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Vasovagal syncope (VVS) or reflex is usually caused by physical and mental stress-related factors, like pain, anxiety, and fear, and it is one of the most frequent complications during dental treatment. Two patients, both with histories of dental phobia and of VVS during vaccination, venipuncture, and dental treatment with local anesthetics, were scheduled for dental treatment under intravenous (IV) sedation. However, both experienced episodes of VVS that occurred during venipuncture using a 24-gauge indwelling needle. We determined that pain was the main trigger of VVS for these patients and attempted to reduce venipuncture-associated pain using 60% lidocaine tape applied 3 hours before venipuncture at their next dental visits, respectively. Use of the lidocaine tape was successful and permitted comfortable placement of the IV catheter without any onset of VVS.

Scleromyxedema (SME) is characterized by widespread waxy papules on the skin, with mucin deposits in the upper dermis. Twenty-one SME cases of myopathy have been reported; of the cases, six showed vacuolar formation, and two showed mucin deposition. We report the first case of SME with mucin-associated vacuolated fibers. A 45-year-old woman with SME developed progressive proximal muscle weakness. Muscle biopsy revealed myopathic changes with numerous vacuoles linked to mucin in the affected muscle fibers, which were heavily immunostained for fibroblast growth factor 2 (FGF2). Despite repeated high dose oral prednisolone and intravenous immunoglobulin administrations, muscle weakness recurred continuingly, culminating in death due to congestive heart failure. Immunotherapy was partly effective in our case, although it was refractory. Treatment responsiveness in patients with SME myopathy varied; however, due to its rarity, the mechanism remains to be elucidated. To address this issue, we investigated muscle specimens immunohistochemically and detected marked upregulation of FGF2 in the affected muscle fibers of our patient. FGF2, a strong myogenesis inhibitor, may exert a suppressive effect on muscle fiber regeneration, which may have conferred refractoriness to our patient's SME myopathy.

Scoliosis may often be associated with a variety of cardiovascular and respiratory conditions or diseases, and depending on the severity of the spinal deformity, it may also complicate anesthetic management because of the difficulty of neck extension and tracheal deformity. Therefore, patients with scoliosis may require careful perioperative anesthetic considerations. A 14-year-old girl was scheduled to undergo extractions and restorative treatment for dental caries under general anesthesia. Her medical history was significant for intellectual disability and autism as well as previously undiagnosed scoliosis. After fixation of a 6.0 Portex® endotracheal tube (ETT), percutaneous oxygen saturation (SpO2) decreased to 93%, peak airway pressures increased, and unilateral lung ventilation was noted. Inadvertent mainstem bronchial intubation was immediately suspected, prompting removal of the Portex ETT and reintubation with a shorter 6.0 Microcuff® ETT. The dental treatment was completed successfully without further incident. Assessment of the ETTs used intraoperatively led to the determination that the distance from the glottis to the carina was considerably shorter than normal for this patient. It was speculated that the Microcuff ETT may be optimal for anesthetic management of scoliosis patients because of its shorter lengths compared with other style ETTs, which may reduce the risk of bronchial intubation in such cases.

Early dark energy (EDE) models have attracted attention in the context of the recent problem of the Hubble tension. Here we extend these models by taking into account the new density fluctuations generated by the EDE which decays around the recombination phase. We solve the evolution of the density perturbations in dark energy fluid generated at the phase transition of EDE as isocurvature perturbations. Assuming that the isocurvature mode is characterized by a power-law power spectrum and is uncorrelated with the standard adiabatic mode, we calculate the CMB angular power spectra. By comparing them to the Planck data using the Markov-Chain Monte Carlo method, we obtained zero-consistent values of the EDE parameters and $H_0=67.56^{+0.65}_{-0.66}~\mathrm{km} \, \mathrm{s}^{-1} \mathrm{Mpc}^{-1}$ at $68 \%$ CL. This $H_0$ value is almost the same as the Planck value in the $\Lambda$CDM model, $H_0=67.36 \pm 0.54~\mathrm{km} \, \mathrm{s}^{-1} \mathrm{Mpc}^{-1}$, and there is still a $\sim 3.5 \sigma$ tension between the CMB and Type Ia supernovae observations. Including CMB lensing, BAO, supernovae and SH0ES data sets, we find $H_0=68.94^{+0.47}_{-0.57}~\mathrm{km} \, \mathrm{s}^{-1} \mathrm{Mpc}^{-1}$ at $68 \%$ CL. The amplitude of the fluctuations induced by the phase transition of the EDE is constrained to be less than $1$--$2$ percent of the amplitude of the adiabatic mode. This is so small that such non-standard fluctuations cannot appear in the CMB angular spectra. In conclusion, the isocurvature fluctuations induced by our simplest EDE phase transition model do not explain the Hubble tension well., Comment: 16 pages, 7 figures

To achieve the challenging goal of simultaneously improving aesthetics and auditory function in the treatment of microtia, we developed an auricular prosthesis incorporating a cartilage conduction hearing aid (APiCHA), which covers a cartilage conduction hearing aid (CC-HA). We evaluated the acoustic characteristics generated by the method of combining these two components using an artificial mastoid and investigated the possibility of clinical translation.The first step in creating an APiCHA is to take molds of both the affected and normal auricles and invert the 3D data of the normal auricle to create data for the auricular prostheses. Grooves were then made inside the prosthetic data to fit the affected ear and a CC-HA, and the APiCHA was made of silicone. The acoustic characteristics were measured using an artificial mastoid, and the results were compared between CC-HA alone and with APiCHA.Compared with CC-HA alone, the gain was approximately 2 dB lower at high frequencies from 1 k Hz and higher, and approximately 2 dB higher at approximately 900 Hz when CC-HA was used with APiCHA. For the other frequencies, the acoustic characteristics were almost the same.The changes in acoustic characteristics caused by the combined use of APiCHA and CC-HA were minimal and did not pose a clinical problem. The combined use of APiCHA and CC-HA can be considered as a non-invasive and clinically applicable treatment option to achieve both aesthetic and auditory improvements for microtia.

Temporal binding refers to the subjective compression of the temporal interval between a voluntary action and its external sensory consequences. While empirical evidence and theoretical accounts have indicated the potential linkage between temporal binding and action outcome prediction mechanisms, several questions regarding the underlying processes and the fundamental nature of temporal binding remain unanswered. Based on the sophisticated classification of predictive processes proposed by Hughes et al. (2013), we conducted a systematic, quantitative review of the binding effect as measured with two representative procedures, i.e., Libet clock procedure and interval estimation procedure. Although both procedures were designed to measure the same phenomenon, we revealed a larger effect size and higher sensitivity to perceptual moderators in binding observed with the clock procedure than with the interval estimation. Moreover, in the former, we observed different characteristics for the two perceptual shifts that comprise temporal binding. Action shifts depended more on whether one can control outcome onsets with voluntary actions. In contrast, outcome shifts depended more on the degree to which participants could predict, rather than control, the action outcome onset. These results indicate that action shift occurs based on the activation of learned action–outcome associations by planning and executing actions, while outcome shift occurs based on comparing predicted and observed outcomes. By understanding the nature of each experimental procedure and each shift, future research can use optimal methods depending on the goal. We discuss, as an example, the implications for the underlying disorders of agency in schizophrenia.

Background Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal-dominant white matter disease, typically characterized by juvenile cognitive decline and frontoparietal white matter lesions. A portion of HDLS patients exhibit preferential motor dysfunctions as their initial symptoms, mimicking multiple sclerosis (MS). However, there is no study comparing this phenotype of HDLS and primary progressive multiple sclerosis (PPMS), which greatly resemble each other. This is the first preliminary study to clarify the clinical and neuroimaging features of motor-predominant HDLS, and compare it with PPMS, using cases whose colony stimulating factor 1 receptor (CSF1R) were sequenced. Methods Clinical and radiological data from Japanese patients at the Department of Neurology, Kyushu University Hospital, Fukuoka, Japan, were evaluated retrospectively and cross-sectionally. Twenty-nine brain and 18 spinal cord magnetic resonance imaging (MRI) scans from four motor-predominant HDLS patients with CSF1R mutations and 15 PPMS patients without CSF1R mutations, were evaluated using an HDLS MRI scoring system. Results Two patients with HDLS were initially diagnosed with MS and received immunotherapy. Clinically, motor-predominant HDLS and PPMS patients resembled each other in onset age and disability. However, motor-predominant HDLS patients had a significantly higher frequency of frontal release signs, lower positivity rates of oligoclonal IgG bands (OCB), and lower IgG index values. Total HDLS MRI scores, total white matter lesions (WMLs), and brain atrophy were similar between the diseases. However, motor-predominant HDLS patients had more marked atrophy of the corpus callosum (CC) body, more WMLs in the deep and subcortical regions of the frontoparietal lobes, fewer WMLs in the occipitotemporal periventricular regions, and more restricted diffusivity lesions on MRI than PPMS patients. There was a stronger association between disease duration and CC index in HDLS, suggesting more rapid progression compared with PPMS. Conclusions Motor-predominant HDLS has characteristic frequent frontal release signs, normal findings for OCB and the IgG index, severe CC body atrophy, abundant deep and subcortical WMLs in the frontoparietal lobes, subtle occipitotemporal lobe periventricular WMLs, and more restricted diffusivity lesions on MRI. Although the present study was limited by the small number of HDLS cases, we propose that immunotherapy should be avoided in such cases.

This work demonstrates a novel 1Tb 3D Flash memory chip that has an area efficiency of 10.4Gb/mm2 in a 3b/cell technology. Using a circuit under array (CUA) design technique and over 170 word-line (WL) layers, the chip achieves 33% higher bit density than prior 3b/cell work [1], and better density than in 4b/cell technology [3]. This paper discusses the challenges advanced 3D Flash memories face: using over 100 WL layers results in large parasitic loads and decreases read/program speed, and its complicated operation increases test costs. On the other hand, as high bandwidth is also required, this chip supports a 2.0Gbps IO transfer rate, while maintaining signal integrity. This work introduces four new key technologies to address these difficulties. 1) Asynchronous independent plane read (AIPR), with a 4-plane architecture to improve system-level performance. 2) Enhanced sensing that enables faster read time $(t_{R})$. 3) IO-DCC (duty cycle correction) training for high-speed DDR operation. 4) A scan chain to improve test coverage and cost effectiveness.

Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).

Shallow landslides occur frequently on the Aso volcanic mountains. The soil materials on the Aso volcanic mountains consist of tephra layers formed by volcanic activities. This study is aimed to specify the physical properties of soil that correlate with the sliding layer of a shallow landslide on the volcanic mountain area. Tephra layers consist of kuroboku and scoria layers and the differences between these layers were specified using the physical properties of soil methods. Results showed that the plasticity index and the fine fraction content can be used for estimating the sliding layer in the Aso volcanic area.

Background and study aims Endoscopic nasobiliary drainage (ENBD) for a malignant stricture in the bile duct has some advantages over endoscopic biliary stenting (EBS). However, ENBD may cause nasopharyngeal discomfort. We developed an external-to-internal convertible endoscopic biliary drainage (ETI-EBD) device that enables both internal and external drainage to occur during a single endoscopy. Patients and methods This device consists of three parts, comprising a 5-Fr ENBD tube (250 cm) (ENBD-t), an 8.5-Fr EBS tube (7 cm) (EBS-t), and an 8-Fr pusher tube for EBS (230 cm) (P-t). The EBS-t is mounted over the ENBD-t at the distal end of the ENBD-t. The P-t is also placed over the ENBD-t. After an endoscopic sphincterotomy, the EBS-t of the device is inserted into the papilla, then the duodenal endoscope is withdrawn, leaving the device in place. After ENBD, only the ENBD-t was withdrawn from the P-t. At this point, the EBS-t was isolated and left without endoscopy or radiography. Results ETI-EBD was successfully placed in all consecutive 21 patients (100 %). The release of EBS-t from ENBD-t wit was successfully completed in 19 patients (90.5 %). There were 4 patients with kink of P-t when exchanging this device from the mouth to the nose. It was difficult for 2 patients to withdraw the ENBD-t because of poor lubrication performance. There were no significant complications associated with the use of the device. Conclusion This device allows for both external and internal biliary drainage with a single endoscopy.

A 77-year-old man showed an asymptomatic meningeal lesion beneath the dura matter in the left fronto-parietal region on MRI during an examination for recurrent hoarsness. The lesion showed no gadolinium enhancement, and extended to neither the sulci nor skull. Neurological examinations revealed hoarseness, cochlear and vestibular dysfunction of the right ear, and mildly decreased Achilles tendon reflexes bilaterally. Laboratory findings showed marked inflammatory responses, but no abnormalities for LDH, IgG4, angiotensin-converting enzyme, or soluble IL-2 receptor. There was no serum monoclonal protein. Autoantibody panels in the serum were unremarkable except for an elevation of anti-type II collagen antibodies to a borderline value. Cerebrospinal fluid analysis disclosed an elevated protein concentration (152 mg/dl) and IgG index (1.41) with normal cell counts, negative results for bacterial/tubercular infection, and a normal cytology. 18F-fluorodeoxyglucose positron emission tomography showed increased uptake in the left frontal region (Max SUV: 7.54). Swelling of the vocal cord, arytenoid cartilage, false vocal cord, and vocal cord palsy on the right side were seen on laryngoscopy, all of which were ameliorated by dexamethasone administration. A meningeal biopsy contained the dura matter and arachnoid, in which a granulation composed of massive mature plasma cells with many Russel bodies, accompanied by occasional lymphocytes and histiocytes were observed. Three months after the biopsy, he developed bilateral auricular chondritis and conjunctivitis. Based on these findings, we diagnosed him with relapsing polychondritis (RP). Prednisolone administration (40 mg/day) improved the chondritis and meningeal lesion. Central nervous system involvement is rare in patients with RP, and meningeal complications, such as aseptic meningitis or pachymeningitis, are mostly observed after the diagnosis of RP. However, due to its rarity, it still remains to be clarified whether a similar pathogenesis of meningeal complications underlies RP. The present case is indicative in that predominant meningeal granuloma arose during chondritis of several portions that had gradually developed, which suggests that meningeal complications could be derived from RP.

This is a case report of anaphylaxis in which the basophil activation test (BAT) was used to identify the etiological agent. Although skin tests are considered the most effective methods for identifying anaphylactic triggers, the test itself presents a risk of inducing anaphylaxis. The BAT is advantageous because of its inherent lack of risk, high sensitivity and specificity to identify the suspected anaphylactic agents, and diagnostic accuracy comparable to conventional skin testing. Therefore, in the future, the BAT is likely to become the preferred test for the detection of allergens over conventional skin tests.

Connexin36 (Cx36) forms gap junctions between neurons, which are called electrical synapses, enabling adjacent neurons to communicate directly. The participation of chemical synapses in neurodegeneration in amyotrophic lateral sclerosis (ALS) has long been indicated, but it remains unclear whether electrical synapses are involved in the pathogenesis of ALS. We performed extensive immunopathological analyses using mutant superoxide dismutase 1 (SOD1G93A) transgenic mice and their littermates to investigate whether Cx36-made electrical synapses are affected in motor neuron diseases. We found that in the lamina IX of the lumbar spinal cord from wild type mice, about half of the Cx36 puncta existed independently of chemical synapse markers, while the rest coexisted with chemical synapse markers, such as vesicular glutamate transporter 1 (VGLUT1), which is a glutamatergic axon terminal marker, and/or glutamate decarboxylase 65 (GAD65), which is a GABAergic axon terminal marker. Cx36 single or Cx36/GAD65 double positive puncta, but not VGLUT1-containing puncta, were preferentially decreased on neuronal and dendritic surfaces of the anterior horn cells in the early stage of SOD1G93A ALS mice. Moreover, in five human autopsied sporadic ALS cases with bulbar or upper limb onset, Cx36 immunoreactivity was diminished in the proximal dendrites and neuropils of well-preserved large motor neurons in the lumbar anterior horns. These findings suggest that downregulation of neuronal and dendritic Cx36 in the spinal anterior horns commonly occurs from the early stage of hereditary and sporadic ALS. Cx36-made electrical synapses without glutamatergic signaling appear to be more vulnerable than other chemical synapses and electrical synapses with glutamatergic signaling in the early stage of motor neuron degeneration, suggesting involvement of Cx36-made electrical synapses in the pathogenesis of human ALS.

Clostridium botulinum produces a large toxin complex (L-TC) comprising botulinum neurotoxin associated with auxiliary nontoxic proteins. A complex of 33- and 17-kDa hemagglutinins (an HA-33/HA-17 trimer) enhances L-TC transport across the intestinal epithelial cell layer via binding HA-33 to a sugar on the cell surface. At least two subtypes of serotype C/D HA-33 exhibit differing preferences for the sugars sialic acid and galactose. Here, we compared the three-dimensional structures of the galactose-binding HA-33 and HA-33/HA-17 trimers produced by the C-Yoichi strain. Comparisons of serotype C/D HA-33 sequences reveal a variable region with relatively low sequence similarity across the C. botulinum strains; the variability of this region may influence the manner of sugar-recognition by HA-33. Crystal structures of sialic acid- and galactose-binding HA-33 are broadly similar in appearance. However, small-angle X-ray scattering revealed distinct solution structures for HA-33/HA-17 trimers. A structural change in the C-terminal variable region of HA-33 might cause a dramatic shift in the conformation and sugar-recognition mode of HA-33/HA-17 trimer.

A 37-old-male with a history of early childhood mental retardation was admitted to our hospital. He experienced recurrent syncopes at 23 years old, and at age 35 gait disturbance and hearing impairment developed gradually and worsened over time. His grandparents were in a consanguineous marriage. He was of short stature and absent of tendon xanthomas. Neurological examinations revealed scanning speech, dysphagia, right sensorineural hearing loss, spasticity in both upper and lower extremities, and spastic gait. Tendon reflexes were brisk throughout, and Babinski and Chaddock reflexes were both positive bilaterally. Laboratory tests revealed elevated lactate and pyruvate concentrations in both serum and cerebrospinal fluid. Fluid attenuated inversion recovery magnetic resonance imaging showed high intensity lesions in the bilateral cerebellar hemispheres, pyramidal tracts in the brainstem, and internal capsules symmetrically. Brain magnetic resonance spectroscopy measurements revealed an elevated lactate/creatine plus phosphocreatine ratio and a decreased N-acetyl-aspartate/creatine plus phosphocreatine ratio in the cerebellum. At this point, mitochondrial diseases, particularly myoclonic epilepsy with ragged-red fibers (MERRF), to be the most likely cause. We performed a biopsy of his left biceps brachii muscle, showing variations in fiber size with occasional central nuclei and very few ragged-red fibers. Blood mitochondrial respiratory enzyme assays showed normal values with elevated citrate synthase activity, and mitochondrial DNA analyses for MERRF revealed no pathogenic mutations. We then explored other possibilities and detected an elevated serum cholestanol concentration of 20.4 μg/ml (reference value

Aims/Introduction We aimed to identify factors – glycemic control, reactive inflammatory biomarkers or vital signs – associated with mortality in diabetic patients admitted to hospital for various infections (non‐intensive care unit). Materials and Methods We retrospectively analyzed the cases of 620 diabetic patients admitted to hospital for various infections (non‐intensive care unit) who underwent glucose monitoring >3 times per day. We extracted data regarding reactive inflammatory biomarkers and vital signs recorded on day 1 of hospital stay, and data on bacteremia and hypoglycemia status, glycemic variability (GV; coefficient of variation and standard deviation) and mean glucose concentrations during the entire hospital stay. Univariate and stepwise multivariate logistic regression analyses were carried out to determine the association between these factors and mortality. Results The mortality rate was 10.1%. Reactive inflammatory biomarkers, vital signs and bacteremia were not associated with mortality. According to the results of the adjusted analysis, hypoglycemia showed a significant positive association with mortality, increasing death risk by 266% (odds ratio [OR] 2.66, 95% confidence interval [95% CI] 1.22–5.83; P = 0.0006). High coefficient of variation and standard deviation values were significantly associated with increased mortality, increasing death risk by 18% (OR 1.18, 95% CI 1.01–1.38; P = 0.03) and 9% (OR 1.09, 95% CI 1.01–1.18; P = 0.03), respectively. Mean glucose concentrations were also significantly associated with mortality, increasing death risk by 5% (OR 1.05, 95% CI 1.02–1.08; P = 0.0008). Conclusions Glycemic indices (especially hypoglycemia and GV), rather than reactive inflammatory biomarkers or vital signs, were associated with mortality in non‐intensive care unit diabetes mellitus patients with infections.

Volcanic fans and volcaniclastic aprons (ring plains) developed at the foot of a volcano preserve the products of high-discharge, sediment-laden lahar flows that originate from a volcano. Geological and geomorphological features of a volcanic fan are important for discussing the flow characteristics and history of far-reaching flows such as lahars. The present study focuses on volcanic-fan deposits at the northern base of Chokai Volcano in northeast Japan. The authors conducted geomorphological analysis, excavation survey at the distal part of the volcanic fan, sedimentary facies analysis, radiocarbon dating, and historical document analysis to understand the flow characteristics and history of far-reaching lahars in relation to changes in the depositional processes and their triggering volcanic activity. Geological observation by manual trenching and coring revealed that the volcanic fan is composed mainly of a series of lahar deposits formed by at least five large lahar events. The 14C ages of the lahar deposits and their correlation with historical documents indicate that the large lahars travelled down the volcanic fan at: the 2nd–5th century BCE (L1); 2nd to 4th century BCE (L2); 5th to 7th century CE (L3); 871 CE (L4); and 1801 CE (L5) after the Kisakata debris avalanche (2.5 ka). According to the stratigraphy, ratio of magmatic fragments and hydrothermally altered material content in the deposits, and correlation with historical documents, these lahar events can be classified into three types in terms of their material source: (1) a cohesive debris flow sourced by the debris avalanche deposit (L1); (2) a non-cohesive lahar by a magmatic eruption (L2, L3, L4, and L5–1 subunit); and (3) a cohesive debris flow by a phreatic eruption (L5–2 subunit). The facies analysis revealed that the different flow behaviors of lahars reflect their sourced volcanic activity. The oldest lahar (L1), incorporating debris avalanche deposit, flowed as hazardous cohesive debris flow; lahars after magmatic eruptions (L2, L3, L4, and L5–1 subunit) tends to be streamflow through the flow transformation of sandy debris flow; and a cohesive lahar (L5–2 subunit) by a phreatic eruption tends to be of small scale. These results indicate that the characteristics of a lahar depend largely on causal volcanic activity.

To assess the risk of active TB in people with DM and the factors associated with this risk. Systematic review and meta-analysis. We searched the literature for studies that reported the effect of DM on TB controlled for the effect of age. Studies that had not established the diagnosis of DM prior to detecting active TB were excluded. Study quality was assessed by Newcastle-Ottawa scale and we conducted a meta-analysis using random-effects models. 14 studies (8 cohort and 6 case-control studies) that involved 22,616,623 participants met the selection criteria and were included in the analysis. There was substantial variation between studies in the estimates of the effect of DM on TB. However, the pooled estimates from 7 high-quality studies showed that diabetic people have a 1.5-fold increased risk of developing active TB versus those without DM (95%CI 1.28-1.76), with relatively small heterogeneity (I2 44%). The increased risk of TB was observed predominantly among DM populations with poor glycaemic control. There is evidence suggesting an increased risk of developing TB among people with DM, and that improving glycaemic control in DM patients would reduce the risk of developing TB. An integrated approach is needed to control the dual burden of DM and TB. This article is protected by copyright. All rights reserved.

I thank Dr. Wasilewski for the valuable comments on our NeuroImage.1 Our patient received irradiation (57.6 Gy/32 fractions) and oral temozolomide (100 mg for 5 d/mo for 14 months); however, the tumor gradually extended to the hypothalamus and he was transferred to another hospital for terminal care. We agree with Dr. Wasilewski's comment that alternative regimens for adult patients with anaplastic pilocytic astrocytoma (APA), especially showing recurrent or aggressive nature, are to be explored and established, and antiangiogenic treatment is one of the powerful tools. In our view, alternative treatments, such as bevacizumab, might be justified only when patients with APA show microvascular proliferations, as observed in our patient.1 We are not fully confident whether tests for BRAF V600E mutant proteins are mandatory, because the gene mutations are found in 6%–8% of extracerebellar pilocytic astrocytomas,2 as well as in other disorders (e.g., pleomorphic xanthoastrocytoma or ganglioglioma).3

Background Hopkins syndrome (HS) is a rare disorder presenting with acute flaccid paralysis of the limbs following an asthma attack. Neurologists encounter a diagnostic challenge if patients without a history of bronchial asthma develop neurologic features mimicking HS following acute respiratory distress. We report a case of HS occurring after a first episode of bronchial asthma associated with enterovirus D68 infection. Case presentation A 5-year-old girl developed acute respiratory distress. On the fourth hospital day, both her legs became paralyzed except for slight muscle contraction in the right lower limb. Tendon reflexes in the lower limbs were diminished and there was a positive Babinski sign on the right. Sensation was normal in all modalities, and there was no uro-rectal disturbance. Spinal magnetic resonance imaging identified T2-hyperintense lesions with spinal cord edema, mainly involving the bilateral T11 to L1 anterior horns, with left side dominance extending to the left posterior horn. The neurological and neuro-radiological findings of our case were suggestive of HS; however, she had no history of bronchial asthma. An acetylcholine inhalation challenge eventually proved the presence of reversible airway hyper-responsiveness, allowing us to diagnose HS. We identified enterovirus D68 in the patient’s intratracheal aspirates using a sensitive polymerase chain reaction assay. Intravenous immunoglobulin administrations at 2 g/kg2 for 5 consecutive days were repeated every month up to four times. After these treatments, the muscle strength of her right lower limb slightly improved while her left lower leg remained completely paralyzed. Conclusion This case emphasizes the importance of provocation tests to reveal the presence of airway hyper-responsiveness when a child shows neurological signs mimicking HS following acute respiratory distress. Furthermore, the present case suggests a possible link between HS and acute flaccid paralysis following lower respiratory tract infection by enterovirus D68.

We herein report a 32-year-old woman with adult-onset reducing body myopathy (RBM) who had a mutation in the four-and-a-half LIM domain 1 gene (FHL1) and showed a marked asymmetrical involvement of sternocleidomastoid and trapezius muscles. At 30 years of age she noticed bilateral foot drop, and over the next two years developed difficulty raising her right arm. At 32 years of age she was admitted to our hospital for a diagnostic evaluation. Neurological examination showed moderate weakness and atrophy of her right sternocleidomastoid muscle, right trapezius muscle, and bilateral upper proximal muscles. There were severe weakness and atrophy of her bilateral tibialis anterior muscles. Her deep tendon reflexes were hypoactive in her upper extremities. Her serum creatine kinase level was mildly increased. Muscle biopsy specimens from the left tibialis anterior muscle revealed marked variation in fiber size, some necrotic or regenerating fibers, and reducing bodies. Gene analysis of FHL1 demonstrated a mutation: a heterozygous missense mutation of c.377G>A (p. C126T) in FHL1. Compared with previous adult-onset RBM cases harboring mutations in FHL1, our case was characterized by asymmetrical atrophy of the sternocleidomastoid and trapezius muscles.

The large toxin complex (L-TC) produced by Clostridium botulinum is formed from the M-TC (BoNT/NTNHA complex) by conjugation of M-TC with HA-33/HA-17 trimer consists of two HA-33 proteins and a single HA-17 protein. This association is mediated by HA-70, which interacts with HA-17. The current study aims to identify the regions of the HA-70 molecule that adhere to the HA-33/HA-17 complex. Products from limited proteolysis of HA-70 were resolved by SDS-PAGE and transferred onto PVDF membranes, where they were probed with HA-33/HA-17 in a far-western blot. Among the HA-70 fragments, HA-33/HA-17 bound to those containing at least the C-terminal half of the HA-70 molecule, but not those carrying the N-terminal half. Additional docking simulation analysis indicated that the HA-70 region Gln420-Tyr575 is responsible for binding to HA-17, which is consistent with the far-western blot data. The findings here reveal additional details concerning the three-dimensional structure of the functional HA sub-complex in the botulinum toxin complex.

Objective Recent evidence has suggested the importance of an aberrantly activated monocyte system in amyotrophic lateral sclerosis (ALS) pathogenesis. However, the roles of each monocyte subset, namely CD14+CD16− classical monocytes, CD14dimCD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes, in ALS remain unknown. We aimed to clarify the alterations in the monocyte subset proportions and the surface marker expressions on each monocyte subset in ALS. Methods Blood samples were collected from 19 ALS patients and 28 healthy controls (HC). The surface expressions of CCR2, CX3CR1, CD64 and CD62L were measured in the three monocyte subsets (classical, non-classical and intermediate) by flow cytometry. Results The percentages of CCR2 and CD62L on CD14+CD16− classical monocytes were significantly lower in ALS patients than in HC (P = 0.0012 and P = 0.0296, respectively). No differences were found in CX3CR1 and CD64 on each monocyte subset. The percentage of intermediate monocytes showed a significant negative correlation with the revised ALS functional rating scale score (r = −0.631, P = 0.0038). Conclusions Reductions in chemotaxis- and adhesion-related molecules on classical inflammatory monocytes are present in ALS, further suggesting the involvement of an aberrant innate immune system in ALS pathogenesis.