Effect of hydroxyethyl starch on the structure of thrombin- and reptilase-induced fibrin gels.
The effect of hydroxyethyl starch (HES), a complex polysaccharide colloid plasma expander, on the structure of fibrin gels was studied turbidimetrically. HES at concentrations as low as 2.5 mg/ml shortened the lag phase of turbidity increase and caused increased fibrin fiber mass/length ratios in both purified fibrin and plasma systems. For purified fibrin gels clotted with thrombin the mass/length ratio increased in a linear fashion from 2.6 to 6.1 X 10(12) daltons/cm as HES increased from 0 to 15 mg/ml. Fiber mass/length ratios for purified fibrin gels clotted with reptilase increased from 1.1 to 6.4 X 10(12) daltons/cm over the same HES concentration range. The addition of 5 mmol/L calcium to either system produced additional increases in fiber size. In 1:10 dilutions of plasma, HES shortened the lag phase, enhanced the rate of turbidity increase, and increased the final gel turbidity. The fiber mass/length ratio for plasma gels clotted with thrombin increased from 0.3 to 1.7 X 10(12) daltons/cm as HES increased from 0 to 20 mg/ml. For plasma gels clotted with reptilase, the fiber mass/length ratio increased from 1.5 to 2.4 X 10(12) daltons/cm over the same HES concentration range. The effects of HES are comparable to those of dextran at concentrations less than 5 mg/ml and can be explained on the basis of HES-enhanced lateral association of fibrin fibers during polymerization.


3D bioprinting mesenchymal stem cell-laden construct with core-shell nanospheres for cartilage tissue engineering.
Cartilage tissue is prone to degradation and has little capacity for self-healing due to its avascularity. Tissue engineering, which provides artificial scaffolds to repair injured tissues, is a novel and promising strategy for cartilage repair. 3D bioprinting offers even greater potential for repairing degenerative tissue by simultaneously integrating living cells, biomaterials, and biological cues to provide a customized scaffold. With regard to cell selection, mesenchymal stem cells (MSCs) hold great capacity for differentiating into a variety of cell types, including chondrocytes, and could therefore be utilized as a cartilage cell source in 3D bioprinting. In the present study, we utilize a tabletop stereolithography-based 3D bioprinter for a novel cell-laden cartilage tissue construct fabrication. Printable resin is composed of 10% gelatin methacrylate (GelMA) base, various concentrations of polyethylene glycol diacrylate (PEGDA), biocompatible photoinitiator, and transforming growth factor beta 1 (TGF-β1) embedded nanospheres fabricated via a core-shell electrospraying technique. We find that the addition of PEGDA into GelMA hydrogel greatly improves the printing resolution. Compressive testing shows that modulus of the bioprinted scaffolds proportionally increases with the concentrations of PEGDA, while swelling ratio decreases with the increase of PEGDA concentration. Confocal microscopy images illustrate that the cells and nanospheres are evenly distributed throughout the entire bioprinted construct. Cells grown on 5%/10% (PEGDA/GelMA) hydrogel present the highest cell viability and proliferation rate. The TGF-β1 embedded in nanospheres can keep a sustained release up to 21 d and improve chondrogenic differentiation of encapsulated MSCs. The cell-laden bioprinted cartilage constructs with TGF-β1-containing nanospheres is a promising strategy for cartilage regeneration.


Regulation of calpactin I phospholipid binding by calpactin I light-chain binding and phosphorylation by p60v-src.
Calpactins I and II are proteins that bind Ca2+, phospholipids, actin and spectrin; they are also major substrates of oncogene and growth-factor-receptor tyrosine kinases. Since calpactins have been proposed to provide a link between membrane lipids and the cytoskeleton, we examined in detail the interactions between purified calpactin I and phospholipid liposomes. We focused on the Ca2+-dependence, the effects of phosphorylation of calpactin I by p60v-src (the protein kinase coded for by the Rous-sarcoma-virus oncogene), and the effects of the binding of calpactin I light chain to calpactin I heavy chain. Binding of the light chain to the heavy chain increased the affinity of calpactin I for phosphatidylserine (PS) liposomes. The opposite effect was observed for phosphorylation by p60v-src; phosphorylation decreased the affinity of calpactin I for PS liposomes. These two opposite effects appeared to be independent, since phosphorylation did not prevent light-chain binding to the heavy chain. Calpactin I was found, by the use of three different techniques, to bind to phospholipid liposomes at less than 10(-8) M free Ca2+. This result is in contrast with those of previous studies, which indicated that greater than 10(-6) M free Ca2+ was required. Our findings suggest that calpactin I may be bound to phospholipids in vivo at Ca2+ concentrations of about 1.5 x 10(-7) M, typical of resting unstimulated cells, and that this interaction may be modulated by light-chain binding and phosphorylation by p60v-src.


Superoxide release by peritoneal and bone marrow-derived mouse macrophages. Modulation by adherence and cell activation.
Macrophages (M phi) activated by BCG and other immune stimuli differ from thioglycollate-elicited M phi (TPM) in releasing O-2 upon initial contact with a foreign substratum. During adherence and spreading, activated M phi release approximately 50% of O-2 levels triggered by phorbol myristate acetate (PMA). The response requires divalent cations (Ca++ or Mg++) and is sensitive to lignocaine, a reversible inhibitor of adhesion. These features distinguish this reaction from the response to PMA, which also triggers substantial release of O-2 from TPM, 60-80% of bacille Calmette--Guérin-activated peritoneal M phi (BCG-PM) activity. During prolonged cultivation as monolayers, peritoneal and bone marrow derived M phi (BMDM) progressively lose their ability to release O-2 in response to PMA and serum-treated zymosan (STZ), although the cells continue to secrete other products and to phagocytose STZ. This loss can be prevented by maintaining peritoneal and BMDM as non-adherent cells in teflon beakers or poly-(2-hydroxyethylmethacrylate) (poly HEMA) coated vessels. High levels of O-2 activity were observed after cultivating TPM on poly-HEMA (300 nmoles O-2/mg/hr after PMA), 10-fold more than adherent controls. BMDM could be induced to release four-fold more O-2, greater than 100 nmoles O-2/mg/hr, after cultivation as non-adherent cells in the absence of L cell-conditioned medium. Our results show that heterogeneity in M phi respiratory burst activity depends on (i) intrinsic differences between populations, (ii) differential responses by activated and non-activated M phi to selective surface stimuli and (iii) modulation by environmental factors which control adherence and growth.


Dysphagia in Mechanically Ventilated ICU Patients (DYnAMICS): A Prospective Observational Trial.
Swallowing disorders may be associated with adverse clinical outcomes in patients following invasive mechanical ventilation. We investigated the incidence of dysphagia, its time course, and association with clinically relevant outcomes in extubated critically ill patients. Prospective observational trial with systematic dysphagia screening and follow-up until 90 days or death. ICU of a tertiary care academic center. One thousand three-hundred four admissions of mixed adult ICU patients (median age, 66.0 yr [interquartile range, 54.0-74.0]; Acute Physiology and Chronic Health Evaluation-II score, 19.0 [interquartile range, 14.0-24.0]) were screened for postextubation dysphagia. Primary ICU admissions (n = 933) were analyzed and followed up until 90 days or death. Patients from an independent academic center served as confirmatory cohort (n = 220). Bedside screening for dysphagia was performed within 3 hours after extubation by trained ICU nurses. Positive screening triggered confirmatory specialist bedside swallowing examinations and follow-up until hospital discharge. Dysphagia screening was positive in 12.4% (n = 116/933) after extubation (18.3% of emergency and 4.9% of elective patients) and confirmed by specialists within 24 hours from positive screening in 87.3% (n = 96/110, n = 6 missing data). The dysphagia incidence at ICU discharge was 10.3% (n = 96/933) of which 60.4% (n = 58/96) remained positive until hospital discharge. Days on feeding tube, length of mechanical ventilation and ICU/hospital stay, and hospital mortality were higher in patients with dysphagia (all p < 0.001). The univariate hazard ratio for 90-day mortality for dysphagia was 3.74 (95% CI, 2.01-6.95; p < 0.001). After adjustment for disease severity and length of mechanical ventilation, dysphagia remained an independent predictor for 28-day and 90-day mortality (excess 90-d mortality 9.2%). Dysphagia after extubation was common in ICU patients, sustained until hospital discharge in the majority of affected patients, and was an independent predictor of death. Dysphagia after mechanical ventilation may be an overlooked problem. Studies on underlying causes and therapeutic interventions seem warranted.


Diameter of basalt columns derived from fracture mechanics bifurcation analysis.
The diameter of columnar joints forming in cooling basalt and drying starch increases with decreasing growth rate. This observation can be reproduced with a linear-elastic three-dimensional fracture mechanics bifurcation analysis, which has been done for a periodic array of hexagonal columnar joints by considering a bifurcation mode compatible with observations on drying starch. In order to be applicable to basalt columns, the analysis has been carried out with simplified stationary temperature fields. The critical diameter differs from the one derived with a two-dimensional model by a mere factor of 1/2. By taking into account the latent heat released at the solidification front, the results agree fairly well with observed column diameters.


E-vitamin infused highly cross-linked polyethylene: RSA results from a randomised controlled trial using 32 mm and 36 mm ceramic heads.
Polyethylene wear has been a major cause of revision of cementless total hip replacements. Highly cross-linked polyethylene has been developed to increase mechanical resistance to wear. However, cross-linking from irradiation of the polyethylene generates free radicals and these can oxidise in vivo and might over time alter the initial mechanical properties. Vitamin-E infused highly cross-linked polyethylene has been developed to reduce the amount of free radicals without compromising the mechanical properties. To measure wear of vitamin E infused highly cross-linked polyethylene and compare wear between 2 different head sizes. In a prospective randomised study between 32 mm and 36 mm Biolox® delta heads in 50 hips we analysed the in vivo wear of the E-poly™ with markerless radiostereometry. Mean (95% CI) wear for the total material was 0.041 mm (0.015-0.066) in the vertical direction and 0.177 mm (0.155-0.200) in the total 3D direction. After the anticipated period of bedding-in we found no statistically significant differences in wear from three months to 2 years in vertical and total 3D directions. Although statistical significant differences between 32 mm and 36 mm heads were found in the total 3D direction we cannot conclude that there are significant clinical important differences in wear comparing these head sizes. This study shows promising early results with very low wear, even for 36 mm heads, but long term follow-up is necessary to evaluate if this polyethylene will provide low wear and good mechanical properties in the long-term.


Back Pain: Clinical Updates in Women's Health Care Primary and Preventive Care Review.
Every age group experiences back pain, a common reason for activity limitation. Management of back pain in a woman is challenging because of physiologic and hormonal changes through the woman's life cycle. The treatment is dictated by etiology and a woman's stage of life or reproductive events, such as pregnancy, breastfeeding, and menopause. Most episodes of low back pain are temporary with minimal long-term sequelae, but recurrent and long-lasting episodes require more thorough clinical evaluation. This monograph describes the anatomy of the spine; illustrates a focused, thorough evaluation, including obtaining a medical history and performing a physical examination; discusses warning signs and symptoms of more serious etiologies; provides recommendations for further testing or referral; and offers case vignettes of common causes of low back pain as a woman progresses from young adulthood to advanced age.


Ecological opportunities and specializations shaped genetic divergence in a highly mobile marine top predator.
Environmental conditions can shape genetic and morphological divergence. Release of new habitats during historical environmental changes was a major driver of evolutionary diversification. Here, forces shaping population structure and ecotype differentiation ('pelagic' and 'coastal') of bottlenose dolphins in the North-east Atlantic were investigated using complementary evolutionary and ecological approaches. Inference of population demographic history using approximate Bayesian computation indicated that coastal populations were likely founded by the Atlantic pelagic population after the Last Glacial Maxima probably as a result of newly available coastal ecological niches. Pelagic dolphins from the Atlantic and the Mediterranean Sea likely diverged during a period of high productivity in the Mediterranean Sea. Genetic differentiation between coastal and pelagic ecotypes may be maintained by niche specializations, as indicated by stable isotope and stomach content analyses, and social behaviour. The two ecotypes were only weakly morphologically segregated in contrast to other parts of the World Ocean. This may be linked to weak contrasts between coastal and pelagic habitats and/or a relatively recent divergence. We suggest that ecological opportunity to specialize is a major driver of genetic and morphological divergence. Combining genetic, ecological and morphological approaches is essential to understanding the population structure of mobile and cryptic species.


3-[(Furan-2-yl)carbon-yl]-1-(pyrimi-din-2-yl)thio-urea.
The title compound, C10H8N4O2S, was synthesized from furoyl isothio-cynate and 2-amino-pyrimidine in dry acetone. The two N-H groups are in an anti conformation with respect to each other and one N-H group is anti to the C=S group while the other is syn. The amide C=S and the C=O groups are syn to each other. The mean plane of the central thio-urea fragment forms dihedral angles of 13.50 (14) and 5.03 (11)° with the furan and pyrimidine rings, respectively. The dihedral angle between the furan and pyrimidine rings is 18.43 (10)°. The mol-ecular conformation is stabilized by an intra-molecular N-H⋯N hydrogen bond generating an S(6) ring motif. In the crystal, mol-ecules are linked by pairs of N-H⋯N and weak C-H⋯S hydrogen bonds to form inversion dimers.


Spatio-temporal model to investigate COVID-19 spread accounting for the mobility amongst municipalities.
The rapid spread of COVID-19 worldwide led to the implementation of various non-pharmaceutical interventions to limit transmission and hence reduce the number of infections. Using telecom-operator-based mobility data and a spatio-temporal dynamic model, the impact of mobility on the evolution of the pandemic at the level of the 581 Belgian municipalities is investigated. By decomposing incidence, particularly into within- and between-municipality components, we noted that the global epidemic component is relatively more important in larger municipalities (e.g., cities), while the local component is more relevant in smaller (rural) municipalities. Investigation of the effect of mobility on the pandemic spread showed that reduction of mobility has a significant impact in reducing the number of new infections.


Expression of perforin and serine esterases by human gamma/delta T cells.
gamma/delta T cells have recently been described in association with a number of disorders, including autoimmune diseases. gamma/delta T cells are thought to play a cytotoxic role, but their mechanism of action is not known. Several granule mediators of cytotoxicity, including a pore-forming protein (perforin), and a family of serine esterases, have been isolated from cytotoxic T lymphocytes (CTL), lymphokine-activated killer (LAK) cells, and natural killer (NK) cells. We demonstrate here that gamma/delta T cells also express these mediators. Northern blots show that gamma/delta T cells express perforin, serine esterase 1 (SE 1), and SE 2. Three polyclonal antisera - raised against murine perforin, a peptide composed of amino acids 1-34 of human perforin, and human peforin expressed in bacteria - all reacted with a 70-kD protein in gamma/delta T cells on Western blots. Immunostaining with antiperforin antisera shows that primary gamma/delta T cells also contain perforin. Electron microscopy reveals that the granules of gamma/delta T cells resemble those of CTL, LAK, and NK cells. Gamma/delta T cells also resemble LAK cells in possessing inclusion bodies in their nuclei. These results imply that gamma/delta T cells resemble other cytolytic lymphocytes in their mechanism of action.


[Antithrombogenic properties of the vascular walls and intravascular platelet activation in ischemic heart disease].
A study of 150 coronary patients demonstrated compromized athrombogenic endothelial properties, as compared to normal subjects whose vascular wall endothelial cells show high anti-aggregation and anti-coagulant activity and prevent intravascular platelet aggregation. The cuff test performed in coronary patients during acute myocardial infarction or an anginal attack induced no release of prostacycline, antithrombin III or plasminogen activators from endothelial cells into the blood flow. Coronary patients demonstrated intravascular platelet activation, impaired platelet release and increased factor 4, thromboxane B2 and beta-thromboglobulin levels.


Complete genome sequence of the apicomplexan, Cryptosporidium parvum.
The apicomplexan Cryptosporidium parvum is an intestinal parasite that affects healthy humans and animals, and causes an unrelenting infection in immunocompromised individuals such as AIDS patients. We report the complete genome sequence of C. parvum, type II isolate. Genome analysis identifies extremely streamlined metabolic pathways and a reliance on the host for nutrients. In contrast to Plasmodium and Toxoplasma, the parasite lacks an apicoplast and its genome, and possesses a degenerate mitochondrion that has lost its genome. Several novel classes of cell-surface and secreted proteins with a potential role in host interactions and pathogenesis were also detected. Elucidation of the core metabolism, including enzymes with high similarities to bacterial and plant counterparts, opens new avenues for drug development.


A portable ventilator with integrated physiologic monitoring for hyperpolarized 129Xe MRI in rodents.
Hyperpolarized (HP) 129Xe MRI is emerging as a powerful, non-invasive method to image lung function and is beginning to find clinical application across a range of conditions. As clinical implementation progresses, it becomes important to translate back to well-defined animal models, where novel disease signatures can be characterized longitudinally and validated against histology. To date, preclinical 129Xe MRI has been limited to only a few sites worldwide with 2D imaging that is not generally sufficient to fully capture the heterogeneity of lung disease. To address these limitations and facilitate broader dissemination, we report on a compact and portable HP gas ventilator that integrates all the gas-delivery and physiologic monitoring capabilities required for high-resolution 3D hyperpolarized 129Xe imaging. This ventilator is MR- and HP-gas compatible, driven by inexpensive microcontrollers and open source code, and allows for precise control of the tidal volume and breathing cycle in perorally intubated mice and rats. We use the system to demonstrate data acquisition over multiple breath-holds, during which lung motion is suspended to enable high-resolution 3D imaging of gas-phase and dissolved-phase 129Xe in the lungs. We demonstrate the portability and versatility of the ventilator by imaging a mouse model of lung cancer longitudinally at 2 Tesla, and a healthy rat at 7 Tesla. We also report the detection of subtle spectroscopic fluctuations in phase with the heart rate, superimposed onto larger variations stemming from the respiratory cycle. This ventilator was developed to facilitate duplication and gain broad adoption to accelerate preclinical 129Xe MRI research.


DLI-IT: a deep learning approach to drug label identification through image and text embedding.
Drug label, or packaging insert play a significant role in all the operations from production through drug distribution channels to the end consumer. Image of the label also called Display Panel or label could be used to identify illegal, illicit, unapproved and potentially dangerous drugs. Due to the time-consuming process and high labor cost of investigation, an artificial intelligence-based deep learning model is necessary for fast and accurate identification of the drugs. In addition to image-based identification technology, we take advantages of rich text information on the pharmaceutical package insert of drug label images. In this study, we developed the Drug Label Identification through Image and Text embedding model (DLI-IT) to model text-based patterns of historical data for detection of suspicious drugs. In DLI-IT, we first trained a Connectionist Text Proposal Network (CTPN) to crop the raw image into sub-images based on the text. The texts from the cropped sub-images are recognized independently through the Tesseract OCR Engine and combined as one document for each raw image. Finally, we applied universal sentence embedding to transform these documents into vectors and find the most similar reference images to the test image through the cosine similarity. We trained the DLI-IT model on 1749 opioid and 2365 non-opioid drug label images. The model was then tested on 300 external opioid drug label images, the result demonstrated our model achieves up-to 88% of the precision in drug label identification, which outperforms previous image-based or text-based identification method by up-to 35% improvement. To conclude, by combining Image and Text embedding analysis under deep learning framework, our DLI-IT approach achieved a competitive performance in advancing drug label identification.


Risk network structure in the early epidemic phase of HIV transmission in Colorado Springs.
This study describes the risk network structure of persons with HIV infection during its early epidemic phase in Colorado Springs, USA, using analysis of community-wide HIV/AIDS contact tracing records (sexual and injecting drug partners) from 1985 to 1999. Paired partner information from other STD/HIV programme records was used to augment network connections. Analyses were conducted with and without this supplemental information. The results suggest that a combined dendritic and cyclic structural network pattern is associated with low to moderate HIV propagation in Colorado Springs, and may account for the absence of intense propagation of the virus.


Right Median Nerve Electrical Stimulation for Acute Traumatic Coma Patients.
The right median nerve as a peripheral portal to the central nervous system can be electrically stimulated to help coma arousal after traumatic brain injury (TBI). The present study set out to examine the efficacy and safety of right median nerve electrical stimulation (RMNS) in a cohort of 437 comatose patients after severe TBI from August 2005 to December 2011. The patients were enrolled 2 weeks after their injury and assigned to the RMNS group (n=221) receiving electrical stimulation for 2 weeks or the control group (n = 216) treated by standard management according to the date of birth in the month. The baseline data were similar. After the 2-week treatment, the RMNS-treated patients demonstrated a more rapid increase of the mean Glasgow Coma Score, although statistical significance was not reached (8.43 ± 4.98 vs. 7.47 ± 5.37, p = 0.0532). The follow-up data at 6-month post-injury showed a significantly higher proportion of patients who regained consciousness (59.8% vs. 46.2%, p = 0.0073). There was a lower proportion of vegetative persons in the RMNS group than in the control group (17.6% vs. 22.0%, p = 0.0012). For persons regaining consciousness, the functional independence measurement (FIM) score was higher among the RMNS group patients (91.45 ± 8.65 vs. 76.23 ± 11.02, p < 0.001). There were no unique complications associated with the RMNS treatment. The current study, although with some limitations, showed that RMNS may serve as an easy, effective, and noninvasive technique to promote the recovery of traumatic coma in the early phase.


Comparison of the synaptosomal uptake inhibition of serotonin by St John's wort products.
Although the number of prescriptions for psychotropic drugs has decreased in recent years, prescriptions for antidepressants are still increasing (Fritze 2002). Hypericum perforatum (St John's wort) is the main psychotherapeutic herbal medicinal product used for treatment of mild-to-moderate depression. The lipophilic constituent hyperforin (2-5% of the extract) demonstrated, similarly to chemical antidepressants, a significant effect on the synaptosomal uptake inhibition of several neurotransmitters in in-vitro assays. In Germany, St John's wort products are distributed via two different markets: products that are pharmacy restricted are only allowed to be distributed in pharmacies; traditionally used products, which do not claim to have a curative character, are allowed to be sold in supermarkets. Depending on the market wherein a St John's wort product is offered, it needs to fulfill the legal requirements regarding pharmaceutical quality, safety and efficacy. Our goal was to compare the quality of St John's wort products distributed in pharmacies with that of those available from supermarkets. Therefore, the quantity of the pharmaceutical active ingredients (the phloroglucinol derivate hyperforin, the flavonoids rutin, hyperoside, isoquercitrin, quercitrin and the biflavonoid biapigenin) was determined by high-performance liquid chromatography (HPLC). The naphthodianthrones hypericines and pseudohypericines were quantified by differential pulse polarography (DPP). The efficacy of the products was investigated by measuring their activity to inhibit serotonin (5-HT) uptake in-vitro using a radio ligand uptake assay. It could be demonstrated that the products were different not only in the concentration of pharmaceutically relevant ingredients but also in showing individual IC50 values (concentration producing half-maximal inhibition) in the serotonin reuptake assay (IC50 values between 3.07 and 17.9 microg extract mL(-1)). The results of our study confirm the assumption that the potency of St John's wort products in inhibiting the uptake of serotonin depends on the amount of hyperforin in their dosage forms. St John's wort products having greater hyperforin content and potency on synaptosomal serotonin uptake inhibition are restricted to be sold only in pharmacies.


Indirect transmission of Escherichia coli O157:H7 occurs readily among swine but not among sheep.
Transmission of Escherichia coli O157:H7 among reservoir animals is generally thought to occur either by direct contact between a naïve animal and an infected animal or by consumption of food or water containing the organism. Although ruminants are considered the major reservoir, there are two reports of human infections caused by E. coli O157:H7 linked to the consumption of pork products or to the contamination of fresh produce by swine manure. The objective of this study was to determine whether E. coli O157:H7 could be transmitted to naïve animals, both sheep and swine, that did not have any direct contact with an infected donor animal. We recovered E. coli O157:H7 from 10/10 pigs with nose-to-nose contact with the infected donor or animals adjacent to the donor and from 5/6 naïve pigs that were penned in the same room as the donor pig but 10 to 20 ft away. In contrast, when the experiment was repeated with sheep, E. coli O157:H7 was recovered from 4/6 animals that had nose-to-nose contact with the infected donor or adjacent animals and from 0/6 naïve animals penned 10 to 20 ft away from the donor. These results suggest that E. coli O157:H7 is readily transmitted among swine and that transmission can occur by the creation of contaminated aerosols.


Fourteen novel lipomycetaceous yeast species isolated from soil in Japan and transfer of Dipodascopsis anomala to the genus Babjevia based on ascospore production phenotype.
Fourteen novel lipomycetaceous yeasts species were isolated from soil samples collected from the Hokkaido, Chiba and Okinawa prefectures of Japan. Phylogenetic analyses of the D1/D2 domains of the large subunit rRNAs and translation elongation factor 1 alpha genes (TEF1-α) revealed that five strains of two species from the soil in Furano-shi, Hokkaido were related to Dipodascopsis anomala and 29 strains representing 12 species from soils in Kamogawa-shi, Chiba and Iriomote Island, Okinawa were in the Myxozyma clade. The two species of Dipodascopsis form globose or ellipsoid ascospores in their sac-like ascus and pseudohyphae. Furthermore, these species produce ascospores in their pseudohyphae and do not produce an acicular ascus, which is common among the three species including D. anomala. Therefore, we propose transferring D. anomala to the genus Babjevia and amending Babjevia. Two novel species were described and included in the genus Babjevia: Babjevia hyphoforaminiformans sp. nov. (holotype NBRC 111233; MycoBank no. MB 829051) and Babjevia hyphasca sp. nov. (holotype NBRC 112965; MycoBank no. MB 829053). The 12 species in the Myxozyma clade produce neither ascospores nor pseudohyphae and have different characteristics in assimilating several carbon sources from each other. Thus, we propose that the novel species of Lipomyces be classified as forma asexualis (f.a.). From Kamogawa-shi, Chiba (19 strains representing five species): Lipomyces melibiosiraffinosiphilus f.a., sp. nov. (holotype NBRC 111411; MycoBank no. MB 829034), Lipomyces kiyosumicus f.a., sp. nov. (holotype NBRC 111424; MycoBank no. MB 829035), Lipomyces chibensis f.a., sp. nov. (holotype NBRC 111413; MycoBank no. MB 829036), Lipomyces kamogawensis f.a., sp. nov. (holotype NBRC 112967; MycoBank no. MB 829037), Lipomyces amatsuensis f.a., sp. nov. (holotype NBRC 111420; MycoBank no. MB 829041). From Iriomote island, Okinawa (10 strains representing seven species): Lipomyces taketomicus f.a., sp. nov. (holotype NBRC 112966; MycoBank no. MB 829042), Lipomyces yaeyamensis f.a., sp. nov. (holotype NBRC 110433; MycoBank no. MB 829050), Lipomyces iriomotensis f.a., sp. nov. (holotype NBRC 110436; MycoBank no. MB 829045), Lipomyces haiminakanus f.a., sp. nov. (holotype NBRC 110435; MycoBank no. MB 829046), Lipomyces komiensis f.a., sp. nov. (holotype NBRC 110440; MycoBank no. MB 829047), Lipomyces nakamensis f.a., sp. nov. (holotype NBRC 110434; MycoBank no. MB 829048), Lipomyces sakishimensis f.a., sp. nov. (holotype NBRC 110439; MycoBank no. MB 829049).


Socio-Psychological Impacts of Hydraulic Fracturing on Community Health and Well-Being.
At the core of the hydraulic fracturing (fracking) debate is the level of perceived risk involved with extractive industries, such as the release of toxic and carcinogenic chemicals, increased population growth, and truck traffic. However, industry supporters of fracking acclaim the benefits of oil and gas drilling, such as energy independence and economic gains. In this study, we examine the perceived impacts of hydraulic fracturing (fracking) on community health and well-being based on interviews with anti-fracking activists in Denton, Texas who were active in the "anti-fracking" community organization, Frack Free Denton (FFD). Emergent from the interviews, we discuss the socio-psychological stressors these community members experienced following the introduction of hydraulic fracturing in the region. Some of the major socio-psychological impacts included perceived physical health risks through anxiety surrounding toxins and carcinogens that may be released through this process. Participants also discussed stress put on community relations, primarily through the form of an "us vs. them" mentality related to the support for, or opposition to, fracking in the community. Moreover, we found anxiety and stress surrounding trust in community members' relationships with governing bodies, such as the federal government, state government, and local governments. This research will allow for a more comprehensive understanding of how fracking can impact the socio-psychological well-being of the community.


[Estimating leaf area index by fusing MODIS and MISR data].
Moderate-resolution imaging spectrometer (MODIS) and multi-angle imaging spectroradiometer (MISR) are two important sensors on TERRA satellite. The authors can have more spectral and multi-angular observations on the land surface objects by combining these two datasets. In the present paper, both MODIS and MISR observations were combined to estimate leaf area index (LAI) of land surface. The adjoining model and trust-region optimal algorithm were introduced into the framework of physical model inversion to speed up the running of the model inversion algorithm. And the algorithm allows the prior knowledge on the retrieved parameters to be input into the inversion procedure. The uncertainty and sensitivity matrix (USM) based analysis is helpful for selecting the observed data subset with more information and less noise to retrieve LAI. The measured LAI in situ and estimated LAI from ETM data were scaling-up to MODIS/MISR LAI product scale, and were taken as the ground truth to evaluate the new approach. The result suggests that combining two sensors datasets can improve the accuracy of LAI estimation, and the developed inversion method in this paper can be applied to the large area remote sensed image data effectively.


HIV risk and preventive interventions in transgender women sex workers.
Worldwide, transgender women who engage in sex work have a disproportionate risk for HIV compared with natal male and female sex workers. We reviewed recent epidemiological research on HIV in transgender women and show that transgender women sex workers (TSW) face unique structural, interpersonal, and individual vulnerabilities that contribute to risk for HIV. Only six studies of evidence-based prevention interventions were identified, none of which focused exclusively on TSW. We developed a deterministic model based on findings related to HIV risks and interventions. The model examines HIV prevention approaches in TSW in two settings (Lima, Peru and San Francisco, CA, USA) to identify which interventions would probably achieve the UN goal of 50% reduction in HIV incidence in 10 years. A combination of interventions that achieves small changes in behaviour and low coverage of biomedical interventions was promising in both settings, suggesting that the expansion of prevention services in TSW would be highly effective. However, this expansion needs appropriate sustainable interventions to tackle the upstream drivers of HIV risk and successfully reach this population. Case studies of six countries show context-specific issues that should inform development and implementation of key interventions across heterogeneous settings. We summarise the evidence and knowledge gaps that affect the HIV epidemic in TSW, and propose a research agenda to improve HIV services and policies for this population.


Rates of molecular evolution and diversification in plants: chloroplast substitution rates correlate with species-richness in the Proteaceae.
Many factors have been identified as correlates of the rate of molecular evolution, such as body size and generation length. Analysis of many molecular phylogenies has also revealed correlations between substitution rates and clade size, suggesting a link between rates of molecular evolution and the process of diversification. However, it is not known whether this relationship applies to all lineages and all sequences. Here, in order to investigate how widespread this phenomenon is, we investigate patterns of substitution in chloroplast genomes of the diverse angiosperm family Proteaceae. We used DNA sequences from six chloroplast genes (6278bp alignment with 62 taxa) to test for a correlation between diversification and the rate of substitutions. Using phylogenetically-independent sister pairs, we show that species-rich lineages of Proteaceae tend to have significantly higher chloroplast substitution rates, for both synonymous and non-synonymous substitutions. We show that the rate of molecular evolution in chloroplast genomes is correlated with net diversification rates in this large plant family. We discuss the possible causes of this relationship, including molecular evolution driving diversification, speciation increasing the rate of substitutions, or a third factor causing an indirect link between molecular and diversification rates. The link between the synonymous substitution rate and clade size is consistent with a role for the mutation rate of chloroplasts driving the speed of reproductive isolation. We find no significant differences in the ratio of non-synonymous to synonymous substitutions between lineages differing in net diversification rate, therefore we detect no signal of population size changes or alteration in selection pressures that might be causing this relationship.


Positive regulation of c-Myc by cohesin is direct, and evolutionarily conserved.
Contact between sister chromatids from S phase to anaphase depends on cohesin, a large multi-subunit protein complex. Mutations in sister chromatid cohesion proteins underlie the human developmental condition, Cornelia de Lange syndrome. Roles for cohesin in regulating gene expression, sometimes in combination with CCCTC-binding factor (CTCF), have emerged. We analyzed zebrafish embryos null for cohesin subunit rad21 using microarrays to determine global effects of cohesin on gene expression during embryogenesis. This identified Rad21-associated gene networks that included myca (zebrafish c-myc), p53 and mdm2. In zebrafish, cohesin binds to the transcription start sites of p53 and mdm2, and depletion of either Rad21 or CTCF increased their transcription. In contrast, myca expression was strongly downregulated upon loss of Rad21 while depletion of CTCF had little effect. Depletion of Rad21 or the cohesin-loading factor Nipped-B in Drosophila cells also reduced expression of myc and Myc target genes. Cohesin bound the transcription start site plus an upstream predicted CTCF binding site at zebrafish myca. Binding and positive regulation of the c-Myc gene by cohesin is conserved through evolution, indicating that this regulation is likely to be direct. The exact mechanism of regulation is unknown, but local changes in histone modification associated with transcription repression at the myca gene were observed in rad21 mutants.


Formation of vascular S-nitrosothiols and plasma nitrates/nitrites following inhalation of diesel emissions.
Epidemiological studies have associated traffic-related airborne pollution with adverse cardiovascular outcomes. Nitric oxide (NO) is a common component of fresh diesel and gasoline engine emissions that rapidly transforms both in the atmosphere and once inhaled. Because of this rapid transformation, limited information is available in terms of potential human exposures and adverse health effects. Young rats were exposed to whole diesel emissions (DE) adjusted to 300 μg/m(3) of particulate matter (containing 3.5 ppm NO) or 0, 3, or 10 ppm NO as a positive control. Animals were also pre-injected (ip) with either saline or N-acetylcysteine (NAC), a precursor of glutathione. Predictably, pure NO exposures led to a concentration-dependent increase in plasma nitrates compared to controls, which lasted for roughly 4 h postexposure. Whole DE exposure for 1 h also led to a doubling of plasma NOx. NAC injection increased the levels of plasma nitrates and nitrites (NOx) in the DE exposure group. Inhibition of nitric oxide symthase (NOS) by N(G)-nitro-L-arginine (L-NNA) did not block the rise in plasma NOx, demonstrating that the increase was entirely due to exogenous sources. Both DE and pure NO exposures paradoxically led to elevated eNOS expression in aortic tissue. Furthermore, coronary arterioles from NO-exposed animals exhibited greater constriction to endothelin-1 compared to controls, consistent with a derangement of the NOS system. Thus, NO may be an important contributor to traffic-related cardiovascular morbidity, although further research is necessary for proper hazard identification.


Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 1. Discovery of a novel tool compound for in vivo proof-of-concept.
Small molecule activators of glucokinase have shown robust efficacy in both preclinical models and humans. However, overactivation of glucokinase (GK) can cause excessive glucose turnover, leading to hypoglycemia. To circumvent this adverse side effect, we chose to modulate GK activity by targeting the endogenous inhibitor of GK, glucokinase regulatory protein (GKRP). Disrupting the GK-GKRP complex results in an increase in the amount of unbound cytosolic GK without altering the inherent kinetics of the enzyme. Herein we report the identification of compounds that efficiently disrupt the GK-GKRP interaction via a previously unknown binding pocket. Using a structure-based approach, the potency of the initial hit was improved to provide 25 (AMG-1694). When dosed in ZDF rats, 25 showed both a robust pharmacodynamic effect as well as a statistically significant reduction in glucose. Additionally, hypoglycemia was not observed in either the hyperglycemic or normal rats.


Prenatal and Postnatal Medical Conditions and the Risk of Brain Tumors in Children and Adolescents: An International Multicenter Case-Control Study.
Previous studies have evaluated the effect of medical diagnostic radiation on brain tumors. Recent cohort studies have reported an increased risk associated with exposure to head CT scans. Information regarding medical conditions, including prenatal and postnatal exposure to medical diagnostic radiation, was obtained from CEFALO, a multicenter case-control study performed in Denmark, Norway, Sweden, and Switzerland through face-to-face interview. Eligible cases of childhood and adolescent brain tumors (CABT) were ages 7 to 19 years, diagnosed between January 1, 2004 and August 31, 2008, and living in the participating countries (n = 352). The cases were matched by age, sex, and region to 646 population-based controls. Prenatal exposure to medical diagnostic radiation and postnatal exposure to X-rays were not associated with CABTs. A higher risk estimate of CABTs, although not statistically significant, was found for exposure to head CT scan (OR, 1.86; 95% confidence interval, 0.82-4.22). The associations with head injury, febrile seizure, fever in the first 12 weeks, and general anesthesia were close to unity. Prenatal or postnatal medical conditions, including medical diagnostic radiation, were not associated with CABTs. On the basis of small numbers of exposed children, we observed a nonsignificant increased risk for CT scans of the head. We have presented additional evidence, suggesting that exposure to head CT scan may be associated with the occurrence of CABTs. Cancer Epidemiol Biomarkers Prev; 26(1); 110-5. ©2016 AACR.


Host immunoglobulin G and complement deposits in the choroid plexus during spontaneous immune complex disease.
Hybrid (NZB x W)F(1) mice spontaneously develop antibodies to nuclear antigens (ANA) and DNA (ADNA) and are an animal model of human systemic lupus erythematosus. Immunofluorescent and electron microscopic observations of the choroid plexus and renal glomeruli of (NZB x W)F(1) mice reveal deposits of host immunoglobulin G (IgG) and the third complement component which appear shortly after the development of ANA and ADNA in the circulation. Additionally, enhancement of ADNA responses accelerates the appearance and severity of IgG deposits in the choroid plexus. The choroid plexus may be a favored site for the deposition of immune complexes and the neuropsychiatric findings in patients with systemic lupus erythematosus and some patients with acute or chronic infections may be related in part to immune complex disease of the choroid plexus.


Visual attention in infants: a study of stimulus complexity, habituation, and sex differences.
A modification of Cohen's (1973) method was used to study responses to patterns of varying complexity in 4-mo.-old infants. Complexity in this context was defined in terms of the number of elements and the degree of internal contour contained in a given pattern. The infants were first presented with small red circles on two trials. This was followed by 16 trials of exposure to either 2 x 2 or 8 x 8 or 24 x 24 small red-circle matrix patterns which again were followed by two further exposures (trials) to the small red circle. Response decrement across trials was measured as a function of fixation, i.e., the duration of time the infant was judged to be looking at the stimulus, and latency, i.e., the time it took the infant to orient toward the stimulus pattern. Infants preferred the more complex patterns. All infants showed decrement in duration of fixation across trials for all three types of pattern. Latency of head turning did not change across trials but differed between pattern types. There were not significant sex differences in habituation rates as measured by duration of fixation and latency.


A descriptive study of the practice patterns of massage new zealand massage therapists.
Massage therapy has grown in popularity, yet little is known globally or in New Zealand about massage therapists and their practices. The aims of this study were to describe the practice patterns of trained Massage New Zealand massage therapists in New Zealand private practice, with regard to therapist characteristics; practice modes and settings, and therapy characteristics; referral patterns; and massage therapy as an occupation. A survey questionnaire was mailed to 66 trained massage therapist members of Massage New Zealand who were recruiting massage clients for a concurrent study of massage therapy culture. Most massage therapists were women (83%), NZ European (76%), and holders of a massage diploma qualification (89%). Massage therapy was both a full- (58%) and part-time (42%) occupation, with the practice of massage therapy being the only source of employment for 70% of therapists. Nearly all therapists (94%) practiced massage for more than 40 weeks in the year, providing a median of 16 - 20 hours of direct client care per week. Most massage therapists worked in a "solo practice" (58%) and used a wide and active referral network. Almost all therapists treated musculoskeletal symptoms: the most common client issues or conditions treated were back pain/problem (99%), neck/shoulder pain/problem (99%), headache or migraine (99%), relaxation and stress reduction (96%), and regular recovery or maintenance massage (89%). The most frequent client fee per treatment was NZ$60 per hour in a clinic and NZ$1 per minute at a sports event or in the workplace. Therapeutic massage, relaxation massage, sports massage, and trigger-point therapy were the most common styles of massage therapy offered. Nearly all massage therapists (99%) undertook client assessment; 95% typically provided self-care recommendations; and 32% combined other complementary and alternative medicine therapies with their massage consultations. This study provides new information about the practice of massage therapy by trained massage therapists. It will help to inform the massage industry and other health care providers, potential funders, and policymakers about the provision of massage therapy in the NZ health care system.


Ascorbic acid antagonizes the sedative effect of diazepam possibly through inhibition of GABA(Aρ₁) and GABA(B1) receptors.
Gamma-aminobutyric acid (GABA) receptors belong to a ligand-gated ion channels family and are markedly expressed at the axon terminals of retinal bipolar cells. Ascorbic acid (AA), a known and vital antioxidant in the brain can modulate GABA receptors. We postulate that AA would antagonize benzodiazepines' effect via GABA receptor(s) interacting pathway. Here, we evaluated the modulatory sedative effect of AA on diazepam (DZP)'s anxiolytic effects in Swiss albino mice. The anxiolytic study was accomplished by using open-field, hole-board, and by swing and light-dark tests taking DZP as a standard anxiolytic drug. To understand the possible modulatory effects of AA, animals were co-administered with AA and DZP and/or its antagonist flumazenil (FLU). Additionally, an in-silico study was undertaken against GABA(A1), GABA(B1), and GABA(Aρ₁) receptors. Data suggest that AA at 25 mg/kg (i.p.) increased (p<0.05) the number of field cross, rearing, number of hole cross, and swing and residence, while decreased grooming and dark residence parameters as compared to the control and DZP groups. In addition, AA and/or FLU combined with DZP (2 mg/kg, i.p.) reversed DZP-mediated sedative effects in mice. Results from in silico study suggest that AA has good interactions with GABA(Aρ₁) and GABA(B1) receptors. In conclusion, DZP is a GABA receptor agonist and AA may reverse DZP-mediated sedative effects in a non-competitive binding fashion in mice through inhibition of GABA(Aρ₁) and GABA(B1) receptors.


Sex ratio influences the motivational salience of facial attractiveness.
The sex ratio of the local population influences mating-related behaviours in many species. Recent experiments show that male-biased sex ratios increase the amount of financial resources men will invest in potential mates, suggesting that sex ratios influence allocation of mating effort in humans. To investigate this issue further, we tested for effects of cues to the sex ratio of the local population on the motivational salience of attractiveness in own-sex and opposite-sex faces. We did this using an effort-based key-press task, in which the motivational salience of facial attractiveness was assessed in samples of faces in which the ratio of male to female images was manipulated. The motivational salience of attractive opposite-sex, but not own-sex, faces was greater in the own-sex-biased (high competition for mates) than in the opposite-sex-biased (low competition for mates) condition. Moreover, this effect was not modulated by participant sex. These results present new evidence that sex ratio influences human mating-related behaviours. They also present the first evidence that the perceived sex ratio of the local population may modulate allocation of mating effort in women, as well as men.


Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity.
Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape1,2. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPR-Cas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH and KAP1 complexes as mediators of immune escape3-5. We also found that amplification of SETDB1 (1q21.3) in human tumours is associated with immune exclusion and resistance to immune checkpoint blockade. SETDB1 represses broad domains, primarily within the open genome compartment. These domains are enriched for transposable elements (TEs) and immune clusters associated with segmental duplication events, a central mechanism of genome evolution6. SETDB1 loss derepresses latent TE-derived regulatory elements, immunostimulatory genes, and TE-encoded retroviral antigens in these regions, and triggers TE-specific cytotoxic T cell responses in vivo. Our study establishes SETDB1 as an epigenetic checkpoint that suppresses tumour-intrinsic immunogenicity, and thus represents a candidate target for immunotherapy.


Repeat, Bilateral Femoral Nerve Blocks With Liposomal Bupivacaine for Analgesia in a Patient With Calciphylaxis: A Case Report.
A 39-year-old woman with juvenile idiopathic arthritis complicated by nonuremic calciphylaxis presented for pain management of bilateral lower extremity wounds requiring frequent dressing changes. Bilateral single-shot femoral nerve blocks using liposomal bupivacaine and 0.25% bupivacaine were performed. The patient reported decreased pain scores and had reduced opioid use for 72 hours postblock. Repeat, bilateral single-shot femoral nerve blocks with liposomal bupivacaine and 0.25% bupivacaine were performed approximately every 72 hours to maintain adequate analgesia. We conclude that off-label use of liposomal bupivacaine in femoral nerve blocks results in prolonged block duration without adverse effects or tachyphylaxis.


Detection of Arbovirus Transmission via Sugar Feeding in a Laboratory Setting.
Most species of mosquitoes consume sugar to survive and during sugar feeding can expectorate virus. Scientists have used this behavior to develop novel methods of mosquito control and arbovirus surveillance. In this study, we use sugar feeding and corresponding viral expectoration to develop an affordable method of monitoring individual mosquitoes for longitudinal data collection. Female Culex tarsalis Coquillett (Diptera: Culicidae) that consumed an infectious bloodmeal of West Nile virus were placed into separate containers and offered a sucrose-soaked cotton wick. Wicks were then collected daily and tested for virus with similar results to those from standard capillary tube method. This yielded a direct longitudinal estimate of the extrinsic incubation period, while using fewer mosquitoes. This approach could be used to further characterize variation in the amount and diversity of expectorated virus over the life span of individual mosquitoes.


Malignant haemangiopericytoma of the mesorectum.
The authors report the case of a malignant haemangiopericytoma found in an uncommon location, namely the mesorectum. Haemangiopericytomas of the mesorectum are rare mesenchymal tumours of vascular origin that usually occur in the musculature of the extremities, retroperitoneum, pelvis (uterus, ovary and urinary bladder), head, neck and lungs. Rare sites include the liver, pancreas, stomach and greater omentum. Because of their rarity the overall experience has not been significant and little has been published concerning such tumours. In addition, the difficult interpretation of the histological evidence and the poor prognosis of the disease may still give rise to problems in terms of clinical management. Haemangiopericytomas of the retrorectal space, however, seem to behave like malignant tumours: the clinical course is poor and survival short, despite radical surgery, due to early distant metastases and local recurrence. Surgery still remains the mainstay of treatment. Adjuvant therapies should be considered.


Intrauterine growth retardation and nonalcoholic Fatty liver disease in children.
Intrauterine growth retardation (IUGR), the most important cause of perinatal mortality and morbidity, is defined as a foetal growth less than normal for the population, often used as synonym of small for gestational age (SGA). Studies demonstrated the relationships between metabolic syndrome (MS) and birthweight. This study suggested that, in children, adolescents, and adults born SGA, insulin resistance could lead to other metabolic disorders: type 2 diabetes (DM2), dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). NAFLD may evolve to nonalcoholic steatohepatitis (NASH), and it is related to the development of MS. Lifestyle intervention, physical activity, and weight reduction represent the mainstay of NAFLD therapy. In particular, a catch-up growth reduction could decrease the risk to develop MS and NAFLD. In this paper, we outline clinical and experimental evidences of the association between IUGR, metabolic syndrome, insulin resistance, and NAFLD and discuss on a possible management to avoid the risk of MS in adulthood.


Coordination between Prefrontal Cortex Clock Gene Expression and Corticosterone Contributes to Enhanced Conditioned Fear Extinction Recall.
Post-traumatic stress disorder (PTSD) is associated with impaired conditioned fear extinction learning, a ventromedial prefrontal cortex (vmPFC)-dependent process. PTSD is also associated with dysregulation of vmPFC, circadian, and glucocorticoid hormone function. Rats have rhythmic clock gene expression in the vmPFC that requires appropriate diurnal circulatory patterns of corticosterone (CORT), suggesting the presence of CORT-entrained intrinsic circadian clock function within the PFC. We examined the role of vmPFC clock gene expression and its interaction with CORT profiles in regulation of auditory conditioned fear extinction learning. Extinction learning and recall were examined in male rats trained and tested either in the night (active phase) or in the day (inactive phase). Using a viral vector strategy, Per1 and Per2 clock gene expression were selectively knocked down within the vmPFC. Circulating CORT profiles were manipulated via adrenalectomy (ADX) ± diurnal and acute CORT replacement. Rats trained and tested during the night exhibited superior conditioned fear extinction recall that was absent in rats that had knock-down of vmPFC clock gene expression. Similarly, the superior nighttime extinction recall was absent in ADX rats, but restored in ADX rats given a combination of a diurnal pattern of CORT and acute elevation of CORT during the postextinction training consolidation period. Thus, conditioned fear extinction learning is regulated in a diurnal fashion that requires normal vmPFC clock gene expression and a combination of circadian and training-associated CORT. Strategic manipulation of these factors may enhance the therapeutic outcome of conditioned fear extinction related treatments in the clinical setting.


Quantitation of Taura syndrome virus by real-time RT-PCR with a TaqMan assay.
A real-time RT-PCR assay was developed using a TaqMan probe to detect and quantify Taura syndrome virus (TSV) in penaeid shrimp. A pair of RT-PCR primers, which amplify a 72 bp DNA fragment, and a TaqMan probe were selected from open reading frame 1 (ORF1) of the TSV genome. The primers and TaqMan probe used in this assay reacted with TSV isolates from Hawaii, Texas, Colombia, Mexico, Belize, Indonesia, and Thailand, but neither with RNA of healthy shrimp nor with an isolate of yellow head virus. A plasmid (pTSV-1) that contains the target TSV sequence was constructed and used to generate positive control RNA through in vitro transcription. The positive control RNA was used to demonstrate that the real-time RT-PCR assay has a detection limit of 100 copies and a log-linear range up to 10(8) copies of TSV RNA. This quantitative method was found to be highly reproducible, with low intra- and inter-assay variation. Coefficient of variation (CVs) values were 0.04-8.9 and 0.05-3.7%, respectively, for replicates within and among assays. This assay was used to quantify TSV in both acutely and chronically infected shrimp in a laboratory experiment. The quantities of TSV in the tissues of pleopods and gills were not significantly different, and there was no difference in TSV levels between the acutely and chronically infected groups. However, in the chronically infected shrimp, the quantities of TSV were one to two orders of magnitude higher in the lymphoid organ than in either gills or pleopods. This assay proved to be specific with high sensitivity, and it can be used to detect and quantify TSV in shrimp samples.


Diversity and specificity of microsatellites within Aspergillus section Fumigati.
Microsatellites (or short tandem repeats, STRs) are the genetic markers of choice for studying Aspergillus fumigatus molecular epidemiology due to its reproducibility and high discrimination power. However, the specificity of these markers must be investigated in a group of isolates from closely related species. The aim of this work was to test a microsatellite-based PCR multiplex previously designed for A. fumigatus in a set of species belonging to section Fumigati, namely Aspergillus fumigatiaffinis, Aspergillus lentulus, Aspergillus novofumigatus, Aspergillus unilateralis, Aspergillus viridinutans, Neosartorya fischeri, Neosartorya hiratsukae, Neosartorya pseudofischeri and Neosartorya udagawae. The reference A. fumigatus strain ATCC 46645 was easily genotyped in standard conditions showing a final electrophoretic profile of 8 expected peaks corresponding to each microsatellite locus. Inversely, no peaks were observed for all other species from section Fumigati, with an exception for marker MC6b in A. unilateralis. By screening the genome sequence of Neosartorya fischeri NRRL 181, the results showed that MC3, MC6a and MC7 might be employed for N. fischeri genotyping since these markers present several repeats of each motif. The accumulation of insertions and deletions was frequently observed in the genomic regions surrounding the microsatellites, including those where the A. fumigatus primers are located. The amplification of microsatellite markers in less stringent amplification conditions resulted in a distinct electrophoretic profile for species within section Fumigati. Therefore, the microsatellite-based PCR multiplex allow simple identification of A. fumigatus and, with a slight modification of temperature conditions, it also allows discriminating other pathogenic species within section Fumigati, particularly A. fumigatiaffinis, N. fischeri and N. udagawae.


Meta-analysis of progesterone supplementation during timed artificial insemination programs in dairy cows.
A systematic review of the literature was performed with the objective to evaluate the effects of progesterone supplementation using a single intravaginal insert during timed artificial insemination (AI) programs on fertility in lactating dairy cows. A total of 25 randomized controlled studies including 8,285 supplemented cows and 8,398 untreated controls were included in the meta-analysis. Information regarding the presence of corpus luteum (CL) at the initiation of the synchronization protocol was available for 6,883 supplemented cows and 6,879 untreated controls in 21 experiments. Studies were classified based on service number (first AI vs. resynchronized AI), use of presynchronization (yes vs. no), and insemination of cows in estrus during the synchronization protocol (inseminated in estrus and timed AI vs. timed AI only). Reproductive outcomes of interest were pregnancy per AI (P/AI) measured on d 32 (27 to 42) and 60 (41 to 71) after AI, and pregnancy loss between d 32 and 60 of gestation. Random effects meta-analyses were conducted and treatment effect was summarized into a pooled risk ratio with the Knapp-Hartung modification (RRK+H). The effect of moderator variables was assessed using meta-regression analyses. Progesterone supplementation increased the risk of pregnancy on d 32 [RRK+H = 1.08; 95% confidence interval (CI) = 1.02-1.14] and 60 after AI (RRK+H = 1.10; 95% CI = 1.03-1.17). The benefit of progesterone supplementation was observed mainly in cows lacking a CL at the initiation of the timed AI program (d 60: RRK+H = 1.18; 95% CI = 1.07-1.30) rather than those with CL (d 60: RRK+H = 1.06; 95% CI = 0.99-1.12). Progesterone supplementation benefited P/AI in studies in which all cows were inseminated at timed AI (d 60: RRK+H = 1.20; 95% CI = 1.10-1.29), but not in studies in which cows could be inseminated in estrus during the timed AI program (d 60: RRK+H = 1.04; 95% CI = 0.92-1.16). Progesterone supplementation tended to reduce the risk of pregnancy loss (RRK+H = 0.84; 95% CI = 0.67-1.00). Service number and presynchronization did not influence the effect of progesterone supplementation on fertility. In summary, progesterone supplementation using a single intravaginal insert during the timed AI program increased P/AI mostly in cows without CL and reduced the risk of pregnancy loss in lactating dairy cows. Insemination of cows in estrus during the synchronization protocol eliminated the benefit of supplemental progesterone on P/AI.


Roles of FAK family kinases in nervous system.
Focal adhesion kinase (FAK) and its related kinase, proline rich tyrosine kinase 2 (PYK2), are major kinases activated by cell-extracellular matrix adhesion. Although they are highly expressed in the nervous system, the functions of these two kinases in the nervous system remained unclear until recently. FAK and PYK2 appear to play an important role in developing nervous system as well as adult brain. Importantly the two kinases are activated by different extracellular stimuli and execute distinct regulatory effects on various aspects of neural developmental processes and neuronal function. This review summarizes the potential roles of FAK and PYK2 in axon path-finding and synaptic plasticity.


Interoperability of population-based patient registries.
Enabling full interoperability within and between population-based patient-registry domains would open up access to a rich and unique source of health data for secondary data usage. Previous attempts to tackle patient-registry interoperability have met with varying degrees of success, but a unifying solution remains elusive. The purpose of this paper is to show by practical example how a solution is attainable via the implementation of an existing framework based of the concept of federated, semantic metadata registries. One important feature motivating the use of this framework is that it can be implemented gradually and independently within each patient-registry domain. By employing linked open data principles, the framework extends the ISO/IEC 11179 standard to provide both syntactic and semantic interoperability of data elements with the means of specifying automated extraction scripts for retrieval of data from different registry content models. The examples provided address the domain of European population-based cancer registries to demonstrate the feasibility of the approach. One of the examples shows how quick gains are derivable by allowing retrieval of aggregated core data sets. The other examples show how aggregated full sets of data and record-level data might also be retrieved from each local registry. An infrastructure of patient-registry domains adhering to the principles of the framework would provide the semantic contexts and inter-linkage of data necessary for automated search and retrieval of registry data. It would thereby also lay the foundation for making registry data serviceable to artificial intelligence (AI) applications.


Concentration, working speed and memory: cognitive problems in young childhood cancer survivors and their siblings.
Cognitive problems can have a negative effect on a person's education, but little is known about cognitive problems in young childhood cancer survivors (survivors). This study compared cognitive problems between survivors and their siblings, determined if cognitive problems decreased during recent treatment periods and identified characteristics associated with the presence of a cognitive problem in survivors. As part of the Swiss Childhood Cancer Survivor Study, a questionnaire was sent to all survivors, aged 8-20 years, registered in the Swiss Childhood Cancer Registry, diagnosed at age <16 years, who had survived ≥ 5 years. Parent-reported (aged 8-15 years) and self-reported (aged 16-20 years) cognitive problems (concentration, working speed, memory) were compared between survivors and siblings. Multivariable logistic regression was used to identify characteristics associated with cognitive problems in survivors. Data from 840 survivors and 247 siblings were analyzed. More often than their siblings, survivors reported problems with concentration (12% vs. 6%; P = 0.020), slow working speed (20% vs. 8%; P = 0.001) or memory (33% vs. 15%; P < 0.001). Survivors from all treatment periods were more likely to report a cognitive problem than were siblings. Survivors of CNS tumors (OR = 2.82 compared to leukemia survivors, P < 0.001) and those who had received cranial irradiation (OR = 2.10, P = 0.010) were most severely affected. Childhood cancer survivors, even those treated recently (2001-2005), remain at risk to develop cognitive problems, suggesting a need to improve therapies. Survivors with cognitive problems should be given the opportunity to enter special education programs.


Two-dimensional van der Waals C60 molecular crystal.
Two-dimensional (2D) atomic crystals, such as graphene and transition metal dichalcogenides et al. have drawn extraordinary attention recently. For these 2D materials, atoms within their monolayer are covalently bonded. An interesting question arises: Can molecules form a 2D monolayer crystal via van der Waals interactions? Here, we first study the structural stability of a free-standing infinite C60 molecular monolayer using molecular dynamic simulations, and find that the monolayer is stable up to 600 K. We further study the mechanical properties of the monolayer, and find that the elastic modulus, ultimate tensile stress and failure strain are 55-100 GPa, 90-155 MPa, and 1.5-2.3%, respectively, depending on the stretching orientation. The monolayer fails due to shearing and cavitation under uniaxial tensile loading. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the monolayer are found to be delocalized and as a result, the band gap is reduced to only 60% of the isolated C60 molecule. Interestingly, this band gap can be tuned up to ±30% using strain engineering. Owing to its thermal stability, low density, strain-tunable semi-conducting characteristics and large bending flexibility, this van der Waals molecular monolayer crystal presents aplenty opportunities for developing novel applications in nanoelectronics.


The international physical activity questionnaire overestimates moderate and vigorous physical activity in HIV-infected individuals compared with accelerometry.
This study evaluates the validity of the last-7-day, self-administered version of the International Physical Activity Questionnaire (IPAQ) long form in HIV-infected people, using accelerometry as the objective criterion. The ActiGraph GT1M accelerometer was worn during all waking hours for 7 days, and the IPAQ was completed on day 7. A total of 30 men were recruited as participants from the Alfred Infectious Disease Clinic, Melbourne, Australia. Self-reported total number of metabolic equivalents minutes per week correlated moderately with accelerometer total activity counts (r = .41, p = .02). However, mean differences showed overreporting with the questionnaire; 546.63 min/wk (95% confidence interval: 217.1-871.2 minutes) for moderate and 295.33 min/wk (95% confidence interval: 88.08-502.6 minutes) for vigorous activity. The IPAQ correlated with accelerometry, but substantial overreporting occurred. The tool may be useful in screening physical activity but should not be used to determine precise levels.


Analysis of particle content of recombinant adeno-associated virus serotype 8 vectors by ion-exchange chromatography.
Advances in adeno-associated virus (AAV)-mediated gene therapy have brought the possibility of commercial manufacturing of AAV vectors one step closer. To realize this prospect, a parallel effort with the goal of ever-increasing sophistication for AAV vector production technology and supporting assays will be required. Among the important release assays for a clinical gene therapy product, those monitoring potentially hazardous contaminants are most critical for patient safety. A prominent contaminant in many AAV vector preparations is vector particles lacking a genome, which can substantially increase the dose of AAV capsid proteins and lead to possible unwanted immunological consequences. Current methods to determine empty particle content suffer from inconsistency, are adversely affected by contaminants, or are not applicable to all serotypes. Here we describe the development of an ion-exchange chromatography-based assay that permits the rapid separation and relative quantification of AAV8 empty and full vector particles through the application of shallow gradients and a strong anion-exchange monolith chromatography medium.


Differential expression and function of synaptotagmin 1 isoforms in Caenorhabditis elegans.
Synaptotagmin 1, encoded by the snt-1 gene in Caenorhabditis elegans, is a major synaptic vesicle protein containing two Ca(2+)-binding (C2) domains. Alternative splicing gives rise to two synaptotagmin 1 isoforms, designated SNT-1A and SNT-1B, which differ in amino acid sequence in the third, fourth, and fifth beta-strands of the second C2 domain (C2B). We report here that expression of either SNT-1 isoform under control of a strong pan-neural promoter fully rescues the snt-1 null phenotype. Furthermore, C-terminal fusions of either isoform with GFP are trafficked properly to synapses and are fully functional, unlike synaptotagmin 1Colon, two colonsGFP fusions in mice. Analysis of isoform expression with genomic GFP reporter constructs revealed that the SNT-1A and-1B isoforms are differentially expressed and localized in the C. elegans nervous system. We also report molecular, behavioral, and immunocytochemical analyses of twenty snt-1 mutations. One of these mutations, md259, specifically disrupts expression of the SNT-1A isoform and has defects in a subset of synaptotagmin 1-mediated behaviors. A second mutation, md220, is an in-frame 9-bp deletion that removes a conserved tri-peptide sequence (VIL) in the second beta-strand of the C2B domain and disrupts the proper intracellular trafficking of synaptotagmin. Site-directed mutagenesis of a functional SNT-1Colon, two colonsGFP fusion protein was used to examine the potential role of the VIL sequence in synaptotagmin trafficking. Although our results suggest the VIL sequence is most likely not a specific targeting motif, the use of SNT-1Colon, two colonsGFP fusions has great potential for investigating synaptotagmin trafficking and localization.


Recognition of duplex RNA by helix-threading peptides.
Many important biological processes, from the interferon antiviral response to the generation of microRNA regulators of translation, involve duplex RNA. Small molecules capable of binding duplex RNA structures with high affinity and selectivity will be useful in regulating these processes and, as such, are valuable research tools and potentially therapeutic. In this paper, the synthesis and duplex RNA-binding properties of EDTA.Fe-modified peptide-intercalator conjugates (PICs) are described. Peptide appendages at the 4- and 9-positions of the planar acridine ring system render these PICs threading intercalators, directing the substituents into both grooves of double helical RNA simultaneously. Directed hydroxyl radical cleavage experiments conducted with varying RNA stem-loop structures indicate a preferred binding polarity with the N- and C-termini of the PIC in the minor and major grooves, respectively. However, this binding polarity is shown to be dependent on both the structure of the PIC and the RNA secondary structure adjacent to the intercalation site. Definition of the minimal RNA structure required for binding to one of these PICs led to the identification of an intercalation site in a pre-microRNA from Caenorhabditis elegans. Results presented will guide both rational design and combinatorial approaches for the generation of new RNA binding PICs and will continue to facilitate the identification of naturally occurring RNA targets for these small molecules.


Social organization of self-management support of persons with diabetes: a health systems comparison.
Identify important organizational elements for providing self-management support (SMS). Semi-structured qualitative interviews conducted in two healthcare systems. Kaiser Permanente Northern California and the Danish Health Care System. 36 managers and healthcare professionals in the two healthcare systems. Elements important to providing self-management support to persons with diabetes. Healthcare professionals' provision of SMS was influenced by healthcare system organization and their perceptions of SMS, the capability and responsibility of healthcare systems, and their roles in the healthcare organization. Enabling factors for providing SMS included: strong leadership; aligned incentives; use of an integrated health information technology (HIT) system; multidisciplinary healthcare provider teams; ongoing training for healthcare professionals; outreach; and quality goals. Barriers to providing SMS included lack of collaboration between providers and skeptical attitudes towards prevention and outreach. Implementation of SMS can be improved by an understanding of the elements that enhance its provision: (1) initiatives seeking to improve collaboration and integration between providers; (2) implementation of an integrated HIT system; and (3) ongoing training of healthcare professionals.


Associations of maternal motor vehicle crashes during pregnancy with offspring's neonatal birth outcomes.
Adverse events in fetuses are well researched but studies on the follow-up health outcomes of infants exposed to maternal motor vehicle crashes (MVCs) during pregnancy have yielded inconsistent results. This study aimed to investigate the association of maternal exposure to MVCs during pregnancy with the risk of adverse neonatal outcomes. This population-based cohort study used data from birth notifications in Taiwan. A total of 19 277 offspring with maternal exposure to MVCs during pregnancy and 76 015 randomly selected comparison offspring without such exposure were selected. Neonatal adverse outcomes were identified from National Health Insurance medical claims data. Conditional logistic regression was used to estimate the unadjusted and adjusted odds ratios (aORs) of neonatal adverse outcomes. Offspring exposed to maternal MVCs during pregnancy had a higher risk of birth defects (aOR, 1.21; 95% CI, 1.04-1.41) than offspring without such exposure. This positive association was sustained with exposure to an MVC during the first or second trimester. A dose-response relationship (P = 0.0023) was observed between the level of injury severity and the risk of birth defects. In the early stages of pregnancy, maternal exposure to MVCs may entail a risk of birth defects in the offspring. The potential mechanisms for the associations of maternal exposure to MVCs with birth defects need further investigation.


The adrenal gland: common disease states and suspected new applications.
The adrenal gland, while small in size, provides a major punch to human metabolism. The interplay between the adrenal cortex hormones aldosterone and cortisol provides needed regulation to human metabolism. Aldosterone regulates the body sodium content affecting blood pressure thru fluid-volume regulation by the kidney. Cortisol, also from the adrenal cortex, contributes to regulation of glucose and protein metabolism. Diseases like addison's disease and Cushing's syndrome that affect the normal levels of these hormones can lead to serious pathologies that need to be detected thru clinical laboratory testing. The inner core of the adrenal gland, called the medulla, houses the catecholamine epinephrine, a fast acting neuropeptide hormone that can influence body action and energy levels quickly. The pheochromocytomas pathology of the adrenal medulla adversely affects the medulla hormones and needs to be recognized by clinical laboratory testing. The overview of the adrenal gland and its potential pathologies needs to be looked at anew in relation to post-traumatic stress disorder to find any linkage that may aid in the treatment and cure of our affected military soldiers. This interrelationship between cortisol and epinephrine in PTSD should be closely evaluated to determine if the suspected linkages are significant.


Fusidic acid and clindamycin resistance in community-associated, methicillin-resistant Staphylococcus aureus infections in children of Central Greece.
In Greece, fusidic acid and clindamycin are commonly used for the empiric therapy of suspected staphylococcal infections. The medical records of children examined at the outpatient clinics or admitted to the pediatric wards of the University General Hospital of Larissa, Central Greece, with community-associated staphylococcal infections from January 2003 to December 2009 were reviewed. Of 309 children (0-14 years old), 21 (6.8%) had invasive infections and 288 (93.2%) skin and soft tissue infections (SSTIs). Thirty-five patients were ≤30 days of age. The proportion of staphylococcal infections caused by a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate increased from 51.5% (69 of 134) in 2003-2006 to 63.4% (111 of 175) in 2007-2009 (P = 0.037). Among the CA-MRSA isolates, 88.9% were resistant to fusidic acid, 77.6% to tetracycline, and 21.1% to clindamycin. Clindamycin resistance increased from 0% (2003) to 31.2% (2009) among the CA-MRSA isolates (P = 0.011). Over the 7-year period, an increase in multidrug-resistant CA-MRSA isolates was observed (P = 0.004). One hundred and thirty-one (93.6%) of the 140 tested MRSA isolates were Panton-Valentine leukocidin-positive. Multilocus sequence typing of 72 CA-MRSA isolates revealed that they belonged to ST80 (n = 61), ST30 (n = 6), ST377 (n = 3), ST22 (n = 1), and ST152 (n = 1). Resistance to fusidic acid was observed in ST80 (58/61), ST30 (1/6), and ST22 (1/1) isolates. In areas with high rate of infections caused by multidrug-resistant CA-MRSA isolates, predominantly belonging to the European ST80 clone, fusidic acid and clindamycin should be used cautiously as empiric therapy in patients with suspected severe staphylococcal infections.


JMJD2B-induced amino acid alterations enhance the survival of colorectal cancer cells under glucose-deprivation via autophagy.
Rationale: Post-translational modifications have emerged as vital players in alterations to tumor metabolism, including amino acid metabolic reprogramming. Jumonji domain-containing protein 2B (JMJD2B) enhances colorectal cancer (CRC) cell survival upon glucose deficiency. In the present study, we hypothesized that JMJD2B affects tumor cell amino acid metabolism in CRC and consequently promotes survival of CRC cells upon glucose deprivation. Methods: Non-target metabolic profiling was used to evaluate the roles of JMJD2B in CRC cell metabolism under glucose starvation. The roles of amino acid alterations induced by JMJD2B on CRC cell survival were determined by cell viability, immunoblotting, and clonogenic assays, and flow cytometry. The underlying mechanisms by which JMJD2B affected CRC cell metabolism were assessed using immunofluorescence staining, chromatin immunoprecipitation assays, electron microscopy in CRC cell lines, and using xenograft models. The correlation between JMJD2B and LC3B expression in human CRC specimens was assessed using immunohistochemistry. Results: Profound metabolic reprogramming was detected in JMJD2B knockdown CRC cells under glucose deficiency, especially those involving amino acid metabolites. Silencing of JMJD2B reduced the levels of certain amino acids that were induced by glucose deficiency. Among these amino acids, asparagine (Asn), phenylalanine (Phe), and histidine (His) promoted CRC cell survival under glucose starvation when JMJD2B was knocked down. Mechanistically, downregulation of JMJD2B inhibited autophagy in CRC cells through epigenetic regulation of microtubule associated protein 1 light chain 3 beta (LC3B), and subsequently decreased intracellular amino acid (Asn, Phe, His) levels under glucose deprivation, thus suppressing the survival of CRC cells. Using a nude mouse xenograft model, we verified that inhibiting JMJD2B could decrease the levels of amino acids (Asn, Phe, His). In addition, the inhibitory effects of JMJD2B-knockdown on tumor growth and amino acids level were rescued by overexpression of LC3B. Furthermore, we observed that the high expression of LC3B was more likely detected in tissuses with high expression of JMJD2B (P < 0.001) in 60 human CRC tissues. Conclusion: These results indicated that JMJD2B sustained the intracellular amino acids derived from autophagy in CRC cells upon glucose deficiency, partly through epigenetic regulation of LC3B, thus driving the malignancy of CRC.


Microcapsules as bio-organs for somatic gene therapy.
Current human gene therapy relies on genetic modification of the patient's own cells. An alternate non-autologous approach is to use universal cell lines engineered to secrete therapeutic products. Protection with immuno-isolation devices would allow the same recombinant cell line to be used for different patients, thus potentially lowering the cost of treatment. The feasibility of this idea has now been demonstrated in vitro and in vivo. Recombinant gene products with potential therapeutic applications (human growth hormone, factor IX, lysosomal enzymes, adenosine deaminase) have been expressed from genetically modified cells after encapsulation with alginate-poly-L-lysine-alginate or hydroxyethyl methacrylate-methyl methacrylate. We have also demonstrated the feasibility of this idea in vivo. After intraperitoneal implantation, genetically modified mouse Ltk- fibroblasts or C2C12 myoblasts encapsulated in alginate-poly-L-lysine-alginate could deliver recombinant gene products (human growth hormone, human factor IX) to the systemic circulation of mice. The clinical efficacy of this novel approach to gene therapy has now been shown in murine models of human diseases. In the Snell dwarf mice deficient in growth hormone production, implantation of encapsulated mouse myoblasts engineered to secrete mouse growth hormone resulted in increases in body weight, length and organ sizes, some to > 25% above those of the controls. In the Gus/Gus mice suffering from the lysosomal storage disease mucopolysaccharidosis type VII due to deficient beta-glucuronidase, implantation of encapsulated mouse fibroblasts engineered to secrete mouse beta-glucuronidase resulted in delivery of normal levels of the enzyme in the plasma and significant correction of the organ histopathology. Hence, delivery of recombinant gene products through bioartificial devices appears to be a promising strategy for the treatment of genetic diseases.


Multiple behavioural impulsivity tasks predict prospective alcohol involvement in adolescents.
We investigated reciprocal prospective relationships between multiple behavioural impulsivity tasks (assessing delay discounting, risk-taking and disinhibition) and alcohol involvement (consumption, drunkenness and problems) among adolescents. We hypothesized that performance on the tasks would predict subsequent alcohol involvement, and that alcohol involvement would lead to increases in behavioural impulsivity over time. Cross-lagged prospective design in which impulsivity and alcohol involvement were assessed five times over 2 years (once every 6 months, on average). Classrooms in secondary schools in North West England. Two hundred and eighty-seven adolescents (51.2% male) who were aged 12 or 13 years at study enrolment. Participants reported their alcohol involvement and completed computerized tasks of disinhibition, delay discounting and risk-taking at each assessment. Cross-sectional and prospective relationships between the variables of interest were investigated using cross-lagged analyses. All behavioural impulsivity tasks predicted a composite index of alcohol involvement 6 months later (all Ps < 0.01), and these prospective relationships were reliable across the majority of time-points. Importantly, we did not observe the converse relationship across time: alcohol involvement did not predict performance on behavioural impulsivity tasks at any subsequent time point. Several measures of impulsivity predict escalation in alcohol involvement in young adolescents, but alcohol use does not appear to alter impulsivity.


An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission.
The endosomal sorting complex required for transport-III (ESCRT-III) catalyzes membrane fission from within membrane necks, a process that is essential for many cellular functions, from cell division to lysosome degradation and autophagy. How it breaks membranes, though, remains unknown. Here, we characterize a sequential polymerization of ESCRT-III subunits that, driven by a recruitment cascade and by continuous subunit-turnover powered by the ATPase Vps4, induces membrane deformation and fission. During this process, the exchange of Vps24 for Did2 induces a tilt in the polymer-membrane interface, which triggers transition from flat spiral polymers to helical filament to drive the formation of membrane protrusions, and ends with the formation of a highly constricted Did2-Ist1 co-polymer that we show is competent to promote fission when bound on the inside of membrane necks. Overall, our results suggest a mechanism of stepwise changes in ESCRT-III filament structure and mechanical properties via exchange of the filament subunits to catalyze ESCRT-III activity.


Keeping it in the family: intergenerational transmission of violence in Cebu, Philippines.
While witnessing violence between parents is one of the most consistent correlates of experiencing intimate partner violence (IPV) in later life, little research exists in developing countries on the effects of witnessing interparental IPV on young adults' involvement with family violence. This study examines the relation between witnessing interparental IPV and young adults' subsequent use and experience with family intimidation and physical abuse (FIPA) in Cebu, Philippines. Using data from the Cebu Longitudinal Health and Nutrition Survey, recent use and experience of FIPA among 21-22 year old young adults was assessed through self-reports from the 2005 survey, and childhood witnessing of interparental IPV assessed from the 2002 survey. Multinomial logistic regression was used to examine the effect of witnessing interparental IPV on young adults' use and experience of FIPA. Among all young adults, witnessing paternal perpetration of IPV predicted using FIPA, and witnessing maternal perpetration predicted experiencing FIPA. Among young adult females only, witnessing reciprocal IPV between parents predicted experiencing FIPA. Witnessing paternal perpetration of IPV among young adult males, maternal perpetration among young adult females, and reciprocal interparental IPV among all young adults predicted young adults both using and experiencing FIPA. Violence prevention efforts should reach all family members through family centered interventions. School based curricula, which largely focus on intimate partner and peer violence, should recognize adolescents' use and experience of violence with family members, and design modules accordingly. Further research on gender differences in family violence is recommended.


Obstetric outcomes of pregnancy complicated by urolithiasis: a retrospective cohort study.
Evaluate the association between urolithiasis during pregnancy and obstetric outcomes outside the context of urological intervention. We conducted a retrospective cohort study of singleton, non-anomalous gestations delivered at 23-42 weeks in California from 2007 to 2011. Maternal outcomes (preterm delivery [early (<32 weeks) and late (<37 weeks)], preeclampsia, gestational diabetes, cesarean deliveries, urinary tract infection [UTI] at delivery, chorioamnionitis, endomyometritis, and maternal sepsis) and newborn outcomes (seizure, respiratory distress syndrome, hypoglycemia, jaundice, and neonatal abstinence syndrome [NAS]) were compared using χ2-tests and multivariable logistic regression. A total of 2,013,767 pregnancies met inclusion criteria, of which 5,734 (0.28%) were complicated by urolithiasis. Stone disease during pregnancy was associated with 30% greater odds of each early (aOR 1.30; 95% CI 1.19-1.43) and late (aOR 1.29; 95% CI 1.18-1.41) preterm delivery. Cesarean delivery, UTI at delivery, gestational hypertension, gestational diabetes, preeclampsia, and sepsis were all significantly positively associated with urolithiasis. Odds of NAS (aOR 2.11; 95% CI 1.27-3.51) and jaundice were significantly greater in the neonates of stone-forming patients (aOR 1.08; 95% CI 1.01-1.16). Urolithiasis during pregnancy was associated with 30% greater odds of preterm delivery and increased risk of myriad metabolic, hypertensive, and infectious disorders of gestation. Neonates born to stone-forming patients were more than twice as likely to develop neonatal abstinence syndrome but did not have significantly greater odds of complications of prematurity.


Femoral strength is better predicted by finite element models than QCT and DXA.
Clinicians and patients would benefit if accurate methods of predicting and monitoring bone strength in-vivo were available. A group of 51 human femurs (age range 21-93; 23 females, 28 males) were evaluated for bone density and geometry using quantitative computed tomography (QCT) and dual energy X-ray absorptiometry (DXA). Regional bone density and dimensions obtained from QCT and DXA were used to develop statistical models to predict femoral strength ex vivo. The QCT data also formed the basis of a three-dimensional finite element (FE) models to predict structural stiffness. The femurs were separated into two groups; a model training set (n = 25) was used to develop statistical models to predict ultimate load, and a test set (n = 26) was used to validate these models. The main goal of this study was to test the ability of DXA, QCT and FE techniques to predict fracture load non-invasively, in a simple load configuration which produces predominantly femoral neck fractures. The load configuration simulated the single stance phase portion of normal gait; in 87% of the specimens, clinical appearing sub-capital fractures were produced. The training/test study design provided a tool to validate that the predictive models were reliable when used on specimens with "unknown" strength characteristics. The FE method explained at least 20% more of the variance in strength than the DXA models. Planned refinements of the FE technique are expected to further improve these results. Three-dimensional FE models are a promising method for predicting fracture load, and may be useful in monitoring strength changes in vivo.


Relationship between carotid atherosclerosis and lumbar spine bone mineral density in postmenopausal women.
Osteoporosis and increased carotid intima-media thickness (IMT) have been associated with atherosclerosis. We investigated the correlation between carotid IMT and lumbar spine bone mineral density (BMD) in postmenopausal women. We studied the carotid IMT in 175 postmenopausal women, including 43 women (control) with normal spinal BMD, 73 women with osteopenia, and 59 women with osteoporosis. Carotid IMT was assessed by ultrasonography. BMD at the lumbar spine (lumbar 2 to 4 vertebrae) was measured by dual-energy X-ray absorptiometry. Age, years since menopause, and carotid IMT were significantly greater in the osteoporosis group than in the control (all p<0.01) and osteopenia groups (all p<0.01). Estradiol was significantly lower in the osteoporosis group than in the control group (p<0.05). BMD was significantly lower in the osteoporosis group than in the osteopenia or control group (both p<0.01) and in the osteopenia group than in the control group (p<0.01). After adjusting for age, years since menopause, and estradiol, women with osteoporosis had significantly greater carotid IMT than controls (p<0.05). The univariate linear regression analysis revealed that carotid IMT was significantly positively correlated with age, years since menopause, and low-density lipoprotein (LDL) cholesterol (all p<0.05) and was significantly negatively correlated with estradiol and BMD (all p<0.05), but showed no significant association with other clinical variables. In multivariate regression analysis, the carotid IMT was significantly positively correlated with LDL cholesterol (p<0.01) and negatively correlated with BMD (p<0.01), but not with other variables. Carotid atherosclerosis might be associated with lumbar spine bone mass in postmenopausal women, suggesting that postmenopausal women with osteoporosis may have more advanced carotid atherosclerosis than those with a normal bone mass.


Predicting Facebook users' online privacy protection: risk, trust, norm focus theory, and the theory of planned behavior.
The present research adopts an extended theory of the planned behavior model that included descriptive norms, risk, and trust to investigate online privacy protection in Facebook users. Facebook users (N = 119) completed a questionnaire assessing their attitude, subjective injunctive norm, subjective descriptive norm, perceived behavioral control, implicit perceived risk, trust of other Facebook users, and intentions toward protecting their privacy online. Behavior was measured indirectly 2 weeks after the study. The data show partial support for the theory of planned behavior and strong support for the independence of subjective injunctive and descriptive norms. Risk also uniquely predicted intentions over and above the theory of planned behavior, but there were no unique effects of trust on intentions, nor of risk or trust on behavior. Implications are discussed.