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Introduction: Low-dose computed tomography screening (LDCT) and lung nodule programs (LNP) promote early lung cancer detection, improve survival; Multidisciplinary Care Programs (MDC) promote guideline-concordant care. The impact of such program-based care on “real-world” lung cancer survival is unquantified. We evaluated outcomes of lung cancer care delivered through structured programs in a community health care system. Methods: We conducted a cohort study linking institutional prospective observational LDCT, LNP and MDC databases with Tumor Registry of Baptist Cancer Center facilities. We categorized all patients diagnosed with lung cancer between 2011 and 2021 into program-based care versus non-program-based care cohorts. We compared patient characteristics, stage distribution, treatment modalities, survival and mortality in each pathway of care. Results: Of 12,148 patients, 237, 1,165, 1,140 and 9,606 were diagnosed through the LDCT, LNP, MDC or no program, respectively; non-program-based care sequentially diminished from 96.3% to 66.5%, diagnosis through LDCT increased from 0.5% to 7.1%, LNP from 3.5% to 20.8%; and MDC alone decreased from a high of 12.8% in 2014 to 5.6% in 2021. Program-based care was associated with earlier stage (p < 0.001), higher surgical resection rates (p < 0.001), greater use of adjuvant therapy (p < 0.001), better aggregate and stage-stratified survival (p < 0.001), and lower all-cause and lung cancer-specific mortality (p < 0.001). Recipients of non-program-based care were considerably less likely to receive lung cancer treatment; results remained consistent when patients receiving no treatment were excluded. Conclusions: Program-based care was associated with substantially better survival. Increasing access to program-based care should be explored as a matter of urgent public policy.

Introduction: We compared NSCLC treatment and survival within and outside a multidisciplinary model of care from a large community health care system. Methods: We implemented a rigorously benchmarked “enhanced” Multidisciplinary Thoracic Oncology Conference (eMTOC) and used Tumor Registry data (2011–2017) to evaluate guideline-concordant care. Because eMTOC was located in metropolitan Memphis, we separated non-MTOC patient by metropolitan and regional location. We categorized National Comprehensive Cancer Network guideline-concordant treatment as “preferred,” or “appropriate” (allowable under certain circumstances). We compared demographic and clinical characteristics across cohorts using chi-square tests and survival using Cox regression, adjusted for multiple testing. We also performed propensity-matched and adjusted survival analyses. Results: Of 6259 patients, 14% were in eMTOC, 55% metropolitan non-MTOC, and 31% regional non-MTOC cohorts. eMTOC had the highest rates of African Americans (34% versus 28% versus 22%), stages I to IIIB (63 versus 40 versus 50), urban residents (81 versus 78 versus 20), stage-preferred treatment (66 versus 57 versus 48), guideline-concordant treatment (78 versus 70 versus 63), and lowest percentage of nontreatment (6 versus 21 versus 28); all p values were less than 0.001. Compared with eMTOC, hazard for death was higher in metropolitan (1.5, 95% confidence interval: 1.4–1.7) and regional (1.7, 1.5–1.9) non-MTOC; hazards were higher in regional non-MTOC versus metropolitan (1.1, 1.0–1.2); all p values were less than 0.05 after adjustment. Results were generally similar after propensity analysis with and without adjusting for guideline-concordant treatment. Conclusions: Multidisciplinary NSCLC care planning was associated with significantly higher rates of guideline-concordant care and survival, providing evidence for rigorous implementation of this model of care.

Spectral image (SI) measurement techniques, such as X-ray absorption fine structure (XAFS) imaging and scanning transmission electron microscopy (STEM) with energy-dispersive X-ray spectroscopy (EDS) or electron energy loss spectroscopy (EELS), are useful for identifying chemical structures in composite materials. Machine-learning techniques have been developed for automatic analysis of SI data and their usefulness has been proven. Recently, an extended measurement technique combining SI with a computed tomography (CT) technique (CT-SI), such as CT-XAFS and STEM-EDS/EELS tomography, was developed to identify the three-dimensional (3D) structures of chemical components. CT-SI analysis can be conducted by combining CT reconstruction algorithms and chemical component analysis based on machine-learning techniques. However, this analysis incurs high-computational costs owing to the size of the CT-SI datasets. To address this problem, this study proposed a fast computational approach for 3D chemical component analysis in an unsupervised learning setting. The primary idea for reducing the computational cost involved compressing the CT-SI data prior to CT computation and performing 3D reconstruction and chemical component analysis on the compressed data. The proposed approach significantly reduced the computational cost without losing information about the 3D structure and chemical components. We experimentally evaluated the proposed approach using synthetic and real CT-XAFS data, which demonstrated that our approach achieved a significantly faster computational speed than the conventional approach while maintaining analysis performance. As the proposed procedure can be implemented with any CT algorithm, it is expected to accelerate 3D analyses with sparse regularized CT algorithms in noisy and sparse CT-SI datasets., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

This study investigates the compositional analysis and growth of β-(In x Ga 1- x ) 2 O 3 thin films on (010) β-Ga 2 O 3 substrates using mist chemical vapor deposition (CVD), including the effects of the growth temperature. We investigated the correlation between In composition and b -axis length in coherently grown films, vital for developing high-electron-mobility transistors and other devices based on β-(In x Ga 1- x ) 2 O 3 . Analytical techniques, including X-ray diffraction (XRD), reciprocal space mapping, and atomic force microscopy, were employed to evaluate crystal structure, strain relaxation, and surface morphology. The study identified a linear relationship between In composition and b -axis length in coherently grown films, facilitating accurate composition determination from XRD peak positions. The films demonstrated high surface flatness with root-mean-square roughness below 0.6 nm, though minor relaxation and granular features emerged at higher In compositions ( x  = 0.083) at the growth temperature of 750°C. XRD results revealed that lattice relaxation were observed at a growth temperature of 700°C despite low In composition. In contrast, at 800°C, the In composition was higher than at 750°C, and coherent growth was achieved. The surface morphology was the flattest at 750°C. These findings indicate that the growth temperature plays a crucial role in the mist CVD growth of β-(In x Ga 1- x ) 2 O 3 thin films. This study offers insights into the relationship between In composition and lattice parameters in coherently grown β-(In x Ga 1- x ) 2 O 3 films, as well as the effect of growth conditions, contributing to the advancement of ultra-wide bandgap semiconductor device development., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by National Institute for Materials Science in partnership with Taylor & Francis Group.)

The design of kinase inhibitors targeting the oncogenic kinase BCR-ABL constitutes a promising paradigm for treating chronic myeloid leukaemia (CML). Nevertheless, the efficacy of imatinib, the first FDA-approved targeted therapy for CML, is curbed by the emergence of resistance. Herein, we report the identification of the 2-methoxyphenyl ureidobenzothiazole AK-HW-90 (2b) as a potent pan-BCR-ABL inhibitor against imatinib-resistant mutants, particularly T315I. A concise array of six compounds 2a - f was designed based on our previously reported benzothiazole lead AKE-5l to improve its BCR-ABL T315I inhibitory activity. Replacing the 6-oxypicolinamide moiety of AKE-5l with o -methoxyphenyl and changing the propyl spacer with phenyl afforded 2a and AK-HW-90 (2b) with IC 50 values of 2.0 and 0.65 nM against BCR-ABL T315I , respectively. AK-HW-90 showed superior anticancer potency to imatinib against multiple cancer cells (NCI), including leukaemia K-562. The obtained outcomes offer AK-HW-90 as a promising candidate for the treatment of CML and other types of cancer.

Background: Persistent high-risk Human papillomavirus (HR-HPV) infections are the main cause of cervical cancer. Cumulative evidence implicates regulatory T cells (Tregs) as a critical factor in the failure to eliminate HPV-induced cancers leading to their persistence and progression to cancer. Also, the WHO recognised cervical cancer as 100% attributable to persistent HR-HPV infection. The province of KwaZulu-Natal (KZN) in South Africa has a high prevalence of cervical cancer and HIV infection., Materials and Methods: We evaluated Treg frequency in dual infection of HR HPV and HIV coinfection using phenotypic markers, CD4, CD25 and intracellular Foxp3, in the peripheral blood of 51 cervical cancer and 46 non-cervical cancer participants and evaluated the effect of HIV on regulatory T cell proportion. Peripheral blood mononuclear cells were surface stained with a cocktail fluorescent labelled CD4 and CD25 and subsequently with APC anti-human FoxP3 (eBioscience). Flow cytometry was performed with FACS analysis. Statistical analysis of results was done using Instat 3 program (GraphpadR). Tregs results were expressed as median ± interquartile range (IQR). Associations of cervical cancer with demographic, clinical and laboratory variables were evaluated by univariate and multivariate logistic regression analysis using SPSS version 27 (IBM)., Results: Tregs frequency was significantly higher in individuals with cervical cancer (11.00 ± 19.79%) compared to controls (1.71 ± 8.91%) (p < 0.0001). HIV infection was associated with an increase in Tregs frequency. In controls a significant difference in Tregs frequency was noted between women living with HIV (6.00 ± 10.57%, n = 9) and those without HIV (1.30 ± 6.10%, n = 37), p = 0.0023. In multivariate logistic regression, Tregs frequency was significantly associated with cervical cancer after controlling for age, smoking, weight loss, presence of STI, HIV and HPV genotype., Discussion/conclusion: Higher Tregs frequency was significantly associated with cervical cancer highlighting the immunosuppressive role of Tregs in cervical cancer. Treg frequency was more strongly associated with cervical cancer than HIV infection. We provide baseline data for monitoring Treg frequencies in response to new preventive and therapeutic strategies in the management of cervical cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Intercalated metal-organic frameworks (iMOFs) based on aromatic dicarboxylate are appealing negative electrode active materials for Li-based electrochemical energy storage devices. They store Li ions at approximately 0.8 V vs. Li/Li + and, thus, avoid Li metal plating during cell operation. However, their fast-charging capability is limited. Here, to circumvent this issue, we propose iMOFs with multi-aromatic units selected using machine learning and synthesized via solution spray drying. A naphthalene-based multivariate material with nanometric thickness allows the reversible storage of Li-ions in non-aqueous Li metal cell configuration reaching 85% capacity retention at 400 mA g -1 (i.e., 30 min for full charge) and 20 °C compared to cycling at 20 mA g -1 (i.e., 10 h for full charge). The same material, tested in combination with an activated carbon-based positive electrode, enables a discharge capacity retention of about 91% after 1000 cycles at 0.15 mA cm -2 (i.e., 2 h for full charge) and 20 °C. We elucidate the charge storage mechanism and demonstrate that during Li intercalation, the distorted crystal structure promotes electron delocalization by controlling the frame vibration. As a result, a phase transition suppresses phase separation, thus, benefitting the electrode's fast charging behavior., (© 2023. The Author(s).)

Molecular dynamics simulation is a method of investigating the behavior of molecules, which is useful for analyzing a variety of structural and dynamic properties and mechanisms of phenomena. However, the huge computational cost of large-scale and long-time simulations is an enduring problem that must be addressed. MD-GAN is a machine learning-based method that can evolve part of the system at any time step, accelerating the generation of molecular dynamics data [Endo et al. , Proceedings of the AAAI Conference on Artificial Intelligence , 2018, 32 ]. For the accurate prediction of MD-GAN, sufficient information on the dynamics of a part of the system should be included with the training data. Therefore, the selection of the part of the system is important for efficient learning. In a previous study, only one particle (or vector) of each molecule was extracted as part of the system. The effectiveness of adding information from other particles to the learning process is investigated in this study. When the dynamics of three particles of each molecule were used in the polyethylene experiment, the diffusion was successfully predicted using the training data with a time length of approximately 40%, compared to the single-particle input. Surprisingly, the unobserved transition of diffusion in the training data was also predicted using this method. The reduced cost for the generation of training MD data achieved in this study is useful for accelerating MD-GAN.

Introduction: Complete and accurate pathology reports are vital to postoperative prognostication and management. We evaluated the impact of three interventions across a diverse group of hospitals on pathology reports of postresection NSCLC., Methods: We evaluated pathology reports for patients who underwent curative-intent surgical resection for NSCLC, at 11 institutions within four contiguous Dartmouth Hospital Referral Regions in Arkansas, Mississippi, and Tennessee from 2004 to 2020, for completeness and accuracy, before and after the following three quality improvement interventions: education (feedback to heighten awareness); synoptic reporting; and a lymph node specimen collection kit. We compared the proportion of pathology reports with the six most important items for postoperative management (specimen type, tumor size, histologic type, pathologic [p] T-category, pN-category, margin status) across the following six patient cohorts: preintervention control, postintervention with four different combinations of interventions, and a contemporaneous nonintervention external control., Results: In the postintervention era, the odds of reporting all key items were eight times higher than those in the preintervention era (OR = 8.3, 95 % confidence interval [CI]: 6.7-10.2, p < 0.0001). There were sixfold and eightfold increases in the odds of accurate pT- and pN-category reporting in the postintervention era compared with the preintervention era (pT OR = 5.7, 95 % CI: 4.7-6.9; pN OR = 8.0, 95 % CI: 6.5-10.0, both p < 0.0001). Within the intervention groups, the odds of reporting all six key items, accurate pT category, and accurate pN-category were highest in patients who received all three interventions., Conclusions: Gaps in the quality of NSCLC pathologic reportage can be identified, quantified, and corrected by rationally designed interventions., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

There have been various studies on the effects of emotional visual processing on subsequent non-emotional auditory stimuli. A previous study with EEG has shown that responses to deviant sounds presented after presenting negative pictures collected more attentional resources than those for neutral pictures. To investigate such a compelling between emotional and cognitive processing, this study aimed to examined pupillary responses to an auditory stimulus after a positive, negative, or neutral emotional state was elicited by an emotional image. An emotional image was followed by a beep sound that was either repetitive or unexpected, and the pupillary dilation was measured. As a result, we found that the early component of the pupillary response to the beep sound was larger for negative and positive emotional states than the neutral emotional state, whereas the late component was larger for the positive emotional state than the negative and neutral emotional states. In addition, the peak latency of the pupillary response was earlier for negative than neutral or positive images. Further, to compensate for the disadvantage of low-temporal resolution of the pupillary data, the pupillary responses were deconvoluted and used in the analysis. The deconvolution analysis of pupillary responses confirmed that the responses to beep sound were more likely to be modulated by the emotional state rather than being influenced by the short presentation interval between the images and sounds. These findings suggested that pupil size index modulations in the compelling situation between emotional and cognitive processing., (© 2021. The Author(s).)

Proton-conductive polymer electrolyte membranes (PEMs) were prepared by infiltrating sulfuric acid (Sa) or phosphoric acid (Pa) into a polystyrene- b -poly(4-vinylpyridine)- b -polystyrene (S-P-S) triblock copolymer. When the molar ratio of acid to pyridyl groups in S-P-S, i.e. , the acid doping level (ADL), is below unity, the P-block/acid phase in the PEMs exhibited a moderately high glass transition temperature ( T g ) of ∼140 °C because of consumption of acids for forming the acid-base complexes between the pyridyl groups and the acids, also resulting in almost no free protons in the PEMs; therefore, the PEMs were totally glassy and exhibited almost no anhydrous conductivity. In contrast, when ADL is larger than unity, the T g s of the phase composed of acid and P blocks were lower than room temperature, due to the excessive molar amount of acid serving as a plasticizer. Such swollen PEMs with excessive amounts of acid releasing free protons were soft and exhibited high conductivities even without humidification. In particular, an S-P-S/Sa membrane with ADL of 4.6 exhibited a very high anhydrous conductivity of 1.4 × 10 -1 S cm -1 at 95 °C, which is comparable to that of humidified Nafion membranes. Furthermore, S-P-S/Sa membranes with lower T g s exhibited higher conductivities than S-P-S/Pa membranes, whereas the temperature dependence of the conductivities for S-P-S/Pa is stronger than that for S-P-S/Sa, suggesting Pa with a lower acidity would not be effectively dissociated into a dihydrogen phosphate anion and a free proton in the PEMs at lower temperatures., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Prompted by the urgent demand for identification of new anticancer agents with improved potency and efficacy, a new series of arylamides incorporating the privileged 2-anilinoquinoline scaffold has been designed, synthesized, and biologically assessed. Aiming at extensive evaluation of the target compounds' potency and spectrum, a panel of 60 clinically important cancer cell lines representing nine cancer types has been used. Compounds 9a and 9c, with piperazine substituted phenyl ring, emerged as the most active members surpassing the anticancer potencies of the FDA-approved drug imatinib. They elicited sub-micromolar or one-digit micromolar GI 50 values over the majority of tested cancer cells including multidrug resistant (MDR) cells like colon HCT-15, renal TK-10 and UO-31, and ovarian NCI/ADR-RES. In vitro mechanistic study showed that compounds 9a and 9c could trigger morphological changes, apoptosis and cell cycle arrest in HCT-116 colon cancer cells. Besides, compound 9c altered microtubule polymerization pattern in a similar fashion to paclitaxel. Kinase screening of 9c disclosed its inhibitory activity over B-RAF V600E and C-RAF kinases with IC 50 values of 0.888 μM and 0.229 μM, respectively. Taken together, the current report presents compounds 9a and 9c as promising broad-spectrum potent anticancer candidates, which could be considered for further development of new anticancer drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Masson SAS.)

We tested the hypothesis that α-lactalbumin inhibits the disruption of intestinal barrier function and liver cirrhosis by restoring gut-liver axis function in thioacetamide (TAA) -treated rats. Rat diets were supplemented with α-lactalbumin replacing 50% of dietary protein. After consuming α-lactalbumin for one week, rats were intraperitoneally injected with TAA twice a week for 14 weeks. The α-lactalbumin-enriched diet significantly inhibited the elevation of plasma alanine aminotransferase, aspartate aminotransferase, and hyaluronic acids. The supplement significantly reduced plasma lipopolysaccharide levels and increased occludin mRNA level. Hepatic fibrosis and regenerative nodules was developed and intestinal villi were shortened by TAA; α-Lactalbumin attenuated these histopathological changes. These results indicated that α-lactalbumin improved intestinal barrier function, suppressing endotoxin levels. These data also suggested that α-lactalbumin ameliorated the impairment of the gut-liver axis by TAA, inhibiting the development of liver cirrhosis.

The flavor deterioration of mayonnaise is induced by iron, which is released from egg yolk phosvitin under acidic conditions and promotes lipid oxidation. To prevent oxidative deterioration, natural components, rather than synthetic chemicals such as ethylenediaminetetraacetic acid have been required by consumers. In the present study, we evaluated the inhibitory effects of three egg white components with the same amino acid composition, namely egg white protein, hydrolysate, and the amino acid mixture, on lipid oxidation in mayonnaise and an acidic egg yolk solution as a model system. We found that the hydrolysate had the strongest inhibitory effect on lipid oxidation among the three components. The mechanism underlying the antioxidant effect was associated with Fe 2+ -chelating activity. Thus, egg white hydrolysate may have the potential as natural inhibitors of lipid oxidation in mayonnaise.

The cyanidation process has been, and still remains, a profitable and highly efficient process for the recovery of precious metals from ores. However, this process has contributed to environmental deterioration and potable water reserve contamination due to the discharge of poorly treated, or untreated, cyanide containing wastewater. The process produces numerous cyanide complexes in addition to the gold cyanocomplex. Additionally, the discharge constituents also include hydrogen cyanide (HCN) - metallic complexes with iron, nickel, copper, zinc, cobalt and other metals; thiocyanate (SCN); and cyanate (CNO). The fate of these complexes in the environment dictates the degree to which these species pose a threat to living organisms. This paper reviews the impact that the cyanidation process has on the environment, the ecotoxicology of the cyanidation wastewater and the treatment methods that are currently utilised to treat cyanidation wastewater. Furthermore, this review proposes an integrated biological approach for the treatment of the cyanidation process wastewater using microbial consortia that is insensitive and able to degrade cyanide species, in all stages of the proposed process., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Waste generated by the electrical and electronic devices is huge concern worldwide. With decreasing life cycle of most electronic devices and unavailability of the suitable recycling technologies it is expected to have huge electronic and electrical wastes to be generated in the coming years. The environmental threats caused by the disposal and incineration of electronic waste starting from the atmosphere to the aquatic and terrestrial living system have raised high alerts and concerns on the gases produced (dioxins, furans, polybrominated organic pollutants, and polycyclic aromatic hydrocarbons) by thermal treatments and can cause serious health problems if the flue gas cleaning systems are not developed and implemented. Apart from that there can be also dissolution of heavy metals released to the ground water from the landfill sites. As all these electronic and electrical waste do posses richness in the metal values it would be worth recovering the metal content and protect the environmental from the pollution. Cyanide leaching has been a successful technology worldwide for the recovery of precious metals (especially Au and Ag) from ores/concentrates/waste materials. Nevertheless, cyanide is always preferred over others because of its potential to deliver high recovery with a cheaper cost. Cyanidation process also increases the additional work of effluent treatment prior to disposal. Several non-cyanide leaching processes have been developed considering toxic nature and handling problems of cyanide with non-toxic lixiviants such as thiourea, thiosulphate, aqua regia and iodine. Therefore, several recycling technologies have been developed using cyanide or non-cyanide leaching methods to recover precious and valuable metals., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The isomaltulose based liquid formula (MHN-01), suppresses postprandial plasma glucose and insulin levels in healthy persons and patients with impaired glucose tolerance (IGT) or type 2 diabetes. MHN-01 intake as a part of breakfast also suppresses glucose and insulin levels after lunch, suggesting second meal effect. The objective of this study was to investigate the effects of nutritional counseling and long-term (24 weeks) MHN-01 ingestion on biomarkers of metabolic syndrome. Forty-one subjects with criteria of metabolic syndrome participated in this study composed with the control period (0-12 week) followed by nutritional counseling and the experimental period (12-36 week) followed by 200 kcal (837 kJ) of MHN-01 or dextrin-based standard balanced liquid formula (SBF) loading as a part of breakfast. In 16 of 41 subjects became to out of criteria for liquid formula loading study during control period (unqualified group). In the unqualified group, several biomarkers were improved. In experimental period, serum HbA1c levels significantly increased in SBF group (n = 12) but did not change in MHN-01 group (n = 10). Thus, intake of 837 kJ MHN-01 as a part of breakfast may be effective for suppression of deteriorating glucose metabolism in metabolic syndrome.

Background: Systemic inflammation is present in chronic obstructive pulmonary disease (COPD). A whey peptide-based enteral diet reduce inflammation in patients with COPD, but its effect on COPD development has not been determined. On the other hand, it is known that short chain fatty acids (SCFAs), which are produced by micro-flora in the gut, attenuates bronchial asthma in mice model., Methods: Mice with elastase-induced emphysema were fed with 1 of 3 diets (control diet, whey peptide-based enteral diet, or standard enteral diet) to determine the effects of whey peptide-based enteral diet on emphysema and on cecal SCFAs., Results: The whey peptide-based enteral diet group exhibited fewer emphysematous changes; significantly lower total cell counts in bronchoalveolar lavage fluid (BALF); and significantly higher cecal SCFA levels than either the control or standard enteral diet groups. The total cell count was inversely correlated with total cecal SCFA levels in these three diet groups., Conclusions: The whey peptide-based enteral diet attenuates elastase-induced emphysema through the suppression of inflammation in the lung. This may be related to the increase in cecal SCFA.

Background: Osteoarthritis (OA) is the most frequent articular disease and a leading cause of disability. There is a need for effective treatments able to slow the progression of disease. Some of the available treatments are dietary supplements providing natural components. Recent studies have shown that estrogen deficiency contributes to the pathophysiological events of OA progression., Methods: We have used the anterior cruciate ligament transection model of OA in ovariectomised rats to study the effects of BIS076, a new formulation of a natural porcine cartilage extract associated with hydroxyapatite (as a source of calcium) and vitamin D3. Cartilage degradation, proteoglycan depletion and synovitis were followed by histochemistry. Effects on bone microstructure were determined by μCT. The levels of biomarkers in serum and inflammatory mediators in knee homogenates were measured by luminex or ELISA., Results: Oral administration of BIS076 reduced articular cartilage damage and serum levels of cartilage degradation markers C-telopeptide of type II collagen and cartilage oligomeric matrix protein, as well as matrix metalloproteinase-3. The local inflammatory response was down-regulated by BIS076 with lower production of pro-inflammatory cytokines and prostaglandin E2 in joint tissues. In addition, BIS076 was effective on metaphyseal bone alterations as this formulation increased volumetric bone mineral density and improved bone micro-architecture. These effects were related to the modification of bone metabolism reflected by changes in bone biomarkers with reductions in the ratio receptor activator of nuclear factor κB ligand/osteoprotegerin and the levels of tartrate-resistant acid phosphatase-5b, suggesting an inhibitory activity of BIS076 on trabecular bone resorption., Conclusions: We have demonstrated the protective properties of a new formulation (BIS076) on joint lesion and bone alterations in an experimental model of OA in ovariectomised rats. This study supports the interest of BIS076 in OA treatments.

A fluid-retention effect is required for beverages that are designed to prevent dehydration. That is, fluid absorbed from the intestines should not be excreted quickly; long-term retention is desirable. Here, we focused on the effect of milk protein on fluid retention, and propose a new effective oral rehydration method that can be used daily for preventing dehydration. We first evaluated the effects of different concentrations of milk protein on fluid retention by measuring the urinary volumes of rats fed fluid containing milk protein at concentrations of 1, 5, and 10%. We next compared the fluid-retention effect of milk protein-enriched drink (MPD) with those of distilled water (DW) and a sports drink (SD) by the same method. Third, to investigate the mechanism of fluid retention, we measured plasma insulin changes in rats after ingesting these three drinks. We found that the addition of milk protein at 5 or 10% reduced urinary volume in a dose-dependent manner. Ingestion of the MPD containing 4.6% milk protein resulted in lower urinary volumes than DW and SD. MPD also showed a higher water reabsorption rate in the kidneys and higher concentrations of plasma insulin than DW and SD. These results suggest that increasing milk protein concentration in a beverage enhances fluid retention, which may allow the possibility to develop rehydration beverages that are more effective than SDs. In addition, insulin-modifying renal water reabsorption may contribute to the fluid-retention effect of MPD.

We report a new type of microcolumn installed in a microchip. The architecture allows use of a nucleic acid sandwich hybridization technique to detect a messenger RNA (mRNA) chain as a target. Data are presented that demonstrate that the expression of a chimeric fusion gene can be detected. The microcolumn was filled with semi-transparent microbeads made of agarose gel that acted as carriers, allowing increased efficiency of the optical detection of fluorescence from the microcolumn. The hybrid between the target trapped on the microbeads and a probe DNA labeled with a fluorescent dye was detected by measuring the intensity of the fluorescence from the microcolumn directly. These results demonstrate an easy and simple method for determining the expression of chimeric fusion genes with no preamplification., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA) in young rats is widely used to study the pathogenesis of OA and possible treatment approaches. As aging is a key factor in the progression of this condition, it is hypothesized that animals may vary in their responses to ACLT according to their age. The histopathological features of young (2month-old) and middle-aged (12month-old) rats in the presence or absence of ACLT were compared. The results indicated that moderate degradative changes can be detected in the knee joints of sham-operated middle-aged rats compared with young animals. After ACLT, cartilage degradation was significantly higher in middle-aged rats in relation to young animals. An increase in interleukin(IL)-1β and IL-17 suggests the presence of a local inflammatory response represented by synovitis in ACLT rats which is not dependent on age. Our study indicates that age is an important factor affecting the pathogenesis of OA changes after ACLT and it should be considered in studies using this experimental model., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Fermentation of sugared tea with a symbiotic culture of acetic acid bacteria and yeast (tea fungus) yields kombucha tea which is consumed worldwide for its refreshing and beneficial properties on human health. Important progress has been made in the past decade concerning research findings on kombucha tea and reports claiming that drinking kombucha can prevent various types of cancer and cardiovascular diseases, promote liver functions, and stimulate the immune system. Considering the widespread reports on kombucha, we recognized the need to review and update the research conducted in relation to kombucha tea, its products and tea fungus. Existing reports have suggested that the protective effects of kombucha tea are as good as those of black tea, however, more studies on kombucha tea and its composition are needed before final conclusions can be made., (© 2014 Institute of Food Technologists®.)

Glycosaminoglycans (GAGs) are distributed in the whole body and play a variety of important physiological roles associated with inflammation, growth, coagulation, fibrinolysis, lipolysis, and cell-matrix biology. Accumulation of undegraded GAGs in lysosomes gives rise to a distinct clinical syndrome, mucopolysaccharidoses. Measurement of each specific GAG in a variety of specimens is urgently required to understand GAG interaction with other molecules, physiological status of patients, and prognosis and pathogenesis of the disease. We established a highly sensitive and accurate tandem mass spectrometry (LC-MS/MS) method for measurements of disaccharides derived from four specific GAGs [dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and chondroitin sulfate (CS)]. Disaccharides were produced by specific enzyme digestion of each GAG, and quantified by negative ion mode of multiple reaction monitoring. Subclasses of HS and GAGs with identical molecular weights can be separated using a Hypercarbcolumn (2.0 mm×50 mm, 5 μm) with an aectonitrile gradient in ammonium acetate (pH 11.0). We also developed a GAG assay by RapidFire with tandem mass spectrometry (RF-MS/MS). The RF system consists of an integrated solid phase extraction robot that binds and de-salts samples from assay plates and directly injects them into a MS/MS detector, reducing sample processing time to ten seconds. RF-MS/MS consequently yields much faster throughput than conventional LC-MS/MS-based methods. However, the RF system does not have a chromatographic step, and therefore, cannot distinguish GAGs that have identical molecular weights. Both methods can be applied to analysis of dried blood spots, blood, and urine specimens. In this article, we compare the assay methods for GAGs and describe their potential applications.

Resveratrol is suggested to have beneficial cardiovascular and renoprotective effects. Resveratrol increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. We hypothesized resveratrol acts as an acute renal vasodilator, mediated through increased NO production and scavenging of reactive oxygen species (ROS). In anesthetized rats, we found 5.0 mg/kg body weight (bw) of resveratrol increased renal blood flow (RBF) by 8% [from 6.98 ± 0.42 to 7.54 ± 0.17 ml·min(-1)·gram of kidney weight(-1) (gkw); n = 8; P < 0.002] and decreased renal vascular resistance (RVR) by 18% from 15.00 ± 1.65 to 12.32 ± 1.20 arbitrary resistance units (ARU; P < 0.002). To test the participation of NO, we administered 5.0 mg/kg bw resveratrol before and after 10 mg/kg bw of the NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME). l-NAME reduced the increase in RBF to resveratrol by 54% (from 0.59 ± 0.05 to 0.27 ± 0.06 ml·min(-1)·gkw(-1); n = 10; P < 0.001). To test the participation of ROS, we gave 5.0 mg/kg bw resveratrol before and after 1 mg/kg bw tempol, a superoxide dismutase mimetic. Resveratrol increased RBF 7.6% (from 5.91 ± 0.32 to 6.36 ± 0.12 ml·min(-1)·gkw(-1); n = 7; P < 0.001) and decreased RVR 19% (from 18.83 ± 1.37 to 15.27 ± 1.37 ARU). Tempol blocked resveratrol-induced increase in RBF (from 0.45 ± 0.12 to 0.10 ± 0.05 ml·min(-1)·gkw(-1); n = 7; P < 0.03) and the decrease in RVR posttempol was 44% of the control response (3.56 ± 0.34 vs. 1.57 ± 0.21 ARU; n = 7; P < 0.006). We also tested the role of endothelium-derived prostanoids. Two days of 10 mg/kg bw indomethacin pretreatment did not alter basal blood pressure or RBF. Resveratrol-induced vasodilation remained unaffected. We conclude intravenous resveratrol acts as an acute renal vasodilator, partially mediated by increased NO production/NO bioavailability and superoxide scavenging but not by inducing vasodilatory cyclooxygenase products.

Inflammation has been implicated in development of the insulin resistance that leads to elevated blood sugar levels associated with type 2 diabetes. It is reported that salsalate, a common non-steroidal anti-inflammatory drug, has been shown to decrease blood glucose concentration in some clinical study. Recently, we found that bovine milk-derived α-lactalbumin had anti-inflammatory activity caused by inhibiting cyclooxygenase-2. In this study, we investigated the effects of chronic administration of α-lactalbumin on glucose tolerance in Goto-Kakizaki (GK) rats, a model of type 2 diabetes. After 10 weeks administration of the α-lactalbumin (300 mg/kg, twice a day), oral glucose tolerance tests revealed significant decrements of blood glucose levels after glucose loading. However, significant differences of insulin levels were not observed among three GK rats groups after glucose loading. α-Lactalbumin treatment enhanced high molecular weight form of adiponectin and suppressed prostaglandin E2 levels in plasma. These results suggest that α-lactalbumin effectively decreased blood glucose levels after glucose loading in GK rat, and the decrements may be due to enhancement of adiponectin.