bluuebunny/crossref_metadata_2025 huggingface dataset:
SIRT6 deacetylase transcriptionally regulates glucose metabolism in heart
Authors: Khan Danish , Sarikhani Mohsen , Dasgupta Subhajit , Maniyadath Babukrishna , Pandit Anwit S. , Mishra Sneha , Ahamed Faiz , Dubey Abhinav , Fathma Nowrin , Atreya Hanudatta S. , Kolthur‐Seetharam Ullas , Sundaresan Nagalingam R.
Published: January 2018

Sirtuins are a family of enzymes, which govern a number of cellular processes essential for maintaining physiological balance. SIRT6, a nuclear sirtuin, is implicated in the development of metabolic disorders. The role of SIRT6 in regulation of cardiac metabolism is unexplored. Although glucose is not the primary energy source of heart, defects in glucose oxidation have been linked to heart failure. SIRT6+/− mice hearts exhibit increased inhibitory phosphorylation of PDH subunit E1α. SIRT6 deficiency enhances FoxO1 nuclear localization that results in increased expression of PDK4. We show that SIRT6 transcriptionally regulates the expression of PDK4 by binding to its promoter. SIRT6+/− hearts show accumulation of lactate, indicating compromised mitochondrial oxidation. SIRT6 deficiency results in decreased oxygen consumption rate and concomitantly lesser ATP production. Mechanistically, SIRT6 deficiency leads to increased FoxO1‐mediated transcription of PDK4. Our findings establish a novel link between SIRT6 and cardiac metabolism, suggesting a protective role of SIRT6 in maintaining cardiac homeostasis.
Hepatic miR‐125b inhibits insulin signaling pathway by targeting PIK3CD
Authors: Du Xiliang , Li Xiaobing , Chen Liang , Zhang Min , Lei Lin , Gao Wenwen , Shi Zhen , Dong Yuhao , Wang Zhe , Li Xinwei , Liu Guowen
Published: January 2018

Insulin resistance is often characterized as the most critical factor contributing to the development of (T2D) type 2 diabetes. MicroRNAs (miRNAs) are endogenous non‐coding short single‐stranded RNAs that function as negative regulators in many physiological and pathological processes. The objective of this study was to evaluate the roles of miR‐125b in the regulation of insulin sensitivity in hepatocytes. We found that hepatic miR‐125b levels were significantly increased in the patients with type 2 diabetes, high fat diet (HFD) mice, ob/ob and db/db mice. In vitro, miR‐125b was also significantly up‐regulated in tumor necrosis factor‐alpha‐ (TNF‐α) and glucosamine‐induced insulin resistance conditions. Furthermore, miR‐125b overexpression impaired the insulin signaling pathway in HepG2 cells, L02c cells, and primary hepatocytes. Inhibition of miR‐125b improved insulin sensitivity, especially in insulin‐resistant cells induced by either TNF‐α or glucosamine. We demonstrated that miR‐125b targeted the 3′‐untranslated region (3′‐UTR) of phosphoinositide 3‐kinase catalytic subunit delta (PIK3CD) mRNA. The hepatic PIK3CD protein levels were markedly decreased in patients with type 2 diabetes, HFD, ob/ob, and db/db mice. Inhibition of PIK3CD markedly attenuated the improvement of insulin sensitivity induced by miR‐125b inhibitors. More importantly, overexpressing miR‐125b in mice causes insulin resistance and impairs glucose homeostasis. Together, these findings indicate that miR‐125b inhibits insulin sensitivity by targeting PIK3CD in hepatocytes, supporting hepatic miR‐125b, or PIK3CD are potential therapeutic target of insulin resistance.
Long noncoding RNA CASC2 regulates hepatocellular carcinoma cell oncogenesis through miR‐362‐5p/Nf‐κB axis
Authors: Zhao Liang , Zhang Yongjian , Zhang Yubao
Published: January 2018

The long non‐coding RNA segment cancer susceptibility candidate 2 (CASC2) has been shown to suppress tumor growth in a variety of cancers, including hepatocellular carcinoma (HCC). However, the mechanism by which CASC2 exerts control over HCC has yet to be established. In the present study, we first demonstrated that CASC2 is downregulated in human HCC tissues and HCC cell lines as compared to adjacent non‐tumor tissues (NTTs) and a liver cell line, respectively. After finding that CASC2 knockdown significantly promotes HCC cells migration and invasion as well as that CASC2 overexpression inhibits cell migration and invasion, we identified the microRNA miR‐362‐5p as an endogenous target of CASC2. Through the use of wild type and mutant CASC2 binding sites inserted into psiCHECK‐2 luciferase reporter plasmids, as well as qRT‐PCR, we determined that CASC2 overexpression reduces miR‐362‐5p expression levels, while inhibiting CASC2 activity increases miR‐362‐5p expression. Past research has shown that miR‐362‐5p stimulates the NF‐κB pathway, which has been implicated in the survival and proliferation of a variety of cancer cells. We therefore investigated the effects of CASC2 expression on NF‐κB pathway activity. Ultimately, we determined that CASC2 regulates HCC cell activity by targeting miR‐362‐5p and thus inhibiting the NF‐κB pathway. The present study not only identifies CASC2 as an important HCC cell regulator, but also suggests its mechanism of action. It therefore provides the basis for designing strategies to target CASC2 activity and thereby inhibit HCC growth and progression.
Glucose enhances aggrecan expression in chondrocytes via the PKCα/p38‐miR141‐3p signaling pathway
Authors: Wu Tsung‐Ju , Fong Yi‐Chin , Lin Chih‐Yang , Huang Yuan‐Li , Tang Chih‐Hsin
Published: January 2018

Aggrecan is a high molecular weight proteoglycan that plays a critical role in cartilage structure and the function of joints, providing intervertebral disc and cartilage with the ability to resist compressive loads. Aggrecan degradation in articular cartilage is a significant event in early‐stage osteoarthritis (OA). Currently, no effective treatment exists for OA other than pain relief. Dextrose (D‐glucose) prolotherapy has shown promising activity in the treatment of different musculoskeletal disorders, including OA. However, little is known about the molecular mechanism of the glucose effect in OA and on the regulation of chondrogenesis. We show for the first time that glucose upregulates aggrecan expression and subsequent chondrogenesis in ATDC5 cells. Moreover, we found that glucose‐induced aggrecan expression is mediated through the protein kinase Cα (PKCα)‐ and p38‐dependent pathway. As demonstrated by microRNA (miR) and luciferase analyses, the glucose‐induced PKCα/p38 signaling axis is responsible for downregulating miR141‐3p which targets to the 3′untranslated region of aggrecan. In summary, we show that glucose enhances chondrogenesis by upregulating aggrecan expression via the PKCα‐p38‐miR141‐3p signaling pathway. This result provides new insights into the mechanism of glucose on chondrogenesis.
Prediction of Vancomycin Dose for Recommended Trough Concentrations in Pediatric Patients With Cystic Fibrosis
Authors: Amin Raid W. , Guttmann Rodney P. , Harris Quianna R. , Thomas Janesha W.
Published: January 2018

Vancomycin is a key antibiotic used in the treatment of multiple conditions including infections associated with cystic fibrosis and methicillin‐resistant Staphylococcus aureus. The present study sought to develop a model based on empirical evidence of optimal vancomycin dose as judged by clinical observations that could accelerate the achievement of desired trough level in children with cystic fibrosis. Transformations of dose and trough were used to arrive at regression models with excellent fit for dose based on weight or age for a target trough. Results of this study indicate that the 2 proposed regression models are robust to changes in age or weight, suggesting that the daily dose on a per‐kilogram basis is determined primarily by the desired trough level. The results show that to obtain a vancomycin trough level of 20 μg/mL, a dose of 80 mg/kg/day is needed. This analysis should improve the efficiency of vancomycin usage by reducing the number of titration steps, resulting in improved patient outcome and experience.
Feedforward control application in aerobic and anoxic biotrickling filters for H2S removal from biogas
Authors: López Luis R , Brito Javier , Mora Mabel , Almenglo Fernando , Baeza Juan A , Ramírez Martín , Lafuente Javier , Cantero Domingo , Gabriel David
Published: January 2018

BACKGROUND

Feedforward control was implemented at laboratory scale in an aerobic and an anoxic biotrickling filter (BTF) operating under fluctuating H2S loading rate (LR) conditions in order to show the capabilities and added value of this control strategy. Dynamic, long‐term tests with variable H2S LR were performed to simulate disturbances in the inlet gas concentration with and without the implementation of a feedforward control loop based on trickling liquid velocity (TLV) and nitrate feeding rate manipulation for the aerobic and anoxic BTFs, respectively.

RESULTS

An average LR of 80 g S‐H2S m–3 h–1 with peaks and valleys of 141 and 28 gS‐H2S m–3 h–1 were tested. At the highest H2S LR, a 68.4% and 62.6% reduction of maximum outlet H2S concentration, and 50.0% and 26.6% reduction of H2S cumulative mass emitted were reached in the aerobic and anoxic BTFs, respectively, thanks to the application of feedforward control strategies. The sulfate selectivity in the aerobic BTF was enhanced up to 100.6 ± 5.0% under controlled conditions. In the anoxic BTF the sulfate selectivity was kept constant at 32.8% ± 0.8%.

CONCLUSION

Despite demonstrating that the feedforward controller significantly reduced the impact of disturbances, the utilization of TLV as manipulated variable in the aerobic reactor showed performance problems. However, the feedforward control through nitrate addition was shown to be an adequate, robust strategy for reducing the impact of load perturbation in anoxic BTFs. © 2018 Society of Chemical Industry
Physiological significance of gravity receptors on larval cephalic cuticle in the silk moth, Antheraea proylei Jolly
Authors: Dey Sudip , Choudhury S.
Published: January 2018

The lateral aspects of larval cephalic cuticle of oak tasar moth, Antheraea proylei, a hybrid between Antheraea pernyi and Antheraea roylei exhibited the presence of gravity receptors in the form of dorsal campaniform sensilla. The distribution pattern and number of dome shaped dorsal campaniform sensilla were found to vary in different larval stages. In the first and second larval stages, 4‐5 sensilla were localized near the apex of the lateral aspects of the cephalic cuticle on either side of the head. From the third larval stage onwards, on the other hand, both the right and left lateral aspects of the cephalic cuticle were covered with innumerable dome shaped dorsal campaniform sensilla. The sensilla were found to be arranged in groups of 3 to 5 on the cephalic cuticle with dome‐free cuticular portion of about 50–100 µm in length between two adjacent groups of the sensilla. The individual dome shaped dorsal campaniform sensillum was either smooth surfaced or was covered with smaller domes through out the surface. The significance of differences in the number and distribution pattern of the dorsal campaniform sensilla among different larval stages in relation to gravity reception and preferred feeding posture are discussed in the light of available literature.
Histological, histochemical, and ultrastructural investigation of the male copulatory apparatus of Haminoea navicula (Gastropoda, Cephalaspidea)
Authors: Lobo‐da‐Cunha Alexandre , Alves Ângela , Oliveira Elsa , Malaquias Manuel António E.
Published: January 2018

Due to its biological and systematic importance, the morphology and function of the male copulatory apparatus of Haminoea navicula, a Cephalaspidea gastropod mollusk, was investigated by light and electron microscopy. These systems are poorly understood in haminoids, but are often used in the taxonomy of the genus. In H. navicula, the male copulatory apparatus comprises the penis within a penial sheath, a seminal duct and the prostate with two lobes. The penis is a muscular structure with a tip covered by spikes formed by muscular cells. The penial sheath consists of muscular tissue folds lined by an epithelium. Below this epithelium, polysaccharide‐secreting cells and pigment cells were observed. A large number of vacuolar cells were found below the ciliated epithelium of the seminal duct. The proximal lobe of the prostate was formed by tubules that could be divided in basal, middle and apical zones, containing cells that secrete polysaccharides and proteins. The tubules of the prostate distal lobe contained a single type of secretory cells with vesicles that were stained by histochemical techniques for detection of polysaccharides and proteins. Ciliated cells were present along the tubules in both lobes of the prostate. This study revealed a complex prostate with five types of secretory cells, which secrete substances that should be involved in the maintenance and eventually also in the maturation of spermatozoa. A comparison with previous publications, shows that the male copulatory apparatus can differ substantially among cephalaspideans, even between H. navicula and non‐European species attributed to this genus.
Prognostic value of neutrophil‐to‐lymphocyte ratio associated with prognosis in HBV‐infected patients
Authors: Gong Jiao , Liang Yan‐Lan , Zhou Wenying , Jie Yusheng , Xiao Cuicui , Chong Yutian , Hu Bo
Published: January 2018

Chronic severe hepatitis B (CSHB) is a critical clinical syndrome with a high mortality rate in China. The prognostic value of neutrophil to lymphocyte ratio (NLR) which is simple, low‐cost, and useful inflammatory marker for hepatitis B virus (HBV)‐infected patients is largely overlooked and without further exploration. This study assesses the association of NLR with prognosis of chronic hepatitis B (CHB) and CSHB patients. Two hundred and eighty subjects, including 79 with chronic hepatitis B (CHB) and 67 with chronic severe hepatitis B (CSHB), and 134 healthy individuals were retrospectively recruited into this study. Blood samples were collected to conduct liver function, prothrombin time activity (PTA), international normalized ratio (INR), HBV DNA measurement, and routine hematological testing. All patients were followed up for at least 3 months. NLR values in patients with CSHB (4.984 ± 3.608) and CHB (2.020 ± 1.182) were significantly higher than those in healthy control (1.638 ± 0.601) and patients with CSHB had the highest NLR values than CHB and healthy control. Increased NLR values were clinically associated with severe liver disease and higher mortality rate. NLR was found to be an independent predictor of mortality in multivariable Cox Regression models (HR = 3.912, 95%CI: 1.587‐9.640, P = 0.003). NLR values are significantly increased in CHB and CSHB patients with the severity of liver disease. Moreover, NLR value is an independent predicting factor for the mortality rate in HBV‐infected patients.
Human respiratory syncytial virus load normalized by cell quantification as predictor of acute respiratory tract infection
Authors: Gómez‐Novo Miriam , Boga José A. , Álvarez‐Argüelles Marta E. , Rojo‐Alba Susana , Fernández Ana , Menéndez María J. , de Oña María , Melón Santiago
Published: January 2018

Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive, and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV‐positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β‐globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (P < 0.001). The viral mean load was 4.81 ± 1.98 log10 copies/1000 cells for patients under the age of 4‐year‐old (P < 0.001). The viral mean loads were 4.51 ± 2.04 cells in patients with low respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (P < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression.
A novel predictor of severe dengue: The aspartate aminotransferase/platelet count ratio index (APRI)
Authors: Zhang Hao , Xie Zhiwei , Xie Xushuo , Ou Yingyan , Zeng Wenting , Zhou Yuanping
Published: January 2018

To evaluate risk factors for the development of dengue into severe dengue in Guangdong. A retrospective analysis of clinical data from 212 dengue patients between June and October 2014. A total of 174 (82.1%) patients in our study had classic dengue, of which 38 (17.9%) had severe diseases. The frequencies of jaundice, pleural effusion, ascites, and vaginal bleeding were significantly different between the two groups (P < 0.05). The routine laboratory test results for alanine aminotransferase, aspertate aminotransferase, albumin, leukocyte count, platelet count, activated partial prothrombin time, prothrombin time, and aspartate aminotransferase/platelet count ratio index showed a significant association with severe dengue (P < 0.01). The areas under the receiver operating characteristic curves (AUC) were 0.727 (95% CI 0.662–0.78), 0.699 (95%CI 0.632–0.760), 0.634 (95%CI 0.565–0.698), 0.757 (95%CI 0.694–0.813), 0.775 (95%CI 0.713–0.829), 0.713 (95%CI 0.647–0.773), 0.719 (95%CI 0.730–0.843), and 0.785 (95%CI 0.724–0.893), respectively. The logistic regression analysis identified three factors, including high WBC (OR 1.52), prolonged PT (OR 1.745). and high APRI (OR 1.05) may be associated with the discrimination criteria to identify patients with and without severe diseases. The combination of the three factors (WBC, PT, and APRI) showed better AUC (0.877) and OR (1.52) scores. Our study indicates that laboratory tests such as WBC, PT, and APRI, helped identify patients at risk of developing severe dengue. The APRI was identified as a valuable predictor of patients with severe dengue. Combining the WBC, PT, and APRI scores allowed a better prediction of severe dengue.
Predictors of treatment efficacy and liver stiffness changes following therapy with Sofosbuvir plus Ribavirin in patients infected with HCV genotype 2
Authors: Ohya Kazuki , Akuta Norio , Suzuki Fumitaka , Fujiyama Shunichiro , Kawamura Yusuke , Kominami Yoko , Sezaki Hitomi , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Suzuki Yoshiyuki , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Kumada Hiromitsu
Published: January 2018

While the combination therapy of ribavirin (RBV) and sofosbuvir (SOF) is effective in genotype 2 HCV infection, the predictors of treatment efficacy and posttreatment changes in α‐fetoprotein (AFP) and liver stiffness (markers of hepatocellular carcinoma), remain unclear. In this study, 302 patients with chronic HCV genotype 2 infection were treated with SOF (400 mg) plus RBV (400‐1000 mg; based on body weight) for 12 weeks. We evaluated the efficacy and safety of treatment, as well as measured serum AFP, liver stiffness, and controlled attenuation parameter (CAP, a surrogate marker of steatosis) at baseline and within 48 weeks of treatment completion. The intention‐to‐treat analysis showed a sustained virological response (SVR) rate of 95.7%. None of the patients discontinued treatment due to side effects. Multivariate analysis identified pretreatment (no treatment with interferon), level of AFP (AFP; <10 μg/L), and RBV/body weight (BW) ratio (≥9.0 mg/kg) as independent predictors of SVR. The SVR rate in patients with two predictors of poor response (AFP ≥10 μg/L and RBV/BW ratio <9.0 mg/kg) was significantly lower than in other patients. In the SVR group, posttreatment AFP level and liver stiffness were significantly lower than at baseline. CAP tended to be higher after treatment than at baseline in all patients. SOF plus RBV combination therapy achieved a high SVR rate and was safe in HCV genotype 2 infected patients. Treatment reduced AFP levels and improved liver stiffness, but increased CAP.
What is changed in HBV molecular epidemiology in Italy?
Authors: Lai Alessia , Sagnelli Caterina , Lo Presti Alessandra , Cella Eleonora , Angeletti Silvia , Spoto Silvia , Costantino Sebastiano , Sagnelli Evangelista , Ciccozzi Massimo
Published: January 2018

Hepatitis B virus (HBV) infection represents the most common cause of chronic liver diseases worldwide. Consequently, to the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced and less than 1% of the population of Western Europe and North America is chronically infected. To date, despite great advances in therapeutics, HBV chronic infection is considered an incurable disease. Ten hepatitis B virus genotypes (A‐J) and several subgenotypes have been identified so far, based on intergroup divergences of 8% and 4%, respectively, in the complete viral genome. HBV‐D genotype has been found throughout the world, with highest prevalence in the Mediterranean area. In the present review, several articles concerning HBV epidemiology, and phylogeny in Italy have been analyzed, mainly focusing on the changes occurred in the last decade.
Very slow decline of hepatitis B virus surface antigen and core related antigen in chronic hepatitis B patients successfully treated with nucleos(t)ide analogues
Authors: Alidjinou Enagnon K. , Michel Charlotte , Canva Valérie , Ajana Faïza , Hober Didier , Bocket Laurence
Published: January 2018

We investigated the decline of hepatitis B virus surface antigen (HBsAg) and core related antigen (HBcrAg) in chronic hepatitis B patients sussessfully treated with nucleos(t)ide analogues. In patients with plasma viral suppression, the baseline median levels of HBsAg and HBcrAg were 3.1 and 3.0 log U/mL, respectively. The levels in naïve patients were 4.2 and 3.6 log U/mL for HBsAg and HBcrAg, respectively. No significant decline was observed in patients with viral suppression within a year period. A low reduction was observed during the first months after treatment initiation, especially regarding HBcrAg. The dynamics of these antigens after viral suppression should be further investigated.
Characteristics of patients with acute peripheral facial palsy showing Varicella zoster virus DNA in saliva
Authors: Chang Dong Sik , Lee Jun , Shin Sun Ae , Lee Ho Yun
Published: January 2018

Infection caused by Varicella zoster virus (VZV) is a common etiology of acute peripheral facial palsy (APFP). We aimed to assess the clinical significance of detecting VZV DNA from the saliva of patients with APFP. Saliva collected from 36 patients with unilateral APFP at initial visit was analyzed to detect VZV DNA by polymerase chain reaction. The House‐Brackmann (HB) scale was used to evaluate FP severity on admission day, at week 2, and at weeks 10‐12 after start of treatment. Among the 28 patients without rash, VZV DNA was detected in 3 patients (10.7%); 6 of 8 patients (75.0%) with rash showed VZV DNA (P = 0.001). VZV DNA‐positive patients had worse hearing than VZV DNA‐negative patients (P < 0.05). A significantly higher proportion of VZV DNA‐negative patients (96.3%) showed complete recovery than VZV DNA‐positive patients (55.6%) (P = 0.006). In conclusion, VZV DNA‐positive patients had worse hearing and incomplete recovery compared to VZV DNA‐negative patients, irrespective of the presence of rash. Tests for the detection of VZV DNA in saliva may be helpful for early differential diagnosis and choosing an appropriate medical treatment of APFP.
Sexual harassment training effectiveness: An interdisciplinary review and call for research
Authors: Roehling Mark V. , Huang Jason
Published: January 2018

Although sexual harassment (SH) training is widespread, has many important consequences for individuals and organizations, and is of demonstrated interest to researchers across a wide range of disciplines, there has never been a comprehensive, interdisciplinary attempt to identify and systematically evaluate relevant research findings. This article addresses that need in the literature. It discusses the legal context of SH training and its relevance to research issues, provides an organizing framework for understanding the primary factors influencing SH training effectiveness, critically reviews empirical research providing evidence of the effectiveness of SH training, and sets forth a research agenda.
Nutrition Delivery and Growth Outcomes in Infants With Gastroschisis
Authors: Hong Charles R. , Zurakowski David , Fullerton Brenna S. , Ariagno Katelyn , Jaksic Tom , Mehta Nilesh M.
Published: January 2018

Background

We aimed to describe nutrient intake and growth in infants with gastroschisis and identify factors associated with impaired growth.

Methods

Retrospective study of neonates who underwent gastroschisis repair from 2010 to 2015. Nutrient intake and weight‐for‐age z scores (WAZ) were recorded.

Results

Data from 60 eligible infants with median (Q1, Q3) gestational age of 36 weeks (35, 37) and birth weight 2418 g (2098, 2665) were analyzed. Median WAZ decreased from −0.71 (−1.08, −0.17) at birth to −1.08 (−1.58, −0.63) at discharge (P < .001); 30% experienced a >1.0 decline in WAZ. Parenteral nutrition (PN) was initiated soon after birth, and 14 (23%) patients had severe intestinal failure. Fourteen patients (23%) experienced central line–associated bloodstream infection (CLABSI) at a rate of 5.0 per 1000 catheter days. Factors independently associated with lower discharge WAZ and greater WAZ decline were CLABSI (P = .02) and prematurity (P = .02). By day 7, energy and protein intake were 90–100 kcal/kg/day and 3 g/kg/day, respectively. Median age to achieve enteral autonomy was 36 days (22, 82). Atresias, CLABSI, prematurity, and staged closure were associated with delayed enteral autonomy (P < .01). Among 34 patients with 1‐year follow‐up, WAZ improved from −1.16 (−1.74, −0.65) at discharge to 0.19 (−0.80, 0.61) at 12 months (P < .001).

Conclusion

Infants with gastroschisis are dependent on PN and have a significant decline in WAZ during their hospital stay, predicted by prematurity and CLABSI. Efforts to prevent CLABSI and optimize enteral autonomy must be prioritized in this cohort.
Soluble Mediators From Lactobacillus rhamnosus Gorbach‐Goldin Support Intestinal Barrier Function in Rats After Massive Small‐Bowel Resection
Authors: Wu Jiang , Yang Kefeng , Wu Wenjie , Tang Qingya , Zhong Yan , Gross Gabriele , Lambers Tim T. , van Tol Eric A. F. , Cai Wei
Published: January 2018

Background

Intestinal barrier plays an essential role in maintaining gastrointestinal health. This study aimed to explore the effects of a soluble mediator preparation derived from Lactobacillus rhamnosus Gorbach‐Goldin (LGG) on intestinal barrier function in a rat model of short bowel syndrome (SBS).

Methods

Six‐week‐old male Sprague‐Dawley rats underwent 80% small‐bowel resection (SBR) and then were supplemented with water (SBS), 5 × 108 colony‐forming unit viable LGG (SBS+LGG), or the LGG soluble mediators (SBS+LSM) in an equivalent dose to LGG by intragastric gavage daily from day 2 throughout day 14 after operation. Rats that underwent bowel transection and reanastomosis were used as the sham group. Body weight, ileum histology, intestinal permeability and bacterial translocation, inflammatory cytokines, and tight junction protein expressions of ileum were evaluated.

Results

Animals undergoing SBR showed higher intestinal permeability and decreased expression of tight junction proteins in the ileum than sham group. Both SBS+LGG and SBS+LSM groups had reduced bacterial translocation and intestinal permeability as compared with the SBS group, with lower levels of serum endotoxin and tumor necrotizing factor alpha in ileum tissues. Moreover, the SBS+LSM group showed better body weight gain, lower endotoxin and FD‐40 levels, and higher expressions of claudin‐1 and claudin‐4 in ileum than the SBS+LGG group.

Conclusion

Enteral supplementation of LSMs or viable LGG can ameliorate intestinal barrier disruption in a rat model of SBS. The LSM preparation not only mimicked biological effects of viable LGG but also was revealed to be more effective in reducing inflammation and supporting intestinal barrier function.
Magnetic dispersive solid‐phase extraction based on graphene oxide/Fe3O4@polythionine nanocomposite followed by atomic absorption spectrometry for zinc monitoring in water, flour, celery and egg
Authors: Babaei Azar , Zeeb Mohsen , Es‐haghi Ali
Published: January 2018

BACKGROUND

Magnetic graphene oxide nanocomposite has been proposed as a promising and sustainable sorbent for the extraction and separation of target analytes from food matrices. Sample preparation based on nanocomposite presents several advantages, such as desired efficiency, reasonable selectivity and high surface‐area‐to‐volume ratio.

RESULTS

A new graphene oxide/Fe3O4@polythionine (GO/Fe3O4@PTh) nanocomposite sorbent was introduced for magnetic dispersive solid‐phase extraction and flame atomic absorption spectrometric detection of zinc(II) in water, flour, celery and egg. To fabricate the sorbent, an oxidative polymerization of thionine on the surface of magnetic GO was applied, while polythionine was simply employed as a surface modifier to improve extraction yield. The properties of the sorbent were characterized by transmission electron microscopy, scanning electron microscopy, X‐ray diffraction, energy‐dispersive X‐ray analysis, vibrating sample magnetometry and Fourier transform–infrared spectroscopy. The calibration curve showed linearity in the range of 0.5–30 ng mL−1. Limits of detection (S/N = 3) and quantification (S/N = 10) were 0.08 and 0.5 ng mL−1, respectively.

CONCLUSION

The method was applied for trace‐level determination of Zn(II) in water and food samples, and its validation was investigated by recovery experiments and analyzing certified reference material. © 2018 Society of Chemical Industry
American cranberries and health benefits – an evolving story of 25 years
Authors: Zhao Shaomin , Liu Haiyan , Gu Liwei
Published: January 2018

Cranberries contain various types of bioactive components. Scientists have been studying cranberries' beneficial effects on urinary tract health since the 20th century. In the 21st century, the protection provided by cranberry phytochemicals against cancer and vascular diseases has drawn more attention from researchers. Anthocyanins, procyanidins, and flavonols in cranberries were all documented to have potential effects on cancer prevention. The cardiometabolic effects of cranberries have been investigated in several clinical trials. It was found that cranberries positively affect atherosclerotic cholesterol profiles and that they reduced several cardiometabolic risk factors. Nowadays, growing evidence suggests other important roles of cranberries in maintaining digestive health. Cranberry juice or cranberries have been shown to inhibit the colonization of H. pylori in stomach, and protect against intestinal inflammation. For future research, clinical trials with improved study design are urgently needed to demonstrate cranberries' benefits on urinary tract health and cardiometabolic diseases. Hypothesis‐driven studies using animals or cell culture are needed to elucidate the mechanisms of cranberries' effects on digestive health. © 2018 Society of Chemical Industry
Validation of clinical prognostic scores for patients treated with curative‐intent for recurrent colorectal liver metastases
Authors: Dupré Aurélien , Rehman Adeeb , Jones Robert P. , Parker Alex , Diaz‐Nieto Rafael , Fenwick Stephen W. , Poston Graeme J. , Malik Hassan Z.
Published: January 2018

Background

Scoring systems were developed to stratify patients with colorectal liver metastases considered for liver resection into different risk groups. Such scores have never been evaluated in recurrent liver metastases. The aim of this study was to evaluate whether these scores are applicable to patients with recurrent colorectal liver metastases and treated with curative intent.

Methods

We retrospectively analyzed data from 375 consecutive patients who underwent liver surgery for colorectal liver metastases between June 2010 and August 2015. Seventy‐three patients developed liver‐limited recurrence treated with curative intent. The predictive value of 6 scores (Fong, Sofocleous, Nagashima, Nordlinger, Konopke, and the Basingstoke index) was assessed in this set of patients.

Results

Median follow‐up was 36.2 months. Overall survival and progression‐free survival were 33.6 and 5.6 months, respectively. When scores were applied for OS, none showed a significant stratification between patients, although Nagashima's score showed a significant difference in overall survival between patients from the low‐risk group and those from the intermediate‐ and high‐risk groups (40.8 vs 30.5 months, P = 0.039). For PFS, only Fong's score showed a statistically significant stratification (6.6 vs 4.7 months, P = 0.027).

Conclusion

Scoring systems are of limited‐value in stratifying patients operated on for recurrent colorectal liver metastases.
Trends of genetic screening in patients with pheochromocytoma and paraganglioma: 15‐year experience in a high‐volume tertiary referral center
Authors: Asban Ammar , Kluijfhout Wouter P. , Drake Frederick T. , Beninato Toni , Wang Elizabeth , Chomsky‐Higgins Kate , Shen Wen T. , Gosnell Jessica E. , Suh Insoo , Duh Quan‐Yang
Published: January 2018

Background and Objectives

Genetic testing for pheochromocytoma and paraganglioma allows for early detection of hereditary syndromes and enables close follow‐up of high‐risk patient. We investigated the trends in genetic testing among patients at a high‐volume referral center and evaluated the prevalence of pheochromocytomas and paragangliomas.

Methods

We reviewed the charts of 129 patients who underwent adrenalectomy for pheochromocytoma and paraganglioma between January 2000 and July 2015. To evaluate for trends in genetic testing, patients were divided by year of diagnosis: 2000‐2005 (group 1, n = 35), 2006‐2010 (group 2, n = 44), and 2011‐2015 (group 3, n = 50).

Results

Among 129 patients the mean age was 47 years and 56% were women. Groups 2 and 3 were more frequently referred for genetic consultation than group 1, 73%, and 94% versus 26% (P < 0.001). A total of 67% followed up on the referral. The prevalence of genetic mutation was 50% (21/42 tested). The percentage with a genetic syndrome was 23%, 28%, and 22% respectively for groups 1, 2, and 3.

Conclusions

Referral for genetic counseling significantly increased in the past 15 years. However, only two‐thirds of patients followed up with genetic counselors and, therefore, clinicians can do more to improve the adherence rate for genetic counseling.
Extraction and identification of matrine‐type alkaloids from Sophora moorcroftiana using double‐templated molecularly imprinted polymers with HPLC–MS/MS
Authors: Ma Xingbin , Lin Hongling , Zhang Jiyu , She Yongxin , Zhou Xuzheng , Li Xiaozhong , Cui Yan , Wang Jing , Rabah Tsdan , Shao Yong
Published: January 2018

Double‐templated molecularly imprinted polymers with specific recognition of three matrine‐type alkaloids were prepared using matrine and oxymatrine as the template molecules. An approach based on double‐templated molecularly imprinted solid‐phase extraction coupled with high‐performance liquid chromatography and tandem mass spectrometry was then developed to extract and purify matrine, oxymatrine, and sophocarpine from Sophora moorcroftiana in the Tibetan plateau herbs. The polymers were characterized by Fourier‐transform infrared spectroscopy and scanning electron microscopy. Their adsorption characteristics were evaluated using adsorption kinetics, isotherms, selectivity, and recycling experiments. This polymer exhibited excellent molecular recognition ability and good selectivity. The obtained polymers as adsorbent was further used for the determination of three matrine‐type alkaloids coupled to high‐performance liquid chromatography with tandem mass spectrometry, the recoveries of three matrines spiked at three concentration levels in samples were 73.25–98.42% (n = 5) with a relative standard deviation less than 6.82%. The limits of detection for the method were 9.23–15.42 μg/kg (S/N = 3). This proposed method was assessed to be an effective method for simultaneous extraction, isolation, and identification of matrine, oxymatrine, and sophocarpine from Sophora moorcroftiana.
Flotation/ultrasound‐assisted microextraction followed by HPLC for determination of fat‐soluble vitamins in multivitamin pharmaceutical preparations
Authors: Shahdousti Parvin , Aghamohammadi Mohammad
Published: January 2018

Dissolved carbon dioxide flotation–emulsification microextraction technique coupled with high‐performance liquid chromatography was developed for separation and determination of fat‐soluble vitamins (A, D3, E, and K3) in multivitamin pharmaceutical preparations. Dissolved carbon dioxide flotation was used to break up the emulsion of extraction solvent in water and to collect the extraction solvent on the surface of aqueous sample in narrowed capillary part of extraction cell. Carbon dioxide bubbles were generated in situ through the addition of 300 μL of concentrated hydrochloric acid into the alkaline sample solution at pH = 11.5 (1% w/v sodium carbonate), which was sonicated to intensify the carbon dioxide bubble generation. Several factors affecting the extraction process were optimized. Under the optimal conditions, the limits of detection were 0.11, 0.47, 0.20 and 0.35 μg/L for A, E, D3, and K3 vitamins in water samples, respectively. The inter‐day and intra‐day precision of the proposed method were evaluated in terms of the relative standard deviation and were <10.5%.
A convenient ultrasound‐assisted saponification for the simultaneous determination of vitamin E isomers in vegetable oil by HPLC with fluorescence detection
Authors: Yang Yi , Lu Dan , Yin Shuo , Yang Danni , Chen Yaling , Li Yongxin , Sun Chengjun
Published: January 2018

An efficient ultrasound‐assisted saponification was developed for simultaneous determination of vitamin E isomers in vegetable oil by high‐performance liquid chromatography with fluorescence detection. The samples were saponified ultrasonically with potassium hydroxide solution for only 7 min, then the analytes were extracted with ether. Vitamin E isomers were separated on a C18 column at 25°C with a mobile phase of methanol/acetonitrile (81:19, v/v) at a flow rate of 0.8 mL/min. Fluorescence detection was operated at 290 nm of excitation wavelength and 327 nm of emission wavelength. Under the optimized conditions, good linearities over the range of 0.001–8.00 μg/mL (r > 0.999) were obtained. Mean recoveries of the method were 88.0–106%, with intra‐ and interday RSDs less than 11.8 and 12.8%, respectively. The detection limits and quantification limits of the method were 0.30–1.8 and 1.0–6.1 μg/kg, respectively. The recoveries of this method were much higher than that of the quick, easy, cheap, effective, rugged, and safe method and direct dilution method, but were similar to those of hot saponification. This proposed method provides reliable, simple, and rapid quantification of vitamin E isomers in vegetable oils. Five kinds of vegetable oils were analyzed, the quantification results were within the ranges reported by other authors.
Ethical issues in pragmatic trials of “standard‐of‐care” interventions in learning health care systems
Authors: Kim Scott Y.H.
Published: January 2018

Introduction

Learning health care systems (LHS) hold the promise of improving medical care by systematically and continuously integrating the delivery of medical services with clinical research. One important type of integration would involve embedding trials that compare interventions that are already commonly in use (as “accepted” or “standard of care”) into the clinical setting—trials that could cost‐effectively improve care. But the traditional requirement of informed consent for clinical trials stands in tension with the conduct of such trials.

Method

Narrative analysis.

Results

Although some have suggested that the idea of LHS makes the distinction between research and ordinary clinical care obsolete, the distinction remains ethically relevant even when it comes to randomized clinical trials (RCTs) that compare standard‐of‐care interventions. This paper presents an ethical framework for analyzing standard‐of‐care RCTs in resolving the tension between such trials and traditional requirements of research ethics.

Conclusion

It is important not to treat all standard‐of‐care RCTs as a monolithic category of special ethical status. Close attention to ethical issues in specific standard‐of‐care RCTs is crucial if the LHS movement is to avoid ethical lapses that could be counterproductive to its long term vision.
FTO regulates the chemo‐radiotherapy resistance of cervical squamous cell carcinoma (CSCC) by targeting β‐catenin through mRNA demethylation
Authors: Zhou Shun , Bai Zhou‐Lan , Xia Di , Zhao Zhi‐Jun , Zhao Ren , Wang Yan‐Yang , Zhe Hong
Published: January 2018

The role of N6‐methyladenosine (m6A) demethylase fat mass and obesity‐associated protein (FTO) in the regulation of chemo‐radiotherapy resistance remains largely unknown. Here, we show that the mRNA level of FTO is elevated in cervical squamous cell carcinoma (CSCC) tissues when compared with respective adjacent normal tissues. FTO enhances the chemo‐radiotherapy resistance both in vitro and in vivo through regulating expression of β‐catenin by reducing m6A levels in its mRNA transcripts and in turn increases excision repair cross‐complementation group 1 (ERCC1) activity. Clinically, the prognostic value of FTO for overall survival is found to be dependent on β‐catenin expression in human CSCC samples. Taken together, these findings uncover a critical function for FTO and its substrate m6A in the regulation of chemo‐radiotherapy resistance, which may bear potential clinical implications for CSCC treatment.
Interaction between caffeine and polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2) on Parkinson's disease risk
Authors: Kim Iris Y. , O'Reilly Éilis J. , Hughes Katherine C. , Gao Xiang , Schwarzschild Michael A. , McCullough Marjorie L. , Hannan Marian T. , Betensky Rebecca A. , Ascherio Alberto
Published: January 2018

Background: Caffeine intake has been inversely associated with Parkinson's disease (PD) risk. This relationship may be modified by polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2), but the results of previous studies have been inconsistent.

Method: We examined the interaction of caffeine intake with GRIN2A‐rs4998386 and CYP1A2‐rs762551 polymorphisms in influencing PD risk among 829 incident cases of PD and 2,754 matched controls selected among participants in the following 3 large prospective ongoing cohorts: the Nurses' Health Study, the Health Professionals' Follow‐up Study, and the Cancer Prevention Study II Nutrition Cohort. Matching factors included cohort, birth year, source of DNA, date of DNA collection, and race. Relative risks and 95% confidence intervals were estimated using conditional logistic models. Interactions were tested both on the multiplicative scale and on the additive scale.

Results: Overall, caffeine intake was associated with a lower PD risk (adjusted relative risk for highest versus lowest tertile = 0.70; 95% confidence interval, 0.57‐0.86; p < .001). In analyses stratified by the GRIN2A‐rs4998386 genotype, the multivariable‐adjusted relative risk of PD comparing the highest to the lowest tertile of caffeine was 0.69 (95% confidence interval, 0.55‐0.88; p < .01) among individuals homozygous for the C allele, and 0.85 (95% confidence interval, 0.55‐1.32; p = .47; pRERI = .43) among carriers for the T allele. Interactions between caffeine and GRIN2A were not significant in either the multiplicative or additive scales. We also did not observe significant interactions for CYP1A2‐rs762551 and incident PD risk.

Conclusion: Our findings do not support the hypothesis of an interaction between the GRIN2A‐rs4998386 or CYP1A2‐rs762551 polymorphism and caffeine intake in determining PD risk. © 2018 International Parkinson and Movement Disorder Society
Strategies to target the Hedgehog signaling pathway for cancer therapy
Authors: Xin Minhang , Ji Xinyue , De La Cruz Ladie Kimberly , Thareja Suresh , Wang Binghe
Published: January 2018

Hedgehog (Hh) signaling is an essential pathway in the human body, and plays a major role in embryo development and tissue patterning. Constitutive activation of the Hh signaling pathway through sporadic mutations or other mechanisms is explicitly associated with cancer development and progression in various solid malignancies. Therefore, targeted inhibition of the Hh signaling pathway has emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Vismodegib, a first‐in‐class Hh signaling pathway inhibitor was approved by the US Food and Drug Administration in 2012, and sonidegib, another potent Hh pathway inhibitor, received FDA's approval in 2015 as a new treatment of locally advanced or metastatic basal cell carcinoma. The clinical success of vismodegib and sonidegib provided strong support for the development of Hh signaling pathway inhibitors via targeting the smoothened (Smo) receptor. Moreover, Hh signaling pathway inhibitors aimed to target proteins, which are downstream or upstream of Smo, have also been pursued based on the identification of additional therapeutic benefits. Recently, much progress has been made in Hh singling and inhibitors of this pathway. Herein, medicinal chemistry strategies, especially the structural optimization process of different classes of Hh inhibitors, are comprehensively summarized. Further therapeutic potentials and challenges are also discussed.
Triangular splitting implementation of RKN‐type Fourier collocation methods for second‐order differential equations
Authors: Wang Bin
Published: January 2018

A triangular splitting implementation of Runge–Kutta–Nyström–type Fourier collocation methods is presented and analyzed in this paper. The proposed implementation relies on a reformulation of the method and on the Crout factorization of a corresponding matrix associated with the method. The excellent behavior of the splitting implementation is confirmed by its performance on a few numerical tests.
Global exponential stability of fractional‐order impulsive neural network with time‐varying and distributed delay
Authors: Srivastava Hari M. , Abbas Syed , Tyagi Swati , Lassoued Dhaou
Published: January 2018

In this article, we present several results on global exponential stability of a fractional‐order cellular neural network with impulses and with time‐varying and distributed delay. By using the Lyapunov‐like function methods in conjunction with the Razumikhin techniques, we derive sufficient condition for the exponential stability with an exponential convergence rate. The obtained outcomes of our present investigation significantly extend and generalize the corresponding results existing in the current literature. Finally, we give 2 illustrative examples to demonstrate the theoretical findings.