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Many studies in recent years have reported cell therapies using embryonic stem cells, induced pluripotent stem cells, and bone marrow-derived mononuclear cells for cerebral ischemia. However, obtaining these cells is challenging, and these cell therapies require complicated procedures to prepare cells for administration. Notably, peripheral blood mononuclear cells (PBMCs) are a useful cell source for clinical applications because cell collection is easier. In this review, we report the therapeutic effects of PBMCs preconditioned by oxygen-glucose deprivation (OGD-PBMCs) on cerebral ischemia. Cell therapies using tissue-protective OGD-PBMCs might be a simple and ideal therapeutic strategy against ischemic stroke.

A novel coronavirus infection, coronavirus disease 2019 (COVID-19), is frequently associated with neuromuscular symptoms. It is characterized by taste and smell disturbances, and nonspecific symptoms such as headache and dizziness. Neuromuscular complications such as cerebrovascular disease, encephalopathy, meningoencephalitis, peripheral neuropathy, and myositis/myopathy have been reported to date. In daily clinical practice, it is important to consider COVID-19 as a differential diagnosis, because these symptoms may be the first warning signs.

Recently, the diagnostic criteria for idiopathic cerebellar ataxia (IDCA) have been proposed in Japan as a diagnosis to replace the clinical concept of cortical cerebellar atrophy, which was originally described as a neuropathological disorder. However, IDCA proposed in Japan may include various diseases such as multiple system atrophy with early stage, rare hereditary ataxias, and autoimmune-mediated cerebellar ataxia. We tackled this significant clinical challenge by detecting anti-cerebellar autoantibodies in patients' sera and identifying their target antigens. We detected anti-cerebellar autoantibodies in the sera of some patients diagnosed with IDCA in Japan. In the future, it will be necessary to confirm the efficacy of immunotherapy for anti-cerebellar autoantibody-positive cases among patients who were thought to be difficult to treat.

The gut microbiota produce hundreds of bioactive compounds, including B-vitamins, which play significant physiological roles in hosts by supporting the fitness of symbiotic species and suppressing the growth of competitive species. B-vitamins are also essential to the host and certain gut bacterium. Although dietary B-vitamins are mainly absorbed from the small intestine, excess B-vitamins unable to be absorbed in the small intestine are supplied to the distal gut. In addition, B-vitamins are supplied from biosynthesis by distal gut microbiota. B-vitamins in the distal colon may perform many important functions in the body. They act as 1) nutrients for a host and their microbiota, 2) regulators of immune cell activity, 3) mediators of drug efficacy, 4) supporters of survival, or the fitness of certain bacterium, 5) suppressors of colonization by pathogenic bacteria, and 6) modulators of colitis. Insights into basic biophysical principles, including the bioavailability of B-vitamins and their derivatives in the distal gut are still not fully elucidated. Here, the function of single B-vitamin in the distal gut including their roles in relation to bacteria are briefly reviewed. The prospect of extending analytical methods to better understand the role of B-vitamins in the gut is also explored., (© 2020 Wiley-VCH GmbH.)

Stroke remains a major cause of serious disability because the brain has a limited capacity to regenerate. In the last two decades, therapies for stroke have dramatically changed. However, half of the patients cannot achieve functional independence after treatment. Presently, cell-based therapies are being investigated to improve functional outcomes. This review aims to describe conventional cell therapies under clinical trial and outline the novel concept of polarized cell therapies based on protective cell phenotypes, which are currently in pre-clinical studies, to facilitate functional recovery after post-reperfusion treatment in patients with ischemic stroke. In particular, non-neuronal stem cells, such as bone marrow-derived mesenchymal stem/stromal cells and mononuclear cells, confer no risk of tumorigenesis and are safe because they do not induce rejection and allergy; they also pose no ethical issues. Therefore, recent studies have focused on them as a cell source for cell therapies. Some clinical trials have shown beneficial therapeutic effects of bone marrow-derived cells in this regard, whereas others have shown no such effects. Therefore, more clinical trials must be performed to reach a conclusion. Polarized microglia or peripheral blood mononuclear cells might provide promising therapeutic strategies after stroke because they have pleiotropic effects. In traumatic injuries and neurodegenerative diseases, astrocytes, neutrophils, and T cells were polarized to the protective phenotype in pre-clinical studies. As such, they might be useful therapeutic targets. Polarized cell therapies are gaining attention in the treatment of stroke and neurological diseases.

Influenza A viruses (IAVs) pose a serious global threat to humans and their livestock. This study aimed to determine the ideal irradiation by ultraviolet-light emitting diodes (UV-LEDs) for IAV disinfection. We irradiated the IAV H1N1 subtype with 4.8 mJ/cm 2 UV using eight UV-LEDs [peak wavelengths (WL) = 365, 310, 300, 290, 280, 270, and 260 nm)] or a mercury low pressure (LP)-UV lamp (Peak WL = 254 nm). Inactivation was evaluated by the infection ratio of Madin-Darby canine kidney (MDCK) cells or chicken embryonated eggs. Irradiation by the 260 nm UV-LED showed the highest inactivation among all treatments. Because the irradiation-induced inactivation effects strongly correlated with damage to viral RNA, we calculated the correlation coefficient ( R AE ) between the irradiant spectrum and absorption of viral RNA. The R AE scores strongly correlated with the inactivation by the UV-LEDs and LP-UV lamp. To increase the R AE score, we combined three different peak WL UV-LEDs (hybrid UV-LED). The hybrid UV-LED ( R AE = 86.3) significantly inactivated both H1N1 and H6N2 subtypes to a greater extent than 260 nm ( R AE = 68.6) or 270 nm ( R AE = 42.2) UV-LEDs. The R AE score is an important factor for increasing the virucidal effects of UV-LED irradiation.

Clinical ethical issues may arise at any stage of multiple system atrophy. Even if there is "bad news," such as sudden death or dementia in the future, the patient has the right to know, but the notification should be made with prudence and consideration for the patient. We also need to recognize that there is insufficient evidence to support clinical ethical judgment. In addition, it is important to promote clinical research and to actively carry out clinical ethical discussions on this disease.

Vibrio parahaemolyticus is a Gram-negative halophilic pathogen that frequently causes acute gastroenteritis and occasional wound infection. V. parahaemolyticus contains several virulence factors, including type III secretion systems (T3SSs) and thermostable direct hemolysin (TDH). In particular, T3SS1 is a potent cytotoxic inducer, and T3SS2 is essential for causing acute gastroenteritis. Although much is known about manipulation of host signaling transductions by the V. parahaemolyticus effector, little is known about the host metabolomic changes modulated by V. parahaemolyticus To address this knowledge gap, we performed a metabolomic analysis of the epithelial cells during V. parahaemolyticus infection using capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS). Our results revealed significant metabolomic perturbations upon V. parahaemolyticus infection. Moreover, we identified that T3SS1's VopQ effector was responsible for inducing the significant metabolic changes in the infected cells. The VopQ effector dramatically altered the host cell's glycolytic, tricarboxylic acid cycle (TCA), and amino acid metabolisms. VopQ effector disrupted host cell redox homeostasis by depleting cellular glutathione and subsequently increasing the level of reactive oxygen species (ROS) production. IMPORTANCE The metabolic response of host cells upon infection is pathogen specific, and infection-induced host metabolic reprogramming may have beneficial effects on the proliferation of pathogens. V. parahaemolyticus contains a range of virulence factors to manipulate host signaling pathways and metabolic processes. In this study, we identified that the T3SS1 VopQ effector rewrites host metabolism in conjunction with the inflammation and cell death processes. Understanding how VopQ reprograms host cell metabolism during the infection could help us to identify novel therapeutic strategies to enhance the survival of host cells during V. parahaemolyticus infection., (Copyright © 2020 Nguyen et al.)

Microbes in the human gut play a role in the production of bioactive compounds, including some vitamins. Although several studies attempted to identify definitive markers for certain vitamin deficiencies, the role of gut microbiota in these deficiencies is unclear. To investigate the role of gut microbiota in deficiencies of four vitamins, B 2 , B 6 , folate, and B 12 , we conducted a comprehensive analysis of metabolites in mice treated and untreated with antibiotics. We identified glycolate (GA) as a novel marker of vitamin B 2 (VB2) deficiency, and show that gut microbiota sense dietary VB2 deficiency and accumulate GA in response. The plasma GA concentration responded to reduced VB2 supply from both the gut microbiota and the diet. These results suggest that GA is a novel marker that can be used to assess whether or not the net supply of VB2 from dietary sources and gut microbiota is sufficient. We also found that gut microbiota can provide short-term compensation for host VB2 deficiency when dietary VB2 is withheld., Competing Interests: The authors declare no conflict of interest.

Cervicogenic headache (CEH) is a lateralized non-pulsative headache syndrome caused by cervical spine disorders. The headache is initiated in the neck, which subsequently spreads to the occipital, frontal, and orbital regions, and is accompanied by ipsilateral shoulder pain. The prevalence of CEH is considered to be 15-20% among cases of chronic headache. With regard to the mechanism of CEH, convergence of upper cervical nerves and trigeminocervical complex might play an important role. However, CEH in many patients has been reported to be associated with middle to lower cervical disorders, which cannot be explained by this theory. We therefore proposed the possibility that the condition reported here is another type of CEH. The treatment of CEH requires a multidisciplinary approach, because pharmacological treatment is often ineffective. (Received August 16 2019; Accepted November 25, 2019; Published March 1, 2020).

A 57-year-old woman with amyotrophic lateral sclerosis (ALS) receiving mechanical ventilation developed intractable right temporal headache. She was diagnosed with brain abscess secondary to chronic suppurative otitis media. In this case, the otitis media was caused by nasopharyngeal reflux associated with eustachian tube muscle weakness and a supine position. In addition, ALS patients under mechanical ventilation have a limited ability to convey their pain. Their complaints are often overlooked because many physicians do not know that pain is common in ALS. Physicians should recognize brain abscess as a severe complication of ALS and listen to the complaints of these patients.

More accurate and early diagnoses of neurodegenerative diseases are required to establish disease-modifying therapies. Obtaining a clear diagnosis of multiple system atrophy (MSA), a neurodegenerative disease, can be challenging because MSA has a number of clinical subtypes and many other diseases, known as mimics, are characterized by symptoms that are similar to those of MSA. This paper discusses the factors that make the clinical diagnosis of MSA difficult. Additionally, this paper introduces an attempt at the new clinical diagnostic criteria establishment in accord with recent clinical trials.

The prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing rapidly and spreading worldwide, particularly in Asia, compared to other regions. In the last ten years, in our hospital, in particular, there has been a < 30% increase. To prevent the spread of ESBL in hospitals and the community, the ultraviolet (UV) A-light-emitting diode (LED) irradiation device was used to inactivate ESBL-E. coli in human livestock and the environment. ESBL-E. coli and E. coli bacterial samples were collected from patients at Tokushima University Hospital (Tokushima City, Japan). The UVA-LED irradiation system had 365 nm single wavelength, and the current of the circuit was set to 0.23 or 0.50 A consistently. Results demonstrated that UVA-LED was useful for the inactivation of ESBL-E. coli and E. coli. The minimum energy dosage required to inactivate ESBL-E. coli and E. coli was 40.76 J/cm2 (45 min) in the first type of UVA-LED and 38.85 J/cm2 (5 min) in the second type. There were no significant differences between ESBL-E. coli and E. coli. The inactivation of ESBL-E. coli was dependent on energy. These findings suggest that UVA-LED with 365 nm single wavelength could be useful for surface decontamination in healthcare facilities. J. Med. Invest. 67 : 163-169, February, 2020.

A 32-year-old woman experienced several episodes of transient numbness on the left side of her face and body. MR angiography revealed severe stenosis in the right middle cerebral artery (MCA). Abnormal collateral vessel networks were not observed, and idiopathic MCA stenosis was diagnosed. She underwent superficial temporal artery (STA)-MCA anastomosis of the right hemisphere. The surgery eliminated the transient ischemic attacks; however, she developed hemiballism in the left side of her face and left upper limb 2 weeks after the surgery. The ballism disappeared 1.5 years after onset without any treatments. A few patients with development of chorea after STA-MCA anastomosis has been reported in moyamoya disease, but not in those with MCA stenoses. It has been previsouly reported that the development of an involuntary movement might be associated with hypermetabolism in the contra lateral striatum after STA-MCA anastomosis. We considered that a similar mechanism may have caused hemiallism in our patient. We need to recognize that STA-MCA anastomosis could cause hemichorea or hemiballism.

Cell therapies that invoke pleiotropic mechanisms may facilitate functional recovery in patients with stroke. Based on previous experiments using microglia preconditioned by oxygen-glucose deprivation, we hypothesized that the administration of peripheral blood mononuclear cells (PBMCs) preconditioned by oxygen-glucose deprivation (OGD-PBMCs) to be a therapeutic strategy for ischemic stroke. Here, OGD-PBMCs were identified to secrete remodelling factors, including the vascular endothelial growth factor and transforming growth factor-β in vitro, while intra-arterial administration of OGD-PBMCs at 7 days after focal cerebral ischemia prompted expression of such factors in the brain parenchyma at 28 days following focal cerebral ischemia in vivo. Furthermore, administration of OGD-PBMCs induced an increasing number of stage-specific embryonic antigen-3-positive cells both in vitro and in vivo. Finally, it was found to prompt angiogenesis and axonal outgrowth, and functional recovery after cerebral ischemia. In conclusion, the administration of OGD-PBMCs might be a novel therapeutic strategy against ischemic stroke.

Tissue plasminogen activator (t-PA) treatment is beneficial for patients with ischemic stroke within 4.5 h of stroke onset, because the risk of intracerebral hemorrhagic transformation (HT) increases with delayed t-PA treatment. The benefits of t-PA thrombolysis are heavily dependent on time to treatment. Development of vasoprotective drugs that attenuate HT after delayed t-PA treatment might improve the prognosis of stroke patients and extend the therapeutic time window of t-PA and endovascular thrombolysis. An angiogenic factor, vascular endothelial growth factor (VEGF), might be associated with the blood-brain barrier (BBB) disruption after focal cerebral ischemia. By using a rat thromboembolic model, delayed t-PA treatment at 4 h after ischemia promoted expression of VEGF in BBB, matrix metalloproteinase-9 (MMP-9) activation, degradation of BBB components, and HT. We demonstrated that HT was inhibited by intravenous administration of an anti-VEGF neutralizing antibody/VEGF receptor antagonist. In addition, for clinical application, reverse translation studies, a path from bedside to bench, are necessary.

We report the case of a 71-year-old man with impaired left finger extension. The presence of nodular fibrosing lesions in his palm suggested Dupuytren contracture as the diagnosis. However, detailed neurological examination revealed muscle weakness associated with C7-Th1 lesions, and needle electromyography revealed denervation within the same distribution. Therefore, the patient was diagnosed with distal-type cervical spondylolisthesis muscular atrophy complicated with Dupuytren contracture. Due to shared symptoms with impaired finger extension, the other two conditions can be overlooked in patients affected by both diseases. Detailed clinical investigation of nodular fibrosing lesions, muscle weakness at the C7-Th1 level, and needle electromyography findings facilitate differential diagnosis of Dupuytren contracture and distal-type cervical spondylolisthesis. (Received June 24, 2019; Accepted September 17, 2019; Published November 1, 2019).

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is a corticosteroid-responsive meningoencephalomyelitis with a poorly understood pathogenesis. We examined and compared the levels of cytokines and biological markers in the cerebrospinal fluid (CSF) of patients with GFAP-A and other neurological disorders. We identified four cytokines (tumor necrosis factor alpha [TNFα], Interleukin [IL]-27, IL-6, and chemokine [C-C motif] ligand 20) and three biological markers (GFAP, S100 calcium-binding protein B, and neurofilament light chain) present at elevated levels in CSF samples during the acute phase of GFAP-A. Additionally, we identified significant correlations between CSF TNFα, IL-27, IL-6, and CSF biological markers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy remain to be elucidated. We describe here the clinical features of 14 patients with GFAP astrocytopathy confirmed by detection of GFAP-IgG in cerebrospinal fluid (CSF). The novel findings of this study are as follows. First, over half of the patients presented with movement disorders (tremor, myoclonus, and ataxia), autonomic dysfunction (mainly urinary dysfunction), and hyponatremia. Second, most patients showed transient elevation of adenosine deaminase activity levels in CSF. Finally, some patients showed bilateral hyperintensities in the posterior part of the thalamus on brain magnetic resonance imaging., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Methylmercury (MeHg) causes severe damage to the central nervous system, and there is increasing evidence of the association between MeHg exposure and vascular dysfunction, hemorrhage, and edema in the brain, but not in other organs of patients with acute MeHg intoxication. These observations suggest that MeHg possibly causes blood-brain barrier (BBB) damage. MeHg penetrates the BBB into the brain parenchyma via active transport systems, mainly the l-type amino acid transporter 1, on endothelial cell membranes. Recently, exposure to mercury has significantly increased. Numerous reports suggest that long-term low-level MeHg exposure can impair endothelial function and increase the risks of cardiovascular disease. The most widely reported mechanism of MeHg toxicity is oxidative stress and related pathways, such as neuroinflammation. BBB dysfunction has been suggested by both in vitro and in vivo models of MeHg intoxication. Therapy targeted at both maintaining the BBB and suppressing oxidative stress may represent a promising therapeutic strategy for MeHg intoxication. This paper reviews studies on the relationship between MeHg exposure and vascular dysfunction, with a special emphasis on the BBB.

The ischemic penumbra is both a concept in understanding the evolution of cerebral tissue injury outcome of focal ischemia and a potential therapeutic target for ischemic stroke. In this review, we examine the evidence that angiogenesis can contribute to beneficial outcomes following focal ischemia in model systems. Several studies have shown that, following cerebral ischemia, endothelial proliferation and subsequent angiogenesis can be detected beginning four days after cerebral ischemia in the border of the ischemic core, or in the ischemic periphery, in rodent and non-human primate models, although initial signals appear within hours of ischemia onset. Components of the neurovascular unit, its participation in new vessel formation, and the nature of the core and penumbra responses to experimental focal cerebral ischemia, are considered here. The potential co-localization of vascular remodeling and axonal outgrowth following focal cerebral ischemia based on the definition of tissue remodeling and the processes that follow ischemic stroke are also considered. The region of angiogenesis in the ischemic core and its surrounding tissue (ischemic periphery) may be a novel target for treatment. We summarize issues that are relevant to model studies of focal cerebral ischemia looking ahead to potential treatments.

Purpose: Mitochondrial encephalopathy with lactic acid and stroke-like episodes (MELAS) is caused by mutations in the mitochondrial DNA. Approximately 80% of MELAS patients have an A > G transition mutation at nucleotide pair 3243 in the mitochondrial DNA, m.3243A > G. There are also MELAS patients with a one-base deletion at nucleotide pair 3271 in the mitochondrial DNA, m.3271delT, but these cases are very rare. We report a case of MELAS with the m.3271delT and describe the retinal structure and electrophysiological alterations., Methods: The retinal structure and function of a 37-year-old woman who was referred to our clinic for of nyctalopia were studied. Standard ophthalmological examinations including the medical history, measurements of the best-corrected visual acuity, intraocular pressures, and slit-lamp biomicroscopy, ophthalmoscopy, fluorescein angiography, fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (ERG), and multifocal electroretinography (mfERG) were performed., Results: Fundus examination showed bilateral hypopigmentary changes of the retinal pigment epithelium which extended from the posterior pole to the equator. Fluorescein angiography showed patchy hyperfluorescence due to window defects at the atrophic areas. Fundus autofluorescence demonstrated mild hyperfluorescent lesions in both eyes. SD-OCT showed that the interdigitation zone was indistinct in both eyes, and the inner nuclear layer was slightly thinner. The amplitudes of the rod, cone, and 30-Hz flicker ERGs were severely reduced, and the implicit times were prolonged. The a- and b-waves of the bright-flash mixed rod-cone ERGs were also reduced. The dark-adapted oscillatory potentials were reduced. The amplitudes of the mfERGs were severely depressed except at the fovea in both eyes., Conclusions: These findings indicate that the RPE atrophy was wider and the rod dysfunction was more severe affected than that of previously reported MELAS cases with the m.3243A > G mutation.

We describe a 62-year-old man who developed subacute visual loss after cord blood stem cell transplantation for malignant lymphoma. Brain magnetic resonance imaging (MRI) showed bilateral hyperintense lesions in the occipital and parietal lobes. A diagnosis of progressive multifocal encephalopathy (PML) was established following brain biopsy and detection of JC virus (JCV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF). He developed optic ataxia and visual inattention, and was then diagnosed as having Bálint syndrome. After he was treated with mefloquine and mirtazapine, his Bálint syndrome and, MRI findings improved and the copy number of JCV DNA in the CSF decreased. In summary, we demonstrate that patient with PML may develop Bálint syndrome and that combination therapy using mefloquine and mirtazapine may be an effective treatment. (Received August 23, 2018; Accepted November 29, 2018; Published March 1, 2019).

Here, we report an autopsy-verified patient with MM2-coritical-type sporadic Creutzfeldt-Jakob disease (MM2C-type sCJD) presenting cortical blindness during a course of glaucoma and age-related macular degeneration, and focus on the difficulties involved in early clinical diagnosis. An 83-year-old man was admitted to our hospital 15 months after the onset of cortical blindness, and 9 months after the onset of progressive dementia. Neurological examination revealed dementia, frontal signs, visual disturbance, dysphagia, myoclonus and exaggerated tendon reflexes in the four extremities. Diffusion-weighted MRI (DW-MRI) showed cortical hyperintensities predominantly in the bilateral occipital lobes. PRNP gene analysis showed no mutations with methionine homozygosity at codon 129. Cerebrospinal fluid (CSF) examination revealed elevation of 14-3-3 and total tau protein. The symptoms progressed gradually, and the patient died of aspiration pneumonia, 30 months after the onset. Neuropathological examination revealed extensive large confluent vacuole-type spongiform changes in the cerebral cortices. Prion protein (PrP) immunostaining showed perivascular and plaque-type PrP deposits. We diagnosed our patient as MM2C-type sCJD. There are two difficulties in the early clinical diagnosis of MM2C-type sCJD with ocular disease in the elderly; delayed utilization of DW-MRI, and accompaniment of ocular disease. For early diagnosis of MM2C-type sCJD, we conclude that clinician should perform DW-MRI for patients with isolated dementia or cortical visual disturbance.

Chronic care patients undergoing hemodialysis for treatment of end-stage renal failure experience higher rates of bloodstream-associated infection due to the patients' compromised immune system and management of the bloodstream through catheters. Staphylococcus species are acommon cause of hemodialysis catheterrelated bloodstream infections. We investigated environmental bacterial contamination of dialysis wards and contamination of hemodialysis devices to determine the source of bacteria for these infections. All bacterial samples were collected by the swab method and the agarose stamp method. And which bacterium were identified by BBL CRYSTAL Kit or 16s rRNA sequences. In our data, bacterial cell number of hemodialysis device was lower than environment of patient surrounds. But Staphylococcus spp. were found predominantly on the hemodialysis device (46.8%), especially on areas frequently touched by healthcare-workers (such as Touch screen). Among Staphylococcus spp., Staphylococcus epidermidis was most frequently observed (42.1% of Staphylococcus spp.), and more surprising, 48.2% of the Staphylococcus spp. indicated high resistance for methicillin. Our finding suggests that hemodialysis device highly contaminated with bloodstream infection associated bacteria. This study can be used as a source to assess the risk of contamination-related infection and to develop the cleaning system for the better prevention for bloodstream infections in patients with hemodialysis. J. Med. Invest. 66 : 148-152, February, 2019.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the upper and lower motor neurons. Currently, only riluzole and edaravone are approved as drugs to treat ALS and new agents with larger effect sizes are warranted. Exploratory analyses in our previous study (study ID #E0302-J081-761) have suggested that high-dose methylcobalamin (E0302) prolonged the overall survival of ALS patients and suppressed ALS progression in patients with a disease duration of less than 12 months., Objective: This clinical trial aims to evaluate the efficacy and safety of E0302 for treatment of ALS patients within one year of onset., Methods: The Japanese early-stage trial of high-dose methylcobalamin for ALS (JETALS) is a prospective, multicenter, placebo-controlled, double-blind, randomized phase III study conducted at 24 tertiary neurology centers and is funded by the Japan Agency for Medical Research and Development. A total of 128 ALS patients within one year of onset were randomized at a 1:1 ratio to receive intramuscular injection with E0302 50 mg or placebo twice a week for 16 weeks. The primary endpoint is changes in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score at 16 weeks. If patients wish to receive E0302 50 mg after the double-blind administration period, E0302 will be provided to them until March 2020 during the continuous administration period., Results: This study began in October 2017 and is being conducted at 24 participating institutions in Japan. The study is in progress and the patient enrollment period is scheduled to end in August 2019, with follow-up scheduled to end in March 2020., Conclusions: This study is being performed to revalidate the efficacy and safety of E0302 in patients with early-stage ALS in the first year of symptom onset. If positive results are obtained, the aim is to apply for E0302 approval as a new drug for the treatment of ALS., Trial Registration: ClinicalTrials.gov NCT03548311; https://clinicaltrials.gov/ct2/show/NCT03548311 (Archived by WebCite at http://www.webcitation.org/74Fw3rDzb)., International Registered Report Identifier (irrid): PRR1-10.2196/12046., (©Ryosuke Oki, Yuishin Izumi, Hiroyuki Nodera, Yasutaka Sato, Hiroshi Nokihara, Kazuaki Kanai, Masahiro Sonoo, Makoto Urushitani, Kazuto Nishinaka, Naoki Atsuta, Nobuo Kohara, Toshio Shimizu, Hitoshi Kikuchi, Masaya Oda, Ken Ikeda, Makiko Nagai, Kiyonobu Komai, Yasuhiro Kojima, Daisuke Kuzume, Sagiri Isose, Shun Shimohama, Koji Abe, Hidefumi Ito, Kazuyuki Noda, Tomohiko Ishihara, Mitsuya Morita, Takayoshi Shimohata, Satoshi Teramukai, Tatsuo Kagimura, Kensuke Noma, Hiroaki Yanagawa, Satoshi Kuwabara, Ryuji Kaji, JETALS. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 21.12.2018.)

Influenza A viruses (IAVs) pose a serious global threat to humans and their livestock, especially poultry and pigs. This study aimed to investigate how to inactivate IAVs by using different ultraviolet-light-emitting diodes (UV-LEDs). We developed sterilization equipment with light-emitting diodes (LEDs) those peak wavelengths were 365 nm (UVA-LED), 310 nm (UVB-LED), and 280 nm (UVC-LED). These UV-LED irradiations decreased dose fluence-dependent plaque-forming units of IAV H1N1 subtype (A/Puerto Rico/8/1934) infected Madin-Darby canine kidney (MDCK) cells, but the inactivation efficiency of UVA-LED was significantly lower than UVB- and UVC-LED. UV-LED irradiations did not alter hemagglutination titer, but decreased accumulation of intracellular total viral RNA in infected MDCK cells was observed. Additionally, UV-LED irradiations suppressed the accumulation of intracellular mRNA (messenger RNA), vRNA (viral RNA), and cRNA (complementary RNA), as measured by strand-specific RT-PCR. These results suggest that UV-LEDs inhibit host cell replication and transcription of viral RNA. Both UVB- and UVC-LED irradiation decreased focus-forming unit (FFU) of H5N1 subtype (A/Crow/Kyoto/53/2004), a highly pathogenic avian IAV (HPAI), in infected MDCK cells, and the amount of FFU were lower than the H1N1 subtype. From these results, it appears that IAVs may have different sensitivity among the subtypes, and UVB- and UVC-LED may be suitable for HPAI virus inactivation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: We evaluated the morphology of amyloid fibrils in the peripheral nervous system using biopsy or autopsy specimens from hereditary transthyretin amyloidosis patients. The impact of amyloid fibril formation on neighboring tissues was also investigated., Methods: Sural nerve biopsy specimens from 34 patients were examined using electron microscopy. Twenty-eight patients had Val30Met mutations, and the remaining 6 patients had non-Val30Met mutations (i.e., Glu54Lys, Pro24Ser, Thr49Ala, Val71Ala, Val94Gly, and Ala97Gly). The patients with the Val30Met mutation included a case from Brazil (supposedly of Portuguese origin), 6 early-onset cases from endemic foci in Japan, and 21 late-onset cases from non-endemic areas in Japan., Results: Long amyloid fibers were abundant in the early-onset Val30Met cases from the Japanese endemic foci and Brazil, whereas the amyloid fibrils were generally short in the late-onset Val30Met and non-Val30Met cases. The amyloid fibrils seemed to mature from dotty structures among amorphous electron-dense extracellular materials and pull surrounding tissues during the maturation process. The distortion of Schwann cells close to amyloid fibril masses was conspicuous, particularly in cases with long amyloid fibrils. Atrophy was conspicuous in non-myelinating Schwann cells and bands of Büngner (i.e., Schwann cell subunits that previously contained myelinated axons), particularly those completely surrounded by amyloid fibrils. In contrast, the myelinated fibers tended to be only partially surrounded by amyloid fibrils and morphologically preserved due to their large size. Only a few demyelinated axons were found., Conclusion: Pre-fibrillar amyloid precursors appear to play a pivotal role during the initial phase of amyloid fibril formation. The mechanical distortion and subsequent atrophy of Schwann cells resulting from the elongation of amyloid fibrils may be related to small-fiber predominant loss, which is a classical characteristic of amyloid neuropathy. Although rather rare, the destruction of myelin (i.e., demyelination) resulting from amyloid deposition may relate to nerve conduction abnormalities mimicking chronic inflammatory demyelinating polyneuropathy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Study Objectives: Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the combination of cerebellar ataxia, parkinsonism, and autonomic disturbance. Patients with MSA frequently have sleep-disordered breathing. In some patients with MSA, central sleep apnea manifests during the disease's natural course or as a treatment effect. Breathing instability may be involved in the development of obstructive sleep apnea (OSA); therefore, we investigated whether breathing instability affects the severity of OSA in patients with MSA., Methods: Patients with MSA and a control group of individuals who were matched for age, body mass index (BMI), and supine apnea-hypopnea index (AHI) were recruited. Breathing instability was evaluated by using polysomnography to determine the irregular pattern with approximate entropy (ApEn) of chest respiratory movements during wakefulness before sleep onset. The ApEn values were compared between the groups. The severity of OSA was evaluated with background parameters and ApEn values by regression analysis., Results: Twenty patients with MSA (9 men; mean age, 61 years; BMI, 24.1 kg/m 2 ; supine AHI, 37.9 events/h) were compared to the control group. The ApEn values were higher in the patients with MSA than those in the control group (1.28 versus 1.11; P < .05). Multiple regression analysis showed that supine AHI was associated with ApEn values but not with BMI in patients with MSA and associated with BMI but not with ApEn values in the individuals in the control group., Conclusions: Patients with MSA had more breathing irregularity. In patients with MSA, breathing instability may be a more influential factor for OSA than BMI., Commentary: A commentary on this article appears in this issue on page 1641., (© 2018 American Academy of Sleep Medicine.)

Campylobacter jejuni is a major cause of bacterial foodborne illness in humans worldwide. Bacterial entry into a host eukaryotic cell involves the initial steps of adherence and invasion, which generally activate several cell-signaling pathways that induce the activation of innate defense systems, which leads to the release of proinflammatory cytokines and induction of apoptosis. Recent studies have reported that the unfolded protein response (UPR), a system to clear unfolded proteins from the endoplasmic reticulum (ER), also participates in the activation of cellular defense mechanisms in response to bacterial infection. However, no study has yet investigated the role of UPR in C. jejuni infection. Hence, the aim of this study was to deduce the role of UPR signaling via induction of ER stress in the process of C. jejuni infection. The results suggest that C. jejuni infection suppresses global protein translation. Also, 12 h of C. jejuni infection induced activation of the eIF2α pathway and expression of the transcription factor CHOP. Interestingly, bacterial invasion was facilitated by knockdown of UPR-associated signaling factors and treatment with the ER stress inducers, thapsigargin and tunicamycin, decreased the invasive ability of C. jejuni. An investigation into the mechanism of UPR-mediated inhibition of C. jejuni invasion showed that UPR signaling did not affect bacterial adhesion to or survival in the host cells. Further, Salmonella Enteritidis or FITC-dextran intake were not regulated by UPR signaling. These results indicated that the effect of UPR on intracellular intake was specifically found in C. jejuni infection. These findings are the first to describe the role of UPR in C. jejuni infection and revealed the participation of a new signaling pathway in C. jejuni invasion. UPR signaling is involved in defense against the early step of C. jejuni invasion and thus presents a potential therapeutic target for the treatment of C. jejuni infection., Competing Interests: The authors have declared that no competing interests exist.

The clinical features of cerebellar ataxia associated with anti-metabotropic glutamate receptor 1 (mGluR1) autoantibodies, a rare autoimmune-mediated cerebellar ataxia, remain to be elucidated. Here, we describe a patient with non-paraneoplastic cerebellar ataxia associated with anti-mGluR1 autoantibodies, who was followed up over 5 years. She presented with relapses and remissions of subacute progressive cerebellar ataxia that were responsive to immunotherapy. Although serum anti-mGluR1 autoantibodies were continuously detected and cerebellar atrophy gradually progressed, repeated intravenous immunoglobulin therapy and oral immunosuppressants ensured cerebellar ataxia remained at almost the same level during the observation period., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To determine predictors of cognitive impairment and frontal dysfunction in patients with multiple system atrophy (MSA)., Methods: We recruited 59 patients with MSA and determined the predictors of a decline in the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores., Results: The MMSE scores negatively correlated with disease duration, Unified MSA Rating Scale (UMSARS) part 1 and 4 scores, and residual urine volume, and positively correlated with the coefficient of variation of electrocardiographic RR intervals. The FAB scores negatively correlated with the UMSARS part 2 score, periventricular hyperintensity grade, and deep white matter hyperintense signal grade. A significant predictor of rapidly progressive cognitive impairment was a high residual urine volume., Conclusions: Impairment of global cognitive function correlates with the long-term disease duration, global disability due to the disease, and autonomic dysfunction, whereas frontal dysfunction correlates with motor function and degeneration of cerebral white matter., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The cerebellum is one of the main targets in the central nervous system for autoimmunity. Immune-mediated cerebellar ataxias include gluten ataxia, GAD antibody-associated cerebellar ataxia, Hashimoto's encephalopathy, and paraneoplastic cerebellar degeneration. Autoimmune cerebellar ataxia may be of either insidious or subacute onset, and vertigo or transient neurological symptoms occur in some patients before the onset of the disease, in contrast to spinocerebellar degeneration. If autoimmune cerebellar ataxia is suspected, early diagnosis and introduction of treatment are very important. For diagnosis, testing for gliadin antibody, TG6 antibody, GAD antibody, thyroid antibody, and anti-neuronal antibodies, including mGluR1, is useful. Magnetic resonance imaging voxel-based morphometry is also useful because it can detect cortical cerebellar atrophy of autoimmune cerebellar ataxia, different from spinocerebellar ataxia. As for treatment, it is important to remove autoimmune triggering factors (e.g.,dietary gluten or neoplasm). When the ataxia symptoms are causing hindrances in the daily life, it is worth considering immunotherapy including IVIg, steroid therapy and so on.

We report a Japanese patient with spinocerebellar ataxia type 31 (SCA31) and sporadic Creutzfeldt-Jakob disease (sCJD). A 52-year-old man developed progressive cognitive impairment after the appearance of cerebellar symptoms. Brain MR diffusion-weighted imaging (DWI) demonstrated a slowly expanding hyperintense lesion in the cerebral cortex. The patient was finally diagnosed as having both SCA31 and sCJD by identification of genetic mutations and by real-time quaking-induced conversion (RT-QUIC) analysis of the cerebrospinal fluid (CSF), respectively. Here, we report the clinical details of this rare combined case, with particular reference to the association between prion protein and the early onset of SCA31.

Several environmental factors during the prenatal period transgenerationally affect the health of newborns in later life. Because low-dose antibiotics have been used for promoting the growth of crops and livestock in agriculture, humans may have ingested residual antibiotics for several decades. However, the effect of prenatal administration of low-dose antibiotics on newborns' health in later life is unclear. In the present study, we found that prenatal treatment of murine mothers with low-dose antibiotics increased the abundance of bacteria of the phylum Firmicutes and the genera Clostridium IV and XIVa in feces from pups. In addition, the body fat percentage of mice in the antibiotic-treated group was higher than those in the control group at 12 weeks of age even though all pups were fed a standard diet. The body fat percentage of all mice was correlated with the abundance of fecal bacteria of Clostridium IV and XIVa . These results predict that low-dose antibiotic administration during the prenatal period affects the gut microbiota of newborns and possibly their health in later life., Competing Interests: No potential conflicts of interest were disclosed.

Campylobacter jejuni invasion is closely related to C. jejuni pathogenicity. The intestinal epithelium contains polarized epithelial cells that form tight junctions (TJs) to provide a physical barrier against bacterial invasion. Previous studies indicated that C. jejuni invasion of non-polarized cells involves several cellular features, including lipid rafts. However, the dynamics of C. jejuni invasion of polarized epithelial cells are not fully understood. Here we investigated the interaction between C. jejuni invasion and TJ formation to characterize the mechanism of C. jejuni invasion in polarized epithelial cells. In contrast to non-polarized epithelial cells, C. jejuni invasion was not affected by depletion of lipid rafts in polarized epithelial cells. However, depletion of lipid rafts significantly decreased C. jejuni invasion in TJ disrupted cells or basolateral infection and repair of cellular TJs suppressed lipid raft-mediated C. jejuni invasion in polarized epithelial cells. In addition, pro-inflammatory cytokine, TNF-α treatment that induce TJ disruption promote C. jejuni invasion and lipid rafts depletion significantly reduced C. jejuni invasion in TNF-α treated cells. These data demonstrated that TJs prevent C. jejuni invasion from the lateral side of epithelial cells, where they play a main part in bacterial invasion and suggest that C. jejuni invasion could be increased in inflammatory condition. Therefore, maintenance of TJs integrity should be considered important in the development of novel therapies for C. jejuni infection.

The number of plant factories in which crops are cultivated in an artificial environment has been increasing every year. In cultivation techniques involving hydroponics, plants are supplied with a circulating nutrient solution, which can become contaminated by pathogens that can propagate and spread throughout plant factories. Therefore, strategies to disinfect hydroponic nutrient solutions are needed. In this study, we developed a new disinfection device equipped with an ultraviolet A (UVA) light emitting diode (LED) that can be used to disinfect hydroponic nutrient solutions in plant factories. We first evaluated the basic disinfection capability of the device and then estimated its bactericidal effect in a small scale model system. The log survival ratio was related to UVA irradiation fluence and the volume of nutrient solution. From the assay results, we devised a kinetics equation to describe the relationship between nutrient solution volume, log survival ratio, and UVA fluence. Together our results show that UVA irradiation could be used to disinfect hydroponic nutrient solutions, and the derived kinetics equations can be used to determine optimal conditions, such as nutrient solution volume, UVA irradiation, and killing activity, to develop devices that disinfect hydroponic nutrient solutions. J. Med. Invest. 65:171-176, August, 2018.

Background/aims: Hyperphosphatemia is a serious complication of late-stage chronic kidney disease (CKD). Intestinal inorganic phosphate (Pi) handling plays an important role in Pi homeostasis in CKD. We investigated whether intestinal alkaline phosphatase 3 (Akp3), the enzyme that hydrolyzes dietary Pi compounds, is a target for the treatment of hyperphosphatemia in CKD., Methods: We investigated Pi homeostasis in Akp3 knockout mice (Akp3-/-). We also studied the progression of renal failure in an Akp3-/- mouse adenine treated renal failure model. Plasma, fecal, and urinary Pi and Ca concentration were measured with commercially available kit, and plasma fibroblast growth factor 23, parathyroid hormone, and 1,25(OH)2D3 concentration were measured with ELISA. Brush border membrane vesicles were prepared from mouse intestine using the Ca2+ precipitation method and used for Pi transport activity and alkaline phosphatase activity. In vivo intestinal Pi absorption was measured with oral 32P administration., Results: Akp3-/- mice exhibited reduced intestinal type II sodium-dependent Pi transporter (Npt2b) protein levels and Na-dependent Pi co-transport activity. In addition, plasma active vitamin D levels were significantly increased in Akp3-/- mice compared with wild-type animals. In the adenine-induced renal failure model, Akp3 gene deletion suppressed hyperphosphatemia., Conclusion: The present findings indicate that intestinal Akp3 deletion affects Na+-dependent Pi transport in the small intestine. In the adenine-induced renal failure model, Akp3 is predicted to be a factor contributing to suppression of the plasma Pi concentration., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

It is thought that posterior reversible encephalopathy syndrome (PRES) is both clinically and radiologically reversible. However, its reversible nature has been challenged based on reports of permanent neurological impairments. The factors that predict the development of irreversible neurological impairment are still unclear. In the present study, we investigated clinical manifestations, laboratory findings, and neuroradiological images to identify predictors of functional outcomes in PRES. We investigated 23 PRES patients. Apparent diffusion coefficient (ADC) reduction was observed in 4 patients in the poor outcome group, whereas no patients presented ADC reduction in the favourable outcome group (p<0.01). Further studies are warranted to evaluate the association between ADC reduction and functional outcome after PRES., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Stroke is a leading cause of morbidity and mortality worldwide, and consists of two types, ischemic and hemorrhagic. Currently, there is no effective treatment to increase the survival rate or improve the quality of life after ischemic and hemorrhagic stroke in the subacute to chronic phases. Therefore, it is necessary to establish therapeutic strategies to facilitate functional recovery in patients with stroke during both phases. Cell-based therapies, using microglia and monocytes/macrophages preconditioned by optimal stimuli and/or any therapies targeting these cells, might be an ideal therapeutic strategy for managing stroke. Microglia and monocytes/macrophages polarize to the classic pro-inflammatory type (M1-like) or alternative protective type (M2-like) by optimal condition. Cell-based therapies using M2-like microglia and monocytes/macrophages might be protective therapeutic strategies against stroke for three reasons. First, M2-like microglia and monocytes/monocytes secrete protective remodeling factors, thus prompting neuronal network recovery via tissue (including neuronal) and vascular remodeling. Second, these cells could migrate to the injured hemisphere through the blood-brain barrier or choroid-plexus. Third, these cells could mitigate the extent of inflammation-induced injuries by suitable timing of therapeutic intervention. Although future translational studies are required, M2-like microglia and monocytes/macrophages therapies are attractive for managing stroke based on their protective functions., Competing Interests: Takayoshi Shimohata is an academic adviser of the ShimoJani LLC biotech company. The other authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Campylobacter jejuni is a foodborne pathogen that induces gastroenteritis. Invasion and adhesion are essential in the process of C. jejuni infection leading to gastroenteritis. The mucosal layer plays a key role in the system of defense against efficient invasion and adhesion by bacteria, which is modulated by several ion channels and transporters mediated by water flux in the intestine. The cystic fibrosis transmembrane conductance regulator (CFTR) plays the main role in water flux in the intestine, and it is closely associated with bacterial clearance. We previously reported that C. jejuni infection suppresses CFTR channel activity in intestinal epithelial cells; however, the mechanism and importance of this suppression are unclear. This study sought to elucidate the role of CFTR in C. jejuni infection. Using HEK293 cells that stably express wild-type and mutated CFTR, we found that CFTR attenuated C. jejuni invasion and that it was not involved in bacterial adhesion or intracellular survival but was associated with microtubule-dependent intracellular transport. Moreover, we revealed that CFTR attenuated the function of the microtubule motor protein, which caused inhibition of C. jejuni invasion, but did not affect microtubule stability. Meanwhile, the CFTR mutant G551D-CFTR, which had defects in channel activity, suppressed C. jejuni invasion, whereas the ΔF508-CFTR mutant, which had defects in maturation, did not suppress C. jejuni invasion, suggesting that CFTR suppression of C. jejuni invasion is related to CFTR maturation but not channel activity. When these findings are taken together, it may be seen that mature CFTR inhibits C. jejuni invasion by regulating microtubule-mediated pathways. We suggest that CFTR plays a critical role in cellular defenses against C. jejuni invasion and that suppression of CFTR may be an initial step in promoting cell invasion during C. jejuni infection., (Copyright © 2017 American Society for Microbiology.)

The sugar alcohol xylitol inhibits the growth of some bacterial species including Streptococcus mutans . It is used as a food additive to prevent caries. We previously showed that 1.5-4.0 g/kg body weight/day xylitol as part of a high-fat diet (HFD) improved lipid metabolism in rats. However, the effects of lower daily doses of dietary xylitol on gut microbiota and lipid metabolism are unclear. We examined the effect of 40 and 200 mg/kg body weight/day xylitol intake on gut microbiota and lipid metabolism in mice. Bacterial compositions were characterized by denaturing gradient gel electrophoresis and targeted real-time PCR. Luminal metabolites were determined by capillary electrophoresis electrospray ionization time-of-flight mass spectrometry. Plasma lipid parameters and glucose tolerance were examined. Dietary supplementation with low- or medium-dose xylitol (40 or 194 mg/kg body weight/day, respectively) significantly altered the fecal microbiota composition in mice. Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella , whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism., Competing Interests: The authors declare no conflict of interest.

Objective: To clarify the clinical features and risk factors of cervicogenic headache (CEH; as diagnosed according to the International Classification of Headache Disorders-Third Edition beta) in patients with cervical spine disorders requiring surgery., Background: CEH is caused by cervical spine disorders. The pathogenic mechanism of CEH is hypothesized to involve a convergence of the upper cervical afferents from the C1, C2, and C3 spinal nerves and the trigeminal afferents in the trigeminocervical nucleus of the upper cervical cord. According to this hypothesis, functional convergence of the upper cervical and trigeminal sensory pathways allows the bidirectional (afferent and efferent) referral of pain to the occipital, frontal, temporal, and/or orbital regions. Previous prospective studies have reported an 86-88% prevalence of headache in patients with cervical myelopathy or radiculopathy requiring anterior cervical surgery; however, these studies did not diagnose headache according to the International Classification of Headache Disorders criteria. Therefore, a better understanding of the prevalence rate, clinical features, risk factors, and treatment responsiveness of CEH in patients with cervical spine disorders requiring surgery is necessary., Methods: We performed a single hospital-based prospective cross-sectional study and enrolled 70 consecutive patients with cervical spine disorders such as cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, cervical spondylotic radiculopathy, and cervical spondylotic myeloradiculopathy who had been scheduled to undergo anterior cervical fusion or dorsal cervical laminoplasty between June 2014 and December 2015. Headache was diagnosed preoperatively according to the International Classification of Headache Disorders-Third Edition beta. The Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire, Neck Disability Index, and a 0-100 mm visual analog scale (VAS) were used to evaluate clinical features, and scores were compared between baseline (ie, preoperatively) and 3, 6, and 12 months post-surgery., Results: The prevalence of CEH in our population was 15/70 (21.4%, 95%CI: 11.8% to 31.0%). The main clinical features were dull and tightening/pressing headache sensations in the occipital region. Headache severity was mild (VAS, 32 ± 11 mm) and only one patient reported use of an oral analgesic. Compared to patients without CEH, patients with CEH had higher frequencies of neck pain (86.7% vs. 50.9%; P = .017), cervical range of motion limitation (ROM) (66.7% vs. 38.2%; P = .049), and higher Neck Disability Index scores (14 vs. 3; P < .001). Among the different cervical spine disorders, the prevalence of CEH was highest in cervical spondylotic myeloradiculopathy patients (60%), being ≤ 20% for all other disorders. Surgical treatments including cervical laminoplasty to relieve abnormal pressure on the spinal cord via a posterior approach, were associated with initial improvements in headache VAS that slightly diminished by 12 months post-surgery (P < .001)., Conclusions: We report a lower prevalence of CEH in patients with cervical spinal disorders requiring surgery than that reported previously. The main clinical features of CEH were mild, dull, and tightening/pressing headache sensations in the occipital region. Potential risk factors for CEH included neck pain, limited cervical ROM, high Neck Disability Index score, and a diagnosis of cervical spondylotic myeloradiculopathy. The further accumulation of patients in a multi-institutional study may be required in order to discuss the diagnostic criteria and pathophysiology of this condition., (© 2017 American Headache Society.)

Objective/background: Multiple system atrophy (MSA) frequently results in the development of sleep-disordered breathing (SDB). Few reports have described the natural course of this phenomenon. The aim of the present study was to determine the natural course of SDB and prognostic factors associated with such conditions in MSA., Patients/methods: Twenty-four consecutive patients were recruited with probable MSA, who had not been treated with continuous positive airway pressure (CPAP) and had undergone overnight polysomnography (PSG) more than once following the development of snoring or stridor. Based on changes in the apnea-hypopnea index (AHI) over the course of the disease, patients were divided into two groups (AHI-maintained and AHI-deteriorated) and the clinical findings were compared., Results: Mean duration between the first and last PSG was 2.4 ± 1.5 years, and patients underwent PSG assessment an average of 2.5 ± 0.6 times during this period. During this interval, AHI increased from 19.4 ± 22.8/hour to 34.4 ± 30.1/hour (p = 0.006), although spontaneous improvement was observed in 29% of patients. Following the first PSG, all patients were diagnosed with obstructive sleep apnea; however, the SDB type changed from obstructive sleep apnea to central sleep apnea in 3 of the 24 (13%) patients during the period between the first and last PSG., Conclusions: Although SDB associated with MSA exacerbates with disease progression, spontaneous improvement in AHI may occur in some patients. Earlier development of snoring or stridor may predict rapid progression of SDB in MSA., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Abstract : Non-caloric artificial sweeteners (NASs) provide sweet tastes to food without adding calories or glucose. NASs can be used as alternative sweeteners for controlling blood glucose levels and weight gain. Although the consumption of NASs has increased over the past decade in Japan and other countries, whether these sweeteners affect the composition of the gut microbiome is unclear. In the present study, we examined the effects of sucralose or acesulfame-K ingestion (at most the maximum acceptable daily intake (ADI) levels, 15 mg/kg body weight) on the gut microbiome in mice. Consumption of sucralose, but not acesulfame-K, for 8 weeks reduced the relative amount of Clostridium cluster XIVa in feces. Meanwhile, sucralose and acesulfame-K did not increase food intake, body weight gain or liver weight, or fat in the epididymis or cecum. Only sucralose intake increased the concentration of hepatic cholesterol and cholic acid. Moreover, the relative concentration of butyrate and the ratio of secondary/primary bile acids in luminal metabolites increased with sucralose consumption in a dose-dependent manner. These results suggest that daily intake of maximum ADI levels of sucralose, but not acesulfame-K, affected the relative amount of the Clostridium cluster XIVa in fecal microbiome and cholesterol bile acid metabolism in mice., Competing Interests: The authors declare no conflict of interest.