bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of insulin resistance on skeletal muscle growth and exercise capacity in type 2 diabetic mouse models
Authors: Ostler Joseph E. , Maurya Santosh K. , Dials Justin , Roof Steve R. , Devor Steven T. , Ziolo Mark T. , Periasamy Muthu
Published: January 2014

Type 2 diabetes mellitus is associated with an accelerated muscle loss during aging, decreased muscle function, and increased disability. To better understand the mechanisms causing this muscle deterioration in type 2 diabetes, we assessed muscle weight, exercise capacity, and biochemistry in db/ db and TallyHo mice at prediabetic and overtly diabetic ages. Maximum running speeds and muscle weights were already reduced in prediabetic db/ db mice when compared with lean controls and more severely reduced in the overtly diabetic db/ db mice. In contrast to db/ db mice, TallyHo muscle size dramatically increased and maximum running speed was maintained during the progression from prediabetes to overt diabetes. Analysis of mechanisms that may contribute to decreased muscle weight in db/ db mice demonstrated that insulin-dependent phosphorylation of enzymes that promote protein synthesis was severely blunted in db/ db muscle. In addition, prediabetic (6-wk-old) and diabetic (12-wk-old) db/ db muscle exhibited an increase in a marker of proteasomal protein degradation, the level of polyubiquitinated proteins. Chronic treadmill training of db/ db mice improved glucose tolerance and exercise capacity, reduced markers of protein degradation, but only mildly increased muscle weight. The differences in muscle phenotype between these models of type 2 diabetes suggest that insulin resistance and chronic hyperglycemia alone are insufficient to rapidly decrease muscle size and function and that the effects of diabetes on muscle growth and function are animal model-dependent.
Disturbed intestinal nitrogen homeostasis in a mouse model of high-fat diet-induced obesity and glucose intolerance
Authors: Do Thi Thu Huong , Hindlet Patrick , Waligora-Dupriet Anne-Judith , Kapel Nathalie , Neveux Nathalie , Mignon Virginie , Deloménie Claudine , Farinotti Robert , Fève Bruno , Buyse Marion
Published: January 2014

The oligopeptide transporter peptide cotransporter-1 Slc15a1 (PEPT1) plays a major role in the regulation of nitrogen supply, since it is responsible for 70% of the dietary nitrogen absorption. Previous studies demonstrated that PEPT1 expression and function in jejunum are reduced in diabetes and obesity, suggesting a nitrogen malabsorption from the diet. Surprisingly, we reported here a decrease in gut nitrogen excretion in high-fat diet (HFD)-fed mice and further investigated the mechanisms that could explain this apparent contradiction. Upon HFD, mice exhibited an increased concentration of free amino acids (AAs) in the portal vein (60%) along with a selective increase in the expression of two AA transporters ( Slc6a20a, Slc36a1), pointing to a specific and adaptive absorption of some AAs. A delayed transit time (+40%) and an increased intestinal permeability (+80%) also contribute to the increase in nitrogen absorption. Besides, HFD mice exhibited a 2.2-fold decrease in fecal DNA resulting from a reduction in nitrogen catabolism from cell desquamation and/or in the intestinal microbiota. Indeed, major quantitative (2.5-fold reduction) and qualitative alterations of intestinal microbiota were observed in feces of HFD mice. Collectively, our results strongly suggest that both increased AA transporters, intestinal permeability and transit time, and changes in gut microbiota are involved in the increased circulating AA levels. Modifications in nitrogen homeostasis provide a new insight in HFD-induced obesity and glucose intolerance; however, whether these modifications are beneficial or detrimental for the HFD-associated metabolic complications remains an open issue.
IL-1β hampers glucose-stimulated insulin secretion in Cohen diabetic rat islets through mitochondrial cytochromecoxidase inhibition by nitric oxide
Authors: Weksler-Zangen Sarah , Aharon-Hananel Genya , Mantzur Carmit , Aouizerat Tzemach , Gurgul-Convey Ewa , Raz Itamar , Saada Ann
Published: January 2014

A high-sucrose, low-copper-diet (HSD) induces inhibition of glucose-sensitive rats (CDs) but not Cohen diabetes-resistant rats (CDr). Copper-supplemented HSD increased activity of the copper-dependent mitochondrial respiratory chain enzyme cytochrome c oxidase (COX) and reversed hyperglycemia. This study examined the mechanism by which interleukin-1β modulates GSIS and the role of COX in this process. We measured COX activity, ATP content, GSIS, iNOS expression, and nitrite production with and without IL-1β, Nω-nitro-l-arginine, copper, or potassium cyanide in isolated islets of CDs and CDr fed different diets. We found reduced COX activity, ATP content, and GSIS in isolated islets of CDs rats fed a regular diet. These were severely reduced following HSD and were restored to regular diet levels on copper-supplemented HSD ( P < 0.01 vs. CDr islets). Potassium cyanide chemically reduced COX activity, decreasing GSIS and thus reinforcing the link between islet COX activity and GSIS. Interleukin-1β (2.5 U/ml) reduced GSIS and COX activity in CDs islets. Exposure to 10 U/ml interleukin-1β decreased GSIS and COX activity in both CDs and CDr islets, inducing a similar nitrite production. Nevertheless, the effect on GSIS was more marked in CDs islets. A significant iNOS expression was detected in CDs on the HSD diet, which was reduced by copper supplementation. Nω-nitro-l-arginine and copper prevented the deleterious effect of interleukin-1β on COX activity and GSIS. We conclude that reduced islet COX activity renders vulnerability to GSIS inhibition on low-copper HSD through two interrelated pathways: 1) by further reducing the activity of COX that is essential for β-cell ATP-production and insulin secretion and 2) by inducing the expression of iNOS and nitric oxide-mediated COX inhibition. We suggest that islet COX activity must be maintained above a critical threshold to sustain adequate GSIS with exposure to low-copper HSD.
Enhanced activation of cellular AMPK by dual-small molecule treatment: AICAR and A769662
Authors: Ducommun Serge , Ford Rebecca J. , Bultot Laurent , Deak Maria , Bertrand Luc , Kemp Bruce E. , Steinberg Gregory R. , Sakamoto Kei
Published: January 2014

AMP-activated protein kinase (AMPK) is a key cellular energy sensor and regulator of metabolic homeostasis. Activation of AMPK provides beneficial outcomes in fighting against metabolic disorders such as insulin resistance and type 2 diabetes. Currently, there is no allosteric AMPK activator available for the treatment of metabolic diseases, and limited compounds are available to robustly stimulate cellular/tissue AMPK in a specific manner. Here we investigated whether simultaneous administration of two different pharmacological AMPK activators, which bind and act on different sites, would result in an additive or synergistic effect on AMPK and its downstream signaling and physiological events in intact cells. We observed that cotreating primary hepatocytes with the AMP mimetic 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) and a low dose (1 μM) of the allosteric activator A769662 produced a synergistic effect on AMPK Thr172 phosphorylation and catalytic activity, which was associated with a more profound increase/decrease in phosphorylation of downstream AMPK targets and inhibition of hepatic lipogenesis compared with single-compound treatment. Mechanistically, we found that cotreatment does not stimulate LKB1, upstream kinase for AMPK, but it protects against dephosphorylation of Thr172 phosphorylation by protein phosphatase PP2Cα in an additive manner in a cell-free assay. Collectively, we demonstrate that AICAR sensitizes the effect of A769662 and promotes AMPK activity and its downstream events. The study demonstrates the feasibility of promoting AMPK activity by using two activators with distinct modes of action in order to achieve a greater activation of AMPK and downstream signaling.
GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents
Authors: Ye Jianping , Hao Zheng , Mumphrey Michael B. , Townsend R. Leigh , Patterson Laurel M. , Stylopoulos Nicholas , Münzberg Heike , Morrison Christopher D. , Drucker Daniel J. , Berthoud Hans-Rudolf
Published: January 2014

Exaggerated GLP-1 and PYY secretion is thought to be a major mechanism in the reduced food intake and body weight after Roux-en-Y gastric bypass surgery. Here, we use complementary pharmacological and genetic loss-of-function approaches to test the role of increased signaling by these gut hormones in high-fat diet-induced obese rodents. Chronic brain infusion of a supramaximal dose of the selective GLP-1 receptor antagonist exendin-9–39 into the lateral cerebral ventricle significantly increased food intake and body weight in both RYGB and sham-operated rats, suggesting that, while contributing to the physiological control of food intake and body weight, central GLP-1 receptor signaling tone is not the critical mechanism uniquely responsible for the body weight-lowering effects of RYGB. Central infusion of the selective Y2R-antagonist BIIE0246 had no effect in either group, suggesting that it is not critical for the effects of RYGB on body weight under the conditions tested. In a recently established mouse model of RYGB that closely mimics surgery and weight loss dynamics in humans, obese GLP-1R-deficient mice lost the same amount of body weight and fat mass and maintained similarly lower body weight compared with wild-type mice. Together, the results surprisingly provide no support for important individual roles of either gut hormone in the specific mechanisms by which RYGB rats settle at a lower body weight. It is likely that the beneficial effects of bariatric surgeries are expressed through complex mechanisms that require combination approaches for their identification.
Intergenerational effects of prenatal ethanol on glucose tolerance and insulin response
Authors: Harper Kathryn M. , Tunc-Ozcan Elif , Graf Evan N. , Redei Eva E.
Published: January 2014

Consequences of prenatal exposure to ethanol (E) include morphological, physiological, and cognitive deficits and are collectively classified as fetal alcohol spectrum disorders. Adult prenatal E exposed offspring show insulin resistance, and given that in utero hyperglycemic environment can cause metabolic disorders in subsequent generations; we investigated the effects of grandmaternal E on functional glucose and insulin responses of the second generation. Sprague-Dawley (S) rat dams, mated with S males, received E-containing liquid diet and two different control diets between gestational days 8 and 20. Additionally, because prenatal E-induced behavioral deficits can be reversed by simultaneous thyroxine (T4) treatment, another group of dams received 0.3 mg/l T4 in their E diet. Their first-generation (F1) offspring were mated with control Brown Norway (B) males or females to produce SB and BS F2 progeny. Dams consuming E during pregnancy were hyperglycemic, and their F1 offspring showed insulin resistance in the glucose tolerance test (GTT). However, F2 responses to GTT varied based on the sex of prenatal E-exposed parent. BS F2 females, and both male and female SB F2 progeny, displayed hypoglycemic and hyperinsulinemic GTT response patterns. Although administering T4 to E dams normalized thyroid function of the F1 generation, it did not reverse their prenatal E-induced metabolic dysfunction. In contrast, administration of T4 to the alcohol-consuming grandmother reversed or alleviated the aberrant GTT responses of the F2 progeny. Prenatal E-induced dysregulation of glucose metabolism can affect the next generation, possibly via ethanol effects on the germline of the F1 fetus.
Comparison of Extraction Methods of Chitin fromGanoderma lucidumMushroom Obtained in Submerged Culture
Authors: Ospina Álvarez Sandra Patricia , Ramírez Cadavid David Alexander , Escobar Sierra Diana Marcela , Ossa Orozco Claudia Patricia , Rojas Vahos Diego Fernando , Zapata Ocampo Paola , Atehortúa Lucía
Published: January 2014

The chitin was isolated from theGanoderma lucidumsubmerged cultures mycelium as potential source of chitin under biotechnological processes. The extraction of chitin was carried out through 5 different assays which involved mainly three phases: pulverization of the mushroom, deproteinization of the mycelia with NaOH solution, and a process of decolorization with potassium permanganate and oxalic acid. The chitin contents extracted from 9-day mycelia were 413, 339, 87, 78, and 144 mg/g−1(milligrams of chitin/grams of dry biomass) for A1, A2, A3, A4, and A5, respectively. Obtained chitin was characterized by X-Ray Diffraction (XRD), by Fourier transform infrared spectroscopy (FTIR), and by thermal analysis (TGA). The results showed thatGanoderma lucidumchitin has similar characteristic of chitin from different fonts. The advantage of the biotechnological processes and the fact thatGanoderma lucidumfungus may be used as a potential raw material for chitin production were demonstrated.
Fully Automated Detection of Corticospinal Tract Damage in Chronic Stroke Patients
Authors: Yang Ming , Yang Ya-ru , Li Hui-jun , Lu Xue-song , Shi Yong-mei , Liu Bin , Chen Hua-jun , Teng Gao-jun
Published: January 2014

Structural integrity of the corticospinal tract (CST) after stroke is closely linked to the degree of motor impairment. However, current methods for measurement of fractional atrophy (FA) of CST based on region of interest (ROI) are time-consuming and open to bias. Here, we used tract-based spatial statistics (TBSS) together with a CST template with healthy volunteers to quantify structural integrity of CST automatically. Two groups of patients after ischemic stroke were enrolled, group 1 (10 patients, 7 men, and Fugl-Meyer assessment (FMA) scores⩽50) and group 2 (12 patients, 12 men, and FMA scores = 100). CST of FAipsi, FAcontra, and FAratiowas compared between the two groups. Relative to group 2, FA was decreased in group 1 in the ipsilesional CST (P<0.01), as well as the FAratio(P<0.01). There was no significant difference between the two subgroups in the contralesional CST (P=0.23). Compared with contralesional CST, FA of ipsilesional CST decreased in group 1 (P<0.01). These results suggest that the automated method used in our study could detect a surrogate biomarker to quantify the CST after stroke, which would facilitate implementation of clinical practice.
Multimode Resource-Constrained Multiple Project Scheduling Problem under Fuzzy Random Environment and Its Application to a Large Scale Hydropower Construction Project
Authors: Xu Jiuping , Feng Cuiying
Published: January 2014

This paper presents an extension of the multimode resource-constrained project scheduling problem for a large scale construction project where multiple parallel projects and a fuzzy random environment are considered. By taking into account the most typical goals in project management, a cost/weighted makespan/quality trade-off optimization model is constructed. To deal with the uncertainties, a hybrid crisp approach is used to transform the fuzzy random parameters into fuzzy variables that are subsequently defuzzified using an expected value operator with an optimistic-pessimistic index. Then a combinatorial-priority-based hybrid particle swarm optimization algorithm is developed to solve the proposed model, where the combinatorial particle swarm optimization and priority-based particle swarm optimization are designed to assign modes to activities and to schedule activities, respectively. Finally, the results and analysis of a practical example at a large scale hydropower construction project are presented to demonstrate the practicality and efficiency of the proposed model and optimization method.
Plasma and Red Cell Reference Intervals of 5-Methyltetrahydrofolate of Healthy Adults in Whom Biochemical Functional Deficiencies of Folate and Vitamin B12Had Been Excluded
Authors: Sobczyńska-Malefora Agata , Harrington Dominic J. , Voong Kieran , Shearer Martin J.
Published: January 2014

5-Methyltetrahydrofolate (5-MTHF) is the predominant form of folate and a strong determinant of homocysteine concentrations. There is evidence that suboptimal 5-MTHF availability is a risk factor for cardiovascular disease independent of homocysteine. The analysis of folates remains challenging and is almost exclusively limited to the reporting of “total” folate rather than individual molecular forms. The purpose of this study was to establish the reference intervals of 5-MTHF in plasma and red cells of healthy adults who had been prescreened to exclude biochemical evidence of functional deficiency of folate and/or vitamin B12. Functional folate and vitamin B12status was assessed by respective plasma measurements of homocysteine and methylmalonic acid in 144 healthy volunteers, aged 19–64 years. After the exclusion of 10 individuals, values for 134 subjects were used to establish the upper reference limits for homocysteine (13 μmol/L females and 15 μmol/L males) and methylmalonic acid (430 nmol/L). Subjects with values below these cutoffs were designated as folate and vitamin B12replete and their plasma and red cell 5-MTHF reference intervals determined,N=126: 6.6–39.9 nmol/L and 223–1041 nmol/L, respectively. The application of these intervals will assist in the evaluation of folate status and facilitate studies to evaluate the relationship of 5-MTHF to disease.
Medium-Term Results of Treatment for Complicated Acute Type B Dissection: A Spanish Experience in a Single Centre
Authors: Alvarez-Garcia Jesus , Stefanov Kiuri Stefan , Fernandez Heredero Alvaro , Salazar Alvarez Andres , Concepcion Rodriguez Nieves Aleicel , Riera de Cubas Luis
Published: January 2014

Objective. To analyze and evaluate medium-term results obtained in endovascular treatment of complicated type B dissection. Methods. Prospective registry and retrospective analysis of the dissections treated with endoprosthesis in 1998 and 2010. Comorbidity, clinical presentation, anatomical characteristics, and evolution were recorded. Actuarial analysis was conducted for survival, follow-up and survival free of endoleaks, and free of reintervention due to relapse and/or progression. Results. Eighteen (18) patients were treated (14 male : 4 female), with a median age of 53 years (range 29–80). Their main symptoms were acute pain in 16 cases and hypertensive crisis in 15. The indications were 10 dissections not controlled by medication, 4 aneurysm dissecans, 2 acute lower limb ischemias, and 2 Type A progressions. Median 1.7 devices were used (range 1–4). Coverage of left subclavian artery was required in 3 cases, and of subclavian and left carotid artery in other 2 cases. There was a 100% technical success. Median follow-up was 43.1 months (1.5–127 range). There were two deaths caused by multiorganic failure, early mortality of 0%, and hospital mortality of 11%. There was a case of Type I Endoleak and 5 cases which required a new intervention due to relapse and/or progression. Cumulative survival at 30 months was 88%; follow-up free of endoleaks at 36 months was 91%. Follow-up free of progression/relapse at 12 months was 88%. Conclusion. Endovascular treatment of complicated type B acute dissection is an effective therapy for this condition, with a low associated mortality and with acceptable survival.
On Fractional Integral Inequalities Involving Hypergeometric Operators
Authors: Baleanu D. , Purohit S. D. , Agarwal Praveen
Published: January 2014

Here we aim at establishing certain new fractional integral inequalities involving the Gauss hypergeometric function for synchronous functions which are related to the Chebyshev functional. Several special cases as fractional integral inequalities involving Saigo, Erdélyi-Kober, and Riemann-Liouville type fractional integral operators are presented in the concluding section. Further, we also consider their relevance with other related known results.
Tumor Initiating Cells and Chemoresistance: Which Is the Best Strategy to Target Colon Cancer Stem Cells?
Authors: Paldino Emanuela , Tesori Valentina , Casalbore Patrizia , Gasbarrini Antonio , Puglisi Maria Ausiliatrice
Published: January 2014

There is an emerging body of evidence that chemoresistance and minimal residual disease result from selective resistance of a cell subpopulation from the original tumor that is molecularly and phenotypically distinct. These cells are called “cancer stem cells” (CSCs). In this review, we analyze the potential targeting strategies for eradicating CSCs specifically in order to develop more effective therapeutic strategies for metastatic colon cancer. These include induction of terminal epithelial differentiation of CSCs or targeting some genes expressed only in CSCs and involved in self-renewal and chemoresistance. Ideal targets could be cell regulators that simultaneously control the stemness and the resistance of CSCs. Another important aspect of cancer biology, which can also be harnessed to create novel broad-spectrum anticancer agents, is the Warburg effect, also known as aerobic glycolysis. Actually, little is yet known with regard to the metabolism of CSCs population, leaving an exciting unstudied avenue in the dawn of the emerging field of metabolomics.
Morphological and Pathogenic Variability amongMacrophomina phaseolinaIsolates Associated with Mungbean (Vigna radiataL.) Wilczek from Pakistan
Authors: Iqbal Umer , Mukhtar Tariq
Published: January 2014

Macrophomina phaseolinais a serious pathogen of many crops. In the present studies, 65 isolates ofMacrophomina phaseolinafrom different agroecological regions of Punjab and Khyber Pakhtunkhwa provinces of Pakistan were analyzed for morphological and pathogenic variability. Regardless of their geographic origins, significant differences were detected among 65 isolates in their radial growth, sclerotial size, and weight as well as in pathogenicity. Sixteen isolates were rated as fast growing, 11 as slow growing, and the rest of the isolates as medium growing. Nine isolates were classified as large sized, 26 as small sized, and the remaining 30 isolates as medium sized. Thirty five isolates were ranked as heavy weight, 12 as low weight, and the rest of isolates were grouped as medium weight. Ten fungal isolates appeared to be least virulent, whereas eight isolates of diverse origin proved to be highly virulent against mungbean cultivars. The remaining isolates were regarded as moderately virulent. No relationship was found among the morphological characters and pathogenicity of the isolates. These morphological and pathogenic variations in various isolates ofM. phaseolinamay be considered important in disease management systems and will be useful in breeding programmes of mungbean cultivars resistant to charcoal rot.
Liver Disease Secondary to Intestinal Failure
Authors: Abu-Wasel Bassam , Molinari Michele
Published: January 2014

IFALD is a common and potentially life-threatening condition for patients with SBS requiring long-term PN. There exists the potential for decreasing its incidence by optimizing the composition and the rate of infusion of parenteral solutions, by advocating a multidisciplinary approach, and by early referral for intestinal-liver transplantation to ensure long-term survival of patients with SBS.
Genomic Analysis of Head and Neck Squamous Cell Carcinoma Cell Lines and Human Tumors: A Rational Approach to Preclinical Model Selection
Authors: Li Hua , Wawrose John S. , Gooding William E. , Garraway Levi A. , Lui Vivian Wai Yan , Peyser Noah D. , Grandis Jennifer R.
Published: January 2014

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide. The increasing amount of genomic information on human tumors and cell lines provides more biologic data to design preclinical studies. We and others previously reported whole-exome sequencing data of 106 HNSCC primary tumors. In 2012, high-throughput genomic data and pharmacologic profiling of anticancer drugs of hundreds of cancer cell lines were reported. Here, we compared the genomic data of 39 HNSCC cell lines with the genomic findings in 106 HNSCC tumors. Amplification of eight genes (PIK3CA, EGFR, CCND2, KDM5A, ERBB2, PMS1, FGFR1, and WHSCIL1) and deletion of five genes (CDKN2A, SMAD4, NOTCH2, NRAS, and TRIM33) were found in both HNSCC cell lines and tumors. Seventeen genes were only mutated in HNSCC cell lines (>10%), suggesting that these mutations may arise through immortalization in tissue culture. Conversely, 11 genes were only mutated in >10% of human HNSCC tumors. Several mutant genes in the EGF receptor (EGFR) pathway are shared both in cell lines and in tumors. Pharmacologic profiling of eight anticancer agents in six HNSCC cell lines suggested that PIK3CA mutation may serve as a predictive biomarker for the drugs targeting the EGFR/PI3K pathway. These findings suggest that a correlation of gene mutations between HNSCC cell lines and human tumors may be used to guide the selection of preclinical models for translational research.

Implications: These findings suggest that a correlation of gene mutations between HNSCC cell lines and human tumors may be used to guide the selection of preclinical models for translational research.

Visual Overview: http://mcr.aacrjournals.org/content/12/4/571/F1.large.jpg.

Mol Cancer Res; 12(4); 571–82. ©2014 AACR.
Efficacy of Different Carrier Gases for Barrier Discharge Plasma Generation Compared to Chlorhexidine on the Survival of Pseudomonas aeruginosa Embedded in Biofilm in vitro
Authors: Matthes R. , Hübner N.-O. , Bender C. , Koban I. , Horn S. , Bekeschus S. , Weltmann K.-D. , Kocher T. , Kramer A. , Assadian O.
Published: January 2014

Because of its antimicrobial properties, nonthermal plasma could serve as an alternative to chemical antisepsis in wound treatment. Therefore, this study investigated the inactivation of biofilm-embedded Pseudomonas aeruginosa SG81 by a surface barrier-discharged (SBD) plasma for 30, 60, 150 and 300 s. In order to optimize the efficacy of the plasma, different carrier gases (argon, argon admixed with 1% oxygen, and argon with increased humidity up to approx. 80%) were tested and compared against 0.1% chlorhexidine digluconate (CHG) exposure for 600 s. The antimicrobial efficacy was determined by calculating the difference between the numbers of colony-forming units (CFU) of treated and untreated biofilms. Living bacteria were distinguished from dead by fluorescent staining and confocal laser scanning microscopy. Both SBD plasmas and CHG showed significant antimicrobial effects compared to the untreated control. However, plasma treatment led to a higher antimicrobial reduction (argon plasma 4.9 log10 CFU/cm2, argon with admixed oxygen 3 log10 CFU/cm2, and with increased gas humidity 2.7 log10 CFU/cm2 after 300 s) compared to CHG. In conclusion, SBD plasma is suitable as an alternative to CHG for inactivation of Pseudomonas aeruginosa embedded in biofilm. Further development of SBD plasma sources and research on the role of carrier gases and humidity may allow their clinical application for wound management in the future.
Chemoradiation Therapy versus Chemotherapy Alone for Gastric Cancer after R0 Surgical Resection: A Meta-Analysis of Randomized Trials
Authors: Min Christine , Bangalore Sripal , Jhawar Sachin , Guo Yu , Nicholson Joseph , Formenti Silvia C. , Leichman Lawrence P. , Du Kevin L.
Published: January 2014

Objective: Current national guidelines include category 1 recommendations for perioperative chemotherapy or adjuvant chemoradiation with surgical resection for patients with stage IB-IIIB gastric cancer. We conducted a meta-analysis of randomized trials in which chemotherapy was prospectively tested against chemoradiation with surgical resection. Methods: We electronically searched PubMed and EMBASE for randomized, controlled clinical trials involving patients with gastric adenocarcinoma, status post-R0 resection. The interventions compared were adjuvant chemotherapy versus chemoradiation, with any chemotherapy regimen. The primary outcomes of interest were disease-free survival and overall survival. The Mantel-Haenszel random-effects model was used to calculate effect sizes. Results: Six trials that included 1,171 patients were evaluated; 599 were randomized to adjuvant chemoradiation and 572 to chemotherapy alone. Chemoradiation was associated with a significant increase in disease-free survival (odds ratio 1.48, 95% confidence interval 1.08-2.03) when compared to chemotherapy alone. However, there was no significant difference in overall survival (odds ratio 1.27, 95% confidence interval 0.95-1.71). Five trials found no statistically significant differences in toxicities between the two groups. Conclusion: In patients with gastric cancer status post-R0 resection, adjuvant chemoradiation was associated with higher disease-free survival when compared to chemotherapy alone. It remains appropriate to design trials testing new systemic agents with radiotherapy.
Clinical Study of the Visual Field Defects Caused by Occipital Lobe Lesions
Authors: Ogawa Katsuhiko , Ishikawa Hiroshi , Suzuki Yutaka , Oishi Minoru , Kamei Satoshi
Published: January 2014

Background: The central visual field is projected to the region from the occipital tip to the posterior portion of the medial area in the striate cortex. However, central visual field disturbances have not been compared with the location of the lesions in the striate cortex. Methods: Thirteen patients with visual field defects caused by partial involvement of the striate cortex were enrolled. The lesions were classified according to their location into the anterior portion, the posterior portion of the medial area, and the occipital tip. Visual field defects were examined by the Goldmann perimetry, the Humphrey perimetry and the auto-plot tangent screen. We defined a defect within the central 10° of vision as a central visual field disturbance. The visual field defects in 13 patients were compared with the location of their lesions in the striate cortex. Results: The medial area was involved in 7 patients with no involvement of the occipital tip. In 2 of them, peripheral homonymous hemianopia without central visual field disturbance was shown, and their lesions were located only in the anterior portion. One patient with a lesion in the posterior portion alone showed incomplete central homonymous hemianopia. Three of 4 patients with lesions located in both the anterior and posterior portions of the medial area showed incomplete central homonymous hemianopia and peripheral homonymous hemianopia. The occipital tip was involved in 6 patients. Five of them had small lesions in the occipital tip alone and showed complete central homonymous hemianopia or quadrantanopia. The other patient with a lesion in the lateral posterior portion and bilateral occipital tip lesions showed bilateral slight peripheral visual field disturbance in addition to complete central homonymous hemianopia on both sides. Conclusions: Lesions in the posterior portion of the medial area as well as the occipital tip caused central visual field disturbance in our study, as indicated in previous reports. Central homonymous hemianopia tended to be incomplete in patients with lesions in the posterior portion in the medial area. In contrast, complete central homonymous hemianopia and quadrantanopia were shown in patients with occipital tip lesions. Our study suggested that the fibers related to the central visual field were sparse in the posterior portion of the medial area in contrast to the occipital tip, and approached the occipital tip with a high concentration of fibers.
Celastrol Induces Apoptosis of Gastric Cancer Cells by miR-21 Inhibiting PI3K/Akt-NF-κB Signaling Pathway
Authors: Sha Min , Ye Jun , Zhang Li-xin , Luan Zheng-yun , Chen Ya-bao , Huang Jun-xing
Published: January 2014

Objective: Celastrol, a plant triterpene, has anticancer effects by increase of apoptosis. In the present study, the mechanism of celastrol on gastric cancer cell apoptosis was examined. Methods: The effect of celastrol on PI3K/Akt and the NF-κB signaling pathway was evaluated with Western blot and luciferase reporter assay. miR-21 expression was determined using real-time PCR. miR-21 inhibitor and miR-21 mimic were used to downregulate and upregulate miR-21 expression, respectively. Results: It was identified that celastrol was capable of inducing apoptosis of gastric cancer cells, which was mediated via inhibiting the activation of PI3K/Akt and NF-κB. A strong activator of Akt, IGF-1 restored NF-κB activity in cells treated with celastrol. Celastrol could also significantly suppress miR-21 expression. Furthermore, miR-21 inhibitor could decrease phospho-Akt expression and NF-κB activity. Notably, upregulation of miR-21 expression can increase PI3K/Akt and NF-κB activity and decrease apoptosis of gastric cancer cells treated with celastrol, which could be reversed by PI3K inhibitor. Conclusions: Our data revealed that the effect of celastrol on apoptosis was due to miR-21 inhibiting the PI3K/Akt-dependent NF-κB pathway.
Pre-End-Stage Renal Disease Care Not Associated with Dialysis Facility Neighborhood Poverty in the United States
Authors: Plantinga Laura C. , Kim Min , Goetz Margarethe , Kleinbaum David G. , McClellan William , Patzer Rachel E.
Published: January 2014

Background: Receipt of nephrology care prior to end-stage renal disease (ESRD) is a strong predictor of decreased mortality and morbidity, and neighborhood poverty may influence access to care. Our objective was to examine whether neighborhood poverty is associated with lack of pre-ESRD care at dialysis facilities. Methods: In a multi-level ecological study using geospatially linked 2007-2010 Dialysis Facility Report and 2006-2010 American Community Survey data, we examined whether high neighborhood poverty (≥20% of households in census tract living below poverty) was associated with dialysis facility-level lack of pre-ESRD care (percentage of patients with no nephrology care prior to dialysis start) in mixed-effects models, adjusting for facility and neighborhood confounders and allowing for neighborhood and regional random effects. Results: Among the 5,184 facilities examined, 1,778 (34.3%) were located in a high-poverty area. Lack of pre-ESRD care was similar in poverty areas (30.8%) and other neighborhoods (29.6%). With adjustment, the absolute increase in percentage of patients at a facility with no pre-ESRD care associated with facility location in a poverty area versus other neighborhood was only 0.08% (95% CI -1.32, 1.47; p = 0.9). Potential effect modification by race and income inequality was detected. Conclusion: Despite previously reported detrimental effects of neighborhood poverty on health, facility neighborhood poverty was not associated with receipt of pre-ESRD care, suggesting no need to target interventions to increase access to pre-ESRD care at facilities in poorer geographic areas.
The Effects of Endothelial Cells-Preserving Technique on Microsurgical Vascular Reconstruction in Biliary Tract Malignancy: Report of Twenty Cases
Authors: Miyagi Shigehito , Nakanishi Wataru , Kawagishi Naoki , Yoshida Hiroshi , Unno Michiaki , Ohuchi Noriaki
Published: January 2014

We describe our experience of resectional surgery with microsurgical reconstruction of the hepatic arteries in 20 cases with biliary tract malignancy. Hepatic artery thrombosis (HAT) is a lethal complication; therefore, it is important to perform microsurgical reconstruction safely. Recently, we adopted the back wall support suture technique with double needle sutures that does not require the damaged short arteries to be turned over. In this technique, each stitch is placed from the inner side to the outer side to keep endothelial cells. The purpose of this study was to develop safety methods. From 2003 to 2012, 20 patients with biliary tract malignancy with possible involvement of the hepatic arteries underwent resectional surgery with microvascular reconstruction (cholangiocarcinoma: n = 15; others: n = 5). For this cohort study, patients were divided into two groups: group I (n = 5) included patients who underwent the conventional ‘twist technique' and group II (n = 15) included patients who underwent the microsurgical back wall support suture technique with double needle sutures and received gabexate mesilate, a strong serine protease inhibitor (40 mg/kg/day) for 7 days. We investigated HAT using Doppler ultrasonography for 10 days. No postoperative mortality was observed. The incidence of HAT was only one case in group I, and there was no significant difference between the two groups. However, the value of the pulsatile index and acceleration time were significantly improved in group II. In conclusion, the back wall support suture technique with gabexate mesilate administration during microvascular reconstruction was found to be safe. It is important to keep endothelial cells healthy for microvascular reconstruction.
Pancreatic Arteriovenous Malformation
Authors: Yamabuki Takumi , Ohara Masanori , Kimura Noriko , Okamura Kunishige , Kuroda Aki , Takahashi Ryo , Komuro Kazuteru , Iwashiro Nozomu
Published: January 2014

An unusual case of pancreatic arteriovenous malformation (P-AVM) combined with esophageal cancer is reported. A 59-year-old man was admitted with upper abdominal pain. Contrast-enhanced computed tomography showed numerous strongly enhanced abnormal vessels and a hypovascular lesion in the area of the pancreatic tail. Angiographic study of the celiac artery confirmed racemose vascular networks in the tail of the pancreas. Endoscopic retrograde pancreatography revealed narrowing and displacement of the main pancreatic duct in the tail of the pancreas. Screening esophagoscopy showed a 0-IIa+IIc type tumor in the lower thoracic esophagus. Histological examination of esophagoscopic biopsies showed squamous cell carcinoma. Based on these findings, P-AVM or pancreatic cancer and esophageal cancer were diagnosed. Video-assisted thoracoscopic esophagectomy and distal pancreatectomy were performed. Histological examination of the resected pancreas revealed abundant abnormal vessels with intravascular thrombi. In addition, rupture of a dilated pancreatic duct with pancreatic stones and both severe atrophy and fibrosis of the pancreatic parenchyma were observed. The final diagnoses were P-AVM consequent to severe chronic pancreatitis and esophageal carcinoma. The patient's postoperative course was relatively good.
Hahnemanns Theorie und Praxis und das moderne Erkenntnisproblem*
Authors: Schmidt Josef M.
Published: January 2014

Anschauen, Wahrnehmen und Erkennen sind in der Medizin keine trivialen Vorgänge. Die moderne konventionelle Medizin hat sich diesbezüglich der Methode des klinischen Experiments und der Statistik sowie dem Ideal einer evidenzbasierten Medizin verschrieben, deren externe Evidenz letztlich auf «Erkenntnis ohne erkennendes Subjekt» im Sinne Karl Poppers beruht. Demgegenüber verfolgt die Homöopathie auch gestalttheoretische und kognitionsbasierte Ansätze wissenschaftlicher Erkenntnis im Sinne Karl Dunckers und Helmut Kienes. Unter Anerkennung der Urteils- und Erfahrungsfähigkeit des einzelnen Arztes ermöglicht dies die methodische Gewinnung interner Evidenz, die einer bloss metaanalytisch ausgerichteten Biomedizin verwehrt bleibt. Medizintheoretisch gesehen erweist sich der ganzheitliche Weg als dem Wesen des Arztberufs angemessener. Aus sozioökonomischen Gründen, die auf Vergesellschaftungsprozesse moderner Subjekte in der Denkform des Geldes und die Begründung der modernen Naturwissenschaft aus diesem Geiste zurückgehen, ist derzeit jedoch das biomedizinische Paradigma an der Macht. Indem Samuel Hahnemann die Homöopathie noch vor der zunehmenden Ökonomisierung der modernen Medizin im 19. Jahrhundert begründete, können er und seine Lehre heute als Leuchtturm einer exemplarischen, unverdorbenen Heilkunst dienen, die es trotz bzw. gerade wegen mannigfaltiger Anfechtungen wiederzubeleben gilt.
Development of a Technique for Left Ventricular Endocardial Pacing via Puncture of the Interventricular Septum
Authors: Betts Tim R. , Gamble James H.P. , Khiani Raj , Bashir Yaver , Rajappan Kim
Published: January 2014

Background—

Left ventricular (LV) pacing through the coronary sinus is the standard approach for cardiac resynchronization therapy. When this route is unavailable, the alternatives have major limitations. LV endocardial pacing through the interventriuclar septum may offer a simpler solution. We describe an initial case series to demonstrate technical feasibility and to describe our refinement of the puncture technique.

Methods and Results—

Ten patients with previous failed coronary sinus lead implant or with nonresponse to cardiac resynchronization therapy and a suboptimal LV lead position were selected. All patients were anticoagulated. Left ventriculography and coronary angiography were performed to identify LV borders and septal vessels. Subclavian vein access was used for a superior approach ventricular transseptal puncture under fluoroscopic guidance, using a steerable sheath and a standard transseptal needle, radiofrequency needle, or radiofrequency energy delivered through a guidewire. An active-fixation pacing lead was successfully delivered to the endocardial wall of the lateral LV in all patients (9 men; age, 62±10 years). LV lead implant procedure time shortened with experience. The use of radiofrequency energy delivered through a guidewire was the most effective technique. Mean threshold and R wave at implant were 0.8±0.3 V and 10.8±3.9 mV. At follow-up (mean, 8.7 months; minimum, 0; and maximum 19), thresholds were stable, and there were no thromboembolic events. Of 9 patients, 8 were classed as clinical responders (1 had inadequate follow-up to assess response).

Conclusions—

LV endocardial pacing through a ventricular septal puncture is a feasible approach for cardiac resynchronization therapy.
T
1
Mapping Detects Pharmacological Retardation of Diffuse Cardiac Fibrosis in Mouse Pressure-Overload Hypertrophy
Authors: Stuckey Daniel J. , McSweeney Sara J. , Thin May Zaw , Habib Josef , Price Anthony N. , Fiedler Lorna R. , Gsell Willy , Prasad Sanjay K. , Schneider Michael D.
Published: January 2014

Background—

Diffuse interstitial fibrosis is present in diverse cardiomyopathies and associated with poor prognosis. We investigated whether magnetic resonance imaging-based T
1
mapping could quantify the induction and pharmacological suppression of diffuse cardiac fibrosis in murine pressure-overload hypertrophy.

Methods and Results—

Mice were subjected to transverse aortic constriction or sham surgery. The angiotensin receptor blocker losartan was given to half the animals. Cine-magnetic resonance imaging performed at 7 and 28 days showed hypertrophy and remodeling and systolic and diastolic dysfunction in transverse aortic constriction groups as expected. Late gadolinium-enhanced magnetic resonance imaging revealed focal signal enhancement at the inferior right ventricular insertion point of transverse aortic constriction mice concordant with the foci of fibrosis in histology. The extracellular volume fraction, calculated from pre- and postcontrast T
1
measurements, was elevated by transverse aortic constriction and showed direct linear correlation with picrosirius red collagen volume fraction, thus confirming the suitability of extracellular volume fraction as an in vivo measure of diffuse fibrosis. Treatment with losartan reduced left ventricular dysfunction and prevented increased extracellular volume fraction, indicating that T
1
mapping is sensitive to pharmacological prevention of fibrosis.

Conclusions—

Magnetic resonance imaging can detect diffuse and focal cardiac fibrosis in a clinically relevant animal model of pressure overload and is sensitive to pharmacological reduction of fibrosis by angiotensin receptor blockade. Thus, T
1
mapping can be used to assess antifibrotic therapeutic strategies.
Risk Stratification for Long-Term Mortality After Percutaneous Coronary Intervention
Authors: Wu Chuntao , Camacho Fabian T. , King Spencer B. , Walford Gary , Holmes David R. , Stamato Nicholas J. , Berger Peter B. , Sharma Samin , Curtis Jeptha P. , Venditti Ferdinand J. , Jacobs Alice K. , Hannan Edward L.
Published: January 2014

Background—

A simple risk score to predict long-term mortality after percutaneous coronary intervention (PCI) using preprocedural risk factors is currently not available. In this study, we created one by simplifying the results of a Cox proportional hazards model.

Methods and Results—

A total of 11 897 patients who underwent PCI from October through December 2003 in New York State were randomly divided into derivation and validation samples. Patients’ vital statuses were tracked using the National Death Index through the end of 2008. A Cox proportional hazards model was fit to predict death after PCI using the derivation sample, and a simplified risk score was created. The Cox model identified 12 separate risk factors for mortality including older age, extreme body mass indexes, multivessel disease, a lower ejection fraction, unstable hemodynamic state or shock, several comorbidities (cerebrovascular disease, peripheral vascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, and renal failure), and a history of coronary artery bypass graft surgery. The C statistics of this model when applied to the validation sample were 0.787, 0.785, and 0.773 for risks of death within 1, 3, and 5 years after PCI, respectively. In addition, the point-based risk score demonstrated good agreement between patients’ observed and predicted risks of death.

Conclusions—

A simple risk score created from a more complicated Cox proportional hazards model can be used to accurately predict a patient’s risk of long-term mortality after PCI.
Incidences, Predictors, and Clinical Outcomes of Acute and Late Stent Malapposition Detected by Optical Coherence Tomography After Drug-Eluting Stent Implantation
Authors: Im Eui , Kim Byeong-Keuk , Ko Young-Guk , Shin Dong-Ho , Kim Jung-Sun , Choi Donghoon , Jang Yangsoo , Hong Myeong-Ki
Published: January 2014

Background—

We investigated the incidences, predictors, and clinical outcomes of acute and late stent malapposition detected by optical coherence tomography (OCT) after drug-eluting stent implantation.

Methods and Results—

We analyzed the OCT images from 351 patients with 356 lesions who received poststent and follow-up OCT examinations. Acute stent malapposition was observed in 62% of lesions. Approximately half of the acute stent malappositions were located within the edges of the stents. Severe diameter stenosis, calcified lesions, and long stents were independent predictors of acute stent malapposition. Follow-up OCT examinations were performed 175±60 days after drug-eluting stent implantation. Thirty-one percent of lesions with acute stent malapposition remained malapposed (late-persistent stent malapposition) and were typically (72%) located within the edges of the stent. The location within the stent edges and the volume of acute stent malapposition were independent predictors of late-persistent stent malapposition. Acute stent malapposition with a volume >2.56 mm
3
differentiated late-persistent stent malapposition from resolved acute stent malapposition. Late-acquired stent malapposition was detected in 15% of all lesions and was usually (61%) located within the stent body. Late-acquired stent malapposition was more frequently associated with plaque/thrombus prolapse on poststent OCT images (70% versus 42%;
P
<0.001). Clinical events, including cardiovascular death, nonfatal myocardial infarction, and stent thrombosis, did not occur in patients with late stent malapposition during the follow-up period of 28.6±10.3 months after drug-eluting stent implantation.

Conclusions—

Acute, late-persistent, and late-acquired stent malapposition had relatively high incidences but different predictors. The clinical outcome of stent malapposition was favorable.