Error analysis of Raven's Coloured Progressive Matrices in children and adolescents with cerebral palsy.

BACKGROUND: Analysis of the errors in the Raven's Coloured Progressive Matrices (RCPM) has been previously performed for children with intellectual disabilities but has not been investigated for those with cerebral palsy (CP). This study aimed to investigate whether the types and positions of errors made by individuals with CP differed from those made by typically developing (TD) controls. METHODS: Forty-five participants with CP aged 4-18 years and 30 TD children aged 3-9 years underwent RCPM testing. We first compared the RCPM performance and error characteristics between the groups and then examined the association between RCPM and the severity of CP and receptive vocabulary in the CP group. RESULTS: The results showed that while mean total scores in the two groups were comparable, the types and positions of errors made by individuals with CP differed from those of TD controls. The development of non-verbal intelligence in children with CP increased with age; when controlling for age, non-verbal intelligence was significantly correlated with all three functional levels of CP severity and receptive vocabulary. CONCLUSIONS: This study provides valuable insights into the problem-solving strategies employed by children with CP.

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients.

BACKGROUND: Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or <1% in Part 1 of CheckMate 227. Here we report efficacy and safety results for the Asian subpopulation. METHODS: Patients with stage IV/recurrent NSCLC were randomized 1 : 1 : 1 to nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy (PD-L1 ≥1%) or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were evaluated among patients in Japan, South Korea, and Taiwan. RESULTS: In the Asian subpopulation with PD-L1 ≥1%, 81 patients received nivolumab plus ipilimumab and 81 received chemotherapy. Median OS was not reached with nivolumab plus ipilimumab versus 24.8 months with chemotherapy; 3-year OS rate was 53% versus 37% [hazard ratio (HR), 0.72; 95% confidence interval (CI) 0.47-1.11]. The 3-year progression-free survival rate was 26% versus 7% (HR, 0.65; 95% CI 0.45-0.96), objective response rate was 56% versus 37%, and median duration of response was 29.0 months (95% CI 15.0 months-not reached) versus 6.9 months (95% CI 3.9-11.1 months). Similar results were observed regardless of tumor PD-L1 expression and in Japanese patients. Grade 3-4 treatment-related adverse events occurred in 40% of patients receiving nivolumab plus ipilimumab and 36% receiving chemotherapy, in the overall Asian subpopulation (tumor PD-L1 expression ≥1% and <1%); no new safety signals were identified. CONCLUSIONS: At 3-year follow-up, nivolumab plus ipilimumab provided durable long-term efficacy benefits versus chemotherapy regardless of tumor PD-L1 expression in the Asian subpopulation, including Japanese patients. Consistent with findings for all randomized patients, these data support the use of nivolumab plus ipilimumab as first-line treatment of Asian patients with advanced NSCLC.

Load distribution and forearm muscle activity during cylinder grip at various grip strength values.

This study aimed to investigate load distribution and forearm muscle activity from strong to weak grip strength, using a cylindrical device (Grip Sensor). We invited 15 students and measured the pressure distribution and forearm muscle activity during grip tasks at 25%, 50%, 75%, and 100% maximum voluntary force (MVF). Pressure data from the Grip Sensor were assigned to seven anatomical regions; the sum of the data from the seven regions (Total force) and proportionate load distribution for each grip task were calculated. Electromyography recorded activity in the extensor carpi radialis longus (ECRL), flexor carpi radialis (FCR), extensor carpi ulnaris (ECU) and flexor carpi ulnaris (FCU) muscles. Forearm muscle activity increased significantly with grip strength (p < 0.05). The load proportion corresponding to the thumb did not significantly change with increasing strength. On the other hand, the fingertip ratio significantly decreased, and the palm ratio significantly increased with increasing strength (p < 0.05). The Grip Sensor showed a shift in the load distribution in the hand from fingertips to palm as grip strength increased. This result indicates that more detailed evaluations of hand function may be possible.

Genetic diversity of Lactobacillus delbrueckii isolated from raw milk in Hokkaido, Japan.

Lactic acid bacteria (LAB) play important roles in acid production and flavor formation in fermented dairy products. Lactic acid bacteria strains with distinct characteristics confer unique features to products. Diverse LAB have been identified in raw milk and traditional fermented milk prepared from raw milk. However, little is known about LAB in raw milk in Japan. To preserve diverse LAB as potential starters or probiotics for future use, we have isolated and identified various kinds of LAB from raw milk produced in Japan. In this study, we focused on Lactobacillus delbrueckii, one of the most important species in the dairy industry. We identified L. delbrueckii subspecies isolated from raw milk in Hokkaido, Japan, by analyzing intraspecific diversity using 4 distinct methods, hsp60 cluster analysis, multilocus sequence analysis, core-genome analysis, and whole-genome analysis based on average nucleotide identity. The subspecies distribution and a new dominant subset of L. delbrueckii from raw milk in Japan were revealed. The discovery of new strains with different genotypes is important for understanding the geographic distribution and characteristics of the bacteria and further their use as a microbial resource with the potential to express unconventional flavors and functionalities. The strains identified in this study may have practical applications in the development of fermented dairy products.

JSCO-ESMO-ASCO-JSMO-TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions.

A Japan Society of Clinical Oncology (JSCO)-hosted expert meeting was held in Japan on 27 October 2019, which comprised experts from the JSCO, the Japanese Society of Medical Oncology (JSMO), the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the Taiwan Oncology Society (TOS). The purpose of the meeting was to focus on what we have learnt from both microsatellite instability (MSI)/deficient mismatch repair (dMMR) biomarkers in predicting the efficacy of anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy, and the neurotrophic tyrosine receptor kinase (NTRK) gene fusions in predicting the efficacy of inhibitors of the tropomyosin receptor kinase (TRK) proteins across a range of solid tumour types. The recent regulatory approvals of the anti-PD-1 antibody pembrolizumab and the TRK inhibitors larotrectinib and entrectinib, based on specific tumour biomarkers rather than specific tumour type, have heralded a paradigm shift in cancer treatment approaches. The purpose of the meeting was to develop international expert consensus recommendations on the use of such tumour-agnostic treatments in patients with solid tumours. The aim was to generate a reference document for clinical practice, for pharmaceutical companies in the design of clinical trials, for ethics committees in the approval of clinical trial protocols and for regulatory authorities in relation to drug approvals, with a particular emphasis on diagnostic testing and patient selection.

Systemic administration of α-lipoic acid suppresses excitability of nociceptive wide-dynamic range neurons in rat spinal trigeminal nucleus caudalis.

Although a modulatory role has been reported for α-lipoic acid (LA) on T-type Ca2+ channels in the nervous system, the acute effects of LA in vivo, particularly on nociceptive transmission in the trigeminal system, remain to be determined. The aim of the present study was to investigate whether acute intravenous LA administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from seventeen SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was significantly and dose-dependently inhibited by LA (1-100 mM, i.v.) and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 5 min. These inhibitory effects lasted for approximately 10 min. These results suggest that acute intravenous LA administration suppresses trigeminal sensory transmission, including nociception, via possibly blocking T-type Ca2+ channels. LA may be used as a therapeutic agent for the treatment of trigeminal nociceptive pain.

Disintegration rate and gamma-ray emission probability per decay measurement of Cu-64.

The procedure followed by the Nuclear Metrology Laboratory (LMN) at the IPEN for the standardization of activity of 64Cu is described. The measurement was carried out in a 4π (PC) ß-γ coincidence system. The activity per unit mass of the solution was determined by the extrapolation technique. The events were registered using a Time to Amplitude Converter (TAC) associated with a Multi-channel Analyzer. The gamma-ray emission probability per decay of the 1345.7keV transition of 64Cu determined with a calibrated REGe gamma-ray spectrometer was (0.472 ± 0.010) %, in agreement with the literature.

A influência da morfina ou tramadol pela via epidural no trânsito gastrintestinal de equinos / Influence of epidural morphine or tramadol in gastrointestinal transit of horses

Os opioides são utilizados na medicina veterinária na analgesia dos animais, porém há restrição quanto ao uso desses fármacos em equinos, pois podem desencadear alterações gastrintestinais, mas a administração pela via epidural minimiza os efeitos adversos. Assim, oito equinos hígidos foram utilizados em três grupos experimentais, objetivando-se avaliar a influência no trânsito gastrintestinal da injeção epidural de morfina (0,2mg/kg), tramadol (1,0mg/kg) ou NaCl 0,9%. Para a avaliação do trânsito gastrintestinal, foi administrada a lignina purificada e enriquecida (Lipe®), pela via oral, a qual posteriormente foi analisada nas fezes. As fezes foram coletadas para investigação desse marcador, antes da epidural e em intervalos até totalizar 48 horas do início do experimento. Os dados foram submetidos à análise de variância (ANOVA) de uma via, com repetições múltiplas. As médias entre cada momento dos grupos e dos momentos dentro de cada grupo foram comparadas pelo teste de Student-Newman-Keuls (P≤0,05). A morfina ou o tramadol administrados pela via epidural não alteraram o tempo médio de retenção da fase líquida, a taxa de passagem e o tempo de trânsito do marcador utilizado. Diante de tais achados, conclui-se que a morfina ou o tramadol pela via epidural não alteram o trânsito gastrintestinal.(AU)

Opioids provide analgesia and are used in veterinary, however there is a restriction regarding the use of these drugs in horses, because may lead to ileus, but epidural opioids minimize those side effects. Eight healthy horses were used in three experimental groups, to evaluate the gastrointestinal influence after epidural morphine (0.2mg / kg), tramadol (1.0mg / kg) or NaCl 0.9%. Intestinal transit was evaluated with the administration of Lipe® (purified enriched isolated lignin) and later analyzed in the feces. Feces were collected before the epidural and at intervals up to 48 hours after the beginning of the experiment. The data were analyzed by a one-way analysis of variance or Friedman or Kruskal-Wallis and Student-Newman Keuls test as a post hoc. A value of P≤ 0.05 was considered significant. Epidural morphine or tramadol did not change the mean time for retention of the liquid phase, passage rate, and the transit time of the marker used. In conclusion, epidural morphine or tramadol does not change gastrointestinal transit.(AU)

Tumor immune microenvironment and nivolumab efficacy in EGFR mutation-positive non-small-cell lung cancer based on T790M status after disease progression during EGFR-TKI treatment.

BACKGROUND: The efficacy of programmed death-1 blockade in epidermal growth factor receptor gene (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) patients with different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR. PATIENTS AND METHODS: We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab after disease progression during EGFR-TKI treatment (cohort A). Programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) density in tumor specimens obtained after acquisition of EGFR-TKI resistance were determined by immunohistochemistry. Whole-exome sequencing of tumor DNA was carried out to identify gene alterations. The relation of T790M status to PD-L1 expression or TIL density was also examined in an independent cohort of 60 patients (cohort B). RESULTS: In cohort A, median progression-free survival (PFS) was 2.1 and 1.3 months for T790M-negative and T790M-positive patients, respectively (P = 0.099; hazard ratio of 0.48 with a 95% confidence interval of 0.20-1.24). Median PFS was 2.1 and 1.3 months for patients with a PD-L1 expression level of ≥1% or <1%, respectively (P = 0.084; hazard ratio of 0.37, 95% confidence interval of 0.10-1.21). PFS tended to increase as the PD-L1 expression level increased with cutoff values of ≥10% and ≥50%. The proportion of tumors with a PD-L1 level of ≥10% or ≥50% was higher among T790M-negative patients than among T790M-positive patients of both cohorts A and B. Nivolumab responders had a significantly higher CD8+ TIL density and nonsynonymous mutation burden. CONCLUSION: T790M-negative patients with EGFR mutation-positive NSCLC are more likely to benefit from nivolumab after EGFR-TKI treatment, possibly as a result of a higher PD-L1 expression level, than are T790M-positive patients.

Does the Age of Donor Kidneys Affect Nocturnal Polyuria in Patients With Successful Real Transplantation?

BACKGROUND: We investigated whether the age of donor kidneys influences the incidence of nocturnal polyuria in patients with successful renal transplantation (RTX). METHODS: Eighty-five patients (45 men and 40 women) undergoing RTX (median age, 47 years) were included in this study. Twenty-four-hour bladder diaries were kept for 3 days, and nocturnal polyuria was defined as a nocturnal polyuria index (nocturnal urine volume/24-hour urine volume) of >0.33. Risk factors for nocturnal polyuria were analyzed in patients with RTX by means of the Mann-Whitney U test, χ2 test, and a logistic regression analysis. RESULTS: End-stage renal disease (ESRD) developed from diabetes mellitus in 16 patients (19%). Sixty-five patients (76%) received pre-transplant dialysis, with a median duration of 5 years. The median serum creatinine level and body mass index at the most recent visit were 1.2 mg/dL and 21.2 kg/m2, respectively. On the basis of the 24-hour bladder diaries, nocturnal polyuria was identified in 48 patients (56%). A logistic regression analysis revealed that diabetes mellitus as the original disease for ESRD was the only risk factor for nocturnal polyuria (odds ratio, 8.95; 95% confidence interval, 2.01-65.3; P = .0028). The age of donor kidneys at examination did not affect the incidence of nocturnal polyuria (P = .9402). CONCLUSIONS: Nocturnal polyuria was not uncommon in patients with successful RTX. Diabetes mellitus as the original disease for ESRD was the only risk factor for nocturnal polyuria, whereas the age of donor kidneys at examination did not affect the incidence of nocturnal polyuria. Thus, nocturnal polyuria is caused by recipient factors but not donor factors.

Consumption and diffusion of dissolved oxygen in sedimentary rocks.

Fe(II)-bearing minerals (e.g., biotite, chlorite, and pyrite) are a promising reducing agent for the consumption of atmospheric oxygen in repositories for the geological disposal of high-level radioactive waste. To estimate effective diffusion coefficients (De, in m2s-1) for dissolved oxygen (DO) and the reaction rates for the oxidation of Fe(II)-bearing minerals in a repository environment, we conducted diffusion-chemical reaction experiments using intact rock samples of Mizunami sedimentary rock. In addition, we conducted batch experiments on the oxidation of crushed sedimentary rock by DO in a closed system. From the results of the diffusion-chemical reaction experiments, we estimated the values of De for DO to lie within the range 2.69×10-11

Non-tuberculous Mycobacteriosis with T-cell Lymphoma in a Red Panda (Ailurus fulgens).

A 9-year-old male red panda (Ailurus fulgens) became emaciated and died. Necropsy examination revealed systemic lymphadenomegaly. The liver, lungs and left kidney contained multifocal yellow nodules. Microscopical examination revealed granulomatous inflammation in the liver, lungs, kidney, spleen and lymph nodes, with numerous acid-fast bacilli. Sequencing of genetic material isolated from the tissues classified the pathogen as Mycobacterium gastri. Lymphoma was found in the liver, lungs, kidney and lymph nodes. The neoplastic cells were strongly labelled for expression of CD3, Ki67 and proliferating cell nuclear antigen by immunohistochemistry. This is the first report of M. gastri infection with T-cell lymphoma in a red panda.