Retinal and Optic Nerve Hemorrhages in the Newborn Infant: One-Year Results of the Newborn Eye Screen Test Study.
To report the birth prevalence, risk factors, characteristics, and location of fundus hemorrhages (FHs) of the retina and optic nerve present in newborns at birth. Prospective cohort study at Stanford University School of Medicine. All infants who were 37 weeks postmenstrual age or older and stable were eligible for screening. Infants with known or suspected infectious conjunctivitis were excluded. Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013, through July 25, 2014, were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test study. Maternal, obstetric, and neonatal factors were obtained from hospital records. The location, retinal layer, and laterality of FH were recorded by 1 pediatric vitreoretinal specialist. Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics, and adverse events. The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self-identified ethnicity as Hispanic or Latino showed a protective effect (OR, 0.43; 95% CI, 0.20-0.94). Other study factors were not significant. Fundus hemorrhages are common among newborns. They often involve multiple areas and layers of the retina. Vaginal delivery was associated with a significantly increased risk of FH, whereas self-identified Hispanic or Latino ethnicity was protective against FH in this study. The long-term consequences of FH on visual development remain unknown.


The Application of Three-Dimensional Printing in Animal Model of Augmentation Rhinoplasty.
The role of three-dimensional (3D) printing has expanded in diverse areas in medicine. As plastic surgery needs to fulfill the different demands from diverse individuals, the applications of tailored 3D printing will become indispensable. In this study, we evaluated the feasibility of using 3D-printed polycaprolactone (PCL) scaffold seeded with fibrin/chondrocytes as a new dorsal augmentation material for rhinoplasty. The construct was surgically implanted on the nasal dorsum in the subperiosteal plane of six rabbits. The implants were harvested 4 and 12 weeks after implantation and evaluated by gross morphological assessment, radiographic imaging, and histologic examination. The initial shape of the implant was unchanged in all cases, and no definite post-operative complications were seen over the 3-month period. Radiologic evaluation confirmed that implants remained in the initial location without migration or extrusion. Histologic evaluations showed that the scaffold architectures were maintained with minimal inflammatory reactions; however, expected neo-chondrogenesis was not definite in the constructs. A new PCL scaffold designed by 3D printing method seeded with fibrin/chondrocytes can be a biocompatible augmentation material in rhinoplasty in the future.


Gax suppresses chemerin/CMKLR1-induced preadipocyte biofunctions through the inhibition of Akt/mTOR and ERK signaling pathways.
Adipose tissue is closely associated with angiogenesis and vascular remodeling. Chemerin is involved in inflammatory reaction and vascular dysfunction. However, the mechanisms of chemerin participating in vascular remodeling and whether Growth arrest-specific homeobox (Gax) can effectively intervene it remain obscured. Here, 3T3-F442A preadipocytes were cultured, injected into athymic mice to model fat pads, and treated respectively with Ad-chemerin, Ad-Gax, or specific inhibitors in vitro and in vivo. MTT, flow cytometry, Western blotting, and imunohisto(cyto)-chemistry analyses showed that chemerin enhanced the expression of FABP4 and VEGF, activated Akt/mTOR and ERK pathways, increased the cell percent of S phase, decreased the percent of G0-G1 phase and apoptotic cells, and augmented neovascular density in fat pads. Inversely, Gax suppressed the expression of these adipogenic and vasifactive markers and these signaling proteins, decreased the percent of S phase cells, and increased those of G0-G1 phase and apoptotic cells, and reduced the neovascular density. Our results indicate that chemerin-CMKLR1 activates Akt/mTOR and ERK pathways and facilitates preadipocyte proliferation, adipogenesis, and angiogenesis. Contrarily, Gax weakens the effect of chemerin on preadipocyte biofunctions.


Pharmacokinetics and pharmacodynamics of cinacalcet in patients with hyperparathyroidism after renal transplantation.
Cinacalcet is a calcimimetic drug for the treatment of secondary hyperparathyroidism (HPT). In a sequential open-label study, ten patients with persistent HPT after renal transplantation received first 30 and then 60 mg oral cinacalcet once daily over 2 weeks each. Cinacalcet steady state oral clearance was 131.1 +/- 20.9 l/h and 92.8 +/- 9.5 l/h (mean +/- SE) after 30 and 60 mg, respectively. Cinacalcet and parathyroid hormone (PTH) concentrations showed an inverse correlation and were fitted to a simple E(max) model (E(max) = 80% reduction vs. baseline, EC(50) = 13 ng/mL). A once daily administration of cinacalcet lowered serum calcium over 24 h without fluctuations. The 8-h fractional urinary excretion of calcium was increased after 60 mg cinacalcet (baseline 0.85 +/- 0.17%, 30 mg 1.53 +/- 0.35%, 60 mg 1.92 +/- 0.37%). Renal function remained stable. Cinacalcet pharmacokinetics and pharmacodynamics showed a pronounced interindividual variability. We conclude that the once daily administration of cinacalcet in patients with secondary HPT after renal transplantation effectively reduced iPTH and serum calcium. The transient calciuria could potentially favor nephrocalcinosis and reduce bone mineral density, suggesting that higher doses of cinacalcet need to be used with caution in renal transplant recipients with severe persistent hyperparathyroidism.


Expression of the intermediate filament protein nestin by sustentacular cells in mature olfactory neuroepithelium.
The intermediate filament protein nestin has been widely used as a marker for proliferating neural progenitor cells in the nervous system. The mammalian olfactory neuroepithelium is a region of the nervous system that robustly supports ongoing neurogenesis, yet where nestin has not been reported to mark proliferating progenitors. Using immunohistochemistry, we examined nestin expression in the mature olfactory neuroepithelium and found it to be tightly restricted to the basal compartment where the olfactory neuronal progenitor cell population resides. The pattern of nestin immunoreactivity was consistent with expression by the endfeet and inferior processes of sustentacular cells rather than basal cells. Using a bank of defined antibody markers, we confirmed nestin's pattern of distribution to be different from that of cytokeratin, vimentin, GBC-1, GAP43, and carnosine. It was highly similar to the pattern of SUS-4 immunoreactivity in the basal region of the neuroepithelium. Following surgical bulbectomy, nestin expression was up-regulated and became evident in the cell bodies of sustentacular cells situated more apically in the neuroepithelium. We have shown nestin to be present in the basal region of the adult olfactory neuroepithelium in the zone that supports ongoing neurogenesis in the adult, but its expression is restricted to the inferior parts of sustentacular cells rather than the neuronal progenitor cells. Nestin may play a potential role in the migration of recently proliferated olfactory neurons on the scaffolding of sustentacular cells in a manner analogous to its proposed role in radial glia during embryonic development of the central nervous system.


Dissecting the mechanism of torso receptor activation.
Regulated activation of receptor tyrosine kinases depends both on the presence of the receptors at the cell surface and on the availability of their ligands. In Drosophila the torso (tor) tyrosine kinase receptor is distributed along the surface of the embryo but it is only activated at the poles by a diffusible extracellular ligand generated at each pole which is trapped by the receptor, thereby impeding further diffusion. However, it is not well understood how this signal is generated, although it is known to depend on the activity of many genes such as torso-like (tsl) and trunk (trk). To further investigate the mechanism involved in the local activation of the tor receptor we have altered the normal expression of the tsl protein by generating females in which the tsl gene is expressed in the oocyte under the control of the tor promoter rather than in the ovarian follicle cells. Analysis of the phenotypes generated by this hybrid gene and its interactions with mutations in other genes in the pathway has enabled us to further dissect the mechanism of tor receptor activation and to define more precisely the role of the different genes acting in this process.


Towards understanding resprouting at the global scale.
Understanding and predicting plant response to disturbance is of paramount importance in our changing world. Resprouting ability is often considered a simple qualitative trait and used in many ecological studies. Our aim is to show some of the complexities of resprouting while highlighting cautions that need be taken in using resprouting ability to predict vegetation responses across disturbance types and biomes. There are marked differences in resprouting depending on the disturbance type, and fire is often the most severe disturbance because it includes both defoliation and lethal temperatures. In the Mediterranean biome, there are differences in functional strategies to cope with water deficit between resprouters (dehydration avoiders) and nonresprouters (dehydration tolerators); however, there is little research to unambiguously extrapolate these results to other biomes. Furthermore, predictions of vegetation responses to changes in disturbance regimes require consideration not only of resprouting, but also other relevant traits (e.g. seeding, bark thickness) and the different correlations among traits observed in different biomes; models lacking these details would behave poorly at the global scale. Overall, the lessons learned from a given disturbance regime and biome (e.g. crown-fire Mediterranean ecosystems) can guide research in other ecosystems but should not be extrapolated at the global scale.


Mathematical analysis of a model for HIV-malaria co-infection.
A deterministic model for the co-interaction of HIV and malaria in a community is presented and rigorously analyzed. Two sub-models, namely the HIV-only and malaria-only sub-models, are considered first of all. Unlike the HIV-only sub-model, which has a globally-asymptotically stable disease-free equilibrium whenever the associated reproduction number is less than unity, the malaria-only sub-model undergoes the phenomenon of backward bifurcation, where a stable disease-free equilibrium co-exists with a stable endemic equilibrium, for a certain range of the associated reproduction number less than unity. Thus, for malaria, the classical requirement of having the associated reproduction number to be less than unity, although necessary, is not sufficient for its elimination. It is also shown, using centre manifold theory, that the full HIV-malaria co-infection model undergoes backward bifurcation. Simulations of the full HIV-malaria model show that the two diseases co-exist whenever their reproduction numbers exceed unity (with no competitive exclusion occurring). Further, the reduction in sexual activity of individuals with malaria symptoms decreases the number of new cases of HIV and the mixed HIV-malaria infection while increasing the number of malaria cases. Finally, these simulations show that the HIV-induced increase in susceptibility to malaria infection has marginal effect on the new cases of HIV and malaria but increases the number of new cases of the dual HIV-malaria infection.


Post-mortem analysis of bone marrow osteoclasts using tartrate-resistant acid phosphatase staining: does histochemistry work and correlate with time since death?
In bone marrow (BM) biopsies, tartrate-resistant acid phosphatase (TRAP) staining represents the gold standard for the characterisation of osteoclasts. TRAP is one of the few enzymes that is histochemically detectable on formalin-fixed paraffin-embedded tissue. This study investigated whether TRAP is also able to visualise BM osteoclasts in autopsy tissue. It was hypothesised that, due to a progressive loss of enzymatic activity in osteoclasts post-mortem, TRAP staining could allow the time of death of a patient to be determined. TRAP-stained BM slides of 96 cases including 51 pathology and 23 forensic autopsies and 22 biopsies were histologically evaluated and their staining intensity (SI) semi-quantitatively graded. In the autopsy cases, the results were correlated with the post-mortem interval (PMI, time span in days between death and autopsy). TRAP staining intensities (TRAP-SIs) did not differ between men and women and showed a steady decrease with age. TRAP-SIs were significantly stronger in biopsies than in autopsy cases. Among the autopsies, TRAP-SIs were highly variable and not dependent on PMI, except for three forensic cases with PMI ≥7 days which showed a complete loss of TRAP stainability. On the whole, the TRAP-SIs of pathology and forensic cases did not differ significantly. This study clearly shows that BM osteoclasts stay TRAP-positive for 7 days post-mortem, although with markedly reduced TRAP-SIs compared with biopsies. Since TRAP-SIs were not correlated with the duration of PMI, TRAP staining of BM osteoclasts cannot serve as a tool to determine the time of death of a patient.


Exploring the feasibility of combining chronic disease patient registry data to monitor the status of diabetes care.
To provide direction and to support improvements in diabetes care, states must be able to measure the effectiveness of interventions and gain feedback on progress. We wanted to know if data from multiple health clinics that are implementing quality improvement strategies could be combined to provide useful measurements of diabetes care processes and control of intermediate outcomes. We combined and analyzed electronic patient health data from clinic sites across Washington State that used the Chronic Disease Electronic Management System (CDEMS) registry. The data were used to determine whether national and state objectives for diabetes care were met. We calculated the percentage of patients that met standards of care in 2004. The pooled dataset included 17,349 adult patients with diabetes from 90 clinics. More than half of patients were above recommended target levels for hemoglobin A1c testing, foot examination, hemoglobin A1c control, and low-density lipoprotein cholesterol control. Fewer patients met recommendations for nephropathy assessment, eye examinations, and blood pressure control. In terms of meeting these standards, rates of diabetes care varied across clinics. CDEMS rates of care were compared with those reported by other data sources, but no consistent pattern of similarities or differences emerged. With committed staff time, provider support, and resources, data from clinical information systems like CDEMS can be combined to address a deficiency in state-level diabetes surveillance and evaluation systems--specifically, the inability to capture clinical biometric values to measure intermediate health outcomes. These data can complement other surveillance and evaluation data sources to help provide a better picture of diabetes care in a state.


A phase III randomized, double-blind, placebo-controlled trial of gabapentin in the management of hot flashes in men (N00CB).
Hot flashes represent a significant problem in men undergoing androgen deprivation therapy. Via a prospective, double-blind, placebo-controlled clinical trial, men with hot flashes, on a stable androgen deprivation therapy program for prostate cancer, received a placebo or gabapentin at target doses of 300, 600, or 900 mg/day. Hot flash frequencies and severities were recorded daily during a baseline week and for 4 weeks while the patients took the study medication. In the 214 eligible patients who began the study drug on this trial, comparing the fourth treatment week to the baseline week, mean hot flash scores decreased in the placebo group by 4.1 units and in the three increasing dose gabapentin groups by, 3.2, 4.6, and 7.0 units. Comparing the three combined gabapentin arms to the placebo arm did not result in significant hot flash differences. Wilcoxon rank-sum P values for change in hot flash scores and frequencies after 4 weeks of treatment were 0.10 and 0.02, comparing the highest dose gabapentin arm to the placebo arm, respectively. The gabapentin was well tolerated in this trial. These results support that gabapentin decreases hot flashes, to a moderate degree, in men with androgen ablation-related vasomotor dysfunction.


Threshold analysis of a chirped-grating distributed-feedback laser with the power series method.
A new and efficient method for analyzing a chirped-grating distributed-feedback (DFB) laser is presented. We show that coupled-wave equations can be solved by use of the power series method. The single-mode gain margin of a linearly chirped-grating DFB laser is calculated for different chirping factors and coupling constants. We found that clearly optimum chirping exists for which the single-mode gain margin is maximum. The gain margins were also calculated for different positions of the cavity center. The effect of facet reflectivities and their phases on the gain margin was investigated. We found that the gain margin is maximum and the spatial hole burning is minimum for the cavity center at the middle of the laser cavity.


Provider satisfaction and patient outcomes associated with a statewide prison telemedicine program in Louisiana.
Health information technology including telemedicine offers potential to improve patient care outcomes. As part of the response to Hurricanes Katrina and Rita in 2005, the Louisiana State University Health Care Services Division expanded its statewide telemedicine program. The aim of this study was to evaluate provider satisfaction and patient outcomes associated with telemedicine when used for the administration of prisoner medical care. Providers completed a survey following each patient encounter in real-time; questions were adapted from standard satisfaction indices. Statistical methods included uni-, bi-, and multivariable including ordinal regression methods to characterize unadjusted and adjusted factors associated with telemedicine use and provider satisfaction, and patient outcomes. Data were collected between December 2007 and May 2008 and were analyzed using SAS and Stata. Out of 737 patient visits, the majority of patients were African American (68.6%), men (92.9%), seen for either infectious disease or mental health (46.2% and 50.2%), with most surveys completed by a physician (63.1%). Most telemedicine encounters were completed (92.8%), a treatment plan was established (97.0%), the provider perceived that the technology was adequate to conduct visit (93.4%), and a follow-up telemedicine appointment was requested (90.8%). Most providers were satisfied with telemedicine for the visit overall (87.0%), believed that telemedicine improved patient prognosis (88.2%), and perceived that the patient was satisfied (83.0%). This study suggests that telemedicine was an effective and accepted method of healthcare provision.


Ab initio study of the structural, electronic, and thermodynamic properties of linear perfluorooctane sulfonate (PFOS) and its branched isomers.
Structural, electronic, and thermodynamic properties of linear perfluorooctane sulfonate (PFOS) and its trifluoromethyl-branched isomers (i.e. 1-CF(3)- to 6-CF(3)-PFOS) were theoretically studied by means of ab initio density functional theory (DFT) calculations with the B3LYP functional and a 6-31++G(d,p) basis set. The anionic form of linear PFOS and its trifluromethyl-branched isomers were considered for the initial construction of the computational models; subsequently, H(+), Li(+), and Na(+) were added as counter-ions to study their effect on the properties under investigation. Insignificant changes with respect to the anions were observed in the structure of both the protonated and salt forms due to the presence of these counter-ions. However, important differences in the electrostatic potential maps as well as HOMO and LUMO molecular orbitals were observed for the various forms of PFOS. The linear and branched PFOS ions were identified as the most suitable compounds for interacting with charged species. Furthermore, in the linear anion, it was observed that the LUMO orbital is diffused along the whole fluoro-carbon chain, whereas it is localized to the region close to the ternary carbon in the 4-CF(3)-PFOS, 5-CF(3)-PFOS, and 6-CF(3)-PFOS isomers. The higher accessibility of the LUMO orbital in these branched anions suggests that they have a higher probability of reacting with free radicals when compared with the linear counterpart. This behavior is reflected in the experimental observation that only the branched PFOS isomers were susceptible to reductive defluorination by reduced vitamin B(12) as we previously reported. The relative stability of the linear and branched PFOS in their different forms computed by comparing their calculated Gibbs free energy showed that 1-CF(3)-, 6-CF(3)-, and linear PFOS are the most favorable structures from a thermodynamic point of view.


Effect of oleuropein on cognitive deficits and changes in hippocampal brain-derived neurotrophic factor and cytokine expression in a rat model of post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. This psychopathological response to traumatic stressors induces learning and memory deficits in rats. Oleuropein (OLE), a major compound in olive leaves, has been reported to possess several pharmacological properties, including anti-cancer, anti-diabetic, anti-atherosclerotic and neuroprotective activities. However, the cognitive effects of OLE and its mechanism of action have remained unclear in PTSD. In this study, we examined whether OLE improved spatial cognitive impairment induced in rats following single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or various doses of OLE for 14 consecutive days after the SPS procedure. The SPS procedure resulted in cognitive impairment in the object recognition task and the Morris water maze test, which was reversed by OLE (100 mg/kg, i.p). Additionally, as assessed by immunohistochemistry and reverse transcription-polymerase chain reaction analysis, the administration of OLE significantly alleviated memory-associated decreases in the levels of brain-derived neurotrophic factor and cAMP response element-binding protein and mRNA in the hippocampus. Together, these findings suggest that OLE attenuated SPS-induced cognitive impairment significantly by inhibiting the expression of pro-inflammatory mediators in the rat brain. Thus, OLE reversed several behavioral impairments triggered by the traumatic stress of SPS and might be a potential useful therapeutic intervention for PTSD.


Behavioral aspects of male circumcision for the prevention of HIV infection.
Male circumcision (MC) can prevent female-to-male HIV transmission and has the potential to significantly alter HIV epidemics. The ultimate impact of MC on HIV prevention will be determined, in part, by behavioral factors. In order to fully realize the protective benefits of MC, factors related to acceptability and sexual risk must be considered. Research shows that acceptability of MC among uncircumcised men is high, and suggests that free and safe circumcision may be taken up in places with high HIV prevalence. Perceptions of adverse effects of MC may, however, limit uptake. Furthermore, considerable risk reduction counseling provided by MC trials limits our ability to understand the impact MC may have on behavior. There is also no evidence that MC protects women with HIV-positive partners or that it offers protection during anal intercourse. Research is urgently needed to better understand and manage the behavioral implications of MC for HIV prevention.


Enhancing the Exploitation of Functional Nanomaterials through Spatial Confinement: The Case of Inorganic Submicrometer Capsules.
Hollow inorganic nanostructures have attracted much interest in the last few years due to their many applications in different areas of science and technology. In this Feature Article, we overview part of our current work concerning the collective use of plasmonic and magnetic nanoparticles located in voided nanostructures and explore the more specific operational issues that should be taken into account in the design of inorganic nanocapsules. Along these lines, we focus our attention on the applications of silica-based submicrometer capsules aiming to stress the importance of creating nanocavities in order to further exploit the great potential of these functional nanomaterials. Additionally, we will examine some of the recent research on this topic and try to establish a perspective for future developments in this area.


Prevalence and seasonal variations of six bee viruses in Apis mellifera L. and Varroa destructor mite populations in France.
A survey of six bee viruses on a large geographic scale was undertaken by using seemingly healthy bee colonies and the PCR technique. Samples of adult bees and pupae were collected from 36 apiaries in the spring, summer, and autumn during 2002. Varroa destructor samples were collected at the end of summer following acaricide treatment. In adult bees, during the year deformed wing virus (DWV) was found at least once in 97% of the apiaries, sacbrood virus (SBV) was found in 86% of the apiaries, chronic bee paralysis virus (CBPV) was found in 28% of the apiaries, acute bee paralysis virus (ABPV) was found in 58% of the apiaries, black queen cell virus (BQCV) was found in 86% of the apiaries, and Kashmir bee virus (KBV) was found in 17% of the apiaries. For pupae, the following frequencies were obtained: DWV, 94% of the apiaries; SBV, 80% of the apiaries; CBPV, none of the apiaries; ABPV, 23% of the apiaries; BQCV, 23% of the apiaries; and KBV, 6% of the apiaries. In Varroa samples, the following four viruses were identified: DWV (100% of the apiaries), SBV (45% of the apiaries), ABPV (36% of the apiaries), and KBV (5% of the apiaries). The latter findings support the putative role of mites in transmitting these viruses. Taken together, these data indicate that bee virus infections occur persistently in bee populations despite the lack of clinical signs, suggesting that colony disease outbreaks might result from environmental factors that lead to activation of viral replication in bees.


Piloting a nationally disseminated, interactive human subjects protection program for community partners: unexpected lessons learned from the field.
Funders, institutions, and research organizations are increasingly recognizing the need for human subjects protections training programs for those engaged in academic research. Current programs tend to be online and directed toward an audience of academic researchers. Research teams now include many nonacademic members, such as community partners, who are less likely to respond to either the method or the content of current online trainings. A team at the CTSA-supported Michigan Institute for Clinical and Health Research at the University of Michigan developed a pilot human subjects protection training program for community partners that is both locally implemented and adaptable to local contexts, yet nationally consistent and deliverable from a central administrative source. Here, the developers of the program and the collaborators who participated in the pilot across the United States describe 10 important lessons learned that align with four major themes: The distribution of the program, the implementation of the program, the involvement of community engagement in the program, and finally lessons regarding the content of the program. These lessons are relevant to anyone who anticipates developing or improving a training program that is developed in a central location and intended for local implementation.


Outcomes of Descemet Membrane Endothelial Keratoplasty (DMEK) Using Surgeon's Prepared Donor DM-Roll in Consecutive 100 Indian Eyes.
Descemet Membrane Endothelial Keratoplasty (DMEK) is now becoming the popular form of endothelial keratoplasty using only donor DM with healthy endothelium as true component lamellar corneal surgery. To analyze the results of visual outcomes, endothelial cell loss and complications of Descemet membrane endothelial keratoplasty in first consecutive 100 Indian eyes. 100 eyes of 95 consecutive patients with endothelial dysfunctions of different etiologies scheduled for DMEK, were included in this study. In each case, surgeon prepared tissue using McCarey Kaufman medium- or Cornisol-preserved donor cornea with a cell count of ≥2500 cells/mm2. Surgical complications, Best Spectacle Corrected Visual Acuity (BSCVA); Endothelial Cell Density (ECD) and Endothelial Cell Loss (ECL) were analyzed for each patient after a minimum follow-up of three months. The Main indication was pseudophakic corneal edema or bullous keratopathy in 52 (52%) eyes. 38 (38%) eyes had Fuchs' dystrophy with various grades of cataract. In 43 phakic eyes, DMEK was combined with cataract surgery and intraocular lens implantation. Mean DM-roll preparation time was 7.5 ± 2.8 min and in 3 eyes, DM-graft were damaged. After 3-months, BSCVA was ≥20/25 in 57 (57.6%) cases. Mean ECD was 2123 ± 438/mm2 (range: 976 - 3208/ mm2) and the mean endothelial cell loss after 3-months was 26.92 ± 13.40 (range: 4.90 - 66.6%). Partial DM detachment occurred in 8 (8.0%) eyes and rebubbling required in 4 eyes. Iatrogenic primary graft failure occurred in one eye. Descemet membrane endothelial keratoplasty is a safe and effective procedure in several types of endothelial diseases among Indian patients with encouraging surgical and visual outcomes. Complications are less and endothelial cell loss percentage is acceptable.


Drug use during pregnancy: validating the Drug Abuse Screening Test against physiological measures.
This study examined the ability of the Drug Abuse Screening Test (DAST-10) to identify prenatal drug use using hair and urine samples as criterion variables. In addition, this study was the first to use "best practices," such as anonymity, ACASI technology, and a written screener, to facilitate disclosure in this vulnerable population. 300 low-income, post-partum women (90.3% African-American) were recruited from their hospital rooms after giving birth. Participation involved (a) completing a computerized assessment battery that contained the DAST-10 and (b) providing urine and hair samples. Twenty-four percent of the sample had a positive drug screen. The sensitivity of the DAST-10 was only .47. Nineteen percent of the sample had a positive toxicology screen but denied drug use on the DAST-10. Findings suggest that brief drug use screeners may have limited utility for pregnant women and that efforts to facilitate disclosure via reassurance and anonymity are unlikely to be sufficient in this population.


Hepatopancreatic multi-transcript expression patterns in the crayfish Cherax quadricarinatus during the moult cycle.
Alterations of hepatopancreatic multi-transcript expression patterns, related to induced moult cycle, were identified in male Cherax quadricarinatus through cDNA microarray hybridizations of hepatopancreatic transcript populations. Moult was induced by X-organ sinus gland extirpation or by repeated injections of 20-hydroxyecdysone. Manipulated males were sacrificed at premoult or early postmoult, and a reference population was sacrificed at intermoult. Differentially expressed genes among the four combinations of two induction methods and two moult stages were identified. Biologically interesting clusters revealing concurrently changing transcript expressions across treatments were selected, characterized by a general shift of expression throughout premoult and early postmoult vs. intermoult, or by different premoult vs. postmoult expressions. A number of genes were differentially expressed in 20-hydroxyecdysone-injected crayfish vs. X-organ sinus gland extirpated males.


Effect of Principal Component Analysis Centering and Scaling on Classification of Mycobacteria from Raman Spectra.
Raman spectroscopy has been used for decades to detect and identify biological substances as it provides specific molecular information. Spectra collected from biological samples are often complex, requiring the aid of data truncation techniques such as principal component analysis (PCA) and multivariate classification methods. Classification results depend on the proper selection of principal components (PCs) and how PCA is performed (scaling and/or centering). There are also guidelines for choosing the optimal number of PCs such as a scree plot, Kaiser criterion, or cumulative percent variance. The goal of this research is to evaluate these methods for best implementation of PCA and PC selection to classify Raman spectra of bacteria. Raman spectra of three different isolates of mycobacteria ( Mycobacterium sp. JLS, Mycobacterium sp. KMS, Mycobacterium sp. MCS) were collected and then passed through PCA and linear discriminant analysis for classification. Principal component analysis implementation as well as PC selection was evaluated by comparing the highest possible classification accuracies against accuracies determined by PC selection methods for each centering and scaling option. Centered and unscaled data provided the best results when selecting PCs based on cumulative percent variance.


Dual mobility cups for preventing early hip arthroplasty dislocation in patients at risk: experience in a county hospital.
Dislocation remains a major concern after hip arthroplasty. We asked whether dual mobility cups (DMC) would improve early hip stability in patients with high risk of dislocation. We followed 34 patients (21 females, 13 males) treated between 2009 and 2012 with cemented DMC for hip revisions caused recurrent hip prosthetic dislocation or as a primary procedure in patients with high risk of instability. Functional outcome and quality of life were evaluated using Harris Hip Score and EQ-5D respectively. We found that the cemented DMC gave stability in 94%. Seven patients (20%) were re-operated due to infection. One patient sustained a periprosthetic fracture. At follow-up (6 to 36 months, mean 18), the mean Harris hip score was 67 (standard deviation: 14) and mean EQ-5D was 0.76 (standard deviation: 0.12). We concluded that treating patients with high risk of dislocation with DMC can give good stability. However, complications such as postoperative infection can be frequent and should be managed carefully.


Impact on patients of expanded, general practice based, student teaching: observational and qualitative study.
To compare patients' enablement and satisfaction after teaching and non-teaching consultations. To explore patients' views about the possible impact that increased community based teaching of student doctors in their practice may have on the delivery of service and their attitudes towards direct involvement with students. Observational study using validated survey instruments (patient enablement index--PEI, and consultation satisfaction questionnaire--CSQ) administered after teaching consultations and non-teaching consultations. Ten focus groups (two from each practice), comprising five with patients participating in prearranged teaching sessions and five with patients not participating in these. Five general practices in west Suffolk and southern Norfolk, England, that teach student doctors on the Cambridge graduate medical course. 240 patients attending teaching consultations (response rate 82%, 196 patients) and 409 patients attending non-teaching consultations (response rate 72%, 294 patients) received survey instruments. Ten focus groups with a total of 34 patients participating in prearranged teaching sessions and 20 patients not participating in these. Scores on the patient enablement index and consultation satisfaction questionnaire, analysed at the level of all patients, allowing for age, sex, general practitioner, and practice, and at the level of the individual general practitioner teacher. Qualitative analysis of focus group data. Patients' enablement or satisfaction was not reduced after teaching consultations compared with non-teaching consultations (mean difference in scores on the patient enablement index and consultation satisfaction questionnaire with adjustment for confounders 2.24% and 1.70%, respectively). This held true for analysis by all patients and by general practitioner teacher. Qualitative data showed that patients generally supported the teaching of student doctors in their practice. However, this support was conditional on receiving sufficient information about reasons for doctors' absence, the characteristics of students, and the nature of teaching planned. Many patients viewed their general practice as different from hospital and expected greater control over students' presence during their consultations. Patients' enablement and satisfaction are not impaired by students' participation in consultations. Patients generally support the teaching of student doctors in their general practice but expect to be provided with sufficient information and to have a choice about participation, so they can give informed consent. Recognising this when organising general practice based teaching is important.


Stress test reactivity in panic disorder.
The psychological and physiological reactivity of 52 patients with panic disorder to mental arithmetic, cold pressor, and 5% carbon dioxide inhalation tests was compared with that of 26 age- and sex-matched normal subjects. In general, patients with panic disorder were neither more physiologically reactive to these stressors than normal subjects nor slower to recover from them, but they were tonically more anxious and much more likely to ask to stop carbon dioxide inhalation or to report panic attacks during this test. Patients who reported panic attacks (46%) had manifested greater anticipatory anxiety before the gas was delivered, accompanied with increased beta-adrenergic cardiac tone. Thus, anticipatory anxiety can be an important factor in panic provocation. Physiological measures varied greatly in their sensitivity to phasic or tonic anxiety. Carbon dioxide stimulated large increases in respiratory minute volume, but these increases were no greater for patients than for normal subjects.


Branched-chain amino acid catabolism is a conserved regulator of physiological ageing.
Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice. We observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs). We further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which we identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner. The transcription factor HLH-15 controls and epistatically synergizes with BCAT-1 to modulate physiological ageing. Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan. Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan.


Higher vitamin D dietary intake is associated with lower risk of alzheimer's disease: a 7-year follow-up.
Hypovitaminosis D is associated with cognitive decline among older adults. The relationship between vitamin D intakes and cognitive decline is not well understood. Our objective was to determine whether the dietary intake of vitamin D was an independent predictor of the onset of dementia within 7 years among women aged 75 years and older. Four hundred and ninety-eight community-dwelling women (mean, 79.8 ± 3.8 years) free of vitamin D supplements from the EPIDemiology of OSteoporosis Toulouse cohort study were divided into three groups according to the onset of dementia within 7 years (ie, no dementia, Alzheimer's disease [AD], or other dementias). Baseline vitamin D dietary intakes were estimated from self-administered food frequency questionnaire. Age, body mass index, initial cognitive performance, education level, physical activity, sun exposure, disability, number of chronic diseases, hypertension, depression, use of psychoactive drugs, and baseline season were considered as potential confounders. Women who developed AD (n = 70) had lower baseline vitamin D intakes (mean, 50.3 ± 19.3 μg/wk) than nondemented (n = 361; mean intake = 59.0 ± 29.9 μg/wk, p = .027) or those who developed other dementias (n = 67; mean intake = 63.6 ± 38.1 μg/wk, p = .010). There was no difference between other dementias and no dementia (p = .247). Baseline vitamin D dietary intakes were associated with the onset of AD (adjusted odds ratio = 0.99 [95% confidence interval = 0.98-0.99], p = .041) but not with other dementias (p = .071). Being in the highest quintile of vitamin D dietary intakes was associated with a lower risk of AD compared with the lower 4 quintiles combined (adjusted odds ratio = 0.23 [95% confidence interval = 0.08-0.67], p = .007). Higher vitamin D dietary intake was associated with a lower risk of developing AD among older women.


Triaging Interventional Pain Procedures During COVID-19 or Related Elective Surgery Restrictions: Evidence-Informed Guidance from the American Society of Interventional Pain Physicians (ASIPP).
The COVID-19 pandemic has worsened the pain and suffering of chronic pain patients due to stoppage of "elective" interventional pain management and office visits across the United States. The reopening of America and restarting of interventional techniques and elective surgical procedures has started. Unfortunately, with resurgence in some states, restrictions are once again being imposed. In addition, even during the Phase II and III of reopening, chronic pain patients and interventional pain physicians have faced difficulties because of the priority selection of elective surgical procedures.Chronic pain patients require high intensity care, specifically during a pandemic such as COVID-19. Consequently, it has become necessary to provide guidance for triaging interventional pain procedures, or related elective surgery restrictions during a pandemic. The aim of these guidelines is to provide education and guidance for physicians, healthcare administrators, the public and patients during the COVID-19 pandemic. Our goal is to restore the opportunity to receive appropriate care for our patients who may benefit from interventional techniques. The American Society of Interventional Pain Physicians (ASIPP) has created the COVID-19 Task Force in order to provide guidance for triaging interventional pain procedures or related elective surgery restrictions to provide appropriate access to interventional pain management (IPM) procedures in par with other elective surgical procedures. In developing the guidance, trustworthy standards and appropriate disclosures of conflicts of interest were applied with a section of a panel of experts from various regions, specialties, types of practices (private practice, community hospital and academic institutes) and groups. The literature pertaining to all aspects of COVID-19, specifically related to epidemiology, risk factors, complications, morbidity and mortality, and literature related to risk mitigation and stratification was reviewed. The evidence -- informed with the incorporation of the best available research and practice knowledge was utilized, instead of a simplified evidence-based approach. Consequently, these guidelines are considered evidence-informed with the incorporation of the best available research and practice knowledge. The Task Force defined the medical urgency of a case and developed an IPM acuity scale for elective IPM procedures with 3 tiers. These included urgent, emergency, and elective procedures. Examples of urgent and emergency procedures included new onset or exacerbation of complex regional pain syndrome (CRPS), acute trauma or acute exacerbation of degenerative or neurological disease resulting in impaired mobility and inability to perform activities of daily living. Examples include painful rib fractures affecting oxygenation and post-dural puncture headaches limiting the ability to sit upright, stand and walk. In addition, emergency procedures include procedures to treat any severe or debilitating disease that prevents the patient from carrying out activities of daily living. Elective procedures were considered as any condition that is stable and can be safely managed with alternatives. COVID-19 continues to be an ongoing pandemic. When these recommendations were developed, different stages of reopening based on geographical regulations were in process. The pandemic continues to be dynamic creating every changing evidence-based guidance. Consequently, we provided evidence-informed guidance. The COVID-19 pandemic has created unprecedented challenges in IPM creating needless suffering for pain patients. Many IPM procedures cannot be indefinitely postponed without adverse consequences. Chronic pain exacerbations are associated with marked functional declines and risks with alternative treatment modalities. They must be treated with the concern that they deserve. Clinicians must assess patients, local healthcare resources, and weigh the risks and benefits of a procedure against the risks of suffering from disabling pain and exposure to the COVID-19 virus.


Cyclooxygenase-2 is up-regulated in proliferative inflammatory atrophy of the prostate, but not in prostate carcinoma.
Cyclooxygenase-2 (COX-2) is the inducible isoform of the rate-limiting enzymes that convert arachidonic acid to proinflammatory prostaglandins as well as a primary target for nonsteroidal anti-inflammatory drugs. Accumulating evidence suggests that up-regulation of COX-2 is associated with carcinogenesis in multiple organ systems including the large bowel, lung, breast, and prostate. In this report, we examine the expression of COX-2 protein and mRNA in prostate tissue containing various lesions and in prostate cancer cell lines. In the cell lines, LNCaP, DU145, PC-3, and TSU, COX-2 protein expression was undetectable under basal conditions but could be induced transiently by phorbol ester treatment in PC-3 and TSU cells, but not in DU145 and LNCaP cells. Immunohistochemical analysis of 144 human prostate cancer cases suggested that, in contrast to several previous reports, there was no consistent overexpression of COX-2 in established prostate cancer or high-grade prostatic intraepithelial neoplasia, as compared with adjacent normal prostate tissue. Positive staining was seen only in scattered cells (<1%) in both tumor and normal tissue regions but was much more consistently observed in areas of proliferative inflammatory atrophy, lesions that have been implicated in prostatic carcinogenesis. Staining was also seen at times in macrophages. Western blotting and quantitative RT-PCR analyses confirmed these patterns of expression. These results suggest that if nonsteroidal anti-inflammatory drugs are indeed chemopreventive and/or chemotherapeutic for prostate cancer, their effects are likely to be mediated by modulating COX-2 activity in non-PCa cells (either inflammatory cells or atrophic epithelial cells) or by affecting a COX-2-independent pathway.


Pharmacologic circumvention of multidrug resistance.
The ability of malignant cells to develop resistance to chemotherapeutic drugs is a major obstacle to the successful treatment of clinical tumors. The phenomenon multidrug resistance (MDR) in cancer cells results in cross-resistance to a broad range of structurally diverse antineoplastic agents, due to outward efflux of cytotoxic substrates by the mdr1 gene product, P-glycoprotein (P-gp). Numerous pharmacologic agents have been identified which inhibit the efflux pump and modulate MDR. The biochemical, cellular and clinical pharmacology of agents used to circumvent MDR is analyzed in terms of their mechanism of action and potential clinical utility. MDR antagonists, termed chemosensitizers, may be grouped into several classes, and include calcium channel blockers, calmodulin antagonists, anthracycline and Vinca alkaloid analogs, cyclosporines, dipyridamole, and other hydrophobic, cationic compounds. Structural features important for chemosensitizer activity have been identified, and a model for the interaction of these drugs with P-gp is proposed. Other possible cellular targets for the reversal of MDR are also discussed, such as protein kinase C. Strategies for the clinical modulation of MDR and trials combining chemosensitizers with chemotherapeutic drugs in humans are reviewed. Several novel approaches for the modulation of MDR are examined.


Reduced bone mineral content and normal serum osteocalcin in non-steroid-treated patients with juvenile rheumatoid arthritis.
To distinguish the effects of juvenile rheumatoid arthritis (JRA) on bone mineralisation from those possibly caused by steroid therapy. Bone mineral status was evaluated in 20 children (five boys and 15 girls) with active JRA who never received steroids. Seven had oligoarticular, nine had polyarticular, and four had systemic JRA. Bone mineral content (BMC) was assessed by single beam photon absorptiometry and expressed as a Z score relative to normal values in healthy children. Serum calcium, phosphate, and alkaline phosphatase were measured by colorimetric methods. Whole parathyroid hormone was assayed by Immuno Radiometric Assay. Serum osteocalcin was measured by specific radioimmunoassay. Nutrient intake was assessed by a 24 hours dietary recall. BMC and nutrient intake were also assessed in an age and sex matched control group. BMC was -1.5 (SEM 0.8) Z scores in patients and 0.4 (0.3) in the control group (p = 0.02). BMC averaged -4.9 (2) Z scores in the systemic JRA group, -1 (0.6) in the polyarticular group and 0.3 (0.7) in oligoarticular JRA patients. Serum calcium, phosphate and osteocalcin values were normal in all patients. No significant difference was found between JRA patients and controls in calcium, phosphate, energy, and protein intake. JRA subjects have significantly reduced BMC even in the absence of any steroid therapy. Bone demineralisation appears to depend more on disease activity and on reduced motility than on reduced nutrient intake.


Misfolded proteins activate factor XII in humans, leading to kallikrein formation without initiating coagulation.
When blood is exposed to negatively charged surface materials such as glass, an enzymatic cascade known as the contact system becomes activated. This cascade is initiated by autoactivation of Factor XII and leads to both coagulation (via Factor XI) and an inflammatory response (via the kallikrein-kinin system). However, while Factor XII is important for coagulation in vitro, it is not important for physiological hemostasis, so the physiological role of the contact system remains elusive. Using patient blood samples and isolated proteins, we identified a novel class of Factor XII activators. Factor XII was activated by misfolded protein aggregates that formed by denaturation or by surface adsorption, which specifically led to the activation of the kallikrein-kinin system without inducing coagulation. Consistent with this, we found that Factor XII, but not Factor XI, was activated and kallikrein was formed in blood from patients with systemic amyloidosis, a disease marked by the accumulation and deposition of misfolded plasma proteins. These results show that the kallikrein-kinin system can be activated by Factor XII, in a process separate from the coagulation cascade, and point to a protective role for Factor XII following activation by misfolded protein aggregates.


Comparative gene expression profiling of adult mouse ovary-derived oogonial stem cells supports a distinct cellular identity.
Perform gene expression profiling of adult mouse ovary-derived oogonial stem cells (OSCs). Experimental animal study. Research laboratory. Adult C57BL/6 female mice. None. Gene expression profiles were compared between freshly isolated and cultured OSCs, as well as between OSCs and embryonic stem cells (ESCs), fetal primordial germ cells (PGCs), and spermatogonial stem cells (SSCs); OSC yield from ovaries versus meiotic gene activation during the estrous cycle was determined. Freshly isolated OSCs, PGCs, and SSCs exhibited distinct gene expression profiles. Cultured OSCs maintained their germline gene expression pattern but gained expression of pluripotency markers found in PGCs and ESCs. Cultured OSCs also expressed the meiotic marker, stimulated by retinoic acid gene 8 (Stra8). In vivo, OSC yield was higher from luteal versus follicular phase ovaries, and this was inversely related to Stra8 expression. Freshly isolated OSCs exhibit a germline gene expression profile that overlaps with, but is distinct from, that of PGCs and SSCs. After in vitro expansion, OSCs activate expression of pluripotency genes found in freshly isolated PGCs. In vivo, OSC numbers in the ovaries fluctuate during the estrous cycle, with the highest numbers noted during the luteal phase. This is followed by activation of Stra8 expression during the follicular phase, which may signify a wave of neo-oogenesis to partially offset follicular loss through atresia and ovulation in the prior cycle.


Bichromatic laser-induced quadrupole-dipole collisional energy transfer in Ca-Sr.
We consider the response of a laser-induced quadrupole-dipole collisional system driven by a strong dressing laser field with the aim of calculating the collisional cross section of a weak inducing laser probe. The addition of a second driving field to the traditional arrangement will cause magnitude changes of the spectra and modify the profile. The calculation results show that the bichromatic laser-induced collisional energy-transfer process can be an efficient way to probe Stark splitting of both the final state and intermediate state. The magnitude and position of the splitting spectral lines are strongly dependent on the intensity of the dressing laser field. The peak cross section almost reduces by a factor of 2 with the presence of the dressing laser. Also, in the antistatic wing, bright and dark lines are periodic, appearing with the increasing of the dressing laser intensity.


Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution.
The Keap1–Nrf2 regulatory pathway plays a central role in the protection of cells against oxidative and xenobiotic damage. Under unstressed conditions, Nrf2 is constantly ubiquitinated by the Cul3–Keap1 ubiquitin E3 ligase complex and rapidly degraded in proteasomes. Upon exposure to electrophilic and oxidative stresses, reactive cysteine residues of Keap1 become modified, leading to a decline in the E3 ligase activity, stabilization of Nrf2 and robust induction of a battery of cytoprotective genes. Biochemical and structural analyses have revealed that the intact Keap1 homodimer forms a cherry-bob structure in which one molecule of Nrf2 associates with two molecules of Keap1 by using two binding sites within the Neh2 domain of Nrf2. This two-site binding appears critical for Nrf2 ubiquitination. In many human cancers, missense mutations in KEAP1 and NRF2 genes have been identified. These mutations disrupt the Keap1–Nrf2 complex activity involved in ubiquitination and degradation of Nrf2 and result in constitutive activation of Nrf2. Elevated expression of Nrf2 target genes confers advantages in terms of stress resistance and cell proliferation in normal and cancer cells. Discovery and development of selective Nrf2 inhibitors should make a critical contribution to improved cancer therapy.


Synthesis, resolution, and in vitro evaluation of three vesicular acetylcholine transporter ligands and evaluation of the lead fluorine-18 radioligand in a nonhuman primate.
The vesicular acetylcholine transporter (VAChT) is a reliable biomarker for assessing cholinergic dysfunction associated with dementia. We recently reported three new potent and selective carbon-11 labeled VAChT radiotracers. Herein, we report the resolution with a Chiralcel OD column of three additional fluorine containing VAChT ligands in which a fluoroethoxy or fluoroethylamino moiety was substituted for the methoxy group. An in vitro competitive binding assay showed that (-)-7 had high potency for VAChT (Ki-VAChT = 0.31 ± 0.03 nM) and excellent selectivity for VAChT versus σ receptors (Ki-σ1 = 1870 ± 250 nM, Ki-σ2 = 5480 ± 140 nM). Three different radiolabeling approaches were explored; the radiosynthesis of (-)-[18F]7 was successfully accomplished via a stepwise two-pot, three-step method with moderate yield (11 ± 2%) and high radiochemical purity (>98%). PET imaging studies in a nonhuman primate indicated that (-)-[18F]7 rapidly entered the brain and accumulated in the VAChT-enriched striatum. The uptake of (-)-[18F]7 in the target striatal area peaked at 10 min and displayed improved clearance kinetics compared to the VAChT tracer [18F]VAT, which has been approved by the Food and Drug Administration (FDA) for first-in-man studies. These studies justify further investigation of (-)-[18F]7 and exploration of the structure-activity relationships of these fluoroethoxy and fluoroethylamino analogs.


Identification of a glutamate/aspartate transporter in the rat cochlea.
The neurotransmitter at the synapses between hair cells and spiral ganglion cells in the cochlea is probably L-glutamate or a similar excitatory amino acid. Glutamate uptake by nerve terminals and glial cells is an important component of neurotransmission at glutamatergic synapses of the central nervous system, for providing a reservoir of transmitter or transmitter precursors and the termination of the released glutamate. Hair cell synapses are not surrounded by glial cells, therefore, the uptake mechanism for glutamate in the cochlea may be unique. cDNA was synthesized from total RNA isolated separately from the rat organ of Corti, spiral ganglia, and lateral wall tissues. The expression of a glutamate/aspartate transporter (GLAST) was detected by DNA amplification with the polymerase chain reaction. The other two members of glutamate transporters in this family were not detected by this method. A partial cDNA encoding to GLAST was identified by sequence analysis in a rat cochlear cDNA library. Data concerning the expression and the molecular structure of the glutamate transporter GLAST in the cochlea may provide important information regarding the neurotransmission process at the hair cell-afferent synapses.


Nodal changes during the early stages of Wallerian degeneration of central nerve fibres.
The nodal changes in central nerve fibres undergoing Wallerian degeneration have been studied during the first 48 hr after section of the dorsal columns of the rat by single fibre teasing and by conventional light and electron microscopic techniques. The earliest changes found at 24 hr consisted of an accumulation of mitochondria, other organelles and lamellar bodies in the nodal axoplasm. Attenuation of the myelin sheath on one side of the node due to detachment of terminal myelin loops and slipping of the outer myelin lamellae was found in some fibres, and varying degrees of nodal widening in others at 24 hr. The functional significance of these early changes in the nodal region is uncertain.


Crystal structure of a novel two domain GH78 family α-rhamnosidase from Klebsiella oxytoca with rhamnose bound.
The crystal structure of the GH78 family α-rhamnosidase from Klebsiella oxytoca (KoRha) has been determined at 2.7 Å resolution with rhamnose bound in the active site of the catalytic domain. Curiously, the putative catalytic acid, Asp 222, is preceded by an unusual non-proline cis-peptide bond which helps to project the carboxyl group into the active centre. This KoRha homodimeric structure is significantly smaller than those of the other previously determined GH78 structures. Nevertheless, the enzyme displays α-rhamnosidase activity when assayed in vitro, suggesting that the additional structural domains found in the related enzymes are dispensible for function.


Predictors of near-term fracture in osteoporotic women aged ≥65 years, based on data from the study of osteoporotic fractures.
Using data from the Study of Osteoporotic Fractures (SOF), several clinical characteristics predictive of near-term (1-year) risk of hip and non-vertebral fracture among elderly osteoporotic women were identified, and a subset of those for hip fracture was incorporated into a risk assessment tool. Additional research is needed to validate study findings. While several risk factors are known to contribute to long-term fracture risk in women with osteoporosis, factors predicting fracture risk over a shorter time horizon, such as over a 1-year period, are less well-established. We utilized a repeated-observations design and data from the Study of Osteoporotic Fractures to identify factors contributing to near-term risk of hip fracture and any non-vertebral fracture, respectively, among osteoporotic women aged ≥65 years. Potential predictors of hip fracture and any non-vertebral fracture over the 1-year period subsequent to each qualifying SOF exam were examined using multivariable frailty models. Because the discriminative ability of the hip fracture model was acceptable, a corresponding risk-prediction tool was also developed. Study population included 2499 women with osteoporosis, who contributed 6811 observations. Incidence of fracture in the 1-year period subsequent to each exam was 2.2% for hip fracture and 6.6% for any non-vertebral fracture. Independent predictors of hip fracture included low total hip T-score, prior fracture, and risk factors for falls (multivariable model c-statistic = 0.71 (95% CI 0.67-0.76)). Independent predictors of any non-vertebral fracture included age, total hip T-score, prior falls, prior fracture, walking speed, Parkinson's disease or stroke, and smoking (multivariable model c-statistic = 0.62 (0.59-0.65)). Several clinical characteristics predictive of hip and non-vertebral fracture within a 1-year follow-up period among elderly women with osteoporosis were identified, and a subset of those for hip fracture was incorporated into a risk assessment tool. Assessment of these risk factors may help guide osteoporosis treatment choices by identifying patients in whom there is urgency to treat. Additional research is needed to validate the findings of this study and the accuracy of the risk assessment tool.


Characteristics of individuals with severe mental illness who use emergency services.
Emergency services are both a safety net and a locus for acute treatment. While the population with severe, persistent mental illness uses emergency services at a high rate, few studies have systematically examined the causes of this service use. This study examines a random sample of 179 people who were high uti- lizers of services from the Los Angeles County Department of Mental Health. Interviews were conducted and 5 years of service use data were studied. Greater use of emergency services was associated with male gender, minority race, severe illness, homelessness, and less family support. Efforts to reduce emergency services need to improve access to appropriate community services, particularly for people who are homeless or lack family support.


Diffuse axonal injury in mild traumatic brain injury: a diffusion tensor imaging study.
Diffuse axonal injury (DAI) is a major complication of traumatic brain injury (TBI) that leads to functional and psychological deficits. Although DAI is frequently underdiagnosed by conventional imaging modalities, it can be demonstrated using diffusion tensor imaging. The aim of this study was to assess the presence and extent of DAI in patients with mild TBI. Forty-six patients with mild TBI and 29 healthy volunteers underwent a magnetic resonance (MR) imaging protocol including: dual-spin echo, fluid-attenuated inversion recovery, T2-weighted gradient echo, and diffusion tensor imaging sequences. In 20 of the patients, MR imaging was performed at a mean of 4.05 days after injury. In the remaining 26, MR imaging was performed at a mean of 5.7 years after injury. In each case, mean diffusivity and fractional anisotropy were measured using both whole-brain histograms and regions of interest analysis. No differences in any of the histogram-derived measures were found between patients and control volunteers. Compared with controls, a significant reduction of fractional anisotropy was observed in patients' corpus callosum, internal capsule, and centrum semiovale, and there were significant increases of mean diffusivity in the corpus callosum and internal capsule. Neither histogram-derived nor regional diffusion tensor imaging metrics differed between the two groups. Although mean diffusivity and fractional anisotropy abnormalities in these patients with TBI were too subtle to be detected with the whole-brain histogram analysis, they are present in brain areas that are frequent sites of DAI. Because diffusion tensor imaging changes are present at both early and late time points following injury, they may represent an early indicator and a prognostic measure of subsequent brain damage.


Restenosis after directional coronary atherectomy: differences between primary atheromatous and restenosis lesions and influence of subintimal tissue resection.
Rates of restenosis were evaluated in 70 patients (74 lesions) after successful directional coronary atherectomy. The extent of vascular tissue resection was correlated with restenosis rates for coronary (n = 59) and vein bypass graft (n = 15) lesions. After 6 months, the overall restenosis rate was 50% (37 of 74 lesions); it was 42% (15 of 36 lesions) when intima alone was resected, 50% (7 of 14 lesions) when media was resected and 63% (15 of 24 lesions) when adventitia was resected. Subintimal tissue resection increased the restenosis rate for vein grafts (43% with intimal resection versus 100% with subintimal resection, p = 0.01) but not for coronary arteries (50% versus 48%). There was no overall difference in restenosis rates after atherectomy between primary lesions and restenosis lesions that occurred after balloon angioplasty (46% versus 54%). Among postballoon angioplasty restenosis lesions, a higher rate of restenosis after atherectomy was found with subintimal than with intimal resection (78% versus 32%, p = 0.01). Tissues from patients undergoing a second atherectomy for restenosis after initial atherectomy (n = 8) demonstrated neointimal hyperplasia that appeared histologically identical to restenotic tissue developing after balloon angioplasty (n = 37). These data suggest that the cellular response to directional coronary atherectomy is characterized by neointimal proliferation similar to that which may develop after balloon angioplasty. The extent of fibrous hyperplasia appears to be related to the depth of tissue resection in vein graft lesions and coronary artery restenosis lesions that occur after balloon angioplasty but not in primary atheromatous coronary artery lesions.


Reconstructing masculinity? A qualitative evaluation of the Stepping Stones and Creating Futures interventions in urban informal settlements in South Africa.
Evidence shows the importance of working with men to reduce intimate partner violence and HIV-risk. Two claims dominate this work. The first is that interventions 'reconstruct' masculinities--these new formations of masculinity exist in opposition to existing ones and are healthier for men and less harmful for women. The second is that to be successful, such interventions need to address men's exclusion from the economy. Using a qualitative longitudinal cohort study of young men who participated in a gender transformative and livelihood strengthening intervention, as well as dyadic interviews with men's main female partners, we explore these claims. Data suggests men saw some improvements in livelihoods and relationships. However, challenging social contexts, including high rates of unemployment, peer networks and a dominant youth masculinity, limited change. Rather than reconstructing masculinity, a more subtle shift was seen with men moving away from 'harmful' aspects of a dominant youth masculinity towards a form of masculinity whereby male power is buttressed by economic provision and attempting to form and support 'households'. Working with men on their livelihoods at an instrumental level encouraged participation in the intervention. Beyond encouragement, men's improving livelihoods afforded men the opportunity to materially demonstrate the social changes - in the form of shifts in masculinity--they were seeking to enact.


Psychosis and Substance Use: Implications for Conditional Release Readiness Evaluations.
In Foucha v. Louisiana (1992), the United States Supreme Court ruled that individuals adjudicated not guilty by reason of insanity (NGRI) could not remain in a forensic hospital if they were no longer mentally ill and dangerous. Since this decision, a variety of important questions have arisen related to the insanity defense and what should happen to insanity acquittees post-adjudication. This article provides an analysis of clinical issues confronting forensic examiners when psychosis as a result of substance abuse is the underlying condition supporting an insanity defense. To accomplish this analysis, this article provides the reader with a review of literature showing the complex relationship between psychosis and substance abuse. Second, this article investigates how substance-induced psychosis may impact both insanity opinions and subsequent conditional release decisions. Third, the article aims to provide research-driven information to assist clinicians in conducting conditional release evaluations. Finally, this paper provides a model for evaluating dangerousness in the context of conditional release evaluations. Given the substantial comorbidity between substance abuse and psychosis, it is critical for researchers and clinicians to consider potential effects of substance abuse when evaluating insanity acquittees for conditional release, especially as substance use relates to future dangerousness. Copyright © 2016 John Wiley & Sons, Ltd.


Tailoring the structure of thin film nanocomposite membranes to achieve seawater RO membrane performance.
Herein we report on the formation and characterization of pure polyamide thin film composite (TFC) and zeolite-polyamide thin film nanocomposite (TFN) reverse osmosis (RO) membranes. Four different physical-chemical post-treatment combinations were applied after the interfacial polymerization reaction to change the molecular structure of polyamide and zeolite-polyamide thin films. Both TFC and TFN hand-cast membranes were more permeable, hydrophilic, and rough than a commercial seawater RO membrane. Salt rejection by TFN membranes was consistently below that of hand-cast TFC membranes; however, two TFN membranes exhibited 32 g/L NaCl rejections above 99.4%, which was better than the commercial membrane under the test conditions employed. The nearly defect-free TFN films that produced such high rejections were achieved only with wet curing, regardless of other post-treatments. Polyamide films formed in the presence of zeolite nanoparticles were less cross-linked than similarly cast pure polyamide films. At the very low nanoparticle loadings evaluated, differences between pure polyamide and zeolite-polyamide membrane water and salt permeability correlated weakly with extent of cross-linking of the polyamide film, which suggests that defects and molecular-sieving largely govern transport through zeolite-polyamide thin film nanocomposite membranes.


A longitudinal study of Junin virus activity in the rodent reservoir of Argentine hemorrhagic fever.
We monitored Junin virus (JV) activity in rodent populations for 30 months at seven mark-recapture grids located in agricultural fields and adjacent roadsides and fence lines in endemic and nonendemic areas of Argentine hemorrhagic fever. Blood and oral swabs taken from rodents captured at five-week intervals were analyzed by enzyme-linked immunosorbent assay for JV antigen (Ag). Calomys laucha and C. musculinus were the most frequently captured rodents, making up 47% and 22% of captures, respectively. Of 41 Ag-positive captures, 37 were C. musculinus and four were C. laucha; 34 were from two trapping grids in the same locality. Antigen-positive Calomys were more frequently male (76%), and were found significantly more frequently among the oldest animals and the largest body mass classes. These patterns, combined with the greater mobility and higher frequencies of wounds among males than females, implicated horizontal transmission as the primary route of JV transmission between rodents. Seasonal maximum levels in JV prevalence (up to 25% of captured Ag-positive C. musculinus) occurred during periods of maximal population densities of Calomys. Spatial distribution of Ag-positive rodents reflected habitat preferences; most Ag-positive C. musculinus were captured from border habitats (roadsides and fence lines), and all Ag-positive C. laucha were captured in crop fields. These distinct, but previously undocumented, habitat preferences suggest that the disease in humans may be related to exposures to the primary reservoir species, C. musculinus, in border habitats rather than in crop fields.


Ability to digest starch assessed noninvasively with a 13CO2 breath test - comparison of results obtained in two groups of different age.
We evaluated the effect of age on the results of a cornflakes breath test that determines the efficiency of starch digestion. Two groups of 12 fasted healthy subjects (group Y, 24.7+/-0.6 years; and group MA, 49.7+/-1.3 years) consumed a 521-kcal test breakfast of 100 g cornflakes naturally abundant in 13C (-14.00 per thousand 13C enrichment relative to the Vienna Pee Dee belemnite standard). Then, the 13CO2 concentration was measured in samples of exhaled air collected over 9 hours. We noted a maximum momentary 13CO2 breath excretion of 7.54+/-0.19% dose/h at 298 +/- 15 minutes in group Y and 7.70+/-0.27% dose/h at 305+/-10 minutes in group MA. The group curves of the cumulative 13C recovery in breath air exhibited a virtually overlapping time course. The 6-hour cumulative 13C recovery was 29.33+/-0.70%dose in group Y and 29.87+/-1.18%dose in group MA. Extending the collection period from 6 to 9 hours produced an increase in the cumulative 13C recovery of 58.4+/-2.1%. The 9-hour cumulative 13C recovery was 46.58+/-1.04%dose in the Y group and 46.93+/-1.84%dose and the MA group. An age difference of more than 2 decades was not associated with a negative impact on the in vivo ability to digest starch. The reference values of the cornflakes breath test can be derived from healthy subjects in a relatively wide age range.


Reprint of: Monocyte subsets in man and other species.
Monocytes are white blood cells that belong to the mononuclear phagocyte system. They derive from precursors in bone marrow, from there they go into blood, where they have a half-life of 1-2 days, and then they migrate into the various tissues. Monocyte subsets were discovered by means of flow cytometry in human blood some 20 years ago and their phenotype and function has been characterized in detail in health and disease. The subset classification as classical, intermediate and non-classical monocytes appears to apply to other species as well, as reviewed in here by comparing data on human monocytes with the respective cells in the mouse, the rat, the pig, the cow and the horse. The data show that the subsets are homologous between the species but there are important differences in subset-specific gene expression such that findings in a given species cannot be directly translated to man.


Reconstitution of cortical Dynein function.
Cytoplasmic dynein is a major microtubule (MT)-associated motor in nearly all eukaryotic cells. A subpopulation of dyneins associates with the cell cortex and the interaction of this cortical dynein with MTs helps to drive processes such as nuclear migration, mitotic spindle orientation, and cytoskeletal reorientation during wound healing. In this chapter, we describe three types of assays in which interactions between cortical dynein and MTs are reconstituted in vitro at increasing levels of complexity. In the first 1D assay, MTs, nucleated from a centrosome attached to a surface, grow against dynein-coated gold barriers. In this assay configuration, the interactions between MTs and dynein attached to a barrier can be studied in great detail. In the second and third assays, a freely moving dynamic aster is placed in either a 2D microfabricated chamber or a 3D water-in-oil emulsion droplet, with dynein-coated boundaries. These assays can be used to study how cortical dynein positions centrosomes. Finally, we discuss future possibilities for increasing the complexity of these reconstituted systems.


Sexual and reproductive behaviour among single women aged 15-24 in eight Latin American countries: a comparative analysis.
A comparative analysis of exposure to sexual activity, contraceptive use, conceptions, and pregnancy resolutions among single women aged 15-24 in eight Latin American countries is presented. Using data from Demographic and Health Surveys complete contraceptive and reproductive histories are constructed for single women aged 15-24 during the 5 year period preceding each survey. Pre-marital conception rates and overall and cause-specific life-table probabilities of contraceptive discontinuation are estimated. Pregnancy outcome and intention status of births are summarized. Trends in virginity, contraceptive protection, and conception rates for five sites are documented. In all eight countries, virginity accounts for over half of all single woman-years of exposure between age 15 and 24. The percentage of sexually active time protected by contraception is less than 20% in five countries, is about 30% in Peru and 50% in Brazil and Colombia. The contribution of condoms to contraceptive protection ranges from one-tenth to one-fifth. Pre-marital conception rates among sexually active single women range from 14.1 per 100 woman-years in Nicaragua to 25.8 in Bolivia. Most pre-marital conceptions ended in live birth, and births that are legitimized by marriage or cohabitation are more likely to be wanted. In five settings, virginity has fallen over time, especially in Northeast Brazil and Colombia, and uptake of condoms has increased faster than use of other methods. Because of pervasive declines in the protective effect of virginity, conception rates among single women in Latin America are rising. Contraceptive uptake, particularly of condoms, is increasing but not sufficiently to offset the decline in virginity.


Change of antibiotic susceptibility testing guidelines from CLSI to EUCAST: influence on cumulative hospital antibiograms.
We studied whether the change in antibiotic susceptibility testing (AST) guidelines from CLSI to EUCAST influenced cumulative antibiograms in a tertiary care hospital in Switzerland. Antibiotic susceptibilities of non-duplicate isolates collected within a one-year period before (period A) and after (period B) changing AST interpretation from CLSI 2009 to EUCAST 1.3 (2011) guidelines were analysed. In addition, period B isolates were reinterpreted according to the CLSI 2009, CLSI 2013 and EUCAST 3.1 (2013) guidelines. The majority of species/drug combinations showed no differences in susceptibility rates comparing periods A and B. However, in some gram-negative bacilli, decreased susceptibility rates were observed when comparing CLSI 2009 with EUCAST 1.3 within period B: Escherichia coli / cefepime, 95.8% (CLSI 2009) vs. 93.1% (EUCAST 1.3), P=0.005; Enterobacter cloacae / cefepime, 97.0 (CLSI 2009) vs. 90.5% (EUCAST 1.3), P=0.012; Pseudomonas aeruginosa / meropenem, 88.1% (CLSI 2009) vs. 78.3% (EUCAST 1.3), P=0.002. These differences were still evident when comparing susceptibility rates according to the CLSI 2013 guideline with EUCAST 3.1 guideline. For P. aeruginosa and imipenem, a trend towards a lower antibiotic susceptibility rate in ICUs compared to general wards turned into a significant difference after the change to EUCAST: 87.9% vs. 79.8%, P=0.08 (CLSI 2009) and 86.3% vs. 76.8%, P=0.048 (EUCAST 1.3). The change of AST guidelines from CLSI to EUCAST led to a clinically relevant decrease of susceptibility rates in cumulative antibiograms for defined species/drug combinations, particularly in those with considerable differences in clinical susceptibility breakpoints between the two guidelines.


Concerted action of the cytosolic sulfotransferase, SULT1A3, and catechol-O-methyltransferase in the metabolism of dopamine in SK-N-MC human neuroblastoma cells.
Conjugation reactions catalyzed by the cytosolic sulfotransferase, SULT1A3, or catechol-O-methyltransferase (COMT) are known to be involved in the regulation and homeostasis of dopamine and other monoamine neurotransmitters. Whether different conjugation reactions may act in a concerted manner, however, remains unclear. The current study aimed to investigate the concerted action of SULT1A3 and COMT in dopamine metabolism. Analysis of the medium of SK-N-MC cells, metabolically labeled with [(35)S]sulfate in the presence of dopamine, revealed the generation and release of predominantly [(35)S]sulfated 3-methyldopamine and, to a lesser extent [(35)S]sulfated dopamine. Addition to the labeling medium of tropolone, a COMT inhibitor, enhanced the production of [(35)S]sulfated dopamine, with a concomitant decrease of [(35)S]sulfated 3-methyldopamine. Enzymatic assays using the eleven known human cytosolic SULTs revealed SULT1A3 as the major enzyme responsible for the sulfation of both dopamine and 3-methyldopamine. Kinetic analysis showed that the catalytic efficiency of SULT1A3 with 3-methyldopamine was 1.6 times than that with dopamine. Using subcellular fractions prepared from SK-N-MC cells, the majority of COMT dopamine-methylating activity was found to be present in the cytosol. Collectively, these results imply a concerted action of sulfation and methylation in the irreversible inactivation and disposal of excess dopamine in SK-N-MC cells.


Structural model and functional significance of pH-dependent talin-actin binding for focal adhesion remodeling.
Actin filament binding by the focal adhesion (FA)-associated protein talin stabilizes cell-substrate adhesions and is thought to be rate-limiting in cell migration. Although F-actin binding by talin is known to be pH-sensitive in vitro, with lower affinity at higher pH, the functional significance of this pH dependence is unknown. Because increased intracellular pH (pH(i)) promotes cell migration and is a hallmark of metastatic carcinomas, we asked whether it increases FA remodeling through lower-affinity talin-actin binding. Talin contains several actin binding sites, but we found that only the COOH-terminal USH-I/LWEQ module showed pH-dependent actin binding, with lower affinity and decreased maximal binding at higher pH. Molecular dynamics simulations and NMR of this module revealed a structural mechanism for pH-dependent actin binding. A cluster of titratable amino acids with upshifted pK(a) values, including His-2418, was identified at one end of the five-helix bundle distal from the actin binding site. Protonation of His-2418 induces changes in the conformation and dynamics of the remote actin binding site. Structural analyses of a mutant talin-H2418F at pH 6.0 and 8.0 suggested changes different from the WT protein, and we confirmed that actin binding by talin-H2418F was relatively pH-insensitive. In motile fibroblasts, increasing pH(i) decreased FA lifetime and increased the migratory rate. However, expression of talin-H2418F increased lifetime 2-fold and decreased the migratory rate. These data identify a molecular mechanism for pH-sensitive actin binding by talin and suggest that FA turnover is pH-dependent and in part mediated by pH-dependent affinity of talin for binding actin.


Characterisation of single domain ATP-binding cassette protien homologues of Theileria parva.
Two distinct genes encoding single domain, ATP-binding cassette transport protein homologues of Theileria parva were cloned and sequenced. Neither of the genes is tandemly duplicated. One gene, TpABC1, encodes a predicted protein of 593 amino acids with an N-terminal hydrophobic domain containing six potential membrane-spanning segments. A single discontinuous ATP-binding element was located in the C-terminal region of TpABC1. The second gene, TpABC2, also contains a single C-terminal ATP-binding motif. Copies of TpABC2 were present at four loci in the T. parva genome on three different chromosomes. TpABC1 exhibited allelic polymorphism between stocks of the parasite. Comparison of cDNA and genomic sequences revealed that TpABC1 contained seven short introns, between 29 and 84 bp in length. The full-length TpABC1 protein was expressed in insect cells using the baculovirus system. Application of antibodies raised against the recombinant antigen to western blots of T. parva piroplasm lysates detected an 85 kDa protein in this life-cycle stage.


Analysis of simultaneous MEG and intracranial LFP recordings during Deep Brain Stimulation: a protocol and experimental validation.
Deep Brain Stimulation (DBS) is an effective treatment for several neurological and psychiatric disorders. In order to gain insights into the therapeutic mechanisms of DBS and to advance future therapies a better understanding of the effects of DBS on large-scale brain networks is required. In this paper, we describe an experimental protocol and analysis pipeline for simultaneously performing DBS and intracranial local field potential (LFP) recordings at a target brain region during concurrent magnetoencephalography (MEG) measurement. Firstly we describe a phantom setup that allowed us to precisely characterise the MEG artefacts that occurred during DBS at clinical settings. Using the phantom recordings we demonstrate that with MEG beamforming it is possible to recover oscillatory activity synchronised to a reference channel, despite the presence of high amplitude artefacts evoked by DBS. Finally, we highlight the applicability of these methods by illustrating in a single patient with Parkinson's disease (PD), that changes in cortical-subthalamic nucleus coupling can be induced by DBS. To our knowledge this paper provides the first technical description of a recording and analysis pipeline for combining simultaneous cortical recordings using MEG, with intracranial LFP recordings of a target brain nucleus during DBS.


Long-term outcomes of percutaneous coronary intervention for unprotected left main coronary artery disease.
This study evaluates the in-hospital, 30 day and long-term results of stenting for unprotected left main coronary artery disease in our institution. Between April 2001 and October 2005 all unprotected left main cases were retrospectively reviewed. Outcomes were obtained by case note review and postal questionnaire; primary care physicians were contacted to complete missing data. We identified 100 consecutive patients who underwent unprotected left main procedures, 1.44% of the institution PCI volume. Indications for a percutaneous strategy were non-surgical candidates (47), emergency revascularisation (25) and patient/physician preference (28). Overall procedural success was 97%. The majority of cases (n=78) were performed with a single-stent strategy. 55% received a drug-eluting stent. There were 7 in-hospital deaths, 5 in the emergency group (cardiogenic shock) and 2 non-CABG candidates. Post hospital discharge long-term clinical follow-up was 651+/-431 days (range 6-1741). There were 8 deaths post discharge. Patients presenting as an emergency had a 72% survival rate at long-term follow-up, non-surgical candidates 83%, and patient/physician preference group had a 100% long-term survival. Multivariate analysis revealed cardiogenic shock (HR=7.9, 95% CI 1.7-3.6, p=0.008), failed thrombolysis (HR=8.5, 95% CI 1.7-41.7, p=0.008) and use of a bare-metal stent (HR=4.4, 1.1-17.0, p=0.034) were independent predictors of mortality. Our data suggest that in contemporary practice stenting for unprotected left main disease can be considered as an alternative treatment to surgery for selected patients. The results of randomised controlled trials are awaited.


Geographic variation in postpartum prescription opioid use: Opportunities to improve maternal safety.
Obstetric delivery is among the most common in-hospital procedures experienced by reproductive-age women, yet there is little literature on patterns of postpartum opioid prescriptions after such episodes. We used claims data from 871,195 vaginal deliveries to 768,455 privately-insured women with an in-hospital delivery between June 2001 and July 2013 to examine the state- and census division-level proportions of women who filled an opioid prescription within four days of hospital discharge after vaginal delivery. Our primary outcome examined the proportion of women who filled an opioid prescription after uncomplicated vaginal delivery (e.g., without forceps extraction, vacuum extraction, or 3rd/4th degree perineal laceration). Secondary outcomes examined state- and census division-level variation in opioid prescription duration (proportion of prescriptions exceeding five days) and dose (proportion of prescriptions exceeding 280 morphine milligram equivalents). We also displayed national temporal trends in opioid prescribing rate and dose for uncomplicated vaginal delivery in comparison to complicated vaginal delivery. Across states, we found a 7-fold variation in postpartum opioid prescription rates (7.6-53.4%), a 5-fold variation in opioid prescriptions for greater than five days' duration (5.1-25.7%), and a 19% absolute difference in opioid prescriptions for greater than 280 morphine milligram equivalents (0-19.3%) following uncomplicated vaginal delivery. These wide variations in postpartum opioid prescription practices suggest opportunities to develop guidelines on postpartum opioid use, to improve prescription safety, and to reduce opioid-related harms among women in the postpartum period.


Ga-Doped Pt-Ni Octahedral Nanoparticles as a Highly Active and Durable Electrocatalyst for Oxygen Reduction Reaction.
Bimetallic PtNi nanoparticles have been considered as a promising electrocatalyst for oxygen reduction reaction (ORR) in polymer electrolyte membrane fuel cells (PEMFCs) owing to their high catalytic activity. However, under typical fuel cell operating conditions, Ni atoms easily dissolve into the electrolyte, resulting in degradation of the catalyst and the membrane-electrode assembly (MEA). Here, we report gallium-doped PtNi octahedral nanoparticles on a carbon support (Ga-PtNi/C). The Ga-PtNi/C shows high ORR activity, marking an 11.7-fold improvement in the mass activity (1.24 A mgPt-1) and a 17.3-fold improvement in the specific activity (2.53 mA cm-2) compared to the commercial Pt/C (0.106 A mgPt-1 and 0.146 mA cm-2). Density functional theory calculations demonstrate that addition of Ga to octahedral PtNi can cause an increase in the oxygen intermediate binding energy, leading to the enhanced catalytic activity toward ORR. In a voltage-cycling test, the Ga-PtNi/C exhibits superior stability to PtNi/C and the commercial Pt/C, maintaining the initial Ni concentration and octahedral shape of the nanoparticles. Single cell using the Ga-PtNi/C exhibits higher initial performance and durability than those using the PtNi/C and the commercial Pt/C. The majority of the Ga-PtNi nanoparticles well maintain the octahedral shape without agglomeration after the single cell durability test (30,000 cycles). This work demonstrates that the octahedral Ga-PtNi/C can be utilized as a highly active and durable ORR catalyst in practical fuel cell applications.


Neutrophil extracellular traps in the host defense against sepsis induced by Burkholderia pseudomallei (melioidosis).
Neutrophil extracellular traps (NETs) are a central player in the host response to bacteria: neutrophils release extracellular DNA (nucleosomes) and neutrophil elastase to entrap and kill bacteria. We studied the role of NETs in Burkholderia pseudomallei infection (melioidosis), an important cause of Gram-negative sepsis in Southeast Asia. In a prospective observational study, circulating nucleosomes and neutrophil elastase were assayed in 44 patients with Gram-negative sepsis caused by B. pseudomallei (melioidosis) and 82 controls. Functional assays included human neutrophil stimulation and killing assays and a murine model of B. pseudomallei infection in which NET function was compromised using DNase. Specified pathogen-free 8- to 12-week-old C57BL/6 mice were sacrificed post-infection to assess bacterial loads, inflammation, and pathology. Nucleosome and neutrophil elastase levels were markedly elevated in patients compared to controls. NETs killed B. pseudomallei effectively, and neutrophils stimulated with B. pseudomallei showed increased elastase and DNA release in a time- and dose-dependent matter. In mice, NET disruption with intravenous DNase administration resulted in decreased nucleosome levels. Although DNase treatment of mice resulted in diminished liver inflammation, no differences were observed in bacterial dissemination or systemic inflammation. B. pseudomallei is a potent inducer of NETosis which was reflected by greatly increased levels of NET-related components in melioidosis patients. Although NETs exhibited antibacterial activity against B. pseudomallei, NET formation did not protect against bacterial dissemination and inflammation during B. pseudomallei-induced sepsis.


What would my avatar do? Gaming, pathology, and risky decision making.
Recent work has revealed a relationship between pathological video game use and increased impulsivity among children and adolescents. A few studies have also demonstrated increased risk-taking outside of the video game environment following game play, but this work has largely focused on one genre of video games (i.e., racing). Motivated by these findings, the aim of the current study was to examine the relationship between pathological and non-pathological video game use, impulsivity, and risky decision making. The current study also investigated the relationship between experience with two of the most popular genres of video games [i.e., first-person shooter (FPS) and strategy] and risky decision making. Consistent with previous work, ~7% of the current sample of college-aged adults met criteria for pathological video game use. The number of hours spent gaming per week was associated with increased impulsivity on a self-report measure and on the temporal discounting (TD) task. This relationship was sensitive to the genre of video game; specifically, experience with FPS games was positively correlated with impulsivity, while experience with strategy games was negatively correlated with impulsivity. Hours per week and pathological symptoms predicted greater risk-taking in the risk task and the Iowa Gambling task, accompanied by worse overall performance, indicating that even when risky choices did not pay off, individuals who spent more time gaming and endorsed more symptoms of pathological gaming continued to make these choices. Based on these data, we suggest that the presence of pathological symptoms and the genre of video game (e.g., FPS, strategy) may be important factors in determining how the amount of game experience relates to impulsivity and risky-decision making.


The architecture of functional lateralisation and its relationship to callosal connectivity in the human brain.
Functional lateralisation is a fundamental principle of the human brain. However, a comprehensive taxonomy of functional lateralisation and its organisation in the brain is missing. Here, we report the first complete map of functional hemispheric asymmetries in the human brain, reveal its low dimensional structure, and its relationship with structural inter-hemispheric connectivity. Our results suggest that the lateralisation of brain functions is distributed along four functional axes: symbolic communication, perception/action, emotion, and decision-making. The similarity between this finding and recent work on neurological symptoms give rise to new hypotheses on the mechanisms that support brain recovery after a brain lesion. We also report that cortical regions showing asymmetries in task-evoked activity have reduced connections with the opposite hemisphere. This latter result suggests that during evolution, brain size expansion led to functional lateralisation to avoid excessive conduction delays between the hemispheres.