacchini, Giampiero; Ciarmiello, Andrea; Frati, Luigi; Mansi, Luigi

2009-01-01

Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and 18 F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington's disease.

Science.gov (United States)

Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S

Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: a decade of the PREDICT-HD study

Directory of Open Access Journals (Sweden)

Jane S Paulsen

2014-04-01

Full Text Available There is growing consensus that intervention and treatment of Huntington disease (HD should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. PREDICT-HD is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest Huntington disease and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease seven to twelve years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.

Inactivation of the Huntington's disease gene (Hdh impairs anterior streak formation and early patterning of the mouse embryo

Directory of Open Access Journals (Sweden)

Conlon Ronald A

2005-08-01

Full Text Available Abstract Background Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE are specified. Conclusion Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in

Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo.

Science.gov (United States)

Woda, Juliana M; Calzonetti, Teresa; Hilditch-Maguire, Paige; Duyao, Mabel P; Conlon, Ronald A; MacDonald, Marcy E

2005-08-18

Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdh(ex4/5) huntingtin deficient embryos. In the absence of huntingtin, expression of nutritive genes appears normal but E7.0-7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease.

Budget Stability, Revenue Volatility, and District Relations: Determinants of Georgia ELOST Distribution to Municipal School Districts

Science.gov (United States)

Reinagel, Tyler P.

2014-01-01

School districts across the United States are often forced into situations where limited public funds must be distributed among multiple districts. These are often reliant on distribution rates negotiated by district leadership and elected officials. An example of this is Georgia's 1% Education Local Option Sales Tax (ELOST). The tax is collected…

Striatal pre-enkephalin overexpression improves Huntington's disease symptoms in the R6/2 mouse model of Huntington's disease.

Directory of Open Access Journals (Sweden)

Stéphanie Bissonnette

Full Text Available The reduction of pre-enkephalin (pENK mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington's disease (HD, due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2-containing green fluorescence protein (GFP-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.

Utilization of Yard for Vegetable Hydroponics in Serut Village, Panti Sub-District, Jember District

OpenAIRE

dewanti, parawita

2018-01-01

Vegetables as a horticultural product is a food source that is always consumed by humans daily, including in urban areas. Assorted Vegetables can be eaten raw or processed and it takes as a decoration on the food. Needs vegetables including lettuce, green pakcoy and other vegetables from day to day continues to increase. Therefore, it needs supply of vegetables from the area around the town of Jember including Serut Village, District Panti Sub-District, Jember District. Serut village has the ...

Test-Retest Reliability of Diffusion Tensor Imaging in Huntington's Disease.

Science.gov (United States)

Cole, James H; Farmer, Ruth E; Rees, Elin M; Johnson, Hans J; Frost, Chris; Scahill, Rachael I; Hobbs, Nicola Z

2014-03-21

Diffusion tensor imaging (DTI) has shown microstructural abnormalities in patients with Huntington's Disease (HD) and work is underway to characterise how these abnormalities change with disease progression. Using methods that will be applied in longitudinal research, we sought to establish the reliability of DTI in early HD patients and controls. Test-retest reliability, quantified using the intraclass correlation coefficient (ICC), was assessed using region-of-interest (ROI)-based white matter atlas and voxelwise approaches on repeat scan data from 22 participants (10 early HD, 12 controls). T1 data was used to generate further ROIs for analysis in a reduced sample of 18 participants. The results suggest that fractional anisotropy (FA) and other diffusivity metrics are generally highly reliable, with ICCs indicating considerably lower within-subject compared to between-subject variability in both HD patients and controls. Where ICC was low, particularly for the diffusivity measures in the caudate and putamen, this was partly influenced by outliers. The analysis suggests that the specific DTI methods used here are appropriate for cross-sectional research in HD, and give confidence that they can also be applied longitudinally, although this requires further investigation. An important caveat for DTI studies is that test-retest reliability may not be evenly distributed throughout the brain whereby highly anisotropic white matter regions tended to show lower relative within-subject variability than other white or grey matter regions.

Hacia una terapia neuroprotectora con cannabinoides en la enfermedad de Huntington : estudios preclínicos y clínicos

OpenAIRE

Valdeolivas Rojas, Sara

2017-01-01

La enfermedad de Huntington (EH) es una enfermedad con herencia autosómica dominante causada por una mutación en el gen IT15, que codifica la proteína huntingtina (HTT). Esta proteína presenta una amplia expresión células de mamíferos y, aunque su función exacta no es totalmente conocida, se sabe que está relacionada con la modulación de procesos celulares tales como transcripción génica, señalización celular, metabolismo energético y neurogénesis. La mutación consiste en una expansión excesi...

Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function

International Nuclear Information System (INIS)

Berent, S.; Giordani, B.; Lehtinen, S.; Markel, D.; Penney, J.B.; Buchtel, H.A.; Starosta-Rubinstein, S.; Hichwa, R.; Young, A.B.

1988-01-01

Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of 18 F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation

Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

Science.gov (United States)

Cui, Shi-Shuang; Ren, Ru-Jing; Wang, Ying; Wang, Gang; Chen, Sheng-Di

2017-08-08

Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

From mild ataxia to huntington disease phenocopy: the multiple faces of spinocerebellar ataxia 17.

Science.gov (United States)

Koutsis, Georgios; Panas, Marios; Paraskevas, George P; Bougea, Anastasia M; Kladi, Athina; Karadima, Georgia; Kapaki, Elisabeth

2014-01-01

Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

Bottleneck analysis at district level to illustrate gaps within the district health system in Uganda

Science.gov (United States)

Kiwanuka Henriksson, Dorcus; Fredriksson, Mio; Waiswa, Peter; Selling, Katarina; Swartling Peterson, Stefan

2017-01-01

ABSTRACT Background: Poor quality of care and access to effective and affordable interventions have been attributed to constraints and bottlenecks within and outside the health system. However, there is limited understanding of health system barriers to utilization and delivery of appropriate, high-impact, and cost-effective interventions at the point of service delivery in districts and sub-districts in low-income countries. In this study we illustrate the use of the bottleneck analysis approach, which could be used to identify bottlenecks in service delivery within the district health system. Methods: A modified Tanahashi model with six determinants for effective coverage was used to determine bottlenecks in service provision for maternal and newborn care. The following interventions provided during antenatal care were used as tracer interventions: use of iron and folic acid, intermittent presumptive treatment for malaria, HIV counseling and testing, and syphilis testing. Data from cross-sectional household and health facility surveys in Mayuge and Namayingo districts in Uganda were used in this study. Results: Effective coverage and human resource gaps were identified as the biggest bottlenecks in both districts, with coverage ranging from 0% to 66% for effective coverage and from 46% to 58% for availability of health facility staff. Our findings revealed a similar pattern in bottlenecks in both districts for particular interventions although the districts are functionally independent. Conclusion: The modified Tanahashi model is an analysis tool that can be used to identify bottlenecks to effective coverage within the district health system, for instance, the effective coverage for maternal and newborn care interventions. However, the analysis is highly dependent on the availability of data to populate all six determinants and could benefit from further validation analysis for the causes of bottlenecks identified. PMID:28581379

7 CFR 982.31 - Grower districts.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Grower districts. 982.31 Section 982.31 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... importance of production in each district and the number of growers in each district; (2) the geographic...

Level II scour analysis for Bridge 30, (HUNTTH00220030), on Town Highway 22, crossing Brush Brook, Huntington, Vermont

Science.gov (United States)

Burns, Ronda L.

1997-01-01

This report provides the results of a detailed Level II analysis of scour potential at structure HUNTTH00220030 on Town Highway 22 crossing Brush Brook, Huntington, Vermont (figures 1–8). A Level II study is a basic engineering analysis of the site, including a quantitative analysis of stream stability and scour (U.S. Department of Transportation, 1993). Results of a Level I scour investigation also are included in Appendix E of this report. A Level I investigation provides a qualitative geomorphic characterization of the study site. Information on the bridge, gleaned from Vermont Agency of Transportation (VTAOT) files, was compiled prior to conducting Level I and Level II analyses and is found in Appendix D.

Report: Wells Band Council Needs to Improve Its Accounting System to Comply With Federal Regulations

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Report #14-2-0316, July 14, 2014. The Wells Band Council’s accounting system did not comply with federal regulations, which resulted in $390,000 of questioned costs and proposed high-risk designation for the grantee.

Conflict Management in Declining School Districts.

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Boyd, William Lowe; Wheaton, Dennis R.

1983-01-01

Professional literature about managing conflicts associated with declining enrollments indicates the existing tension in this area. A research study shows that, while upper-middle class districts may succeed using a rational approach to decision making, lower class districts, for various reasons, may not. Special problems of urban districts are…

Differences in Food and Beverage Marketing Policies and Practices in US School Districts, by Demographic Characteristics of School Districts, 2012.

Science.gov (United States)

Merlo, Caitlin L; Michael, Shannon; Brener, Nancy D; Coffield, Edward; Kingsley, Beverly S; Zytnick, Deena; Blanck, Heidi

2016-12-15

Foods and beverages marketed in schools are typically of poor nutritional value. School districts may adopt policies and practices to restrict marketing of unhealthful foods and to promote healthful choices. Students' exposure to marketing practices differ by school demographics, but these differences have not yet been examined by district characteristics. We analyzed data from the 2012 School Health Policies and Practices Study to examine how food and beverage marketing and promotion policies and practices varied by district characteristics such as metropolitan status, size, and percentage of non-Hispanic white students. Most practices varied significantly by district size: a higher percentage of large districts than small or medium-sized districts restricted marketing of unhealthful foods and promoted healthful options. Compared with districts whose student populations were majority (>50%) non-Hispanic white, a higher percentage of districts whose student populations were minority non-Hispanic white (≤50% non-Hispanic white) prohibited advertising of soft drinks in school buildings and on school grounds, made school meal menus available to students, and provided families with information on school nutrition programs. Compared with suburban and rural districts, a higher percentage of urban districts prohibited the sale of soft drinks on school grounds and used several practices to promote healthful options. Preliminary findings showing significant associations between district demographics and marketing policies and practices can be used to help states direct resources, training, and technical assistance to address food and beverage marketing and promotion to districts most in need of improvement.

40 CFR 63.6105 - What are my general requirements for complying with this subpart?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true What are my general requirements for... Turbines General Compliance Requirements § 63.6105 What are my general requirements for complying with this..., oxidation catalyst emission control device or other air pollution control equipment, and monitoring...

Jordan Lake Watershed Protection District

Data.gov (United States)

Town of Chapel Hill, North Carolina — Polygon representing the area of the Jordan Lake Watershed Protection District. The Watershed Protection District (PDF) is a sensitive area of land that drains to...

VT Data - Overlay District 20170710, South Burlington

Data.gov (United States)

Vermont Center for Geographic Information — Overlay data for the City of South Burlington included in this data:Flood Plain Overlay DistrictTraffic Overlay DistrictInterstate Highway Overlay DistrictScenic...

Differences in Food and Beverage Marketing Policies and Practices in US School Districts, by Demographic Characteristics of School Districts, 2012

Science.gov (United States)

Michael, Shannon; Brener, Nancy D.; Coffield, Edward; Kingsley, Beverly S.; Zytnick, Deena; Blanck, Heidi

2016-01-01

Introduction Foods and beverages marketed in schools are typically of poor nutritional value. School districts may adopt policies and practices to restrict marketing of unhealthful foods and to promote healthful choices. Students’ exposure to marketing practices differ by school demographics, but these differences have not yet been examined by district characteristics. Methods We analyzed data from the 2012 School Health Policies and Practices Study to examine how food and beverage marketing and promotion policies and practices varied by district characteristics such as metropolitan status, size, and percentage of non-Hispanic white students. Results Most practices varied significantly by district size: a higher percentage of large districts than small or medium-sized districts restricted marketing of unhealthful foods and promoted healthful options. Compared with districts whose student populations were majority (>50%) non-Hispanic white, a higher percentage of districts whose student populations were minority non-Hispanic white (≤50% non-Hispanic white) prohibited advertising of soft drinks in school buildings and on school grounds, made school meal menus available to students, and provided families with information on school nutrition programs. Compared with suburban and rural districts, a higher percentage of urban districts prohibited the sale of soft drinks on school grounds and used several practices to promote healthful options. Conclusion Preliminary findings showing significant associations between district demographics and marketing policies and practices can be used to help states direct resources, training, and technical assistance to address food and beverage marketing and promotion to districts most in need of improvement. PMID:27978408

Accountability in district nursing practice: key concepts.

Science.gov (United States)

Griffith, Richard

2015-03-01

Public trust and confidence in district nurses is essential to the nurse-patient relationship that underpins effective care and treatment. That trust and confidence has even greater focus for district nurses who care for patients in their own homes. Those patients need to be able to count on the professionalism and probity of their district nurses. The professionalism and probity of district nurses is based on their accountability, which protects the public by imposing standards on district nurses and holds them answerable for their acts and omissions. This is the first of a series of articles on accountability in district nursing practice to mark the introduction of the revised Nursing and Midwifery Code on the 31 March 2015. This month's article considers the key concepts of accountability.

75 FR 43958 - Turlock Irrigation District and Modesto Irrigation District; Notice of Application for Amendment...

Science.gov (United States)

2010-07-27

... to the Turlock Irrigation District's Tuolumne Substation; (2) 23-mile-long, 69-kV Don Pedro-Hawkins Line extending from the Don Pedro switchyard to the Turlock Irrigation District's Hawkins Substation...

School District Cash Management. Program Audit.

Science.gov (United States)

New York State Legislative Commission on Expenditure Review, Albany.

New York State law permits school districts to invest cash not immediately needed for district operation and also specifies the kinds of investments that may be made in order to ensure the safety and liquidity of public funds. This audit examines cash management and investment practices in New York state's financially independent school districts.…

Reading a District Budget: Reporter Guide

Science.gov (United States)

McNeil, Michele

2013-01-01

Every school budget tells a story--about a district's spending plan, its priorities, goals, and financial health. The challenge is to wade through the jargon and numbers to unlock that story. Although budgets can vary significantly from district to district, and state to state, this primer seeks to introduce reporters to the fundamental components…

Are patients at risk for psychological maladjustment during fertility treatment less willing to comply with treatment? Results from the Portuguese validation of the SCREENIVF

NARCIS (Netherlands)

Lopes, V.; Canavarro, M.C.; Verhaak, C.M.; Boivin, J.; Gameiro, S.

2014-01-01

STUDY QUESTION: Do patients at risk for psychological maladjustment during fertility treatment present lower intentions to comply with recommended treatment than patients not at risk? SUMMARY ANSWER: Patients at risk of psychological maladjustment present similar high intentions to comply with

Interim district energy implementation

Energy Technology Data Exchange (ETDEWEB)

Fearnley, R.; Susak, W. [City of Vancouver, BC (Canada); Johnstone, I. [BCG Services Inc., Vancouver, BC (Canada)

2001-07-01

The concept of district energy was introduced in the City of North Vancouver, a city of 45,000, in 1997. A preliminary study was completed in 1997, followed by a tour of some district energy facilities in Finland in the same year. In 1999 a large district energy study was completed by a consultant. The study indicated the need for an investment of $15 million to implement district heating in the City. Lack of sufficient financial resources and immediately connectable heat load, the project was considered a non-starter. Some of the other factors leading to shelving the project included no current significant pricing advantages over competing energy sources and no current opportunity for cogeneration, given the low price that BC Hydro is willing to pay for independently produced power. The project, although shelved for the moment, has not been discarded. Planning and exploration are continuing, aided by the City's commitment to energy efficiency and conservation, its long term planning horizon and its significant influence over the development of some prime real estate.

Regional District Attorney's Offices - Alaska Department of Law

Science.gov (United States)

District Stephen B. Wallace, District Attorney Physical Address: 204 Chief Eddie Hoffman Hwy. Bethel, AK Hours M-TH 8-4:30, F 8-12 Kenai - 3rd Judicial District Scot H. Leaders, District Attorney Trading Bay

Energy supply and urban planning projects: Analysing tensions around district heating provision in a French eco-district

International Nuclear Information System (INIS)

Gabillet, Pauline

2015-01-01

Through the analysis of energy supply choices, this article explores the way in which energy priorities and their climate-related features are incorporated into urban public policy. These choices must take account of different factors, as is the case with district heating, which is justified as a vehicle of renewable energy while subject to pressure in eco-districts because its techno-economic balances are destabilised by falls in demand. Our study focuses particularly on the city of Metz (France), which has chosen district heating as the primary source for provision for the municipal area and for its first eco-district. We analyse the tensions within these choices, with particular attention to the way in which they are negotiated inside municipal departments and with the local energy operator. This enables us to explore the tensions in defining the scale that governs decisions and the linkages between energy-related and urban priorities. - Highlights: • Analyses of tensions in the choice of energy supplies for eco-districts. •District heating networks can be vehicles of renewable energy. • District heating networks are threatened by drops in energy consumption. • Energy supply issues oppose urban planning and energy policy in municipal departments. • Technical and financial adjustments can be made by the municipality to justify its energy choices

New Mexico State Forestry Districts

Data.gov (United States)

Earth Data Analysis Center, University of New Mexico — This dataset contains boundaries of the New Mexico Forestry Districts, plus the names of the district offices. It is in a vector digital structure digitized from a...

Agricultural Land Use in Ahlat District

Directory of Open Access Journals (Sweden)

Necmettin ELMASTAŞ

2009-12-01

Full Text Available Ahlat district has suitable topography for growing of agricultural products. Almost half of Ahlat district is suitable for agricultural. Today, 32.7% of the land use in Ahlat is agricultural area. 90% of agricultural area is dry farming area. 10% of agricultural area is irrigated. 60.3%of land use in Ahlat district is pasturage area. The economy of Ahlat is based on agricultural and animal husbandry. Today, agricultural products such as wheat, potato and sugar beet are grown in agricultural areas. Ahlat district has some problems like unplanned production, irrigation and marketing.

Late-onset Huntington's disease: diagnostic and prognostic considerations.

Science.gov (United States)

Koutsis, Georgios; Karadima, Georgia; Kladi, Athina; Panas, Marios

2014-07-01

To address diagnostic and prognostic issues in patients with late-onset Huntington's disease (HD). We analyzed a cohort of 41 late-onset (≥60 years) HD patients and compared them to 39 late-onset patients referred for HD testing that were negative for the HD-expansion and to 290 usual-onset (20-59 years) HD patients. Disease severity was assessed by the Total Functional Capacity Scale. Late-onset HD comprised 11.5% of our HD cohort. In total, 70.7% of late-onset HD patients had positive family history compared to 15.4% of late-onset expansion-negative patients (p < 0.001). Clinical features at onset or presentation could not usefully distinguish between late-onset expansion-positive and negative patients, excepting hemichorea, which was absent from the HD group (p = 0.024). Chorea was the first clinical feature in 53.7% and a presenting feature in 90.2% of late-onset HD. The mutation hit rate for late-onset patients was 51.3%, lower than in usual-onset patients (p = 0.04). Frequencies of chorea, cognitive impairment and psychiatric manifestations at onset or presentation were not significantly different between late-onset and usual-onset HD patients. Gait unsteadiness however was more common at presentation in late-onset HD (p = 0.007). Late-onset HD patients reached a severe stage of illness on average 2.8 years earlier than usual-onset HD patients (p = 0.046). A positive family history suggestive of HD, although absent in a third of patients, remains a helpful clue in diagnosing late-onset HD. Prognosis of late-onset HD in terms of Total Functional Capacity appears no better and shows a trend of being somewhat less favorable compared to usual-onset HD. Copyright © 2014 Elsevier Ltd. All rights reserved.

District heating in Flensburg

Energy Technology Data Exchange (ETDEWEB)

Prinz, W.

1981-01-01

The majority of our population, but also of our authorities, are still skeptical or even disapproving towards district heating. The reasons of this negative attitude are partly psychological - e.g. the individualism of the Swiss and their dislike for too centralised structures and ''forced connections'' - but also the existence of finished gas supply networks and the fear of considerable pre-investments and torn streets over years. The following article - held as a speech on the information meeting ''District heating and the possible contribution of nuclear energy'' organised by the Swiss Association for Atomic Energy in Bern shows a practical problem solving at the example of the district heating in Flensburg and deals with these questions.

Shortage of energy increases profitability of district heating

International Nuclear Information System (INIS)

2003-01-01

Increased demand will cause the price of district heating to increase, but not to the level of the price of electricity. The cheapest heating alternative in Denmark, Norway and Sweden is district heating. In Norway, district heating is developed primarily for commercial buildings and housing cooperatives. Thirty per cent of all buildings under construction are prepared for district heating and the percentage will increase strongly in the coming time. The total net production of district heating in Norway in 2001 was 2000 GWh, which is only a small part of the total potential for district heating

[Efficiency of Brazilian States and the Federal District in the public kidney transplant system based on DEA (Data Envelopment Analysis) and the Malmquist index].

Science.gov (United States)

Costa, Cassia Kely Favoretto; Balbinotto Neto, Giácomo; Sampaio, Luciano Menezes Bezerra

2014-08-01

The objective of this study was to evaluate the efficiency of Brazilian States and the Federal District in the public kidney transplant system and their productivity trends from 2006 to 2011. The authors used Data Envelopment Analysis (DEA) with slack and the Malmquist index with slack. Inputs included spending on hospital services and health professionals in the system. The output was the number of kidney transplants performed in each State. The data showed a significant discrepancy between States in the number of kidney transplants. The transplant system's inefficiency may result from inadequate management, failure to comply with national guidelines, inactive hospital transplant committees, and overburdened hospital staff. Institutional changes promoted by the Brazilian Ministry of Health (procedures improvement and standardization) failed to increase productivity in most States during this period.

Sleep-related modifications of EEG connectivity in the sensory-motor networks in Huntington Disease: An eLORETA study and review of the literature.

Science.gov (United States)

Piano, Carla; Imperatori, Claudio; Losurdo, Anna; Bentivoglio, Anna Rita; Cortelli, Pietro; Della Marca, Giacomo

2017-07-01

To evaluate EEG functional connectivity in the sensory-motor network, during wake and sleep, in patients with Huntington Disease (HD). 23 patients with HD and 23 age- and sex-matched healthy controls were enrolled. EEG connectivity analysis was performed by means of exact Low Resolution Electric Tomography (eLORETA). In wake, HD patients showed an increase of delta lagged phase synchronization (T=3.60; p<0.05) among Broadman's Areas (BA) 6-8 bilaterally; right BA 6-8 and right BA 1-2-3; left BA 1-2-3 and left BA 4. In NREM, HD patients showed an increase of delta lagged phase synchronization (T=3.56; p<0.05) among left BA 1-2-3 and right BA 6-8. In REM, HD patients showed an increase of lagged phase synchronization (T=3.60; p<0.05) among the BA 6-8 bilaterally (delta band); left BA 1-2-3 and right BA 1-2-3 (theta); left BA 1-2-3 and right BA 4 (theta); left BA 1-2-3 and right BA 1-2-3 (alpha). Our results may reflect an abnormal function of the motor areas or an effort to counterbalance the pathological motor output. Our results may help to understand the pathophysiology of sleep-related movement disorders in Huntington's Disease, and to define therapeutically strategies. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Understanding the organisational culture of district health services: Mahalapye and Ngamiland health districts of Botswana.

Science.gov (United States)

Nkomazana, Oathokwa; Mash, Robert; Phaladze, Nthabiseng

2015-11-30

Botswana has a shortage of health care workers, especially in primary healthcare. Retention and high performance of employees are closely linked to job satisfaction and motivation, which are both highest where employees' personal values and goals are realised. The aim of the study was to evaluate employees' personal values, and the current and desired organisational culture of the district health services as experienced by the primary health care workers. The study was conducted in the Ngamiland and Mahalapye health districts. This was a cross sectional survey. The participants were asked to select 10 values that best described their personal, current organisational and desired organisational values from a predetermined list. Sixty and 67 health care workers completed the survey in Mahalapye and Ngamiland districts, respectively. The top 10 prevalent organisational values experienced in both districts were: teamwork, patient satisfaction, blame, confusion, job insecurity, not sharing information and manipulation. When all the current values were assessed, 32% (Mahalapye) and 36% (Ngamiland) selected by health care workers were potentially limiting organisational effectiveness. The organisational values desired by health care workers in both districts were: transparency, professional growth, staff recognition, shared decision-making, accountability, productivity, leadership development and teamwork. The experience of the primary health care workers in the two health districts were overwhelmingly negative, which is likely to contribute to low levels of motivation, job satisfaction, productivity and high attrition rates. There is therefore urgent need for organisational transformation with a focus on staff experience and leadership development.

Mitochondrial DNA levels in Huntington disease leukocytes and dermal fibroblasts.

Science.gov (United States)

Jędrak, Paulina; Krygier, Magdalena; Tońska, Katarzyna; Drozd, Małgorzata; Kaliszewska, Magdalena; Bartnik, Ewa; Sołtan, Witold; Sitek, Emilia J; Stanisławska-Sachadyn, Anna; Limon, Janusz; Sławek, Jarosław; Węgrzyn, Grzegorz; Barańska, Sylwia

2017-08-01

Huntington disease (HD) is an inherited neurodegenerative disorder caused by mutations in the huntingtin gene. Involvement of mitochondrial dysfunctions in, and especially influence of the level of mitochondrial DNA (mtDNA) on, development of this disease is unclear. Here, samples of blood from 84 HD patients and 79 controls, and dermal fibroblasts from 10 HD patients and 9 controls were analysed for mtDNA levels. Although the type of mitochondrial haplogroup had no influence on the mtDNA level, and there was no correlation between mtDNA level in leukocytes in HD patients and various parameters of HD severity, some considerable differences between HD patients and controls were identified. The average mtDNA/nDNA relative copy number was significantly higher in leukocytes, but lower in fibroblasts, of symptomatic HD patients relative to the control group. Moreover, HD women displayed higher mtDNA levels in leukocytes than HD men. Because this is the largest population analysed to date, these results might contribute to explanation of discrepancies between previously published studies concerning levels of mtDNA in cells of HD patients. We suggest that the size of the investigated population and type of cells from which DNA is isolated could significantly affect results of mtDNA copy number estimation in HD. Hence, these parameters should be taken into consideration in studies on mtDNA in HD, and perhaps also in other diseases where mitochondrial dysfunction occurs.

Pitfalls in the detection of cholesterol in Huntington's disease models.

Science.gov (United States)

Marullo, Manuela; Valenza, Marta; Leoni, Valerio; Caccia, Claudio; Scarlatti, Chiara; De Mario, Agnese; Zuccato, Chiara; Di Donato, Stefano; Carafoli, Ernesto; Cattaneo, Elena

2012-10-11

Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington's disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it.

Predictive gene testing for Huntington disease and other neurodegenerative disorders.

Science.gov (United States)

Wedderburn, S; Panegyres, P K; Andrew, S; Goldblatt, J; Liebeck, T; McGrath, F; Wiltshire, M; Pestell, C; Lee, J; Beilby, J

2013-12-01

Controversies exist around predictive testing (PT) programmes in neurodegenerative disorders. This study sets out to answer the following questions relating to Huntington disease (HD) and other neurodegenerative disorders: differences between these patients in their PT journeys, why and when individuals withdraw from PT, and decision-making processes regarding reproductive genetic testing. A case series analysis of patients having PT from the multidisciplinary Western Australian centre for PT over the past 20 years was performed using internationally recognised guidelines for predictive gene testing in neurodegenerative disorders. Of 740 at-risk patients, 518 applied for PT: 466 at risk of HD, 52 at risk of other neurodegenerative disorders - spinocerebellar ataxias, hereditary prion disease and familial Alzheimer disease. Thirteen percent withdrew from PT - 80.32% of withdrawals occurred during counselling stages. Major withdrawal reasons related to timing in the patients' lives or unknown as the patient did not disclose the reason. Thirty-eight HD individuals had reproductive genetic testing: 34 initiated prenatal testing (of which eight withdrew from the process) and four initiated pre-implantation genetic diagnosis. There was no recorded or other evidence of major psychological reactions or suicides during PT. People withdrew from PT in relation to life stages and reasons that are unknown. Our findings emphasise the importance of: (i) adherence to internationally recommended guidelines for PT; (ii) the role of the multidisciplinary team in risk minimisation; and (iii) patient selection. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

Ontario Power Authority district energy research report : final report

International Nuclear Information System (INIS)

2010-02-01

This paper presented an analysis of the technical and economic characteristics of district energy in Ontario. The market context for district energy was evaluated, and institutional issues that may influence the future development and operation of district energy systems in Ontario were explored. Technical, economic, and environmental analyses of district energy based on different neighbourhood sizes, types, and district energy systems were presented. Three case studies were included to demonstrate real world district energy applications. A set of interviews conducted with representatives of the province's district energy supply chain was also provided in order to provide a framework for district energy opportunities and challenges within the province. 22 tabs., 16 figs.

Fisheries Districts

Data.gov (United States)

Vermont Center for Geographic Information — The Fisheries districts data layer is part of a larger dataset that contains administrative boundaries for Vermont's Agency of Natural Resources. The dataset...

Wastewater Districts

Data.gov (United States)

Vermont Center for Geographic Information — The Wastewater districts layer is part of a larger dataset that contains administrative boundaries for Vermont's Agency of Natural Resources. The dataset includes...

Wildlife Districts

Data.gov (United States)

Vermont Center for Geographic Information — The Wildlife Districts layer is part of a larger dataset contains administrative boundaries for Vermont's Agency of Natural Resources. The dataset includes feature...

Rural district hospitals - essential cogs in the district health system - and primary healthcare re-engineering.

Science.gov (United States)

le Roux, K W D P; Couper, I

2015-06-01

The re-engineering of primary healthcare (PHC) is regarded as an essential precursor to the implementation of National Health Insurance in South Africa, but improvements in the provision of PHC services have been patchy. The authors contend that the role of well- functioning rural district hospitals as a hub from which PHC services can be most efficiently managed has been underestimated, and that the management of district hospitals and PHC clinics need to be co-located at the level of the rural district hospital, to allow for proper integration of care and effective healthcare provision.

Warden Districts

Data.gov (United States)

Vermont Center for Geographic Information — This dataset is a representation overlay of warden (areas of responsibility). The Vermont Warden Districts layer is part of a dataset that contains administrative...

Park Districts

Data.gov (United States)

Vermont Center for Geographic Information — The Parks Districts layer is part of a dataset contains administrative boundaries for Vermont's Agency of Natural Resources. The dataset includes feature classes for...

Energy Assessment of Automated Mobility Districts

Energy Technology Data Exchange (ETDEWEB)

Chen, Yuche [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

2017-08-03

Automated vehicles (AVs) are increasingly being discussed as the basis for on-demand mobility services, introducing a new paradigm in which a fleet of AVs displace private automobiles for day-to-day travel in dense activity districts. This project examines such a concept to displace privately owned automobiles within a region containing dense activity generators (jobs, retail, entertainment, etc.), referred to as an automated mobility district (AMDs). The project reviews several such districts including airport, college campuses, business parks, downtown urban cores, and military bases, with examples of previous attempts to meet the mobility needs apart from private automobiles, some with automated technology and others with more traditional transit based solutions. The issues and benefits of AMDs are framed within the perspective of intra-district, inter-district, and border issues, and the requirements for a modeling framework are identified to adequately reflect the breadth of mobility, energy, and emissions impact anticipated with AMDs.

A good year for district heating

International Nuclear Information System (INIS)

Bakken, Stein Arne

2003-01-01

In Norway, high prices on electric power have caused economic progress for the district heating companies. The price of district heating is determined by the prices of power and fuel oil. However, the government wants to remove the tax on electricity to the industry, which is the district heating companies' major group of customers, along with public buildings. This is likely to entail a great loss of income

District heating in sequential energy supply

International Nuclear Information System (INIS)

Persson, Urban; Werner, Sven

2012-01-01

Highlights: ► European excess heat recovery and utilisation by district heat distribution. ► Heat recovery in district heating systems – a structural energy efficiency measure. ► Introduction of new theoretical concepts to express excess heat recovery. ► Fourfold potential for excess heat utilisation in EU27 compared to current levels. ► Large scale excess heat recovery – a collaborative challenge for future Europe. -- Abstract: Increased recovery of excess heat from thermal power generation and industrial processes has great potential to reduce primary energy demands in EU27. In this study, current excess heat utilisation levels by means of district heat distribution are assessed and expressed by concepts such as recovery efficiency, heat recovery rate, and heat utilisation rate. For two chosen excess heat activities, current average EU27 heat recovery levels are compared to currently best Member State practices, whereby future potentials of European excess heat recovery and utilisation are estimated. The principle of sequential energy supply is elaborated to capture the conceptual idea of excess heat recovery in district heating systems as a structural and organisational energy efficiency measure. The general conditions discussed concerning expansion of heat recovery into district heating systems include infrastructure investments in district heating networks, collaboration agreements, maintained value chains, policy support, world market energy prices, allocation of synergy benefits, and local initiatives. The main conclusion from this study is that a future fourfold increase of current EU27 excess heat utilisation by means of district heat distribution to residential and service sectors is conceived as plausible if applying best Member State practice. This estimation is higher than the threefold increase with respect to direct feasible distribution costs estimated by the same authors in a previous study. Hence, no direct barriers appear with

Forestry Districts

Data.gov (United States)

Vermont Center for Geographic Information — The Forestry Districts layer is part of a dataset that contains administrative boundaries for Vermont's Agency of Natural Resources. This is a layer file which...

The situation of district heating, district cooling and energy supply in Hungary

International Nuclear Information System (INIS)

Sigmond, Gy.

2009-01-01

District heating represents with 650.000 heated dwellings approximately 15% of the Hungarian residential heating market. Since 1990 there is stagnation at the number of connected dwellings because erection of large settlements with prefab buildings has been stopped, and latter ones represent more than 75% of the dwelling heating market. During the same period, residential heat demand shrunk by 33%, because metering of hot water consumption resulted in changing consumer habits, and because of slowly but step by step refurbishment of buildings and heating systems. In Hungary district heating is present in all large and most of the medium size cities, in 92 cities together. Out of them, there is also a single village with a local district heating system, which heats more than 60% of cottages. The capacity os systems is spreading to a large extent. Approximately 36-36% of all heated dwellings are in Budapest and in 10 large cities in the country, while 148 of the total 202 systems have less than 10 MW capacities. In the fuel structure of district heating it is characteristic the overwhelming role of natural gas consumption, which has exceeded 80% already. Only a few numbers of heating power plants are fuelled by crown coal. The use of renewables is growing continuous, but, together with waste and waste energy, it amounts merely 8% of the total fuel use. Oil consumption is negligible. Currently the most promising DH-market is the service sector (public buildings and commercial consumers). DH-companies can sell their surplus supply capacities on the competitive market. Residential market can be preserved only with better legal conditions and with improving of demand side management. The industrial heat market can be gained when the erection of new power plants will be harmonized with industrial development in the frame of territorial planning. District cooling is just at the beginning in Hungary. Many new commercial and office buildings are erected with air conditioning

Altered hypothalamic protein expression in a rat model of Huntington's disease.

Directory of Open Access Journals (Sweden)

Wei-na Cong

Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

Epidemiological Study of Huntington's Disease in the Province of Ferrara, Italy.

Science.gov (United States)

Carrassi, Erika; Pugliatti, Maura; Govoni, Vittorio; Sensi, Mariachiara; Casetta, Ilaria; Granieri, Enrico

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of CAG triplet repeat. We aimed to reappraise HD epidemiology in a northern Italian population, in relation to introduction of genetic testing. Through ICD-9M code 333.4 and medical fare exemption code RF0080, HD cases were identified from administrative health data and medical records from the Units of Neurology and Genetics, Ferrara University Hospital, and from other provincial neurological structures. HD mean annual incidence rate in 1990-2009 was 0.3 per 100,000 (95% CI 0.2-0.5). All incident cases were found to have symptoms of the disease's classic form, and neither juvenile nor the rigid Westphal variant was detected. The mean (SD) age at onset was 50.2 (12.7 years; range 32-82 years), 54.9 (14.6) for men and 45.8 (9.4) for women. On prevalence day, December 31, 2014, HD prevalence was 4.2 per 100,000 (95% CI 2.4-7.0), with a male:female ratio of 1:2. The prevalence and incidence of HD in our population were lower than the prevalence and incidence reported for other European and Italian populations, but higher compared to those of Asia, Africa, and Eastern Europe. Compared to previous studies, HD incidence and prevalence did not change significantly. © 2017 S. Karger AG, Basel.

The Role of School District Science Coordinators in the District-Wide Appropriation of an Online Resource Discovery and Sharing Tool for Teachers

Science.gov (United States)

Lee, Victor R.; Leary, Heather M.; Sellers, Linda; Recker, Mimi

2014-06-01

When introducing and implementing a new technology for science teachers within a school district, we must consider not only the end users but also the roles and influence district personnel have on the eventual appropriation of that technology. School districts are, by their nature, complex systems with multiple individuals at different levels in the organization who are involved in supporting and providing instruction. Varying levels of support for new technologies between district coordinators and teachers can sometimes lead to counterintuitive outcomes. In this article, we examine the role of the district science coordinator in five school districts that participated in the implementation of an online resource discovery and sharing tool for Earth science teachers. Using a qualitative approach, we conducted and coded interviews with district coordinators and teachers to examine the varied responsibilities associated with the district coordinator and to infer the relationships that were developed and perceived by teachers. We then examine and discuss two cases that illustrate how those relationships could have influenced how the tool was adopted and used to differing degrees in the two districts. Specifically, the district that had high support for online resource use from its coordinator appeared to have the lowest level of tool use, and the district with much less visible support from its coordinator had the highest level of tool use. We explain this difference in terms of how the coordinator's promotion of teacher autonomy took distinctly different forms at those two districts.

Understanding the organisational culture of district health services: Mahalapye and Ngamiland health districts of Botswana

Directory of Open Access Journals (Sweden)

Oathokwa Nkomazana

2015-11-01

Full Text Available Background: Botswana has a shortage of health care workers, especially in primary healthcare. Retention and high performance of employees are closely linked to job satisfaction and motivation, which are both highest where employees’ personal values and goals are realised. Aim: The aim of the study was to evaluate employees’ personal values, and the current and desired organisational culture of the district health services as experienced by the primary health care workers. Setting: The study was conducted in the Ngamiland and Mahalapye health districts. Method: This was a cross sectional survey. The participants were asked to select 10 values that best described their personal, current organisational and desired organisational values from a predetermined list. Results: Sixty and 67 health care workers completed the survey in Mahalapye and Ngamiland districts, respectively. The top 10 prevalent organisational values experienced in both districts were: teamwork, patient satisfaction, blame, confusion, job insecurity, not sharing information and manipulation. When all the current values were assessed, 32% (Mahalapye and 36% (Ngamiland selected by health care workers were potentially limiting organisational effectiveness. The organisational values desired by health care workers in both districts were: transparency, professional growth, staff recognition, shared decision-making, accountability, productivity, leadership development and teamwork. Conclusions: The experience of the primary health care workers in the two health districts were overwhelmingly negative, which is likely to contribute to low levels of motivation, job satisfaction, productivity and high attrition rates. There is therefore urgent need for organisational transformation with a focus on staff experience and leadership development.

Patterns of False Memory in Patients with Huntington's Disease.

Science.gov (United States)

Chen, I-Wen; Chen, Chiung-Mei; Wu, Yih-Ru; Hua, Mau-Sun

2017-06-01

Increased false memory recognition in patients with Huntington's disease (HD) has been widely reported; however, the underlying memory constructive processes remain unclear. The present study explored gist memory, item-specific memory, and monitoring ability in patients with HD. Twenty-five patients (including 13 patients with mild HD and 12 patients with moderate-to-severe HD) and 30 healthy comparison participants (HC) were recruited. We used the Deese-Roediger-McDermott (DRM) paradigm to investigate participants' false recognition patterns, along with neuropsychological tests to assess general cognitive function. Both mild and moderate-to-severe patients with HD showed significant executive functioning and episodic memory impairment. On the DRM tasks, both HD patient groups showed significantly impaired performance in tasks assessing unrelated false recognition and item-specific memory as compared to the HC group; moderate-to-severe patients performed more poorly than mild patients did. Only moderate-severe patients exhibited significantly poorer related false recognition index scores than HCs in the verbal DRM task; performance of HD patient groups was comparable to the HC group on the pictorial DRM task. It appears that diminished verbatim memory and monitoring ability are early signs of cognitive decline during the HD course. Conversely, gist memory is relatively robust, with only partial decline during advanced-stage HD. Our findings suggest that medial temporal lobe function is relatively preserved compared to that of frontal-related structures in early HD. Thus, gist-based memory rehabilitation programs might be beneficial for patients with HD. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Monomeric, Oligomeric and Polymeric Proteins in Huntington Disease and Other Diseases of Polyglutamine Expansion

Directory of Open Access Journals (Sweden)

Guylaine Hoffner

2014-03-01

Full Text Available Huntington disease and other diseases of polyglutamine expansion are each caused by a different protein bearing an excessively long polyglutamine sequence and are associated with neuronal death. Although these diseases affect largely different brain regions, they all share a number of characteristics, and, therefore, are likely to possess a common mechanism. In all of the diseases, the causative protein is proteolyzed, becomes abnormally folded and accumulates in oligomers and larger aggregates. The aggregated and possibly the monomeric expanded polyglutamine are likely to play a critical role in the pathogenesis and there is increasing evidence that the secondary structure of the protein influences its toxicity. We describe here, with special attention to huntingtin, the mechanisms of polyglutamine aggregation and the modulation of aggregation by the sequences flanking the polyglutamine. We give a comprehensive picture of the characteristics of monomeric and aggregated polyglutamine, including morphology, composition, seeding ability, secondary structure, and toxicity. The structural heterogeneity of aggregated polyglutamine may explain why polyglutamine-containing aggregates could paradoxically be either toxic or neuroprotective.

Nanopublications for exposing experimental data in the life-sciences: a Huntington's Disease case study.

Science.gov (United States)

Mina, Eleni; Thompson, Mark; Kaliyaperumal, Rajaram; Zhao, Jun; der Horst, van Eelke; Tatum, Zuotian; Hettne, Kristina M; Schultes, Erik A; Mons, Barend; Roos, Marco

2015-01-01

Data from high throughput experiments often produce far more results than can ever appear in the main text or tables of a single research article. In these cases, the majority of new associations are often archived either as supplemental information in an arbitrary format or in publisher-independent databases that can be difficult to find. These data are not only lost from scientific discourse, but are also elusive to automated search, retrieval and processing. Here, we use the nanopublication model to make scientific assertions that were concluded from a workflow analysis of Huntington's Disease data machine-readable, interoperable, and citable. We followed the nanopublication guidelines to semantically model our assertions as well as their provenance metadata and authorship. We demonstrate interoperability by linking nanopublication provenance to the Research Object model. These results indicate that nanopublications can provide an incentive for researchers to expose data that is interoperable and machine-readable for future use and preservation for which they can get credits for their effort. Nanopublications can have a leading role into hypotheses generation offering opportunities to produce large-scale data integration.

From Mild Ataxia to Huntington Disease Phenocopy: The Multiple Faces of Spinocerebellar Ataxia 17

Directory of Open Access Journals (Sweden)

Georgios Koutsis

2014-01-01

Full Text Available Introduction. Spinocerebellar ataxia 17 (SCA 17 is a rare autosomal dominant cerebellar ataxia (ADCA caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

Exploring the ethos of district nursing, 1885-1985.

Science.gov (United States)

Madsen, Wendy

2013-06-01

The history of district nursing in Australia explored in this paper reveals a continuity in the essential values held by district nurses for over a century. These nurses practised holistic, family-centred nursing from the very origins of district nursing service. The events surrounding the establishment of Community Health Centres in the 1970s challenged district nurses to reconsider their role, while at the same time reconfirming their essential ethos. These values that underpinned district nursing practice and challenges to these values are examined in this paper.

Boise geothermal district heating system

Energy Technology Data Exchange (ETDEWEB)

Hanson, P.J.

1985-10-01

This document describes the Boise geothermal district heating project from preliminary feasibility studies completed in 1979 to a fully operational system by 1983. The report includes information about the two local governments that participated in the project - the City of Boise, Idaho and the Boise Warm Springs Water District. It also discusses the federal funding sources; the financial studies; the feasibility studies conducted; the general system planning and design; design of detailed system components; the legal issues involved in production; geological analysis of the resource area; distribution and disposal; the program to market system services; and the methods of retrofitting buildings to use geothermal hot water for space heating. Technically this report describes the Boise City district heating system based on 170/sup 0/F water, a 4000 gpm production system, a 41,000 foot pipeline system, and system economies. Comparable data are also provided for the Boise Warm Springs Water District. 62 figs., 31 tabs.

VT Data - Overlay District 20070306, Marlboro

Data.gov (United States)

Vermont Center for Geographic Information — Cartographic version of overlay district (surface water buffer), Marlboro, Vermont. Base zoning districts are in a separate shapefile. Data were originally created...

Generation of induced pluripotent stem cell line, CSSi004-A (2962, from a patient diagnosed with Huntington's disease at the presymptomatic stage

Directory of Open Access Journals (Sweden)

Eris Bidollari

2018-04-01

Full Text Available Huntington's disease (HD is an incurable, autosomal dominant, hereditary neurodegenerative disorder that typically manifests itself in midlife. This pathology is linked to the deregulation of multiple, as yet unknown, cellular processes starting before HD onset. A human iPS cell line was generated from skin fibroblasts of a subject at the presymptomatic life stage, carrying a polyglutamine expansion in HTT gene codifying Huntingtin protein. The iPSC line contained the expected CAG expansion, expressed the expected pluripotency markers, displayed in vivo differentiation potential to the three germ layers and had a normal karyotype.

Fire and EMS Districts, Fire District boundaries within Sedgwick County. Cover is programmatically derived from taxing unit districts. Used for Public Safety map rolls. Primary attribute is fire district name. Published to scfiredia.shp., Published in 2008, 1:1200 (1in=100ft) scale, Sedgwick County Government.

Data.gov (United States)

NSGIC Local Govt | GIS Inventory — Fire and EMS Districts dataset current as of 2008. Fire District boundaries within Sedgwick County. Cover is programmatically derived from taxing unit districts....

U.S. Coast Guard (USCG) Districts

Data.gov (United States)

Department of Homeland Security — This layer is a polygonal dataset that represents land and maritime boundaries for each representative United States Coast Guard district, which includes district 1,...

Clinical utility of FDG-PET in amyotrophic lateral sclerosis and Huntington's disease.

Science.gov (United States)

Agosta, Federica; Altomare, Daniele; Festari, Cristina; Orini, Stefania; Gandolfo, Federica; Boccardi, Marina; Arbizu, Javier; Bouwman, Femke; Drzezga, Alexander; Nestor, Peter; Nobili, Flavio; Walker, Zuzana; Pagani, Marco

2018-05-01

To evaluate the incremental value of FDG-PET over clinical tests in: (i) diagnosis of amyotrophic lateral sclerosis (ALS); (ii) picking early signs of neurodegeneration in patients with a genetic risk of Huntington's disease (HD); and detecting metabolic changes related to cognitive impairment in (iii) ALS and (iv) HD patients. Four comprehensive literature searches were conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on these four diagnostic scenarios. The availability of evidence was good for FDG-PET utility to support the diagnosis of ALS, poor for identifying presymptomatic subjects carrying HD mutation who will convert to HD, and lacking for identifying cognitive-related metabolic changes in both ALS and HD. After the Delphi consensual procedure, the panel did not support the clinical use of FDG-PET for any of the four scenarios. Relative to other neurodegenerative diseases, the clinical use of FDG-PET in ALS and HD is still in its infancy. Once validated by disease-control studies, FDG-PET might represent a potentially useful biomarker for ALS diagnosis. FDG-PET is presently not justified as a routine investigation to predict conversion to HD, nor to detect evidence of brain dysfunction justifying cognitive decline in ALS and HD.

Co-segregation of Huntington disease and hereditary spastic paraplegia in 4 generations.

Science.gov (United States)

Panas, Marios; Karadima, Georgia; Kalfakis, Nikolaos; Vassilopoulos, Dimitris

2011-07-01

Huntington disease (HD) is an autosomal dominant neurodegenerative disease characterized by choreic hyperkinesias, cognitive decline, and psychiatric manifestations, caused by an increased number of CAG repeats in the IT15 gene on chromosome 4p16.3. Silver syndrome is a rare autosomal dominant form of complicated hereditary spastic paraplegia, characterized by lower limb spasticity in addition to amyotrophy of the small muscles of the hands. In addition to the previously identified locus SPG17 on chromosome 11q12-q14, a new locus (SPG38) on chromosome 4p16-p15 has been recently identified, a region that includes the HD gene. We present a Greek family with 5 members diagnosed with HD in 4 generations. All affected members also presented with clinical features of Silver syndrome showing severe spastic paraplegia and prominent atrophy of all small hand muscles bilaterally. None of the other family members showed features of either HD or spastic paraplegia. The reported coexistence of Silver syndrome with HD in 4 generations is not fortuitous, suggesting that these 2 distinct genetic disorders are in linkage disequilibrium. Although rare, it is reasonable to expect additional similar cases. Clinical neurologists should perhaps investigate this possibility in cases combining features of HD and involvement of the upper and lower motor neurons.

The role of oxidative stress in Huntington's disease: are antioxidants good therapeutic candidates?

Science.gov (United States)

Gil-Mohapel, Joana; Brocardo, Patricia S; Christie, Brian R

2014-04-01

Huntington's disease (HD) is the most common polyglutamine neurodegenerative disorder in humans, and is caused by a mutation of an unstable expansion of CAG repeats within the coding region of the HD gene, which expresses the protein huntingtin. Although abnormal protein is ubiquitously expressed throughout the organism, cell degeneration occurs mainly in the brain, and there, predominantly in the striatum and cortex. The mechanisms that account for this selective neuronal death are multifaceted in nature and several lines of evidence suggest that mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and oxidative stress (an imbalance between pro-oxidant and antioxidant systems resulting in oxidative damage to proteins, lipids and DNA) might play important roles. Over time, this can result in the death of the affected neuronal populations. In this review article we present an overview of the preclinical and clinical studies that have indicated a link between oxidative stress, neurodegeneration, and cell death in HD. We also discuss how changes in ROS production affect neuronal survival, highlighting the evidence for the use of antioxidants including essential fatty acids, coenzyme Q10, and creatine, as potential therapeutic strategies for the treatment of this devastating neurodegenerative disorder.

VT Data - Overlay District 20170228, Richmond

Data.gov (United States)

Vermont Center for Geographic Information — The following overlay districts are included in the data:Shoreline Protection OverlayFlood Hazard OverlayDetails about these overlay districts, as well as zoning...

The Development of the Comic Spirit in 17th Century England from James Shirley to William Congreve. Curriculum Projects, April 7-June 16, 1992. The Huntington Theatre Company Master Works Study in Restoration Comedy.

Science.gov (United States)

Huntington Theatre Co., Boston, MA.

Developed by the participants of the Huntington Theatre Company's Master Works Study in Restoration Comedy, this collection presents one-day lesson plans and curriculum projects for teaching Restoration comedy. The collection offers 15 one-day lesson plans and 15 curriculum projects (ranging over several weeks) suitable for secondary school…

25 CFR 161.308 - Must a permittee comply with standards of conduct if granted a permit?

Science.gov (United States)

2010-04-01

... grazing operations in accordance with the principles of sustained yield management, agricultural resource management planning, sound conservation practices, and other community goals as expressed in Navajo Nation laws, agricultural resource management plans, and similar sources. (b) Comply with all applicable laws...

About the marshallian industrial district and the theory of the contemporary district. A brief critical reconstruction

Directory of Open Access Journals (Sweden)

Giacomo Becattini

2002-01-01

Full Text Available As a departing point, the paper presents the historical genesis of the concept of industrial district focusing on the scientific views of the pioneer of this field, Alfred Marshall. The concept has its origins in the observation of the current industrial reality, mainly of the British one. The purpose is to give an explanation to the difficulties of the classic theory and to study the challenges of the class conflicts. The economic conditions which launched British industrial districts were present, grosso modo, in Italy after the second World War. Some contributions have dealt with the little industrialisation of some Italian regions and using Marshallian thoughts have rediscovered the industrial districts phenomenon. This is the starting point of a high number of scientific contribution in Italy and abroad. Some of these international studies, particularly the ones made by Spanish experts, are quoted. The text analyses the link between districts-made in Italy with the competitive advantages of Italian products in many economic activities (i.e. clothing, shoes, furniture, etc.. Finally, in the third part the paper reviews some new contributions on the industrial district in Italy.

Decentralization in Zambia: resource allocation and district performance.

Science.gov (United States)

Bossert, Thomas; Chitah, Mukosha Bona; Bowser, Diana

2003-12-01

Zambia implemented an ambitious process of health sector decentralization in the mid 1990s. This article presents an assessment of the degree of decentralization, called 'decision space', that was allowed to districts in Zambia, and an analysis of data on districts available at the national level to assess allocation choices made by local authorities and some indicators of the performance of the health systems under decentralization. The Zambian officials in health districts had a moderate range of choice over expenditures, user fees, contracting, targeting and governance. Their choices were quite limited over salaries and allowances and they did not have control over additional major sources of revenue, like local taxes. The study found that the formula for allocation of government funding which was based on population size and hospital beds resulted in relatively equal per capita expenditures among districts. Decentralization allowed the districts to make decisions on internal allocation of resources and on user fee levels and expenditures. General guidelines for the allocation of resources established a maximum and minimum percentage to be allocated to district offices, hospitals, health centres and communities. Districts tended to exceed the maximum for district offices, but the large urban districts and those without public district hospitals were not even reaching the minimum for hospital allocations. Wealthier and urban districts were more successful in raising revenue through user fees, although the proportion of total expenditures that came from user fees was low. An analysis of available indicators of performance, such as the utilization of health services, immunization coverage and family planning activities, found little variation during the period 1995-98 except for a decline in immunization coverage, which may have also been affected by changes in donor funding. These findings suggest that decentralization may not have had either a positive or

The Nation's Report Card Reading 2009 Trial Urban District Snapshot Report. Austin Independent School District. Grade 8, Public Schools

Science.gov (United States)

National Center for Education Statistics, 2010

2010-01-01

Each district that participated in the National Assessment of Educational Progress (NAEP) 2009 Trial Urban District Assessment in reading receives a one-page snapshot report that presents key findings and trends in a condensed format. This report presents the results for Austin Independent School District's student achievement in reading. In 2009,…

The Nation's Report Card Reading 2009 Trial Urban District Snapshot Report. Austin Independent School District. Grade 4, Public Schools

Science.gov (United States)

National Center for Education Statistics, 2010

2010-01-01

Each district that participated in the National Assessment of Educational Progress (NAEP) 2009 Trial Urban District Assessment in reading receives a one-page snapshot report that presents key findings and trends in a condensed format. This report presents the results for Austin Independent School District's student achievement in reading. In 2009,…

Redesigning the District Operating System

Science.gov (United States)

Hodas, Steven

2015-01-01

In this paper, we look at the inner workings of a school district through the lens of the "district operating system (DOS)," a set of interlocking mutually-reinforcing modules that includes functions like procurement, contracting, data and IT policy, the general counsel's office, human resources, and the systems for employee and family…

An evaluation of the effectiveness of the EPA comply code to demonstrate compliance with radionuclide emission standards at three manufacturing facilities

International Nuclear Information System (INIS)

Smith, L.R.; Laferriere, J.R.; Nagy, J.W.

1991-01-01

Measurements of airborne radionuclide emissions and associated environmental concentrations were made at, and in the vicinity of, two urban and one suburban facility where radiolabeled chemicals for biomedical research and radiopharmaceuticals are manufactured. Emission, environmental and meteorological measurements were used in the EPA COMPLY code and in environmental assessment models developed specifically for these sites to compare their ability to predict off-site measurements. The models and code were then used to determine potential dose to hypothetical maximally exposed receptors and the ability of these methods to demonstrate whether these facilities comply with proposed radionuclide emission standards assessed. In no case did the models and code seriously underestimate off-site impacts. However, for certain radionuclides and chemical forms, the EPA COMPLY code was found to overestimate off-site impacts by such a large factor as to render its value questionable for determining regulatory compliance. Recommendations are offered for changing the code to enable it to be more serviceable to radionuclide users and regulators

Oregon School Bond Manual. Fifth Edition.

Science.gov (United States)

Oregon State Dept. of Education, Salem.

To help school districts comply with Oregon's school bond laws, this manual provides guidelines for school district attorneys and personnel in the issuance and sale of school bonds. The document describes the proper time sequence of the bonding procedure, including elections, school board authorizations, necessary certificates, bond registration…

No intention to comply with influenza and pneumococcal vaccination : behavioural determinants among smokers and non-smokers

NARCIS (Netherlands)

Looijmans-van den Akker, I; van den Heuvel, P.M.; Verheij, Th J M; van Delden, J J M; van Essen, G A; Hak, E

OBJECTIVE: Smoking increases the risk for influenza and pneumococcal disease, but vaccination uptake is lower among smokers than non-smokers. We therefore aimed to determine reasons for not complying with vaccination among smokers and non-smokers. METHOD: In 2005 a self-administered questionnaire

4th Generation District Heating (4GDH)

DEFF Research Database (Denmark)

Lund, Henrik; Werner, Sven; Wiltshire, Robin

2014-01-01

This paper defines the concept of 4th Generation District Heating (4GDH) including the relations to District Cooling and the concepts of smart energy and smart thermal grids. The motive is to identify the future challenges of reaching a future renewable non-fossil heat supply as part...... of the implementation of overall sustainable energy systems. The basic assumption is that district heating and cooling has an important role to play in future sustainable energy systems – including 100 percent renewable energy systems – but the present generation of district heating and cooling technologies will have...

Predictors of Workplace Disability in a Premanifest Huntington's Disease Cohort.

Science.gov (United States)

Goh, Anita M Y; You, Emily; Perin, Stephanie; Clay, Fiona J; Loi, Samantha; Ellis, Kathryn; Chong, Terence; Ames, David; Lautenschlager, Nicola

2018-01-01

Huntington's disease (HD) is an inherited neurodegenerative disease involving motor, cognitive, and psychiatric/behavioral impairments that will eventually affect work role functioning. Few objective data exist regarding predictors of workplace disability in HD. The authors explored the predictors of work impairment and disability in a cross-sectional cohort of 656 employed, premanifest HD (preHD) individuals. In this cohort-the majority of whom were female, urban-dwelling, married/partnered, and working full-time, with minimal cognitive impairment, good function, minimal motor abnormality, and no indication of significant mental health issues-the number of participants who reported that they had missed work due to HD was low (2.4%). However, 12% of the study sample reported experiencing impairment while working due to preHD, 12.2% reported work-related activity impairment due to preHD, and 12.7% reported impairment in their overall work ability. Higher numbers of CAG repeats on the mutant allele and having more motor symptoms were associated with significantly higher odds of experiencing workplace impairment. Importantly, several modifiable factors were also found to predict workplace disability. Specifically, higher levels of anxiety symptoms were associated with significantly higher odds of experiencing workplace impairment. Good mental and physical health served as protective factors, where good physical health was associated with 6% lower odds of experiencing impairment or missing work time and good mental health was associated with of 10%-12% lower. The results provide important new knowledge for the development of future targeted intervention trials to support preHD individuals in maintaining their work roles as long as possible.

Drosophila eye color mutants as therapeutic tools for Huntington disease.

Science.gov (United States)

Green, Edward W; Campesan, Susanna; Breda, Carlo; Sathyasaikumar, Korrapati V; Muchowski, Paul J; Schwarcz, Robert; Kyriacou, Charalambos P; Giorgini, Flaviano

2012-01-01

Huntington disease (HD) is a fatal inherited neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein (htt). A pathological hallmark of the disease is the loss of a specific population of striatal neurons, and considerable attention has been paid to the role of the kynurenine pathway (KP) of tryptophan (TRP) degradation in this process. The KP contains three neuroactive metabolites: 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN), and kynurenic acid (KYNA). 3-HK and QUIN are neurotoxic, and are increased in the brains of early stage HD patients, as well as in yeast and mouse models of HD. Conversely, KYNA is neuroprotective and has been shown to be decreased in HD patient brains. We recently used a Drosophila model of HD to measure the neuroprotective effect of genetic and pharmacological inhibition of kynurenine monoxygenase (KMO)-the enzyme catalyzing the formation of 3-HK at a pivotal branch point in the KP. We found that KMO inhibition in Drosophila robustly attenuated neurodegeneration, and that this neuroprotection was correlated with reduced levels of 3-HK relative to KYNA. Importantly, we showed that KP metabolites are causative in this process, as 3-HK and KYNA feeding experiments modulated neurodegeneration. We also found that genetic inhibition of the upstream KP enzyme tryptophan-2,3-dioxygenase (TDO) was neuroprotective in flies. Here, we extend these results by reporting that genetic impairment of KMO or TDO is protective against the eclosion defect in HD model fruit flies. Our results provide further support for the possibility of therapeutic KP interventions in HD.

Suburban District Leadership Does Matter

Science.gov (United States)

Thompson, Eustace; France, Roxanne Garcia

2015-01-01

The increased demand for educational reform and accountability has resulted in a renewed focus on the relationship between building leaders and district leaders, particularly on how district leaders can support principals to ensure the academic success of students. The No Child Left Behind Act of 2001 (NCLB) and Race to the Top (RttT) legislations…

Louisiana State Senate Districts from LEGIS source data, Geographic NAD83, LOSCO (2004) [la_senate_districts_LEGIS_2003

Data.gov (United States)

Louisiana Geographic Information Center — Louisiana State Senate Districts. The district boundaries are the result of legislative acts and redistricting. Reapportionment (redistricting) occurs during the...

Role and Function Sub District in the Implementation of Local Government in Semarang City and District of Semarang Central Java Province

Directory of Open Access Journals (Sweden)

Gunawan

2014-12-01

Full Text Available Sub district in performing common functions government implementation and administration functions of the tasks that have been submitted by District City in accordance with the Law No. 32 Year 2004 on Regional Government and Government Regulation No. 19 Year 2008 on the District experienced a bottleneck in its application in the form of authority, institutional, resource human resources and management districts, the study used a qualitative approach, purposive sampling areas that have been submitted and have not been handed over authority to the districts, the results showed that the authority has submitted both the mayor and the regent was not fully submitted, institution or organization not adjust districts Government Regulation No. 19 in 2008, the quality and quantity of human resources become a bottleneck in the implementation of tasks and discretionary attributive.

Effective team management by district nurses.

Science.gov (United States)

Bliss, Julie

2004-12-01

This article considers the key role played by the district nurse in managing the district nursing team in order to provide high quality health care. It considers how the district nurse can use key managerial roles (interpersonal, informational and decision-making) in order to ensure unity within the team. The importance of shared goals and trust to achieve unity is explored and a strategy for managing conflict is discussed. Finally, the article suggests a set of ground rules which could be used to facilitate effective team working.

Louisiana State House Districts from LEGIS source data, Geographic NAD83, LOSCO (2004) [la_house_districts_LEGIS_2004

Data.gov (United States)

Louisiana Geographic Information Center — Louisiana State House Districts. The district boundaries are the result of legislative acts and redistricting. Reapportionment (redistricting) occurs during the next...

29 CFR 575.9 - Failure to comply with the terms and conditions of the waiver.

Science.gov (United States)

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Failure to comply with the terms and conditions of the waiver. 575.9 Section 575.9 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS WAIVER OF CHILD LABOR PROVISIONS FOR AGRICULTURAL EMPLOYMENT OF 10 AND 11...

A Tale of Two Districts

Science.gov (United States)

Simon, Mark

2012-01-01

These days, everyone seems to be wringing their hands about how to construct new evaluation systems that will make teachers better. This unnecessary angst has led to crazy experiments in reform that have embraced churn for the sake of churn, put school districts at risk, and demoralized many of the most talented teachers. A few school districts,…

Brain energy metabolism and dopaminergic function in Huntington's disease measured in vivo using positron emission tomography

International Nuclear Information System (INIS)

Leenders, K.L.; Frackowiak, R.S.; Quinn, N.; Marsden, C.D.

1986-01-01

A 48-year-old man with typical Huntington's disease was investigated with computed tomography (CT) and positron emission tomography. Regional cerebral blood flow, oxygen extraction, oxygen and glucose utilization, L-Dopa uptake, and dopamine (D2) receptor binding were measured using several positron-labelled tracers. CT showed slight atrophy of the head of caudate but no cortical atrophy, although distinct frontal lobe dysfunction was present on psychometric testing. Oxygen and glucose metabolism and cerebral blood flow were decreased in the striata and to a lesser extent in frontal cortex. Cerebral blood flow was in the low normal range throughout the remainder of the brain. A normal metabolic ratio was found in all regions, since the changes in glucose utilization paralleled those in oxygen consumption. The capacity of the striatum to store dopamine as assessed by L-[ 18 F]-fluorodopa uptake was normal, but dopamine (D2) receptor binding was decreased when compared to normal subjects

Internal control reporting and accounting quality : Insight "comply-or-explain" internal control regime

OpenAIRE

Cao Thi Thanh, Huyen; Cheung, Tina

2010-01-01

Nowadays, there exist two reporting regimes, rules-based and principle-based (comply-or-explain). In the rules-based environment, researchers have studied the relationship between internal control quality and accounting quality. Prior studies have suggested that reports on internal control are an effective way for investors to evaluate the quality of the firm‟s internal control. By having a sound system of internal control, it creates reliance upon the firm‟s financial reporting. Therefore, t...

Generation of induced pluripotent stem cells from transgenic minipigs expressing the N-terminal part of the human mutant huntingtin - a new way to study pathogenesis of Huntington´s disease

Czech Academy of Sciences Publication Activity Database

Lišková, Irena; Vodička, P.; Juhás, Štefan; Klempíř, J.; Motlík, Jan

2015-01-01

Roč. 78, Suppl 2 (2015), s. 18-19 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * huntingtin * induced pluripotent stem cells Subject RIV: FH - Neurology

Return on Educational Investment: 2014. A District-by-District Evaluation of U.S. Educational Productivity

Science.gov (United States)

Boser, Ulrich

2014-01-01

In 2011, the Center of American Progress (CAP) released the first-ever attempt to evaluate the productivity of almost every major school district in the country. That project developed a set of relatively simple productivity metrics in order to measure the achievement that a school district produces relative to its spending, while controlling for…

49 CFR Figure 2 to Subpart B of... - Example of a Multi-Level Car Complying with Window Location and Staggering Requirements-§§ 238...

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Example of a Multi-Level Car Complying with Window Location and Staggering Requirements-§§ 238.113 and 238.114 2 Figure 2 to Subpart B of Part 238.... 238, Subpt. B, Fig. 2 Figure 2 to Subpart B of Part 238—Example of a Multi-Level Car Complying with...

Tremor in neurodegenerative ataxias, Huntington disease and tic disorder.

Science.gov (United States)

Rudzińska, M; Krawczyk, M; Wójcik-Pędziwiatr, M; Szczudlik, A; Tomaszewski, T

2013-01-01

Tremor is the most prevalent movement disorder, defined as rhythmic oscillations of a body part, caused by alternating or synchronic contractions of agonistic or antagonistic muscles. The aim of the study was to assess prevalence and to characterize parameters of tremor accompanying de-generative ataxias, Huntington disease (HD) and tic disorders in comparison with a control group. Forty-three patients with degenerative ataxias, 28 with HD and 26 with tic disorders together with 51 healthy controls were included in the study. For each participant, clinical and instrumental assessment (accelerometer, electromyography [EMG], graphic tablet) of hand tremor was performed. Frequency and severity of tremor were assessed in three positions: at rest (rest tremor), with hands extended (postural tremor), during the 'finger-to-nose' test and during Archimedes spiral drawing (kinetic tremor). Based on the mass load test, the type of tremor was determined as essential tremor type or enhanced physiological tremor type. The incidence of tremor in the accelerometry in patients with degenerative ataxia (50%) significantly differs from controls (10%) (p = 0.001). The dominant tremor was postural, low-intense, with 7-Hz frequency, essential tremor (23%) or other tremor type (23%), while enhanced physiological tremor was the least frequent (2%). Tremor in patients with HD and tic disorders was found in 10% and 20% of patients, respectively, similarly to the control group. Tremor was mild, postural and of essential tremor type, less frequently of enhanced physiological tremor type. No correlation between severity of tremor and severity of disease was found. The prevalence of tremor is considerably higher among patients with degenerative ataxias compared with HD, tic disorder and the control group. The most common type of tremor accompanying ataxias, HD and tic disorders is essential tremor type.

Advances in the understanding of early Huntington's disease using the functional imaging techniques of PET and SPET

International Nuclear Information System (INIS)

Andrews, T.C.; Brooks, D.J.

1998-01-01

The functional imaging techniques of positron emission tomography (PET) and single photon emission tomography (SPET) have been used to study regional brain function in Huntington's disease (HD) in vivo. Reduced striatal glucose metabolism and dopamine receptor binding are evident in all symptomatic HD patients and in ∼50% of asymptomatic adult mutation carriers. These characteristics correlate with clinical measures of disease severity. Reduced cortical glucose metabolism and dopamine receptor binding, together with reduced striatal and cortical opioid receptor binding, have also been demonstrated in symptomatic patients with HD. Repeat PET measures of striatal function have been used to monitor the progression of this disease objectively. In the future, functional imaging will provide a valuable way of assessing the efficacy of both fetal striatal cell implants and putative neuroprotective agents, such as nerve growth factors. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Targeting kynurenine 3-monooxygenase (KMO): implications for therapy in Huntington's disease.

Science.gov (United States)

Thevandavakkam, Mathuravani A; Schwarcz, Robert; Muchowski, Paul J; Giorgini, Flaviano

2010-12-01

Huntington's disease (HD) is an adult onset neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein. Recent work has shown that perturbation of kynurenine pathway (KP) metabolism is a hallmark of HD pathology, and that changes in brain levels of KP metabolites may play a causative role in this disease. The KP contains three neuroactive metabolites, the neurotoxins 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN), and the neuroprotectant kynurenic acid (KYNA). In model systems in vitro and in vivo, 3-HK and QUIN have been shown to cause neurodegeneration via a combination of excitotoxic mechanisms and oxidative stress. Recent studies with HD patient samples and in HD model systems have supported the idea that a shift away from the synthesis of KYNA and towards the formation of 3-HK and QUIN may trigger the neuropathological features observed in HD. The enzyme kynurenine 3-monooxygenase (KMO) is located at a critical branching point in the KP such that inhibition of this enzyme by either pharmacological or genetic means shifts the flux in the pathway towards the formation of KYNA. This intervention ameliorates disease-relevant phenotypes in HD models. Here we review the work implicating the KP in HD pathology and discuss the potential of KMO as a therapeutic target for this disorder. As several neurodegenerative diseases exhibit alterations in KP metabolism, this concept has broader implications for the treatment of brain diseases.

Theory of mind and empathy in preclinical and clinical Huntington's disease.

Science.gov (United States)

Adjeroud, Najia; Besnard, Jérémy; El Massioui, Nicole; Verny, Christophe; Prudean, Adriana; Scherer, Clarisse; Gohier, Bénédicte; Bonneau, Dominique; Allain, Philippe

2016-01-01

We investigated cognitive and affective Theory of Mind (ToM) and empathy in patients with premanifest and manifest Huntington's disease (HD). The relationship between ToM performance and executive skills was also examined. Sixteen preclinical and 23 clinical HD patients, and 39 healthy subjects divided into 2 control groups were given a French adaptation of the Yoni test (Shamay-Tsoory, S.G., Aharon-Peretz, J. (2007). Dissociable prefrontal networks for cognitive and affective theory of mind: a lesion study. Neuropsychologia, 45(3), 3054-67) that examines first- and second-order cognitive and affective ToM processing in separate conditions with a physical control condition. Participants were also given questionnaires of empathy and cognitive tests which mainly assessed executive functions (inhibition and mental flexibility). Clinical HD patients made significantly more errors than their controls in the first- and second-order cognitive and affective ToM conditions of the Yoni task, but exhibited no empathy deficits. However, there was no evidence that ToM impairment was related to cognitive deficits in these patients. Preclinical HD patients were unimpaired in ToM tasks and empathy measures compared with their controls. Our results are consistent with the idea that impaired affective and cognitive mentalizing emerges with the clinical manifestation of HD, but is not necessarily part of the preclinical stage. Furthermore, these impairments appear independent of executive dysfunction and empathy. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Swedish district heating - owners, prices and profitability

International Nuclear Information System (INIS)

Andersson, Sofie; Werner, S.

2001-01-01

Owners, prices and profitability are examined in this report for 152 Swedish district heating companies during 1999. Only public information available has been used: Prices from a national annual consumer study, energy supplied, lengths of district heating pipes installed, and average prices for energy supplied. These companies are responsible for 96 % of all district heat supplied in Sweden. District heating systems owned by municipalities were responsible for 65 % of all district heat supply, while the share of power companies was 34 %. Other private owners accounted for 1 %. Only 12 % of the board members are women and more than 40 % of the companies have no woman in the board. The prices gathered by the annual consumer study are good estimates of the price level of district heating in Sweden. The average revenues are only 4,1 % lower than the effective average of prices gathered. Price of district heating decrease with size and market share. Use of combined heat and power plants decrease prices slightly. Lower prices with size can mainly be explained by lower energy supply costs. Calculated rates of return in relation to calculated replacement values increase slightly by size and are almost independent of age and market share. The purport of these conclusions is that the district heating companies share the cost reduction from size with their customers, while the whole benefit from high market shares is repaid to the customers. Calculated rates of return vary among the owner groups examined. Lower rates are accepted by municipalities, while power companies have higher rates at the average costs used. Total replacement costs for the 152 companies has been estimated to 89 billion Swedish crowns or 10 billion Euro. Only correlation analyses using one dimension have been used in this study. A higher degree of quality can be obtained by using multi-dimensional analyses

Stakeholder Experiences in District-University Administrator Preparation Partnerships

Science.gov (United States)

Sanzo, Karen L.; Wilson, Jacob McKinley, III

2016-01-01

Our qualitative study explores the lived experiences of district stakeholders in university-district leadership preparation programs. Collaborative partnerships between school districts and universities focused on developing quality school leader are a part of recent efforts to provide the field of public education with exemplary leadership. The…

31 CFR 30.6 - Q-6: How does a TARP recipient comply with the requirement under § 30.4 (Q-4) of this part that...

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Q-6: How does a TARP recipient comply... recipient's employees? 30.6 Section 30.6 Money and Finance: Treasury Office of the Secretary of the Treasury TARP STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.6 Q-6: How does a TARP recipient comply...

31 CFR 30.5 - Q-5: How does a TARP recipient comply with the requirements under § 30.4 (Q-4) of this part that...

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Q-5: How does a TARP recipient comply... recipient? 30.5 Section 30.5 Money and Finance: Treasury Office of the Secretary of the Treasury TARP STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.5 Q-5: How does a TARP recipient comply with the...

FOUNDING OF THE DISTRICT HOSPITAL IN NIS

Directory of Open Access Journals (Sweden)

Misa Zivic

2007-01-01

Full Text Available After the liberation of Nis from the Turks which took place on January 11th, 1878, there were two military hospitals: one was next to The Skull Tower and the other on the road to Leskovac and there was Islahana the civil institution which was not the forerunner of the district hospital in Nis. At first, they founded the military hospital in Nis in 1878 and then they founded The District Hospital on July 17th in 1881. The first director of the District hospital was Anton Zajicek. He is also the first graduated medical doctor in Nis. The District Hospital was situated on the left bank of the Nisava river in a private house.

41 CFR 102-80.80 - With what general accident and fire prevention policy must Federal agencies comply?

Science.gov (United States)

2010-07-01

... agencies must— (a) Comply with the occupational safety and health standards established in the Occupational... Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 80-SAFETY AND ENVIRONMENTAL MANAGEMENT Accident and Fire Prevention § 102...

A Case of Attempted Suicide in Huntington's Disease: Ethical and Moral Considerations.

Science.gov (United States)

Furfari, Kristin; Zehnder, Nichole; Abbott, Jean

2016-01-01

A 62-year-old female with Huntington's disease presented after a suicide attempt. Her advance directive stated that she did not want intubation or resuscitation, which her family acknowledged and supported. Despite these directives, she was resuscitated in the emergency department and continued to state that she would attempt suicide again. Her suicidality in the face of a chronic and advancing illness, and her prolonged consistency in her desire to take her own life, left careproviders wondering how to provide ethical, respectful care to this patient. Tension between the ethical principles of autonomy and beneficence is central in this case. The patient's narrative demonstrated that her suicide was an autonomous decision, free from coercion or disordered thinking from mental illness. Beneficence then would seem to necessitate care aligned with the patient's desire to end her life, which created ethical uneasiness for her family and careproviders. The case highlights several end-of-life ethical considerations that have received much recent attention. With ongoing discussions about the legalization of aid in dying across the country, caregivers are challenged to understand what beneficence means in people with terminal illnesses who want a say in their death. This case also highlights the profound moral distress of families and careproviders that arises in such ethically challenging scenarios. Copyright 2016 The Journal of Clinical Ethics. All rights reserved.

The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

Directory of Open Access Journals (Sweden)

Frentzel Stefan

2010-06-01

Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

Co-sponsored second quarter progress review conference on district heating

Energy Technology Data Exchange (ETDEWEB)

None

1980-01-01

A summary of the progress review conference on district heating and cooling systems is presented. The agenda and lists of speakers and attendees are presented. A history of district heating and some present needs and future policies are given and an excerpt from the National District Heating Program Strategy (DOE, March 1980) is included. Following the presentation, District Heating and Cooling Systems Program, by Alan M. Rubin, a fact sheet on DOE's Integrated Community Energy Systems Program and information from an oral presentation, District Heating and Cooling Systems for Communities Through Power Plant Retrofit Distribution Network, are given. The Second Quarterly Oral Report to the US DOE on the District Heating and Cooling Project in Detroit; the executive summary of the Piqua, Ohio District Heating and Cooling Demonstration Project; the Second Quarterly Report of the Moorehead, Minnesota District Heating Project; and the report from the Moorehead, Minnesota mayor on the Hot Water District Heating Project are presented.

Crafting Legitimacy in District-Community Partnerships

Science.gov (United States)

Lechasseur, Kimberly

2017-01-01

Background/Context: Partnering across districts, schools, and other community organizations has become ubiquitous as a policy for promoting change. Despite growing attention to and scholarship on district-community partnerships, there is little examination of the organizational mechanisms involved in sustaining them. Purpose/Objectives: This study…

School Finance Reform: Can It Support California's College- and Career-Ready Goal? Report 2

Science.gov (United States)

Perry, Mary

2013-01-01

For decades, when California's state leaders have wanted to see local school districts respond to shifts in policy and expectations they relied on the state-controlled school finance system to leverage local change. Through the use of categorical programs and earmarked funding, they created incentives for districts that complied and penalties for…

Neuroendocrine and neurotrophic signaling in Huntington's disease: Implications for pathogenic mechanisms and treatment strategies.

Science.gov (United States)

Bartlett, Danielle M; Cruickshank, Travis M; Hannan, Anthony J; Eastwood, Peter R; Lazar, Alpar S; Ziman, Mel R

2016-12-01

Huntington's disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine tract in the huntingtin protein. Circadian, sleep and hypothalamic-pituitary-adrenal (HPA) axis disturbances are observed in HD as early as 15 years before clinical disease onset. Disturbances in these key processes result in increased cortisol and altered melatonin release which may negatively impact on brain-derived neurotrophic factor (BDNF) expression and contribute to documented neuropathological and clinical disease features. This review describes the normal interactions between neurotrophic factors, the HPA-axis and circadian rhythm, as indicated by levels of BDNF, cortisol and melatonin, and the alterations in these intricately balanced networks in HD. We also discuss the implications of these alterations on the neurobiology of HD and the potential to result in hypothalamic, circadian, and sleep pathologies. Measurable alterations in these pathways provide targets that, if treated early, may reduce degeneration of brain structures. We therefore focus here on the means by which multidisciplinary therapy could be utilised as a non-pharmaceutical approach to restore the balance of these pathways. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington's disease.

Directory of Open Access Journals (Sweden)

Daniel Todd

Full Text Available Huntington's disease (HD is a devastating, genetic neurodegenerative disease caused by a tri-nucleotide expansion in exon 1 of the huntingtin gene. HD is clinically characterized by chorea, emotional and psychiatric disturbances and cognitive deficits with later symptoms including rigidity and dementia. Pathologically, the cortico-striatal pathway is severely dysfunctional as reflected by striatal and cortical atrophy in late-stage disease. Brain-derived neurotrophic factor (BDNF is a neuroprotective, secreted protein that binds with high affinity to the extracellular domain of the tropomyosin-receptor kinase B (TrkB receptor promoting neuronal cell survival by activating the receptor and down-stream signaling proteins. Reduced cortical BDNF production and transport to the striatum have been implicated in HD pathogenesis; the ability to enhance TrkB signaling using a BDNF mimetic might be beneficial in disease progression, so we explored this as a therapeutic strategy for HD. Using recombinant and native assay formats, we report here the evaluation of TrkB antibodies and a panel of reported small molecule TrkB agonists, and identify the best candidate, from those tested, for in vivo proof of concept studies in transgenic HD models.

Is Swedish district heating operating on an integrated market? – Differences in pricing, price convergence, and marketing strategy between public and private district heating companies

International Nuclear Information System (INIS)

Åberg, M.; Fälting, L.; Forssell, A.

2016-01-01

The deregulation of the Swedish electricity market in 1996 made it possible to operate municipal district heating commercially. Until that time district heating had been organized mainly as municipal utilities. After 1996 district heating is instead expected to function on a market. In competitive and integrated markets, prices are expected to be equal, or converging. To find out if district heating operates on an integrated market the differences in price levels, price convergence, price strategy, and business goals, among municipal, private and state owned district heating companies are investigated. Price statistics was used along with results from a questionnaire that was answered by representatives for 109 Swedish district heating companies. The results show that prices among district heating systems do not converge significantly and that variations in prices among municipal systems are larger than among private and state owned systems. Furthermore, despite the fact that district heating is supposed to be commercial, a vast majority of district heating companies apply cost-based pricing and not market pricing. The municipal companies give priority to political goals before financial goals. The conclusion is that a Swedish integrated market for heat has not yet evolved, and some district heating price-controlling mechanism is necessary. - Highlights: • Price statistics and owner type data were used along with results from a questionnaire. • Results show that prices among district heating systems do not converge. • Municipal district heating companies still apply cost-based pricing to a large extent. • District heating companies are not operating on an integrated market for heat. • Some price-controlling mechanism for district heating is necessary.

Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

Science.gov (United States)

Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

2016-07-01

Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

EMQN/CMGS best practice guidelines for the molecular genetic testing of Huntington disease.

Science.gov (United States)

Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E

2013-05-01

Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these laboratories, the European Molecular Genetics Quality Network has organized a yearly external quality assessment (EQA) scheme for molecular genetic testing of HD for over 10 years. EQA compares a laboratory's output with a fixed standard both for genotyping and reporting of the results to the referring physicians. In general, the standard of genotyping is very high but the clarity of interpretation and reporting of the test result varies more widely. This emphasizes the need for best practice guidelines for this disorder. We have therefore developed these best practice guidelines for genetic testing for HD to assist in testing and reporting of results. The analytical methods and the potential pitfalls of molecular genetic testing are highlighted and the implications of the different test outcomes for the consultand and his or her family members are discussed.

The Medicinal Chemistry of Natural and Semisynthetic Compounds against Parkinson's and Huntington's Diseases.

Science.gov (United States)

Zanforlin, Enrico; Zagotto, Giuseppe; Ribaudo, Giovanni

2017-11-15

Among the diseases affecting the central nervous system (CNS), neurodegenerations attract the interest of both the clinician and the medicinal chemist. The increasing average age of population, the growing number of patients, and the lack of long-term effective remedies push ahead the quest for novel tools against this class of pathologies. We present a review on the state of the art of the molecules (or combination of molecules) of natural origin that are currently under study against two well-defined pathologies: Parkinson's disease (PD) and Huntington's disease (HD). Nowadays, very few tools are available for preventing or counteracting the progression of such diseases. Two major parameters were considered for the preparation of this review: particular attention was reserved to these research works presenting well-defined molecular mechanisms for the studied compounds, and where available, papers reporting in vivo data were preferred. A literature search for peer-reviewed articles using PubMed, Scopus, and Reaxys databases was performed, exploiting different keywords and logical operators: 91 papers were considered (preferentially published after 2015). The review presents a brief overview on the etiology of the studied neurodegenerations and the current treatments, followed by a detailed discussion of the natural and semisynthetic compounds dividing them in different paragraphs considering their several mechanisms of action.

Transgenic animal models for study of the pathogenesis of Huntington's disease and therapy.

Science.gov (United States)

Chang, Renbao; Liu, Xudong; Li, Shihua; Li, Xiao-Jiang

2015-01-01

Huntington's disease (HD) is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner.

Influencing Swedish homeowners to adopt district heating system

Energy Technology Data Exchange (ETDEWEB)

Mahapatra, Krushna; Gustavsson, Leif [Ecotechnology, Mid Sweden University, Akademigatan 1, 831 25 Oestersund (Sweden)

2009-02-15

Improved energy efficiency and greenhouse gas mitigation could be achieved by replacing resistance heaters with district heating system. In 2005, only about 8% of the Swedish detached houses had district heating system. The expansion of such systems largely depends on homeowners' adoption decisions. And, to motivate homeowners to adopt district heating, it is essential to understand their decision-making process. In this context, in June 2005 we carried out a questionnaire survey of about 700 homeowners who lived in the city of Oestersund in houses with resistance heaters (baseline survey). About 84% of the respondents did not intend to install a new heating system. Since then these homeowners were influenced by (a) an investment subsidy by the Swedish government to replace resistance heaters with district heating, a brine/water-based heat pump, or a biomass-based heating system and (b) a marketing campaign by the municipality-owned district heating company. This paper analyses how these two measures influenced about 78% of the homeowners to adopt the district heating system. For this purpose we carried out a follow-up survey of the same homeowners in December 2006 (resurvey). Results showed that the investment subsidy and the marketing campaign created a need among the homeowners to adopt a new heating system. The marketing campaign was successful in motivating them to adopt the district heating system. The marketing strategy by the district heating company corresponds to the results obtained in the baseline survey. (author)

Influencing Swedish homeowners to adopt district heating system

International Nuclear Information System (INIS)

Mahapatra, Krushna; Gustavsson, Leif

2009-01-01

Improved energy efficiency and greenhouse gas mitigation could be achieved by replacing resistance heaters with district heating system. In 2005, only about 8% of the Swedish detached houses had district heating system. The expansion of such systems largely depends on homeowners' adoption decisions. And, to motivate homeowners to adopt district heating, it is essential to understand their decision-making process. In this context, in June 2005 we carried out a questionnaire survey of about 700 homeowners who lived in the city of Ostersund in houses with resistance heaters (baseline survey). About 84% of the respondents did not intend to install a new heating system. Since then these homeowners were influenced by (a) an investment subsidy by the Swedish government to replace resistance heaters with district heating, a brine/water-based heat pump, or a biomass-based heating system and (b) a marketing campaign by the municipality-owned district heating company. This paper analyses how these two measures influenced about 78% of the homeowners to adopt the district heating system. For this purpose we carried out a follow-up survey of the same homeowners in December 2006 (resurvey). Results showed that the investment subsidy and the marketing campaign created a need among the homeowners to adopt a new heating system. The marketing campaign was successful in motivating them to adopt the district heating system. The marketing strategy by the district heating company corresponds to the results obtained in the baseline survey

Influencing Swedish homeowners to adopt district heating system

Energy Technology Data Exchange (ETDEWEB)

Mahapatra, Krushna; Gustavsson, Leif [Ecotechnology, Mid Sweden University, Akademigatan 1, 831 25 Oestersund (Sweden)

2009-02-15

Improved energy efficiency and greenhouse gas mitigation could be achieved by replacing resistance heaters with district heating system. In 2005, only about 8% of the Swedish detached houses had district heating system. The expansion of such systems largely depends on homeowners' adoption decisions. And, to motivate homeowners to adopt district heating, it is essential to understand their decision-making process. In this context, in June 2005 we carried out a questionnaire survey of about 700 homeowners who lived in the city of Oestersund in houses with resistance heaters (baseline survey). About 84% of the respondents did not intend to install a new heating system. Since then these homeowners were influenced by (a) an investment subsidy by the Swedish government to replace resistance heaters with district heating, a brine/water-based heat pump, or a biomass-based heating system and (b) a marketing campaign by the municipality-owned district heating company. This paper analyses how these two measures influenced about 78% of the homeowners to adopt the district heating system. For this purpose we carried out a follow-up survey of the same homeowners in December 2006 (resurvey). Results showed that the investment subsidy and the marketing campaign created a need among the homeowners to adopt a new heating system. The marketing campaign was successful in motivating them to adopt the district heating system. The marketing strategy by the district heating company corresponds to the results obtained in the baseline survey. (author)

Progressive microstructural changes of the occipital cortex in Huntington's disease.

Science.gov (United States)

Odish, Omar F F; Reijntjes, Robert H A M; van den Bogaard, Simon J A; Roos, Raymund A C; Leemans, Alexander

2018-02-28

In this study we longitudinally investigated the rate of microstructural alterations in the occipital cortex in different stages of Huntington's disease (HD) by applying an automated atlas-based approach to diffusion MRI data. Twenty-two premanifest (preHD), 10 early manifest HD (early HD) and 24 healthy control subjects completed baseline and two year follow-up scans. The preHD group was stratified based on the predicted years to disease onset into a far (preHD-A) and near (preHD-B) to disease onset group. Clinical and behavioral measures were collected per assessment time point. An automated atlas-based DTI analysis approach was used to obtain the mean, axial and radial diffusivities of the occipital cortex. We found that the longitudinal rate of diffusivity change in the superior occipital gyrus (SOG), middle occipital gyrus (MOG), and inferior occipital gyrus (IOG) was significantly higher in early HD compared to both preHD and controls (all p's ≤ 0.005), which can be interpreted as an increased rate of microstructural degeneration. Furthermore, the change rate in the diffusivity of the MOG could significantly discriminate between preHD-B compared to preHD-A and the other groups (all p's ≤ 0.04). Finally, we found an inverse correlation between the Stroop Word Reading task and diffusivities in the SOG and MOG (all p's ≤ 0.01). These findings suggest that measures obtained from the occipital cortex can serve as sensitive longitudinal biomarkers for disease progression in preHD-B and early HD. These could in turn be used to assess potential effects of proposed disease modifying therapies.

A Longitudinal Study of School Districts' Sustained Improvement

Science.gov (United States)

Sampson, Pauline M.

2011-01-01

In this longitudinal study of one region in the state of Texas, there was an examination of district leadership and the sustaining of high student achievement for their districts. The results of this study suggest that sustained improvement of student achievement is very difficult. The districts that had sustained improvement had stable district…

English Language Teaching in Spain: Do Textbooks Comply with the Official Methodological Regulations? A Sample Analysis

Science.gov (United States)

Criado, Raquel; Sanchez, Aquilino

2009-01-01

The goal of this paper is to verify up to what point ELT textbooks used in Spanish educational settings comply with the official regulations prescribed, which fully advocate the Communicative Language Teaching Method (CLT). For that purpose, seven representative coursebooks of different educational levels and modalities in Spain--secondary, upper…

49 CFR Figure 2b to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2B Figure 2B to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113 and...

49 CFR Figure 2a to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2A Figure 2A to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113 and...

ACT250 Districts

Data.gov (United States)

Vermont Center for Geographic Information — The ACT 250 Districts layer is part of a larger dataset that contains administrative boundaries for Vermont's Agency of Natural Resources. The dataset includes...

Groundwater Managment Districts

Data.gov (United States)

Kansas Data Access and Support Center — This dataset outlines the location of the five Groundwater Management Districts in Kansas. GMDs are locally formed and elected boards for regional groundwater...

Comprehensive District Reform: Philadelphia's Grand Experiment.

Science.gov (United States)

Useem, Elizabeth; Balfanz, Robert

2002-01-01

This report describes "Philadelphia's Grand Experiment" in comprehensive school district reform, from its conception through its initial months of implementation. In 2001, as part of the remedy for low student performance, the governor ordered the state to take over governance of the Philadelphia School District, with a substantial…

Salaryfax for Nine Districts 1972-73.

Science.gov (United States)

Albuquerque Public Schools, NM.

This study compares salaries as well as benefits of school district personnel in the nine metropolitan school districts that include Albuquerque, New Mexico; Denver, Colorado; El Paso, Texas; Memphis, Tennessee; Phoenix and Tucson, Arizona; Wichita, Kansas; and Mobile, Alabama. The tables aggregate all the elements in the total compensation…

Thermodynamic calculation of a district energy cycle

International Nuclear Information System (INIS)

Hoehlein, B.; Bauer, A.; Kraut, G.; Scherberich, F.D.

1975-08-01

This paper presents a calculation model for a nuclear district energy circuit. Such a circuit means the combination of a steam reforming plant with heat supply from a high-temperature nuclear reactor and a methanation plant with heat production for district heating or electricity production. The model comprises thermodynamic calculations for the endothermic methane reforming reaction as well as the exothermic CO-hydrogenation in adiabatic reactors and allows the optimization of the district energy circuit under consideration. (orig.) [de

Floodplain District Permit

Data.gov (United States)

Montgomery County of Maryland — The purpose of a Floodplain District Permit (FPDP) is to control floodplain development in order to protect persons and property from danger and destruction and to...

2006 Southwest Florida Water Management District (SWFWMD) Lidar: North District

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This data set is one component of a digital terrain model (DTM) for the Southwest Florida Water Management District's FY2006 Digital Orthophoto (B089) and LiDAR...

The fog of war: Why the environmental crusade for anadromous fish species in California could disarm the State’s local vector control districts in their war against mosquitoes

Directory of Open Access Journals (Sweden)

Stephen M. Siptroth

2011-12-01

Full Text Available In California, local mosquito and vector control districts have successfully controlled mosquito and vector-borne diseases by improving drainage patterns and applying pesticides. The Bay-Delta Conservation Plan, which is a proposed habitat conservation plan for the Sacramento-San Joaquin Bay-Delta estuary, proposes to add over 70,000 acres of habitat in the Delta to improve conditions for threatened and endangered aquatic and terrestrial species. This habitat could also be a suitable mosquito breeding habitat, which will be located in close proximity to urban and suburban communities. Wetland management practices and continued pesticide applications in the Delta could mitigate the effects of a new mosquito breeding habitat. Recent legal developments, however, require districts to obtain and comply with Clean Water Act permits, which restrict the application of pesticides in or near waters of the United States. Moreover, the U.S. Environmental Protection Agency has taken the first step in a rulemaking process that could further limit or prohibit the use of certain vector control pesticides in the Delta. In the near term and until less harmful methods for mosquito control are available, local vector control districts’ application of mosquito control pesticides should be exempt from Clean Water Act permit requirements.

A novel humanized mouse model of Huntington disease for preclinical development of therapeutics targeting mutant huntingtin alleles

DEFF Research Database (Denmark)

Southwell, Amber L; Skotte, Niels H; Villanueva, Erika B

2017-01-01

transgenes in Hu128/21 mice match the human HTT exon 1 reference sequence. Conversely, the BACHD transgene carries a floxed, synthetic exon 1 sequence. Hu128/21 mice will be useful for investigations of human HTT that cannot be addressed in Hu97/18 mice, for developing therapies targeted to exon 1......Huntington disease (HD) is a neurodegenerative disease caused by a mutation in the huntingtin (HTT) gene. HTT is a large protein, interacts with many partners and is involved in many cellular pathways, which are perturbed in HD. Therapies targeting HTT directly are likely to provide the most global......-length, genomic human HTT transgenes heterozygous for the HD mutation and polymorphisms associated with HD in populations of East Asian descent and in a minority of patients from other ethnic groups. Hu128/21 mice display a wide variety of HD-like phenotypes that are similar to YAC128 mice. Additionally, both...

ESC-Derived BDNF-Overexpressing Neural Progenitors Differentially Promote Recovery in Huntington's Disease Models by Enhanced Striatal Differentiation

Directory of Open Access Journals (Sweden)

Tina Zimmermann

2016-10-01

Full Text Available Huntington's disease (HD is characterized by fatal motoric failures induced by loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport of the neurotrophin BDNF (brain-derived neurotrophic factor. By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as a potential HD therapy approach. Transplantation of purified neural progenitors was analyzed in a quinolinic acid (QA chemical and two genetic HD mouse models (R6/2 and N171-82Q on the basis of distinct behavioral parameters, including CatWalk gait analysis. Explicit rescue of motor function by BDNF neural progenitors was found in QA-lesioned mice, whereas genetic mouse models displayed only minor improvements. Tumor formation was absent, and regeneration was attributed to enhanced neuronal and striatal differentiation. In addition, adult neurogenesis was preserved in a BDNF-dependent manner. Our findings provide significant insight for establishing therapeutic strategies for HD to ameliorate neurodegenerative symptoms.

Sexual behavior, body image, and partnership in chronic illness: a comparison of Huntington's disease and multiple sclerosis.

Science.gov (United States)

Reininghaus, Eva; Reininghaus, Bernd; Fitz, Werner; Hecht, Karen; Bonelli, Raphael Maria

2012-08-01

Huntington's disease (HD) and multiple sclerosis (MS) are both chronic progressive illnesses posing a serious challenge to affected patients and families. Sexual dysfunction in HD as well as in MS is a very common problem, although it is unclear whether the dysfunction is caused by the chronic illness itself or by the sociopsychiatric burden related to the illness. Twenty-nine patients with HD and 27 patients with MS each participated in a semistructured interview and several standardized questionnaires concerning partnership, sexual function, and body image. The results display significant differences in both patient groups, displaying higher sexual desire and activity in HD patients, but MS patients also reported fewer sexual problems compared to the norming values. Conversely, the MS patients' relationships seemed to be stable despite subjectively perceived lower initiative on sexual activities. The results are discussed under the possible influences of the underlying organic changes and the psychosocial consequences of chronic progressive disorders.

Should a Physician Comply with a Parent's Demands for a Forensic Exam on a 16-Year-Old Trauma Patient?

Science.gov (United States)

Bowdler, Michelle; Kent, Hannah

2018-01-01

Physicians must remain vigilant about their ethical duties to patients, especially in high-stakes situations. The question raised by this case-whether a physician should comply with a parent's demand for treatment against her underage child's wishes-is not one of life or death in which a guardian might more credibly argue her judgment should stand. Given that forcing a rape kit exam on a patient who refuses to give assent could be further traumatizing, we argue that the physician should not comply. Deciding upon a course of action in this situation will involve considering what is in the patient's best interest and what constitutes a physician's appropriate role in gathering evidence for criminal investigations. © 2018 American Medical Association. All Rights Reserved.

Challenges Encountered by Connecticut Partner School Districts when Implementing Legislatively Required District Improvement Plans: An Exploratory Study

Science.gov (United States)

Martins, Meghan G.

2010-01-01

This research developed a survey that measures the degree to which challenges are experienced by school and district leaders, and teachers, when attempting to implement legislatively required District Improvement Plans (DIPs). The data indicate that there are certainly challenges when implementing DIPs and that teachers report experiencing a…

Factors Influencing Teacher Job Satisfaction and Their Alignment with Current District Practices in a Suburban School District

Science.gov (United States)

Dickens, Kimberly Rae

2010-01-01

School districts across the country make many decisions that impact teachers' satisfaction both positively and negatively. With statistics reporting a significant number of teachers leaving the profession in the first 5 years of experience, determining the reasons for teacher dissatisfaction are important in shaping district practices to be more…

78 FR 58049 - Proposed Establishment of the Adelaida District, Creston District, El Pomar District, Paso Robles...

Science.gov (United States)

2013-09-20

... Shallow, well- Deep alluvial Deep to moderate Mostly shallow drained, residual soils, with clay, depth... neither an approval nor an endorsement by TTB of the wine produced in that area. Requirements Section 4.25... Adelaida District viticultural area are hillside residual soils, which generally have shallow rooting...

Location - Managed Facility - St. Paul District (MVP)

Data.gov (United States)

Army Corps of Engineers, Department of the Army, Department of Defense — St. Paul District - US Army Corps of Engineers Managed Facility locations. District headquarters, Natural Resource, Recreation, Lock and Dam, and Regulatory offices...

Analysis of Marketing Efficiency of Beef Cattle on "Tirto Sari" Livestock at Sub District of Samboja, District of Kutai Kartanegara, East Kalimantan

OpenAIRE

Riansyah Comdeca Surya Pratama; Koesnoto Supranianondo

2017-01-01

The purpose of this study is to find out the marketing efficiency of beef cattle on “Tirto Sari” livestock at Sub District of Samboja, District of Kutai Kartanegara, East Kalimantan. The result of this study indicates that there are four varieties in terms of beef cattle marketing on “Tirto Sari” livestock at Sub District of Samboja, District of Kutai Kartanegara, East Kalimantan: direct marketing of marketing type I, intermediate marketing of marketing type II and III and long-processed mark...

Sustainable residential districts : the residents' role in project success

NARCIS (Netherlands)

Abdalla, G.

2012-01-01

Sustainable residential districts have been realized worldwide. These districts are promoted to be efficient in the use of natural materials and sustainable energy resources. Realization of sustainable residential districts can strongly contribute to achieve environmental objectives as imposed by

Building community while complying with the Affordable Care Act in the Lehigh Valley of Pennsylvania.

Science.gov (United States)

Mathews, A Lanethea; Coyle, Bonnie S; Deegan, Michele Moser

2015-01-01

The Affordable Care Act (ACA) requires nonprofit hospitals to conduct community health needs assessments (CHNA) every 3 years. Best practices for CHNAs are still emerging and, along with growing economic pressures, contribute to uncertainty about the short- and long-term costs hospitals will face as a result of the ACA. This article describes a community-based partnership coordinated by a nonprofit hospital and a consortium of academic institutions as a model for conducting a CHNA. Similar partnerships offer key advantages in complying with the ACA: local academic institutions are existing stakeholders in the community--they possess research expertise and have a vested interested in shaping implementation strategies to improve health; the process of collaborating itself helps to generate community resources, conceive of community health as a shared and iterative enterprise, and mobilize community partners in supporting long-term health priorities. No CHNA is ever perfect, but there are compelling reasons for nonprofit hospitals to seek community-based partnerships, not only because such partnerships comply with the law but, more importantly, because they hold great promise for linking the CHNA process and results to the health realities of local communities, ultimately bolstering community engagement while creating shared health priorities.

DRUG MANAGEMENT REVIEWS IN DISTRICT DRUG MANAGEMENT UNIT AND GENERAL HOSPITAL

Directory of Open Access Journals (Sweden)

Max Joseph Herman

2009-12-01

Full Text Available Drug is one of the essential elements in healthcare that should be effectively and efficiently managed. Following thedecentralization in 2001 in Indonesia, drug management has changed in district drug management units and also in District General Hospitals. Certainly this condition influences the sustainability of drug access in primary health care such as in Community Health Center and District General Hospital, especially in drug financing policy. A cross sectional descriptive study to obtain information on drug management in public healthcare in district had been carried out between July and December 2006 in 10 District Public Drug Management Units from 10 district health offices and 9 district general hospitals as samples. Data were collected by interviewing heads of Drug Section in District Health Offices and heads of Hospital Pharmacies using structured questionnaires and observing drug storage in District Drug Management Units, Community Health Centers, and Hospital Pharmacies. Results of the study show that drug planning in District Health Offices and General Hospitals did not meet the basic real need in some districts nor District Hospitals. The minimum health service standards had no been achieved yet. Furthermore, drug procurement, storage and recording as well as reporting was not good enough either, such as shown by the existence of expired drugs. Lead time for drug delivery to community health centers in some districts was longer than the average of lead time in the past 3 years.

Sudbury District Energy - a public/private partnership model

International Nuclear Information System (INIS)

Prudhomme, H.

1999-01-01

The issue of public/private partnership as it relates to the Sudbury District Energy Project was discussed. When completed, it will be the first cogeneration-based district heating and cooling project involving private sector/public sector partnership in Canada. The equal partners include Toromont Energy and Sudbury Hydro. Sudbury Hydro is a community owned energy and communications utility. It was the first electric utility in Ontario to retail natural gas in the new competitive market place. The Sudbury District Energy Project began in 1996, when the utility began the development of a community district energy system in partnership with the City of Sudbury. At the time, the downtown district heating/cooling system supplied cold and hot water to Sudbury's Wellness Centre. In 1998, Toromont Energy accepted a 50/50 partnership arrangement between themselves and the public sector partners to form the Sudbury District Energy Corporation. Sudbury Hydro will benefit from the project because it will reduce their peak loads and it will also be an alternate source of revenue. It is expected that the project will displace 39,600 tons of carbon dioxide, a greenhouse gas which contributes to global warming

Molecular diagnosis of Huntington disease in Brazilian patients Diagnóstico molecular da doença de Huntington em pacientes brasileiros

Directory of Open Access Journals (Sweden)

TEREZA C. LIMA E SILVA

2000-03-01

Full Text Available Huntington disease (HD is a progressive neurodegenerative disorder with autosomal dominant inheritance, characterized by choreiform movements and cognitive impairment. Onset of symptoms is around 40 years of age and progression to death occurs in approximately 10 to 15 years from the time of disease onset. HD is associated with an unstable CAG repeat expansion at the 5' and of the IT15 gene. We have genotyped the CAG repeat in the IT15 gene in 44 Brazilian individuals (42 patients and 2 unaffected family members belonging to 34 unrelated families thought to segregate HD. We found one expanded CAG allele in 32 individuals (76% belonging to 25 unrelated families. In these HD patients, expanded alleles varied from 43 to 73 CAG units and normal alleles varied from 18 to 26 CAGs. A significant negative correlation between age at onset of symptoms and size of the expanded CAG allele was found (r=0.6; p=0.0001; however, the size of the expanded CAG repeat could explain only about 40% of the variability in age at onset (r2=0.4. In addition, we genotyped 25 unrelated control individuals (total of 50 alleles and found normal CAG repeats varying from 16 to 33 units. The percentage of heterozigocity of the normal allele in the control population was 88%. In conclusion, our results showed that not all patients with the "HD" phenotype carried the expansion at the IT15 gene. Furthermore, molecular diagnosis was possible in all individuals, since no alleles of intermediate size were found. Therefore, molecular confirmation of the clinical diagnosis in HD should be sought in all suspected patients, making it possible for adequate genetic counseling.A doença de Huntington (HD é afecção neurodegenerativa com padrão de herança autossômica dominante caracterizada por movimentos involuntários coreiformes e alterações cognitivas. O início dos sintomas ocorre em torno dos 40 de idade, progredindo até a morte em um período de aproximadamente 10 a 15 anos ap

25 CFR 166.213 - Must I comply with any standards of conduct if I am granted a permit?

Science.gov (United States)

2010-04-01

... grazing operations in accordance with the principles of sustained yield management, agricultural resource management planning, sound conservation practices, and other community goals as expressed in tribal laws, agricultural resource management plans, and similar sources. (b) Comply with all applicable laws, ordinances...

Evaluating Recall and Recognition Memory Using the Montreal Cognitive Assessment: Applicability for Alzheimer's and Huntington's Diseases.

Science.gov (United States)

Van Liew, Charles; Santoro, Maya S; Goldstein, Jody; Gluhm, Shea; Gilbert, Paul E; Corey-Bloom, Jody

2016-12-01

We sought to investigate whether the Montreal Cognitive Assessment (MoCA) could provide a brief assessment of recall and recognition using Huntington disease (HD) and Alzheimer disease (AD) as disorders characterized by different memory deficits. This study included 80 participants with HD, 64 participants with AD, and 183 community-dwelling control participants. Random-effects hierarchical logistic regressions were performed to assess the relative performance of the normal control (NC), participants with HD, and participants with AD on verbal free recall, cued recall, and multiple-choice recognition on the MoCA. The NC participants performed significantly better than participants with AD at all the 3 levels of assessment. No difference existed between participants with HD and NC for cued recall, but NC participants performed significantly better than participants with HD on free recall and recognition. The participants with HD performed significantly better than participants with AD at all the 3 levels of assessment. The MoCA appears to be a valuable, brief cognitive assessment capable of identifying specific memory deficits consistent with known differences in memory profiles. © The Author(s) 2016.

LBH589, A Hydroxamic Acid-Derived HDAC Inhibitor, is Neuroprotective in Mouse Models of Huntington's Disease.

Science.gov (United States)

Chopra, Vanita; Quinti, Luisa; Khanna, Prarthana; Paganetti, Paolo; Kuhn, Rainer; Young, Anne B; Kazantsev, Aleksey G; Hersch, Steven

2016-12-15

Modulation of gene transcription by HDAC inhibitors has been shown repeatedly to be neuroprotective in cellular, invertebrate, and rodent models of Huntington's disease (HD). It has been difficult to translate these treatments to the clinic, however, because existing compounds have limited potency or brain bioavailability. In the present study, we assessed the therapeutic potential of LBH589, an orally bioavailable hydroxamic acid-derived nonselective HDAC inhibitor in mouse models of HD. The efficacy of LBH589 is tested in two HD mouse models using various biochemical, behavioral and neuropathological outcome measures. We show that LBH589 crosses the blood brain barrier; induces histone hyperacetylation and prevents striatal neuronal shrinkage in R6/2 HD mice. In full-length knock-in HD mice LBH589-treatment improves motor performance and reduces neuronal atrophy. Our efficacious results of LBH589 in fragment and full-length mouse models of HD suggest that LBH589 is a promising candidate for clinical assessment in HD patients and provides confirmation that non-selective HDAC inhibitors can be viable clinical candidates.

Solar district heating and cooling: A review

DEFF Research Database (Denmark)

Perez-Mora, Nicolas; Bava, Federico; Andersen, Martin

2018-01-01

and decentralized solar district heating as well as block heating. For the different technologies, the paper describes commonly adopted control strategies, system configurations, types of installation, and integration. Real‐world examples are also given to provide a more detailed insight into how solar thermal...... technology can be integrated with district heating. Solar thermal technology combined with thermally driven chillers to provide cooling for cooling networks is also included in this paper. In order for a technology to spread successfully, not only technical but also economic issues need to be tackled. Hence......Both district heating and solar collector systems have been known and implemented for many years. However, the combination of the two, with solar collectors supplying heat to the district heating network, is relatively new, and no comprehensive review of scientific publications on this topic could...

The path dependence of district manager decision-space in Ghana

Science.gov (United States)

Kwamie, Aku; van Dijk, Han; Ansah, Evelyn K; Agyepong, Irene Akua

2016-01-01

The district health system in Ghana today is characterized by high resource-uncertainty and narrow decision-space. This article builds a theory-driven historical case study to describe the influence of path-dependent administrative, fiscal and political decentralization processes on development of the district health system and district manager decision-space. Methods included a non-exhaustive literature review of democratic governance in Ghana, and key informant interviews with high-level health system officials integral to the development of the district health system. Through our analysis we identified four periods of district health system progression: (1) development of the district health system (1970–85); (2) Strengthening District Health Systems Initiative (1986–93); (3) health sector reform planning and creation of the Ghana Health Service (1994–96) and (4) health sector reform implementation (1997–2007). It was observed that district manager decision-space steadily widened during periods (1) and (2), due to increases in managerial profile, and concerted efforts at managerial capacity strengthening. Periods (3) and (4) saw initial augmentation of district health system financing, further widening managerial decision-space. However, the latter half of period 4 witnessed district manager decision-space contraction. Formalization of Ghana Health Service structures influenced by self-reinforcing tendencies towards centralized decision-making, national and donor shifts in health sector financing, and changes in key policy actors all worked to the detriment of the district health system, reversing early gains from bottom-up development of the district health system. Policy feedback mechanisms have been influenced by historical and contemporary sequencing of local government and health sector decentralization. An initial act of administrative decentralization, followed by incomplete political and fiscal decentralization has ensured that the balance of

The path dependence of district manager decision-space in Ghana.

Science.gov (United States)

Kwamie, Aku; van Dijk, Han; Ansah, Evelyn K; Agyepong, Irene Akua

2016-04-01

The district health system in Ghana today is characterized by high resource-uncertainty and narrow decision-space. This article builds a theory-driven historical case study to describe the influence of path-dependent administrative, fiscal and political decentralization processes on development of the district health system and district manager decision-space. Methods included a non-exhaustive literature review of democratic governance in Ghana, and key informant interviews with high-level health system officials integral to the development of the district health system. Through our analysis we identified four periods of district health system progression: (1) development of the district health system (1970-85); (2) Strengthening District Health Systems Initiative (1986-93); (3) health sector reform planning and creation of the Ghana Health Service (1994-96) and (4) health sector reform implementation (1997-2007). It was observed that district manager decision-space steadily widened during periods (1) and (2), due to increases in managerial profile, and concerted efforts at managerial capacity strengthening. Periods (3) and (4) saw initial augmentation of district health system financing, further widening managerial decision-space. However, the latter half of period 4 witnessed district manager decision-space contraction. Formalization of Ghana Health Service structures influenced by self-reinforcing tendencies towards centralized decision-making, national and donor shifts in health sector financing, and changes in key policy actors all worked to the detriment of the district health system, reversing early gains from bottom-up development of the district health system. Policy feedback mechanisms have been influenced by historical and contemporary sequencing of local government and health sector decentralization. An initial act of administrative decentralization, followed by incomplete political and fiscal decentralization has ensured that the balance of power has

Intention to comply with post-exposure management among nurses exposed to blood and body fluids in Taiwan: application of the theory of planned behaviour.

Science.gov (United States)

Ko, N-Y; Yeh, S-H; Tsay, S-L; Ma, H-J; Chen, C-H; Pan, S-M; Feng, M-C; Chiang, M-C; Lee, Y-W; Chang, L-H; Jang, J-F

2011-04-01

Nurses are at significant risk from occupationally acquired bloodborne virus infections following a needlestick and sharps injury. This study aimed to apply the theory of planned behaviour (TPB) to predict nurses' intention to comply with occupational post-exposure management. A cross-sectional survey was applied to select registered nurses who worked in human immunodeficiency virus (HIV)-designated hospitals. An anonymous, self-administered questionnaire based on the TPB was distributed to 1630 nurses and 1134 (69.5%) questionnaires were returned. From these, a total of 802 nurses (71%) reported blood and body fluid exposure incidents during 2003-2005 and this group was used for analysis. Only 44.6% of the 121 exposed nurses who were prescribed post-exposure prophylaxis (PEP) by infectious disease doctors returned to the clinic for interim monitoring, and only 56.6% of exposed nurses confirmed their final serology status. Structural equation modelling was used to test the TPB indicating perceived behavioural control (the perception of the difficulty or ease of PEP management, β=0.58), subjective norm (the perception of social pressure to adhere to PEP, β=0.15), and attitudes (β=0.12) were significant direct effects on nurses' intention to comply with post-exposure management. The hypothesised model test indicated that the model fitted with the expected relationships and directions of theoretical constructs [χ(2) (14, N=802)=23.14, P=0.057, GFI=0.987, RMSEA=0.039]. The TPB model constructs accounted for 54% of the variance in nurses' intention to comply with post-exposure management. The TPB is an appropriate model for predicting nurses' intention to comply with post-exposure management. Healthcare facilities should have policies to decrease the inconvenience of follow-up to encourage nurses to comply with post-exposure management. Copyright © 2010 the Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

A study of Huntington disease-like syndromes in black South African patients reveals a single SCA2 mutation and a unique distribution of normal alleles across five repeat loci.

Science.gov (United States)

Baine, Fiona K; Peerbhai, Nabeelah; Krause, Amanda

2018-07-15

Huntington disease (HD) is a progressive neurodegenerative disease, characterised by a triad of movement disorder, emotional and behavioural disturbances and cognitive impairment. The underlying cause is an expanded CAG repeat in the huntingtin gene. For a small proportion of patients presenting with HD-like symptoms, the mutation in this gene is not identified and they are said to have a HD "phenocopy". South Africa has the highest number of recorded cases of an African-specific phenocopy, Huntington disease-like 2 (HDL2), caused by a repeat expansion in the junctophilin-3 gene. However, a significant proportion of black patients with clinical symptoms suggestive of HD still test negative for HD and HDL2. This study thus aimed to investigate five other loci associated with HD phenocopy syndromes - ATN1, ATXN2, ATXN7, TBP and C9orf72. In a sample of patients in whom HD and HDL2 had been excluded, a single expansion was identified in the ATXN2 gene, confirming a diagnosis of Spinocerebellar ataxia 2. The results indicate that common repeat expansion disorders do not contribute significantly to the HD-like phenotype in black South African patients. Importantly, allele sizing reveals unique distributions of normal repeat lengths across the associated loci in the African population studied. Copyright © 2018 Elsevier B.V. All rights reserved.

The challenge of juvenile Huntington disease: to test or not to test.

Science.gov (United States)

Koutsis, Georgios; Karadima, Georgia; Kladi, Athina; Panas, Marios

2013-03-12

In a cohort of patients with suspected juvenile-onset Huntington disease (HD), we compared HD expansion-positive and -negative cases in order to identify parameters that may allow differentiating between them and may act as a guide to clinicians contemplating genetic testing. We analyzed the clinical and genetic characteristics of 76 juvenile-onset patients referred consecutively for HD genetic testing over a 16-year period. In total, 24 patients were positive for the HD expansion (7.8% of our HD cohort). Mean age at onset of expanded cases was similar to unexpanded cases. All expanded cases had a family history of genetically confirmed HD compared to only 13.5% of unexpanded cases (p = 0.000). Clinical symptoms at onset or at presentation could not differentiate between expanded and unexpanded patients. Although criteria suggested by previous reports allowed statistical differentiation between the 2 groups, they were not sufficiently sensitive and specific to be used in clinical context and performed less satisfactorily than presence of a family history of HD alone. A diagnosis of juvenile HD should be primarily contemplated in symptomatic children with a family history of HD, although a proportion of these will test negative. With no family history of HD, juvenile HD is very unlikely and genetic testing should never delay searching for other causes. The specific nature of symptoms at onset or at presentation is of limited value in guiding the decision to test or not to test.

An electrophysiological analysis of altered cognitive functions in Huntington disease.

Science.gov (United States)

Münte, T F; Ridao-Alonso, M E; Preinfalk, J; Jung, A; Wieringa, B M; Matzke, M; Dengler, R; Johannes, S

1997-09-01

Neuropsychological deficits are a main feature of Huntington disease (HD) with previous data suggesting involvement of memory functions and visual processing. To increase the knowledge about cognitive malfunction in HD in the domains of visual processing and memory by the use of modern electrophysiological techniques (event-related potentials [ERPs]). A case-control design was used. Three ERP paradigms were used; a parallel visual search paradigm allowed for the simultaneous processing of a multi-element visual array in search of a target stimulus, while a serial search paradigm with varied numbers of distractor items necessitated a serial one by one scanning of the arrays. The third experiment was a word-recognition memory task. The measurements were obtained in a neurophysiological laboratory of a university hospital. Nine patients with HD and 9 control subjects matched for age, sex, and education were studied. Components of averaged ERPs were quantified by latency and amplitude measures and subjected to statistical analysis. Behavioral measures (search time, hit rate, and recognition accuracy) were assessed as well. The early visual components showed a significant latency shift (delay of about 50 milliseconds) in HD. In the search paradigms the P3 components differentiating target and standard stimuli were virtually absent in HD as was the ERP effect indexing word recognition. This was accompanied by a marked delay in search times and lower hit rates in the search tasks and a grossly reduced recognition accuracy in the memory task. The results suggest marked impairments of patients with HD in early visual sensory processing (early components). Deficits in visual search might be attributed to an impairment to deploy attentional resources across the visual field and/or an inability to control eye movements. The ERPs in the memory task differed grossly from similar data obtained by others in patients with Alzheimer disease, suggesting a different neural basis for

β-Defensin genomic copy number does not influence the age of onset in Huntington's Disease.

Science.gov (United States)

Vittori, Angelica; Orth, Michael; Roos, Raymund A C; Outeiro, Tiago F; Giorgini, Flaviano; Hollox, Edward J

2013-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also been shown to play a modulatory role. Recent evidence suggests that neuroinflammations is a pivotal factor in the pathogenesis of HD, and that targeting this process may have important therapeutic ramifications. The human β-defensin 2 (hBD2)- encoded by DEFB4- is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore, DEFB4 may contribute to the neuroinflammatory processes observed in HD. In this study we tested the hypothesis that copy number variation (CNV) of the β-defensin region, including DEFB4, modifies the AO in HD. We genotyped β-defensin CNV in 490 HD individuals using the paralogue ratio test and found no association between β-defensin CNV and onset of HD. We conclude that it is unlikely that DEFB4 plays a role in HD pathogenesis.

Echolalia or functional repetition in conversation--a case study of an individual with Huntington's disease.

Science.gov (United States)

Saldert, Charlotta; Hartelius, Lena

2011-01-01

In this case study, we investigated the use of repetition in an individual with a neurogenic communication disorder. We present an analysis of interaction in natural conversations between a woman with advanced Huntington's disease (HD), whose speech had been described as sometimes characterised by echolalia, and her personal assistant. The conversational interaction is analysed on a sequential level, and recurrent patterns are explored. Although the ability of the person with HD to interact is affected by chorea, word retrieval problems and reduced comprehension, she takes an active part in conversation. The conversational partner's contributions are often adapted to her communicative ability as they are formulated as questions or suggestions that can be elaborated on or responded to with a simple 'yes' or 'no'. The person with HD often repeats the words of her conversational partner in a way that extends her contributions and shows listenership, and this use of repetition is also frequent in ordinary conversations between non-brain-damaged individuals. The results show that the conversation partners in this case cooperate in making the conversation proceed and evolve, and that verbal repetition is used in a way that works as a strategy for compensating for the impairment.

Early Detection of Apathetic Phenotypes in Huntington's Disease Knock-in Mice Using Open Source Tools.

Science.gov (United States)

Minnig, Shawn; Bragg, Robert M; Tiwana, Hardeep S; Solem, Wes T; Hovander, William S; Vik, Eva-Mari S; Hamilton, Madeline; Legg, Samuel R W; Shuttleworth, Dominic D; Coffey, Sydney R; Cantle, Jeffrey P; Carroll, Jeffrey B

2018-02-02

Apathy is one of the most prevalent and progressive psychiatric symptoms in Huntington's disease (HD) patients. However, preclinical work in HD mouse models tends to focus on molecular and motor, rather than affective, phenotypes. Measuring behavior in mice often produces noisy data and requires large cohorts to detect phenotypic rescue with appropriate power. The operant equipment necessary for measuring affective phenotypes is typically expensive, proprietary to commercial entities, and bulky which can render adequately sized mouse cohorts as cost-prohibitive. Thus, we describe here a home-built, open-source alternative to commercial hardware that is reliable, scalable, and reproducible. Using off-the-shelf hardware, we adapted and built several of the rodent operant buckets (ROBucket) to test Htt Q111/+ mice for attention deficits in fixed ratio (FR) and progressive ratio (PR) tasks. We find that, despite normal performance in reward attainment in the FR task, Htt Q111/+ mice exhibit reduced PR performance at 9-11 months of age, suggesting motivational deficits. We replicated this in two independent cohorts, demonstrating the reliability and utility of both the apathetic phenotype, and these ROBuckets, for preclinical HD studies.

Government Districts, Other, Sedgwick County Board of County Commissioner district boundaries. Derived from countywide Elections coverage. Primary attributes include District number and respresentative name. Includes district number annotation. Published to scbocc_a.shp., Published in 2008, 1:1200 (1in=100ft) scale, Sedgwick County Government.

Data.gov (United States)

NSGIC Local Govt | GIS Inventory — Government Districts, Other dataset current as of 2008. Sedgwick County Board of County Commissioner district boundaries. Derived from countywide Elections coverage....

the creation of new districts in Uganda

African Journals Online (AJOL)

User

However, it focuses also on the financial burden that these newly created districts place on the locality and ..... Reports on one of the newly created districts paint a grim picture: “For more than 10 .... of the Consolidated Fund for such grants.80.

Dantrolene is neuroprotective in Huntington's disease transgenic mouse model

Directory of Open Access Journals (Sweden)

Chen Xi

2011-11-01

Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs. Our group has previously demonstrated that calcium (Ca2+ signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128. Moreover, we demonstrated that deranged intracellular Ca2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT MSNs. In previous studies we also observed abnormal neuronal Ca2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2 and spinocerebellar ataxia 3 (SCA3 mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. Results The application of caffeine and glutamate resulted in increased Ca2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Httexp nuclear aggregates. Conclusions Our results support the hypothesis that deranged Ca2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that Ryan

Dantrolene is neuroprotective in Huntington's disease transgenic mouse model.

Science.gov (United States)

Chen, Xi; Wu, Jun; Lvovskaya, Svetlana; Herndon, Emily; Supnet, Charlene; Bezprozvanny, Ilya

2011-11-25

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs). Our group has previously demonstrated that calcium (Ca2+) signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128). Moreover, we demonstrated that deranged intracellular Ca2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT) MSNs. In previous studies we also observed abnormal neuronal Ca2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2) and spinocerebellar ataxia 3 (SCA3) mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. The application of caffeine and glutamate resulted in increased Ca2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg) twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Httexp nuclear aggregates. Our results support the hypothesis that deranged Ca2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that RyanR inhibitors and Ca2+ signaling stabilizers such as

District heating in Italy: Extent of use

International Nuclear Information System (INIS)

Sacchi, E.

1992-01-01

The Author surveys the trend that has been established over the last two decades in the use of district heating in Italy. Comparison with the European situation reveals that Italy is lagging behind. The reason for this the Author states is the Italian public's aversion to unknown risks involved in the utilization of innovative technologies associated with cogeneration/district heating (current preference is given to autonomous methane fuelled building space heating systems), and the current opinion of some misinformed public administrations that cogeneration/district heating plants are too costly. Citing the successful campaign by the natural gas industry to promote the public acceptance of methane as a safe, readily available and competitively priced energy source, he suggests that similar efforts be made to have the public also accept cogeneration (with methane fired gas turbines)/district heating as being safe and environmentally, as well as, economically beneficial

Nuclear power for district heating

International Nuclear Information System (INIS)

Lyon, R.B.; Sochaski, R.O.

1975-09-01

Current district heating trends are towards an increasing use of electricity. This report concerns the evaluation of an alternative means of energy supply - the direct use of thermal energy from CANDU nuclear stations. The energy would be transmitted via a hot fluid in a pipeline over distances of up to 40 km. Advantages of this approach include a high utilization of primary energy, with a consequent reduction in installed capacity, and load flattening due to inherent energy storage capacity and transport delays. Disadvantages include the low load factors for district heating, the high cost of the distribution systems and the necessity for large-scale operation for economic viability. This requirement for large-scale operation from the beginning could cause difficulty in the implementation of the first system. Various approaches have been analysed and costed for a specific application - the supply of energy to a district heating load centre in Toronto from the location of the Pickering reactor station about 40 km away. (author)

Six psychotropics for pre-symptomatic & early Alzheimer's (MCI, Parkinson's, and Huntington's disease modification

Directory of Open Access Journals (Sweden)

Edward C Lauterbach

2016-01-01

Full Text Available The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs, including Alzheimer's disease (AD, Parkinson's disease (PD, and Huntington's disease (HD, has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow. Mild cognitive impairment (MCI phase of AD: salutary human randomized controlled trial findings for low-dose lithium and, in selected patients, donepezil await replication. Pre-symptomatic AD: human epidemiological data indicate that lithium reduces AD risk. Animal model studies (AMS reveal encouraging results for quetiapine, lithium, donepezil, and memantine. Early PD: valproate AMS findings show promise. Pre-symptomatic PD: lithium and valproate AMS findings are encouraging. Early HD: uncontrolled clinical data indicate non-progression with lithium, fluoxetine, donepezil, and memantine. Pre-symptomatic HD: lithium and valproate are auspicious in AMS. Many other promising findings awaiting replication (valproate in MCI; lithium, valproate, fluoxetine in pre-symptomatic AD; lithium in early PD; lithium, valproate, fluoxetine in pre-symptomatic PD; donepezil in early HD; lithium, fluoxetine, memantine in pre-symptomatic HD are reviewed. Dose- and stage-dependent effects are considered. Suggestions for signal-enhancement in human trials are provided for each NDD stage.

VT Data - Cons/Rec Overlay District 20110301, Winhall

Data.gov (United States)

Vermont Center for Geographic Information — Conservation and Recreatioal Protection overaly districts for the Town of Winhall, Vermont. Other overlay districts (Transfer of Development Rights, and Scenic...

13 CFR 304.1 - Designation of Economic Development Districts: Regional eligibility.

Science.gov (United States)

2010-01-01

... Development Districts: Regional eligibility. 304.1 Section 304.1 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE ECONOMIC DEVELOPMENT DISTRICTS § 304.1 Designation of Economic Development Districts: Regional eligibility. Upon the request of a District Organization (as...

Performance of District Disaster Management Teams after ...

African Journals Online (AJOL)

Introduction: Uganda is vulnerable to several natural, man-made and a hybrid of disasters including drought, famine, floods, warfare, and disease outbreaks. We assessed the district disaster team's performance, roles and experiences following the training. Findings: The disasters most commonly experienced by the district ...

Understanding District-Charter Collaboration Grants. Final Report

Science.gov (United States)

Tuttle, Christina; McCullough, Moira; Richman, Scott; Booker, Kevin; Burnett, Alyson; Keating, Betsy; Cavanaugh, Michael

2016-01-01

In November 2012, the Bill & Melinda Gates Foundation invested in seven innovative district-charter partnerships with "the potential capacity and commitment to accelerate student college ready rates through deep collaboration and sharing of best practices" (District-Charter Collaboration Grant Request for Proposal [RFP]). These…

Solar heat storages in district heating networks

Energy Technology Data Exchange (ETDEWEB)

Ellehauge, K. (Ellehauge og Kildemoes, AArhus (DK)); Engberg Pedersen, T. (COWI A/S, Kgs. Lyngby (DK))

2007-07-15

This report gives information on the work carried out and the results obtained in Denmark on storages for large solar heating plants in district heating networks. Especially in Denmark the share of district heating has increased to a large percentage. In 1981 around 33% of all dwellings in DK were connected to a district heating network, while the percentage in 2006 was about 60% (in total 1.5 mio. dwellings). In the report storage types for short term storage and long term storages are described. Short term storages are done as steel tanks and is well established technology widely used in district heating networks. Long term storages are experimental and used in connection with solar heating. A number of solar heating plants have been established with either short term or long term storages showing economy competitive with normal energy sources. Since, in the majority of the Danish district heating networks the heat is produced in co-generation plants, i.e. plants producing both electricity and heat for the network, special attention has been put on the use of solar energy in combination with co-generation. Part of this report describes that in the liberalized electricity market central solar heating plants can also be advantageous in combination with co-generation plants. (au)

Profiles of Merit Pay Provisions in Ohio School Districts

Science.gov (United States)

Willis, Chris; Ingle, W. Kyle

2018-01-01

A small number of districts in Ohio from a variety of locales have adopted merit pay provisions. Using Springer's (2009) taxonomy of teacher compensation, we analyzed compensation provisions of these districts. We asked: What are the characteristics of these districts? What criteria are used to determine merit? Who is determining who receives…

Genetic Counselling for Predictive Testing in Huntington's Disease in One Centre since 1993. Gender-Specific Aspects of Decision-Making.

Science.gov (United States)

Arning, Larissa; Witt, Constantin N; Epplen, Jörg T; Stemmler, Susanne

2015-01-01

The discovery of the mutation causing Huntington's disease (HD) in 1993 allowed direct mutation analysis and predictive testing to identify currently unaffected carriers with a sensitivity and specificity of virtually 100%. The present study was designed to comprehensively profile the participants who sought predictive testing for HD between 1993 and 2009 in our Huntington centre. Using a retrospective design, we analysed the written documentation of the counselling sessions for all referrals for predictive mutation testing in this time span. Six hundred sixty-three individuals at risk for HD requested predictive testing. Roughly half (n = 333) completed the protocol and received their test result. In general our findings are in accordance with other reports: most participants share an a priori risk of 50% (91.1%); more females request testing (58.5%); and those who ask for the result are mostly in their 30 s (mean = 35.1 years). Of those at 50% or 25% prior risks, 47.4% and 22.7%, respectively, tested positive in accordance with the respective risk of inheriting HD. Generally, more participants with an affected mother than father sought genetic testing (52.5% versus 47.5%). Interestingly, this difference was especially evident in the group of females who finally withdrew from testing (59.1%, p = 0.040). Men, in particular those who decided in favour of the test, were more often accompanied by their partner in the pre-test counselling session than vice versa (67.9% versus 44.7%, p = 0.003). On the other hand, significantly more men who were being tested did not have a companion in the pre-test session as compared with men who decided against the test (40.0% versus 25.7%, p = 0.012). During the first four years of predictive testing (1993–1996) more participants completed the protocol and received their test result as in later years. Yet, in this early time span significantly fewer females finally decided in favour of the test (48.4%, p = 0.005). These findings

Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice

Directory of Open Access Journals (Sweden)

Jack C. Reidling

2018-01-01

Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP-grade human embryonic stem cell-derived neural stem cell (hNSC line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF in both models. These findings hold promise for future development of stem cell-based therapies.

Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease

Directory of Open Access Journals (Sweden)

Piotr Hadaczek

2016-01-01

Full Text Available Huntington's disease (HD is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV, AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP, with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease.

Local business models for district heat production; Kaukolaemmoen paikalliset liiketoimintamallit

Energy Technology Data Exchange (ETDEWEB)

Hakala, L.; Pesola, A.; Vanhanen, J.

2012-12-15

Local district heating business, outside large urban centers, is a profitable business in Finland, which can be practiced with several different business models. In addition to the traditional, local district heating business, local district heat production can be also based on franchising business model, on integrated service model or on different types of cooperation models, either between a local district heat producer and industrial site providing surplus heat or between a local district heat producer and a larger district heating company. Locally available wood energy is currently utilized effectively in the traditional district heating business model, in which a local entrepreneur produces heat to consumers in the local area. The franchising model is a more advanced version of the traditional district heating entrepreneurship. In this model, franchisor funds part of the investments, as well as offers centralized maintenance and fuel supply, for example. In the integrated service model, the local district heat producer offers also energy efficiency services and other value-added services, which are based on either the local district heat suppliers or his partner's expertise. In the cooperation model with industrial site, the local district heating business is based on the utilization of the surplus heat from the industrial site. In some cases, profitable operating model approach may be a district heating company outsourcing operations of one or more heating plants to a local entrepreneur. It can be concluded that all business models for district heat production (traditional district heat business model, franchising, integrated service model, cooperative model) discussed in this report can be profitable in Finnish conditions, as well for the local heat producer as for the municipality - and, above all, they produce cost-competitive heat for the end-user. All the models were seen as viable and interesting and having possibilities for expansion Finland

6 CFR 5.48 - Considerations in determining whether the Department will comply with a demand or request

Science.gov (United States)

2010-01-01

... Litigation § 5.48 Considerations in determining whether the Department will comply with a demand or request... governing the case or matter in which the demand arose; (2) Whether compliance is appropriate under the... need to avoid spending the time and money of the United States for private purposes; (6) The need to...

22 CFR 172.8 - Considerations in determining whether the Department will comply with a demand or request.

Science.gov (United States)

2010-04-01

... in determining whether the Department will comply with a demand or request. (a) In deciding whether... applicable rules of discovery or the rules of procedure governing the case or matter in which the demand... for the conduct of official business; (5) The need to avoid spending the time and money of the United...

Smallholder agricultural technology development in Soroti district ...

African Journals Online (AJOL)

Mo

National Agricultural Advisory and Development Services (NAADS) in Soroti district. The study shows that .... important additions are HIV/AIDS, basic principles of nutrition ... in supplying inputs to farmers and technology delivery, while the .... Table 3. Social differentiation of NAADS and FFS groups in Soroti district 2004.

Inventory Control of Fixed Assets by School District Personnel.

Science.gov (United States)

Jensen, Paul E.

By July 1, 1966, each school district in New York State was required to install a system of property accounting. This pamphlet provides a suggested method of property accounting to assist school districts in meeting this requirement. In addition, suggestions are made to help the districts record the information needed for fire insurance purposes.…

The waste disposal facility in the Aube District

International Nuclear Information System (INIS)

Torres, Patrice

2013-06-01

The waste disposal facility in the Aube district is the second surface waste disposal facility built in France. It is located in the Aube district, and has been operated by Andra since 1992. With a footprint of 95 hectares, it is licensed for the disposal of 1 million cubic meters of low- and intermediate-level, short-lived waste packages. The CSA is located a few kilometers away another Andra facility, currently in operation for very-low-level waste, and collection and storage of non-nuclear power waste (the Cires). Contents: Andra in the Aube district, an exemplary industrial operator - The waste disposal facility in the Aube district (CSA); Low- and intermediate-level, short-lived radioactive waste (LILW-SL); The LILW-SL circuit; Protecting present and future generations