Higher oxytocin concentrations occur in subjects who build affiliative relationships with companion robots.

Building affiliative relationships with others is important for mental health. Recently, robots have been expected to play a role in improving mental health, but there is little scientific evidence as to whether they can build affiliative relationships with humans. To investigate that, we conducted studies combining behavior, physiology and questionnaires for companion robot Owners and Non-Owners. The results reveal that the steady-state concentration of oxytocin, a hormone related to affiliative relationships, was significantly higher in Owners than in Non-Owners. In addition, the Owners showed more behaviors indicative of intimacy than the Non-Owners. These results suggest that humans can build affiliative relationships with robots. Fifteen minutes of contact with the robot decreased the concentration of cortisol in both groups, suggesting that even a brief contact can contribute to improving mental health. Therefore, relationships between humans and robots may be one option to improve mental health and enhance well-being.

Simultaneous measurement of the size and methylation of chromosome 4qA-D4Z4 repeats in facioscapulohumeral muscular dystrophy by long-read sequencing.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder characterized by asymmetric muscle wasting and weakness. FSHD can be subdivided into two types: FSHD1, caused by contraction of the D4Z4 repeat on chromosome 4q35, and FSHD2, caused by mild contraction of the D4Z4 repeat plus aberrant hypomethylation mediated by genetic variants in SMCHD1, DNMT3B, or LRIF1. Genetic diagnosis of FSHD is challenging because of the complex procedures required. METHODS: We applied Nanopore CRISPR/Cas9-targeted resequencing for the diagnosis of FSHD by simultaneous detection of D4Z4 repeat length and methylation status at nucleotide level in genetically-confirmed and suspected patients. RESULTS: We found significant hypomethylation of contracted 4q-D4Z4 repeats in FSHD1, and both 4q- and 10q-D4Z4 repeats in FSHD2. We also found that the hypomethylation in the contracted D4Z4 in FSHD1 is moderately correlated with patient phenotypes. CONCLUSIONS: Our method contributes to the development for the diagnosis of FSHD using Nanopore long-read sequencing. This finding might give insight into the mechanisms by which repeat contraction causes disease pathogenesis.

Bile acid abnormality induced by intestinal dysbiosis might explain lipid metabolism in Parkinson's disease.

Intestinal dysbiosis refers to an imbalance in the intestinal flora. The concept of small intestinal bacterial overgrowth (SIBO), a condition of abnormal proliferation of the small intestine microbiota, has been proposed as a form of small intestine dysbiosis. In Parkinson's disease patients, weight loss and metabolic disorders such as lipid abnormalities are frequently encountered. This was a prospective investigation of the presence of SIBO using the lactulose breath test, Parkinson's disease symptoms, medications, abdominal symptoms, and blood data involving 39 Parkinson's disease patients. Of the 39 patients, 19 were positive for SIBO, 16 were negative, and 4 were equivocal. SIBO-positive patients had a significantly smaller dopaminergic drug load (dopamine replacement of Parkinson's disease drug potency) (P = 0.009) and significantly lower serum triglyceride (TG) (P = 0.024) and total bilirubin (P = 0.019) levels. No relationship was seen between the presence or absence of SIBO and motor or abdominal symptoms. The following hypothesis was developed with regard to the possibility that intestinal bacterial overgrowth has various effects that are exhibited via bile acid metabolism in Parkinson's disease patients. Serum bilirubin levels become higher as bilirubin metabolism declines with decreases in the intestinal bacteria. At the same time, bile acid is broken down due to increased intestinal bacteria, and lipid absorption decreases. This induces low serum TG levels and leads to weight loss. By a similar mechanism, there is less absorption of vitamin D as bile acid levels decrease, leading to osteoporosis and fractures. The possibility that some of the non-motor manifestations accompanying Parkinson's disease are caused by intestinal dysbiosis needs to be considered.

Impact of Aspiration Pneumonia on the Clinical Course of Progressive Supranuclear Palsy: A Retrospective Cohort Study.

INTRODUCTION: Although aspiration pneumonia is the most common complication of progressive supranuclear palsy (PSP), the clinical impact of aspiration pneumonia on disease course and survival has not been fully estimated. Thus, we retrospectively analyzed the prognostic factors and clinical consequences of pneumonia in PSP. METHODS: The clinical course of patients with aspiration pneumonia was surveyed. The association between baseline clinical features (2 years from disease onset) and latency to the initial development of pneumonia was investigated using survival time and Cox regression analyses. RESULTS: Ninety patients with a clinical diagnosis of PSP were observed for 5.1±3.8 years (mean±SD), and 22 had aspiration pneumonia. Subsequently, 20 patients (91%) had to discontinue oral feeding entirely and 13 (59%) died, whereas, of 68 patients without pneumonia, only three patients (4%) died. Time to initial development of pneumonia was strongly correlated with survival time (Spearman R = 0.92, P<0.001), with a mean latency of 2.3 years to death. Among baseline clinical features, early fall episodes and cognitive decline were significant predictors of pneumonia (P = 0.001 and P<0.001, respectively, log rank test). Cox regression analysis demonstrated that early fall episodes (adjusted hazard ratio: 3.9, 95% confidence interval: 1.2-12.5, P = 0.03) and cognitive decline (adjusted hazard ratio: 5.2, 95% confidence interval: 1.4-19.3, P = 0.02) independently predicted pneumonia. By contrast, dysphagia was not associated with pneumonia (P = 0.2, log rank test). CONCLUSION: Initial development of pneumonia indicates an unfavorable clinical course and predicts survival time (mean survival time 2.3 years). Patients with early falls and cognitive decline were at high risk of early development of pneumonia.

[Two cases of hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P)].

We, herein, report two independent cases with hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) inherited in an autosomal dominant fashion. Their common clinical features are slowly progressive proximal dominant muscular atrophy, fasciculations and mild to moderate distal sensory disturbance with areflexia. Nerve conduction study revealed an absence of sensory nerve action potentials, in contrast to almost normal compound muscle action potentials. Gene analysis in both patients elucidated heterozygous mutation (c.854C>T, p.Pro285Leu) in the TFG, which is an identical mutation, already described by Ishiura et al. Okinawa and Shiga are two foci of HMSN-P in Japan. Eventually, one patient is from Okinawa and the other is from a mountain village in Shiga prefecture. When we see a patient who has symptoms suggestive of motor neuron disease with sensory neuropathy, HMSN-P should be considered as a differential diagnosis despite the patient's actual resident place.

Microvascular disturbance with decreased pericyte coverage is prominent in the ventral horn of patients with amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS) there is emerging evidence for vasculature disturbance. The aim of this study was to investigate the area of predominant vasculature disturbance in ALS. We used immunohistochemistry to quantitatively evaluate the microvascular density (MVD) and pericyte coverage (PC) in the lumbar spinal cord of 25 ALS patients and six controls. In controls, MVD was almost equal in the ventral horn (VH) and dorsal horn (DH). In the VH of ALS, MVD was significantly increased, and PC was significantly decreased compared with the DH in ALS and the VH in controls (p < 0.001), possibly reflecting that PC is an essential requirement for the vasculature in the VH. We then found a significant relationship between the severity of aberrant angiogenesis and the use of artificial respiratory support (ARS). In conclusion, vasculature disturbance is observed in all ALS patients including patients with ARS. Therefore, breakdown of the blood-spinal cord barrier due to aberrant angiogenesis with decreased PC may be responsible for the predominant neuronal death in the VH in ALS.

[A case of optic neuritis associated with lymphocytic hypophysitis revealed by pattern-reversal VEP].

Lymphocytic hypophysitis (LYH) is a rare neuroendocrine disorder characterized by autoimmune inflammation of the pituitary gland. Visual disturbance is one of the most common and serious symptoms of LYH. Most of the visual symptoms in LYH are secondary to compression of the optic chiasm and some reports have described direct inflammatory involvement of the optic pathways. We describe a 30-year-old man with a 9-day history of bilateral blurred vision. Ophthalmic examination demonstrated severely impaired vision without temporal hemianopsia. Hypothyroidism, hypocortisolism, and hypogonadism were detected in laboratory tests. Central diabetes insipidus was diagnosed by a hypertonic saline infusion test. MRI revealed thickening of the pituitary stalk and enlargement of the hypophysis, which was enhanced with gadolinium. High intensity of the posterior lobe was not recognized on T1-weighted images. These findings established a clinical diagnosis of lymphocytic panhypophysitis. Methylprednisolone pulse therapy was introduced and his visual acuity gradually recovered. The anterior pituitary function improved, but desmopressin was still required. Pattern-reversal visual evoked potentials (VEP) have been widely used to detect optic nerve lesions caused by multiple sclerosis and brain tumors. However, there have been no previous reports of their usefulness for LYH. The P100 latency in our case was slightly prolonged and the amplitude was markedly reduced. These findings are similar to ischemic optic neuropathy and other conditions in which axonal damage is prominent. The prolonged latency and low amplitude on VEP examination in this case showed rapid improvement in parallel with the recovery of visual acuity. Taken together, our case implies the usefulness of pattern-reversal VEP for the diagnosis of optic neuritis in LYH, especially for the evaluation of its pathogenic mechanisms.

[Case of Hashimoto's encephalopathy with diffuse white matter lesions on diffusion-weighted MRI].

A 65-year-old woman was admitted to our hospital because of subacute deterioration of cognitive function. On admission, she presented with marked disorientation of time and place and inability to carry out commands. Mini-Mental State Examination score was 5/30. Although routine laboratory examinations including thyroid function, vitamin B1 and B12, serum syphilitic reaction, sIL-2 receptor level, titers of herpes simplex and zoster viruses, and HIV antibody were normal, titers of anti-thyroglobulin (TG) antibodies and thyroid peroxidase (TPO) antibodies were elevated. Cerebrospinal fluid showed normal findings. Brain MRI revealed diffuse high intensity in the white matter on diffusion- and T2-weighted images, mimicking leukoencephalopathy. We made a diagnosis of Hashimoto's encephalopathy, based on clinical features and high titers of anti-thyroid antibodies. Following administration of steroid hormone, her cognitive impairment gradually improved, associated with decrease of the white matter abnormality on MRI. Hashimoto's encephalopathy should be kept in mind in the differential diagnosis of subacute leukoencephalopathy with cognitive decline.

[A case of high-aged idiopathic spinal cord herniation from dural defect].

Idiopathic spinal cord herniation was assumed to be a rare disease. However, the incidence of discovering this condition appears to have been increasing recently with advances in neuroradiological diagnosis using magnetic resonance imaging (MRI) and computed tomographic myelogram (CTM). We present herein an operated case of high-aged idiopathic spinal cord herniation. A 71-year-old female presented with spastic paresis of the right lower limb and sensory disturbance of pain and temperature below the level of the left Th4 dermatome, consistent with Brown-Séquard syndrome. MRI and CTM revealed right ventral displacement of the spinal cord and dilatation of the dorsal subarachnoid space at Th2/3. Laminectomy of Th1-3 was performed, herniated spinal cord was untethered and repositioned, and the dural defect was sealed with GORE-TEX dura substitute. Postoperative MRI revealed normal location of the spinal cord and neurological state improved slightly. The patient was discharged 1 month after the operation. Among many cases of spinal cord herniations, this is considered to be a rare case of idiopathic spinal cord herniation in an elderly patient.