bluuebunny/crossref_metadata_2025 huggingface dataset:
The Modes of Evolutionary Emergence of Primal and Late Pandemic Influenza Virus Strains from Viral Reservoir in Animals: An Interdisciplinary Analysis
Authors: Shoham Dany
Published: November 2011

Based on a wealth of recent findings, in conjunction with earliest chronologies pertaining to evolutionary emergences of ancestral RNA viruses, ducks, Influenzavirus A (assumingly within ducks), and hominids, as well as to the initial domestication of mallard duck (Anas platyrhynchos), jungle fowl (Gallus gallus), wild turkey (Meleagris gallopavo), wild boar (Sus scrofa), and wild horse (Equus ferus), presumed genesis modes of primordial pandemic influenza strains have multidisciplinarily been configured. The virological fundamentality of domestication and farming of those various avian and mammalian species has thereby been demonstrated and broadly elucidated, within distinctive coevolutionary paradigms. The mentioned viral genesis modes were then analyzed, compatibly with common denominators and flexibility that mark the geographic profile of the last 18 pandemic strains, which reputedly emerged since 1510, the antigenic profile of the last 10 pandemic strains since 1847, and the genomic profile of the last 5 pandemic strains since 1918, until present. Related ecophylogenetic and biogeographic aspects have been enlightened, alongside with the crucial role of spatial virus gene dissemination by avian hosts. A fairly coherent picture of primary and late evolutionary and genomic courses of pandemic strains has thus been attained, tentatively. Specific patterns underlying complexes prone to generate past and future pandemic strains from viral reservoir in animals are consequentially derived.
Tumor Evasion from T Cell Surveillance
Authors: Töpfer Katrin , Kempe Stefanie , Müller Nadja , Schmitz Marc , Bachmann Michael , Cartellieri Marc , Schackert Gabriele , Temme Achim
Published: November 2011

An intact immune system is essential to prevent the development and progression of neoplastic cells in a process termed immune surveillance. During this process the innate and the adaptive immune systems closely cooperate and especially T cells play an important role to detect and eliminate tumor cells. Due to the mechanism of central tolerance the frequency of T cells displaying appropriate arranged tumor‐peptide‐specific‐T‐cell receptors is very low and their activation by professional antigen‐presenting cells, such as dendritic cells, is frequently hampered by insufficient costimulation resulting in peripheral tolerance. In addition, inhibitory immune circuits can impair an efficient antitumoral response of reactive T cells. It also has been demonstrated that large tumor burden can promote a state of immunosuppression that in turn can facilitate neoplastic progression. Moreover, tumor cells, which mostly are genetically instable, can gain rescue mechanisms which further impair immune surveillance by T cells. Herein, we summarize the data on how tumor cells evade T‐cell immune surveillance with the focus on solid tumors and describe approaches to improve anticancer capacity of T cells.
Electrocardiographic Characteristics of Ventricular Arrhythmia Originating from the Left Coronary Cusp
Authors: Kossaify Antoine , Saoudi Nadir , Succar Sami
Published: November 2011

Aortic cusps originating arrhythmias are rare; they have special electrocardiogram features that help to locate the site of origin. We report on a 20-year-old male patient without structural heart disease presenting with accelerated idioventricular rhythm; electrocardiogram analysis was typical of left coronary cusp origin.
Prevention of Preterm Labour: 2011 Update on Tocolysis
Authors: Hubinont C. , Debieve F.
Published: November 2011

The aim of this paper is to review available data about drugs for preventing preterm labour. Tocolytic therapy includesβadrenergic receptor agonists, NO donors, magnesium sulphate, prostaglandin-synthase inhibitors, oxytocin receptor antagonists, calcium-channel blockers, progesterone, 17-α-hydroxyprogesterone caproate, and antibiotics. Their specific effects on myometrial contractility, their safety, their efficiency, and side effects profile for the mother and the fetus are presented. The main question of why and for what reasons tocolysis should be administrated is discussed.
Diffusion Tensor MRI to Assess Damage in Healthy and Dystrophic Skeletal Muscle after Lengthening Contractions
Authors: McMillan Alan B. , Shi Da , Pratt Stephen J. P. , Lovering Richard M.
Published: November 2011

The purpose of this study was to determine if variables calculated from diffusion tensor imaging (DTI) would serve as a reliable marker of damage after a muscle strain injury in dystrophic (mdx) and wild type (WT) mice. Unilateral injury to the tibialis anterior muscle (TA) was induced in vivo by 10 maximal lengthening contractions. High resolution T1‐ and T2‐weighted structural MRI, including T2 mapping and spin echo DTI was acquired on a 7T small animal MRI system. Injury was confirmed by a significant loss of isometric torque (85% in mdx versus 42% in WT). Greater increases in apparent diffusion coefficient (ADC), axial, and radial diffusivity (AD and RD) of the injured muscle were present in the mdx mice versus controls. These changes were paralleled by decreases in fractional anisotropy (FA). Additionally, T2 was increased in the mdx mice, but the spatial extent of the changes was less than those in the DTI parameters. The data suggest that DTI is an accurate indicator of muscle injury, even at early time points where the MR signal changes are dominated by local edema.
Topical Review: Design, Fabrication, and Applications of Hybrid Nanostructured Array
Authors: Zhu Shaoli , Zhou Wei
Published: November 2011

Nanohybrid materials have been widely used in the material chemistry research areas. In this paper, we mainly discussed the hybrid nanostructures used for nanobiosensor applications. It is one of the most promising and rapidly emerging research areas in nanotechnology field. Design, fabrication, and applications of hybrid nanostructures are reviewed, respectively. Finite difference time domain (FDTD) methods are applied to design different materials of hybrid nanostructures. Nanosphere lithography (NSL) is used to fabricate our designed hybrid nanostructures. Moreover, protein A and staphylococcal enterotoixn B (SEB), an enterotoxin, are detected by our designed hybrid nanostructures. From all the experiment results, we can see that our designed hybrid nanostructures are one of important nanohybrid materials. They have many potential applications in the nanobiosensor in the future.
Is Mesh Becoming More Popular? Dilemmas in Urogynecology: A National Survey
Authors: Condrea Alexander , Netzer Itamar , Ginath Shimon , Eldor-Itskovitz Joseph , Golan Abraham , Lowenstein Lior
Published: November 2011

The use of vaginal mesh in pelvic organ prolapse (POP) repair surgery has become more common in recent years. The purpose of the current study was to evaluate the common practice of Israeli urogynecologists, and to determine whether surgical practice has changed over the last two years.Methods. In 2009 and again in 2011, a survey was mailed to all urogynecologists affiliated with an academic institute in Israel. The survey consisted of 7 Likert-scale items and 3 open questions; the latter inquired about preferred type of surgery in three clinical scenarios.Results. Of 22 practitioners, 15 responded to the survey. The number of urogynecologists who reported using vaginal mesh for the repair of primary POP increased from 47 to 67% from 2009 to 2011. The number who would not use vaginal mesh in POP repair of elderly patients dropped from 60 to 3%. Finally, for the treatment of a 35-year-old patient with stage III uterine prolapse who desired to preserve fertility, 13% recommended the used vaginal mesh in 2009 compared with 47% in 2011.Conclusion. A survey of practitioners shows that the use of vaginal mesh for the repair of primary and recurrent pelvic organ prolapse has become more common among Israeli urogynecologists.
Primary Sclerosing Cholangitis: Diagnostic and Therapeutic Problems
Authors: Gotthardt Daniel , Chahoud Fadi , Sauer Peter
Published: November 2011

Progressive destruction of bile ducts in primary sclerosing cholangitis (PSC) may lead to end-stage liver disease, portal hypertension and liver failure. The diagnosis of PSC is made by characteristic multifocal stricturing and dilation of intrahepatic and/or extrahepatic bile ducts observed by cholangiography. Magnetic resonance cholangiography is considered to have comparable accuracy to endoscopic retrograde cholangiography (ERC) in the diagnosis of PSC, but its accuracy is limited in early stages of PSC. Up to 60% of patients with PSC develop a dominant stricture of the intra- or extrahepatic biliary tree. Patients may present with jaundice, pruritus or ascending cholangitis. Therefore, in patients with an increase in serum bilirubin and/or worsening pruritus, progressive bile duct dilation on imaging studies and/or cholangitis seen via ERC, it is recommended to exclude a dominant stricture. However, in a considerable number of patients without symptoms, a dominant stricture can be detected on the cholangiogram. The cholangiographic findings and the clinical presentation make it difficult to distinguish PSC from cholangiocarcinoma. The accuracy in the distinction between these two conditions is still rather disappointing, despite the combined use of imaging, endoscopic biopsy, and cytology. Medical, endoscopic, and surgical therapies aim to slow the progression of the disease. It is generally agreed upon that patients with symptoms from dominant strictures like cholangitis, jaundice, pruritus or worsening biochemical indices are candidates for endoscopic therapy. Although the best therapeutic endoscopic approach for these patients is still under discussion, a number of reports have documented clinical and radiographic improvement in patients following endoscopic dilation with or without placement of a biliary stent. Furthermore, indirect evidence by retrospective studies suggests that endoscopic therapy may improve survival.
Technicalities of Colonoscopy: Endoscopic Microscopy – Where Are We Heading?
Authors: Bisschops Raf
Published: November 2011

Confocal laser endomicroscopy (CLE) is a new endoscopic imaging tool enabling in vivo histology during ongoing endoscopy. Basically, three different patterns can be seen in the colon: normal, neoplastic and inflammatory mucosa. Several pilot studies have shown an excellent correlation with classical histology. However, what could be the future indications of CLE? (1) Differentiating neoplastic from inflammatory changes constitutes a promising diagnostic tool in screening for dysplasia in ulcerative colitis. This can help to further increase the efficacy of chromoendoscopy in dysplasia detection and reduce the number of biopsies. The possibility to differentiate sporadic adenoma from dysplasia-associated lesion or mass could have an immediate impact on patient management. (2) The diagnosis of collagenous colitis depends on multiple random biopsies. Case series have shown that CLE can guide the endoscopist to take more representative biopsies to make the diagnosis. Large prospective trials are needed to confirm this finding. (3) An interesting clinical application is graft-versus-host disease (GVHD). A pilot study showed that it was possible to predict the presence of GVHD in 14/19 patients with GVHD out of 35 patients who were referred for diarrhea after stem cell transplantation. (4) CLE for standard polyp surveillance is probably redundant since it will not change patient management at this stage. Moreover, it can currently not differentiate between classical hyperplastic and sessile serrated adenomas. (5) Future additional technological improvements of the system with faster Z-scanning, deeper light penetration and 3D reconstruction will help to improve the quality of CLE. Reports on in vivo molecular imaging and assessment of physiological changes provide a promising glance at the future possibilities of CLE imaging.
The Missed Colorectal Cancer Problem
Authors: Faiss S.
Published: November 2011

Background/Aims: Colonoscopy is currently regarded as the gold standard for the detection of polyps and cancers in the colon and rectum, and is the preferred method of screening for colorectal cancer in Europe and the USA. However, evidence shows that polyps and other lesions can be missed during colonoscopy due to several reasons. Methods: An unsystematic review of the literature concerning the issues of missed colorectal cancers and interval cancers during colonoscopy was performed and the most important articles described. Results: According to the literature there are various reasons for interval and/or missed colorectal cancers: incomplete bowel cleaning, incomplete colonoscopy, short withdrawal time, incomplete resection of adenomas, rapid tumor progression, sessile serrated adenomas and the examiner him- or herself. Conclusion: For the minimization of missed neoplasias and even cancers it is necessary to perform screening colonoscopy after an optimal bowel preparation. Furthermore, colonoscopy should be performed in an ‘optimal setting’ with adequate withdrawal time and complete resection of all polypoid lesions by experienced examiners followed by an adequate histological work-up including the knowledge about sessile serrated adenomas.
Capsule Endoscopy and Crohn’s Disease
Authors: Hartmann Dirk
Published: November 2011

Capsule endoscopy has been shown to detect small bowel inflammatory changes better than any other imaging modality. Selection criteria have been optimized to increase the yield of capsule endoscopy in patients suspected of having Crohn’s disease. Capsule endoscopy allows for earlier diagnosis of Crohn’s disease of the small bowel and improved diagnosis of colitis in patients where it is unclear if they suffer from Crohn’s or ulcerative colitis. A test capsule is available to assess for small bowel strictures and thus avoid capsule retention. It is envisioned that the manner in which we treat Crohn’s disease in the future will change, based on earlier diagnosis and treatment aimed at mucosal healing rather than symptom improvement.
Colonoscopy Screening: Status in Europe
Authors: Riemann J.F.
Published: November 2011

Europe has made significant progress in recent years by introducing population-based screening programs for colorectal cancer. Due to excellent evidence-based results on the basis of large prospective randomized trials, mass screening using the fecal occult blood test is currently the procedure of choice. Endoscopy-based programs do afford quality insurance programs which are outlined in the recommendations of the European Commission.
Role of Acid Suppression in the Development and Progression of Dysplasia in Patients with Barrett’s Esophagus
Authors: Kastelein F. , Spaander M.C.W. , Biermann K. , Vucelic B. , Kuipers E.J. , Bruno M.J.
Published: November 2011

Barrett’s esophagus (BE) usually develops in patients with gastroesophageal reflux disease and therefore it has been suggested that esophageal acid exposure plays an import role in the initiation of BE and its progression towards esophageal adenocarcinoma (EAC). The mechanisms whereby acid exposure causes BE are not completely revealed and the potential role of esophageal acid exposure in carcinogenesis is unclear as well. Since acid exposure is thought to play an important role in the progression of BE, therapies aimed at preventing the development of EAC have primarily focused on pharmacological and surgical acid suppression. In clinical practice, acid suppression is effective in relieving reflux symptoms and decreases esophageal acid exposure in most patients. However, in some individuals, pathological acid exposure persists and these patients continue to be at risk for developing dysplasia or EAC. To date, published trials suggest that acid suppression is able to prevent the development and progression of dysplasia in patients with BE, but definite and compelling proof is still lacking. This article reviews the mechanisms of acid-induced carcinogenesis in BE and the role of acid suppression in the prevention of neoplastic progression.
Acid Secretion and Gastric Surgery
Authors: Lundell Lars
Published: November 2011

It was long believed that there were major differences in the pathophysiology between the three major categories of peptic ulcers. The unifying feature was that all peptic ulcers occurred in a mucosal compartment exposed to acid-pepsin secretions. All ulcers tended to heal more rapidly when acid secretion was more readily neutralized or inhibited. Decreased local resistance was considered to be present in primarily acute and chronic gastric ulcer. Surgery for peptic ulcer intended to reduce acid secretion, which also resulted in a diminished pepsin enzyme activity. The corresponding reduction could be accomplished either by gastric resection, different vagotomies or a combination of resections and vagotomies. Most of the procedures were basically abandoned at the time of introduction of modern medical therapeutic strategies. For duodenal ulcer and prepyloric ulcer diseases, various vagotomies were generally recommended or combined with antrectomy. Partial gastrectomy or antrectomy with gastroduodenostomy was the standard procedure for treatment of type 1 gastric ulcer. The great caveat associated with surgical procedures for elective treatment of uncomplicated peptic ulcer disease is confined to operative mortality, postoperative morbidity, and late postoperative metabolic sequelae. The only remaining indication today of remedial gastric surgery for peptic ulcer disease is when there is a defined risk for gastric cancer in an unhealed gastric ulcer and very seldom in a case with recurrent or therapy-resistant peripyloric ulcer.
Acid Inhibition and Peptic Ulcer Bleeding
Authors: Štimac D. , Franjić N. , Krznarić Ž.
Published: November 2011

Peptic ulcer bleeding is one of the most common emergency situations in medicine. Combined pharmacological and endoscopic therapy together with emerging interventional radiological procedures are successfully treating peptic ulcer disease, reserving surgical procedures for only a small portion of patients unresponsive to ‘conventional’ therapy. Technological advancement has seen a great improvement in the field of endoscopic treatment in the form of various methods of hemostasis. However, pharmacological therapy with proton pump inhibitors still plays the central role in the peptic ulcer bleeding treatment algorithm.
Long-Term Acid Inhibition: Benefits and Harms
Authors: Tepeš Bojan
Published: November 2011

Proton pump inhibitors (PPIs) are the drugs of choice in the therapy of acid-related disorders. PPIs are as a class remarkably safe. Serious adverse events such as acute interstitial nephritis are extremely rare. Some reports in recent years have placed some concern on the long-term use of PPIs. Long-term therapy with PPIs can cause hypochlorhydria, hypergastrinemia and has interactions on hepatic cytochrome P450 enzymes which might increase the risk of infectious complications, nutritional deficiencies and drug-drug interactions. The vast majority of data came from retrospective case-control or cohort studies which are prone to confounders. At the moment we cannot conclude that long-term PPI use causes anemia, osteoporosis and bone fractures, increases the risk for pulmonary or enteric infections, has an effect on GUT mucosa, polyp or tumor formation, or that PPI use increases the risk of cardiovascular events in patients on PPIs and clopidogrel. We need prospective randomized trials to be able to definitely answer the questions raised in epidemiologic studies. Maintenance therapy with PPIs should be started only if strict indications for that therapy are fulfilled.
Etiopathogenetic Principles and Peptic Ulcer Disease Classification
Authors: Tytgat G.N.J.
Published: November 2011

Ulceration corresponds to tissue loss, breaching the muscularis mucosae. When ulcers develop in the acid-peptic environment of the gastroduodenum, they are traditionally called peptic ulcer (PUD). Ulcers never develop spontaneously in a healthy gastroduodenal mucosa. Ulceration is the ultimate consequence of a disequilibrium between aggressive injurious factors and defensive mucosa-protective factors. The dominant aggressors are strong acid and high proteolytic (pepsin) activity in gastric secretions. The dominant defensors are the phospholipid surfactant layer, covering the mucus bicarbonate gel, the mucus bicarbonate layer covering the epithelium, the tight junctional structures between the epithelial cells, restricting proton permeability, and the epithelial trefoil peptides, contributing to healing after injury. Initially, acid-peptic aggression was considered the overwhelming cause of PUD, supported by the pioneering work of Schwartz, launching the dictum ‘no acid, no ulcer’. This led to the universal therapy directed against intragastric acidity, also interfering with peptic activity when the pH was >4. The therapeutic sequence went from large doses of antacids to H2-receptor antagonists and finally to proton pump inhibitors (PPIs). The longer the intragastric pH was >3, the quicker ulcer healing was seen. Unfortunately, ulcers often recurred after stopping therapy, demanding maintenance therapy to keep the ulcers healed and to prevent the need for surgery (vagotomy, partial gastric resection). Later on, the emphasis gradually shifted to weakening/failing of the defensive factors, raising the vulnerability of the gastroduodenal mucosa to luminal secretions. Leading injurious mechanisms jeopardizing the mucosal integrity are numerous: infections, especially Helicobacter pylori, drug-induced injury, particularly acetylsalicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs), physicochemical and caustic injury, vascular disorders, interfering with perfusion, etc. Currently the leading cause of PUD is H. pylori infection. Standard triple eradication therapy is losing interest in favor of quadruple therapy (PPI, bismuth, tetracycline, metronidazole). H. pylori-induced PPI is rapidly disappearing in the Western world, in contrast to drug-induced ulcer disease and what is called idiopathic PUD. Partial prophylaxis of ASA/NSAID-induced ulceration is possible with PPI maintenance therapy, but novel ways to strengthen the mucosal defense are urgently awaited.
Update Lecture: Benign Diseases of the Exocrine Pancreas
Authors: Mössner Joachim
Published: November 2011

A brief overview on the physiology and regulation of digestive enzyme secretion by the exocrine pancreas is presented. Knowledge about the physiology of the exocrine pancreas should help for a better understanding of the pathophysiology of both acute and chronic pancreatitis. In the pathophysiology of acute pancreatitis, fusion of zymogen granules with lysosomes, which leads to intracellular activation of trypsinogen, is still regarded as a key step in pathophysiology. The role of activation by cathepsins and the role of autoactivation of trypsinogen are still under debate. Studies on genetic alterations in various forms of human chronic pancreatitis can be interpreted that an imbalance between protease inhibitors and active proteases plays a key role. Toxic Ca2+ signals by excessive liberation from the endoplasmic reticulum may play another role. The mortality of necrotizing pancreatitis is still high. Early mortality is caused by a systemic inflammatory response syndrome with or without concomitant infection of necrosis; late mortality by multi-organ failure syndrome due to sepsis. Therapy of necroses should be performed as late as possible. A step-up approach using CT-guided and/or transgastric endoscopic necrosectomy seems to be superior to a primary surgical approach. A brief overview of the German S3 guidelines, not yet published, regarding diagnosis and treatment of chronic pancreatitis is presented.
Early and Presenting Symptoms of Dementia with Lewy Bodies
Authors: Auning Eirik , Rongve Arvid , Fladby Tormod , Booij Jan , Hortobágyi Tibor , Siepel Françoise J. , Ballard Clive , Aarsland Dag
Published: November 2011

Background/Aims: To explore the presenting and early symptoms of dementia with Lewy bodies (DLB). Method: Patients with mild dementia fulfilling diagnostic criteria for DLB (n = 61) and Alzheimer’s disease (AD) (n = 109) were recruited from outpatient dementia clinics in western Norway. At diagnosis, caregivers were asked which symptom had been the presenting symptom of dementia. Results: Caregivers reported that memory impairment was the most common presenting symptom in DLB (57%), followed by visual hallucinations (44%), depression (34%), problem solving difficulties (33%), gait problems (28%), and tremor/stiffness (25%). In contrast, 99% of AD carers reported impaired memory as a presenting symptom, whereas visual hallucinations were a presenting symptom in 3% of the AD cases. Conclusion: DLB should be suspected in predementia cases with visual hallucinations.
GTG Mutation in the Start Codon of the Androgen Receptor Gene in a Family of Horses with 64,XY Disorder of Sex Development
Authors: Révay T. , Villagómez D.A.F. , Brewer D. , Chenier T. , King W.A.
Published: November 2011

Genetic sex in mammals is determined by the sex chromosomal composition of the zygote. The X and Y chromosomes are responsible for numerous factors that must work in close concert for the proper development of a healthy sexual phenotype. The role of androgens in case of XY chromosomal constitution is crucial for normal male sex differentiation. The intracellular androgenic action is mediated by the androgen receptor (AR), and its impaired function leads to a myriad of syndromes with severe clinical consequences, most notably androgen insensitivity syndrome and prostate cancer. In this paper, we investigated the possibility that an alteration of the equine AR gene explains a recently described familial XY, SRY + disorder of sex development. We uncovered a transition in the first nucleotide of the AR start codon (c.1A>G). To our knowledge, this represents the first causative AR mutation described in domestic animals. It is also a rarely observed mutation in eukaryotes and is unique among the >750 entries of the human androgen receptor mutation database. In addition, we found another quiet missense mutation in exon 1 (c.322C>T). Transcription of AR was confirmed by RT-PCR amplification of several exons. Translation of the full-length AR protein from the initiating GTG start codon was confirmed by Western blot using N- and C-terminal-specific antibodies. Two smaller peptides (25 and 14 amino acids long) were identified from the middle of exon 1 and across exons 5 and 6 by mass spectrometry. Based upon our experimental data and the supporting literature, it appears that the AR is expressed as a full-length protein and in a functional form, and the observed phenotype is the result of reduced AR protein expression levels.
Disorders of Sexual Development in Poultry
Authors: Lambeth L.S. , Smith C.A.
Published: November 2011

Sex in birds is determined genetically, as in mammals. However, in birds, female is the heterogametic sex (ZW), while the male is homogametic (ZZ). Although the exact mechanism of avian sex determination is still unclear, genes on one or both of the sex chromosomes must control sexual differentiation of the embryonic gonads into testes or ovaries, and eventually all other sexually dimorphic features. In this review of disorders of sexual development in poultry, we focus upon the gonads and external dimorphisms. Abnormalities of sexual development in poultry can be broadly divided into 2 types: those due to disturbances in sex hormone production by the gonads, and those due to abnormal inheritance of sex chromosomes. Recent studies on gynandromorphic chickens (half male, half female) point to the importance of genetic over hormonal factors in controlling sexual development in fowl.
No Acid, No Ulcer: Dragutin (Carl) Schwarz (1868–1917), the Man Ahead of His Time
Authors: Fatović-Ferenčić Stella , Banić Marko
Published: November 2011

Dragutin (Carl) Schwarz (1868–1917) was born in Varaždin (part of the Austro-Hungarian Monarchy then, northwestern part of Croatia today). As many Croats of the period he enrolled in the Vienna School of Medicine and graduated in 1891. After spending some time in a few clinics of the Monarchy, he returned to his homeland in 1895. Named the primary physician of the surgical department of Charity Brothers’ Hospital in Zagreb, he motivated lively activities there and became the prominent member of the medical community. Apart from his impressive surgical work, Carl Schwarz is primarily remembered for his dictum ‘No acid, no ulcer’ (1910) which was proven to be true in the decades that followed. This short editorial aims at recalling those visionary observations ever inviting and challenging further investigations.
Hybrid Open Endovascular Technique for Aortic Thoracoabdominal Pathologies
Authors: Moulakakis Konstantinos G. , Mylonas Spyridon N. , Avgerinos Efthimios D. , Kakisis John D. , Brunkwall Jan , Liapis Christos D.
Published: November 2011

Background—

Many authors using a hybrid debranching strategy for the treatment of thoracoabdominal pathologies have reported disappointing results and the initial enthusiasm for the technique has given way to criticism and ambiguity. The aim of the present meta-analysis study was to assess the safety and efficacy of the technique in patients with thoracoabdominal aortic aneurysms or other aortic pathologies.

Methods and Results—

A multiple electronic search was performed on all articles describing hybrid open endovascular repair. Separate meta-analyses were conducted for technical success, visceral graft patency, spinal cord ischemia symptoms, renal insufficiency, and other complications as well as 30-day/in-hospital mortality.

Nineteen publications with a total of 507 patients were analyzed. The pooled estimates for primary technical success and visceral graft patency were 96.2% (95% CI, 93.5%–98.2%) and 96.5% (95% CI, 95.2%–97.8%) respectively. A pooled rate of 7.5% (95% CI, 5.0%–11.0%) for overall spinal cord ischemia symptoms was observed; whereas for irreversible paraplegia the pooled rate was 4.5% (95% CI, 2.5%–7.0%). The pooled estimate for renal failure was 8.8% (95% CI, 3.9%–15.5%). The pooled 30-day/in-hospital mortality rate was 12.8% (95% CI, 8.6%–17.0%). During the mean follow-up period of 34.5 (95% CI, 31.5–37.5) months, a total of 119 endoleaks were identified in 111 patients (22.7%).

Conclusions—

The repair of thoracoabdominal pathologies by means of hybrid procedures in patients who are poor surgical candidates is still associated with significant morbidity and mortality rates. Future studies may substantiate whether the technique is amenable to amelioration and improvement.
Protection Against Myocardial Infarction and No-Reflow Through Preservation of Vascular Integrity by Angiopoietin-Like 4
Authors: Galaup Ariane , Gomez Elisa , Souktani Rachid , Durand Mélanie , Cazes Aurélie , Monnot Catherine , Teillon Jérémie , Le Jan Sébastien , Bouleti Claire , Briois Gaëlle , Philippe Josette , Pons Sandrine , Martin Valérie , Assaly Rana , Bonnin Philippe , Ratajczak Philippe , Janin Anne , Thurston Gavin , Valenzuela David M. , Murphy Andrew J. , Yancopoulos George D. , Tissier Renaud , Berdeaux Alain , Ghaleh Bijan , Germain Stéphane
Published: November 2011

Background—

Increased permeability, predominantly controlled by endothelial junction stability, is an early event in the deterioration of vascular integrity in ischemic disorders. Hemorrhage, edema, and inflammation are the main features of reperfusion injuries, as observed in acute myocardial infarction (AMI). Thus, preservation of vascular integrity is fundamental in ischemic heart disease. Angiopoietins are pivotal modulators of cell–cell junctions and vascular integrity. We hypothesized that hypoxic induction of angiopoietin-like protein 4 (ANGPTL4) might modulate vascular damage, infarct size, and no-reflow during AMI.

Methods and Results—

We showed that vascular permeability, hemorrhage, edema, inflammation, and infarct severity were increased in
angptl4
-deficient mice. We determined that decrease in vascular endothelial growth factor receptor 2 (VEGFR2) and VE-cadherin expression and increase in Src kinase phosphorylation downstream of VEGFR2 were accentuated after ischemia-reperfusion in the coronary microcirculation of
angptl4
-deficient mice. Both events led to altered VEGFR2/VE-cadherin complexes and to disrupted adherens junctions in the endothelial cells of
angptl4
-deficient mice that correlated with increased no-reflow. In vivo injection of recombinant human ANGPTL4 protected VEGF-driven dissociation of the VEGFR2/VE-cadherin complex, reduced myocardial infarct size, and the extent of no-reflow in mice and rabbits.

Conclusions—

These data showed that ANGPTL4 might constitute a relevant target for therapeutic vasculoprotection aimed at counteracting the effects of VEGF, thus being crucial for preventing no-reflow and conferring secondary cardioprotection during AMI.
Continuous Time Series of Catchment-Averaged Sensible Heat Flux from a Large Aperture Scintillometer: Efficient Estimation of Stability Conditions and Importance of Fluxes under Stable Conditions
Authors: Samain Bruno , Defloor Willem , Pauwels Valentijn R. N.
Published: November 2011

A large aperture scintillometer (LAS) observes the intensity of the atmospheric turbulence across large distances, which is related to the path-averaged sensible heat flux H. In this paper, two problems in the derivation of continuous series of H from LAS data are investigated and the importance of nighttime H fluxes is assessed. First, as an LAS is unable to determine the sign of H, the transition from unstable to stable conditions is evaluated in order to make continuous H series. Therefore, different algorithms to judge the atmospheric stability for an LAS installed over a distance of 9.5 km have been tested. The diurnal cycle of the refractive index structure parameter, , results in the best suitable, operational algorithm. A second issue is the humidity correction for LAS data, which is performed by using the Bowen ratio (β). As β is taken from ground-based measurements with data gaps, the number of resulting H values is reduced. Not including this humidity correction results in a marginal error in H, but increases the completeness of the H series. Applying these conclusions to the 2-yr time series of the LAS results in an almost-continuous H time series. As the majority of the time steps has been found to be under stable conditions, there is a clear impact of Hstable on H24h—the 24-h average of H. For stable conditions, Hstable values are mostly negative, and hence lower than the H = 0 W m−2 assumption as mostly adopted. For months where stable conditions prevail (winter), H24h is overestimated using this assumption, and calculation of Hstable is recommended.
Ground source heat pumps: observations from United Kingdom ground thermal response tests
Authors: Underwood CP
Published: November 2011

The United Kingdom is experiencing a period of rapid growth in the use of ground source heat pump systems. Most installations in the United Kingdom use vertical ‘borehole’ heat-exchanger arrays, the design of which depends on four parameters: formation thermal conductivity, formation heat capacity, heat-exchanger resistance and heat-exchanger grout material heat capacity. Conventionally, two of these parameters (conductivity and resistance) are obtained from a thermal response test carried out on a trial heat exchanger at the site of interest by fitting thermal response data to classical line-source heat conduction theory. This test method gives no information on the heat capacities of the formation and grout material and requires an assumption about the former to enable the heat-exchanger resistance parameter to be extracted. In this work, a new method is developed for extracting all four parameters using a trust-region search algorithm in conjunction with a detailed numerical model of the test heat exchanger. Results give excellent agreement between the fitted-model predictions of heat-exchanger outlet water temperature and measured outlet water temperature for 13 test cases. A further advantage of the method developed here is that it can be used with data sets that contain disturbances and discontinuities.

Practical applications: Most of the ground source heat pump installations in the United Kingdom use vertical ‘borehole’ heat-exchanger arrays. The design of these arrays requires information about the rock formation thermal conductivity and volume specific heat capacity and the borehole heat-exchanger thermal resistance and grout material volume specific heat capacity. These design parameters are usually obtained from a thermal response test carried out on a trial heat exchanger at the site of interest. In this work, thermal response test results from 13 UK sites are presented and a new method for obtaining the four design parameters is developed and proposed.
A Cost-Effectiveness Analysis Comparing 3 Anterior Cruciate Ligament Graft Types
Authors: Genuario James W. , Faucett Scott C. , Boublik Martin , Schlegel Theodore F.
Published: November 2011

Background: Anterior cruciate ligament (ACL) reconstruction, despite being one of the most common surgical interventions, is also one of the least agreed upon surgeries when it comes to optimum graft choice. Three graft choices stand among the most widely used in this procedure: (1) bone–patellar tendon–bone autograft (BPTB), (2) quadruple hamstring tendon autograft (HS), and (3) allograft.

Hypothesis: Bone–patellar tendon–bone ACL reconstruction is the most cost-effective method of ACL reconstruction.

Study Design: Economic and decision analysis; Level of evidence, 2.

Methods: A simplified decision tree model was created with theoretical patients assigned equally to 1 of 3 ACL reconstruction cohorts based on graft type. These treatment arms were further divided into outcome arms based on probabilities from the literature. The terminal outcomes were assigned a health state/utility score and a societal cost. Utilities were calculated from real clinic patients via the time trade-off questionnaire. Costs were literature based. An incremental cost-effectiveness ratio of $50 000/quality-adjusted life year (QALY) was used as the threshold for cost-effectiveness.

Results: Hamstring tendon autograft was the least costly ($5375/surgery) and most effective (0.912) graft choice, dominating both BPTB and allograft reconstructions. Allograft was both the most costly and least effective strategy for the average patient undergoing ACL reconstruction. However, if baseline costs of BPTB could be reduced (by $500) or the effectiveness increased (anterior knee pain <15% or postoperative instability <7%), then BPTB became an incrementally cost-effective choice. In addition, if the effectiveness of HS could be reduced (instability >29% or revision rates >7%), then BPTB also became incrementally cost-effective.

Conclusions: This model suggests that hamstring autograft ACL reconstruction is the most cost-effective method of surgery for the average patient with ACL deficiency. However, specific clinical scenarios that change postoperative probabilities of the different complications may sway surgeons to choose either allografts or BPTB. Cost-effectiveness analysis is not intended to replace individual clinician judgment but rather is intended to examine both the effectiveness and costs associated with theoretical groups undergoing specific multifactorial decisions.
Prospective Randomized Clinical Evaluation of Conventional Single-Bundle, Anatomic Single-Bundle, and Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction
Authors: Hussein Mohsen , van Eck Carola F. , Cretnik Andrej , Dinevski Dejan , Fu Freddie H.
Published: November 2011

Background: Three different techniques of anterior cruciate ligament (ACL) reconstruction—conventional (transtibial) single bundle (CSB), anatomic single bundle (ASB), and anatomic double bundle (ADB)—have been described.

Purpose: To determine if double-bundle reconstruction is needed to restore rotational stability or if anatomic placement of a single bundle can yield similar results.

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: From December 2005 to December 2007, 320 patients were prospectively randomized into 3 groups: ADB, ASB, and CSB reconstruction. The average follow-up was 51.15 months (range, 39-63 months). At the final follow-up, 281 patients were available. In all groups, hamstring tendons were used with suspensory fixation on the femoral side and bioabsorbable interference screw fixation on the tibial side. The outcomes were evaluated by an independent blinded observer using the Lysholm score and subjective International Knee Documentation Committee (IKDC) form. The KT-1000 arthrometer was used to evaluate anteroposterior stability, and the pivot-shift test was used to determine rotational stability.

Results: Anatomic single-bundle reconstruction resulted in better anteroposterior and rotational stability than CSB reconstruction (average side-to-side difference for anterior tibial translation was 1.6 mm in the ASB group vs 2.0 mm in the CSB group; P = .002). Negative pivot shift was 66.7% vs 41.7% ( P = .003). In other parameters, the differences between groups were not statistically significant. The results of the ADB group were also superior to the ASB group for anteroposterior and rotational stability (average side-to-side difference for anterior tibial translation was 1.2 mm in the ADB group vs 1.6 mm in the ASB group; P = .002). Negative pivot shift was 93.1% vs 66.7%, respectively ( P < .001), and range of motion was also significantly different ( P = .005). The Lysholm score was 90.9, 91.8, and 93.0 in the CSB, ASB, and ADB groups, respectively. The difference was significant only when we compared ADB and CSB ( P = .025). Subjective IKDC scores were 90.2, 90.6, and 92.1 in the CSB, ASB, and ADB groups, respectively. The difference was not significant.

Conclusion: Anatomic double-bundle ACL reconstruction is significantly superior to conventional single-bundle ACL reconstruction and better than anatomic single-bundle reconstruction. Anatomic single-bundle reconstruction was superior to conventional single-bundle reconstruction. However, these differences are small and may not be clinically relevant.
In vivo biodistribution of carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles in rats
Authors: Pereira V.H. , Salgado A.J. , Oliveira J.M. , Cerqueira S.R. , Frias A.M. , Fraga J.S. , Roque S. , Falcão A.M. , Marques F. , Neves N.M. , Mano J.F. , Reis R.L. , Sousa N.
Published: November 2011

Carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles, comprised of a PAMAM dendrimer core grafted with chains of CMCht, have recently been proposed for intracellular drug delivery. In previous reports, these nanoparticles had lower levels of cytotoxicity when compared with traditional dendrimers. In this study, the short-term in vivo biodistribution of fluorescein isothiocyanate (FITC)-labeled CMCht/PAMAM dendrimer nanoparticles after intravenous (IV) injections in Wistar Han rats was determined. The brain, liver, kidney, and lung were collected at 24, 48, and 72 h after injection and stained with phalloidin–tetramethylrhodamine isothiocyanate (TRITC, red) and 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI, blue) to trace the nanoparticles within these tissues. The liver, kidney, and lung were also stained for hematoxylin and eosin to assess any morphological alterations of these organs. CMCht/PAMAM dendrimer nanoparticles were observed within the vascular space and parenchyma of liver, kidney, and lung and in the choroid plexus, after each injection period. No particles were observed in the brain parenchyma, nor any apparent deleterious histological changes were observed within these organs. The CMCht/PAMAM dendrimer nanoparticles were stable in circulation for a period of up to 72 h, targeting the main organs/systems through internalization by the cells present in their parenchyma. These results provide positive indicators to their potential use in the future as intracellular drug delivery systems.
Cell survival and proliferation after encapsulation in a chemically modified Pluronic® F127 hydrogel
Authors: Lippens Evi , Swennen Ives , Gironès Jordi , Declercq Heidi , Vertenten Geert , Vlaminck Lieven , Gasthuys Frank , Schacht Etienne , Cornelissen Ria
Published: November 2011

Pluronic® F127 is a biocompatible, injectable, and thermoresponsive polymer with promising biomedical applications. In this study, a chemically modified form, i.e., Pluronic ALA-L with tailored degradation rate, was tested as an encapsulation vehicle for osteoblastic cells. UV cross-linking of the modified polymer results in a stable hydrogel with a slower degradation rate. Toxicological screening showed no adverse effects of the modified Pluronic ALA-L on the cell viability. Moreover, high viability of embedded cells in the cross-linked Pluronic ALA-L was observed with life/death fluorescent staining during a 7-day-culture period. Cells were also cultured on macroporous, cross-linked gelatin microbeads, called CultiSpher-S® carriers, and encapsulated into the modified cross-linked hydrogel. Also, in this situation, good cell proliferation and migration could be observed in vitro. Preliminary in vivo tests have shown the formation of new bone starting from the injected pre-loaded CultiSpher-S® carriers.
Modeling the commons as a game with vector payoffs
Authors: Lejano Raul P. , Ingram Helen
Published: November 2011

Since Hardin first formulated the tragedy of the commons, researchers have described various ways that commons problems are solved, all based on the model of individual rationality. Invariably, these institutional solutions involve creating some system of property rights. We formulate an alternative model, one not founded on property rights but on decision-making around so-called vector payoffs. The model is formalized and an existence proof provided. The new model is shown to be effective in explaining some anomalous results (e.g., unanticipated cooperation) in the experimental games literature that run counter to the rational model. We then use the case of the buffalo commons to illustrate how the new model affords alternative explanations for examples like the rise and fall of the buffalo herds in the Great Plains. We find the vector payoff model to complement, though not displace, that of individual rationality.
Guest Editorial
Authors: Andreopoulos Andreas , Messer Neil , Song Robert
Published: November 2011

A collection of papers from a conference entitled ‘Eastern Orthodox and Western Christian Approaches to Bioethics’ is presented in this issue. This Editorial introduces the papers and identifies recurrent themes and questions: first, the complex relationship between faith, ethics, law and professional practice; secondly, the modes and tasks of Christian ethics or moral theology in relation to bioethical issues; thirdly, the kinds of service that academic theologians should offer to the churches, their leaders and Christians in relevant professions; fourth and finally, the continuity or discontinuity between different Christian traditions.