Dynamics of depressive states among university students in Japan during the COVID-19 pandemic: an interrupted time series analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic was reported to have increased depression among university students which was associated with impairments in their campus lives. This study examined changes in depressive states among Japanese university students during the COVID-19 pandemic. METHODS: A secondary data analysis from a factorial randomized controlled trial involving smartphone-based cognitive-behavioral therapy was performed. Six cohorts (N = 1626) underwent an 8-week intervention during the spring or autumn of 2019-2021, with a 9-month follow-up. We evaluated participants' depressive states weekly using the Patient Health Questionnaire-9 (PHQ-9) during the intervention, with monthly evaluations thereafter. The follow-up periods included Japan's four states of emergency (SOEs) to control COVID-19. Hypothesizing that SOEs caused a sudden worsening of depressive states, Study 1 compared the cohorts' PHQ-9 scores, and Study 2 employed time series analysis with a mixed-effects model to estimate identified changes in PHQ-9 scores. RESULTS: Although no changes in depressive states were observed in relation to the SOEs, Study 1 identified sudden increases in PHQ-9 scores at the 28-week evaluation point, which corresponded to the beginning of the new academic year for the three autumn cohorts. In contrast, the three spring cohorts did not exhibit similar changes. Study 2 showed that, for all three autumn cohorts (n = 522), the 0.60-point change was significant (95% CI 0.42-0.78; p < .001) at 28 weeks; that is, when their timeline was interrupted. CONCLUSIONS: While the results do not indicate any notable impact of the SOEs, they highlight the influence of the new academic year on university students' mental health during COVID-19. Trial registration UMIN, CTR-000031307. Registered on February 14, 2018.

Impact of sea-level rise on cross-shore sediment transport on fetch-limited barrier reef island beaches under modal and cyclonic conditions.

A one-dimensional wave model is combined with an analytical sediment transport model to investigate the likely influence of sea-level rise on net cross-shore sediment transport on fetch-limited barrier reef and lagoon island beaches. The modelling considers if changes in the nearshore wave height and wave period in the lagoon induced by different water levels over the reef flat are likely to lead to net offshore or onshore movement of sediment. The results indicate that the effects of SLR on net sediment movement are highly variable and controlled by the bathymetry of the reef and lagoon. A significant range of reef-lagoon bathymetry, and notably shallow and narrow reefs, appears to lead hydrodynamic conditions and beaches that are likely to be stable or even accrete under SLR. Loss of reef structural complexity, particularly on the reef flat, increases the chance of sediment transport away from beaches and offshore.

A wavelength modulation system for highly sensitive absorption spectroscopy.

We developed a newly designed wavelength modulation (WM) system for highly sensitive absorption spectroscopy. In our system, the WM is realized by yawing an output mirror in a monochromator. In order to control an amplitude Δλ of the WM in a wide range, we employed a forced vibration of a permanent magnet driven by a magnetic field of a solenoid. Our system has an advantage of that the WM amplitude Δλ can be adjusted in extensively wide range from 0.08 nm to 11 nm only by tuning a driving frequency of the applying current to the solenoid, because we utilize a resonance phenomenon of the forced vibration for adjustment of the WM amplitude. By using our system, we measured WM absorption spectra of a Cu(2)O thin film and found clearly spectral structures for weak 2-4P excitonic resonances in the WM absorption spectra.

Fault lubrication during earthquakes.

The determination of rock friction at seismic slip rates (about 1 m s(-1)) is of paramount importance in earthquake mechanics, as fault friction controls the stress drop, the mechanical work and the frictional heat generated during slip. Given the difficulty in determining friction by seismological methods, elucidating constraints are derived from experimental studies. Here we review a large set of published and unpublished experiments (∼300) performed in rotary shear apparatus at slip rates of 0.1-2.6 m s(-1). The experiments indicate a significant decrease in friction (of up to one order of magnitude), which we term fault lubrication, both for cohesive (silicate-built, quartz-built and carbonate-built) rocks and non-cohesive rocks (clay-rich, anhydrite, gypsum and dolomite gouges) typical of crustal seismogenic sources. The available mechanical work and the associated temperature rise in the slipping zone trigger a number of physicochemical processes (gelification, decarbonation and dehydration reactions, melting and so on) whose products are responsible for fault lubrication. The similarity between (1) experimental and natural fault products and (2) mechanical work measures resulting from these laboratory experiments and seismological estimates suggests that it is reasonable to extrapolate experimental data to conditions typical of earthquake nucleation depths (7-15 km). It seems that faults are lubricated during earthquakes, irrespective of the fault rock composition and of the specific weakening mechanism involved.

Towards a compatible probiotic-antibiotic combination therapy: assessment of antimicrobial resistance in the Japanese probiotics.

AIM: To determine the antimicrobial resistance of the Japanese probiotics available in the market without a pharmacist's supervision. METHODS AND RESULTS: A total of 43 isolates were obtained from 40 samples of probiotics (30 dairy products and 10 products in tablet form). Isolates were identified using 16S rRNA gene sequencing and tested for their susceptibility to 14 antimicrobials. They were screened using PCR for some antibiotic resistance genes. Inactivation of cefepime, clarithromycin and vancomycin by different inocula of 11 strains was evaluated using the antibiotic inactivation bioassay. None of the dairy probiotics showed a level of constitutive resistance or carried inducible resistance genes, making them suitable to be administrated with macrolides. Among the probiotics in tablet form only Enterococcus faecium strains carrying the msrC gene showed an MIC(90) of 4 µg ml(-1). Extended-spectrum ß-lactams, tetracyclines and ampicillin exhibited powerful germicidal activity against the vast majority of the probiotic strains. CONCLUSIONS: There is a limited choice of the Japanese probiotics that can be administered with clinically used antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Japanese probiotics are widely distributed all over the world. Through the findings of our study, we have attempted to provide guidance for clinicians interested in using the Japanese probiotics in combination with antibiotics.

Reproducibility of 24-hour dietary recall for vitamin intakes by middle-aged Japanese men and women.

OBJECTIVE: To examine the reproducibility of 24-hour dietary recall for estimating dietary vitamin intakes by middle-aged Japanese men and women. METHODS AND RESULTS: The subjects were 132 men and 130 women aged 40-69 years, selected from participants in cardiovascular risk surveys conducted in 4 communities. The reproducibility of the 24-hour dietary recall was tested by comparing nutrient and food intake for two recalls conducted on the same season 1 year apart, designated as recalls 1 and 2. Differences in mean values between two recalls were tested using analysis of variance, and Spearman rank correlation coefficients for the two recalls were calculated for nutrient and food intakes. Mean values of energy and vitamins for both sexes were generally similar for the two recalls. The reproducibility of recall by men was high for vitamin B2, folate, pantothenic acid, and vitamin C and by women for vitamin B2, moderate by men for vitamins A, E, K, B1, B6 and niacin, and by women for vitamins A, E, K, B1, B6 and niacin, folate, pantothenic acid and vitamin C, and low by both men and women for vitamins D and B12. The reproducibility during 1985-1999 was generally lower than that of 1973-1984, but that for folate, pantothenic acid and vitamin C remained to be moderate in 1984-1999. CONCLUSIONS: Although the reproducibility of 24-hour dietary recall varies among vitamins, moderate and sustained reproducibility was observed for folate, vitamin C and pantothenic acid.

Nocturnal intermittent hypoxia and the development of type 2 diabetes: the Circulatory Risk in Communities Study (CIRCS).

AIMS/HYPOTHESIS: Although the associations between obstructive sleep apnoea and type 2 diabetes mellitus have been reported in cross-sectional design studies, findings on the prospective association between the two conditions are limited. We examined prospectively the association between nocturnal intermittent hypoxia as a surrogate marker of obstructive sleep apnoea and risk of type 2 diabetes. METHODS: A total of 4,398 community residents aged 40 to 69 years who had participated in sleep investigation studies between 2001 and 2005 were enrolled. Nocturnal intermittent hypoxia was assessed by pulse-oximetry and defined by the number of oxygen desaturation measurements < or =3% per h, with five to <15 per h corresponding to mild and 15 events or more per h corresponding to moderate-to-severe nocturnal intermittent hypoxia, respectively. The development of type 2 diabetes was defined by: (1) fasting serum glucose > or =7.00 mmol/l (126 mg/dl); (2) non-fasting serum glucose > or =11.1 mmol/l (200 mg/dl); and/or (3) initiation of glucose-lowering medication or insulin therapy. Multivariable model accounted for age, sex, BMI, smoking status, current alcohol intake, community, borderline type 2 diabetes, habitual snoring, excessive daytime sleepiness, sleep duration and (for women) menopausal status. RESULTS: By the end of 2007, 92.2% of participants had been followed up (median follow-up duration [interquartile range] 3.0 [2.9-4.0] years) and 210 persons identified as having developed diabetes. The multivariable-adjusted hazard ratio (95% CI) for developing type 2 diabetes was 1.26 (0.91-1.76) among those with mild nocturnal intermittent hypoxia and 1.69 (1.04-2.76) among those with moderate-to-severe nocturnal intermittent hypoxia (p = 0.03 for trend). CONCLUSIONS/INTERPRETATION: Nocturnal intermittent hypoxia was associated with increased risk of developing type 2 diabetes among middle-aged Japanese.

Molecular characterization of antimicrobial resistance in Salmonella isolated from animals in Japan.

AIMS: To investigate the prevalence of integrons and antimicrobial resistance genes in Salmonella recovered from animals in Japan. METHODS AND RESULTS: Forty-eight out of ninety-four (51.1%) Salmonella isolates showed multidrug resistance phenotypes and harboured at least one antimicrobial resistance gene. Twenty-two out of forty-seven (46.8%) Salmonella enterica serovar Typhimurium that were multidrug-resistant were of definitive phage type DT104. Class 1 integrons were identified in 34/94 isolates (36.2%): 21 isolates containing two gene cassettes, aadA2 and bla(PSE-1), and 13 containing one gene cassette, aadA1, aadA2 or bla(PSE-1). Class 2 integrons containing estX-sat2-aadA1 gene cassettes were only identified in Salmonella Enteritidis. The beta-lactamase-encoding gene, bla(TEM), was only detected in S. Typhimurium. The plasmid-mediated quinolone resistance gene, qnrS1, was identified in S. Typhimurium and Salmonella Thompson. CONCLUSIONS: Our results characterized integrons and antimicrobial resistance genes in Salmonella of animal origin. To the best of our knowledge, this is the first report of qnrS in Salmonella from Japan and also the first report of qnrS in S. Thompson. SIGNIFICANCE AND IMPACT OF THE STUDY: Little is known about the molecular basis of antimicrobial resistance in Salmonella isolated from animals. This study provides useful data on the incidence of integrons and resistance genes in Salmonella of animal origin.

Alveolar bone regeneration using absorbable poly(L-lactide-co-epsilon-caprolactone)/beta-tricalcium phosphate membrane and gelatin sponge incorporating basic fibroblast growth factor.

The aim of this study was to evaluate the effects of combining a porous poly(L-lactide-co-epsilon-caprolactone)/beta-tricalcium phosphate membrane and gelatin sponge incorporating basic fibroblastic growth factor (bFGF) on bone regeneration in mandibular ridges. Four full-thickness saddle-type defects (10 mm long x 5 mm deep) were symmetrically created in both edentulous mandibular alveolar ridges of 6 beagles. The dome-shaped membrane was secured to each defect site, and a gelatin sponge containing 200 microg bFGF was implanted on the left side of each defect (experimental group). Only the membranes (control group) were secured to the defect sites on the right. Three and 6 months later, 3 animals were killed. Bone regeneration was analyzed by soft X-ray photographs, micro-computed tomography (CT) images, and peripheral quantitative CT (pQCT), and then examined histologically. Soft X-ray examination revealed an increase in new bone volume in the experimental group 6 months postoperatively. pQCT showed that immature bone density was higher in the experimental group. Micro-CT images revealed well formed new bone along the original contour of the dome-shaped membrane in the experimental group. Histologically, inflammatory infiltration of tissue surrounding the membranes was slight. These results suggest that combining the poly(L-lactide-co-epsilon-caprolactone)/beta-tricalcium phosphate membrane and bFGF-gelatin sponge is promising for alveolar ridge reconstruction.

G-protein beta-3 subunit C825T polymorphism, sodium and arterial blood pressure: a community-based study of Japanese men and women.

Epidemiological evidence on gene-environment effects of the G-protein beta-3 subunit C825T polymorphisms and sodium on blood pressure in the free-living general population is limited. We examined the associations between the C825T polymorphism and blood pressure levels, stratified by the sodium variables estimated by 24-h urinary sodium excretion and a dietary questionnaire, among 1,471 men and women aged 30-74 from a community in Japan. Our a priori hypothesis was that individuals with the 825T allele have elevated blood pressure among subjects with a high sodium intake. Among the whole group, the systolic blood pressure level was +2.2 mmHg (p = 0.10) higher in TT than CC genotype individuals after adjustment for sex, age, antihypertensive medication use, body mass index, and alcohol consumption. This difference was more evident among individuals with low sodium excretion (+4.5 mmHg, p = 0.01), low present sodium intake (+3.2 mmHg, p = 0.11), and low past sodium intake (+4.8 mmHg, p = 0.02). No associations were observed among those with high sodium variables. Our results indicate that the G-protein beta-3 subunit C825T polymorphism is associated with higher systolic blood pressure levels in a large free-living Japanese population, and more specifically in women with a low sodium intake. This finding helps to explain part of the discrepancy between the previously reported genetic association among different ethnic groups.

Type 2 diabetes and risk of non-embolic ischaemic stroke in Japanese men and women.

AIMS/HYPOTHESIS: The aim of this study was to examine the relationship between type 2 diabetes and risk of ischaemic stroke in Asian populations. METHODS: We conducted a 17-year prospective cohort study in 10,582 Japanese individuals (4287 men and 6295 women) aged 40-69 years living in five communities in Japan. All subjects were free of stroke and CHD at baseline. Diabetes was defined as a fasting glucose level of >/=7.0 mmol/l, a non-fasting glucose of >/=11.1 mmol/l, or receiving medication for diabetes. RESULTS: The risk of non-embolic ischaemic stroke was approximately two-fold higher in diabetic subjects than in subjects with normal glucose levels. The multivariate relative risk after adjustment for age, community, hypertensive status, BMI, triceps and subscapular skinfold thickness (TSF and SSF), and other known cardiovascular risk factors was 1.8 (95% CI 1.0-3.2) for men and 2.2 (1.2-4.0) for women. This excess risk was primarily observed among non-hypertensive subjects and individuals with higher values for measures of adiposity (BMI, TSF and SSF values above the median), particularly those with higher values for SSF. The association between non-embolic ischaemic stroke and glucose abnormality was particularly strong among non-hypertensive subjects with higher SSF values: the multivariate relative risk was 1.9 (1.0-3.7) for borderline diabetes and 4.9 (2.5-9.5) for diabetes. CONCLUSIONS/INTERPRETATION: In this cohort, type 2 diabetes was a significant risk factor for non-embolic ischaemic stroke, particularly in non-hypertensive and non-lean individuals. Due to the nationwide decrease in blood pressure and increase in mean BMI among the Japanese population, with current levels approaching those observed in Western countries, the impact of glucose abnormalities on risk of ischaemic stroke represents a forthcoming public health issue in Japan.

Elevated plasma level of differentiation inhibitory factor nm23-H1 protein correlates with risk factors for myelodysplastic syndrome.

We measured plasma nm23-H1 level (nm23-H1), a differentiation inhibitory factor, by an enzyme-linked immunosorbent assay (ELISA) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). The nm23-H1 in AA was not significantly elevated when compared to normal subjects (6.66 +/- 1.20 ng/ml vs 5.13 +/- 0.81 ng/ml; P = 0.274). In contrast, MDS patients had significantly high levels of nm23-H1 compared not only to normal subjects (11.16 +/- 1.42 vs 5.13 +/- 0.81 ng/ml; P = 0.0004) but also to those of the AA group (11.16 +/- 1.42 ng/ml vs 6.66 +/- 1.20 ng/ml; P = 0.018). In the MDS group of patients, no significant difference was observed in the nm23-H1 levels between patients with refractory anemia (RA) and RA with excess blasts (RAEB)/RAEB in transformation (10.71 +/- 1.61 ng/ml vs 9.24 +/- 2.66 ng/ml; P = 0.672). Of the patients with RA, patients with low risk according to the International Prognostic Scoring System (IPSS) had significantly low levels of nm23-H1 compared to those of IPSS INT-1 level cases (6.40 +/- 1.36 ng/ml vs 13.05 +/- 2.50 ng/ml; P = 0.0028), suggesting that nm23-H1 may be useful as a prognostic marker for MDS, especially in low risk patients.

Telomere dynamics in myelodysplastic syndromes and acute leukemic transformation.

Myelodysplastic syndromes (MDS) are characterized by cytopenias in the blood and dysplastic features in the hematopoietic cells. Although the impact of cytogenetic abnormalities is considerable for prognosis, the exact genetic mechanism of MDS remains undetermined. In this study we assessed cytogenetic changes, microsatellite alterations, and telomere dynamics in order to obtain further insight into the pathogenesis of MDS. Thirty-three percentage of MDS patients and 60% of post-MDS acute leukemia (post-MDS AML) had de novo microsatellite changes. In the MDS phase, however, > 60% of patients showed reduction of telomere lengths without microsatellite changes, indicating that telomere reduction in most MDS patients does not seem to be directly linked to genome instability, or that reduction of telomere length does not induce microsatellite changes in the MDS phase. Some MDS patients had microsatellite changes without telomerase elevation, indicating that genome instability might accumulate during the disease progression in some MDS patients, and this condition (cellular senescence) may be related to ineffective hemopoiesis in MDS patients. In contrast, 40% of post-MDS AML patients had elevated telomerase activity with microsatellite changes, indicating that approximately 40% of patients with post-MDS AML patients had accumulation of genome instability resulting in elevated telomerase activity in an attempt to obtain genetic stability. However, the remaining MDS patients had microsatellite changes without telomerase up-regulation, suggesting that some MDS had genome instability even after leukemic transformation. Most MDS patients with elevated telomerase activity in the AML phase had elevated telomerase activity even in the MDS phase without apparent change in telomere length before and after leukemic transformation. These findings indicate that telomerase activity in the MDS phase may be independent of telomere length, although telomere shortening seems to be related to genomic instability, and this process may be linked to apoptosis of MDS cells.

The R3 region, one of three major repetitive regions of human herpesvirus 6, is a strong enhancer of immediate-early gene U95.

An immediate-early (IE) gene of human herpesvirus 6 (HHV-6), U95, has similarity at the amino acid level to the murine cytomegalovirus (MCMV) IE2 gene and is related to the human cytomegalovirus (HCMV) US22 gene family. Sequence analyses of U95 cDNA clones revealed that the transcription start site was located about 1.6 kbp upstream of the putative initiating ATG and that the transcript consisted of two exons. A single intron extended from nucleotides 142589 to 144229, which contained ORF U94. A protein with a molecular mass of about 120 kDa was translated from this cDNA clone in an in vitro transcription-translation assay. The transcription start site was found to be 220 bp downstream of the R3 region by primer extension analysis. HHV-6 has three repetitive elements, R1, R2, and R3, in or near the IE-A locus. R3 is composed of 24 copies of a 104- to 107-bp sequence element, which contains multiple putative binding sites for cellular transcription factors such as AP2 and NF-kappaB, and its biological significance has yet to be elucidated. The region between -710 and +46 relative to the transcription start site of U95 was analyzed in this study. Deletion from -710 to -396, corresponding to three copies of an R3 unit, decreased the promoter activity by 15-fold, and coexpression of IkappaBalpha(S32A/S36A) repressed it to almost the same level. Electrophoretic mobility shift assays showed that NF-kappaB family members p50 and c-Rel bound to NF-kappaB sites derived from the R3 region. These results demonstrate that R3 strongly enhances the U95 promoter activity and that NF-kappaB and binding sites for NF-kappaB in the R3 region play an important role in its activation. Because U95 promoter activity correlated with the number of R3 units, which each contained an NF-kappaB site, the repetitive organization of R3 is important for regulating U95 transcription.

Successful treatment with cyclosporin A for myelodysplastic syndrome with erythroid hypoplasia associated with T-cell receptor gene rearrangements.

Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has not yet been clearly defined. We report four patients with MDS with erythroid hypoplasia who received immunosuppressive therapy. All were elderly, had severe transfusion-dependent anaemia, morphological evidence of myelodysplasia and a low percentage (3.2-13.6%) of erythroid precursors. Administration of cyclosporin A (CsA) improved their anaemia; all transfusion-dependent patients achieved transfusion-independence. An inverted CD4/8 ratio was seen in three patients who also demonstrated T-cell receptor (TCR)-beta and -gamma gene rearrangements by Southern blotting and clonality by polymerase chain reaction. Treatment with CsA can be an attractive alternative treatment for patients with MDS with erythroid hypoplasia, which may be associated with a clonal abnormality in T cells.