Impact of COVID-19 on the mental health of primary schoolchildren during the later phase of the pandemic: A case report of an 18-month longitudinal survey in a Japanese primary school.

Background: Drastic changes such as school closures and stay-at-home measures due to the global COVID-19 pandemic, may have long-term negative effects on children's mental health; however, longitudinal studies after 2021 are limited. This study aimed to observe the long-term effects of the COVID-19 pandemic on children's mental health by exploring changes in their mental health over a period of 18 months. Study design: We conducted a longitudinal study at Chiba Prefecture in Japan, focusing on schoolchildren's mental health changes. Methods: Data were obtained from the Strengths and Difficulties Questionnaire (SDQ) questionnaire conducted at single primary school three times from October 2021 to March 2023 which and included 183 participants. This study adopted a linear-mixed model to evaluate changes in children's SDQ scores, with sex and grade as the independent variables, and participants as a random effect. Results: Regarding changes in SDQ scores, there were no significant changes in the total difficulty scores or in each subscale; Emotional Symptoms, Conduct Problems, Hyperactivity/Inattention, Peer Problems, and Prosocial Behavior. There was no statistically significant interaction between changes in SDQ scores and sex. Conclusions: This report indicates that the impact of the COVID-19 pandemic on the mental health of Japanese primary schoolchildren was negligible in the later phase of the pandemic. However, the impact may differ from country to country owing to factors such as social restrictions during the COVID-19 pandemic.

Immunosuppression Modification by Everolimus With Minimization of Calcineurin Inhibitors Recovers Kidney Graft Function Even in Patients With Very Late Conversion and Also With Poor Graft Function.

BACKGROUND: Although kidney graft survival within 5 years after transplantation is now achieved in >95% of recipients, chronic graft deterioration remains a factor limiting long-term survival. Chronic nephrotoxicity induced by calcineurin inhibitors (CNIs) is one of the major causes of chronic graft injury; thus, minimization of CNIs by administration of everolimus (EVR) is expected to relieve their toxic effects. METHODS: Fifty-six kidney transplant recipients receiving CNI-based immunosuppression (tacrolimus, n = 34; cyclosporine, n = 22) were analyzed. The average posttransplant period at conversion was 7.4 years and no less than 3 years. Conversion of immunosuppression was accomplished by reducing CNI by 40% in dose and beginning EVR at 1 or 1.5 mg. Changes in graft function were examined, and adverse effects were evaluated. RESULTS: Significant improvement in graft function was observed quickly after EVR administration, and it had persisted for 1 year after conversion as a 7% increase in estimated glomerular filtration rate. No obvious acute rejection was observed. Further analyses concerning "timing of EVR conversion" and "graft function at conversion" were performed. Graft function was significantly improved even in patients with late conversion at 2 to 10 years. The estimated glomerular filtration rate was significantly improved even in patients with poor function. CONCLUSIONS: We concluded that this modification to the immunosuppressive regimen, as expected, reduced CNI nephrotoxicity. Our results showed that even patients with very late conversion or poor graft function also benefited from EVR conversion with CNI minimization.

Fat-tailed gene flow in the dioecious canopy tree species Fraxinus mandshurica var. japonica revealed by microsatellites.

Pollen flow, seed dispersal and individual reproductive success can be simultaneously estimated from the genotypes of adults and offspring using stochastic models. Using four polymorphic microsatellite loci, gene flow of the wind-pollinated and wind-seed-dispersed dioecious tree species, Fraxinus mandshurica var. japonica, was quantified in a riparian forest, in northern Japan. In a 10.5-ha plot, 74 female adults, 76 male adults and 292 current-year seedlings were mapped and genotyped, together with 200 seeds. To estimate dispersal kernels of pollen and seeds, we applied normal, exponential power, Weibull, bivariate t-distribution kernels, and two-component models consisting of two normal distribution functions, one with a small and one with a large variance. A two-component pollen flow model with a small contribution (26.1%) from short-distance dispersal (sigma = 7.2 m), and the rest from long-distance flow (sigma = 209.9 m), was chosen for the best-fitting model. The average distance that integrated pollen flows inside and outside the study plot was estimated to be 196.8 m. Tree size and flowering intensity affected reproduction, and there appeared to be critical values that distinguished reproductively successful and unsuccessful adults. In contrast, the gene flow model that estimated both pollen and seed dispersal from established seedlings resulted in extensive seed dispersal, and the expected spatial genetic structures did not satisfactorily fit with the observations, even for the selected model. Our results advanced small-scale individual-based parentage analysis for quantifying fat-tailed gene flow in wind-mediated species, but also clarified its limitations and suggested future possibilities for gene flow studies.

On methods of spatial analysis for genotyped individuals.

Spatial autocorrelation methods have commonly been applied to individual-based spatial genetic studies, although their properties and the relations among the statistics have not been carefully examined. This paper first introduces a reformulation of widely used spatial statistics using point processes. When Moran's I statistics are applied to allele frequencies within an individual, the frequencies are no longer continuous variables but have only three discrete values and specific interpretations of Moran's I statistics and the number of alleles in common (NAC) can be expressed as the weighted sum of join-count statistics. The distributions of minor genotypes are amplified in Moran's I depending on the allele frequency in the population, while NAC uses a constant weighting system. Under the point process framework, spatial analysis can be conducted on the common theoretical base, from individual locations to genetic distributions of different levels, (for example, genotype and allele). The methodology is demonstrated by application to field data for molecular ecological studies of Fagus crenata population dynamics.

[Local advanced lung cancer invaded thoracic vertebral bodies with unruptured cerebral aneurysm].

A 57-year-old man presented with the chief complaint of left shoulder pain in June 2001, and paridrosis of left upper trunk and left upper limb in July 2001. Head magnetic resonance imaging (MRI) showed 8 mm sized unrupture aneurysm of left middle cerebral artery, and chest computed tomography (CT) showed the lung tumor invaded thoracic vertebral bodies. The local advanced lung carcinoma (cT4N0M0) and unrupture aneurysm of left middle cerebral artery was diagnosed. The prevented clipping of unrupture aneurysm was performed at 11th September 2001, and left upper lobectomy, hemivertebrectomy and reconstruction of thoracic vertebral body (Th 3-5) with Modul' ICS at 12th October 2001. The pathological findings revealed squamous cell carcinoma. The staging was pT4N0M0, IIIB. The postoperative course was uneventful. After the radiotherapy (50 Gy), chemotherapy (gemcitabine and vinorelbine) was performed. But the radiation pneumonia was occurred and chemotherapy was intermitted. The steroid was administrated due to the radiation pneumonia, and the complication was improved. He discharged at 17th April 2002 and had no recurrence. The prevented clipping of unrupture cerebral aneurysm and the reconstruction of thoracic vertebral body (Th 3-5) with Modul' ICS were useful for the radical operation of the local advanced lung cancer.

The appearance of a different DNA sequence may decrease nucleotide diversity.

Nucleotide diversity may be decreased when a different DNA sequence type appears in a population. This undesirable property in a genetic diversity index is demonstrated by mathematical examples. The possibility of this phenomenon in natural populations is briefly discussed.

FR901451, a novel inhibitor of human leukocyte elastase from Flexibacter sp. I. Producing organism, fermentation, isolation, physico-chemical and biological properties.

A novel human leukocyte elastase (HLE) inhibitor, FR901451 was discovered in the fermentation broth of a bacteria. The bacteria was identified as Flexibacter sp. No. 758. FR901451 has a molecular weight of 1269 and a molecular formula of C60H79N13O18. The mode of inhibition against HLE is competitive, with a Ki value of 9.8 x 10(-9) M.

Isolation, identification, and biological activities of oxidative metabolites of FK506, a potent immunosuppressive macrolide lactone.

To characterize structures and biological activities of FK506 metabolites, FK506 was incubated with liver microsomes prepared from phenobarbital-treated rats in the presence of NADPH generating system under aerobic condition. Oxidative metabolites formed in the reaction medium were isolated and identified. Purified samples were analyzed by HPLC, mass spectrometry, and NMR spectroscopy. M-I, M-II, and M-III were the O-demethylated metabolites at the 13-, 31-, and 15-positions of FK506, respectively, and M-IV was the monohydroxylated metabolite at the 12-position. M-I was the dominant metabolite in this reaction system. M-II and M-III retained the tetrahydropyrane ring in their structures like FK506, but M-I and M-IV had rearranged structures in which the tetrahydropyrane ring was changed to a tetrahydrofuran ring. Measuring the immunosuppressive activity in the mouse mixed lymphocyte reaction system, IC50 values for M-I, M-II, M-III, M-IV, and FK506 were 1.65, 0.23, > 127, 5.52, and 0.15 nM, respectively. Reactivity of the metabolites with mouse anti-FK506 monoclonal antibody was studied and immunocross-reactivity of M-I, M-II, M-III, and M-IV with the antibody were nil, 109.0, 90.5, and 8.8% of FK506, respectively. These results indicate that rat hepatic microsomes oxidatively metabolize FK506 to four metabolites, and some of them exhibit pharmacological activity.

Solvent dependence of optical rotation of (S)-N-[1-(2-fluorophenyl)- 3,4,6,7-tetrahydro-4-oxo-pyrrolo[3,2,1-jk][1,4]benzodiazepine-3-yl]- 1H-indole-2-carboxamide.

A new cholecystokinin-A antagonist, (S)-N-[1-(2-fluorophenyl)- 3,4,6,7-tetrahydro-4-oxo-pyrrolo[3,2,1-jk][1,4]benzodiazepine-3-yl]- 1H-indole-2-carboxamide (FR120480; 1), is a chiral compound that shows considerable solvent dependence of its optical rotation. Not only the absolute values, but also the signs (+ or -) for this compound change in various solvents. The optical rotation of 1 inherently correlated to the electron donating property characterized by donor number of the solvent. The 1H NMR study implied that hydrogen bonds were formed between electron donor groups of the solvents and the NH groups of indole and amide of 1. In accordance with the NMR results, X-ray crystallography of the tetrahydrofuran solvate of 1 showed that hydrogen bond formation occurred between the oxygen atom of tetrahydrofuran and the amide group of 1.

[Studies on the beneficial effect of levocarnitine chloride (LC-80) on organic acidemias, especially propionic acidemia and methylmalonic acidemia].

The beneficial effect of LC-80 in the therapy for organic acidemias, especially propionic acidemia and methylmalonic acidemia, was compared with those of its optical isomers, d-carnitine chloride (d-isomer) and dl-carnitine chloride (dl-isomer) in rat liver mitochondria. LC-80 at concentrations of 5 and 10 mM did not inhibit the mitochondrial function, while the d-isomer at a concentration of 5 mM significantly reduced the respiratory control ratio (RCR) of mitochondria. In addition, the dl-isomer at concentrations of 10 and 20 mM also significantly reduced RCR in a concentration-dependent manner. Thus, it seems likely that the d-isomer inhibits the mitochondrial function. On the other hand, the inhibition of mitochondrial function induced by a preincubation with propionate (4.76 mM) was significantly reversed by LC-80 (5 and 10 mM) in a concentration-dependent manner, while the d-isomer (5 mM) had no effect on the inhibitory effect of propionate. Moreover, although the dl-isomer (10 and 20 mM) significantly reversed the inhibitory effect of propionate as compared with the d-isomer, its effect was significantly weaker as compared with the effect of LC-80. The substrate specificity of rat liver mitochondrial carnitine acetyltransferase (CAT) was more potent with propionyl CoA than with acetyl CoA. Kinetic studies indicate that the d-isomer is a competitive inhibitor of CAT. These results suggest that LC-80 is useful in the clinical treatment of organic acidemias, whereas the d-isomer has a harmful effect in clinical application.