CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia.
To estimate protective potential of citicoline in a model of birth asphyxia, the drug was given to 7-day old rats subjected to permanent unilateral carotid artery occlusion and exposed for 65 min to a hypoxic gas mixture. Daily citicoline doses of 100 or 300 m/kg, or vehicle, were injected intraperitoneally for 7 consecutive days beginning immediately after the end of the ischemic-hypoxic insult, and brain damage was assessed by gross zorphology score and weight deficit two weeks after the insult. Caspase-3, alpha-fodrin, Bcl-2, and Hsp70 levels were assessed at 0, 1, and 24 h after the end of the hypoxic insult in another group of rat pups subjected to the same insult and given a single dose of 300 m/kg of citicoline or the vehicle. Citicoline markedly reduced caspase-3 activation and Hsp70 expression 24 h after the insult, and dose-dependently attenuated brain damage. In the context of the well-known excellent safety profile of citicoline, these data suggest that clinical evaluation of the efficacy of the drug in human birth asphyxia may be warranted.


Cannabinoids for Treatment of MS Symptoms: State of the Evidence.
Cannabis and cannabinoids have been used medically and recreationally for thousands of years and recently there has been a growing body of research in this area. With increased access now that medical marijuana is available in many jurisdictions, patients and providers want to know more about the evidence for benefits and risks of cannabinoid use. This paper provides an overview of the available cannabinoid-based formulations, a summary of the highest quality evidence for the use of cannabinoids for treating spasticity and pain associated with multiple sclerosis (MS), and a discussion of possible dosing regimens based on information from these studies. Two recent high-quality systematic reviews concluded that the only strong evidence for medical marijuana in neurological disorders was for reducing the symptoms of patient-reported spasticity and central pain in MS and that the only complementary and alternative medicine (CAM) intervention in MS with strong supportive evidence was cannabinoids. Based on this review, they concluded that nabiximols (Sativex oral spray), oral cannabis extract (OCE), and synthetic tetrahydrocannabinol (THC) are probably effective at reducing patient-reported symptoms of spasticity in people with MS, but OCE and synthetic THC were not found to be effective for reducing physician-administered measures of spasticity. In addition, nabiximols, OCE, and synthetic THC are probably effective at reducing MS-related pain. Cannabinoids were generally well-tolerated. However, cannabis use has been associated with an increased risk of psychosis and schizophrenia in at-risk individuals, there is growing evidence that cannabis can increase the risk for cardiovascular diseases, including myocardial infarction (MI), hypertension, heart failure, and stroke, and a recently recognized adverse effect of cannabis is cannabinoid hyperemesis syndrome. The medical use of cannabinoids remains controversial. While cannabinoids have been studied for a variety of neurologic disorders, there is strongest evidence to indicate benefits in treatment of spasticity and neuropathic pain in multiple sclerosis. Although the best dose for an individual remains uncertain, most participants in the studies discussed in this paper used between 20 and 40 mg of THC a day in divided doses. Adverse events in studies were generally more common in the groups using cannabinoid products but serious adverse events were rare and cannabis products were generally well-tolerated. Cannabis use does appear to be associated with increased risk of certain adverse events, including psychosis, cardiovascular diseases, and cannabinoid hyperemesis syndrome.


Delivery challenges for fluoride, chlorhexidine and xylitol.
The progression or reversal of dental caries is determined by the balance between pathological and protective factors. It is well established that a) fluoride inhibits demineralization and enhances remineralization, b) chlorhexidine reduces the cariogenic bacterial challenge, and c) xylitol is non-cariogenic and has antibacterial properties. The challenge that we face is how best to deliver these anti-caries entities at true therapeutic levels, over time, to favorably tip the caries balance. High caries risk people, including children with Early Childhood Caries (ECC), are a special challenge, since high cariogenic bacterial activity can override fluoride therapy. Current fluoride and chlorhexidine varnishes deliver all their activity within about 24 hours. Early studies with experimental slow release fluoride devices retained elevated levels of fluoride for months in a therapeutic range but have not been pursued. Preventive dentistry has largely ignored the benefits of reducing the bacterial challenge, partially due to primitive and inadequate delivery systems. For example, Chlorhexidine applied as a rinse partially reduces some bacteria but not others that are hiding within the biofilm. Better antibacterials and better delivery systems are needed. Xylitol delivered by gum or lozenge appears to be effective clinically in reducing cariogenic bacteria and caries levels, but novel systems that deliver therapeutic amounts when needed would be a major advance, especially for young children. Reducing the cariogenic bacterial challenge and enhancing the effect of fluoride by the use of new sustained-delivery systems would have a major effect on dealing with caries as a disease.


Fatal and severe box jellyfish stings, including Irukandji stings, in Malaysia, 2000-2010.
Jellyfish are a common cause of injury throughout the world, with fatalities and severe systemic events not uncommon after tropical stings. The internet is a recent innovation to gain information on real-time health issues of travel destinations, including Southeast Asia. We applied the model of internet-based retrospective health data aggregation, through the Divers Alert Network Asia-Pacific (DAN AP), together with more conventional methods of literature and media searches, to document the health significance, and clinical spectrum, of box jellyfish stings in Malaysia for the period January 1, 2000 to July 30, 2010. Three fatalities, consistent with chirodropid envenomation, were identified for the period-all tourists to Malaysia. Non-fatal chirodropid stings were also documented. During 2010, seven cases consistent with moderately severe Irukandji syndrome were reported to DAN and two representative cases are discussed here. Photographs of chirodropid (multi-tentacled), carybdeid (four-tentacled) box jellyfish, and of severe sting lesions were also submitted to DAN during this period. This study suggests that the frequency and severity of jellyfish stings affecting tourists in Southeast Asia have been significantly underestimated. Severe and fatal cases of chirodropid-type stings occur in coastal waters off Peninsular Malaysia and Sabah, Borneo. Indeed, the first Malaysian cases consistent with Irukandji-like syndrome are reported here. Reports to DAN, a provider of emergency advice to divers, offer one method to address the historic lack of formalized reporting mechanisms for such events, for photo-documentation of the possible culprit species and treatment advice. The application of marine stinger prevention and treatment principles throughout the region may help reduce the incidence and severity of such stings. Meanwhile travelers and their medical advisors should be aware of the hazards of these stings throughout the Asia-Pacific.


Loading protocols for implant-supported overdentures in the edentulous jaw: a systematic review and meta-analysis.
High survival rates have frequently been reported for immediately loaded implants. The aim of this systematic review was to compare immediately loaded with early and conventional loaded implants for overdenture treatment with regard to their 1-year survival rates. Systematic database (Medline, Embase, CENTRAL) and hand searches were performed to identify prospective studies reporting on loading protocols for two-piece implants with micro-rough surfaces and diameters > 3 mm. Studies were grouped according to loading protocol, jaw, number of implants per jaw, and splinting. Meta-analyses of comparative reports were performed based on the calculated risk difference (RD). Descriptive analyses included the remainder prospective studies. Two investigators extracted the data independently. Kappa statistics served to evaluate the inter-investigator agreement. Of the 3,142 identified articles, 58 were included for data extraction. They comprised 11 studies comparing loading protocols as well as a further 47 prospective reports. Comparative studies were only available for mandibular overdentures. The meta-analysis revealed a statistical tendency to support conventional over immediate loading (RD: -0.03, 95% confidence interval: -0.06, 0.00). The descriptive analysis of studies with lower evidence demonstrated partially contradictory findings. There, reported survival rates for immediately loaded implants lay between 81.6% and 100%, but depended on the number of implants placed. Most investigators preferred verifying an initial high insertion torque (≥ 35 Ncm) or ISQ value (≥ 60) before considering an implant for an immediate or early loading protocol. Although all three loading protocols provide high survival rates, early and conventional loading protocols are still better documented than immediate loading and seem to result in fewer implant failures during the first year. Only a few prospective case series are available to document immediate loading of implants supporting an overdenture in the edentulous maxilla.


The market triumph of ecotourism: an economic investigation of the private and social benefits of competing land uses in the Peruvian Amazon.
Annual revenue flow to developing countries for ecotourism (or nature-based tourism) could be as large as US$ 210×10(12), providing an enormous financial incentive against habitat loss and exploitation. However, is ecotourism the most privately and/or socially valuable use of rainforest land? The question is rarely answered because the relevant data, estimates of profits and fixed costs, are rarely available. We present a social cost-benefit analysis of land use in an ecotourism cluster in the Tambopata region of Amazonian Peru. The net present value of ecotourism-controlled land is given by the producer surplus (profits plus fixed costs of ecotourism lodges): US$ 1,158 ha(-1), which is higher than all currently practiced alternatives, including unsustainable logging, ranching, and agriculture. To our knowledge, this is the first sector-wide study of profitability and producer surplus in a developing-country ecotourism sector and the first to compare against equivalent measures for a spectrum of alternative uses. We also find that ecotourism-controlled land sequesters between 5.3 to 8.7 million tons of above-ground carbon, which is equivalent to between 3000-5000 years of carbon emissions from the domestic component of air and surface travel between the gateway city of Cusco and the lodges, at 2005 emission rates. Ecotourism in Tambopata has successfully monetized the hedonic value of wild nature in Amazonian Peru, and justifies the maintenance of intact rainforest over all alternative uses on narrow economic grounds alone.


Planning for translational research in genomics.
Translation of research findings into clinical practice is an important aspect of medical progress. Even for the early stages of genomics, research aiming to deepen understandings of underlying mechanisms of disease, questions about the ways in which such research ultimately can be useful in medical treatment and public health are of key importance. Whilst some research data may not apparently lend themselves to immediate clinical benefit, being aware of the issues surrounding translation at an early stage can enhance the delivery of the research to the clinic if a medical application is later found. When simple steps are taken during initial project planning, the pathways towards the translation of genomic research findings can be managed to optimize long-term benefits to health. This piece discusses the key areas of collaboration agreements, distribution of revenues and recruitment and sample collection that are increasingly important to successful translational research in genomics.


An integrative feminist model: the evolving feminist perspective on intimate partner violence.
The feminist perspective on intimate partner violence is a predominant model in the field, although not immune to criticism. In this research, frontline workers in the violence against women movement responded to critiques of the feminist model. The project used a focus group and a modified grounded theory analysis. Participants agreed with some criticisms, including an overreliance on a punitive criminal justice system, but reported skepticism toward proposed alternatives. Findings led to the development of the Integrative Feminist Model, which expands the feminist perspective in response to critiques, new research, and alternative theories while retaining a gendered analysis of violence.


The protein composition of mitotic chromosomes determined using multiclassifier combinatorial proteomics.
Despite many decades of study, mitotic chromosome structure and composition remain poorly characterized. Here, we have integrated quantitative proteomics with bioinformatic analysis to generate a series of independent classifiers that describe the approximately 4,000 proteins identified in isolated mitotic chromosomes. Integrating these classifiers by machine learning uncovers functional relationships between protein complexes in the context of intact chromosomes and reveals which of the approximately 560 uncharacterized proteins identified here merits further study. Indeed, of 34 GFP-tagged predicted chromosomal proteins, 30 were chromosomal, including 13 with centromere-association. Of 16 GFP-tagged predicted nonchromosomal proteins, 14 were confirmed to be nonchromosomal. An unbiased analysis of the whole chromosome proteome from genetic knockouts of kinetochore protein Ska3/Rama1 revealed that the APC/C and RanBP2/RanGAP1 complexes depend on the Ska complex for stable association with chromosomes. Our integrated analysis predicts that up to 97 new centromere-associated proteins remain to be discovered in our data set.


Factors to consider in evaluating the appropriateness of restraints during forensic evaluations.
Forensic examiners frequently conduct evaluations with individuals who may be regarded as dangerous. To manage this situation, forensic examiners may prefer examinees to wear restraints. Available literature indicates that the use of restraints may be both physically and psychologically detrimental and thus possibly both reduces the yield and limits the utility of psychological test data. Although there is a lack of research addressing this concern, one must use the available information to inform the decision on utilization of restraints during forensic evaluations. In addition, professional ethics, test standards and norms, the reported adverse effects of restraints on both psychiatric patients and inmates, and the concept of forced medication are reviewed to help assess the appropriateness of restraints during forensic evaluations. This analysis provides forensic examiners with insight and recommendations to determine if the use of restraints is best practice during forensic evaluations, particularly within the United States.


Acute responses to resistance training and safety.
Resistance training is widely used in fitness programs for healthy individuals of all ages and has become accepted as part of the exercise rehabilitation process for patients with coronary artery disease. It is only during the past decade that the acute circulatory responses to resistance exercise have been investigated directly, using intra-arterial measurement techniques and two-dimensional echocardiography. This review examines the factors that influence the acute circulatory responses to resistance training. These include the number of repetitions, the absolute and relative load, the muscle mass engaged in the lifting, the joint angle, and the Valsalva maneuver. There is discussion of the responses in patients with coronary artery disease and the effects of resistance training on the acute responses. The review ends with a discussion of the safety of this form of exercise and concludes that it is safe and appropriate for most healthy individuals and many of those with different diseases.


Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage.
Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection.


Mobile phone emissions and human brain excitability.
To test-via Transcranial Magnetic Stimulation (TMS)-the excitability of each brain hemisphere after 'real' or 'sham' exposure to the electromagnetic field (EMF) generated by a mobile phone operating in the Global System for Mobile Communication (GSM). Fifteen male volunteers attended two experimental sessions, one week apart, in a cross-over, double-blind paradigm. In one session the signal was turned ON (EMF-on, real exposure), in the other it was turned OFF (EMF-off, sham exposure), for 45 minutes. Motor Evoked Potentials (MEPs) were recorded using a paired-pulse paradigm (testing intracortical excitability with 1 to 17 ms interstimulus intervals), both before and at different times after exposure to the EMF. Short Intracortical Inhibition (SICI) and Facilitation (ICF) curves were evaluated both on the exposed and non-exposed hemispheres. Tympanic temperature was collected during each session. The intracortical excitability curve becomes significantly modified during real exposure, with SICI being reduced and ICF enhanced in the acutely exposed brain hemisphere as compared to the contralateral, non-exposed hemisphere or to sham exposure. Tympanic temperature showed no significant main effect or interactions. These results demonstrate that GSM-EMFs modify brain excitability. Possible implications and applications are discussed.


Genetic ablation of petal and stamen primordia to elucidate cell interactions during floral development.
Two models have been proposed to explain the coordinated development of the four whorls of floral organs. The spatial model predicts that positional information defines the four whorls simultaneously, and that individual organs develop independently of surrounding tissues. The sequential model suggests that inductive events between the outer and inner whorl primordia are required for appropriate organogenesis. To test these models we have genetically ablated second and third whorl floral organ primordia to determine if organ identity, number or position are perturbed in the first or fourth whorls. We used diphtheria toxin to specifically ablate floral cells early in development in Nicotiana tabacum and in Arabidopsis thaliana. Second and third whorl expression of the diphtheria toxin A chain coding sequence (DTA) was conferred by the Arabidopsis APETALA3 (AP3) promoter. Both Nicotiana and Arabidopsis flowers that express the AP3-DTA construct lack petals and stamens; it appears that the second and third whorl cells expressing this construct arrest early in floral development. These results show that first and fourth whorl development is normal and can proceed without information from adjacent second and third whorl primordia. We propose that positional information specifies the establishment of all four whorls of organs prior to the expression of AP3 in the floral meristem.


Does preoperative symptom classification impact prognosis in patients with clinically localized upper-tract urothelial carcinoma managed by radical nephroureterectomy?
To evaluate if preoperative symptom classification could refine prediction of outcomes for patients with clinically localized upper-tract urothelial carcinoma (UTUC) managed by radical nephroureterectomy (RNU). Data on 654 patients with localized UTUC who underwent RNU were reviewed. Preoperative symptoms were classified as incidental (S1), local (S2), and systemic (S3). Clinical and pathologic data were compared between the cohorts. Kaplan-Meier analyses and Cox proportional hazard modeling were used to determine recurrence-free and cancer-specific survival amongst the symptom cohorts. Symptom classification was S1 in 213 (33%) patients, S2 in 402 (61%), and S3 in 39 (6%). S3 symptoms were associated with advanced pathology, including higher stage, grade, and lymph node (LN) positivity. Five and 10-year recurrence-free and cancer-specific survival estimates were similar for patients with S1 and S2 symptoms (P = 0.75 and 0.58, respectively), but was worse for patients with S3 symptoms (P < 0.001 for both). On multivariate analysis adjusting for final pathologic stage, grade, and LN status, S3 symptoms were not an independent predictor of recurrence (HR 1.44, P = 0.19) or death due to disease (HR 1.66, P = 0.07). Addition of symptom classification, however, increased the accuracy of a model consisting of stage, grade, and LNs for prediction of recurrence-free and cancer-specific survival by 1.4% and 1.3%, respectively (P < 0.001 for both). Local symptoms do not confer worse prognosis compared with patients with incidentally detected UTUC. However, systemic symptoms are associated with worse outcomes despite apparently effective RNU. Patients with systemic symptoms may harbor micrometastatic disease and could potentially benefit from a more rigorous metastatic evaluation or perioperative chemotherapy regimens.


Policies and interventions on employment relations and health inequalities.
The association between certain increasingly pervasive employment conditions and serious health inequalities presents a significant policy challenge. A critical starting point is the recognition that these problems have not arisen in a policy vacuum. Rather, policy frameworks implemented by governments over the past 35 years, in conjunction with corporate globalization (itself facilitated by neoliberal policies), have undermined preexisting social protection policies and encouraged the growth of health-damaging forms of work organization. After a brief description of the context in which recent developments should be viewed, this article describes how policies can be reconfigured to address health-damaging employment conditions. A number of key policy objectives and entry points are identified, with a summary of policies for each entry point, relating to particular employment conditions relevant to rich and poor countries. Rather than trying to elaborate these policy interventions in detail, the authors point to several critical issues in relation to these interventions, linking these to illustrative examples.


Attention but not awareness modulates the BOLD signal in the human V1 during binocular suppression.
Although recent psychophysical studies indicate that visual awareness and top-down attention are two distinct processes, it is not clear how they are neurally dissociated in the visual system. Using a two-by-two factorial functional magnetic resonance imaging design with binocular suppression, we found that the visibility or invisibility of a visual target led to only nonsignificant blood oxygenation level-dependent (BOLD) effects in the human primary visual cortex (V1). Directing attention toward and away from the target had much larger and robust effects across all study participants. The difference in the lower-level limit of BOLD activation between attention and awareness illustrates dissociated neural correlates of the two processes. Our results agree with previously reported V1 BOLD effects on attention, while they invite a reconsideration of the functional role of V1 in visual awareness.


Outcomes associated with ablation compared to combined ablation and transilluminated powered phlebectomy in the treatment of venous varicosities.
Patients with painful varicose veins and venous insufficiency can be treated by eliminating axial reflux only or by eliminating axial reflux plus phlebectomy with transilluminated powered phlebectomy. This study was undertaken with the aim of determining and improving signs and symptoms of venous disease (measured by venous clinical severity score) and complications (by routine surveillance ultrasound and long-term post-operative follow up) for each treatment strategy. We performed a retrospective evaluation of prospectively collected data from 979 limbs undergoing procedures for significant varicose veins and venous insufficiency from March 2008 until June 2014 performed at a single tertiary referral hospital. Patient demographics, Clinical Etiology Anatomy and Pathophysiology classification, venous clinical severity scores pre- and post-procedure, treatment chosen, and peri-operative complications were collected; descriptive statistics were calculated and unadjusted surgical outcomes for patients stratified by the procedure performed. Multivariable logistic regression was used to evaluate the relationship between procedure type and thrombotic complications after adjusting for patient characteristics, severity of disease, pre-operative anticoagulation, and post-operative compression. Venous clinical severity scores improved more with radiofrequency ablation + transilluminated powered phlebectomy as compared to radiofrequency ablation alone (3.8 ± 3.4 vs. 3.2 ± 3.1, p = 0.018). Regarding deep venous thrombosis, there was no significant difference between radiofrequency ablation + transilluminated powered phlebectomy vs. radiofrequency ablation alone. There was no statistical difference in asymptomatic endovenous heat-induced thrombosis or infection, although there were slightly more hematomas and cases of asymptomatic superficial thrombophlebitis with combined therapy. On multivariable analysis, only procedure type predicted thrombotic complications. Ablation of axial reflux plus transilluminated powered phlebectomy produces improved outcomes as measured by venous clinical severity score, with slight increases in minor post-operative complications and should be strongly considered as initial therapy when patients present with significant symptomatic varicose veins and superficial venous insufficiency. Implementation of a standardized thromboprophylaxis protocol with individual risk assessment results in few significant thrombotic complications amongst high-risk patients, thus potentially obviating the need for routine post-operative duplex.


Quality of Life and General Health After Elective Surgery for Cervical Spine Pathologies: Determining a Valid and Responsive Metric of Health State Utility.
As part of the Affordable Care Act, health utility metrics are being investigated to define a cost-effective, value-based health care model. EuroQOL-5D (EQ-5D) and Short Form-6D (SF-6D) are commonly used quality-of-life instruments. Domains in the EQ-5D questionnaire are thought to be less responsive in measuring quality of life after cervical surgery. To evaluate the validity and responsiveness of SF-6D and EQ-5D in determining health and quality of life after elective cervical spine surgery. A total of 420 patients undergoing elective cervical spine surgery over a period of 2 years were enrolled in a prospective longitudinal registry. Patient-reported outcomes Neck Disability Index (NDI), EQ-5D, and SF-12 were recorded. Based on previously published equations, SF-6D was calculated using NDI and SF-12 scores. Patients were asked whether "surgery met their expectations" (meaningful improvement). The validity and relative responsiveness of SF-6D (NDI), SF-6D (SF-12), and EQ-5D to discriminate between meaningful and nonmeaningful improvement were calculated. Sixty-six percent of patients (277) reported a level of improvement after surgery that met their expectations (meaningful improvement). SF-6D (NDI) (area under the curve [AUC] = 0.69) was a more valid discriminator of meaningful improvement compared with the SF-6D (SF-12) (AUC = 0.65) and EQ-5D (AUC = 0.62). SF-6D (NDI) was also a more responsive measure compared with SF-6D (SF-12) and EQ-5D (standardized response mean difference: 0.66, 0.48, and 0.44, respectively). SF-6D is a more valid and responsive measure of general health and quality of life compared with EQ-5D. SF-6D derived from disease-specific disability scores was more valid and responsive than that derived from the generic preference-based SF-12. Cost-effective studies should use SF-6D as a measure of QALY after cervical spine surgery.


Influence of light-curing sources on polymerization reaction kinetics of a restorative system.
To determine the effect of using a variety of commercial light-curing units on polymerization of a dentin-bonding agent (Adper Single Bond) and of a resin composite (Filtek Z250). Infrared (IR) spectra were obtained kinetically at one scan/second at 2 cm(-1) resolution for a period of 5 minutes and were analyzed for: maximum conversion rate (%/s), time into exposure when maximum rate occurred (seconds), conversion at maximum rate (%), and total conversion (%) at 300 seconds by comparison of aliphatic-to-aromatic absorption IR peak ratios, before and after polymerization. Light units used were: QTH 540 mW/cm2 (XL3000); LED 750 mW/cm2 (Elipar FreeLight 2); PAC 2,130 mW/cm2 (ARC II). Exposure followed manufacturers' recommendations: dentin bonding agent for 10 seconds, RC for 20 seconds (QTH), and 10 seconds (LED and PAC). Polymerization kinetics was evaluated at the bottom surface (2.5 mm thick) for the resin composite and as a thin film for the dentin bonding agent on the diamond surface of an attenuated total reflectance accessory in the IR spectrometer. Values (n = 5) were compared using ANOVA and Tukey's pairwise post-hoc test: pre-set alpha 0.05. PAC produced the highest total conversion and conversion rate for the resin composite (P < 0.05). Total conversion was lower for dentin bonding adhesive using PAC than with LED or QTH (P < 0.05). LED provided the highest proportion of conversion at the maximum rate with respect to conversion at 300 seconds for both materials. QTH demonstrated the lowest maximum rate value that occurred at a longer time into exposure (P < 0.05). Polymerization kinetic parameters varied greatly between the restorative materials as well as among light-curing unit types when compared to values observed when using a QTH light as control.


Deep learning(s) in gaming disorder through the user-avatar bond: A longitudinal study using machine learning.
Gaming disorder [GD] risk has been associated with the way gamers bond with their visual representation (i.e., avatar) in the game-world. More specifically, a gamer's relationship with their avatar has been shown to provide reliable mental health information about the user in their offline life, such as their current and prospective GD risk, if appropriately decoded. To contribute to the paucity of knowledge in this area, 565 gamers (Mage = 29.3 years; SD =10.6) were assessed twice, six months apart, using the User-Avatar-Bond Scale (UABS) and the Gaming Disorder Test. A series of tuned and untuned artificial intelligence [AI] classifiers analysed concurrently and prospectively their responses. Findings showed that AI models learned to accurately and automatically identify GD risk cases, based on gamers' reported UABS score, age, and length of gaming involvement, both concurrently and longitudinally (i.e., six months later). Random forests outperformed all other AIs, while avatar immersion was shown to be the strongest training predictor. Study outcomes demonstrated that the user-avatar bond can be translated into accurate, concurrent and future GD risk predictions using trained AI classifiers. Assessment, prevention, and practice implications are discussed in the light of these findings.


Dispersal range of Anopheles sinensis in Yongcheng City, China by mark-release-recapture methods.
Studying the dispersal range of Anopheles sinensis is of major importance for understanding the transition from malaria control to elimination. However, no data are available regarding the dispersal range of An. sinensis in China. The aim of the present study was to study the dispersal range of An. sinensis and provide the scientific basis for the development of effective control measures for malaria elimination in China. Mark-Release-Recapture (MRR) experiments were conducted with 3000 adult wild An. sinensis in 2010 and 3000 newly emerged wild An. sinensis in 2011 in two villages of Yongcheng City in Henan Province. Marked An. sinensis were recaptured daily for ten successive days using light traps. The overall recapture rates were 0.83% (95% CI, 0.50%~1.16%) in 2010 and 1.33% (95% CI, 0.92%~1.74%) in 2011. There was no significant difference in the recapture rates of wild An. sinensis and newly emerged An. sinensis. The majority of An. sinensis were captured due east at study site I compared with most in the west at study site II. Eighty percent and 90% of the marked An. sinensis were recaptured within a radius of 100 m from the release point in study site I and II, respectively, with a maximum dispersal range of 400 m within the period of this study. Our results indicate that local An. sinensis may have limited dispersal ranges. Therefore, control efforts should target breeding and resting sites in proximity of the villages.


Measuring Handrim Wheelchair Propulsion in the Lab: A Critical Analysis of Stationary Ergometers.
There are many ways to simulate handrim wheelchair propulsion in the laboratory. Ideally, these would be able to, at least mechanically, simulate field conditions. This narrative review provides an overview of the lab-based equipment used in published research and critically assesses their ability to simulate and measure wheelchair propulsion performance. A close connection to the field can only be achieved if the instrument can adequately simulate frictional losses and inertia of real-life handrim wheelchair propulsion, while maintaining the ergonomic properties of the wheelchair-user interface. Lab-based testing is either performed on a treadmill or a wheelchair ergometer (WCE). For this study WCEs were divided into three categories: roller, flywheel, and integrated ergometers. In general, treadmills are mechanically realistic, but cannot simulate air drag and acceleration tasks cannot be performed; roller ergometers allow the use of the personal wheelchair, but calibration can be troublesome; flywheel ergometers can be built with commercially-available parts, but inertia is fixed and the personal wheelchair cannot be used; integrated ergometers do not employ the personal wheelchair, but are suited for the implementation of different simulation models and detailed measurements. Lab-based equipment is heterogeneous and there appears to be little consensus on how to simulate field conditions.


Amblyopia risk factors in infants with congenital nasolacrimal duct obstruction.
This study aims to report the prevalence of amblyopia risk factors in patients with congenital nasolacrimal duct obstructions. We recruited patients who were treated for congenital nasolacrimal duct obstruction from April 2007 to December 2011 at Korea University Ansan Hospital. We evaluated visual acuity and refraction, performed strabismus test and slit-lamp examination, and assessed marginal reflex distance 1 (MRD1) to rule out amblyopia risk factors. We examined 26 children among 115 patients. Ten patients underwent probing procedure and 16 underwent Monoka stent intubation. Nine (35%) patients showed amblyopia risk factors, which occurred in the same eye as the congenital nasolacrimal duct obstruction in 8 (89%) patients. Seven out of 9 patients had refractive error alone, and 2 patients had both refractive error and strabismus. One (11%) had anisometropia, 2 (22%) had hyperopia, and 8 (89%) had astigmatism. Children with congenital nasolacrimal duct obstruction had a higher prevalence of amblyopia risk factors than children in the general population. Children with congenital nasolacrimal duct obstruction require special attention and treatments for refractive error. We recommend early treatment, such as probing or intubation, for congenital nasolacrimal duct obstruction.


Acute Stress Time-dependently Modulates Multiple Memory Systems.
Acute stress has been shown to modulate the engagement of different memory systems, leading to preferential expression of stimulus-response (SR) rather than episodic context memory when both types of memory can be used. However, questions remain regarding the cognitive mechanism that underlies this bias in humans-specifically, how each form of memory is individually influenced by stress in order for SR memory to be dominant. Here we separately measured context and SR memory and investigated how each was influenced by acute stress after learning (Experiment 1) and before retrieval (Experiment 2). We found that postlearning stress, in tandem with increased adrenergic activity during learning, impaired consolidation of context memory and led to preferential expression of SR rather than context memory. Preretrieval stress also impaired context memory, albeit transiently. Neither postlearning nor preretrieval stress changed the expression of SR memory. However, individual differences in cortisol reactivity immediately after learning were associated with variability in initial SR learning. These results reveal novel cognitive mechanisms by which stress can modulate multiple memory systems.


Team talk and team activity in simulated medical emergencies: a discourse analytical approach.
Communication errors can reduce patient safety, especially in emergency situations that require rapid responses by experts in a number of medical specialties. Talking to each other is crucial for utilizing the collective expertise of the team. Here we explored the functions of "team talk" (talking between team members) with an emphasis on the talk-work relationship in interdisciplinary emergency teams. Five interdisciplinary medical emergency teams were observed and videotaped during in situ simulations at an emergency department at a university hospital in Norway. Team talk and simultaneous actions were transcribed and analysed. We used qualitative discourse analysis to perform structural mapping of the team talk and to analyse the function of online commentaries (real-time observations and assessments of observations based on relevant cues in the clinical situation). Structural mapping revealed recurring and diverse patterns. Team expansion stood out as a critical phase in the teamwork. Online commentaries that occurred during the critical phase served several functions and demonstrated the inextricable interconnections between team talk and actions. Discourse analysis allowed us to capture the dynamics and complexity of team talk during a simulated emergency situation. Even though the team talk did not follow a predefined structure, the team members managed to manoeuvre safely within the complex situation. Our results support that online commentaries contributes to shared team situation awareness. Discourse analysis reveals naturally occurring communication strategies that trigger actions relevant for safe practice and thus provides supplemental insights into what comprises "good" team communication in medical emergencies.


[Communication with patients who have medically unexplained symptoms: an art and a skill].
The relationship between doctors and patients often becomes tense when the patient has medically unexplained symptoms: doctors may experience frustration because they feel ill-equipped to provide their patients with a plausible explanation of the symptoms. Patients often feel that their doctor does not take them seriously and would like to understand why they are having symptoms. Research into the effect of the quality of the doctor-patient relationship and doctor-patient communication where medically unexplained symptoms are concerned has led to some recommendations for communication. A thorough exploration of all dimensions of the symptoms, i.e. the somatic, cognitive, emotional, behavioural and social dimensions, almost always yields starting points for explaining what is happening to the patient and for therapy. The provision of an explanation which is acceptable to the doctor as well as to the patient is an important condition for drawing up and carrying out therapy. If the doctor expresses confidence in the prognosis and outcome, this has a favourable effect on the development of the symptoms.


Synergistic Activity with NOTCH Inhibition and Androgen Ablation in ERG-Positive Prostate Cancer Cells.
The oncogenic activation of the ETS-related gene (ERG) due to gene fusions is present in over half of prostate cancers in Western countries. Because of its high incidence and oncogenic role, ERG and components of ERG network have emerged as potential drug targets for prostate cancer. Utilizing gene expression datasets, from matched normal and prostate tumor epithelial cells, an association of NOTCH transcription factors with ERG expression status was identified, confirming that NOTCH factors are direct transcriptional targets of ERG. Inhibition of ERG in TMPRSS2-ERG-positive VCaP cells led to decreased levels of NOTCH1 and 2 proteins and downstream transcriptional targets and partially recapitulated the phenotypes associated with ERG inhibition. Regulation of NOTCH1 and 2 genes by ERG were also noted with ectopic ERG expression in LNCaP (ERG-negative prostate cancer) and RWPE-1 (benign prostate-derived immortalized) cells. Furthermore, inhibition of NOTCH by the small-molecule γ-secretase inhibitor 1, GSI-1, conferred an increased sensitivity to androgen receptor (AR) inhibitors (bicalutamide and enzalutamide) or the androgen biosynthesis inhibitor (abiraterone) in VCaP cells. Combined treatment with bicalutamide and GSI-1 showed strongest inhibition of AR, ERG, NOTCH1, NOTCH2, and PSA protein levels along with decreased cell growth, cell survival, and enhanced apoptosis. Intriguingly, this effect was not observed in ERG-negative prostate cancer cells or immortalized benign/normal prostate epithelial cells. These data underscore the synergy of AR and NOTCH inhibitors in reducing the growth of ERG-positive prostate cancer cells.Implications: Combinational targeting of NOTCH and AR signaling has therapeutic potential in advanced ERG-driven prostate cancers. Mol Cancer Res; 15(10); 1308-17. ©2017 AACR.


454 Pyrosequencing-based assessment of bacterial diversity and community structure in termite guts, mounds and surrounding soils.
Termites constitute part of diverse and economically important termite fauna in Africa, but information on gut microbiota and their associated soil microbiome is still inadequate. In this study, we assessed and compared the bacterial diversity and community structure between termites' gut, their mounds and surrounding soil using the 454 pyrosequencing-based analysis of 16S rRNA gene sequences. A wood-feeder termite (Microcerotermes sp.), three fungus-cultivating termites (Macrotermes michaelseni, Odontotermes sp. and Microtermes sp.), their associated mounds and corresponding savannah soil samples were analyzed. The pH of the gut homogenates and soil physico-chemical properties were determined. The results indicated significant difference in bacterial community composition and structure between the gut and corresponding soil samples. Soil samples (Chao1 index ranged from 1359 to 2619) had higher species richness than gut samples (Chao1 index ranged from 461 to 1527). The bacterial composition and community structure in the gut of Macrotermes michaelseni and Odontotermes sp. were almost identical but different from that of Microtermes and Microcerotermes species, which had unique community structures. The most predominant bacterial phyla in the gut were Bacteroidetes (40-58 %), Spirochaetes (10-70 %), Firmicutes (17-27 %) and Fibrobacteres (13 %) while in the soil samples were Acidobacteria (28-45 %), Actinobacteria (20-40 %) and Proteobacteria (18-24 %). Some termite gut-specific bacterial lineages belonging to the genera Dysgonomonas, Parabacteroides, Paludibacter, Tannerella, Alistipes, BCf9-17 termite group and Termite Treponema cluster were observed. The results not only demonstrated a high level of bacterial diversity in the gut and surrounding soil environments, but also presence of distinct bacterial communities that are yet to be cultivated. Therefore, combined efforts using both culture and culture-independent methods are suggested to comprehensively characterize the bacterial species and their specific roles in these environments.


Ultrafast amidation of esters using lithium amides under aerobic ambient temperature conditions in sustainable solvents.
Lithium amides constitute one of the most commonly used classes of reagents in synthetic chemistry. However, despite having many applications, their use is handicapped by the requirement of low temperatures, in order to control their reactivity, as well as the need for dry organic solvents and protective inert atmosphere protocols to prevent their fast decomposition. Advancing the development of air- and moisture-compatible polar organometallic chemistry, the chemoselective and ultrafast amidation of esters mediated by lithium amides is reported. Establishing a novel sustainable access to carboxamides, this has been accomplished via direct C-O bond cleavage of a range of esters using glycerol or 2-MeTHF as a solvent, in air. High yields and good selectivity are observed while operating at ambient temperature, without the need for transition-metal mediation, and the protocol extends to transamidation processes. Pre-coordination of the organic substrate to the reactive lithium amide as a key step in the amidation processes has been assessed, enabling the structural elucidation of the coordination adduct [{Li(NPh2)(O[double bond, length as m-dash]CPh(NMe2))}2] (8) when toluene is employed as a solvent. No evidence for formation of a complex of this type has been found when using donor THF as a solvent. Structural and spectroscopic insights into the constitution of selected lithium amides in 2-MeTHF are provided that support the involvement of small kinetically activated aggregates that can react rapidly with the organic substrates, favouring the C-O bond cleavage/C-N bond formation processes over competing hydrolysis/degradation of the lithium amides by moisture or air.


Bioaccessibility, bioavailability and toxicity of commercially relevant iron- and chromium-based particles: in vitro studies with an inhalation perspective.
Production of ferrochromium alloys (FeCr), master alloys for stainless steel manufacture, involves casting and crushing processes where particles inevitably become airborne and potentially inhaled. The aim of this study was to assess potential health hazards induced by inhalation of different well-characterized iron- and chromium-based particles, i.e. ferrochromium (FeCr), ferrosiliconchromium (FeSiCr), stainless steel (316L), iron (Fe), chromium (Cr), and chromium(III)oxide (Cr2O3), in different size fractions using in vitro methods. This was done by assessing the extent and speciation of released metals in synthetic biological medium and by analyzing particle reactivity and toxicity towards cultured human lung cells (A549). The amount of released metals normalized to the particle surface area increased with decreasing particle size for all alloy particles, whereas the opposite situation was valid for particles of the pure metals. These effects were evident in artificial lysosomal fluid (ALF) of pH 4.5 containing complexing agents, but not in neutral or weakly alkaline biological media. Chromium, iron and nickel were released to very low extent from all alloy particles, and from particles of Cr due to the presence of a Cr(III)-rich protective surface oxide. Released elements were neither proportional to the bulk nor to the surface composition after the investigated 168 hours of exposure. Due to a surface oxide with less protective properties, significantly more iron was released from pure iron particles compared with the alloys. Cr was predominantly released as Cr(III) from all particles investigated and was strongly complexed by organic species of ALF. Cr2O3 particles showed hemolytic activity, but none of the alloy particles did. Fine-sized particles of stainless steel caused however DNA damage, measured with the comet assay after 4 h exposure. None of the particles revealed any significant cytotoxicity in terms of cell death after 24 h exposure. It is evident that particle and alloy characteristics such as particle size and surface composition are important aspects to consider when assessing particle toxicity and metal release from alloy particles compared to pure metal particles. Generated results clearly elucidate that neither the low released concentrations of metals primarily as a result of protective and poorly soluble surface oxides, nor non-bioavailable chromium complexes, nor the particles themselves of occupational relevance induced significant acute toxic response, with exception of DNA damage from stainless steel.


Epidemiology of restaurant-associated foodborne disease outbreaks, United States, 1998-2013.
Although contamination of food can occur at any point from farm to table, restaurant food workers are a common source of foodborne illness. We describe the characteristics of restaurant-associated foodborne disease outbreaks and explore the role of food workers by analysing outbreaks associated with restaurants from 1998 to 2013 reported to the Centers for Disease Control and Prevention's Foodborne Disease Outbreak Surveillance System. We identified 9788 restaurant-associated outbreaks. The median annual number of outbreaks was 620 (interquartile range 618-629). In 3072 outbreaks with a single confirmed aetiology reported, norovirus caused the largest number of outbreaks (1425, 46%). Of outbreaks with a single food reported and a confirmed aetiology, fish (254 outbreaks, 34%) was most commonly implicated, and these outbreaks were commonly caused by scombroid toxin (219 outbreaks, 86% of fish outbreaks). Most outbreaks (79%) occurred at sit-down establishments. The most commonly reported contributing factors were those related to food handling and preparation practices in the restaurant (2955 outbreaks, 61%). Food workers contributed to 2415 (25%) outbreaks. Knowledge of the foods, aetiologies, and contributing factors that result in foodborne disease restaurant outbreaks can help guide efforts to prevent foodborne illness.


Glycemic Management in the Bariatric Surgery Population: A Review of the Literature.
Obesity is a worldwide epidemic often complicated by multiple comorbidities, including type 2 diabetes mellitus (T2DM). Bariatric surgery is an increasingly common and effective weight-loss strategy for obese patients that may result in resolution of metabolic-related disease states, such as T2DM. Although bariatric surgery has many positive outcomes for patients, dietary and pathophysiologic changes can create difficult-to-control blood glucose, especially in the immediate perioperative setting. Depending on oral antidiabetic agent and insulin needs preoperatively, many patients require cessation of oral agents and reduction or cessation of insulin. Unfortunately, despite available perioperative bariatric surgery guidelines, no specific recommendations for perioperative oral antidiabetic agent or insulin management exist. The purpose of this article is to review the current body of evidence for blood glucose management in the setting of bariatric surgery. An English-language PubMed and MEDLINE search was conducted from 1964 through March 2018 using the following search terms alone and in various combinations: bariatric surgery, gastric banding, laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), glucose management, insulin, and oral antidiabetic agent. Five articles were identified evaluating insulin management in the perioperative bariatric surgery setting, which were separated into two categories: immediate perioperative insulin management and long-term postoperative insulin management. Overall, various blood glucose management insulin protocols were evaluated. All studies included some type of insulin reduction in the perioperative setting. No studies identified specifically evaluated down-titration or discontinuation of oral antidiabetic agents. Given the lack of specific guideline recommendations, limitations of standardized insulin protocols, and inconsistency of outcomes studied, perioperative insulin at reduced doses compared to previous maintenance doses coupled with frequent blood glucose monitoring is reasonable. An opportunity exists for successful protocols to be addressed in future, larger studies.


Determinants and significance of cerebral oximetry after cardiac arrest: A prospective cohort study.
To study the determinants and the evolution of cerebral oximetry determined by near-infrared spectroscopy after out-of-hospital cardiac arrest of cardiac origin during therapeutic hypothermia and rewarming, and to compare cerebral oximetry values between patients with good and bad prognosis. In this prospective, non-interventional, single center study, all consecutive patients between 18 and 80 years admitted for out-of-hospital cardiac arrest (OHCA) with a no flow less than 10min, a low flow of less than 50min and a persistent coma after ROSC with Glasgow score equal or less than seven at baseline were included. Between February 2012 and January 2013, 43 patients were admitted for OHCA in our ICU. Twenty-two patients (51%) were discharged with no or minimal neurologic complications (CPC 1-2). Mortality rate in the ICU was 46.5%. Cerebral oximetry (rSO2) was correlated with temperature, heart rhythm, PaO2, hemoglobin, and mean arterial pressure. Mean rSO2 during the 48 first hours was not different between patients with good and bad neurologic outcomes, respectively, 61.8 (5.9) vs. 58.1 (8.8), P=0.13, as during the period of hypothermia. The minimal value of rSO2 during the first 48h was significantly different between patients with good prognosis and those with bad prognosis, respectively, 45.0 (6.8) vs. 31.7 (15.0), P=0.0009. In this prospective cohort of OHCA patients, main determinants of rSO2 were systemic variables. Monitoring of rSO2 does not allow discriminating patients with good or bad outcome, but could be useful for identifying vulnerable periods for the development of neurologic injury.


The social phobia psychotherapy research network. The first multicenter randomized controlled trial of psychotherapy for social phobia: rationale, methods and patient characteristics.
This paper presents the Social Phobia Psychotherapy Research Network. The research program encompasses a coordinated group of studies adopting a standard protocol and an agreed-on set of standardized measures for the assessment and treatment of social phobia (SP). In the central project (study A), a multicenter randomized controlled trial, refined models of manualized cognitive-behavioral therapy and manualized short-term psychodynamic psychotherapy are compared in the treatment of SP. A sample of 512 outpatients will be randomized to either cognitive-behavioral therapy, short-term psychodynamic psychotherapy or waiting list. Assessments will be made at baseline, at the end of treatment and 6 and 12 months after the end of treatment. For quality assurance and treatment integrity, a specific project using highly elaborated measures has been established (project Q). Study A is complemented by 4 interrelated add-on projects focusing on attachment style (study B1), on cost-effectiveness (study B2), on variation in the serotonin transporter gene in SP (study C1) and on structural and functional deviations of the hippocampus and amygdala (study C2). Thus, the Social Phobia Psychotherapy Research Network program enables a highly interdisciplinary research into SP. The unique sample size achieved by the multicenter approach allows for studies of subgroups (e.g. comorbid disorders, isolated vs. generalized SP), of responders and nonresponders of each treatment approach, for generalization of results and for a sufficient power to detect differences between treatments. Psychological and biological parameters will be related to treatment outcome, and variables for differential treatment indication will be gained. Thus, the results provided by the network may have an important impact on the treatment of SP and on the development of treatment guidelines for SP.


[Diagnosis of Helicobacter pylori infection].
Helicobacter pylori (H. pylori) infection can be diagnosed either by invasive techniques requiring endoscopy and biopsy (histological examination, culture, polymerase chain reaction) and or noninvasive techniques (urea breath test, serology, urine or blood, detection of H. pylori antigen in stool specimen). At present, no single test can be absolutely sufficient to detect the colonization by H. pylori, and a combination of above two tests is recommended if feasible. Because all the tests have their pitfalls and limitations, the choice of tests should depend on the clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy, and the availability of the tests. It is important to know which test in a certain clinical setting gives the best outcome. Some clinical circumstances warrant invasive studies, principally in patients with alarm symptoms (bleeding, weight loss, etc.) as well as older patients with new-onset dyspepsia. Endoscopy may also be advisable in patients who have failed eradication therapy and need culture to examine antimicrobial sensitivity testing to determine appropriate regimen. Recent Western studies have also demonstrated that a strategy of 'test and treat' for H. pylori in uninvestigated, young (<45 years), dyspeptic patients in primary care is safe and reduces the need for endoscopy. Therefore, it is necessary to hold a second consensus meeting for the diagnosis and treatment of H. pylori infection in Korea for the renewal of clinical guidelines in primary, secondary, and tertiary care based an evidence-based analysis.


Computational Approach to Evaluation of Optical Properties of Membrane Probes.
Computed optical properties of membrane probes are typically evaluated in the gas phase, i.e. neglecting the influence of the membrane. In this study, we examine how and to what extent a membrane influences the one- and two-photon absorption (1PA and 2PA, respectively) properties for a number of cholesterol analogs and thereby also evaluate the validity of the common gas phase approach. The membrane is modeled using the polarizable embedding scheme both with and without the effective external field extension of the polarizable embedding model. The shifts in excitation energies and 1PA oscillator strengths compared to the gas phase are relatively small, while the 2PA cross section is more affected. The electric field inside the membrane induces a larger change in the permanent electric dipole moment upon excitation of the analogs compared to the gas phase, which leads to an almost 2-fold increase in the 2PA cross section for one cholesterol analog. The relative trends observed in the membrane are the same as in the gas phase, and the use of gas phase calculations for qualitative comparison and design of cholesterol membrane probes is thus a useful and computationally efficient strategy.


Estimation and discrimination of stochastic biochemical circuits from time-lapse microscopy data.
The ability of systems and synthetic biologists to observe the dynamics of cellular behavior is hampered by the limitations of the sensors, such as fluorescent proteins, available for use in time-lapse microscopy. In this paper, we propose a generalized solution to the problem of estimating the state of a stochastic chemical reaction network from limited sensor information generated by microscopy. We mathematically derive an observer structure for cells growing under time-lapse microscopy and incorporates the effects of cell division in order to estimate the dynamically-changing state of each cell in the colony. Furthermore, the observer can be used to discrimate between models by treating model indices as states whose values do not change with time. We derive necessary and sufficient conditions that specify when stochastic chemical reaction network models, interpreted as continuous-time Markov chains, can be distinguished from each other under both continual and periodic observation. We validate the performance of the observer on the Thattai-van Oudenaarden model of transcription and translation. The observer structure is most effective when the system model is well-parameterized, suggesting potential applications in synthetic biology where standardized biological parts are available. However, further research is necessary to develop computationally tractable approximations to the exact generalized solution presented here.


SPECT [I-123]iomazenil measurement of the benzodiazepine receptor in panic disorder.
Alterations in benzodiazepine receptor function have long been hypothesized to play a role in anxiety. Animal models of anxiety involving exposure to chronic stress have shown a specific decrease in benzodiazepine receptor binding in frontal cortex and hippocampus. The purpose of this study was to examine benzodiazepine receptor binding patients with panic disorder and comparison subjects. A quantitative measure related to benzodiazepine receptor binding (Distribution Volume (DV)) was obtained with single photon emission computed tomography (SPECT) imaging of [123I]iomazenil and measurement of radioligand concentration in plasma in patients with panic disorder and healthy controls. DV image data were analyzed using statistical parametric mapping (spm96). A decrease in measures of benzodiazepine receptor binding (DV) was found in left hippocampus and precuneus in panic disorder patients relative to controls. Panic disorder patients who had a panic attack compared to patients who did not have a panic attack at the time of the scan had a decrease in benzodiazepine receptor binding in prefrontal cortex. Findings of a decrease in left hippocampal and precuneus benzodiazepine receptor binding may be related to alterations in benzodiazepine receptor binding, or other factors including changes in GABAergic transmission or possible endogenous benzodiazepine compounds. Benzodiazepine receptor function in prefrontal cortex appears to be involved in changes in state-related panic anxiety.


Visible light to switch-on desorption from goethite.
Switching adsorption-desorption by visible light could provide the possibility for a wide range of applications that require controlled release-on-demand. Here, we demonstrate a visible-light controlled desorption behavior in aqueous suspensions for the first time. We observed cationic dye adsorption on amphoteric goethite α-FeOOH in the dark and release during visible light exposure at a pH value slightly over the isoelectric point of goethite. During this process, the dye does not degrade. Desorption is triggered by local heating due to light absorption in narrow band gap goethite, α-FeOOH.


Wrongful life claims and negligent selection of gametes or embryos in infertility treatments: a quest for coherence.
This article discusses an anomaly in the English law of reproductive liability: that is, an inconsistency between the law's approach to wrongful life claims and its approach to cases of negligent selection of gametes or embryos in infertility treatments (the selection cases). The article begins with an account of the legal position, which brings into view the relevant inconsistency: while the law treats wrongful life claims as non-actionable, it recognises a cause of action in the selection cases, although the selection cases bear a relevant resemblance to wrongful life claims. The article then considers arguments that may be invoked in an attempt to reconcile the above two strands of the law. Three of these counterarguments consist in attempts to distinguish the selection cases from wrongful life claims. It is argued that these attempts fail to reveal a valid basis for treating these situations differently. A fourth possible counterargument levels against the present analysis a charge of reductio ad absurdum. It is shown that this argument suffers from a fundamental flaw caused by confusion between different senses of the term "identity". Finally, the article discusses possible changes to the legal position that could rectify the problem. It argues that one of these changes, which focuses on legal redress for violation of personal autonomy, is particularly apt to resolve the problem at hand, but also highlights the need for further inquiry into the broader implications of introducing this form of redress into the law of torts.


Bone growth and remodelling after fracture.
We used a rabbit model to investigate the mechanism by which the angulation of fractures is corrected in children. We produced a transverse proximal tibial fracture in one leg of 12 eight-week-old New Zealand white rabbits and measured bone alignment and length and the patterns of bone growth and remodelling. The angle between the joint surfaces changed rapidly to correct the alignment of the limb as a result of asymmetrical growth of epiphyseal plates. In an adult with closed plates, the angle between the joint surfaces cannot therefore improve. The angle at the fracture itself showed slow improvement because of bone drift and the asymmetrical growth of the epiphyseal plates. Remodelling corrected the shape of the bone in the region of the fracture. Periosteal division on the convex side increased the growth of the epiphyseal plate on that side, thus slowing the correction. The effect was relatively small, providing an indication that factors other than the periosteum are important in inducing correction. External torsional deformities developed because of helical growth at the plate. This was probably caused by abnormal posture which induced a torque at the growth plate. Helical growth is the mechanism by which rotational deformities can occur and correct.


Physicochemical characterization and antioxidant activity of Palestinian honey samples.
Physicochemical characteristics, main minerals, and antioxidant activity were determined for Palestinian honey samples belonging to different floral and geographical origins. The features of the analyzed samples were within the established international standards for honey quality control. One clear exception was the hydroxymethylfurfural (HMF) of the Ziziphus sample purchased from the Jericho region, which is the lowest city in the word characterized by a hot desert climate. The observed HMF value was 81.86 ± 2.64 mg/kg being two folds the maximum allowed in honey samples (40 mg/kg). As a second objective of the present work, the parameters were divided into two groups with different discriminatory power. The assessed physicochemical parameters, and the antioxidant activities, specific to the botanical origin discrimination, were used to run the first PCA. A strong correlation could be seen between the bioactive compounds and the antioxidant activities despite the geographical origin of the samples. Thyme and Ziziphus samples were the best samples, while citrus sample presented the lowest activity. Regarding the geographical discrimination, Ash and mineral contents in addition to the electrical conductivity were used. The output PCA conserved high represent ability of the data in the two-first components being 82.72% and 9.60%. A little discrimination between the samples produced in the north and those produced in the south of the country, but it was not perfect. The intervention of the botanical variability could be the reason.


Preimplantation genetic diagnosis for achondroplasia: genetics and gynaecological limits and difficulties.
We report the first attempts at preimplantation genetic diagnosis (PGD) and IVF and their accompanying difficulties for achondroplasia (ACH) patients. A PGD test was developed using fluorescent single cell PCR on lymphoblasts from patients and controls and from blastomeres from surplus IVF embryos. A specific digestion control based on the use of two fluorochromes was elaborated. Ovarian stimulation and oocyte retrieval were carried out using conventional protocols. We performed 88 single cell tests for which amplification was obtained in 86 (97.7%) single lymphoblasts. Allele drop out (ADO) was observed in two out of 53 (3.7%) heterozygous lymphoblasts. If we combine the results from the blastomere testing from surplus embryos with those from PGD cycles and re-analysis after PGD, we obtained a PCR signal in 84% of cases of which 91% were correctly diagnosed at the G380 locus. A total of six cycles were performed resulting in three embryo transfers. We observed difficulties in ovarian stimulation and oocyte retrieval with affected female patients. No pregnancy was obtained. A PGD test for ACH is now available at our centre but our initial practice raises questions on the feasibility of such a test, specially with affected female patients.


Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype.
The 9q subtelomeric deletion syndrome (9qSTDS) is clinically characterised by moderate to severe mental retardation, childhood hypotonia and facial dysmorphisms. In addition, congenital heart defects, urogenital defects, epilepsy and behavioural problems are frequently observed. The syndrome can be either caused by a submicroscopic 9q34.3 deletion or by intragenic EHMT1 mutations leading to haploinsufficiency of the EHMT1 gene. So far it has not been established if and to what extent other genes in the 9q34.3 region contribute to the phenotype observed in deletion cases. This study reports the largest cohort of 9qSTDS cases so far. By a multiplex ligation dependent probe amplification (MLPA) approach, the authors identified and characterised 16 novel submicroscopic 9q deletions. Direct sequence analysis of the EHMT1 gene in 24 patients exhibiting the 9qSTD phenotype without such deletion identified six patients with an intragenic EHMT1 mutation. Five of these mutations predict a premature termination codon whereas one mutation gives rise to an amino acid substitution in a conserved domain of the protein. The data do not provide any evidence for phenotype-genotype correlations between size of the deletions or type of mutations and severity of clinical features. Therefore, the authors confirm the EHMT1 gene to be the major determinant of the 9qSTDS phenotype. Interestingly, five of six patients who had reached adulthood had developed severe psychiatric pathology, which may indicate that EHMT1 haploinsufficiency is associated with neurodegeneration in addition to neurodevelopmental defect.


Preoperative and postoperative stance analysis in dogs with patellar luxation confirms lameness improvement after surgery.
To document and compare preoperative and postoperative stance analysis measurements in animals with naturally occurring patellar luxation. 131 client-owned dogs surgically treated for naturally occurring unilateral or bilateral patella luxation between March 30, 2015, and February 12, 2020. Weight bearing as a percent body weight on each limb was recorded with the use of a platform device for analyzing stance (PetSafe Stance Analyzer; LiteCure LLC, Companion Animal Health) preoperatively and postoperatively for all dogs. Signalment, limb affected, lameness grade, luxation direction, luxation grade, and surgical procedure were collected from patient records and assessed for the effects of these variables on weight bearing preoperatively or at the first or second postoperative recheck examination. There were 61 males and 70 females, with a mean age and body weight of 4.62 years and 13.01 kg, included in the study. As age increased, body weight decreased in these dogs (P = .025). There was a statistically significant improvement in lameness after surgery (P = .008) at the second postoperative recheck examination. Lameness significantly decreased as postoperative time increased (P < .001, r = 0.503). As age increased, lameness at the initial visit decreased compared to younger dogs but not significantly (P = .062). There was no significant effect of preoperative luxation grade, luxation direction, surgical procedure, or sex when comparing initial lameness or lameness at recheck examination. Surgical correction of patella luxation improves lameness as measured by postoperative stance analysis. Preoperative luxation grade or direction, surgical procedure performed, and sex of the animal did not significantly affect outcome in this group of dogs.


Optical influence of ship wakes.
The optical variations observed within ship wakes are largely due to the generation of copious amounts of air bubbles in the upper ocean, a fraction of which accumulate as foam at the surface, where they release scavenged surfactants. Field experiments were conducted to test previous theoretical predictions of the variations in optical properties that result from bubble injection in the surface ocean. Variations in remote-sensing reflectance and size distribution of bubbles within the ship-wake zone were determined in three different optical water types: the clear equatorial Pacific Ocean, moderately turbid coastal waters, and very turbid coastal waters, the latter two of which were offshore of New Jersey. Bubbles introduced by moving vessels increased the backscattering in all cases, which in turn enhanced the reflectance over the entire visible and infrared wave bands. The elevated reflectance had different spectral characteristics in the three locations. The color of ship wakes appears greener in the open ocean, whereas little change in color was observed in near-coastal turbid waters, consistent with predictions. Colorless themselves, bubbles increase the reflected radiance and change the color of the ocean in a way that depends on the spectral backscattering and absorption of the undisturbed background waters. For remote observation from aircraft or satellite, the foam and added surfactants further enhance the reflectance to a degree dependent on the illumination and the viewing geometry.


Discriminative analysis of regional evolution of iron and myelin/calcium in deep gray matter of multiple sclerosis and healthy subjects.
Combined R2* and quantitative susceptibility (QS) has been previously used in cross-sectional multiple sclerosis (MS) studies to distinguish deep gray matter (DGM) iron accumulation and demyelination. We propose and apply discriminative analysis of regional evolution (DARE) to define specific changes in MS and healthy DGM. Longitudinal (baseline and 2-year follow-up) retrospective study. Twenty-seven relapsing-remitting MS (RRMS), 17 progressive MS (PMS), and corresponding age-matched healthy subjects. 4.7T 10-echo gradient-echo acquisition. Automatically segmented caudate nucleus (CN), thalamus (TH), putamen (PU), globus pallidus, red nucleus (RN), substantia nigra, and dentate nucleus were retrospectively analyzed to quantify regional volumes, bulk mean R2*, and bulk mean QS. DARE utilized combined R2* and QS localized changes to compute spatial extent, mean intensity, and total changes of DGM iron and myelin/calcium over 2 years. We used mixed factorial analysis for bulk analysis, nonparametric tests for DARE (α = 0.05), and multiple regression analysis using backward elimination of DGM structures (α = 0.05, P = 0.1) to regress bulk and DARE measures with the follow-up Multiple Sclerosis Severity Score (MSSS). False detection rate correction was applied to all tests. Bulk analysis only detected significant (Q ≤ 0.05) interaction effects in RRMS CN QS (η = 0.45; Q = 0.004) and PU volume (η = 0.38; Q = 0.034). DARE demonstrated significant group differences in all RRMS structures, and in all PMS structures except the RN. The largest RRMS effect size was CN total R2* iron decrease (r = 0.74; Q = 0.00002), and TH mean QS myelin/calcium decrease for PMS (r = 0.70; Q = 0.002). DARE iron increase using total QS demonstrated the highest correlation with MSSS (r = 0.68; Q = 0.0005). DARE enabled discriminative assessment of specific DGM changes over 2 years, where iron and myelin/calcium changes were the primary drivers in RRMS and PMS compared to age-matched controls, respectively. Specific DARE measures of MS DGM correlated with follow-up MSSS, and may reflect complex disease pathology. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.


RetroMine, or how to provide in-depth retrospective studies from Medline in a glance: the hepcidin use-case.
The rapid expansion of biomedical literature has provoked an increased development of advanced text mining tools to rapidly extract relevant events from the continuously increasing amount of knowledge published periodically in PubMed. However, bioinvestigators are still reluctant to use these tools for two reasons: i) a large volume of events is often extracted upon a query, and this volume is hard to manage, and ii) background events dominate search results and overshadow more pertinent published information, especially for domain experts. In this paper, we propose an approach that incorporates the temporal dimension of published events to the process of information extraction to improve data selection and prioritize more pertinent periodically published knowledge for scientists. Indeed, instead of providing the total knowledge associated with a PubMed query, which is usually a mix of trivial background information and non-background information, we propose a method that incorporates time and selects non background and highly relevant biological entities and events published over time for bioinvestigators. Before excluding background events from the total knowledge extracted, a quantification of their amount is also provided. This work is illustrated by a case study regarding Hepcidin gene publications over a decade, a duration that is sufficiently long enough to generate alternative views on the overall data extracted.


Transcription dynamics stabilizes nucleus-like layer structure in chromatin brush.
We use a brush of DNA in a solution of transcriptional machinery and histone proteins to theoretically predict that this brush shows phase separation due to the instability arising from the disassembly of nucleosomes during transcription. In the two-phase coexistent state, collapsed chains (with relatively large nucleosome occupancy) lie at the grafting surface and swollen chains (with relatively small nucleosome occupancy) are distributed at the space above the collapsed chains, analogous to the structure of chromatin in differentiated cells. This layer structure is stabilized by the lateral osmotic pressure of swollen chains. For a relatively small grafting density, DNA brushes show tricritical points because the entropic elasticity with respect to the lateral excursion of swollen chains balances with the lateral osmotic pressure of these chains. At the tricritical points, DNA brushes show large fluctuations of local nucleosome concentration, which may be reminiscent of the fluctuations observed in embryonic stem cells.


Shape recognition of microbial cells by colloidal cell imprints.
We have engineered a class of colloids which can recognize the shape and size of targeted microbial cells and selectively bind to their surfaces. These imprinted colloid particles, which we called "colloid antibodies", were fabricated by partial fragmentation of silica shells obtained by templating the targeted microbial cells. We successfully demonstrated the shape and size recognition between such colloidal imprints and matching microbial cells. High percentage of binding events of colloidal imprints with the size matching target particles was achieved. We demonstrated selective binding of colloidal imprints to target microbial cells in a binary mixture of cells of different shapes and sizes, which also resulted in high binding selectivity. We explored the role of the electrostatic interactions between the target cells and their colloid imprints by pre-coating both of them with polyelectrolytes. Selective binding occurred predominantly in the case of opposite surface charges of the colloid cell imprint and the targeted cells. The mechanism of the recognition is based on the amplification of the surface adhesion in the case of shape and size match due to the increased contact area between the target cell and the colloidal imprint. We also tested the selective binding for colloid imprints of particles of fixed shape and varying sizes. The concept of cell recognition by colloid imprints could be used for development of colloid antibodies for shape-selective binding of microbes. Such colloid antibodies could be additionally functionalized with surface groups to enhance their binding efficiency to cells of specific shape and deliver a drug payload directly to their surface or allow them to be manipulated using external fields. They could benefit the pharmaceutical industry in developing selective antimicrobial therapies and formulations.


Mood instability, mental illness and suicidal ideas: results from a household survey.
There is weak and inconsistent evidence that mood instability (MI) is associated with depression, post traumatic stress disorder (PTSD) and suicidality although the basis of this is unclear. Our objectives were first to test whether there is an association between depression and PTSD, and MI and secondly whether MI exerts an independent effect on suicidal thinking over and above that explained by common mental disorders. We used data from the Adult Psychiatric Morbidity Survey 2007 (N = 7,131). Chi-square tests were used to examine associations between depression and PTSD, and MI, followed by regression modelling to examine associations between MI and depression, and with PTSD. Multiple logistic regression analyses were used to assess the independent effect of MI on suicidal thinking, after adjustment for demographic factors and the effects of common mental disorder diagnoses. There are high rates of MI in depression and PTSD and the presence of MI increases the odds of depression by 10.66 [95% confidence interval (CI) 7.51-15.13] and PTSD by 8.69 (95% CI 5.90-12.79), respectively, after adjusting for other factors. Mood instability independently explained suicidal thinking, multiplying the odds by nearly five (odds ratio 4.82; 95% CI 3.39-6.85), and was individually by some way the most important single factor in explaining suicidal thoughts. MI is strongly associated with depression and PTSD. In people with common mental disorders MI is clinically significant as it acts as an additional factor exacerbating the risk of suicidal thinking. It is important to enquire about MI as part of clinical assessment and treatment studies are required.


In Vitro Exposure to PC-1005 and Cervicovaginal Lavage Fluid from Women Vaginally Administered PC-1005 Inhibits HIV-1 and HSV-2 Infection in Human Cervical Mucosa.
Our recent phase 1 trial demonstrated that PC-1005 gel containing 50 μM MIV-150, 14 mM zinc acetate dihydrate, and carrageenan (CG) applied daily vaginally for 14 days is safe and well tolerated. Importantly, cervicovaginal lavage fluid samples (CVLs) collected 4 or 24 h after the last gel application inhibited HIV-1 and human papillomavirus (HPV) in cell-based assays in a dose-dependent manner (MIV-150 for HIV-1 and CG for HPV). Herein we aimed to determine the anti-HIV and anti-herpes simplex virus 2 (anti-HSV-2) activity of PC-1005 in human cervical explants after in vitro exposure to the gel and to CVLs from participants in the phase 1 trial. Single HIV-1BaL infection and HIV-1BaL-HSV-2 coinfection explant models were utilized. Coinfection with HSV-2 enhanced tissue HIV-1BaL infection. In vitro exposure to PC-1005 protected cervical mucosa against HIV-1BaL (up to a 1:300 dilution) in single-challenge and cochallenge models. CG gel (PC-525) provided some barrier effect against HIV-1BaL at the 1:100 dilution in a single-challenge model but not in the cochallenge model. Both PC-1005 and PC-525 at the 1:100 dilution inhibited HSV-2 infection, pointing to a CG-mediated protection. MIV-150 and CG in CVLs inhibited HIV (single-challenge or cochallenge models) and HSV-2 infections in explants in a dose-dependent manner (P < 0.05). Stronger inhibition of HIV-1 infection by CVLs collected 4 h after the last gel administration was observed compared to infection detected in the presence of baseline CVLs. The anti-HIV and anti-HSV-2 activity of PC-1005 gel in vitro and CVLs in human ectocervical explants supports the further development of PC-1005 gel as a broad-spectrum on-demand microbicide.


Anticancer Properties of Essential Oils: An Overview.
Essential oils are complex mixtures of low molecular weight compounds extracted from plants. Their main constituents are terpenes and phenylpropanoids, which are responsible for their biological and pharmaceutical properties, such as insecticidal, parasiticidal, antimicrobial, antioxidant, anti-inflammatory, analgesic, antinociceptive, anticarcinogenic, and antitumor properties. Cancer is a complex genetic disease considered as a serious public health problem worldwide, accounting for more than 8 million deaths annually. The activities of prevention and treatment of different types of cancer and the medicinal potential of essential oils are addressed in this review. Several studies have demonstrated anti-carcinogenic and antitumor activity for many essential oils obtained from various plant species. They may be used as a substitution to or in addition to conventional anti-cancer therapy. Although many studies report possible mechanisms of action for essential oils compounds, more studies are necessary in order to apply them safely and appropriately in cancer therapy.


Role of early second-trimester uterine artery Doppler screening to predict small-for-gestational-age babies in nulliparous women.
Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown. We sought to determine the utility of early second-trimester uterine artery Doppler studies as a predictor of small-for-gestational-age neonates. Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospective cohort study at 8 institutions across the United States. Participants were seen at 3 study visits during pregnancy and again at delivery. Three indices of uterine artery Doppler flow (resistance index, pulsatility index, and diastolic notching) were measured in the right and left uterine arteries between 16 weeks 0 days' and 22 weeks 6 days' gestation. Test characteristics for varying thresholds in the prediction of small for gestational age (defined as birthweight <5th percentile for gestational age [Alexander growth curve]) were evaluated. Uterine artery Doppler indices, birthweight, and gestational age at birth were available for 8024 women. Birthweight <5th percentile for gestational age occurred in 358 (4.5%) births. Typical thresholds for the uterine artery Doppler indices were all associated with birthweight <5th percentile for gestational age (P < .0001 for each), but the positive predictive values for these cutoffs were all <15% and areas under receiver operating characteristic curves ranged from 0.50-0.60. Across the continuous scales for these measures, the areas under receiver operating characteristic curves ranged from 0.56-0.62. Incorporating maternal age, early pregnancy body mass index, race/ethnicity, smoking status prior to pregnancy, chronic hypertension, and pregestational diabetes in the prediction model resulted in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63-0.66. In this large prospective cohort, early second-trimester uterine artery Doppler studies were not a clinically useful test for predicting small-for-gestational-age babies.


Fixated in unfamiliar territory: Mapping estimates across typical and atypical number lines.
Adults (N = 72) estimated the location of target numbers on number lines that varied in numerical range (i.e., typical range 0-10,000 or atypical range 0-7,000) and spatial orientation (i.e., the 0 endpoint on the left [traditional] or on the right [reversed]). Eye-tracking data were used to assess strategy use. Participants made meaningful first fixations on the line, with fixations occurring around the origin for low target numbers and around the midpoint and endpoint for high target numbers. On traditional direction number lines, participants used left-to-right scanning and showed a leftward bias; these effects were reduced for the reverse direction number lines. Participants made fixations around the midpoint for both ranges but were less accurate when estimating target numbers around the midpoint on the 7,000-range number line. Thus, participants are using the internal benchmark (i.e., midpoint) to guide estimates on atypical range number lines, but they have difficulty calculating the midpoint, leading to less accurate estimates. In summary, both range and direction influenced strategy use and accuracy, suggesting that both numerical and spatial processes influence number line estimation.


Long-term outcome and toxicities of intraoperative radiotherapy for high-risk neuroblastoma.
To review a historical cohort of consecutively accrued patients with high-risk neuroblastoma treated with intraoperative radiotherapy (IORT) to determine the therapeutic effect and late complications of this treatment. Between 1986 and 2002, 31 patients with newly diagnosed high-risk neuroblastoma were treated with IORT as part of multimodality therapy. Their medical records were reviewed to determine the outcome and complications. Kaplan-Meier probability estimates of local control, progression-free survival, and overall survival at 36 months after diagnosis were recorded. Intraoperative radiotherapy to the primary site and associated lymph nodes achieved excellent local control at a median follow-up of 44 months. The 3-year estimate of the local recurrence rate was 15%, less than that of most previously published series. Only 1 of 22 patients who had undergone gross total resection developed recurrence at the primary tumor site. The 3-year estimate of local control, progression-free survival, and overall survival was 85%, 47%, and 60%, respectively. Side effects attributable to either the disease process or multimodality treatment were observed in 7 patients who developed either hypertension or vascular stenosis. These late complications resulted in the death of 2 patients. Intraoperative radiotherapy at the time of primary resection offers effective local control in patients with high-risk neuroblastoma. Compared with historical controls, IORT achieved comparable control and survival rates while avoiding many side effects associated with external beam radiotherapy in young children. Although complications were observed, additional analysis is needed to determine the relative contributions of the disease process and specific components of the multimodality treatment to these adverse events.


[Health and social harm related alcohol].
Alcohol affects the brain and most organs and systems, and its use is related to a large number of health problems. These include mental, neurological, digestive, cardiovascular, endocrine, metabolic, perinatal, cancerous, and infectious diseases, as well as intentional and non-intentional injuries. Physiopathological mechanisms still remain unraveled, though direct toxicity of ethanol and its metabolites, nutritional deficit and intestinal microbial endotoxin absorption have been suggested, all of which would be further modulated by use patterns and genetic and environmental factors. Individually it is difficult to precisely predict who will or will not suffer health consequences. At population level several disorders show a linear or exponential dose-response relationship, as is the case with various cancer types, hepatopathies, injuries, and probably risky behaviors such as unsafe sex. Other health problems such as general mortality in people above 45 years of age, ischemic disease or diabetes mellitus show a J-shaped relationship with alcohol use. The overall effect of alcohol on the global burden of disease is highly detrimental, despite the possible beneficial effect on cardiovascular disease. Large differences are found by country, age, gender, socioeconomic and other factors. Disease burden is mostly related with alcohol's capacity to produce dependence and with acute intoxication. Often alcohol also produces negative consequences for other people (violence, unattended family or work duties, etc) which are generally not taken into account when evaluating burden of disease. The aim of this study was to describe the main alcohol-related social and health harms, as well as their generating mechanisms, using secondary data sources.


Breath-hold PET/CT-guided tumour ablation under general anaesthesia: accuracy of tumour image registration and projected ablation zone overlap.
To assess single-breath-hold combined positron-emission tomography/computed tomography (PET/CT) for accuracy of tumour image registration and projected ablation volume overlap in patients undergoing percutaneous PET/CT-guided tumour-ablation procedures under general anaesthesia. Eight patients underwent 12 PET/CT-guided tumour-ablation procedures to treat 20 tumours in the lung, liver, or adrenal gland. Using breath-hold PET/CT, the centre of the tumour was marked on each PET and CT acquisition by four readers to assess two- (2D) and three-dimensional (3D) spatial misregistration. Overlap of PET and CT projected ablation volumes were compared using the Dice similarity coefficient (DSC). Interobserver differences were assessed with repeated measure analysis of variance (ANOVA). Technical success and local progression rates were noted. Mean tumour 2D PET/CT misregistrations were 1.02 mm (range 0.01-5.02), 1.89 (0.03-7.85), and 3.05 (0-10) in the x, y, and z planes. Mean 3D misregistration was 4.4 mm (0.36-10.74). Mean projected PET/CT ablation volume DSC was 0.72 (±0.19). No significant interobserver differences in 3D misregistration (p=0.73) or DSC (p=0.54) were observed. Technical success of ablations was 100%; one (5.3%) of 19 tumours progressed. Accurate spatial registration of tumours and substantial overlap of projected ablation volumes are achievable when comparing PET and CT acquisitions from single-breath-hold PET/CT. The results suggest that tumours visible only at PET could be accurately targeted and ablated using this technique.


Disparate mesenchyme-lineage tendencies in mesenchymal stem cells from human bone marrow and umbilical cord blood.
Bone marrow and umbilical cord blood are reported to be the main sources of mesenchymal stem cells (MSCs), which have been proposed for many clinical applications. This study evaluated and quantitated the differentiation potential of bone marrow-derived MSCs (bmMSCs) and cord blood-derived MSCs (cbMSCs) by in vitro induction. Results indicated that cbMSCs had a significantly stronger osteogenic potential but lower capacity for adipogenic differentiation than bmMSCs. Leptin, an important regulator of mesenchymal differentiation, has a significantly stronger effect of promoting osteogenesis and inhibiting adipogenesis in bmMSCs than in cbMSCs. Moreover, Cbfa1 mRNA expression in bmMSCs and cbMSCs was affected to different degrees by leptin during osteogenesis. In contrast, leptin reduced PPARgamma2 mRNA expression to the same level during adipogenesis in both types of MSCs. These results demonstrate the disparate capacities of MSCs from bone marrow and cord blood and suggest that they be used differently in experimental and therapeutic studies. In addition, the disparate differentiation tendencies of MSCs from different sources should be considered in further applications.