Studies of the metabolism of parathion with an apparently homogeneous preparation of rabbit liver cytochrome P-450.
The metabolism of parathion has been examined by use of a reconstituted mixed-function oxidase enzyme system isolated from the livers of phenobarbital-pretreated rabbits. The cytochrome P-450 used in these studies was apparently homogeneous as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by assay of the preparation for contaminating microsomal enzymes and enzyme activity. These studies revealed that the apparently homogeneous preparation of cytochrome P-450, in the presence of the appropriate cofactors, can catalyze the conversions of parathion to both paraoxon and diethyl phosphorothioic acid. The present studies have also shown that parathion is metabolized by the reconstituted mixed-function oxidase enzyme system to diethyl phosphoric acid, a product which, in previous studies with intact liver microsomes, had been thought to arise exclusively from the hydrolysis of paraoxon by a microsomal esterase(s). The available data suggest that all three of the products of the metabolism of parathion by the reconstituted mixed-function oxidase enzyme system, namely, paraoxon, diethyl phosphorothioic acid, and diethyl phosphoric acid, are formed nonenzymatically by breakdown by different pathways of a common enzymatically formed intermediate. This common intermediate is thought to be the sulfine derivative of parathion formed in the mixed-function oxidase-catalyzed addition of an oxygen atom to one of the unshared electron pairs of the thiono-sulfur atom.


Drosophila Psf2 has a role in chromosome condensation.
The condensation state of chromosomes is a critical parameter in multiple processes within the cell. Failures in the maintenance of appropriate condensation states may lead to genomic instability, mis-expression of genes, and a number of disease states. During cell proliferation, replication of DNA represents an ongoing challenge for chromosome packaging as DNA must be unpackaged for replication and then faithfully repackaged. An integral member of the DNA replication machinery is the GINS complex which has been shown to stabilize the CMG complex which is required for processivity of the Mcm2-7 helicase complex during S phase. Through examination of the phenotypes associated with a null mutation in Psf2, a member of the evolutionarily conserved GINS complex, we find that Drosophila Psf2 likely has a role in establishing chromosome condensation and that the defects associated with this mis-condensation impact M phase progression, genomic stability, and transcriptional regulation.


Molecular characterization of two anther-specific genes encoding putative RNA-binding proteins, AtRBP45s, in Arabidopsis thaliana.
RRM (RNA-recognition motif) domain is important for the post-transcriptional regulation of gene expression including RNA processing. In our previous study, we found one anther- and/or pollen-specific gene (LjRRM1, previously named as LjMfb-U93) in model legume, Lotus japonicus. Because of the richness of genomic information of another model plant, Arabidopsis thaliana, for functional analysis, we identified and characterized the orthologous genes in A. thaliana. By comparison of the partial nucleotide sequence of LjRRM1 to the public database, we identified three homologous genes (AtRBP45a, AtRBP45b, and AtRBP45c) in A. thaliana genome. Based on promoter analysis, both AtRBP45a and AtRBP45c were specifically expressed in immature anther tissues (tapetum cells) and mature pollen grains of transgenic plants. This expression pattern of AtRBP45a and AtRBP45c is quite similar to that of LjRRM1, indicating that AtRBP45a and AtRBP45c would be orthologous to LjRRM1. Because in another previous experiment, it was shown that proteins having RRM domains were related to pre-mRNA maturation, and as a conclusion, it is possible that LjRRM1, AtRBP45a, and AtRBP45c genes encoding RNA-binding proteins are functionally involved in the repression of translation in mature pollen grains in L. japonicus and A. thaliana.


Insights Into Collaborative Networks Of Nonprofit, Private, And Public Organizations That Address Complex Health Issues.
Community networks that include nonprofit, public, and private organizations have formed around many health issues, such as chronic disease management and healthy living and eating. Despite the increases in the numbers of and funding for cross-sector networks, and the growing literature about them, there are limited data and methods that can be used to assess their effectiveness and analyze their designs. We addressed this gap in knowledge by analyzing the characteristics of 260 cross-sector community health networks that collectively consisted of 7,816 organizations during the period 2008-15. We found that nonprofit organizations were more prevalent than private firms or government agencies in these networks. Traditional types of partners in community health networks such as hospitals, community health centers, and public health agencies were the most trusted and valued by other members of their networks. However, nontraditional partners, such as employer or business groups and colleges or universities, reported contributing relatively high numbers of resources to their networks. Further evidence is needed to inform collaborative management processes and policies as a mechanism for building what the Robert Wood Johnson Foundation describes as a culture of health.


Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice.
Adult stem cells occur in niches that balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, stem cells outside their niche often display fate flexibility. Here we show that super-enhancers underlie the identity, lineage commitment and plasticity of adult stem cells in vivo. Using hair follicle as a model, we map the global chromatin domains of hair follicle stem cells and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters ('epicentres') of transcription factor binding sites undergo remodelling upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, hair follicle stem cells dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicentres, enabling their genes to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.


Contribution of paramedics in primary and urgent care: a systematic review.
Within the UK, there are now opportunities for paramedics to work across a variety of healthcare settings away from their traditional ambulance service employer, with many opting to move into primary care. To provide an overview of the types of clinical roles paramedics are undertaking in primary and urgent care settings within the UK. A systematic review. Searches were conducted of MEDLINE, CINAHL, Embase, the National Institute for Health and Care Excellence, the Journal of Paramedic Practice, and the Cochrane Database from January 2004 to March 2019 for papers detailing the role, scope of practice, clinician and patient satisfaction, and costs of paramedics in primary and urgent care settings. Free-text keywords and subject headings focused on two key concepts: paramedic and general practice/primary care. In total, 6765 references were screened by title and/or abstract. After full-text review, 24 studies were included. Key findings focused on the description of the clinical role, the clinical work environment, the contribution of paramedics to the primary care workforce, the clinical activities they undertook, patient satisfaction, and education and training for paramedics moving from the ambulance service into primary care. Current published research identifies that the role of the paramedic working in primary and urgent care is being advocated and implemented across the UK; however, there is insufficient detail regarding the clinical contribution of paramedics in these clinical settings. More research needs to be done to determine how, why, and in what context paramedics are now working in primary and urgent care, and what their overall contribution is to the primary care workforce.


Low polyethylene creep and wear following mobile-bearing unicompartmental knee replacement.
The Oxford unicompartmental knee replacement (UKR) has a fully congruent mobile bearing to minimise wear. However, with younger higher demand patients, wear remains a concern. The aim of this study was to quantify the wear rate of Phase 3 Oxford UKR bearings over the course of 5 years and to identify the factors that influence it. 40 medial Oxford UKRs recruited for a randomised study of cemented and cementless fixation were studied with Radiostereometric analysis (RSA) at 1 week, 3 months, 6 months, 1 year, 2 years, and 5 years post-operatively and bearing thickness was calculated. Penetration, defined as the change in thickness compared to the 1-week measurement, was determined. Creep (early penetration) and wear (late penetration at a constant rate) were calculated. The influence of demographic factors, Oxford Knee Score (OKS), Tegner score, fixation and bearing overhang (determined by RSA) on wear was analysed. After 6 months the penetration rate was constant, indicating that wear alone was occurring. The wear rate was 0.07 mm/year (SD 0.03). The creep was 0.06 mm with about 95% occurring during the first 3 months. There was no significant relationship between fixation (cemented/cementless), age, component size, OKS and Tegner score with wear rate. Increasing BMI was associated with decreasing wear (p = 0.042). 37/40 bearings overhung the tibia to some extent and 23/40 overhung the tibia medially. An increase in the area of overhang (p = 0.036), amount of medial overhang (p = 0.028) and distance between the bearing and tibial wall (p = 0.019) were associated with increased wear. Bearings that did not overhang (0.06 mm/year) had less wear (p = 0.025) than those that did (0.08 mm/year). There was no relationship (p = 0.6) between the femoral contact area and wear. During the first three to six months after implantation, the bearing becomes 0.06 mm thinner due to creep. The combined wear rate of the upper and lower surfaces of the bearing is constant (0.07 mm/year). The wear is lower if the bearing does not overhang the tibia so surgeons should aim for the bearing to be close to the tibial wall. The orientation of the femoral component does not influence wear. Retrospective Study, Level III.


Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit.
Alterations in the FHIT gene at 3p14.2 occur as early and frequent events in the development of several common human cancers. The ability of human Fhit-negative cells to form tumors in nude mice is suppressed by stable reexpression of Fhit protein. Fhit protein is a diadenosine P1,P3-triphosphate (ApppA) hydrolase whose fungal and animal homologs form a branch of the histidine triad (HIT) superfamily of nucleotide-binding proteins. Because the His-96 --> Asn substitution of Fhit, which retards ApppA hydrolase activity by seven orders of magnitude, did not block tumor-suppressor activity in vivo, we determined whether this mutation affected ApppA binding or particular steps in the ApppA catalytic cycle. Evidence is presented that His-96 --> Asn protein binds ApppA well and forms an enzyme-AMP intermediate extremely poorly, suggesting that Fhit-substrate complexes are the likely signaling form of the enzyme. The cocrystal structure of Fhit bound to Ado-p-CH2-p-ps-Ado (IB2), a nonhydrolyzable ApppA analog, was refined to 3.1 A, and the structure of His-96 --> Asn Fhit with IB2 was refined to 2.6 A, revealing that two ApppA molecules bind per Fhit dimer; identifying two additional adenosine-binding sites on the dimer surface; and illustrating that His-98 is positioned to donate a hydrogen bond to the scissile bridging oxygen of ApppA substrates. The form of Fhit bound to two ApppA substrates would present to the cell a dramatically phosphorylated surface, prominently displaying six phosphate groups and two adenosine moieties in place of a deep cavity lined with histidines, arginines, and glutamines.


Which medical interview behaviors are associated with patient satisfaction?
The objective of this study was to investigate the association between several medical interview behaviors and patient satisfaction. The subjects were 158 new patients who visited an outpatient facility of a university hospital in Japan. All medical interviews were videotaped and reviewed by a trained rater using a medical interview rating scale (Takemura Medical Interview Rating Scale) for evaluating medical interview behaviors. To measure patient satisfaction, a self-administered questionnaire was also developed. Both the rating scale and the questionnaire were assessed for validity and reliability beforehand. A significant positive association was found between the behaviors of reflection and legitimation on the one hand, and patient satisfaction on the other. The positive association between reflection and patient satisfaction existed after adjusting for both the duration of the interview and the other medical interview behaviors used. The association between legitimation and patient satisfaction also existed after adjusting for the duration of the medical interview but disappeared after adjusting for the other medical interview behaviors used. When we investigated the strength of the relationship between each medical interview behavior and patient satisfaction, reflection was found to be the strongest determinant of patient satisfaction. This research revealed a significant positive association between reflection or legitimation and patient satisfaction in an actual clinical practice setting.


Cell-based therapeutics: the next pillar of medicine.
Two decades ago, the pharmaceutical industry-long dominated by small-molecule drugs-was revolutionized by the the advent of biologics. Today, biomedicine sits on the cusp of a new revolution: the use of microbial and human cells as versatile therapeutic engines. Here, we discuss the promise of this "third pillar" of therapeutics in the context of current scientific, regulatory, economic, and perceptual challenges. History suggests that the advent of cellular medicines will require the development of a foundational cellular engineering science that provides a systematic framework for safely and predictably altering and regulating cellular behaviors.


Cost and health status analysis after autologous chondrocyte implantation and mosaicplasty: a retrospective comparison.
Chondral defects of the knee cartilage are prevalent. Autologous chondrocyte implantation (ACI) and mosaicplasty are increasingly used to treat symptomatic knee defects. This study assessed the costs and health status outcomes after ACI and mosaicplasty. Patients were eligible to participate in this cross-sectional study if they received ACI or mosaicplasty at the Royal National Orthopaedic Hospital between 1997 and 2001 or were on a waiting list for ACI. Secondary-care resource use was collected to 2 years postoperatively using a resource collection proforma. Participants responded to postal questions about sociodemographic characteristics and knee-related (Modified Cincinnati Knee Rating System) and general health status (EQ-5D). Fifty-three ACI, twenty mosaicplasty, and twenty-two patients waiting for ACI participated. The average cost per patient was higher for ACI (10,600 pounds sterling: 95 percent confidence interval [CI], 10,036 pounds sterling-11,214 pounds sterling) than mosaicplasty (7,948 pounds sterling: 95 percent CI, 6,957 pounds sterling-9,243 pounds sterling). Postoperatively, ACI and mosaicplasty patients (combined) experienced better health status than those waiting for ACI. ACI patients tended to have better health status outcomes than mosaicplasty patients (not statistically significant). Estimated average EQ-5D social tariff improvements for quality-adjusted life year (QALY) calculations were 0.23 (ACI) and 0.06 (mosaicplasty). Average costs per QALY were 23,043 pounds sterling (ACI) and 66,233 pounds sterling (mosaicplasty). The incremental cost effectiveness ratio (ICER) for providing ACI over mosaicplasty was 16,349 pounds sterling. Average costs were higher for ACI than mosaicplasty. However, both the estimated cost per QALY and ICER for providing ACI over mosaicplasty fell beneath an implicit English funding threshold of 30,000 pounds sterling per QALY. Prospective studies should include measures of utility to confirm the estimated cost utility ratios of ACI and mosaicplasty.


Schizophrenia: a neuropathological perspective.
It is probable that all schizophrenics have abnormalities in the medial temporal lobe, which differ in degree but not in kind. The structures of the medial temporal lobe are believed to have a crucial role in the integration and processing of the output from the association cortex. Dysfunction of this system could result in the clinical symptoms that form the core of the schizophrenia syndrome. The structural differences appear to fit the profile of a disturbance in the normal pattern of brain development. The asymmetrical patterns of normal brain development explain how such a disturbance simultaneously affecting both hemispheres could, disproportionately, affect the left (dominant) hemisphere. Epidemiological and pathological evidence points to aberrant genetic mechanisms as being the cause of the developmental anomaly in the majority of cases; environmental factors probably play a minor role. Despite the great progress made in solving the enigma of the structural changes in the brains of schizophrenics, the cause(s) of the changes--the aberrant genetic mechanism controlling brain development--may prove difficult to define.


Factors affecting child marriage and contraceptive use among Rohingya girls in refugee camps.
Background: Rohingya girls living in the refugee camps in Bangladesh are disproportionately vulnerable to child marriages and teenage pregnancies. This study examines the factors affecting child marriage and contraceptive use among Rohingya girls who have experienced child marriages. Methods: We collected and analysed quantitative and qualitative data from adolescent Rohingya girls (age 10-19 years) who experienced child marriages. The quantitative data (n=96) came from a cross-sectional survey, and the qualitative data (n=18) from in-depth interviews conducted in the world's largest refugee camp located in Cox's Bazar, Bangladesh. We also interviewed service providers (n=9) of reproductive healthcare services to gain their perspectives regarding contraceptive use among these young girls. We used descriptive statistics to characterise the girls' demographic profiles, ages at their first marriages, and contraceptive use. Thematic analysis was used for the qualitative data to identify key factors influencing child marriage and contraceptive use among these girls. Findings: On average, the adolescent female participants had been 15.7 years old when they were first married. Over 80% had given birth during the two years before the survey or were pregnant during time of the data collection. The main factors that influenced child marriage were found to be perceptions regarding the physical and mental maturity for marriage, social norms, insecurity, family honour, preferences for younger brides and the relaxed enforcement of the minimum legal age for marriage. A third (34%) of the girls said they were using contraceptives on the week when the study was conducted. The desire for children, religious beliefs, misapprehension about contraception and long waiting periods in facility-based health services and current service provision were the main factors influencing contraceptive use. Depo Provera injections and pills were the dominant methods of contraception. Contraceptive use during the period between marriage and the first childbirth is rare. Interpretation: Girl child marriage is common in Rohingya camps. Contraceptive use is rare among newly married girls before they give birth for the first time. The involvement of female and male Rohingya volunteers for outreach services can be catalytic in promoting contraceptive use. Funding: La Trobe Asia, La Trobe University, Melbourne, Australia. Bengali translation of the abstract in Appendix 1.


Patterns and predictors of change in trauma-focused treatments for war-related posttraumatic stress disorder.
We evaluated patterns and predictors of change from three efficacy trials of trauma-focused cognitive-behavioral treatments (TF-CBT) among service members (N = 702; mean age = 32.88; 89.4% male; 79.8% non-Hispanic/Latino). Rates of clinically significant change were also compared with other trials. The trials were conducted in the same setting with identical measures. The primary outcome was symptom severity scores on the PTSD Symptom Scale-Interview Version (PSS-I; Foa, Riggs, Dancu, & Rothbaum, 1993). Symptom change was best explained by baseline scores and individual slopes. TF-CBT was not associated with better slope change relative to Present-Centered Therapy, a comparison arm in 2 trials. Lower baseline scores (β = .33, p < .01) and higher ratings of treatment credibility (β = -.22, p < .01) and expectancy for change (β = -.16, p < .01) were associated with greater symptom change. Older service members also responded less well to treatment (β = .09, p < .05). Based on the Jacobson and Truax (1991) metric for clinically significant change, 31% of trial participants either recovered or improved. Clinicians should individually tailor treatment for service members with high baseline symptoms, older patients, and those with low levels of credibility and expectancy for change. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Squaraine dyes in molecular recognition and self-assembly.
Squaraine dye molecules and their derivatives are gaining significant interest in the field of supramolecular chemistry, both in host-guest recognition and self-assembly. The unique structure and properties of squaraine molecules has led to extensive research into their use as sensors. This feature article covers the most recent studies (2004-2009) in the development, characterization, and application of squaraine dye-based molecular sensors, self-assembly, and their use in polymeric materials and biological applications.


Trajectory of self-care behaviour in patients with heart failure: the impact on clinical outcomes and influencing factors.
Patients' self-care behaviour is still suboptimal in many heart failure (HF) patients and underlying mechanisms on how to improve self-care need to be studied. (1) To describe the trajectory of patients' self-care behaviour over 1 year, (2) to clarify the relationship between the trajectory of self-care and clinical outcomes, and (3) to identify factors related to changes in self-care behaviour. In this secondary analysis of the COACH-2 study, 167 HF patients (mean age 73 years) were included. Self-care behaviour was assessed at baseline and after 12 months using the European Heart Failure Self-care Behaviour scale. The threshold score of ⩾70 was used to define good self-care behaviour. Of all patients, 21% had persistent poor self-care behaviour, and 27% decreased from good to poor. Self-care improved from poor to good in 10%; 41% had a good self-care during both measurements. Patients who improved self-care had significantly higher perceived control than those with persistently good self-care at baseline. Patients who decreased their self-care had more all-cause hospitalisations (35%) and cardiovascular hospitalisations (26%) than patients with persistently good self-care (2.9%, p < 0.05). The prevalence of depression increased at 12 months in both patients having persistent poor self-care (0% to 21%) and decreasing self-care (4.4% to 22%, both p < 0.05). Perceived control is a positive factor to improve self-care, and a decrease in self-care is related to worse outcomes. Interventions to reduce psychological distress combined with self-care support could have a beneficial impact on patients decreasing or persistently poor self-care behaviour.


In Vivo Evolution of CMY-2 to CMY-33 β-Lactamase in Escherichia coli Sequence Type 131: Characterization of an Acquired Extended-Spectrum AmpC Conferring Resistance to Cefepime.
Cefepime is frequently prescribed to treat infections caused by AmpC-producing Gram-negative bacteria. CMY-2 is the most common plasmid-mediated AmpC (pAmpC) β-lactamase. Unfortunately, CMY variants conferring enhanced cefepime resistance have been reported. Here, we describe the evolution of CMY-2 to an extended-spectrum AmpC (ESAC) in clonally identical Escherichia coli isolates obtained from a patient. The CMY-2-producing E. coli isolate (CMY-2-Ec) was isolated from a wound. Thirty days later, one CMY-33-producing E. coli isolate (CMY-33-Ec) was detected in a bronchoalveolar lavage fluid sample. Two weeks before the isolation of CMY-33-Ec, the patient received cefepime. CMY-33-Ec and CMY-2-Ec were identical by repetitive extragenic palindromic-PCR (rep-PCR), being of hyperepidemic sequence type 131 (ST131) but showing different β-lactam MICs (e.g., cefepime MIC, 16 and ≤ 0.5 μg/ml for CMY-33-Ec and CMY-2-Ec, respectively). Identical CMY-2-Ec isolates were also found in a rectal swab. CMY-33 differs from CMY-2 by a Leu293-Ala294 deletion. Expressed in E. coli strain DH10B, both CMYs conferred resistance to ceftazidime (≥ 256 μg/ml), but the cefepime MICs were higher for CMY-33 than CMY-2 (8 versus 0.25 μg/ml, respectively). The kcat/Km or inhibitor complex inactivation (kinact)/Ki app (μM(-1) s(-1)) indicated that CMY-33 possesses an extended-spectrum β-lactamase (ESBL)-like spectrum compared to that of CMY-2 (e.g., cefoxitin, 0.2 versus 0.4; ceftazidime, 0.2 versus not measurable; cefepime, 0.2 versus not measurable; and tazobactam, 0.0018 versus 0.0009, respectively). Using molecular modeling, we show that a widened active site (∼ 4-Å shift) may play a significant role in enhancing cefepime hydrolysis. This is the first in vivo demonstration of a pAmpC that under cephalosporin treatment expands its substrate spectrum, resembling an ESBL. The prevalence of CMY-2-Ec isolates is rapidly increasing worldwide; therefore, awareness that cefepime treatment may select for resistant isolates is critical.


Human activity recognition using wearable sensors, discriminant analysis, and long short-term memory-based neural structured learning.
Healthcare using body sensor data has been getting huge research attentions by a wide range of researchers because of its good practical applications such as smart health care systems. For instance, smart wearable sensor-based behavior recognition system can observe elderly people in a smart eldercare environment to improve their lifestyle and can also help them by warning about forthcoming unprecedented events such as falls or other health risk, to prolong their independent life. Although there are many ways of using distinguished sensors to observe behavior of people, wearable sensors mostly provide reliable data in this regard to monitor the individual's functionality and lifestyle. In this paper, we propose a body sensor-based activity modeling and recognition system using time-sequential information-based deep Neural Structured Learning (NSL), a promising deep learning algorithm. First, we obtain data from multiple wearable sensors while the subjects conduct several daily activities. Once the data is collected, the time-sequential information then go through some statistical feature processing. Furthermore, kernel-based discriminant analysis (KDA) is applied to see the better clustering of the features from different activity classes by minimizing inner-class scatterings while maximizing inter-class scatterings of the samples. The robust time-sequential features are then applied with Neural Structured Learning (NSL) based on Long Short-Term Memory (LSTM), for activity modeling. The proposed approach achieved around 99% recall rate on a public dataset. It is also compared to existing different conventional machine learning methods such as typical Deep Belief Network (DBN), Convolutional Neural Network (CNN), and Recurrent Neural Network (RNN) where they yielded the maximum recall rate of 94%. Furthermore, a fast and efficient explainable Artificial Intelligence (XAI) algorithm, Local Interpretable Model-Agnostic Explanations (LIME) is used to explain and check the machine learning decisions. The robust activity recognition system can be adopted for understanding peoples' behavior in their daily life in different environments such as homes, clinics, and offices.


Use of real time continuous glucose monitoring and intravenous insulin in type 1 diabetic mothers to prevent respiratory distress and hypoglycaemia in infants.
Pregnancy in Type 1 diabetic patients is a precarious condition, both for mother and fetus with increased the risk of prematurity and, immediately after delivery with risk of respiratory distress syndrome and hypoglycaemia in newborns. A strict control and monitoring of diabetes throughout pregnancy is important in reducing the impact of the disease on the fetus and newborn. In recent years many new technologies have been introduced to ameliorate diabetes monitoring, where the last is the Real-time Continuous Glucose Monitoring System (RT-CGMS). In the last three years, 72 h continuous glucose monitoring system (RT-CGMS) (Medtronic, CA) was performed in 18 pregnant women with Type 1 diabetes in two moments of pregnancy: during treatment with betamethasone to prevent respiratory distress and during delivery. In both cases insulin was administered intravenous and the dose was changed on the basis of glycaemia. The results present the use of this new technique during two topics moments of pregnancy of type 1 diabetes patients when is very important intensively to monitor diabetes and to obtain the well being of the fetus. No infant experimented hypoglycaemia or respiratory distress syndrome at the moment and in the first hours after the birth. We wish to stress the importance reducing glycaemia during administration of betamethasone and during labor. It is conceivable that the scarce attention paid to monitoring glucose levels in diabetic mothers during labor in gynaecological world may be due to the difficulty in glucose monitoring with the devices until now available. Hopefully, our anecdotal account may prompt improvements with RT-CGMS, and may lead to a better approach to the problem, thereby changing the prognosis of infants born to diabetic mothers.


Risk models including high-risk cardiovascular procedures: clinical predictors of mortality and morbidity.
While isolated coronary artery bypass grafting (CABG) poses major risks as well as benefits to cardiovascular surgery, procedures such as thoracic aortic surgery and combined CABG surgeries are also important contributors to mortality and morbidity. The objective of this study was to create and validate risk models including high-risk cardiovascular procedures to improve quality. The Japan Cardiovascular Surgery Database of patients enrolled cardiovascular surgical patients between January 2005 and December 2007. Data were collected at presentation and by physician review of clinical records and were verified through third-party surgeons' auditing. We analyzed 36780 procedures in 120 hospitals. Using logistic regression, risk models were generated and validated by split-sample validation. In this analysis, 11948 procedures were isolated CABG, 11760 were valve surgeries, and 8440 were thoracic aortic surgeries. In a 30-day operative mortality risk model, 37 variables were significantly associated with outcome. In comparison to isolated CABG, the odds ratios (ORs) for a 30-day mortality were 1.81 for valve surgery (2.62 in mitral valve replacement and 2.72 in aortic valve plus mitral valve procedures) and 2.36 for thoracic aortic surgery (4.34 if indicated by rupture, 3.16 if involving only arch, 4.38 if involving distal aorta, 3.75 if descending, and 5.97 if thoraco-abdominal aorta). CABG combined with other procedures (n=3599) had increased risks in each morbidity risk model (OR: 1.21 in reoperation, 1.60 in stroke, 1.23 in dialysis, 1.97 in infection, and 1.40 in prolonged ventilation). The predictive power of our models is valued by a C-statistic of 0.830 for a 30-day postoperative mortality, 0.639 for reoperation, 0.726 for stroke, 0.817 for dialysis, 0.692 for infection, and 0.796 for prolonged ventilation. Though performance of isolated CABG surgery was stable in this era, CABG combined with valve or thoracic aortic surgery was still a high-risk procedure. Given better recognition of high patient risk from these models, earlier targeted perioperative interventions may reduce adverse effects.


Retrograde neurotrophic signaling in rat retinal ganglion cells is transmitted via the ERK5 but not the ERK1/2 pathway.
Neurotrophic deprivation is considered an important event in glaucomatous retinal ganglion cell (RGC) death. However, the mitogen-activated protein kinase (MAPK) pathway transmitting axonal neurotrophic signals in RGC has not been identified. We investigated the involvement of ERK5 and ERK1/2 in retrograde axonal neurotrophic signaling in rats. Adult Sprague-Dawley rats were used. Retinal immunostaining for ERK5 and MEK5 was performed. Levels of total and phosphorylated ERK5 and ERK1/2 were analyzed in retinal lysate by quantitative Western blotting. The effects of age, brain-derived neurotrophic factor (BDNF) stimulation at RGC soma (intravitreal injection) or axon ending (superior colliculus [SC] injection), axonal tyrosine kinase receptor (Trk) receptor inhibition with genistein, and acute axonal damage by optic nerve transection (ONT) were investigated at time points from 24 hours to 5 days. ERK5 and MEK5 were present in RGCs and glial cells. Phospho-ERK5 levels increased in retina and decreased in brain with age (n = 4; P = 0.039). Phosphorylation of ERK5 but not ERK1/2 was increased or decreased by SC injection of BDNF or genistein, respectively (BDNF at 48 hours [p-ERK5: P = 0.01; p-ERK1/2: P = 0.55, n = 8]; genistein at 48 hours [p-ERK5: P = 0.01; p-ERK1/2: P = 0.5, n = 5]). ONT showed a similar trend. BDNF stimulation at the RGC soma increased both p-ERK5 and p-ERK1/2 (P = 0.035 and P = 0.032, respectively; n = 6; at 48 hours). ERK5 is present in RGCs. Retina and brain p-ERK5 levels develop differently with age. The response of ERK5 but not ERK1/2 to BDNF stimulation or inhibition at the RGC axon ending indicates that retrograde neurotrophic signals in the rat optic nerve may be mediated by the ERK5 pathway.


Powassan Virus: An Emerging Arbovirus of Public Health Concern in North America.
Powassan virus (POWV, Flaviviridae) is the only North American member of the tick-borne encephalitis serogroup of flaviviruses. It is transmitted to small- and medium-sized mammals by Ixodes scapularis, Ixodes cookei, and several other Ixodes tick species. Humans become infected with POWV during spillover transmission from the natural transmission cycles. In humans, POWV is the causative agent of a severe neuroinvasive illness with 50% of survivors displaying long-term neurological sequelae. POWV was recognized as a human pathogen in 1958 when a young boy died of severe encephalitis in Powassan, Ontario, and POWV was isolated from the brain autopsy of this case. Two distinct genetic lineages of POWV are now recognized: POWV (lineage I) and deer tick virus (lineage II). Since the index case in 1958, over 100 human cases of POWV have been reported, with an apparent rise in disease incidence in the past 16 years. This recent increase in cases may represent a true emergence of POWV in regions where the tick vector species are prevalent, or it could represent an increase in POWV surveillance and diagnosis. In the past 5 years, both basic and applied research for POWV disease has intensified, including phylogenetic studies, field surveillance, case studies, and animal model development. This review provides an overview of POWV, including the epidemiology, transmission, clinical disease, and diagnosis of POWV infection. Recent research developments and future priorities with regard to the disease are emphasized.


Development and implementation of a nutrition intervention programme in North West Pakistan: a realist framework.
Maternal and infant malnutrition is prevalent in rural regions of NW Pakistan. This article reports on the use of a combination of a realist Context-Mechanism-Outcome framework and participatory appraisal methods to facilitate the development of a locally sensitive and responsive nutritional intervention programme. Data were gathered through a series of focus group (FG) discussions with local lady health workers, as well as pregnant and breastfeeding women attending an Emergency Field Hospital in North West Pakistan between May 2008 and March 2009. A nutrition intervention programme was implemented that involved cookery demonstration kitchens and free food supplements, coupled with nutrition and healthcare information and advice for pregnant and breastfeeding women. Subsequent FG discussions revealed that the programme had a positive impact on knowledge gained by women in the community and generated an openness to receiving and spreading knowledge. The framework, which rested on the use of a double feedback loop, involving local women, lady health workers, local researchers and UK-based researchers, has enabled not only the establishment of the programme, but has also given the local team the tools to apply for, and gain, further funding for the development of nutrition support services. The development of such methodological tools, which empower local researchers and service providers (wherever located) to operationalize local knowledge and assess interventions, is particularly relevant in international financially-constrained contexts.


Toward ambulatory arteriovenous CO2 removal: initial studies and prototype development.
Extracorporeal arteriovenous carbon dioxide removal (AVCO2R) using percutaneous cannulae and a low resistance gas exchanger achieves near total CO2 removal, allowing lung rest and potentially improving survival. AVCO2R, redesigned to allow ambulation, has potential as treatment for severe chronic obstructive pulmonary disease or rehabilitation before lung transplant. The purposes of this study were to 1) determine the optimal ambulatory access for AVCO2 removal and 2) develop a prototype Ambulatory-AVCO2R gas exchanger. Initially, reinforced Gore-Tex 6 mm (two) and 8 mm (four) grafts were anastomosed to sheep carotid arteries and jugular veins as a loop in parallel to the cranial circulation to determine blood flow capabilities. Blood flow was 100-150 ml/min with a 14 gauge dialysis needle, and transected 6 mm Gore-Tex grafts achieved 500-900 ml blood flow, whereas transected 8 mm grafts achieved up to 2000 ml/min flow. The polytetrafluoroethylene (PTFE) loops were then connected to our newly developed ultra low resistance pumpless gas exchanger for ambulatory AVCO2R. The average pressure gradient across the prototype Ambulatory-AVCO2R gas exchangers (n = 5) was 2.8 +/- 0.8 mm Hg, and mean CO2 removal was 104.8 +/- 14.0 ml/min, with an average blood flow of 900 ml/min. We conclude that an 8 mm Gore-Tex reinforced graft arteriovenous loop supplies ample blood flow for our new ultra low resistance Ambulatory-AVCO2R to achieve near total CO2 removal.


Long-term Outcomes of Military Service in Aging and the Life Course: A Positive Re-envisioning.
Most research on military service focuses on its short-term negative consequences, especially the mental and physical injuries of those deployed in warzones. However, studies of long-term outcomes reveal surprisingly positive effects of military service--both those early in adulthood that grow over time and others that can emerge later in life. These multidomain effects have been found in veterans of World War II and the Korean War and are now being seen in veterans of the Vietnam War. Although some are directly attributable to public policies such as the GI Bill, which facilitate educational and economic gains, there are personal developmental gains as well, including autonomy, emotional maturity and resilience, mastery, and leadership skills, that lead to better health and well-being in later life. These long-term effects vary across persons, change over time within persons, and often reflect processes of cumulative advantage and disadvantage. We propose a life-span model of the effects of military service that provides a perspective for probing both long-term positive and negative outcomes for aging veterans. We further explicate the model by focusing on both sociocultural dynamics and individual processes. We identify public-use data that can be examined to evaluate this model, and offer a set of questions that can be used to assess military service. Finally, we outline an agenda for dedicated inquiry into such effects and consider policy implications for the health and well-being of aging veterans in later life.


Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences study.
Illicit drug use is identified in Healthy People 2010 as a leading health indicator because it is associated with multiple deleterious health outcomes, such as sexually transmitted diseases, human immunodeficiency virus, viral hepatitis, and numerous social problems among adolescents and adults. Improved understanding of the influence of stressful or traumatic childhood experiences on initiation and development of drug abuse is needed. We examined the relationship between illicit drug use and 10 categories of adverse childhood experiences (ACEs) and total number of ACEs (ACE score). A retrospective cohort study of 8613 adults who attended a primary care clinic in California completed a survey about childhood abuse, neglect, and household dysfunction; illicit drug use; and other health-related issues. The main outcomes measured were self-reported use of illicit drugs, including initiation during 3 age categories: <or=14 years, 15 to 18 years, or as an adult (>or=19 years); lifetime use for each of 4 birth cohorts dating back to 1900; drug use problems; drug addiction; and parenteral drug use. Each ACE increased the likelihood for early initiation 2- to 4-fold. The ACE score had a strong graded relationship to initiation of drug use in all 3 age categories as well as to drug use problems, drug addiction, and parenteral drug use. Compared with people with 0 ACEs, people with >or=5 ACEs were 7- to 10-fold more likely to report illicit drug use problems, addiction to illicit drugs, and parenteral drug use. The attributable risk fractions as a result of ACEs for each of these illicit drug use problems were 56%, 64%, and 67%, respectively. For each of the 4 birth cohorts examined, the ACE score also had a strong graded relationship to lifetime drug use. The ACE score had a strong graded relationship to the risk of drug initiation from early adolescence into adulthood and to problems with drug use, drug addiction, and parenteral use. The persistent graded relationship between the ACE score and initiation of drug use for 4 successive birth cohorts dating back to 1900 suggests that the effects of adverse childhood experiences transcend secular changes such as increased availability of drugs, social attitudes toward drugs, and recent massive expenditures and public information campaigns to prevent drug use. Because ACEs seem to account for one half to two third of serious problems with drug use, progress in meeting the national goals for reducing drug use will necessitate serious attention to these types of common, stressful, and disturbing childhood experiences by pediatric practice.


Ddc1 checkpoint protein and DNA polymerase ɛ interact with nick-containing DNA repair intermediate in cell free extracts of Saccharomyces cerevisiae.
To characterize proteins that interact with base excision/single-strand interruption repair DNA intermediates in cell free extracts of Saccharomyces cerevisiae, we used a combination of photoaffinity labeling with the protein identification by MALDI-TOF-MS peptide mapping. Photoreactive analogue of dCTP, namely exo-N-[4-(4-azido-2,3,5,6,-tetrafluorobenzylidenehydrazinocarbonyl)-butylcarbamoyl]-2'-deoxycytidine-5'-triphosphate, and [(32)P]-labeled DNA duplex containing one nucleotide gap were used to generate nick-containing DNA with a photoreactive dCMP residue at the 3'-margin of the nick. This photoreactive DNA derivative was incubated with the yeast cell extract and after UV irradiation a number of proteins were labeled. Two of the crosslinked proteins were identified as the catalytic subunit of DNA polymerase ɛ and Ddc1 checkpoint protein. Labeling of DNA polymerase ɛ catalytic subunit with the nick-containing DNA repair intermediate indicates that the DNA polymerase is involved in the DNA repair synthesis in yeast, at least at DNA single-strand interruptions. Crosslinking of Ddc1 to DNA nicks took place independently of the other components of checkpoint clamp, Mec3 and Rad17, suggesting that the protein alone is able to recognize DNA single-strand breaks. Indeed, purified GST-tagged Ddc1 protein was efficiently crosslinked to nick-containing DNA. The interaction of Ddc1 with DNA nicks may provide a link between the DNA damage checkpoint and DNA base excision/single-strand breaks repair pathways in yeast. In addition, we found that absence of Ddc1 protein greatly influences the overall pattern of other proteins crosslinked to DNA nick. We suggested that this last effect of Ddc1 is at least partially due to its capacity to prevent proteolytic degradation of the DNA-protein adducts.


Post-cycloaddition modification of a porous MOF for improved GC separation of ethanol and water.
An olefin-containing pyridinium derivative, 1-(4-carboxybenzyl)-4-[2-(4-pyridyl)-vinyl]-pyridinium chloride (HBCbpeCl) has been introduced into a novel 2D metal-organic framework with rare right- and left-handed spiral nanotubular channels arranged alternately in the structure. The 1D channel is modified by positively-charged pyridinium segments, which shows high affinities to Lewis basic molecules such as methanol, ethanol, and water vapor. Additionally, the BCbpe molecules in the structure have been directed through cation-π interactions to be aligned antiparallel to each other with the C[double bond, length as m-dash]C double bond arranged properly for [2 + 2] photocycloaddition, which can be triggered to undergo structural transformation from 2D to 3D. This post-cycloaddition modification strategy has been used to separate alcohols and water, which includes a successful adjustment of large tailor-made channels by the [2 + 2] cycloaddition reaction. The gas-chromatographic separation experiments show that ethanol can be better separated from water through a column filled with a post-cycloaddition modified sample than the as-synthesized one.


Complete sequence and gene map of a human major histocompatibility complex. The MHC sequencing consortium.
Here we report the first complete sequence and gene map of a human major histocompatibility complex (MHC), a region on chromosome 6 which is essential to the immune system. When it was discovered over 50 years ago the region was thought to specify histocompatibility genes, but their nature has been resolved only in the last two decades. Although many of the 224 identified gene loci (128 predicted to be expressed) are still of unknown function, we estimate that about 40% of the expressed genes have immune system function. Over 50% of the MHC has been sequenced twice, in different haplotypes, giving insight into the extraordinary polymorphism and evolution of this region. Several genes, particularly of the MHC class II and III regions, can be traced by sequence similarity and synteny to over 700 million years ago, clearly predating the emergence of the adaptive immune system some 400 million years ago. The sequence is expected to be invaluable for the identification of many common disease loci. In the past, the search for these loci has been hampered by the complexity of high gene density and linkage disequilibrium.


ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes.
Autophagy, an important catabolic pathway implicated in a broad spectrum of human diseases, begins by forming double membrane autophagosomes that engulf cytosolic cargo and ends by fusing autophagosomes with lysosomes for degradation. Membrane fusion activity is required for early biogenesis of autophagosomes and late degradation in lysosomes. However, the key regulatory mechanisms of autophagic membrane tethering and fusion remain largely unknown. Here we report that ATG14 (also known as beclin-1-associated autophagy-related key regulator (Barkor) or ATG14L), an essential autophagy-specific regulator of the class III phosphatidylinositol 3-kinase complex, promotes membrane tethering of protein-free liposomes, and enhances hemifusion and full fusion of proteoliposomes reconstituted with the target (t)-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) syntaxin 17 (STX17) and SNAP29, and the vesicle (v)-SNARE VAMP8 (vesicle-associated membrane protein 8). ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain, and stabilizes the STX17-SNAP29 binary t-SNARE complex on autophagosomes. The STX17 binding, membrane tethering and fusion-enhancing activities of ATG14 require its homo-oligomerization by cysteine repeats. In ATG14 homo-oligomerization-defective cells, autophagosomes still efficiently form but their fusion with endolysosomes is blocked. Recombinant ATG14 homo-oligomerization mutants also completely lose their ability to promote membrane tethering and to enhance SNARE-mediated fusion in vitro. Taken together, our data suggest an autophagy-specific membrane fusion mechanism in which oligomeric ATG14 directly binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion.


Chest wall mechanics during pressure support ventilation.
During pressure support ventilation (PSV) a part of the breathing pattern is controlled by the patient, and synchronization of respiratory muscle action and the resulting chest wall kinematics is a valid indicator of the patient's adaptation to the ventilator. The aim of the present study was to analyze the effects of different PSV settings on ventilatory pattern, total and compartmental chest wall kinematics and dynamics, muscle pressures and work of breathing in patients with acute lung injury. In nine patients four different levels of PSV (5, 10, 15 and 25 cmH2O) were randomly applied with the same level of positive end-expiratory pressure (10 cmH2O). Flow, airway opening, and oesophageal and gastric pressures were measured, and volume variations for the entire chest wall, the ribcage and abdominal compartments were recorded by opto-electronic plethysmography. The pressure and the work generated by the diaphragm, rib cage and abdominal muscles were determined using dynamic pressure-volume loops in the various phases of each respiratory cycle: pre-triggering, post-triggering with the patient's effort combining with the action of the ventilator, pressurization and expiration. The complete breathing pattern was measured and correlated with chest wall kinematics and dynamics. At the various levels of pressure support applied, minute ventilation was constant, with large variations in breathing frequency/ tidal volume ratio. At pressure support levels below 15 cmH2O the following increased: the pressure developed by the inspiratory muscles, the contribution of the rib cage compartment to the total tidal volume, the phase shift between rib cage and abdominal compartments, the post-inspiratory action of the inspiratory rib cage muscles, and the expiratory muscle activity. During PSV, the ventilatory pattern is very different at different levels of pressure support; in patients with acute lung injury pressure support greater than 10 cmH2O permits homogeneous recruitment of respiratory muscles, with resulting synchronous thoraco-abdominal expansion.


Air pollution and diseases of the respiratory tracts in pre-school children: A transfer function model.
The purpose of the present statistical analysis was the assessment of the relation between time series of environmental factors and of frequencies of diseases of the respiratory system in pre-school children. During about one year, daily measurements of air pollutants and climatic variables were taken. During the same period of time two series of medical data were collected: (i) The daily relative number of pre-school children, exhibiting diseases of the respiratory tracts who either came to the outpatients' clinic of the children's hospital or were reported by paediatricians in Basle (ENTRIES). (ii) The daily relative frequency of symptoms of the respiratory tracts observed in a group of randomly selected pre-school children (SYMPTOMS).By means of transfer function models the relation between the two target variables and the 'explaining' variables was analysed. Several practical problems did arise: Choice of the appropriate transformation of the different series, interpretation of the crosscorrelation function using different methods of 'prewhitening', time splitting and nonstationarity of the crosscorrelation structure. In particular, it was found that after prewhitening the crosscorrelation function between the explanatory series SO2 and the response series SYMPTOMS changes with time. While during the 'winter period' an instantaneous relation between these two series (and to a lesser extent between NO2 and SYMPTOMS) was identified, no such relation was found for the other seasons.


Intensive care unit versus hospital floor: a comparative study of postoperative management of patients with adolescent idiopathic scoliosis.
Patients undergoing posterior spinal instrumentation and fusion surgery for adolescent idiopathic scoliosis were admitted to the intensive care unit until two years ago, at which time we changed our protocol to admit these patients to the general hospital floor following a brief stay in a postanesthesia care unit. This study compared postoperative management on a hospital floor with that in the intensive care unit for patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion. A retrospective review of 124 consecutive patients with adolescent idiopathic scoliosis treated with spinal fusion from August 2007 to August 2010 was performed. Inclusion criteria were a diagnosis of adolescent idiopathic scoliosis and posterior spinal instrumentation and fusion surgery. Of 124 patients, sixty-six were managed postoperatively in the intensive care unit and fifty-eight, on the hospital floor. The mean age at the time of surgery was fourteen years. A mean of eleven vertebral levels (range, six to fifteen levels) were fused. No significant difference between the groups was found with respect to the mean age at the time of surgery, mean weight, mean preoperative and postoperative Cobb angles, and mean number of levels fused (p ≥ 0.12). However, the use of analgesic and antianxiety medication, number of postoperative blood tests, days of hospital stay, and number of physical therapy sessions were significantly decreased in the floor group compared with the intensive care unit group (p ≤ 0.05). No patient from the floor group had to be admitted to the intensive care unit. The mean charge was $33,121 for the floor group and $39,252 for the intensive care unit group (p < 0.001). Initial postoperative management of patients with adolescent idiopathic scoliosis following a posterior spinal instrumentation and fusion surgery on a general hospital floor, rather than in an intensive care unit, was associated with a shorter hospital stay, fewer blood tests, less analgesic and antianxiety medication usage, and fewer physical therapy sessions at this high-volume, academic, tertiary-care children's hospital. In addition to improved patient outcomes, there was a significant decrease of 16% in hospital charges for the group that did not go to the intensive care unit.


What does the language we use about arthritis mean to people who have osteoarthritis? A qualitative study.
To explore the meanings and issues surrounding the use of existing medical terms for osteoarthritis from the perspective of members of the public who have consulted healthcare practitioners for arthritic symptoms and from lay people who have not sought a consultation. Five qualitative focus groups of 6-8 respondents and six individual in-depth interviews were conducted amongst a purposive sample of men and women aged 45 years and over, with a spread of and a range of socio-economic groupings. Key terms were used as stimulus materials. Focus groups and individual interviews were audio taped, fully transcribed and underwent line by line analysis, identifying concepts and coded. Patients were familiar with many of the terms such as arthritis, osteoarthritis, rheumatism, inflammation, etc. but their level of comprehension varied. Most terms had little emotional impact. Terms used to describe pathophysiology elicited negative emotional impact, especially in women. Terms such as rehabilitation and "self management" were poorly understood and produced negative emotional impact. Healthcare professionals should not assume that patients' familiarity with medical terms correlate to understanding the term. They should be aware of the potential for negative emotional impact related to some terms. Implications for Rehabilitation Few of the existing medical terms were understood and accepted by lay participants in the way discussed and expected by health professionals. Misunderstandings, unintended meanings and negative emotional responses to terms were common within the study focus groups. Cutting the jargon and checking understanding of seemingly simple medical terms is important to improve communication with patients. As patient access to treatment notes and correspondence increases in the UK, the impact of written terms, as well as verbal, needs careful consideration and attention.


A radiographic study of the position and prevalence of the maxillary arterial endosseous anastomosis using cone beam computed tomography.
This study was designed to investigate the prevalence and course of the vascular canals in the maxillary sinus walls and to measure the distance between the sinus floor, the edentulous alveolar crest, and the vascular canal using cone beam computed tomography (CBCT). The maxillary sinus CBCT scans of 250 patients scheduled for implant surgery were examined. The vertical and mediolateral positions of the vascular canals or notches were investigated on the CBCT images. The location of each tooth was confirmed using a diagnostic template for implant placement. Statistical analyses were performed to verify whether the mean artery position was significantly different according to each tooth location, gender, and age. A maxillary arterial endosseous anastomosis was observed in 52.8% of patients. The mean perpendicular distance from the sinus floor to the vascular canal was shortest in the first molar region (7.58 ± 3.19 mm) and longest in the first premolar region (9.2 ± 3.22 mm). The mean distance from the alveolar crest to the vascular canal was shortest in the first molar region (14.79 ± 4.04 mm) and longest in the first premolar region (18.92 ± 4.86 mm). These distances were significantly different according to tooth position. The mean distances from the alveolar crest and the sinus floor to the vascular canal did not decrease with age. The mediolateral position of the canals was also significantly different depending on tooth position. With this information about the branch of the posterior superior alveolar artery from CBCT, unnecessary bleeding during implant placement should be more easily preventable. The use of CBCT is recommended as a routine procedure prior to sinus floor elevation.


Synthesis of heterobimetallic gold(i) ferrocenyl-substituted 1,2,3-triazol-5-ylidene complexes as potential anticancer agents.
1,2,3-Triazol-5-ylidene (trz) complexes of gold(i) containing a ferrocenyl substituent on the C4-position of the trz ring were synthesized to yield the neutral heterobimetallic gold(i) trz chlorido (2), gold(i) trz phenyl (3), and the cationic gold(i) trz triphenylphospine (5) complexes. In order to compare the effect of silver(i) as central metal vs. gold(i), [Ag(trz)2]+ (4) was also prepared, while variation of the C4-1,2,3-triazol-5-ylidene substituent from a ferrocenyl to a phenyl group was done to prepare the monometallic analogue of 5, namely the cationic Au(i) trz triphenylphosphine complex 6. The complexes were characterised with spectroscopic and electrochemical methods, and the single crystal X-ray structures of 2-6 were determined. NMR stability studies of 5 as a representative example of the series of complexes were performed to confirm the stability of the complexes in the solvent dimethylsulfoxide and in aqueous solution. The anti-cancer potential of 5 was evaluated against the lung cancer cell lines A549 and H1975, and the human embryonic kidney cell line (HEK-293) was used as a non-cancer model. IC50 values of 0.89, 0.23 and 5.43 μM, respectively, were obtained for A549, H1975 and HEK-293, respectively, indicating the activity and selectivity of 5 for cancer cells. Fluorescence microscopy experiments as a preliminary mode-of-action study evidenced an apoptotic cell death mechanism rather than necrotic cell death.


An evaluation of the core physical exam in patients with minor peripheral chief complaints.
We sought to determine (1) how often and why emergency medicine resident physicians perform core physical exams in patients with minor peripheral chief complaints (MCCs); and (2) the clinical impact this practice. This prospective observational study was conducted at an urban emergency department with a 4 year emergency medicine residency. Charts of all emergency department patients presenting with MCCs in June-September 2003 were reviewed by blinded assistants for documentation of (1) core physical exams; (2) abnormal core physical exam findings; and (3) additional work up, treatment or follow up related to abnormal core physical exam findings. In May-June 2004 all emergency medicine residents were asked how often they perform core physical exams on emergency department patients with MCCs and their motivating factors for this practice. 297 patients met MCC inclusion/exclusion criteria. Among the 591 total cardiac, lung and abdominal exams performed, 8 (1.4%, 95% confidence interval (CI) 0.7% to 2.7%) were abnormal and only 1 (0.1%, 95% CI 0% to 0.1%) finding led to further testing (ECG); none prompted change in treatment or follow up. All 46 eligible emergency medicine residents were evaluated; 72% (33) performed core physical exams in half or more patients with MCCs. Their primary reasons were to screen the underserved emergency department population, the belief that such exams are standard of care, and establishment of physician-patient rapport. Because they want to screen an underserved population, establish rapport, and meet what they believe is a standard of care, most emergency medicine residents performed core exams on patients with MCCs. Abnormal core physical exam findings are unusual and rarely lead to further testing or change in management.


The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak.
Motivated by the rapid spread of coronavirus disease 2019 (COVID-19) in mainland China, we use a global metapopulation disease transmission model to project the impact of travel limitations on the national and international spread of the epidemic. The model is calibrated on the basis of internationally reported cases and shows that, at the start of the travel ban from Wuhan on 23 January 2020, most Chinese cities had already received many infected travelers. The travel quarantine of Wuhan delayed the overall epidemic progression by only 3 to 5 days in mainland China but had a more marked effect on the international scale, where case importations were reduced by nearly 80% until mid-February. Modeling results also indicate that sustained 90% travel restrictions to and from mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.


Who's afraid of forensic psychiatry?
Forensic psychiatry has come under mounting criticism from the press and other medical professionals, largely for its participation in the insanity defense. The author argues that the expertise available from the specialty is of increasing importance to psychiatry as a whole, as more and more legal issues become relevant to the practice of general psychiatry, and should be actively encouraged and legitimized rather than ostracized. All psychiatrists should be exposed to forensic principles and practices during their training, and the ability of forensic psychiatrists to serve as transducers between the clinical and the legal/judicial should be increasingly used to present the clinical viewpoint effectively in courts and legislatures.


Protein kinase C activation induces tyrosine phosphorylation of the NR2A and NR2B subunits of the NMDA receptor.
The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, which plays crucial roles in synaptic plasticity and development. We have recently shown that potentiation of NMDA receptor function by protein kinase C (PKC) appears to be mediated via activation of non-receptor tyrosine kinases. The aim of this study was to test whether this effect could be mediated by direct tyrosine phosphorylation of the NR2A or NR2B subunits of the receptor. Following treatment of rat hippocampal CA1 mini-slices with 500 nM phorbol 12-myristate 13-acetate (PMA) for 15 min, samples were homogenized, immunoprecipitated with anti-NR2A or NR2B antibodies and the resulting pellets subjected to Western blotting with antiphosphotyrosine antibody. An increase in tyrosine phosphorylation of both NR2A (76 +/- 11% above control) and NR2B (41 +/- 11%) was observed. This increase was blocked by pretreatment with the selective PKC inhibitor chelerythrine, with the tyrosine kinase inhibitor Lavendustin A or with the Src family tyrosine kinase inhibitor PP2. PMA treatment also produced an increase in the phosphorylation of serine 890 on the NR1 subunit, a known PKC site, at 5 min with phosphorylation returning to near basal levels by 10 min while tyrosine phosphorylation of NR2A and NR2B was sustained for up to 15 min. These results suggest that the modulation of NMDA receptor function seen with PKC activation may be the result of tyrosine phosphorylation of NR2A and/or NR2B.


Psychopathology and resident status - comparing asylum seekers, refugees, illegal migrants, labor migrants, and residents.
This study aimed to describe, compare, and predict mental health outcomes of different migrant groups and native residents in Switzerland. Asylum seekers (n=65); refugees holding permanent protection visas (n=34); illegal migrants (n=21); labor migrants (n=26); and residents (n=56) completed an assessment by questionnaire. Main outcome variables were symptoms of posttraumatic stress, anxiety and depression. It was tested whether resident status predicted psychopathology over and above the influence of control variables including social desirability, traumatic event types and post-migration resources. Asylum seekers (54.0%) and refugees (41.4%) fulfilled criteria of PTSD most frequently. Clinically relevant symptoms of anxiety and depression were most frequently reported by asylum seekers (84.6% and 63.1%, resp.) and illegal migrants (both 47.6%). Resident status contributed to psychopathology over and above the influence of control variables. Overall, asylum seekers, refugees, and illegal migrants showed high psychiatric morbidity. Differences in resident status appear to be specifically associated with mental health outcomes. This association persists even when controlling for social desirability, post-migration resources and traumatic events. This emphasizes the importance of current socio-political living conditions for mental health, even with respect to the psychopathological sequelae of past traumatic experiences.


Influence of the anion on lone pair formation in Sn(II) monochalcogenides: a DFT study.
The electronic structure of SnO, SnS, SnSe, and SnTe in the rocksalt, litharge, and herzenbergite structures has been calculated using density functional theory. Comparison of the distorted and undistorted structures allows for an explanation of the unusual experimentally observed structural transitions seen along the Sn(II) monochalcogenides. Analysis of the electronic structure shows a strong anion dependence of the Sn(II) lone pair, with the Sn(5s) and Sn(5p) states too far apart to couple directly. However, the interaction of Sn(5s) with anion states of appropriate energy produce a filled antibonding Sn(5s)-anion p combination which allows coupling of Sn(5s) and Sn(5p) to occur, resulting in a sterically active asymmetric density on Sn. While the interaction between Sn(5s) and O(2p) is strong, interactions of Sn with S, Se, and Te become gradually weaker, resulting in less high energy 5s states and hence weaker lone pairs. The stability of the distorted structures relative to the symmetric structures of higher coordination is thereby reduced, which induces the change from highly distorted litharge SnO to highly symmetric rocksalt SnTe seen along the series.


Can ovarian infertility be treated with bone marrow- or ovary-derived germ cells?
A year ago, reproductive biologists and general public were astonished with evidence reported by Johnson et al. in Nature 428:145 that mammalian ovaries possess persisting large germline stem cells, which allegedly enable follicular renewal in adult females. Recently, the same research group declared such view obscure, and reported that mammalian oocytes originate from putative germ cells in bone marrow and are distributed by peripheral blood to the ovaries (Cell 122:303). While neglecting available data on the germ cell origin from the ovarian surface epithelium (OSE) in adult mouse and human females and complexity of follicular renewal in humans, the authors widely extrapolated their observations on formation of allogeneic oocytes after bone marrow (or blood) transplantation in ovaries of adult mice treated with cytostatics to clinical implications in the public media. Yet, the resulting outcome that such allogeneic oocytes may enable the propagation of ovarian cycles is a poor alleviation for the women with ovarian infertility. Women lacking primary follicles, or carrying follicles with low quality eggs persisting in aging ovaries, are not concerned about the lack of menstrual cycles or ovarian steroids, but about virtually no chance of having genetically related children. Johnson et al. also reported that the germ cell formation in bone marrow disappears in ovariectomized mice. Such observation, however, raises solid doubts on the bone marrow origin of oocytes. Since germ cells developing from the OSE cells of adult human ovaries during periodical follicular renewal are known to enter blood vessels in order to enable formation of primary follicles at distant ovarian sites, they also contaminate peripheral blood and hence bone marrow. Better knowledge on the complexity of follicular renewal in humans and exploration of a potential of human OSE cells to produce new oocytes in vitro are essential for novel approaches to the autologous treatment of premature ovarian failure and age induced ovarian infertility.


The pursuit of excellence in nursing care: what does it mean?
This study explores the meaning of excellence in nursing care held by nurses. Qualitative data were collected from 156 undergraduate and postgraduate nurses by means of an open-ended questionnaire. Respondents were asked to reflect on practice which enabled a clear understanding of the meanings given to excellence in nursing care. In addition, details of their nursing background, level of nursing experience, and demographics were sought. Responses were content-analysed for themes by three coders. Four major themes emerged: (1) professionalism, (2) holistic care, (3) practice, (4) humanism. The fourth theme comprised three sub-themes: (a) enabling personal qualities, (b) nurse patient relationships, and (c) nurse-health team relationships. Responses revealed that professionalism constituted an all-encompassing theme subsuming all others. Findings suggested that the client is the central focus of excellent nursing care at all times. According to these respondents, nurses who deliver excellent nursing care implement nursing in a professional and competent manner, demonstrate a holistic approach to caring, possess certain personal qualities which enhance practice, and relate to patients, families, peers, hospital administrators and community members in a competent, cooperative manner. An important aspect of this study is the differential quality of responses provided by respondents, who were students enrolled in a nursing degree programme compared to respondents who were state-registered nurses and concurrently undertaking higher degree studies. The final result is suggestive of the stages of transition through which nurses pass in their quest for excellence.


The first microbiological contamination assessment by deep-sea drilling and coring by the D/V Chikyu at the Iheya North hydrothermal field in the Mid-Okinawa Trough (IODP Expedition 331).
During the Integrated Ocean Drilling Program (IODP) Expedition 331 at the Iheya North hydrothermal system in the Mid-Okinawa Trough by the D/V Chikyu, we conducted microbiological contamination tests of the drilling and coring operations. The contamination from the drilling mud fluids was assessed using both perfluorocarbon tracers (PFT) and fluorescent microsphere beads. PFT infiltration was detected from the periphery of almost all whole round cores (WRCs). By contrast, fluorescent microspheres were not detected in hydrothermally active core samples, possibly due to thermal decomposition of the microspheres under high-temperature conditions. Microbial contamination from drilling mud fluids to the core interior subsamples was further characterized by molecular-based evaluation. The microbial 16S rRNA gene phylotype compositions in the drilling mud fluids were mainly composed of sequences of Beta- and Gammaproteobacteria, and Bacteroidetes and not archaeal sequences. The phylotypes that displayed more than 97% similarity to the sequences obtained from the drilling mud fluids were defined as possible contaminants in this study and were detected as minor components of the bacterial phylotype compositions in 13 of 37 core samples. The degree of microbiological contamination was consistent with that determined by the PFT and/or microsphere assessments. This study suggests a constructive approach for evaluation and eliminating microbial contamination during riser-less drilling and coring operations by the D/V Chikyu.


Number of cerebral lesions predicts freedom from new brain metastases after radiosurgery alone in lung cancer patients.
Numerous patients with few brain metastases receive radiosurgery, either alone or in combination with whole-brain irradiation. The addition of whole-brain irradiation to radiosurgery reduces the rate of intracerebral failures, particularly the development of new cerebral lesions distant from those treated with radiosurgery. Less intracerebral failures mean less neurocognitive deficits. However, whole-brain irradiation itself may lead to a decline in neurocognitive functions. Therefore, a number of physicians have reservations with regard to adding whole-brain irradiation to radiosurgery. Prognostic factors that allow an estimation of the risk of developing new cerebral metastases can facilitate the decision regarding additional whole-brain irradiation. Since primary tumors show a different biology and clinical course, prognostic factors should be identified separately for each primary tumor leading to brain metastasis. The present study investigated 10 characteristics in a series of 98 patients receiving radiosurgery alone for 1-2 cerebral metastases from lung cancer, the most common primary tumor associated with brain metastasis. These characteristics included radiosurgery dose, age, gender, performance status, histology, number of cerebral lesions, maximum total diameter of cerebral lesions, main location of cerebral lesions, extracranial spread and interval from first diagnosis of lung cancer to administration of radiosurgery. On univariate analysis, the number of cerebral lesions prior to radiosurgery (1 vs. 2 lesions) was the only characteristic significantly associated with freedom from new brain metastases (P=0.002). In cases of 2 lesions, 73% of patients developed new cerebral lesions within 1 year. On multivariate analysis, the number of brain metastases remained significant (risk ratio, 2.46; 95% confidence interval, 1.34-4.58; P=0.004). Given the high rates of new cerebral lesions in patients with 2 brain metastases, these patients should be strongly considered for additional whole-brain irradiation.


From compliance to concordance in diabetes.
Compliance is a key concept in health care and affects all areas of health care including diabetes. Non-compliance has previously been a label attached to many patients without much thought having been given to the causes of poor compliance. Over the last few decades there has been a large volume of research focusing on compliance that has exposed the multitude of factors affecting compliance. Even the definition is not clear cut and so comparability between studies is not without difficulties. A better understanding of the factors affecting compliance, including the doctor/patient relationship, has allowed the evolution of "concordance". Concordance views the patient as being the equal of the healthcare provider and as having a right to make informed decisions. In a condition such as diabetes, which has many potential long term complications, it is vital that concordance is embraced in the healthcare system in order to improve care.


Sleep Mediates the Relationship Between Depression and Cognitive Impairment in Older Men.
Sleep and depression are strongly associated with cognitive impairment. The role of sleep disturbances in the adverse effect of depression on cognitive dysfunction in older adults remains unclear. This study explored the mediating effect of self-reported sleep disturbances on the relationship between depression and cognitive impairment in older adults according to sex differences. This study derived data from the 2009 Taiwan National Health Interview Survey and included 2,175 community-dwelling adults aged 65 years and older (men = 991; women = 1,184). Sleep disturbances were measured using self-reported survey questions. The Center for Epidemiological Studies Depression scale was used to assess depression. The Mini-Mental State Examination was used to evaluate cognitive impairment. A higher proportion of female older persons had cognitive impairment and depression than male older persons (cognition: 24.4% vs. 11.5%; depression: 17.0% vs. 10.8%). The meditating effect of sleep was detected in only men. Difficulty in initiating sleep was a complete mediator of the adverse effect of depression on cognitive impairment (Sobel test: p = .03). In summary, difficultly in initiating sleep may be a crucial, treatable mediator of the adverse effect of depression on cognitive impairment in older men.


On the Monte Carlo simulation of electron transport in the sub-1 keV energy range.
The validity of "classic" Monte Carlo (MC) simulations of electron and positron transport at sub-1 keV energies is investigated in the context of quantum theory. Quantum theory dictates that uncertainties on the position and energy-momentum four-vectors of radiation quanta obey Heisenberg's uncertainty relation; however, these uncertainties are neglected in "classical" MC simulations of radiation transport in which position and momentum are known precisely. Using the quantum uncertainty relation and electron mean free path, the magnitudes of uncertainties on electron position and momentum are calculated for different kinetic energies; a validity bound on the classical simulation of electron transport is derived. In order to satisfy the Heisenberg uncertainty principle, uncertainties of 5% must be assigned to position and momentum for 1 keV electrons in water; at 100 eV, these uncertainties are 17 to 20% and are even larger at lower energies. In gaseous media such as air, these uncertainties are much smaller (less than 1% for electrons with energy 20 eV or greater). The classical Monte Carlo transport treatment is questionable for sub-1 keV electrons in condensed water as uncertainties on position and momentum must be large (relative to electron momentum and mean free path) to satisfy the quantum uncertainty principle. Simulations which do not account for these uncertainties are not faithful representations of the physical processes, calling into question the results of MC track structure codes simulating sub-1 keV electron transport. Further, the large difference in the scale at which quantum effects are important in gaseous and condensed media suggests that track structure measurements in gases are not necessarily representative of track structure in condensed materials on a micrometer or a nanometer scale.


You're having fun when time flies: the hedonic consequences of subjective time progression.
Seven studies tested the hypothesis that people use subjective time progression in hedonic evaluation. When people believe that time has passed unexpectedly quickly, they rate tasks as more engaging, noises as less irritating, and songs as more enjoyable. We propose that felt time distortion operates as a metacognitive cue that people implicitly attribute to their enjoyment of an experience (i.e., time flew, so the experience must have been fun). Consistent with this attribution account, the effects of felt time distortion on enjoyment ratings were moderated by the need for attribution, the strength of the "time flies" naive theory, and the presence of an alternative attribution. These findings suggest a previously unexplored process through which subjective time progression can influence the hedonic evaluation of experiences.


The Drosophila melanogaster gypsy transposable element encodes putative gene products homologous to retroviral proteins.
We determined the complete nucleotide sequence of the gypsy element present at the forked locus of Drosophila melanogaster in the f1 allele. The gypsy element shares more homology with vertebrate retroviruses than with the copia element of D. melanogaster or the Ty element of Saccharomyces cerevisiae, both in overall organization and at the DNA sequence level. This transposable element is 7,469 base pairs long and encodes three putative protein products. The long terminal repeats are 482 nucleotides long and contain transcription initiation and termination signals; sequences homologous to the polypurine tract and tRNA primer binding site of retroviruses are located adjacent to the long terminal repeats. The central region of the element contains three different open reading frames. The second one encodes a putative protein which shows extensive amino acid homology to retroviral proteins, including gag-specific protease, reverse transcriptase, and DNA endonuclease.


PfeIK1, a eukaryotic initiation factor 2alpha kinase of the human malaria parasite Plasmodium falciparum, regulates stress-response to amino-acid starvation.
Post-transcriptional control of gene expression is suspected to play an important role in malaria parasites. In yeast and metazoans, part of the stress response is mediated through phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha), which results in the selective translation of mRNAs encoding stress-response proteins. The impact of starvation on the phosphorylation state of PfeIF2alpha was examined. Bioinformatic methods were used to identify plasmodial eIF2alpha kinases. The activity of one of these, PfeIK1, was investigated using recombinant protein with non-physiological substrates and recombinant PfeIF2alpha. Reverse genetic techniques were used to disrupt the pfeik1 gene. The data demonstrate that the Plasmodium falciparum eIF2alpha orthologue is phosphorylated in response to starvation, and provide bioinformatic evidence for the presence of three eIF2alpha kinases in P. falciparum, only one of which (PfPK4) had been described previously. Evidence is provided that one of the novel eIF2alpha kinases, PfeIK1, is able to phosphorylate the P. falciparum eIF2alpha orthologue in vitro. PfeIK1 is not required for asexual or sexual development of the parasite, as shown by the ability of pfeik1- parasites to develop into sporozoites. However, eIF2alpha phosphorylation in response to starvation is abolished in pfeik1- asexual parasites This study strongly suggests that a mechanism for versatile regulation of translation by several kinases with a similar catalytic domain but distinct regulatory domains, is conserved in P. falciparum.


A conditional mouse model of synovial sarcoma: insights into a myogenic origin.
Synovial sarcoma is an aggressive soft-tissue malignancy marked by a unique t(X;18) translocation leading to expression of a chimeric SYT-SSX fusion protein. We report here a mouse model of synovial sarcoma based on conditional expression of the human SYT-SSX2. Using this model, we have identified myoblasts as a potential source of synovial sarcoma. Remarkably, within the skeletal muscle lineage, while expression of the oncoprotein in immature myoblasts leads to induction of synovial sarcoma with 100% penetrance, its expression in more differentiated cells induces myopathy without tumor induction. We also show that early widespread expression of the fusion protein disrupts normal embryogenesis, causing lethality.


Agrobacterium tumefaciens exoR controls acid response genes and impacts exopolysaccharide synthesis, horizontal gene transfer, and virulence gene expression.
Agrobacterium tumefaciens is a facultative plant pathogen and the causative agent of crown gall disease. The initial stage of infection involves attachment to plant tissues, and subsequently, biofilms may form at these sites. This study focuses on the periplasmic ExoR regulator, which was identified based on the severe biofilm deficiency of A. tumefaciens exoR mutants. Genome-wide expression analysis was performed to elucidate the complete ExoR regulon. Overproduction of the exopolysaccharide succinoglycan is a dramatic phenotype of exoR mutants. Comparative expression analyses revealed that the core ExoR regulon is unaffected by succinoglycan synthesis. Several findings are consistent with previous observations: genes involved in succinoglycan biosynthesis, motility, and type VI secretion are differentially expressed in the ΔexoR mutant. In addition, these studies revealed new functional categories regulated by ExoR, including genes related to virulence, conjugation of the pAtC58 megaplasmid, ABC transporters, and cell envelope architecture. To address how ExoR exerts a broad impact on gene expression from its periplasmic location, a genetic screen was performed to isolate suppressor mutants that mitigate the exoR motility phenotype and identify downstream components of the ExoR regulatory pathway. This suppression analysis identified the acid-sensing two-component system ChvG-ChvI, and the suppressor mutant phenotypes suggest that all or most of the characteristic exoR properties are mediated through ChvG-ChvI. Subsequent analysis indicates that exoR mutants are simulating a response to acidic conditions, even in neutral media. This work expands the model for ExoR regulation in A. tumefaciens and underscores the global role that this regulator plays on gene expression.


The co-benefits for health of investing in active transportation.
Amid growing concerns about the impact of rising obesity and physical inactivity levels, climate change, population growth, increasing traffic congestion and declining oil supplies, multiple sectors are now promoting active transportation as an alternative to driving. This paper considers the health benefits and co-benefits of investing in active transportation, enabling comparison of policy options to optimise societal objectives aimed at creating healthy, socially and environmentally sustainable communities. Policies promoting the use of both energy-efficient motor vehicles and increased active transportation would almost double the impact on greenhouse gas emissions and would reduce disease burden by increasing physical activity. More co-benefit and economic analyses research is required to inform 'joined-up' policy solutions.


Fatigue resistance and failure mode of novel-design anterior single-tooth implant restorations: influence of material selection for type III veneers bonded to zirconia abutments.
This study assessed the fatigue resistance and failure mode of type III porcelain and composite resin veneers bonded to custom zirconia implant abutments. Twenty-four standardized zirconia implant abutments were fabricated. Using the CEREC 3 machine, type III veneers of standardized shape were milled in ceramic Vita Mark II or in composite resin Paradigm MZ100. The intaglio surfaces of the restorations were hydrofluoric acid etched and silanated (Mark II) or airborne-particle abraded and silanated (MZ100). The fitting surface of the abutments was airborne-particle abraded, cleaned, and inserted into a bone level implant (BLI RC SLActive 10 mm). All veneers (n=24) were adhesively luted with a zirconia primer (Z-Prime Plus), adhesive resin (Optibond FL) and a pre-heated light-curing composite resin (Filtek Z100). Cyclic isometric chewing (5 Hz) was simulated, starting with a load of 40 N, followed by stages of 80, 120, 160, 200, 240, and 280 N (20,000 cycles each). Samples were loaded until fracture or to a maximum of 140,000 cycles. Groups were compared using the life table survival analysis (Logrank test at P=.05). Mark II and MZ100 specimens fractured at an average load of 216 N and 229 N (survival rate of 17% and 8%), respectively, with no difference in survival probability (P=.18). Among the fractured samples, 40% of the failures were at the abutment level for Mark II and 27% were at the abutment level for MZ100. No exclusive adhesive failures were observed. Type III Mark II and Paradigm MZ100 veneers showed similar fatigue resistance when bonded to custom non-retentive zirconia implant abutments. The bond was strong enough to induce abutment fractures. MZ100 presented a higher percentage of "friendly" failures, i.e. maintaining the restoration-abutment adhesive interface and the abutment itself intact.


Evaluation of a Strategy Aiming to Enclose the Pulmonary Veins With Contiguous and Optimized Radiofrequency Lesions in Paroxysmal Atrial Fibrillation: A Pilot Study.
This study sought to evaluate the safety and the acute and 1 year outcomes of an ablation protocol aiming to enclose the PV with a contiguous and optimized RF circle by targeting region-specific criteria for lesion depth assessed by ablation index and interlesion distance. Reconnections after pulmonary vein (PV) isolation are explained by insufficient lesion depth and/or discontiguity of radiofrequency (RF) lesions. A total of 130 consecutive patients with paroxysmal atrial fibrillation (AF) underwent PV encircling using a contact force-sensing catheter. RF was delivered targeting interlesion distance ≤6 mm and ablation index ≥400 at posterior wall and ≥550 at anterior wall. Recurrence was defined as any AF, atrial tachycardia (AT), or atrial flutter (AFL) (AF/AT/AFL >30 s) on Holter electrocardiographs at 3, 6, and 12 months. Procedure and RF time per circle were 155 ± 28 min and 17 ± 5 min, respectively. Incidence of first-pass and adenosine-proof isolation were 98% and 98%, respectively. One short-lived transient ischemic attack was observed. At 12 months, single-procedure freedom from AF/AT/AFL was 91.3% in those 104 patients off antiarrhythmic drug therapy and 96.2% in those 26 patients on antiarrhythmic drug therapy. Single-procedure freedom from both AF/AT/AFL and antiarrhythmic drug therapy was 73.1%. This study suggests that an ablation protocol respecting strict criteria for lesion depth and contiguity results in acute durable PV isolation followed by a high single-procedure arrhythmia-free survival at 1 year. A prospective, multicenter trial is ongoing.


Experimental evolution of an RNA virus in wild birds: evidence for host-dependent impacts on population structure and competitive fitness.
Within hosts, RNA viruses form populations that are genetically and phenotypically complex. Heterogeneity in RNA virus genomes arises due to error-prone replication and is reduced by stochastic and selective mechanisms that are incompletely understood. Defining how natural selection shapes RNA virus populations is critical because it can inform treatment paradigms and enhance control efforts. We allowed West Nile virus (WNV) to replicate in wild-caught American crows, house sparrows and American robins to assess how natural selection shapes RNA virus populations in ecologically relevant hosts that differ in susceptibility to virus-induced mortality. After five sequential passages in each bird species, we examined the phenotype and population diversity of WNV through fitness competition assays and next generation sequencing. We demonstrate that fitness gains occur in a species-specific manner, with the greatest replicative fitness gains in robin-passaged WNV and the least in WNV passaged in crows. Sequencing data revealed that intrahost WNV populations were strongly influenced by purifying selection and the overall complexity of the viral populations was similar among passaged hosts. However, the selective pressures that control WNV populations seem to be bird species-dependent. Specifically, crow-passaged WNV populations contained the most unique mutations (~1.7× more than sparrows, ~3.4× more than robins) and defective genomes (~1.4× greater than sparrows, ~2.7× greater than robins), but the lowest average mutation frequency (about equal to sparrows, ~2.6× lower than robins). Therefore, our data suggest that WNV replication in the most disease-susceptible bird species is positively associated with virus mutational tolerance, likely via complementation, and negatively associated with the strength of selection. These differences in genetic composition most likely have distinct phenotypic consequences for the virus populations. Taken together, these results reveal important insights into how different hosts may contribute to the emergence of RNA viruses.


Pulmonary hypertension experience in an expert university hospital.
Pulmonary artery hypertension (PAH) is characterized by remodeling of the small pulmonary arteries, leading to a progressive increase in pulmonary vascular resistance and right ventricular failure. In this study, we aimed to share our 10 years of experience dealing with pulmonary hypertension (PH) and provide information in real-life settings in terms of demographics, clinical course, PH subgroup distribution, and treatment patterns in patients with PAH in a tertiary center. In this retrospective, single-center, observational study, we screened the patients who applied to PH outpatient clinic of İstanbul University Institute of Cardiology due to the suspicion of PAH between 2008 and 2017. While group 1, 4, and 5 PH patients were included, group 2 and 3 PH patients were excluded from the study. Our study group comprised 162 patients (115 females, 71%). The female:male ratio was 2.4. The mean age was 52±16 years. Most (86.4%) of the patients were in group 1 PH (PAH). The rest (13.6%, n=22) of the patients were in group 4 PH (chronic thromboembolic PH). In group 1 PH, 45.7% of patients (n=64) were classified as having idiopathic PAH (IPAH) after excluding the alternative diagnosis using PH diagnostic algorithm. The remaining 54.3% of group 1 PH patients (n=76) had various diseases that caused PAH, which is called associated PAH (APAH); APAH group included PAH associated with congenital heart diseases (n=70), connective tissue disorders (scleroderma, n=4) and portal hypertension (n=2). Our data provides important information in real-life settings in terms of demographics, clinical course, PH subgroup distribution, and treatment patterns in patients with PAH in a reference tertiary center in Turkey.