Association of subclinical carotid atherosclerosis with immediate memory and other cognitive functions.

AIM: To clarify whether carotid atherosclerosis and its risk factors are associated with cognitive decline. METHODS: We evaluated 206 individuals who visited our center for health screening. We carried out physical examinations, blood tests, intima-media thickness (IMT) measurement by carotid ultrasonography, brain magnetic resonance imaging scanning and cognitive function assessments. A total of 30 individuals, who had significant cerebrovascular lesions detected in magnetic resonance imaging scans, were excluded. To detect early cognitive decline, we defined "cognitive impairment (CI)" when a patient satisfied at least one of three criteria. These were Mini-Mental State Examination score <24, clock-drawing test score <4 coexisting with forgetfulness and Wechsler Memory Scale-revised delayed recall score below the normal range for the duration of education (>16 years of education: ≥9, 10-15 years: ≥5, 0-9 years: ≥3). RESULTS: Among 176 individuals, 27 were placed in the CI group. IMT was significantly higher in the CI group as compared with the non-CI group (mean ± SD: 2.0 ± 1.0 vs 1.7 ± 0.7, P = 0018 by Student's t-test). Other atherosclerotic risk factors, such as blood pressure, low-density lipoprotein cholesterol, and hemoglobin A1c, were not significantly different between the two groups. In multivariate analysis, maximum IMT was associated with impaired immediate recall score on Wechsler Memory Scale-revised, independent of the presence of deep white matter hyperintensities on the magnetic resonance imaging scan. CONCLUSIONS: Subclinical carotid atherosclerosis, defined as thickened IMT, could be a marker for early stages of CI, especially for immediate memory recall. The impairment is presumably caused by inducing cerebral microvascular dysfunction in the frontal lobe. Geriatr Gerontol Int 2018; 18: 65-71.

Evaluation of preferable insertion routes for esophagogastroduodenoscopy using ultrathin endoscopes.

AIM: To evaluate the discomfort associated with esophagogastroduodenoscopy (EGD) using an ultrathin endoscope through different insertion routes. METHODS: This study (January 2012-March 2013) included 1971 consecutive patients [male/female (M/F), 1158/813, 57.5 ± 11.9 years] who visited a single institute for annual health checkups. Transnasal EGD was performed in 1394 patients and transoral EGD in 577. EGD-associated discomfort was assessed using a visual analog scale score (VAS score: 0-10). RESULTS: Multivariate analysis revealed gender (M vs F: 4.02 ± 2.15 vs 5.06 ± 2.43) as the only independent predictor of the VAS score in 180 patients who underwent EGD for the first time; whereas it revealed gender (M vs F 3.60 ± 2.20 vs 4.84 ± 2.37), operator, age group (A: < 39 years; B: 40-49 years; C: 50-59 years; D: 60-69 years; E: > 70 years; A/B/C/D/E: 4.99 ± 2.32/4.34 ± 2.49/4.19 ± 2.31/3.99 ± 2.27/3.63 ± 2.31), and type of insertion as independent predictors in the remaining patients. Subanalysis for gender, age group, and insertion route revealed that the VAS score decreased with age regardless of gender and insertion route, was high in female patients regardless of age and insertion route, and was low in males aged over 60 years who underwent transoral insertion. CONCLUSION: Although comprehensive analysis revealed that the insertion route may not be an independent predictor of the VAS score, transoral insertion may reduce EGD-associated discomfort in elderly patients.

CpG demethylation enhances alpha-synuclein expression and affects the pathogenesis of Parkinson's disease.

BACKGROUND: Alpha-synuclein (SNCA) gene expression is an important factor in the pathogenesis of Parkinson's disease (PD). Gene multiplication can cause inherited PD, and promoter polymorphisms that increase SNCA expression are associated with sporadic PD. CpG methylation in the promoter region may also influence SNCA expression. METHODOLOGY/PRINCIPAL FINDINGS: By using cultured cells, we identified a region of the SNCA CpG island in which the methylation status altered along with increased SNCA expression. Postmortem brain analysis revealed regional non-specific methylation differences in this CpG region in the anterior cingulate and putamen among controls and PD; however, in the substantia nigra of PD, methylation was significantly decreased. CONCLUSIONS/SIGNIFICANCE: This CpG region may function as an intronic regulatory element for SNCA gene. Our findings suggest that a novel epigenetic regulatory mechanism controlling SNCA expression influences PD pathogenesis.

Supramaximal responses can be elicited in hand muscles by magnetic stimulation of the cervical motor roots.

BACKGROUND: The amplitude of compound muscle action potentials (CMAPs) evoked in response to magnetic cervical motor root stimulation (MRS) has rarely been used as a diagnostic parameter because of the difficulty in obtaining supramaximal CMAPs. OBJECTIVE: To clarify whether supramaximal CMAPs could be elicited by MRS, and if so, whether their amplitude and area could be used to evaluate the conduction of proximal motor roots. METHOD: With the use of a custom-made high-power magnetic stimulator, the CMAPs evoked in response to MRS of the first dorsal interosseous, abductor digiti minimi, and abductor pollicis brevis (APB) muscles were compared with those evoked by electrical stimulation at the wrist, brachial plexus, and cervical motor roots. The collision technique was also used to exclude volume conduction. The correlation between MRS-induced CMAP latency and body height was evaluated. RESULTS: In 32 of 36 normal subjects, supramaximal CMAPs were obtained in response to MRS. The size of CMAPs occurring in response to MRS was the same as the size of those occurring in response to high-voltage electrical cervical motor root stimulation. The collision technique revealed that the APB muscle was highly contaminated by volume conduction from adjacent muscles. CMAP latency correlated significantly with body height. CONCLUSIONS: Supramaximal CMAPs can be obtained in most normal subjects. In subjects exhibiting confirmed supramaximal CMAPs in response to MRS, not only the latency of these CMAPs but also their amplitude and area can be clinically useful, excluding CMAPs in the APB muscle.

Intranuclear degradation of polyglutamine aggregates by the ubiquitin-proteasome system.

Huntington disease and its related autosomal-dominant polyglutamine (pQ) neurodegenerative diseases are characterized by intraneuronal accumulation of protein aggregates. Studies on protein aggregates have revealed the importance of the ubiquitin-proteasome system as the front line of protein quality control (PQC) machinery against aberrant proteins. Recently, we have shown that the autophagy-lysosomal system is also involved in cytoplasmic aggregate degradation, but the nucleus lacked this activity. Consequently, the nucleus relies entirely on the ubiquitin-proteasome system for PQC. According to previous studies, nuclear aggregates possess a higher cellular toxicity than do their cytoplasmic counterparts, however degradation kinetics of nuclear aggregates have been poorly understood. Here we show that nuclear ubiquitin ligases San1p and UHRF-2 each enhance nuclear pQ aggregate degradation and rescued pQ-induced cytotoxicity in cultured cells and primary neurons. Moreover, UHRF-2 is associated with nuclear inclusion bodies in vitro and in vivo. Our data suggest that UHRF-2 is an essential molecule for nuclear pQ degradation as a component of nuclear PQC machinery in mammalian cells.

Severe hypokinesis caused by paraneoplastic anti-Ma2 encephalitis associated with bilateral intratubular germ-cell neoplasm of the testes.

We report a 40-year-old man with severe hypokinesis as paraneoplastic manifestation of a microscopic "carcinoma in situ" of the testis. The young age of the patient, along with progressive neurologic deterioration, detection of anti-Ma2 antibodies, and ultrasound findings of bilateral microcalcifications, led to bilateral orchiectomy, revealing the tumor in both testes. After orchiectomy, neurological symptoms stabilized, but the patient eventually died of systemic complications caused by his severe neurological deficits. Anti-Ma2 paraneoplastic encephalitis should be considered in patients with severe hypokinesis, and intensive investigation and aggressive approach to treatment is encouraged to prevent progression of the neurological deficits.