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Adverse childhood experiences have been linked to psychopathology due to reduced social networks or social thinning. However, evidence of the temporal associations between adverse childhood experiences, social networks, and psychopathology was lacking, as few studies assessed social networks repeatedly. Further, their underlying neurocognitive and biological mechanisms related to hypervigilance and inflammation remain unclear. This study aimed to clarify these associations using a three-wave population-based cohort study during the COVID-19 pandemic (n = 465), where we leveraged repeated social network assessments. Self-reported questionnaires assessed adverse childhood experiences, social network size and diversity, psychological distress, and hypervigilance regarding COVID-19. Blood tests were conducted to measure inflammation markers. Individuals with more adverse childhood experiences demonstrated lesser increases in their social networks than those without adverse childhood experiences. Decreased network sizes were associated with severe psychological distress, but this association did not remain after adjusting for baseline distress. On the other hand, reduced network diversities were associated with increased psychological distress. We did not find any paths through hypervigilance regarding COVID-19 and inflammation that explain associations between adverse childhood experiences, social thinning, and psychological distress. These findings emphasize the significant social network changes in the associations between adverse childhood experiences and psychopathology., (© 2024. The Author(s).)

Background: The specific long-term sequela of coronavirus disease 2019 (COVID-19), also known as long COVID of the Omicron variant remain unclear, due to a lack of cohort studies that include non-COVID patients with cold-like symptoms. The study was conducted to examine specific sequelae symptoms after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which is considered the Omicron variant, compared with patients who were never-infected., Methods: In this retrospective cohort study, we sent questionnaires in November 2022, targeting those who visited our fever outpatient unit of a single institution from July to September 2022. SARS-CoV-2 infection status was determined by SARS-CoV-2 polymerase chain reaction (PCR) test results during the study period collected in electronic medical records. Clinical characteristics at 30 days or more since the date of SARS-CoV-2 PCR test were assessed by the questionnaires. Multiple logistic regression was performed to investigate the independent association between SARS-CoV-2 infection and possible sequelae symptoms., Results: In total, valid responses were received from 4,779 patients (mean age: 41.4 years, standard deviation: 19.8 years old). Among them, 3,326 (69.6%) and 1,453 (30.4%) were SARS-CoV-2 PCR test positive and never-infected, respectively. We found that patients with SARS-CoV-2 infection were more likely to have a loss of taste or smell [odds ratio (OR) 4.55, 95% confidence interval (CI): 1.93, 10.71], hair loss (OR 3.19, 95% CI: 1.67, 6.09), neurocognitive symptoms (OR 1.95, 95% CI: 1.43, 2.65), and respiratory symptoms (OR 1.23, 95% CI: 1.03, 1.47) than never-infected patients. SARS-CoV-2 infection was not associated with common cold symptoms, chronic physical distress, or diarrhea as sequelae symptoms. Further, SARS-CoV-2 vaccination showed protective effects on sequelae of loss of taste or smell and hair loss., Conclusions: Loss of taste or smell, hair loss, neurocognitive symptoms, and respiratory symptoms were found to be specific sequelae of the SARS-CoV-2 Omicron variant. It is important not to miss these symptoms that follow SARS-CoV-2 infection and to recognize and manage the long COVID., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1672/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Introduction: COVID-19 have changed our lifestyle and little is known how our lifestyle associated with flourishing during COVID-19. This study examined the association between lifestyle, including sleep time, drinking, and smoking, and flourishing during the COVID-19 pandemic in Japan., Methods: We used the population-based study, Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) survey conducted in November 2021 to examine the association between lifestyle such as sleeping time, drinking and smoking, and flourishing ( n = 473). Flourishing was assessed with the flourishing index, a 10-item multidimensional scale with five domains. Multivariate linear regression analysis was performed adjusted for sex, age, income, and education., Results: We found that the flourishing index was significantly lower in the group that slept less than 6 h than in the group that slept 6-8 h (coef = -0.49, SE = 0.17, p < 0.01). We also found that drinking once to several times/week showed higher flourishing than those who almost never drink (coef = 0.57, SE = 0.19, p < 0.01). Smoking was not associated with flourishing., Discussion: Sleep duration and drinking habit, but not smoking, may be important for flourishing during the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shibata, Yamaoka, Nawa, Nishimura, Koyama, Kuramochi and Fujiwara.)

Background: Repeated emergence of variants with immune escape capacity and waning immunity from vaccination are major concerns for COVID-19. We examined whether the surge in Omicron subvariant BA.5 cases was due to immune escape or waning immunity through vaccine effectiveness (VE) evaluation., Methods: A test-negative case-control study was conducted in 16 clinics/hospitals during the BA.1/BA.2-dominant and BA.5-dominant periods. VE against symptomatic infection was estimated after adjusting for age, sex, comorbidity, occupation, testing frequency, prior infection, close contact history, clinic/hospital, week, and preventive measures. Absolute VE (aVE) was calculated for 2/3/4 doses, compared to the unvaccinated. Relative VE (rVE) was calculated, comparing 3 vs 2 and 4 vs 3 doses., Results: 13,025 individuals were tested during the BA.1/BA.2-dominant and BA.5-dominant periods with similar baseline characteristics. For BA.1/BA.2, aVE was 52 % (95 %CI:34-66) 14 days-3 months post-dose 2, 42 % (29-52) > 6 months post-dose 2, 71 % (64-77) 14 days-3 months post-dose 3, and 68 % (52-79) 3-6 months post-dose 3. rVE was 49 % (38-57) 14 days-3 months post-dose 3 and 45 % (18-63) 3-6 months post-dose 3. For BA.5, aVE was 56 % (27-73) 3-6 months post-dose 2, 32 % (12-47) > 6 months post-dose 2, 70 % (61-78) 14 days-3 months post-dose 3, 59 % (48-68) 3-6 months post-dose 3, 50 % (29-64) > 6 months post-dose 3, and 74 % (61-83) ≥ 14 days post-dose 4. rVE was 56 % (45-65) 14 days-3 months post-dose 3, 39 % (27-48) 3-6 months post-dose 3, 25 % (-2-45) > 6 months post-dose 3, and 30 % (-6-54) ≥ 14 days post-dose 4., Conclusions: Booster doses initially provided high protection against BA.5 at a level similar to that against BA.1/BA.2. However, the protection seemed shorter-lasting against BA.5, which likely contributed to the surge. Furthermore, rVE post-dose 4 was low even among recent vaccinees. These results support the introduction of variant-containing vaccines and emphasize the need for vaccines with longer duration of protection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In the COVID-19 pandemic, lockdown and acryl partitions were adopted as countermeasures against droplets/aerosol infections; however, these countermeasures restrict communication. In this study, a blocking device was developed using negative ions and an electric field. The device blocks mists simulating droplets/aerosol by a maximum of 89% but transmits light and sound, which is important for communication. The device demonstrated effective blocking performance for aerosol, including the COVID-19 virus spread from patients in a clinic. Our device can help prevent infections without disrupting communication., (© 2023. Springer Nature Limited.)

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022., (© 2023. The Author(s).)

In this multicenter, prospective, test-negative, case-control study in Japan, the effectiveness of both BA.1-containing and BA.4/BA.5-containing bivalent coronavirus disease 2019 mRNA vaccines against symptomatic infection during the BA.5-dominant period was high compared with no vaccination (65% and 76%) and moderate compared with monovalent vaccines administered over half a year earlier (46% combined)., Competing Interests: Potential conflicts of interest. TA is an unpaid consultant for the World Health Organization. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Although several coronavirus disease 2019 (COVID-19) vaccines initially showed high efficacy, there have been concerns because of waning immunity and the emergence of variants with immune escape capacity., Methods: A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic severe acute respiratory syndrome coronavirus 2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period compared with unvaccinated individuals., Results: The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received messenger RNA (mRNA)-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% confidence interval [CI], 82-93) 14 days to 3 months after dose 2 and 87% (95% CI, 38-97) 3 to 6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI, 37-70) 14 days to 3 months since dose 2, 52% (95% CI, 40-62) 3 to 6 months after dose 2, 49% (95% CI, 34-61) 6+ months after dose 2, and 74% (95% CI, 62-83) 14+ days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (ie, mask wearing/high-risk behaviors) yielded similar estimates, respectively., Conclusions: In Japan, where most are infection-naïve, and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level., Competing Interests: Potential conflicts of interest . T. A. is an unpaid consultant for the World Health Organization. The other authors declare no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency, but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5., Competing Interests: Declaration of interests Y.Y. and T.N. are founders and shareholders of HiLung, Inc. Y.Y. is a co-inventor of patents (PCT/JP2016/057254; “method for inducing differentiation of alveolar epithelial cells,” PCT/JP2016/059786, “method of producing airway epithelial cells”)., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2., Competing Interests: Declaration of interests Y.Y. and T.N. are founders and shareholders of HiLung, Inc. J.K. is an employee of HiLung, Inc. Y.Y. is a co-inventor of patents (PCT/JP2016/057254; “Method for inducing differentiation of alveolar epithelial cells,” PCT/JP2016/059786, “Method of producing airway epithelial cells”)., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

In the face of unknown risks, including the coronavirus disease 2019 (COVID-19) pandemic, we tend to have stigmatized perceptions. The current study aimed to examine the association of social engagements with the level of stigmatization of COVID-19 infection among the general population. The data of 429 participants of the Utsunomiya COVID-19 seroprevalence neighborhood association (U-CORONA) study, a population-based cohort study conducted in Utsunomiya City, Japan, were analyzed. Their stigmatized perception of people with COVID-19 infection was evaluated via a questionnaire for the situation if they or others in their community were to get infected. The association between social engagements (community social capital, social network diversity, and social network size) and stigmatization were analyzed by a multiple linear regression model with generalized estimating equations. Overall, females reported a higher stigmatized perception of people with COVID-19 than males. Lower education and depressive symptoms were also positively associated with higher stigmatization, while age, household income, and comorbidities were not. People with higher community social capital reported lower stigmatization (B = -0.69, 95% CI = -1.23 to -0.16), while social network diversity and social network size did not show an association with stigmatization. We found an association between community social capital and stigmatization, suggesting that enhancing their community social capital, but not social network diversity and size, has the potential to mitigate the levels of stigmatization.

Soon after the emergence and global spread of the SARS-CoV-2 Omicron lineage BA.1, another Omicron lineage, BA.2, began outcompeting BA.1. The results of statistical analysis showed that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralization experiments revealed that immunity induced by COVID vaccines widely administered to human populations is not effective against BA.2, similar to BA.1, and that the antigenicity of BA.2 is notably different from that of BA.1. Cell culture experiments showed that the BA.2 spike confers higher replication efficacy in human nasal epithelial cells and is more efficient in mediating syncytia formation than the BA.1 spike. Furthermore, infection experiments using hamsters indicated that the BA.2 spike-bearing virus is more pathogenic than the BA.1 spike-bearing virus. Altogether, the results of our multiscale investigations suggest that the risk of BA.2 to global health is potentially higher than that of BA.1., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The clinical characteristics of patients with N501Y mutation in SARS-CoV-2 variants (N501YV) is not fully understood, especially in the setting of general practice. In this retrospective cohort study, COVID-19 patients admitted to one general practitioner clinic between 26 March and 26 May 2021 were retrospectively analyzed. The characteristics, clinical symptoms and radiological findings before treatment were compared between N501YV and wild-type 501N. Twenty-eight patients were classified as wild-type 501N and 24 as N501YV. The mean (±standard deviation) age was 37.4 (±16.1) years, with no significant difference between groups. Among clinical symptoms, prevalence of fever of 38 degrees Celsius (°C) or higher was significantly higher in the N501YV group than in the wild-type 501N group ( p = 0.001). Multivariate analysis showed that fever of 38 °C or higher remained significantly associated with N501YV (adjust odds ratio [aOR]: 6.07, 95% confidence interval [CI]: 1.68 to 21.94). For radiological findings, the lung involvement area was significantly larger in patients infected with N501YV ( p = 0.013). In conclusion, in the N501YV group, fever of 38 °C or higher and extensive pneumonia were more frequently observed compared to the wild-type 501N group. There was no significant difference in terms of other demographics and clinical symptoms.

In the face of the global coronavirus disease 2019 (COVID-19) pandemic, billions of people were forced to stay at home due to the implementation of social distancing and lockdown policies. As a result, individuals lost their social relationships, leading to social isolation and loneliness. Both social isolation and loneliness are major risk factors for poor physical and mental health status through enhanced chronic inflammation; however, there might be an interplay between social isolation and loneliness on the association with chronic inflammation. We aimed to clarify the link between social relationships and inflammation in the context of the COVID-19 pandemic by distinguishing whether social isolation only, loneliness only, or both were associated with chronic inflammation markers among community-dwelling adults. The data of 624 people (aged 18-92 years, mean 51.4) from the Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) study, which targeted randomly sampled households in Utsunomiya city, Japan, were analyzed. Social isolation was assessed as a structural social network by asking the number of social roles they have on a daily basis. Loneliness was measured with the UCLA loneliness scale. As chronic inflammation biomarkers, neutrophil-to-lymphocyte ratio (NLR) and the concentration of high-sensitivity C-reactive protein (CRP) were measured. Generalized estimating equations method was employed to take into account the correlations within households. Isolated-Lonely condition (i.e., being both socially isolated and feeling lonely) was associated with higher NLR among men (B = 0.141, 95%CI = -0.01 to 0.29). Interestingly, Nonisolated-Lonely condition (i.e., not socially isolated but feeling lonely) was associated with lower CRP among women (B = -0.462, 95%CI = -0.82 to -0.10) and among the working-age population (B = -0.495, 95%CI = -0.76 to -0.23). In conclusion, being both socially isolated and feeling lonely was associated with chronic inflammation. Assessing both social isolation and loneliness is critical for proper interventions to mitigate the impact of poor social relationships on health, especially in the context of the COVID-19 pandemic., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Face mask use is a critical behavior to prevent the spread of SARS-CoV-2. We aimed to evaluate the association between social integration and face mask use during the COVID-19 pandemic in a random sample of households in Utsunomiya City, Greater Tokyo, Japan. Data included 645 adults in the Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) study, which was conducted after the first wave of the pandemic, between 14 June 2020 and 5 July 2020, in Utsunomiya City. Social integration before the pandemic was assessed by counting the number of social roles, based on the Cohen's social network index. Face mask use before and during the pandemic was assessed by questionnaire, and participants were categorized into consistent mask users, new users, and current non-users. Multinomial logistic regression analysis was used to examine the association between lower social integration score and face mask use. To account for possible differential non-response bias, non-response weights were used. Of the 645 participants, 172 (26.7%) were consistent mask users and 460 (71.3%) were new users, while 13 (2.0%) were current non-users. Lower social integration level was positively associated with non-users (RRR: 1.76, 95% CI: 1.10, 2.82). Social integration may be important to promote face mask use.

Objective: Coronavirus disease 2019 (COVID-19) has spread worldwide, including Japan. However, little is known about the clinical symptoms which discriminate between COVID-19 and non-COVID-19 among outpatients in general practitioner clinics, which is important for efficient case detection. The aim of this study was to investigate the clinical symptoms to discriminate between COVID-19 and non-COVID-19 cases among outpatients in general practitioner clinics during the second wave of the COVID-19 pandemic in Japan in August 2020., Methods: The records of 360 patients who visited a clinic with suspicion of infectious disease and underwent COVID-19 PCR test between 1 and 14 August 2020 were used. The patients filled out a questionnaire on possible clinical symptoms and transmission routes. Multivariate logistic regression was used to investigate the association between clinical symptoms and COVID-19 status., Results: COVID-19-positive patients were 17 (4.7%). Multiple logistic regression analyses showed that anosmia (odds ratio (OR), 25.94 95% confidence interval (CI), 7.15-94.14; p < 0.001), headache (OR, 3.31 95% confidence interval (CI), 0.98-11.20; p = 0.054), sputum production (OR, 3.32 CI, 1.01-10.90; p = 0.048) and history of visiting an izakaya or bar (OR, 4.23 CI, 0.99-18.03; p = 0.051) were marginally significantly associated withbeing COVID-19 positive. This model showed moderate predictive power (area under receiver operating characteristic curve = 0.870 CI, 0.761 to 0.971)., Conclusions: We found that anosmia, headache, sputum production, history of visiting an izakaya or bar were associated with COVID-19, which can be used to detect patients with COVID-19 in out-patient clinics in Japan. The findings of this study need to be verified in other clinics and hospitals in Japan and other countries with universal healthcare coverages.

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open-label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40-160 mg/day or febuxostat 10-60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio-ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (-2.9 and -2.5 mg/dl; both p < 0.001) and morning home systolic BP (-3.6 and -5.1 mm Hg; both p < 0.01) after 24 weeks' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin-creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (-20.8%; p = 0.021), but not febuxostat (-8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks' treatment., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: A seroepidemiological study was conducted on a random sample of households in Utsunomiya City, Tochigi Prefecture, Greater Tokyo, Japan, to assess the seroprevalence of SARS-CoV-2., Methods: The level of IgG antibodies in the blood of the recruited subjects was assessed using chemiluminescence immunoassay analysis. In addition, the population-based prevalence of SARS-CoV-2 was estimated., Results: Three positive afebrile cases were confirmed. The estimated unweighted prevalence and weighted prevalence of SARS-CoV-2 infection were 0.40% and 1.23%, respectively., Conclusions: This study suggests that the prevalence of SARS-CoV-2 may have been underestimated. Wider testing strategies may lead to revealing more SARS-CoV-2 cases., Competing Interests: Authors declare no conflict of interests for this article., (© 2020 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.)

Rationale: Bird-related hypersensitivity pneumonitis is induced by inhalation of avian antigen. Evaluation to avoid repeated exposure to avian antigen is a key part of the treatment for bird-related hypersensitivity pneumonitis. It can be difficult, however, to reliably evaluate exposure to the antigen because bird-related hypersensitivity pneumonitis in its chronic form may be caused by unrecognized and indirect exposure., Objective: The purpose of the present study is to establish a method for measuring environmental avian antigen in patients with chronic bird-related hypersensitivity pneumonitis and to evaluate the clinical utility of the method., Methods: The amount of avian antigen was measured in samples of dust collected from the household environments of patients with chronic bird-related hypersensitivity pneumonitis. The patients whose clinical progress could be followed by periodic pulmonary function tests for 1 year were classified into a deterioration group and a stable group. Age, sex, smoking status, FVC % predicted, and the amount of avian antigen in household dust samples at the diagnosis of bird-related hypersensitivity pneumonitis, as well as survival, were determined and evaluated for each group. The total number of subjects was 23., Measurements and Main Results: The clinical condition deteriorated in 11 patients and remained stable in 12. The amount of avian antigen in household dust samples was significantly higher for the deterioration group than for the stable group. In logistic regression analysis, avian antigen was the only variable found to be significant for distinguishing between the two groups. The patients with higher amounts household dust avian antigen had a poor prognosis in the survival analysis. Avian antigen was the only variable to significantly influence the prognosis of chronic bird-related hypersensitivity pneumonitis., Conclusions: The levels of exposure to avian antigen were related to disease progression and prognosis in chronic bird-related hypersensitivity pneumonitis.

During animal development, cells undergo dynamic changes in position and gene expression. A collection of quantitative information about morphological dynamics under a wide variety of gene perturbations would provide a rich resource for understanding the molecular mechanisms of development. Here, we created a database, the Worm Developmental Dynamics Database (http://so.qbic.riken.jp/wddd/), which stores a collection of quantitative information about cell division dynamics in early Caenorhabditis elegans embryos with single genes silenced by RNA-mediated interference. The information contains the three-dimensional coordinate values of the outlines of nuclear regions and the dynamics of the outlines over time. The database provides free access to 50 sets of quantitative data for wild-type embryos and 136 sets of quantitative data for RNA-mediated interference embryos corresponding to 72 of the 97 essential embryonic genes on chromosome III. The database also provides sets of four-dimensional differential interference contrast microscopy images on which the quantitative data were based. The database will provide a novel opportunity for the development of computational methods to obtain fresh insights into the mechanisms of development. The quantitative information and microscopy images can be synchronously viewed through a web browser, which is designed for easy access by experimental biologists.

To clarify the clinical symptoms of the influenza A virus during the 2009 pandemic influenza outbreak, we describe the clinical features of outpatients diagnosed with type A influenza by use of the rapid influenza diagnostic test (RIDT) from September to December 2009. Questionnaires were used to collect prospective data on 1,122 cases with influenza-like illness at our medical institutions. The independent predictors of influenza A virus were identified on the basis of demographic features and the clinical symptoms of the patients who tested positive for influenza A virus in the RIDT test. Of the 1,122 cases tested, 389 (34.7%) were positive for the influenza A virus. The median age of the influenza-positive patients was 14, and 58.9% of the patients were male. The symptoms fever, cough, rhinorrhea, and headache were statistically dominant. A history of recent contact with persons suffering from influenza or influenza-like illness at home, school, or in the workplace was significantly more common in the positive group than in the negative group. Pneumonia was observed in 2 (0.5%) of the positive patients, but the symptoms were only severe enough to require hospitalization in 1 of the 2. No deaths were observed among the 389 RIDT-positive patients. Although the spread of influenza A virus was both rapid and extensive, mainly among children under the age of 18, it seemed to be mild. Appropriate interpretation of the RIDT on the basis of recent clinical information, and early treatment with antiviral drugs might help to prevent severe illness from influenza pandemics in the future.

Background: In the management of hypersensitivity pneumonitis (HP), antigen avoidance is crucial to prevent the progression of disease. Indirect and unrecognized exposure to the antigen may continue for a long time if persistence of the causative antigen is not recognized. To make a correct assessment of the patients' environment, we tried to establish the methods to detect indoor and outdoor avian antigens., Methods: Sixteen patients with bird-related HP, 4 asymptomatic breeders, and 6 healthy controls were examined. We prepared anti-pigeon dropping extracts (PDE) polyclonal antibody from rabbits. Air samples and house dust samples were analyzed by an antigen-capture ELISA with signal amplification using catalyzed reporter deposition., Results: In air samples, avian antigen could be detected in patients with HP (0.73 +/- 0.53 ng/m3) and asymptomatic breeders (0.63 +/- 0.23 ng/m3). In house dust samples, the amount of avian antigen was higher in patients with HP (2.4 +/- 1.8 microg/g) and asymptomatic breeders (4.1 +/- 2.3 microg/g) than in the controls (0.1 +/- 0.2 microg/g)., Conclusions: Detection of indoor and outdoor avian antigen might contribute to the correct diagnosis and appropriate managements of bird-related HP.

We experienced a case of triple-negative recurrent breast carcinoma achieving a significant improvement by oral S- 1, a fluoropyrimidine-class anticancer drug and zoledronic acid(ZOL), a third generation bisphosphonate(BP). / Against metastases to orbital foramen, chest wall and bone, the oral treatment with S-1 was started at 80 mg/day everyday for 4 weeks, followed by a 2-week rest interval as 1 cycle, and ZOL was injected at 4 mg every 4 weeks. After 2 cycles of treatment, the level of tumor markers and tumor sizes became reduced. Twelve cycles after the initiation of the therapy, recrudescence of the metastatic lesions was not recognized, and no other metastases were recognized in any organ. In the course of the treatment, no adverse drug reactions to S-1 occurred in the patient. For treatment of recurrent breast carcinoma, S-1 is considered to be a useful and tolerable anticancer drug, and combination treatment of S-1 and ZOL is thought to be effective.

The clinical features of chronic hypersensitivity pneumonitis (HP) are similar to idiopathic interstitial pneumonias (IIPs) including idiopathic pulmonary fibrosis (IPF). We report 2 cases of chronic summer-type HP with insidious onset. They were misdiagnosed as having IIPs before referral to our hospital. Anti-trichosporon antibodies were positive in these cases. Their disease progressed due to the intermittent or continuous exposure to the antigen. Chronic summer-type HP should be included in the list of differential diagnosis of chronic interstitial lung diseases. Environmental investigation for an accurate diagnosis is important to convince the patient of the necessity to strictly avoid any future exposure to antigen.

Background and Objectives: Peptidyl prolyl cis-trans isomerase (Pin1) isomerizes only phosphorylated serine or threonine residues preceding proline in certain proteins and affects the protein function. Pin1 interacts with many signaling pathways, including Wnt signaling pathway that is crucial for colorectal tumorigenesis. Pin1 promotes cyclin D1 over-expression directly or through the stabilization of beta-catenin. Pin1 is over-expressed in some cancers such as prostate and breast cancers. This study aimed to determine whether Pin1 plays a role in colorectal tumorigenesis through the upregulation of beta-catenin and cyclin D1., Methods: Immunohistochemical analyses were performed on 105 colorectal cancer tissue samples using anti-Pin1, anti-beta-catenin, and anti-cyclin D1 antibodies. We examined the relationships between Pin1 expression and clinicopathological factors, prognosis, and beta-catenin/cyclin D1 expression., Results: High Pin1 expression was observed in 40 cases (38%) and positively correlated with histological type (P=0.0240), depth of invasion (P=0.0051), and staging (P=0.0027) of colorectal tumors. High Pin1 expression was also correlated with the over-expressions of both beta-catenin (P=0.0225) and cyclin D1 (P=0.0137)., Conclusions: These results suggest that Pin1 plays an important role in colorectal tumorigenesis, presumably by increasing beta-catenin and cyclin D1 expressions., (Copyright (c) 2006 Wiley-Liss, Inc.)

A 74-year-old man was admitted to our hospital because of exertional dyspnea in January 2003. He had first noticed slight exertional dypnea in 1997, which had since gradually progressed. He has been a dentist since the age of 23. Chest radiography demonstrated bilateral reticular shadows, infiltrates, and thickened pleural adhesion, which had progressed for one year and five months. Chest CT scans disclosed irregular peribronchial opacities, centrilobular nodules, and interlobular septal lines. Bronchoalveolar lavage fluid showed an increase in total cells and lymphocytosis with an increased CD 4/CD 8 ratio. Transbronchial lung biopsy demonstrated fibrosis around bronchioles, involving adjacent alveolar structures and scattered birefringent particles under polarized light. Energy-dispersive X-ray analysis (EDXA) of the small particles around the bronchioles using electron microscopy showed high peaks for silicon (Si) and aluminium (Al). Pneumoconiosis, possibly induced by some of the mechanical and technical procedures of dentistry, was diagnosed.