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1.
Cancer Res ; 2019 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-31740444

RESUMEN

Emerging evidence indicates the deubiquitinase USP22 regulates transcriptional activation and modification of target substrates to promote pro-oncogenic phenotypes. Here, in vivo characterization of tumor-associated USP22 upregulation and unbiased interrogation of USP22-regulated functions in vitro demonstrated critical roles for USP22 in prostate cancer (PCa). Specifically, clinical datasets validated that USP22 expression is elevated in PCa, and a novel murine model demonstrated a hyperproliferative phenotype with prostate-specific USP22 overexpression. Accordingly, upon overexpression or depletion of USP22, enrichment of cell cycle and DNA repair pathways was observed in the USP22-sensitive transcriptome and ubiquitylome using PCa models of clinical relevance. Depletion of USP22 sensitized cells to genotoxic insult, and the role of USP22 in response to genotoxic insult was further confirmed using mouse adult fibroblasts from the novel murine model of USP22 expression. As it was hypothesized that USP22 deubiquitylates target substrates to promote pro-tumorigenic phenotypes, analysis of the USP22-sensitive ubiquitylome identified the nucleotide excision repair protein, XPC, as a critical mediator of the USP22-mediated response to genotoxic insult. Thus, XPC undergoes deubiquitylation as a result of USP22 function and promotes USP22-mediated survival to DNA damage. Combined, these findings reveal unexpected functions of USP22 as a driver of pro-tumorigenic phenotypes and have significant implications on the role of USP22 in therapeutic outcomes.

2.
Cogn Neuropsychiatry ; 24(6): 389-405, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31550981

RESUMEN

Objective: To determine the relationship between language abnormalities and broader cognitive impairment and thought disorder by examining language and cognition in schizophrenia and aphasia (a primary language disorder).Methods: Cognitive and linguistic profiles were measured with a battery of standardised tests, and compared in a clinical population of n = 50 (n = 30 with schizophrenia and n = 20 with aphasia) and n = 61 non-clinical comparisons (n = 45 healthy controls and n = 16 non-affected first-degree relatives of patients with schizophrenia).Results: Both clinical groups showed linguistic deficits. Verbal impairment was more severe in participants with aphasia, whereas non-verbal performance was more affected in participants with schizophrenia. In schizophrenia, but not in aphasia, verbal and non-verbal performance were associated. Formal thought disorder was associated with impairment in executive function and in grammatical, but not naming, tasks.Conclusion: While patients with schizophrenia and aphasia showed language impairments, the nature and cognitive basis of these impairments may be different; language performance disassociates from broader cognitive functioning in aphasia but may be an intrinsic expression of a broader cognitive impairment in schizophrenia. Thought disorder may represent a core malfunction of grammatical processing. Results suggests that communicative ability may be a valid target in cognitive remediation strategies in schizophrenia.

3.
Bipolar Disord ; 2019 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-31491048

RESUMEN

BACKGROUND: Impairments in affective cognition are part of the neurocognitive profile and possible treatment targets in bipolar disorder (BD), but the findings are heterogeneous. The International Society of Bipolar Disorder (ISBD) Targeting Cognition Task Force conducted a systematic review to (i) identify the most consistent findings in affective cognition in BD, and (ii) provide suggestions for affective cognitive domains for future study and meta-analyses. METHODS: The review included original studies reporting behavioral measures of affective cognition in BD patients vs controls following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Searches were conducted on PubMed/MEDLINE, EMBASE, and PsychInfo from inception until November 2018. RESULTS: A total of 106 articles were included (of which nine included data for several affective domains); 41 studies assessed emotional face processing; 23 studies investigated reactivity to emotional words and images; 3 investigated explicit emotion regulation; 17 assessed implicit emotion regulation; 31 assessed reward processing and affective decision making. In general, findings were inconsistent. The most consistent findings were trait-related difficulties in facial emotion recognition and implicit emotion regulation, and impairments in reward processing and affective decision making during mood episodes. Studies using eye-tracking and facial emotion analysis revealed subtle trait-related abnormalities in emotional reactivity. CONCLUSION: The ISBD Task Force recommends facial expression recognition, implicit emotion regulation, and reward processing as domains for future research and meta-analyses. An important step to aid comparability between studies in the field would be to reach consensus on an affective cognition test battery for BD.

4.
Nat Commun ; 10(1): 2276, 2019 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-31123312

RESUMEN

Solar flares often involve the acceleration of particles to relativistic energies and the generation of high-intensity bursts of radio emission. In some cases, the radio bursts can show periodic or quasiperiodic intensity pulsations. However, precisely how these pulsations are generated is still subject to debate. Prominent theories employ mechanisms such as periodic magnetic reconnection, magnetohydrodynamic (MHD) oscillations, or some combination of both. Here we report on high-cadence (0.25 s) radio imaging of a 228 MHz radio source pulsating with a period of 2.3 s during a solar flare on 2014-April-18. The pulsating source is due to an MHD sausage mode oscillation periodically triggering electron acceleration in the corona. The periodic electron acceleration results in the modulation of a loss-cone instability, ultimately resulting in pulsating plasma emission. The results show that a complex combination of MHD oscillations and plasma instability modulation can lead to pulsating radio emission in astrophysical environments.

5.
J Neurol ; 266(7): 1716-1726, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31006825

RESUMEN

BACKGROUND: Lewy body dementia (LBD) and Alzheimer's disease (AD) are common forms of degenerative dementia. While they are characterized by different clinical profiles, attentional deficits are a common feature. The objective of this study was to investigate how attentional problems in LBD and AD differentially affect different aspects of reaction time performance and to identify possible structural neural correlates. METHODS: We studied reaction time data from an attention task comparing 39 LBD patients, 28 AD patients, and 22 age-matched healthy controls. Data were fitted to an ex-Gaussian model to characterize different facets of the reaction time distribution (mean reaction time, reaction time variability, and the subset of extremely slow responses). Correlations between ex-Gaussian parameters and grey and white matter volume were assessed by voxel-based morphometry. RESULTS: Both dementia groups showed an increase in extremely slow responses. While there was no difference between AD and controls with respect to mean reaction time and variability, both were significantly increased in LBD patients compared to controls and AD. There were widespread correlations between mean reaction time and variability and grey matter loss in AD, but not in LBD. CONCLUSIONS: This study shows that different aspects of reaction time performance are differentially affected by AD and LBD, with a difference in structural neural correlates underlying the observed behavioural deficits. While impaired attentional performance is linked to brain atrophy in AD, in LBD it might be related to functional or microstructural rather than macrostructural changes.

6.
Brain ; 142(6): 1767-1782, 2019 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-30938426

RESUMEN

Lewy body dementia includes dementia with Lewy bodies and Parkinson's disease dementia and is characterized by transient clinical symptoms such as fluctuating cognition, which might be driven by dysfunction of the intrinsic dynamic properties of the brain. In this context we investigated whole-brain dynamics on a subsecond timescale in 42 Lewy body dementia compared to 27 Alzheimer's disease patients and 18 healthy controls using an EEG microstate analysis in a cross-sectional design. Microstates are transiently stable brain topographies whose temporal characteristics provide insight into the brain's dynamic repertoire. Our additional aim was to explore what processes in the brain drive microstate dynamics. We therefore studied associations between microstate dynamics and temporal aspects of large-scale cortical-basal ganglia-thalamic interactions using dynamic functional MRI measures given the putative role of these subcortical areas in modulating widespread cortical function and their known vulnerability to Lewy body pathology. Microstate duration was increased in Lewy body dementia for all microstate classes compared to Alzheimer's disease (P < 0.001) and healthy controls (P < 0.001), while microstate dynamics in Alzheimer's disease were largely comparable to healthy control levels, albeit with altered microstate topographies. Correspondingly, the number of distinct microstates per second was reduced in Lewy body dementia compared to healthy controls (P < 0.001) and Alzheimer's disease (P < 0.001). In the dementia with Lewy bodies group, mean microstate duration was related to the severity of cognitive fluctuations (ρ = 0.56, PFDR = 0.038). Additionally, mean microstate duration was negatively correlated with dynamic functional connectivity between the basal ganglia (r = - 0.53, P = 0.003) and thalamic networks (r = - 0.38, P = 0.04) and large-scale cortical networks such as visual and motor networks in Lewy body dementia. The results indicate a slowing of microstate dynamics and disturbances to the precise timing of microstate sequences in Lewy body dementia, which might lead to a breakdown of the intricate dynamic properties of the brain, thereby causing loss of flexibility and adaptability that is crucial for healthy brain functioning. When contrasted with the largely intact microstate dynamics in Alzheimer's disease, the alterations in dynamic properties in Lewy body dementia indicate a brain state that is less responsive to environmental demands and might give rise to the apparent slowing in thinking and intermittent confusion which typify Lewy body dementia. By using Lewy body dementia as a probe pathology we demonstrate a potential link between dynamic functional MRI fluctuations and microstate dynamics, suggesting that dynamic interactions within the cortical-basal ganglia-thalamic loop might play a role in the modulation of EEG dynamics.

7.
Neuroimage Clin ; 22: 101812, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30991620

RESUMEN

We studied the dynamic functional connectivity profile of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) compared to controls, how it differs between the two dementia subtypes, and a possible relation between dynamic connectivity alterations and temporally transient clinical symptoms in DLB. Resting state fMRI data from 31 DLB, 29 AD, and 31 healthy control participants were analyzed using dual regression to determine between-network functional connectivity. Subsequently, we used a sliding window approach followed by k-means clustering and dynamic network analyses to study dynamic functional connectivity. Dynamic connectivity measures that showed significant group differences were tested for correlations with clinical symptom severity. Our results show that AD and DLB patients spent more time than controls in sparse connectivity configurations with absence of strong positive and negative connections and a relative isolation of motor networks from other networks. Additionally, DLB patients spent less time in a more strongly connected state and the variability of global brain network efficiency was reduced in DLB compared to controls. There were no significant correlations between dynamic connectivity measures and clinical symptom severity. An inability to switch out of states of low inter-network connectivity into more highly and specifically connected network configurations might be related to the presence of dementia in general as it was observed in both AD and DLB. In contrast, the loss of global efficiency variability in DLB might indicate the presence of an abnormally rigid brain network and the lack of economical dynamics, factors which could contribute to cognitive slowing and an inability to respond appropriately to situational demands.

8.
PLoS One ; 14(2): e0210394, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30721241

RESUMEN

OBJECTIVES: To explore cognitive performance in chronic fatigue syndrome (CFS) examining two cohorts. To establish findings associated with CFS and those related to co-morbid depression or autonomic dysfunction. METHODS: Identification and recruitment of participants was identical in both phases, all CFS patients fulfilled Fukuda criteria. In Phase 1 (n = 48) we explored cognitive function in a heterogeneous cohort of CFS patients, investigating links with depressive symptoms (HADS). In phase 2 (n = 51 CFS & n = 20 controls) participants with co-morbid major depression were excluded (SCID). Furthermore, we investigated relationships between cognitive performance and heart rate variability (HRV). RESULTS: Cognitive performance in unselected CFS patients is in average range on most measures. However, 0-23% of the CFS sample fell below the 5th percentile. Negative correlations occurred between depressive symptoms (HAD-S) with Digit-Symbol-Coding (r = -.507, p = .006) and TMT-A (r = -.382, p = .049). In CFS without depression, impairments of cognitive performance remained with significant differences in indices of psychomotor speed (TMT-A: p = 0.027; digit-symbol substitution: p = 0.004; digit-symbol copy: p = 0.007; scanning: p = .034) Stroop test suggested differences due to processing speed rather than inhibition. Both cohorts confirmed relationships between cognitive performance and HRV (digit-symbol copy (r = .330, p = .018), digit-symbol substitution (r = .313, p = .025), colour-naming trials Stroop task (r = .279, p = .050). CONCLUSION: Cognitive difficulties in CFS may not be as broad as suggested and may be restricted to slowing in basic processing speed. While depressive symptoms can be associated with impairments, co-morbidity with major depression is not itself responsible for reductions in cognitive performance. Impaired autonomic control of heart-rate associates with reductions in basic processing speed.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Cognición , Trastorno Depresivo Mayor/fisiopatología , Síndrome de Fatiga Crónica/fisiopatología , Frecuencia Cardíaca , Adulto , Enfermedades del Sistema Nervioso Autónomo/patología , Estudios de Cohortes , Comorbilidad , Trastorno Depresivo Mayor/patología , Síndrome de Fatiga Crónica/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad
10.
Clin Teach ; 16(5): 519-524, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30560577

RESUMEN

BACKGROUND: Cancer care is typically delivered by a range of health professionals, and is frequently a uniprofessional pre-registration clinical placement. A workplace-based, 6-hour interprofessional education (IPE) pilot on cancer care, led by clinical tutors, was undertaken in a New Zealand hospital, accompanied by an external evaluation. The pilot involved a cohort of 21 dietetic, medicine, pharmacy, physiotherapy and radiation therapy students. The aim of the evaluation was to determine student and tutor reactions to IPE, and any changes in perceptions and attitudes. METHODS: The evaluation used focus groups to collect data: two student groups and one tutor group. Focus groups were audio-recorded, transcribed; the content was coded and then analysed. RESULTS: Both students and tutors reported benefits from having IPE in the workplace environment, with cancer care seen as a suitable topic. Students reported a better understanding of professional roles, skills and the provision of collaborative care, and suggested other professions should be included in future IPE. Patient selection needed to be better tailored for physiotherapy students to ensure uniform relevance. As a result of competing demands, tutors found that they needed an 18-month lead time to establish the IPE programme. Tutors felt that the programme had gone relatively smoothly and that they had benefitted from forming closer interpersonal relationships, but noted considerable unanticipated and unremunerated preparation time. DISCUSSION: This short workplace-based IPE programme elicited a positive student and tutor response, but highlighted the need for improvements: broadening the topic area, targeted patient selection, including more professions and providing administrative support for tutors. Cancer care was generally seen as a suitable topic.

11.
Front Aging Neurosci ; 10: 347, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30519184

RESUMEN

Lewy body dementia (LBD) and Alzheimer's disease (AD) are common forms of dementia that have different clinical profiles but are both commonly associated with attentional deficits. The aim of this study was to investigate efficiency of different attentional systems in LBD and AD and its association with brain structural abnormalities. We studied reaction time (RT) data from 45 LBD, 31 AD patients and 22 healthy controls (HCs) using the Attention Network Test (ANT) to assess the efficiency of three different attentional systems: alerting, orienting and executive conflict. Voxel-based morphometry (VBM) was used to investigate relations between different attention components and cortical volume. Both dementia groups showed slower overall RTs than controls, with additional slowing in LBD relative to AD. There was a significant alerting effect in controls which was absent in the dementia groups, the executive conflict effect was greater in both dementia groups compared to controls, but the orienting effect did not differ between groups. Mean RT in AD was negatively correlated with occipital gray matter (GM) volume and in LBD orienting efficiency was negatively related to occipital white matter (WM) volume. Given that previous studies in less impaired patients suggest a maintenance of the alerting effect, the absent alerting effect in our study suggests a loss of alerting efficiency with dementia progression. While orienting was largely preserved, it might be related to occipital structural abnormalities in LBD. Executive function was markedly impaired in both dementia groups, however, the absence of relations to brain volume suggests that it might be more related to functional rather than macrostructural pathophysiological changes.

12.
EMBO Mol Med ; 2018 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-30467127

RESUMEN

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance "BRCA-ness". These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting.

13.
J Interprof Care ; : 1-3, 2018 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-30358458

RESUMEN

In New Zealand undergraduate health professional degrees focus on aspects of indigenous (Maori) health. Formal and informal feedback suggests that for individual students the impact of those components in respect of Maori health varies. Separate and sequential interprofessional groups of students from seven health professions participated in an innovative and immersive Interprofessional programme. All participating students had prior exposure during their respective degrees to theoretical perspectives of indigenous health. At the end of each and every 5-week long programme each cohort of student contributed to a focus group discussion. Analysis revealed that for these groups of students the real-life exposure to an indigenous community was positively regarded and, in some instances, transformative. The students also reported that the 'lived' experience in an indigenous community built upon and in many cases extended prior learning of indigenous health. Whilst the results are encouraging it must be noted that the students who were exposed to this experience represented less than 10% of the entire student population. It is clear that a key challenge for us is to enable more students to be exposed to this powerful learning experience.

14.
Pacing Clin Electrophysiol ; 41(4): 383-388, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29435997

RESUMEN

BACKGROUND: Barriers to successful left ventricular lead placement within the coronary venous anatomy may include focal stenoses, thromboses, phrenic nerve stimulation, vessel tortuosity, small vessel caliber, nonexcitable tissue, and valve presence. A large series describing the utilization of coronary venous angioplasty (CVAP) for relief of these issues is absent in the literature. OBJECTIVE: We report our experience on all patients treated with CVAP in a single-center 13-year experience. METHODS: Forty-seven patients with CVAP (64% male, mean age 67 ± 12 years) were treated by five different implanting physicians for approved cardiac resynchronization therapy indications. The reason for CVAP was categorized by obstacle (focal occlusion, valve presence, small caliber vessel) and location. The number, type, and size of balloon used, inflation characteristics, complications, and success of lead deployment crossing the point of intervention were all tabulated. RESULTS: Seventy-seven percent of patients (36/47) had successful CVAP. The most common reason for intervention was a focal occlusion (24/47; 51%), followed by valve presence (13/47; 28%), and small vessel caliber (10/47; 21%). Focal occlusions were most successfully managed with CVAP (23/24; 96%), followed by small vessel caliber (7/10; 70%) and valve presence (6/13; 46%). The reason for failure was most commonly due to failure to relieve the obstruction (5/11; 45%), thrombosis (3/11; 27.3%), dissection (2/11; 18.2%), and inability to pass the balloon through the occlusion (1/11; 9.0%). There were no significant complications developed from CVAP utilization. CONCLUSION: In a large analysis, CVAP can be safely and successfully performed in the majority of instances required.

15.
BMJ Open ; 8(1): e018510, 2018 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-29358432

RESUMEN

INTRODUCTION: Interprofessional practice is recognised as an important element of safe and effective healthcare. However, few studies exist that evaluate how preregistration education contributes to interprofessional competencies, and how these competencies develop throughout the early years of a health professional's career. This quasiexperimental study will gather longitudinal data during students' last year of preregistration training and their first 3 years of professional practice to evaluate the ongoing development of interprofessional competencies and the influence that preregistration education including an explicit interprofessional education (IPE) programme may have on these. METHODS AND ANALYSIS: Participants are students and graduates from the disciplines of dentistry, dietetics, medicine, nursing, occupational therapy, oral health, pharmacy and physiotherapy recruited before their final year of study. A subset of these students attended a 5-week IPE immersion programme during their final year of training. All data will be collected via five written or electronic surveys completed at 12-month intervals. Each survey will contain the Attitudes Towards Health Care Teams Scale and the Team Skills Scale, as well as quantitative and free-text items to explore vocational satisfaction, career trajectories and influences on these. Students who attend the IPE programme will complete additional free-text items to explore the effects of this programme on their careers. Quantitative analysis will compare scores at each time point, adjusted for baseline scores, for graduates who did and did not participate in the IPE programme. Associations between satisfaction data and discipline, professional setting, location and IPE participation will also be examined. Template analysis will explore free-text themes related to influences on career choices including participation in preregistration IPE. ETHICS AND DISSEMINATION: This study has received approval from the University of Otago Ethics Committee (D13/019). Results will be disseminated through peer-reviewed publications, conferences and stakeholder reports. Findings will inform future IPE developments and health workforce planning.


Asunto(s)
Selección de Profesión , Personal de Salud/educación , Relaciones Interprofesionales , Grupo de Atención al Paciente , Práctica Profesional , Actitud del Personal de Salud , Humanos , Estudios Longitudinales , Nueva Zelanda , Proyectos de Investigación , Encuestas y Cuestionarios
16.
Bipolar Disord ; 20(3): 260-274, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29345037

RESUMEN

OBJECTIVES: The current study examines prevalence of cognitive impairment in four mood disorder samples, using four definitions of impairment. The impact of premorbid IQ on prevalence was examined, and the influence of treatment response. METHODS: Samples were: (i) 58 inpatients in a current severe depressive episode (unipolar or bipolar), (ii) 69 unmedicated outpatients in a mild to moderate depressive episode (unipolar or bipolar), (iii) 56 outpatients with bipolar disorder, in a depressive episode, and (iv) 63 outpatients with bipolar disorder, currently euthymic. Cognitive assessment was conducted after treatment in Studies 1 (6 weeks of antidepressant treatment commenced on admission) and 2 (16-week course of cognitive behaviour therapy or schema therapy), allowing the impact of treatment response to be assessed. All mood disorder samples were compared with healthy control groups. RESULTS: The prevalence of cognitive impairment was highest for the inpatient depression sample (Study 1), and lowest for the outpatient depression sample (Study 2). Substantial variability in rates was observed depending on the definition of impairment used. Correcting cognitive performance for premorbid IQ had a significant impact on the prevalence of cognitive impairment in the inpatient depression sample. There was minimal evidence that treatment response impacted on prevalence of cognitive impairment, except in the domain of psychomotor speed in inpatients. CONCLUSIONS: As interventions aiming to improve cognitive outcomes in mood disorders receive increasing research focus, the issue of setting a cut-off level of cognitive impairment for screening purposes becomes a priority. This analysis demonstrates important differences in samples likely to be recruited depending on the definition of cognitive impairment and begins to examine the importance of premorbid IQ in determining who is impaired.

17.
Clin Teach ; 15(5): 413-418, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28949071

RESUMEN

BACKGROUND: This pilot study aimed to gain the perceptions of first-year students using a wiki as a learning tool for the Bachelor of Radiation Therapy degree in New Zealand. Literature suggests that wikis have great potential as an educational tool for both lecturers and students, because they encourage collaborative learning and resource sharing. In 2015, the 'Otago Wiki' platform was introduced as a part of the degree. METHODS: The first-year students were allocated into groups of four. Using the 'Otago Wiki' tool, each group created their own wiki page by addressing assigned tasks over the course of the year that related to a fictional patient. At the end of the year they were invited to participate in an online Survey Monkey™ questionnaire, which 15/26 students completed. We used a conventional approach to code the free-text responses for our content analysis. RESULTS: Three main themes emerged from the qualitative data: group work experience; developing a greater self-awareness of radiation therapy; and improving the learning experience. Although there is room for improvement, the quantitative data indicate that most students found the wiki to be a valuable group exercise, helping them to understand the patient experience. CONCLUSION: Overall, the students' perceptions of the wiki as a learning tool indicated that it was a worthwhile experience. Moving forward, wikis will continue to be used and incorporated into other modules in the first year. Setting clearer goals for each task would enable the students to use their time more efficiently in the future. Literature suggests that wikis have great potential as an educational tool for both lecturers and students.

18.
Neuroimage Clin ; 17: 24-30, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29021956

RESUMEN

OBJECTIVE: Investigate global and regional grey and white matter volumes in patients with Chronic Fatigue Syndrome (CFS) using magnetic resonance imaging (MRI) and recent voxel-based morphometry (VBM) methods. METHODS: Forty-two patients with CFS and thirty healthy volunteers were scanned on a 3-Tesla MRI scanner. Anatomical MRI scans were segmented, normalized and submitted to a VBM analysis using randomisation methods. Group differences were identified in overall segment volumes and voxel-wise in spatially normalized grey matter (GM) and white matter (WM) segments. RESULTS: Accounting for total intracranial volume, patients had larger GM volume and lower WM volume. The voxel-wise analysis showed increased GM volume in several structures including the amygdala and insula in the patient group. Reductions in WM volume in the patient group were seen primarily in the midbrain, pons and right temporal lobe. CONCLUSION: Elevated GM volume in CFS is seen in areas related to processing of interoceptive signals and stress. Reduced WM volume in the patient group partially supports earlier findings of WM abnormalities in regions of the midbrain and brainstem.


Asunto(s)
Síndrome de Fatiga Crónica/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto , Análisis de Varianza , Mapeo Encefálico , Trastornos del Conocimiento/diagnóstico por imagen , Trastornos del Conocimiento/etiología , Síndrome de Fatiga Crónica/complicaciones , Femenino , Humanos , Procesamiento de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis de Regresión , Índice de Severidad de la Enfermedad
19.
Hum Brain Mapp ; 39(3): 1118-1129, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29193464

RESUMEN

Dementia with Lewy bodies (DLB) is a common form of dementia and is characterized by cognitive fluctuations, visual hallucinations, and Parkinsonism. The phenotypic expression of the disease may, in part, relate to alterations in functional connectivity within and between brain networks. This resting-state study sought to clarify this in DLB, how networks differed from Alzheimer's disease (AD), and whether they were related to clinical symptoms in DLB. Resting-state networks were estimated using independent component analysis. We investigated functional connectivity changes in 31 DLB patients compared to 31 healthy controls and a disease comparator group of 29 AD patients using dual regression and FSLNets. Within-network connectivity was generally decreased in DLB compared to controls, mainly in motor, temporal, and frontal networks. Between-network connectivity was mainly intact; only the connection between a frontal and a temporal network showed increased connectivity in DLB. Differences between AD and DLB were subtle and we did not find any significant correlations with the severity of clinical symptoms in DLB. This study emphasizes the importance of reduced connectivity within motor, frontal, and temporal networks in DLB with relative sparing of the default mode network. The lack of significant correlations between connectivity measures and clinical scores indicates that the observed reduced connectivity within these networks might be related to the presence, but not to the severity of motor and cognitive impairment in DLB patients. Furthermore, our results suggest that AD and DLB may show more similarities than differences in patients with mild disease.

20.
PLoS One ; 12(10): e0186885, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29053742

RESUMEN

IMPORTANCE: Chronic fatigue syndrome (CFS) is characterised by a constellation of symptoms diagnosed with a number of different polythetic criteria. Heterogeneity across these diagnostic criteria is likely to be confounding research into the as-yet-unknown pathophysiology underlying this stigmatised and debilitating condition and may diagnose a disease spectrum with significant implications for clinical management. No studies to date have objectively investigated this possibility using a validated measure of CFS symptoms-the DePaul Symptom Questionnaire (DSQ). OBJECTIVE: To examine whether current CFS diagnostic criteria are identifying different disease phenotypes using the DSQ. DESIGN: Case control study. SETTING: Clinical Research Facility of the Royal Victoria Infirmary, Newcastle upon Tyne, UK. PARTICIPANTS: 49 CFS subjects and ten matched, sedentary community controls, excluded for co-morbid depression. MAIN OUTCOMES AND MEASURES: Self-reported autonomic and cognitive features were assessed with the Composite Autonomic Symptom Score (COMPASS) and Cognitive Failures Questionnaire (COGFAIL) respectively. Objective autonomic cardiovascular parameters were examined using the Task Force® Monitor and a battery of neuropsychological tests administered for objective cognitive assessment. RESULTS: Self-reported autonomic and cognitive symptoms were significantly greater in CFS subjects compared to controls. There were no statistically significant differences in objective autonomic measures between CFS and controls. There were clinically significant differences between DSQ subgroups on objective autonomic testing. Visuospatial memory, verbal memory and psychomotor speed were significantly different between DSQ subgroups. CONCLUSIONS AND RELEVANCE: The finding of no significant differences in objective autonomic testing between CFS and control subjects may reflect the inclusion of sedentary controls or exclusion for co-morbid depression. Consistent exclusion criteria would enable better delineation of these two conditions and their presenting symptoms. Findings across CFS subgroups suggest subjects have a different disease burden on subjective and objective measures of function, autonomic parameters and cognitive impairment when categorised using the DSQ. Different CFS criteria may at best be diagnosing a spectrum of disease severities and at worst different CFS phenotypes or even different diseases. This complicates research and disease management and may contribute to the significant stigma associated with the condition.


Asunto(s)
Síndrome de Fatiga Crónica/diagnóstico , Fenotipo , Adulto , Anciano , Estudios de Casos y Controles , Síndrome de Fatiga Crónica/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
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