Notes

Autoimmune Liver disease: Serum Autoantibodies inside Medical Apply.
Perceiving speech in noise (SIN) is important for health and well-being and decreases with age. Musicians show improved speech-in-noise abilities and reduced age-related auditory decline, yet it is unclear whether short term music engagement has similar effects. In this randomized control trial we used a pre-post design to investigate whether a 12-week music intervention in adults aged 50-65 without prior music training and with subjective hearing loss improves well-being, speech-in-noise abilities, and auditory encoding and voluntary attention as indexed by auditory evoked potentials (AEPs) in a syllable-in-noise task, and later AEPs in an oddball task. Age and gender-matched adults were randomized to a choir or control group. Choir participants sang in a 2-hr ensemble with 1-hr home vocal training weekly; controls listened to a 3-hr playlist weekly, attended concerts, and socialized online with fellow participants. From pre- to post-intervention, no differences between groups were observed on quantitative measures of well-being or behavioral speech-in-noise abilities. In the choir group, but not the control group, changes in the N1 component were observed for the syllable-in-noise task, with increased N1 amplitude in the passive condition and decreased N1 latency in the active condition. During the oddball task, larger N1 amplitudes to the frequent standard stimuli were also observed in the choir but not control group from pre to post intervention. Findings have implications for the potential role of music training to improve sound encoding in individuals who are in the vulnerable age range and at risk of auditory decline.We report a rare case of asymptomatic aplastic or twig-like middle cerebral artery (Ap/T-MCA) with small unruptured aneurysms at the origin (A1) of the anomalous collateral artery containing plexiform (twig-like) networks and in the anterior communicating artery. In Ap/T-MCA, other cerebrovascular systems are usually considered to exhibit normal findings not associated with atherosclerosis. At first admission, atherosclerotic M1 occlusion was suspected because of the patient's risk factors and multiple stenoses in major intracranial arteries. Cerebral blood flow (CBF) studies revealed reduction of resting CBF and vascular reserve in the ipsilateral MCA territory. After 5 years, a diagnosis of Ap/T-MCA was reached based on detailed image examination and intraoperative findings during aneurysm clipping in combination with extracranial-intracranial (EC-IC) bypass. It should be noted that atherosclerosis can coexist with Ap/T-MCA, which is considered a congenital anomaly in which bleeding often occurs due to a ruptured aneurysm within the fragile collateral vessels. In previous reports, A1 aneurysms at the origins of the collateral arteries ruptured even when they were small. Aggressive radical surgery using EC-IC bypass can be considered for the treatment of unruptured aneurysms associated with Ap/T-MCA, but further research is needed. (Received September 14, 2020; Accepted November 4, 2020; Published 1 April, 2021).Anorexia nervosa (AN) is a serious psychiatric disorder characterized by disturbances in body- and self-perception and excessive weight loss. AN is sometimes refractory to conventional treatments such as medication and psychological therapy. Therefore, the neurosurgery for psychiatric disorders (NPD) has been studied. While the efficacy of NPD has previously been reported and is currently being studied, it is not performed in Japan. We introduce the results of representative studies that investigated functional neurosurgery for AN. (Received May 22, 2020; Accepted November 20, 2020; Published April 1, 2021).Although the involvement of genomic factors in bipolar disorder is clear, its neural basis remains a question. We proposed the mitochondrial dysfunction hypothesis of bipolar disorder in 2000 and have since been testing it. Our results showed that mitochondrial DNA (mtDNA) polymorphisms affected mitochondrial Ca2+ concentration, and mitochondrial Ca2+ uptake and intracellular Ca2+ signaling were altered. gp91ds-tat in vitro Spontaneous repetitive depressive episodes were seen in mice in which mtDNA mutations accumulated in the brain (mutant Polg transgenic mice). We searched for the brain regions with the accumulation of mutant mtDNA in these mice, and found that it was most abundant in the paraventricular nucleus of the thalamus (PVT). Neural circuit manipulation of the PVT caused similar repetitive hypoactive episodes, suggesting that the PVT may be involved in causing bipolar disorder.Galcanezumab, a CGRP monoclonal antibody drug, has been approved by the U.S. Food and Drug Administration (FDA) for the prevention of recurrent cluster headaches. This was done after a randomized, double-blind, placebo-controlled trial found it to be effective and safe. Similarly sphenopalatine ganglion stimulation has been found to be effective and safe in a randomized, controlled trial as an acute treatment for chronic cluster headache. This article reviews the mechanisms of action of these therapies and their clinical trial results, clinical uses, and prospects in Japan.Migraine and cluster headache are common headache disorders that impact patients' quality of life. The pharmacotherapy for acute headache attacks is sometimes ineffective, and the adherence to preventive medications is low due to their side effects and/or lack of efficacy. Recently, several non-invasive neuromodulation devices for primary headache disorders have been launched and attracted the attention of patients and physicians because of their practicality, safety, and the possibility of becoming new treatment options. In this review, we describe external trigeminal nerve stimulation (eTNS), non-invasive vagal nerve stimulation (nVNS), and single-pulse transcranial magnetic stimulation (sTMS) which have been well studied in recent randomized sham-controlled trials and open-label studies. We also describe their mechanisms of action and adverse events.Migraine is a common and debilitating neurological disorder characterized by recurrent headaches of moderate-to-severe intensity. Because of its high prevalence, migraine causes a considerable financial burden on society. There is ample evidence showing that migraine is a complex neurological disorder that involves not only the trigeminovascular and autonomic systems, but also the hypothalamus and cerebral cortex. Calcitonin gene-related peptide (CGRP) was originally discovered as a 37-amino acid neuropeptide derived from a calcitonin gene splicing variant, is enriched in trigeminal ganglion neurons. Much attention has been paid to CGRP since it was found to be released from trigeminal terminals in animal migraine models. Subsequent studies demonstrated that CGRP administration induced migraine-like headaches specifically in migraineurs, thus highlighting its pivotal role CGRP in the development of migraine attacks. Monoclonal antibodies targeting CGRP and its receptor exhibited consistent efficacy for migraine prophylaxis with excellent safety profiles in clinical trials. Furthermore, emerging data support the long-term safety and efficacy of these antibodies. On the other hand, there are several concerns that have newly surfaced in the real-world setting. In this review, the development and perspective of anti-migraine therapeutic strategies using CGRP-related antibodies are discussed.The calcitonin gene-related peptide (CGRP) has been shown to play a major role in the pathophysiology of migraine in recent years. Studies have suggested that blocking CGRP signaling is an effective preventive and therapeutic strategy in patients with migraine. Triptans, considered the mainstay of antimigraine treatment cause vasoconstriction; however, gepants and ditans (two novel classes of therapeutic agents) inhibit CGRP release but do not show a vasoconstrictor effect. Both these drugs are awaiting clinical approval in Japan as antimigraine medications that can be administered to patients with cardiovascular risk factors and to those with triptan-refractory migraine.Migraine is the sixth most common cause of disability worldwide. Historically, three theories regarding the etiology of headache have been suggested vascular, neuronal, and trigeminovascular. However, the mechanism of migraine is still unknown. The advantages of studying the premonitory phase are several as it is the earliest clinical change during a migraine attack, and hence, is likely to disclose brain areas involved right at the beginning. Studying this phase may also allow to reveal the generator of migraine. In human neurophysiology, human functional neuroimaging, and preclinical biochemical studies, the relationship between the premonitory phase and hypothalamus has been suggested. On the other hand, calcitonin gene-related peptide (CGRP) has now been firmly established as a key player in migraine. Trigeminal CGRP and its roles in vasodilation, neurogenic inflammation, and peripheral sensitization are likely to be the most relevant peripheral actions causing the condition. CGRP could also be acting as a neuromodulator of light aversion, central sensitization, and cortical spreading depression (CSD).Carbohydrate recognition by lectins governs critical host-microbe interactions. MpPA14 (Marinomonas primoryensis PA14 domain) lectin is a domain of a 1.5-MDa adhesin responsible for a symbiotic bacterium-diatom interaction in Antarctica. Here, we show that MpPA14 binds various monosaccharides, with l-fucose and N-acetylglucosamine being the strongest ligands (dissociation constant [Kd ], ∼150 μM). High-resolution structures of MpPA14 with 15 different sugars bound elucidated the molecular basis for the lectin's apparent binding promiscuity but underlying selectivity. MpPA14 mediates strong Ca2+-dependent interactions with the 3,4-diols of l-fucopyranose and glucopyranoses, and it binds other sugars via their specific minor isomers. Thus, MpPA14 only binds polysaccharides like branched glucans and fucoidans with these free end groups. Consistent with our findings, adhesion of MpPA14 to diatom cells was selectively blocked by l-fucose, but not by N-acetyl galactosamine. The MpPA14 lectin homolog present in a Vi our work gives critical insight into an antiadhesion strategy to treat bacterial infections.Leishmania are sandfly-transmitted protists that induce granulomatous lesions in their mammalian host. Although infected host cells in these tissues can exist in different activation states, the extent to which intracellular parasites stages also exist in different growth or physiological states remains poorly defined. Here, we have mapped the spatial distribution of metabolically quiescent and active subpopulations of Leishmania mexicana in dermal granulomas in susceptible BALB/c mice, using in vivo heavy water labeling and ultra high-resolution imaging mass spectrometry. Quantitation of the rate of turnover of parasite and host-specific lipids at high spatial resolution, suggested that the granuloma core comprised mixed populations of metabolically active and quiescent parasites. Unexpectedly, a significant population of metabolically quiescent parasites was also identified in the surrounding collagen-rich, dermal mesothelium. Mesothelium-like tissues harboring quiescent parasites progressively replaced macrophage-rich granuloma tissues following treatment with the first-line drug, miltefosine.
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