Ιατρικά Άρθρα Αλέξανδρος Γ. Σφακιανάκης: 02/08/17

Τετάρτη 8 Φεβρουαρίου 2017

IJMS, Vol. 18, Pages 77: Gypenoside XVII Prevents Atherosclerosis by Attenuating Endothelial Apoptosis and Oxidative Stress: Insight into the ERα-Mediated PI3K/Akt Pathway

Phytoestrogens are estrogen-like compounds of plant origin. The pharmacological activities of phytoestrogens are predominantly due to their antioxidant, anti-inflammatory and lipid-lowering properties, which are mediated via the estrogen receptors (ERs): estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) and possibly G protein-coupled estrogen receptor 1 (GPER). Gypenoside XVII (GP-17) is a phytoestrogen that is widely used to prevent cardiovascular disease, including atherosclerosis, but the mechanism underlying these therapeutic effects is largely unclear. This study aimed to assess the anti-atherogenic effects of GP-17 and its mechanisms in vivo and in vitro. In vivo experiments showed that GP-17 significantly decreased blood lipid levels, increased the expression of antioxidant enzymes and decreased atherosclerotic lesion size in ApoE−/− mice. In vitro experiments showed that GP-17 significantly prevented oxidized low-density lipoprotein (Ox-LDL)-induced endothelial injury. The underlying protective mechanisms of GP-17 were mediated by restoring the normal redox state, up-regulating of the ratio of Bcl-2 to Bax and inhibiting the expression of cleaved caspase-3 in Ox-LDL-induced human umbilical vein endothelial cell (HUVEC) injury. Notably, we found that GP-17 treatment predominantly up-regulated the expression of ERα but not ERβ. However, similar to estrogen, the protective effect of GP-17 could be blocked by the ER antagonist ICI182780 and the phosphatidylinositol 3-kinase (PI3K) antagonist LY294002. Taken together, these results suggest that, due to its antioxidant properties, GP-17 could alleviate atherosclerosis via the ERα-mediated PI3K/Akt pathway.

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IJMS, Vol. 18, Pages 333: MicroRNAs: New Insight in Modulating Follicular Atresia: A Review

Our understanding of the post-transcriptional mechanisms involved in follicular atresia is limited; however, an important development has been made in understanding the biological regulatory networks responsible for mediating follicular atresia. MicroRNAs have come to be seen as a key regulatory actor in determining cell fate in a wide range of tissues in normal and pathological processes. Profiling studies of miRNAs during follicular atresia and development have identified several putative miRNAs enriched in apoptosis signaling pathways. Subsequent in vitro and/or in vivo studies of granulosa cells have elucidated the functional role of some miRNAs along with their molecular pathways. In particular, the regulatory roles of some miRNAs have been consistently observed during studies of follicular cellular apoptosis. Continued work should gradually lead to better understanding of the role of miRNAs in this field. Ultimately, we expect this understanding will have substantial benefits for fertility management at both the in vivo or/and in vitro levels. The stable nature of miRNA holds remarkable promise in clinical use as a diagnostic tool and in reproductive medicine to solve the ever-increasing fertility problem. In this review, we summarize current knowledge of the involvement of miRNAs in follicular atresia, discuss the challenges for further work and pinpoint areas for future research.

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Chinese Abstracts – Volume 5 Issue 1 *

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Re-appraisal and consideration of minimally invasive surgery in colorectal cancer

Throughout history, surgeons have been on a quest to refine the surgical treatment options for their patients and to minimize operative trauma. During the last three decades, there have been tremendous advances in the field of minimally invasive colorectal surgery, with an explosion of different technologies and approaches offered to treat well-known diseases. Laparoscopic surgery has been shown to be equal or superior to open surgery. The boundaries of laparoscopy have been pushed further, in the form of single-incision laparoscopy, natural-orifice transluminal endoscopic surgery and robotics. This paper critically reviews the pathway of development of minimally invasive surgery, and appraises the different minimally invasive colorectal surgical approaches available to date.

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Current status of intestinal and multivisceral transplantation

Clinical-nutritional autonomy is the ultimate goal of patients with intestinal failure (IF). Traditionally, patients with IF have been relegated to lifelong parenteral nutrition (PN) once surgical and medical rehabilitation attempts at intestinal adaptation have failed. Over the past two decades, however, outcome improvements in intestinal transplantation have added another dimension to the therapeutic armamentarium in the field of gut rehabilitation. This has become possible through relentless efforts in the standardization of surgical techniques, advancements in immunosuppressive therapies and induction protocols and improvement in postoperative patient care. Four types of intestinal transplants include isolated small bowel transplant, liver-small bowel transplant, multivisceral transplant and modified multivisceral transplant. Current guidelines restrict intestinal transplantation to patients who have had significant complications from PN including liver failure and repeated infections. From an experimental stage to the currently established therapeutic modality for patients with advanced IF, outcome improvements have also been possible due to the introduction of tacrolimus in the early 1990s. Studies have shown that intestinal transplant is cost-effective within 1–3 years of graft survival compared with PN. Improved survival and quality of life as well as resumption of an oral diet should enable intestinal transplantation to be an important option for patients with IF in addition to continued rehabilitation. Future research should focus on detecting biomarkers of early rejection, enhanced immunosuppression protocols, improved postoperative care and early referral to transplant centers.

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Irritable bowel syndrome and diet

Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and is one of the most commonly diagnosed gastrointestinal diseases. The impact of IBS on the general population is large due to its high prevalence, suboptimal medical treatments and significant economic burden. The pathophysiology of IBS is complex and treatments are often symptom-specific. The most common therapeutic approaches for IBS include education and reassurance, lifestyles (especially nutrition-based interventions), peripherally acting medications (which typically target motility), centrally acting medications (which target visceral hypersensitivity and pain) and psychological interventions (which aim to reduce the effects of stress or symptom-specific anxiety). A beneficial dietary approach might include the following measures: a diet low in fermentable oligo-,di- and monosaccharides and polyols (FODMAPs), limitation or exclusion of gas-producing foods and/or lactose and gluten and fiber supplementation in selected cases. New therapeutic agents, namely nutraceutics, are also an interesting option in the management of IBS patients. This paper will focus on available dietary interventions for IBS and will review the evidence for nutrition-based therapies.

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Esophageal food impaction during cultural holidays and national athletic events

Background: Although intrinsic risk factors contributing to esophageal food impaction are well established, whether social behavior affects its occurrence has not yet been examined.Methods: We conducted a retrospective review of the gastroenterology endoscopy procedural documentation software for the period of 2001–2012 to identify all patients who presented to our emergency department for esophageal foreign-body removal at the time of national athletic events and holidays associated with dietary indiscretions.Results: We found that adults undergoing emergent esophagogastroduodenoscopy during periods celebrating cultural holidays and national athletic events were more likely to experience esophageal food impaction compared with those undergoing emergent endoscopy during periods not associated with these events (36.8% vs 3.6%; P < 0.001): a 10-fold increase. During a national holiday/athletic event period, the most common impacted food item was turkey (50%) followed by chicken (29%) and beef (21%).Conclusions: Esophageal food impaction is more likely to occur on American holidays and national athletic events and is associated with large meals. Patients with intrinsic risk factors should be advised to modify their diet during cultural events associated with tachyphagia and large meals to prevent esophageal food impaction.

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Postoperative excessive gain in visceral adipose tissue as well as body mass index are associated with adverse outcomes of an ileal pouch

Background: There are no published studies on the impact of visceral adipose tissue (VAT) change on outcomes of restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA). The aim of this historic cohort study was to evaluate the impact of excessive VAT gain on the outcomes of inflammatory bowel disease (IBD) patients with IPAA.Methods: We evaluated all eligible patients with at least two sequential CT scans after pouch construction from our prospectively maintained Pouchitis Registry between 2002 and 2014. The visceral fat area (VFA) was measured on CT images. The study group comprised patients with a significant VAT gain (> 15%), and the control group was those without. The adverse outcomes of the pouch were defined as the new development of chronic pouch inflammation (chronic pouchitis, chronic cuffitis or Crohn’s disease of the pouch), anastomotic sinus and the combination of above (the composite adverse outcome) or pouch failure, after the inception CT.Results: Of 1564 patients in the Registry, 59 (3.8%) with at least 2 CT scans after pouch surgery were included. Twenty-nine patients (49.2%) were in the study group, and 30 (50.8%) were in the control group. The median duration from the inception to the latest CT was 552 (range: 31–2598) days for the entire cohort. We compared the frequency of new chronic pouch inflammation (13.8% vs 3.3%, P = 0.195), new pouch sinus (10.3% vs 0%, P = 0.112), composite adverse pouch outcome (24.1% vs 3.3%, P = 0.026) or pouch failure (10.3% vs 6.7%, P = 0.671) between the two groups. Kaplan-Meier plot for time-to-pouch failure between the pouch patients with or without excessive body mass index (BMI) gain (> 10%) showed statistical difference (P = 0.011). Limited stepwise multivariate analysis showed that excessive VAT gain (odds ratio = 12.608, 95% confidence interval: 1.190–133.538, P = 0.035) was an independent risk factor for the adverse pouch comes.Conclusions: In this cohort of ileal pouch patients, excessive VAT gain as well as gain in BMI after pouch construction was found to be associated with poor long-term outcomes.

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Serum albumin predicts survival in patients with hilar cholangiocarcinoma

Background and aims: Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma.Methods: All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation.Results: A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P < 0.01), cancer antigen 19‐9 ≤200 U/mL (P = 0.03), carcinoembryonic antigen ≤10 ìg/L (P < 0.01) or patients without a history of cirrhosis (P < 0.01) or diabetes (P = 0.02) were associated with a greater length of overall survival. A serum albumin level >3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14–0.70) with a survival benefit of 44 weeks.Conclusion: This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival.

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Recurrence and survival rates of inflammatory bowel disease-associated colorectal cancer following postoperative chemotherapy: a comparative study

Background and Aim: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC, suggesting differences in tumor behavior and response to treatment. We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD.Methods: Search of the Cleveland Clinic’s CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010. Twenty-one patients were excluded due to incomplete clinical data. Propensity score-matching based on age, surgery intent, CRC site, tumor grade, American Joint Committee on Cancer (AJCC) stage and T stage was used to match IBD and non-IBD patients (1:4). Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival, respectively.Results: Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC. Among IBD patients, 29 (66%) had ulcerative colitis, 14 (32%) had Crohn’s disease, and one (2%) had indeterminate colitis. Mean IBD diagnosis age was 28.1 ± 14.5 years, and mean IBD duration at time of CRC treatment was 21.5 ± 12.6 years. Ten (23%) IBD patients had tumor recurrence compared with 34 (19%) non-IBD patients (P = .074). There was no significant difference in disease-free survival (hazard ratio [HR] = 0.60; 95% CI: 0.35–1.05; P = 0.074) or overall survival (HR = 0.87; 95% CI: 0.54–1.4; P = 0.58) between IBD and non-IBD patients.Conclusion: Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD. Prospective studies are needed to confirm these findings and guide therapeutic decisions.

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Nationwide trends of hospital admissions for acute cholecystitis in the United States

Background and aims: Acute cholecystitis is a fairly common inpatient diagnosis among the gastrointestinal disorders. The aim of this study was to use a national database of US hospitals to evaluate the incidence and costs of hospital admissions associated with acute cholecystitis.Method: We analyzed the National Inpatient Sample Database (NIS) for all patients in which acute cholecystitis (ICD-9 codes: 574.00, 574.01, 574.30, 574.31, 574.60, 574.61 or 575.0) was the principal discharge diagnosis from 1997 to 2012. The NIS is the largest all-payer inpatient database in the United States and contains data from approximately 8 million hospital stays each year. The statistical significance of the difference in the number of hospital discharges, lengths of stay and associated hospital costs over the study period was determined by using the Chi-square test for trends.Results: In 1997, there were 149 661 hospital admissions with a principal discharge diagnosis of acute cholecystitis, which increased to 215 995 in 2012 ( P < 0.001). The mean length of stay for acute cholecystitis decreased by 17% between 1997 and 2012 (i.e. from 4.7 days to 3.9 days; (P < 0.05). During the same time period, however, mean hospital charges have increased by 195.4 % from US$14 608 per patient in 1997 to US$43 152 per patient in 2012 ( P < 0.001).Conclusion: The number of inpatient discharges related to acute cholecystitis has increased significantly in the United States over the last 16 years, along with a great increase in the associated hospital charges. However, there has been a gradual decline in the mean length of stay. Inpatient costs associated with acute cholecystitis contribute significantly to the total healthcare bill. Further research on cost-effective evaluation and management of acute cholecystitis is required.

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Gastric transposition as a valid surgical option for esophageal replacement in pediatric patients: experience from three Italian medical centers

Background: Esophageal replacement in children is an option that is confined to very few situations including long-gap esophageal atresia and esophageal strictures unresponsive to other therapies (peptic or caustic ingestion). The purpose of our work was to describe the experience of gastric transposition in three Italian centers.Methods: This is a retrospective study. The data were extrapolated from a prospective database. We included all patients who had undergone gastric transposition in the last 15 years.Results: In the 15-year period, eight infants and children (3 males and 5 females) underwent gastric transposition for esophageal replacement. Six patients had long-gap esophageal atresia, and two had caustic esophageal stenosis. There were no deaths in the series. Three patients had an early postoperative complication: two had a self-limited salivary fistula at three weeks, and one (a patient with jejunostomy) had a jejunal perforation treated surgically. One late complication, anastomotic stricture, was recorded that required two endoscopic dilatations. The median follow-up was 60 months (range: 18–144 months). At final clinical follow-up, six patients had no eating problems, and two patients had some difficulties with eating (jejunostomy in situ), but they underwent logopedic therapy with improved outcomes. All patients had an increase in body weight and height postoperatively.Conclusion: Our small study reports the clinical experience of three Italian centers in which gastric transposition was performed with excellent results, both in terms of surgical technique (simplicity, reproducibility, complication rate) and clinical follow-up (good oral feeding of young patients, normal social life and regular growth curves).

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The effect of disc-shaped gastric resection of anastomosis site on reducing postoperative dysphagia and stricture after esophagogastric anastomosis in patients with esophageal cancer

Background: Esophagectomy remains the most reliable technique for managing esophageal cancer, but anastomotic complications including postoperative leak, ischemia and stricture negatively affect outcomes of this specific surgery. The aim of this study was to evaluate the effects of a novel method of esophagogastric anastomosis for reducing postoperative dysphagia and stricture formation.Methods: Eighty patients who were scheduled for esophagectomy due to esophageal cancer were randomly assigned into two groups: intervention and control (40 each). In the control group, the esophagogastric anastomosis was performed with a linear gastric incision, whilst in the intervention group a new method of disc-shaped gastric resection for anastomosis was applied. Postoperative outcomes were compared between the two groups.Results: The incidence of postoperative dysphagia and anastomotic stricture was significantly lower in the disc-shaped resection group (dysphagia 45% vs 75%, P = 0.02; stricture 12.5% vs 32.5%, P = 0.03), whilst the length of stay in an intensive care unit (ICU), anastomotic leakage and other complications were not significantly different between the two groups (all P > 0.05).Conclusion: Anastomotic complications can be reduced by improving surgical techniques. The decreased incidence of postoperative dysphagia and anastomotic stricture in our study may be partly due to providing the proper diameter for the site of anastomosis when using the disc-shaped gastric resection method. Hence, this new method can improve the clinical outcomes of patients who undergo esophagectomy with esophagogastric anastomosis.

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Ciliated hepatic foregut cyst: report of three cases and review of imaging features

Ciliated hepatic foregut cysts (CHFCs) are rare cystic lesions which are most commonly asymptomatic. They can be clinically important as they may, on rare occasions, undergo malignant transformation or cause mass effect if significantly enlarged. Three cases of CHFCs are presented in this article and their imaging features are reviewed.

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Liver metastasis from hepatoid adenocarcinoma of the esophagus mimicking hepatocellular carcinoma

Alpha-fetoprotein (AFP)-producing adenocarcinoma, histologically mimicking hepatocellular carcinoma (HCC), is a distinct entity known as hepatoid adenocarcinoma (HAC). Reported cases of HAC arising from the esophagus are extremely rare. Due to common liver metastasis and elevated AFP levels in patients with esophageal HAC, differentiation of HAC with liver metastasis from HCC could be challenging. We describe a case of esophageal HAC that presented with a liver mass showing hepatoid features and elevated serum AFP levels. Initial presentation was suspicious for HCC. Upon further diagnostic work-up, the patient was diagnosed with esophageal HAC with liver metastasis. The distinction between these two entities is particularly important because HAC is more aggressive, and its therapeutic options are very limited.

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Diagnosis of primary squamous cell carcinoma of the pancreas using endoscopic ultrasound-guided core needle biopsy

Primary squamous cell carcinoma (SCC) of the pancreas is a particularly rare entity. Diagnosis of this tumor is tentatively made after ruling out metastatic SCC from another primary site and adenosquamous carcinoma (ASC) of the pancreas. Here we discuss the case of a 76-year-old woman who was found to have a solitary pancreatic lesion and multiple hepatic lesions. Results of computed tomography-guided biopsy of the liver lesions were consistent with a metastatic carcinoma displaying squamous differentiation; therefore, an endoscopic ultrasound (EUS)-guided core-needle biopsy (CNB) of the pancreatic mass was performed. Meticulous histopathological examination of the pancreatic specimen at multiple levels revealed moderately well-differentiated SCC with no glandular component. An extensive metastatic work-up did not reveal an extra-pancreatic origin for this SCC; hence, a diagnosis of primary SCC of the pancreas was established. To our knowledge, this is the first report of the diagnosis of a primary SCC of the pancreas using EUS-guided CNB. We believe that CNB has a diagnostic yield equivalent to that of fine-needle aspiration for recognizing pancreatic adenocarcinoma; however, when cytological examinations reveal atypical squamous epithelial cells suggestive of malignancy, CNB may provide a better tissue specimen, from which to determine the presence of a glandular component. Such an assessment will differentiate pancreatic SCC from ASC.

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Did people actually bowl at Bowling Green?

Bowling Green has a history that has withstood the test of time.

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Machine-learning analysis of heart motion predicts survival

2017_02_07_12_37_55_292_2017_02_08_machi A machine-learning survival model based on 3D cardiac motion predicts outcomes...

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CMR, scintigraphy do more to prevent unnecessary angiography

Mobile App Spotlight: CMR Pocket Guide

MRI rules out competing diagnoses in ARVC/D

T1 mapping speeds myocardial assessment in cardiac MR

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Radiology learns the lessons of Ebola crisis

2017_02_08_13_26_24_514_Ebola_virus_red_ Researchers from a top London teaching hospital with extensive experience of...

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MRI sheds light on Zika virus, severe joint deformities

U.K. releases Ebola guidelines for the ED

H7N9 bird flu pneumonia scans show common imaging findings

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Karolinska promotes digital technology for better care

Karolinska University Hospital in Sweden is challenging its colleagues in the...

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Karolinska visiting professor cleared of fraud charges

Karolinska team uses fMRI to create 'out-of-body' sensation

PACS lies at digital heart of the new Karolinska

GE, Karolinska finalize long-term deal

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Machine learning in radiology targets efficiency

2014_07_25_13_26_17_310_cyber_informatic While artificial intelligence is unlikely to replace radiologists any time...

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Hard Brexit signals rocky road for radiology

Back to the future: Top themes from RSNA 2016

3 things every radiologist must know about analytics

Deconstructed PACS: It's not all bad news

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U.K. hospital group blames PACS for huge backlog

Kettering General Hospital National Health Service (NHS) Foundation Trust in...

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GE to modernize five Kuwait hospitals

GE places miniature neonatal MRI prototype in U.K.

GE pays tribute to Bucharest site

GE purchases expanded rights to Rapiscan stress agent

BIR, GE partner on radiation safety travel award

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Pixyl receives capital for software

Startup neurology and radiology software firm Pixyl has received an investment...

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New PET tracer advances prostate cancer detection

2017_02_01_11_37_20_278_BBN-RGD_PET_JNM_ Researchers have developed a new PET radiotracer designed to detect both early...

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New therapeutic agent could treat prostate cancer

Prostate CAD boosts detection for most readers

Blue Earth PET radiotracer IDs prostate cancer recurrence

Oncology Systems aids prostate cancer trial

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Interventional radiology market slated for strong gains

The global interventional radiology market generated 12.9 billion euros in...

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Global optical imaging market to see double-digit growth

Global ultrasound market set to reach $11B by 2023

Electronic health records market to reach $24B by 2020

Optical imaging market to grow at double-digit rate

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Leaders in Healthcare conference wraps up Arab Health

Arab Health 2017 concluded on 2 February in Dubai with the Leaders in Healthcare...

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Parizel calls for more standardization of MRI protocols

Dubai deputy ruler opens Arab Health 2017

Breast screening debate spreads to Middle East

UAE offers open, cosmopolitan environment

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Elekta unveils ESTRO partnership

Radiation oncology vendor Elekta is collaborating with the European Society...

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Varian claims favorable ruling in Elekta patent suit

Judge finds in favor of Elekta in dispute with Varian

Elekta lands large order from India

Elekta to install MR-linac in the U.K.

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Breast screening organizers get creative to boost uptake

2017_02_03_12_36_36_788_2017_02_06_leban A new study from Lebanon of 2,400 women older than 40 has found that fewer...

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Breast screening debate spreads to Middle East

Stereotactic breast biopsies: Room for improvement?

Irish advocate caution on breast screening for under 40s

Improving the patient experience benefits everyone

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Italians put finishing touches to image quality method

2017_02_06_15_51_10_539_2017_02_07_dbt_4 Italian researchers have proved a combination of phantoms, an automatic software...

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Mechanical imaging can cut breast screening recalls

Breast screening debate spreads to Middle East

Irish advocate caution on breast screening for under 40s

Cochrane group again takes aim at breast screening

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Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model

Publication date: 10 March 2017
Source:Journal of Controlled Release, Volume 249
Author(s): Fan Zhang, J. Trent Magruder, Yi-An Lin, Todd C. Crawford, Joshua C. Grimm, Christopher M. Sciortino, Mary Ann Wilson, Mary E. Blue, Sujatha Kannan, Michael V. Johnston, William A. Baumgartner, Rangaramanujam M. Kannan
Hypothermic circulatory arrest (HCA) provides neuroprotection during cardiac surgery but entails an ischemic period that can lead to excitotoxicity, neuroinflammation, and subsequent neurologic injury. Hydroxyl polyamidoamine (PAMAM) dendrimers target activated microglia and damaged neurons in the injured brain, and deliver therapeutics in small and large animal models. We investigated the effect of dendrimer size on brain uptake and explored the pharmacokinetics in a clinically-relevant canine model of HCA-induced brain injury. Generation 6 (G6, ~6.7nm) dendrimers showed extended blood circulation times and increased accumulation in the injured brain compared to generation 4 dendrimers (G4, ~4.3nm), which were undetectable in the brain by 48h after final administration. High levels of G6 dendrimers were found in cerebrospinal fluid (CSF) of injured animals with a CSF/serum ratio of ~20% at peak, a ratio higher than that of many neurologic pharmacotherapies already in clinical use. Brain penetration (measured by drug CSF/serum level) of G6 dendrimers correlated with the severity of neuroinflammation observed. G6 dendrimers also showed decreased renal clearance rate, slightly increased liver and spleen uptake compared to G4 dendrimers. These results, in a large animal model, may offer insights into the potential clinical translation of dendrimers.

Graphical abstract

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Xanthine dehydrogenase-1 silencing in Aedes aegypti mosquitoes promotes a blood feeding-induced adulticidal activity [Research]

Aedes aegypti has 2 genes encoding xanthine dehydrogenase (XDH). We analyzed XDH1 and XDH2 gene expression by real-time quantitative PCR in tissues from sugar- and blood-fed females. Differential XDH1 and XDH2 gene expression was observed in tissues dissected throughout a time course. We next exposed females to blood meals supplemented with allopurinol, a well-characterized XDH inhibitor. We also tested the effects of injecting double-stranded RNA (dsRNA) against XDH1, XDH2, or both. Disruption of XDH by allopurinol or XDH1 by RNA interference significantly affected mosquito survival, causing a disruption in blood digestion, excretion, oviposition, and reproduction. XDH1-deficient mosquitoes showed a persistence of serine proteases in the midgut at 48 h after blood feeding and a reduction in the uptake of vitellogenin by the ovaries. Surprisingly, analysis of the fat body from dsRNA-XDH1-injected mosquitoes fell into 2 groups: one group was characterized by a reduction of the XDH1 transcript, whereas the other group was characterized by an up-regulation of several transcripts including XDH1, glutamine synthetase, alanine aminotransferase, catalase, superoxide dismutase, ornithine decarboxylase, glutamate receptor, and ammonia transporter. Our data demonstrate that XDH1 plays an essential role and that XDH1 has the potential to be used as a metabolic target for Ae. aegypti vector control.—Isoe, J., Petchampai, N., Isoe, Y. E., Co, K., Mazzalupo, S., Scaraffia, P. Y. Xanthine dehydrogenase-1 silencing in Aedes aegypti mosquitoes promotes a blood feeding–induced adulticidal activity.

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Altered methylation of specific DNA loci in the liver of Bhmt-null mice results in repression of Iqgap2 and F2rl2 and is associated with development of preneoplastic foci [Research]

Folate B₁₂–dependent remethylation of homocysteine is important, but less is understood about the importance of the alternative betaine-dependent methylation pathway—catalyzed by betaine-homocysteine methyltransferase (BHMT)—for establishing and maintaining adequate DNA methylation across the genome. We studied C57Bl/6J Bhmt (betaine-homocysteine methyltransferase)-null mice at age 4, 12, 24, and 52 wk (N = 8) and observed elevation of S-adenosylhomocysteine concentrations and development of preneoplastic foci in the liver (increased placental glutathione S-transferase and cytokeratin 8-18 activity; starting at 12 wk). At 4 wk, we identified 63 differentially methylated CpGs (DMCs; false discovery rate < 5%) proximal to 81 genes (across 14 chromosomes), of which 18 were differentially expressed. Of these DMCs, 52% were located in one 15.5-Mb locus on chromosome 13, which encompassed the Bhmt gene and defined a potentially sensitive region with mostly decreased methylation. Analyzing Hybrid Mouse Diversity Panel data, which consisted of 100 inbred strains of mice, we identified 97 DMCs that were affected by Bhmt genetic variation in the same region, with 7 overlapping those found in Bhmt-null mice (P < 0.001). At all time points, we found a hypomethylated region mapping to Iqgap2 (IQ motif-containing GTPase activating protein 2) and F2rl2 (proteinase-activated receptor-3), 2 genes that were also silenced and underexpressed, respectively.—Lupu, D. S., Orozco, L. D., Wang, Y., Cullen, J. M., Pellegrini, M., Zeisel, S. H. Altered methylation of specific DNA loci in the liver of Bhmt-null mice results in repression of Iqgap2 and F2rl2 and is associated with development of preneoplastic foci.

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Its time to redefine inflammation [Review]

Inflammation has been defined for many years as the response to tissue injury and infection. We are now forced to reconsider this definition by the avalanche of reports that molecules and cells associated with inflammation are activated or expressed in high concentration in a large variety of states in the absence of tissue injury or infection. Modest increases in concentration of C-reactive protein, a circulating marker of inflammation, have been reported to be associated with an astounding number of conditions and lifestyles felt to be associated with poor health; these conditions represent or reflect minor metabolic stresses. In recent years we have learned that inflammation is triggered by sentinel cells that monitor for tissue stress and malfunction—deviations from optimal homeostasis—and that molecules that participate in the inflammatory process play a role in restoring normal homeostasis. Accordingly, we suggest that inflammation be redefined as the innate immune response to potentially harmful stimuli such as pathogens, injury, and metabolic stress.—Antonelli, M., Kushner, I. It’s time to redefine inflammation.

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Viruses comprise an extensive pool of mobile genetic elements in eukaryote cell cultures and human clinical samples [Research]

Viruses shape a diversity of ecosystems by modulating their microbial, eukaryotic, or plant host metabolism. The complexity of virus–host interaction networks is progressively fathomed by novel metagenomic approaches. By using a novel metagenomic method, we explored the virome in mammalian cell cultures and clinical samples to identify an extensive pool of mobile genetic elements in all of these ecosystems. Despite aseptic treatment, cell cultures harbored extensive and diverse phage populations with a high abundance of as yet unknown and uncharacterized viruses (viral dark matter). Unknown phages also predominated in the oropharynx and urine of healthy individuals and patients infected with cytomegalovirus despite demonstration of active cytomegalovirus replication. The novelty of viral sequences correlated primarily with the individual evaluated, whereas relative abundance of encoded protein functions was associated with the ecologic niches probed. Together, these observations demonstrate the extensive presence of viral dark matter in human and artificial ecosystems.—Thannesberger, J., Hellinger, H.-J., Klymiuk, I., Kastner, M.-T., Rieder, F. J. J., Schneider, M., Fister, S., Lion, T., Kosulin, K., Laengle, J., Bergmann, M., Rattei, T., Steininger, C. Viruses comprise an extensive pool of mobile genetic elements in eukaryote cell cultures and human clinical samples.

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A C-terminal Tail Region in the Rous Sarcoma Virus Integrase Provides High Plasticity of Functional Integrase Oligomerization during Intasome Assembly [Molecular Biophysics]

The retrovirus integrase (IN) inserts the viral cDNA into the host DNA genome. Atomic structures of five different retrovirus INs complexed with their respective viral DNA or branched viral/target DNA substrates have indicated these intasomes are composed of IN subunits ranging from tetramers, to octamers or to hexadecamers. IN precursors are monomers, dimers or tetramers in solution. But, how intasome assembly is controlled remains unclear. Therefore, we sought to unravel the functional mechanisms in different intasomes. We produced kinetically stabilized Rous sarcoma virus (RSV) intasomes with human immunodeficiency virus type-1 strand transfer inhibitors which interact simultaneously with IN and viral DNA within intasomes. We examined the ability of RSV IN dimers to assemble two viral DNA molecules into intasomes containing IN tetramers in contrast to one possessing IN octamers. We observed that the last 18 residues of the C-terminus (tail region) of IN (1-286) determined whether an IN tetramer or octamer assembled with viral DNA. A series of truncations of the tail region indicated that these 18 residues are critical for the assembly of an intasome containing IN octamers but not for an intasome containing IN tetramers. The C-terminally truncated IN (1-269 residues) produced an intasome that contained tetramers, but failed to produce an intasome with octamers. Both intasomes have similar catalytic activities. The results suggest a high degree of plasticity for functional multimerization and reveals a critical role of the C-terminal tail region of IN in higher order oligomerization of intasomes, potentially informing future strategies to prevent retroviral integration.

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SERINC5 Inhibits HIV-1 Fusion Pore Formation by Promoting Functional Inactivation of Envelope Glycoproteins [Cell Biology]

The host proteins, SERINC3 and SERINC5, have been recently shown to incorporate into HIV-1 particles and compromise their ability to fuse with target cells - an effect that is antagonized by the viral Nef protein. Env glycoproteins from different HIV-1 isolates exhibit a broad range of sensitivity to SERINC-mediated restriction, and the mechanism by which SERINCs interfere with HIV-1 fusion remains unclear. Here, we show that incorporation of SERINC5 into virions in the absence of Nef inhibits the formation of small fusion pores between viruses and cells. Strikingly, we found that SERINC5 promotes spontaneous functional inactivation of sensitive, but not resistant Env glycoproteins. Although SERINC5-Env interaction was not detected by co-immunoprecipitation, incorporation of this protein enhanced the exposure of the conserved gp41 domains and sensitized the virus to neutralizing antibodies and gp41-derived inhibitory peptides. These results imply that SERINC5 restricts HIV-1 fusion at a step prior to small pore formation by selectively inactivating sensitive Env glycoproteins, likely through altering their conformation. The increased HIV-1 sensitivity to anti-gp41 antibodies and peptides suggests that SER5 also delays refolding of the remaining fusion-competent Env trimers.

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Breaking confinement: unconventional peptide presentation by major histocompatibility (MHC) class I allele HLA-A*02:01 [Immunology]

Peptide antigen-presentation by Major Histocompatibility Class (MHC) I proteins initiates CD8+ T cell mediated immunity against pathogens and cancers. MHC I molecules typically bind peptides with nine amino acids in length with both ends tucked inside the major A and F binding pocket. It has been known for a while that longer peptides can also bind by either bulging out of the groove in the middle of the peptide or by binding in a zig-zag fashion inside the groove. In a recent study, we identified an alternative binding conformation of naturally occurring peptides from Toxoplasma gondii bound by HLA-A*02:01. These peptides were extended at the C-terminus (PΩ) and contained charged amino acids not more than 3 residues after the anchor amino acid at PΩ, which enabled them to open the F pocket and expose their C-terminal extension into the solvent. Here, we show that the mechanism of F pocket opening is dictated by the charge of the first charged amino acid found within the extension. While positively charged amino acid result in the Tyr84 swing, amino acids that are negatively charged induce a not previously described Lys146 lift. Further, we demonstrate that the peptides with alternative binding modes have properties that fit very poorly to the conventional MHC class I pathway, and suggest they are presented via alternative means, potentially including cross-presentation via the MHC class II pathway.

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Stability and ligand promiscuity of type A carbohydrate-binding modules are illustrated by the structure of Spirochaeta thermophila StCBM64C [Enzymology]

Deconstruction of cellulose, the most abundant plant cell wall polysaccharide, requires the cooperative activity of a large repertoire of microbial enzymes. Modular cellulases contain non-catalytic type A Carbohydrate-Binding Modules (CBMs) that specifically bind to the crystalline regions of cellulose, thus promoting enzyme efficacy through proximity and targeting effects. Although type A CBMs play a critical role in cellulose recycling, their mechanism of action remains poorly understood. Here we produced a library of recombinant CBMs representative of the known diversity of type A modules. The binding properties of 40 CBMs, in fusion with an N-terminal green fluorescence protein (GFP) domain, revealed that type A CBMs possess the ability to recognize different crystalline forms of cellulose and chitin over a wide range of temperatures, pHs and ionic strengths. A Spirochaeta thermophila CBM64, in particular, displayed plasticity in its capacity to bind both crystalline and soluble carbohydrates under a wide range of extreme conditions. The structure of S. thermophila StCBM64C revealed an untwisted, flat, carbohydrate-binding interface comprising the side chains of four tryptophan residues in a coplanar linear arrangement. Significantly, two highly conserved asparagine side chains, each one located between two tryptophan residues, are critical to insoluble and soluble glucan recognition but not to bind xyloglucan. Thus, CBM64 compact structure and its extended and versatile ligand interacting platform illustrates how type A CBMs target their appended plant cell wall degrading enzymes to a diversity of recalcitrant carbohydrates under a wide range of environmental conditions.

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Structural insights into the broad substrate specificity of a novel Endo-glycoceramidase I belonging to a new subfamily of GH5 glycosidase [Lipids]

Endoglycoceramidases (EGCases) specifically hydrolyze the glycosidic linkage between the oligosaccharide and the ceramide moieties of various glycosphingolipids, and they have received substantial attention in the emerging field of glycosphingolipidology. However, the mechanism regulating the strict substrate specificity of these GH5 glycosidases has not been identified. In this study, we report a novel EGCase I from Rhodococcus equi 103S (103S_EGCase I) with remarkably broad substrate specificity. Based on phylogenetic analyses, the enzyme may represent a new subfamily of GH5 glycosidases. The X-ray crystal structures of 103S_EGCase I alone and in complex with its substrates monosialodihexosylganglioside (GM3) and monosialotetrahexosylganglioside (GM1) enabled us to identify several structural features that may account for its broad specificity. Compared with EGCase II from Rhodococcus sp. M-777 (M777_EGCase II), which possesses strict substrate specificity, 103S_EGCase I possesses a longer α7-helix and a shorter loop4, which forms a larger substrate-binding pocket that could accommodate more extended oligosaccharides. In addition, loop2 and loop8 of the enzyme adopt a more open conformation, which also enlarges the oligosaccharide-binding cavity. Based on this knowledge, a rationally designed experiment was performed to examine the substrate specificity of EGCase II. The truncation of loop4 in M777_EGCase II increased its activity toward GM1 (163%). Remarkably, the S63G mutant of M777_EGCase II showed a broader substrate spectra and significantly increased activity toward bulky substrates (up to >1370-fold for fucosyl-GM1). Collectively, the results presented here reveal the exquisite substrate recognition mechanism of EGCases and provide an opportunity for further engineering of these enzymes.

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ERK Kinases Phosphorylate Lin28a to Modulate P19 Cell Proliferation and Differentiation [Cell Biology]

Lin28a, originally discovered in the nematode Caenorhabditis elegans and highly conserved across species, is a well characterized regulator of let-7 miRNAs and is implicated in cell proliferation and pluripotency control. However, little is known about how Lin28a function is modulated at post-translational level and thereby responds to major signaling pathways. Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser200. By editing lin28a gene with Crispr/Cas9 based method, we generated P19 mouse embryonic carcinoma (EC) stem cells expressing Lin28a-S200A (phospho-deficient) and Lin28a-S200D (phospho-mimetic) mutants respectively to study the functional impact of S200 phosphorylation. Lin28a-S200D expressing cells, but not Lin28a-S200A expressing or control P19 EC cells, displayed impaired inhibition of let-7 miRNA and resulted in decreased Cyclin D1, while Lin28a-S200A knock-in cells express less let-7s miRNA, proliferate faster, and exhibit differentiation defect upon Retinoic Acid induction. Therefore our results support that ERK kinases mediated-Lin28a phosphorylation may be an important mechanism for pluripotent cells to facilitate the escape from self-renewal cycle and start differentiation process.

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Improving consent form documentation and introduction of procedure-specific labels in a district general hospital

Informed consent is an important aspect in patient care. Failings in this area may result in patient dissatisfaction or litigation. The aim of this project was to assess our practice in consenting and institute changes to maintain best practice. A consecutive series of 140 patients undergoing elective and trauma procedures were randomly identified over a nine-month period. The consent forms were reviewed and the following information collected: patient/ consenter details, procedure, legibility, if copy was offered/ given to patient and adequacy of procedure-specific complications listed (scored 0-3). The issues identified included: 25% of consents were not fully legible particularly in the complications section. 62% were noted to have inadequate complications listed (score 0 [>5 risks missing]) when compared to an accepted standard. None of the consent form copies were offered or given to the patients. Focused teaching to juniors as well as procedure-specific complication stickers were implemented to improve the documentation of complications. Following several improvement cycles all consents (100%) were fully legible and had the adequate procedure-specific labels with all complications listed. There was an increase to 38% of consent forms offered to patients. We have asked surgeons in the department to comment on which consent method they prefer and all consenters felt that the procedure-specific labels where easier to read and understand. Departmental education as well as introduction of simple procedure-specific complication stickers has resulted in significant improvements in practice.

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Optimizing the electronic health record to standardize administration and documentation of nutritional supplements

Malnutrition in hospitalized patients is a major cause for hospital re-admission, pressure ulcers and increased hospital costs. Methods to improve the administration and documentation of nutritional supplements for hospitalized patients are needed to improve patient care, outcomes and resource utilization. Staff at a medium-sized academic health science center hospital in the southeastern United States noted that nutritional supplements ordered for patients at high risk for malnutrition were not offered or administered to patients in a standardized manner and/or not documented clearly in the electronic health record as per prescription. This paper reports on a process improvement project that redesigned the ordering, administration and documentation process of oral nutritional supplements in the electronic health record. By adding nutritional products to the medication order sets and adding an electronic nutrition administration record (ENAR) tab, the multidisciplinary team sought to standardize nutritional supplement ordering, documentation and administration at prescribed intervals. This process improvement project used a triangulated approach to evaluating pre- and post-process change including: medical record reviews, patient interviews, and nutrition formula room log reports. Staff education and training was carried out prior to initiation of the system changes. This process change resulted in an average decrease in the return of unused nutritional formula from 76% returned at baseline to 54% post-process change. The process change resulted in 100% of nutritional supplement orders having documentation about nutritional medication administration and/or reason for non-administration. Documentation in the ENAR showed that 41% of ONS orders were given and 59% were not given. Significantly more patients reported being offered the ONS product (p=0.0001) after process redesign and more patients (5% before ENAR and 86% after ENAR reported being offered the correct type, amount and frequency of nutritional products (p=0.0001). ENAR represented an effective strategy to improve administration and documentation of nutritional supplements for hospitalized patients.

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Crosstalk between stromal cells and cancer cells in pancreatic cancer: new insights into stromal biology

Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide. Increasing evidence has confirmed the pivotal role of stromal components in the regulation of carcinogenesis, invasion, metastasis, and therapeutic resistance in PC. Interaction between neoplastic cells and stromal cells builds a specific microenvironment, which further modulates the malignant properties of cancer cells. Instead of being a “passive bystander”, stroma may play a role as a “partner in crime” in PC. However, the role of stromal components in PC is complex and requires further investigation.

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Response to the Letter to the Editor on : "A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets," Cancer Lett. 2016 Nov 28;382(2):203-214

Thank you for highlighting that the computational discovery of the multi-cancer nature of the COL11A1-based signature, as well as the creation of a corresponding multi-cancer gene list using COL11A1 as a seed, has been published in 2010 by Kim et. [1]. Due to our focus on the pan-cancer gene signature of cancer-associated fibroblasts (CAFs) exclusively in primary cancers [2], we did not discuss multiple studies, including our own studies in ovarian cancer, that have identified almost identical gene signatures in comparisons between cancers of different stages of progression.

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A Chemical Genomics Approach to Drug Reprofiling in Oncology: Antipsychotic Drug Risperidone as a Potential Adenocarcinoma Treatment

Drug reprofiling is emerging as an effective paradigm for discovery of cancer treatments. Herein, an antipsychotic drug is immobilised using the Magic Tag® chemical genomics tool and screened against a T7 bacteriophage displayed library of polypeptides from Drosophila melanogaster, as a whole genome model, to uncover an interaction with a section of 17-β-HSD10, a proposed prostate cancer target. A computational study and enzyme inhibition assay with full length human 17-β-HSD10 identifies risperidone as a drug reprofiling candidate.

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3D Kidney Segmentation from Abdominal Images Using Spatial-Appearance Models

Kidney segmentation is an essential step in developing any noninvasive computer-assisted diagnostic system for renal function assessment. This paper introduces an automated framework for 3D kidney segmentation from dynamic computed tomography (CT) images that integrates discriminative features from the current and prior CT appearances into a random forest classification approach. To account for CT images’ inhomogeneities, we employ discriminate features that are extracted from a higher-order spatial model and an adaptive shape model in addition to the first-order CT appearance. To model the interactions between CT data voxels, we employed a higher-order spatial model, which adds the triple and quad clique families to the traditional pairwise clique family. The kidney shape prior model is built using a set of training CT data and is updated during segmentation using not only region labels but also voxels’ appearances in neighboring spatial voxel locations. Our framework performance has been evaluated on in vivo dynamic CT data collected from 20 subjects and comprises multiple 3D scans acquired before and after contrast medium administration. Quantitative evaluation between manually and automatically segmented kidney contours using Dice similarity, percentage volume differences, and 95th-percentile bidirectional Hausdorff distances confirms the high accuracy of our approach.

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HHV8/EBV Coinfection Lymphoproliferative Disorder: Rare Entity with a Favorable Outcome

HHV8/EBV-associated germinotropic lymphoproliferative disorder (GLD) is a challenging diagnosis given its rarity, the particular clinical presentation, and the lack of expression of markers usually used in establishing hematopoietic lineage. We report a new case of HHV8/EBV GLD in an immunocompetent 78-year-old woman. The diagnosis was made in an incidentally discovered lymphadenopathy. Histological examination showed a nodular lymphoid proliferation centered by aggregates of atypical plasmablastic cells admixed with small lymphoid cells. Tumor cells were strongly positive with EMA, HHV8, LMP1, CD38, CD138, and kappa light chains. They were negative with common lymphoma-associated markers (CD20, CD3, CD15, CD30, CD10, and bcl2). In situ hybridization confirmed the monotypic kappa light chains and the EBV infection (EBER+). A polyclonal pattern of Ig gene rearrangement was detected by PCR analysis. In the adjacent lymph node parenchyma, some germinal centers mimicked Castleman disease. In this case, the differential diagnosis was discussed with an early stage of large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease. The clinical presentation, the immunophenotype, and the molecular results helped to make the accurate diagnosis. Through the review of the nine previously reported cases in literature, we discuss the clinical and pathologic features and the differential diagnosis of HHV8/EBV GLD.

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Severe Preeclampsia in the Setting of Myasthenia Gravis

Myasthenia gravis (MG) is a rare autoimmune disease that leads to progressive muscle weakness and is common during female reproductive years. The myasthenic mother and her newborn must be observed carefully, as complications during all stages of pregnancy and the puerperium may arise suddenly. Preeclampsia is a common obstetrical condition for which magnesium sulfate is used for seizure prophylaxis. However, magnesium sulfate is strongly contraindicated in MG as it impairs already slowed nerve-muscle connections. Similarly, many first-line antihypertensive medications, including calcium channels blockers and β-blockers, may lead to MG exacerbation. This case describes the effective obstetrical management of a patient with MG who developed severe preeclampsia. The effective use of levetiracetam and various antihypertensive medications including intravenous labetalol is described. A review of the ten reported cases of MG complicated by preeclampsia is examined to aggregate observations of clinical care, with focus on delivery methods, anticonvulsants, and antihypertensive medications.

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Affine-Invariant Geometric Constraints-Based High Accuracy Simultaneous Localization and Mapping

In this study we describe a new appearance-based loop-closure detection method for online incremental simultaneous localization and mapping (SLAM) using affine-invariant-based geometric constraints. Unlike other pure bag-of-words-based approaches, our proposed method uses geometric constraints as a supplement to improve accuracy. By establishing an affine-invariant hypothesis, the proposed method excludes incorrect visual words and calculates the dispersion of correctly matched visual words to improve the accuracy of the likelihood calculation. In addition, camera’s intrinsic parameters and distortion coefficients are adequate for this method. 3D measuring is not necessary. We use the mechanism of Long-Term Memory and Working Memory (WM) to manage the memory. Only a limited size of the WM is used for loop-closure detection; therefore the proposed method is suitable for large-scale real-time SLAM. We tested our method using the CityCenter and Lip6Indoor datasets. Our proposed method results can effectively correct the typical false-positive localization of previous methods, thus gaining better recall ratios and better precision.

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A Giant-Cell Lesion with Cellular Cannibalism in the Mandible: Case Report and Review of Brown Tumors in Hyperparathyroidism

A small radiolucent area in the mandible was discovered in a 58-year-old woman with no oral complaints. The patient’s history included only hypertension. The lesion was considered as an inflammatory cyst and was enucleated. Three months later, a CT revealed the presence of a cyst-like lesion in the mandible with thin expanded buccal cortical plate, localized erosion, and a polylobate appearance on the lingual aspect of the cortical plate. The histological diagnosis of the lesion was central giant-cell granuloma (CGCG). The lesion was thoroughly enucleated. Nevertheless, another X-ray carried out six months later revealed multiple bilateral osteolytic areas throughout the jaw. In addition, widespread cortical plate erosion was observed, as well as signs of root resorption and periodontal enlargement. There was no sign of neurological involvement, although the nerves appeared to be dislocated. After full blood chemistry analysis and detailed collection of radiographs, the final diagnosis was brown tumors in primary hyperparathyroidism. This case report demonstrates how dental clinicians may be the first-line specialists who identify a complex systemic disease before other clinicians. Finally, it highlights the role of cellular cannibalism in predicting the clinical aggressiveness of brown tumors as well as in other giant-cell lesions.

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The Effects of Acupuncture Stimulation for Brain Activation and Alcohol Abstinence Self-Efficacy: Functional MRI Study

We attempted to investigate whether acupuncture stimulation at HT7 can have an effect on brain activation patterns and alcohol abstinence self-efficacy. Thirty-four right-handed healthy subjects were recruited for this study. They were randomly assigned into two groups: the HT7 (Shenmen) group and the LI5 (Yangxi) group. Acupuncture stimulation was performed using a block paradigm during fMRI scanning. Additionally, the Korean version of Alcohol Abstinence Self-Efficacy Scale (AASES) was used to determine the effect of acupuncture stimulation on self-efficacy to abstain from alcohol use. According to the result of fMRI group analysis, the activation induced by HT7 stimulation was found on the bilateral postcentral gyrus, inferior parietal lobule, inferior frontal gyrus, claustrum, insula, and anterior lobe of the cerebellum, as well as on the left posterior lobe of the cerebellum (, uncorrected). According to the AASES analysis, the interaction effect for gender and treatment was marginally significant (, ). For female group, the simple main effect of treatment was significant (, ), indicating that the mean change score was higher in the HT7 stimulation than in the LI5 stimulation. Therefore, our study has provided evidence to support that HT7 stimulation has a positive therapeutic effect on the alcohol-related diseases.

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Airborne Position and Orientation System for Aerial Remote Sensing

The airborne Position Orientation System (POS) can accurately measure space-time reference information and plays a vital role in aerial remote sensing system. It may be applied in a direct georeference system for optical camera and a motion imaging system for Synthetic Aperture Radar (SAR), which further advances efficiency and quality of imaging sensors. In this paper, the operation principle and components of airborne POS are introduced. Some key technologies of airborne POS are summarized. They include the error calibration and compensation, initial alignment, lever arm error modeling, time synchronization, and integrated estimation method. A high precision airborne POS has been developed and applied to a variety of aerial remote sensing systems.

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Resveratrol Attenuates Copper-Induced Senescence by Improving Cellular Proteostasis

Copper sulfate-induced premature senescence (CuSO4-SIPS) consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms. Using CuSO4-SIPS WI-38 fibroblasts, resveratrol is shown to attenuate typical senescence alterations on cell morphology, senescence-associated beta-galactosidase activity, and cell proliferation. The mechanisms implicated in this antisenescence effect seem to be independent of senescence-associated genes and proteins regulation but are reliant on cellular proteostasis improvement. In fact, resveratrol supplementation restores copper-induced increased protein content, attenuates BiP level, and reduces carbonylated and polyubiquitinated proteins by autophagy induction. Our data provide compelling evidence for the beneficial effects of resveratrol by mitigating CuSO4-SIPS stressful consequences by the modulation of protein quality control systems. These findings highlight the importance of a balanced cellular proteostasis and add further knowledge on molecular mechanisms mediating resveratrol antisenescence effects. Moreover, they contribute to identifying specific molecular targets whose modulation will prevent age-associated cell dysfunction and improve human healthspan.

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Vitamin K Deficiency Presenting in an Infant with an Anterior Mediastinal Mass: A Case Report and Review of the Literature

We report a case of a 1-month-old infant with spontaneous thymic hemorrhage secondary to severe vitamin K deficiency. He was brought to medical attention due to scrotal bruising and during evaluation was noted to be tachypneic and hypoxemic. Chest X-ray revealed an enlarged cardiothymic silhouette, and a follow-up echocardiogram revealed a mass in the anterior mediastinum. Routine laboratory work-up revealed severe coagulopathy. Further questioning revealed the patient had not received prophylactic vitamin K at birth. The coagulopathy resolved with administration of vitamin K, and a biopsy confirmed the anterior mediastinal mass was due to spontaneous thymic hemorrhage.

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Research on Modeling Intrahousehold Interactions from the Perspective of Space-Time Constraints

Interactions among family members can yield valuable information for interpreting individual travel decisions. Typically, each family member plays a set role and travel decisions are made by considering the combined needs of household members. This study investigates both multiactivity and multiperson interactions in urban nuclear families and proposes the novel concepts of “activity-restriction degree” and “activity-constraint niche” to quantify the degree of space-time constraints within time geography. A structural equation model is employed to analyze intrahousehold interactions based on individual activity-travel patterns during the workday. The results indicate that the links between family members reflect behavioral responses (with constraints) between individuals and other family members. Household interaction constraints not only influence individual travel decisions but also affect the realization of the household activity for everyone. These interactions lead to reasonable adjustments and mutual support and to the identification of efficient activity patterns that meet the demands of the entire household.

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Target Transportation of Auxin on Mesoporous Au/SiO2 Nanoparticles as a Method for Somaclonal Variation Increasing in Flax (L. usitatissimum L.)

Development of methods for direct delivery of different bioactive substances into the cell is a promising and intensively approached area of research. It has become a subject of serious research for multidisciplinary team of scientists working in such areas as physics, biology, and biotechnology. Plant calluses were grown on medium supplemented with different nanoparticles to be used as a model for biotechnological research. Gold nanoparticles with mesoporous silica coating were used as hormone carriers, since they possess many of critical properties required for cellular transportation instrument. Some of those properties are great biocompatibility and controlled release of carried molecules. Significant changes in hormones common impact were detected. The great increase in ploidy numbers, embryogenesis, induction, and methylation level was observed when compared to the “conventional” methods of targeted hormones delivery that embrace usage of Au nanoparticles as a main hormone carrier. The authors suppose the research under consideration can provide a new pathway to the design of a novel targeted plant hormone and bioactive substances carrier.

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Geoffroea decorticans for Biofuels: A Promising Feedstock

In this work, chañar (Geoffroea decorticans) fruit is evaluated as a potential feedstock for biodiesel and biomass pellets production with reference to some relevant properties. The fatty acid profile of this oil (83% unsaturated acids) is found to be comparable to similar seed oils which have been attempted for biodiesel production. As a result, the methyl esters (biodiesel) obtained from this oil exhibits high quality properties. Chañar biodiesel quality meets all other biodiesel international standards (ASTM D6751 and EN 14214). Moreover, the husk that surrounds the kernel showed a high potential for usage as densified solid fuels. The results demonstrate that chañar husks pellets have a higher calorific value when compared with other biomass pellets, typically, approximately 21 MJ kg−1 with 1.8% of ashes (which is equivalent to that obtained from the combustion of pellets produced from forest wastes). This study indicates that chañar can be used as a multipurpose energy crop in semiarid regions for biodiesel and densified solid fuels (pellets) production.

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Electrochemical Skin Conductance May Be Used to Screen for Diabetic Cardiac Autonomic Neuropathy in a Chinese Population with Diabetes

Aims. This study aimed to assess whether the electrochemical skin conductance (ESC) could be used to screen for diabetic cardiac autonomic neuropathy (DCAN) in a Chinese population with diabetes. Methods. We recruited 75 patients with type 2 diabetes mellitus (T2DM) and 45 controls without diabetes. DCAN was diagnosed by the cardiovascular autonomic reflex tests (CARTs) as gold standard. In all subjects ESCs of hands and feet were also detected by SUDOSCAN™ as a new screening method. The efficacy was assessed by receiver operating characteristic (ROC) curve analysis. Results. The ESCs of both hands and feet were significantly lower in T2DM patients with DCAN than those without DCAN ( versus , , and versus , ). The ROC curve analysis showed the areas under the ROC curve were both 0.75 for ESCs of hands and feet in screening DCAN. And the optimal cut-off values of ESCs, sensitivities, and specificities were 76 μS, 76.7%, and 75.6% for hands and 75 μS, 80.0%, and 60.0% for feet, respectively. Conclusions. ESC measurement is a reliable and feasible method to screen DCAN in the Chinese population with diabetes before further diagnosis with CARTs.

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The Effect of High Intensity Focused Ultrasound Keratoplasty on Rabbit Anterior Segment

Purpose. To evaluate the safety of high-intensity focused ultrasound keratoplasty as a treatment for presbyopia by examining its effect on the rabbit anterior segment. Methods. The right corneas of 36 New Zealand rabbits were treated with HIFU keratoplasty. The animals were sacrificed at 1, 7, 15, 30, 60, and 90 days after operation. Collagen type I, MMP-2, and MMP-9 were evaluated using immunohistochemistry. For the detection of apoptosis, the TUNEL method was applied. The SOD and MDA levels were analyzed with assay kits. Results. Collagen type I, MMP-2, and MMP-9 levels were altered after the operation but returned to normal within 90 days. The apoptotic index (AI) of the corneal cells decreased from 1 to 30 days gradually. No apoptosis was observed in the epithelial cells of the lens, and the SOD and MDA levels were normal at any time point. Conclusion. After HIFU keratoplasty, the histomorphology of the cornea changed, the corneal collagen type I levels decreased, the corneal MMP-2 and MMP-9 levels increased, and the corneal cells underwent apoptosis for a period of time. Ninety days after the operation, the levels returned to normal, and the lenses were not affected. Thus, HIFU presents good biological safety for eyes.

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Description of Weak Halogen Bonding Using Various Levels of Symmetry-Adapted Perturbation Theory Combined with Effective Core Potentials

The present work starts with providing a description of the halogen bonding (XB) interaction between the halogen atom of MH3X (where M = C–Pb and X = I, At) and the N atom of HCN. This interaction leads to the formation of stable yet very weakly bound MH3X⋯NCH complexes for which the interaction energy () between MH3X and HCN is calculated using various symmetry-adapted perturbation theory (SAPT) methods combined with the def2-QZVPP basis set and midbond functions. This basis set assigns effective core potentials (ECPs) not only to the I or At atom directly participating in the XB interaction with HCN but also to the M atom when substituted with Sn or Pb. Twelve SAPT methods (or levels) are taken into consideration. According to the SAPT analysis of , the XB interaction in the complexes shows mixed electrostatic-dispersion nature. Next, the accuracy of SAPT is evaluated by comparing with CCSD(T) reference data. This comparison reveals that high-order SAPT2+ method and the much less computationally demanding SAPT(DFT) method perform very well in describing of the complexes. However, the accuracy of these methods decreases dramatically if they are combined with the so-called Hartree-Fock correction.

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Centralized Data-Sampling Approach for Global Synchronization of Fractional-Order Neural Networks with Time Delays

In this paper, the global synchronization problem is investigated for a class of fractional-order neural networks with time delays. Taking into account both better control performance and energy saving, we make the first attempt to introduce centralized data-sampling approach to characterize the synchronization design strategy. A sufficient criterion is given under which the drive-response-based coupled neural networks can achieve global synchronization. It is worth noting that, by using centralized data-sampling principle, fractional-order Lyapunov-like technique, and fractional-order Leibniz rule, the designed controller performs very well. Two numerical examples are presented to illustrate the efficiency of the proposed centralized data-sampling scheme.

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RELAP5 Simulation of PKL Facility Experiments under Midloop Conditions

Nuclear power plant risk has to be quantified in full power and in other modes of operation. This latter situation corresponds to low power and shutdown modes of operation in which the residual heat removal (RHR) system is required to extract the heat generated in the core. These accidental sequences are great contributors to the total plant risk. Thus, it is important to analyze the plant behavior to establish the accident mitigation measures required. In this way, PKL facility experimental series were undertaken to analyze the plant behavior in other modes of operation when the RHR is lost. In these experiments, the plant configurations were changed to analyze the influence of steam generators secondary side configurations, the temperature inside the pressurizer, and the inventory level on the plant behavior. Moreover, different accident management measures were proposed in each experiment to reach the conditions to restart the RHR. To understand the physical phenomena that takes place inside the reactor, the experiments are simulated with thermal-hydraulic codes, and this makes it possible to analyze the code capabilities to predict the plant behavior. This work presents the simulation results of four experiments included in PKL experimental series obtained using RELAP5/Mod3.3.

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Spectrum of Congenital Anomalies among Surgical Patients at a Tertiary Care Centre over 4 Years

Introduction. Congenital anomalies are important causes of childhood death, chronic illness, and disability in many countries. Congenital malformations are rapidly emerging as one of the major worldwide problems. Aim. To study the percentage of various congenital anomalies among the patients admitted in Department of Pediatric Surgery at a tertiary care centre over a period of four years from 2011 to 2015 in our centre. Results. Neural tube defects were found to be the most common anomalies in 24.3% of the children admitted. Other common anomalies were anorectal malformation (20.7%), tracheoesophageal fistula (20%), and intestinal obstruction (14.84%). Majority (60.5%) of the patients were males. Conclusion. Congenital malformations are rapidly emerging as one of the major worldwide problems as they can result in long-term disability, which may have significant impacts on individuals, families, health-care systems, and societies. Regular antenatal visits and prenatal diagnosis are recommended for prevention, early intervention, and even planned termination, when needed.

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Introducing Weather Factor Modelling into Macro Traffic State Prediction

Adverse weather has significant impacts on road conditions and traffic dynamics. It is observed that adverse weather as a set of exogenous factors lowers the free flow speed, shifts critical density, decreases flow capacity, and makes the freeway more prone to congestion. This paper proposes a weather factor model to be plugged into a macroscopic traffic prediction model, so that under bad weather traffic variables can be more accurately and reasonably estimated and predicted for traffic control use. To be specific, weather-specific fundamental diagrams are built by introducing weather factors to free flow speed, capacity, and critical density. The weather factors are modelled by selected weather measurements. Weather factor parameters are trained by recent historical weather and traffic data and then can be put into real-time macro traffic prediction and control. The traffic prediction model in the case study is METANET model, in which fundamental diagram parameters are one source of input. The weather-specific prediction error and conventional prediction error are compared. Real data collected by loop detectors on Whitemud Drive, Edmonton, Canada, is used for parameter calibration and prediction error evaluation. The results show that the proposed weather models reasonably improved the accuracy of macro traffic state prediction model compared to conventional model.

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Determination of Levels of Organochlorine, Organophosphorus, and Pyrethroid Pesticide Residues in Vegetables from Markets in Dar es Salaam by GC-MS

This study investigated the levels of pesticides and metabolites in vegetables from major markets in Dar es Salaam city, Tanzania. Samples of fresh cabbage, spinach, and onions from the markets were analysed for pesticide residues. Extraction was performed using acetone followed by dichloromethane : cyclohexane mixture and the extracts were cleaned up using Florisil. The compounds were determined by gas chromatography-mass spectrometry (GC-MS). Pesticides and metabolites were detected in 72.2% of the samples. The detected pesticide residues and their highest mean concentrations were p,p′-DDT 4.00 × 10−3 mg/kg, p,p′-DDD 6.40 × 10−1 mg/kg, o,p′-DDD 1.00 × 10−2 mg/kg, α-endosulfan 6.00 × 10−1 mg/kg, β-endosulfan 2.10 × 10−1 mg/kg, chlorpyrifos 3.00 mg/kg, and cypermethrin 4.00 × 10−2 mg/kg. The most frequently detected compounds were p,p′-DDD and chlorpyrifos. The order of contamination was spinach > cabbage > onions. Generally, there were no significant variations in concentrations of pesticide residues among samples and sampling sites, which indicated similarities in contamination patterns. The concentrations of contaminants were above the maximum residue limits (MRLs) in 33.3–50% of the samples. The findings indicated risks and concerns for public health.

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Synthetic food additive dye “Tartrazine” triggers amorphous aggregation in cationic myoglobin

Publication date: May 2017
Source:International Journal of Biological Macromolecules, Volume 98
Author(s): Nasser Abdulatif Al-Shabib, Javed Masood Khan, Mohd Shahnawaz Khan, Mohd Sajid Ali, Abdulrahman M. Al-Senaidy, Mohammad A. Alsenaidy, Fohad Mabood Husain, Hamad A. Al-Lohedan
Protein aggregation, a characteristic of several neurodegenerative diseases, displays vast conformational diversity from amorphous to amyloid-like aggregates. In this study, we have explored the interaction of tartrazine with myoglobin protein at two different pHs (7.4 and 2.0). We have utilized various spectroscopic techniques (turbidity, Rayleigh light scattering (RLS), intrinsic fluorescence, Congo Red and far-UV CD) along with microscopy techniques i.e. atomic force microscopy (AFM) and transmission electron microscopy (TEM) to characterize the tartrazine-induced aggregation in myoglobin. The results showed that higher concentrations of tartrazine (2.0–10.0mM) induced amorphous aggregation in myoglobin at pH 2.0 via electrostatic interactions. However, tartrazine was not able to induce aggregation in myoglobin at pH 7.4; because of strong electrostatic repulsion between myoglobin and tartrazine at this pH. The tartrazine-induced amorphous aggregation process is kinetically very fast, and aggregation occurred without the formation of a nucleus. These results proposed that the electrostatic interaction is responsible for tartrazine-induced amorphous aggregation. This study may help in the understanding of mechanistic insight of aggregation by tartrazine.

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Effect of starch type on the physico-chemical properties of edible films

Publication date: May 2017
Source:International Journal of Biological Macromolecules, Volume 98
Author(s): Ewelina Basiak, Andrzej Lenart, Frédéric Debeaufort
Food preservation is mostly related to packaging in oil-based plastics, inducing environmental problems, but this drawback could be limited by using edible/biodegradable films and coatings. Physical and chemical properties were assessed and reflect the role of the starch type (wheat, corn or potato) and thus that of the amylose/amylopectin ratio, which influences thickness, colour, moisture, wettability, thermal, surface and mechanical properties. Higher amylose content in films induces higher moisture sensitivity, and thus affects the mechanical and barrier properties. Films made from potato starch constitute a greater barrier for oxygen and water vapour though they have weaker mechanical properties than wheat and corn starch films. Starch species with higher amylose content have lower wettability properties, and better mechanical resistance, which strongly depends on the water content due to the hydrophilic nature of starch films, so they could be used for products with higher water activity, such as cheese, fruits and vegetables. It especially concerns wheat starch systems, and the contact angle indicates less hydrophilic surfaces (above 90°) than those of corn and potato starch films (below 90°). The starch origin influences optical properties and thickness: with more amylose, films are opalescent and thicker; with less, they are transparent and thinner.

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Isolation and partial characterization of starch from banana cultivars grown in Colombia

Publication date: May 2017
Source:International Journal of Biological Macromolecules, Volume 98
Author(s): A. Chávez-Salazar, L.A. Bello-Pérez, E. Agama-Acevedo, F.J. Castellanos-Galeano, C.I. Álvarez-Barreto, G. Pacheco-Vargas
Banana starch is resistant to hydrolysis by digestive enzymes due to its structure and dietary fibre content. Starch was isolated from the following three cultivars of Colombian Musaceae: Gros Michel (dessert), Dominico Harton and FHIA 20 (cooking); also, the amylose and amylopectin contents, morphology of the granules, thermal properties, pasting, molecular characteristics and digestibility were determined. The total starch content, amylose content and digestibility (gelatinized starch) were higher in cooking varieties; the purity and gelatinization temperature were similar for the three varieties, but the enthalpy was higher in the dessert variety. The three varieties showed higher viscosities in the pasting profile compared to commercial maize starch in both acid and neutral conditions. Starch granules presented with heterogeneous sizes and shapes (elongated and ovals) that had birefringence. The Dominico Hartón variety showed the lowest rapidly digestible starch (RDS) value in the gelatinized sample that is in agreement with the greater proportion of long chains.

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Efficient separation of mannan–protein mixtures by ionic liquid aqueous two-phase system, comparison with lectin affinity purification

Publication date: May 2017
Source:International Journal of Biological Macromolecules, Volume 98
Author(s): Alžbeta Čížová, Jana Korcová, Pavol Farkaš, Slavomír Bystrický
Analysis of carbohydrates from complex biological samples often requires their isolation from proteins and other contaminants to avoid interference. An effective separation of mannan–protein mixtures by 1-butyl-3-methylimidazolium bromide/K2HPO4 ionic liquid aqueous two-phase system (IL-APTS) is reported. Extraction efficiency of bovine serum albumin (BSA) ranged from 92% to 97% while extraction efficiency of mannan reached values from 95% to about 100% depending on phase and/or model sample composition. On the contrary, lower efficiency of BSA removal (73–84%) was recorded for lectin affinity purification with concanavalin A–triazine bead cellulose (Con A-TBC); the low mannan-binding capacity was limiting factor here. The size exclusion chromatography pattern of model mannan–BSA samples after both IL-APTS and Con A-TBC treatments were consistent with the spectrophotometric component analysis. In case of biological experiment, the ionic liquid separation technique was superior in pre-purification of 2-aminobenzamide-labelled mannan from cell culture medium prior to HPLC-FLD analysis.

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Sensor development of 1,2 Dichlorobenzene based on polypyrole/Cu-doped ZnO (PPY/CZO) nanocomposite embedded silver electrode and their antimicrobial studies

Publication date: May 2017
Source:International Journal of Biological Macromolecules, Volume 98
Author(s): Aftab Aslam Parwaz Khan, Anish Khan, Mohammed M. Rahman, Abdullah M. Asiri, Mohammad Oves
Cu-doped ZnO nanopowders and their composites of polypyrole (PPY)/CZO were prepared by a gel combustion method and an in-situ polymerization process, respectively. The synthesized nanocomposite are characterized by X-ray powder diffractometry (XRD), scanning electron microscopy (SEM), FTIR, and TGA studies. Then the PPY/CZO/AgE nanocomposites were used for potential application in chemical sensing by easy and reliable I–V method, where 1,2 dichlorobenzene (1,2-DCB) is considered as a model target compound. The chemical sensor performances are exhibited the higher sensitivity, good stability, and repeatability of the sensor enhanced significantly using PPY/CZO/AgE of thin-film with conducting binders on silver electrodes (AgE; Surface area: 0.0216cm²). The calibration plot is linear over the large dynamic range (0.35nM∼3.5mM), where the sensitivity (∼2.702μAmM⁻¹cm⁻²) and detection limit (∼0.34nM) is calculated based on signal/noise ratio (∼^3N/S) in short response time. Finally, it is concluded that the structural and optical characteristics could be encompassed to a broad-scale in PPY/CZO/AgE composites and efficient chemical sensor applications for environmental fields. Simultaneously PPY/CZO composites was also evaluated against Gram positive bacteria Bacillus subtilis, Gram negative bacteria Escherichia coli and antibiotics (Amoxicillin) using the agar plate.

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Improved thermal-stability and mechanical properties of type I collagen by crosslinking with casein, keratin and soy protein isolate using transglutaminase

Publication date: May 2017
Source:International Journal of Biological Macromolecules, Volume 98
Author(s): Xiaomeng Wu, Yaowei Liu, Anjun Liu, Wenhang Wang
The inferior thermal- stability of collagen hinders its extensive application in food industry, including edible packaging. To improve the thermal- stability and mechanical properties of collagen, we attempted to crosslink collagen with some proteins possessing excellent thermal stability (i. e., casein, keratin and soy protein isolate (SPI)). Observed from the SDS- PAGE and particle size distribution, some complexes with higher molecule weight and relative bigger size particle occurred in the protein mixture, especially after TGase crosslinking. Importantly, the crosslinking greatly improved the thermal- stable property of protein complex, especially that of the collagen- casein complex judged from differential scanning calorimetric (DSC). Moreover, the crosslinking enhanced the mechanical properties of the combined films in terms of tensile strength (TS) and elongation at break (EAB). Also, some obvious differences in morphology of proteins before and after TGase crosslinking were observed by scanning electron microscopy (SEM). These impacts of TGase crosslinking with heat- resistant proteins on collagen features were associated with the conformational changes of the protein complex analyzed by Fourier transform infrared spectroscopy (FTIR). In conclusion, TGase crosslinking with higher thermally stable proteins could be an effective method to contribute to collagen’ application in food packaging field.

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Πληροφορίες

Τετάρτη 8 Φεβρουαρίου 2017

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