[Percutaneous Endovascular Aortic Repair with Local Anesthesia - One Day Surgery].
To evaluate the results of the abdominal aortic aneurism endovascular treatment (EVAR), percutaneously and with local anesthesia, according to the concept of one day surgery. Unicentric, retrospective analysis of patients with aorto-iliac aneurysmal disease, consecutively treated by EVAR with percutaneous access trough the Preclose technique (pEVAR), according to the outpatient criteria, with one overnight stay in the hospital. The technical success, exclusion of the aneurysmal sac, endoleak, re-intervention and mortality were evaluated. Twenty consecutive patients (all male; mean age 74.65 years) were treated by EVAR with percutaneous access and local anesthesia, from which 95% (19) presented with abdominal aortic aneurysm and 5% (1) common iliac aneurysm. All implants were sucessfully performed, with an initial endoleak rate of 10% (2), determined by one type 1a endoleak successfully corrected intra-operatively and one type 2a endoleak diagnosed in the first imaging control, which sealed spontaneously on the second control. Initial technical success for percutaneous closure was 97.5%, with one case reported of femoral pseudo-aneurism, posteriorly treated by percutaneous thrombin injection. Median length of stay was one day [1-10], with a mean follow-up of 11.4 months [1-36]. Both the re-intervention and mortality rate are 0% for the selected period. Our one day surgery model for the outpatient treatment of abdominal aortic aneurysm by the pEVAR technique is innovative, safe and effective, as long as the selection criteria are respected.


Transcriptome-wide sequencing provides insights into geocarpy in peanut (Arachis hypogaea L.).
A characteristic feature of peanut is the subterranean fructification, geocarpy, in which the gynophore ('peg'), a specialized organ that transitions from upward growth habit to downward outgrowth upon fertilization, drives the developing pod into the soil for subsequent development underground. As a step towards understanding this phenomenon, we explore the developmental dynamics of the peanut pod transcriptome at 11 successive stages. We identified 110 217 transcripts across developmental stages and quantified their abundance along a pod developmental gradient in pod wall. We found that the majority of transcripts were differentially expressed along the developmental gradient as well as identified temporal programs of gene expression, including hundreds of transcription factors. Thought to be an adaptation to particularly harsh subterranean environments, both up- and down-regulated gene sets in pod wall were enriched for response to a broad array of stimuli, like gravity, light and subterranean environmental factors. We also identified hundreds of transcripts associated with gravitropism and photomorphogenesis, which may be involved in the geocarpy. Collectively, this study forms a transcriptional baseline for geocarpy in peanut as well as provides a considerable body of evidence that transcriptional regulation in peanut aerial and subterranean fruits is complex.


The tyranny of the averages and the indiscriminate use of risk factors in public health: The case of coronary heart disease.
Modern medicine is overwhelmed by a plethora of both established risk factors and novel biomarkers for diseases. The majority of this information is expressed by probabilistic measures of association such as the odds ratio (OR) obtained by calculating differences in average "risk" between exposed and unexposed groups. However, recent research demonstrates that even ORs of considerable magnitude are insufficient for assessing the ability of risk factors or biomarkers to distinguish the individuals who will develop the disease from those who will not. In regards to coronary heart disease (CHD), we already know that novel biomarkers add very little to the discriminatory accuracy (DA) of traditional risk factors. However, the value added by traditional risk factors alongside simple demographic variables such as age and sex has been the subject of less discussion. Moreover, in public health, we use the OR to calculate the population attributable fraction (PAF), although this measure fails to consider the DA of the risk factor it represents. Therefore, focusing on CHD and applying measures of DA, we re-examine the role of individual demographic characteristics, risk factors, novel biomarkers and PAFs in public health and epidemiology. In so doing, we also raise a more general criticism of the traditional risk factors' epidemiology. We investigated a cohort of 6103 men and women who participated in the baseline (1991-1996) of the Malmö Diet and Cancer study and were followed for 18 years. We found that neither traditional risk factors nor biomarkers substantially improved the DA obtained by models considering only age and sex. We concluded that the PAF measure provided insufficient information for the planning of preventive strategies in the population. We need a better understanding of the individual heterogeneity around the averages and, thereby, a fundamental change in the way we interpret risk factors in public health and epidemiology.


Phosphoproteome analysis during larval development and metamorphosis in the spionid polychaete Pseudopolydora vexillosa.
The metamorphosis of the spionid polychaete Pseudopolydora vexillosa includes spontaneous settlement onto soft-bottom habitats and morphogenesis that can be completed in a very short time. A previous study on the total changes to the proteome during the various developmental stages of P. vexillosa suggested that little or no de novo protein synthesis occurs during metamorphosis. In this study, we used multicolor fluorescence detection of proteins in 2-D gels for differential analysis of proteins and phosphoproteins to reveal the dynamics of post-translational modification proteins in this species. A combination of affinity chromatography, 2D-PAGE, and mass spectrometry was used to identify the phosphoproteins in pre-competent larvae, competent larvae, and newly metamorphosed juveniles. We reproducibly detected 210, 492, and 172 phosphoproteins in pre-competent larvae, competent larvae, and newly metamorphosed juveniles, respectively. The highest percentage of phosphorylation was observed during the competent larval stage. About 64 stage-specific phosphoprotein spots were detected in the competent stage, and 32 phosphoproteins were found to be significantly differentially expressed in the three stages. We identified 38 phosphoproteins, 10 of which were differentially expressed during metamorphosis. These phosphoproteins belonged to six categories of biological processes: (1) development, (2) cell differentiation and integrity, (3) transcription and translation, (4) metabolism, (5) protein-protein interaction and proteolysis, and (6) receptors and enzymes. This is the first study to report changes in phosphoprotein expression patterns during the metamorphosis of the marine polychaete P. vexillosa. The higher degree of phosphorylation during the process of attaining competence to settle and metamorphose may be due to fast morphological transitions regulated by various mechanisms. Our data are consistent with previous studies showing a high percentage of phosphorylation during competency in the barnacle Balanus amphitrite and the bryozoan Bugula neritina. The identified phosphoproteins may play an important role during metamorphosis, and further studies on the location and functions of important proteins during metamorphosis are warranted.


Analysis of anthrax and plague biowarfare vaccine interactions with human monocyte-derived dendritic cells.
The anti-biowarfare anthrax and plague vaccines require repeated dosing to achieve adequate protection. To test the hypothesis that this limited immunogenicity results from the nature of vaccine interactions with the host innate immune system, we investigated molecular and cellular interactions between vaccines, dendritic cells (DCs), and T cells and explored the potential for adjuvants (pertussis) to boost induction of host immunity. Human monocyte-derived DCs were matured in the presence of vaccines and analyzed for their ability to induce Th1/Th2 development from naive T cells, expression of cell surface maturation/costimulation molecules, and cytokine production. The vaccines showed different behavior patterns. Although the plague vaccine is equivalent to control maturation factors in maturation and stimulation of DCs and induces strong MLR and Th outgrowth, the anthrax vaccine is a poor inducer of DC maturation, as indicated by low levels of HLA-DR, CD86, and CD83 induction and minimal proinflammatory cytokine production. Interestingly, however, anthrax vaccine-treated DCs stimulate Th1 and Th2 outgrowth and a limited MLR response. There was no sustained negative modulatory effects of the anthrax vaccine on DCs, and its limited stimulatory effects could be overridden by coculture with pertussis. These results were supported by analysis of anthrax vaccine recall responses in subjects vaccinated using pertussis as an adjuvant, who demonstrate anthrax-specific effector T cell responses. These data show that the anthrax vaccine is a suboptimal DC stimulus that may in part explain the observation that it requires repeated administration in vivo and offer a rational basis for the use of complementary DC-maturing adjuvants in combined immunotherapy.


Self-organizing path integration using a linked continuous attractor and competitive network: path integration of head direction.
A key issue is how networks in the brain learn to perform path integration, that is update a represented position using a velocity signal. Using head direction cells as an example, we show that a competitive network could self-organize to learn to respond to combinations of head direction and angular head rotation velocity. These combination cells can then be used to drive a continuous attractor network to the next head direction based on the incoming rotation signal. An associative synaptic modification rule with a short term memory trace enables preceding combination cell activity during training to be associated with the next position in the continuous attractor network. The network accounts for the presence of neurons found in the brain that respond to combinations of head direction and angular head rotation velocity. Analogous networks in the hippocampal system could self-organize to perform path integration of place and spatial view representations.


Epidemiological characteristics of Salmonella Typhimurium isolated from animals and feed in Poland.
Fifty-seven Salmonella Typhimurium strains isolated from poultry, swine and animal feed in Poland during the years 1979-1998 and 2000-2002 were analysed with conventional and molecular techniques. Antimicrobial resistance as well as multiresistance was found, respectively, in 80.1% and 56.1% of the isolates and most frequently among isolates from 2000-2002. Of several phage types noted, DT104 was prevalent among poultry, swine and feed isolates. DT104, U302 and non-typable strains had a multiple resistant profile (ACSSuT) due to the presence of class I integrons. Pulse-field gel electrophoresis of XbaI and BlnI digest showed high genomic similarity between the strains and confirmed clonal spread of S. Typhimurium infections. Plasmid profiling allowed further differentiation of the strains. We have, therefore, confirmed the appearance of S. Typhimurium DT104 showing genome integrated integron-mediated antimicrobial resistance in Poland. These findings are significant for public and animal health risks and document the dissemination of DT104 epidemic strains into new geographical regions.


No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset.
An impaired cerebrospinal venous drainage, defined as chronic cerebrospinal venous insufficiency (CCSVI), has been recently hypothesized to be the possible cause of multiple sclerosis (MS). We investigated this hypothesis by studying the occurrence of CCSVI in clinically isolated syndromes (CISs) suggestive of MS. Fifty consecutive patients presenting with a CIS and evidence of dissemination in space of the inflammatory lesions (ie, possible MS [pMS]) underwent a detailed diagnostic workup, including extracranial and transcranial venous echo-color Doppler sonography (ECDS-TCDS). Those with CCSVI underwent selective venography. Fifty healthy subjects (HCs) age-matched and gender-matched with pMS patients (HC1); 60 patients with transient global amnesia (TGA); and 60 healthy subjects age-matched and gender-matched with TGA patients (HC2) constituted the control groups and underwent ECDS-TCDS. Mean age of pMS patients was 33.0 ± 8.5 years (range, 14-50); 35 (70%) were female (female:male ratio, 2.3). TCDS was normal in all pMS patients. One or more abnormal ECDS findings were observed in 26 of 50 (52.0%) pMS patients, in 35 of 110 (31·8%) HCs (HC1+HC2), and in 41 of 60 (68.3%) TGA patients. Eight (16%) pMS patients fulfilled the diagnosis of CCSVI. Selective phlebography performed in 7 of these patients (1 denied consent) did not show venous anomalies. Our findings do not support a cause-effect relationship between CCSVI and pMS. Further studies are warranted to clarify whether CCSVI is associated with later disease stages and characterizes the progressive forms of MS.


p107 inhibits G1 to S phase progression by down-regulating expression of the F-box protein Skp2.
Cell cycle progression is negatively regulated by the pocket proteins pRb, p107, and p130. However, the mechanisms responsible for this inhibition are not fully understood. Here, we show that overexpression of p107 in fibroblasts inhibits Cdk2 activation and delays S phase entry. The inhibition of Cdk2 activity is correlated with the accumulation of p27, consequent to a decreased degradation of the protein, with no change of Thr187 phosphorylation. Instead, we observed a marked decrease in the abundance of the F-box receptor Skp2 in p107-overexpressing cells. Reciprocally, Skp2 accumulates to higher levels in p107-/- embryonic fibroblasts. Ectopic expression of Skp2 restores p27 down-regulation and DNA synthesis to the levels observed in parental cells, whereas inactivation of Skp2 abrogates the inhibitory effect of p107 on S phase entry. We further show that the serum-dependent increase in Skp2 half-life observed during G1 progression is impaired in cells overexpressing p107. We propose that p107, in addition to its interaction with E2F, inhibits cell proliferation through the control of Skp2 expression and the resulting stabilization of p27.


Second Chern number of a quantum-simulated non-Abelian Yang monopole.
Topological order is often quantified in terms of Chern numbers, each of which classifies a topological singularity. Here, inspired by concepts from high-energy physics, we use quantum simulation based on the spin degrees of freedom of atomic Bose-Einstein condensates to characterize a singularity present in five-dimensional non-Abelian gauge theories-a Yang monopole. We quantify the monopole in terms of Chern numbers measured on enclosing manifolds: Whereas the well-known first Chern number vanishes, the second Chern number does not. By displacing the manifold, we induce and observe a topological transition, where the topology of the manifold changes to a trivial state.


Comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B: a systematic review.
Chronic viral hepatitis B remains a global public health concern. Currently, several drugs, such as tenofovir and adefovir, are recommended for treatment of patients with chronic hepatitis B. tenofovir is a nucleoside analog with selective activity against hepatitis b virus and has been shown to be more potent in vitro than adefovir. But the results of trials comparing tenofovir and adefovir in the treatment of chronic hepatitis B were inconsistent. However, there was no systematic review on the comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B. To evaluate the comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B we conducted a systematic review and meta-analysis of clinical trials. We searched PUBMED, Web of Science, EMBASE, CNKI, VIP database, WANFANG database, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Review. Finally six studies were left for analysis which involved 910 patients in total, of whom 576 were included in tenofovir groups and 334 were included in adefovir groups. At the end of 48-week treatment, tenofovir was superior to adefovir at the HBV-DNA suppression in patients[RR = 2.59; 95%CI(1.01-6.67), P = 0.05]. While there was no significant difference in the ALT normalization[RR = 1.15; 95%CI(0.96-1.37), P = 0.14], HBeAg seroconversion[RR = 1.32; 95%CI(1.00-1.75), P = 0.05] and HBsAg loss rate[RR = 1.19; 95%CI(0.74-1.91), P = 0.48]. More high-quality, well-designed, randomized controlled, multi-center trails are clearly needed to guide evolving standards of care for chronic hepatitis B.


Association of insulin receptor substrate-1 with integrins.
Insulin stimulation was found to promote association of the alpha v beta 3 integrin (a vitronectin receptor) with insulin receptor substrate-1 (IRS-1), an intracellular protein that mediates insulin signaling by binding other signaling molecules, including growth factor receptor-bound protein 2 (Grb2) and phosphatidylinositol-3' kinase. Insulin-treated cells expressing the alpha v beta 3 integrin showed 2.5 times more DNA synthesis when plated on vitronectin than on other substrates, whereas cells expressing another vitronectin receptor, alpha v beta 5, did not show this difference. The association between integrin and IRS-1 may be a mechanism for the synergistic action of growth factor and extracellular matrix receptors.


Education by general practitioners or education and exercises by physiotherapists for patients with whiplash-associated disorders? A randomized clinical trial.
Randomized clinical trial. To compare the effectiveness of education and advice given by general practitioners (GPs) with education, advice, and active exercise therapy given by physiotherapists (PTs) for patients with whiplash-associated disorders. Available evidence from systematic reviews has indicated beneficial effects for active interventions in patients with whiplash-associated disorders. However, it remained unclear which kind of active treatment was most effective. Whiplash patients with symptoms or disabilities at 2 weeks after accident were recruited in primary care. Eligible patients still having symptoms or disabilities at 4 weeks were randomly allocated to GP care or physiotherapy. GPs and PTs treated patients according to a dynamic multimodal treatment protocol primarily aimed to increase activities and influence unfavorable psychosocial factors for recovery. We trained all health care providers about the characteristics of the whiplash problem, available evidence regarding prognosis and treatment, and protocol of the interventions. The content of the information provided to patients during treatment depended on the treatment goals set by the GPs or PTs. Also, the type of exercises chosen by the PTs depended on the treatment goals, and it was not explicitly necessary that exercise therapy was provided in all patients. Primary outcome measures included neck pain intensity, headache intensity, and work activities. Furthermore, an independent blinded assessor measured functional recovery, cervical range of motion, disability, housekeeping and social activities, fear of movement, coping, and general health status. We assessed outcomes at 8, 12, 26, and 52 weeks after the accident. A total of 80 patients were randomized to either GP care (n = 42) or physiotherapy (n = 38). At 12 and 52 weeks, no significant differences were found concerning the primary outcome measures. At 12 weeks, physiotherapy was significantly more effective than GP care for improving 1 of the measures of cervical range of motion (adjusted mean difference 12.3 degrees ; 95% confidence interval [CI] 2.7-21.9). Long-term differences between the groups favored GP care but were statistically significant only for some secondary outcome measures, including functional recovery (adjusted relative risk 2.3; 95% CI 1.0-5.0), coping (adjusted mean difference 1.7 points; 95% CI 0.2-3.3), and physical functioning (adjusted mean difference 8.9 points; 95% CI 0.6-17.2). We found no significant differences for the primary outcome measures. Treatment by GPs and PTs were of similar effectiveness. The long-term effects of GP care seem to be better compared to physiotherapy for functional recovery, coping, and physical functioning. Physiotherapy seems to be more effective than GP care on cervical range of motion at short-term follow-up.


A review of air exchange rate models for air pollution exposure assessments.
A critical aspect of air pollution exposure assessments is estimation of the air exchange rate (AER) for various buildings where people spend their time. The AER, which is the rate of exchange of indoor air with outdoor air, is an important determinant for entry of outdoor air pollutants and for removal of indoor-emitted air pollutants. This paper presents an overview and critical analysis of the scientific literature on empirical and physically based AER models for residential and commercial buildings; the models highlighted here are feasible for exposure assessments as extensive inputs are not required. Models are included for the three types of airflows that can occur across building envelopes: leakage, natural ventilation, and mechanical ventilation. Guidance is provided to select the preferable AER model based on available data, desired temporal resolution, types of airflows, and types of buildings included in the exposure assessment. For exposure assessments with some limited building leakage or AER measurements, strategies are described to reduce AER model uncertainty. This review will facilitate the selection of AER models in support of air pollution exposure assessments.


Pseudomonas aeruginosa pyocyanin causes airway goblet cell hyperplasia and metaplasia and mucus hypersecretion by inactivating the transcriptional factor FoxA2.
The redox-active exotoxin pyocyanin (PCN) can be recovered in 100 µM concentrations in the sputa of bronchiectasis patients chronically infected with Pseudomonas aeruginosa (PA). However, the importance of PCN within bronchiectatic airways colonized by PA remains unrecognized. Recently, we have shown that PCN is required for chronic PA lung infection in mice, and that chronic instillation of PCN induces goblet cell hyperplasia (GCH), pulmonary fibrosis, emphysema and influx of immune cells in mouse airways. Many of these pathological features are strikingly similar to the mouse airways devoid of functional FoxA2, a transcriptional repressor of GCH and mucus biosynthesis. In this study, we postulate that PCN causes and exacerbates GCH and mucus hypersecretion in bronchiectatic airways chronically infected by PA by inactivating FoxA2. We demonstrate that PCN represses the expression of FoxA2 in mouse airways and in bronchial epithelial cells cultured at an air-liquid interface or conventionally, resulting in GCH, increased MUC5B mucin gene expression and mucus hypersecretion. Immunohistochemical and inhibitor studies indicate that PCN upregulates the expression of Stat6 and EGFR, both of which in turn repress the expression of FoxA2. These studies demonstrate that PCN induces GCH and mucus hypersecretion by inactivating FoxA2.


A short delay from out of hospital cardiac arrest to call for ambulance increases survival.
To describe the relative impact on survival of the delay from estimated time of collapse to call for an ambulance among patients who suffer from a bystander witnessed out of hospital cardiac arrest of a cardiac aetiology. A majority of all ambulance organizations in Sweden (covering 85% of Sweden inhabitants) participate in a National survey of out of hospital cardiac arrest. In all there were 9340 patients with a bystander witnessed cardiac arrest of a cardiac aetiology in whom cardiopulmonary resuscitation (CPR) was attempted participating in this survey. Survival at one month among patients with a delay between estimated time of collapse and call for ambulance of < or =4 min (median) was 6.9% versus 2.8% among patients with a median of >4 min (P<0.0001). When adjusting for age, sex, initial rhythm, estimated interval between collapse and start of CPR, place of arrest and the interval between call for ambulance and arrival of the rescue team, the odds ratio for survival was 0.70 (0.95% CI. 0.58-0.84) per unit increase of the natural logarithm of delay in minutes between collapse and call. Among patients with a bystander witnessed out of hospital cardiac arrest of a cardiac aetiology increased delay from estimated time of collapse to call for an ambulance decreased the chance of survival.


A Template for Authoring and Adapting Genomic Medicine Content in the eMERGE Infobutton Project.
The Electronic Medical Records and Genomics (eMERGE) Network is a national consortium that is developing methods and best practices for using the electronic health record (EHR) for genomic medicine and research. We conducted a multi-site survey of information resources to support integration of pharmacogenomics into clinical care. This work aimed to: (a) characterize the diversity of information resource implementation strategies among eMERGE institutions; (b) develop a master template containing content topics of important for genomic medicine (as identified by the DISCERN-Genetics tool); and (c) assess the coverage of content topics among information resources developed by eMERGE institutions. Given that a standard implementation does not exist and sites relied on a diversity of information resources, we identified a need for a national effort to efficiently produce sharable genomic medicine resources capable of being accessed from the EHR. We discuss future areas of work to prepare institutions to use infobuttons for distributing standardized genomic content.


Periodic shock-emission from acoustically driven cavitation clouds: a source of the subharmonic signal.
Single clouds of cavitation bubbles, driven by 254kHz focused ultrasound at pressure amplitudes in the range of 0.48-1.22MPa, have been observed via high-speed shadowgraphic imaging at 1×10(6) frames per second. Clouds underwent repetitive growth, oscillation and collapse (GOC) cycles, with shock-waves emitted periodically at the instant of collapse during each cycle. The frequency of cloud collapse, and coincident shock-emission, was primarily dependent on the intensity of the focused ultrasound driving the activity. The lowest peak-to-peak pressure amplitude of 0.48MPa generated shock-waves with an average period of 7.9±0.5μs, corresponding to a frequency of f0/2, half-harmonic to the fundamental driving. Increasing the intensity gave rise to GOC cycles and shock-emission periods of 11.8±0.3, 15.8±0.3, 19.8±0.2μs, at pressure amplitudes of 0.64, 0.92 and 1.22MPa, corresponding to the higher-order subharmonics of f0/3, f0/4 and f0/5, respectively. Parallel passive acoustic detection, filtered for the fundamental driving, revealed features that correlated temporally to the shock-emissions observed via high-speed imaging, p(two-tailed) < 0.01 (r=0.996, taken over all data). Subtracting the isolated acoustic shock profiles from the raw signal collected from the detector, demonstrated the removal of subharmonic spectral peaks, in the frequency domain. The larger cavitation clouds (>200μm diameter, at maximum inflation), that developed under insonations of peak-to-peak pressure amplitudes >1.0MPa, emitted shock-waves with two or more fronts suggesting non-uniform collapse of the cloud. The observations indicate that periodic shock-emissions from acoustically driven cavitation clouds provide a source for the cavitation subharmonic signal, and that shock structure may be used to study intra-cloud dynamics at sub-microsecond timescales.


Maternal linuron exposure alters testicular development in male offspring rats at the whole genome level.
Linuron is a widely used herbicide; its toxicity on the male reproductive system has been recognized. The current study was designed to explore the molecular mechanism underlying linuron-induced reproductive toxicity. Pregnant rats received daily oral gavage of linuron at the dose of 120mg/kg/d from gestation day (GD)12 to GD17. Tissues from male offspring rats were collected for pathological examination and microarray gene expression profiling. Changes in gene expression were further verified by quantitative real-time RT-PCR. Data showed that linuron-exposed offspring rats had a decreased sperm count (88% of controls) and disrupted acrosome formation. There were evident damages in seminiferous tubules and abnormal morphology in mesenchymal cells in samples from linuron-exposed animals. Microarray analysis indicated that the expressions of testosterone synthesis-associated genes, i.e., Star, P450scc, 3β-Hsd, Abp, Cox7a2, Pcna, p450c17and17β-Hsd were significantly altered by linuron exposure, along with other genes involving in cell proliferation and apoptosis, such as c-myc, S6K, Apaf1, and TSC1. These data indicate that linuron upon entering male offspring body can directly or indirectly interact with the androgen production and function; linuron-induced alteration in genes encoding testosterone synthesis is likely a major factor in linuron-induced male reproductive toxicity.


The relationship of self-report of quality to practice size and health information technology.
Assessment of patient safety culture has recently expanded in inpatient settings, but the majority of medical encounters occurs in office settings, and less is known about the determinants of perceived quality and safety in ambulatory care. The Medical Office Survey of Patient Safety was developed to assess perceived quality of care and patient safety culture in medical offices, including a domain to assess the quality criteria as defined by the Institute of Medicine: patient-centered, effective, timely, efficient, and equitable. We surveyed 6534 clinicians and staff in 306 medical practices from 11 practice based research networks (PBRNs) in 16 states. We collected data on office size, ownership, and use of health information technologies (HIT) and assessed perceived patient safety and quality of care with the Medical Office Survey of Patient Safety's overall quality domain. Using a mixed model that adjusted for the role of respondents, we examined the relationship between perceived safety and quality of care and office size, ownership, and the degree of implementation of HIT. Small practices (3-15 personnel) reported the highest proportion of positive perceptions of quality and safety. The lowest proportion of positive perceptions of quality and safety occurred in large (41-70 personnel) and very large practices (>70 personnel). After controlling for office size, we found no relationship between perceived quality and safety and practice ownership. The relationship of HIT implementation to perceived quality and safety was not clear. We found the highest proportion of positive perceptions in practices with the least HIT and those with the most HIT and the lowest proportion in practices with intermediate levels of HIT. Personnel in small practices reported the highest overall quality and safety of care, and perceived quality and safety declined with increasing office size. No clear relationship was found between perceived quality and safety and implementation of HIT.


The global elimination of blinding trachoma: progress and promise.
Trachoma is the world's leading cause of preventable blindness. It affects approximately 150 million people living in the world's poorest, rural communities and causes an estimated loss of $2.9 billion in productivity annually. In 1985, the Edna McConnell Clark Foundation joined with the World Health Organization to support studies on trachoma epidemiology and control, resulting in the elaboration of the surgery, antibiotics, facial cleanliness and environmental improvement (SAFE) strategy as the basis for the elimination of this blinding disease. Founded in 1998 by the Clark Foundation and Pfizer, Inc., the International Trachoma Initiative (ITI) is the only organization dedicated to eliminating blinding trachoma through support to national control programs. The availability of donated Zithromax (azithromycin) by Pfizer, Inc. has been paramount to the support of the ITI for implementation of SAFE in 10 country programs. The program has made considerable progress in four years. More than seven million individuals have received treatment, resulting in a cumulative reduction of 50% in active disease rates in children. More than 60,000 have also benefited from lid surgery that has halted progression to blindness. Morocco is expecting to attain the elimination of blinding trachoma by 2005. However, the challenges facing the goal of global elimination by 2020 involve a vital program expansion, increased financial and technical support, environmental improvement, and continued advocacy efforts.


Reconstruction of full-thickness defects with bovine-derived collagen/elastin matrix: a series of challenging cases and the first reported post-burn facial reconstruction.
Reconstruction of full-thickness defects may benefit from integration of dermal substitutes, which serve as a foundation for split-thickness skin grafts, thus enhancing short and long-term results. We present a series of 7 patients who were treated between 2010 and 2012 for complicated full-thickness defects by the second-generation collagen/elastin matrix Matriderm® covered by a split-thickness skin graft. The defects resulted from malignancy resection, trauma, and post-burn scar reconstruction. Overall graft take was excellent and no complications were noted regarding the dermal substitute. Graft quality was close to normal skin in terms of elasticity, pliability, texture, and color. Good contour and cushioning of defects in weight bearing areas was also achieved. Matriderm was found to be a useful adjunct to full-thickness defect reconstruction, especially in difficult areas where the desired result is a scar of the highest quality possible.


Activated carbons prepared from wood particleboard wastes: characterisation and phenol adsorption capacities.
The problems of valorisation of particleboard wastes on one hand, and contamination of aqueous effluents by phenolic compounds on the other hand, are simultaneously considered in this work. Preparation of activated carbons from a two steps thermo-chemical process, formerly designed for generating combustible gases, is suggested. The resultant carbonaceous residue is activated with steam at 800 degrees C. Depending on the preparation conditions, surface areas within the range 800-1300 m(2)/g are obtained, close to that of a commercial activated carbon (CAC) specially designed for water treatment and used as a reference material. The present work shows that particleboard waste-derived activated carbons (WAC) are efficient adsorbents for the removal of phenol from aqueous solutions, with maximum measured capacities close to 500 mg/g. However, most of times, the adsorption capacities are slightly lower than that of the commercial material in the same conditions, i.e., at equilibrium phenol concentrations below 300 ppm. Given the extremely low cost of activated carbons prepared from particleboard waste, it should not be a problem to use it in somewhat higher amounts than what is required with a more expensive commercial material. Phenol adsorption isotherms at 298 K were correctly fitted by various equations modelling type I and type II isotherms for CAC and WAC, respectively. Phenol adsorption isotherms of type II were justified by a 3-stages adsorption mechanism.


Cost-effectiveness of the Norwegian breast cancer screening program.
The Norwegian Breast Cancer Screening Programme (NBCSP) has a nation-wide coverage since 2005. All women aged 50-69 years are invited biennially for mammography screening. We evaluated breast cancer mortality reduction and performed a cost-effectiveness analysis, using our microsimulation model, calibrated to most recent data. The microsimulation model allows for the comparison of mortality and costs between a (hypothetical) situation without screening and a situation with screening. Breast cancer incidence in Norway had a steep increase in the early 1990s. We calibrated the model to simulate this increase and included recent costs for screening, diagnosis and treatment of breast cancer and travel and productivity loss. We estimate a 16% breast cancer mortality reduction for a cohort of women, invited to screening, followed over their complete lifetime. Cost-effectiveness is estimated at NOK 112,162 per QALY gained, when taking only direct medical costs into account (the cost of the buses, examinations, and invitations). We used a 3.5% annual discount rate. Cost-effectiveness estimates are substantially below the threshold of NOK 1,926,366 as recommended by the WHO guidelines. For the Norwegian population, which has been gradually exposed to screening, breast cancer mortality reduction for women exposed to screening is increasing and is estimated to rise to ∼30% in 2020 for women aged 55-80 years. The NBCSP is a highly cost-effective measure to reduce breast cancer specific mortality. We estimate a breast cancer specific mortality reduction of 16-30%, at the cost of 112,162 NOK per QALY gained.


Long-Term Exposure to Ambient Air Pollution and Cognitive Function Among Hispanic/Latino Adults in San Diego, California.
Hispanics/Latinos in the United States are more likely to live in neighborhoods with greater exposure to air pollution and are projected to have the largest increase in dementia among race/ethnic minority groups. We examined the associations of air pollution with performance on cognitive function tests in Hispanic/Latino adults. We used data from the San Diego site of the Hispanic Community Health Study/Study of Latinos, an ongoing cohort of Hispanics/Latinos. This analysis focused on individuals ≥45 years of age who completed a neurocognitive battery examining overall mental status, verbal learning, memory, verbal fluency, and executive function (n = 2,089). Air pollution (PM2.5 and O3) before study baseline was assigned to participants' zip code. Logistic and linear regression were used to estimate the associations of air pollution on overall mental status and domain-specific standardized test scores. Models accounted for complex survey design, demographic, and socioeconomic characteristics. We found that for every 10μg/m3 increase in PM2.5, verbal fluency worsened (β: -0.21 [95%CI: -0.68, 0.25]). For every 10 ppb increase in O3, verbal fluency and executive function worsened (β: -0.19 [95%CI: -0.34, -0.03]; β: -0.01 [95%CI: -0.01, 0.09], respectively). We did not identify any detrimental effect of pollutants on other domains. Although we found suggestions that air pollution may impact verbal fluency and executive function, we observed no consistent or precise evidence to suggest an adverse impact of air pollution on cognitive level among this cohort of Hispanic/Latino adults.


Applications of artificial intelligence in battling against covid-19: A literature review.
Colloquially known as coronavirus, the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), that causes CoronaVirus Disease 2019 (COVID-19), has become a matter of grave concern for every country around the world. The rapid growth of the pandemic has wreaked havoc and prompted the need for immediate reactions to curb the effects. To manage the problems, many research in a variety of area of science have started studying the issue. Artificial Intelligence is among the area of science that has found great applications in tackling the problem in many aspects. Here, we perform an overview on the applications of AI in a variety of fields including diagnosis of the disease via different types of tests and symptoms, monitoring patients, identifying severity of a patient, processing covid-19 related imaging tests, epidemiology, pharmaceutical studies, etc. The aim of this paper is to perform a comprehensive survey on the applications of AI in battling against the difficulties the outbreak has caused. Thus we cover every way that AI approaches have been employed and to cover all the research until the writing of this paper. We try organize the works in a way that overall picture is comprehensible. Such a picture, although full of details, is very helpful in understand where AI sits in current pandemonium. We also tried to conclude the paper with ideas on how the problems can be tackled in a better way and provide some suggestions for future works.


Effect of Quiet Eye and Quiet Mind Training on Motor Learning Among Novice Dart Players.
In sport such as darts, athletes are particularly challenged by demands for concentration, skills underpinned by implicit learning, and fine motor skill control. Several techniques have been proposed to improve the implicit learning of such skills, including quiet eye training (QET) and quiet mind training (QMT). Here, the authors tested whether and to what extent QET or QMT, compared with a control condition, might improve skills among novice dart players. In total, 30 novice dart players were randomly assigned either to the QET, QMT, or a control condition. Dart playing skills were assessed four times: at the baseline, 7 days later, under stress conditions, and at the study's end. Over time, errors reduced, but more so in the QET and QMT conditions than in the control condition. The pattern of the results indicates that, among novice dart players and compared with a control condition, both QET and QMT provide significant improvements in implicit learning.


The influence of stochastic and selective forces in the population divergence of female colour polymorphism in damselflies of the genus Ischnura.
Disentangling the relative importance and potential interactions of selection and genetic drift in driving phenotypic divergence of species is a classical research topic in population genetics and evolutionary biology. Here, we evaluate the role of stochastic and selective forces on population divergence of a colour polymorphism in seven damselfly species of the genus Ischnura, with a particular focus on I. elegans and I. graellsii. Colour-morph frequencies in Spanish I. elegans populations varied greatly, even at a local scale, whereas more similar frequencies were found among populations in eastern Europe. In contrast, I. graellsii and the other five Ischnura species showed little variation in colour-morph frequencies between populations. F(ST)-outlier analyses revealed that the colour locus deviated strongly from neutral expectations in Spanish populations of I. elegans, contrasting the pattern found in eastern European populations, and in I. graellsii, where no such discrepancy between morph divergence and neutral divergence could be detected. This suggests that divergent selection has been operating on the colour locus in Spanish populations of I. elegans, whereas processes such as genetic drift, possibly in combination with other forms of selection (such as negative frequency-dependent selection), appear to have been present in other regions, such as eastern Europe. Overall, the results indicate that both selective and stochastic processes operate on these colour polymorphisms, and suggest that the relative importance of factors varies between geographical regions.


Characterization of estrogen and progesterone receptors and the dissociated regulation of growth and progesterone receptor stimulation by estrogen in MDA-MB-134 human breast cancer cells.
We have examined the properties of the estrogen receptor and progesterone receptor in MDA-MB-134 human breast cells and have evaluated the effects of estrogen on cell proliferation and progesterone receptor levels in these cells as indices of hormonal sensitivity. These cells contain high levels of estrogen receptor (approximately 1.5 pmol/mg DNA) and low levels of progesterone receptor (0.15 pmol/mg DNA). More than 80% of the estrogen receptor is found in the nuclear fraction in the absence of estrogen, and the Kd of the receptor for estradiol is approximately 1.5 X 10(-10) M. Upon exposure to estradiol, the receptors become occupied, but there is no processing or apparent decrease in either nuclear or total cellular estrogen receptor content, as can be seen in MCF-7 human breast cancer cells. The nuclear estrogen receptor sediments as a 4.6 S species on high salt sucrose gradients, and it can be detected on sodium dodecyl sulfate-polyacrylamide gel immunoblot analysis as a species of molecular weight 65,000, identical to that of the MCF-7 estrogen receptor, using the monoclonal antibodies D75P3 gamma and H222Sp gamma prepared against the MCF-7 estrogen receptor. The estrogen receptor shows binding selectivity for estrogens and antiestrogens, and its affinity for ligands follows the order diethylstilbestrol (190%) greater than estradiol (100%) greater than estriol (13%) greater than tamoxifen (3%), as expected for estrogen receptor. Hence the receptor appears normal in many of its physicochemical properties and in terms of its binding affinity and specificity for estrogens and antiestrogens. Control cells contain low levels of progesterone receptor that display high affinity (Kd = 6 X 10(-9) M) for the synthetic progestin R5020, but exposure to estradiol (10(-11)-10(-7)M) fails to increase cellular progesterone receptor levels. In contrast, estradiol markedly stimulates the rate of cell proliferation, while tamoxifen suppresses the growth of control and of estradiol treated cells. Hence, our data show that these cells, which contain substantial levels of estrogen receptor, respond to estrogen with enhanced cell proliferation but fail to have their progesterone receptor level modulated by estradiol. These cells represent an interesting and unusual situation in which estrogenic regulation of proliferation and the stimulation of progesterone receptor are dissociated. These cells should prove useful in further evaluation of estrogenic regulation of cell proliferation and specific protein synthesis in human breast cancer.


The future of baccalaureate degrees for nurses.
PROBLEM. Unlike other professional healthcare disciplines, the profession of nursing has multiple levels of entry. Recently, several states have proposed legislation to mandate completion of baccalaureate education after 10 years of nursing licensure. METHODS. This article examines the proposals, statistics, strategies, and other relevant literature on baccalaureate education for nurses and the positive outcomes associated with a more highly educated nursing workforce. FINDINGS. The proposal recognizes the entry level preparation provided by associate degree nurses and is an innovative solution that offers a balance between multiple entry levels into practice and continued educational preparation. CONCLUSIONS. Through a combination of the entry level preparation of associate degree nurses and baccalaureate education, a stronger nursing workforce can be created and patient outcomes and quality of care improved.


Sec34p, a protein required for vesicle tethering to the yeast Golgi apparatus, is in a complex with Sec35p.
A screen for mutants of Saccharomyces cerevisiae secretory pathway components previously yielded sec34, a mutant that accumulates numerous vesicles and fails to transport proteins from the ER to the Golgi complex at the restrictive temperature (Wuestehube, L.J., R. Duden, A. Eun, S. Hamamoto, P. Korn, R. Ram, and R. Schekman. 1996. Genetics. 142:393-406). We find that SEC34 encodes a novel protein of 93-kD, peripherally associated with membranes. The temperature-sensitive phenotype of sec34-2 is suppressed by the rab GTPase Ypt1p that functions early in the secretory pathway, or by the dominant form of the ER to Golgi complex target-SNARE (soluble N-ethylmaleimide sensitive fusion protein attachment protein receptor)-associated protein Sly1p, Sly1-20p. Weaker suppression is evident upon overexpression of genes encoding the vesicle tethering factor Uso1p or the vesicle-SNAREs Sec22p, Bet1p, or Ykt6p. This genetic suppression profile is similar to that of sec35-1, a mutant allele of a gene encoding an ER to Golgi vesicle tethering factor and, like Sec35p, Sec34p is required in vitro for vesicle tethering. sec34-2 and sec35-1 display a synthetic lethal interaction, a genetic result explained by the finding that Sec34p and Sec35p can interact by two-hybrid analysis. Fractionation of yeast cytosol indicates that Sec34p and Sec35p exist in an approximately 750-kD protein complex. Finally, we describe RUD3, a novel gene identified through a genetic screen for multicopy suppressors of a mutation in USO1, which suppresses the sec34-2 mutation as well.


Phorbol myristate acetate: a mitogen selective for a T-lymphocyte subpopulation.
Phorbol myristate acetate (pma) is a potent mitogen for human peripheral blood lymphocytes (PBL) comparable to phytohemagglutinin (PHA) in potency. Inactivation of PHA-responsive lymphocytes by 5'-bromodeoxyuridine and light treatment left the PMA response intact and nice versa. Experiments separating lymphocytes by rosetting with sheep erythrocytes (SRBC) demonstrated that the PMA-responsive lymphocytes segregate with those that have a high affinity for SRBC to a greater than PHA- or concanavalin A (Con A)-responsive cells. These results indicate that a PMA-responsive population in human peripheral blood resides within the T-lymphocyte population and appears to have a high affinity for SRBC and to be distinct from that responding to PHA and Con A. PMA may be useful clinically to assay the size and function of the high affinity or "active" rosette population.


Antisense oligonucleotides as therapeutic agents--is the bullet really magical?
Because of the specificity of Watson-Crick base pairing, attempts are now being made to use oligodeoxynucleotides (oligos) in the therapy of human disease. However, for a successful outcome, the oligo must meet at least six criteria: (i) the oligos can be synthesized easily and in bulk; (ii) the oligos must be stable in vivo; (iii) the oligos must be able to enter the target cell; (iv) the oligos must be retained by the target cell; (v) the oligos must be able to interact with their cellular targets; and (vi) the oligos should not interact in a non-sequence-specific manner with other macromolecules. Phosphorothioate oligos are examples of oligos that are being considered for clinical therapeutic trials and meet some, but not all, of these criteria. The potential use of phosphorothioate oligos as inhibitors of viral replication is highlighted.


Pre-operative Neurocognitive Function Was More Susceptible to Decline in Isocitrate Dehydrogenase Wild-Type Subgroups of Lower-Grade Glioma Patients.
Background: Neuropsychological deficits frequently occur in diffuse lower-grade glioma (DLGG) patients, but their relationship with molecular subgroups based on the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) is unclear. Methods: All patients enrolled for this study were divided into different subgroups according to the molecular-integrated 2016 CNS WHO and morphology-centric 2007 CNS WHO to compare their neurocognitive function (NCF) dysfunction. Univariate and multivariate analyses were used to assess the independent factors for NCF decline. The performance of NCF changes for discrimination of IDH and 1p19q status was evaluated by receiver operating characteristic (ROC). Results: There was no significant difference in the clinical characteristics among the molecular and morphologic subgroups. In the molecular subgroups, significant differences in NCF alterations were found in terms of attention function, working memory and executive function in grade II glioma patients; in addition to these changes in NCF, memory function and abstract thinking were also significantly different in grade III glioma patients. The pairwise comparison further confirmed that patients with astrocytoma (A)/anaplastic astrocytoma (AA) with isocitrate dehydrogenase wild-type (IDHwt) glioma were more susceptible to severe cognitive decline in terms of the NCF performance described above. For the morphologic subgroups, only working memory was significantly different in grade III glioma patients. The distribution proportion was significantly different among each subgroup of DLGG (grade II, P = 0.001; grade III, P = 0.002). The proportion of extensive NCF decline (≥5 tests) was 4, 12, and 50% in the IDH mutant oligodendroglioma (IDHm-O), IDHm-A, and IDHwt-A subgroups, and this proportion was 33, 60, and 93% in the IDHm-AO, IDHm-AA, and IDHwt-AA subgroups, respectively. In multivariate regression analysis, molecular types were independent factors for NCF alterations after adjusted the factors of tumor and demographics (p < 0.05). ROC curves suggested combined NCF tests model showed an advantage in the differentiation of IDH status. Conclusions: NCF alteration is closely related to molecular-integrated subgroups with varying degrees and frequencies in DLGG. Patients with IDHwt gliomas are more susceptible to suffer from severe and extensive NCF decline than other subgroups.


No extreme bipolar glaciation during the main Eocene calcite compensation shift.
Major ice sheets were permanently established on Antarctica approximately 34 million years ago, close to the Eocene/Oligocene boundary, at the same time as a permanent deepening of the calcite compensation depth in the world's oceans. Until recently, it was thought that Northern Hemisphere glaciation began much later, between 11 and 5 million years ago. This view has been challenged, however, by records of ice rafting at high northern latitudes during the Eocene epoch and by estimates of global ice volume that exceed the storage capacity of Antarctica at the same time as a temporary deepening of the calcite compensation depth approximately 41.6 million years ago. Here we test the hypothesis that large ice sheets were present in both hemispheres approximately 41.6 million years ago using marine sediment records of oxygen and carbon isotope values and of calcium carbonate content from the equatorial Atlantic Ocean. These records allow, at most, an ice budget that can easily be accommodated on Antarctica, indicating that large ice sheets were not present in the Northern Hemisphere. The records also reveal a brief interval shortly before the temporary deepening of the calcite compensation depth during which the calcite compensation depth shoaled, ocean temperatures increased and carbon isotope values decreased in the equatorial Atlantic. The nature of these changes around 41.6 million years ago implies common links, in terms of carbon cycling, with events at the Eocene/Oligocene boundary and with the 'hyperthermals' of the Early Eocene climate optimum. Our findings help to resolve the apparent discrepancy between the geological records of Northern Hemisphere glaciation and model results that indicate that the threshold for continental glaciation was crossed earlier in the Southern Hemisphere than in the Northern Hemisphere.


Three-dimensional echocardiography in evaluation of left ventricular indices.
Accurate determination of left ventricular mass, volume, ejection fraction, and wall motion is important for clinical decision making. Currently, M-mode and two-dimensional echocardiography (2DE) have been routinely used for this purpose. Although these 1D or 2D modalities provide excellent diagnostic and prognostic information, they have a number of technical limitations including the time required to perform the procedure and operator-dependent image acquisitions. In addition, they are inherently limited by geometric assumption of three-dimensional (3D) left ventricular structures based on 2D slices. With the improvement in transducer technology and software development, 3D echocardiography (3DE) has become widely available. Left ventricular quantitation by 3DE has been demonstrated to be accurate by multiple studies that compared 3DE with reference techniques. In addition, 3DE measurements were found to be more reproducible and less variable than 2DE. Real time 3DE imaging has potential advantages in stress echocardiography including rapid acquisition, unlimited number of planes, avoidance of foreshortening, and precise segment matching. This is a major step forward in our diagnostic armamentarium for the evaluation of ischemia. In this review, we summarized the current evidence of 3DE for left ventricular evaluation.


Regulation of fibroblast motility by the protein tyrosine phosphatase PTP-PEST.
The protein tyrosine phosphatase PTP-PEST is a cytosolic enzyme that displays a remarkable degree of selectivity for tyrosine-phosphorylated p130(Cas) as a substrate, both in vitro and in intact cells. We have investigated the physiological role of PTP-PEST using Rat1 fibroblast-derived stable cell lines that we have engineered to overexpress PTP-PEST. These cell lines exhibit normal levels of tyrosine phosphorylation of the majority of proteins but have significantly lower levels of tyrosine phosphorylation of p130(Cas) than control cells. Initial cellular events occurring following integrin-mediated attachment to fibronectin (cell attachment and spreading) are essentially unchanged in cells overexpressing PTP-PEST; similarly, the extent and time course of mitogen-activated protein kinase activation in response to integrin engagement is unchanged. In contrast, the reduced phosphorylation state of p130(Cas) is associated with a considerably reduced rate of cell migration and a failure of cells overexpressing PTP-PEST to accomplish the normally observed redistribution of p130(Cas) to the leading edge of migrating cells. Furthermore, cells overexpressing PTP-PEST demonstrate significantly reduced levels of association of p130(Cas) with the Crk adaptor protein. Our results suggest that one physiological role of PTP-PEST is to dephosphorylate p130(Cas), thereby controlling tyrosine phosphorylation-dependent signaling events downstream of p130(Cas) and regulating cell migration.


Proliferation and adhesion of periodontal ligament cells on synthetic biominerals.
Hydroxiapatite (HA) has been suggested as a useful biomaterial to support the regeneration of tissues. In this study, we investigated the adhesion of periodontal ligament (PDL) cells on octacalcium phosphate (OCP) and its hydrolyzed apatitic product (HL), which are known precursors of HA. Rat PDL cells were cultured on OCP or HL-coated dishes. Cell proliferation and adhesion and mRNA expression of collagen I, fibronectin integrin subunits were examined. Cell adhesion inhibition assays were carried out by GRGDSPK (Gly-Arg-Gly-Asp-Ser-Pro-Lys). In early culture period, the cell number of PDL cells was lower on OCP and HL than that on control without any coating. However, the cell number on OCP or HL caught up with control later period. mRNA expression level of collagen I and fibronectin on OCP and HL were similar among OCP HL and control, although they differed early in the culture period. Integrin subunits were expressed on both OCP and HL as well as on control. Cell adhesion was inhibited by RGD inhibitor peptide. Our findings indicated that rat PDL cells produce collagen I and fibronectin on OCP and HL, and then show increased cell numbers depending on adhesion to the matrices through integrins.


Experiment LEND of the NASA Lunar Reconnaissance Orbiter for high-resolution mapping of neutron emission of the Moon.
The scientific objectives of neutron mapping of the Moon are presented as 3 investigation tasks of NASA's Lunar Reconnaissance Orbiter mission. Two tasks focus on mapping hydrogen content over the entire Moon and on testing the presence of water-ice deposits at the bottom of permanently shadowed craters at the lunar poles. The third task corresponds to the determination of neutron contribution to the total radiation dose at an altitude of 50 km above the Moon. We show that the Lunar Exploration Neutron Detector (LEND) will be capable of carrying out all 3 investigations. The design concept of LEND is presented together with results of numerical simulations of the instrument's sensitivity for hydrogen detection. The sensitivity of LEND is shown to be characterized by a hydrogen detection limit of about 100 ppm for a polar reference area with a radius of 5 km. If the presence of ice deposits in polar "cold traps" is confirmed, a unique record of many millions of years of lunar history would be obtained, by which the history of lunar impacts could be discerned from the layers of water ice and dust. Future applications of a LEND-type instrument for Mars orbital observations are also discussed.


Sub-microlitre dialysis system to enable trace level peptide detection from volume-limited biological samples using MALDI-TOF-MS.
The detection of peptides with mass spectrometry from volume-limited biological samples is a challenging task due to low sample volume, a broad range of peptide concentrations down to trace levels, endogenous high proteins and salt levels. Previously, a microspotting method was presented for trace-level peptide detection with MALDI-MS from sub-microlitre samples with biological salt levels. However, in the presence of proteins, peptide signals are significantly reduced. This paper presents a novel dialysis device for removal of proteins from sub-microlitre samples using a semipermeable hollow fiber membrane to enhance peptide detection. A dialysis device was constructed to perform sub-microlitre dialysis to remove proteins from complex samples. Angiotensin I was used as a model peptide in the presence of 350 mg L(-1) BSA prepared in physiological saline to mimic biological samples. In the absence of BSA, clear angiotensin I peaks were seen at 250 pM, yet in the presence of the BSA, 10 nM angiotensin I was barely detected. After dialysis, peak detection was improved to a 500 pM level. Protein removal and peptide recovery (approximately 66%) were determined using CE-LIF. Clinical vitreous samples as low as 200 nL were successfully dialyzed in 30 min and a 3-fold increase in peptide peaks were detected with greatly improved signals. This method is simple and can be a useful technique for trace level peptide detection from volume-limited biological samples.


Control perceptions in patients with rheumatoid arthritis: the impact of the medical consultation.
To identify factors that patients perceive as influencing control in living with the symptoms of rheumatoid arthritis (RA). A sample of 40 patients with RA were recruited randomly from an out-patient population. The participants of the sample were interviewed in depth by one researcher to identify perceptions of control. They also completed two self-administered questionnaires, the Health Assessment Questionnaire and the Rheumatology Attitude Index. Four major categories were identified that positively influenced perceptions of control in patients living with the consequences of RA. These included: (i) the reduction of physical symptoms; (ii) social support matching perceived need; (iii) the provision of information; and (iv) the medical consultation. Components of the consultation included patient involvement, provision of information, feedback and reassurance, empathy and access to an expert. The categories identified can be influenced by health-care professionals in the management of the patient, and if the medical consultation is utilized to its full potential it can play a major role in enabling patients with RA to manage the daily symptoms of their condition.


[Transcatheter radiofrequency ablation in supraventricular tachycardia in children: immediate results and mid-term follow-up].
The purpose of this study was to evaluate the efficacy and safety of radiofrequency ablation of supraventricular tachycardias due to a reentry circuit in a group of closely followed-up pediatric patients. Forty-six pediatric patients (mean age 12.6 years, range 3-18) underwent a total of 48 radiofrequency ablation procedures for reciprocating supraventricular tachycardia. Thirty-nine had an orthodromic reentry tachycardia, 6 an atrioventricular node reentry tachycardia and 1 a permanent junctional reciprocating tachycardia. To ablate the overt accessory pathways, the Kent potential (K) was identified and then the shortest A-K, and delta wave-K intervals were measured. The shortest V-A interval was identified for those concealed. For the left-sided accessory pathways, we used the retrograde transaortic approach in 10 procedures and the transseptal approach in 18. Atrioventricular node reentry tachycardia was ablated at the site where the slow-pathway electrogram was recorded. Follow-up clinical data, electrocardiogram, 24-hours Holter monitoring and transesophageal atrial stimulation were obtained and evaluated. Early: We performed a total of 48 procedures. Among 41 procedures performed in the 39 patients with accessory pathway, 38 were successful (92,6%). Mean fluoroscopy time was 31 +/- 18 min. For left sided accessory pathways, mean fluoroscopy time of procedures with retrograde approach was 45 +/- 10 min and with transseptal 23 +/- 12 min (p < 0.01). Ablation of slow-pathway in patients with intranodal reentry tachycardia was successful in 3/6 cases (50%). The patient with permanent junctional reciprocating tachycardia was successfully ablated. Late: All patients are alive and none was lost during the follow-up after a mean time of 12.9 months (range 5-33). Success at last follow-up was 100% in patients with an accessory pathway and 33% in patients with atrioventricular node reentry. In patient with permanent junctional reciprocating tachycardia, the arrhythmia appeared again one month after the procedure, thus a second successful attempt was performed. Major complications (6,5%) including a right femoral vein thrombosis (one patient), an hematoma without pulse loss (one patient) and a non-sustained monomorphic ventricular tachycardia (one patient). Our data show high efficacy of radiofrequency ablation in pediatric patients with accessory pathways. The risks are low at follow-up evaluation, but might be helpful a longer-term follow-up in order to evaluate the risk of a long fluoroscopy time and the arrhythmogenic effect of the scar.


Assessment of coping with stress in patients with Schizophrenia in a Community Mental Health Centre, in Turkey.
To assess schizophrenia patients' approach toward coping with stress in terms of demographic variables. The cross-sectional descriptive study was conducted at the State Hospital Community Mental Health Centre, Turkey, from November 1, 2013, to April 30, 2014 and comprised patients diagnosed with schizophrenia. Data was collected using Sociodemographic Information Form and the Coping Assessment Questionnaire Inventory. It was analysed using SPSS 18. Of the 53 patients, 14(26.4%) were females and 39(73.5%) were males. The overall mean age was 38±10.66 years. Highest mean score was recorded for the emotion-focussed coping subscale which was 63.49±10.64. Female patients used emotional social support, focussing on problems and venting emotions techniques (p<0.05). Patients who did not use alcohol received higher scores from religious coping subscales, while patients who used alcohol scored higher from substance use and dysfunctional coping subscales (p<0.05). Most schizophrenia patients were found to be using emotion-focussed coping methods.


High-frequency ultrasound in the 21st century.
The beginnings of skin ultrasound date back to about 50 years ago. However, the dynamic progress of skin ultrasound took place in the last twenty years, when the unprecedented development of computer technologies occurred, which resulted in the popularization of and easier access to modern ultrasound equipment. Skin tests can be performed with both classic scanners equipped with broadband transducers with a minimum frequency of 15 MHz, and specially dedicated skin systems with high-frequency scanners, which are equipped with mechanical transducers with a frequency of 20 MHz to up to 100 MHz. Owing to technologically advanced machines, ultrasonography has proved to be useful in many areas. The aim of this study was to present the current knowledge and possibilities of skin imaging using high-frequency ultrasonography. Te paper discusses technical aspects, types of devices available on the market, as well as methods for the analysis of ultrasound skin images and parameters useful in their interpretation. We also present current applications of skin ultrasound, with particular emphasis on dermatology and aesthetic medicine. In the field of dermatology, we discussed imaging of focal lesions as well as an assessment of pathologically changed skin and treatment monitoring. We also focused on the use of high-frequency ultrasonography in aesthetic medicine and cosmetology. The popularity of this method is constantly growing in these fields, and ultrasound is now used in everyday practice to assess the skin, plan and monitor procedures, as well as to treat potential complications. High-frequency ultrasonography is a highly effective method for skin evaluation, although still underappreciated in may fields. Further research is needed to standardize this modality, as well as to implement training for operators, and to popularize this imaging technique.


Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an Increased Risk of Alzheimer Disease: Taiwan Diabetes Study.
The relationship between glycemic variability and the incidence of Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to examine visit-to-visit variations in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) represented by the coefficient of variation (CV) and to determine whether they were independently associated with AD, irrespective of HbA1c and other traditional risk factors in such patients. Patients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD (n = 16,706) were included in the study. Potential risk factors were analyzed using extended Cox proportional hazards regression models for competing risk of mortality on AD incidence. During a median follow-up of 8.88 years, 831 incident cases of AD were identified, with a crude incidence rate of 3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle behaviors, diabetes-related variables, FPG and HbA1c, drug-related variables, and comorbidities, both FPG CV and HbA1c CV were found to be significant predictors of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06-1.52) for the third tertile in FPG CV and 1.32 (95% CI 1.11-1.58) for the third tertile in HbA1c CV. FPG CV and HbA1c CV are independently associated with AD. The associations between glycemic variability and AD demonstrated in this study suggest a linked pathophysiological mechanism, which is worthy of further investigation. Further research is required to confirm our results and to evaluate whether FPG CV and HbA1c CV can be valuable therapeutic targets for patients with T2DM at risk.


Retrospective study of prevalence of face fractures in southern Brazil.
Trauma has been an important public health problem worldwide. Facial injuries are among the most common types of trauma treated at emergency departments, associated or not with injuries in other anatomic sites. The patterns of facial fractures are usually affected by geography and socioeconomic conditions. To investigate the prevalence of facial fractures in Lages, state of Santa Catarina, southern Brazil, from September 2003 to August 2008. Cross-sectional, retrospective, epidemiological study. Data on patients' gender, age, etiological agent, and facial region affected by fracture were collected from the charts of patients treated with facial fractures. Qualitative variables were expressed as absolute and relative frequencies, and quantitative variables as means and standard deviation. The Chi-square test was used to evaluate the association between gender, traffic accidents and facial region affected. The association between etiological agents and facial region affected was assessed using the chi-square test and the adjusted residuals analysis. 492 patients presented with oral and maxillofacial trauma, with 988 facial fractures; 80.9% of the patients were men, and the most frequent age group was 21-30 years (29.5%). The most frequent causes of fractures were: Traffic accidents in 27.9%, physical assault in 14.9%, and bicycle falls in 10.5%; several other causes scored below 10%. Regular publication of epidemiological data is extremely important for the implementation of prevention campaigns and for an increased awareness of the etiology of fractures affecting the face and other anatomic sites.


FeetBeat: A Flexible Iontronic Sensing Wearable Detects Pedal Pulses and Muscular Activities.
Human feet have long been considered in close association with whole-body health, from which abundant cardiovascular and skeletomuscular information can be extracted. In this study, we aim to develop the world's first foot-based wearable system that can detect both pedal pulses and muscular activities, referred to as FeetBeat. Utilizing the flexible iontronic sensing technology, we have constructed and characterized a five-unit sensing array for detection of both pedal pulse signals and muscular activities. It is integrated into the tongue of an athletic shoe for real-time signal acquisition. Additionally, the linear array allows alignment-free capture of pulse signals and also provides a spatial reference to muscular activities. An ultrahigh sensitivity of up to 1 nF/mmHg has been achieved for individual units, with a range of 1 to 200 mmHg. The pedal pulse waveforms have been detected to derive vital health signs, such as heart rates (HR) and respiratory rates, of which the pulse-derived HR is compared with the electrocardiogram. Moreover, individual tendon responses have been acquired to analyze different pedal gestures, from which multi-channel signals can be used to distinguish different activities. The FeetBeat device has shown the potential to be the world's first wearable platform to simultaneously analyze both vital signals and body activities from the measurable pedal pulse waveforms and muscular responses in a natural and unobtrusive fashion. The data-collecting wearable system provides a highly valuable means to assess the personalized health as well as daily activities on a continuous basis.


The Indianapolis Flux Experiment (INFLUX): A test-bed for developing urban greenhouse gas emission measurements.
The objective of the Indianapolis Flux Experiment (INFLUX) is to develop, evaluate and improve methods for measuring greenhouse gas (GHG) emissions from cities. INFLUX's scientific objectives are to quantify CO2 and CH4 emission rates at 1 km resolution with a 10% or better accuracy and precision, to determine whole-city emissions with similar skill, and to achieve high (weekly or finer) temporal resolution at both spatial resolutions. The experiment employs atmospheric GHG measurements from both towers and aircraft, atmospheric transport observations and models, and activity-based inventory products to quantify urban GHG emissions. Multiple, independent methods for estimating urban emissions are a central facet of our experimental design. INFLUX was initiated in 2010 and measurements and analyses are ongoing. To date we have quantified urban atmospheric GHG enhancements using aircraft and towers with measurements collected over multiple years, and have estimated whole-city CO2 and CH4 emissions using aircraft and tower GHG measurements, and inventory methods. Significant differences exist across methods; these differences have not yet been resolved; research to reduce uncertainties and reconcile these differences is underway. Sectorally- and spatially-resolved flux estimates, and detection of changes of fluxes over time, are also active research topics. Major challenges include developing methods for distinguishing anthropogenic from biogenic CO2 fluxes, improving our ability to interpret atmospheric GHG measurements close to urban GHG sources and across a broader range of atmospheric stability conditions, and quantifying uncertainties in inventory data products. INFLUX data and tools are intended to serve as an open resource and test bed for future investigations. Well-documented, public archival of data and methods is under development in support of this objective.


Dual roles for the ER membrane protein complex in flavivirus infection: viral entry and protein biogenesis.
Hundreds of cellular host factors are required to support dengue virus infection, but their identity and roles are incompletely characterized. Here, we identify human host dependency factors required for efficient dengue virus-2 (DENV2) infection of human cells. We focused on two, TTC35 and TMEM111, which we previously demonstrated to be required for yellow fever virus (YFV) infection and others subsequently showed were also required by other flaviviruses. These proteins are components of the human endoplasmic reticulum membrane protein complex (EMC), which has roles in ER-associated protein biogenesis and lipid metabolism. We report that DENV, YFV and Zika virus (ZIKV) infections were strikingly inhibited, while West Nile virus infection was unchanged, in cells that lack EMC subunit 4. Furthermore, targeted depletion of EMC subunits in live mosquitoes significantly reduced DENV2 propagation in vivo. Using a novel uncoating assay, which measures interactions between host RNA-binding proteins and incoming viral RNA, we show that EMC is required at or prior to virus uncoating. Importantly, we uncovered a second and important role for the EMC. The complex is required for viral protein accumulation in a cell line harboring a ZIKV replicon, indicating that EMC participates in the complex process of viral protein biogenesis.


Towards understanding the aetiology and pathophysiology of the emetic reflex: novel approaches to antiemetic drugs.
The introduction of 5-HT3 antagonists, such as ondansetron, as antiemetic agents has transformed the management of patients receiving chemotherapy or radiation therapy. Studies in animal models with NK1 antagonists suggest that these represent a new class of antiemetic agents having a broader spectrum of activity than 5-HT3 antagonists. Compounds of this class may prove to be more effective in man against delayed emesis induced by cisplatin, post-operative nausea and vomiting and motion sickness. Thus, they have the potential to complement 5-HT3 antagonists and so provide a further advance in the management of nausea and vomiting.


7-ketocholesterol-induced inflammation: involvement of multiple kinase signaling pathways via NFκB but independently of reactive oxygen species formation.
7-Ketocholesterol (7KCh) accumulates in oxidized lipoprotein deposits and is known to be involved in macrophage foam cell formation and atherosclerosis. 7-KCh is present in the primate retina and is associated with oxidized lipoprotein deposits located in the choriocapillaris, Bruch's membrane, and retinal pigment epithelium (RPE). 7-KCh can also be formed in the retina as a consequence of light-induced iron release. The purpose of this study was to examine the signaling pathways involved in the 7KCh-mediated inflammatory response focusing on three cytokines, VEGF, IL-6, and IL-8. ARPE-19 cells were treated with 7KCh solubilized in hydroxypropyl-β-cyclodextrin. Cytokines were quantified by qRT-PCR (mRNA) and ELISA (protein) using commercially available products. NFκB activation was determined by IκBα mRNA induction. Treatment of ARPE-19 cells with 15 μM 7KCh markedly induced the expression of VEGF, IL-6, and IL-8. No increase in NOX-4 expression or ROS formation was detected. 7KCh induced the phosphorylation of ERK1/2 and p38MAPK, and inhibitors to these kinases markedly reduced the cytokine expression but did not affect the IκBα mRNA expression. By contrast, inhibition of PI3K and PKCζ significantly decreased the cytokine and IκBα mRNA expression. Inhibition of the IκB kinase complex essentially ablated all cytokine induction. 7KCh induces cytokines via three kinase signaling pathways, AKT-PKCζ-NFκB, p38 MAPK, and ERK. The MAPK/ERK pathways seem to preferentially enhance cytokine induction downstream from NFκB activation. The results of this study suggest that 7KCh activates these pathways through interactions in the plasma membrane, but the mechanism(s) remains unknown.


Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study.
The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup.


Physiological Factors Which Influence Cognitive Performance in Military Personnel.
To identify and detail physiological factors that influence cognition in military personnel. Maintenance of cognitive and task performance is important under several scenarios, none more so than in a military context. Personnel are prepared for and trained to tolerate many of the stressors they encounter; however, consideration of stressors typically extends only as far as the physical, psychological, and environmental requirements of a given task. While considering these factors certainly characterizes the broader picture, several physiological states and traits can influence cognition and thus, should also be considered. A systematic review of the electronic databases Medline (PubMed), EMBASE (Scopus), PsycINFO, and Web of Science was conducted from inception up to January 2019. Eligibility criteria included current military personnel, an outcome of cognition, and the assessment of a physiological factor. The search returned 60,564 records, of which 60 were included in the review. Eleven studies examined the impact of demographic factors on cognition, 16 examined fatigue, 10 investigated nutrition, and 24 the impact of biological factors on cognitive performance. Factors identified as having a positive impact on cognition include aerobic fitness, nutritional supplementation, and visual acuity. In contrast, factors identified as having a negative impact include fatigue arising from sustained operations, dehydration, undernutrition, and an exaggerated physiological stress response to a cognitive task or a stressor. A further subset of these factors was considered modifiable. The modifiable factors identified provide avenues for training and preparation to enhance cognition in ways previously unconsidered.


Comparison of Wearable Activity Tracker with Actigraphy for Sleep Evaluation and Circadian Rest-Activity Rhythm Measurement in Healthy Young Adults.
The purpose of this study was to evaluate the applicability of data obtained from a wearable activity tracker (Fitbit Charge HR) to medical research. This was performed by comparing the wearable activity tracker (Fitbit Charge HR) with actigraphy (Actiwatch 2) for sleep evaluation and circadian rest-activity rhythm measurement. Sixteen healthy young adults (female participants, 62.5%; mean age, 22.8 years) wore the Fitbit Charge HR and the Actiwatch 2 on the same wrist; a sleep log was recorded over a 14-day period. We compared the sleep variables and circadian rest-activity rhythm measures with Wilcoxon signed-rank tests and Spearman's correlations. The periods and acrophases of the circadian rest-activity rhythms and the sleep start times did not differ and correlated significantly between the Fitbit Charge HR and the Actiwatch 2. The Fitbit Charge HR tended to overestimate the sleep durations compared with the Actiwatch 2. However, the sleep durations showed high correlation between the two devices for all days. We found that the Fitbit Charge HR showed high accuracy in sleep evaluation and circadian rest-activity rhythm measurement when compared with actigraphy for healthy young adults. The results suggest that the Fitbit Charge HR could be applicable on medical research as an alternative tool to actigraphy for sleep evaluation and measurement of the circadian rest-activity rhythm.


Hydrogen peroxide in the regulation of erythropoietin (Epo) gene expression in hepatocellular carcinoma cells.
The present studies were designed and carried out to determine if hydrogen peroxide (H2O2) is involved in the regulation of erythropoietin (Epo) gene expression and stimulation of Epo production in the hepatocellular (Hep 3B) cells. Hep 3B cells were incubated with varying concentrations of H2O2 for periods of 6 hours or 24 hours. In other experiments Hep 3B cells were incubated for 24 hours with or without increasing concentrations of catalase and in the presence of H2O2. Culture medium levels of Epo were determined and quantitation of Epo mRNA was also made. The results indicate that H2O2 increases the levels of Epo mRNA and Epo hormone production in Hep 3B cells, and that catalase, the specific scavenger of hydrogen peroxide, inhibits Epo production in these cells. Based on these findings, it is concluded that H2O2 takes part in the signal transduction mechanisms in Epo production. It is recommended that further studies be undertaken to find out the source of the hydrogen peroxide in the hepatocellular carcinoma cells.


Effects of fish oil supplementation on inflammatory acne.
Given that acne is a rare condition in societies with higher consumption of omega-3 (n-3) relative to omega-6 (n-6) fatty acids, supplementation with n-3 may suppress inflammatory cytokine production and thereby reduce acne severity. 13 individuals with inflammatory acne were given three grams of fish oil containing 930 mg of EPA to their unchanged diet and existing acne remedies for 12 weeks. Acne was assessed using an overall severity grading scale, total inflammatory lesion counts, and colorimetry. There was no significant change in acne grading and inflammatory counts at week 12 compared to baseline. However, there was a broad range of response to the intervention on an individual basis. The results showed that acne severity improved in 8 individuals, worsened in 4, and remained unchanged in 1. Interestingly, among the individuals who showed improvement, 7 were classified as having moderate to severe acne at baseline, while 3 of the 4 whose acne deteriorated were classified as having mild acne. There is some evidence that fish oil supplementation is associated with an improvement in overall acne severity, especially for individuals with moderate to severe acne. Divergent responses to fish oil in our pilot study indicates that dietary and supplemental lipids are worthy of further investigation in acne.


A descriptive and comparative study of two Early Pleistocene immature scapulae from the TD6.2 level of the Gran Dolina cave site (Sierra de Atapuerca, Spain).
Here we present the descriptive and comparative study of two immature scapulae recovered from the TD6.2 level of the Gran Dolina cave site (Sierra de Atapuerca, Spain) and assigned to Homo antecessor. This is the first time that data on the morphology and dimensions of the scapulae of a European late Early Pleistocene hominin population are provided. Considering the state of development and the linear dimensions, the scapula ATD6-116 could belong to a child of about 2-4 years. The morphology of ATD6-116 clearly departs from that of the Australopithecus afarensis juvenile specimen DIK-1-1, pointing to functional differences in locomotor behavior between Australopithecus and the late Early Pleistocene hominins. The immature scapula ATD6-118 belonged to an immature individual with a development of the scapula equivalent to that of adolescents of recent human populations. The scapulae ATD6-118 and KNM-WT 15000 present a similar state of development. Although the scapula KNM-WT 15000 is clearly larger than ATD6-118, these two specimens share some characteristics such as their relative narrowness and the value of the axilloglenoid and spinoglenoid angles. The glenoid fossa of ATD6-116 show a lateral orientation, whereas in ATD6-118 the glenoid fossa is slightly cranially oriented, but still within the range of variation of modern humans. The glenoid index of both ATD6-116 and ATD6-118 is low in accordance to the values usually observed in other early hominins, thus showing the primitive condition for this feature. Both scapulae show a ventrally placed axillary sulcus. The presence of this primitive feature in ATD-116 confirms that the shape of the axillary border has a genetic basis and it is not related to physical activity.


Nicotine stimulates pancreatic cancer xenografts by systemic increase in stress neurotransmitters and suppression of the inhibitory neurotransmitter gamma-aminobutyric acid.
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality in Western countries. We have shown previously that four representative human PDAC cell lines were regulated by beta-adrenoreceptors via cyclic adenosine 3',5'-monophosphate (cAMP)-dependent signaling. In the current study, we have tested the hypothesis that nicotine stimulates the growth of PDAC xenografts in nude mice by increasing the systemic levels of the stress neurotransmitters adrenaline and noradrenaline, which are the physiological agonists for beta-adrenoreceptors and that inhibition by gamma-aminobutyric acid (GABA) of the adenylyl cyclase-dependent pathway downstream of adrenoreceptors blocks this effect. The size of xenografts from PDAC cell line Panc-1 was determined 30 days after inoculation of the cancer cells. Stress neurotransmitters in serum as well as cAMP in the cellular fraction of blood and in tumor tissue were assessed by immunoassays. Levels of GABA, its synthesizing enzymes GAD65 and GAD67 and beta-adrenergic signaling proteins in the tumor tissue were determined by western blotting. Nicotine significantly increased the systemic levels of adrenaline, noradrenaline and cAMP while increasing xenograft size and protein levels of cAMP, cyclic AMP response element-binding protein and p-extracellular signal-regulated kinase 1/2 in the tumor tissue. Nicotine additionally reduced the protein levels of both GAD isozymes and GABA in tumor tissue. Treatment with GABA abolished these responses to nicotine and blocked the development of xenografts in mice not exposed to nicotine. These findings suggest that the development and progression of PDAC is subject to significant modulation by stimulatory stress neurotransmitters and inhibitory GABA and that treatment with GABA may be useful for marker-guided cancer intervention of PDAC.


Sex differences in neurodevelopmental abnormalities caused by early-life anaesthesia exposure: a narrative review.
Exposure to anaesthetic drugs during the fetal or neonatal period induces widespread neuronal apoptosis in the brains of rodents and non-human primates. Hundreds of published preclinical studies and nearly 20 clinical studies have documented cognitive and behavioural deficits many months or years later, raising the spectre that early life anaesthesia exposure is a long-term, perhaps permanent, insult that might affect the quality of life of millions of humans. Although the phenomenon of anaesthesia-induced developmental neurotoxicity is well characterised, there are important and lingering questions pertaining to sex differences and neurodevelopmental sequelae that might occur differentially in females and males. We review the relevant literature on sex differences in the field of anaesthesia-induced developmental neurotoxicity, and present an emerging pattern of potential sex-dependent neurodevelopmental abnormalities in rodent models of human infant anaesthesia exposure.


Epidemiology, appropriateness, and cost of vancomycin use.
Pharmaceutical costs, which approach $40 billion annually, account for about 8% of health care costs. Prescription drugs represent 5% to 20% of the total hospital budget, and antimicrobials account for 20% to 50% of hospital pharmaceutical costs. At one university hospital, the percentage of patients receiving antimicrobials increased from 31.8% in 1988 to 53.1% in 1994. Receipt of vancomycin has been associated with the emergence of resistant enterococci and has resulted in Centers for Disease Control and Prevention (CDC) recommendations for its use. Studies show that vancomycin use is increasing, that dosing is often inappropriate, that certain populations (such as oncology, neurosurgery, and cardiovascular surgery patients) are more likely to receive vancomycin, and that often use is not consistent with CDC recommendations. Few studies have assessed the cost of vancomycin use; those that have show that it is costly. Further studies of vancomycin use are needed, so that use can be improved through focused educational programs.


The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial.
Nucleoside analogues form the backbone of many therapeutic regimens in oncology and require the presence of intracellular enzymes for their activation. A ProTide is comprised of a nucleoside fused to a protective phosphoramidate cap. ProTides are easily incorporated into cells whereupon the cap is cleaved and a preactivated nucleoside released. 3'-Deoxyadenosine (3'-dA) is a naturally occurring adenosine analogue with established anticancer activity in vitro but limited bioavailability due to its rapid in vivo deamination by the circulating enzyme adenosine deaminase, poor uptake into cells, and reliance on adenosine kinase for its activation. In order to overcome these limitations, 3'-dA was chemically modified to create the novel ProTide NUC-7738. We describe the synthesis of NUC-7738. We determine the IC50 of NUC-7738 using pharmacokinetics (PK) and conduct genome-wide analyses to identify its mechanism of action using different cancer model systems. We validate these findings in patients with cancer. We show that NUC-7738 overcomes the cancer resistance mechanisms that limit the activity of 3'-dA and that its activation is dependent on ProTide cleavage by the enzyme histidine triad nucleotide-binding protein 1. PK and tumor samples obtained from the ongoing first-in-human phase I clinical trial of NUC-7738 further validate our in vitro findings and show NUC-7738 is an effective proapoptotic agent in cancer cells with effects on the NF-κB pathway. Our study provides proof that NUC-7738 overcomes cellular resistance mechanisms and supports its further clinical evaluation as a novel cancer treatment within the growing pantheon of anticancer ProTides.