Dietary recommendations for the prevention of depression.
Major depressive disorder is a common, chronic condition that imposes a substantial burden of disability globally. As current treatments are estimated to address only one-third of the disease burden of depressive disorders, there is a need for new approaches to prevent depression or to delay its progression. While in its early stages, converging evidence from laboratory, population research, and clinical trials now suggests that dietary patterns and specific dietary factors may influence the risk for depression. However, largely as a result of the recency of the nutritional psychiatry field, there are currently no dietary recommendations for depression. The aim of this paper is to provide a set of practical dietary recommendations for the prevention of depression, based on the best available current evidence, in order to inform public health and clinical recommendations. Five key dietary recommendations for the prevention of depression emerged from current published evidence. These comprise: (1) follow 'traditional' dietary patterns, such as the Mediterranean, Norwegian, or Japanese diet; (2) increase consumption of fruits, vegetables, legumes, wholegrain cereals, nuts, and seeds; (3) include a high consumption of foods rich in omega-3 polyunsaturated fatty acids; (4) replace unhealthy foods with wholesome nutritious foods; (5) limit your intake of processed-foods, 'fast' foods, commercial bakery goods, and sweets. Although there are a number of gaps in the scientific literature to date, existing evidence suggests that a combination of healthful dietary practices may reduce the risk of developing depression. It is imperative to remain mindful of any protective effects that are likely to come from the cumulative and synergic effect of nutrients that comprise the whole-diet, rather than from the effects of individual nutrients or single foods. As the body of evidence grows from controlled intervention studies on dietary patterns and depression, these recommendations should be modified accordingly.


Nicotinic Acid Phosphoribosyltransferase Regulates Cancer Cell Metabolism, Susceptibility to NAMPT Inhibitors, and DNA Repair.
In the last decade, substantial efforts have been made to identify NAD+ biosynthesis inhibitors, specifically against nicotinamide phosphoribosyltransferase (NAMPT), as preclinical studies indicate their potential efficacy as cancer drugs. However, the clinical activity of NAMPT inhibitors has proven limited, suggesting that alternative NAD+ production routes exploited by tumors confer resistance. Here, we show the gene encoding nicotinic acid phosphoribosyltransferase (NAPRT), a second NAD+-producing enzyme, is amplified and overexpressed in a subset of common types of cancer, including ovarian cancer, where NAPRT expression correlates with a BRCAness gene expression signature. Both NAPRT and NAMPT increased intracellular NAD+ levels. NAPRT silencing reduced energy status, protein synthesis, and cell size in ovarian and pancreatic cancer cells. NAPRT silencing sensitized cells to NAMPT inhibitors both in vitro and in vivo; similar results were obtained with the NAPRT inhibitor 2-hydroxynicotinic acid. Reducing NAPRT levels in a BRCA2-deficient cancer cell line exacerbated DNA damage in response to chemotherapeutics. In conclusion, NAPRT-dependent NAD+ biosynthesis contributes to cell metabolism and to the DNA repair process in a subset of tumors. This knowledge could be used to increase the efficacy of NAMPT inhibitors and chemotherapy. Cancer Res; 77(14); 3857-69. ©2017 AACR.


Platelet-Rich Fibrin Facilitates One-Stage Cartilage Repair by Promoting Chondrocytes Viability, Migration, and Matrix Synthesis.
The main aim of this study is to develop a one-stage method to combine platelet-rich fibrin (PRF) and autologous cartilage autografts for porcine articular cartilage repair. The porcine chondrocytes were treated with different concentrations of PRF-conditioned media and were evaluated for their cell viability and extracellular glycosaminoglycan (GAG) synthesis during six day cultivation. The chemotactic effects of PRF on chondrocytes on undigested cartilage autografts were revealed in explant cultures. For the in vivo part, porcine chondral defects were created at the medial femoral condyles of which were (1) left untreated, (2) implanted with PRF combined with hand-diced cartilage grafts, or (3) implanted with PRF combined with device-diced cartilage grafts. After six months, gross grades, histological, and immunohistochemical analyses were compared. The results showed that PRF promotes the viability and GAG expression of the cultured chondrocytes. Additionally, the PRF-conditioned media induce significant cellular migration and outgrowth of chondrocytes from undigested cartilage grafts. In the in vivo study, gross grading and histological scores showed significantly better outcomes in the treatment groups as compared with controls. Moreover, both treatment groups showed significantly more type II collagen staining and minimal type I collagen staining as compared with controls, indicating more hyaline-like cartilage and less fibrous tissue. In conclusion, PRF enhances the viability, differentiation, and migration of chondrocytes, thus, showing an appealing capacity for cartilage repair. The data altogether provide evidences to confirm the feasibility of a one-stage, culture-free method of combining PRF and cartilage autografts for repairing articular cartilage defects. From translational standpoints, these advantages benefit clinical applications by simplifying and potentiating the efficacy of cartilage autograft transplants.


Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies.
Dietary carotenoids have been hypothesized to protect against epithelial cancers. The authors analyzed the associations between intakes of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and lycopene) and risk of colorectal cancer using the primary data from 11 cohort studies carried out in North America and Europe. Carotenoid intakes were estimated from food frequency questionnaires administered at baseline in each study. During 6-20 years of follow-up between 1980 and 2003, 7,885 incident cases of colorectal cancer were diagnosed among 702,647 participants. The authors calculated study-specific multivariate relative risks and then combined them using a random-effects model. In general, intakes of specific carotenoids were not associated with colorectal cancer risk. The pooled multivariate relative risks of colorectal cancer comparing the highest quintile of intake with the lowest ranged from 0.92 for lutein + zeaxanthin to 1.04 for lycopene; only for lutein + zeaxanthin intake was the result borderline statistically significant (95% confidence interval: 0.84, 1.00). The associations observed were generally similar across studies, for both sexes, and for colon cancer and rectal cancer. These pooled data did not suggest that carotenoids play an important role in the etiology of colorectal cancer.


Dose-dependent effect of cannabinoid WIN-55,212-2 on myelin repair following a demyelinating insult.
Dysfunctions in the endocannabinoid system have been associated with experimental animal models and multiple sclerosis patients. Interestingly, the endocannabinoid system has been reported to confer neuroprotection against demyelination. The present study aims to assess the effects of the cannabinoid agonist WIN-55,212-2 in cuprizone fed animals on myelin repair capacity. Animals exposed to cuprizone were simultaneously treated withWIN-55,212-2, behaviorally tested and finally the corpus callosum was exhaustively studied by Western blotting, qRT-PCR and a myelin staining procedure. We report that the long-term administration of WIN-55,212-2 reduced the global amount of CB1 protein. Histological analysis revealed clear demyelination after being fed cuprizone for three weeks. However, cuprizone-fed mice subjected to 0.5 mg/Kg of WIN-55,212-2 displayed no differences when compared to controls during demyelination, although there was a robust increase in the myelinated axons during the remyelination phase. These animals displayed better performance on contextual fear conditioning which was in turn non-attributable to an antinociceptive effect. In contrast, a 1 mg/Kg dosage caused a remarkable demyelination accompanied by limited potential for myelin repair. Upon drug administration while mice ongoing demyeliniation, the expression of Aif1 (microglia) and Gfap (astrocytes) followed a dose-dependent manner whereas the expression of both markers was apparently attenuated during remyelination. Treatment with vehicle or 0.5 mg/Kg of the drug during demyelination increased the expression of Pdgfra (oligodendrocyte precursor cells) but this did not occur when 1 mg/Kg was administered. In conclusion, the drug at 0.5 mg/Kg did not alter myelin architecture while 1 mg/Kg had a deleterious effect in this model.


Retrospective comparison of management of gastro-enteritis in hospitalised children.
In Hong Kong, bacterial pathogens, the majority of them Salmonellae, cause approximately one-third of paediatric admissions for diarrhoea. This study retrospectively reviewed inpatient gastro-enteritis management, with particular focus on antibiotic use. Antibiotics are generally recommended for Salmonella gastro-enteritis in infants under 3 months of age but not for older infants and children unless they are so toxic that bacteraemia is suspected. Three groups of children admitted with acute gastro-enteritis were randomly identified from a computerised discharge database. Based on pathological reports held in the case records department, the final groups for analysis were Salmonella (n = 86), rotavirus (n = 55) and non-specified (n = 126). Epi Info version 6 (CDC, Atlanta) was used for data entry and analysis. Compared with a combined rotavirus/non-specified group, the Salmonella group were significantly more likely to have blood (OR 6.1, 95% CI 3.2-11.7, p < 0.0001) and mucus (OR 4.8, 95% CI 2.6-8.9, p < 0.0001) in the stool, fever during admission (OR 3.6, 95% CI 1.6-8.4, p = 0.001), more stools per day (median 6.2 vs 4.2, p < 0.0001), a longer stay in hospital (median 3.4 vs 2 days, p < 0.0001) and to be younger (median 7.1 vs 14.6 mths, p < 0.0001). The Salmonella group were more likely to have been given antibiotics (38% vs 15%, OR 3.6, 95% CI 1.9-6.9, p < 0.0001) but age did not influence the likelihood that antibiotics would be given.


Conceptual framework and pilot study to benchmark phylogenomic databases based on reference gene trees.
Phylogenomic databases provide orthology predictions for species with fully sequenced genomes. Although the goal seems well-defined, the content of these databases differs greatly. Seven ortholog databases (Ensembl Compara, eggNOG, HOGENOM, InParanoid, OMA, OrthoDB, Panther) were compared on the basis of reference trees. For three well-conserved protein families, we observed a generally high specificity of orthology assignments for these databases. We show that differences in the completeness of predicted gene relationships and in the phylogenetic information are, for the great majority, not due to the methods used, but to differences in the underlying database concepts. According to our metrics, none of the databases provides a fully correct and comprehensive protein classification. Our results provide a framework for meaningful and systematic comparisons of phylogenomic databases. In the future, a sustainable set of 'Gold standard' phylogenetic trees could provide a robust method for phylogenomic databases to assess their current quality status, measure changes following new database releases and diagnose improvements subsequent to an upgrade of the analysis procedure.


Nanovolume kinase inhibition assay using a sol-gel-derived multicomponent microarray.
We report on the development of a new class of kinase microarrays based on the coimmobilization of both kinase and substrate components within a single pin-printed sol-gel microarray element and the use of such arrays for nanovolume inhibition assays. We successfully immobilized the alpha-catalytic subunit of cAMP-dependent protein kinase (PKA) and the peptide substrate kemptide within sol-gel-derived microarrays for the purpose of monitoring phosphorylation and inhibition. Using Pro-Q Diamond stain as an end-point indicator of phosphorylation, we demonstrate the selective detection of phosphoproteins over nonphosphorylated controls and the ability to detect phosphorylated proteins over a 500-fold concentration range. Limits of detection for the phosphoprotein beta-casein were 7.5 pg, and the detectable signal remained linear up to 3.75 ng of protein per array spot. PKA is demonstrated to be active when coentrapped with two different substrates, and inhibition assays for PKA with the inhibitors H7 and H89 demonstrate the ability to detect kinase inhibition as well as derive IC50 plots from a single array using an overprinting method to deliver approximately 0.6 nL of reagent per array element, or a total of 72 nL of reagents to generate a full, 12-point IC50 curve in pentuplicate.


Modeling of crossbred cattle growth, comparison between cubic and piecewise random regression models.
Two analyses, cubic and piecewise random regression, were conducted to model growth of crossbred cattle from birth to about two years of age, investigating the ability of a piecewise procedure to fit growth traits without the complications of the cubic model. During a four-year period (1994-1997) of the Australian "Southern Crossbreeding Project", mature Hereford cows (N = 581) were mated to 97 sires of Angus, Belgian Blue, Hereford, Jersey, Limousin, South Devon, and Wagyu breeds, resulting in 1141 steers and heifers born over four years. Data included 13 (for steers) and eight (for heifers) live body weight measurements, made approximately every 50 days from birth until slaughter. The mixed model included fixed effects of sex, sire breed, age (linear, quadratic and cubic), and their interactions between sex and sire breed with age. Random effects were sire, dam, management (birth location, year, post-weaning groups), and permanent environmental effects and for each of these when possible, their interactions with linear, quadratic and cubic growth. In both models, body weights of all breeds increased over pre-weaning period, held fairly steady (slightly flattening) over the dry season then increased again towards the end of the feedlot period. The number of estimated parameters for the cubic model was 22 while for the piecewise model it was 32. It was concluded that the piecewise model was very similar to the cubic model in the fit to the data; with the piecewise model being marginally better. The piecewise model seems to fit the data better at the end of the growth period.


Fat Intravasation from Intraosseous Flush and Infusion Procedures.
The primary study objective was to delineate the procedural aspects of intraosseous (IO) infusions responsible for fat intravasation by testing the hypothesis that the fat content of effluent blood increases during IO infusions. IO cannulas were inserted into the proximal tibiae of 35 anesthetized swine (Sus scrofa, 50.1 ± 3.5 kg) and intravasated fat was assessed using a lipophilic fluoroprobe (Nile red) and by vascular ultrasound imaging. Effluent blood bone marrow fat was assessed at baseline, during flush, and with regimens of controlled infusion pressures (73-300 mmHg) and infusion flow rates (0.3-3.0 mL per second). Fat intravasation was also assessed with IO infusions at different tibial cannulation sites and in the distal femur. In 7 animals, the lipid uptake of alveolar macrophages and lung tissue assessed for fat embolic burden using oil red O stain 24 hours post infusion. Additionally, bone marrow shear-strain was assessed radiographically with IO infusions. Fat intravasation was observed during all IO infusion regimens, with subclinical pulmonary fat emboli persisting 24 hours post infusion. It was noted that initial flush was a significant factor in fat intravasation, low levels of intravasation occurred with infusions ≤300 mmHg, fat intravasation and bone marrow shear-strain increased with IO infusion rates, and intravasation was influenced by cannula insertion site. Ultrasound findings suggest that echogenic particles consistent with fat emboli are carried in fast and slow venous blood flow fields. Echo reflective densities were observed to rise to the nondependent endovascular margins and coalesce in accordance with Stoke's law. In addition, ultrasound findings suggested that intravasated bone marrow fat was thrombogenic. Results suggest that in swine the intravasation of bone marrow fat is a common consequence of IO infusion procedures and that its magnitude is influenced by the site of cannulation and infusion forces. Although the efficacy and benefits of IO infusions for emergent care are well established, emergency care providers also should be cognizant that infusion procedures affect bone marrow fat intravasation.


Report of recombinant norovirus GII.g/GII.12 in Beijing, China.
Norovirus (NoV) has been recognized as the most important cause of nonbacterial acute gastroenteritis affecting all age group people in the world. Genetic recombination is a common occurance in RNA viruses and many recombinant NoV strains have been described since it was first reported in 1997. However, the knowledge of recombinant NoV in China is extremely limited. A total of 685 stool specimens were tested for NoV infection from the acute gastroenteritis patients who visited one general hospital in Beijing from April 2009 to November 2011. The virus recombination was identified by constructing phylogenetic trees of two genes, further SimPlot and the maximum chi-square analysis. The overall positive rate was 9.6% (66/685). GII.4 New Orleans 2009 and GII.4 2006b variants were the dominant genotype. Four GII.g/GII.12 and one GII.12/GII.3 recombinant strains were confirmed, and all derived from adult outpatients. The predictive recombination point occurred at the open reading frame (ORF)1/ORF2 overlap. The GII.g ORF1/GII.12ORF2 recombinant has been reported in several countries and it was the first report of this recombinant in China.


Genetic susceptibility to autoimmune thyroid disease: past, present, and future.
Autoimmune thyroid diseases (AITD), including Graves' disease and Hashimoto's thyroiditis, arise due to complex interactions between environmental and genetic factors. There are sound data coming from epidemiological, family, and twin studies demonstrating a strong genetic influence on the development of AITD. In this review we summarize the new findings on the genetic susceptibility to AITD focusing on emerging mechanisms of susceptibility. Candidate gene analysis, whole-genome linkage screening, genome-wide association studies, and whole-genome sequencing are the major technologies that have advanced this field, leading to the identification of at least seven genes whose variants have been associated with AITD. One of the major ones is the HLA-DR gene locus. Recently, it was shown that substitution of the neutral amino acids Ala or Gln with arginine at position beta 74 in the HLA-DR peptide-binding pocket is key to the etiology of both Graves' disease and Hashimoto's thyroiditis. Several other genes have also been shown to confer susceptibility to AITD. These can be classified into two groups: (i) immune regulatory genes (cytotoxic T lymphocyte-associated protein 4, CD40, protein tyrosine phosphatase-22, and CD25) and (ii) thyroid-specific genes (thyroglobulin and thyrotropin receptor genes). The influence of individual genes on the development of AITD when assessed in a population appears to be weaker than would be expected from the data showing strong genetic susceptibility to AITD. Two possible mechanisms explaining this discrepancy are gene-gene interactions and subset effects. Significant progress has been made in our understanding of the immunogenetic mechanisms leading to thyroid autoimmunity. For the first time we are beginning to unravel these mechanisms at the molecular level. It is hoped that these new data will be translated into novel therapies and prevention strategies in AITD, such as costimulatory blockade.


Robust adaptive phase-shifting demodulation for testing moving wavefronts.
Optical interferometers are very sensitive when environment perturbations affect its optical path. The wavefront under test is not static at all. In this paper, it is proposed a novel and robust phase-shifting demodulation method. This method estimates the interferogram's phase-shifting locally, reducing detuning errors due to environment perturbations like vibrations and/or miscalibrations of the Phase-Shifting Interferometry setup. As we know, phase-shifting demodulation methods assume that the wavefront under test is static and there is a global phase-shifting for all pixels. The demodulation method presented here is based on local weighted least-squares, letting each pixel have its own phase-shifting. This is a different and better approach, considering that all previous works assume a global phase-shifting for all pixels of interferograms. Seeing this method like a black box, it receives an interferogram sequence of at least 3 interferograms and returns the modulating phase or wavefront under test. Here it is not necessary to know the phase shifts between the interferograms. It does not assume a global phase-shifting for the interferograms, is robust to the movements of the wavefront under test and tolerates miscalibrations of the optical setup.


A cell-penetrating ARF peptide inhibitor of FoxM1 in mouse hepatocellular carcinoma treatment.
The forkhead box m1 (Foxm1) transcription factor is essential for initiation of carcinogen-induced liver tumors; however, whether FoxM1 constitutes a therapeutic target for liver cancer treatment remains unknown. In this study, we used diethylnitrosamine/phenobarbital treatment to induce hepatocellular carcinomas (HCCs) in either WT mice or Arf(-/-)Rosa26-FoxM1b Tg mice, in which forkhead box M1b (FoxM1b) is overexpressed and alternative reading frame (ARF) inhibition of FoxM1 transcriptional activity is eliminated. To pharmacologically reduce FoxM1 activity in HCCs, we subjected these HCC-bearing mice to daily injections of a cell-penetrating ARF(26-44) peptide inhibitor of FoxM1 function. After 4 weeks of this treatment, HCC regions displayed reduced tumor cell proliferation and angiogenesis and a significant increase in apoptosis within the HCC region but not in the adjacent normal liver tissue. ARF peptide treatment also induced apoptosis of several distinct human hepatoma cell lines, which correlated with reduced protein levels of the mitotic regulatory genes encoding polo-like kinase 1, aurora B kinase, and survivin, all of which are transcriptional targets of FoxM1 that are highly expressed in cancer cells and function to prevent apoptosis. These studies indicate that ARF peptide treatment is an effective therapeutic approach to limit proliferation and induce apoptosis of liver cancer cells in vivo.


The incidence and risk factors of arrhythmias in the early period after cardiac surgery in pediatric patients.
Rhythm disturbances that develop after pediatric surgery for heart disease significantly increase mortality and morbidity risk. The aim of this study was to determine incidence rates of different arrhythmias and identify risk factors for these disturbances in this patient group. The study involved 580 children in the pediatric cardiovascular intensive care unit who had undergone cardiac surgery between May 2001 and December 2002. Each was followed until discharge. The patient who sustained arrhythmia was recorded. Fifty-one of the patients (8.8%, mean age 1.7+/-2.3 years) developed arrhythmias. Twenty-one (41.1%) had supraventricular tachycardia, 12 (23.5%) had junctional ectopic tachycardia, 10 (19.6%) had complete atrioventricular block, 3 (5.8%) had ventricular arrhythmias, and 5 (9.8%) had atrial fibrillation and atrioventricular dissociation. There was a trend toward higher incidence of arrhythmia (rate, 43.1%) in the 0-6 months age group. The incidence rates of arrhythmia after certain procedures were as follows: 75% after Rastelli operation, 16.7% after total anomalous pulmonary venous return repair, 13.8% after ventricular septal defect repair, 12.8% after the arterial switch operation or arterial switch with ventricular septal defect closure for transposition of the great arteries, 12.5% after atrioventricular septal defect repair, 12.1% after total correction of tetralogy of Fallot, 9.1% after bidirectional cava-pulmonary connection and Fontan procedure, and 6.6% after other miscellaneous procedures. The mean cardiopulmonary bypass time was 105.4+/-54.1 min. At the time of arrhythmia appearance, the mean values for electrolyte (sodium 144+/-5 mEq/L, potassium 3.78+/-0.91 mEq/L, ionized calcium 1.15+/-0.33 mmol/L) and arterial blood gas parameters (pH 7.40+/-0.12 and HCO3 24.7+/-6.3 mmol/L) were all in the normal range. Fifteen (29.4%) of the patients with arrhythmias died and in 7 of these cases, the death was directly linked to resistant arrhythmia. Arrhythmias can be life-threatening especially in the early period after pediatric heart surgery. The incidence of arrhythmia in this series was 8.8%. The results identified type of operation as a major risk factor for arrhythmia after pediatric heart surgery and they also suggest that age may be important as well.


Mutations in the human cytomegalovirus UL27 gene that confer resistance to maribavir.
Previous drug selection experiments resulted in the isolation of a human cytomegalovirus (CMV) UL97 phosphotransferase mutant resistant to the benzimidazole compound maribavir (1263W94), reflecting the anti-UL97 effect of this drug. Three other CMV strains were plaque purified during these experiments. These strains showed lower-grade resistance to maribavir than the UL97 mutant. Extensive DNA sequence analyses showed no changes from the baseline strain AD169 in UL97, the genes involved in DNA replication, and most structural proteins. However, changes were identified in UL27 where each strain contained a different mutation (R233S, W362R, or a combination of A406V and a stop at codon 415). The mutation at codon 415 is predicted to truncate the expressed UL27 protein by 193 codons (32% of UL27) with a loss of nuclear localization. The expression of full-length UL27 as a green fluorescent fusion protein in uninfected fibroblasts resulted in nuclear and nucleolar fluorescence, whereas cytoplasmic localization was observed when codons 1 to 415 were similarly expressed. Viable UL27 deletion mutants were created by recombination and showed slight growth attenuation and maribavir resistance in cell culture. Marker transfer experiments confirmed that UL27 mutations conferred maribavir resistance. The UL27 sequence was well conserved in a sample of 16 diverse clinical isolates. Mutation in UL27, a betaherpesvirus-specific early gene of unknown biological function, may adapt the virus for growth in the absence of UL97 activity.


Milk thistle: a future potential anti-osteoporotic and fracture healing agent.
Osteoporosis is a progressive disease of the skeleton characterised by bone fragility due to a reduction in bone mass and possibly to alteration in bone architecture that lead to a propensity to fracture with minimum trauma. Most osteoporotic fractures occur at locations rich in trabecular or cancellous bone and usually related to post menopausal women. Recently, silymarin received attention due to its alternative beneficial effect on bone formation. It is a mixture of flavonoids with powerful antioxidant properties. This review focuses on the use of milk thistle or silymarin for the treatment of osteoporosis that may be related to fracture bone. Silymarin shows potent antioxidant herb that may modulate multiple genes in favour of helping to build bone and prevent bone loss. In the mouse fracture healing model, silymarin supplementation improved tibial healing with elevated BMD and serum levels of ALP and osteocalcin. Silymarin also demonstrated clear estrogenic antiosteoporotic effects in bone structure. Silymarin appears to play a crucial role to prevent bone loss and might regulate osteogenesis and may be beneficial for fracture healing. If silymarin is considered for the use of post menopausal women, it may be used for the treatment of osteoporosis. It would be of great benefit to postmenopausal women to develop an oestrogen antagonist that is as potent and efficacious as oestrogen in preventing bone loss without the major side effect associated with HRT.


Duke Surgery Patient Safety: an open-source application for anonymous reporting of adverse and near-miss surgical events.
Studies have shown that 4% of hospitalized patients suffer from an adverse event caused by the medical treatment administered. Some institutions have created systems to encourage medical workers to report these adverse events. However, these systems often prove to be inadequate and/or ineffective for reviewing the data collected and improving the outcomes in patient safety. To describe the Web-application Duke Surgery Patient Safety, designed for the anonymous reporting of adverse and near-miss events as well as scheduled reporting to surgeons and hospital administration. SOFTWARE ARCHITECTURE: DSPS was developed primarily using Java language running on a Tomcat server and with MySQL database as its backend. Formal and field usability tests were used to aid in development of DSPS. Extensive experience with DSPS at our institution indicate that DSPS is easy to learn and use, has good speed, provides needed functionality, and is well received by both adverse-event reporters and administrators. This is the first description of an open-source application for reporting patient safety, which allows the distribution of the application to other institutions in addition for its ability to adapt to the needs of different departments. DSPS provides a mechanism for anonymous reporting of adverse events and helps to administer Patient Safety initiatives. The modifiable framework of DSPS allows adherence to evolving national data standards. The open-source design of DSPS permits surgical departments with existing reporting mechanisms to integrate them with DSPS. The DSPS application is distributed under the GNU General Public License.


Do females with patellofemoral pain have abnormal hip and knee kinematics during gait?
Our objective was to test the hypothesis that females with patellofemoral pain (PFP) have increased hip adduction, hip medial rotation, and knee valgus (medial collapse) during the stance phase of gait. Twenty subjects with PFP and 20 pain-free subjects participated. Subjects underwent three-dimensional motion analysis during free speed and fast speed walking. Hip frontal and transverse plane angles and knee frontal plane angles were calculated at two time points (peak knee extensor moment [PkMOM], and maximum knee extension/hyperextension angle [MxExt]) and averaged over three trials. Within each walking task, Student's t-tests compared group differences in all variables. A post hoc analysis was performed, which compared a subgroup of four PFP subjects (those whose pain level was above 30/100) to pain-free subjects. Initially, there were no group differences during free speed walking. During fast speed walking, subjects with PFP had less hip adduction at PkMOM and greater hip adduction at MxExt. The subgroup of PFP subjects had greater hip adduction at PkMOM and greater knee valgus at MxExt during free speed walking and greater hip adduction and knee valgus at MxExt during fast speed walking. During low-level tasks, frontal plane components of medial collapse were present at the hip and knee in a subgroup of PFP subjects with higher pain levels. Symptom behavior may be important in identifying individuals with medial collapse movement impairments.


The spatio-temporal spectrum of turbulent flows.
Identification and extraction of vortical structures and of waves in a disorganised flow is a mayor challenge in the study of turbulence. We present a study of the spatio-temporal behavior of turbulent flows in the presence of different restitutive forces. We show how to compute and analyse the spatio-temporal spectrum from data stemming from numerical simulations and from laboratory experiments. Four cases are considered: homogeneous and isotropic turbulence, rotating turbulence, stratified turbulence, and water wave turbulence. For homogeneous and isotropic turbulence, the spectrum allows identification of sweeping by the large-scale flow. For rotating and for stratified turbulence, the spectrum allows identification of the waves, precise quantification of the energy in the waves and in the turbulent eddies, and identification of physical mechanisms such as Doppler shift and wave absorption in critical layers. Finally, in water wave turbulence the spectrum shows a transition from gravity-capillary waves to bound waves as the amplitude of the forcing is increased.


Base excision repair in physiology and pathology of the central nervous system.
Relatively low levels of antioxidant enzymes and high oxygen metabolism result in formation of numerous oxidized DNA lesions in the tissues of the central nervous system. Accumulation of damage in the DNA, due to continuous genotoxic stress, has been linked to both aging and the development of various neurodegenerative disorders. Different DNA repair pathways have evolved to successfully act on damaged DNA and prevent genomic instability. The predominant and essential DNA repair pathway for the removal of small DNA base lesions is base excision repair (BER). In this review we will discuss the current knowledge on the involvement of BER proteins in the maintenance of genetic stability in different brain regions and how changes in the levels of these proteins contribute to aging and the onset of neurodegenerative disorders.


Clinical effect of point mutations in myelodysplastic syndromes.
Myelodysplastic syndromes are clinically heterogeneous disorders characterized by clonal hematopoiesis, impaired differentiation, peripheral-blood cytopenias, and a risk of progression to acute myeloid leukemia. Somatic mutations may influence the clinical phenotype but are not included in current prognostic scoring systems. We used a combination of genomic approaches, including next-generation sequencing and mass spectrometry-based genotyping, to identify mutations in samples of bone marrow aspirate from 439 patients with myelodysplastic syndromes. We then examined whether the mutation status for each gene was associated with clinical variables, including specific cytopenias, the proportion of blasts, and overall survival. We identified somatic mutations in 18 genes, including two, ETV6 and GNAS, that have not been reported to be mutated in patients with myelodysplastic syndromes. A total of 51% of all patients had at least one point mutation, including 52% of the patients with normal cytogenetics. Mutations in RUNX1, TP53, and NRAS were most strongly associated with severe thrombocytopenia (P<0.001 for all comparisons) and an increased proportion of bone marrow blasts (P<0.006 for all comparisons). In a multivariable Cox regression model, the presence of mutations in five genes retained independent prognostic significance: TP53 (hazard ratio for death from any cause, 2.48; 95% confidence interval [CI], 1.60 to 3.84), EZH2 (hazard ratio, 2.13; 95% CI, 1.36 to 3.33), ETV6 (hazard ratio, 2.04; 95% CI, 1.08 to 3.86), RUNX1 (hazard ratio, 1.47; 95% CI, 1.01 to 2.15), and ASXL1 (hazard ratio, 1.38; 95% CI, 1.00 to 1.89). Somatic point mutations are common in myelodysplastic syndromes and are associated with specific clinical features. Mutations in TP53, EZH2, ETV6, RUNX1, and ASXL1 are predictors of poor overall survival in patients with myelodysplastic syndromes, independently of established risk factors. (Funded by the National Institutes of Health and others.).


Anti-Cancer Potential of Homemade Fresh Garlic Extract Is Related to Increased Endoplasmic Reticulum Stress.
The use of garlic and garlic-based extracts has been linked to decreased incidence of cancer in epidemiological studies. Here we examine the molecular and cellular activities of a simple homemade ethanol-based garlic extract (GE). We show that GE inhibits growth of several different cancer cells in vitro, as well as cancer growth in vivo in a syngeneic orthotopic breast cancer model. Multiple myeloma cells were found to be especially sensitive to GE. The GE was fractionated using solid-phase extractions, and we identified allicin in one GE fraction; however, growth inhibitory activities were found in several additional fractions. These activities were lost during freeze or vacuum drying, suggesting that the main anti-cancer compounds in GE are volatile. The anti-cancer activity was stable for more than six months in −20 °C. We found that GE enhanced the activities of chemotherapeutics, as well as MAPK and PI3K inhibitors. Furthermore, GE affected hundreds of proteins involved in cellular signalling, including changes in vital cell signalling cascades regulating proliferation, apoptosis, and the cellular redox balance. Our data indicate that the reduced proliferation of the cancer cells treated by GE is at least partly mediated by increased endoplasmic reticulum (ER) stress.


Playing the computer game Tetris prior to viewing traumatic film material and subsequent intrusive memories: Examining proactive interference.
Visuospatial working memory (WM) tasks performed concurrently or after an experimental trauma (traumatic film viewing) have been shown to reduce subsequent intrusive memories (concurrent or retroactive interference, respectively). This effect is thought to arise because, during the time window of memory consolidation, the film memory is labile and vulnerable to interference by the WM task. However, it is not known whether tasks before an experimental trauma (i.e. proactive interference) would also be effective. Therefore, we tested if a visuospatial WM task given before a traumatic film reduced intrusions. Findings are relevant to the development of preventative strategies to reduce intrusive memories of trauma for groups who are routinely exposed to trauma (e.g. emergency services personnel) and for whom tasks prior to trauma exposure might be beneficial. Participants were randomly assigned to 1 of 2 conditions. In the Tetris condition (n = 28), participants engaged in the computer game for 11 min immediately before viewing a 12-min traumatic film, whereas those in the Control condition (n = 28) had no task during this period. Intrusive memory frequency was assessed using an intrusion diary over 1-week and an Intrusion Provocation Task at 1-week follow-up. Recognition memory for the film was also assessed at 1-week. Compared to the Control condition, participants in the Tetris condition did not report statistically significant difference in intrusive memories of the trauma film on either measure. There was also no statistically significant difference in recognition memory scores between conditions. The study used an experimental trauma paradigm and findings may not be generalizable to a clinical population. Compared to control, playing Tetris before viewing a trauma film did not lead to a statistically significant reduction in the frequency of later intrusive memories of the film. It is unlikely that proactive interference, at least with this task, effectively influences intrusive memory development. WM tasks administered during or after trauma stimuli, rather than proactively, may be a better focus for intrusive memory amelioration.


The effect of surgical glove powder on cleavage of two-cell mouse embryos in an in vitro fertilization programme.
The effect of surgical glove powder on the development of early mouse embryos was studied. Embryos from F1 hybrid mice (C57 B1/6 X CBA) were suspended in Whittingham's T6 growth medium with 10% human serum, using Petri dishes (Falcon 3001). Contamination was brought about by a sterile, powdered, surgical glove touching the surface of the growth medium for less than a second in group I, and in group II the same procedure was followed but the glove was rinsed beforehand with sterile, four times distilled water and air-dried. In the control group (group III) no contamination with surgical glove powder occurred. In group I only 9 of 137 embryos (7%) reached the blastocyst stage, in contrast with 110 of 196 (56%) in group II and 258 of 287 (90%) in group III. The differences in results between groups I and III, groups I and II, and groups II and III were found to be statistically significant (P less than 0,001) by the chi-square test. It is concluded that surgical gloves are a potent inhibitor of early embryonic growth. In an in vitro fertilization programme including follicle aspiration and embryo transfer, contamination of embryos with these gloves should be avoided at all costs.


Three modes of adaptive speciation in spatially structured populations.
Adaptive speciation with gene flow via the evolution of assortative mating has classically been studied in one of two different scenarios. First, speciation can occur if frequency-dependent competition in sympatry induces disruptive selection, leading to indirect selection for mating with similar phenotypes. Second, if a subpopulation is locally adapted to a specific environment, then there is indirect selection against hybridizing with maladapted immigrants. While both of these mechanisms have been modeled many times, the literature lacks models that allow direct comparisons between them. Here we incorporate both frequency-dependent competition and local adaptation into a single model and investigate whether and how they interact in driving speciation. We report two main results. First, we show that individually, the two mechanisms operate under separate conditions, hardly influencing each other when one of them alone is sufficient to drive speciation. Second, we also find that the two mechanisms can operate together, leading to a third speciation mode in which speciation is initiated by selection against maladapted migrants but completed by within-deme competition in a distinct second phase. While this third mode bears some similarity to classical reinforcement, it is considerably faster, and both newly formed species go on to coexist in sympatry.


Hypothalamic hamartomas associated with epilepsy: ultrastructural features.
Hypothalamic hamartomas (HHs) are associated with a catastrophic form of childhood epilepsy and are intrinsically epileptogenic for the gelastic seizures that are peculiar to this disorder. The cellular mechanisms of seizure generation within HH tissue are unknown. Hypothalamic hamartoma tissue consists of well-differentiated neurons interspersed with glial cells. Based on intrinsic electrophysiologic properties, we hypothesized that small and large HH neurons would have different ultrastructural features. Surgically resected HH tissue samples from 7 patients with refractory epilepsy were studied using electron microscopy. Models of neurons were made from reconstruction of serial sections. Nissl body density, polyribosome density, glycogen density, and the ratio of nuclear area to cytoplasmic area differed significantly between small and large neurons. Abundant small neurons were found in clusters and elaborated terminals that made symmetric, putatively inhibitory, synapses. Symmetric synapses were found predominantly on the soma and proximal dendrites of large projection-like neurons, whereas asymmetric, putatively excitatory, synapses were found primarily on distal dendrites. All samples showed unusual dendritic varicosities. The presence of these morphologically and functionally distinct neurons, the large number of nerve fibers in the neuropil, and the presence of inhibitory and excitatory synapses suggest that HH tissue has the necessary substrate to generate seizures.


Prasterone (DHEA) and mania.
To inform clinicians and investigators of the potential for severe mania in conjunction with the use of prasterone (DHEA; dehydroepiandrosterone). A 31-year-old Hispanic man was admitted on a 72-hour observation period from a neighboring hospital after threatening to kill himself, family members, and a friend. A loaded rifle was found under his bed. The family confirmed that he had begun using DHEA several weeks prior to his mood and behavioral changes. He denied any past violence, but had once been given an unsubstantiated diagnosis of bipolar disorder. He used alcohol episodically, and had difficulties controlling his anger while intoxicated. Although he improved with valproate, his threats of homicide led to involuntary commitment. Several studies and case reports strongly suggest that anabolic steroids can induce significant psychiatric difficulties, including mania, impaired cognition, and overt psychosis. Although the Food and Drug Administration noted in 1985 that the efficacy and safety of DHEA were never confirmed, the agent continues to be sold over the counter. Several groups have used DHEA in the treatment of AIDS, memory loss, and depression, but reported no serious adverse events; however, recent studies indicate that severe psychiatric symptoms can develop in a subset of users. Although uncertain, potential risk factors include high doses of DHEA; history of mood disorder; concurrent use of alcohol, street drugs, or antidepressants; and cytochrome P450 polymorphisms. The use of DHEA in those under age 35 years may be especially risky, as endogenous DHEA concentrations peak at age 20-30 years. Those using or investigating DHEA should be cognizant of the potential for severe psychiatric complications.


Expanding the chemical diversity of CK2 inhibitors.
None of the already described CK2 inhibitors did fulfill the requirements for successful clinical settings. In order to find innovative CK2 inhibitors based on new scaffolds, we have performed a high-throughput screening of diverse chemical libraries. We report here the identification and characterization of several classes of new inhibitors. Whereas some share characteristics of previously known CK2 inhibitors, others are chemically unrelated and may represent new opportunities for the development of better CK2 inhibitors. By combining structure-activity relationships with a docking procedure, we were able to determine the binding mode of these inhibitors. Interestingly, beside the identification of several nanomolar ATP-competitive inhibitors, one class of chemical inhibitors displays a non-ATP competitive mode of inhibition, a feature that suggests that CK2 possess distinct druggable binding sites. For the most promising inhibitors, selectivity profiling was performed. We also provide evidence that some chemical compounds are inhibiting CK2 in living cells. Finally, the collected data allowed us to draw the rules about the chemical requirements for CK2 inhibition both in vitro and in a cellular context.


Networks with controlled chirality via self-assembly of chiral triblock terpolymers.
Nanonetwork-structured materials can be found in nature and synthetic materials. A double gyroid (DG) with a pair of chiral networks but opposite chirality can be formed from the self-assembly of diblock copolymers. For triblock terpolymers, an alternating gyroid (GA) with two chiral networks from distinct end blocks can be formed; however, the network chirality could be positive or negative arbitrarily, giving an achiral phase. Here, by taking advantage of chirality transfer at different length scales, GA with controlled chirality can be achieved through the self-assembly of a chiral triblock terpolymer. With the homochiral evolution from monomer to multichain domain morphology through self-assembly, the triblock terpolymer composed of a chiral end block with a single-handed helical polymer chain gives the chiral network from the chiral end block having a particular handed network. Our real-space analyses reveal the preferred chiral sense of the network in the GA, leading to a chiral phase.


Information Seeking and Satisfaction with Information Sources Among Spouses of Men with Newly Diagnosed Local-Stage Prostate Cancer.
Information sources about prostate cancer treatment and outcomes are typically designed for patients. Little is known about the availability and utility of information for partners. The objectives of our study were to evaluate information sources used by partners to understand prostate cancer management options, their perceived usefulness, and the relationship between sources used and satisfaction with treatment experience. A longitudinal survey of female partners of men newly diagnosed with local-stage prostate cancer was conducted in three different geographic regions. Partners and associated patients were surveyed at baseline (after patient diagnosis but prior to receiving therapy) and at 12 months following diagnosis. Information sources included provider, literature, friends or family members, Internet websites, books, traditional media, and support groups. Utility of an information source was defined as whether the partner would recommend it to caregivers of other patients with local-stage prostate cancer. Our study cohort included 179 partner-patient pairs. At diagnosis, partners consulted an average of 4.6 information sources. Non-Hispanic white partners were more likely than others to use friends and family as an information source (OR = 2.44, 95% CI (1.04, 5.56)). More educated partners were less likely to use support groups (OR = 0.31, 95% CI (0.14, 0.71)). At 12-month follow-up, partners were less likely to recommend books (OR = 0.23, 95% CI (0.11, 0.49)) compared to baseline. Partners consulted a large number of information sources in researching treatment options for local-stage prostate cancer and the types of sources accessed varied by race/ethnicity and educational attainment. Additional resources to promote selection of high-quality non-provider information sources are warranted to enable partners to better aid patients in their treatment decision-making process.


Relationship between disease course in the temporomandibular joints and mandibular growth rotation in patients with juvenile idiopathic arthritis followed from childhood to adulthood.
To investigate the relationship between radiographic JIA disease course in the TMJs and mandibular growth rotation, compared with growth in healthy individuals. From a larger series of JIA patients followed from childhood to adulthood, 26 were included; 11 without and 15 with bilateral radiographic TMJ involvement. Joint morphology and function were assessed at baseline, 2-, 4-, 6- and 27 years follow-up. Mandibular growth rotation (anterior, posterior or none) was assessed from cephalometric evaluations at childhood and adulthood, with observations from 16 healthy individuals as controls. TMJ disease course and mandibular growth rotation were assessed independently and their relationship analysed. Non-parametric statistical methods were applied to test differences between groups. In the normal TMJ group of JIA patients the joint morphology was similar at the follow-ups and all patients had good function both in childhood and in adulthood. The mandibular growth rotation was similar to that of healthy controls, i.e. predominantly in anterior direction. In the abnormal TMJ group different JIA TMJ disease courses were observed and associated with changes in the mandibular growth rotation (p = 0.007).Progressing JIA TMJ disease course was related to posterior mandibular growth rotation and improving disease course to anterior mandibular growth rotation. A relationship was found between JIA disease course in the TMJs and mandibular growth rotation, suggesting that a favourable growth could be regained in patients with improvement in TMJ morphology and/or TMJ function. To confirm this, further research on larger patient series is needed.


Effect of cadmium and selenium on the antioxidant defense system in rat kidneys.
To examine effects of exogenous Cd on the kidney antioxidant defense system (AOS) and the possible protective role of Se against Cd toxicity, male Wistar albino rats (2 months old) were exposed during 30 days to oral intake of 200 ppm Cd (as CdCl2), 0.l ppm Se (as Na-selenite) or to the same doses of Cd / Se, simultaneously. Marked accumulation of Cd (23.44 +/- 0.69 micrograms/g w.m.) and marked alterations of AOS, resulting in kidney injury (renal pseudohypertrophy), were found in Cd-treated rats. Activities of total superoxide dismutase (SOC, EC 18.104.22.168), manganese-containing superoxide dismutase (MnSOD) and selenium-dependent glutathione peroxidase (Se GSH-Px, EG 22.214.171.124) were significantly reduced, whereas that of glutathione-S-transferase (CST, EC 188.8.131.52) and vitamin E (vit E) concentration were significantly increased in the kidneys of Cd-treated rats. Kidney catalase (CAT, EC 220.127.116.11) activity, ascorbic acid (AsA) and red blood cell glutathione (GSH, GSSG) levels were not markedly influenced by CD uptake. In kidneys of Se treated rats, the activities of total SOD, copper-zinc-containing superoxide dismutase (CuZnSOD) and GST were significantly increased Activities of kidney CAT and Se GSH-Px were largely unchanged, whereas significant increases of the kidney AsA and vit E concentrations occurred. In Cd + Se-cotreated rats, the kidney activities of MnSOD, CAT and Se GSH-Px, as well as vit E concentration, were the same as in controls, whereas CuZnSOD and GST activities and concentration of AsA exceeded normal values. These data indicate that Se only partially improves the AOS that is insufficient to prevent Cd-induced nephrotoxicity.


Solution structure of the sixth LDL-A module of the LDL receptor.
The low-density lipoprotein receptor (LDLR) is the primary mechanism for uptake of plasma cholesterol into cells and serves as a prototype for an entire class of cell surface receptors. The amino-terminal domain of the receptor consists of seven LDL-A modules; the third through the seventh modules all contribute to the binding of low-density lipoproteins (LDLs). Here, we present the NMR solution structure of the sixth LDL-A module (LR6) from the ligand binding domain of the LDLR. This module, which has little recognizable secondary structure, retains the essential structural features observed in the crystal structure of LDL-A module five (LR5) of the LDLR. Three disulfide bonds, a pair of buried residues forming a hydrophobic "mini-core", and a calcium-binding site that serves to organize the C-terminal lobe of the module all occupy positions in LR6 similar to those observed in LR5. The striking presence of a conserved patch of negative surface electrostatic potential among LDL-A modules of known structure suggests that ligand recognition by these repeats is likely to be mediated in part by electrostatic complementarity of receptor and ligand. Two variants of LR6, identified originally as familial hypercholesterolemia (FH) mutations, have been investigated for their ability to form native disulfide bonds under conditions that permit disulfide exchange. The first, E219K, lies near the amino-terminal end of LR6, whereas the second, D245E, alters one of the aspartate side chains that directly coordinate the bound calcium ion. After equilibration at physiologic calcium concentrations, neither E219K nor D245E folds to a unique disulfide isomer, indicating that FH mutations both within and distant from the calcium-binding site give rise to protein-folding defects.


Potential role of NF-kappaB in adult neural stem cells: the underrated steersman?
Neural stem cells are precursors of neurons and glial cells. During brain development, these cells proliferate, migrate and differentiate into specific lineages. Recently neural stem cells within the adult central nervous system were identified. Informations are now emerging about regulation of stem cell proliferation, migration and differentiation by numerous soluble factors such as chemokines and cytokines. However, the signal transduction mechanisms downstream of these factors are less clear. Here, we review potential evidences for a novel central role of the transcription factor nuclear factor kappa B (NF-kappaB) in these crucial signal transduction processes. NF-kappaB is an inducible transcription factor detected in neurons, glia and neural stem cells. NF-kappaB was discovered by David Baltimore's laboratory as a transcription factor in lymphocytes. NF-kappaB is involved in many biological processes such as inflammation and innate immunity, development, apoptosis and anti-apoptosis. It has been recently shown that members of the NF-kappaB family are widely expressed by neurons, glia and neural stem cells. In the nervous system, NF-kappaB plays a crucial role in neuronal plasticity, learning, memory consolidation, neuroprotection and neurodegeneration. Recent data suggest an important role of NF-kappaB on proliferation, migration and differentiation of neural stem cells. NF-kappaB is composed of three subunits: two DNA-binding and one inhibitory subunit. Activation of NF-kappaB takes place in the cytoplasm and results in degradation of the inhibitory subunit, thus enabling the nuclear import of the DNA-binding subunits. Within the nucleus, several target genes could be activated. In this review, we suggest a model explaining the multiple action of NF-kappaB on neural stem cells. Furthermore, we discuss the potential role of NF-kappaB within the so-called brain cancer stem cells.


Initial evidence that OPRM1 genotype moderates ventral and dorsal striatum functional connectivity during alcohol cues.
Endogenous opioids and striatal dopamine have been implicated in cue-induced alcohol craving and have been hypothesized to play a role in goal-directed, as opposed to habitual, alcohol use. This initial study examines dorsal and ventral striatal functional connectivity during alcohol-cue processing as a function of the A118G single-nucleotide polymorphism of the mu-opioid receptor (OPRM1) gene. Seventeen individuals with alcohol dependence (6 females; 90% Caucasian; mean age = 29.4) underwent blood oxygen level-dependent functional magnetic resonance imaging, while performing an alcohol taste-cues task. Psychophysiological interaction analyses investigated associations of the OPRM1 genotype with ventral and dorsal striatum functional connectivity, using the ventral striatum and the caudate as the seed region, respectively. Compared to A-allele homozygotes, G-allele carriers of the OPRM1 gene showed (i) greater activation of the insula and orbitofrontal cortex and (ii) stronger negative fronto-striatal functional connectivity for both ventral and dorsal striatal seed regions during processing of alcohol versus water cues. These preliminary findings suggest that, relative to A-allele homozygotes, G-allele carriers show unstable frontal regulation over reward and/or habit-driven inputs from the striatum resulting from greater reward sensitivity combined with limited self-control resources.


May-Thurner syndrome: old acquaintance, new perspective : Case report.
May-Thurner syndrome (MTS) results from a frequent anatomic variant in which compression of the left common iliac vein between the body of the fifth lumbar vertebra and the pulsating right common iliac artery can cause deep venous thrombosis (DVT) of the left lower limb. While anticoagulation remains the mainstay treatment of acute DVT, catheter-directed thrombolysis combined with stenting provides a safe and effective method for relieving acute symptoms and preventing postthrombotic syndrome in patients with MTS. In this article the diagnostic and treatment methods are presented in the case report of a 65-year-old woman with MTS who suffered iliofemoral DVT. Knowledge of anatomy is crucial for understanding and recognizing MTS as well as for treating MTS with endovascular procedures.


Transcriptional profiling reveals potential involvement of microvillous TRPM5-expressing cells in viral infection of the olfactory epithelium.
Understanding viral infection of the olfactory epithelium is essential because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection. Herein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of mCherry as a marker for olfactory sensory neurons and for eGFP in OMP-H2B::mCherry/TRPM5-eGFP transgenic mice (Mus musculus). We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells compared to olfactory sensory neurons. Our study provides new insights into a potential role for TRPM5-expressing microvillous cells in viral infection of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells indicates that they are likely involved in the inflammatory response elicited by viral infection of the olfactory epithelium.


Aerobic granular sludge technology: an alternative to activated sludge?
Laboratory experiments have shown that it is possible to cultivate aerobic granular sludge in sequencing batch reactors. In order to direct future research needs and the critical points for successful implementation at large scale, a full detailed design of a potential application was made. The design was based on the laboratory results, and two variants of a full-scale sewage treatment plant based on Granular sludge Sequencing Batch Reactors (GSBRs) were evaluated. As a reference a conventional treatment plant based on activated sludge technology was designed for the same case. Based on total annual costs both GSBR variants proved to be more attractive than the reference alternative (7-17% lower costs). From a sensitivity analysis it appeared that the GSBR technology was less sensitive to the land price and more sensitive to a rain weather flow (RWF). This means that the GSBR technology becomes more attractive at lower permissible RWF/DWF ratios and higher land prices. The footprint of the GSBR variants was only 25% compared to the reference. However, the GSBR with primary treatment only cannot meet the present effluent standards for municipal wastewater in The Netherlands, mainly because of a too high suspended solids concentration in the effluent. A growing number of sewage treatment plants in the Netherlands are going to be faced with more stringent effluent standards. In general, activated sludge plants will have to be extended with a post treatment step (e.g. sand filtration) or be transformed into Membrane Bioreactors. In this case a GSBR variant with primary treatment as well as post treatment can be an attractive alternative.


A laccase associated with lignification in loblolly pine xylem.
Peroxidase has been thought to be the only enzyme that oxidizes monolignol precursors to initiate lignin formation in plants. A laccase was purified from cell walls of differentiating xylem of loblolly pine and shown to coincide in time and place with lignin formation and to oxidize monolignols to dehydrogenation products in vitro. These results suggest that laccase participates in lignin biosynthesis and therefore could be an important target for genetic engineering to modify wood properties or to improve the digestibility of forage crops.


What particulars are referred to in Electronic Health Record data? A case study in integrating Referent Tracking into an EHR application.
Referent Tracking (RT) advocates the use of instance unique identifiers to refer to the entities comprising the subject matter of patient health records. RT promises many benefits to those who use health record data to improve patient care. To further the adoption of the paradigm we provide an illustration of how data from an EHR application needs to be decomposed in order to make it accord with the tenets of RT. We describe the ontological principles on which this decomposition is based in order to allow integration efforts to be applied in similar ways to other EHR applications. We find that an ordinary statement from an EHR contains a surprising amount of "hidden" data that are only revealed by its decomposition according to these principles.


Role of inositol lipid breakdown in the generation of intracellular signals. State of the art lecture.
Many hormones, neurotransmitters, and secretagogues act by increasing the intracellular free Ca2+ concentration in target cells. The initial event following binding of agonists to specific receptors in the plasma membrane involves a receptor-mediated activation of a guanosine nucleotide-binding protein (G protein), which induces a Ca2+-independent activation of phospholipase C. This novel, presently uncharacterized G protein is inactivated by pertussis toxin-catalyzed adenosine 5'-diphosphate ribosylation in some but not all cell types. Phospholipase C catalyzes the breakdown of inositol lipids, notably phosphatidylinositol 4,5-bisphosphate, with the production of inositol phosphates and 1,2-diacylglycerol. Inositol 1,4,5-trisphosphate (IP3) is responsible for a rapid mobilization of intracellular Ca2+ by activating Ca2+ efflux from a subpopulation of the endoplasmic reticulum. The properties of this process are consistent with its being a ligand-activated ion channel with electrogenic Ca2+ efflux being charge-compensated by K+ influx. Sustained hormonal responses require extracellular Ca2+ and a prolonged elevation of the cytosolic free Ca2+. This is brought about by hormone-mediated changes of Ca2+ flux across the plasma membrane involving both an inhibition of Ca2+ efflux and an activation of Ca2+ influx. This review summarizes recent findings concerning the role of G proteins in receptor coupling to phospholipase C; the regulation of enzymes of phosphoinositide metabolism; the evidence for IP3 being a Ca2+-mobilizing second messenger and its mechanism of action; the formation of new inositol phosphates and their possible significance; the relation of intracellular Ca2+ mobilization and plasma membrane Ca2+ fluxes to the kinetics of the hormone-induced cytosolic free Ca2+ transient; and the possible roles of protein kinase C in influencing the hormone-mediated functional response.


Component processes in contour integration: a direct comparison between snakes and ladders in a detection and a shape discrimination task.
In contour integration, a relevant question is whether snakes and ladders are processed similarly. Higher presentation time thresholds for ladders in detection tasks indicate this is not the case. However, in a detection task only processing differences at the level of element linking and possibly contour localization might be picked up, while differences at the shape encoding level cannot be noticed. In this study, we make a direct comparison of detection and shape discrimination tasks to investigate if processing differences in the visual system between snakes and ladders are limited to contour detection or extend to higher level contour processing, like shape encoding. Stimuli consisted of elements that were oriented collinearly (snakes) or orthogonally (ladders) to the contour path and were surrounded by randomly oriented background elements. In two tasks, six experienced subjects either detected the contour when presented with a contour and a completely random stimulus or performed a shape discrimination task when presented with two contours with different curvature. Presentation time was varied in 9 steps between 8 and 492 ms. By applying a generalized linear mixed model we found that differences in snake and ladder processing are not limited to a detection stage but are also apparent at a shape encoding stage.


Chronic cerebrospinal venous insufficiency as a cause of multiple sclerosis: controversy and reality.
Multiple sclerosis (MS) is a relapsing and progressive disorder of the central nervous system. It is characterized most commonly by episodes of clinical worsening, followed by clinical improvement. Pathologically, MS is associated with focal areas of myelin destruction, inflammation, and axonal transection ("demyelinating plaques") in the brain and spinal cord. Traditionally, MS has been considered an autoimmune disorder, with the primary pathophysiology arising from an errant immune system. Recent work has raised the possibility that MS is not caused primarily by an immune abnormality but may instead arise from venous anomalies affecting the jugular and/or azygos venous systems. This condition has been called chronic cerebrospinal venous insufficiency (CCSVI). It has been proposed that CCSVI may be pathogenic in MS, causing venous back pressure and iron deposition, with a secondary immune response. Some investigators have proceeded to unblinded nonrandomized angioplasty and stenting procedures in patients with CCSVI, with anecdotal reports of symptom improvement. Because of conflicting data on the presence of CCSVI and the absence of controlled trials of CCSVI intervention, the current standard of clinical care is neither to evaluate multiple sclerosis (MS) patients for CCSVI anomalies, nor to intervene with procedures to alter such anomalies. There is intense interest and ongoing work to evaluate the presence of venous anomalies in MS patients as well as in normal controls and patients with other neurologic conditions; to characterize such anomalies, if present; and to further understand whether the concept of a "backpressure" pathology is borne out by the evidence. If CCSVI is indeed a pathogenic mechanism for some subset of the MS population, this would dramatically change the focus of attention for therapeutic endeavors and monitoring for this population and would bring MS therapeutics firmly into the area of vascular intervention. On the other hand, the history of MS research contains many novel and potentially paradigm-shifting ideas that were later disproved by other investigators.


Use of the P167 recombinant antigen for serodiagnosis of Helicobacter bilis.
Helicobacter bilis is widespread among research mouse colonies. Serodiagnosis of Helicobacter infections involves use of bacterial lysates or membrane antigen preparations that lack specificity, necessitating the need to identify a specific and sensitive antigen. A previously reported recombinant protein (P167) was evaluated for use as an H. bilis-specific antigen for serologic testing. Seventy-six mice naturally infected with Helicobacter spp. were identified from commercially bred or sentinel mice. Infection was confirmed and speciated by use of cecal specimen culture and fecal polymerase chain reaction (PCR) analysis, followed by restriction enzyme digest of the amplicon. Forty-one mice were determined to be monoinfected with H. bilis, 27 mice were determined to be monoinfected with H. hepaticus, and eight mice were infected with another species of Helicobacter. Serum was diluted 1:100 to evaluate the immunoreactivity to enzyme-linked immunosorbent assay preparations of H. bilis membrane extract and the immunodominant C and D fragments of the p167 gene. The sensitivity was greatest for the membrane extract preparation (76%), whereas sensitivity to the P167C and D recombinants was lower (62 and 51%, respectively). However, the specificity of the membrane extract preparation was low (87%), compared with the much improved specificity of the recombinant P167C and D fragments (96 and 96%, respectively). These findings suggest that the recombinant P167C and D fragments of the p167 gene product from H. bilis can be used as specific reagents in the serodiagnosis of H. bilis infection in mice.


Subgroup identification in clinical trials: an overview of available methods and their implementations with R.
Randomized controlled trials (RCTs) usually enroll heterogeneous study population, and thus it is interesting to identify subgroups of patients for whom the treatment may be beneficial or harmful. A variety of methods have been developed to do such kind of post hoc analyses. Conventional generalized linear model is able to include prognostic variables as a main effect and predictive variables in an interaction with treatment variable. A statistically significant and large interaction effect usually indicates potential subgroups that may have different responses to the treatment. However, the conventional regression method requires to specify the interaction term, which requires knowledge of predictive variables or becomes infeasible when there is a large number of feature variables. The Least Absolute Shrinkage and Selection Operator (LASSO) method does variable selection by shrinking less clear effects (including interaction effects) to zero and in this way selects only certain variables and interactions for the model. There are many tree-based methods for subgroup identification. For example, model-based recursive partitioning incorporates parametric models such as generalized linear models into trees. The model incorporated is usually a simple model with only the treatment as covariate. Predictive and prognostic variables are found and incorporated automatically via the tree. The present article gives an overview of these methods and explains how to perform them using the free software environment for statistical computing R (version 3.3.2). A simulated dataset is employed for illustrating the performance of these methods.


Quantitative evaluation of apically extruded debris during root canal instrumentation with ProTaper Universal, ProTaper Next, WaveOne, and self-adjusting file systems.
The aim of this study was to compare the amount of apically extruded debris during preparation with ProTaper Universal (Dentsply Maillefer, Ballaigues, Switzerland), ProTaper Next (Dentsply Maillefer), a reciprocating single-file (WaveOne; VDW GmbH, Munich, Germany), and a self-adjusting file (SAF; ReDent Nova, Ra'anna, Israel). Fifty-six intact mandibular premolar teeth were randomly assigned to four groups. The root canals were prepared according to the manufacturers' instructions using the ProTaper Universal, ProTaper Next, WaveOne, and SAF. Apically extruded debris was collected in preweighted Eppendorf tubes during instrumentation. The net weight of the apically extruded debris was determined by subtracting the preweights and postweights of the tubes. The data were statistically analyzed using the one-way analysis of variance and the least significant difference tests at a significance level of P < 0.05. A measurable amount of debris was apically extruded in all groups, and the amounts of debris extrusion in the groups were statistically significant (P < 0.001). The ProTaper Next and WaveOne groups resulted in less debris extrusion than the ProTaper Universal group (P < 0.05), and the SAF group resulted in the least debris extrusion. Within the limitations of the present study, it can be concluded that all systems extruded debris beyond the apical foramen.


Emergent magnetism at transition-metal-nanocarbon interfaces.
Charge transfer at metallo-molecular interfaces may be used to design multifunctional hybrids with an emergent magnetization that may offer an eco-friendly and tunable alternative to conventional magnets and devices. Here, we investigate the origin of the magnetism arising at these interfaces by using different techniques to probe 3d and 5d metal films such as Sc, Mn, Cu, and Pt in contact with fullerenes and rf-sputtered carbon layers. These systems exhibit small anisotropy and coercivity together with a high Curie point. Low-energy muon spin spectroscopy in Cu and Sc-C60 multilayers show a quick spin depolarization and oscillations attributed to nonuniform local magnetic fields close to the metallo-carbon interface. The hybridization state of the carbon layers plays a crucial role, and we observe an increased magnetization as sp3 orbitals are annealed into sp2-π graphitic states in sputtered carbon/copper multilayers. X-ray magnetic circular dichroism (XMCD) measurements at the carbon K edge of C60 layers in contact with Sc films show spin polarization in the lowest unoccupied molecular orbital (LUMO) and higher π*-molecular levels, whereas the dichroism in the σ*-resonances is small or nonexistent. These results support the idea of an interaction mediated via charge transfer from the metal and dz-π hybridization. Thin-film carbon-based magnets may allow for the manipulation of spin ordering at metallic surfaces using electrooptical signals, with potential applications in computing, sensors, and other multifunctional magnetic devices.


Lone mothers in Sweden: trends in health and socioeconomic circumstances, 1979-1995.
To study trends in the health and socioeconomic circumstances of lone mothers in Sweden over the years 1979-1995, and to make comparisons with couple mothers over the same period. Analysis of data from the annual Survey of Living Conditions (ULF), conducted by Statistics Sweden from 1979-1995. Comparison of demographic, socioeconomic and health status of lone and couple mothers and how these have varied over the 17 years of the study. Main outcome measures include prevalence of self perceived general health and limiting longstanding illness. All lone mothers (n = 2776) and couple mothers (n = 16,935) aged 16 to 64 years in a random sample of the Swedish population in a series of cross sectional surveys carried out each year between 1979 and 1995. The socioeconomic conditions of lone mothers deteriorated during the period 1979-1995, with increasing unemployment and poverty rates. Lone mothers had worse health status than couple mothers throughout the period. In comparison with the first two periods, the prevalence of less than good health increased among both lone and couple mothers from the late 1980s onwards. For lone and couple mothers who were poor, their rates of less than good health were similar in the early 1980s, but in 1992-95 poor lone mothers were significantly more likely to report less than good health than poor couple mothers. Unemployed lone mothers had particularly high rates of ill health throughout the study period. As in other European countries, lone mothers are emerging as a vulnerable group in society in Sweden, especially in the economic climate of the 1990's. While they had very low rates of poverty and high employment rates in the 1980s, their situation has deteriorated with the economic recession of the 1990's. The health status of lone mothers, particularly those who are unemployed or poor, appears worse than that of couple mothers and in some circumstances may be deteriorating. Further study is needed to elucidate the mechanisms mediating their health disadvantage compared with couple mothers.


Environmental levels of the antiviral oseltamivir induce development of resistance mutation H274Y in influenza A/H1N1 virus in mallards.
Oseltamivir (Tamiflu®) is the most widely used drug against influenza infections and is extensively stockpiled worldwide as part of pandemic preparedness plans. However, resistance is a growing problem and in 2008-2009, seasonal human influenza A/H1N1 virus strains in most parts of the world carried the mutation H274Y in the neuraminidase gene which causes resistance to the drug. The active metabolite of oseltamivir, oseltamivir carboxylate (OC), is poorly degraded in sewage treatment plants and surface water and has been detected in aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to the substance. To assess if resistance can develop under these circumstances, we infected mallards with influenza A/H1N1 virus and exposed the birds to 80 ng/L, 1 µg/L and 80 µg/L of OC through their sole water source. By sequencing the neuraminidase gene from fecal samples, we found that H274Y occurred at 1 µg/L of OC and rapidly dominated the viral population at 80 µg/L. IC₅₀ for OC was increased from 2-4 nM in wild-type viruses to 400-700 nM in H274Y mutants as measured by a neuraminidase inhibition assay. This is consistent with the decrease in sensitivity to OC that has been noted among human clinical isolates carrying H274Y. Environmental OC levels have been measured to 58-293 ng/L during seasonal outbreaks and are expected to reach µg/L-levels during pandemics. Thus, resistance could be induced in influenza viruses circulating among wild ducks. As influenza viruses can cross species barriers, oseltamivir resistance could spread to human-adapted strains with pandemic potential disabling oseltamivir, a cornerstone in pandemic preparedness planning. We propose surveillance in wild birds as a measure to understand the resistance situation in nature and to monitor it over time. Strategies to lower environmental levels of OC include improved sewage treatment and, more importantly, a prudent use of antivirals.


Angiotensin receptor and tumor necrosis factor-α activation contributes to glucose intolerance independent of systolic blood pressure in obese rats.
Pathological activation of the renin-angiotensin system and inflammation are associated with hypertension and the development of metabolic syndrome (MetS). The contributions of angiotensin receptor type 1 (AT1) activation, independent of blood pressure, and inflammation to glucose intolerance and renal damage are not well defined. Using a rat model of MetS, we hypothesized that the onset of glucose intolerance is primarily mediated by AT1 activation and inflammation independent of elevated systolic blood pressure (SBP). To address this hypothesis, we measured changes in SBP, adiposity, plasma glucose and triglyceride levels, and glucose tolerance in six groups of rats: 1) lean, strain control Long-Evans Tokushima Otsuka (LETO; n = 5), 2) obese Otsuka Long-Evans Tokushima Fatty (OLETF; n = 8), 3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg; n = 8), 4) OLETF + tumor necrosis factor-α (TNF-α) inhibitor (ETAN; 1.25 mg etanercept/kg; n = 6), 5) OLETF + TNF-α inhibitor + angiotensin receptor blocker (ETAN+ARB; 1.25 mg etanercept/kg + 10 mg olmesartan/kg; n = 6), and 6) OLETF + calcium channel blocker (CCB; 5 mg amlodipine/kg; n = 7). ARB and ETAN+ARB were most effective at decreasing SBP in OLETF, and ETAN did not offer any additional reduction. Glucose tolerance improved in ARB, ETAN, and ETAN+ARB compared with OLETF, whereas CCB had no detectable effect. Furthermore, all treatments reduced adiposity, whereas ETAN alone normalized urinary albumin excretion. These results suggest that AT1 activation and inflammation are primary factors in the development of glucose intolerance in a setting of MetS and that the associated increase in SBP is primarily mediated by AT1 activation.


The effect of cimetidine on PBL from healthy donors and melanoma patients: augmentation of T cell responses to TCGF mitogens and alloantigens and of TCGF production.
The effect of cimetidine, an H-2 receptor antagonist, on activation of PBL from both normal individuals and melanoma patients was studied. It has been shown that cimetidine enhanced, though moderately, the production of TCGF from normal PBL after PHA-P stimulation. In addition, cimetidine significantly augmented TCGF-induced proliferation of normal PBL, as well as proliferation induced by allogeneic cells (MLC) by PPD, Con A, and PHA. In PBL samples where coincubation with cimetidine had limited or no effect, preincubation of PBL with cimetidine prior to the addition of IL-2 and other T cell activators showed a significant enhancement effect. This effect mediated by cimetidine was further demonstrated on PBL from melanoma patients whose T cell responses were initially low. The possibilities are discussed that: (a) cimetidine treatment inactivates suppressor cell activity, thus enhancing T cell mediated responses; or (b) cimetidine may act directly at effector cell level.


Temperature dependent bacteriophages of a tropical bacterial pathogen.
There is an increasing awareness of the multiple ways that bacteriophages (phages) influence bacterial evolution, population dynamics, physiology, and pathogenicity. By studying a novel group of phages infecting a soil borne pathogen, we revealed a paradigm shifting observation that the phages switch their lifestyle according to temperature. We sampled soil from an endemic area of the serious tropical pathogen Burkholderia pseudomallei, and established that podoviruses infecting the pathogen are frequently present in soil, and many of them are naturally occurring variants of a common virus type. Experiments on one phage in the related model B. thailandensis demonstrated that temperature defines the outcome of phage-bacteria interactions. At higher temperatures (37°C), the phage predominantly goes through a lytic cycle, but at lower temperatures (25°C), the phage remains temperate. This is the first report of a naturally occurring phage that follows a lytic or temperate lifestyle according to temperature. These observations fundamentally alter the accepted views on the abundance, population biology and virulence of B. pseudomallei. Furthermore, when taken together with previous studies, our findings suggest that the phenomenon of temperature dependency in phages is widespread. Such phages are likely to have a profound effect on bacterial biology, and on our ability to culture and correctly enumerate viable bacteria.


Influence of salinity on prevalence of the parasite Loxothylacus panopaei in the xanthid Panopeus obesus in SW Florida.
This study was conducted to examine the potential influence of salinity, a proxy for freshwater inflow, on the prevalence of the castrator parasite Loxothylacus panopaei on saltmarsh mud crabs Panopeus obesus on SW Florida oyster reefs. Spatial and seasonal patterns of the presence of potential host crabs and the prevalence of the parasite were assessed in the Caloosahatchee, Estero, and Faka Union estuaries. Lift nets (1 m2) containing 5 1 of oyster clusters were deployed on intertidal reefs at 3 sites along the salinity gradient of each estuary. Nets were deployed during 3 seasonally dry and 3 seasonally wet months for a period of 30 d. P. obesus densities tended to increase downstream in higher salinity waters, with crabs being absent from the upper station in the Caloosahatchee during both seasons and absent from the upper station of the Faka Union during wet months. Parasite prevalence was reduced upstream in each estuary during wet months compared to dry months, and for those estuaries that experienced higher relative levels of freshwater inflow. Furthermore, parasite prevalence was positively correlated with the mean salinity of capture of host crabs. Based on the distribution of P. obesus and the above patterns related to salinity, it appears that freshwater inflow and seasonal rains might regulate the prevalence of this parasite in SW Florida by creating spatiotemporal, low salinity refuges for its host.


Outcome after major renovascular injuries: a Western trauma association multicenter report.
Major renal vascular injuries are uncommon and are frequently associated with a poor outcome. In addition to renal dysfunction, posttraumatic renovascular hypertension may result, although the true incidence of this complication is unknown. The objective of this study was to describe the factors contributing to outcome after major renovascular trauma. We hypothesized that the highest percentage of renal salvage would be achieved by minimizing the time from injury to repair. This was a retrospective chart review over a 16-year period conducted at six university trauma centers of patients with American Association for the Surgery of Trauma grade IV/V renal injuries surviving longer than 24 hours. Postinjury renal function with poor outcome was defined as renal failure requiring dialysis, serum creatinine greater than or equal to 2 mg/dL, renal scan showing less than 25% function of the injured kidney, postinjury hypertension requiring treatment, or delayed nephrectomy. Data collected for analysis included demographics, mechanism of injury, presence of shock, presence of hematuria, associated injuries, type of renal injury (major artery, renal vein, segmental artery), type of repair (primary vascular repair, revascularization, observation, nephrectomy), time from injury to definitive renal surgery, and type of surgeon performing the operation (urologist, vascular surgeon, trauma surgeon). Eighty-nine patients met inclusion criteria; 49% were injured from blunt mechanisms. Patients with blunt injuries were 2.29 times more likely to have a poor outcome compared with those with penetrating injuries. Similarly, the odds ratio of having a poor outcome with a grade V injury (n = 32) versus grade IV (n = 57) was 2.2 (p = 0.085). Arterial repairs had significantly worse outcomes than vein repairs (p = 0.005). Neither the time to definitive surgery nor the operating surgeon's specialty significantly affected outcome. Ten percent (nine patients) developed hypertension or renal failure postoperatively: three had immediate nephrectomies, four had arterial repairs with one intraoperative failure requiring nephrectomy, and two were observed. Of the 20 good outcomes for grade V injuries, 15 had immediate nephrectomy, 1 had a renal artery repair, 1 had a bypass graft, 1 underwent a partial nephrectomy, and 2 were observed. Factors associated with a poor outcome following renovascular injuries include blunt trauma, the presence of a grade V injury, and an attempted arterial repair. Patients with blunt major vascular injuries (grade V) are likely to have associated major parenchymal disruption, which contributes to the poor function of the revascularized kidney. These patients may be best served by immediate nephrectomy, provided that there is a functioning contralateral kidney.


Multiple organ carcinogenicity of 1,3-butadiene in B6C3F1 mice after 60 weeks of inhalation exposure.
Groups of 50 male and 50 female B6C3F1 mice were exposed 6 hours per day, 5 days per week, for 60 to 61 weeks to air containing 0, 625, or 1250 parts per million 1,3-butadiene. These concentrations are somewhat below and slightly above the Occupational Safety and Health Administration standard of 1000 parts per million for butadiene. The study was designed for 104-week exposures but had to be ended early due to cancer-related mortality in both sexes at both exposure concentrations. There were early induction and significantly increased incidences of hemangiosarcomas of the heart, malignant lymphomas, alveolar-bronchiolar neoplasms, squamous cell neoplasms of the forestomach in males and females and acinar cell carcinomas of the mammary gland, granulosa cell neoplasms of the ovary, and hepatocellular neoplasms in females. Current workplace standards for exposure to butadiene should be reexamined in view of these findings.


Vegetable oils as carbon and energy source for Aureobasidium melanogenum in batch cultivation.
Dark homogenous fungal-based layers called biofinishes and vegetable oils are key ingredients of an innovative wood protecting system. The aim of this study was to determine which of the vegetable oils that have been used to generate biofinishes on wood will provide carbon and energy for the biofinish-inhabiting fungus Aureobasidium melanogenum, and to determine the effect of the oil type and the amount of oil on the cell yield. Aureobasidium melanogenum was cultivated in shake flasks with different types and amounts of carbon-based nutrients. Oil-related total cell and colony-forming unit growth were demonstrated in suspensions with initially 1% raw linseed, stand linseed, and olive oil. Oil-related cell growth was also demonstrated with raw linseed oil, using an initial amount of 0.02% and an oil addition during cultivation. Nile red staining showed the accumulation of fatty acids inside cells grown in the presence of oil. In conclusion, each tested vegetable oil was used as carbon and energy source by A. melanogenum. The results indicated that stand linseed oil provides less carbon and energy than olive and raw linseed oil. This research is a fundamental step in unraveling the effects of vegetable oils on biofinish formation.


Effects of fatigue from resistance training on barbell back squat biomechanics.
Exhaustive resistance training programs that have been previously referred to as extreme conditioning protocols have increased in popularity in military and civilian populations in recent years. However, because of their highly fatiguing nature, proprioception is likely altered during such programs that would significantly affect the safety and efficacy of such programs. Therefore, the purpose of this study was to assess the alterations in movement patterns that result from extreme conditioning protocols and to evaluate if these protocols can be deemed safe and effective. Twelve men (age 24 ± 4.2 years, height 173.1 ± 3.6 cm, weight 76.9 ± 7.8 kg, body fat percentage 9.0 ± 2.2%) and 13 women (age 24.5 ± 3.8 years, height 166.9 ± 8.5 cm, weight 66.1 ± 9.2 kg, body fat percentage 18.6 ± 4.0%) with at least 6 months of resistance training experience involving barbell bench press, barbell deadlift, and barbell back squat performed a highly fatiguing resistance training workout. During the barbell back squat, a 2-dimensional analysis was performed where the knee and hip angles were recorded throughout the 55 repetitions of the workout. At the early stages of the protocol, knee angle was significantly lower in men and in women demonstrating less knee flexion. Also, hip angle was significantly lower early in the program in men and in women, demonstrating a greater forward lean. The technique changes that occur in high repetition sets do not favor optimal strength development and may increase the risk of injury, clearly questioning the safety and efficacy of such resistance training programming. This is likely a display of self-preservation by individuals who are faced with high repetition programs.


Altered flow-induced arterial remodeling in vimentin-deficient mice.
The endothelial cytoskeleton plays a key role in arterial responses to acute changes in shear stress. We evaluated whether the intermediate filament protein vimentin is involved in the structural responses of arteries to chronic changes in blood flow (BF). In wild-type mice (V+/+) and in vimentin-deficient mice (V-/-), the left common carotid artery (LCA) was ligated near its bifurcation, and 4 weeks later, the structures of the occluded and of the contralateral arteries were evaluated and compared with the structures of arteries from sham-operated mice. Body weight and mean carotid artery BF did not differ between the strains, but LCA and right carotid artery (RCA) diameter (737+/-14 microm [LCA] and 723+/-14 microm [RCA] for V-/- versus 808+/-20 microm [LCA] and 796+/-20 microm [RCA] for V+/+) and medial cross-sectional area (CSAm) were significantly smaller in V-/- (21+/-1 and 22+/-2 x 10(3) microm(2) for LCA and RCA, respectively) than in V+/+ (28+/-2 and 28+/-3 x 10(3) microm(2) for LCA and RCA, respectively). In V+/+, LCA ligation eliminated BF in the occluded vessel (before ligation, 0. 35+/-0.02 mL/min) and increased BF from 0.34+/-0.02 to 0.68+/-0.04 mL/min in the RCA. In V-/-, the BF change in the occluded LCA was comparable (from 0.38+/-0.05 mL/min to zero-flow rates), but the BF increase in the RCA was less pronounced (from 0.33+/-0.02 to 0. 50+/-0.05 mL/min). In the occluded LCA of V+/+, arterial diameter was markedly reduced (-162 microm), and CSAm was significantly increased (5 x 10(3) microm(2)), whereas in the high-flow RCA of V+/+, carotid artery diameter and CSAm were not significantly modified. In the occluded LCA of V-/-, arterial diameter was reduced to a lesser extent (-77 microm) and CSAm was increased to a larger extent (10 x 10(3) microm(2)) than in V+/+. In contrast to V+/+, the high-flow RCA of V-/- displayed a significant increase in diameter (52 microm) and a significant increase in CSAm (5 x 10(3) microm(2)). These observations provide the first direct evidence for a role of the cytoskeleton in flow-induced arterial remodeling. Furthermore, they dissociate (1) between acute and chronic arterial responses to altered BF, (2) between alterations of lumen diameter and wall mass during arterial remodeling, and (3) between developmental and imposed flow-induced arterial remodeling.


Impact of beta blockers on patients undergoing transcatheter aortic valve replacement: the OCEAN-TAVI registry.
There is paucity of data on optimal medical treatment, including use of beta blockers for patients undergoing transcatheter aortic valve replacement (TAVR). The study aimed to investigate the association of beta blockers and clinical outcomes following TAVR. We examined data of 2563 patients who underwent TAVR between October 2013 and May 2017 obtained from a prospective multicentre cohort registry, the optimised catheter valvular intervention-TAVI registry. We compared the 2-year cardiovascular and non-cardiovascular mortality and in-hospital outcomes between patients with and without preprocedural beta-blocker administration by propensity score matching (PSM). Preprocedural beta blockers were prescribed in 867 patients (33.8%). After PSM, the incidence of in-hospital congestive heart failure was significantly lower in patients with preprocedural beta blocker (p=0.046). No differences were found in 2-year cardiovascular and non-cardiovascular mortality. In the subgroup analyses, beta-blocker administration was associated with a lower cardiovascular mortality within 2 years in patients with a history of coronary artery bypass grafting (CABG; log-rank p=0.017), presence of peripheral artery disease (PAD; log-rank p=0.003) and brain natriuretic peptide (BNP) ≥400 pg/mL (log-rank p=0.003). When stratified by postprocedural left ventricular ejection fraction (post-LVEF), beta-blocker administration was associated with a lower cardiovascular mortality among patients with post-LVEF <50% (log-rank p=0.024). Preprocedural beta-blocker administration was not associated with 2-year cardiovascular and non-cardiovascular mortality in overall, but was associated with a lower 2-year cardiovascular mortality in patients with a history of CABG, presence of PAD, BNP ≥400 pg/mL and post-LVEF <50%. The findings must be validated using randomised trials.