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As the demand for highly efficient yet aesthetically pleasing, complex building envelope structures is rising worldwide, computational analysis and generative design tools are becoming ever so relevant. Previous methods for achieving a natural distribution of structural or shading elements in non-uniform façades are mostly based either on computer-generated pseudo-randomness or a literal biomorphic approach where a naturally occurring pattern is directly projected on the façade surface. As an alternative, this research introduces a novel technique for optimisation that utilises a two-dimensional Power Spectrum Analysis, suitable for numerically assessing the alignment of designed geometry with natural patterns. By integrating this optimisation method into the design process, the façade pattern generation can be automated and optimal design can be selected by evaluating multiple design solutions. Instead of using repetitive geometrical patterns or generated pseudo-randomness, patterns objectively similar to those occurring in nature can be created without directly copying natural structures. The distribution of the structural and shading elements controls the way natural light permeates the building and, considering the data gathered from images of natural scenes, this method can be used to design structures not only with optimal structural and energy performance but also with visual and psychological occupant comfort in mind.

BackgroundDrug-induced lung disease (DILD) is a considerable and potentially fatal adverse event with poorly understood risk factors. Large-scale, data-driven analyses investigating regional discrepancies in DILD incidence are lacking. The aim of this study was to investigate the potential association among DILD prevalence, regional differences and other factors based on large-scale data base.MethodsThis retrospective observational study analyzed spontaneous adverse event reports from the FDA Adverse Event Reporting System (FAERS) database between January 2010 and December 2020. Regional disparities in DILD incidence were assessed among reports from the United States of America (USA), the European Union (EU), and Japan (JP). Using multivariate logistic regression accounting for age, sex, and reporting years, we calculated the reporting odds ratios (RORs) with 95% confidence intervals. Subgroup analyses were performed for different types of anticancer agents, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), and cytotoxic agents.ResultsRegional differences in RORs were observed for anticancer drugs in reports from JP and the EU compared with those from the USA (JP, ROR 4.432; EU, ROR 1.291) and for non-anticancer drugs (JP, ROR 3.481; EU, ROR 1.086). Significantly higher RORs were observed for all anticancer drug regimens reported in JP than in the USA (TKIs, ROR 3.274; ICIs, ROR 2.170; ADCs, ROR 2.335; cytotoxic agents, ROR 3.989). The EU reports exhibited higher RORs for TKIs and cytotoxic agents than the USA reports, with no significant differences in ICIs or ADCs (TKIs, ROR 1.679; ICIs, ROR 1.041; ADCs, ROR 1.046; cytotoxic agents, ROR 1.418).ConclusionThe prevalence of DILD in JP, the EU, and the USA differed. These findings have important implications in evaluating the safety profiles of drugs and patient safety in drug development and clinical practice. This study is the first to identify regional differences in DILDs using a large global database.

Abstract Background The activity level of alkaline phosphatase, a zinc-requiring enzyme in the serum, is used to indicate zinc nutritional status; however, it does not correlate with serum zinc levels or subjective symptoms of taste disorder in many cases. Hence, this study focused on the total activity of alkaline phosphatase, a zinc-requiring enzyme. The total alkaline phosphatasa activity level in the saliva was measured before and after zinc supplementation, and the results were compared with serum zinc levels. Case presentation This study included patients with hypozincemia, specifically a patient with zinc-deficient taste disorder (patient 1: a 69-year-old Japanese woman) and a patient with glossodynia with zinc deficiency (patient 2: an 82-year-old Japanese woman). Saliva samples were collected, and blood tests were performed before and after zinc supplementation. Subjective symptoms and serum zinc levels were simultaneously evaluated. Zinc supplementation was performed using zinc acetate hydrate or Polaprezinc. Conclusions Total alkaline phosphatase activity levels were found to be associated with serum zinc levels and subjective symptoms. A further study with a higher number of patients is necessary to confirm whether total alkaline phosphatase activity levels more accurately reflect the amounts of zinc in the body than serum zinc levels.

Abstract Background The long time required for bone uptake of radiopharmaceutical material after injection for bone scintigraphy is a burden for patients with poor health. Thus, to assess whether the uptake time could be reduced for single-photon emission computed tomography (SPECT) of the jawbone, this study evaluated differences in maximum standardized uptake values (SUVmax) within patients using SPECT imaging at 2 and 3 hours after radiopharmaceutical injection. Methods A total of 33 patients undergoing treatment or in post-treatment follow-up for medication-related osteonecrosis of the jaw, who visited our hospital between July 2020 and August 2021 and could receive SPECT twice on the same day, were enrolled in the study. Patients were injected with technetium-99 m hydroxymethylene diphosphonate (Tc-99 m HMDP) intravenously. The SUVmax for healthy parietal bones and jawbone lesions were calculated from the SPECT images using quantitative analysis software, and the SUVmax were compared between 2- and 3-hour uptake times. Results After exclusion, 30 patients were included in the study. In the 2-hour and 3-hour images, the median SUVmax of the parietal bones were 1.90 and 1.81, respectively, and those of the jawbone lesions were 9.25 and 9.39, respectively. The limits of agreement (LOA) ranged from − 0.33 to 0.25 in the parietal bones, and the %LOA ranged from − 9.8 to 17.3% in the jawbone lesions, showing high equivalence between the two uptake durations. The SUVmax showed no clinical differences between the 2- and 3-hour uptake durations for Tc-99 m HMDP SPECT of the jawbone. Conclusions The results of this study justify a 2–3-hour uptake window when performing quantitative SPECT of the jawbone. Therefore, the minimum uptake time can potentially be reduced to only 2 hours.

Background: Patients with circulatory failure have high mortality rates and require prompt assessment of microcirculation. Despite the improvement in hemodynamic parameters, microcirculatory dysfunction persists. We measured subcutaneous regional tissue oxygen saturation (rSO2) with near-infrared spectroscopy (NIRS), which can assess microcirculation in patients with circulatory failure. Methods: A finger-worn oximeter with NIRS measured rSO2 in the forehead, thenar eminence, thumb, and knees. First, the rSO2 was measured in healthy adult volunteers (n = 10). Circulatory failure was defined as a systolic blood pressure ≤ 90 mmHg and lactate ≥ 2 mmol/L. The study included 35 patients without circulatory failure and SOFA score of 0 at ICU admission and 38 patients with circulatory failure at ICU admission. Both groups included a single-center prospective study of patients who were transported to the ICU of the Nihon University Hospital. The rSO2 was measured only on ICU admission in the non-circulatory failure group and later in the circulatory failure group. Results: In the volunteer group, rSO2 at each site was approximately 58%. The rSO2 was significantly lower in the circulatory failure group than in the non-circulatory failure group (knee, p < 0.01). In the circulatory failure group, knee rSO2 showed a significant negative correlation with SOFA score (Day 0, ρ = −0.37, p = 0.02; Day 1, ρ = −0.53, p < 0.01; Day 2, ρ = −0.60, p < 0.01). Conclusions: Subcutaneous knee rSO2 was associated with SOFA score and was considered an indicator of microcirculatory dysfunction and organ damage.

Background/purpose: Delayed healing of the extraction socket is not uncommon when tooth extraction is performed on patients taking prednisolone. This study aimed to identify specific dosage of prednisolone and factors associated with delayed healing of the extraction socket in patients taking prednisolone. Materials and methods: This single-center retrospective study included 80 patients who underwent tooth extraction under local anesthesia and were taking prednisolone orally. Patients were divided into the nondelayed healing group (n = 50) and delayed healing group (n = 30), and their background and dosage of prednisolone were compared. Results: The dosage of prednisolone was significantly higher in the delayed healing group than in the nondelayed healing group. A receiver operating characteristics curve analysis resulted in moderate accuracy when the cutoff value was set at 8.0, with 67% sensitivity, 76% specificity, and 0.765 area under the curve. The multivariate logistic regression analysis revealed that prednisolone dosage >8.0 mg/day (odds ratio [OR], 10.8; 95% confidence interval [CI], 2.79–41.6) and osteosclerotic changes beyond the alveolar bone around the tooth to be extracted (OR, 10.3; 95% CI, 2.81–37.8) in X-ray imaging had significant effects on delayed healing. Conclusion: The results of this study suggested that delayed healing following tooth extractions in patients taking prednisolone was related to a dosage of 8.0 mg/day or higher and osteosclerotic changes.

The asymmetric simple exclusion process (ASEP) is a paradigmatic nonequilibrium many-body system that describes the asymmetric random walk of particles with exclusion interactions in a lattice. Although the ASEP is recognized as an exactly solvable model, most of the exact results obtained so far are limited to one-dimensional systems. Here, we construct the exact steady states of the ASEP with closed and periodic boundary conditions in arbitrary dimensions. This is achieved through the concept of transition decomposition, which enables the treatment of the multidimensional ASEP as a composite of the one-dimensional ASEPs.

Abstract Background Reactive thrombocytosis occurs secondary to systemic infections, inflammatory, and other conditions. The relationship between thrombocytosis and acute pancreatitis (AP) in inflammatory diseases is uncertain. This study aimed to evaluate the clinical significance of thrombocytosis in AP patients during hospitalization. Methods Subjects within 48 h of AP onset were consecutively enrolled over 6 years. Platelet counts of ≥ 450,000/µL were defined as thrombocytosis,

Burning mouth syndrome (BMS) is a chronic oral pain disorder. There is a theory that BMS is a form of nociplastic pain. A standard treatment for BMS has not yet been established. Kampo medicine is a traditional oriental medicine. The purpose of this study is to evaluate the effectiveness of Rikkosan—a traditional Japanese herbal medicine (Kampo)—in the treatment of BMS. A single-center retrospective study was conducted on 20 patients who were diagnosed with BMS and treated with Rikkosan alone (total daily dose; 7.5 g) three times daily for approximately 4 weeks (29.5 ± 6.5 days). Rikkosan was dissolved in hot water and taken internally. They had an average age of 63 years, and 90% were being treated for other illnesses, but their medication status was the same during this study period, except for Rikkosan. No adverse events were observed in patients. Numerical rating scale (NRS) or visual analog scale (VAS)/10 scores decreased significantly between the time of the initiation of Rikkosan and one month after (−2.1 ± 1.2, p < 0.05). Rikkosan has a short-term effect of reducing NRS by two levels in BMS patients.

Abstract Background Risk management in the post-marketing phase is crucial to minimize health problems caused by drugs. Because ethnic factors may affect drug safety, the objective of this study was to explore concrete approaches to reflecting ethnic factors in risk management under multi-regional drug development. Methods We assessed Pharmaceuticals and Medical Devices Agency (PMDA) review reports on antineoplastic drugs approved as new molecular entities in the last 10 years to identify any differences in the incidence of adverse drug reactions (ADRs) related to myelosuppression, hepatic impairment, renal impairment, and interstitial lung disease between Japanese and non-Japanese populations. In addition, we investigated how those ADRs were handled in the labeling of each drug. Results In total, 44 drugs were available for comparing the incidence of ADRs between Japanese and non-Japanese populations. Of these, 32 drugs had a higher incidence of ADRs in the Japanese population. However, the incidence of ADRs in the Japanese population was described in the labeling for 7 drugs, and only the incidence in the overall population in multi-regional phase III trials was described in the labeling for the remaining 25 drugs. Of these 25 drugs, two drugs were immediately placed under emergency safety control measures after approval because of the high incidence of ADRs in Japanese patients. Conclusions For drugs that might cause serious ADRs and with a higher incidence in the Japanese population, information should be provided on the incidence in the Japanese population as well as in the overall population.

Abstract Background Ethyl loflazepate (EL) is a benzodiazepine derivative that has been reported to activate the gustatory cortex. Our department routinely uses EL as a first-line treatment for idiopathic and psychogenic taste disorders, although little has been reported in the literature with respect to patient outcomes, so we conducted a retrospective study examining its safety and efficacy. Methods Between 2008 and 2020, 49 patients (14 males and 35 females; mean age, 62.1 years) were diagnosed with taste disorders and received EL as their only treatment for > 14 days. Severity of taste disorder was evaluated using the paper disc method by Sakai et al., and treatment efficacy was evaluated using the Visual Analog Scale, wherein patients gave subjective ratings for their symptoms (reductions by > 50% after administration of EL for 4 weeks were defined as improvements). Results Results showed that the improvement rates for patients with idiopathic and psychogenic taste disorders were 55 and 70%, respectively. Additionally, the majority (78%) improved within 2 weeks, and side effects were mild (seven cases with drowsiness and one case with dizziness). Conclusions We conclude that EL is an appropriate first-line medication for patients with idiopathic and psychogenic taste disorders.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. Many patients with COPD experience exacerbations that require hospitalization, which is associated with an increased risk of in-hospital death and impaired ability to perform activities of daily living (ADL). Declining ability to perform ADL is a critical issue for these patients. Objectives: To identify predictors of poor clinical outcomes, including in-hospital death and low ability to perform ADL at discharge, in patients who are hospitalized with exacerbation of COPD. Design: This retrospective study involved a cohort of patients with exacerbation of COPD who were admitted to Iwata City Hospital in Japan between July 2015 and October 2019. Methods: We collected clinical data, measured the cross-sectional area of the erector spinae muscles (ESM CSA ) on computed tomography (CT) scans at admission, and investigated the associations of poor clinical outcomes (in-hospital death and severe dependence when performing ADL, defined as a Barthel Index (BI) of ⩽40 at discharge) with clinical parameters. Results: Overall, 207 patients were hospitalized for exacerbation of COPD during the study period. The incidence of poor clinical outcomes was 21.3%, and the in-hospital mortality rate was 6.3%. Multivariate logistic regression analyses showed that older age, long-term oxygen therapy, an elevated D-dimer concentration, and a reduced ESM CSA on chest CT at admission were significantly associated with poor clinical outcomes (in-hospital death and a BI of ⩽40). Conclusion: Hospitalization for exacerbation of COPD was associated with high rates of in-hospital mortality and a BI of ⩽40 at discharge, which may be predicted by assessment of ESM CSA .

Abstract Background Basal cell carcinoma (BCC) is the most common cancer worldwide. Most of BCCs can be detected in the early stages and are generally well controlled with local resection. Despite the high incidence of BCC, metastasis is rarely observed. Metastatic BCCs generally have an aggressive phenotype and are refractory to conventional treatment. Case presentation We describe a rare case of BCC in which a series of local relapses culminated in metastasis into the oral cavity 10 years after the first diagnosis of cutaneous BCC. We performed surgical resection and postoperative radiotherapy in this patient; 11 months after the final course of radiotherapy, the BCC remains stable, and the patient continues to be monitored regularly. Conclusions Because metastatic BCC is refractory to current treatment and difficult to control, his treatment history and the pathohistological features of BCC had to be considered in posttreatment planning.

Study Design Prospective cohort study (open-label, single-arm, and non-blinded). Purpose This study aims to determine the effects of systemic administration of tocilizumab, an anti-interleukin-6 (IL-6) receptor antibody on refractory low back pain and leg symptoms. Overview of Literature IL-6 overexpression is associated with neuropathic pain pathogenesis, which is potentially followed by chronic low back pain, including leg pain and numbness. This finding suggest that inhibition of IL-6 at the site of pain or in the transmission pathway could provide novel therapeutic targets for chronic low back pain. Methods This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months’ chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. Results Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. Conclusions Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1–4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.

Background: Carcinoma cuniculatum (CC) is a rare subtype of squamous cell carcinoma that is difficult to diagnose owing to the lack of cellar atypia and/or associated oral epithelial dysplasia. The prognosis is good given proper resection, but it often has a poor prognosis with recurrence. We present the case of a 78-year-old man who visited our department with an ulcer around the implant in tooth 35. With Nikolsky’s phenomenon in the gingiva, a detailed examination revealed pemphigus vulgaris. Steroid administration remarkably improved the oral symptoms but caused osteomyelitis and rapid bone destruction, leading to pathological fracture. After multiple biopsies, mandibular segment resection was performed with a diagnosis of mandibular osteomyelitis, and no malignant findings were found. Four months later, the wound reopened, a white keratinized lesion appeared, and a biopsy revealed CC. Unresectable tumor infiltration was already observed, but the patient died of aspiration pneumonia 15 months after diagnosis. Conclusions: It took 20 months to make a definitive diagnosis of CC in this case. Pemphigus vulgaris may have made the diagnosis particularly difficult. Since other CCs are often diagnosed with osteomyelitis or odontogenic keratocyst preoperatively, we recommend keeping in mind the possibility of CC in refractory cases.

We report a 68-year-old woman with tracheobronchitis and laryngitis associated with Crohn's disease (CD), which was discovered during the evaluation of suspected lung cancer. She had no symptoms induced by these upper airway diseases (UADs). Bronchoscopy revealed swelling of the epiglottis with edematous change and a mass like epiglottis fold. There were nodular and edematous changes in the trachea and bilateral main bronchus. Histological findings demonstrated infiltration by numerous lymphocytes and plasma cells. Dexamethasone as the premedication for chemotherapy against lung cancer was efficacious for these extraintestinal manifestations of CD. Our case was rare in that bronchial lesion and UADs appeared concomitantly.

Abstract Background Burning mouth syndrome (BMS) is a chronic condition characterized by pain in the oral cavity. Kampo medicine is a traditional Japanese medical system that has its roots partly in ancient Chinese medicine. The purpose of this study is to evaluate the efficacy of rikkosan—a traditional Japanese herbal medicine (Kampo)—in the treatment of primary BMS. Main body A single-center retrospective study was conducted in 32 patients who were diagnosed with primary BMS and treated with rikkosan alone through gargling (2.5 g rikkosan dissolved in 50 mL hot water) three times daily. Patients were asked to evaluate their pain using a numerical rating scale (NRS) at first visit and after 1 month. One patient had stomatitis as a side effect after gargling with rikkosan, however, no side effects were observed in other patients. Overall NRS scores decreased significantly between the first visit (7.6 ± 2.7) and the 1-month visit (5.6 ± 2.8). Conclusions Rikkosan may be an effective treatment for primary BMS.

A soliton is a class of solitary-wave solutions having specific mathematical properties, which universally appears in integrable systems. A quantum dark soliton is an emerging concept having theoretical and experimental relevance. Although recent studies have proposed quantum states with density profiles similar to those of classical dark solitons, the concept of quantum dark solitons is not yet fully established in that their collision dynamics have not been examined. Here, we first construct dark soliton states that possess stable scattering properties that are unique to solitons using the Lieb-Liniger model, establishing a direct link between quantum and classical dark soliton theories.

The emergence of quasiparticles is a universal property in integrable systems. String-type quasiparticles, which are characterized by the string solutions of Bethe equations, play fundamental roles in the analysis of their physics. Through an investigation of the Bethe equations in the asymmetric simple exclusion process, we reveal the existence of string solutions in the presence of non-Hermiticity resulting from asymmetrical hopping. Because of the non-Hermiticity, the string solutions exhibit exotic properties such as the complexification of the center of string solutions and the delocalization of Bethe quantum numbers. In addition, we find the picture of string-type quasiparticles collapses in the strong-asymmetry regime. The collapse of string solutions characterizes the transition of eigenstates from bound states to scattering states.

Non-small cell lung cancer (NSCLC), one of the deadliest types of cancers worldwide, has been the target of immunotherapy due to its high immune antigenicity. With the addition of immune-checkpoint inhibitors (ICIs), including anti-PD-1/PD-L1 antibodies, as an indispensable and powerful regimen for the treatment of this lethal disease, the median survival time for patients with stage IV NSCLC is approximately 2 years. In contrast, the response rate to ICIs remains less than 50%, even if the patients are selected using biomarkers such as PD-L1. Pharmaceutical companies have begun to develop additional anti-PD-1/PD-L1 antibodies to overcome resistance and are devising further immunotherapy combinations. More than 20 anti-PD-1/PD-L1antibodies have been approved or are currently in development. Numerous combination therapies are under development, and several combination therapies have provided positive results in randomized controlled trials. This review aimed to examine the current status of approved and investigational anti-PD-1/PD-L1antibodies for NSCLC in Japan, the United States, the European Union, and China. Further, this review discusses the challenges and future perspectives for developing new ICIs in alignment with the global developments in Japan.

Introduction: Although recent advances in chemotherapy for lung cancer are remarkable, most clinical trials have excluded patients with interstitial lung disease (ILD) due to the concern of developing acute exacerbation (AE) of ILD. Hence, accumulating original evidence of cancer treatment for this population is important. Methods: Between 2016 and 2020, a prospective observational study was conducted across 11 Japanese hospitals. Patients with chemotherapy- naïve , inoperable, advanced lung cancer with ILD were included. The primary outcome was the frequency of AE-ILD after registration; the secondary outcomes were the risk factor of AE-ILD and the efficacy of chemotherapy. Results: Among 124 patients enrolled, 109 patients who received chemotherapy were analyzed. The median age was 72 years, and the majority showed usual interstitial pneumonia (UIP)/probable UIP pattern upon chest computed tomography. The median percent-predicted forced vital capacity (%FVC) was 81% (interquartile range: 66–95%). After registration, 23 patients (21.1%; 95% confidence interval [CI]: 14.4–29.7%) developed AE-ILD. The logistic analysis revealed that lower %FVC slightly but significantly increased the risk of AE-ILD (odds ratio per 10% decrease: 1.27; 95% CI: > 1.00–1.62). Overall response rates/median overall survival times in non-small-cell lung cancer and small-cell lung cancer for the first-line chemotherapy were 41% (95% CI: 31–53)/8.9 months (95% CI: 7.6–11.8) and 91% (95% CI: 76–98)/12.2 months (95% CI: 9.2–14.5), respectively. Conclusion: AE-ILD during chemotherapy is a frequent complication among patients with lung cancer with ILD, particularly those with lower %FVC. Conversely, even in this population, passable treatment response can be expected.

Abstract Objectives Epigenetic phenomena are changes in gene expression not involving the DNA sequence. DNA methylation is a major occurrence underlying epigenetic changes in human cells. Although aberrant DNA methylation is well documented in malignant lesions, limited information has been shown on the involvement of DNA methylation in oral lichen planus and oral lichenoid lesions (OLP). The present study aimed to investigate DNA methylation of E‐cadherin and p16 in OLP, and compare the findings with those in non‐inflamed gingiva (Non), radicular cyst (RC), and oral squamous cell carcinoma (SCC). Materials and methods Paraffin‐embedded surgical biopsy specimens were sliced, DNA was extracted, bisulfite treatment was applied, and methylation‐specific polymerase chain reaction was performed. Immunohistochemistry was performed to observe the relative expression patterns of these genes. Results E‐cadherin was hypermethylated in OLP (p

Abstract The DNA demethylating agent, 5-Azacytidine (5Aza), and histone deacetylase inhibitor, valproic acid (Vpa), can improve the reprogramming efficiencies of pluripotent cells. This study aimed to examine the roles of 5Aza and Vpa in the dedifferentiation of epithelial cell rests of Malassez (ERM) into stem-like cells. Additionally, the ability of stem-like cells to differentiate into mesenchymal cells was evaluated. ERM was cultured in embryonic stem cell medium (ESCM) with 1 µM of 5Aza, or 2 mM of Vpa, or a combination of 5Aza and Vpa. The cells stimulated with both 5Aza and Vpa were named as progenitor-dedifferentiated into stem-like cells (Pro-DSLCs). The Pro-DSLCs cultured in ESCM alone for another week were named as DSLCs. The stem cell markers were significantly higher in the DSLCs than the controls (no additions). The mRNA and protein levels of the endothelial, mesenchymal stem, and osteogenic cell markers were significantly higher in the Pro-DSLCs and DSLCs than the controls. The combination of a demethylating agent and a deacetylated inhibitor induced the dedifferentiation of ERM into DSLCs. The Pro-DSLCs derived from ERM can be directly reprogrammed into mesenchymal-like cells without dedifferentiation into stem-like cells. Isolated ERM treated with epigenetic agents may be used for periodontal regeneration.

Objectives: Staphylococcus aureus is an important nosocomial pathogen that produces various extracellular toxins. Epigallocatechin gallate (EGCg) is a polyphenol that is abundant in green tea. EGCg displays strong antibacterial activity against Gram-positive bacteria. The effect of EGCg on gene expression by S. aureus was investigated to clarify the mechanism underlying its antibacterial action. Methods: Microarray analysis was performed on S. aureus treated with or without 500 mg/L EGCg. Differentially expressed genes were identified and their changes at the transcription level were confirmed using real-time quantitative polymerase chain reaction (qPCR). The membrane potential of cells treated with or without EGCg were observed under fluorescence microscopy. Results: Microarray analysis revealed that EGCg treatment of S. aureus resulted in increased and decreased transcription of 75 and 72 genes, respectively. Increased transcription exceeding 1-log2-fold change of genes related to membrane transport included gntP, gntK, rumA, SAOUHSC_02723, SAOUHSC_01311, and vraS. Decreased transcription was observed in genes involved in toxin production and stress response (hlgA, SAOUHSC_01110, hly, hlgB, efb, and hlgC). All changes in transcription were confirmed using real-time qPCR. The membrane potential of S. aureus treated with 500 mg/L EGCg markedly decreased, indicating that EGCg damaged the cell membrane. Conclusions: S. aureus increases the transcription of genes involved in membrane transport to recover membrane function. EGCg can potentially serve as a natural antibacterial agent to control the growth and toxin production of S. aureus.

Background Several studies have previously demonstrated the survival benefit of both EGFR‐TKI treatment and chemotherapy in patients with non‐small cell lung cancer (NSCLC) harboring EGFR mutations. The aim of the present study was to clarify the factors influencing the treatment sequence after failure of EGFR‐TKI therapy, focusing on the number of organs with metastasis (hereafter, metastatic organs). Methods Between January 2010 and December 2016, consecutive patients with EGFR‐mutated NSCLC who were started on first‐line EGFR‐TKI were reviewed. The factors influencing withholding systemic chemotherapy and the post‐progression survival (PPS) after failure of EGFR‐TKI were investigated. Results A total of 393 patients were started on first‐line EGFR‐TKI during the study period. After excluding patients maintained on EGFR‐TKI or who received osimertinib targeting secondary EGFR T790M, 297 patients were included in the analysis. Among these, 180 (60.6%) received chemotherapy after failure of EGFR‐TKI (TKI‐Ct group), while the remaining 117 (39.4%) received no chemotherapy (TKI‐only group). Multivariate analysis identified older age (≥75 years: odds ratio [OR] = 0.25, 95% confidence interval [CI]: 0.11–0.43, P

Anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl-tRNA synthetase (ARS) antibodies are two major myositis-specific autoantibodies with distinct clinical features. However, the clinical course remains unclear in patients with clinically amyopathic dermatomyositis (CADM)-interstitial lung disease (ILD) who have co-existing anti-MDA5 and anti-ARS antibodies. Here, we describe the case of a 32-year-old woman with CADM-ILD who had anti-MDA5 and anti-PL12 antibodies. Her serum ferritin level was within the normal range. However, chest computed tomography revealed bilateral lower-lobe consolidation and ground-glass opacities. Treatment with prednisolone and immunosuppressants was successful in improving the skin lesion and ILD, but relapse occurred on reducing the dose of prednisolone. These clinical features match those of anti-ARS antibody-positive dermatomyositis-ILD. Because these two conditions show significantly different clinical features and require different intensities of treatment, clinicians should carefully follow-up these patients throughout the course of the disease.

Summary: Medication-related osteonecrosis of jaws (MRONJ) is one of the most complicated inflammatory conditions in oral and maxillofacial region. It is very difficult to correctly evaluate the degree and extent of necrosis and infection. This refractory osteonecrosis often needs extended surgery, leading to impaired quality-of-life. We have performed hyperbaric oxygen therapy (HBO) combined with conservative surgery for advanced cases. We have appraised the value of FDG-PET and 3-phase bone scintigraphy in the diagnosis and management of this condition. MRONJ showed significantly higher SUVmax on FDG-PET than the others. Although the 3 phase pool bone images did not change significantly, perfusion and static bone image as well as PET showed remarkable response to HBO for MRONJ. SUVmax after HBO was significantly lower than those of before HBO. These preliminary results indicate that FDG-PET is useful for monitoring the effect of HBO for MRONJ.

Introduction: Limb muscle mass measurement using dual-energy X-ray absorptiometry (DXA) is considered the gold standard for the diagnosis of sarcopenia. Moreover, bioelectrical impedance analysis (BIA) is also recognized as a beneficial tool considering its high correlation with DXA. However, it remains to be elucidated whether DXA and BIA can accurately measure trunk lean mass. The aim of this study was to investigate the correlation between DXA and BIA measurements of trunk muscle mass and the cross-sectional area (CSA) of trunk muscles measured using magnetic resonance imaging (MRI) and to compare measures of trunk muscle mass obtained using DXA and BIA in patients with low back pain (LBP). Methods: In total, 65 patients participated in the study. The correlation between DXA and BIA measurements and the CSA of trunk and paraspinal muscles at the L4-5 level were calculated. In addition, the correlation between DXA and BIA measurements of trunk muscle mass and the differences between these two measurements were determined. Results: The correlation coefficient between DXA and BIA trunk muscle mass measurement and trunk muscle CSA was 0.74 and 0.56 for men and 0.69 and 0.44 for women, respectively. DXA and BIA measurement values showed a significantly moderate correlation with the CSA of the erector spinae (ES) and psoas major (PM). The multifidus (MF) CSA did not correlate with measurements of DXA and BIA in both men and women. Although DXA and BIA measurements were significantly correlated, a significant difference between these two measurements was found. BIA overestimated the trunk muscle mass significantly compared with DXA. Conclusions: Trunk muscle mass measured with DXA and BIA was correlated with the CSA of most trunk muscles. Although the measurement of DXA and BIA showed a high correlation, BIA overestimated trunk muscle mass compared with DXA. Both DXA and BIA are beneficial for measuring trunk muscle mass.

Background Although non‐small cell lung cancers (NSCLCs) harboring EGFR mutations initially respond well to EGFR‐tyrosine kinase inhibitors (TKIs), they typically progress after approximately one year. The EGFR T790M mutation is the most common resistance mechanism. NSCLCs with T790M respond well to osimertinib; however, the heterogeneity of NSCLCs may limit the efficacy. Some patients exhibit a mixed response (MR), in which some lesions shrink and others progress, but little is known of the incidence and characteristics of such a response. We sought to determine the frequency and clinical course in MR patients. Methods We retrospectively reviewed the records of patients who had received osimertinib for NSCLC with EGFR T790M. Results Between April and December 2016, 48 patients were administered osimertinib. Seven patients (15%) exhibited one of two MR types: (i) progressive lesions that did not include the re‐biopsy site (5 patients), and (ii) progressive lesions that included the re‐biopsy site (2 patients). The most frequent progressive sites were liver and lung metastases (4 patients). Three patients continued osimertinib following an MR, one of whom had received local therapy for liver metastasis and achieved disease control on osimertinib for an additional four months. Conclusion An MR was detected in 15% of NSCLC patients with T790M. This finding suggests that several different resistance mechanisms are active within a single patient who develops resistance to EGFR‐TKIs. Osimertinib is basically effective for tumors that acquire resistance to EGFR‐TKIs as a result of T790M mutation. Therefore, additional local therapy may be beneficial for patients who develop an MR to osimertinib.

Abstract Background Evaluation of knee and lower limb function alone is not sufficient to assess gait. For accurate assessment of gait abnormality, gait oscillation should also be measured. The goal of this analysis was to assess the influence of the knee joint on gait oscillation during gait and stair-stepping in patients with osteoarthritis of the knee. Methods In 33 patients diagnosed with knee osteoarthritis and 33 healthy adults as the control group, we examined acceleration (anterior and lateral directions) and gait barycentric factors (single-support phase and ratio of center of gravity maximum values) during gait and stair-stepping. Results Acceleration in the anterior direction in the sacral region was greater in healthy adults than in osteoarthritis (OA) patients during gait and stair-down. Acceleration in the anterior direction in the dorsal vertebral region was greater in OA patients than in healthy adults during (up and down) stair-stepping. Acceleration in the lateral direction in the sacral region was greater in healthy adults than in OA patients during stair-up. Acceleration in the lateral direction in the dorsal vertebral region was greater in OA patients than in healthy adults during stair-stepping. The single-support phase was close to 1 for gait and stair-stepping in healthy adults and OA patients. The single-support time was largely the same for gait and stair-stepping in healthy adults. On the other hand, the single-support time was longer for stair-stepping than for gait in OA patients. The ratio of the center of gravity maximum values was greater for the sacral region than for the dorsal vertebral region. There was a significant difference in the stair-stepping ratio of the center of gravity maximum values between healthy adults and OA patients for the sacral region. Conclusion We considered that knee OA influenced acceleration in the anterior and lateral direction in the dorsal vertebral and the ratio of the center of gravity maximum values on gait oscillation.

Background: Changes in atmospheric pressure are suggested to trigger headaches. This pilot study was made to determine craniofacial sensations accompanying short phases of changing barometric pressure. Methods: In a crossover design, 15 adult healthy subjects were exposed in a climate chamber to 8 min phases of barometric pressure lowering by 0, 20 and 40 hPa. The subjects rated their sensations of ear pressure, head compression and the occurrence of headache every minute on a visual analogue scale (VAS, range 0–10). Pulse rate was recorded as a parameter for autonomic functions. Results: Nearly all subjects experienced ear pressure and half of them compression of their head at variable degrees. These sensations started in most subjects during the phase of lowering barometric pressure and increased to an average rating of about 3 VAS when returning to ambient atmospheric pressure. Heart rate slightly decreased during this phase. Three subjects reported mild to moderate headache for various durations within these phases. Conclusions: Changes in barometric pressure can be associated with sensations of ear pressure and head compression and may trigger headaches. The generation of these sensations is discussed with regard to convergent trigeminal innervation of the ear, the paranasal sinuses and the cranial meninges.

To elucidate the relationship between chronic pain conditions with cast immobilization and autonomic function, we investigated the functional changes of the autonomic nervous system in conscious rats with chronic post-cast pain (CPCP) induced by a two-week cast immobilization of one hind limb. We telemetrically examined the time courses of systolic arterial blood pressure (SBP), heart rate (HR), and the middle-frequency (MF) component obtained from the power spectral analysis of SBP variability as a vasomotor sympathetic index. We also investigated the baroreflex sensitivity to phentolamine, an α-adrenoceptor antagonist, and the SBP and HR responses to a low ambient temperature (LT; 9.0 ± 0.2°C) exposure, a sympathetic stimulant. Rats exposed to cast immobilization exhibited mechanical allodynia lasting for at least 10 weeks after cast removal in the calf area (skin and muscle) of the bilateral hind limbs. Under resting conditions, the SBP, HR, and MF components were significantly increased during cast immobilization (all p < 0.001). Following cast removal, these parameters gradually decreased and within 1 week reached lower than baseline levels, lasting for over 10 weeks. Phentolamine administration (10 mg/kg, intraperitoneally) significantly decreased the SBP before and during cast immobilization (before, p < 0.001; during, p = 0.001) but did not lower the SBP after cast removal. The baroreflex gain after phentolamine administration, calculated as the HR increase divided by the SBP reduction, was significantly increased after cast removal (p = 0.002). The SBP increase on LT exposure was significantly greater after cast removal than that before cast immobilization, suggesting hypersensitivity to sympathetic neurotransmitters. These results revealed that, in the CPCP model, sympathetic activation was augmented during cast immobilization, which then decreased after cast removal and remained below normal levels with persisting pain behaviors. Additionally, the responsiveness of the autonomic nervous system was impaired in the CPCP model.

A 41-year-old man presented with multiple superficial lymph nodes (LNs) swollen with elevated levels of serum immunoglobulin (Ig)G4 and C-reactive protein. Histological findings of his left inguinal LN revealed lymphoplasmacytic infiltration with numerous IgG4-positive plasma cells; IgG4+/IgG+ plasma cell ratio >40%. Chest computed tomography (CT) showed poorly defined centrilobular nodules, interlobular septal thickening, consolidations, and mediastinal LNs swelling. Bronchoalveolar lavage fluid (BALF) showed elevated eosinophils. A surgical lung biopsy showed focal dense eosinophil infiltration, in addition to lymphoplasmacytic infiltration, but few IgG4+ plasma cells. The diagnosis of multicentric Castleman disease (MCD) was made because of serum interleukin-6elevation. Treatment with prednisolone and tocilizumab improved his symptoms and lung lesions. This case shows that overlapping clinical and pathological features of MCD and IgG4-related disease may present in a single patient, showing the difficulty in distinguishing between these two diseases.

Abstract We present a 67‐year‐old man with allergic bronchopulmonary aspergillosis (ABPA), whose chest computed tomography (CT) scans showed localized circumferential bronchial wall thickening in the right main bronchus to middle truncus. Chest CT scans showed high‐attenuation mucus in the right B8 bronchus. Bronchoscopy showed narrowing of the right main bronchus and inspissated mucus plugging in the right B8 bronchus. Histological examination of the right main bronchus revealed bronchial inflammation with numerous neutrophils and plasma cells. Treatment with corticosteroid and antifungal agents resulted in resolution of the symptoms and right bronchial lesions. The clinical course may indicate that the bronchial lesions were associated with ABPA.

We herein describe a case of an 83-year-old man who presented with epigastralgia, vomiting, and abdominal distention. The physical abdominal examination revealed mild tenderness. Computed tomography revealed intramural gastric gas spread throughout the stomach, intraabdominal free gas, and hepatic portal venous gas. We diagnosed gastric emphysema with intraabdominal free gas and hepatic portal venous gas. We selected a wait-and-watch approach because physical examination did not show any peritoneal signs, although the radiological examinations showed remarkable findings. As a result, he received conservative therapy with fasting, intravenous infusion of antibiotics, and gastric decompression by nasogastric intubation. The patient was relieved of the symptoms, and follow-up computed tomography showed that all the abnormal gas disappeared soon after the treatment. In conclusion, the intramural gastric gas even with both intraabdominal free gas and hepatic portal venous gas does not always require surgical intervention. In case clinicians including general surgeons and physicians encounter intraabdominal free gas with hepatic portal venous gas, gastric emphysema should be considered in the different diagnosis. Lack of knowledge may lead to misdiagnosis, which may result in unnecessary surgical intervention.

We report a clinical case of a patient with hereditary angioedema (HAE, Type III) in which, by implementing careful preoperative preparations to prevent the occurrence of edema, good course was achieved without the prophylactic administration of C1-inhibitor (C1–INH). We recommended the prophylactic administration of Berinert P, a human plasma-derived C1–INH formulation; however, due to the risk of developing a viral infection, both the patient and her mother refused to receive Berinert P. In cases where C1–INH cannot be administered as a prophylactic measure, it is essential to make sufficient preparations, including urgent tracheotomy, to prevent sudden occurrence of edema, with the cooperation of the anesthesiologist.

Bronchoscopic findings often show mucoid impaction in patients with allergic bronchopulmonary aspergillosis (ABPA); however, endobronchial mucosal nodular lesions have not been reported. We herein present the first such case of a 52-year-old woman with ABPA with endobronchial mucosal nodular lesions. The endobronchial lesions were located in the orifice of the mucoid impaction, and disappeared after 4 weeks of treatment with prednisolone and itraconazole. Aspergillus fumigatus was cultured from bronchial lavage fluid collected from the site of mucoid impaction. Based on these clinical findings, we speculate that the bronchial lesions were caused by an inflammatory and allergic reaction to Aspergillus antigens. Keywords: Aspergillus fumigatus, Eosinophilic granulomatosis with polyangiitis, Eosinophilic pneumonia, Mucoid impaction

Study Design Cross-sectional observational study. Purpose To compare measurements of appendicular skeletal muscle mass (ASMM) and whole fat mass (WFM) obtained using dualenergy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) among patients with low back pain (LBP). Moreover, the study investigated the correlation between BIA-based ASMM and DXA-based bone mineral density (BMD). Overview of the Literature If reliable, BIA may be a useful alternative to DXA as a screening tool for sarcopenia and osteoporosis among patients with LBP. Methods Measurements were performed in 130 patients, including BMD of the lumbar spine and femoral neck. The correlation between DXA and BIA as well as between BIA-ASMM and BMD were evaluated. Results BIA and DXA were highly correlated in both male and female patients (r =0.73–0.90, p

Introduction: Osteoporosis and sarcopenia are said to be similar disorders. However, few reports have described the effects of anti-osteoporosis drugs on muscle mass in clinical practice. Methods: We selected 150 postmenopausal women with osteoporosis treated by minodronate (osteoporosis medication [OM] group) and 50 postmenopausal women without osteoporosis who did not receive treatment (no osteoporosis [NO] group). The OM group was further divided into two treatment subgroups: a combination of monthly minodronate and daily activated vitamin D vs. monthly minodronate alone. We measured lumbar spine and femoral neck bone mineral density (BMD) with dual-energy X-ray absorptiometry and muscle mass of the upper limbs, lower limbs, and trunk with bioelectrical impedance analysis at baseline and after 6 months. Results: The OM and NO groups contained 130 and 37 patients, respectively (mean age: 73.9 ± 8.3 and 74.1 ± 10.0 years, respectively). In the OM group, lumbar spine BMD significantly increased after 6 months, while lower limb muscle mass significantly decreased. In the NO group, lumbar spine BMD and lower limb muscle mass did not significantly change after 6 months. In the OM group, BMD of the lumbar spine significantly increased but the lower limb muscle mass significantly decreased after 6 months relative to the NO group. In the combination therapy subgroup of the OM group muscle mass decreased significantly less than in the minodronate-alone subgroup. Conclusions: In postmenopausal women with osteoporosis, minodronate can increase BMD but cannot increase muscle mass. However, simultaneous use of activated vitamin D can suppress muscle mass decrease. The combination of activated vitamin D and minodronate may be useful for treating osteoporosis in postmenopausal women.

Introduction: Discogenic back pain remains poorly understood with respect to etiopathogenesis, despite being a considerable burden. We sought to examine the expression of vascular endothelial growth factor in injured intervertebral discs in rat caudal vertebrae. Methods: Forty-eight male Sprague Dawley rats were assigned to 2 groups according to disc puncture injury: puncture (n = 32) or non-puncture (n = 16). Disc puncture was performed percutaneously such that the incision would be in the primary plane of motion for the coccygeal discs 5-6, 6-7, and 7-8. A 26-gauge needle was used to puncture each disc 10 times. Punctured discs were examined histologically by hematoxylin and eosin staining at 1, 7, 14, and 28 days post-injury. Results: Vascular endothelial growth factor was localized immunohistochemically, and determined quantitatively using an enzyme-linked immunosorbent assay. Peak inflammation occurred on the 7th day post-injury, but tissue degeneration continued until day 28. Local expression of vascular endothelial growth factor tended to be highest in the annulus fibrosus on the 7th and 14th days after puncture injury. The level of vascular endothelial growth factor was highest 1-day post-injury, and then gradually decreased thereafter. Furthermore, vascular endothelial growth factor levels in the puncture group were significantly higher than those in the non-puncture control group (p < 0.05). Conclusions: We found increased expression of the inflammatory cytokine vascular endothelial growth factor in injured intervertebral discs, suggesting that vascular endothelial growth factor may be clinically important in discogenic back pain.

Introduction: Failed spinal fusion surgery sometimes requires salvage surgery when symptomatic, especially with postsurgical decrease in intervertebral disc height followed by foraminal stenosis. For such cases, an anterior approach to lumbar lateral interbody fusion (LLIF) provides safe, direct access to the pathological disc space and a potential improvement in the fusion rate. One LLIF approach, oblique lateral interbody fusion (OLIF), targets the oblique lateral window of the intervertebral discs to achieve successful lateral interbody fusion. The current technical note describes spinal revision surgery using the OLIF procedure. Technical Note: The subjects were patients with leg pain and/or lower back pain derived from decreased intervertebral height followed by foraminal stenosis due to failed spinal fusion surgery. These patients underwent additional OLIF surgery and posterior fusion with no additional posterior direct decompression. Their outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scores at baseline and final follow-up. Bony union was also evaluated using computed tomography images at final follow-up. Six subjects were evaluated, with two representative cases described in detail. Four patients had an adjacent segment disorder, and the other two patients had pseudarthrosis due to postoperative infection. The mean JOA score improved from 5.7 ± 5.4 to 21.2 ± 2.3, with a mean recovery rate of 65.0%. All cases showed intervertebral bony union. Conclusions: We introduced a salvage strategy for failed posterior spine fusion surgery cases using the OLIF procedure. Patients effectively achieved recovered intervertebral and foraminal height with no additional posterior direct decompression.

An 85-year-old man who did not have any hematological or respiratory disorders was transferred to our hospital because of progressive dyspnea. Computed tomography (CT) findings showed ground-glass opacities with a centrilobular distribution and centrilobular micronodules with a “tree-in-bud” pattern. A biopsy of the lungs showed lymphocytic infiltrations in the parenchyma and these were positive for B cell markers. A diagnosis of chronic lymphocytic leukemia (CLL) was made and direct pulmonary involvement of CLL was confirmed simultaneously. One month after initiation of chemotherapy, his symptoms improved and a chest CT scan showed marked resolution. Pulmonary infiltrates of CLL should be included in the differential diagnosis when these signs are encountered on CT. Keywords: Chronic lymphocytic leukemia, Pulmonary infiltrate, Centrilobular micronodule, “Tree-in-bud” pattern

We report the case of an incisional hernia through the wound made for iliac bone harvest for re-operative cervical fusion surgery. A 50-year old woman underwent revision anterior cervical discectomy and fusion (ACDF) using a poly ether ether ketone cage and titanium alloy locking plate for adjacent segment disease after prior ACDF. As an autograft, iliac cancellous bone was again harvested from the left iliac crest, using the prior surgical scar. Although only cancellous bone from the medial side of the iliac bone was collected, leaving the iliac crest intact, she complained of a protrusion from the left lower abdomen, of which diagnosis was an incisional hernia through the iliac bone harvest site. Formation of an incisional hernia at the iliac bone harvest site is a possible complication after spine surgery. Care must be taken for oblique abdominal muscle repair around the iliac bone harvest site, particularly in re-operative cases. Keywords: Incisional hernia, Iliac crest, Bone graft, Spinal fusion surgery

We study quantum double dark-solitons, which give pairs of notches in the density profiles, by constructing corresponding quantum states in the Lieb–Liniger model for the one-dimensional Bose gas. Here, we expect that the Gross–Pitaevskii (GP) equation should play a central role in the long distance mean-field behavior of the 1D Bose gas. We first introduce novel quantum states of a single dark soliton with a nonzero winding number. We show them by exactly evaluating not only the density profile but also the profiles of the square amplitude and phase of the matrix element of the field operator between the N-particle and (N−1)-particle states. For elliptic double dark-solitons, the density and phase profiles of the corresponding states almost perfectly agree with those of the classical solutions, respectively, in the weak coupling regime. We then show that the scheme of the mean-field product state is quite effective for the quantum states of double dark solitons. Assigning the ideal Gaussian weights to a sum of the excited states with two particle-hole excitations, we obtain double dark-solitons of distinct narrow notches with different depths. We suggest that the mean-field product state should be well approximated by the ideal Gaussian weighted sum of the low excited states with a pair of particle-hole excitations. The results of double dark-solitons should be fundamental and useful for constructing quantum multiple dark-solitons.

Background: Bee pollen (BP) has a broad range of beneficial effects on health. The aim of this study was to examine the effect of BP on the oral environment, including the microbiome and antimicrobial peptides. Methods: C57BL/6J mice were randomly divided into two groups: control and BP. The BP group was fed with a 5% BP diet for 1 month. Swabs from the oral and buccal mucosa and samples of the intestinal stool were collected. Genomic DNA was extracted and the microbiome was analyzed via 16S rRNA sequencing. Results: BP inhibited the growth of P. gingivalis at a concentration of >2.5%. The metagenomic study showed that the abundance of genus Lactococcus was significantly elevated in the oral and intestinal microbiomes of the BP group when compared to those of the control group. Significant alterations in alpha and beta diversity were observed between the oral microbiomes of the two groups. The mRNA levels of beta-defensin-2 and -3 were significantly upregulated in the buccal mucosa of the BP group. Conclusion: A BP diet may have a beneficial effect on oral and systemic health by modulating the bacterial flora and antimicrobial peptides of the oral cavity. Further investigations are needed to clarify how a BP diet affects overall human health.

Introduction: Oblique lateral interbody fusion (OLIF) can achieve recovery of lumbar lordosis (LL) in minimally invasive manner. The current study aimed to evaluate the location of lateral intervertebral cages during OLIF in terms of LL correction. Methods: The subjects were patients who underwent OLIF for lumbar degenerative diseases, including lumbar spinal stenosis, spondylolisthesis, and discogenic low back pain. Their clinical outcome was evaluated using visual analogue scale on lower back pain (LBP), leg pain and numbness. The following parameters were retrospectively evaluated on plain radiographic images and computed tomography scans before and at 1 year after OLIF: the intervertebral height, vertebral translation, and sagittal angle. The cage position was defined by equally dividing the caudal endplate into five zones (I to V), and its association with segmental lordosis restoration was analyzed. Subjects were also evaluated for a postoperative endplate injury. Results: Eighty patients (121 fused levels) with lumbar degeneration who underwent OLIF were included. There were no significant specific distribution in preoperative disc pathology such as disc angle, height, and translation. After OLIF, sagittal alignment was improved with an average correction angle of 3.8º at the instrumented segments in a level-independent fashion. All cases showed significant improvement in clinical outcomes, and had improvement in the radiological parameters (P

Study DesignAn experimental animal study.PurposeTo evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin gene-related peptide (CGRP) in the dorsal ganglia in a rat model.Overview of LiteratureIncreased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury.MethodsThrough abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti-VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 µg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 µL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1–L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP.ResultsCompared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p

Study DesignObservational study.PurposeTo assess the correlation among inflammatory cytokine expression levels, degree of intervertebral disk (IVD) degeneration, and predominant clinical symptoms observed in degenerative disk disease (DDD).Overview of LiteratureLow back pain (LBP) is associated with inflammatory cytokine expression levels, including those of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and nerve growth factor (NGF). However, the association between cytokine expression levels and the physiological mechanisms of disk degeneration and clinical pain remain controversial.MethodsUsing the enzyme-linked immunosorbent assay, TNF-α, IL-6, and NGF expression levels were analyzed in 58 IVD samples that were harvested from patients with lumbar DDD. Patient samples were grouped according to the degree of IVD degeneration using the Pfirrmann grading system and magnetic resonance imaging, and the correlations between the disease groups and each cytokine expression level were assessed. In addition, on the basis of their predominant preoperative symptoms, the patients were assigned to either an LBP or leg pain group to determine the correlation among these disease manifestations and individual cytokine expression levels.ResultsA gradual increase in TNF-α (R=0.391) and IL-6 (R=0.388) expression levels correlated with the degree of IVD degeneration, whereas NGF (R=0.164) expression levels exhibited a minimal decrease with disease progression. Regarding the predominant clinical manifestation, only the LBP group exhibited a significant increase in TNF-α expression levels (p=0.002).ConclusionsThese results suggested that TNF-α and IL-6 play an important role in the pathophysiology of IVD degeneration at any stage, whereas NGF plays an important role during the early disease stages. Moreover, because TNF-α expression levels were significantly high in the LBP group, we propose that they are involved in LBP onset or progression.

Background: The flavor of Japanese sake (frequently referred to as Seisyu in Japanese academic contexts) has improved in recent years and demand for sake is on the rise globally. Methods: Our analysis is based on a review of literature and secondary data examination of existing statistics. Results: Quality control is achieved through the use of acid from polished rice. One use for acid may be for rice flavors, which are regionally specific and therefore may lead to a reconsideration of geographical indications. Conclusion: The use of acid and collaboration with the local and regional community is observed in wine production. Similar processes are observed with Japanese sake, and this implies that wine and sake may have similar futures. Visits to sake breweries have potential in the spheres of tourism, regional branding, and destination management.