Soluble APP-α and APP-ß in cerebrospinal fluid as potential biomarkers for differential diagnosis of mild cognitive impairment.

OBJECTIVES: Concentrations of soluble amyloid precursor proteins-α (sAPPα) and -ß (sAPPß) in cerebrospinal fluid (CSF) may reflect the neuropathology of Alzheimer's disease (AD). We previously reported that the concentrations of both sAPPα and sAPPß were significantly higher in patients with mild cognitive impairment (MCI) due to AD (MCI-AD) than in control subjects without cognitive impairment. The present study analyzed whether these sAPPs are useful in the differential diagnosis of MCI. METHODS: A modified and sensitive method was used to analyze concentrations of sAPPα and sAPPß in CSF of patients with MCI-AD (n = 30) and MCI due to other causes (MCI-others) (n = 24). Phosphorylated tau (p-tau) and amyloid ß-protein 42 (Aß42) were also analyzed using standard methods. RESULTS: CSF concentrations of sAPPα and sAPPß were significantly higher in the MCI-AD than in the MCI-others group (p < 0.001). Furthermore, concentrations of both sAPPα and sAPPß were highly correlated with the concentration of p-tau, consistent with our previous report. CONCLUSIONS: Measurement of both sAPPs in CSF using sensitive methods can be helpful in the precise differential diagnosis of patients with MCI.

Non-motor manifestations in ALS patients with tracheostomy and invasive ventilation.

INTRODUCTION: This study aimed to investigate non-motor manifestations in amyotrophic lateral sclerosis (ALS) patients with tracheostomy and invasive ventilation (TIV) and their relevance to disease progression. METHODS: Sixty-seven ALS patients with TIV were enrolled, and followed-up prospectively. The patients were classified at the final evaluation into two subgroups according to the duration of TIV use or disease stage measured by communication impairment. We identified non-motor manifestations and investigated their frequencies and differences across the stages. RESULTS: The non-motor manifestations were macroglossia (22.4%), unstable blood pressure (38.8%), hypothermia (26.9%), dysuria (50.7%), and hyperglycemia (12.1%). These manifestations occurred significantly more frequently in patients with TIV ≥5 years than in patients with TIV <5 years, and more in patients with severe communication impairment than in those with preserved communication ability. DISCUSSION: Non-motor manifestations are observed at a high rate in ALS patients with TIV, and are possibly related to disease progression. Muscle Nerve 57: 735-741, 2018.

Marked preservation of the visual and olfactory pathways in ALS patients in a totally locked-in state.

MATERIALS AND METHODS: The present paper examines the brains and spinal cords in 7 patients with amyotrophic lateral sclerosis (ALS) receiving artificial respirator support in a totally locked-in state (TLS) neuropathologically in order to clarify whether any anatomical structures in the central nervous system are preserved. RESULTS AND CONCLUSION: We found that the visual and olfactory pathways, hypothalamus, nucleus basalis of Meynert, and commissura anterior were remarkably well preserved, whereas the somatosensory, auditory, and gustatory pathways in the brain stem and/or spinal cord showed severe deterioration.

Experimental study using phantom models of cerebral aneurysms and 4D-DSA to measure blood flow on 3D-color-coded images.

BACKGROUND: The current 3D-iFlow application can only measure the arrival time of contrast media through intensity values. If the flow rate could be estimated by 3D-iFlow, patient-specific hemodynamics could be determined within the scope of normal diagnostic management, eliminating the need for additional resources for blood flow rate estimation. OBJECTIVE: The aim of this study is to develop and validate a method for measuring the flow rate by data obtained from 3D-iFlow images - a prototype application in Four-dimensional digital subtraction angiography (4D-DSA). METHODS: Using phantom model and experimental circuit with circulating glycerin solution, an equation for the relationship between contrast media intensity and flow rate was developed. Applying the equation to the aneurysm phantom models, the derived flow rate was evaluated. RESULTS: The average errors between the derived flow rate and setting flow rate became larger when the glycerin flow and the X-rays from the X-ray tube of the angiography system were parallel to each other or when the measurement point included overlaps with other contrast enhanced areas. CONCLUSION: Although the error increases dependent on the imaging direction and overlap of contrast enhanced area, the developed equation can estimate the flow rate using the image intensity value measured on 3D-iFlow based on 4D-DSA.

Alternating-current electrolysis for the production of phenol from benzene.

Works both ways: phenol was produced by both anodic and cathodic benzene oxidations over the V(x)O(y)-Sn(0.9)In(0.1)P(2)O(7) electrode in an electrochemical cell, thus allowing the use of AC electrolysis for phenol production. AC electrolysis was found to be more efficient and selective toward phenol production than DC electrolysis.

Body Weight Gain Is Associated with the Disease Stage in Advanced Amyotrophic Lateral Sclerosis with Invasive Ventilation.

We investigated the incidence of weight gain and its related factors in patients with amyotrophic lateral sclerosis (ALS) who underwent tracheostomy and invasive ventilation (TIV). Seventy-eight patients with ALS and TIV were enrolled and followed up prospectively. We clarified the clinical profiles of patients with increased weight following TIV and examined chronological variations in their body mass index (BMI), energy intake, and serum albumin levels. Post follow-up, we determined their disease stage according to their communication impairment (stage I to V) and investigated factors associated with BMI increase following TIV. Patients with a post-TIV BMI increase ≥1.86 kg/m2 demonstrated a higher incidence of ophthalmoplegia (76.2%), total quadriplegia (61.9%), severe communication impairment (stage V; 33.3%), and hypoalbuminemia than those with a BMI increase <1.86 kg/m2. Patients with stage V communication impairment exhibited a larger and faster BMI decrease before TIV (mean -4.2 kg/m2 and -2.5 kg/m2/year, respectively); a larger BMI increase (mean +4.6 kg/m2) following TIV, despite lower energy intake; and lower albumin levels post follow-up than those with lower-stage communication impairment. Multilevel linear regression analysis demonstrated an independent association between communication impairment stages (stage V) and a post-TIV BMI increase (p = 0.030). Weight gain and hypoalbuminemia during TIV in patients with ALS were associated with the disease stage and may be attributable to the neurodegenerative processes that are peculiar to ALS.

Immunoglobulin G4-related Disease Accompanied by Peripheral Neuropathy: A Report of Two Cases.

Due to its rarity and the limited literature, the clinicopathological characteristics of peripheral nerve involvement in immunoglobulin G4 (IgG4)-related disease are unknown. We present two cases of IgG4-related disease, accompanied by peripheral neuropathy, presenting as unilateral ptosis (case 1) and sclerosing cholangitis (case 2), respectively. In both cases, sural nerve biopsy indicated vasculitis as the underlying pathophysiology; the peripheral neuropathy was refractory to corticosteroid therapy. In contrast to the previously proposed pathomechanism of IgG4-related neuropathy (direct lymphoplasmacytic infiltration), the pathological findings in our cases suggest that vasculitis occurs secondary to systemic autoimmune conditions.

Observation of domain wall bimerons in chiral magnets.

Topological defects embedded in or combined with domain walls have been proposed in various systems, some of which are referred to as domain wall skyrmions or domain wall bimerons. However, the experimental observation of such topological defects remains an ongoing challenge. Here, using Lorentz transmission electron microscopy, we report the experimental discovery of domain wall bimerons in chiral magnet Co-Zn-Mn(110) thin films. By applying a magnetic field, multidomain structures develop, and simultaneously, chained or isolated bimerons arise as the localized state between the domains with the opposite in-plane components of net magnetization. The multidomain formation is attributed to magnetic anisotropy and dipolar interaction, and domain wall bimerons are stabilized by the Dzyaloshinskii-Moriya interaction. In addition, micromagnetic simulations show that domain wall bimerons appear for a wide range of conditions in chiral magnets with cubic magnetic anisotropy. Our results promote further study in various fields of physics.

[Successful treatment of multiple sinus thromboses and meningitis due to aspergilli and alpha-streptococci with preemptive antimycotic therapy: a case report].

A 62-year-old immunocompetent woman presented with 11 days of headache, 2 days of right eye ache and 1 day of fever and lethargy. Neurological examination revealed nuchal stiffness, right proptosis, bilateral ptosis, and right abducens palsy. Cerebrospinal fluid (CSF) examination revealed elevated white cell count (164 /microl) and protein level (115 mg/dl). Cranial MRI showed sphenoid sinusitis, thromboses of the right superior ophthalmic vein, bilateral cavernous sinuses, left sphenoparietal sinus and left sigmoid sinus, and enhanced meninges. Purulent meningitis and multiple mycotic cerebral venous sinus thromboses were diagnosed. After empirical therapy with meropenem, fever persisted and CSF cell count further elevated (668/microl on day 3). Additional treatment with liposomal amphotericin B (L-AMB) and low-dose heparin from day 3 ameliorated her symptoms and lowered her CSF cell count. Laboratory test on admission later revealed elevated serum aspergillus antigen (index = 3.6) and positive blood culture for streptococcus viridans. L-AMB was replaced by voriconazole due to skin rash, and the latter was changed to itraconazole due to drug-induced hepatitis. She was discharged without complication and has been free of recurrence for 7 months. Aspergillus has a propensity to invade cerebral vessels and meninges, causing local thrombosis and meningitis with high mortality and morbidity. Direct penetration from adjacent sphenoid sinus can be a cause of cavernous sinus thrombosis, due to extreme thinness of the wall of sphenoid sinus. Cerebral venous sinuses lack valves, and this may facilitate the spread of mycotic thrombus to the other sinuses. Early preemptive treatment with antimycotic agents brought a favorable outcome to our patient.

Fuel cell and electrolyzer using plastic waste directly as fuel.

The effective utilization of plastic waste, including its use as an energy or chemical resource, has attracted much attention. Nevertheless, energy recovery from plastics via incineration generates air pollutants and toxic compounds, while chemical conversion requires significant energy inputs, especially in the case of gasification. Herein, we report the electrochemical conversion of plastics into electricity or hydrogen without the use of special procedures. When a mixture of plastic solid combined with an acidic solution was fed into an electrochemical cell, the solid was found to dissolve in the solution at 100 °C or higher, followed by the release of protons from the anode to the cathode according to a multi-electron oxidation reaction. This oxidation reaction required an anode that was sufficiently porous so as to allow transport of the reactants. Taking the sponge sample as an example, the dissolved polyurethane had a molecular weight of 2000 or higher, the transport of which was facilitated using a carbon support with a pore diameter of approximately 10 nm. In addition, carbon black having an ordered porous structure exhibited better reagent transport compared to a disordered porous carbon black with similar pore diameters. As a consequence, this cell continuously provided power densities on the order of mW cm-2 in the fuel cell mode and generated hydrogen at a low cell voltage of 0.55 V in the electrolyzer mode, using plastics as fuels at an operational temperature of 200 °C.

Glycogen synthase kinase-3beta is associated with Parkinson's disease.

We immunohistochemically examined the expression of glycogen synthase kinase-3beta (GSK-3beta) in the brains of Parkinson's disease (PD) patients. GSK-3beta was localized in punctate structures in the cytosol of subsets of neurons in the midbrain and upper pons. GSK-3beta was also localized in Lewy bodies (LBs) as was phosphorylated GSK-3beta (Ser9) (pGSK-3beta (Ser9)). Both GSK-3beta and pGSK-3beta (Ser9) were localized specifically in the halo of LBs. The core of LBs was negative for GSK-3beta, while pGSK-3beta (Ser9) was present in only a small number of LB cores. Cortical LBs were positive for pGSK-3beta (Ser9) but not for GSK-3beta. Neither GSK-3beta nor pGSK-3beta (Ser9) was present in glial cytoplasmic inclusions (GCIs) in the brains of multiple system atrophy (MSA) patients. Our results suggest that GSK-3beta plays a role in the pathogenesis of PD but not in that of MSA.

Humidity Driven Transition from Insulator to Ionic Conductor in Portland Cement.

This work aims to assess ionic conduction in anhydrous cement particles and hydrated cement pastes with aging periods of 5-25 days. When a cement sample was humidified (relative humidity = 100%) over the range of 50-100 °C, it exhibited bulk conductivities of 10-3-10-2 S cm-1, regardless of the hydration level, whereas the interfacial conductivities varied in the range of 10-7-10-3 S cm-1, depending on the structural defects or conduction pathways of the sample. Both the bulk and interfacial conductivities were increased to 0.01 S cm-1 or higher at 100 °C, although the sample required previous moistening with water mist. The major charge carrier in the sample was determined to be hydroxide ions, and the total ion transport number was approximately 1. Exposing the sample to a mixture of carbon dioxide and water vapor caused a decrease in the bulk and interfacial conductivities; however, the bulk conductivity was returned to the initial value by treatment with an acid.

Body weight variation predicts disease progression after invasive ventilation in amyotrophic lateral sclerosis.

Weight loss is an independent predictor of survival in the early stages of amyotrophic lateral sclerosis (ALS). However, the effects of weight variations on the functional prognosis after tracheostomy and invasive ventilation (TIV) in ALS remain unknown. This prospective cohort study aimed to investigate the relationship between weight loss before TIV and disease progression after TIV in ALS patients. Sixty ALS patients with TIV were enrolled and classified into subgroups based on the rate of decline in body mass index, from onset to TIV utilization (ΔBMI). During follow-up, we assessed the patients for presence of communication impairments, ophthalmoplegia, total quadriplegia, mouth opening disability, and dysuria. We analyzed the relationship between ΔBMI and the communication stage or motor disabilities. The log-rank test showed that patients with a ΔBMI ≥ 1.7 kg/m2/year showed a shorter period of preserved communication ability (p = 0.0001), shorter time to develop ophthalmoplegia (p = 0.0001), total quadriplegia (p < 0.0001), mouth opening disability (p < 0.0001), and dysuria (p = 0.0455). Cox multivariate analyses showed that a larger ΔBMI was an independent prognostic factor for the early development of ophthalmoplegia (p = 0.0400) and total quadriplegia (p = 0.0445). Weight loss in the early stages of ALS predicts disease progression in patients with advanced stages of ALS using TIV.

High cognitive function of an ALS patient in the totally locked-in state.

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive degeneration of upper and lower motor neurons. Patients with ALS progressively lose their ability to control voluntary movements and occasionally enter the totally locked-in state (TLS), in which they cannot move any part of their bodies including the eyes. In this study, we clarified the preserved abilities and reorganization of the motor system of a 73-year-old patient with ALS in the TLS using optical topography, a recently developed extension of near-infrared spectroscopy. The patient performed four cognitive tasks: dichotic listening, covert singing, word fluency, and motor imagery. The bilateral prefrontal and bilateral sensorimotor areas were activated during the two language-related tasks (dichotic listening task and the word fluency), the right prefrontal and sensorimotor areas during the covert singing task, and the right prefrontal and dorsal sensorimotor areas during the motor imagery task. Contralateral sensorimotor activation was not observed in the motor imagery task. These results suggest that cognitive functions can be preserved in ALS in the TLS, with sensorimotor areas playing an important role.

Chronic Brachial Plexus Neuritis That Developed into Typical Neuralgic Amyotrophy and Positively Responded to Immunotherapy.

Based on the hypothesis that autoimmunity plays a role in the pathogenesis of neuralgic amyotrophy (NA), immunotherapy is sometimes administered. Early intervention is recommended for a good prognosis. We herein report the case of a 55-year-old man who presented with neuralgia, weakness, and muscle atrophy in his right shoulder girdle and upper arm, which progressed for ten months following a marine sports accident. The patient was diagnosed with NA. His neurological deficits gradually improved after several courses of immunotherapy, suggesting that in addition to being effective for treating early-stage disease, immunotherapy may be effective for treating chronic cases.

Intermediate-temperature electrolysis of energy grass Miscanthus sinensis for sustainable hydrogen production.

Biohydrogen produced from the electrolysis of biomass is promising because the onset voltages are less than 1.0 V and comparable to those of water and alcohol-water electrolysis. The present study focuses on Miscanthus sinensis as a model grass because of its abundance and ease of cultivation in Japan. The electrochemical performance and hydrogen formation properties of electrolysis cells using grass as a biohydrogen source were evaluated at intermediate temperature to achieve electrolysis. The components, such as holocellulose, cellulose, lignin, and extractives, were separated from Miscanthus sinensis to understand the reactions of Miscanthus sinensis in the electrolysis cell. The relatively high resistivity and low current-voltage performance of an electrolysis cell using lignin were responsible for degradation of the electrolysis properties compared to those with pure cellulose or holocellulose as biohydrogen resources. Biohydrogen was formed according to Faraday's law and evolved continuously at 0.1 A cm-2 for 3,000 seconds.

Long-term use of a neural prosthesis in progressive paralysis.

Brain-computer interfaces (BCIs) enable communication with others and allow machines or computers to be controlled in the absence of motor activity. Clinical studies evaluating neural prostheses in amyotrophic lateral sclerosis (ALS) patients have been performed; however, to date, no study has reported that ALS patients who progressed from locked-in syndrome (LIS), which has very limited voluntary movement, to a completely locked-in state (CLIS), characterized by complete loss of voluntary movements, were able to continue controlling neural prostheses. To clarify this, we used a BCI system to evaluate three late-stage ALS patients over 27 months. We employed steady-state visual evoked brain potentials elicited by flickering green and blue light-emitting diodes to control the BCI system. All participants reliably controlled the system throughout the entire period (median accuracy: 83.3%). One patient who progressed to CLIS was able to continue operating the system with high accuracy. Furthermore, this patient successfully used the system to respond to yes/no questions. Thus, this CLIS patient was able to operate a neuroprosthetic device, suggesting that the BCI system confers advantages for patients with severe paralysis, including those exhibiting complete loss of muscle movement.

Operation of a P300-based brain-computer interface by patients with spinocerebellar ataxia.

OBJECTIVE: We investigated the efficacy of a P300-based brain-computer interface (BCI) for patients with spinocerebellar ataxia (SCA), which is often accompanied by cerebellar impairment. METHODS: Eight patients with SCA and eight age- and gender-matched healthy controls were instructed to input Japanese hiragana characters using the P300-based BCI with green/blue flicker. All patients depended on some assistance in their daily lives (modified Rankin scale: mean 3.5). The chief symptom was cerebellar ataxia; no cognitive deterioration was present. A region-based, two-step P300-based BCI was used. During the P300 task, eight-channel EEG data were recorded, and a linear discriminant analysis distinguished the target from other nontarget regions of the matrix. RESULTS: The mean online accuracy in BCI operation was 82.9% for patients with SCA and 83.2% for controls; no significant difference was detected. CONCLUSION: The P300-based BCI was operated successfully not only by healthy controls but also by individuals with SCA. SIGNIFICANCE: These results suggest that the P300-based BCI may be applicable for patients with SCA.