Comparison of risk factors for SARS-CoV-2 infection among healthcare workers during Omicron and Delta dominance periods in Japan.

BACKGROUND: The risk factors for coronavirus disease (COVID-19) among healthcare workers (HCWs) might have changed since the emergence of the highly immune evasive Omicron variant. AIM: To compare the risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs during the Delta- and Omicron-predominant periods. METHODS: Using data from repeated serosurveys among the staff of a medical research centre in Tokyo, two cohorts were established: Delta period cohort (N = 858) and Omicron period cohort (N = 652). The potential risk factors were assessed using a questionnaire. Acute/current or past SARS-CoV-2 infection was identified by polymerase chain reaction or anti-nucleocapsid antibody tests, respectively. Poisson regression was used to calculate the risk ratio (RR) of infection risk. FINDINGS: The risk of SARS-CoV-2 infection during the early Omicron-predominant period was 3.4-fold higher than during the Delta-predominant period. Neither working in a COVID-19-related department nor having a higher degree of occupational exposure to SARS-CoV-2 was associated with an increased infection risk during both periods. During the Omicron-predominant period, infection risk was higher among those who spent ≥30 min in closed spaces, crowded spaces, and close-contact settings without wearing mask (≥3 times versus never: RR: 6.62; 95% confidence interval: 3.01-14.58), whereas no such association was found during the Delta period. CONCLUSION: Occupational exposure to COVID-19-related work was not associated with the risk of SARS-CoV-2 infection in the Delta or Omicron period, whereas high-risk behaviours were associated with an increased infection risk during the Omicron period.

ZFP521 contributes to pre-B-cell lymphomagenesis through modulation of the pre-B-cell receptor signaling pathway.

ZFP521 was previously identified as a putative gene involved in induction of B-cell lymphomagenesis. However, the contribution of ZFP521 to lymphomagenesis has not been confirmed. In this study, we sought to elucidate the role of ZFP521 in B-cell lymphomagenesis. To this end, we used a retroviral insertion method to show that ZFP521 was a target of mutagenesis in pre-B-lymphoblastic lymphoma cells. The pre-B-cell receptor (pre-BCR) signaling molecules BLNK, BTK and BANK1 were positively regulated by the ZFP521 gene, leading to enhancement of the pre-BCR signaling pathway. In addition, c-myc and c-jun were upregulated following activation of ZFP521. Stimulation of pre-BCR signaling using anti-Vpreb antibodies caused aberrant upregulation of c-myc and c-jun and of Ccnd3, which encodes cyclin D3, thereby inducing the growth of pre-B cells. Stimulation with Vpreb affected the growth of pre-B cells, and addition of interleukin (IL)-7 receptor exerted competitive effects on pre-B-cell growth. Knockdown of BTK and BANK1, targets of ZFP521, suppressed the effects of Vpreb stimulation on cell growth. Furthermore, in human lymphoblastic lymphoma, analogous to pre-B-cell lymphoma in mice, the expression of ZNF521, the homolog of ZFP521 in humans, was upregulated. In conclusion, our data showed that the ZFP521 gene comprehensively induced pre-B-cell lymphomagenesis by modulating the pre-B-cell receptor signaling pathway.

Skewed X chromosome inactivation in fraternal female twins results in moderately severe and mild haemophilia B.

Female carriers of haemophilia B are usually asymptomatic; however, the disease resulting from different pathophysiological mechanisms has rarely been documented in females. In this study, we investigated the mechanisms responsible for haemophilia B in fraternal female twins. We sequenced the factor IX gene (F9) of the propositus, her father, a severe haemophilia B patient and the other family members. X chromosome inactivation was assessed by the methylation-sensitive HpaII-PCR assay using X-linked polymorphisms in human phosphoglycerate kinase 1 gene (PGK1) and glutamate receptor ionotropic AMPA 3 gene (GRIA3). The twins were found to be heterozygotes with a nonsense mutation (p.Arg384X) inherited from their father. The propositus, more severely affected twin, exhibited a significantly higher percentage of inactivation in the maternally derived X chromosome carrying a normal F9. The other twin also showed a skewed maternal X inactivation, resulting in a patient with mild haemophilia B. Thus, the degree of skewing of maternal X inactivation is closely correlated with the coagulation parameters and the clinical phenotypes of the twins. Furthermore, we identified a crossing-over in the Xq25-26 region of the maternal X chromosome of the more severely affected twin. This crossing-over was absent in the other twin, consistent with their fraternal state. Differently skewed X inactivation in the fraternal female twins might cause moderately severe and mild haemophilia B phenotypes, respectively.

A nosocomial parvovirus B19 infection-induced transient aplastic crisis in a patient with chronic renal failure.

A male patient aged 67 years with chronic renal failure (CRF), who had undergone hemodialysis since June 3, complained of dyspnea while walking on June 23, 1998. Rapidly progressive anemia and severe reticulocytopenia were noted. Serological tests showed that parvovirus B19- (B19) specific IgM antibody, but not IgG antibody, was present in the patient's serum. B19 DNA was detected in the patient's serum by the polymerase chain reaction (PCR). Therefore, a definite diagnosis of transient aplastic crisis induced by B19 was made. On June 10, prior to the appearance of this case, a female nurse aged 27 years working in our hemodialysis center, complained of cough, fever and arthralgia. Another female nurse, aged 35 years, developed similar symptoms on July 3. Both nurses had a positive IgM titer against B19, but were negative for IgG, indicating an acute B19 infection. These findings led us to suspect that this series of B19 infection was spread by nosocomial transmission. Although some cases of B19 infection have been reported to occur in laboratory staffs, the B19 nosocomial infection has not been described in the literature. We also suggest that a transient aplastic crisis due to B19 infection could lead to severe anemia in cases of CRF whose erythropoiesis is maintained by a recombinant human erythropoietin.

A case of clinically and neuropathologically atypical corticobasal degeneration with widespread iron deposition.

A 65-year-old woman was admitted to our hospital for forgetfulness, depression and eccentric behavior that had been first noticed 2 years prior to admission. She showed memory impairment, perseveration and repeated violent actions, but no limb-kinetic apraxia. She died 12 years after the onset of symptoms. At autopsy, the unfixed brain weighed 820 g. Atrophy was circumscribed in the frontal lobe on both sides. The globus pallidus and the caudate nucleus were markedly atrophic and gold yellow in color, and the substantia nigra was strikingly pale. The cortical area showed neuronal loss and status spongiosus of the second and third cortical layers with ballooned neurons. Marked neuronal loss was observed in the dorsomedial nucleus of the thalamus, Meynert basal nucleus and substantia nigra. With Holzer stain, fibrillary gliosis was found to be severe in the frontal lobe, globus pallidus, subthalamic nucleus, hippocampus, dorsomedial nucleus of thalamus, substantia nigra, pontine tegmentum and inferior olivary nucleus. With Bielschowsky-Hirano stain, neurofibrillary tangles were observed in the cortex, hippocampus, substantia nigra, dentate nucleus, subthalamic nucleus, pontine nucleus, the inferior olivary nucleus, dorsomedial nucleus of the thalamus and, to a lesser extent, the neostriatum. Strikingly numerous argyrophilic and tau-positive threads were present in the cerebral white matter. These neuropathological findings corresponded to corticobasal degeneration, but lesions characteristic of progressive supranuclear palsy were also found. Moreover, widespread iron deposition throughout the central nervous system was the most striking finding of the present case. To our knowledge, such a case has not been reported in the literature to date.

An electron spin resonance study on alkylperoxyl radical in thin-sliced renal tissues from ferric nitrilotriacetate-treated rats: the effect of alpha-tocopherol feeding.

Formation of excess free radical causes cellular oxidative stress, which has been shown to be associated with a variety of pathologic conditions. While electron spin resonance (ESR) spectroscopy has been the only method to demonstrate the presence of free radicals, its application to tissue samples has been challenging. We report here the successful ESR detection in thin-sliced fresh tissues or frozen sections in a rat model. Ferric nitrilotriacetate (Fe-NTA) induces oxidative renal tubular damage that ultimately leads to high incidence of renal carcinoma in rodents. Twenty minutes after administration of 5 mg iron/kg Fe-NTA to rats, a thin-slice of the kidney was mounted on a tissue-type cell and analyzed by ESR spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). An ESR signal from alkylperoxyl radical adduct was obtained, and the signal was inversely proportional to renal alpha-tocopherol content which was modulated through diet. Furthermore, we undertook ex vivo study using frozen sections. Fe-NTA (1 mM) was added to a rat kidney frozen section for 10 min. After washing the specimen was mounted on a tissue-type cell and analyzed with ESR spin trapping using DMPO. Alkylperoxyl radical signal was dependent on thickness, incubation time and renal tissue levels of alpha-tocopherol, and was reduced by preincubation with catalase or dimethyl sulfoxide but not with alpha-tocopherol outside tissue. This versatile method facilitates identification of free radicals in pathologic conditions, and may be useful for selection of antioxidants.

Determination of inorganic acids by ion chromatography with n-tetradecylphosphocholine (zwitterionic surfactant) as the stationary phase and pure water as the mobile phase.

A new ion chromatographic (IC) system, in which n-tetradecylphosphocholine (TDPC, a phosphobetaine type of zwitterionic surfactant) was used as the stationary phase, pure water as the mobile phase, and conductivity as the method of detection, has been developed for the determination of inorganic acids. Five model acids, HCl, HNO3, HClO4, H2SO4, and H3PO4, were separated to baseline and eluted in the order H3PO4 > HCl > HNO3 > H2SO4 > HClO4. When peak areas were plotted against the concentrations of the acids in samples, linear calibration curves were obtained. Ultimate determination limits were approximately 1 mmol L(-1), but the discrimination of the method between solutions of different concentration was better than 10 micromol L(-1) for those model analytes. Salts of divalent cations could also be separated, but they were eluted faster than the acids. No separation was observed for the salts of monovalent cations. This newly proposed approach is applicable to the simultaneous determination of the inorganic acids (produced by reactions of NOx, SOx, and HCl with water) in aerosols.

Structure-activity relationships of triterpenoid derivatives extracted from Gymnema inodorum leaves on glucose absorption.

The leaves of Gymnema inodorum (GI) have been known to be effective for some diseases including diabetes mellitus, rheumatic arthritis and gout. The crude saponin mixtures extracted from GI leaves inhibited glucose absorption in the isolated intestinal tract and suppressed the increased blood glucose in rats. In this study, we examined the relationship between chemical structure and pharmacological activity of the four components from GI leave extracts (GiA-1, GiA-2, GiA-5 and GiA-7). These components were the derivatives of (3beta,4alpha,16beta)-16,23,28-trihydroxyolean-12-en-3-yl-beta-D-glucopyranosiduroic acid. GiA-2, GiA-5 and GiA-7 that have suppressive effects on the high K+-induced contraction, an increase in deltaPD and the increased blood glucose level in the glucose tolerance test have -H at the 21st position and -CH2OH at 4beta of aglycon. On the other hand, GiA-1 that does not have any effects on the three parameters mentioned above has -H at the 21st position and -CH3 at 4beta of aglycon. In conclusion, it is suggested that the inhibitory effect of triterpenoids in Gymnema leaves on glucose absorption from the intestinal tract relies on -CH2OH at 4beta.

Phylogenetic relationship and mode of evolution of yeast DNA topoisomerase II gene in the pathogenic Candida species.

We have determined the nucleotide sequences of about 55% of the region of the DNA topoisomerase II gene (approximately 2.3 kb) isolated from the pathogenic Candida species, C. dubliniensis, C. parapsilosis, C. tropicalis, C. krusei, C. kefyr, C. guilliermondii and C. lusitaniae. Evolutionary relationships among nine Candida species including those of C. albicans and C. glabrata were studied based on the DNA topoisomerase II gene. The nucleotide sequences of 2192 bp, which covered two catalytic domains, ATPase and cutting/resealing, were subjected to phylogenetic analysis. Sequence comparison and evolutionary analysis have revealed that the Candida species tested here are not monophyletic, and the two strains within the species C. tropicalis and C. parapsilosis are too diverse to be in a single species. A wide variety of divergence was observed among the functional domains of DNA topoisomerase II, suggesting that Candida species were in different evolutionary paths at least as regarding the DNA topoisomerase II gene. Sequence information and the observation on the species-specific manner of molecular evolution of DNA topoisomerase II in Candida will be applied to develop a method of identification and characterization of the Candida species in both natural and clinical isolates.

Accuracy of Digora system in detecting artificial peri-implant bone defects.

This study was done to compare the diagnostic accuracy in detecting simulated intrabony defects around fixtures using Digora (DIG; Sordex Orion Corporation, Helsinki, Finland) compared with Ektaspeed Plus film (PLS; Eastman Kodak Co., Rochester, NY). Three titanium implant fixtures were placed in molar areas of three cadavers. Bone defects were created in the interproximal alveolar crest. Exposure time was adjusted to a PLS film and reduced to 1/5 only for DIG (1/5 DIG). The results of four observers were assessed. Sensitivity, specificity, accuracy, and under the receiver operator characteristic curve (ROC) area were evaluated. Statistical analyses were performed by using Friedman test and one-way ANOVA test. Mean sensitivity/specificity were 0.60/0.85 (DIG), 0.54/0.81 (1/5 DIG), and 0.64/0.58 (PLS). There were no statistically significant differences in the diagnostic accuracies. Digora had an equivalent performance to radiographic film in detecting intrabony defects adjacent to the implants, notwithstanding the amount of 1/5 of the exposure time.

Controlled release of hepatocyte growth factor from gelatin hydrogels based on hydrogel degradation.

This paper investigates the controlled release of hepatocyte growth factor (HGF) by biodegradable gelatin hydrogels and their HGF-induced angiogenic effect. Hydrogels of different degradabilities were prepared through chemical crosslinking gelatin with varied amounts of glutaraldehyde. When the gelatin hydrogels were radioiodinated and subcutaneously implanted into the back of mice, the remaining radioactivity of the hydrogels decreased with time. However, the remaining period became longer when the concentration of glutaraldehyde used for hydrogel preparation increased. Following implantation of gelatin hydrogels incorporating 125I-labeled HGF, the HGF radioactivity retained in the mouse subcutis for longer time periods as the glutaraldehyde concentration becomes higher. The time profile of HGF remaining in every gelatin hydrogel was in good accordance with that of hydrogel degradation, indicating HGF release as a result of hydrogel biodegradation. The gelatin hydrogel incorporating HGF histologically induced angiogenic change around the implanted hydrogel. Gelatin hydrogels incorporating 5 and 10 microg HGF significantly enhanced the number of capillaries newly formed around the implanted site. This was in marked contrast to free HGF of same dose form and HGF-free, empty gelatin hydrogel. The gelatin hydrogel incorporating HGF induced VEGF around the implanted site. In vitro bioassay revealed that HGF molecules interacting with gelatin, still exhibited the biological activity. The interacted HGF would be released from gelatin hydrogels only when they were degraded to generate water-soluble gelatin fragments. It is possible that the HGF associating gelatin fragments of bioactivating, results in induced angiogenic effect.

Endosseous titanium implants as anchors for mesiodistal tooth movement in the beagle dog.

The purpose of this study was to determine the anchorage potential of titanium implants (Branemark; 3.75 x 7 mm) with the use of a sectional arch wire technique for orthodontic mesiodistal tooth movement, as assessed by the osseointegration of implants and tooth movement. Two implants were surgically placed in healed mandibular extraction sites of the second and third premolars on each side in 4 adult male beagle dogs. The implants were surgically uncovered 18 weeks later, and second-stage abutments with soldered edgewise tubes were attached. Segmented edgewise rectangular archwires (0.017 x 0. 025 inch) with a T-loop or an L-loop were placed between the implants and the fourth premolars on both sides as the anchorage unit. One segment in each dog served as a loaded side, and the archwire was calibrated to produce 200 g of lateral force on the fourth premolar. The contralateral segment served as an unloaded side and was not subjected to orthodontic force. Sectional wires were activated biweekly 24, 28, 28, and 32 weeks, respectively, depending on the magnitude and the appearance of mesial tipping movement of the fourth premolar. After mandibular impressions were taken to measure the distance between the first molar and the fourth premolar, the animals were euthanized and dissected mandibles were prepared. The specimens were then embedded in polyester resin and cut to take backscattered electron images. On the basis of these images, the percentage of peri-implant bone volume was calculated and defined as an index of osseointegration. The differences between the initial and final fourth premolar to first molar distances varied (7.40, 8.85, 10.50, and 3.30 mm) on the loaded side, whereas the unloaded side showed no movement. Not only was there no statistical difference in the percent of peri-implant bone volume between the loaded and unloaded sides, but there was also no statistical difference between the compression and tension sides in both loaded and unloaded implants, which suggests that the implants maintained rigid osseointegration. In conclusion, the present study demonstrated that endosseous titanium implants can function as anchors for long-term orthodontic mesiodistal movement.

Novel method to enhance sternal healing after harvesting bilateral internal thoracic arteries with use of basic fibroblast growth factor.

BACKGROUND: Poor healing of the sternum often limits the use of bilateral internal thoracic arteries (BITAs) in coronary bypass surgery, especially for diabetic patients. We have reported that basic fibroblast growth factor (bFGF) enhanced regeneration of the skull. This study was designed to evaluate the effects of topical use of bFGF on sternal healing after removing the BITAs. METHODS AND RESULTS: Forty-five Wistar rats were subjected to median sternotomy and were divided into 3 groups: 15 had the BITAs removed and had a bFGF sheet applied on the posterior table of the sternum (group A), 15 had just the BITAs removed (group B), and 15 had intact BITAs (group C). Five and 10 rats were euthanized 2 and 4 weeks after surgery, respectively, in all 3 groups. Peristernal blood flow, measured with use of a noncontact laser flowmeter, decreased after removal of the BITAs (P:<0.001). Four weeks after the surgery, PBF markedly increased only in group A (9.7+/-1.2, 6.5+/-0.6, and 8.2+/-0.5 mL x min(-1) x 100 g(-1) for groups A, B, and C, respectively; P:<0.01 by ANOVA). Four weeks after surgery, the following findings were obtained only in group A: (1) nearly completely healed sternum filled with regenerated bone tissue, (2) marked angiogenesis around the sternum, and (3) osteoblasts in an active form around the edge of the sternum. CONCLUSIONS: The results suggest that use of the bFGF sheet offset the sternal ischemia and accelerated sternal healing. This method may help to decrease sternal necrosis in high-risk patients or allow extended use of BITAs in coronary bypass surgery.

Strain relaxation in InAs/GaAs(111)A heteroepitaxy

We have studied strain-relaxation processes in InAs heteroepitaxy on GaAs(111)A using rocking-curve analysis of reflection high-energy electron diffraction. Strain relaxation in the direction parallel to the surface occurs at approximately 1.5 bilayers (BL) thickness. On the other hand, the lattice constant in the direction normal to the surface remains almost unchanged below approximately 3 BL thickness and is estimated to be approximately 3.3 A. This value, slightly larger than that of bulk GaAs (3.26 A), does not quite reach the value predicted by classical elastic theory, 3.64 A. The present result has been supported by the first-principles total-energy calculations.

Inhibition by dietary tea polyphenols of chemical mediator release from rat peritoneal exudate cells.

Male Wistar rats were given purified diets containing safflower (SAF), perilla (PER), or palm (PAL) oils with or without 1% tea polyphenols (TP) for 3 weeks, and chemical mediator releasing activity from rat peritoneal exudate cells (PEC) was measured. Histamine releasing activity was not influenced by TP, while histamine release and intracellular histamine content were significantly increased in the PAL-fed group. On the contrary, leukotriene B4 (LTB4) release was significantly lower in rats fed PER than in those fed SAF and PAL, and TP significantly decreased the release in all fat groups. TP also significantly inhibited the release of LTB5, which was generated only in rats fed PER. TP significantly decreased the proportion of arachidonic acid (AA) in PEC in the SAF-fed group and that of eicosapentaenoic acid (EPA), the precursor of LTB5 in the PER-fed group, but did not influence that of AA in the PAL- and PER-fed group. These results suggest that ingestion of TP improves type I allergic symptom through the inhibition of LT release though the inhibition by TP could not be totally explained by the reduction of substrate fatty acid.

An autopsy case with clinically and molecular genetically diagnosed Huntington's disease with only minimal non-specific neuropathological findings.

An autopsy case with clinically and molecular genetically diagnosed Huntington's disease (HD) accompanied with minimal non-specific neuropathological features was reported. When the patient was 45 years old, he had faulty memory, mood swing, personality change and agitation. Neurological and psychiatric examinations revealed choreoathetoid movements in limbs and trunk, generalized hyperreflexia and mental deterioration. However, cerebellar ataxia and muscle rigidity were not disclosed. Neuroimaging study did not show a definite atrophy of heads of caudate nuclei. Neuroacanthocytosis and Wilson's disease were ruled out by the peripheral blood examination and serum Cu and ceruloplasmin examination. At the age of 55 he died of pneumonia. Post-mortem examination revealed minimal non-specific neuropathological features for HD (Vonsattel's grade 0), that is, no visible fibrillary gliosis in the striatum, and few neuronal loss and only proliferation of astrocytes (astrocytosis) in the striatum. Molecular-genetic study the patient's brain tissues and his youngest son's blood was performed. These studies revealed 40 CAG repeats in the patient, 56 CAG repeats in his youngest son. These results suggest they may be HD. Vonsattel et al. [ 1998] insist that grade 0 comprises 1% of all HD brains, and grade 1 comprises 4% of all HD brains. But we could not find any reports in which the clinical and neuropathological features were described in detail on the cases with clinically and molecular genetically diagnosed HD without specific pathological findings. Therefore, we present in detail the clinical and neuropathological features of such case.

Controlled release of vascular endothelial growth factor by use of collagen hydrogels.

In vivo profile of vascular endothelial growth factor (VEGF) release from collagen hydrogels was investigated comparing that of hydrogel degradation while angiogenesis induced by the released VEGF was assessed. Collagen sponges were chemically cross-linked with different amounts of glutaraldehyde for various time periods. When 125I-labeled collagen hydrogels incorporating VEGF were subcutaneously implanted into the back subcutis of mice, the hydrogel radioactivity decreased with time, the decrement profile depending on the cross-linking conditions. The radioactivity was retained for longer time periods as the glutaraldehyde concentration and cross-linking time increased. Implantation study of collagen hydrogels incorporating 125I-labeled VEGF revealed that the remaining VEGF radioactivity decreased with time and the retention period was prolonged with the decreased hydrogel biodegradation. The slower the hydrogel degradation, the longer the period of VEGF retention. The collagen hydrogel incorporating VEGF induced significant angiogenesis around the implanted hydrogel, in marked contrast to VEGF in the solution form and VEGF-free empty hydrogel. The retention period of angiogenesis became longer with a decrease of the in vivo degradation rate of hydrogels. It is possible that the slower degraded hydrogel achieves a longer period of VEGF release, resulting in prolonged angiogenetic effect. We concluded that in our hydrogel system, biologically-active VEGF was released as a result of in vivo degradation of the hydrogel.

Characterization of an outer membrane protein gene, pgmA, and its gene product from Porphyromonas gingivalis.

A gene upstream from fimA, the gene encoding fimbrilin, on the chromosome of Porphyromonas gingivalis was sequenced and shown to be the gene encoding an outer membrane protein in this organism based on homology and biochemical analyses. Therefore, the gene (formerly ORF5) was designated pgmA, the P. gingivalis outer membrane protein A gene. The gene product, PgmA, was sensitive to protease, and was detected as a 60-kDa protein from wild-type strains with trichloroacetic acid treatment, which was carried out to destroy intrinsic proteases, and from protease-deficient mutants without this treatment prior to electrophoresis. PgmA was indeed present in the membrane fraction. Its nature was determined to be that of outer membrane proteins in gram-negative bacteria based on attempts at differential extraction of inner membrane proteins with detergents. No evidence has been found thus far from functional analyses that this protein is related to fimbrial morphogenesis and functions or to serum resistance of this organism.