tbuckley/cabot-search huggingface dataset:
Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation
Authors: Aoife P. Kiely, Helen Ling, Yasmine T. Asi, Eleanna Kara, Christos Proukakis, Anthony H. Schapira, Huw R. Morris, Helen C. Roberts, Steven Lubbe, Patricia Limousin, Patrick A. Lewis, Andrew J. Lees, Niall Quinn, John Hardy, Seth Love, Tamas Revesz, Henry Houlden, Janice L. Holton
Journal: Molecular Neurodegeneration (2015)

We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson’s disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case. All three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural hypotension and transiently levodopa responsive parkinsonism. Detailed post-mortem neuropathological analysis was performed in all cases. All three G51D cases had abundant α-synuclein pathology with characteristics of both PD and MSA. These included widespread cortical and subcortical neuronal α-synuclein inclusions together with small numbers of inclusions resembling glial cytoplasmic inclusions (GCIs) in oligodendrocytes. In contrast the H50Q and SNCA duplication cases, had α-synuclein pathology resembling idiopathic PD without GCIs. Phosphorylated α-synuclein was present in all inclusions types in G51D cases but was more restricted in SNCA duplication and H50Q mutation. Inclusions were also immunoreactive for the 5G4 antibody indicating their highly aggregated and likely fibrillar state. Our characterisation of the clinical and neuropathological features of the present small series of G51D SNCA mutation cases should aid the recognition of this clinico-pathological entity. The neuropathological features of these cases consistently share characteristics of PD and MSA and are distinct from PD patients carrying the H50Q or SNCA duplication.
Infective endocarditis, rheumatoid factor, and anticardiolipin antibodies.
Authors: R A Asherson, M Tikly, H Staub, P T Wilmshurst, D J Coltart, M Khamashta, G R Hughes
Journal: Annals of the Rheumatic Diseases (1990)

Serum samples from 22 patients with infective endocarditis were analysed for the presence of antibodies to cardiolipin, false positive Venereal Disease Research Laboratory (VDRL) test, and rheumatoid factor in order to determine the prevalence of anticardiolipin antibodies, their level, and to ascertain whether there was any correlation with the presence of rheumatoid factor. Although the latex test was positive in 10/22 (45%) patients, anticardiolipin antibodies, usually of a low level, were raised in only four (18%), and the VDRL test was positive in two patients in whom other antibodies were negative. These results show a clear discordance between these three tests, indicating that B cell production of these antibodies is separate and distinct. As with other infections which result in anticardiolipin antibody production, no thrombotic events were encountered.
UNDERGRADUATE PSYCHIATRIC EDUCATION AS REFLECTED IN FINAL EXAMINATIONS
Authors: CHARLES WATKINS, EDWARD KNIGHT
Journal: American Journal of Psychiatry (1959)

Only general suppositions can emerge from a survey of this sort with regard to content of the examinations. These are: There is a definite trend in the direction of teaching human behavior as a basic science. It seems to be implemented by the use of clinical material rather than basic psychological, cultural and neurophysiological data. Human behavior as a basic science is often approached by simply teaching the standardized conventional psychoanalytic theory of personality development, without adequately relating this approach to cultural and biological factors. There is some hint of a peculiar dilemma facing psychiatric educators. Clinical psychoanalytic material was used to outline basic science phenomena. In clinical handling of patients these same principles could not be directly applied with ease, thus the handling of patients was by the usual pragmatic psychiatric methods. It is probable that this occurs because intensive psychotherapy is not usually possible during medical training. Therefore basic psychoanalytic science was not really integrated with clinical practice even though clinical analytic material was used in first two years.
Functional variants of OCTN cation transporter genes are associated with Crohn disease
Authors: Vanya D Peltekova, Richard F Wintle, Laurence A Rubin, Christopher I Amos, Qiqing Huang, Xiangjun Gu, Bill Newman, Mark Van Oene, David Cescon, Gordon Greenberg, Anne M Griffiths, Peter H St George-Hyslop, Katherine A Siminovitch
Journal: Nature Genetics (2004)
Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study
Authors: Stephanie JB Vos, Chengjie Xiong, Pieter Jelle Visser, Mateusz S Jasielec, Jason Hassenstab, Elizabeth A Grant, Nigel J Cairns, John C Morris, David M Holtzman, Anne M Fagan
Journal: The Lancet Neurology (2013)
Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: A 12-month randomized, prospective, open- label trial
Authors: Dawn M. Torres, Frances J. Jones, Janet C. Shaw, Christopher D. Williams, John A. Ward, Stephen A. Harrison
Journal: Hepatology (2011)

Medication combinations that improve the efficacy of thiazolidinediones or ameliorate weight-gain side effects of therapy represent an attractive potential treatment for (NASH). The aim of this randomized, open-label trial was to assess the efficacy of rosiglitazone and metformin in combination versus rosiglitazone and losartan, compared to rosiglitazone alone, after 48 weeks of therapy. A total of 137 subjects with biopsy-proven NASH were enrolled and randomly assigned to receive either 4 mg twice-daily of rosiglitazone, 4 mg of rosiglitazone and 500 mg of metformin twice-daily, or 4 mg of rosiglitazone twice-daily and 50 mg of losartan once-daily for 48 weeks. Patients were screened for other etiologies of chronic liver disease, including daily alcohol intake in excess of 20 g. Repeat liver biopsy was performed after 48 weeks of therapy and reviewed in a blinded fashion by a single expert hepatopathologist. The primary aim of the study was to assess for differences between treatment groups in the improvement of steatosis, hepatocellular inflammation, and fibrosis. In total, 108 subjects completed the trial. Primary outcome revealed no significant difference between treatment groups in all histologic parameters (steatosis, P = 0.137; hepatocellular inflammation, P = 0.320; fibrosis, P = 0.229). Overall improvement in steatosis, hepatocellular inflammation, ballooning degeneration, and fibrosis was observed ( P ≤ 0.001). Serum aminotransferases were reduced in all three groups ( P &lt; 0.001 within treatment, P &gt; 0.05 between groups). Metformin did not significantly mitigate weight gain ( P = 0.051). Conclusions: Forty-eight weeks of combination therapy with rosiglitazone and metformin or rosiglitazone and losartan confers no greater benefit than rosiglitazone alone with respect to histopathology. (Hepatology 2011;)
Cancer treatment and survivorship statistics, 2012
Authors: Rebecca Siegel, Carol DeSantis, Katherine Virgo, Kevin Stein, Angela Mariotto, Tenbroeck Smith, Dexter Cooper, Ted Gansler, Catherine Lerro, Stacey Fedewa, Chunchieh Lin, Corinne Leach, Rachel Spillers Cannady, Hyunsoon Cho, Steve Scoppa, Mark Hachey, Rebecca Kirch, Ahmedin Jemal, Elizabeth Ward
Journal: CA A Cancer Journal for Clinicians (2012)

Although there has been considerable progress in reducing cancer incidence in the United States, the number of cancer survivors continues to increase due to the aging and growth of the population and improvements in survival rates. As a result, it is increasingly important to understand the unique medical and psychosocial needs of survivors and be aware of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. To highlight the challenges and opportunities to serve these survivors, the American Cancer Society and the National Cancer Institute estimated the prevalence of cancer survivors on January 1, 2012 and January 1, 2022, by cancer site. Data from Surveillance, Epidemiology, and End Results (SEER) registries were used to describe median age and stage at diagnosis and survival; data from the National Cancer Data Base and the SEER-Medicare Database were used to describe patterns of cancer treatment. An estimated 13.7 million Americans with a history of cancer were alive on January 1, 2012, and by January 1, 2022, that number will increase to nearly 18 million. The 3 most prevalent cancers among males are prostate (43%), colorectal (9%), and melanoma of the skin (7%), and those among females are breast (41%), uterine corpus (8%), and colorectal (8%). This article summarizes common cancer treatments, survival rates, and posttreatment concerns and introduces the new National Cancer Survivorship Resource Center, which has engaged more than 100 volunteer survivorship experts nationwide to develop tools for cancer survivors, caregivers, health care professionals, advocates, and policy makers.
Vehicle exhaust exposure in an incident case-control study of adult asthma
Authors: L. Modig, B. Järvholm, E. Rönnmark, L. Nyström, B. Lundbäck, C. Andersson, B. Forsberg
Journal: European Respiratory Journal (2006)

The objective of this case-control study was to evaluate whether traffic-related air pollution exposure at home increases the risk of asthma in adults and to compare two commonly used exposure variables and differences between urban and rural living. Incident cases of asthma and matched controls of subjects aged 20-60 yrs were recruited in Luleå, Sweden. In total 203 cases and 203 controls were enrolled in the study. Exposure was estimated by traffic flow and measured levels of outdoor nitrogen dioxide (NO2) in the surrounding environment of each home, respectively. The relationship between measured levels of NO2 and traffic flow was studied using linear regression. The results indicated a nonsignificant tendency between living in a home close to a high traffic flow and an increased risk of asthma. The association between asthma and measured NO2 was weak and not significant, but the skin-prick test result acted as an effect modifier with a borderline significant association among positives. The correlation between traffic flow and outdoor NO2 was low. The results suggest that living close to high traffic flows might increase the asthma incidence in adults, while the tendency for nitrogen dioxide was only seen among atopics. Traffic flow and nitrogen dioxide had a lower than expected correlation.
Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal
Authors: Margaret G. Distler, Leigh D. Plant, Greta Sokoloff, Andrew J. Hawk, Ivy Aneas, Gerald E. Wuenschell, John Termini, Stephen C. Meredith, Marcelo A. Nobrega, Abraham A. Palmer
Journal: Journal of Clinical Investigation (2012)

Glyoxalase 1 (Glo1) expression has previously been associated with anxiety in mice; however, its role in anxiety is controversial, and the underlying mechanism is unknown. Here, we demonstrate that GLO1 increases anxiety by reducing levels of methylglyoxal (MG), a GABAA receptor agonist. Mice overexpressing Glo1 on a Tg bacterial artificial chromosome displayed increased anxiety-like behavior and reduced brain MG concentrations. Treatment with low doses of MG reduced anxiety-like behavior, while higher doses caused locomotor depression, ataxia, and hypothermia, which are characteristic effects of GABAA receptor activation. Consistent with these data, we found that physiological concentrations of MG selectively activated GABAA receptors in primary neurons. These data indicate that GLO1 increases anxiety by reducing levels of MG, thereby decreasing GABAA receptor activation. More broadly, our findings potentially link metabolic state, neuronal inhibitory tone, and behavior. Finally, we demonstrated that pharmacological inhibition of GLO1 reduced anxiety, suggesting that GLO1 is a possible target for the treatment of anxiety disorders.
A serum microRNA classifier for early detection of hepatocellular carcinoma: a multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study
Authors: Xue-Jia Lin, Yutian Chong, Zhi-Wei Guo, Chen Xie, Xiao-Jing Yang, Qi Zhang, Sheng-Ping Li, Yujuan Xiong, Yunfei Yuan, Jun Min, Wei-Hua Jia, Yusheng Jie, Min-Shan Chen, Mei-Xian Chen, Jian-Hong Fang, Chunxian Zeng, Yaojun Zhang, Rong-Ping Guo, Yuankai Wu, Guoli Lin, Limin Zheng, Shi-Mei Zhuang
Journal: The Lancet Oncology (2015)
Metaphor muddles in communication theory
Authors: Drew Rendall, Paul Vasey
Journal: Behavioral and Brain Sciences (2002)

Shanker &amp; King (S&amp;K) argue that information-theoretic approaches to communication are too rigid to capture the ebb and flow of communicative interactions. They advocate instead a dynamic systems approach based on the metaphor of dance. We focus on two problems arising from the dance metaphor: first, that its inherently cooperative tone contradicts basic tenets of behavioral biology; and second, that it risks obscuring rather than clarifying the details of communicative interactions.
Use of letrozole in assisted reproduction: a systematic review and meta-analysis
Authors: A. Requena, J. Herrero, J. Landeras, E. Navarro, J. L. Neyro, C. Salvador, R. Tur, J. Callejo, M. A. Checa, M. Farre, J. J. Espinos, F. Fabregues, M. Grana-Barcia
Journal: Human Reproduction Update (2008)

Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis.A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled.Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66-2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73-2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70-2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78-1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67-2.91).Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.
Medical treatment for benign prostatic hyperplasia.
Authors: C. Chapple
Journal: BMJ (1992)

Advisory Committee's latest report shows that more career registrar posts have already been approved5 than were envis- aged in the "do nothing" projections in Achieving a Balance.Preferentially increasing the staff grade while delaying or curtailing the expansion of consultant numbers will appeal to hard pressed managers seeking to provide adequate services with inadequate budgets.Indeed there may still be, as Dowie contends, "a substantial reservoir" of people qualified and willing to undertake such posts.Most junior doctors, how- ever, undoubtedly still want to train as consultants.Many of the report's recommendations should receive the wholehearted support of all doctors.They include the setting up of more preregistration posts in general practice, further research into the workloads of individual specialties, skill substitution, the costing of the use of hospital doctors' time, and better statistical support for planning medical manpower.We should not be content, however, to support a system in which many career grade hospital staff never achieve the status of fully trained specialists.What is needed is a fundamental reappraisal of where services are delivered and by whom.This is particularly pertinent at present, given that we face a growing elderly population, a fall in the number of applicants for medical school, and the possibility of a pan-European shortfall of medical staff within the next 15 years.6Perhaps the time has come to blow the dust off the Short report7 at last.
ApoE4 induces Aβ42, tau, and neuronal pathology in the hippocampus of young targeted replacement apoE4 mice
Authors: Ori Liraz, Anat Boehm-Cagan, Daniel M Michaelson
Journal: Molecular Neurodegeneration (2013)

Abstract Background Recent findings suggest that the pathological effects of apoE4, the most prevalent genetic risk factor for Alzheimer’s disease (AD), start many years before the onset of the disease and are already detectable at a young age. In the present study we investigated the extent to which such pathological and cognitive impairments also occur in young apoE4 mice. Results This study revealed that the levels of the presynaptic glutamatergic vesicular transporter, VGlut, in the CA3, CA1, and DG hippocampal subfields were lower in hippocampal neurons of young (4-month-old) apoE4-targeted replacement mice than in those of the apoE3 mice. In contrast, the corresponding inhibitory GABAergic nerve terminals and perikarya were not affected by apoE4. This synaptic effect was associated with hyperphosphorylation of tau in these neurons. In addition, apoE4 increased the accumulation of neuronal Aβ42 and induced mitochondrial changes, both of which were specifically pronounced in CA3 neurons. Spatial navigation behavioral studies revealed that these hippocampal pathological effects of apoE4 are associated with corresponding behavioral impairments. Time-course studies revealed that the effects of apoE4 on tau hyperphosphorylation and the mitochondria were already apparent at the age of 1 month and that the apoE4-driven accumulation of neuronal Aβ and reduced VGlut levels evolve later and are apparent at the age of 2–4 months. Furthermore, the levels of tau phosphorylation decrease in apoE3 mice and increase in apoE4 mice between 1 and 4 months, whereas the levels of Aβ42 decrease in apoE3 mice and are not affected in apoE4 mice over the same time period. Conclusions These findings show that apoE4 stimulates the accumulation of Aβ42 and hyperphosphorylated tau and reduces the levels of VGlut in hippocampal neurons of young apoE4-targeted replacement mice and that these neurochemical effects are associated with cognitive impairments. This model is not associated with hypothesis-driven mechanistic manipulations and is thus most suitable for unbiased studies of the mechanisms underlying the pathological effects of apoE4.
Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial
Authors: EWFW Alton, M Stern, R Farley, A Jaffe, SL Chadwick, J Phillips, J Davies, SN Smith, J Browning, MG Davies, ME Hodson, SR Durham, D Li, PK Jeffery, M Scallan, R Balfour, SJ Eastman, SH Cheng, AE Smith, D Meeker, DM Geddes
Journal: The Lancet (1999)
Complexity science: Coping with complexity: educating for capability
Authors: S. W Fraser, T. Greenhalgh
Journal: BMJ (2001)

This is the last in a series of four articles 

Recent high profile scandals in the United Kingdom have highlighted the changing values by which the National Health Service is judged.1 The public expects, and the government has promised to deliver, a health service that is ever safer, constantly up to date, and focused on patients' changing needs. Successful health services in the 21st century must aim not merely for change, improvement, and response, but for changeability, improvability, and responsiveness.

Educators are therefore challenged to enable not just competence, but also capability (box). Capability ensures that the delivery of health care keeps up with its ever changing context. Education providers must offer an environment and process that enables individuals to develop sustainable abilities appropriate for a continuously evolving organisation. Recent announcements in the United Kingdom of a “university for the NHS,”2 a “national leadership programme,”3 and “workforce confederations”4 raise the question of what kind of education and training will help the NHS to deliver its goals

#### Capability is more than competence

Competence —what individuals know or are able to do in terms of knowledge, skills, attitude

Capability —extent to which individuals can adapt to change, generate new knowledge, and continue to improve their performance

#### Summary points

Traditional education and training largely focuses on enhancing competence (knowledge, skills, and attitudes)

In today's complex world, we must educate not merely for competence, but for capability (the ability to adapt to change, generate new knowledge, and continuously improve performance)

Capability is enhanced through feedback on performance, the challenge of unfamiliar contexts, and the use of non-linear methods such as story telling and small group, problem based learning

Education for capability must focus on process (supporting learners to construct their own learning goals, receive feedback, reflect, and consolidate) and avoid goals with rigid and prescriptive content

The …
Communication of end-of-life decisions in European intensive care units
Authors: Simon Cohen, Charles Sprung, Peter Sjokvist, Anne Lippert, Bara Ricou, Mario Baras, Seppo Hovilehto, Paulo Maia, Dermot Phelan, Konrad Reinhart, Karl Werdan, Hans-Henrik Bulow, Tom Woodcock
Journal: Intensive Care Medicine (2005)