Analysis of hand environment factors contributing to the hand surface infection barrier imparted by lactic acid.

BACKGROUND: Organic acids on the surface of human hands contribute to the barrier against transient pathogens. This is the first study to explore the synergistic contribution of lactic acid and other hand environment-related features on the antibacterial properties of the hand surface. MATERIALS AND METHODS: We estimated the contribution of fingerprint depth, skin pH, stratum corneum water content, skin temperature, and sweat rate of the hands to the infection barrier using an observational survey of 105 subjects. The relationship between each factor and the antibacterial activity of the hands was analyzed using Pearson's correlation coefficient. We performed molecular dynamics simulations to study the interaction between lactic acid and bacterial membranes. RESULTS: The amount of lactic acid on the hands and skin temperature contributed positively to the antimicrobial activity (r = 0.437 and P = 3.18 × 10-6 , r = 0.500 and P = 5.66 × 10-8 , respectively), while the skin pH contributed negatively (r = -0.471, P = 3.99 × 10-7 ). The predicted value of the combined antimicrobial effect of these parameters was [antimicrobial activity] = 0.21 × [lactic acid] - 0.25 × [skin pH] + 0.26 × [skin temperature] + 0.98. The coefficient of determination (R2 ) was 0.50. CONCLUSION: The increase in the amount of non-ionic lactic acid due to lower pH and improvement in the fluidity of the cell membrane due to higher temperatures enable the efficient transport of lactic acid into cells and subsequent antimicrobial activity. The proposed mechanism could help to develop an effective hand infection barrier technology.

[Left Paraganglioma in the Posterior Mediastinum].

A 69-year-old man with hypertension was referred for an abnormal shadow detected on chest computed tomography(CT) at a medical checkup. Enhanced CT showed a highly enhanced posterior mediastinal tumor of 34×27 mm. Magnetic resonance imaging (MRI) revealed a low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Thus, a neurogenic tumor was suspected and the surgery was performed. The tumor was carefully dissected as it was hyper-vascular and hemorrhagic. Immediately after tumor resection, the patient's blood pressure rapidly decreased, and phenylephrine hydrochloride was needed to maintain the blood pressure. The pathological diagnosis was paraganglioma.

[Tumor-induced Hypophosphatemic Osteomalacia Caused by a Chest Wall Tumor].

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disease characterized by hypophosphatemia and skeletal undermineralization. Overproduction of fibroblast growth factor 23( FGF23) from the responsible tumor is reported to be a causative factor. Removing the tumor is the only effective treatment for TIO, but identifying the tumor is sometimes difficult. A 43-year-old man complained of heel pain 4 years earlier, and the pain gradually expanded to the whole body. As a blood test showed the elevation of the serum FGF23 level and hypophosphatemia, he was diagnosed with FGF23-related hypophosphatemia. Chest computed tomography (CT) showed a 10-mm nodule in the right chest wall. Venous sampling for FGF23 revealed considerable elevation of the FGF23 level in the right subclavian vein. Therefore, a chest wall tumor was suspected as the tumor responsible for TIO, and surgical resection was performed. After surgery, hypophosphatemia improved within several days, and the FGF23 level also normalized.

Pharmacodynamic change in plasma angiogenic proteins: a dose-escalation phase 1 study of the multi-kinase inhibitor lenvatinib.

BACKGROUND: Lenvatinib (E7080), an oral multi-kinase inhibitor, has inhibitory action on tumor cell proliferation and tumor angiogenesis in preclinical models. We evaluated correlations between pharmacodynamic (PD) biomarkers with patient clinical outcomes in a lenvatinib phase 1 dose-escalation study. METHODS: Plasma angiogenic proteins were evaluated as potential PD biomarkers of response to lenvatinib in a dose-escalation phase 1 study. Lenvatinib was administered to 27 patients by twice-daily dosing in 3-week cycles; 2 weeks of treatment followed by 1 week of rest until discontinuation. Blood samples for plasma proteins were collected on days 1 (baseline), 8, and 15 of cycle 1, and days 1, 8, and 15 of cycle 2. Selected clinical outcomes, including tumor shrinkage and adverse events (AEs), were used for correlative analyses of pharmacokinetic parameters and PD biomarkers. RESULTS: Tumor shrinkage and changes in PD biomarkers (increased vascular endothelial growth factor [VEGF] and stromal cell-derived factor 1 alpha [SDF1α] levels and decreased soluble VEGF receptor 2 [sVEGFR2] levels) significantly correlated with increasing lenvatinib exposure. Observed changes in levels of VEGF, SDF1α, and sVEGFR2 were maintained on day 15 of cycle 1, but returned to baseline during the 1-week rest period, and similar changes were induced by reinstitution of treatment in cycle 2. The worst grades of hypertension, proteinuria, and fatigue were associated with changes in VEGF and HGF at day 8 of cycle 1. Maximum tumor shrinkage was correlated with increased SDF1α levels. Decreased sVEGFR2 level was also correlated with tumor shrinkage and frequency of hypertension, proteinuria, and fatigue. Tumor shrinkage significantly correlated with the worst grade of proteinuria, but not with hypertension or fatigue. CONCLUSION: PD biomarker changes observed in plasma angiogenic proteins are correlated with lenvatinib-induced tumor shrinkage and AEs. Our findings warrant further assessment of plasma proteins associated with angiogenesis as potential biomarkers of lenvatinib activity. TRIAL REGISTRATION: ClinicalTrial.gov: NCT00280397 (January 20, 2006).

Successful telaprevir treatment in combination of cyclosporine against recurrence of hepatitis C in the Japanese liver transplant patients.

Telaprevir (TVR) is a protease inhibitor used in combination with pegylated interferon alfa-2b and ribavirin for hepatitis C, and TVR strongly inhibits CYP3A4 and CYP3A5. We reported successful TVR treatment of liver transplant patients with recurrence of hepatitis C during receiving immunosuppressive therapy. Before initiation of triple therapy, all patients switched from tacrolimus to cyclosporine, which has a lower inhibitory effect on CYP3A4 and CYP3A5 than tacrolimus. To avoid graft failure, we measured the cyclosporine blood concentrations at 0, 2, and 6 h after administration to maintain the target level (150-200 ng/mL) within 1 week after initiation of TVR and adjusted the dose of cyclosporine. The dose of cyclosporine was decreased 0.24-0.40 fold in all patients after initiation of TVR treatment. In 3 patients, the dose of TVR was decreased two-thirds of starting dose because of adverse effects, including anorexia and skin rash. However, the HCV RNA level rapidly decreased to undetectable levels within 1 month. Furthermore, all patients completed the TVR therapy in 12 weeks and did not experience liver graft rejection. In addition, we found the rapid elimination of inhibitory effect of TVR on the disposition of cyclospirne in the all four cases and therefore, rapid increase in the dosage of cyclosporine would be required immediately after the end of TVR administration. These results suggest that frequent measurement of cyclosporine levels was important for successful TVR triple therapy and prevention of rejection.

Uniportal left S1 + 2 segmentectomy.

The left upper lobe is one of the largest lobes of the lung; left upper segmentectomy is well established among thoracic surgeons. In uniportal left S1 + 2 segmentectomy, dissection of the vasculature, bronchus, and intersegmental plane can be performed anteriorly. Given that the fissureless technique is commonly used in uniportal video-assisted thoracoscopic surgery, S1 + 2 segmentectomy exhibits high affinity with the unidirectional approach. We have frequently performed left S1 + 2 segmentectomy for early non-small cell lung cancer located in the apical segment, since this procedure has the potential to preserve pulmonary function over tri-segmentectomy. Herein, we introduce our approach to uniportal left S1 + 2 segmentectomy as a minimally invasive alternative for preserving lung function.

Scribble mis-localization induces adaptive resistance to KRAS G12C inhibitors through feedback activation of MAPK signaling mediated by YAP-induced MRAS.

Tumor cells evade targeted drugs by rewiring their genetic and epigenetic networks. Here, we identified that inhibition of MAPK signaling rapidly induces an epithelial-to-mesenchymal transition program by promoting re-localization of an apical-basal polarity protein, Scribble, in oncogene-addicted lung cancer models. Mis-localization of Scribble suppressed Hippo-YAP signaling, leading to YAP nuclear translocation. Furthermore, we discovered that a RAS superfamily protein MRAS is a direct target of YAP. Treatment with KRAS G12C inhibitors induced MRAS expression, which formed a complex with SHOC2, precipitating feedback activation of MAPK signaling. Abrogation of YAP activation or MRAS induction enhanced the efficacy of KRAS G12C inhibitor treatment in vivo. These results highlight a role for protein localization in the induction of a non-genetic mechanism of resistance to targeted therapies in lung cancer. Furthermore, we demonstrate that induced MRAS expression is a key mechanism of adaptive resistance following KRAS G12C inhibitor treatment.

Prognostic significance of preoperative haemoglobin A1c level in patients with lung adenocarcinoma.

OBJECTIVES: We investigated the influence of the preoperative haemoglobin A1c (HbA1c) value on the prognosis and pathology of patients with lung adenocarcinoma who underwent surgery. METHODS: We reviewed the medical records of 400 lung adenocarcinoma patients who underwent lobectomy with mediastinal lymph node dissection between 2009 and 2013 using a prospectively maintained database. We stratified 400 patients into 4 groups according to the preoperative HbA1c value as follows: HbA1c ≤ 5.9 (n = 296), 6.0 ≤ HbA1c ≤ 6.9 (n = 70), 7.0 ≤ HbA1c ≤ 7.9 (n = 21) and HbA1c ≥ 8.0 (n = 12). We compared the recurrence-free survival and overall survival (OS) among these 4 groups. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. RESULTS: The median follow-up period was 61.2 months. On comparing the recurrence-free survival and OS rates among these 4 groups, we found that these rates among patients in the HbA1c ≥ 8.0 group were significantly poorer compared with the other 3 groups (5-year recurrence-free survival: HbA1c ≤ 5.9, 70.4%; 6.0 ≤ HbA1c ≤ 6.9, 69.7%; 7.0 ≤ HbA1c ≤ 7.9, 70.7%; ≥8.0 HbA1c, 18.8%; P = 0.002; and 5-year OS: HbA1c ≤ 5.9, 88.7%; 6.0 ≤ HbA1c ≤ 6.9, 80.6%; 7.0 ≤ HbA1c ≤ 7.9, 90.2%; ≥8.0 HbA1c, 66.7%; P = 0.046). Patients in the HbA1c ≥ 8.0 group had significantly more tumours with vascular invasion (P = 0.041) and experienced distant metastasis significantly more often (P = 0.028) than those with other values. A multivariate analysis revealed that preoperative HbA1c ≥ 8.0 [hazard ratio (HR) 2.33; P = 0.026] and lymph node metastasis (HR 3.94; P < 0.001) were significant independent prognostic factors for recurrence. CONCLUSIONS: Our results revealed that preoperative HbA1c ≥ 8.0 is associated to poor prognosis due to the occurrence of distant metastasis and we should carefully follow these patients after surgery. CLINICAL REGISTRATION NUMBER: Hyogo Cancer Center, G-57.

Lactic acid as a major contributor to hand surface infection barrier and its association with morbidity to infectious disease.

Although the surface of the human hands contains high antimicrobial activity, studies investigating the precise components involved and the relationship between natural antimicrobial activity and morbidity in infectious diseases are limited. In this study, we developed a method to quantitatively measure the antimicrobial activity of hand surface components. Using a clinical survey, we validated the feasibility of our method and identified antimicrobial factors on the surface of the human hand. In a retrospective observational study, we compared the medical histories of the participants to assess infectious diseases. We found that the antimicrobial activity on the surface of the hands was significantly lower in the high morbidity group (N = 55) than in the low morbidity group (N = 54), indicating a positive association with the history of infection in individuals. A comprehensive analysis of the hand surface components indicated that organic acids, especially lactic acid and antimicrobial peptides, are highly correlated with antimicrobial activity. Moreover, the application of lactic acid using the amount present on the surface of the hand significantly improved the antimicrobial activity. These findings suggest that hand hygiene must be improved to enhance natural antimicrobial activity on the surface of the hands.

Pleural invasion, epidermal growth factor receptor mutation and carcinoembryonic antigen level affect pleural lavage cytology-positive status in non-small-cell lung cancer.

OBJECTIVES: Pleural invasion (pl) is strongly associated with the pleural lavage cytology (PLC) status. We analysed tumours with pl and evaluated the relationship between the PLC status and pl. METHODS: We retrospectively reviewed 428 surgically treated patients who had been diagnosed with non-small-cell lung cancer with pl and had their PLC status examined between 2000 and 2016. We investigated the influence of a PLC-positive status on the prognosis and searched for the factors predictive of a PLC-positive status. RESULTS: Seventy-eight (18%) patients were PLC positive. The recurrence-free survival of PLC-positive patients was significantly worse than that of PLC-negative patients in pl1 and pl2, but not in pl3 (5-year recurrence-free survival rate, PLC positive versus PLC negative: pl1, 22.0% vs 60.0%, P = 0.002; pl2, 30.4% vs 59.7%, P = 0.015; pl3, 50.0% vs 59.6%, P = 0.427). A multivariable analysis showed that the degree of pl (pl2-3 versus pl1) [odds ratio (OR) 5.34, P < 0.001] was an independent predictive factor for PLC positivity. Epidermal growth factor receptor (EGFR) mutation positivity (OR 5.48, P = 0.042) and carcinoembryonic antigen (CEA) ≥5 ng/ml (OR 3.78, P = 0.042) were associated with a PLC-positive status in patients with pl2-3. We found that the PLC-positive rate in patients with pl2-3 was 35.6%; however, if the tumour was EGFR mutation positive and had CEA ≥5 ng/ml, the PLC-positive rate increased to 77%. CONCLUSIONS: If a tumour was suspected of being pl2-3 and had EGFR mutation positivity and CEA ≥5 ng/ml, the PLC-positive rate was extremely high. CLINICAL TRIAL REGISTRATION NUMBER: Hyogo Cancer Center, G-138.

Thoracoscopic left S1 + 2 segmentectomy as a good resolution for preserving pulmonary function.

OBJECTIVES: Segmentectomies such as S1 + 2, S1 + 2+3 and S4 + 5 segmentectomy are used to treat patients with non-small-cell lung cancer (NSCLC) in the left upper lobe. However, the preservable lung volume and changes after such segmentectomies remain unknown. We compared the residual pulmonary function after thoracoscopic segmentectomy or lobectomy in the left upper lobe and examined the efficacy of S1 + 2 segmentectomy regarding postoperative pulmonary function. METHODS: Patients with left upper lobe NSCLC who underwent thoracoscopic segmentectomy or lobectomy were included. Spirometry and computed tomography were performed before and 6 months after resection, and the ipsilateral preserved lobe volume was calculated using 3-dimensional computer tomography. The percentage of postoperative/preoperative forced expiratory volume in 1 s and actual/predicted regional forced expiratory volume in 1 s (preservation rate) in the residual lobe were compared. RESULTS: Eighty-eight patients underwent lobectomy and 70 patients underwent segmentectomy (23 S1 + 2, 35 S1 + 2+3 and 12 S4 + 5 segmentectomies). The percentage of postoperative/preoperative forced expiratory volume in 1 s was 97 in S1 + 2, 82 in S1 + 2+3, 86 in S4 + 5 segmentectomy and 73 in left upper lobectomy, indicating that segmentectomy could be a meaningful approach to preserve pulmonary function. The preservation rate was 83% in S1 + 2 and 62% in S1 + 2+3 segmentectomy and was significantly higher in S1 + 2 than in S1 + 2+3 segmentectomy (P < 0.001). CONCLUSIONS: Postoperative pulmonary function and the preservable lung volume of the residual lobe after thoracoscopic S1 + 2 segmentectomy were well-preserved among other segmentectomies and lobectomy. Thoracoscopic S1 + 2 segmentectomy is a good alternative for preserving postoperative function.

Pneumatocele triggered by continuous positive airway pressure after lung resection.

A pneumatocele is a cystic change of the lung that is caused by a check valve in the bronchiole due to infection, trauma and positive-pressure ventilation. We herein report a case of pneumatocele triggered by using of continuous positive airway pressure (CPAP) for sleep apnea syndrome (SAS) after pulmonary resection. A 69-year-old man underwent right upper lobectomy for lung cancer and developed interstitial pneumonia (IP) 10th postoperative day (POD). He was treated with steroid pulse therapy (solmedrol 500 mg × 3 days), and thereafter with oral steroid therapy (predonin 30mg/day). Well responded to the steroid therapy, IP was improved. However, he noticed bloody sputum 29th POD, and chest computed tomography showed a giant cystic lesion on the dorsal right lower lobe. We resected the cyst and the pathological findings revealed that the cystic lesion was pneumatocele, and CPAP was strongly suspected of triggering this disease.

DLL3 expression is a predictive marker of sensitivity to adjuvant chemotherapy for pulmonary LCNEC.

BACKGROUND: The mammalian Notch family ligands delta-like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated. METHODS: We reviewed the medical records of 70 LCNEC patients undergoing surgical resection between 2001 and 2015 using a prospectively maintained database. We performed immunohistochemistry for DLL3 and investigated the correlation between the sensitivity of LCNEC to platinum-based adjuvant chemotherapy. RESULTS: DLL3 expression was positive in 26 (37.1%) LCNEC patients. A total of 23 patients (32.9%) received platinum-based adjuvant chemotherapy. Among patients with DLL3 expression-positive tumors, no difference was found in the five-year overall survival (OS) or recurrence-free survival (RFS) between patients with and without adjuvant chemotherapy (surgery + chemotherapy vs. surgery alone, five-year OS: 58.3% vs. 35.7% P = 0.36, five-year RFS: 41.7% vs. 35.7% P = 0.74). In contrast, among patients with DLL3-negative tumors, significantly greater five-year OS and RFS rates were observed for patients with adjuvant chemotherapy than for those without it (surgery + chemotherapy vs. surgery alone: five-year OS: 90.0% vs. 26.9% P<0.01, five-year RFS: 80.0% vs. 21.7% P < 0.01). A multivariate analysis for the RFS revealed that adjuvant chemotherapy was a significant independent prognostic factor among patients with DLL3-negative tumors (hazard ratio [HR]: 0.05, 95% confidence interval [CI]: 0.01-0.41, P < 0.01), although it was not a factor among patients with DLL3-positive tumors (HR: 0.73, 95% CI: 0.23-2.27, P = 0.58). CONCLUSIONS: Our results revealed that DLL3 is a predictive marker of sensitivity to platinum-based adjuvant chemotherapy for LCNEC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: DLL3 was a predictive marker of sensitivity to platinum-based adjuvant chemotherapy for LCNEC. Among patients with DLL3 expression-negative LCNEC, platinum-based adjuvant chemotherapy significantly improved the OS and RFS, although it did not do so among patients with DLL3 expression-positive LCNEC. WHAT THIS STUDY ADDS: Our results suggest that DLL3 expression-positive LCNEC may be better treated with other types of adjuvant chemotherapy, such as the anti-DLL3 therapies if these effects are confirmed by ongoing clinical research.

A rare resected case of pulmonary rhabdomyosarcoma.

Rhabdomyosarcoma is a well-known neoplasm in children that frequently occurs in the extremities, the head and neck region, and the genitourinary tract. To the best of our knowledge, pulmonary primary rhabdomyosarcoma in adults is exceedingly rare, and few resected cases have been reported. We report a case of pulmonary primary rhabdomyosarcoma that was surgically resected then treated with adjuvant chemotherapy (vincristine, actinomycin-D and cyclophosphamide). At 9 months after surgery, the patient is free from disease. Although the prognosis of rhabdomyosarcoma is unfavorable, surgical resection and adjuvant therapy could be a potential treatment strategy for pulmonary primary rhabdomyosarcoma.

Evaluation of the Residual Lung Function After Thoracoscopic Segmentectomy Compared With Lobectomy.

BACKGROUND: Segmentectomy has shown a beneficial effect on preserving lung function after resection. However, the preservable lung volume and changes after thoracoscopic segmentectomy remain unknown. We compared the residual lung function after thoracoscopic segmentectomy and lobectomy, using a novel three-dimensional computed tomography-based volumetric method. METHODS: Seventy-four patients who received thoracoscopic segmentectomy were matched to the 74 patients who received thoracoscopic lobectomy. Spirometry and computed tomography were performed before and 6 months after resection, and the ipsilateral residual preserved and nonoperated lobe volume and the contralateral lung volume were calculated using three-dimensional computed tomography. The percentage of actual/predicted regional forced expiratory volume in 1 second (the preservation rate) in each lobe (measured by volumetry and spirometry) was compared with the extent of resection and procedural difficulty (typical or atypical segmentectomy). RESULTS: The postoperative lung function was significantly more well preserved in segmentectomy than in lobectomy. After segmentectomy and lobectomy, the regional forced expiratory volume in 1 second of the ipsilateral unaffected lobe was increased in comparison with the preoperative value, whereas that of the residual lobe rescued by segmentectomy was decreased. The preservation rates of the residual and unaffected lobes were inversely and positively correlated, respectively, with the extent of the resected segment. The preservation rates of the residual lobe after typical or atypical segmentectomy were not significantly different. CONCLUSIONS: Although the decrease in the actual lung function of the residual lobe was greater than predicted and increased with increasing extent of resection, segmentectomy preserved the whole lung function better than lobectomy.

Asymmetric [2 + 2] olefin cross photoaddition in a self-assembled host with remote chiral auxiliaries.

Remote chirality at the periphery of a self-assembled cage brings about the slight twist of aromatic rings, which is yet sufficient to induce considerable asymmetric induction (up to 50% ee) in the hitherto unknown [2 + 2] cross photoadditions of fluoranthenes.

Coexpression of WUSCHEL related homeobox (WOX) 2 with WOX8 or WOX9 promotes regeneration from leaf segments and free cells in Nicotiana tabacum L.

To examine the effect of the ectopic expression of three Arabidopsis genes, including WOX2, WOX8 and WOX9, on the regenerative competency of tissues and cells cultured in vitro, we developed a transgenic variety of Nicotiana tabacum, in which these genes were under the transcriptional control of a chemical-inducible expression system. We designed a two-step culture method to feasibly demonstrate the effect as follows. Leaf segments of approximately 10 mm2 were prepared from transgenic plants and their hybrids and cultured in a liquid medium based on modified Murashige and Skoog medium supplemented with an auxin, 2,4-dichrorophenoxyacetic acid and/or an expression inducer ß-estradiol for 10 days in dark. The segments were subsequently cultured on a solidified medium in the absence of both the auxin and inducer in light for 3 weeks. We observed remarkable regeneration of plantlets only in segments derived from the hybrids possessing two transgenes, WOX2 combined with WOX8 or WOX9, but no regeneration in the segments derived from their parental lines. We also observed that free cells released from the hybrid explants in the liquid medium developed into embryo-like structures due to the transient application of the inducer. In a wide range of species including recalcitrants, the effect of the coexpression of these genes may be useful for developing an alternative to conventional protocols that requires cytokinin.

Dietary patterns and blood levels of PCDDs, PCDFs, and dioxin-like PCBs in 1656 Japanese individuals.

The association between dietary patterns and blood dioxin levels has not been fully investigated. The present study population consisted of 755 men and 901 women (aged 15-73years) living in 90 different areas of 30 prefectures of Japan. Dietary habits were assessed by inquiring about the consumption frequency of 28 foods, food groups and beverages. In addition, the blood levels of 29 polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzo-furans (PCDFs), and dioxin-like polychlorinated biphenyl (DL-PCBs) congeners were determined by high-resolution gas chromatography/mass spectrometry. The median total toxicity equivalent (TEQ) in the blood, which was calculated on the basis of the toxicity equivalency factors of WHO (2005), was 16 pg TEQg(-1) lipid. Principal component analysis identified five dietary patterns: Healthy diet (high intake of vegetables and fruits); Meat/High fat intake (high intake of meat, meat products, and eggs); Seafood and Alcohol (high intake of fish, shellfish, and alcoholic beverages); Miscellaneous; and Milk products and Alcohol intake (high intake of milk, Milk products, and alcoholic beverages). After adjusting for sex, age, body mass index, and smoking habits, the Seafood and Alcohol pattern scores were significantly related to higher blood levels of total TEQ and PCDDs/PCDFs/DL-PCBs, and the Milk products and Alcohol pattern scores were correlated with higher blood levels of DL-PCBs. More detailed analysis showed that the intake frequencies for alcoholic beverages and seafood were independently and positively associated with total TEQ and the TEQ of PCDFs and DL-PCBs. The association between alcoholic beverage intake and PCDDs was also significant. Analysis of dietary patterns may be useful for identifying the dietary characteristics of individuals with a high dioxin body burden.

Both [2+2] and [2+4] additions of inert aromatics via identical ternary host-guest complexes.

A self-assembled coordination cage enables inert aromatics to undergo both [2+2] and [2+4] cycloadditions by encapsulating them within the cavity. Aceanthrylene reacts with a maleimide derivative under thermal and photo-irradiation conditions to give a product as a single regio- and stereoisomer.

cis9, trans11-Conjugated Linoleic Acid Differentiates Mouse 3T3-L1 Preadipocytes into Mature Small Adipocytes through Induction of Peroxisome Proliferator-activated Receptor γ.

Dietary conjugated linoleic acid (CLA) has been reported to exhibit a number of therapeutic effects in animal models and patients, such as anti-hypertensive, anti-hyperlipidemic, anti-arteriosclerotic, anti-carcinogenic, and anti-diabetic effects. However, the underlying mechanism is not well-characterized. In the present study, the effects of cis(c)9, trans(t)11-CLA on the differentiation of mouse 3T3-L1 preadipocytes into mature adipocytes were examined. Treatment with c9, t11-CLA in the presence of insulin, dexamethasone, and 3-isobutyl-1-methyl-xanthine (differentiation cocktail) significantly stimulated the accumulation of triacylglycerol. The microscopic observation of cells stained by Oil Red O demonstrated that c9, t11-CLA increases the amount and proportion of small mature adipocytes secreting adiponectin, a benign adipocytokine, when compared to the differentiation cocktail alone. Furthermore, c9, t11-CLA increased bioactive peroxisome proliferator-activated receptor γ (PPARγ) levels in a nuclear extract of 3T3-L1 cells, suggesting the enhancing effect of this fatty acid on the nuclear transmission of PPARγ, a master regulator of adipocyte differentiation, in 3T3-L1 cells. These results suggest that the therapeutic effects of c9, t11-CLA on lifestyle-related diseases are partially due to the enhanced formation of small adipocytes from preadipocytes via PPARγ stimulation.