The effectiveness of dance movement therapy for individuals with Down syndrome: a pilot randomised controlled trial.

BACKGROUND: Individuals with Down syndrome (DS) exhibit deficits in static and dynamic balance abilities and maladaptive functions. This study aimed to determine the effectiveness of dance movement therapy (DMT) group intervention in individuals with DS. METHODS: The 31 participating individuals with DS, aged 5-29 years, were randomly divided into intervention (n = 16) and control (n = 15) groups. Posturography was used for static balance measurement, timed up and go test for dynamic balance measurement and the Achenbach System of Empirically Based Assessment (ASEBA) questionnaire for adaptive function and behavioural problem measurement in participants before and after the DMT interventions. The intervention group underwent 60-min DMT intervention once a week for 10 times, while the control group had usual daily activities. RESULTS: The results revealed a statistically significant difference and large effect sizes in dynamic balance [(f(1, 29) = 4.52, P = 0.04, ηp 2 = 0.14)] in the intervention group compared with the control group. There were no statistically significant differences in static balance and ASEBA scores between the groups. CONCLUSIONS: This study found that the DMT interventions helped to improve the dynamic balance in individuals with DS.

Non-invasive classification of single and double-yolk eggs using Vis-NIR spectroscopy and multivariate analysis.

1. This study was conducted to develop an efficient technique for separating double-yolked (DY) from single-yolked (SY) light brown broiler eggs with comparable shape and size, that were hard to distinguish merely by their external characteristics, using Vis-NIR transmission spectroscopy combined with multivariate analysis.2. Spectroscopic transmission (200-900 nm) was measured after collecting the eggs, and the yolk number was verified by breaking the eggs after boiling. The absorbance of important spectral wavelengths sensitive to yolk amount were identified using feature selection techniques (Principal Component Analysis and Genetic Algorithm).3. Discriminant analysis (DA) and support vector machine (SVM) classifiers were used to develop classification models for DY and SY eggs using the selected important spectral wavelengths.4. When compared to alternative nonlinear techniques, the developed model applying linear discriminant analysis produced greater accuracies in the first (96%) and second (100%) experiments, implying lower inter-egg variability from spectral data and a linear relationship between classes. However, the position and orientation of yolks in DY eggs may limit the classification accuracy of the eggs.

Artificial intelligence for the automated single-shot assessment of psoriasis severity.

BACKGROUND: PASI score is globally used to assess disease activity of psoriasis. However, it is relatively complicated and time-consuming, and the score will vary due to the inconsistent subjectivity between dermatologists. Therefore, an AI system capable of assessing psoriasis severity will be useful. OBJECTIVES: To propose a simplified PASI system (Single-Shot PASI) and associated AI models capable of assessing psoriasis severity. METHODS: Overall, 705 psoriasis images of the trunk's front and back were used in our research. Considering the relatively small number of images, we used data augmentation techniques to expand the data. A psoriasis expert's scores were used as teacher data. Various convolutional neural network models and hyperparameters were adjusted using a fivefold cross-validation. From these adjustments, we discovered that fine-tuning Imagenet2012-pretrained InceptionV3 whose last linear layer was replaced by a two-layer perceptron (30 hidden units and five output units) exhibited the best performance. RESULTS: To validate our deep learning system, 10 images were selected as test sets and were excluded from the training sets. The AI assessment of Single-Shot PASI was almost consistent with the clinical severity. We examined whether AI assistance would affect human scoring. In this study, 13 dermatologists and 9 medical students were invited as evaluators. Mean absolute differences from AI scores and standard deviation among evaluators reduced with AI assistance. In addition, the evaluator's scores got close to the teacher's score with AI's assistance. CONCLUSIONS: We proposed a Single-Shot PASI system and developed an associated AI system capable of assessing psoriasis severity simply by uploading a single clinical image. An easy-to-use scoring system and our freely available AI software would help dermatologists and patients with psoriasis.

Longitudinal association between polypharmacy and development of pruritus: a Nationwide Cohort Study in a Japanese Population.

BACKGROUND: Although polypharmacy is known to cause side-effects due to drug-drug interactions, dermatological symptoms triggered by polypharmacy are not fully addressed. OBJECTIVE: To investigate whether polypharmacy is associated with the risk of pruritus. METHOD: A cohort study was performed to examine cross-sectional and longitudinal relationships between polypharmacy and pruritus in a general population. Data were collected from the Norm Study conducted in 2016 and 2017, which is a nationwide survey based on a self-administered questionnaire with Japanese representative participants aged 16-84 years. Presence of polypharmacy which was defined as concurrent use of ≥5 prescribed drugs. Primary outcomes were the presence of severe pruritus at baseline for the cross-sectional analysis and the development of severe pruritus after one year for the longitudinal analysis. Multivariable modified Poisson regression analyses were performed to estimate risk ratios (RRs) and 95% confidence intervals (95%CIs) with adjustment for potential confounders (age, gender, smoking habits, drinking habits, depressive symptoms, moderate activities based on IPAQ score and presence of 11 comorbid conditions including skin disease). RESULTS: The study included 3126 participants (mean age, 48.7 years); nearly half (49.8%) were male. In all, 332 participants (10.3%) had polypharmacy in the cross-sectional analysis. Participants with polypharmacy were more likely to present with severe pruritus at baseline than those who were not using drugs (adjusted RR = 1.52 [95%CI 1.15-2.01, P = 0.003]). The longitudinal analysis (n = 1803) was limited to those without severe pruritus at baseline; participants with polypharmacy at baseline were more likely to develop severe pruritus after a one-year follow-up period than those not using drugs (adjusted RR = 1.46 [95%CI 1.14-1.87, P = 0.002]). CONCLUSION: Polypharmacy was associated with the presence of pruritus at baseline and may predict the future risk of developing pruritus.

Non-destructive sex-specific monitoring of early embryonic growth rate in light brown broiler eggs using light transmission and its correlation with hatching time and chick weight.

1. Monitoring early embryonic growth rate (EGR) has significant economic and animal welfare benefits. This study focuses on monitoring sex-specific early EGR using light transmission, and correlating this with hatching time and chick weight. For broiler eggs in particular, spectral masking of the light brown eggshells needed to be addressed. This was done using longitudinal visible transmission spectroscopy combined with eggshell colour image analysis. 2. Prior to incubation, colour images of eggs were captured followed by daily measurements of transmission spectra of eggs from days one to nine of incubation. The sex of the eggs was subsequently verified 2 d after hatching. 3. To accurately and sensitively determine sex differences in EGR using light transmission, while minimising interference from eggshell colour and thickness, the ratio of longitudinal transmissions was determined to be most effective at 575 and 610 nm. 3. Embryonic growth was detectable from d 3 (72 h) of incubation, 24 h earlier than previously reported lateral transmission measurements. However, at this time, low blood levels meant that no significant sex-differences (P > 0.05) for the mean T575/T610 ratio were detectable. This may have been due, in part, to spectral masking from the light brown eggshells. At d 7, female embryos had a significantly lower (P < 0.05) mean T575/T610 ratio than males. 4. Although the T575/T610 ratio had low correlations with hatching time and hatch-weight of chicks, this could be a good starting point for further non-destructive investigations for such predictions. 5. In conclusion, the methodology had the sensitivity to differentiate sex-specific early EGR in broiler eggs, even with pigmented eggshells, and has the potential to advance precision hatchery management and poultry research.

Coexistence of osteoporosis and atherosclerosis in pheochromocytoma: new insights into its long-term management.

Osteoporosis and atherosclerosis frequently coexist in patients with pheochromocytoma. The presence of osteoporosis may predict that of atherosclerosis and vice versa in patients with PHEO. These findings have implications for the long-term management of the pheochromocytoma and its potential chronic complications. INTRODUCTION: Pheochromocytoma (PHEO), a catecholamine-producing tumor, is often found incidentally, and it may be present for years before it is diagnosed. However, long-term exposure to catecholamines excess may induce chronic complications, such as osteoporosis and atherosclerosis. We aimed to evaluate concomitant osteoporosis and atherosclerosis in patients with PHEO. METHODS: Fifty-one patients with PHEO and 51 patients with a non-functional adrenal tumor were compared radiographically for the prevalence of vertebral fracture (VF), a typical osteoporotic fracture, and abdominal aortic calcification (AAC). RESULTS: In patients with PHEO, the prevalence of AAC was higher in those with VF (58%) than in those without (6%, p < 0.001). AAC was associated with VF after adjusting for age and sex (odds ratio, 1.53; 95% confidence interval, 1.07-2.46; p = 0.003) in patients with PHEO. The degree of catecholamine excess correlated with the presence of VF and AAC (p = 0.007). The prevalence of VF was higher in patients with PHEO (37%) than those with non-functional AT (12%, p = 0.005), but the prevalence of AAC was comparable between the two groups (25% and 19%, p = 0.636). VF and AAC more frequently coexisted in patients with PHEO (22%) than in those with non-functional AT (2%, p = 0.003). CONCLUSION: This study represents the first demonstration that osteoporosis and atherosclerosis frequently coexist in patients with PHEO. The presence of osteoporosis may predict that of atherosclerosis and vice versa in patients with PHEO. These findings have implications for the long-term management of the PHEO and its potential chronic complications.

Sarcopenic obesity is associated with a faster decline in renal function in people with type 2 diabetes.

AIM: To evaluate the association between sarcopenic obesity and the decline in estimated GFR in people with type 2 diabetes. METHODS: We enrolled 745 people with type 2 diabetes (mean age 64.6 years, 53.6% men). Body composition was evaluated using dual-energy X-ray absorptiometry. Skeletal muscle index, calculated as appendicular non-fat mass (kg) divided by height squared (m2 ), was used to determine sarcopenia. Sarcopenic obesity was defined as the coexistence of sarcopenia and a ratio of android to gynoid fat mass greater than the median values in each gender. The association of sarcopenic obesity both with the annual rate of decline in estimated GFR and a >30% decline in estimated GFR was evaluated using multivariate linear regression models and Cox proportional hazard models, respectively. RESULTS: Participants with sarcopenic obesity were at an increased risk of a high annual rate of decline in estimated GFR, even after adjustment for the confounding variables (standardized ß = -0.228, P <0.001). Sarcopenic obesity was also significantly associated with risk of a >30% decline in estimated GFR (hazard ratio 4.52, 95% CI 2.16-9.47; P < 0.01) in multivariate model. CONCLUSIONS: Sarcopenic obesity evaluated by dual energy X-ray absorptiometry is associated with a faster decline in renal function in people with type 2 diabetes.

Nondestructive sex-specific monitoring of early embryonic development rate in white layer chicken eggs using visible light transmission.

1. Sex-specific variations in early embryonic development rates may pre-empt later variations in embryonic development through to pipping and hatching. Given that erythropoiesis (blood production) can be equated with early embryonic growth rate, it was hypothesised that blood pigment haemoglobin can act as a specific spectral fingerprint for changes in growth rate. Moreover, by measuring longitudinal, rather than lateral, spectral transmission through the egg, a more consistent spectrum with a higher signal-to-noise ratio could be captured.2. Longitudinal visible transmission (T575/T598 ratio), which is sensitive to haemoglobin, was used to monitor sex-specific early embryonic development rate in white layer chicken eggs from d 0 to 8 of incubation. The sex of these eggs was subsequently confirmed two days after hatching.3. Embryonic development was detectable from d 3 (72 h) of incubation, 36 h earlier than previously reported lateral spectral measurements, supporting the greater sensitivity of longitudinal measurements.4. At d 3, the mean T575/T598 ratio for male embryos was significantly lower (P < 0.001) (i.e. higher absorbance of haemoglobin) than for female embryos, which was thought to be due to sex-differences in early embryogenesis. On the other hand, female embryos had a significantly lower (P < 0.05) mean T575/T598 ratio than male embryos at d 7 of incubation, presumably due to the combined effects of oestrogen synthesis receptors and enzymes on erythropoiesis in female embryos at this time.5. In conclusion, the proposed methodology has the sensitivity to differentiate sex-specific embryonic development rates during early incubation and the potentiality to advance precision incubation management and poultry research.

A case with good response to belimumab for lupus nephritis complicated by IgG4-related disease.

Immunoglobulin (Ig)G4-related disease (IgG4-RD) is an unusual complication of systemic lupus erythematosus (SLE). We report a case in which belimumab proved efficacious for not only SLE, but also IgG4-RD. A 58-year-old Japanese woman had suffered from photodermatosis and erythema on the limbs for 20 years. She presented in slight fever and fatigue since 2016. Laboratory data showed hypergammaglobulinemia, proteinuria and positive results for anti-nuclear antibody and anti-double-stranded DNA antibody. Furthermore, elevated levels of serum IgG4 were detected. Contrast-enhanced computed tomography disclosed multiple areas of poor enhancement in the kidneys. The patient was diagnosed with lupus nephritis and IgG4-RD from renal biopsy. Treatment was started with prednisolone at 40 mg/day and mycophenolate mofetil. Proteinuria and serological findings improved initially, but tapering the dose of glucocorticoid proved difficult. After treatment was started with belimumab, clinical symptoms and proteinuria resolved completely. The dose of glucocorticoid was successfully tapered and serum concentration of IgG4 fell further. This appears to represent the first report of a case in which both SLE and IgG4-RD were effectively treated using belimumab.

Trajectory of criterion symptoms of major depression under newly started antidepressant treatment: sleep disturbances and anergia linger on while suicidal ideas and psychomotor symptoms disappear early.

OBJECTIVE: In modern psychiatry, depression is diagnosed with the diagnostic criteria; however, the trajectory of each of the criterion symptoms is unknown. This study aims to examine this. METHODS: We made repeated assessments of the nine diagnostic criterion symptoms with the Patient Health Questionnaire-9 (PHQ-9) among 2011 participants of a 25-week pragmatic randomised controlled trial of sertraline and/or mirtazapine for hitherto untreated major depressive episodes. The changes from baseline were estimated with the mixed-effects model with repeated measures. The time to disappearance of each symptom was modeled using the Kaplan-Meier survival analysis. RESULTS: The total score on PHQ-9 was 18.5 (SD = 3.9, n = 2011) at baseline, which decreased to 15.3 (5.2, n = 2011) at week 1, to 11.5 (5.9, n = 1953) at week 3, to 7.8 (6.0, n = 1927) at week 9, and to 6.0 (5.9, n = 1910) at week 25. Suicidal ideas, psychomotor symptoms decreased rapidly, while anergia and sleep disturbance also decreased but only slowly. The survival analyses confirmed the primary analyses. CONCLUSIONS: Upon initiation of antidepressant treatment, patients with newly treated major depressive episodes can expect their suicidal ideas and psychomotor symptoms to disappear first but sleep disturbances and anergia to linger on.

High incidence and early onset of nivolumab-induced pneumonitis: four case reports and literature review.

BACKGROUND: Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody used as an immune checkpoint inhibitor, is commonly employed for its anti-tumor effects against various types of malignant tumors. However, its administration is complicated by immune-related adverse events (irAEs), including pneumonitis. CASE PRESENTATION: We present a case series of four patients with malignant melanoma, non-small cell lung cancer, and hypopharyngeal carcinoma who demonstrated pneumonitis induced by nivolumab, and further review clinicopathological characteristics of these patients in comparison with those of previously reported patients with nivolumab-induced pneumonitis. In our series, 20% of patients who were treated with nivolumab developed pneumonitis, all of which occurred approximately 2 weeks after the initiation of nivolumab treatment. Prompt recognition of the nivolumab-induced pneumonitis allowed for successful resolution. Computed tomography scan images of the patients demonstrated predominantly cryptogenic organizing pneumonia patterns. All patients were males, who had been heavily treated with antitumor drugs prior to nivolumab. CONCLUSIONS: Our case series showed that nivolumab had a high incidence of drug-induced pneumonitis with early onset, supporting the need for renewed attention to nivolumab-induced pneumonitis, particularly in patients with a history of heavy antitumor treatments.

Internalization of a novel, huge lectin from Ibacus novemdentatus (slipper lobster) induces apoptosis of mammalian cancer cells.

An N-acetyl sugar-binding lectin (termed iNoL) displaying cytotoxic activity against human cancer cells was isolated from the slipper lobster Ibacus novemdentatus (family Scyllaridae). iNoL recognized monosaccharides containing N-acetyl group, and glycoproteins (e.g., BSM) containing oligosaccharides with N-acetyl sugar. iNoL was composed of five subunits (330, 260, 200, 140, and 30 kDa), which in turn consisted of 70-, 40-, and 30-kDa polypeptides held together by disulfide bonds. Electron microscopic observations and gel permeation chromatography indicated that iNoL was a huge (500-kDa) molecule and had a polygonal structure under physiological conditions. iNoL displayed cytotoxic (apoptotic) effects against human cancer cell lines MCF7 and T47D (breast), HeLa (ovarian), and Caco2 (colonic), through incorporation (internalization) into cells. The lectin was transported into lysosomes via endosomes. Its cytotoxic effect and incorporation into cells were inhibited by the co-presence of N-acetyl-D-mannosamine (ManNAc). Treatment of HeLa cells with iNoL resulted in DNA fragmentation and chromatin condensation, through activation of caspase-9 and -3. In summary, the novel crustacean lectin iNoL is incorporated into mammalian cancer cells through glycoconjugate interaction, and has cytotoxic (apoptotic) effects.

Comparison of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout: a phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study.

WHAT IS KNOWN AND OBJECTIVE: There are no clinical reports that have compared topiroxostat, a selective xanthine oxidase inhibitor, with allopurinol in serum urate-lowering efficacy. The aim of this study was to compare the efficacy and safety of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout. METHODS: A phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study conducted in Japan. Patients who had inadequate serum urate levels (a gout patient: serum urate level ≥416·4 µmol/L; an asymptomatic hyperuricemic patient with specific complications (urinary lithiasis, hypertension, hyperlipidemia and/or diabetes): serum urate level ≥475·8 µmol/L; and an asymptomatic hyperuricemic patient with no specific complications: serum urate level ≥535·3 µmol/L) were randomized to topiroxostat 120 mg/day or allopurinol 200 mg/day, with an equal allocation ratio, for 16 weeks. To prevent the onset of gouty arthritis by rapid serum urate reduction, these doses were increased in a stepwise manner. The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit. RESULTS AND DISCUSSION: Overall, 206 patients were randomly assigned to topiroxostat and allopurinol. Two hundred and three patients (allopurinol: n = 105, topiroxostat: n = 98) received at least one dose of the study drug and had their serum urate level assessed at least once. The baseline characteristics were comparable between groups. The mean age of patients was 53·0 ± 11·4 years and 99% of patients were male. The primary efficacy endpoint was -34·3 ± 11·1% in the allopurinol group (n = 105) and -36·3 ± 12·7% in the topiroxostat group (n = 98). Non-inferiority of the serum urate-lowering efficacy of topiroxostat to allopurinol was proved by the predefined non-inferiority margin (95% confidence interval, -5·3 to 1·3%). The overall incidences of adverse events and adverse drug reactions were similar between both groups. WHAT IS NEW AND CONCLUSION: Topiroxostat 120 mg/day provides non-inferior serum urate reduction compared with allopurinol 200 mg/day and is well tolerated in Japanese hyperuricemic patients with or without gout.

Long-time correlation in non-Markovian dephasing of an exciton-phonon system in InAs quantum dots.

We have observed a time-correlated frequency fluctuation in non-Markovian dephasing of excitons in InAs quantum dots using a six-wave mixing technique. In this measurement, the arrival times of the excitation pulses were controlled to eliminate the influence of Markovian dephasing and to measure the pure non-Markovian behavior. The experimental result shows that the time correlation of the frequency fluctuation due to exciton-phonon interactions was maintained in the quantum dots for over 10 ps. This long-time correlation is caused by the modification of the phonon coupling distribution.

Sialyl-glycoconjugates in cholesterol-rich microdomains of P388 cells are the triggers for apoptosis induced by Rana catesbeiana oocyte ribonuclease.

SBL/RC-RNase was originally isolated from frog (Rana catesbeiana) oocytes and purified as a novel sialic acid-binding lectin (SBL) that displayed strong anti-cancer activity. SBL was later shown to be identical to a ribonuclease (RC-RNase) from oocytes of the same species. The administration of SBL/RC-RNase induced apoptosis (with nuclear condensation and DNA fragmentation) in mouse leukemia P388 cells but did not kill umbilical vein endothelial or fibroblast cells derived from normal tissues. The cytotoxic activity of SBL/RC-RNase was inhibited by desialylation of P388 cells and/or the co-presence of free bovine submaxillary mucin. FACS analysis showed that SBL/RC-RNase was incorporated into cells after attachment to cholesterol-rich microdomains. Addition of the cholesterol remover methyl-ß-cyclodextrin reduced SBL/RC-RNase-induced apoptosis. Apoptosis occurred through the caspase-3 pathway following activation of caspase-8 by SBL/RC-RNase. A heat shock cognate protein (Hsc70) and a heat shock protein (Hsp70) (each 70 kDa) on the cell membrane were shown to bind to SBL/RC-RNase by mass spectrometric and flow cytometric analyses. Quercetin, an inhibitor of Hsc70 and Hsp70, significantly reduced SBL/RC-RNase-induced apoptosis. Taken together, our findings suggest that sialyl-glycoconjugates present in cholesterol-rich microdomains form complexes with Hsc70 or Hsp70 that act as triggers for SBL/RC-RNase to induce apoptosis through a pathway involving the activation of caspase-3 and caspase-8.