Why do patients with Parkinson's disease fall? A cross-sectional analysis of possible causes of falls.

Background: Falls in Parkinson’s disease (PD) are associated with significant injury, disability, hospitalization, and reduced quality of life. Aims: To identify modifiable medical causes of falls in a cohort of PD patients. Methods: Eighty seven PD patients were interviewed and examined using validated scales assessing motor and nonmotor aspects of PD, comorbidities and medication use. The frequency of falls in the last month was the primary outcome measure. Falls were hypothesized to be associated with increasing age, advanced motor severity, particularly axial features (e.g., freezing and postural instability), and dyskinesia. Nonmotor features hypothesized to be associated with falls included; cognitive impairment, psychosis, sleep disorders, cardiovascular dysfunction, and ophthalmological and medical comorbidities. Results: Fallers had longer disease duration, higher Levodopa-equivalent doses, greater ‘On’ time with dyskinesia (all P<0.005), and higher scores on some Movement Disorder Society-Unified Parkinson’s Disease Rating Scale items, particularly axial scores. However, patients with falls did not differ from non-fallers in age or overall motor UPDRS scores. Severity of psychosis, executive cognitive impairment, autonomic (particularly cardiovascular) dysfunction and sleep disturbances (particularly REM sleep behavioral disorder) were significantly associated with falls (all P<0.005). Fallers more frequently reported use of antidepressants (both tricyclics and SSRIs) and neuroleptics (P<0.001), but not hypnotics. There was no difference in medical comorbidities, ophthalmological assessments, fatigue, and apathy scores between the groups. In logistic regression analysis, cardiovascular dysfunction, antidepressant use, and REM sleep behavioral disorder were significantly associated with falls. Conclusions: The causes of falls in PD are multifactorial and extend beyond motor impairment and dyskinesia; addressing these in patients already treated with dopaminergic medications has the potential to improve this important complication of PD

Non-motor and neuropsychiatric features of Parkinson's disease

This thesis focuses on non-motor symptoms (NMS) of Parkinson’s disease (PD), particularly the neuropsychiatric symptoms of visual hallucinations, apathy and impulse control disorders. A clinical cohort study and pathology study were performed. PD patients (N=94) were recruited and each underwent neurological examination for motor aspects of the disease, detailed multi-domain cognitive assessment including executive and visuoperceptive function, and a battery of validated non-motor assessments for symptoms including mood, apathy, sleep, fatigue, psychosis, autonomic function, disability and health-related quality of life (QOL). A subgroup (N=50) also had detailed ophthalmological examination. In the autopsy study, the presence of ante-mortem visual hallucinations (VH) in PD donors was correlated with Lewy body (LB) density and distribution at different cortical locations. The clinical study examined the impact of NMS on QOL and found that NMS, particularly depression, had stronger association with QOL than motor scores, but despite this NMS were often under-reported by their treating neurologist. A significant proportion of pathologically confirmed PD patients presented exclusively with NMS and this led to misdiagnosis and, in some cases, inappropriate investigations and treatment. An aetiological model of VH was proposed and examined; factors investigated included dopaminergic medication, higher cortical function, sleep and ophthalmic pathology. Clinical associations of VH were rapid eye movement sleep behaviour disorder, autonomic function, and executive and visuoperceptive cortical function. There was however no clear association with co-existing ophthalmic pathology. In the post-mortem analysis, LB involvement at corresponding cortical areas was confirmed, including frontal (executive) and temporal and trans-entorhinal (visuoperception) cortices. A meta-analysis of studies reporting pathological gambling was performed and an association with dopaminergic medication, particularly dopamine agonist therapy, and co-existing psychopathology was confirmed

Glycoprotein IIb/IIIa Inhibitors Use and Outcome after Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction

Aims. We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors on long-term outcomes following percutaneous coronary intervention (PCI) after non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that these agents are associated with improved short-term outcomes. However, many trials were undertaken before the routine use of P2Y12 inhibitors. Recent studies yield conflicting results and registry data have suggested that GP IIb/IIIa inhibitors may cause more bleeding than what trials indicate. Methods and Results. This retrospective observational study involves 3047 patients receiving dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all-cause mortality. Major adverse cardiac events (MACE) were a secondary outcome. Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes, multivariate analysis (including propensity scoring) showed no benefit for either survival (P=0.136) or MACE (P=0.614). GP IIb/IIIa inhibitor use was associated with an increased risk of major bleeding (P=0.021). Conclusion. Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk. After multivariate adjustment we observed no improvement in MACE or survival and an increased risk of major bleeding

Beta cell lipotoxicity in the development of type 2 diabetes:the need for species-specific understanding

The propensity to develop type 2 diabetes (T2D) is known to have both environmental and hereditary components. In those with a genetic predisposition to T2D, it is widely believed that elevated concentrations of circulatory long-chain fatty acids (LC-FFA) significantly contribute towards the demise of insulin-producing pancreatic β-cells - the fundamental feature of the development of T2D. Over 25 years of research support that LC-FFA are deleterious to β-cells, through a process termed lipotoxicity. However, the work underpinning the theory of β-cell lipotoxicity is mostly based on rodent studies. Doubts have been raised as to whether lipotoxicity also occurs in humans. In this review, we examine the evidence, both in vivo and in vitro, for the pathogenic effects of LC-FFA on β-cell viability and function in humans, highlighting key species differences. In this way, we aim to uncover the role of lipotoxicity in the human pathogenesis of T2D and motivate the need for species-specific understanding.</p

Structural Parameters of Seven SMC Intermediate-Age and Old Star Clusters

We present structural parameters for the seven intermediate-age and old star clusters NGC121, Lindsay 1, Kron 3, NGC339, NGC416, Lindsay 38, and NGC419 in the Small Magellanic Cloud. We fit King profiles and Elson, Fall, and Freeman profiles to both surface-brightness and star count data taken with the Advanced Camera for Surveys aboard the Hubble Space Telescope. Clusters older than 1 Gyr show a spread in cluster core radii that increases with age, while the youngest clusters have relatively compact cores. No evidence for post core collapse clusters was found. We find no correlation between core radius and distance from the SMC center, although consistent with other studies of dwarf galaxies, some relatively old and massive clusters have low densities. The oldest SMC star cluster, the only globular NGC121, is the most elliptical object of the studied clusters. No correlation is seen between ellipticity and distance from the SMC center. The structures of these massive intermediate-age (1-8 Gyr) SMC star clusters thus appear to primarily result from internal evolutionary processes.Comment: 16 pages, 13 figure

Asymptotic diophantine approximation:the multiplicative case

Let $\alpha$ and $\beta$ be irrational real numbers and 0<\F<1/30. We prove a precise estimate for the number of positive integers $q\leq Q$ that satisfy \|q\alpha\|\cdot\|q\beta\|<\F. If we choose \F as a function of $Q$ we get asymptotics as $Q$ gets large, provided \F Q grows quickly enough in terms of the (multiplicative) Diophantine type of $(\alpha,\beta)$, e.g., if $(\alpha,\beta)$ is a counterexample to Littlewood's conjecture then we only need that \F Q tends to infinity. Our result yields a new upper bound on sums of reciprocals of products of fractional parts, and sheds some light on a recent question of L\^{e} and Vaaler.Comment: To appear in Ramanujan Journa

The merger history, AGN and dwarf galaxies of Hickson Compact Group 59

Compact group galaxies often appear unaffected by their unusually dense environment. Closer examination can, however, reveal the subtle, cumulative effects of multiple galaxy interactions. Hickson Compact Group (HCG) 59 is an excellent example of this situation. We present a photometric study of this group in the optical (HST), infrared (Spitzer) and X-ray (Chandra) regimes aimed at characterizing the star formation and nuclear activity in its constituent galaxies and intra-group medium. We associate five dwarf galaxies with the group and update the velocity dispersion, leading to an increase in the dynamical mass of the group of up to a factor of 10 (to 2.8e13 Msun), and a subsequent revision of its evolutionary stage. Star formation is proceeding at a level consistent with the morphological types of the four main galaxies, of which two are star-forming and the other two quiescent. Unlike in some other compact groups, star-forming complexes across HCG 59 closely follow mass-radius scaling relations typical of nearby galaxies. In contrast, the ancient globular cluster populations in galaxies HCG 59A and B show intriguing irregularities, and two extragalactic HII regions are found just west of B. We age-date a faint stellar stream in the intra-group medium at ~1 Gyr to examine recent interactions. We detect a likely low-luminosity AGN in HCG 59A by its ~10e40 erg/s X-ray emission; the active nucleus rather than star formation can account for the UV+IR SED. We discuss the implications of our findings in the context of galaxy evolution in dense environments.Comment: 38 pages, 17 figures. Please visit "http://tinyurl.com/isk-hcg59" for a full-resolution PDF. Accepted for publication in the Astrophysical Journa