Combination of cytoplasmic and nuclear patterns on Hep-2 antinuclear antibody is useful as a screening test for anti-synthetase syndrome.

OBJECTIVE: This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other antinuclear antibody (ANA)-associated rheumatic diseases (AARD) using a combination of cytoplasmic and non-cytoplasmic ANA (ncANA) patterns. METHODS: This retrospective observational study included patients with AARDs such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), and polymyositis/dermatomyositis (PM/DM) who underwent ANA screening between April 2012 and December 2021. Variables included age, sex, ANA patterns (Cytoplasmic and ncANA), and titers. Logistic regression analysis of Cytoplasmic and ncANA patterns was performed to differentiate ASS from other AARDs. RESULT: The 981 diagnosed cases of AARDs consisted of SS (n = 451), SSc (n = 264), SLE (n = 201), PM/DM (n = 104), MCTD (n = 52), and ASS, including PM/DM (n = 64). Of these, 155 patients had ≥2 overlapping diseases; however, there was no overlap between AARDs and ASS. ASS is more likely to occur when the cytoplasmic titer is positive and the ncANA <320. Receiver operating characteristic (ROC) analysis of the Cytoplasmic and ncANA range revealed an area under the ROC curve (AUC) of 0.885 (95% CI: 0.844 to 0.927). CONCLUSION: It is important to detect cytoplasmic patterns as an ANA screening test for ASS diagnosis, even if the titer is low. Additionally, combining the cytoplasmic and ncANA patterns yields more accurate ASS screening results.

The influence of low-intensity resistance training combined with neuromuscular electrical stimulation on autonomic activity in healthy adults: A randomized controlled cross-over trial.

BACKGROUND: Low-intensity resistance training (RT) combined with neuromuscular electrical stimulation (NMES) is one method of exercise to improve the deterioration of physical function. However, it is unclear whether low-intensity RT combined with NMES (RT + NMES) can be safely implemented. OBJECTIVE: This study aimed to examine the influence of low-intensity RT + NMES on autonomic activity and cardiovascular responses in healthy adults. METHODS: This study was an open-label, randomized controlled cross-over trial. The exercise intensity of isometric knee extension RT was set to 40% of the maximum voluntary contraction (peak torque). NMES was adjusted to a biphasic asymmetrical waveform with the frequency maintained at 50 Hz and a phase duration of 300 µ s. The difference in the change in autonomic activity and cardiovascular responses was compared by assessing heart rate variability, blood pressure, and heart rate during RT and RT + NMES . RESULTS: Twenty healthy male college students (mean age 21 . 0 ± 0 . 6 years) participated in this study. The ratio of low- and high-frequency components of heart rate variability, systolic blood pressure, and heart rate increased during exercise in the RT and RT + NMES sessions ( P < 0.05). There were no significant differences in autonomic activity and cardiovascular responses throughout the sessions during RT and RT + NMES . CONCLUSION: In conclusion, our results demonstrated that low-intensity RT + NMES was safe and did not induce excessive autonomic and cardiovascular responses in healthy adults.

Helimagnetic Structure and Heavy-Fermion-Like Behavior in the Vicinity of the Quantum Critical Point in Mn_{3}P.

Antiferromagnet Mn_{3}P with Neel temperature T_{N}=30 K is composed of Mn tetrahedrons and zigzag chains formed by three inequivalent Mn sites. Due to the nearly frustrated lattice with many short Mn-Mn bonds, competition of the exchange interactions is expected. We here investigate the magnetic structure and physical properties including pressure effect in single crystals of this material, and reveal a complex yet well-ordered helimagnetic structure. The itinerant character of this materials is strong, and the ordered state with small magnetic moments is easily suppressed under pressure, exhibiting a quantum critical point at ∼1.6 GPa. The remarkable mass renormalization, even in the ordered state, and an incoherent-coherent crossover in the low-temperature region, characterize an unusual electronic state in Mn_{3}P, which is most likely effected by the underlying frustration effect.

Menthol-induced cutaneous stimulation combined with self-paced walking training improves knee extension performance in untrained older healthy females.

[Purpose] The present study aimed to investigate whether self-paced walking training utilizing the facilitating effect of skin cooling with menthol gel application was effective in untrained older healthy females. [Participants and Methods] Forty-two untrained healthy older females (aged 60-69 years) were divided into the following three groups: (i) Walking training with menthol group: GM, (ii) Walking training group: GW, and (iii) Control group: GC. The participants in GM and GW performed self-paced walking for 30 minutes a day, 2 times a week, for 6 weeks. Menthol gel was applied to the front of the thigh of the participants in GM. Maximal voluntary contraction and rate of force development were measured pre- and post-training and walking speed was measured during the training. The number of steps taken and walking speed in daily activity were measured and the average of these parameters per day were calculated. [Results] The main findings were [1] knee extension muscle strength increased in GM and GW, and [2] rate of force development only improved in GM. [Conclusion] These results suggest that walking training utilizing the facilitating effect of skin cooling enhances muscle function in untrained older healthy females and that the present skin cooling method with menthol gel application may be recommended as a training strategy.

The effects of skin cold stimulation on quadriceps muscle activity during walking in older adults.

Purpose: Given that walking speed declines with ageing and decreasing walking speed restricts activities of daily living (ADL), it is important for the old to maintain walking speed in order to prevent affecting ADL. Although skin cold stimulation (SCS) facilitates instantaneous muscle activity, which occurs during walking, the effects of SCS on muscle activity during walking remain unclear. Thus, the present study aimed to investigate the effect of SCS during walking in older adults.Methods: Seventeen community-dwelling healthy older adults (73 ± 6 years old) participated in this study. Walking speed at a comfortable pace and the electromyographic (EMG) activity of the vastus lateralis (VL) and biceps femoris (BF) were measured. SCS, which maintains the skin temperature at 25 °C, was applied to the front of the thigh during the procedures. Walking speed, root mean square EMG (rmsEMG) and mean power frequency (MPF) were compared under SCS and control conditions.Results: SCS significantly increased the walking speed (p < 0.01) and the rmsEMG of the vastus lateralis (p = 0.032). No change in the rmsEMG of the BF was observed, and SCS had no effect on MPF of both the VL and BF. Furthermore, a significant relationship was observed between these changes (r = 0.619, p = 0.042).Conclusion: SCS increased the EMG activity of the VL while increasing walking speed. Our results suggest that SCS is an effective strategy that can be included in daily life in order to improve walking ability of older adults.

Effect of stimulation of cold receptors with menthol on EMG activity of quadriceps muscle during low load contraction.

PURPOSE: Facilitatory and inhibitory responses of spinal motor neurons are influenced by somatosensory input from the skin. The purpose of this study, employing electromyography, was to examine the neuromuscular changes that occur with menthol applied to the skin over the quadriceps muscle. METHODS: Forty-two healthy volunteers performed isometric knee extensions at 35% maximum voluntary contraction (MVC) in three groups (Adult Placebo, Adult Menthol, Older Adult Menthol). Stimulation used was application of 5% menthol gel to the skin. Surface electromyography (sEMG) from the vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF) was recorded using miniature pair electrodes. RESULTS: Root mean square electromyography (rmsEMG) in VL and VM significantly increased with menthol stimulation both in Adult and Older Adult, but no significant difference was observed between Adult Menthol and Older Adult Menthol. There was a significant decrease in mean power frequency (MPF) in VM with menthol stimulation in Older Adult, but no significant changes were observed in Adult Menthol. CONCLUSION: Neuromuscular modulation was observed with the application of menthol gel at low loads in the present study. These findings could lead to a new method of muscular training that targets the recruitment of fast type muscle safe for older adults.

Collateral Flow and White Matter Disease in Patients with Internal Carotid Artery Occlusion.

BACKGROUND: When an internal carotid artery (ICA) occludes, a patient may develop cerebral infarction (CI). We investigated whether CI caused by ICA occlusion (ICAO) is associated with collateral flow through the anterior and posterior communicating arteries (ACoA and PCoA). METHODS: In 100 patients with ICAO, we investigated CI and white matter disease by performing an MRI and the anatomy of the ACoA and PCoA were investigated by performing magnetic resonance angiography. All patients were divided into the symptomatic CI group or the no-CI group. The collateral flow pathway was estimated by the anterior cerebral artery (ACA)-PCoA score and the collateral flow volume after ICAO was estimated by the middle cerebral artery (MCA) flow score, based on how well the MCA was visualized. RESULTS: Of 100 patients with ICAO, the symptomatic CI group included 36 patients. ACA-PCoA score and white matter disease grades were significantly higher in the CI group (indicating poor collateral flow). More than 80% of patients with an ACA-PCoA score of 4 (poor collateral) experienced symptomatic CI. Thirty-one symptomatic CI patients (86%) had an MCA flow score of 1 or 2 (decreased MCA flow). CONCLUSION: The ACA-PCoA score and white matter disease grade may suggest an increased risk of CI following ICAO.

Glucose and GTP-binding protein-coupled receptor cooperatively regulate transient receptor potential-channels to stimulate insulin secretion [Review].

In pancreatic ß-cells, glucose-induced closure of the ATP-sensitive K+ (KATP) channel is an initial process triggering glucose-stimulated insulin secretion (GSIS). This KATP-channel dependent pathway has been believed to be a central mechanism for GSIS. However, since the resting membrane potential of cells is determined by the balance of the net result of current amplitudes in outward and inward directions, it must be taken into consideration that not only KATP channel inhibition but also inward current via the basal opening of non-selective cation channels (NSCCs) plays a crucial role in membrane potential regulation. The basal activity of NSCCs is essential to effectively evoke depolarization in concert with KATP channel closure that is dependent on glucose metabolism. The present study summarizes recent findings regarding the roles of NSCCs in GSIS and GTP-binding protein coupled receptor-(GPCR) operated potentiation of GSIS.

Detection of an unconventional superconducting phase in the vicinity of the strong first-order magnetic transition in CrAs using (75)As-nuclear quadrupole resonance.

Pressure-induced superconductivity was recently discovered in the binary helimagnet CrAs. We report the results of measurements of nuclear quadrupole resonance for CrAs under pressure. In the vicinity of the critical pressure P(c) between the helimagnetic (HM) and paramagnetic (PM) phases, a phase separation is observed. The large internal field remaining in the phase-separated HM state indicates that the HM phase disappears through a strong first-order transition. This indicates the absence of a quantum critical point in CrAs; however, the nuclear spin-lattice relaxation rate 1/T(1) reveals that substantial magnetic fluctuations are present in the PM state. The absence of a coherence effect in 1/T(1) in the superconducting state provides evidence that CrAs is the first Cr-based unconventional superconductor.

A risk stratification model for high-flow nasal cannula use in patients with coronavirus disease 2019 in Japan: A single-center retrospective observational cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has put a strain on the healthcare system, and sudden changes in disease status during home treatment have become a serious issue. Therefore, prediction of disease severity and allocation of sufficient medical resources, including high-flow nasal cannula (HFNC), to patients in need are important. We aimed to determine risk factors for the need of HFNC use in COVID-19. METHODS: This was a single-center retrospective observational cohort study including all eligible hospitalized adult patients aged ≥18 years diagnosed with COVID-19 between April 14, 2020 and August 5, 2021 who were treated in the study hospital. The primary outcome is the need for HFNC. Nineteen potential predictive variables, including patient characteristics at hospital admission, were screened using least absolute shrinkage and selection operator and logistic regression to construct a predictive risk score. Accuracy of the risk score was determined using area under the receiver operating characteristic curve. RESULTS: The study cohort included 148 patients. The rate of the need for HFNC was 22.9%. Among the 19 potential variables, percutaneous oxygen saturation (SpO2) <92% (odds ratio [OR] 7.50, 95% confidence interval [CI] 2.806-20.82) and IL-6 (OR 1.021, 95% CI 1.010-1.033) were included in developing the risk score, which was termed interleukin (IL)-6-based COVID-19 severity (IBC-S) score. CONCLUSIONS: The IBC-S score, an easy-to-use risk score based on parameters available at the time of hospital admission, predicted the need for HFNC in patients with COVID-19. The IBC-S score based on interleukin-6 and SpO2 might aid in determining patients who should be transported to a tertiary medical institution or an isolation facility.

Herpes Zoster Ophthalmicus Initially Diagnosed As Cluster Headache, Complicated by Delayed Eruption.

Herpes zoster ophthalmicus (HZO) manifests as a consequence of the reactivation of the Varicella-zoster virus (VZV) and primarily affects the ophthalmic division of the trigeminal nerve. Identification of the vesicular eruption is central to the diagnostic process; however, the delayed manifestation of this cutaneous phenomenon poses a challenge to timely and accurate diagnosis. This report elucidates the case of a 61-year-old Japanese male with painful trigeminal neuropathy attributed to VZV that was initially diagnosed as cluster headache, mainly due to the delayed cutaneous eruption. Contrary to the expected pattern of cluster headache presentations, there was no discernible fluctuation in headache severity. The transient improvement of symptoms following interventions tailored for cluster headache management, including pure oxygen inhalation and subcutaneous sumatriptan injection, inadvertently contributed to a delay in accurate diagnosis. The importance of distinguishing HZO from cluster headache is emphasized, particularly in cases involving elderly patients or those with persistent cephalo-ophthalmalgia without the characteristic fluctuation of symptoms. In cases where clinical suspicion of HZO is raised, cerebrospinal fluid analysis should be performed. This approach is consistent with the overall goal of facilitating a prompt and accurate diagnosis.

Fukuchi-Manabe Score for Infection Control Measures During the Very Early COVID-19 Pandemic Period When Access to Reverse Transcription-Polymerase Chain Reaction Testing Was Poor in Japan: A Single-Center Observational Prospective Cohort Study.

BACKGROUND: During the early stages of the COVID-19 pandemic in Japan, access to reverse transcription-polymerase chain reaction (RT-PCR) testing was limited. All patients with COVID-19 required hospitalization, and isolation of suspected COVID-19 patients had not yet been implemented. With the recently acquired evidence on COVID-19, it is important to develop a risk stratification system for isolation rooms in the context of limited resources for better resource management. OBJECTIVE: This study aimed to develop and validate a COVID-19 risk-scoring strategy, the Fukuchi-Manabe score, to safely stratify and manage isolation rooms, personal protective equipment (PPE), and RT-PCR testing in the context of limited RT-PCR testing and a short supply of PPE. METHODS: This single-center prospective study consecutively enrolled suspected COVID-19 adult inpatients between March 1 and August 31, 2020. The primary and secondary outcomes were a positive RT-PCR test and the occurrence of nosocomial infections during the study period, respectively. Factors related to patient history, symptoms, chest computed tomography findings, and laboratory data suggestive of COVID-19 were scored, totaled, and divided into four categories ("probable," "possible," "less likely," and "non-suspicious") based on the likelihood of COVID-19. Sensitivity, specificity, and positive and negative predictive values were evaluated for each probability category. FINDINGS: Twenty of 224 inpatients were positive on the RT-PCR test, including 18 "probable" patients (90.0%), one "possible" patient, and one "less likely" patient. The area under the curve (AUC) (95% confidence interval: 0.841-0.977), sensitivity, and specificity were 0.909, 90.0%, and 80.4%, respectively. The positive and negative predictive values and accuracy for the "probable" category were 0.90, 0.80, and 0.82, respectively. The mean and standard deviation of AUCs, validated by bootstrap analysis, were 0.910±0.034. No nosocomial infections were observed. CONCLUSION: The Fukuchi-Manabe score will be helpful when other novel pathogens emerge in the future before the availability of genetic testing methods.

Wearing masks is easy but taking them off is difficult - A situation in Japan during COVID-19 pandemic and after.

Background: Masks are well accepted in Japan, where they were already part of daily life even before the COVID-19 pandemic. Unlike many other countries where mask mandates were lifted as soon as the pandemic was under control, Japan was one of the last countries to ease mask-wearing guidelines. Even after the formal announcement to allow masks-off in mid-March 2023, many Japanese still voluntarily wear masks. In this work, possible reasons for this extreme "mask-affinity" of Japanese people were studied by exploring various information sources including tweets (now known as X posts) and subsequent text-analysis, online news, and medical literature. Methods: An observational study was conducted based on tweets prospectively collected during 5 months from June 26th, 2022 to November 26th, 2022. Tweets with the hashtag "mask (in Japanese)" were collected weekly via the Twitter application programming interface by using R version 4.0.3 to gauge public opinions. The word clouds to allow intuitive understanding of the key words were drawn from the tokenized text. Results: The data collection period included the 7th flareups of the newly infected cases i.e. "the 7th surge". In total, 161,592 tweets were collected. Word clouds for 1) before the 7th surge based on 18,000 tweets on June 26th and 2) during/after the 7th surge based on 143,592 tweets between July-November were created with the R package "wordcloud2". The results indicated that the people wanted to take off masks due to the heat in summer, then shifted again toward mask-wearing along with the 7th surge but with a certainly growing "no-mask" sentiment. Conclusions: Subsequent review of domestic information sources suggested that various factors, not only well-known peer pressure, may have contributed the public's mask affinity in Japan. This work revealed an aspect of Japanese struggle toward adaptation to life in an unexpected pandemic by focusing on masks as our closest daily adjunct over the past 3 years of isolation.Trial registration: not applicable.

Consecutive Serious Medical Concomitants Associated With Extremely Severe Anorexia Nervosa in a Patient With Body Mass Index of 10.2 Kilograms per Square Meter: A Case Report.

Anorexia nervosa (AN) is often accompanied by numerous medical complications and mental disorders. There are few specialized AN facilities in Japan, resulting in the unmet medical needs of patients with AN. A 37-year-old Japanese woman was admitted to the hospital after experiencing a disturbance of consciousness. Her body mass index was 10.2 kg/m2. She developed the following serious medical concomitants associated with extremely severe AN: hypothermia, shock liver, refractory hypoglycemia, acute gastric mucosal bleeding, gelatinous marrow transformation, catheter-related bloodstream infection and infective endocarditis due to ß-lactamase-negative Staphylococcus aureus, aspiration pneumonia, intracranial hemorrhage, candidemia, and osmotic demyelination syndrome in the pons, which led to a fatal condition that quickly worsened after we started treatment. The patient was able to overcome several serious concomitants and be discharged from the hospital after multidisciplinary treatment team care. AN is associated with increased rates of all-cause mortality. It is important to take an interdisciplinary approach with emergency physicians, intensivists, hematologists, gastroenterologists, psychiatrists, clinical psychologists, a nutrition support team with a nationally registered nutritionist and hospitalists, and hospitalization as required based on appropriate medical evaluation with good patient and family rapport. Furthermore, social and educational efforts aimed at preventing the development of AN are necessary.

Effectiveness of initiating advance care planning among older outpatients through intervention by physicians trained in a model discussion video: A randomized controlled trial.

AIM: This study aimed to assess the impact of a physician-led intervention on advance care planning (ACP) introduction among older outpatients using a model discussion video. METHODS: This prospective interventional study included Japanese general practice outpatients aged ≥65 years. All participants received an ACP leaflet. Co-researchers were trained using a model discussion video based on the "Serious Illness Conversation Guide," and provided ACP introduction explanations to the intervention group to ensure intervention content consistency. The control group received the ACP leaflet only, with no standardized explanations. The primary outcome was ACP discussion occurrence. Secondary outcomes included ACP engagement (assessed through the 4-item ACP Engagement Survey), engagement score for advance directives acquisition and score for surrogate decision-maker identification, and anxiety incidence (assessed through Generalized Anxiety Disorder-7). RESULTS: This study included 48 participants: 25 (52.1%) in the intervention group and 23 (47.9%) in the control group. Regarding primary outcome, the intervention group had significantly more ACP discussions compared with the control group (92.0% vs 26.1%, adjusted odds ratio 50.2, P = 0.0012). Regarding secondary outcomes, the intervention group showed greater readiness (mean scores for the 4-item Engagement Survey [P = 0.0001], engagement score for advance directives acquisition [P = 0.01] and score for surrogate decision-maker determination [P = 0.03]) than the control group, without increasing anxiety. CONCLUSIONS: This physician-led ACP introduction for older patients in a Japanese general practice setting enhanced ACP readiness and stimulated discussions, without increasing anxiety. The model discussion video for ACP introduction might effectively train physicians in general practice settings. Geriatr Gerontol Int 2024; ••: ••-••.

Metastatic Pleomorphic Carcinoma of the Lung with Extensive Chromosomal Rearrangements: An Autopsy Case with a Literature Review.

We herein report a 47-year-old man who presented with progressive paraparesis. Imaging revealed a right upper pulmonary nodule, massive bilateral adrenal metastases, thoracolumbar vertebral osteolysis, and subcutaneous nodules. A biopsy of the right buttock nodule revealed a poorly differentiated metastatic carcinoma with high programmed cell death-ligand 1 expression and extensive chromosomal rearrangements. The patient died 10 days after the initiation of pembrolizumab treatment. Autopsy findings confirmed pulmonary pleomorphic carcinoma with extensive metastases. Quantification of chromosomal rearrangements revealed a jump-up mutation from the normal karyotype, followed by a further incremental increase in the degree of deviation.

A community-based cross-sectional and longitudinal study uncovered asymptomatic proteinuria in Japanese adults with low body weight.

Although proteinuria is highly prevalent in obese individuals, the association between proteinuria and low body weight is equivocal. In this study we determine whether low body weight is more strongly associated with proteinuria compared with normal weight. The association between body mass index (BMI) and proteinuria was examined in a cross-sectional study of 62,582 asymptomatic individuals aged 20-70 years without known kidney diseases recruited, based on the results of medical checkups in 1999. We also examined the incidence of recurrent or nonrecurrent proteinuria in an 8-year longitudinal analysis of 12,493 individuals without proteinuria at baseline. The prevalence of proteinuria showed a J-shaped relationship with BMI. Multivariate regression analysis showed that BMI of 27.0 kg/m(2) and above or 18.9 kg/m(2) and less was significantly associated with proteinuria relative to BMI 21.0-22.9 kg/m(2), even after adjusting for relevant cardiometabolic risk factors. In the longitudinal study, similar J-shaped relationships between the incident rates of proteinuria and baseline BMI groups were observed at post-baseline checkups. Baseline BMI 27.0 kg/m(2) and above was associated with significantly greater risk for recurrent and nonrecurrent proteinuria, whereas BMI 18.9 kg/m(2) and less was only associated with nonrecurrent proteinuria. Thus, obesity and low body weight may be associated with different types of proteinuria independent of cardiometabolic risk factors.

Change in EMG with skin friction at different frequencies during elbow flexion.

Modulation of muscle activation in superficial and deeper regions may be induced by tactile stimulation. The purpose of this study was to examine changes in muscle activation with skin friction. Subjects performed an isometric elbow flexion at 30% maximal voluntary cotraction (MVC) with skin friction at different frequencies (0.5-2.7 Hz). Surface electromyography (S-EMG) and intramuscular EMG were obtained from the elbow flexor muscles (BBS: short head of biceps brachii, BBL: long head of biceps brachii, BRA: brachialis). S-EMG activity decreased at a higher frequency of 2.7 Hz and increased linearly with an increase in skin friction frequency (0.5-2.7 Hz) in BBS. A decrease in high-threshold motor unit (HT-MU) firing rate in superficial regions and an increase in low-threshold motor unit (LT-MU) firing rate in deeper regions were observed with skin friction (2.7 Hz) in BBS. The actions of inhibitory interneurons may be influenced by cutaneous afferent input with skin friction. Muscle activation of BBS depended on the intensity of the stimulus. Skin friction over BBS results in an inhibitory response in superficial regions of BBS, most likely due to the increase in firing rate of low-threshold cutaneous mechanoreceptors.

Malignancy-related Hypercalcemia Caused by Metameric Cutaneous Metastasis of Parathyroid Hormone-related Protein-producing Bladder Carcinoma with Squamous Cell Differentiation: An Autopsy Case of Cobb Syndrome.

A 74-year-old woman was admitted with hypercalcemia and prolonged disturbance of consciousness. The left buttock to the anterior aspect of the left thigh was swollen and erythematous, with a collection of 1.0-cm large, firm, elastic nodules distributed in a zosteriform pattern in the L1-L4 region. Based on autopsy findings, a very rare case of Cobb syndrome was diagnosed due to a spinal vascular malformation at the Th12-L4 level and L5 vertebral hemangioma. Cobb syndrome-associated cutaneous metastasis extending along the same metamere was complicated by immunohistochemically proven parathyroid hormone-related protein-producing advanced bladder carcinoma in this case.