Dystonia and Parkinson's disease: What is the relationship?

Dystonia and Parkinson's disease are closely linked disorders sharing many pathophysiological overlaps. Dystonia can be seen in 30% or more of the patients suffering with PD and sometimes can precede the overt parkinsonism. The response of early dystonia to the introduction of dopamine replacement therapy (levodopa, dopamine agonists) is variable; dystonia commonly occurs in PD patients following levodopa initiation. Similarly, parkinsonism is commonly seen in patients with mutations in various DYT genes including those involved in the dopamine synthesis pathway. Pharmacological blockade of dopamine receptors can cause both tardive dystonia and parkinsonism and these movement disorders syndromes can occur in many other neurodegenerative, genetic, toxic and metabolic diseases. Pallidotomy in the past and currently deep brain stimulation largely involving the GPi are effective treatment options for both dystonia and parkinsonism. However, the physiological mechanisms underlying the response of these two different movement disorder syndromes are poorly understood. Interestingly, DBS for PD can cause dystonia such as blepharospasm and bilateral pallidal DBS for dystonia can result in features of parkinsonism. Advances in our understanding of these responses may provide better explanations for the relationship between dystonia and Parkinson's disease

Fluid dynamics of droplet generation from corneal tear film during non-contact tonometry in the context of pathogen transmission

Noninvasive ocular diagnostics demonstrate a propensity for droplet generation and present a potential pathway of distribution for pathogens such as the severe acute respiratory syndrome coronavirus 2. High-speed images of the eye subjected to air puff tonometry (glaucoma detection) reveal three-dimensional, spatiotemporal interaction between the puff and tear film. The interaction finally leads to the rupture and breakup of the tear film culminating into sub-millimeter sized droplet projectiles traveling at speeds of 0.2 m/s. The calculated droplet spread radius ( ∼ 0.5 m) confirms the likelihood of the procedure to generate droplets that may disperse in air as well as splash on instruments, raising the potential of infection. We provide a detailed physical exposition of the entire procedure using high fidelity experiments and theoretical modeling. We conclude that air puff induced corneal deformation and subsequent capillary waves lead to flow instabilities (Rayleigh-Taylor, Rayleigh-Plateau) that lead to tear film ejection, expansion, stretching, and subsequent droplet formation

Hepatolithiasis with biliary ascariasis – a case report

BACKGROUND: Biliary ascariasis is regarded as possible etiological factor for hepatolithiasis. Here we report one case of a patient with hepatolithiasis with biliary ascariasis who developed a liver abscess, which was treated with partial hepatectomy. CASE PRESENTATION: A young adult female presented with epigastric pain and vomiting with repeated attacks of cholangitis. ERCP showed evidence of multiple intrahepatic calculi with the development of abscess in the left lobe of liver. The patient underwent partial hepatectomy and was found to have biliary ascariasis on histology. She was treated with antihelmenthic therapy and has had an uneventful postoperative period of 2 years. CONCLUSION: Biliary ascariasis with hepatolithiasis, although rare, should be considered in endemic countries

Risk assessment and suicide by patients with schizophrenia in secondary mental healthcare: a case-control study

Objectives: To investigate the role of risk assessment in predicting suicide in patients with schizophrenia spectrum disorders (SSDs) receiving secondary mental healthcare. We postulated that risk assessment plays a limited role in predicting suicide in these patients. Design: Retrospective case–control study. Setting: Anonymised electronic mental health record data from the South London and Maudsley National Health Service (NHS) Foundation Trust (SLaM) (London, UK) linked with national mortality data. Participants: In 242 227 SLaM service users up to 31 December 2013, 635 suicides were identified. 96 (15.1%) had a SSD diagnosis. Those who died before 1 January 2007 (n=25) were removed from the analyses. Thus, 71 participants with SSD who died from suicide over the study period (cases) were compared with 355 controls. Main outcome measure: Risk of suicide in relation to risk assessment ratings. Results: Cases were younger at first contact with services (mean±SD 34.5±12.6 vs 39.2±15.2) and with a higher preponderance of males (OR=2.07, 95% CI 1.18 to 3.65, p=0.01) than controls. Also, suicide occurred within 10 days after last contact with services in half of cases, with the most common suicide methods being hanging (14) and jumping (13). Cases were more likely to have the following ‘risk assessment’ items previously recorded: suicidal history (OR=4.42, 95% CI 2.01 to 9.65, p<0.001), use of violent method (OR=3.37, 95% CI 1.47 to 7.74, p=0.01), suicidal ideation (OR=3.57, 95% CI 1.40 to 9.07, p=0.01) and recent hospital discharge (OR=2.71, 95% CI 1.17 to 6.28, p=0.04). Multiple regression models predicted only 21.5% of the suicide outcome variance. Conclusions: Predicting suicide in schizophrenia is highly challenging due to the high prevalence of risk factors within this diagnostic group irrespective of outcome, including suicide. Nevertheless, older age at first contact with mental health services and lack of suicidal history and suicidal ideation are useful protective markers indicative of those less likely to end their own lives

LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11

In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin. When LHX2 is absent, active histone marks at the Fezf2 and Sox11 loci are increased. Loss of LHX2 produces an increase, and overexpression of LHX2 causes a decrease, in layer 5 Fezf2 and CTIP2-expressing neurons. Our results provide mechanistic insight into how LHX2 acts as a necessary and sufficient regulator of genes that control cortical neuronal subtype identity

Clinical Rounds With Nutrition Support Services

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68406/2/10.1177_011542659400900273.pd

Functional similarities between pigeon \u27milk\u27 and mammalian milk : induction of immune gene expression and modification of the microbiota

Pigeon &lsquo;milk&rsquo; and mammalian milk have functional similarities in terms of nutritional benefit and delivery of immunoglobulins to the young. Mammalian milk has been clearly shown to aid in the development of the immune system and microbiota of the young, but similar effects have not yet been attributed to pigeon &lsquo;milk&rsquo;. Therefore, using a chicken model, we investigated the effect of pigeon &lsquo;milk&rsquo; on immune gene expression in the Gut Associated Lymphoid Tissue (GALT) and on the composition of the caecal microbiota. Chickens fed pigeon &lsquo;milk&rsquo; had a faster rate of growth and a better feed conversion ratio than control chickens. There was significantly enhanced expression of immune-related gene pathways and interferon-stimulated genes in the GALT of pigeon &lsquo;milk&rsquo;-fed chickens. These pathways include the innate immune response, regulation of cytokine production and regulation of B cell activation and proliferation. The caecal microbiota of pigeon &lsquo;milk&rsquo;-fed chickens was significantly more diverse than control chickens, and appears to be affected by prebiotics in pigeon &lsquo;milk&rsquo;, as well as being directly seeded by bacteria present in pigeon &lsquo;milk&rsquo;. Our results demonstrate that pigeon &lsquo;milk&rsquo; has further modes of action which make it functionally similar to mammalian milk. We hypothesise that pigeon &lsquo;lactation&rsquo; and mammalian lactation evolved independently but resulted in similarly functional products

Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus

Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical changes that distinguish between the different stages of disease. Our aim is to understand these changes through Raman mapping studies. Raman spectral mapping was used to analyse 20-μm sections of tissue from 29 snap-frozen oesophageal biopsies. Contiguous haematoxylin and eosin sections were reviewed by a consultant pathologist. Principal component analysis was used to identify the major differences between the spectra across each map. Pseudocolour score maps were generated and the peaks of corresponding loads identified enabling visualisation of the biochemical changes associated with malignancy. Changes were noted in the distribution of DNA, glycogen, lipids and proteins. The mean spectra obtained from selected regions demonstrate increased levels of glycogen in the squamous area compared with increased DNA levels in the abnormal region. Raman spectroscopy is a highly sensitive and specific technique for demonstration of biochemical changes in the carcinogenesis of Barrett's oesophagus. There is potential for in vivo application for real-time endoscopic optical diagnosis

Health and Oral Health Care Needs and Health Care-Seeking Behavior Among Homeless Injection Drug Users in San Francisco

Few existing studies have examined health and oral health needs and treatment-seeking behavior among the homeless and injection drug users (IDUs). This paper describes the prevalence and correlates of health and oral health care needs and treatment-seeking behaviors in homeless IDUs recruited in San Francisco, California, from 2003 to 2005 (N = 340). We examined sociodemographic characteristics, drug use patterns, HIV status via oral fluid testing, physical health using the Short Form 12 Physical Component Score, self-reported needs for physical and oral health care, and the self-reported frequency of seeking medical and oral health care. The sample had a lower health status as compared to the general population and reported a frequent need for physical and oral health care. In bivariate analysis, being in methadone treatment was associated with care-seeking behavior. In addition, being enrolled in Medi-Cal, California’s state Medicaid program, was associated with greater odds of seeking physical and oral health care. Methamphetamine use was not associated with higher odds of needing oral health care as compared to people who reported using other illicit drugs. Homeless IDUs in San Francisco have a large burden of unmet health and oral health needs. Recent cuts in Medi-Cal’s adult dental coverage may result in a greater burden of oral health care which will need to be provided by emergency departments and neighborhood dental clinics