Goal-orientated cognitive rehabilitation for dementias associated with Parkinson's disease―A pilot randomised controlled trial

OBJECTIVE: To examine the appropriateness and feasibility of cognitive rehabilitation for people with dementias associated with Parkinson's in a pilot randomised controlled study. METHODS: This was a single-blind pilot randomised controlled trial of goal-oriented cognitive rehabilitation for dementias associated with Parkinson's. After goal setting, participants were randomised to cognitive rehabilitation (n = 10), relaxation therapy (n = 10), or treatment-as-usual (n = 9). Primary outcomes were ratings of goal attainment and satisfaction with goal attainment. Secondary outcomes included quality of life, mood, cognition, health status, everyday functioning, and carers' ratings of goal attainment and their own quality of life and stress levels. Assessments were at 2 and 6 months following randomisation. RESULTS: At 2 months, cognitive rehabilitation was superior to treatment-as-usual and relaxation therapy for the primary outcomes of self-rated goal attainment (d = 1.63 and d = 1.82, respectively) and self-rated satisfaction with goal attainment (d = 2.04 and d = 1.84). At 6 months, cognitive rehabilitation remained superior to treatment-as-usual (d = 1.36) and relaxation therapy (d = 1.77) for self-rated goal attainment. Cognitive rehabilitation was superior to treatment as usual and/or relaxation therapy in a number of secondary outcomes at 2 months (mood, self-efficacy, social domain of quality of life, carers' ratings of participants' goal attainment) and at 6 months (delayed recall, health status, quality of life, carer ratings of participants' goal attainment). Carers receiving cognitive rehabilitation reported better quality of life, health status, and lower stress than those allocated to treatment-as-usual. CONCLUSIONS: Cognitive rehabilitation is feasible and potentially effective for dementias associated with Parkinson's disease

The flow of city life: An analysis of cinematography and urban form in New York and Los Angeles

This dissertation uses quantitative data on city cinematography and the morphological study of filming locations to identify how differences in ways of seeing cities, as shaped by cinematographic choices, are anchored both in differences in what is physically present as well as in differences in frameworks and expectations about what might be interesting or important to see. Four films are evaluated that are set in Los Angeles and New York, two cities recognized as paradigms in American urbanism: The Naked City (1948), The Long Goodbye (1970), Goodfellas (1990), and Pulp Fiction (1994). In general, the New York movies suggest the embeddedness of the individual in the city and its social life in ways tied closely to urban form, with the visual presentation of the street acting as an index to the position of the individual within the narrative. Los Angeles, by contrast, presents the city as a series of enclaves linked by infrastructure. The street as a sociologically relevant entity hardly exists, with the exception of a handful of chase scenes, as though only crisis can catalyze direct encounters with the streets of Los Angeles. Within individual movies, the depiction of city form reveals directorial idioms in the presentation of the narrative. The Naked City exploits corner shots to impart greater visual interest to the presentation of activity in the streets. The Long Goodbye shows the degradation of the distinction between public and private space as concurrent with a city form and culture that resists decoding. Goodfellas develops a grammar of views on the street that corresponds to the relationships of individual characters to overlapping social groups over time. Pulp Fiction mainly presents city locations as decontextualized to focus on dialogue and relationships, to sculpt urban form to meet the exigencies of the narrative, and to all the more powerfully introduce surprise. In the concluding chapter, the qualities of the city as presented in Goodfellas and Pulp Fiction and both of the cities are diagrammed and discussed relative to architectural precedents and ideas that might inform architectural design.Ph.D

Diphenyleneiodonium acutely inhibits reactive oxygen species production by mitochondrial complex I during reverse, but not forward electron transport

AbstractWe investigated the effects of diphenyleneiodonium (DPI) on superoxide production by complex I in mitochondria isolated from rat skeletal muscle. Superoxide production was measured indirectly as hydrogen peroxide production. In a conventional medium containing chloride, DPI strongly inhibited superoxide production by complex I driven by reverse electron transport from succinate. In principle, this inhibition could be explained by an observed decrease in the mitochondrial pH gradient caused by the known chloride–hydroxide antiport activity of DPI. In a medium containing gluconate instead of chloride, DPI did not affect the pH gradient. In this gluconate medium, DPI still inhibited superoxide production driven by reverse electron transport, showing that the inhibition of superoxide production was not dependent on changes in the pH gradient. It had no effect on superoxide production during forward electron transport from NAD-linked substrates in the presence of rotenone (to maximise superoxide production from the flavin of complex I) or antimycin (to maximise superoxide production from complex III), suggesting that the effects of DPI were not through inhibition of the flavin. We conclude that DPI has the novel and potentially very useful ability to prevent superoxide production from the site in complex I that is active during reverse electron transport, without affecting superoxide production during forward electron transport

Aula interactiva para la sensibilización sobre la problemática de Asbesto en Colombia y la promoción de iniciativas que generen articulación para un trabajo en red.

La realidad en torno a la minería, la industrialización entre otros, ha cargado a lasociedad con diversas problemáticas que en ocasiones han derivado en la generaciónde patologías y/o afectaciones en la calidad de vida de los ciudadanos. Es así como laindustria, debería ser regulada a profundidad de manera que pueda prevenirse ocontrolarse cualquier tipo de afectación que los procesos industriales puedan ejercersobre su entorno, máxime cuando ello involucra el bienestar de seres humanos.Frente a esta situación y atendiendo un poco a la coyuntura actual, en nuestrosemillero de investigación (SISMA – Semillero de Investigación en Salud y MedioAmbiente) se ha despertado un interés por indagar sobre el asbesto o amianto, comose conoce mundialmente; un material del que se ha demostrado que representa undaño irreparable sobre la población que tiene contacto directo o indirecto con él a talpunto que en muchas ocasiones conduce a la muerte.Por lo anterior, se hace necesario generar una estrategia pedagógica y didáctica queacerque esta problemática a la ciudadanía y le brinde herramientas conceptuales,históricas y hasta legislativas para tratar el tema como un problema de salud pública ylograr que día a día las comunidades, especialmente las aledañas a los lugares dondese utiliza este material en la manufactura, comprenda que está poniendo en riesgo suintegridad

Coding of Barrett's oesophagus with high-grade dysplasia in national administrative databases: a population-based cohort study.

OBJECTIVES: The International Classification of Diseases 10th Revision (ICD-10) system used in the English hospital administrative database (Hospital Episode Statistics (HES)) does not contain a specific code for oesophageal high-grade dysplasia (HGD). The aim of this paper was to examine how patients with HGD were coded in HES and whether it was done consistently. SETTING: National population-based cohort study of patients with newly diagnosed with HGD in England. The study used data collected prospectively as part of the National Oesophago-Gastric Cancer Audit (NOGCA). These records were linked to HES to investigate the pattern of ICD-10 codes recorded for these patients at the time of diagnosis. PARTICIPANTS: All patients with a new diagnosis of HGD between 1 April 2013 and 31 March 2014 in England, who had data submitted to the NOGCA. OUTCOMES MEASURED: The main outcome assessed was the pattern of primary and secondary ICD-10 diagnostic codes recorded in the HES records at endoscopy at the time of diagnosis of HGD. RESULTS: Among 452 patients with a new diagnosis of HGD between 1 April 2013 and 31 March 2014, Barrett's oesophagus was the only condition coded in 200 (44.2%) HES records. Records for 59 patients (13.1%) contained no oesophageal conditions. The remaining 193 patients had various diagnostic codes recorded, 93 included a diagnosis of Barrett's oesophagus and 57 included a diagnosis of oesophageal/gastric cardia cancer. CONCLUSIONS: HES is not suitable to support national studies looking at the management of HGD. This is one reason for the UK to adopt an extended ICD system (akin to ICD-10-CM)

Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

Abstract Introduction Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model. Methods DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund’s adjuvant (CFA) or incomplete Freund’s adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression. Results Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA/CII group and IL-1β, tumor necrosis factor-α, transforming growth factor-β, IL-6 and IL-23 in the IFA/CII group. Conclusions Chronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.http://deepblue.lib.umich.edu/bitstream/2027.42/112639/1/13075_2013_Article_4062.pd

Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors

<i>N</i>-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa <i>Trypanosoma brucei</i> (<i>T. brucei</i>), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated <i>T. brucei</i> NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (<b>1</b>) as a starting point for the design of a class of potent, brain penetrant inhibitors of <i>T. brucei</i> NMT