bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Residence Restrictions in Preventing Sex Offense Recidivism
Authors: Nobles Matt R. , Levenson Jill S. , Youstin Tasha J.
Published: July 2012

Many municipalities have recently extended residence restrictions for sex offenders beyond the provisions of state law, although the efficacy of these measures in reducing recidivism has not been empirically established. This study used arrest histories in Jacksonville, Florida, to assess the effects of a recently expanded municipal 2,500-foot residence restriction ordinance on sex crimes and sex offense recidivism. Using a quasiexperimental design, pre- and posttest measures of recidivism were compared, and no significant differences in citywide sex crimes or recidivist sex crimes were found. In addition, time-series analysis revealed no significant differences in sex crime trends over time when compared with nonsex crimes from the same offender sample. After controlling for several demographic factors, individual-level multivariate results indicate that the timing of the residence restriction policy was not associated with a meaningful change in sex crime arrests or sex offender recidivism after the policy implementation date, suggesting that the residence restriction did not achieve its intended goal of reducing recidivism.
The Chicken and the Bath Water: Exploring a Basic Limit to the Vegetarian Ideal
Authors: Webb Stephen H.
Published: July 2012

Critics of the animal rights movement often point out that a perfectly vegetarian world would result in a drastic reduction of the number of farm animals. This article is the first to systematically analysis the merits of this objection. The article provides several alternative ways of naming the objection, including “the animal elimination problem,” “the carnivore’s claim,” and “the chicken and the bathwater dilemma.” It also compares the animal elimination problem to the goal of humane societies to spay and neuter companion animals. The ways in which the animal welfare movement avoids this problem by substituting compassion for rights is also explored. A potentially fatal flaw of the “animal elimination” objection is the difficulty of talking about future or theoretical entities. Can animals not yet born have rights? Moreover, does it make sense to say that animals born into suffering might wish to never have been born? Several hypothetical scenarios are developed to address these questions. The author argues that the animal elimination problem does stall on the puzzle of assigning interests to hypothetical animals, yet there is a moral intuition about our relationship to the future that is worth considering. On secular grounds, there are no strong reasons to claim that we have duties to animals not yet existing, but Christian theology complicates the picture. The article ends with an exploration of the commands in Genesis to both humans and nonhuman animals to procreate and fill the world. The author concludes that Christians do have a duty to bring future animals into existence if they can do so within moral limits prescribed by the Genesis narrative itself.
Web-Based Survey of Current Trends in Hemodynamic Monitoring After Congenital Heart Surgery
Authors: Rossi Anthony F. , Checchia Paul A. , Lopez Leo , Seiden Howard S. , Burke Redmond P.
Published: July 2012

Strategies for monitoring patients recovering after congenital heart surgery have evolved considerably as technology continues to progress. Monitoring techniques traditionally centered around the comprehensive physical examination have been replaced by a number of revolutionary technologies developed to objectively evaluate various components of the cardiovascular system. Despite scant evidence that these methodologies actually improve outcomes, some have been embraced by clinicians. We developed an Internet survey designed to describe current practices of clinicians who care for patients after congenital heart surgery. There were 162 respondents to our survey with the majority from the United States. The views of cardiologists, intensivists, those dual trained in both cardiology and critical care medicine, and surgeons are all robustly represented in the results. Serial lactate monitoring was the strategy that was utilized most often by respondents (94%), followed by multisite near-infrared spectrometry (NIRS, 67%). There were 78% who utilized the combination of serial lactate and NIRS monitoring. Serial lactate monitoring was the technique that was thought to best represent cardiovascular well-being after heart surgery (40%). The results of this survey suggest that despite the paucity of evidence that clinical outcomes of patients recovering after congenital heart surgery are improved by any of these monitoring techniques, there is almost universal acceptance to monitor patients with serial lactate monitoring, NIRS monitoring, or a combination of these techniques.
Intensive Care and Perioperative Management of Neonates With Functionally Univentricular Hearts
Authors: Villa Chet R. , Marino Bradley S. , Jacobs Jeffrey P. , Cooper David S.
Published: July 2012

Although mortality rates for patients with univentricular hearts continue to fall, the course in the intensive care unit is remarkable for significant morbidity and utilization of significant resources. Preoperative patient management focuses on balancing competing circulations, pulmonary and systemic, which exist in parallel rather than in series, as in the normal circulation. Postoperative patient management focuses on optimizing systemic output, respiratory status, and mitigating the effects of cardiopulmonary bypass. In this article, we review pre- and postoperative intensive care management in neonates with a univentricular heart.
Unusual Combination of Hypoplastic Left Ventricle, Atrioventricular Septal Defect With Restrictive Ventricular Septal Defect, and Common Arterial Trunk
Authors: Tripathi Ravi Ranjan , Sridhar Anuradha , Chidambaram Shanthi
Published: July 2012

We describe rare cases of common arterial trunk (truncus arteriosus communis) with unbalanced atrioventricular septal defect, left ventricular hypoplasia, and restrictive ventricular septal defect. The embryology, hemodynamics, and the clinical implications of this complex combination are discussed.
Aortopulmonary Window With the Absence of Left Pulmonary Artery
Authors: Talwar Sachin , Garg Pankaj , Kothari Shyam Sunder , Gulati Gurpreet Singh , Anderson Robert H. , Airan Balram
Published: July 2012

We report an unusual combination of an aortopulmonary window with the absence of intrapericardial left pulmonary artery. The morphogenesis of this condition is briefly discussed.
Giant Left Atrial Appendage Aneurysm in a Neonate
Authors: Clarke James R. , Zvaigzne Cheryl G. , Disler Dal , Giuffre R. Michael , Rebeyka Ivan M. , Patton David J.
Published: July 2012

Giant aneurysm of the left atrial appendage (LAA) is a rare condition typically presenting in adulthood. This case report describes the investigations and surgical management of a giant LAA aneurysm in a neonate, emphasizing the role of echocardiography and cardiovascular magnetic resonance imaging in preoperative evaluation as well as challenges in surgical repair of this defect.
Modified Technique for the Implantation of Berlin Heart Excor Ventricular Assist Device in Children
Authors: Botha Phil , Hasan Asif , Perri Gianluigi , Filippelli Sergio , Griselli Massimo
Published: July 2012

The Berlin Heart Excor (BHE) assist device has become our standard mechanical support device for long-term support in children with heart failure. We report two useful surgical modifications for the implantation of the BHE in the pediatric population, improving ease of implantation as well as subsequent surgical procedures at the time of explantation or transplantation. The first modification entails the use of a polytetrafluoroethylene graft for cannulation via the innominate artery for arterial perfusion during cardiopulmonary bypass. This graft is preserved and reused for institution of bypass at the time of transplantation or explantation of the device after recovery. The second modification consists of an extension of the BHE arterial cannula using a length of knitted polyester graft. This allows for improved positioning of the arterial cannula in the ascending aorta or main pulmonary artery, facilitates vascular anastomosis, and improves hemostasis.
Anatomic Biventricular Repair in Right Isomerism With Noncommitted Ventricular Septal Defect
Authors: Katewa Ashish , Marwah Ashutosh , Singh Vishal , Ramaswamy Arun , Sharma Rajesh
Published: July 2012

Biventricular repair in right atrial isomerism is rarely feasible due to associated anomalies of venous connection, ventricular imbalance, nonroutabilty of the interventricular communication, a common atrioventricular junction, and inadequate pulmonary arterial branches. These patients are also often not ideal for univentricular repair due to some of the above associations. We describe a novel surgical technique that was utilized in such a patient for biventricular repair of a child with right atrial isomerism with total anomalous pulmonary venous connection, regurgitant common atrioventricular valve, hypoplastic left ventricle, nonroutable ventricular septal defect, and pulmonary stenosis.
Right Pulmonary Artery to Left Atrial Fistula
Authors: Kavarana Minoo N. , Devaney Eric J. , Torres Maria L. , Cotts Timothy
Published: July 2012

Right pulmonary artery to left atrial fistula is a rare congenital vascular anomaly which usually presents with cyanosis, clubbing, dyspnea, and signs and symptoms of a right to left shunt. Paradoxical embolism to the brain resulting in cerebral abscess formation and death is a rare and ominous complication that has been described. We describe an unusual presentation with abdominal pain resulting from splenic infarction.
Mycotic Aneurysm Complicating a Covered Stent Implanted for Coarctation of the Aorta in a Child
Authors: Sridhar Anuradha , Tripathi Ravi Ranjan , Sundaram Meenakshi , Subramanyan Raghavan , Vaijyanath Prashanth , Cherian Kotturathu Mammen
Published: July 2012

A mycotic aneurysm associated with a covered stent in the thoracic aorta of a 12-year-old child was successfully managed by excision and replacement with aortic homograft. On follow-up, there was unobstructed flow through the homograft. This case highlights the need for high index of suspicion for mycotic aneurysm and prompt surgical intervention in children with coarctation of aorta who present with features of infective endocarditis.
Outcome After Two-Patch Repair of Complete Common Atrioventricular Canal Defects in Patients Weighing Four Kilograms or Less
Authors: Levenbrown Yosef , Bhat A. Majeed , Hossain Jobayer , Derby Christopher , Pizarro Christian
Published: July 2012

Background: Early repair of a complete common atrioventricular canal defect (CCAVCD) may benefit patients who exhibit congestive heart failure and failure to thrive. However, concern about increased risk and fragility of valve tissue has commonly led to delaying the surgical repair until the patients achieve a predetermined weight. We report our experience with a strategy of early repair independent of age or weight . Methods: Between 2003 and 2009, 32 patients underwent two-patch repair of CCAVCD at our institution; 22 patients weighed between 2.5 and 4 kg (group #1) and 10 weighed more than 4 kg (group #2). Medical records and echocardiographic studies were reviewed to determine whether there was a difference in the incidence of mortality, rate of reintervention, and complications between the two groups. Results: Operative mortality was 3.1% (1 of 32), with one additional death two years after repair, for an overall mortality of 6.25%. Median duration of mechanical ventilation, median hospital stay, and intropic score was similar between both groups. Freedom from valve reintervention was 91% in group #1 (20 of 22), and 89% in group #2 (8 of 9, p = 1.00). Conclusions: Complete common atrioventricular canal defect can be repaired safely and effectively in patients under 4 kg. Although mortality was not increased, smaller patients have a tendency for longer intensive care and hospital stay as well as a higher incidence of atrioventricular valve regurgitation. However, valve function improved during the period of follow-up and did not impact the freedom from reintervention.
Retrospective Database Research in Pediatric Cardiology and Congenital Heart Surgery
Authors: Zampi Jeffrey D. , Donohue Janet E. , Charpie John R. , Yu Sunkyung , Hanauer David A. , Hirsch Jennifer C.
Published: July 2012

Background: Secondary use of data, whether from clinical information systems or registries, for carrying out clinical research in rare diseases is a common practice but is fraught with potential errors. We sought to elucidate some of the limitations of database research and describe possible solutions to overcome these limitations. Methods: Using a disease model of a rare postsurgical outcome, we evaluated the ability of four different data sources to correctly identify patients who had that outcome both as individual databases and also when used in conjunction with each other. These results were compared with manual chart review. Results: The sensitivity of the various databases to pick up a rare and specific outcome was poor (9.9%-37%), while the specificities were fairly good (91%-96.7%). By combining the databases, the sensitivity was increased to as much as 56.8% without a large decrease in the specificity (85.2%-91.6%). The electronic medical record (EMR) search engine had the highest sensitivity (96.9%) and a high specificity (89.3%) with a very high negative predictive value (99.4%). Conclusion: For rare and specific diseases or outcomes, a single data source search methodology can miss large numbers of patients and potentially bias study results. Combining overlapping databases can improve the ability to capture these rare diseases or outcomes. While chart review remains the most accurate way to obtain complete case capture, new tools like EMR search engines can facilitate the efficiency of this process without sacrificing search quality.
Three Pledget Technique for Closure of Muscular Ventricular Septal Defects
Authors: Sharma Rajesh , Katewa Ashish
Published: July 2012

We propose a modification of the simple, horizontal mattress, pledgetted suture technique for closing the small muscular ventricular septal defect (VSD) by interposing an oversized third pledget on the left ventricular (LV) aspect of the defect.
Ventricular Septation for Double Inlet Left Ventricle
Authors: Kurosawa Hiromi , Arai Tatsuta , Imai Yasuharu , Matsumura Goki
Published: July 2012

Ventricular septation is a biventricular repair for certain types of functionally univentricular hearts. Double inlet left ventricle (DILV) is one type of functionally univentricular heart which in certain instances is amenable to ventricular septation. Thirty-four patients underwent ventricular septation for DILV from 1971 to 2000. Hospital death occurred in seven and late death in two. Mean follow-up period was 15 years. Actuarial survival rate was 73.3% (24 patients) at 15 years, 73.3% (15 patients) at 20 years, 73.3% (five patients) at 25 years, and 73.3% (one patient) at 30 to 40 years. Ventricular septation is an alternative to Fontan operation for selected patients with single ventricle, DILV.
New Mössbauer measurements of Fe3+/ΣFe in chromites from the mantle section of the Oman ophiolite: evidence for the oxidation of the sub-oceanic mantle
Authors: Rollinson H. , Adetunji J. , Yousif A. A. , Gismelseed A. M.
Published: July 2012

Room temperature Mössbauer and electron-probe measurements of Fe3+/ΣFe in chromite from the mantle section of the Oman ophiolite define two groups of samples: a low Fe3+/ΣFe group (with Fe3+/ΣFe = 0.21–0.36) have cr# = Cr/(Cr + Al) in the range 0.49–0.75, whereas a smaller more geographically localized high Fe3+/ΣFe group (with Fe3+/ΣFe = 0.71–0.78) have a more restricted range of cr# ratios of 0.72–0.75. The low Fe3+/ΣFe chromitites have very variable Fe3+/ΣFe ratios. They are thought to have crystallized from melts that have interacted with depleted mantle and thereby acquired their variable Fe3+/ΣFe ratio. The high Fe3+/ΣFe chromitites are restricted to one small area of the mantle and their high oxidation state is thought to be post magmatic. They are either the product of later heating, related to melt flux or interaction with a later oxidising melt. A difference in oxygen fugacity between the MORB-depleted harzburgite host, which is at the quartz–fayalite–magnetite (QFM) buffer and the later chromite-bearing melts (QFM + 2) implies that there is a real difference in the oxidation state of the MORB and arc-magma sources.
Susceptibility to scrapie and disease phenotype in sheep: cross-PRNP genotype experimental transmissions with natural sources
Authors: González Lorenzo , Jeffrey Martin , Dagleish Mark P , Goldmann Wilfred , Sisó Sílvia , Eaton Samantha L , Martin Stuart , Finlayson Jeanie , Stewart Paula , Steele Philip , Pang Yvonne , Hamilton Scott , Reid Hugh W , Chianini Francesca
Published: July 2012

It has long been established that the sheep Prnp genotype influences the susceptibility to scrapie, and some studies suggest that it can also determine several aspects of the disease phenotype. Other studies, however, indicate that the source of infection may also play a role in such phenotype. To address this question an experiment was set up in which either of two different natural scrapie sources, AAS from AA136 Suffolk and VVC from VV136 Cheviot sheep, were inoculated into AA136, VA136 and VV136 sheep recipients (n = 52). The immunohistochemical (IHC) profile of disease-associated PrP (PrPd) accumulation in the brain of recipient sheep was highly consistent upon codon 136 homologous and semi-homologous transmission, but could be either similar to or different from those of the inoculum donors. In contrast, the IHC profiles were highly variable upon heterologous transmission (VVC to AA136 and AAS to VV136). Furthermore, sheep of the same Prnp genotype could exhibit different survival times and PrPd profiles depending on the source of infection, and a correlation was observed between IHC and Western blot profiles. It was found that additional polymorphisms at codons 112 or 141 of AA136 recipients resulted in a delayed appearance of clinical disease or even in protection from infection. The results of this study strongly suggest that the scrapie phenotype in sheep results from a complex interaction between source, donor and recipient factors, and that the Prnp genotype of the recipient sheep does not explain the variability observed upon codon 136 heterologous transmissions, arguing for other genetic factors to be involved.
Protein genes in repetitive sequence—antifreeze glycoproteins in Atlantic cod genome
Authors: Zhuang Xuan , Yang Chun , Fevolden Svein-Erik , Cheng C-H Christina
Published: July 2012

Background

Highly repetitive sequences are the bane of genome sequence assembly, and the short read lengths produced by current next generation sequencing technologies further exacerbates this obstacle. An adopted practice is to exclude repetitive sequences in genome data assembly, as the majority of repeats lack protein-coding genes. However, this could result in the exclusion of important genotypes in newly sequenced non-model species. The absence of the antifreeze glycoproteins (AFGP) gene family in the recently sequenced Atlantic cod genome serves as an example.

Results

The Atlantic cod (Gadus morhua) genome was assembled entirely from Roche 454 short reads, demonstrating the feasibility of this approach. However, a well-known major adaptive trait, the AFGP, essential for survival in frigid Arctic marine habitats was absent in the annotated genome. To assess whether this resulted from population difference, we performed Southern blot analysis of genomic DNA from multiple individuals from the North East Arctic cod population that the sequenced cod belonged, and verified that the AFGP genotype is indeed present. We searched the raw assemblies of the Atlantic cod using our G. morhua AFGP gene, and located partial AFGP coding sequences in two sequence scaffolds. We found these two scaffolds constitute a partial genomic AFGP locus through comparative sequence analyses with our newly assembled genomic AFGP locus of the related polar cod, Boreogadus saida. By examining the sequence assembly and annotation methodologies used for the Atlantic cod genome, we deduced the primary cause of the absence of the AFGP gene family from the annotated genome was the removal of all repetitive Roche 454 short reads before sequence assembly, which would exclude most of the highly repetitive AFGP coding sequences. Secondarily, the model teleost genomes used in projection annotation of the Atlantic cod genome have no antifreeze trait, perpetuating the unawareness that the AFGP gene family is missing.

Conclusions

We recovered some of the missing AFGP coding sequences and reconstructed a partial AFGP locus in the Atlantic cod genome, bringing to light that not all repetitive sequences lack protein coding information. Also, reliance on genomes of model organisms as reference for annotating protein-coding gene content of a newly sequenced non-model species could lead to omission of novel genetic traits.
Evolutionary analysis of the ENTH/ANTH/VHS protein superfamily reveals a coevolution between membrane trafficking and metabolism
Authors: De Craene Johan-Owen , Ripp Raymond , Lecompte Odile , Thompson Julie D , Poch Olivier , Friant Sylvie
Published: July 2012

Background

Membrane trafficking involves the complex regulation of proteins and lipids intracellular localization and is required for metabolic uptake, cell growth and development. Different trafficking pathways passing through the endosomes are coordinated by the ENTH/ANTH/VHS adaptor protein superfamily. The endosomes are crucial for eukaryotes since the acquisition of the endomembrane system was a central process in eukaryogenesis.

Results

Our in silico analysis of this ENTH/ANTH/VHS superfamily, consisting of proteins gathered from 84 complete genomes representative of the different eukaryotic taxa, revealed that genomic distribution of this superfamily allows to discriminate Fungi and Metazoa from Plantae and Protists. Next, in a four way genome wide comparison, we showed that this discriminative feature is observed not only for other membrane trafficking effectors, but also for proteins involved in metabolism and in cytokinesis, suggesting that metabolism, cytokinesis and intracellular trafficking pathways co-evolved. Moreover, some of the proteins identified were implicated in multiple functions, in either trafficking and metabolism or trafficking and cytokinesis, suggesting that membrane trafficking is central to this co-evolution process.

Conclusions

Our study suggests that membrane trafficking and compartmentalization were not only key features for the emergence of eukaryotic cells but also drove the separation of the eukaryotes in the different taxa.
An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA)
Authors: Liang C Jason , Budoff Matthew J , Kaufman Joel D , Kronmal Richard A , Brown Elizabeth R
Published: July 2012

Background

Extent of atherosclerosis measured by amount of coronary artery calcium (CAC) in computed tomography (CT) has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS). These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS) for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods

Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor.

Results

Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26) and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179). Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224). The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected.

Conclusions

The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.
Epidemiologic trends in chronic renal replacement therapy over forty years: A Swiss dialysis experience
Authors: Lehmann Petra Rhyn , Ambühl Manon , Corleto Domenica , Klaghofer Richard , Ambühl Patrice M
Published: July 2012

Background

Long term longitudinal data are scarce on epidemiological characteristics and patient outcomes in patients on maintenance dialysis, especially in Switzerland. We examined changes in epidemiology of patients undergoing renal replacement therapy by either hemodialysis or peritoneal dialysis over four decades.

Methods

Single center retrospective study including all patients which initiated dialysis treatment for ESRD between 1970 and 2008. Analyses were performed for subgroups according to dialysis vintage, based on stratification into quartiles of date of first treatment. A multivariate model predicting death and survival time, using time-dependent Cox regression, was developed.

Results

964 patients were investigated. Incident mean age progressively increased from 48 ± 14 to 64 ± 15 years from 1stto 4thquartile (p < 0.001), with a concomitant decrease in 3- and 5-year survival from 72.2 to 67.7%, and 64.1 to 54.8%, respectively. Nevertheless, live span continuously increased from 57 ± 13 to 74 ± 11 years (p < 0.001). Patients transplanted at least once were significantly younger at dialysis initiation, with significantly better survival, however, shortened live span vs. individuals remaining on dialysis. Among age at time of initiating dialysis therapy, sex, dialysis modality and transplant status, only transplant status is a significant independent covariate predicting death (HR: 0.10 for transplanted vs. non-transplanted patients, p = 0.001). Dialysis vintage was associated with better survival during the second vs. the first quartile (p = 0.026).

Discussion

We document an increase of a predominantly elderly incident and prevalent dialysis population, with progressively shortened survival after initiation of renal replacement over four decades, and, nevertheless, a prolonged lifespan. Analysis of the data is limited by lack of information on comorbidity in the study population.

Conclusions

Survival in patients on renal replacement therapy seems to be affected not only by medical and technical advances in dialysis therapy, but may mostly reflect progressively lower mortality of individuals with cardiovascular and metabolic complications, as well as a policy of accepting older and polymorbid patients for dialysis in more recent times. This is relevant to make demographic predictions in face of the ESRD epidemic nephrologists and policy makers are facing in industrialized countries.
Perinatal stress, brain inflammation and risk of autism-Review and proposal
Authors: Angelidou Asimenia , Asadi Shahrzad , Alysandratos Konstantinos-Dionysios , Karagkouni Anna , Kourembanas Stella , Theoharides Theoharis C
Published: July 2012

Background

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by varying deficits in social interactions, communication, and learning, as well as stereotypic behaviors. Despite the significant increase in ASD, there are few if any clues for its pathogenesis, hampering early detection or treatment. Premature babies are also more vulnerable to infections and inflammation leading to neurodevelopmental problems and higher risk of developing ASD. Many autism “susceptibility” genes have been identified, but “environmental” factors appear to play a significant role. Increasing evidence suggests that there are different ASD endophenotypes.

Discussion

We review relevant literature suggestingin uteroinflammation can lead to preterm labor, while insufficient development of the gut-blood–brain barriers could permit exposure to potential neurotoxins. This risk apparently may increase in parents with “allergic” or autoimmune problems during gestation, or if they had been exposed to stressors. The presence of circulating auto-antibodies against fetal brain proteins in mothers is associated with higher risk of autism and suggests disruption of the blood–brain-barrier (BBB). A number of papers have reported increased brain expression or cerebrospinal fluid (CSF) levels of pro-inflammatory cytokines, especially TNF, which is preformed in mast cells. Recent evidence also indicates increased serum levels of the pro-inflammatory mast cell trigger neurotensin (NT), and of extracellular mitochondrial DNA (mtDNA), which is immunogenic. Gene mutations of phosphatase and tensin homolog (PTEN), the negative regulator of the mammalian target of rapamycin (mTOR), have been linked to higher risk of autism, but also to increased proliferation and function of mast cells.

Premature birth and susceptibility genes may make infants more vulnerable to allergic, environmental, infectious, or stress-related triggers that could stimulate mast cell release of pro-inflammatory and neurotoxic molecules, thus contributing to brain inflammation and ASD pathogenesis, at least in an endophenotype of ASD patients.
Thrombolytic effects of Douchi Fibrinolytic enzyme from Bacillus subtilis LD-8547 in vitro and in vivo
Authors: Yuan Jun , Yang Jing , Zhuang Zhenhong , Yang Yanling , Lin Ling , Wang Shihua
Published: July 2012

Background

Today, thrombosis is one of the most widely occurring diseases in modern life. Drugs with thrombolytic functions are the most effective methods in the treatment of thrombosis. Among them, Douchi fibrinolytic enzyme (DFE) is a promising agent. DFE was isolated from Douchi, a typical and popular soybean-fermented food in China, and it can dissolve fibrin directly and efficiently. A strain, Bacillus subtilis LD-8547 produced DFE with high fibrinolytic activity has been isolated in our lab previously.

Results

In the study, thrombolytic effect of DFE from Bacillus subtilis LD-8547 was studied in vitro and in vivo systematically. The results showed that DFE played a significant role in thrombolysis and anticoagulation in vitro. And the thrombolytic effects correlated with DFE in a dose-dependent manner. In vivo, the acute toxicity assay showed that DFE had no obvious acute toxicity to mice. Test of carrageenan-induced thrombosis in mice indicated that the DFE significantly prevented tail thrombosis, and arterial thrombosis model test indicated that Douchi fibrinolytic enzyme DFE had thrombolytic effect on carotid thrombosis of rabbits in vivo. Other results in vivo indicated that DFE could increase bleeding and clotting time obviously.

Conclusions

The DFE isolated from Bacillus subtilis LD-8547 has obvious thrombolytic effects in vitro and in vivo. This function demonstrates that this enzyme can be a useful tool for preventing and treating clinical thrombus.
Structural characterization of S100A15 reveals a novel zinc coordination site among S100 proteins and altered surface chemistry with functional implications for receptor binding
Authors: Murray Jill I , Tonkin Michelle L , Whiting Amanda L , Peng Fangni , Farnell Benjamin , Cullen Jay T , Hof Fraser , Boulanger Martin J
Published: July 2012

Background

S100 proteins are a family of small, EF-hand containing calcium-binding signaling proteins that are implicated in many cancers. While the majority of human S100 proteins share 25-65% sequence similarity, S100A7 and its recently identified paralog, S100A15, display 93% sequence identity. Intriguingly, however, S100A7 and S100A15 serve distinct roles in inflammatory skin disease; S100A7 signals through the receptor for advanced glycation products (RAGE) in a zinc-dependent manner, while S100A15 signals through a yet unidentified G-protein coupled receptor in a zinc-independent manner. Of the seven divergent residues that differentiate S100A7 and S100A15, four cluster in a zinc-binding region and the remaining three localize to a predicted receptor-binding surface.

Results

To investigate the structural and functional consequences of these divergent clusters, we report the X-ray crystal structures of S100A15 and S100A7D24G, a hybrid variant where the zinc ligand Asp24 of S100A7 has been substituted with the glycine of S100A15, to 1.7 Å and 1.6 Å resolution, respectively. Remarkably, despite replacement of the Asp ligand, zinc binding is retained at the S100A15 dimer interface with distorted tetrahedral geometry and a chloride ion serving as an exogenous fourth ligand. Zinc binding was confirmed using anomalous difference maps and solution binding studies that revealed similar affinities of zinc for S100A15 and S100A7. Additionally, the predicted receptor-binding surface on S100A7 is substantially more basic in S100A15 without incurring structural rearrangement.

Conclusions

Here we demonstrate that S100A15 retains the ability to coordinate zinc through incorporation of an exogenous ligand resulting in a unique zinc-binding site among S100 proteins. The altered surface chemistry between S100A7 and S100A15 that localizes to the predicted receptor binding site is likely responsible for the differential recognition of distinct protein targets. Collectively, these data provide novel insight into the structural and functional consequences of the divergent surfaces between S100A7 and S100A15 that may be exploited for targeted therapies.
Translation and validation of the vertigo symptom scale into German: A cultural adaption to a wider German-speaking population
Authors: Gloor-Juzi Thomas , Kurre Annette , Straumann Dominik , de Bruin Eling D
Published: July 2012

Background

Dizziness and comorbid anxiety may cause severe disability of patients with vestibulopathy, but can be addressed effectively with rehabilitation. For an individually adapted treatment, a structured assessment is needed. The Vertigo Symptom Scale (VSS) with two subscales assessing vertigo symptoms (VSS-VER) and associated symptoms (VSS-AA) might be used for this purpose. As there was no validated VSS available in German, the aim of the study was the translation and cross-cultural adaptation in German (VSS-G) and the investigation of its reliability, internal and external validity.

Methods

The VSS was translated into German according to recognized guidelines. Psychometric properties were tested on 52 healthy controls and 202 participants with vestibulopathy. Internal validity and reliability were investigated with factor analysis, Cronbach’s α and ICC estimations. Discriminant validity was analysed with the Mann–Whitney-U-Test between patients and controls and the ROC-Curve. Convergent validity was estimated with the correlation with the Hospital Anxiety Subscale (HADS-A), Dizziness Handicap Inventory (DHI) and frequency of dizziness.

Results

Internal validity: factor analysis confirmed the structure of two subscales. Reliability: VSS-G: α = 0.904 and ICC (CI) =0.926 (0.826, 0.965). Discriminant validity: VSS-VER differentiate patients and controls ROC (CI) =0.99 (0.98, 1.00). Convergent validity: VSS-G correlates with DHI (r = 0.554) and frequency (T = 0.317). HADS-A correlates with VSS-AA (r = 0.452) but not with VSS-VER (r = 0.186).

Conclusions

The VSS-G showed satisfactory psychometric properties to assess the severity of vertigo or vertigo-related symptoms. The VSS-VER can differentiate between healthy subjects and patients with vestibular disorders. The VSS-AA showed some screening properties with high sensitivity for patients with abnormal anxiety.
A national study of chaplaincy services and end-of-life outcomes
Authors: Flannelly Kevin J , Emanuel Linda L , Handzo George F , Galek Kathleen , Silton Nava R , Carlson Melissa
Published: July 2012

Background

Medicine has long acknowledged the role of chaplains in healthcare, but there is little research on the relationship between chaplaincy care and health outcomes. The present study examines the association between chaplaincy services and end-of-life care service choices.

Methods

HealthCare Chaplaincy purchased the AHA survey database from the American Hospital Association. The Dartmouth Atlas of Health Care database was provided to HealthCare Chaplaincy by The Dartmouth Institute for Health Policy & Clinical Practice, with the permission of Dartmouth Atlas Co-Principal Investigator Elliot S. Fisher, M.D., M.P.H. The Dartmouth Atlas of Health Care is available interactively on-line athttp://www.dartmouthatlas.org/. Patient data are aggregated at the hospital level in the Dartmouth Atlas of Health Care. IRB approval was not sought for the project because the data are available to the public through one means or another, and neither database contains data about individual patients, i.e. all the variables are measures of hospital characteristics. We combined and analyzed data from the American Hospital Association’s Annual Survey and outcome data from The Dartmouth Atlas of Health Care in a cross-sectional study of 3,585 hospitals. Two outcomes were examined: the percent of patients who (1) died in the hospital, and (2) were enrolled in hospice. Ordinary least squares regression was used to measure the association between the provision of chaplaincy services and each of the outcomes, controlling for six factors associated with hospital death rates.

Results and discussion

The analyses found significantly lower rates of hospital deaths (β = .04,p < .05) and higher rates of hospice enrollment (β = .06,p < .001) for patients cared for in hospitals that provided chaplaincy services compared to hospitals that did not.

Conclusions

The findings suggest that chaplaincy services may play a role in increasing hospice enrollment. This may be attributable to chaplains’ assistance to patients and families in making decisions about care at the end-of-life, perhaps by aligning their values and wishes with actual treatment plans. Additional research is warranted.
Improving treatment intensification to reduce cardiovascular disease risk: a cluster randomized trial
Authors: Selby Joe V , Schmittdiel Julie A , Fireman Bruce , Jaffe Marc , Ransom Laura J , Dyer Wendy , Uratsu Connie S , Reed Mary E , Kerr Eve A , Hsu John
Published: July 2012

Background

Blood pressure, lipid, and glycemic control are essential for reducing cardiovascular disease (CVD) risk. Many health care systems have successfully shifted aspects of chronic disease management, including population-based outreach programs designed to address CVD risk factor control, to non-physicians. The purpose of this study is to evaluate provision of new information to non-physician outreach teams on need for treatment intensification in patients with increased CVD risk.

Methods

Cluster randomized trial (July 1-December 31, 2008) in Kaiser Permanente Northern California registry of members with diabetes mellitus, prior CVD diagnoses and/or chronic kidney disease who were high-priority for treatment intensification: blood pressure ≥ 140 mmHg systolic, LDL-cholesterol ≥ 130 mg/dl, or hemoglobin A1c ≥ 9%; adherent to current medications; no recent treatment intensification). Randomization units were medical center-based outreach teams (4 intervention; 4 control). For intervention teams, priority flags for intensification were added monthly to the registry database with recommended next pharmacotherapeutic steps for each eligible patient. Control teams used the same database without this information. Outcomes included 3-month rates of treatment intensification and risk factor levels during follow-up.

Results

Baseline risk factor control rates were high (82-90%). In eligible patients, the intervention was associated with significantly greater 3-month intensification rates for blood pressure (34.1 vs. 30.6%) and LDL-cholesterol (28.0 vs 22.7%), but not A1c. No effects on risk factors were observed at 3 months or 12 months follow-up. Intervention teams initiated outreach for only 45-47% of high-priority patients, but also for 27-30% of lower-priority patients. Teams reported difficulties adapting prior outreach strategies to incorporate the new information.

Conclusions

Information enhancement did not improve risk factor control compared to existing outreach strategies at control centers. Familiarity with prior, relatively successful strategies likely reduced uptake of the innovation and its potential for success at intervention centers.

Trial registration

ClinicalTrials.gov Identifier NCT00517686
PGM2 overexpression improves anaerobic galactose fermentation in Saccharomyces cerevisiae
Authors: Garcia Sanchez Rosa , Hahn-Hägerdal Bärbel , Gorwa-Grauslund Marie F
Published: July 2012

Background

In Saccharomyces cerevisiae galactose is initially metabolized through the Leloir pathway after which glucose 6-phosphate enters glycolysis. Galactose is controlled both by glucose repression and by galactose induction. The gene PGM2 encodes the last enzyme of the Leloir pathway, phosphoglucomutase 2 (Pgm2p), which catalyses the reversible conversion of glucose 1-phosphate to glucose 6-phosphate. Overexpression of PGM2 has previously been shown to enhance aerobic growth of S. cerevisiae in galactose medium.

Results

In the present study we show that overexpression of PGM2 under control of the HXT7' promoter from an integrative plasmid increased the PGM activity 5 to 6 times, which significantly reduced the lag phase of glucose-pregrown cells in an anaerobic galactose culture. PGM2 overexpression also increased the anaerobic specific growth rate whereas ethanol production was less influenced. When PGM2 was overexpressed from a multicopy plasmid instead, the PGM activity increased almost 32 times. However, this increase of PGM activity did not further improve aerobic galactose fermentation as compared to the strain carrying PGM2 on the integrative plasmid.

Conclusion

PGM2 overexpression in S. cerevisiae from an integrative plasmid is sufficient to reduce the lag phase and to enhance the growth rate in anaerobic galactose fermentation, which results in an overall decrease in fermentation duration. This observation is of particular importance for the future development of stable industrial strains with enhanced PGM activity.
Silencing of a large microRNA cluster on human chromosome 14q32 in melanoma: biological effects of mir-376a and mir-376c on insulin growth factor 1 receptor
Authors: Zehavi Liron , Avraham Roi , Barzilai Aviv , Bar-Ilan Dalia , Navon Roy , Sidi Yechezkel , Avni Dror , Leibowitz-Amit Raya
Published: July 2012

Background

Metastatic melanoma is a devastating disease with limited therapeutic options. MicroRNAs (miRNAs) are small non coding RNA molecules with important roles in post-transcriptional gene expression regulation, whose aberrant expression has been implicated in cancer.

Results

We show that the expression of miRNAs from a large cluster on human chromosome 14q32 is significantly down-regulated in melanoma cell lines, benign nevi and melanoma samples relative to normal melanocytes. This miRNA cluster resides within a parentally imprinted chromosomal region known to be important in development and differentiation. In some melanoma cell lines, a chromosomal deletion or loss-of-heterozygosity was observed in the cis-acting regulatory region of this cluster. In several cell lines we were able to re-express two maternally-induced genes and several miRNAs from the cluster with a combination of de-methylating agents and histone de-acetylase inhibitors, suggesting that epigenetic modifications take part in their silencing. Stable over-expression of mir-376a and mir-376c, two miRNAs from this cluster that could be re-expressed following epigenetic manipulation, led to modest growth retardation and to a significant decrease in migration in-vitro. Bioinformatic analysis predicted that both miRNAs could potentially target the 3'UTR of IGF1R. Indeed, stable expression of mir-376a and mir-376c in melanoma cells led to a decrease in IGF1R mRNA and protein, and a luciferase reporter assay indicated that the 3'UTR of IGF1R is a target of both mir-376a and mir-376c.

Conclusions

Our work is the first to show that the large miRNA cluster on chromosome 14q32 is silenced in melanoma. Our results suggest that down-regulation of mir-376a and mir-376c may contribute to IGF1R over-expression and to aberrant negative regulation of this signaling pathway in melanoma, thus promoting tumorigenesis and metastasis.
ROS accumulation and IGF-IR inhibition contribute to fenofibrate/PPARα -mediated inhibition of Glioma cell motility in vitro
Authors: Drukala Justyna , Urbanska Katarzyna , Wilk Anna , Grabacka Maja , Wybieralska Ewa , Del Valle Luis , Madeja Zbigniew , Reiss Krzysztof
Published: July 2012

Background

Glioblastomas are characterized by rapid cell growth, aggressive CNS infiltration, and are resistant to all known anticancer regimens. Recent studies indicate that fibrates and statins possess anticancer potential. Fenofibrate is a potent agonist of peroxisome proliferator activated receptor alpha (PPARα) that can switch energy metabolism from glycolysis to fatty acid β-oxidation, and has low systemic toxicity. Fenofibrate also attenuates IGF-I-mediated cellular responses, which could be relevant in the process of glioblastoma cell dispersal.

Methods

The effects of fenofibrate on Glioma cell motility, IGF-I receptor (IGF-IR) signaling, PPARα activity, reactive oxygen species (ROS) metabolism, mitochondrial potential, and ATP production were analyzed in human glioma cell lines.

Results

Fenofibrate treatment attenuated IGF-I signaling responses and repressed cell motility of LN-229 and T98G Glioma cell lines. In the absence of fenofibrate, specific inhibition of the IGF-IR had only modest effects on Glioma cell motility. Further experiments revealed that PPARα-dependent accumulation of ROS is a strong contributing factor in Glioma cell lines responses to fenofibrate. The ROS scavenger, N-acetyl-cysteine (NAC), restored cell motility, improved mitochondrial potential, and increased ATP levels in fenofibrate treated Glioma cell lines.

Conclusions

Our results indicate that although fenofibrate-mediated inhibition of the IGF-IR may not be sufficient in counteracting Glioma cell dispersal, PPARα-dependent metabolic switch and the resulting ROS accumulation strongly contribute to the inhibition of these devastating brain tumor cells.
Oxidized low density lipoprotein, stem cells, and atherosclerosis
Authors: Yang Hui , Mohamed Ahmed Salah Salem , Zhou Sheng-hua
Published: July 2012

Oxidized low density lipoprotein (ox-LDL), a risk factor of atherosclerosis, facilitates the formation and vulnerability of atherosclerotic plaque, thus contributing to several clinical complications. Stem cells participate in vascular repair after damage and atherosclerosis is a process of inflammation accompanied with vascular injury. Researchers have proposed that stem cells participate in the formation of atherosclerotic plaque. Also, because ox-LDL is capable of inducing toxic effects on stem cells, it is reasonable to postulate that ox-LDL promotes the progress of atherosclerosis via acting on stem cells. In the present article, we review the relationship between ox-LDL, stem cells, and atherosclerosis and a portion of the associated mechanisms.