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Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG-exp/ACAGG-exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG-exp and truncating variants supports the loss-of-function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG-exp and AAGGG-exp. RNA fluorescence in situ hybridization of the 2 patients revealed CCTGT- and CCCTT-containing RNA foci, respectively, in neuronal nuclei of tissues with neuronal loss. Our findings suggest that RNA toxicity may be involved in the pathogenesis of CANVAS. ANN NEUROL 2024;95:607-613., (© 2023 American Neurological Association.)

Sixteen strains of basidiomycetous yeasts were evaluated for their capability to produce ergothioneine (EGT), an amino acid derivative with strong antioxidant activity. The cells were cultured in either two synthetic media or yeast mold (YM) medium for 72 h, after which cytosolic constituents were extracted from the cells with hot water. After analyzing the extracts via liquid chromatography-mass spectrometry (LC-MS), we found that all strains produced varying amounts of EGT. The EGT-producing strains, including Ustilago siamensis, Anthracocystis floculossa, Tridiomyces crassus, Ustilago shanxiensis, and Moesziomyces antarcticus, were subjected to flask cultivation in YM medium. U. siamensis CBS9960 produced the highest amount of EGT at 49.5 ± 7.0 mg/L after 120 h, followed by T. crassus at 30.9 ± 1.8 mg/L. U. siamensis was also cultured in a jar fermenter and produced slightly higher amounts of EGT than under flask cultivation. The effects of culture conditions, particularly the addition of precursor amino acids, on EGT production by the selected strains were also evaluated. U. siamensis showed a 1.5-fold increase in EGT production with the addition of histidine, while U. shanxiensis experienced a 1.8-fold increase in EGT production with the addition of methionine. These results suggest that basidiomycetous yeasts could serve an abundant source for natural EGT producers., (© 2024. The Author(s).)

Research on cardiomyopathy models using engineered heart tissue (EHT) created from disease-specific induced pluripotent stem cells (iPSCs) is advancing rapidly. However, the study of restrictive cardiomyopathy (RCM), a rare and intractable cardiomyopathy, remains at the experimental stage because there is currently no established method to replicate the hallmark phenotype of RCM, particularly diastolic dysfunction, in vitro. In this study, we generated iPSCs from a patient with early childhood-onset RCM harboring the TNNI3 R170W mutation (R170W-iPSCs). The properties of R170W-iPSC-derived cardiomyocytes (CMs) and EHTs were evaluated and compared with an isogenic iPSC line in which the mutation was corrected. Our results indicated altered calcium kinetics in R170W-iPSC-CMs, including prolonged tau, and an increased ratio of relaxation force to contractile force in R170W-EHTs. These properties were reversed in the isogenic line, suggesting that our model recapitulates impaired relaxation of RCM, i.e., diastolic dysfunction in clinical practice. Furthermore, overexpression of wild-type TNNI3 in R170W-iPSC-CMs and -EHTs effectively rescued impaired relaxation. These results highlight the potential efficacy of EHT, a modality that can accurately recapitulate diastolic dysfunction in vitro, to elucidate the pathophysiology of RCM, as well as the possible benefits of gene therapies for patients with RCM., (© 2024 The Authors. Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.)

Background: Despite the suggestion that direct compression by granuloma and ischemia resulting from vasculitis can cause nerve fiber damage, the mechanisms underlying sarcoid neuropathy have not yet been fully clarified., Methods: We examined the clinicopathological features of sarcoid neuropathy by focusing on electrophysiological and histopathological findings of sural nerve biopsy specimens. We included 18 patients with sarcoid neuropathy who had non-caseating epithelioid cell granuloma in their sural nerve biopsy specimens., Results: Although electrophysiological findings suggestive of axonal neuropathy were observed, particularly in the lower limbs, all but three patients showed ≥1 abnormalities in nerve conduction velocity or distal motor latency. Additionally, a conduction block was observed in 11 of the 16 patients for whom waveforms were assessed; five of them fulfilled motor nerve conduction criteria strongly supportive of demyelination as defined in the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline for chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, sural nerve biopsy specimens revealed a mild to moderate degree of myelinated fiber loss. Fibrinoid necrosis was observed in one patient, and electron microscopy analysis revealed demyelinated axons close to granulomas in six patients., Conclusions: Patients with sarcoid neuropathy may meet the EAN/PNS electrophysiological criteria for CIDP due to the frequent presence of conduction blocks. Based on our results, in addition to the ischemic damage resulting from granulomatous inflammation, demyelination may play an important role in the mechanism underlying sarcoid neuropathy., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

This study aimed to test our hypothesis that the cerebellum plays an important role in the generation of the optical-geometric illusion known as the Poggendorff illusion, the mechanism of which has been explained by accumulated experience with natural scene geometry. A total of 79 participants, comprising 28 patients with isolated cerebellar stroke, 27 patients with isolated cerebral stroke and 24 healthy controls, performed Poggendorff illusion tasks and 2 different control tasks. We also investigated core brain regions underpinning changes in the experience of the illusion effect using multivariate lesion-symptom mapping. Our results indicate that patients with isolated cerebellar stroke were significantly less likely to experience the Poggendorff illusion effect than patients with isolated cerebral stroke or healthy controls (74.6, 90.5 and 89.8%, respectively; F (2,76) = 6.675, P = 0.002). However, there were no inter-group differences in the control tasks. Lesion-symptom mapping analysis revealed that the brain lesions associated with the reduced frequency of the Poggendorff illusion effect were mainly centred on the right posteromedial cerebellar region, including the right lobules VI, VII, VIII, IX and Crus II. Our findings demonstrated, for the first time, that patients with cerebellar damage were significantly less likely to experience the Poggendorff illusion effect and that right posteromedial cerebellar lesions played an important role in this effect. These results provide new insight into alterations of a geometric illusion effect in patients with cerebellar disorders and pave the way for future clinical use of the illusion task to detect cerebellar abnormalities., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Buccofacial apraxia (BFA) is associated with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) as well as with the severity of apraxia of speech (AOS), a core symptom of nfvPPA. However, an association with agrammatism has not been established. The aim of this study was to examine the association between BFA and agrammatism in nfvPPA and to determine differences in atrophic regions in primary progressive aphasia (PPA) with and without BFA. Seventy-four patients with PPA were recruited, including 34, 15, 10, and 15 patients with nfvPPA, semantic variant PPA, logopenic variant PPA, and unclassified PPA, respectively. All patients underwent language examination and BFA evaluations. Voxel-based morphometry (VBM) was performed to determine whether atrophy of a specific lesion correlated with the presence of BFA. BFA was observed in 20 and 3 patients with nfvPPA and unclassified PPA, respectively. In a comparison of patients with nfvPPA with and without BFA, the BFA group showed significantly worse spontaneous speech and writing in the Western Aphasia Battery. The agrammatism ratio or the ratio of agrammatic errors to the total number of particles was higher in the BFA group; however, the severity of prosodic and phonetic components of AOS did not differ between the two groups. VBM showed that the severity of BFA correlated with atrophy of the opercular and triangular areas of the inferior frontal gyrus to a part of the left middle frontal gyrus. BFA has a different anatomical basis from AOS in patients with nfvPPA and that BFA is characterized by more anterior degeneration compared to that of AOS., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the relationship between increases in the luteinizing hormone (LH) profiles in the serum and vaginal mucus of cows induced by gonadotropin-releasing hormone (GnRH). Samples for LH determination were collected from Japanese Black beef cows during estrus, which was induced with a controlled internal progesterone-releasing device and the administration of cloprostenol immediately before GnRH administration and every 30 min from the start of GnRH administration until 6.5 h. The peak serum LH concentration was clearly identified at 2.5 h post-GnRH administration, with serum concentrations returning to near-pre-GnRH-administration values after 6.5 h, whereas the peak vaginal mucus LH concentration was identified 4.5 h after GnRH administration. These results indicate that the LH secretion peak in vaginal mucus appeared about 2 h after peak LH secretion in the serum., Competing Interests: The contact author has declared that none of the authors has any competing interests., (Copyright: © 2022 Naoaki Yoshimura et al.)

A 39-year-old man exhibited ocular flutter and cerebellar ataxia following a subacute disturbance of consciousness and partial seizure. He was diagnosed with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy by tissue- and cell-based antibody assays. Brain single-photon emission computed tomography detected a significant increase in blood flow in the fastigial nucleus, a critical region for eye saccade control. Immunotherapies diminished the ocular flutter and reduced hyperperfusion in the fastigial nucleus. This case suggests that autoimmune GFAP astrocytopathy can cause ocular flutter and provides strong imaging evidence supporting the hypothesis that ocular flutter is caused by hyperactivity or disinhibition of the fastigial nucleus., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Ultrasonography (US) is a noninvasive and patient-friendly tool for the evaluation of peripheral nerves. In motor neuron diseases, amyotrophic lateral sclerosis (ALS) has been reported to show the atrophy of peripheral nerves on US. However, the US findings are still unclear in spinal and bulbar muscular atrophy (SBMA), an adult-onset lower motor neuron disease caused by an abnormal CAG repeat expansion in the androgen receptor gene., Methods: We prospectively recruited and evaluated 11 patients with genetically confirmed SBMA and 9 patients with ALS diagnosed according to the revised El Escorial ALS criteria or the Awaji electrodiagnostic criteria. The C5-C7 cervical nerve roots and the median and ulnar nerves were evaluated ultrasonographically., Results: The cross-sectional areas (CSAs) of the C6 and C7 nerve roots, the median nerve in the upper arm and forearm, and the ulnar nerve in the upper arm were smaller in patients with SBMA than those in patients with ALS (p < 0.05), whereas the CSAs of the C5 nerve root and the ulnar nerve in the forearm were not smaller., Conclusions: US showed that the peripheral nerves in patients with SBMA were thinner than those in patients with ALS despite similar degrees of weakness and motor neuron loss. Possible causes include additional sensory nerve involvement and longer disease duration in patients with SBMA than those in patients with ALS., (© 2022. Fondazione Società Italiana di Neurologia.)

Guillain-Barré syndrome (GBS) has occasionally occurred in people who have received coronavirus disease 2019 (COVID-19) vaccines. Dysgeusia is rare symptom of GBS. We herein report a rare case of sensory ataxic GBS with dysgeusia just after the second dose of the Pfizer-BioNTech COVID-19 vaccine. Although autoantibodies against glycolipids were not detected, immunotherapy with intravenous immunoglobulin and methylprednisolone pulse therapy effectively ameliorated the symptoms. Our report suggests that the COVID-19 vaccine may induce various clinical subtypes of GBS, including a rare variant with sensory ataxia and dysgeusia.

Objective: Simultanagnosia is a rare neuropsychological symptom characterized by difficulty recognizing global structures while preserving perception of local detail. The condition is classified into ventral and dorsal types. Clinical presentation of ventral simultanagnosia includes a reduced ability to recognize multiple visual stimuli rapidly, that is, part-by-part recognition. Here, we report a case of ventral simultanagnosia with a unique presentation; when short-duration visual stimuli were presented, the patient could perform global recognition by improving his part-by-part approach. To investigate the relationship between local and global perception bias and the duration of the present stimulus, we conducted a visual perception test using hierarchically organized Navon figures., Methods/results: The patient was a 62-year-old right-handed man who suffered from cerebral infarction in the right occipitotemporal lobe. He had no language dysfunction but exhibited left unilateral neglect, prosopagnosia, and ventral-type simultanagnosia. We conducted a visual perception test using the Navon figures and control figures as a visual stimulus. We randomly presented the figures for intervals of 0.2 or 20 s and let the patient report all the letters (global and/or local element) that he recognized. Global elements of the Navon letter were recognized a rate of 0% and 78.3% at intervals of 20 and 0.2 s, respectively, indicating that shorter presentation made the part-by-part approach less likely to manifest., Conclusions: We assumed that the simultanagnosia in this case was caused by failure to maintain the initially perceived global information for a long period of time during visual presentation, due to right occipitotemporal damage., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Introduction: The basal ganglia and related dopaminergic cortical areas are important neural systems underlying motor learning and are also implicated in impulse control disorders (ICDs). Motor learning impairments and ICDs are frequently observed in Parkinson's disease (PD). Nevertheless, the relationship between motor learning ability and ICDs has not been elucidated., Methods: We examined the relationship between motor learning ability and gambling propensity, a possible symptom for prodromal ICDs, in PD patients. Fifty-nine PD patients without clinical ICDs and 43 normal controls (NC) were administered a visuomotor rotation perturbation task and the Iowa Gambling Task (IGT) to evaluate motor learning ability and gambling propensity, respectively. Participants also performed additional cognitive assessments and underwent brain perfusion SPECT imaging., Results: Better motor learning ability was significantly correlated with lower IGT scores, i.e., higher gambling propensity, in PD patients but not in NC. The higher scores on assessments reflecting prefrontal lobe function and well-preserved blood perfusion in prefrontal areas were correlated with lower IGT scores along with better motor learning ability., Conclusions: Our findings suggest that better motor learning ability and higher gambling propensity are based on better prefrontal functions, which are in accordance with the theory that the prefrontal cortex is one of the common essential regions for both motor learning and ICDs.

Background: Anticoagulation therapy, especially using heparin or recently developed oral direct factor Xa inhibitors (DiXals), is recommended as first-line treatment for cancer-related venous thromboembolism (VTE). However, the preventive efficacy of these anticoagulants for cancer-associated ischemic stroke is still unknown. We retrospectively investigated the efficacy of subcutaneous unfractionated heparin (UFH) and DiXals for preventing the recurrence of cancer-associated cryptogenic ischemic stroke with VTE., Methods: We retrospectively studied consecutive patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE who received subcutaneous UFH or oral DiXaIs at 9 hospitals., Result: Fifty-three patients (24 treated with UFH and 29 treated with DiXaIs) were enrolled. Of these, 47 demonstrated systemic metastasis (cancer stage IV). During 30-day follow-up after initiation of anticoagulation therapy, recurrent ischemic stroke was observed in only 1 patient (4%) in the UFH group and in 9 patients (31%) in the DiXal group. The incidence of major bleeding complications was similar between the 2 groups (4% and 10%, respectively). The cumulative risk of ischemic stroke recurrence within 30 days was lower with UFH than with DiXals (competing risk analysis, p = 0.008). In the DiXal group, patients who experienced recurrence showed significantly higher D-dimer levels than those without recurrence., Conclusion: In patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE, UFH demonstrated a lower rate of recurrent ischemic stroke than DiXaIs, and there were no differences in bleeding risk between the 2 treatments. D-dimer levels at stroke onset increased the risk of recurrence in the DiXal group but not in the UFH group., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aquired apraxia of speech is a disorder that impairs speech production, despite intact peripheral neuromotor function. Its pathomechanism remains to be established. Neurodegenerative lesion models provide an unequalled opportunity to explore the neural correlates of apraxia of speech, which is present in a subset of patients diagnosed with non-semantic variants of primary progressive aphasia. The normalized pairwise variability index, an acoustic measure of speech motor programming, has shown high sensitivity and specificity for apraxia of speech in cross-sectional studies. Here, we aimed to examine the strength of the pairwise variability index and overall word duration (i.e. articulation rate) as markers of progressive motor programming deficits in primary progressive aphasia with apraxia of speech. Seventy-nine individuals diagnosed with primary progressive aphasia (39 with non-fluent variant and 40 with logopenic variant) and 40 matched healthy controls participated. Patients were followed-up annually (range 1-6 years, median number of visits = 2). All participants completed a speech assessment task and a high-resolution MRI. Our analyses investigated trajectories of speech production (e.g. pairwise variablity index and word duration) and associations with cortical atrophy in the patients. At first presentation, word duration differentiated the nonfluent and logopenic cases statistically, but the range of scores overlapped substantially across groups. Longitudinally, we observed progressive deterioration in pairwise variability index and word duration specific to the non-fluent group only. The pairwise variability index showed particularly strong associations with progressive atrophy in speech motor programming brain regions. Of novelty, our results uncovered a key role of the right frontal gyrus in underpinning speech motor programming changes in non-fluent cases, highlighting the importance of right-brain regions in responding to progressive neurological changes in the speech motor network. Taken together, our findings validate the use of a new metric, the pairwise variability index, as a robust marker of apraxia of speech in contrast to more generic measures of speaking rate. Sensitive/specific neuroimaging biomarkers of the emergence and progression of speech impairments will be useful to inform theories of the pathomechanisms underpinning impaired speech motor control. Our findings justify developing more sensitive measures of rhythmic temporal control of speech that may enable confident detection of emerging speech disturbances and more sensitive tracking of intervention-related changes for pharmacological, neuromodulatory and behavioural interventions. A more reliable detection of speech disturbances has relevance for patient care, with predominance of progressive apraxia of speech a high-risk factor for later diagnosis of progressive supranuclear palsy or corticobasal degeneration., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Purpose: The presence of hemispatial neglect adversely affects functional outcomes in stroke patients; consequently, it warrants early targeted rehabilitative intervention. Nevertheless, hemispatial neglect in the acute phase of stroke has often been underdiagnosed. In this study, we aimed to detect hemispatial neglect at the bedside in acute stroke patients by measuring eye movements using video-oculography (VOG)., Methods: Forty-seven patients with acute unilateral supratentorial stroke were enrolled. We quantitatively measured horizontal saccade (latency, velocity, and amplitude) and smooth pursuit (gain) at the bedside using VOG and compared these variables with scores on the Behavioral Inattention Test (BIT), a screening battery to assess hemispatial neglect., Results: Contralesional saccade latency, velocity, and amplitude, and ipsilesional smooth pursuit gain were suppressed compared with those in the opposite directions (p = 0.08, 0.02, 0.04, and 0.02, respectively). These directional ocular hypokinesia values correlated with the total BIT score (correlation coefficients -0.53, 0.48, 0.51, and 0.39, respectively). The association was significant even after adjusting for age and stroke severity., Conclusions: Eye movement measurements performed using VOG significantly correlated with the tendency for hemispatial neglect in acute supratentorial stroke patients. Bedside VOG measurement may be a simple biomarker for detecting hemispatial neglect even in patients in the supine position during the acute phase of stroke., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Foreign accent syndrome (FAS) is a rare speech disorder characterized by the emergence of a foreign accent. To date, more than a hundred cases of FAS have been reported, and the impression of accent change is regarded to be the result of a combination of segmental deficits (i.e., phonetic distortions and phonemic paraphasias) and supra-segmental changes (i.e., stress, pitch, or rhythm variation). The most common etiology of FAS is stroke, followed by other causes. Various lesion locations have been identified to cause FAS. Owing to various heterogeneous etiologies and lesion locations, it remains controversial whether there is enough consistency or universality to treat FAS as a "syndrome".

Background: Mild cognitive impairment (MCI) in Parkinson's disease (PD) is considered a risk factor for PD with dementia (PDD). Verbal fluency tasks are widely used to assess executive function in PDD. However, in cases of PD with MCI (PD-MCI), the relative diagnostic accuracy of different qualitative verbal fluency measures and their related neural mechanisms remain unknown., Objective: This study aimed to investigate the relative diagnostic accuracy of qualitative (clustering and switching) verbal fluency strategies and their correlates with functional imaging in PD-MCI., Methods: Forty-five patients with PD (26 with MCI and 19 without MCI) and 25 healthy controls underwent comprehensive neurocognitive testing and resting-state functional magnetic resonance imaging. MCI in patients with PD was diagnosed according to established clinical criteria. The diagnostic accuracy of verbal fluency measures was determined via receiver operating characteristic analysis. Changes in brain functional connectivity between groups and across clinical measures were assessed using seed-to-voxel analyses., Results: Patients with PD-MCI generated fewer words and switched less frequently in semantic and phonemic fluency tasks compared to other groups. Switching in semantic fluency showed high diagnostic accuracy for PD-MCI and was associated with reduced functional connectivity in the salience network., Conclusion: Our results indicate that reduced switching in semantic fluency tasks is a sensitive and specific marker for PD-MCI. Qualitative verbal fluency deficits and salience network dysfunction represent early clinical changes observed in PD-MCI.

Background: Foreign accent syndrome (FAS) is a rare acquired speech disorder wherein an individual's spoken accent is perceived as "foreign." Most reported cases involve left frontal brain lesions, but it is known that various other lesions can also cause FAS. To determine whether heterogeneous FAS-causing lesions are localized to a common functional speech network rather than to a single anatomical site, we employed a recently validated image analysis technique known as "lesion network mapping.", Methods: We identified 25 published cases of acquired neurogenic FAS without aphasia, and mapped each lesion volume onto a reference brain. We next identified the network of brain regions functionally connected to each FAS lesion using a connectome dataset from normative participants. Network maps were then overlapped to identify common network sites across the lesions., Results: Classical lesion overlap analysis showed heterogeneity in lesion anatomical location, consistent with prior reports. However, at least 80% of lesions showed network overlap in the bilateral lower and middle portions of the precentral gyrus and in the medial frontal cortex. The left lower portion of the precentral gyrus is suggested to be the location of lesions causing apraxia of speech (AOS), and the middle portion is considered to be a larynx-specific motor area associated with the production of vowels and stop/nasal consonants and with the determination of pitch accent., Conclusions: The lesions that cause FAS are anatomically heterogeneous, but they share a common functional network located in the bilateral posterior region of the frontal lobe. This network specifically includes not only the lower portion of the central gyrus, but also its middle region, which is referred to as the larynx motor cortex and is known to be associated with phonation. Our findings suggest that disrupted networks in FAS might be anatomically different from those in AOS., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We herein report a 33-year-old woman who was an asymptomatic hepatitis B virus (HBV) carrier and presented with distal muscle weakness in the legs and asymmetrical paresthesia in the distal extremities. A nerve biopsy specimen revealed fibrinoid necrosis associated with inflammatory infiltration in the perineural space, and deposition of hepatitis B core antigen and C4d complement was detected in the vascular endothelial cells as well as around the vessels. She was diagnosed with HBV-related vasculitic neuropathy and treated with intravenous immunoglobulin (IVIG). Her symptoms completely subsided after eight weeks. Vasculitic neuropathy rarely develops in the chronic inactive stages of HBV infection. This is the first report of an HBV-inactive carrier with vasculitic neuropathy successfully treated with IVIG.

Background: Children with severe motor and intellectual disabilities (SMID) are at a high risk of malnutrition and often require tube feeding to maintain their nutritional status. However, determining their energy requirements is difficult since inadequate dietary intake, severe neurological impairment, respiratory assistance, and cognitive impairment are all factors that affect malnutrition in SMID., Aim: This study investigated the factors affecting malnutrition and identified problems affecting the nutritional status of children with SMID., Methods: Forty-two children with SMID with oral motor dysfunction who were receiving home medical care at one of four hospitals were enrolled. Their nutritional status was assessed using a 3-day dietary record, anthropometric measurements, and laboratory tests. The clinical findings associated with malnutrition were compared, and a body mass index (BMI) z-score less than -2SD was defined as malnutrition. The relationship between BMI z-score and other potential predictors was also investigated., Results: Thirty-three (79%) children received tube feeding, and 20 (48%) experienced malnutrition. The median age of the malnourished children was older than that of non-malnourished children. Respiratory assistance was significantly correlated with higher BMI z-score, independent of other potential confounders such as nutrition method, muscle tonus, and energy intake. Cholesterol levels were significantly higher in children receiving a standard infant formula beyond 3 years of age than in those who switched to enteral formula before 3 years of age., Conclusions: Malnutrition in children with SMID was mainly associated with age or respiratory condition. Energy requirements should be regularly re-evaluated with considering these factors., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

In this study, we investigate the tylosin degradation in sheep feces during composting. The sheep feces containing tylosin were composted using the laboratory-scale composting units. Tylosin was degraded during composting, and the half-life of tylosin degradation decreased with increasing temperature from 40 °C to 65 °C. The tylosin degradation in sheep feces can be attributed to the microorganisms in the feces and not to heating because tylosin did not degrade over a period of 48 h at temperatures of 0 °C-65 °C in sterilized water. The artificial rainwater solution extracted from the composted sample did not inhibit the growth of Raphidocelis subcapitata, a type of green alga. Our results indicate that composting the feces containing tylosin is effective in degrading tylosin, which may result in the preservation of agricultural fields as well as nearby aquatic environments., Competing Interests: Declaration of competing interest The following authors have affiliations with organizations with direct or indirect financial interest in the subject matter discussed in the manuscript:, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Sleep is one of the essential behaviors in mammalian health and welfare. In this study, we focused on how concentrate-rich diets (Conc) can influence the sleep of cattle. We hypothesized that Conc would suppress the daily sleep of cows because of behavioral frustration according to shorter eating and rumination. We subjected six Japanese black cows according to crossover experimental design. There were two diet treatments. In the Conc group, 70% of required TDN was supplied by concentrate and 30% by grass silage. On the other hand, in roughage fed group (Rough), all required TDN was supplied by grass silage. Maintenance behaviors, postures of cows, and sleep posture were measured by electronic devices. Cows fed with Conc spent less time in eating and rumination and spent more time in rest than Rough. However, contrary to our hypothesis, cows fed with Conc showed longer daily sleep posture duration (96.2 min/day vs. 69.1 min/day) and more frequent sleep posture bouts (15.4 times/day vs. 11.1 times/day) than Rough. We discussed about following possible explanations why cows fed with Conc slept longer as satisfaction, illness, displacement behavior, and shifting sleep posture., (© 2020 Japanese Society of Animal Science.)

Oral treatment for elderly outpatients with pneumonia is becoming increasingly important in this super-aged society from the perspective of cost-effectiveness and limited hospital capacities. We evaluated the efficacy and safety of two oral respiratory quinolones, sitafloxacin and garenoxacin, in elderly patients with pneumonia. This randomized, multicenter, open-label trial was conducted among patients aged ≥65 years with clinically and radiographically confirmed pneumonia in Japan. Patients were randomly assigned (1:1) to receive either sitafloxacin (100 mg/day) or garenoxacin (400 mg/day) for 3-10 days. The primary efficacy endpoint was the clinical cure rate at 5-10 days after the end of treatment. From December 2013 to November 2017, we enrolled 120 patients at 11 hospitals and randomly assigned 59 patients to the sitafloxacin group (1 patient withdrew) and 61 patients to the garenoxacin group. These included 30 patients with nursing and healthcare-associated pneumonia (NHCAP) (18 receiving sitafloxacin, 12 receiving garenoxacin) and 37 patients with aspiration pneumonia (16 receiving sitafloxacin, 21 receiving garenoxacin). The clinical cure rates in the sitafloxacin and garenoxacin groups were 88.5% (95% confidence interval: 76.6-95.6) and 88.9% (95% confidence interval: 77.4-95.8), respectively. No significant differences were observed in the incidence rates of drug-related adverse events between the sitafloxacin (20.7%; 12/58 patients) and garenoxacin (27.9%; 17/61 patients) groups. The most common adverse event was hepatic dysfunction, which occurred in seven patients in each group. We conclude that sitafloxacin and garenoxacin are comparably effective and safe for the treatment of pneumonia, including NHCAP and aspiration pneumonia, in elderly patients., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A 24-year-old Japanese man exhibited slowly progressive gait disturbance from childhood to young adulthood. Physical and physiological examinations showed the involvement of both upper and lower motor neurons, fulfilling the diagnostic criteria for amyotrophic lateral sclerosis (ALS). Mild cognitive impairment and subclinical sensory involvement were also observed. A genetic analysis revealed novel compound heterozygous mutations, c.767C>T (p.Thr256Ile) and c.800A>G (p.Asp267Gly), in the vaccinia-related kinase 1 gene (VRK1). This is the first report of a Japanese patient with a motor neuron disease phenotype caused by VRK1 mutations. This diagnosis should be considered in atypical cases of juvenile-onset and slowly progressive types of motor neuron disease.

The aim of this study was to clarify cow's sleep behavior on farm and to examine the influence of some environment and management factors on cow's sleep. Total 85 behavior data (summer 41, autumn 44) were corrected from 12 commercial tie-stall dairy farm in northern Tohoku area. Daily duration, bout frequency, and averaged bout duration of sleep and lying were measured. Even though there was no significant difference in any lying measurements, daily duration, bout frequency, and averaged bout duration of sleep was significantly different among farms (p < 0.01, p < 0.01, and p < 0.05, respectively). However, we could not find that any managements influence on sleep. There was significant seasonal difference in daily sleep duration (p < 0.01) and sleep bout frequency (p < 0.05). On the other hand, daily lying duration and averaged lying bout duration were significantly different between seasons (p < 0.001 and p < 0.05, respectively). Primiparous cows slept longer and more frequent than multiparous (both p < 0.001). Milk solid-non-fat content was positively correlated with daily sleep duration (p < 0.05) and bout frequency (p < 0.01). These results might imply the productive importance of sleep related with anabolic hormones release., (© 2019 Japanese Society of Animal Science.)

Essential hypersomnia (EHS) is a lifelong disorder characterized by excessive daytime sleepiness without cataplexy. EHS is associated with human leukocyte antigen (HLA)-DQB1*06:02, similar to narcolepsy with cataplexy (narcolepsy). Previous studies suggest that DQB1*06:02-positive and -negative EHS are different in terms of their clinical features and follow different pathological pathways. DQB1*06:02-positive EHS and narcolepsy share the same susceptibility genes. In the present study, we report a genome-wide association study with replication for DQB1*06:02-negative EHS (408 patients and 2247 healthy controls, all Japanese). One single-nucleotide polymorphism, rs10988217, which is located 15-kb upstream of carnitine O-acetyltransferase (CRAT), was significantly associated with DQB1*06:02-negative EHS (P = 7.5 × 10 -9 , odds ratio = 2.63). The risk allele of the disease-associated SNP was correlated with higher expression levels of CRAT in various tissues and cell types, including brain tissue. In addition, the risk allele was associated with levels of succinylcarnitine (P = 1.4 × 10 -18 ) in human blood. The leading SNP in this region was the same in associations with both DQB1*06:02-negative EHS and succinylcarnitine levels. The results suggest that DQB1*06:02-negative EHS may be associated with an underlying dysfunction in energy metabolic pathways.

Objective: Environmental change is one of the stressful events in livestock production. Change in environment disturbs cow behavior and cows require several days to regain a stable behavioral pattern. Sleeping posture (SP) and lying posture (LP) have been used as indicators for animal that are relaxed and well-acclimated to their environment. The aim of this study was to examine the time required by Japanese black cows for stabilization of SP and LP after moving into new environment., Methods: Seven pregnant Japanese black cows were used. Cows were moved into new tie-stall shed and their sleeping and lying posture measured 17 times during 35 experimental days. Both SP and LP were detected by accelerometer fixed on middle occipital and hip-cross, respectively. Daily total time, frequency, and average bout of both SP and LP were calculated., Results: Daily SP time was the shortest on day 1 and increased to the highest on day 3. It then decreased until day 9, after that stabilized about 65 min/d till the end of experiment. Daily LP time changed in same manner as daily SP time. The average SP bout was the longest on day 1, and then decreased to stable level on day 7. On the other hand, the average LP bout was the shortest on day 1, and it increased to stable level on day 7., Conclusion: These results showed that pregnant Japanese black cows needed 1 week to stabilize their SP. However, there were different change patterns between the average SP and LP bout, even though the change pattern of daily SP and LP time were similar.

Steroid pulse therapy with methylprednisolone (mPSL) succinate ester is the most common treatment for neuromyelitis optica (NMO); no cases of anaphylaxis have been reported to date. Here, we report two cases of anaphylactic shock induced by mPSL pulse therapy in patients with NMO and concurrent systemic lupus erythematosus. Both patients had received several courses of mPSL pulse therapy without any problems previously. Repeated mPSL pulse therapy and comorbid humoral autoimmune disease might increase the risk of anaphylaxis. Corticosteroids without succinate esters should be considered as an alternative therapy to prevent anaphylaxis.

Antibiotics administered to livestock are partly excreted with urine and feces. As livestock excrement is used as manure on agricultural fields, soil may be contaminated by excreted antibiotics, potentially resulting in the development of antibiotic-resistant bacteria. Therefore, it is necessary to determine the amount of antibiotic administered to livestock that could spread to agricultural fields through manure application. This study reveals the excretion ratio of tylosin from sheep. After developing an analysis procedure for tylosin in urine and feces from sheep, a tylosin excretion study was performed with two sheep. Tylosin was excreted in urine and feces for four days, after which its concentrations dropped below the limits of quantification (urine: 0.5μg/kg, feces: 2.4μg/kg). The total excretion ratio was 11% on average. The results of our study can provide useful knowledge for treating excrement in order to prevent the spread of antibiotics to agricultural fields through manure application., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Enzymes belonging to the aspartase/fumarase superfamily catalyze elimination of various functional groups from succinate derivatives and play an important role in primary metabolism and aromatic compound degradation. Recently, an aspartase/fumarase superfamily enzyme, CreD, was discovered in cremeomycin biosynthesis. This enzyme catalyzes the elimination of nitrous acid from nitrosuccinate synthesized from aspartate by CreE, a flavin-dependent monooxygenase. Nitrous acid generated by this pathway is an important precursor of the diazo group of cremeomycin. CreD is the first aspartase/fumarase superfamily enzyme that was reported to catalyze the elimination of nitrous acid, and therefore we aimed to analyze its reaction mechanism. The crystal structure of CreD was determined by the molecular replacement native-single anomalous diffraction method at 2.18 Å resolution. Subsequently, the CreD-fumarate complex structure was determined at 2.30 Å resolution by the soaking method. Similar to other aspartase/fumarase superfamily enzymes, the crystal structure of CreD was composed of three domains and formed a tetramer. Two molecules of fumarate were observed in one subunit of the CreD-fumarate complex. One of them was located in the active site pocket formed by three different subunits. Intriguingly, no histidine residue, which usually functions as a catalytic acid in aspartase/fumarase superfamily enzymes, was found around the fumarate molecule in the active site. Based on the mutational analysis, we propose a catalytic mechanism of CreD, in which Arg325 acts as a catalytic acid., Databases: The crystal structures of CreD and the CreD-fumarate complex were deposited to PDB under the accession numbers 5XNY and 5XNZ, respectively., Enzymes: Nitrosuccinate lyase CreD, EC4.3., (© 2018 Federation of European Biochemical Societies.)

Background: Although inflammation in the central nervous system is responsible for multiple neurological diseases, the lack of appropriate biomarkers makes it difficult to evaluate inflammatory activities in these diseases. Therefore, a new biomarker reflecting neuroinflammation is required for accurate diagnosis, appropriate therapy, and comprehension of pathogenesis of these neurological disorders. We previously reported that the cerebrospinal fluid (CSF) concentration of lateral olfactory tract usher substance (LOTUS), which promotes axonal growth as a Nogo receptor 1 antagonist, negatively correlates with disease activity in multiple sclerosis, suggesting that variation in LOTUS reflects the inflammatory activities and is a useful biomarker to evaluate the disease activity. To extend this observation, we analyzed the variation of LOTUS in the CSF of patients with bacterial and viral meningitis, which are the most common neuroinflammatory diseases., Methods: CSF samples were retrospectively obtained from patients with meningitis (n = 40), who were followed up by CSF study at least twice, and from healthy controls (n = 27). Patients were divided into bacterial (n = 14) and viral meningitis (n = 18) after exclusion of eight patients according to the criteria of this study. LOTUS concentrations, total protein levels, and CSF cell counts in the acute and recovery phases were analyzed chronologically. We also used lipopolysaccharide-injected mice as a model of neuroinflammation to evaluate LOTUS mRNA and protein expression in the brain., Results: Regardless of whether meningitis was viral or bacterial, LOTUS concentrations in the CSF of patients in acute phase were lower than those of healthy controls. As the patients recovered from meningitis, LOTUS levels in the CSF returned to the normal range. Lipopolysaccharide-injected mice also exhibited reduced LOTUS mRNA and protein expression in the brain., Conclusions: CSF levels of LOTUS correlated inversely with disease activity in both bacterial and viral meningitis, as well as in multiple sclerosis, because neuroinflammation downregulated LOTUS expression. Our data strongly suggest that variation of CSF LOTUS is associated with neuroinflammation and is useful as a biomarker for a broader range of neuroinflammatory diseases.

Background: In dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), it is still debated whether white matter hyperintensities (WMH) on MRI reflect atherosclerotic cerebrovascular changes or Alzheimer's disease (AD)-related pathology such as cerebral amyloid angiopathy. To examine AD-related pathology in DLB and PDD, we compared the severity of WMH and medial temporal lobe atrophy among patients with DLB, PDD, non-demented PD (PDND), and AD., Methods: We retrospectively studied sex- and age-matched outpatients with AD, DLB, PDD, and PDND, as well as subjects without central nervous system disorders as normal controls (n=50 each). All subjects underwent 1.5-T MRI examinations, and WMH detected by T2-weighted images or fluid-attenuated inversion recovery images were semiquantified according to the Fazekas method. Medial temporal lobe atrophy (MTA) was visually assessed by the MTA score., Results: WMH were more prominent in AD, DLB, and PDD patients than in PDND patients and normal controls (NCs). DLB as well as AD showed more severe WMH than PDD. Visual assessment of medial temporal lobe atrophy showed that AD patients had the most severe atrophy, followed by DLB, PDD, and PDND patients, and NC subjects in that order. MTA scores showed significant correlations with WMH severity., Conclusion: Our results indicated that DLB was more similar to AD than to PDD in terms of MRI findings, suggesting that WMH in DLB may reflect mainly AD-related pathology rather than atherosclerotic cerebrovascular changes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Sleep is one of the essential behaviors for mammals. The aims of this study were to validate the use of accelerometer for measuring sleeping posture of cattle. Duration of sleeping posture of seven Japanese Black cows from 19.00 to 07.00 hours was measured by both accelerometer and video, and a total of 67 accelerometer and video measurement sets were collected. We calculated Cohen's κ coefficient between accelerometer and video measurements and 91.5% of the κ-values were >0.80. Intra- and inter-observer coefficient of variance showed that specific acceleration waveform patterns of sleeping posture could be easily and accurately detected by independent observers. There were no significant differences in the frequency of sleeping posture occurrences between accelerometer and video measurements. We compared averaged sleeping posture bout, and the total sleeping posture time between accelerometer and video measurements using regression. In each trait, the slope was close to 1 and the intercept was not different from 0, which showed a strong agreement between accelerometer and video measurements. This shows that an accelerometer could accurately detect sleeping postures of cattle. We conclude that adequate measurements of sleeping postures can be made using an accelerometer., (© 2017 Japanese Society of Animal Science.)

The aim of this study is to identify the factors that comprise farmer attitudes toward dairy cows and jobs in Japan, and examine the relationship between these attitudes and dairy productivity. At first, we executed a questionnaire survey to determine factors that comprise attitudes of farmers toward their jobs and dairy cows, and three factors were extracted. These were named as 'Positive beliefs to cows', 'Negative beliefs to cows' and 'Job satisfaction', respectively. Second, we examined the relationships between attitude and dairy productivity in 35 dairy farms. The positive beliefs scores correlated positively both with milk yield and milk urea nitrogen concentration. We found there to be three farm groups by cluster analysis using three attitude score. The group B farms showed significantly higher positive beliefs scores and job satisfaction scores; on the other hand, the group C farms showed significantly lower positive beliefs scores and higher negative belief scores. The milk yield in group B was significantly higher than that in group C. This study showed that Japanese farmers' attitudes toward cows considerably resemble those seen in previous studies in Western cultures. Positive attitudes toward cows could enhance stockmanship, and could improving animal welfare and productivity., (© 2016 Japanese Society of Animal Science.)

Background and Objectives: Differences in anthropometry and food acceptance among tasters and non-tasters of 6-n-propylthiouracil has been well studied in Western countries. However, reports on this issue from Asian countries are still limited., Methods and Study Design: Healthy Japanese students attending Nara Women's University (n=153) were recruited and classified into 3 groups based on taste sensitivity to a 0.32 mM 6-npropylthiouracil solution as scored on a labeled magnitude scale. Accordingly, the study population consisted of 34 non-tasters, 78 medium-tasters, and 41 super-tasters. Self-reported food intake was assessed using a food frequency questionnaire. Self-reported food preferences were established using a food checklist listing 63 food items., Results: Although subjects in the 6-n-propylthiouracil non-taster group showed a significantly higher body height and weight than subjects in the taster groups, body mass index was comparable among three groups. Intakes of calories, 3 macronutrients, β-carotene and vitamin C did not differ significantly between groups, but the intake of green and yellow vegetables was significantly lower in the taster groups. Among the 5 factors defined by a factor analysis performed with 277 age- and BMI-matched Japanese female students, the taster groups showed a significantly reduced preference for green and cruciferous vegetables alone., Conclusions: To the best of our knowledge, this is the first comprehensive report investigating associations between anthropometry, food intake, and food preference in relation to 6-n-propylthiouracil sensitivity in Asian countries. The effect of this tendency towards an aversion to vegetables including cruciferous ones among females on living a healthy life remains to be investigated.

The aim of this study was to analyze the pattern of magnetic resonance diffusion-weighted imaging (DWI) findings in status epilepticus in terms of clinical characteristics. Participants comprised 106 patients with status epilepticus who were admitted to our hospital and underwent DWI. Forty-five patients (42.5 %) showed abnormal findings on DWI and were divided into two groups, comprising 26 patients (24.5 %) with cortex lesions alone and 19 patients (17.9 %) with cortex and pulvinar lesions in the same hemisphere. A long duration of status epilepticus (>120 min) tended to be more prevalent among patients with cortex and pulvinar lesions (57.9 %) than among patients with cortex lesions alone (30.8 %) by univariate and multivariate analyses. Todd's palsy tended to be more frequent in patients with abnormalities on DWI (24/45, 53.3 %) than in patients with normal DWI (21/61, 34.4 %). Six of the 26 patients with cortex lesions alone (23.1 %) had taken anti-epileptic drugs before the attack compared to none of the 19 patients with both cortex and pulvinar lesions. The trend toward a longer duration of status epilepticus in patients with both cortex and pulvinar lesions favors a spreading pattern of seizure discharge from cortex to pulvinar via cortico-pulvinar pathways, and anti-epileptic drugs might, to some extent, prevent spreading of seizure discharge from cortex to pulvinar. In addition, existence of high-intensity areas on DWI at the onset of epilepsy may be a predictive factor for the occurrence of Todd's palsy.

To investigate the neural substrate of typewriting Japanese words and to detect the difference between the neural substrate of typewriting and handwriting, we conducted a functional magnetic resonance imaging (fMRI) study in 16 healthy volunteers. All subjects were skillful touch typists and performed five tasks: a typing task, a writing task, a reading task, and two control tasks. Three brain regions were activated during both the typing and the writing tasks: the left superior parietal lobule, the left supramarginal gyrus, and the left premotor cortex close to Exner's area. Although typing and writing involved common brain regions, direct comparison between the typing and the writing task revealed greater left posteromedial intraparietal cortex activation in the typing task. In addition, activity in the left premotor cortex was more rostral in the typing task than in the writing task. These findings suggest that, although the brain circuits involved in Japanese typewriting are almost the same as those involved in handwriting, there are brain regions that are specific for typewriting.

Background and Objectives: Recent reports indicate that the incidence of nontuberculous mycobacterial-lung disease (NTM-LD) is increasing. This study aimed to investigate the epidemiology and clinical features of NTM-LD patients in Nagasaki prefecture, Japan to identify the negative prognostic factors for NTM-LD in Japan., Methods: The medical records of patients newly diagnosed with NTM-LD in eleven hospitals in Nagasaki prefecture between January 2001 and February 2010 were reviewed. Data regarding the annual population of each region and the incidence of all forms of tuberculosis were collected to assess geographic variations in NTM-LD incidence, isolates, and radiological features., Results: A total 975 patients were diagnosed with NTM-LD. The incidence increased over the study period and reached 11.0 and 10.1 per 100,000 population in 2008 and 2009, respectively. M. intracellulare was the most common pathogen in the southern region, and M. avium most common in other regions. The most common radiographic pattern was the nodular-bronchiectatic pattern. Age >60 years, body mass index <18.5 kg/m2, underlying lung disease, and cavitary pattern were the negative prognostic factors at the 1-year follow-up., Conclusions: The incidence of NTM-LD has been increasing in Nagasaki prefecture. The isolates and radiographic features of patients vary markedly by region.

Mitochondrial complex III (CIII) deficiency comprises a group of complex and heterogeneous genetic disorders. TTC19 mutations constitute a rare cause of CIII deficiency and are associated with neurological disorders in childhood and adulthood. Herein, we describe a 27-year-old Japanese man with cerebellar ataxia, spastic paraparesis, loss of deep sensation, mild frontal lobe dysfunction and transient psychiatric symptoms. Brain magnetic resonance imaging showed cerebellar atrophy and bilateral high-intensity signals in the inferior olives and regions adjacent to periaqueductal gray matter, on T2-weighted images. On whole-exome sequencing, we detected a novel homozygous frameshift mutation c.157&#95;158dup [p.Pro54Alafs*48] in TTC19. Mitochondrial enzyme assays confirmed mild impairment of CIII enzymatic activity in lymphoblasts, which was consistent with TTC19-related CIII deficiency. His symptoms and radiological findings demonstrated an early stage or mild form of this disease, and further clarify the characteristics of patients with rare TTC19 mutations.

Objective: To compare the utility of Gram staining, a urinary antigen detection kit and a sputum antigen detection kit were examined for the rapid and early detection of pneumococcal pneumonia and lower respiratory infectious diseases., Methods: A newly developed sputum pneumococcal antigen detection kit (RAPIRUN), Gram staining, and urinary antigen detection kit (BinaxNOW) were comparatively evaluated for their ability to detect Streptococcus pneumoniae in patients with pneumonia or lower respiratory tract infection. Sputum culture results were used as a standard for comparison. Furthermore, the pneumococcus-positive rates in culture and rapid tests were compared using polymerase chain reaction (PCR) as a reference., Results: Of the 169 patients studied, 54 (32.0%) tested positive for S. pneumoniae in culture. S. pneumoniae detection sensitivities for Gram staining, RAPIRUN, and BinaxNOW were 75.9%, 90.7%, and 53.7%, respectively; thus, RAPIRUN had a significantly higher sensitivity than BinaxNOW (p<0.001). For patients with ≥10(5) copies/μg of pneumococcal surface protein A DNA PCR analysis, the detection rates of culture, Gram staining, and RAPIRUN were 85.2%, 72.1%, and 82.0%, respectively, however, the detection rate of BinaxNOW was only 47.5%. Comparisons among 45 patients with culture-positive pneumococcal pneumonia revealed that RAPIRUN had a significantly higher detection rate than BinaxNOW in the mild cases (p<0.006), regardless of the number of days from onset (p<0.03)., Conclusion: RAPIRUN is a rapid testing kit that detects S. pneumoniae in sputum with a high sensitivity and specificity. It is a particularly more useful detection kit than BinaxNOW for early and mild community-acquired pneumonia in pre-treatment patients whose sputum specimens can be obtained.

Background: Carnitine plays a pivotal role in a variety of cellular functions. Carnitine deficiency often occurs in severely disabled patients, especially under valproic acid administration. However, the possible causative factors underlying carnitine deficiency have not been fully identified. The present study aimed at clarifying the association of various anthropometric and biochemical variables, including dietary intake of carnitine, with carnitine levels in severely disabled patients., Methods: Twenty-six severely disabled patients (mean age: 14.1 years; s.d. 7.8) were enrolled. Plasma carnitine levels were evaluated by an enzyme cycling assay. Estimation of the dietary intake of carnitine was made based on dietary records over a 3-day period., Results: Plasma total and free carnitine levels in patients were significantly lower than those in controls obtained from the previous report. However, the ratios of free carnitine to total carnitine did not change significantly. Free carnitine levels were well correlated with a nutritional intake of carnitine. Administration of not only valproic acid but also other anti-epileptic drugs was found to cause a significant decrease of free carnitine levels after adjusting the nutritional intake of carnitine. Among various anthropometric or biochemical variables, albumin and uric acid showed a significant correlation with free carnitine levels., Conclusions: Physicians should be aware of the fact that severely disabled patients are at risk for carnitine deficiency even in the absence of valproic acid administration, and pay more attention to the nutritional intake of carnitine., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Aim: Epidemiological research on thinness, particularly in early childhood, is limited. This study tracked thin children aged 5 years back to birth, compared them with normal-weight children and investigated the relationship with parental thinness., Methods: We enrolled 2678 children (50.5% boys) aged 5 years and attending kindergarten or nursery in the Nara Prefecture of Japan. The children's height and weight at birth, 1.5 years and 3.5 years, were obtained from mother-child health records. Child thinness was defined as having a body mass index (BMI) of less than the fifth percentile of the reference values for Japanese children, and parental thinness was defined as a BMI of <18.5., Results: The overall prevalence of thinness at 5 years of age was 4%, with no significant difference between genders. At every age, weight z-scores and BMI percentiles were significantly lower in thin children than normal-weight children. The increment in weight z-scores between birth and the age of 1.5 years was significantly lower in thin children. The only parental link was paternal thinness and thinness in boys., Conclusion: Careful observation of body weight from birth is important to reduce thinness at 5 years of age. Paternal thinness may be a risk factor for thinness in boys., (©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: A nutritional assessment of pediatric patients with cancer is important to improve their outcome. The number of longitudinal nutritional studies during treatment, however, is limited. The purpose of this study was to investigate the longitudinal changes in anthropometric measures and serum albumin level during chemotherapy in patients with acute lymphoblastic leukemia (ALL)., Methods: We retrospectively reviewed the charts of 23 patients (19 boys, four girls) with ALL from April 2007 to March 2010. The median age at diagnosis was 4.5 years. Bodyweight, height, and serum albumin levels were measured at the start and the end point of each chemotherapy phase., Results: At diagnosis, two patients (8.7%) were underweight and five patients (21.7%) were overweight according to body mass index z-score, while five patients were underweight and three (13.0%) were overweight according to Waterlow score. The prevalence of malnourished patients did not change significantly throughout chemotherapy by either assessment. The absolute scores in either assessment were significantly reduced at the sanctuary treatment phase. Low serum albumin (<3.2 g/dL) was found in two patients at diagnosis. Mean albumin decreased significantly at the induction and the re-induction phases., Conclusions: Given that nutritional status under a similar chemotherapeutic regimen as assessed by anthropometric measures and albumin level differed among patients, careful observation of the nutritional status and intervention may be necessary at different phases of chemotherapy., (© 2014 Japan Pediatric Society.)

Aim: Several studies show that hyperuricaemia, abnormally high levels of uric acid in the blood, frequently occurs in adult Down's syndrome patients, but paediatric research is scarce. We aimed to clarify its prevalence in paediatric Down's syndrome patients and its association with lifestyle-related laboratory variables and nutritional intake, to consider possible effects in later life., Methods: We compared 52 Down's syndrome patients, from one to 15 years of age, with age-matched controls. Hyperuricaemia was defined using reference values established for children, as uric acid z-scores of more than 2.0. Nutritional intake was estimated using 3-day dietary records., Results: Hyperuricaemia occurred in 17 Down's patients (32.7%) and was significantly higher in Down's patients than the controls. The prevalence was also significantly higher in males. There were no significant differences between hyperuricaemia-positive and hyperuricaemia-negative patients in terms of age, body mass index standard deviation scores, fasting blood glucose, insulin, homeostasis model assessment-insulin resistance and triglyceride, and purine body intake was similar. There were differences in high-density lipoprotein cholesterol., Conclusion: We found high rates of hyperuricaemia from early childhood in Down's syndrome patients. This suggests careful management of Down's syndrome patients, as hyperuricaemia is an independent risk factor for lifestyle-related diseases in adulthood., (©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Spinocerebellar degeneration (SCD) is a progressive neurodegenerative disorder in which cerebellar ataxia causes motor disability. There are no widely applicable methods for objective evaluation of ataxia in SCD. An objective system to evaluate ataxia is necessary for use in clinical trials of newly developed medication and rehabilitation. The aim of this study was to develop a simple method to quantify the degree of upper-limb ataxia. Forty-nine patients with SCD participated in this study. Patients were instructed to trace an Archimedean spiral template, and the gap between the template spiral and the drawn spiral (gap area; GA) was measured using Image J software. Ataxia was rated using the Scale for the Assessment and Rating of Ataxia (SARA) and cerebellar volume was evaluated in 37 patients using an axial cross-section of magnetic resonance images that were obtained within 6 months of clinical evaluation. Regression analysis was performed to assess the relation between GA and patient age, disease duration, SARA score, and cerebellar volume. GA was significantly related to total SARA score (r = 0.660, p < 0.001), the posture and gait (r = 0.551, p < 0.001), speech (r = 0.527, p < 0.001), hand movements (r = 0.553, p < 0.001), and heel-shin slide (r = 0.367, p = 0.036) SARA subscores, and cerebellar volume (r = 0.577, p < 0.001) but was not related to patient age (r = 0.176, p = 0.227) or disease duration (r = 0.236, p = 0.103). GA is a simple, useful method to objectively quantify the degree of cerebellar ataxia, especially upper-limb ataxia, and can be widely adopted in various settings, including clinical trials.