A case of autoimmune pulmonary alveolar proteinosis during the course of treatment of rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositis.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny. CASE PRESENTATION: A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal. CONCLUSIONS: This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.

Radiographic knee osteoarthritis severity has no impact on fall risk: the locomotive syndrome and health outcomes in the aizu cohort study (LOHAS): a cross-sectional study.

BACKGROUND: To investigate factors that have an impact on the risk of falls and determine whether radiographic knee osteoarthritis (KOA) is a factor involved in falls independent of knee pain, psychological factors, and physical function. METHODS: A cross-sectional analysis was conducted on 1083 subjects for the 2009 Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study (LOHAS). A logistic regression analysis was performed to examine the relationship between radiographic KOA and fall history. RESULTS: Fall history was significantly associated with the severity of knee pain. Compared to subjects with no knee pain, the odds ratio (OR) was 1.53 times higher in the subjects with mild knee pain (95% confidence interval [CI]: 1.04-2.25), 1.69 times higher in those with moderate knee pain (95%CI: 1.03-2.79), and 2.98 times higher in those with severe knee pain (95%CI: 1.67-5.30). In subjects with depression, the OR was 1.91 (95%CI: 1.25-2.92), and in those with decreased mobility, the OR was 1.70 (95%CI: 1.08-2.69). Age, gender, knee crepitus, BMI, OLST, and sleeping pill use were not significantly associated with fall risk. In a multivariate analysis, radiographic KOA severity was not significantly associated with fall risk (OR 0.81, 95%CI 0.44-1.50 in mild OA; OR 1.10, 95%CI 0.57-2.14 in severe OA). CONCLUSION: Knee pain, decreased mobility, and depression, but not the radiographic KOA severity, were significantly associated with a fall risk. Regardless of the individual's radiographic KOA severity, the risk of falls may be reduced by treating his/her knee pain, mobility problems, and/or psychological factors.

Contributions of Resin Cast Etching to Visualising the Osteocyte Lacuno-Canalicular Network Architecture in Bone Biology and Tissue Engineering.

Recent years have witnessed an evolution of imaging technologies towards sophisticated approaches for visualising cells within their natural environment(s) and for investigating their interactions with other cells, with adjacent anatomical structures, and with implanted biomaterials. Resin cast etching (RCE) is an uncomplicated technique involving sequential acid etching and alkali digestion of resin embedded bone to observe the osteocyte lacuno-canalicular network using scanning electron microscopy. This review summarises the applicability of RCE to bone and the bone-implant interface. Quantitative parameters such as osteocyte size, osteocyte density, and number of canaliculi per osteocyte, and qualitative metrics including osteocyte shape, disturbances in the arrangement of osteocytes and canaliculi, and physical communication between osteocytes and implant surfaces can be investigated. Ageing, osteoporosis, long-term immobilisation, spinal cord injury, osteoarthritis, irradiation, and chronic kidney disease have been shown to impact osteocyte lacuno-canalicular network morphology. In addition to titanium, calcium phosphates, and bioactive glass, observation of direct connectivity between osteocytes and cobalt chromium provides new insights into the osseointegration potential of materials conventionally viewed as non-osseointegrating. Other applications include in vivo and in vitro testing of polymer-based tissue engineering scaffolds and tissue-engineered ossicles, validation of ectopic osteochondral defect models, ex vivo organ culture of whole bones, and observing the effects of gene dysfunction/deletion on the osteocyte lacuno-canalicular network. Without additional contrast staining, any resin embedded specimen (including clinical biopsies) can be used for RCE. The multitude of applications described here attest to the versatility of RCE for routine use within correlative analytical workflows, particularly in biomaterials science.

Cell-autonomous light sensitivity via Opsin3 regulates fuel utilization in brown adipocytes.

Opsin3 (Opn3) is a transmembrane heptahelical G protein-coupled receptor (GPCR) with the potential to produce a nonvisual photoreceptive effect. Interestingly, anatomical profiling of GPCRs reveals that Opn3 mRNA is highly expressed in adipose tissue. The photosensitive functions of Opn3 in mammals are poorly understood, and whether Opn3 has a role in fat is entirely unknown. In this study, we found that Opn3-knockout (Opn3-KO) mice were prone to diet-induced obesity and insulin resistance. At the cellular level, Opn3-KO brown adipocytes cultured in darkness had decreased glucose uptake and lower nutrient-induced mitochondrial respiration than wild-type (WT) cells. Light exposure promoted mitochondrial activity and glucose uptake in WT adipocytes but not in Opn3-KO cells. Brown adipocytes carrying a defective mutation in Opn3's putative G protein-binding domain also exhibited a reduction in glucose uptake and mitochondrial respiration in darkness. Using RNA-sequencing, we identified several novel light-sensitive and Opn3-dependent molecular signatures in brown adipocytes. Importantly, direct exposure of brown adipose tissue (BAT) to light in living mice significantly enhanced thermogenic capacity of BAT, and this effect was diminished in Opn3-KO animals. These results uncover a previously unrecognized cell-autonomous, light-sensing mechanism in brown adipocytes via Opn3-GPCR signaling that can regulate fuel metabolism and mitochondrial respiration. Our work also provides a molecular basis for developing light-based treatments for obesity and its related metabolic disorders.

Sustained antitumor response to lenvatinib with weekend-off and alternate-day administration in chemotherapy-refractory thymic carcinoma: a case report.

Lenvatinib is a multitargeted kinase inhibitor and maintaining its dose intensity has been shown to be beneficial in patients with thyroid and hepatocellular carcinomas. However, most patients require lenvatinib interruption and dose reduction due to the high incidence of adverse events (AEs). Lenvatinib was recently approved in Japan for patients with unresectable thymic carcinoma; however, real-world evidence of its clinical benefit is limited. Here, we report the case of chemotherapy-refractory thymic carcinoma in a patient who was administered a starting dose of lenvatinib using a 5-day on/2-day off (weekend-off) protocol, followed by alternate-day administration after fatigue onset derived from overt or subclinical hypothyroidism. Consequently, the patient exhibited a durable response to lenvatinib, with a 17-month progression-free survival without any severe or intolerable AEs. The present case suggests that maintaining lenvatinib dose intensity using such alternative administration regimens contributes to favorable clinical outcomes in thymic carcinoma.

Gender differences on preoperative psychologic factors affecting acute postoperative pain in patients with lumbar spinal disorders.

BACKGROUND: Psychosexual factors are one of the preoperative factors influencing acute postoperative pain. Because of gender differences in pain, the preoperative factors that influence acute postoperative pain may also differ between males and females. However, there have been no reports on such factors in patients with spinal disorders that focused on gender differences. Therefore, the purpose of this study was to examine the preoperative factors that influence acute postoperative pain, focusing on gender differences. METHODS: The subjects were 75 males and 60 females admitted for surgery for lumbar spinal disorders. Preoperatively, the following were assessed: low back pain using the Numeric Rating Scale (NRS); anxiety and depression using the Japanese version of the Hospital Anxiety and Depression Scale (HADS); catastrophic thinking using the Pain Catastrophizing Scale (PCS); psychiatric problems using the Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP); and neurological assessments. Acute postoperative pain was also assessed using the NRS within 48 h, postoperatively. Based on these data, we analyzed gender differences in preoperative factors affecting acute postoperative pain in patients with lumbar spinal disorders. RESULTS: Postoperative NRS and preoperative PCS scores were higher in females compared to males. In the males, the coefficient of determination of the multiple regression equation was 0.088, and PCS (ß = 0.323, p = 0.015) was extracted as a significant factor. In the females, the coefficient of determination of the multiple regression equation was 0.075, and BS-POP (ß = 0.300, p = 0.019) was extracted as a significant factor. CONCLUSION: Preoperative factors influencing acute postoperative pain for patients with lumbar spinal disorders vary by gender. It was suggested that males should be screened using PCS. In females, on the other hand, PCS alone is not sufficient for evaluation. It was suggested that evaluation using BS-POP should be considered in addition to PCS.

Vitamin D receptor-mediated skewed differentiation of macrophages initiates myelofibrosis and subsequent osteosclerosis.

Myelofibrosis in myeloproliferative neoplasms (MPNs) with mutations such as JAK2V617F is an unfavorable sign for uncontrollable disease progression in the clinic and is complicated with osteosclerosis whose pathogenesis is largely unknown. Because several studies have revealed that macrophages are an indispensable supporter for bone-forming osteoblasts, we speculated that macrophages might play a significant role in the proliferation of collagen-producing myofibroblasts in marrow fibrotic tissues. Here, we show that myelofibrosis critically depends on macrophages whose differentiation is skewed by vitamin D receptor (VDR) signaling. In our novel myelofibrosis model established by transplantation of VDR+/+ hematopoietic stem/progenitor cells into VDR-/- mice, donor-derived F4/80+ macrophages proliferated together with recipient-derived α-smooth muscle actin-positive myofibroblasts, both of which comprised fibrotic tissues with an indistinguishable spindle-shaped morphology. Interfering VDR signals, such as low vitamin D diet and VDR deficiency in donor cells as well as macrophage depletion prevented myelofibrosis in this model. These interventions also ameliorated myelofibrosis in JAK2V617F-driven murine MPNs likely in a transforming growth factor-ß1- or megakaryocyte-independent manner. These results suggest that VDR and macrophages may be novel therapeutic targets for MPNs with myelofibrosis.

Biofilm formation of Staphylococcus epidermidis imaged using atmospheric scanning electron microscopy.

Staphylococcus epidermidis are gram-positive bacteria that form a biofilm around implanted devices and develop an infection into a chronic state. Recently, it has been revealed that microvesicles have important roles in biofilm formation and intercellular communication among bacteria. However, biofilm formation of Staphylococcus epidermidis, and its relation to microvesicle secretion, is poorly understood because of the difficulty required to preserve the delicate water-rich morphology of biofilm for high-resolution observations. Here, we successfully imaged the microvesicles secreted from Staphylococcus epidermidis and the subsequent process of their integration into biofilm using liquid-phase imaging using atmospheric scanning electron microscopy (ASEM). In the biofilm, cells were connected by nanotube-like structures attached by microvesicles, and surrounded by extracellular polymeric substances. Cells cultured in the ASEM specimen holder were aldehyde-fixed and stained using positively charged nanogold labelling and/or using National Center for Microscopy and Imaging Research method. The samples immersed in aqueous radical scavenger glucose buffer were imaged by the inverted SEM of ASEM. Information regarding the morphologies of microvesicles, nanotube-like fibrils, and biofilm formed by Staphylococcus epidermidis is expected to be useful to elucidate the biological mechanism of biofilm formation and to develop a medicine against biofilms and their associated infections.

Prediction of oral intake recovery for inpatients with aspiration pneumonia by videoendoscopic evaluation using the Hyodo-Komagane score in Japan.

OBJECTIVE: To verify the validity of the prediction of oral intake recovery for inpatients with aspiration pneumonia using the Hyodo-Komagane score. BACKGROUND: Patients admitted for treatment of aspiration pneumonia sometimes have difficulty in resuming oral intake due to decreased swallowing function. Predicting whether the swallowing function will recover enough to achieve oral ingestion at discharge is an important factor in developing a treatment strategy. No studies have investigated the prediction of oral intake recovery using videoendoscopic examination. METHODS: Subjects were 65 patients who were admitted to an acute care hospital for the treatment of aspiration pneumonia. The patients were divided into two groups, the oral feeding group and the tube feeding group, according to their oral intake status at discharge or transfer. Logistic regression analysis was performed using the condition that tube feeding was not required as an objective variable and the items with significant differences between the two groups as explanatory variables. Additionally, the receiver operating characteristic curve was used to identify patients who could take food orally at discharge. RESULTS: The odds ratios for the Hyodo-Komagane score and the pharyngeal clearance score were 1.485 and 3.379, respectively. When the cut-off values of the Hyodo-Komagane score and the pharyngeal clearance score were 6 and 1, the sensitivity was 0.88 and 0.91, and the specificity was 0.64 and 0.70, respectively. CONCLUSION: The Hyodo-Komagane score and especially the pharyngeal clearance score are useful indices to predict oral intake recovery for inpatients with aspiration pneumonia.

Biofilm Spreading by the Adhesin-Dependent Gliding Motility of Flavobacterium johnsoniae: 2. Role of Filamentous Extracellular Network and Cell-to-Cell Connections at the Biofilm Surface.

Flavobacterium johnsoniae forms a thin spreading colony on nutrient-poor agar using gliding motility. As reported in the first paper, WT cells in the colony were sparsely embedded in self-produced extracellular polymeric matrix (EPM), while sprB cells were densely packed in immature biofilm with less matrix. The colony surface is critical for antibiotic resistance and cell survival. We have now developed the Grid Stamp-Peel method whereby the colony surface is attached to a TEM grid for negative-staining microscopy. The images showed that the top of the spreading convex WT colonies was covered by EPM with few interspersed cells. Cells exposed near the colony edge made head-to-tail and/or side-to-side contact and sometimes connected via thin filaments. Nonspreading sprB and gldG and gldK colonies had a more uniform upper surface covered by different EPMs including vesicles and filaments. The EPM of sprB, gldG, and WT colonies contained filaments ~2 nm and ~5 nm in diameter; gldK colonies did not include the latter. Every cell near the edge of WT colonies had one or two dark spots, while cells inside WT colonies and cells in SprB-, GldG-, or GldK-deficient colonies did not. Together, our results suggest that the colony surface structure depends on the capability to expand biofilm.

Biofilm Spreading by the Adhesin-Dependent Gliding Motility of Flavobacterium johnsoniae. 1. Internal Structure of the Biofilm.

The Gram-negative bacterium Flavobacterium johnsoniae employs gliding motility to move rapidly over solid surfaces. Gliding involves the movement of the adhesin SprB along the cell surface. F. johnsoniae spreads on nutrient-poor 1% agar-PY2, forming a thin film-like colony. We used electron microscopy and time-lapse fluorescence microscopy to investigate the structure of colonies formed by wild-type (WT) F. johnsoniae and by the sprB mutant (ΔsprB). In both cases, the bacteria were buried in the extracellular polymeric matrix (EPM) covering the top of the colony. In the spreading WT colonies, the EPM included a thick fiber framework and vesicles, revealing the formation of a biofilm, which is probably required for the spreading movement. Specific paths that were followed by bacterial clusters were observed at the leading edge of colonies, and abundant vesicle secretion and subsequent matrix formation were suggested. EPM-free channels were formed in upward biofilm protrusions, probably for cell migration. In the nonspreading ΔsprB colonies, cells were tightly packed in layers and the intercellular space was occupied by less matrix, indicating immature biofilm. This result suggests that SprB is not necessary for biofilm formation. We conclude that F. johnsoniae cells use gliding motility to spread and maturate biofilms.

The role of PI3K/Akt/mTOR signaling in dose-dependent biphasic effects of glycine on vascular development.

Glycine, a non-essential amino acid, exerts concentration-dependent biphasic effects on angiogenesis. Low-doses of glycine promote angiogenesis, whereas high-doses cause anti-angiogenesis. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling participates in angiogenesis of both physiological development, and pathological events including tumor and inflammation. We assessed the role of PI3K/Akt/mTOR signaling in vascular development, and the interaction with glycine, using transgenic zebrafish Tg(fli1a:Myr-mCherry)ncv1 embryos expressing fluorescent proteins in vascular endothelial cells. Treatment with inhibitors of mTORC1 (rapamycin and everolimus), mTORC1/mTORC2 (KU0063794), PI3K (LY29400), and Akt (Akt inhibitor) decreased the development of intersegmental vessels (ISVs). These inhibitors cancelled the angiogenic effects of a low-dose of glycine, while acted synergistically with a high-dose of glycine in anti-angiogenesis. mTOR signaling regulates the gene expression of vascular endothelial growth factor (VEGF), a major angiogenic factor, and nitric oxide (NO) synthase (NOS), an enzyme for the synthesis of an angiogenic mediator NO. Expressions of VEGF and NOS were consistent with the vascular features induced by glycine and an mTOR inhibitor. Our results suggest that PI3K/Akt/mTOR signaling may interact with dose-dependent biphasic effects of exogenous glycine on in vivo angiogenesis. mTOR signaling is a key target for cancer therapy, thus, the combining mTOR inhibitors with glycine may be a potential approach for controlling angiogenesis.

Glycine exerts dose-dependent biphasic effects on vascular development of zebrafish embryos.

Glycine, a non-essential amino acid, is involved in both angiogenesis and anti-angiogenesis. We hypothesized that glycine would exert dose-dependent different effects on angiogenesis. In this study, we investigated the effects of a broad range of concentrations of glycine on vascular development using transgenic zebrafish Tg(fli1a:Myr-mCherry)ncv1 embryos. Effects of glycine transporter (GlyT) inhibitors (sarcosine and bitopertin) and a glycine receptor (GlyR) inhibitor (strychnine) were also examined in embryos in the absence or presence of glycine. After exposure to glycine and inhibitors, intersegmental vessels (ISVs) were observed by fluorescent microscopy. Low concentrations of glycine promoted the development of ISVs, whereas high concentrations reduced it. These effects of glycine could generally be reversed by treatment with GlyT and GlyR inhibitors. Furthermore, expressions of vascular endothelial growth factor (VEGF) (an angiogenic factor) and nitric oxide synthase (NOS) (an enzyme for nitric oxide synthesis) were associated with the dose-dependent effects of glycine. Our results suggest that glycine exerts dose-dependent biphasic effects on vascular development, which rely on GlyTs and GlyRs, and correlate with the expression of VEGF and NOS genes. At low concentrations, glycine acted as an angiogenic factor. In contrast, at high concentrations, glycine induced anti-angiogenesis. This evidence provides a novel insight into glycine as a unique target in angiogenic and anti-angiogenic therapy.

Network of Palladium-Based Nanorings Synthesized by Liquid-Phase Reduction Using DMSO-H2O: In Situ Monitoring of Structure Formation and Drying Deformation by ASEM.

We developed a liquid-phase synthesis method for Pd-based nanostructure, in which Pd dissolved in dimethyl sulfoxide (DMSO) solutions was precipitated using acid aqueous solution. In the development of the method, in situ monitoring using atmospheric scanning electron microscopy (ASEM) revealed that three-dimensional (3D) Pd-based nanonetworks were deformed to micrometer-size particles possibly by the surface tension of the solutions during the drying process. To avoid surface tension, critical point drying was employed to dry the Pd-based precipitates. By combining ASEM monitoring with critical point drying, the synthesis parameters were optimized, resulting in the formation of lacelike delicate nanonetworks using citric acid aqueous solutions. Precipitation using HCl acid aqueous solutions allowed formation of 500-nm diameter nanorings connected by nanowires. The 3D nanostructure formation was controllable and modifiable into various shapes using different concentrations of the Pd and Cl ions as the parameters.

G-CSF-induced sympathetic tone provokes fever and primes antimobilizing functions of neutrophils via PGE2.

Granulocyte colony-stimulating factor (G-CSF) is widely used for peripheral blood stem/progenitor mobilization. G-CSF causes low-grade fever that is ameliorated by nonsteroidal anti-inflammatory drugs (NSAIDs), suggesting the activation of arachidonic acid (AA) cascade. How G-CSF regulated this reaction was assessed. G-CSF treatment in mice resulted in fever, which was canceled in prostaglandin E synthase (mPGES-1)-deficient mice. Mobilization efficiency was twice as high in chimeric mice lacking mPGES-1, specifically in hematopoietic cells, suggesting that prostaglandin E2 (PGE2) from hematopoietic cells modulated the bone marrow (BM) microenvironment. Neutrophils from steady-state BM constitutively expressed mPGES-1 and significantly enhanced PGE2 production in vitro by ß-adrenergic stimulation, but not by G-CSF, which was inhibited by an NSAID. Although neutrophils expressed all ß-adrenergic receptors, only ß3-agonist induced this phenomenon. Liquid chromatography-tandem mass spectrometry traced ß-agonist-induced PGE2 synthesis from exogenous deuterium-labeled AA. Spontaneous PGE2 production was highly efficient in Gr-1high neutrophils among BM cells from G-CSF-treated mice. In addition to these in vitro data, the in vivo depletion of Gr-1high neutrophils disrupted G-CSF-induced fever. Furthermore, sympathetic denervation eliminated both neutrophil priming for PGE2 production and fever during G-CSF treatment. Thus, sympathetic tone-primed BM neutrophils were identified as one of the major PGE2 producers. PGE2 upregulated osteopontin, specifically in preosteoblasts, to retain progenitors in the BM via EP4 receptor. Thus, the sympathetic nervous system regulated neutrophils as an indispensable PGE2 source to modulate BM microenvironment and body temperature. This study provided a novel mechanistic insight into the communication of the nervous system, BM niche components, and hematopoietic cells.

Verification of 5-Aminolevurinic Radiodynamic Therapy Using a Murine Melanoma Brain Metastasis Model.

Melanoma is a highly aggressive cancer with a propensity for brain metastases. These can be treated by radiotherapy, but the radiation-resistant nature of melanoma makes the prognosis for melanoma patients with brain metastases poor. Previously, we demonstrated that treatment of mice with subcutaneous melanoma with 5-aminolevurinic acid (5-ALA) and X-rays in combination, ("radiodynamic therapy (RDT)"), instead of with 5-ALA and laser beams ("photodynamic therapy"), improved tumor suppression in vivo. Here, using the B16-Luc melanoma brain metastasis model, we demonstrate that 5-ALA RDT effectively treats brain metastasis. We also studied how 5-ALA RDT damages cells in vitro using a B16 melanoma culture. Cell culture preincubated with 5-ALA alone increased intracellular photosensitizer protoporphyrin IX. On X-ray irradiation, the cells enhanced their ∙OH radical generation, which subsequently induced γH2AX, a marker of DNA double-strand breaks in their nuclei, but decreased mitochondrial membrane potential. After two days, the cell cycle was arrested. When 5-ALA RDT was applied to the brain melanoma metastasis model in vivo, suppression of tumor growth was indicated. Therapeutic efficacy in melanoma treatment has recently been improved by molecular targeted drugs and immune checkpoint inhibitors. Treatment with these drugs is now expected to be combined with 5-ALA RDT to further improve therapeutic efficacy.

Positive Emotion and its Changes during Pregnancy: Adjunct Study of Japan Environment and Children's Study in Miyagi Prefecture.

During pregnancy, women experience various emotional changes. Previous research has investigated positive emotion influenced childbirth outcomes positively. This study explored the extent of positive emotion which pregnant women aware of their own pregnancy life subjectively and variables related to the changes thereof. This was an adjunct study of the Japan Environment and Children's Study which is a nationwide epidemiological study to identify the impact of environmental factors on health and development of children in Miyagi Prefecture. Data were collected at 12 weeks (T1) and 24-28 weeks (T2) of gestation. Participants were 3,513 pregnant women. Women's degree of positive emotion was assessed through a numeric rating scale. We also measured related variables, including obstetric factors, physical health status, mental health status, and social situation, using the 8-Item Short Form Health Survey, Kessler-6, and family APGAR score, along with demographic data. Analyses included correlations among variables related to the change in positive emotion. The extent of positive emotion was significantly related with health-related quality of life and satisfaction with family relationships during pregnancy. The women whose positive emotion decreased from T1 to T2 tended to have lower morning sickness symptoms, be unemployed, lower physical and mental health status, and a higher risk of psychological distress in middle pregnancy. Importantly, even discomfort like morning sickness, physical symptoms that indicate being pregnant, might make women to confirm pregnancy. Moreover, employment and satisfaction with family relationships are especially crucial for pregnant women to spend comfortable maternity life.

Analysis of Streptococcus pneumoniae and Haemophilus influenzae isolated from middle ear fluid before and after the introduction of government subsidies for pneumococcal and H. influenzae type b vaccines in Japan.

This study aimed to identify trends in frequency, serotype, and antimicrobial susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolated from middle ear fluid specimens of children aged≤15 years (mean, 2 years), before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and the H. influenzae type b vaccine, at a pediatric facility in Japan. Sixty-six S. pneumoniae and 88 H. influenzae strains were isolated from 820 middle ear fluid samples. Serotyping and antimicrobial susceptibility testing were performed. The study time-frame was divided into period 1 (2007-2010) and period 2 (2011-2014), according to the availability of vaccine public funding. The S. pneumoniae detection rate decreased from 9.6% in period 1-6.1% in period 2 (p = 0.042). PCV7 serotypes decreased from 56.8% to 9.1% (p = 0.0002). No significant change was observed for the 13-valent pneumococcal conjugate vaccine (PCV13) serotypes: 72.7% in period 1 and 59.1% in period 2. Penicillin-resistant strains (penicillin G-MIC ≥2 µg/mL) decreased from 25% to 4.5% (p = 0.038). Detection rates for H. influenzae did not change significantly: 10.3% in period 1 and 11.3% in period 2. Serotypes were mostly non-typeable: 97.9% in period 1 and 90.2% in period 2, and only one serotype b strain was isolated in each period. The frequency of ampicillin-resistant strains (MIC ≥4 µg/mL) did not change. These results show a preventative effect of PCV7 on otitis media due to S. pneumoniae. PCV7 was replaced with PCV13 in 2013 in Japan; therefore, a further decrease in pneumococcal otitis media is anticipated in the future.

Influence of living environment and subjective economic hardship on new-onset of low back pain for survivors of the Great East Japan Earthquake.

BACKGROUND: The Great East Japan Earthquake and subsequent tsunami devastated the northeastern part of Japan. Low back pain is thought to increase after a natural disaster and is related to various factors. The aim of this study was to examine the influencing factors of "Living environment" and "Subjective economic hardship" on new-onset of low back pain in the chronic phase for the survivors of the earthquake evaluated by a self-report questionnaire. METHODS: A panel study was conducted with the Great East Japan Earthquake survivors at 2 and 3 years after the disaster. New-onset of low back pain was defined as low back pain absent at the 1st period (2 years after the earthquake) and present at the 2nd period (3 years after the earthquake). Living environment was divided into 4 categories (1. Living in the same house as before the earthquake, 2. Living in a prefabricated house, 3. Living in a new house, 4. Others: Living in an apartment, house of relatives or acquaintance). Subjective economic hardship was obtained using the following self-report question: "How do you feel about the current economic situation of your household?" The response alternatives were "Normal", "A little bit hard", "Hard", and "Very hard". A univariate and multivariate logistic regression models were used. RESULTS: 1357 survivors consented to join this study. There was no significant association between new-onset of low back pain and living environment. There was significant association between new-onset of low back pain and "A little hard" (OR = 1.6, 95% CI = 1.07-2.40), "Hard" (OR = 2.2, 95% CI = 1.56-3.74), and "Very hard" (OR = 3.19, 95% CI = 1.84-5.53) in subjective economic hardship. CONCLUSIONS: Subjective economic hardship was significantly associated with new-onset of low back pain in the chronic phase for survivors of the Great East Japan Earthquake.

Posttranscriptional modulation of cytokine production in T cells for the regulation of excessive inflammation by TFL.

Posttranscriptional machinery regulates inflammation and is associated with autoimmunity as well as tumorigenesis in collaboration with transcription factors. We previously identified the tumor suppressor gene transformed follicular lymphoma (TFL) on 6q25 in a patient with follicular lymphoma, which transformed into diffuse large B cell lymphoma. TFL families have a common RNase domain that governs macrophage-mediated inflammation. In human peripheral blood, TFL is dominantly expressed at the glycine- and tryptophan-rich cytoplasmic processing bodies of T lymphocytes, and it is persistently upregulated in activated T cells. To address its physiological role, we established TFL(-/-) mice in which TFL(-/-) lymphocytes proliferated more rapidly than TFL(+/+) upon stimulation with inappropriate cytokine secretion, including IL-2, IL-6, and IL-10. Moreover, TFL inhibited the synthesis of cytokines such as IL-2, IL-6, IL-10, TNF-α, and IL-17a by 3' untranslated region RNA degradation. Experimental autoimmune encephalitis induced in TFL(-/-) mice demonstrated persistent severe paralysis. CNS-infiltrated CD4(+) T cells in TFL(-/-) mice contained a higher proportion of Th17 cells than did those in TFL(+/+) mice during the resolution phase, and IL-17a mRNA levels were markedly increased in TFL(-/-) cells. These results suggest that TFL may play an important role in attenuating local inflammation by suppressing the infiltration of Th17 cells in the CNS during the resolution phase of experimental autoimmune encephalitis. TFL is a novel gradual and persistent posttranscriptional regulator, and the TFL-driven attenuation of excessive inflammation could contribute to recovery from T cell-mediated autoimmune diseases.