Genetic and Environmental Factors in Parkinson's Disease Converge on Immune Function and Inflammation

Idiopathic Parkinson's disease (iPD) is a movement disorder characterized by the degeneration of dopaminergic neurons and aggregation of the protein α-synuclein. Patients with iPD vary in age of symptom onset, rate of progression, severity of motor and non-motor symptoms, and extent of central and peripheral inflammation. Genetic and environmental factors are believed to act synergistically in iPD pathogenesis. We propose that environmental factors (pesticides and infections) increase the risk for iPD via the immune system and that the role of PD risk genes in immune cells is worthy of investigation. This review highlights the major PD-relevant genes expressed in immune cells and key environmental factors that activate immune cells and, alone or in combination with other factors, may contribute to iPD pathogenesis. By reviewing these interactions, we seek to enable the future development of immunomodulatory approaches to prevent or delay onset of iPD. © 2020 International Parkinson and Movement Disorder Society     

Identification of blast cells in the peripheral blood of patients with acute leukaemia using the Technicon H-1

The Technicon H-1 counter represents a refinement of the cytochemistry-based technology of its predecessors, the H6000 and the Hemalog-D. It also has a new channel, the basophil-lobularity channel, which is said to enhance the sensitivity of leukaemic blast detection in comparison with previous instruments. To evaluate this facility, 35 adult patients with acute leukaemia at different phases of their disease were monitored for the presence of circulating leukaemic blasts during a 4-week period. The ability of the H-1 to detect blasts was compared to a careful manual review of a blood and bone marrow smear. Using the latter review as the standard, the sensitivity was 83.8% with a specificity of 78%. Exclusion of patients with severe leucopenia (less than 1.0 x 10(9)/l) increased the specificity to 89%, with little alteration in the sensitivity. We were unable to confirm the high degree of sensitivity claimed in previous reports. The H-1 blast flag, however, would appear useful for screening patients who are off therapy or on maintenance regimens.     

EFFECTS OF NORMAL AGING ON LOWER EXTREMITY LOADING AND COORDINATION DURING RUNNING IN MALES AND FEMALES

Background

Runners sustain high injury rates. As greater numbers of individuals continue to run past the age of 60, normal physiological changes that occur with aging may further contribute to injuries. Male and female runners demonstrate different mechanics and injury rates. However, whether these mechanics further diverge as runners age and whether or not this potential divergence in mechanics may or may not be associated with a potential for increased injury risk is unknown.

Hypothesis/Purpose

The purpose of this study was to compare measures of loading and lower extremity coupling during running with respect to age and sex. It was hypothesized that males and females would demonstrate increasingly diverging mechanics with increased age.

Methods

Forty‐one subjects were placed in four groups: younger males (n=13), younger females (n=6), older males (n=16), and older females (n=6). Ten running trials were collected and analyzed for each subject. Kinematic data were collected and reconstructed using a nine‐camera motion analysis system and commercial software. Vertical loading rate (VLR), initial (GRF₁) and peak vertical ground reaction force (GRF₂) and lower leg joint coupling were calculated for each subject. Analysis was performed using a 2‐factor ANOVA (sex X age) to determine differences between groups during the stance phase of running.

Results

Compared to younger subjects, older subjects demonstrated higher GRF₁ per body weight (Y: 1.70 (0.19), O: 1.96 (0.23), p < 0.01), higher VLR in body weight/second (Y: 44.17 (6.73), O: 52.76 (8.39), p < 0.01) and lower GRF₂ per body weight (Y: 2.47 (0.18), O: 2.35 (0.18), p=0.04). However, no differences existed between males and females or further diverged in the older subjects. There were no differences between or within groups in joint coupling. Finally, no significant differences were seen between sexes and no interactions were found between any variables in the current study.

Conclusions

Older runners experience greater GRF₁ and VLR and lower GRF₂. These are factors previously associated with tibial loading and stress fractures. Males and females do not differ on these factors suggesting older female runners may be at no greater risk than younger runners or male runners for lower extremity bony injury based on normal mechanics.

Level of Evidence

3     

Diagnosis of pulmonary amyloidosis by transbronchial biopsy

Previously reported cases of pulmonary parenchymal amyloidosis were diagnosed by open lung biopsy or postmortem examination. We describe 3 patients who were found to have amyloid deposits within the lung parenchyma by flexible fiberoptic bronchoscopy. In each case, the diagnosis was suspected when a waxy eosinophilic substance was observed within the alveolar walls of transbronchial biopsy specimens stained with hematoxylin-eosin. When stained with Congo red and examined under polarized light, this amorphous material exhibited the apple-green birefringence characteristic of amyloid fibrils. We suggest that a diagnosis of pulmonary amyloidosis can be made by transbronchial biopsy provided the appropriate histologic stains are employed. Special stains for amyloid should be obtained whenever histologic sections from transbronchial biopsy specimens reveal amorphous eosinophilic material within the alveolar septa or within the walls of small vessels.     

Normalization of Maximal Cardiovascular Variables for Body Size in Premenarcheal Girls

Previous studies have indicated the importance of allometric scaling of VO_2max for body size. However, no information is available on adjusting maximal cardiac output (Q _max) and stroke volume (SV_max) for body dimensions. The allometric exponent b was determined for the equation Y=aX ^b (where Y is the physiological outcome and X is the anthropometric variable) for VO_2max, Q _max, and SV_max relative to mass, height, and body surface area (BSA) in 24 premenarcheal girls (mean age 12.2 years) during cycle testing. Values for b were 1.08 and 1.05 for BSA relative to Q _max and SV_max, approximating that of 1.0 using the traditional ratio standard (cardiac index and stroke index). Exponents of body mass relative to VO_2max, Q _max, and SV_max (0.55, 0.55, and 0.59, respectively) eliminated the effects of body size, but the ratio standard (M ^1.0) did not. In this group of subjects, use of the ratio standard BSA was an appropriate means of adjusting maximal values of Q and SV for body size.     

A de novo complex karyotype with two independent balanced translocations and a double inversion of chromosome 6 presenting with multiple congenital anomalies

We report a 4-year-old female with a de novo complex karyotype with multiple chromosomal rearrangements and a distinctive phenotype. Her medical history is significant for having been a twin born at 35 weeks gestation, breech presentation, with feeding problems and poor growth as an infant, gastroesophageal reflux disease, peripheral pulmonic stenosis, omphalocele, high myopia, and severe mental retardation. She is small for her age with microcephaly, posteriorly sloping forehead, shallow orbits, long palpebral fissures, prominent nose, wide mouth, absent uvula, kyphosis, brachydactyly, bridged palmar crease, and hypertonia. Peripheral blood lymphocytes revealed a karyotype of 46,XX,t(1;12)(p22.3;q21.3),inv(6)(p24q23),t(7;18)(q11.2;q21.2) in all cells. Parental karyotypes and that of her twin were normal. Spectral Karyotyping (SKY) and fluorescence in situ hybridization (FISH) with whole chromosome paints for chromosomes 1, 6, 7, 12, and 18 did not reveal additional rearrangements. Prometaphase G-banding analysis suggested that the "inverted" chromosome 6 might contain a cryptic rearrangement. Although no deletion nor duplication was detected using metaphase comparative genomic hybridization (CGH), multicolor high resolution banding (mBAND) demonstrated a double inversion of chromosome 6, resulting in a final karyotype as above but including der(6)(pter --> p23::q21 --> q22.3::q21 --> p23::q22.3 --> qter).