Using Patient-Derived Induced Pluripotent Stem Cells to Identify Parkinson's Disease-Relevant Phenotypes.

PURPOSE OF REVIEW: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting older individuals. The specific cause underlying dopaminergic (DA) neuron loss in the substantia nigra, a pathological hallmark of PD, remains elusive. Here, we highlight peer-reviewed reports using induced pluripotent stem cells (iPSCs) to model PD in vitro and discuss the potential disease-relevant phenotypes that may lead to a better understanding of PD etiology. Benefits of iPSCs are that they retain the genetic background of the donor individual and can be differentiated into specialized neurons to facilitate disease modeling. RECENT FINDINGS: Mitochondrial dysfunction, oxidative stress, ER stress, and alpha-synuclein accumulation are common phenotypes observed in PD iPSC-derived neurons. New culturing technologies, such as directed reprogramming and midbrain organoids, offer innovative ways of investigating intraneuronal mechanisms of PD pathology. PD patient-derived iPSCs are an evolving resource to understand PD pathology and identify therapeutic targets.

An accelerometry-based system for the assessment of balance and postural sway.

The aim of this investigation was to develop an inexpensive, efficient system for the clinical assessment of static and dynamic balance and postural sway using accelerometry-based measurements. Subjects consisted of 10 young (range 18-32 years) and 10 older (range 69-86 years) individuals screened for polypharmacy and history of cardiovascular, neurological or orthopedic health conditions. A lightweight uniaxial accelerometer and general-purpose microcomputer were used to obtain measurements of postural sway. Customized software was written to acquire the data and provide a real-time display consisting of amplitude and frequency characteristics of the sway profile. Intraclass reliability coefficients greater than R = 0.75 were obtained in both eyes-open and challenging-standing balance tasks. Preliminary results demonstrate that the instrumentation can be used to discriminate among balance tasks and to differentiate healthy older adults from those with a tendency toward frequent falls. Moreover, the technique described yields a simple-to-administer, inexpensive procedure that can be conducted in the home or another natural environment. Accelerometry also allows for balance training and re-learning, using tasks that might ordinarily pose a balance challenge for the older or frail adult.

Motor unit discharge behavior in older adults during maximal-effort contractions.

A reduction in maximal force production is a common observation in older individuals. In an effort to determine whether aging is accompanied by reductions in central motoneuron drive limiting motor performance, motor unit discharge records were obtained from seven young (21-33 yr) and seven older (> 67 yr) adults. Informed consent was obtained from all subjects. The task required the subject to perform a maximal abduction of the second digit under isometric conditions. Motor unit potentials in the first dorsal interosseous were monitored by using a selective four-wire needle electrode and identified off-line with the aid of a Dantec electromyograph. The maximal discharge rate in the older adults (31.1 impulses/s) was significantly smaller (P < 0.05) than that in the younger subjects (50.9 impulses/s). These findings suggest that reductions in maximal force capability in older adults are partially due to an impaired ability to fully drive the surviving motor units.

[Medical examination of workers exposed to lead in the Philippines].

The medical examination of workers exposed to lead was conducted as part of the activity of the Occupational Safety and Health Center (OSHC) Project in the Philippines (JICA Project). The subjects of the medical examination were 21 male and 193 female workers of a semi-conductor plant (abbreviated A company), 59 male and 6 female workers of a refrigerator manufacture (B company); 199 male workers of a storage battery manufacturer (C company); and 107 male and 6 female workers of a lead smelter (D company). Among the examination items were questions regarding occupational history, subjective complaints and objective signs, determination of blood lead levels, urine delta aminolevulinic acid levels, and examination for anemia. The survey was conducted from June to September in 1990. The following results were obtained: 1) The mean age of the workers ranged from 21.8 to 33.8 years. Those of companies A and B were younger than those of companies C and D. The mean employment duration of males at C company was 10.7 yr, and the longest among the four companies. That in both sexes for A company was 1.8 yr and the shortest among the above mentioned companies. 2) The blood lead geometric mean levels of companies C and D showed the highest concentration. The level in males of C company was 64.5 micrograms/dl and that of D company was 80.8 micrograms/dl. The level in females of A company was 9.9 micrograms/dl and the lowest in concentration. The urine delta aminolevulinic acid geometric mean levels were less than 6.0 mg/l in the four companies. There was no company having hemoglobin mean values less than 14.0 g/dl in males or less than 12.0 g/dl in females. 3) The proportion of blood lead levels of 60 micrograms/dl or more was 67.3% in males of C company, and 89.7% in males and 16.7% in females of D company. The proportion of urine delta aminolevulinic acid levels of 6 mg/l or more was 1.0% in females of A company, 20.1% in males of C company, and 43.0% in males of D company. The proportion of hemoglobin values less than 14.0 g/dl in males or less than 12.0 g/dl in females was 4.7% in females of A company, 1.7% in males of B company, 3.5% in males of C company, and 12.1% in males of D company.(ABSTRACT TRUNCATED AT 400 WORDS)

Urinary metabolite levels and symptoms in Filipino workers using organic solvents.

To compare symptoms with urinary metabolite levels, 900 workers from 7 organic solvent-using industries were studied. Urinary metabolites were determined using a high performance liquid chromatograph. Urinary hippuric acid concentrations exceeding the reference value (2.5 g/g creatinine) were found in 78 (8.7%) workers. However, only 3 (0.3%) and 1 (0.1%) of the participants exceeded the reference value for mandelic (0.8 g/g creatinine) and total methylhippuric acid (1.5 g/g creatinine), respectively. The sum of the values of the ratio of measured urinary metabolite concentration to the corresponding ACGIH's biological exposure indices (BEI) [(HA/BEI of HA + MHA/BEI of MHA + MA/BEI of MA)] exceeded 1.0 in 166 (18.4%) workers. Majority of them were from the footwear manufacturing industry (63/129 or 49.2%). Questionnaire interviews were also administered to determine the prevalence of symptoms while at work (acute symptoms) or within the past 6 months (chronic symptoms). Urinary metabolite levels of individual and mixed solvents were compared with the symptoms of all workers. Analysis using Spearman's rank correlation showed in workers whose urinary hippuric acid exceeded 3.75 g/g creatine (1.5 x BEI), significant correlation between their hippuric acid levels and subjective complaints. Workers whose sum of the values of the ratio of measured urinary metabolite concentration to corresponding BEI exceeded 1.5 were selected and comparing this level with their symptoms, significant correlation was also noted in some complaints.