Modulation of pain perception through transcranial alternating current stimulation and its nonlinear relationship with the simulated electric field magnitude.

BACKGROUND: Oscillatory activities observed in multiple regions are closely associated with the experience of pain. Specifically, oscillatory activities within the theta- and beta-frequency bands, observed in the left dorsolateral prefrontal cortex (DLPFC), have been implicated in pain perception among healthy individuals and those with chronic pain. However, their physiological significance remains unclear. METHODS: We explored the modulation of pain perception in healthy individuals by theta- and beta-band transcranial alternating current stimulation (tACS) over the left DLPFC and examined the relationship between the modulation effect and magnitude of the electric field elicited by tACS in the left DLPFC using computational simulation. RESULTS: Our findings revealed that both theta- and beta-tACS increased the heat pain threshold during and after stimulation. Notably, the simulated electric field magnitude in the left DLPFC exhibited an inverted U-shaped relationship with the pain modulation effect for theta-tACS. CONCLUSIONS: Our study findings suggested that there would be an optimal electric field strength to produce a high analgesic effect for theta-tACS. SIGNIFICANCE: The application of theta- and beta-tACS interventions targeting the left DLPFC might facilitate the treatment of chronic pain. Furthermore, the attainment of effective pain modulation via theta-tACS over the DLPFC warrants the use of optimal stimulus intensity.

Predicting habitual water intake from lifestyle questions.

OBJECTIVE: Previous studies have used selective recall and descriptive dietary record methods, requiring considerable effort for assessing food and water intake. This study created a simplified lifestyle questionnaire to predict habitual water intake (SQW), accurately and quickly assessing the habitual water intake. We also evaluated the validity using descriptive dietary records as a cross-sectional study. SUBJECTS AND METHODS: First, we used crowdsourcing and machine learning to collect data, predict water intake records, and create questionnaires. We collected 305 lifestyle-related questions as predictor variables and selective recall methods for assessing water intake as an outcome variable. Random forests were used for the machine learning models because of their interpretability and accurate estimation. Random forest and single regression correlation analysis were augmented by the synthetic minority oversampling that trained the model. We separated the data by sex and evaluated our model using unseen hold-out testing data, predicting the individual and overall habitual water intake from various sources, including non-alcoholic beverages, alcohol, and food. RESULTS: We found a 0.60 Spearman's correlation coefficient for total water intake between the predicted and the selective recall method values, reflecting the target value to be achieved. This question set was then used for feasibility tests. The descriptive dietary record method helped to obtain a ground-truth value. We categorized the data by gender, season, and source: non-alcoholic beverages, alcohol, food, and total water intake, and the correlation was confirmed. Consequently, our results showed a Pearson's correlation coefficient of 0.50 for total water intake between the predicted and the selective recall method values. CONCLUSIONS: We hypothesize that dissemination of SQW can lead to better health management by easily determining the habitual water intake.

Effect of baseline urinary glucose levels on the relationship between sodium-glucose cotransporter 2 inhibitors and serum uric acid in Japanese patients with type 2 diabetes mellitus.

In patients with type 2 diabetes mellitus (T2DM), controlling serum uric acid (SUA) and blood glucose levels is important. Moreover, sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease SUA levels by accelerating urinary uric acid excretion. We investigated the effect of baseline urinary glucose levels on the relationship between SGLT2 inhibitors and SUA levels. We conducted a retrospective observational study using the electronic medical records of patients with T2DM of Kindai University Nara Hospital (April 2013 to March 2022). We divided the patients into two groups according to their baseline urinary glucose levels: the N-UG group, which included patients with negative urinary glucose strip test results (-), and the P-UG group, which included patients with positive urinary glucose strip test results (± or more). The changes in SUA levels before and after SGLT2 inhibitor administration were investigated. For comparison, the changes in SUA levels before and after the prescription of antidiabetic agents, excluding SGLT2 inhibitors, were also investigated. Our results revealed that SGLT2 inhibitors significantly decreased the SUA levels in patients in the N-UG group but tended to decrease its levels in those in the P-UG group. Regardless of the urinary glucose status at baseline, the administration of SGLT2 inhibitors may be useful for patients with T2DM to prevent the complications of hyperuricemia.

Time-dependent changes in serum magnesium levels in patients receiving cetuximab with low baseline serum sodium levels.

Cetuximab causes electrolyte abnormalities, such as hypomagnesemia, hypokalemia, and hypocalcemia. However, little is known about the relationships between the onset of hypomagnesemia, patient background before administration, and time-dependent changes in serum magnesium levels. Therefore, we examined the patient backgrounds that influenced the onset of hypomagnesemia and the time-dependent changes in serum magnesium levels in patients receiving cetuximab. A retrospective study was performed to investigate patients with advanced or recurrent colorectal cancer or head and neck cancer, treated with a cetuximab regimen from 2012 to 2020 at Kindai University Nara Hospital. In total, 52 patients who met the inclusion criteria were enrolled in this study. The serum magnesium level was significantly lower in the hyponatremia before the administration group than in the non-hyponatremia group (p < 0.001). Univariate logistic regression analysis revealed that the baseline serum sodium levels (odds ratio [OR]: 0.741, 95% confidence interval [CI]: 0.588-0.934) and the combination of magnesium oxide tablet (OR: 0.997, 95% CI: 0.995-0.999) were one of the independent factors for hypomagnesemia. These results indicated that hyponatremia before administration may be an indicator of serum magnesium levels after administration of cetuximab. Cetuximab-induced hypomagnesemia may be predicted using baseline serum sodium levels, and hypomagnesemia may be prevented by administration of magnesium oxide tablets. Our findings provided new evidence for the management of serum magnesium levels in patients receiving cetuximab.

Metallic Glacial Glass Formation by a First-Order Liquid-Liquid Transition.

The glacial phase, with an apparently glassy structure, can be formed by a first-order transition in some molecular-glass-forming supercooled liquids. Here we report the formation of metallic glacial glass (MGG) from the precursor of a rare-earth-element-based metallic glass via the first-order phase transition in its supercooled liquid. The excellent glass-forming ability of the precursor ensures the MGG to be successfully fabricated into bulk samples (with a minimal critical diameter exceeding 3 mm). Distinct enthalpy, structure, and property changes are detected between MGG and metallic glass, and the reversed "melting-like" transition from the glacial phase to the supercooled liquid is observed in fast differential scanning calorimetry. The kinetics of MGG formation is reflected by a continuous heating transformation diagram, with the phase transition pathways measured at different heating rates taken into account. The finding supports the scenario of liquid-liquid transition in metallic-glass-forming liquids.

T-cell/Histiocyte-rich Large B-cell Lymphoma of the Larynx in a Juvenile Japanese Macaque (Macaca fuscata).

An 11-month-old female Japanese macaque (Macaca fuscata), born in captivity in a research institute, suddenly died without clinical signs. Necropsy examination revealed a nodular mass protruding from the left ventral aspect of the larynx, compressing the epiglottis anteriorly. Histopathologically, the laryngeal mass was comprised of medium- to large-sized atypical cells. Immunohistochemically, these were positive for CD20 and partially positive for CD79α. Among the atypical cells were CD3+ T cells and CD68+ histiocytes. Based on the findings, this case was diagnosed as T-cell/histiocyte-rich large B-cell lymphoma. Epstein-Barr virus (EBV)-encoded small RNAs were frequently detected in the atypical cells by in-situ hybridization, which was consistent with the finding that the macaque was seropositive for EBV antigen. This is the first report showing the potential association of simian lymphocryptovirus, the simian homologue of EBV, with lymphoma in a juvenile non-human primate.

Distortion of Local Atomic Structures in Amorphous Ge-Sb-Te Phase Change Materials.

The local atomic structures of amorphous Ge-Sb-Te phase-change materials have yet to be clarified and the rapid crystal-amorphous phase change resulting in distinct optical contrast is not well understood. We report the direct observation of local atomic structures in amorphous Ge_{2}Sb_{2}Te_{5} using "local" reverse Monte Carlo modeling dedicated to an angstrom-beam electron diffraction analysis. The results corroborated the existence of local structures with rocksalt crystal-like topology that were greatly distorted compared to the crystal symmetry. This distortion resulted in the breaking of ideal octahedral atomic environments, thereby forming local disordered structures that basically satisfied the overall amorphous structure factor. The crystal-like distorted octahedral structures could be the main building blocks in the formation of the overall amorphous structure of Ge-Sb-Te.

Performance and serum biochemical profile of Japanese quail supplemented with silymarin and contaminated with aflatoxin B1.

The aim of this study was to evaluate the hepatoprotective effect of silymarin in diets contaminated or not with aflatoxin B1 (AFB1) on the productive performance and serum biochemical profile of Japanese quail (Coturnix coturnix japonica) in the laying phase. A total of 240 12-week-old Japanese quail was used in a completely randomized design in a 3 × 2 factorial scheme (additives x contaminated or not with AFB1 - 1,500 µg/kg), totaling 6 treatments and 5 replicates of 8 birds each. The additives used were silymarin (500 g/ton), adsorbent (1 kg/ton), and a control diet (without additive). Of the total aflatoxin content, 84.64% was AFB1; 4.28% was AFB2; 11.07% was AFG1; and AFG2 was not detected. The data were submitted to ANOVA, and means were compared by Tukey's test. There was no interaction (P > 0.05) between the additive and AFB1 on performance parameters. However, the inclusion of AF in diets reduced (P < 0.05) egg weight and feed intake, impairing feed conversion compared to the unchallenged groups. There was an increase (P < 0.05) in blood concentrations of aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and creatine kinase (CK) in birds challenged with AFB1, regardless of the additive used, characterizing a possible alteration in hepatic metabolism. Serum total protein and globulin levels were reduced (P < 0.05) in birds challenged with toxins. The consumption of diets contaminated with 1,500 µg AFB1/kg altered hepatic function in quail, impairing productive performance and egg weight. The concentrations of silymarin and adsorbent evaluated in this study were not able to mitigate the negative effect of toxins on the metabolism and performance of laying quail.

Comparison of ultrasonographic joint and tendon findings in hands between early, treatment-naïve patients with systemic lupus erythematosus and rheumatoid arthritis.

Although both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) may lead to joint deformity, SLE arthritis is typically non-erosive and often accompanied by Jaccoud's deformity. Therefore, we examined characteristics of joint and tendon lesions in patients with SLE and RA by ultrasonography. Fifteen treatment-naïve SLE patients and 40 treatment-naïve RA patients with joint symptoms were included in this study. The hand joints and related tendons were ultrasonographically examined using grey-scale (GS) and power Doppler (PD). Joint involvement was comparably observed in patients with SLE and RA (80% versus 95%, p = 0.119). However, tendon involvement was more frequent in SLE than in RA (93% versus 65%, p = 0.045), especially in the wrist joints (73% versus 40%, p = 0.037). When we investigated the intensity of US findings, the joint synovitis score (GS + PD) per affected joint was lower in SLE than RA (2.0 versus 2.6, p = 0.019), while tendon inflammation score was not significantly different (2.1 versus 2.2, p = 0.738). Finally, the examination of concordance between joint and tendon involvement in the same finger revealed that joint lesion appeared in only 49% of fingers having tendon involvement in the SLE group, which was significantly less than 74% in the RA group ( p = 0.010). Thus, as compared with RA, SLE arthropathy is characterized by the predominance of tenosynovitis/periextensor tendon inflammation, which is likely to develop independently from joint synovitis.

An ultrahigh volumetric capacitance of squeezable three-dimensional bicontinuous nanoporous graphene.

Graphene with a large specific surface area and high conductivity has a large specific capacitance. However, its volumetric capacitance is usually very low because the restacking of 2D graphene sheets leads to the loss of the large ion-accessible surface area. Here we report squeezable bicontinuous nanoporous nitrogen-doped graphene, which is extremely flexible and can tolerate large volume contraction by mechanical compression without the face-to-face restacking occurring. The compressed nanoporous N-doped graphene with a large ion accessible surface area and high conductivity shows an ultrahigh volumetric capacitance of ∼300 F cm-3 together with excellent cycling stability and high rate performance.

Initial Atomic Motion Immediately Following Femtosecond-Laser Excitation in Phase-Change Materials.

Despite the fact that phase-change materials are widely used for data storage, no consensus exists on the unique mechanism of their ultrafast phase change and its accompanied large and rapid optical change. By using the pump-probe observation method combining a femtosecond optical laser and an x-ray free-electron laser, we substantiate experimentally that, in both GeTe and Ge_{2}Sb_{2}Te_{5} crystals, rattling motion of mainly Ge atoms takes place with keeping the off-center position just after femtosecond-optical-laser irradiation, which eventually leads to a higher symmetry or disordered state. This very initial rattling motion in the undistorted lattice can be related to instantaneous optical change due to the loss of resonant bonding that characterizes GeTe-based phase change materials. Based on the amorphous structure derived by first-principles molecular dynamics simulation, we infer a plausible ultrafast amorphization mechanism via nonmelting.

Intrinsic correlation between ß-relaxation and spatial heterogeneity in a metallic glass.

ß-relaxation has long been attributed to localized motion of constituent molecules or atoms confined to isolated regions in glasses. However, direct experimental evidence to support this spatially heterogeneous scenario is still missing. Here we report the evolution of nanoscale structural heterogeneity in a metallic glass during ß-relaxation by utilizing amplitude-modulation dynamic atomic force microscopy. The successive degeneration of heterogeneity during ß-relaxation can be well described by the Kohlrausch-Williams-Watts equation. The characteristic relaxation time and activation energy of the heterogeneity evolution are in accord with those of excess enthalpy release by ß-relaxation. Our study correlates ß-relaxation with nanoscale spatial heterogeneity and provides direct evidence on the structural origins of ß-relaxation in metallic glasses.

Efficient enzymatic production of hydroxy fatty acids by linoleic acid Δ9 hydratase from Lactobacillus plantarum AKU 1009a.

AIMS: This study aims to produce hydroxy fatty acids efficiently. METHODS AND RESULTS: Escherichia coli overexpressing linoleic acid Δ9 hydratase from Lactobacillus plantarum AKU 1009a was employed to produce hydroxy fatty acids with industrial potential. We found that 280 g l(-1) of linoleic acid (1 mol l(-1)) was converted into (S)-10-hydoxy-cis-12-octadecenoic acid (HYA) with a high conversion rate of 98% (mol/mol) and more than 99·9% enantiomeric excess (e.e.) by recombinant E. coli cells in the presence of FAD and NADH. In the same way, many kinds of C18 unsaturated fatty acids with Δ9 carbon double bond (280 g l(-1)) were converted into corresponding 10-hydroxy fatty acids with the conversion rates over 95% (mol/mol). We also produced HYA at a high rate of accumulation (289 g l(-1) ) with a high yield (97 mol%) in a reaction mixture that contained glucose instead of NADH. CONCLUSIONS: We developed a process for producing several types of hydroxy fatty acids with high accumulation rates and high yields. SIGNIFICANCE AND IMPACT OF THE STUDY: Hydroxy fatty acids are important materials for the chemical, food, cosmetic and pharmaceutical industries, and thus they have recently attracted much interest in a variety of research fields. However, the mass production of hydroxy fatty acids has been limited. This method of hydroxy fatty acids production will facilitate the widespread application of hydroxy fatty acids in various industries.

Histopathological and immunohistochemical features of atypical epithelial tumours of the gland of the third eyelid in seven dogs.

This report documents the histopathological and immunohistochemical features of atypical epithelial tumours of the gland of the third eyelid (GTE) in seven dogs. Cases 1 and 2 were diagnosed as myoepithelioma, comprising of compressive proliferations of interlacing bundles of neoplastic spindle cells expressing cytokeratin 14, p63, calponin and α-smooth muscle actin. Cases 3, 4 and 5 were diagnosed as complex carcinomas comprising of atypical glandular cells expressing cytokeratin 8/18, together with spindle-shaped or round neoplastic cells expressing cytokeratin 14, p63, calponin and α-smooth muscle actin. Cases 6 and 7 were diagnosed as basal cell adenocarcinomas (BCACs) comprising of a mixed proliferation of glandular and basal-type cells expressing cytokeratin 14 and p63. Therefore, in addition to glandular components, these tumours may include neoplastic cells with a myoepithelial or basal cell phenotype. Hence, there is diversity in the features of epithelial neoplasia of the GTE in dogs, similar to tumours in human salivary and lacrimal glands.

Characterization of spontaneous malignant lymphomas in Japanese macaques (Macaca fuscata).

Lymphomas are common spontaneous tumors in nonhuman primates but remain poorly characterized in Japanese macaques (Macaca fuscata). This study examined 5 cases of spontaneous malignant lymphoma in Japanese macaques, focusing on the immunophenotypes and presence of simian lymphocryptoviruses, which are Epstein-Barr virus-related herpesviruses in nonhuman primates. The macaques with lymphoma were 5 to 28 years old, indicating that lymphomas develop over a wide age range. The common macroscopic findings were splenomegaly and enlargement of lymph nodes. Histologic and immunohistochemical analyses revealed that all cases were non-Hodgkin type and exhibited a T-cell phenotype, positive for CD3 but negative for CD20 and CD79α. The lymphomas exhibited diverse cellular morphologies and were subdivided into 3 types according to the World Health Organization classification. These included 3 cases of peripheral T-cell lymphoma, not otherwise specified; 1 case of T-cell prolymphocytic leukemia; and 1 case of an unclassifiable T-cell lymphoma. Positive signals were detected by in situ hybridization in 2 of the 4 examined cases using probes for the Epstein-Barr virus-encoded small RNA (EBER). Furthermore, the presence of M. fuscata lymphocryptovirus 2, a macaque homolog of Epstein-Barr virus, was demonstrated in EBER-positive cases by polymerase chain reaction amplification followed by direct sequencing. Immunohistochemistry using antibody to the Epstein-Barr virus-encoded nuclear antigen 2 was negative, even in the EBER-positive cases. The present study suggests that T-cell lymphoma is more common than B-cell lymphoma in Japanese macaques and that M. fuscata lymphocryptovirus 2 is present in some cases.

A novel automated detection system for swallowing sounds during eating and speech under everyday conditions.

The wave analysis of swallowing sounds has been receiving attention because the recording process is easy and non-invasive. However, up until now, an expert has been needed to visually examine the entire recorded wave to distinguish swallowing from other sounds. The purpose of this study was to establish a methodology to automatically distinguish the sound of swallowing from sound data recorded during a meal in the presence of everyday ambient sound. Seven healthy participants (mean age: 26·7 ± 1·3 years) participated in this study. A laryngeal microphone and a condenser microphone attached to the nostril were used for simultaneous recording. Recoding took place while participants were taking a meal and talking with a conversational partner. Participants were instructed to step on a foot pedal trigger switch when they swallowed, representing self-enumeration of swallowing, and also to achieve six additional noise-making tasks during the meal in a randomised manner. The automated analysis system correctly detected 342 out of the 352 self-enumerated swallowing events (sensitivity: 97·2%) and 479 out of the 503 semblable wave periods of swallowing (specificity: 95·2%). In this study, the automated detection system for swallowing sounds using a nostril microphone was able to detect the swallowing event with high sensitivity and specificity even under the conditions of daily life, thus showing potential utility in the diagnosis or screening of dysphagic patients in future studies.

Development of a speech-discriminating electromyogram system for routine ambulatory recordings for the low-level masseter muscle activity.

Previous work suggests a relationship between sustained low-level tooth clenching and the aetiology of myogenous temporomandibular disorder (TMD) pain. This study aimed to establish a reliable system with which to evaluate low-level electromyographic (EMG) activity related to low-level tooth clenching while discriminating speech activity, which is one of the most common facial muscle activities to be discriminated from low-level clenching. This device should facilitate the clinical evaluation of awake muscle activity in TMD patients. Eight female and eight male subjects (38.9 ± 11.3 years) participated in the study to evaluate the validity of estimation of speech duration. Actual speech duration was defined by one examiner by pointing out the timing of beginning and end point of each speech on wave-editing software. Speech duration, as detected by a voice sensor system, which was activated by a voice loudness of 54.71 ± 5.00 dB, was significantly correlated with the above actual speech duration (P < 0.01, R(2) = 0.9935). An actual recording with the system was carried out in one TMD patient and one healthy volunteer and revealed that the duration of diurnal EMG activity higher than 5% MVC was 1649.16 s and 95.99 s, respectively. As the voice sensor system adopted in this study could define the exact onset and offset of each segment of speech, EMG activity during speech could be precisely discriminated. The results of this study demonstrate that the EMG system with voice sensor system would be an effective tool for the evaluation of low-level masticatory muscle activity.

Raman characterization of pseudocapacitive behavior of polypyrrole on nanoporous gold.

The practical applications of high-capacitance polypyrrole (PPy) as an active material for electrochemical supercapacitors are mainly limited by their poor cycling stability. By utilizing nanoporous gold enhanced Raman scattering of PPy, we investigated ex situ and in situ the structural origins of the low electrochemical stability of PPy. This study provided direct evidence that the stability degradation of PPy is caused by the irreversible transition between oxidation and reduction states of PPy, which is associated with the permanent deformation of PPy molecular chains subjected to applied potentials.

Susceptibility of BALB/c-nu/nu mice and BALB/c mice to equine herpesvirus 9 infection.

This study aimed to clarify the timing and infectivity of equine herpesvirus 9 (EHV-9) infection in BALB/c-nu/nu mice and their immunocompetent counterpart (BALB/c). Following intranasal inoculation with 10(5) PFU of EHV-9, specimens from 8 mice per group were collected at different times postinoculation (PI) and assessed using histopathology, immunohistochemistry for viral antigen, and quantitative real-time polymerase chain reaction for ORF30 gene expression. In BALB/c-nu/nu mice, EHV-9 antigen was abundant in olfactory epithelia of all inoculated animals, and in the olfactory bulb of 1 animal. In contrast, only 1 BALB/c mouse per time point had rhinitis, with mild to moderate immunopositivity starting from 12 to 48 h PI, followed by a gradual virus clearance at 72 h PI. Statistically, significant differences were noted in the immunohistochemistry reactions between the 2 mouse strains, indicating that BALB/c-nu/nu is more susceptible to infection. Relative expression levels of ORF30 gene in olfactory epithelia were significantly different between the 2 groups, with the exception of 12 h PI, when BALB/c-nu/nu animals showed dramatic increases in ORF30 gene expression level until 48 h PI, followed by a decline in expression level until the end of experiment. In contrast, the expression level in brains showed no differences between mouse strain except at 96 h PI. In both strains, the highest messenger RNA expression was detected at 48 h PI, followed by a decline in BALB/c mice, proving a rapid clearance of virus in BALB/c and a gradual slowing down of the increased expression levels in BALB/c-nu/nu.