Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation

The chronic low-grade inflammation in adipose tissue plays a causal role in obesity-induced insulin resistance and its associated pathophysiological consequences. In this study, we investigated the effects of extracts of Broussonetia papyrifera root bark (PRE) and its bioactive components on inflammation and insulin sensitivity. PRE inhibited TNF-alpha-induced NF-kappa B transcriptional activity in the NF-kappa B luciferase assay and pro-inflammatory genes' expression by blocking phosphorylation of I kappa B and NF-kappa B in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-kappa B phosphorylation and pro-inflammatory genes' expression. Furthermore, PRE activated AMP-activated protein kinase (AMPK) and reduced lipogenic genes' expression in both adipose tissue and liver. Finally, we identified broussoflavonol B (BF) and kazinol J (KJ) as bioactive constituents to suppress pro-inflammatory responses via activating AMPK in 3T3-L1 adipocytes. Taken together, these results indicate the therapeutic potential of PRE, especially BF or KJ, in metabolic diseases such as obesity and type 2 diabetes

Internal evaluation of a physically-based distributed model using data from a Mediterranean mountain catchment

An evaluation of the performance of a physically-based distributed model of a small Mediterennean mountain catchment is presented. This was carried out using hydrological response data, including measurements of runoff, soil moisture, phreactic surface level and actual evapotranspiration. A-priori model parameterisation was based as far as possible on property data measured in the catchment. Limited model calibration was required to identify an appropriate value for terms controlling water loss to a deeper regional aquifer. The model provided good results for an initial calibration period, when judge in terms of catchment discharge. However, model performance for runoff declined substantially when evaluated againts a consecutive, rather drier, period of data. Evaluation against other catchment responses allowed identification of the problems responsible for the observed lack of model robustness in flow simulation. In particular, it was shown that an incorrect parameterisation of the soil water was preventing adequate representation of drainage from soils during hydrogeraph recessions. This excess moisture was then being removed via an overestimation of evapotranspiration. It also appeared that the model underestimated canopy interception. The results presented here suggest that model evaluation against catchment scale variables summarising its water balance can be of great use in identifying problems with model parameterisation, even for distributed models. Evaluation using spatially distributed data yielded less useful information on model performance, owing to the relative sparseness of data points, and problems of mismatch of scale between the measurement and the model grid.This work was carried out as part of project VAHMPIRE (Validating Hydrological Models using Process Studies and Internal Data from Research Basins: tools for assessing the hydrological impacts of environmental change), which was funded by the European Commission Framework IV Environment and Climate Program (Contract No. ENV4- CT95-0134). Simulations were carried out on a UNIX workstation funded jointly by UK Nirex Ltd. and NERC grant GR3/ E0009.Peer Reviewe

Clinical Outcomes of Non-carbapenem Treatment for Urinary Tract Infections Caused by Extended-spectrum β-lactamase-producing

Purpose The purpose of this study was to investigate the clinical outcomes of non-carbapenem treatment for urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) in young children. Methods We retrospectively reviewed the medical records of children under 2 years of age who were diagnosed and treated for UTIs caused by ESBL-producing E. coli from September 2014 to March 2020. Results Forty-three children under 2 years of age were treated with non-carbapenem antimicrobials for UTIs caused by ESBL-producing E. coli without bloodstream infections. The overall clinical and microbiological success rates for empirical antimicrobial treatment were 90.7% and 97.7%. Three of the patients (7.0%) experienced a relapse of UTI within a month. An in vitro susceptibility test showed that two patients were sensitive and one was resistant to the antimicrobial treatments. Furthermore, there were no significant differences in the time to defervescence, clinical success, microbiological success, and relapse rate between the susceptible (n=13) and non-susceptible groups (n=30). Conclusion In this study, the overall relapse rate of patients treated with non-carbapenem antimicrobials was 7.0%. The patients showed high success rates in the clinical and microbiological responses to the non-carbapenems regardless of the results of the in vitro antimicrobial susceptibility test. These results provide evidence that non-carbapenems may be viable alternative treatments for UTIs caused by ESBL-producing E. coli

Determination of Thyroid Volume by Ultrasonography among Schoolchildren in Philippines

Objective. Iodine deficiency is defined by the goiter and the urinary iodine concentration. However, a lack of local thyroid volume reference data resulted in the vague definition of goiter, especially in school-aged children. The aim of this paper was to determine the thyroid volumes by ultrasonography in schoolchildren aged 6 to 12 years living in Cagayan areas in Philippine. Methods. Cross-sectional thyroid ultrasonographic data of 158 schoolchildren aged 6–12 years from Tuguegarao and Lagum in Cagayan valley, Philippine were used. Thyroid volumes were compared based on logistic issue and urban and rural area and compared with other previously reported data. Results. The mean values of thyroid volume in Tuguerago and Lagum were 2.99 ± 1.34 mL and 2.42 ± 0.92 mL. The thyroid size was significantly in association with age (P < 0.00), weight (P < 0.00), height (P < 0.00), and BSA (P < 0.00) by Pearson's correlation. The median thyroid volumes of schoolchildren investigated in this study were generally low compared to international reference data by age group but not by BSA. Conclusions. We propose for the first time local reference ultrasound values for thyroid volumes in 6–12 aged schoolchildren that should be used for monitoring iodine deficiency disorders

PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPAR?? at Ser273

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPAR gamma at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPAR gamma at Ser273, the molecular mechanism of PPAR gamma dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPAR gamma phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPAR gamma at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders

Interferometric detection of prostate specific antigen based on enzyme immunoassay

AbstractInterferometric detection of Prostate-specific antigen (PSA) based on enzyme immunoassay are investigated. Refractive index changes of substrate are measured for PSA detection. Michelson scheme of optical interferometer was used so as to be applicable to a disposable fluidic chip. When interferometer is used for the measurements of refractive index changes, the detection is over 8 times more sensitive than that of absorbance changes for the same amount of target protein

Gomisin A Suppresses Colorectal Lung Metastasis by Inducing AMPK/p38-Mediated Apoptosis and Decreasing Metastatic Abilities of Colorectal Cancer Cells

Gomisin A (G.A) is a dietary lignan compound from Schisandra chinensis. In this study, the effect of G.A on the proliferation and metastasis of colorectal cancer (CRC) cells was investigated using several CRC cell lines and a lung metastasis mouse model. Both oral and intraperitoneal administration of G.A (50 mg/kg) inhibited lung metastasis of CT26 cells. Various concentrations of G.A were incubated with CRC cell lines and their viability was determined using a cell counting kit-8 assay. G.A significantly decreased the viability of various CRC cell lines, whereas it did not change the proliferation of normal colon cells. G.A induced G0/G1 phase arrest and apoptosis of CT26 and HT29 cells by regulating cyclin D1/cyclin-dependent kinase 4 (CDK4) expression and apoptotic proteins such as caspases and B-cell lymphoma-2 (Bcl-2) family proteins, respectively. G.A-induced apoptosis was mediated by AMPK/p38 activation in CRC cells. A non-cytotoxic concentration of G.A inhibited epithelial–mesenchymal transition of CRC cells by modulating E-cadherin and N-cadherin expression levels. Moreover, the migration and invasion of CRC cells were reduced by G.A treatment. Especially, G.A decreased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities. G.A ameliorated lung metastasis of CRC cells by decreasing cell survival and metastatic abilities of CRC cells. Thus, G.A might be a potential novel therapeutic agent for metastatic CRC

Readout-segmented echo-planar imaging in diffusion-weighted mr imaging in breast cancer: comparison with single-shot echo-planar imaging in image quality

Objective: The purpose of this study was to compare the image quality of standard single-shot echo-planar imaging (ss-EPI) and that of readout-segmented EPI (rs-EPI) in patients with breast cancer. Materials and Methods: Seventy-one patients with 74 breast cancers underwent both ss-EPI and rs-EPI. For qualitative comparison of image quality, three readers independently assessed the two sets of diffusion-weighted (DW) images. To evaluate geometric distortion, a comparison was made between lesion lengths derived from contrast enhanced MR (CE-MR) images and those obtained from the corresponding DW images. For assessment of image parameters, signal-to-noise ratio (SNR), lesion contrast, and contrast-to-noise ratio (CNR) were calculated. Results: The rs-EPI was superior to ss-EPI in most criteria regarding the qualitative image quality. Anatomical structure distinction, delineation of the lesion, ghosting artifact, and overall image quality were significantly better in rs-EPI. Regarding the geometric distortion, lesion length on ss-EPI was significantly different from that of CE-MR, whereas there were no significant differences between CE-MR and rs-EPI. The rs-EPI was superior to ss-EPI in SNR and CNR. Conclusion: Readout-segmented EPI is superior to ss-EPI in the aspect of image quality in DW MR imaging of the breast

Hepatogastric fistula caused by direct invasion of hepatocellular carcinoma after transarterial chemoembolization and radiotherapy

A 63-year-old man with a history of hepatitis-B-related hepatocellular carcinoma (HCC) in the left lateral portion of the liver received repeated transcatheter arterial chemoembolization (TACE) and salvage radiotherapy. Two months after completing radiotherapy, he presented with dysphagia, epigastric pain, and a protruding abdominal mass. Computed tomography showed that the bulging mass was directly invading the adjacent stomach. Endoscopy revealed a fistula from the HCC invading the stomach. Although the size of the mass had decreased with the drainage through the fistula, and his symptoms had gradually improved, he died of cancer-related bleeding and hepatic failure. This represents a case in which an HCC invaded the stomach and caused a hepatogastric fistula after repeated TACE and salvage radiotherapy

Etanercept treatment for pediatric toxic epidermal necrolysis induced by deflazacort: a case report and literature review

Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disorder commonly caused by drugs. TEN is often treated with corticosteroids, intravenous immunoglobulin (IVIG), or cyclosporine; however, the efficacy of these treatments is controversial. Etanercept (a TNF-α antagonist) was proven to decrease skin-healing time in a randomized clinical trial. Herein, we report the case of a 44-month-old boy who developed TEN due to deflazacort as the probable culprit drug and was successfully treated with etanercept. The patient presented to the emergency department complaining of erythematous maculopapular rashes and vesicles all over the face and body, with vesicles on the hands, feet, and trunk. Symptoms started 4 days before presentation, with edema of the upper lip, which progressed to erythematous macules over the body. He was started on deflazacort for nephrotic syndrome 21 days before the visit. Approximately 20% of the body surface area (BSA) was covered by vesicular lesions. Under the diagnosis of Steven Johnson syndrome/TEN, deflazacort was discontinued, and intravenous dexamethasone (1.5 mg/kg/day), a 5-day course of IVIG (0.4 mg/kg/day), and cyclosporine (3 mg/kg/day) were administered. The lesions seemed to be stationary for 3 days, but on the 6th day of hospitalization, when IVIG was discontinued, the vesicular lesions progressed to approximately 60% of the BSA. Etanercept 0.8 mg/kg was administered subcutaneously. Lesions stopped progressing, and bullous lesions started epithelialization. However, on the 15th day, around 30% of the BSA was still involved; thus, a second dose of etanercept was administered. No acute or sub-acute complications were observed. In conclusion, the use of etanercept in children with TEN that is not controlled with conventional therapy is both effective and safe