Speech-based characterization of dopamine replacement therapy in people with Parkinson's disease.

People with Parkinson's (PWP) disease are under constant tension with respect to their dopamine replacement therapy (DRT) regimen. Waiting too long between doses results in more prominent symptoms, loss of motor function, and greater risk of falling per step. Shortened pill cycles can lead to accelerated habituation and faster development of disabling dyskinesias. The Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the gold standard for monitoring Parkinson's disease progression but requires a neurologist to administer and therefore is not an ideal instrument to continuously evaluate short-term disease fluctuations. We investigated the feasibility of using speech to detect changes in medication states, based on expectations of subtle changes in voice and content related to dopaminergic levels. We calculated acoustic and prosodic features for three speech tasks (picture description, reverse counting, and diadochokinetic rate) for 25 PWP, each evaluated "ON" and "OFF" DRT. Additionally, we generated semantic features for the picture description task. Classification of ON/OFF medication states using features generated from picture description, reverse counting and diadochokinetic rate tasks resulted in cross-validated accuracy rates of 0.89, 0.84, and 0.60, respectively. The most discriminating task was picture description which provided evidence that participants are more likely to use action words in ON than in OFF state. We also found that speech tempo was modified by DRT. Our results suggest that automatic speech assessment can capture changes associated with the DRT cycle. Given the ease of acquiring speech data, this method shows promise to remotely monitor DRT effects.

Prevalence and characteristics of e-cigarette users among Malaysian current and ex-smokers.

INTRODUCTION: Electronic cigarettes (ECs) are new devices that have been accepted widely by both smokers and non-smokers. However, the evidence on EC used in Malaysia is scarce. The objective of this study was to determine the prevalence of EC use and the socio-demographic and smoking characteristics associated with current EC use among Malaysian current and ex-smokers. METHODS: This was a sub-analysis of data from a cross-sectional, national-population- based EC study conducted from May to June in 2016 in Malaysia. A detailed description of the sampling methods can be found in the National E-cigarette Survey (NECS) 2016 report. Briefly, data were obtained from 1396 individuals who had ever been smokers, i.e., 957 (68.6%) current smokers and 439 (31.4%) ex-smokers. RESULTS: Current EC use was found predominantly among current smokers (8.0%) as compared with ex-smokers (4.3%). Among current smokers, the main reasons given for smoking ECs were wanting to try it (44.7%), followed by intention to quit tobacco smoking (15.8%) and to reduce tobacco smoking (10.5%). Using multiple logistic regression analysis, we found that among current smokers, current EC users were more likely to be younger, i.e., 18-44 years (aOR= 4.83, 95% CI= 1.97-11.86, p=0.001), urban residents (aOR= 1.89, 95% CI= 1.15-3.11, p=0.012), single/ divorced/ widowed (aOR= 2.11, 95% CI= 1.24-3.61, p=0.006) and students (aOR= 2.25, 95% CI= 1.01-5.01, p=0.048). Among exsmokers, only younger respondents (18-44 years old) was reported as being more likely to be current EC users (aOR= 3.81, 95% CI= 1.14-12.76, p=0.030). CONCLUSION: This study showed that currently using and ever having used ECs were more prevalent among current smokers. The reasons given for initiating EC use among current smokers were mainly wanting to try it, followed by intention to quit and to reduce tobacco smoking. Current EC use appears to be common among current smokers who are younger, urban residents, single/divorced/widowed and students. Therefore, EC cessation intervention strategies and policies should target these high-prevalence groups.

Prevalence of smoking and its associated factors with smoking among elderly smokers in Malaysia: findings from a nationwide population-based study.

BACKGROUND: The determination of smoking prevalence and its associated factors among the elderly could provide evidence-based findings to guide the planning and implementation of policy in order to will help in reducing the morbidity and mortality of smoking-related diseases, thus increase their quality of life. This paper describes the rate of smoking and identifies the factor(s) associated with smoking among the elderly in Malaysia. METHODS: A representative sample of 2674 respondents was obtained via a two-stage sampling method in proportion to population size. Face-to-face interviews were conducted using a set of standardized validated questionnaire. Data was weighted by taking into consideration the complex sampling design and non-response rate prior to data analysis. Univariable and multivariable logistic regression were used to determine the factor/s associated with smoking. RESULTS: The prevalence of non-smokers, ex-smokers and current smokers among Malaysians aged 60 years and above were 36.3 % (95 % CI = 32.7-39.8), 24.4 % (95 % CI = 21.2-27.5) and 11.9 % (95 % CI = 9.5-14.3), respectively. Current smokers were significantly more prevalent in men (28.1 %) than in women (2.9 %), but the prevalence declined with advancing age, higher educational attainment, and among respondents with known diabetes, hypertension and hypercholesterolemia. Multivariable analysis revealed that males (aOR, 18.6, 95 % CI 10.9-31.9) and other Bumiputras (aOR 2.58, 95 % CI 1.29-5.15) were more likely to smoke. in addition, elderly with lower educational attainment (aOR, 1.70, 95 % CI 1.24-7.41) and those without/unknown hypertension also reported higher likelihood to be current smokers (aOR 1.98, 95 % CI 1.35-2.83). However, there were no significant associations between respondents with no/unknown diabetes or hypercholesterolemia with smoking. CONCLUSIONS: In short, smoking is common among elderly men in Malaysia. Therefore, intervention programs should integrate the present findings to reduce the smoking rate and increase the smoking cessation rate among the elderly in Malaysia and subsequently to reduce the burden of smoking-related disease.

Tuberculosis in Malaysia: predictors of treatment outcomes in a national registry.

OBJECTIVES: To determine treatment outcomes and associated predictors of all patients registered in 2012 with the Malaysian National Tuberculosis (TB) Surveillance Registry. METHODS: Sociodemographic and clinical data were analysed. Unfavourable outcomes included treatment failure, transferred out and lost to follow-up, treatment defaulters, those not evaluated and all-cause mortality. RESULTS: In total, 21 582 patients were registered. The mean age was 42.36 ± 17.77 years, and 14.2% were non-Malaysians. The majority were new cases (93.6%). One fifth (21.5%) had unfavourable outcomes; of these, 46% died, 49% transferred out or defaulted and 1% failed treatment. Predictors of unfavourable outcomes were older age, male sex, foreign citizenship, lower education, no bacille Calmette-Guérin (BCG) vaccination scar, treatment in tertiary settings, smoking, previous anti-tuberculosis treatment, human immunodeficiency virus infection, not receiving directly observed treatment, advanced chest radiography findings, multidrug-resistant TB (MDR-TB) and extra-pulmonary TB. For all-cause mortality, predictors were similar except for rural dwelling and nationality (higher mortality among locals). Absence of BCG scar, previous treatment for TB and MDR-TB were not found to be predictors of all-cause mortality. Indigenous populations in East Malaysia had lower rates of unfavourable treatment outcomes. CONCLUSIONS: One fifth of TB patients had unfavourable outcomes. Intervention strategies should target those at increased risk of unfavourable outcomes and all-cause mortality.

Factors influencing the role of primary care providers as gatekeepers in the Malaysian public healthcare system.

Primary care providers play an important gatekeeping role in ensuring appropriate referrals to secondary care facilities. This cross-sectional study aimed to determine the level, pattern and rate of referrals from health clinics to hospitals in the public sector, and whether the placement of resident family medicine specialist (FMS) had made a significant difference. The study was carried out between March and April in 2012, involving 28 public primary care clinics. It showed that the average referral rate was 1.56% for clinics with resident FMS and 1.94% for those without resident FMS, but it was not statistically significant. Majority of referred cases were considered appropriate (96.1%). Results of the multivariate analysis showed that no prior consultation with senior healthcare provider and illnesses that were not severe and complex were independently associated with inappropriate referrals. Severity, complexity or uncertain diagnosis of patients' illness or injury significantly contributed to unavoidable referrals. Adequate facilities or having more experienced doctors could have avoided 14.5% of the referrals. The low referral rate and very high level of appropriate referrals could indicate that primary care providers in the public sector played an effective role as gatekeepers in the Malaysian public healthcare system.

Prevalence, awareness, treatment and control of diabetes mellitus among the elderly: The 2011 National Health and Morbidity Survey, Malaysia.

Diabetes mellitus is an important cardiovascular risk factor. The objective of this study was to provide population-based estimates on the prevalence, awareness, treatment and control rate of diabetes among the older persons in Malaysia. Analysis of secondary data from a cross-sectional national population-based survey was done, which was conducted in 2011 throughout Malaysia. A total of 2764 respondents (15.5%) were older persons. The overall prevalence of diabetes among older persons was 34.4% in which 65.2% were aware of their diabetes status. Out of those who were aware, 87.5% had been treated. Only 21.8% of those treated had their diabetes controlled. The results of multiple logistic regression showed that the factors associated with higher awareness rates were women, Indians and higher income groups; factors associated with higher treatment rates were urban residents and those who were married and widow/widower/ divorcee. There was a high overall prevalence, awareness and treatment rate of diabetes among older persons in Malaysia but with suboptimal control rate.

Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis.

Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

Temporal variation in parasuicide among Singaporean Chinese.

OBJECTIVE: The aim of this study was to determine whether there is any temporal variation in the incidence of parasuicide within the Chinese community and, if possible, to correlate the findings with prevailing cultural and social influences. METHOD: All patients of Chinese origin referred to a teaching hospital in Singapore between 1990 and 1994 were included in the study. The cases were divided by sex and aggregated for the month and day of the week in which the parasuicides occurred. RESULTS: Cases of parasuicide peaked on Mondays, while the lowest incidences occurred on Saturdays. The peak months were June, August and September with a trough in December and January. CONCLUSIONS: The findings may not be amenable to any single explanation but the peak months coincided with the month of the Hungry Ghosts, which is believed to be a particularly inauspicious period, while the trough occurred during a festive period. Similarly, looking at the student population, the peaks coincided with the examination period. It appears that social and cultural factors play a significant role in the temporal variation in parasuicide in Singapore.

The differential in vitro stimulation of 3',5'-cyclic nucleotide phosphodiesterase by calcium binding proteins.

A heterogeneous class of proteins exhibit within their sequence a particular structure, named EF-hand, able to bind calcium with high affinity. These calcium binding proteins have been described in most cells and tissues and are suggested to work as calcium buffers, thereby participating in the regulation of calcium-dependent cellular activity. Recent circumstantial evidences suggest that calcium binding proteins may serve other functions as well, possibly as enzyme modulators. Since 3',5'-cyclic nucleotide phosphodiesterase is a well-known calmodulin-modulated enzyme, in this work we studied the effect in vitro of different purified calcium binding proteins on the activity of this enzyme. Among the proteins tested, calmodulin and recombinant rat brain parvalbumin could stimulate the 3',5'-cyclic nucleotide phosphodiesterase activity in vitro, whereas rabbit muscle parvalbumin, rat renal and brain calbindin D28K, and bovine brain S-100B were ineffective. Immunoprecipitation with the specific antiserum completely abolished either calmodulin or recombinant brain parvalbumin activation of 3',5'-cyclic nucleotide phosphodiesterase. Moreover, while the presence of calcium in the incubation mixture was critical in the calmodulin-mediated stimulation of the enzyme, it did not modify the effect of the recombinant brain parvalbumin. We suggest that, in addition to calmodulin, parvalbumin may be a regulator of 3',5'-cyclic nucleotide phosphodiesterase, and possibly of other yet to be identified enzymes in certain tissues.

Effect of conversion from a fee-for-service plan to a capitation reimbursement system on a circumscribed outpatient radiology practice of 20,000 persons.

PURPOSE: To assess the effect of a capitation reimbursement plan with attendant changes in service arrangements on the utilization of radiologic services, financially on the payer, and on the satisfaction of patients and referring physicians. MATERIALS AND METHODS: Outpatient radiologic services for a defined population of 20,000 company employees and their dependents were converted from a point-of-service managed care plan to a capitation payment plan. Under the capitation plan, nonemergent outpatient diagnostic imaging was performed at a newly constructed imaging center staffed by general radiologists. All cross-sectional images and certain projectional studies were also over-read (read again after the initial reading by local radiologists) by subspecialists. Utilization data obtained before and after the conversion were analyzed. The financial effect on the employer and the satisfaction of patients and physicians were also assessed. RESULTS: Quality imaging services were provided under the capitation plan with financial savings by the employer. Use was higher for cross-sectional imaging, especially magnetic resonance imaging studies, and was lower for nonmammographic plain radiography. Consumer satisfaction was high. CONCLUSION: Under certain conditions, conversion to a capitation system for imaging can lead to improved quality of care and decreased overall health-care costs.

Expression of calbindin-D28K in motoneuron hybrid cells after retroviral infection with calbindin-D28K cDNA prevents amyotrophic lateral sclerosis IgG-mediated cytotoxicity.

Calbindin-D28K and/or parvalbumin appear to influence the selective vulnerability of motoneurons in amyotrophic lateral sclerosis (ALS). Their immunoreactivity is undetectable in motoneurons readily damaged in human ALS, and in differentiated motoneuron hybrid cells [ventral spinal cord (VSC 4.1 cells)] that undergo calcium-dependent apoptotic cell death in the presence of ALS immunoglobulins. To provide additional evidence for the role of calcium-binding proteins in motoneuron vulnerability, VSC 4.1 cells were infected with a retrovirus carrying calbindin-D28K cDNA under the control of the promoter of the phosphoglycerate kinase gene. Differentiated calbindin-D28K cDNA-infected cells expressed high calbindin-D28K and demonstrated increased resistance to ALS IgG-mediated toxicity. Treatment with calbindin-D28K antisense oligodeoxynucleotides, which significantly decreased calbindin-D28K expression, rendered these cells vulnerable again to ALS IgG toxicity.

Calbindin D28K forms a Ca(2+)-dissociable complex with mellitin in vitro.

Calbindin D28K (CB), a cytosolic calcium binding protein (CBP), forms a macromolecular complex with the polypeptide mellitin (ME) the absence of calcium, which can be reversibly dissociated by the addition of Ca2+. The molar ratio of CB:ME constituted in this complex is 1:4, suggesting that CB interacts with the tetrameric form of ME. Like free tetrameric ME, the CB:ME complex does not migrate into 15% non-denaturing polyacrylamide electrophoretic gels, although both constituents migrate normally after irreversible complex denaturation by heating in sodium dodecyl sulphate (SDS). The interaction of these two proteins can be distinguished from the association of calmodulin (CM) with ME, which forms a reversibly dissociable, equimolar complex in the presence of Ca2+ and a stable non-migrating complex (molar ratio = 1:12) in its absence. Thus, CB and CM appear to bind ME under different Ca2+ regulatory control, suggesting possible roles for CB as a Ca(2+)-dependent regulatory binding protein.

beta-Amyloid1-40 increases expression of beta-amyloid precursor protein in neuronal hybrid cells.

Studies of cell injury and death in Alzheimer's disease have suggested a prominent role for beta-amyloid peptide (beta-AP), a 40-43-amino-acid peptide derived from a larger membrane glycoprotein, beta-amyloid precursor protein (beta-APP). Previous experiments have demonstrated that beta-AP induces cytotoxicity in a neuronal hybrid cell line (MES 23.5) in vitro. Here, we demonstrate that beta-APP mRNA content is increased 3.5-fold in 24 h after treatment with beta-AP1-40. Accompanying beta-AP1-40-induced cell injury, levels of cell-associated beta-APP and a C-terminal intermediate fragment are increased up to 15-fold, and levels of secreted forms of beta-APP and 12- and 4-kDa fragments are also increased. Application of beta-APP antisense oligodeoxynucleotide reduces both cytotoxicity and beta-APP expression. 6-Hydroxydopamine application or glucose deprivation causes extensive cell damage, but they do not increase beta-APP expression. These results suggest a selective positive feedback mechanism whereby beta-AP may induce cytotoxicity and increase levels of potentially neurotrophic as well as amyloidogenic fragments of beta-APP with the net consequence of further neuronal damage.

Technical considerations in planning a distributed teleradiology system.

A large-scale teleradiology project is under way to link a Florida imaging center to the UCLA Department of Radiology. The initial goal is to provide Florida patients in a routine clinical practice environment with subspecialty consultation by academic radiologists. The plan then calls for the addition of other domestic and international sites. Technical issues in planning to establish the necessary teleradiology infrastructure include wide area network design, image compression, distributed archiving, and special viewing station features. Special emphasis is placed on archive design that makes intelligent use of information, such as triggering events from the radiological information system (RIS) for image prefetching and visual cues from photo-icons for full-size image retrieval. Concepts such as teleconsultation and remote procedure monitoring are aimed at providing the same level of services at distant sites that would be available in-house. This article highlights the system design parameters that must be considered to engineer a scalable distributed teleradiology system.

The role of calcium-binding proteins in selective motoneuron vulnerability in amyotrophic lateral sclerosis.

The factors contributing to selective motoneuron loss in amyotrophic lateral sclerosis (ALS) remain undefined. To investigate whether calcium-binding proteins contribute to selective motoneuron vulnerability in ALS, we compared calbindin-D28K and parvalbumin immunoreactivity in motoneuron populations in human ALS, and in a ventral spinal cord hybrid cell line selectively vulnerable to the cytotoxic effects of ALS IgG. In human autopsy specimens, immunoreactive calbindin-D28k and parvalbumin were absent in motoneuron populations lost early in ALS (i.e., cortical and spinal motoneurons, lower cranial nerve motoneurons), while motoneurons damaged late or infrequently in the disease (i.e., Onuf's nucleus motoneurons, oculomotor, trochlear, and abducens nerve neurons) expressed markedly higher levels of immunoreactive calbindin-D28K and/or parvalbumin. Motoneuron-neuroblastoma VSC 4.1 hybrid cells lost immunoreactive calbindin-D28k and parvalbumin following dibutyryl-cyclic AMP-induced differentiation and were killed by IgG from ALS patients. Undifferentiated calbindin/parvalbumin-reactive VSC 4.1 cells were not killed, nor were other cell lines expressing high levels of calbindin-D28K and parvalbumin immunoreactivity (substantia nigra-neuroblastoma hybrid cells and N18TG2 neuroblastoma parent cells). These studies suggest that decreased calbindin-D28K and parvalbumin immunoreactivity may help explain the selective vulnerability of motoneurons in ALS.

The effect of irreversible image compression on diagnostic accuracy in thoracic imaging.

RATIONALE AND OBJECTIVES: Digital image compression reduces the storage requirements and network traffic on picture archiving and communications systems. Full-frame bit-allocation (FFBA) is an irreversible image-compression method based on the discrete cosine transform that provides for high compression ratios with a high degree of image fidelity. METHODS: One hundred twenty-two posteroanterior chest radiographs were obtained on patients in an ambulatory patient setting, including 30 cases of interstitial lung disease, 45 images containing combinations of lung nodules (N = 37) or mediastinal masses (N = 39), and 47 normal images containing none of the pathology for which we were testing. The images were digitized (nominal 2 K x 2 K x 12-bit resolution), printed on a 35 x 35-cm hard copy format, and compressed at an approximate compression ratio of 20:1. Observer performance tests were conducted with five radiologists using receiver operating characteristics analysis on digitized uncompressed and compressed hard copy images. RESULTS: There were no significant differences between the two display conditions for the detectability of any of the thoracic abnormalities. CONCLUSIONS: Our preliminary results suggest that irreversible image compression at ratios of 20:1 may be acceptable for use in digital thoracic imaging.