[Embolization of esophageal varices by the transjugular route in severe digestive hemorrhage in cirrhotic patients. Prospective study of 83 patients].
A prospective study was undertaken to assess the results of embolization of esophageal varices by the transjugular approach, in 83 patients with advanced cirrhosis (65 p. 100 Child's class C) admitted with severe bleeding (mean of 10 units of blood per patient). Embolization was successfully completed in 65 patients (78 p. 100) and complete obliteration was achieved in 50 (60 p. 100). Twenty-nine procedures were performed on actively bleeding patients. Cessation of bleeding was observed in 22 (76 p. 100). Excluding the 5 patients in whom embolization could not be achieved, the success rate was 92 p. 100. Embolization was attempted as an elective procedure in 54 patients who were not actively bleeding. Recurrent hemorrhage occurred in 18 patients (33 p. 100) during the first month of follow-up. Finally, 38 patients rebled and 57 died. No accident could be ascribed to the procedure. It is concluded that: (a) the transjugular approach proved to be safe in actively bleeding patients with severe cirrhosis; (b) variceal obliteration effectively controlled active bleeding. The efficacy of this procedure was limited in time. The use of embolization is further hindered by a consistent failure rate and by the development of new therapeutic modalities, such as sclerotherapy.


An alternative strategy for perinatal verbal autopsy coding: single versus multiple coders.
To determine the comparability between cause of death (COD) by a single physician coder and a two-physician panel, using verbal autopsy. The study was conducted between May 2007 and June 2008. Within a week of a perinatal death in 38 rural remote communities in Guatemala, the Democratic Republic of Congo, Zambia and Pakistan, VA questionnaires were completed. Two independent physicians, unaware of the others decisions, assigned an underlying COD, in accordance with the causes listed in the chapter headings of the International classification diseases and related health problems, 10th revision (ICD-10). Cohen's kappa statistic was used to assess level of agreement between physician coders. There were 9461 births during the study period; 252 deaths met study enrolment criteria and underwent verbal autopsy. Physicians assigned the same COD for 75% of stillbirths (SB) (K = 0.69; 95% confidence interval: 0.61-0.78) and 82% early neonatal deaths (END) (K = 0.75; 95% confidence interval: 0.65-0.84). The patterns and proportion of SBs and ENDs determined by the physician coders were very similar compared to causes individually assigned by each physician. Similarly, rank order of the top five causes of SB and END was identical for each physician. This study raises important questions about the utility of a system of multiple coders that is currently widely accepted and speculates that a single physician coder may be an effective and economical alternative to VA programmes that use traditional two-physician panels to assign COD.


Comparison of intravenous ephedrine with phenylephrine for the maintenance of arterial blood pressure during elective caesarean section under spinal anaesthesia.
Hypotension is a major concern of the anaesthetists whenever subarachnoid block is performed especially in obstetric patients. Vasopressors have been shown to be more effective at limiting spinal hypotension than other treatment of hypotension like preloading and left uterine displacement. The aim of the study is to compare the effect of bolus intravenous Ephedrine with Phenylephrine for the maintenance of arterial blood pressure during elective caesarean section under spinal anaesthesia. This was a randomized, double blind, controlled study of sixty two healthy parturients American Society of Anesthesiologists' (ASA) status 1 and 2 at term with singleton pregnancy who consented to subarachnoid block at University College Hospital, Ibadan, Nigeria. The parturients were preloaded with 10 ml per kg of crystalloid before the induction of spinal anaesthesia with injection of 2.5 ml of 0.5% hyperbaric Bupivacaine at L3/L4 levels. Ephedrine 5 mg (group A; n = 31) or phenylephrine 100 ug (group B; n = 31) was given for the maintenance of arterial blood pressure. Results showed that the incidence of hypotension in the 62 patients was 24.2%. Both vasopressors effectively restored both the systolic and the diastolic blood pressure. There was significant difference in heart rate between the two groups. Nausea occurred in both groups and was found in hypotensive patients, no patient vomited during the procedure. The mean APGAR Scores were similar for the two groups; no baby had Apgar score of < 8 in either group. We concluded that phenylephrine is safe and can be used as effectively as Ephedrine. Its administration results in higher blood pressure than Ephedrine in parturients undergoing Caesarean Section under spinal anaesthesia.


Why are fewer women rising to the top? A life history gender analysis of Cambodia's health workforce.
An adequate and qualified health workforce is critical for achieving Universal Health Coverage (UHC) and responding to the Sustainable Development Goals (SDGs). Frontline health workers who are mainly women, play important roles in responses to crisis. Despite women making up the vast majority of the health workforce, men occupy the majority of leadership positions. This study aims to understand the career progression of female health workers by exploring how gender norms influence women's upward career trajectories. A qualitative methodology deployed a life history approach was used to explore the perspectives and experiences of health workers in Battambang province, Cambodia. Twenty male and female health managers were purposively selected based five criteria: age 40 and above, starting their career during 1980s or 1990s, clinical skills, management roles and evidence of career progression. Themes and sub-themes were developed based on available data and informed by Tlaiss's (2013) social theory framework in order to understand how gender norms, roles and relations shape the career of women in the health industry. The findings from life histories show that gender norms shape men's and women's career progression at different levels of society. At the macro level, social, cultural, political, and gender norms are favorably changing by allowing more women to enter medical education; however, leadership is bias towards men. At the meso organziational level, empowerment of women in the health sector has increased with the support of gender working groups and women's associations. At the micro individual level, female facility managers identified capacity and qualifications as important factors in helping women to obtain leadership positions. While Cambodia has made progress, it still has far to go to achieve equality in leadership. Promoting gender equity in leadership within the health workforce requires a long vision and commitment along with collaboration among different stakeholders and across social structures. If more women are not able to obtain leadership roles, the goals of having an equitable health system, promoting UHC, and responding to the SDGs milestones by leaving no one behind will remain unattainable objectives.


A Solar Altitude Angle Model for Efficient Solar Energy Predictions.
Sunlight is one of the most frequently used ambient energy sources for energy harvesting in wireless sensor networks. Although virtually unlimited, solar radiation experiences significant variations depending on the weather, the season, and the time of day, so solar-powered nodes commonly employ solar prediction models to effectively adapt their energy demands to harvesting dynamics. We present in this paper a novel energy prediction model that makes use of the altitude angle of the sun at different times of day to predict future solar energy availability. Unlike most of the state-of-the-art predictors that use past energy observations to make predictions, our model does not require one to maintain local energy harvesting patterns of past days. Performance evaluation shows that our scheme is able to provide accurate predictions for arbitrary forecasting horizons by performing just a few low complexity operations. Moreover, our proposal is extremely simple to set up since it does not require any particular tuning for each different scenario or location.


Australian surfers' awareness of 'surfer's ear'.
To assess awareness of external auditory exostosis (EAE) among Australian surfers. This is a cross-sectional observational study, assessing professional and recreational Australian surfers. Currently, active surfers over 18 years of age, surfing year-round, were eligible to participate. After initial screening, individuals were asked to complete a questionnaire. All included volunteers underwent bilateral otoscopic examination, to assess the presence and severity of EAE. A total of 113 surfers were included in the study and were divided into two groups, based on surfing status: 93 recreational surfers and 20 professional surfers. Recreational surfers were significantly older (p<0.005), more experienced (greater years surfing; p<0.005), with lower prevalence of otological symptoms (p<0.05). The most common symptoms were water trapping, impacted wax and hearing loss. Prevalence of EAE was high for both groups (95% in the professional surfers and 82.8% in the recreational surfers); however, recreational surfers had mild grade EAE (grade 1) as the most common presentation, as opposed to professionals who had severe grade EAE (grade 3) as the most common presentation (p<0.05 between groups). Awareness of the term 'surfer's ear' was high for both groups, as was knowledge of prevention options. However, fewer considered the condition to be preventable, and an even lower number reported regular use of prevention methods. Australian surfers had a high level of awareness of EAE; however, few reported using prevention methods, despite having a high prevalence of the condition. Health practitioners should screen susceptible individuals in order to recommend appropriate preventive measures.


YjbH is a novel negative effector of the disulphide stress regulator, Spx, in Bacillus subtilis.
In the soil bacterium Bacillus subtilis Spx is a key regulator that controls expression, positively or negatively, of several genes in response to certain oxidative stresses that lead to the formation of unwanted disulphide bonds. Here we characterized the yjbH gene and show that it encodes a novel effector of Spx. The yjbH gene is part of the yjbIH operon that encodes a truncated haemoglobin (YjbI) and a predicted 34 kDa cytosolic protein of unknown function (YjbH). Deletion of yjbIH or yjbH has pleiotropic effects and affects growth, sporulation and competence development. Cells lacking yjbIH display a reduced sensitivity to the thiol oxidant diamide and show an apparent down- or upregulation of several transcripts that belong to the Spx regulon. Twenty-two suppressor mutations that bypass the defects conferred by yjbH were isolated. These mutations were identified as six deletions, three nonsense and 11 missense substitutions in the spx gene. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed that mutations in yjbIH or yjbH do not affect the level of spx transcription. The combined data from the present work show that strains lacking yjbIH or yjbH overproduce Spx under unperturbed growth. The elevated Spx concentration cannot be attributed to an increased spx expression but is likely to result from control at the post-transcriptional level. YjbH is proposed to affect the cellular concentration of Spx by modulating proteolysis via the ClpXP protease.


Creating a scale to measure motivation to achieve academically: linking attitudes and behaviours using Rasch measurement.
Motivation to Achieve Academically has been used in many educational and other studies in many countries and the large majority has not used an interval level scale based on a good theoretical model in which the items are linked to behaviour. One, to create an interval level, unidimensional scale of Motivation, with attitude items linked to behaviour items, based on a conceptual model of Motivation, involving Striving for Excellence (Standards, Goals, Tasks, Effort, Values and Ability), Desire to Learn (Interest, Learning from Others and Responsibility for Learning), and Rewards (Extrinsic, Intrinsic and Social). Two, to analyse its psychometric properties using the Extended Logistic Model of Rasch (Andrich, 1988a, 1988b; Rasch, 1980/1960). Three, to investigate the structure and meaning of the scale. The convenience person sample was 239 first-year students selected for three special entry programmes at an Australian university. The stem-item sample was initially 45, reduced to 24, that fitted the measurement model to form a valid and reliable scale. Based on recent literature, a conceptual model of Motivation was devised and items written in line with the model. Data were collected by self-report questionnaire and analysed with the computer program Rasch Unidimensional Measurement Models (RUMM) (Andrich, Lyne, Sheridan, & Luo, 1998). A scale was created in which the Motivation measures were calibrated on the same scale as the item 'difficulties'. Twenty-four Motivation items fitted the model and were 'easier' than their corresponding behaviour items, as conceptualised. They formed an excellent scale in which the proportion of observed variance considered true was 0.93. Items from all aspects of the Motivation model named in the aims above, except Ability and Extrinsic Rewards, fitted the measurement model. The Rasch model and the RUMM computing program were very useful in creating a unidimensional, interval level scale of Motivation to achieve academically, with good psychometric properties.


Tracheal reconstruction: mucosal survival on porous titanium.
To investigate whether porous titanium can provide a better support for revascularization of a mucosal graft ideal for tracheal reconstruction. In patients with laryngotracheal stenosis or tumor, the mucosa with supporting structures can be damaged, resulting in a defect that has to be reconstructed. Autologous tissues like cartilage and mucosa have been used for reconstruction. The main problem has been incomplete mucosal reepithelialization. In the first experiment, porous titanium or ear cartilage was combined with mucosa and implanted subcutaneously in athymic mice for different periods of time. In the second experiment, using rabbits, surgically created defects were reconstructed with porous titanium and mucosa on a pedicled fascia flap using a 2-stage procedure. The implants were analyzed with emphasis on angiogenesis and mucosal survival. Male New Zealand white rabbits and nude athymic mice (BALB-c nu/nu). Normal mucosa having a submucosal layer with vital cells was noted on top of the titanium. Multiple blood vessels were observed extending from the muscle layer through the titanium. Cytokeratin expression was detected in the suprabasal and basal layers of the mucosal epithelium. In contrast, the mucosa on cartilage showed no vital cells and no cytokeratin expression. In the rabbit experiment, all animals survived the reconstruction. The titanium was well integrated to the adjacent tracheal cartilage and surrounding tissues, supporting a fully vital mucosa. Porous titanium is an inert biomaterial that provides support and allows easy revascularization of a mucosal graft. Titanium, in combination with viable autologous tissues, is a good alternative for tracheal reconstruction.


Feasibility of Augmenting Ankle Exoskeleton Walking Performance With Step Length Biofeedback in Individuals With Cerebral Palsy.
Most people with cerebral palsy (CP) suffer from impaired walking ability and pathological gait patterns. Seeking to improve the effectiveness of gait training in this patient population, this study developed and assessed the feasibility of a real-time biofeedback mechanism to augment untethered ankle exoskeleton-assisted walking performance in individuals with CP. We selected step length as a clinically-relevant gait performance target and utilized a visual interface with live performance scores. An adaptive ankle exoskeleton control algorithm provided assistance proportional to the real-time ankle moment. We assessed lower-extremity gait mechanics and muscle activity in seven ambulatory individuals with CP as they walked with adaptive ankle assistance alone and with ankle assistance plus step-length biofeedback. We achieved our technical validation goal by demonstrating a strong correlation between estimated step length and real step length (R = 0.771, p < 0.001). We achieved our clinical feasibility goal by demonstrating that biofeedback-plus-assistance resulted in a 14% increase in step length relative to baseline (p ≤ 0.05), while no difference in step length was observed for assistance alone. Additionally, we observed near immediate improvements in lower-extremity posture, moments, and positive power relative to baseline for biofeedback-plus-assistance (p < 0.05), with none, or more-limited improvements observed for assistance alone. Our findings suggest that providing real-time biofeedback and using step length as the target can be effective for increasing the rate at which individuals with CP improve their gait mechanics when walking with wearable ankle assistance.


How the COVID-19 pandemic has changed our lives: A study of psychological correlates across 59 countries.
This study examined the impact of the COVID-19 pandemic and subsequent social restrictions or quarantines on the mental health of the global adult population. A sample of 6,882 individuals (Mage = 42.30; 78.8% female) from 59 countries completed an online survey asking about several pandemic-related changes in life and psychological status. Of these participants, 25.4% and 19.5% reported moderate-to-severe depression (DASS-21) and anxiety symptoms (GAD-7), respectively. Demographic characteristics (e.g. higher-income country), COVID-19 exposure (e.g., having had unconfirmed COVID-19 symptoms), government-imposed quarantine level, and COVID-19-based life changes (e.g., having a hard time transitioning to working from home; increase in verbal arguments or conflict with other adult in home) explained 17.9% of the variance in depression and 21.5% in anxiety symptoms. In addition to posing a high risk to physical health, the COVID-19 pandemic has robustly affected global mental health, so it is essential to ensure that mental health services reach individuals showing pandemic-related depression and anxiety symptoms.


Extended mechanical force measurements using structured illumination microscopy.
Quantifying cell generated mechanical forces is key to furthering our understanding of mechanobiology. Traction force microscopy (TFM) is one of the most broadly applied force probing technologies, but its sensitivity is strictly dependent on the spatio-temporal resolution of the underlying imaging system. In previous works, it was demonstrated that increased sampling densities of cell derived forces permitted by super-resolution fluorescence imaging enhanced the sensitivity of the TFM method. However, these recent advances to TFM based on super-resolution techniques were limited to slow acquisition speeds and high illumination powers. Here, we present three novel TFM approaches that, in combination with total internal reflection, structured illumination microscopy and astigmatism, improve the spatial and temporal performance in either two-dimensional or three-dimensional mechanical force quantification, while maintaining low illumination powers. These three techniques can be straightforwardly implemented on a single optical set-up offering a powerful platform to provide new insights into the physiological force generation in a wide range of biological studies. This article is part of the Theo Murphy meeting issue 'Super-resolution structured illumination microscopy (part 1)'.


Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders.
To characterize the role of rare complete human knockouts in autism spectrum disorders (ASDs), we identify genes with homozygous or compound heterozygous loss-of-function (LoF) variants (defined as nonsense and essential splice sites) from exome sequencing of 933 cases and 869 controls. We identify a 2-fold increase in complete knockouts of autosomal genes with low rates of LoF variation (≤ 5% frequency) in cases and estimate a 3% contribution to ASD risk by these events, confirming this observation in an independent set of 563 probands and 4,605 controls. Outside the pseudoautosomal regions on the X chromosome, we similarly observe a significant 1.5-fold increase in rare hemizygous knockouts in males, contributing to another 2% of ASDs in males. Taken together, these results provide compelling evidence that rare autosomal and X chromosome complete gene knockouts are important inherited risk factors for ASD.


Epigenetic changes in umbilical cord mesenchymal stromal cells upon stimulation and culture expansion.
Mesenchymal stromal cells (MSCs) are studied for their immunotherapeutic potential. Prior to therapeutic use, MSCs are culture expanded to obtain the required cell numbers and, to improve their efficacy, MSCs may be primed in vitro. Culture expansion and priming induce phenotypical and functional changes in MSCs and thus standardisation and quality control measurements come in need. We investigated the impact of priming and culturing on MSC DNA methylation and examined the use of epigenetic profiling as a quality control tool. Human umbilical cord-derived MSCs (ucMSCs) were cultured for 3 days with interferon (IFN)γ, transforming growth factor (TGF)β or a multi-factor combination (MC; IFNγ, TGFβ and retinoic acid). In addition, ucMSCs were culture expanded for 14 days. Phenotypical changes and T-cell proliferation inhibition capacity were examined. Genome-wide DNA methylation was measured with Infinium MethylationEPIC Beadchip. Upon priming, ucMSCs exhibited a different immunophenotype and ucMSC(IFNγ) and ucMSC(MC) had an increased capacity to inhibit T-cell proliferation. DNA methylation patterns were minimally affected by priming, with only one significantly differentially methylated site (DMS) in IFNγ- and MC-primed ucMSCs associated with autophagy activity. In contrast, 14 days after culture expansion, ucMSCs displayed minor phenotypical and functional changes but showed >4000 significantly DMSs, mostly concerning genes involved in membrane composition, cell adhesion and transmembrane signalling. These data show that DNA methylation of MSCs is only marginally affected by priming, whereas culture expansion and subsequent increased cellular interactions have a large impact on methylation. On account of this study, we suggest that DNA methylation analysis is a useful quality control tool for culture expanded therapeutic MSCs.


Having older siblings is associated with gut microbiota development during early childhood.
Evidence suggests that early life infections, presence of older siblings and furred pets in the household affect the risk of developing allergic diseases through altered microbial exposure. Recently, low gut microbial diversity during infancy has also been linked with later development of allergies. We investigated whether presence of older siblings, furred pets and early life infections affected gut microbial communities at 9 and 18 months of age and whether these differences were associated with the cumulative prevalence of atopic symptoms of eczema and asthmatic bronchitis at 3 years of age. Bacterial compositions and diversity indices were determined in fecal samples collected from 114 infants in the SKOT I cohort at age 9 and 18 months by 16S rRNA gene sequencing. These were compared to the presence of older siblings, furred pets and early life infections and the cumulative prevalence of diagnosed asthmatic bronchitis and self-reported eczema at 3 years of age. The number of older siblings correlated positively with bacterial diversity (p = 0.030), diversity of the phyla Firmicutes (p = 0.013) and Bacteroidetes (p = 0.004) and bacterial richness (p = 0.006) at 18 months. Further, having older siblings was associated with increased relative abundance of several bacterial taxa at both 9 and 18 months of age. Compared to the effect of having siblings, presence of household furred pets and early life infections had less pronounced effects on the gut microbiota. Gut microbiota characteristics were not significantly associated with cumulative occurrence of eczema and asthmatic bronchitis during the first 3 years of life. Presence of older siblings is associated with increased gut microbial diversity and richness during early childhood, which could contribute to the substantiation of the hygiene hypothesis. However, no associations were found between gut microbiota and atopic symptoms of eczema and asthmatic bronchitis during early childhood and thus further studies are required to elucidate whether sibling-associated gut microbial changes influence development of allergies later in childhood.


Genetic diversity and phylogeography in two diploid ferns, Asplenium fontanum subsp. fontanum and A. petrarchae subsp. bivalens, in the western Mediterranean.
Asplenium fontanum subsp. fontanum and A. petrarchae subsp. bivalens are diploid rock ferns of limestone outcrops of the western Mediterranean region. Asplenium fontanum subsp. fontanum occurs from Valencia through northeastern Spain to the Alpes-Maritimes and Swiss Jura. Asplenium petrarchae subsp. bivalens occurs only on Majorca, in Valencia and possibly in southern Spain. We analysed allozyme and chloroplast genetic marker diversity in 75 populations of A. fontanum subsp. fontanum and 12 populations of A. petrarchae subsp. bivalens sampled from across their respective ranges. The two species show similar levels of species and population genetic diversity to one another and to other diploid European Asplenium taxa. Both are predominantly outbreeding, as indicated by F(IS) = 0.108 and 0.167 respectively. Substantial between-population differentiation results largely from differentiation between regions. Isolation by distance operates over limited geographic ranges, up to 50 km. In A. fontanum subsp. fontanum, the major geographical differentiation between Valencia and the rest of the taxon range probably represents an ancient range fragmentation. A less pronounced differentiation divides populations in the SW from those in the NE of the range, with evidence for a biogeographic link between the eastern Pyrenees and southeastern France. High diversity in the Pyrenees may either represent ancient population differentiation, or a suture zone. In A. petrarchae subsp. bivalens, populations on Majorca exhibit a subset of the genetic diversity present in Valencia, although the two regions are strongly differentiated by differing allele frequencies. Dispersal from the mainland may have founded Majorcan populations, although a role for in situ island survival cannot be excluded.


Assessing health status and quality-of-life instruments: attributes and review criteria.
The field of health status and quality of life (QoL) measurement - as a formal discipline with a cohesive theoretical framework, accepted methods, and diverse applications--has been evolving for the better part of 30 years. To identify health status and QoL instruments and review them against rigorous criteria as a precursor to creating an instrument library for later dissemination, the Medical Outcomes Trust in 1994 created an independently functioning Scientific Advisory Committee (SAC). In the mid-1990s, the SAC defined a set of attributes and criteria to carry out instrument assessments; 5 years later, it updated and revised these materials to take account of the expanding theories and technologies upon which such instruments were being developed. This paper offers the SAC's current conceptualization of eight key attributes of health status and QoL instruments (i.e., conceptual and measurement model; reliability; validity; responsiveness; interpretability; respondent and administrative burden; alternate forms; and cultural and language adaptations) and the criteria by which instruments would be reviewed on each of those attributes. These are suggested guidelines for the field to consider and debate; as measurement techniques become both more familiar and more sophisticated, we expect that experts will wish to update and refine these criteria accordingly.


Exercise-based cardiac rehabilitation in heart transplant recipients.
Heart transplantation is considered to be the gold standard treatment for selected patients with end-stage heart disease when medical therapy has been unable to halt progression of the underlying pathology. Evidence suggests that aerobic exercise training may be effective in reversing the pathophysiological consequences associated with cardiac denervation and prevent immunosuppression-induced adverse effects in heart transplant recipients. To determine the effectiveness and safety of exercise-based rehabilitation on the mortality, hospital admissions, adverse events, exercise capacity, health-related quality of life, return to work and costs for people after heart transplantation. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO) and Web of Science Core Collection (Thomson Reuters) to June 2016. We also searched two clinical trials registers and handsearched the reference lists of included studies. We included randomised controlled trials (RCTs) of parallel group, cross-over or cluster design, which compared exercise-based interventions with (i) no exercise control (ii) a different dose of exercise training (e.g. low- versus high-intensity exercise training); or (iii) an active intervention (i.e. education, psychological intervention). The study population comprised adults aged 18 years or over who had received a heart transplant. Two review authors independently screened all identified references for inclusion based on pre-specified inclusion criteria. Disagreements were resolved by consensus or by involving a third person. Two review authors extracted outcome data from the included trials and assessed their risk of bias. One review author extracted study characteristics from included studies and a second author checked them against the trial report for accuracy. We included 10 RCTs that involved a total of 300 participants whose mean age was 54.4 years. Women accounted for fewer than 25% of all study participants. Nine trials which randomised 284 participants to receive exercise-based rehabilitation (151 participants) or no exercise (133 participants) were included in the main analysis. One cross-over RCT compared high-intensity interval training with continued moderate-intensity training in 16 participants. We reported findings for all trials at their longest follow-up (median 12 weeks).Exercise-based cardiac rehabilitation increased exercise capacity (VO2peak) compared with no exercise control (MD 2.49 mL/kg/min, 95% CI 1.63 to 3.36; N = 284; studies = 9; moderate quality evidence). There was evidence from one trial that high-intensity interval exercise training was more effective in improving exercise capacity than continuous moderate-intensity exercise (MD 2.30 mL/kg/min, 95% CI 0.59 to 4.01; N = 16; 1 study). Four studies reported health-related quality of life (HRQoL) measured using SF-36, Profile of Quality of Life in the Chronically Ill (PLC) and the World Health Organization Quality Of Life (WHOQoL) - BREF. Due to the variation in HRQoL outcomes and methods of reporting we were unable to meta-analyse results across studies, but there was no evidence of a difference between exercise-based cardiac rehabilitation and control in 18 of 21 HRQoL domains reported, or between high and moderate intensity exercise in any of the 10 HRQoL domains reported. One adverse event was reported by one study.Exercise-based cardiac rehabilitation improves exercise capacity, but exercise was found to have no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients whose health is stable.There was no evidence of statistical heterogeneity across trials for exercise capacity and no evidence of small study bias. The overall risk of bias in included studies was judged as low or unclear; more than 50% of included studies were assessed at unclear risk of bias with respect to allocation concealment, blinding of outcome assessors and declaration of conflicts of interest. Evidence quality was assessed as moderate according to GRADE criteria. We found moderate quality evidence suggesting that exercise-based cardiac rehabilitation improves exercise capacity, and that exercise has no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients. Cardiac rehabilitation appears to be safe in this population, but long-term follow-up data are incomplete and further good quality and adequately-powered trials are needed to demonstrate the longer-term benefits of exercise on safety and impact on both clinical and patient-related outcomes, such as health-related quality of life, and healthcare costs.


Suicide among animals: a review of evidence.
Naturalists have not identified suicide in nonhuman species in field situations, despite intensive study of thousands of animal species. In this review, evidence on suicidal behavior among animals is analyzed to discover analogies with human suicidal behavior. Literature was retrieved by exploring Medline/PubMed and PsychINFO databases (1967-2007) and through manual literature searches. Keyword terms were "suicide or suicidal behavior" and "animal or animal behavior." Few empirical investigations have been carried out on this topic. Nevertheless, sparse evidence supports some resemblance between the self-endangering behavior observed in the animal kingdom, particularly in animals held in captivity or put under pressure by environmental challenges, and suicidal behavior among humans. Animal models have contributed to the study of both normal and pathological human behaviors: discovering some correlates of suicide among animals could be a valid contribution to the field.


Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy.
Anaemia frequently complicates peginterferon/ribavirin therapy for chronic hepatitis C infection. Better prediction of anaemia, ribavirin dose reduction or erythropoietin (EPO) need, may enhance patient management. Inosine triphosphatase (ITPA) genetic variants are associated with ribavirin-induced anaemia and dose reduction; however, their impact in real-life clinic patient cohorts remains to be defined. We studied 193 clinic patients with chronic hepatitis C infection of mixed viral genotype (genotype 1/4 n = 123, genotype 2/3, n = 70) treated with peginterferon/ribavirin. Patients were genotyped for ITPA polymorphisms rs1127354 and rs7270101 using Taqman primers. Hardy-Weinberg equilibrium was present. Estimated ITPA deficiency was graded on severity (0-3, no deficiency/mild/moderate/severe, n = 126/40/24/3, respectively). Multivariable models tested the association with anaemia at 4 weeks of treatment [including decline in haemoglobin (g/dL); haemoglobin <10 g/dL and haemoglobin decline >3 g/dL]; ribavirin dose reduction and EPO use and explored sustained viral response (SVR) to peginterferon/ribavirin. More severe ITPA deficiency was associated with less reduction in haemoglobin level (P <0.001; R(2) = 0.34), less ribavirin dose reduction (OR 0.42; (95% CI = 0.23-0.77); P = 0.005) and less EPO use [OR 0.53; (0.30-0.94); P = 0.029]. ITPA deficiency was associated with SVR [OR: 1.70; (1.02-2.83); P = 0.041] independently of clinical covariates (adjusted R(2) = 0.31). In this clinical cohort, ITPA deficiency helped predict the risk of on-treatment anaemia, ribavirin dose reduction, need for EPO support and was associated with SVR. For patients on HCV regimens including peginterferon/ribavirin, testing for ITPA deficiency may have clinical utility.


Displacement of oropharyngeal structures during suction-swallowing cycles.
Suction ability plays an important role in supporting oral nutrition and needs special care following neurological disorders and tumor-associated defects. However, the details of suction are still poorly understood. The present study evaluates displacement of orofacial structures during suction and deglutition based on manometric controlled MRI. Nine healthy subjects were scanned wearing an intraoral mouthpiece for water intake by suction and subsequent swallowing. Suction-swallowing cycles were identified by intraoral negative pressure. Midsagittal MRI slices (3 T; temporal resolution 0.53 s) were analyzed at rest, suction and pharyngeal swallowing. The mandibular displacement was measured as the distance between the anterior nasal spine and the inferior point of the mandible. Following areas were defined: subpalatal compartment (SCA), retrolingual (RLA), epipharyngeal (EPA) and mouth floor area (MFA). During rest, an average distance of 7 cm was observed between the mandibular measurement points. The measured SCA was 3.67 cm(2), the RLA 6.98 cm(2), the EPA 9.00 cm(2) and the MFA 15.21 cm(2) (average values). At the end of suction, the mandibular distance reduces (to 6.88 cm), the SCA increases significantly (to 5.96 cm(2); p = 0.0002), the RLA decreases (to 6.45 cm(2)), the EPA increases (to 10.59 cm(2)) and the MFA decreases (to 15.02 cm(2)). During deglutition, the mandible lifted significantly (to 6.81 cm; p = 0.0276), the SCA reduced to zero, the RLA was not measurable, the EPA reduces significantly (to 3.01 cm(2); p < 0.0001) and the MFA increases (to 16.36 cm(2)). According to these observations, a combined displacement of the tongue in an anteroposterior direction with active tongue dorsum-velum contact appears to be the predominant activity during suction and responsible for the expansion of the subpalatal area.


Microbial communities associated with anaerobic benzene degradation in a petroleum-contaminated aquifer.
Microbial community composition associated with benzene oxidation under in situ Fe(III)-reducing conditions in a petroleum-contaminated aquifer located in Bemidji, Minn., was investigated. Community structure associated with benzene degradation was compared to sediment communities that did not anaerobically oxidize benzene which were obtained from two adjacent Fe(III)-reducing sites and from methanogenic and uncontaminated zones. Denaturing gradient gel electrophoresis of 16S rDNA sequences amplified with bacterial or Geobacteraceae-specific primers indicated significant differences in the composition of the microbial communities at the different sites. Most notable was a selective enrichment of microorganisms in the Geobacter cluster seen in the benzene-degrading sediments. This finding was in accordance with phospholipid fatty acid analysis and most-probable-number-PCR enumeration, which indicated that members of the family Geobacteraceae were more numerous in these sediments. A benzene-oxidizing Fe(III)-reducing enrichment culture was established from benzene-degrading sediments and contained an organism closely related to the uncultivated Geobacter spp. This genus contains the only known organisms that can oxidize aromatic compounds with the reduction of Fe(III). Sequences closely related to the Fe(III) reducer Geothrix fermentans and the aerobe Variovorax paradoxus were also amplified from the benzene-degrading enrichment and were present in the benzene-degrading sediments. However, neither G. fermentans nor V. paradoxus is known to oxidize aromatic compounds with the reduction of Fe(III), and there was no apparent enrichment of these organisms in the benzene-degrading sediments. These results suggest that Geobacter spp. play an important role in the anaerobic oxidation of benzene in the Bemidji aquifer and that molecular community analysis may be a powerful tool for predicting a site's capacity for anaerobic benzene degradation.


Self-reported physical activity and objective aerobic fitness: differential associations with gray matter density in healthy aging.
Aerobic fitness (AF) and self-reported physical activity (srPA) do not represent the same construct. However, many exercise and brain aging studies interchangeably use AF and srPA measures, which may be problematic with regards to how these metrics are associated with brain outcomes, such as morphology. If AF and PA measures captured the same phenomena, regional brain volumes associated with these measures should directly overlap. This study employed the general linear model to examine the differential association between objectively-measured AF (treadmill assessment) and srPA (questionnaire) with gray matter density (GMd) in 29 cognitively unimpaired community-dwelling older adults using voxel based morphometry. The results show significant regional variance in terms of GMd when comparing AF and srPA as predictors. Higher AF was associated with greater GMd in the cerebellum only, while srPA displayed positive associations with GMd in occipito-temporal, left perisylvian, and frontal regions after correcting for age. Importantly, only AF level, and not srPA, modified the relationship between age and GMd, such that higher levels of AF were associated with increased GMd in older age, while decreased GMd was seen in those with lower AF as a function of age. These results support existing literature suggesting that both AF and PA exert beneficial effects on GMd, but only AF served as a buffer against age-related GMd loss. Furthermore, these results highlight the need for use of objective PA measurement and comparability of tools across studies, since results vary dependent upon the measures used and whether these are objective or subjective in nature.


Dual-coil magnetomotive optical coherence tomography for contrast enhancement in liquids.
Magnetomotive optical coherence tomography (MM-OCT) is a functional extension of OCT which utilizes magnetically responsive materials that are modulated by an external magnetic field for contrast enhancement and for elastography to assess the structural and viscoelastic properties of the surrounding tissues. Traditionally, magnetomotive contrast relies on the interaction between the displacement of magnetic particles induced by an external magnetic field and the micro-environmental restoring (elastic) force acting on the particles. When the restoring force from a sample containing magnetic particles is weak or non-existent, the MM-OCT signal-to-noise ratio (SNR) can degrade significantly. We have developed a novel solenoid configuration to enable MM-OCT imaging in samples that do not have an elastic restoring force, such as liquids. This coil configuration may potentially enable real-time MM-OCT imaging.


Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits.
Irritable bowel syndrome (IBS) patients show pain hypersensitivity and hypercontractility in response to colonic or rectal distention. Aims were to determine whether predominant bowel habits and IBS symptom severity are related to pain sensitivity, colon motility, or smooth muscle tone. One hundred twenty-nine patients classified as IBS with diarrhea (IBS-D, N = 44), IBS with constipation (IBS-C, N = 29), mixed IBS (IBS-M, N = 45), and unspecified IBS (IBS-U, N = 11) based on stool consistency, and 30 healthy controls (HC) were studied. A manometric catheter containing a 600-mL capacity plastic bag was positioned in the descending colon. Pain threshold was assessed using a barostat. Motility was assessed for 10 min with the bag minimally inflated (individual operating pressure [IOP]), 10 min at 20 mmHg above the IOP, and for 15-min recovery following bag inflation. Motility was also recorded for 30 min following an 810-kcal meal. Compared with HC, IBS patients had lower pain thresholds (medians 30 vs 40 mmHg, P < 0.01), but IBS subtypes were not different. IBS symptom severity was correlated with pain thresholds (rho =-0.36, P < 0.001). During distention, the motility index (MI) was significantly higher in IBS compared with HC (909 +/- 73 vs 563 +/- 78, P < 0.01). Average barostat bag volume at baseline was higher (muscle tone lower) in HC compared with IBS-D and IBS-M but not compared with IBS-C. The baseline MI and bag volume differed between IBS-D and IBS-C and correlated with symptoms of abdominal distention and dissatisfaction with bowel movements. Pain thresholds and MI during distention were uncorrelated. Pain sensitivity and colon motility are independent factors contributing to IBS symptoms. Treatment may need to address both, and to be specific to predominant bowel habit.


Video time encoding machines.
We investigate architectures for time encoding and time decoding of visual stimuli such as natural and synthetic video streams (movies, animation). The architecture for time encoding is akin to models of the early visual system. It consists of a bank of filters in cascade with single-input multi-output neural circuits. Neuron firing is based on either a threshold-and-fire or an integrate-and-fire spiking mechanism with feedback. We show that analog information is represented by the neural circuits as projections on a set of band-limited functions determined by the spike sequence. Under Nyquist-type and frame conditions, the encoded signal can be recovered from these projections with arbitrary precision. For the video time encoding machine architecture, we demonstrate that band-limited video streams of finite energy can be faithfully recovered from the spike trains and provide a stable algorithm for perfect recovery. The key condition for recovery calls for the number of neurons in the population to be above a threshold value.


Immediate occlusal loading of NanoTite PREVAIL implants: a prospective 1-year clinical and radiographic study.
Recently, a new implant surface texture, featuring application of nanometer-scale calcium phosphate has been shown to enhance early bone fixation and formation in preclinical studies and in human histomorphometric studies, which may be beneficial in immediate loading situations. The purpose of the present prospective clinical study was to, during 1 year, clinically and radiographically evaluate a nanometer scale surface modified implant placed for immediate loading of fixed prostheses in both maxillary and mandibular regions. Thirty-five out of 38 patients who needed implant treatment and met inclusion criteria agreed to participate in the study and were consecutively enrolled. Surgical implant placement requirements consisted of a final torque of a least 25 Ncm prior to final seating and an implant stability quotient above 55. A total of 102 NanoTite PREVAIL (NTP) implants (BIOMET 3i, Palm Beach Gardens, FL, USA) (66 maxillary and 36 mandibular) were placed by one investigator, and the majority of these were placed in posterior regions (65%) and in soft bone (69%). A total of 44 prosthetic constructions were evaluated consisting of 14 single-tooth restorations, 26 fixed partial dentures, and four complete fixed restorations. All provisional constructions were delivered within 1 hour, and the final constructions placed after 4 months. Implants were monitored for clinical and radiographic outcomes at follow-up examinations scheduled for 3, 6, and 12 months. Of the 102 study implants, one implant failed. The simple cumulative survival rate value at 1 year was 99.2%. The average marginal bone resorption was 0.37 mm (SD 0.39) during the first year in function. According to the success criteria of Albrektsson and Zarb, success grade 1 was found with 93% of the implants. Although limited to the short follow-up, immediate loading of NanoTite Prevail implants seems to be a viable option in implant rehabilitation, at least when a good initial fixation is achieved.


Rural, Pregnant, and Opioid Dependent: A Systematic Review.
The nature, impact, and treatment of substance use during pregnancy are well described for women living in urban settings. Less is known about pregnant substance-using women living in rural communities. The objective of this review is to describe the existing evidence for the management of substance use in pregnant women living in rural areas. A systematic review of the literature was conducted using PubMed, Embase, and the Cochrane Database of Systematic Reviews, and the quality of the evidence was assessed using the GRADE system. Twenty-two articles that met the inclusion criteria were identified. Descriptive studies document high rates of smoking, marijuana, and polysubstance use among rural, substance-using pregnant women compared to their urban counterparts. Management of substance use disorders is limited by access to and acceptability of treatment modalities. Several innovative, integrated addiction and prenatal care programs have been developed, which may serve as models for management of substance use during pregnancy in rural settings.


Recurrent atretic parietal cephalocele in adult and radiological findings.
Atretic parietal cephaloceles are an extremely rare and occult form of congenital herniations that involve the meninges, remnants of glial cells or central nervous system structures. They are detected as subscalp lesions that are covered by skin. In the literature, atretic parietal cephaloceles have been reported in children in 59 cases and in two cases in adults. We present here a case of a recurrent atretic parietal cephalocele that we recently observed in an adult. This case indicates that an atretic parietal cephalocele should always be considered in the differential diagnosis of subscalp lesions. Radiologic diagnosis is a lifesaving measure that can be undertaken before an operation. Additionally, regular follow-up magnetic resonance imaging is recommended for each case with remnant lesions due to the slow growth of these masses.


PhoB activates Escherichia coli O157:H7 virulence factors in response to inorganic phosphate limitation.
Enterohemorrhagic Escherichia coli (EHEC), an emerging food- and water-borne hazard, is highly pathogenic to humans. In the environment, EHEC must survive phosphate (Pi) limitation. The response to such Pi starvation is an induction of the Pho regulon including the Pst system that senses Pi variation. The interplay between the virulence of EHEC, Pho-Pst system and environmental Pi remains unknown. To understand the effects of Pi deprivation on the molecular mechanisms involved in EHEC survival and virulence under Pho regulon control, we undertook transcriptome profiling of the EDL933 wild-type strain grown under high Pi and low Pi conditions and its isogenic ΔphoB mutant grown in low Pi conditions. The differentially expressed genes included 1067 Pi-dependent genes and 603 PhoB-dependent genes. Of these 131 genes were both Pi and PhoB-dependent. Differentially expressed genes that were selected included those involved in Pi homeostasis, cellular metabolism, acid stress, oxidative stress and RpoS-dependent stress responses. Differentially expressed virulence systems included the locus of enterocyte effacement (LEE) encoding the type-3 secretion system (T3SS) and its effectors, as well as BP-933W prophage encoded Shiga toxin 2 genes. Moreover, PhoB directly regulated LEE and stx2 gene expression through binding to specific Pho boxes. However, in Pi-rich medium, constitutive activation of the Pho regulon decreased LEE gene expression and reduced adherence to HeLa cells. Together, these findings reveal that EHEC has evolved a sophisticated response to Pi limitation involving multiple biochemical strategies that contribute to its ability to respond to variations in environmental Pi and to coordinating the virulence response.


Cocultivation of phytopathogenic Fusarium and Alternaria strains affects fungal growth and mycotoxin production.
A laboratory study was conducted to evaluate the influence of cocultivation of toxigenic Fusarium (F.) and Alternaria (A.) fungi with respect to growth and mycotoxin production. Fusarium culmorum Fc13, Fusarium graminearum Fg23 and two Alternaria tenuissima isolates (At18 and At220) were simultaneously or consecutively co-incubated on wheat kernels in an in vitro test system. Fungal biomass was quantified by determining ergosterol content. Three Fusarium toxins (DON, NIV and ZON) and three Alternaria toxins (AOH, AME and ALT) were analysed by a newly developed HPLC/MS/MS method. In simultaneous cocultures, the fungal biomass was enhanced up to 460% compared with individual cultures; Alternaria toxins were considerably depressed down to <5%. Combining At18 and At220 with Fg23 inhibited the toxin production of both fungal partners. In contrast, Fc13 increased its DON and ZON production in competitive interaction with both A. strains. The interfungal competitive effects aid the understanding of the processes of competition of both fungi in natural environments and the involvement of mycotoxins as antifungal factors. Cocultivation significantly affects fungal growth and mycotoxin production of phytopathogenic Alternaria and Fusarium strains. The impact of mycotoxins on the interfungal competition is highlighted.


The magnitude of neurotoxicity in patients with multiple myeloma and the impact of dose modifications: results from the population-based PROFILES registry.
The aim of this analysis is to assess (1) self-reported chemotherapy-induced peripheral neuropathy (CIPN) symptoms; (2) its association with sociodemographic and clinical characteristics; and (3) treatment dose modifications and its influence on the magnitude of neurotoxicity in a population-based cohort of patients with multiple myeloma (MM). MM patients (n = 156), diagnosed between 2000 and 2014, filled out the EORTC QLQ-CIPN20 (65% response). Data on treatment, outcomes, and dose modifications were extracted from the medical files. Fifty-three percent of patients reported at least one and on average three neuropathy symptoms that bothered them the most during the past week, with tingling toes/feet as most reported. In multivariate analysis, thalidomide, especially higher cumulative dose, was associated with neuropathy (β = 0.26, CI 95% 0.27-15.34, p = 0.04) and CIPN was not associated with age, sex, time since last course of therapy, number of prior therapies, osteoarthritis, or diabetes. Dose modifications were often applied (65%). Although not statistically significant, a trend towards higher sensory (22 vs. 15 vs. 12, p = 0.22) and motor neuropathy scores (21 vs. 15 vs. 11, p = 0.36) was observed among patients receiving dose modification because of CIPN (31%) compared to those receiving a dose modification for another reason or no dose modification, without altering treatment response. CIPN is a common dose limiting side effect in patients with MM. Severity of CIPN was mainly affected by treatment with thalidomide. In spite of dose modifications, patients still reported somewhat higher neuropathy scores without altered response rates. Early dose modification based on a more reliable tool for CIPN measurements may prove value.


Determinants of the increase in ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients.
To examine metabolic factors that influence ketone production after sodium-glucose cotransport inhibitor (SGLT2) administration. Fasting plasma glucose (FPG), insulin, glucagon, free fatty acid and ketone concentrations were measured in 15 type 2 diabetes mellitus (T2DM) and 16 non-diabetic subjects before and at day 1 and day 14 after treatment with empagliflozin. Empagliflozin caused a 38 mg/dL reduction in FPG concentration in T2DM patients. However, it caused only a small but significant (7 mg/dL) reduction in the FPG concentration in impaired fasting glucose (IFG) subjects and did not affect FPG concentration in normal glucose tolerant (NGT) subjects. Empagliflozin caused a significant increase in mean plasma glucagon, free fatty acid (FFA) and ketone concentrations in T2DM subjects. However, empagliflozin did not cause a significant change in mean plasma insulin, glucagon or ketone concentrations in non-diabetic subjects. An index that integrates change in plasma glucose, insulin and FFA concentration at day 1 strongly correlates with plasma ketone concentration at day 1 (r = 0.85, P < .001) and day 14 (r = 0.63, r = 0.01) and predicts, with 86% sensitivity and 83% specificity, subjects at the top tertile for plasma ketone concentration after empagliflozin treatment. Results of the present study demonstrate that SGLT2 inhibition exerts different metabolic effects in non-diabetic individuals as compared to diabetic patients.


In search of sexual pleasure and fidelity: vaginal practices in KwaZulu-Natal, South Africa.
Vaginal practices, such as intra-vaginal cleansing, drying and tightening, are suspected of placing women at higher risk of acquiring HIV and STIs. Yet, there is limited understanding of what these practices entail, what motivates women to undertake them and what their socio-cultural and historical meanings are. This paper explores the range of vaginal practices used by women in KwaZulu-Natal, South Africa and locates these within the context of local patterns of migration and understandings of sexual health and pleasure. Study activities took place at an urban and rural site employing qualitative research techniques: semi-structured interviewing and an additional ethnographic component in the rural site. Vaginal practices were believed to be ubiquitous and a wide range of substances and procedures were described. Strong motivations for vaginal practices included women's desire to enhance men's sexual pleasure, ensure men's fidelity and exercise agency and control in their relationships. The common use of traditional medicines in this quest to maintain stable relationships and affect the course of love, suggests a complexity that cannot be captured by simple terms like 'dry sex'. We argue instead that any interventions to change women's reliance on vaginal practices must recognise and attend to the broader social contexts in which they are embedded.


Statistical and methodological issues in microbicide trial design.
Microbicide trials aim to measure the effect of a microbicide in reducing the risk of acquiring human immunodeficiency virus. Such trials present a number of challenging issues from design and conduct through to analysis and reporting. This begins with the initial identification of the target trial population. Prevention trials need to identify those at risk of human immunodeficiency virus infection. This can be more difficult in the general population compared with treatment trials that can target specific patient groups who have a confirmed diagnosis of the disease of interest. Consequently, microbicide trial participants will inevitably be recruited who are never at risk of HIV infection. In this chapter we outline the main features of microbicide trial design, key issues during conduct and analysis, and discuss the challenges specific to these types of clinical trials.


Drug permeability across a phospholipid vesicle based barrier: 3. Characterization of drug-membrane interactions and the effect of agitation on the barrier integrity and on the permeability.
Recently, we reported on the development and structural characterization of a phospholipid vesicle based barrier useful for medium throughput screening of passive drug permeability. Here, we investigate the physical and functional integrity of the phospholipid vesicle based barriers to agitation by stirring or shaking, and whether agitation affects drug permeability of sulpiride, metoprolol and testosterone. In addition, three drugs (caffeine, naproxen and sulphasalazine) which were shown in a previous study to affect the electrical resistance of the barriers, were investigated for their influence on the permeability of a simultaneously applied hydrophilic marker (calcein), and on the thermotropic phase transition of the phospholipid bilayers using differential scanning calorimetry (DSC). Electrical resistance measurements indicated that the barriers should withstand shaking speeds up to 150rpm without losing their integrity, but significant release of phospholipids from the membrane barriers to the donor and acceptor chambers was observed under agitation >or=150rpm. When using agitation up to 100rpm no increase in permeability was observed for sulpiride, metoprolol and testosterone. The phospholipid vesicle-based barrier thus differ from other permeability models in that agitation does not lead to an increase in permeability, not even for highly lipophilic drugs such as testosterone. This is explained by the different morphology of the vesicle-based barrier which is containing a 100microm thick layer of mostly aqueous compartments immobilised within a matrix of phospholipids vesicles. Sulphasalazine and naproxen were shown to decrease the electrical resistance and increase the permeability of the hydrophilic marker calcein. The DSC experiments showed that these two drugs probably interact with the head groups of the phospholipids. In contrast, caffeine gave an increase in electrical resistance and a decrease in permeability of calcein. From the DSC experiments no signs of interaction of caffeine with the phospholipid bilayer could be observed.


Modeling large regions in proteins: applications to loops, termini, and folding.
Template-based methods for predicting protein structure provide models for a significant portion of the protein but often contain insertions or chain ends (InsEnds) of indeterminate conformation. The local structure prediction "problem" entails modeling the InsEnds onto the rest of the protein. A well-known limit involves predicting loops of ≤12 residues in crystal structures. However, InsEnds may contain as many as ~50 amino acids, and the template-based model of the protein itself may be imperfect. To address these challenges, we present a free modeling method for predicting the local structure of loops and large InsEnds in both crystal structures and template-based models. The approach uses single amino acid torsional angle "pivot" moves of the protein backbone with a C(β) level representation. Nevertheless, our accuracy for loops is comparable to existing methods. We also apply a more stringent test, the blind structure prediction and refinement categories of the CASP9 tournament, where we improve the quality of several homology based models by modeling InsEnds as long as 45 amino acids, sizes generally inaccessible to existing loop prediction methods. Our approach ranks as one of the best in the CASP9 refinement category that involves improving template-based models so that they can function as molecular replacement models to solve the phase problem for crystallographic structure determination.


Turning meiosis into mitosis.
Apomixis, or asexual clonal reproduction through seeds, is of immense interest due to its potential application in agriculture. One key element of apomixis is apomeiosis, a deregulation of meiosis that results in a mitotic-like division. We isolated and characterised a novel gene that is directly involved in controlling entry into the second meiotic division. By combining a mutation in this gene with two others that affect key meiotic processes, we created a genotype called MiMe in which meiosis is totally replaced by mitosis. The obtained plants produce functional diploid gametes that are genetically identical to their mother. The creation of the MiMe genotype and apomeiosis phenotype is an important step towards understanding and engineering apomixis.


Historical Introgression from Wild Relatives Enhanced Climatic Adaptation and Resistance to Pneumonia in Sheep.
How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667-248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.


Risk Factors Analysis of Postoperative Pleural Effusion after Liver Resection.
Pulmonary complications remain relatively high in morbidities that arise after liver surgery and are associated with increased length of hospital stay and higher cost. Identification of possible risk factors in this retrospective analysis may help reduce operative morbidity and achieve better outcomes. In all, 363 consecutive patients underwent elective hepatectomies between July 2008 and November 2013 and these were identified and analyzed retrospectively. Patient demographics and perioperative variables were collected. The main outcome was an analysis of risk factors associated with postoperative pleural effusion (PPE). Of 363 patients receiving hepatectomies, 80 patients (22.0%) developed pulmonary complications. The predominant pulmonary complication in this series is pleural effusion (76 patients, 95%). Univariate analysis found that older age, higher body mass index (BMI), chronic obstructive lung disease, asthma, heart disease, hepatitis C infection, heavy smoking, American Society of Anesthesiology class III and IV, hepatectomy site, combined surgeries, perioperative blood transfusion, and cirrhosis of liver were associated with PPE. Only older age, higher BMI, asthma, heavy smoker, combined gastrointestinal surgeries, and perioperative blood transfusion were identified as independent risk factors in multivariate analysis. This study identifies 6 risk factors for PPE. Identification and management of some of these factors could possibly reduce morbidity and improve short-term surgical outcomes.


Managing Religion and Morality Within the Abortion Experience: Qualitative Interviews With Women Obtaining Abortions in the U.S.
Most women in the United States are religious, and most major religions in the United States doctrinally disapprove of abortion. A substantial proportion of U.S. women have abortions. Although relationships among religious beliefs, abortion attitudes, behaviors, and stigma have been found in previous research, the relationship between stigma and religion is understudied. In-depth interviews conducted with 78 women having abortions at nine sites in the United States found religion to permeate abortion stigma manifestations and management strategies identified in previous research, for religious and religiously affiliated respondents as well as those who did not claim a religious affiliation. Health-care providers, religious leaders, researchers, and advocates need to recognize the influence religion has on the experience of obtaining an abortion for all women in the United States.


Nutrition assessment: the reproducibility of subjective global assessment in patients requiring mechanical ventilation.
The detection of malnutrition in the intensive care unit (ICU) is critical to appropriately address its contribution on outcomes. The primary objective of this investigation was to determine if nutritional status could be reliably classified using subjective global assessment (SGA) in mechanically ventilated (MV) patients. Fifty-seven patients requiring MV >48 h in a university-affiliated medical ICU were evaluated in this cross-sectional study over a 3-month period. Nutritional status was categorized independently by two registered dietitians using SGA. Frequencies, means (+ s.d.), χ (2) and t-tests were used to describe the population characteristics; agreement between raters was evaluated using the κ statistic. On admission, the average patient was 50.4 (±14.2) years of age, overweight (body mass index: 29.0±9.2kg/m(2)), had an acute physiology and chronic health evaluation II score of 24 (±10) and respiratory failure. Fifty percent (n=29) of patients were categorized as malnourished. Agreement between raters was 95% before consensus, reflecting near perfect agreement (κ=0.90) and excellent reliability. Patients categorized as malnourished were more often admitted to the hospital floor before the ICU (n=32; 56%), reported decreased dietary intake (69 vs 46%, P=0.02) and exhibited signs of muscle wasting (45 vs 7%, P<0.001, respectively) and fat loss (52 vs 7%, P<0.001, respectively) on physical exam when compared with normally nourished individuals. SGA can serve as a reliable nutrition assessment technique for detecting malnutrition in patients requiring MV. Its routine use should be incorporated into future studies and clinical practice.


Balancing the 2 Hemispheres in Simple Calculation: Evidence From Direct Cortical Electrostimulation.
How do the parietal lobes contribute to simple calculation? Clinical and neuroimaging methods, which are based mainly on correlational evidence, have provided contrasting results so far. Here we used direct cortical electrostimulation during brain surgery to causally infer the role of the left and right parietal lobes in simple calculation. Stimulation provoked errors for addition and multiplication in different parietal areas on both hemispheres. Crucially, an innovative qualitative error analysis unveiled the functional contrast of the 2 parietal lobes. Right or left stimulation led to different types of substitution errors in multiplication, unveiling the function of the more active hemisphere. While inhibition of the left hemisphere led mainly to approximation errors, right hemisphere inhibition enhanced retrieval within a stored repertory. These results highlight the respective roles of each hemisphere in the network: rote retrieval of possible solutions by the left parietal areas and approximation to the correct solution by the right hemisphere. The bilateral orchestration between these functions guarantees precise calculation.


Insights into coronary collateral formation from a novel porcine semiacute infarction model.
For patients with severe ischemic heart disease, complete revascularization by a percutaneous coronary intervention or coronary artery bypass grafting is often not achieved and may still cause residual angina. In case of progressive coronary artery occlusions, therapeutic arteriogenesis constitutes a promising strategy for increasing blood supply to the ischemic myocardium. Whether the formation of collaterals in the hypofused myocardium is angiogenetic in nature or based on preformed coronary artery anastomoses remains debatable. The objectives of this research were (i) the development of an appropriate research methodology to study a humanoid animal semiacute infarction model with low mortality and (ii) to answer the question of whether collateral revascularization follows a pre-existing 'blueprint'. A porcine model was chosen in which a step-wise vessel occlusion was performed by implantation of a copper stent into the distal left anterior descending artery. Vessel occlusion and collateral development were confirmed in vivo every 14 days up to day 56 by repeated coronary angiography and myocardial perfusion measurement using cardiac MRI. After the completion of the in-vivo imaging studies, animals were euthanized and collateral growth was evaluated using microcomputer tomography. Our porcine model of semiacute noninvasive coronary artery occlusion confirmed the existence of preformed coronary anastomoses and the proliferation of functional vessels in hypoperfused myocardium. Repetitive intra-animal MRIs showed the functional impact of these growing collaterals. The confirmation of preformed coronary anastomoses during the process of collateralization (natural bypasses) offers a preclinical avenue to carry out arteriogenetic pharmaceutical research in patients with ischemic heart disease.


Population-based post-crisis psychological distress: an example from the SARS outbreak in Taiwan.
As a result of the severe acute respiratory syndrome (SARS) pandemic, the World Health Organization placed Taiwan on the travel alert list from May 21 to July 5, 2003. The aim of this study was to explore the post-crisis psychological distress among residents in Taiwan after the SARS epidemic. The target population consisted of a nationwide representative sample of residents aged > or = 18 years. Data were collected using computer assisted telephone interview systems by stratified random sampling according to geographic area. The survey (n = 1278) was conducted in November 2003, about 4 months after resolution of the SARS crisis in Taiwan. The maximum deviation of sampling error at the 95% confidence level was +/- 2.74%. Psychological distress was measured by a question related to subject's changes in perception of life, plus the five-item Brief Symptom Rating Scale. Multivariate logistic regression was used to examine the correlation of psychological distress. About 9.2% of the participants reported that their perceptions of life became more pessimistic following the SARS crisis. The prevalence of psychiatric morbidity was 11.7%. Major predictors of higher levels of pessimism after the SARS epidemic included demographic factors, perception of SARS and preparedness, knowing people or having personal experiences of SARS-related discrimination, and individual worries and psychiatric morbidity. The correlates of symptomatic cases, as indicated by the five-item Brief Symptom Rating Scale, included age > or = 50 years, senior high school graduate, and worries about recurrence of SARS. Psychological distress was significantly correlated with demographic factors and perception regarding the SARS epidemic. It is suggested that marketing of mental health education should be segmented according to age and education level, which should enhance crisis communication for newly emerging infectious diseases among community populations.


An implantable guide-screw system for brain tumor studies in small animals.
To overcome the problems associated with using stereotactic techniques to establish intracranial xenografts in nude mice and to treat engrafted tumors with intratumoral therapies (such as gene or viral therapies), the authors developed an implantable guide-screw system. In this study, they describe the guide-screw system, its method of implantation, and their experience with establishing xenografts and delivering intratumoral therapy. The system consists of a 2.6-mm guide screw with a central 0.5-mm diameter hole that accepts the 26-gauge needle of a Hamilton syringe. The screw is implanted into a small drill hole made 2.5 mm lateral and 1 mm anterior to the bregma. A stylet is used to cap the screw between treatments. Tumor cells or therapeutic agents are injected in a freehand fashion by using a Hamilton syringe and a 26-gauge needle fitted with a cuff to determine the depth of injection. To test this system, guide screws were successfully implanted in 44 (98%) of 45 nude mice. After 1 to 2 weeks of recovery, 38 mice were inoculated with U87MG cells and killed 5 days later. On histological studies in 37 (97%) of these animals, xenografts were evident within the caudate nucleus (mean diameter 2.5 mm). To determine whether injections into the center of an established xenograft could be reproducibly achieved with the guide-screw system, an adenovirus vector containing the beta-galactosidase gene was injected 3 days after cell implantation in 15 of the mice. All of these animals demonstrated transduced cells within the tumor. To demonstrate that engrafted animals have a uniform survival time that is indicative of reproducible tumor growth, the survival of six mice was assessed after engraftment with U87MG cells. All six animals died within 28 to 35 days. The guide-screw system allows a large number of animals to be rapidly and reproducibly engrafted and for intratumoral treatments to be accurately delivered into established xenografts.


Visualizing the distribution of synapses from individual neurons in the mouse brain.
Proper function of the mammalian brain relies on the establishment of highly specific synaptic connections among billions of neurons. To understand how complex neural circuits function, it is crucial to precisely describe neuronal connectivity and the distributions of synapses to and from individual neurons. In this study, we present a new genetic synaptic labeling method that relies on expression of a presynaptic marker, synaptophysin-GFP (Syp-GFP) in individual neurons in vivo. We assess the reliability of this method and use it to analyze the spatial patterning of synapses in developing and mature cerebellar granule cells (GCs). In immature GCs, Syp-GFP is distributed in both axonal and dendritic regions. Upon maturation, it becomes strongly enriched in axons. In mature GCs, we analyzed synapses along their ascending segments and parallel fibers. We observe no differences in presynaptic distribution between GCs born at different developmental time points and thus having varied depths of projections in the molecular layer. We found that the mean densities of synapses along the parallel fiber and the ascending segment above the Purkinje cell (PC) layer are statistically indistinguishable, and higher than previous estimates. Interestingly, presynaptic terminals were also found in the ascending segments of GCs below and within the PC layer, with the mean densities two-fold lower than that above the PC layer. The difference in the density of synapses in these parts of the ascending segment likely reflects the regional differences in postsynaptic target cells of GCs. The ability to visualize synapses of single neurons in vivo is valuable for studying synaptogenesis and synaptic plasticity within individual neurons as well as information flow in neural circuits.


Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making.
The somatic marker hypothesis proposes that decision-making is a process that depends on emotion. Studies have shown that damage of the ventromedial prefrontal (VMF) cortex precludes the ability to use somatic (emotional) signals that are necessary for guiding decisions in the advantageous direction. However, given the role of the amygdala in emotional processing, we asked whether amygdala damage also would interfere with decision-making. Furthermore, we asked whether there might be a difference between the roles that the amygdala and VMF cortex play in decision-making. To address these two questions, we studied a group of patients with bilateral amygdala, but not VMF, damage and a group of patients with bilateral VMF, but not amygdala, damage. We used the "gambling task" to measure decision-making performance and electrodermal activity (skin conductance responses, SCR) as an index of somatic state activation. All patients, those with amygdala damage as well as those with VMF damage, were (1) impaired on the gambling task and (2) unable to develop anticipatory SCRs while they pondered risky choices. However, VMF patients were able to generate SCRs when they received a reward or a punishment (play money), whereas amygdala patients failed to do so. In a Pavlovian conditioning experiment the VMF patients acquired a conditioned SCR to visual stimuli paired with an aversive loud sound, whereas amygdala patients failed to do so. The results suggest that amygdala damage is associated with impairment in decision-making and that the roles played by the amygdala and VMF in decision-making are different.


A blocking-free microfluidic fluorescence heterogeneous immunoassay for point-of-care diagnostics.
In this article, a rapid, sensitive, and disposable microfluidic immunosensor is presented for point-of-care (POC) testing and clinical diagnosis. For the first time, the blocking process is eliminated from a microfluidic heterogeneous immunoassay by using protein A functionalized polydimethylsiloxane microchannels. The nonspecific binding of the assay is maintained around the chip background level by using a pair of antibodies with different affinity to protein A under optimized experimental conditions. C-reactive protein (CRP), a biomarker for inflammation and cardiovascular disease risk assessment, is selected as a model analyte to demonstrate the sensitivity of this blocking-free microfluidic heterogeneous immunoassay. A four parameter logistic function is used to model and assess the data. The limit of detection obtained is 0.54 μg/mL, which is lower than the cut-off value for clinical diagnosis. The overall assay is completed in 5 min. The protein A modified PDMS chips wet-stored at 4°C can maintain biofunctionality up to 14 months. The developed blocking-free microfluidic heterogeneous immunoassay will immediately provide benefits to most immunosensing microdevices targeted for POC diagnostics by shortening analysis time, simplifying fluid transportation, reducing sample consumption, and lowering waste generation.


Comparison of induction methods for supersaturation: pH shift versus solvent shift.
In order to investigate the supersaturation propensity of drugs in a simple and small-scale setup, induction of supersaturation is often performed via solvent shift. For weak bases, a potentially more biorelevant induction method would be a pH shift, as it is often hypothesized that the induction method will impact the supersaturation and precipitation. However, this has not been investigated systematically in a pharmaceutical context. This study investigates the impact of the induction method of supersaturation for nine basic drugs, A0619, A2853, albendazole, cinnarizine, dipyridamole, intraconazole, JNJ39393406, ketoconazole, and posaconazole, on four parameters: highest apparent degree of supersaturation, induction time, precipitation rate and solid form of the precipitate, using a novel standardized small-scale supersaturation and precipitation method. For eight of the nine drugs, the same highest apparent degree of supersaturation was obtained with both induction methods. For the induction time, precipitation rate and the solid form of the precipitate, no systematic differences between the induction methods were detected, however individual drugs did show differences. The study shows that, if a drug is sufficiently soluble at low pH, the solvent shift and pH shift induction methods of supersaturation yield comparable results.


A new US-UK diagnostic project: mood elevation and depression in first-year undergraduates at Oxford and Stanford universities.
To investigate differences in prevalence of mood elevation, distress and depression among first-year undergraduates at Oxford and Stanford universities. An online survey was sent to Oxford and Stanford first-year undergraduate students for two consecutive years in the winter of 2005 and 2006. Students completed a survey that assessed mood symptoms and medication use. Both universities had similar rates of distress by General Health Questionnaire (Oxford - 42.4%; Stanford - 38.3%), depression by Primary Care Evaluation of Mental Disorders (Oxford - 6.2%; Stanford - 6.6%), and psychotropic and non-psychotropic medication usage (psychotropic: Oxford - 1.5%; Stanford 3.5%; nonpsychotropic: Oxford - 13.3%; Stanford - 18%). Oxford had higher rates of mood elevation by Mood Disorder Questionnaire (MDQ) (Oxford - 4%; Stanford - 1.7%). Oxford and Stanford students have similar rates of mood distress, depression and general medication usage. Students at Oxford have a higher prevalence of MDQ scores that possibly indicate a bipolar disorder, while Stanford students are prescribed more psychotropics.


Omental pedicle grafting in the treatment of postcardiotomy sternotomy infection.
Postcardiotomy sternal infection occurred in 20 (2%) of 1007 patients undergoing cardiac surgery between September 1985 and December 1987, a 10-fold increase over the preceding 33 months (4 [0.24%] of 1627 patients). Cultures were sterile in 5 patients and yielded staphylococci in 12 and a variety of bowel organisms in 3. The cause for the increased occurrence of sternal wound infection is unclear after multivariate analysis, although infections have precipitously dropped subsequent to changing to cefuroxime sodium antibiotic prophylaxis. Treatment has evolved to appropriate antibiotics and early débridement of involved sternum and cartilage. Rewiring the sternum is not attempted. If gross purulence is not present, primary closure is accomplished using muscle flaps (2 patients) or omental pedicle grafts (17 patients). In the presence of gross purulence, the wound is packed open for 5 days and then closed in the above fashion. Two patients required skin grafts for primary closure. The omental pedicle flap is preferred due to simplicity and improved coverage of the sternal defect inferiorly. Nineteen patients healed primarily. A superficial wound infection was drained in 1 patient. Midline incisional hernias developed in 3 muscular patients. Omentum is now harvested through a left subcostal incision. Hospital stay was under 2 weeks in 13 patients. One death occurred due to multisystem failure prior to completion of wound closure. In our experience, early sternal débridement and omental pedicle grafting with primary closure is appropriate therapy for postcardiotomy sternotomy infections. The presence of gross purulence may require 5 days of open packing prior to omental grafting. No significant complications occurred, and mortality was low. A left subcostal incision for omental harvesting is utilized to avoid the occurrence of delayed incisional hernias.


Potential role of cannabidiol for seizure control in a patient with recurrent glioma.
Glioma-related epilepsy significantly impact on patients' quality of life, and can often be difficult to treat. Seizures cause significant morbidity for example neurocognitive deterioration, which may result from seizures themselves or due to adverse effects from antiepileptic drugs. Management of tumour with surgery, radiotherapy and chemotherapy may contribute to seizure control, but tumour related epilepsy is often refractory despite adequate treatment with standard anti-epileptic medications. Given the increasing interest in medicinal cannabis (or cannabidiol or CBD) as an anti-epileptic drug, CBD may help with seizure control in glioma patients with treatment-refractory seizures. Here we present a case of a young lady with recurrent glioma who had refractory seizures despite multiple anti-epileptic agents, who had significant benefit with CBD.


Association of bilirubin and malondialdehyde levels with retinopathy in type 2 diabetes mellitus.
Bilirubin as an antioxidant and malondialdehyde (MDA) as an oxidant have been shown to be associated with various complications of type 2 diabetes mellitus (DM). The aim was to measure the levels of serum bilirubin and MDA in type 2 DM patients with and without diabetic retinopathy (DR) and to correlate them with severity of DR. A total number of 120 subjects out of which 40 were controls without type 2 DM and the rest 80 were type 2 DM patients were included in the study. Of those 80 diabetics, 44 patients did not have DR and 36 patients had DR. The total bilirubin, direct bilirubin, indirect bilirubin were higher in controls as compared to cases (P = 0.017, 0.033, 0.024). Serum MDA levels were found to be higher in diabetics as compared to controls (P = 0.00). The values of all the three parameters, that is, total bilirubin, direct bilirubin and indirect bilirubin were lower in patients with retinopathy as compared to those without retinopathic changes (P = 0.00, 0.020, and 0.007). Subjects were assigned to quartiles based on serum total bilirubin concentration. The prevalence of DR was significantly lower among persons with the highest bilirubin quartile compared to those with the lowest quartile. The severity of DR was inversely proportional to the total bilirubin levels (P = 0.001). The multiple logistic regression analysis showed total bilirubin to be associated with prevalence of DR (P = 0.035). The levels of total bilirubin were significantly lower in patients with DR and also in the late stages of retinopathy as compared to those without retinopathy and in controls but MDA levels did not show any association with DR.


Evaluation of Measles-Mumps-Rubella Vaccination Among Newly Arrived Refugees.
To assess US availability and use of measles-mumps-rubella (MMR) vaccination documentation for refugees vaccinated overseas. We selected 1500 refugee records from 14 states from March 2013 through July 2015 to determine whether overseas vaccination records were available at the US postarrival health assessment and integrated into the Advisory Committee on Immunization Practices schedule. We assessed number of doses, dosing interval, and contraindications. Twelve of 14 (85.7%) states provided data on 1118 (74.5%) refugees. Overseas records for 972 (86.9%) refugees were available, most from the Centers for Disease Control and Prevention's Electronic Disease Notification system (66.9%). Most refugees (829; 85.3%) were assessed appropriately for MMR vaccination; 37 (3.8%) should have received MMR vaccine but did not; 106 (10.9%) did not need the MMR vaccine but were vaccinated. Overseas documentation was available at most clinics, and MMR vaccinations typically were given when needed. Further collaboration between refugee health clinics and state immunization information systems would improve accessibility of vaccination documentation.


Functional integrity of desensitized beta-adrenergic receptors.
The adenylate cyclase-coupled beta 2-adrenergic receptor of the frog erythrocyte has served as a useful model system for elucidating the mechanisms of catecholamine-induced densensitization. In this system, it has been previously demonstrated that agonist-induced refractoriness is associated with sequestration of the beta-adrenergic receptors in vesicles away from the cell surface and from their effector unit, the adenylate cyclase system (Stadel, J.M., Strulovici, B., Nambi, P., Lavin, T.N., Briggs, M.M., Caron, M.G., and Lefkowitz, R.J. (1983) J. Biol. Chem. 258, 3032-3038). These internalized beta-adrenergic receptors appear to be structurally intact as assessed by photoaffinity labeling, but their functional status has previously been unknown. In the present studies, we sought to assess the functionality of the sequestered vesicular receptors by fusing them to Xenopus laevis erythrocytes. This cell is suitable for such studies, since it has almost no detectable beta-adrenergic receptor or catecholamine-sensitive adenylate cyclase, but contains prostaglandin E1-stimulable adenylate cyclase. Fusion of beta-adrenergic receptor-containing vesicles from desensitized frog erythrocytes with X. laevis erythrocytes results in a 30-fold stimulation of the hybrid adenylate cyclase by the beta-adrenergic agonist isoproterenol. This effect was entirely blocked by the beta-antagonist propranolol. The catecholamine-sensitive adenylate cyclase activity established in the vesicle-Xenopus hybrids showed the characteristic agonist potency series of the donor frog erythrocyte beta 2-adrenergic receptor. Fusion of vesicles from desensitized frog erythrocytes in which the beta-adrenergic receptors had been inactivated with the group specific reagent dicyclohexylcarbodiimide, or of vesicles derived from control frog erythrocytes, which contain low amounts of beta-adrenergic receptor, did not establish catecholamine-sensitive adenylate cyclase activity in the hybrids. These data demonstrate that beta-adrenergic receptors internalized during desensitization retain their functionality when recoupled to an adenylate cyclase system from a different source. The functional uncoupling of these receptors during desensitization is thus more likely due to their sequestration away from the other components of the adenylate cyclase than to any alterations in the receptors themselves.


Exploring child dental service use among migrant families in metropolitan Melbourne, Australia.
This study describes and explores factors related to dental service use among migrant children. A cross-sectional analysis of baseline data from Teeth Tales, an exploratory trial implementing a community based child oral health promotion intervention. The sample size and target population was 600 families with 1-4 year old children from Iraqi, Lebanese and Pakistani backgrounds residing in metropolitan Melbourne. Participants were recruited into the study using purposive and snowball sampling techniques. Most (88%; 550/625) children had never visited the dentist (mean (SD) age 3.06 years (1.11)). In the fully adjusted model the variable most significantly associated with child dental visiting was parent reported 'no reason for child to visit the dentist' (OR = 0.07, p < 0.001). Of those children whose parents reported their child had no reason to visit the dentist, 22% (37/165) experienced dental caries with 8% (13/165) at the level of cavitation. Dental service use by migrant preschool children was very low. The relationship between perceived dental need and dental service use is currently not aligned. One in 10 children of select migrant background had visited a dentist, which is in the context of 1 in 3 with dental caries. To improve utilization, health services should consider organizational cultural competence, outreach and increased engagement with the migrant community.


Adherence and barriers to H. pylori treatment in Arctic Canada.
Helicobacter pylori infection is an emerging health concern to some northern Canadian Aboriginal communities and their clinicians. Clinicians in the north perceive H. pylori infection to be a major clinical problem because they find H. pylori infection in many patients evaluated for common stomach complaints, leading to frequent demand for treatment, which often fails. Moreover, public health authorities identified the need for information to develop locally appropriate H. pylori control strategies. We described adherence and identified barriers to completing treatment among H. pylori-positive participants in a community-based project inspired by local concerns about H. pylori infection risks. In 2008, 110 H. pylori-positive participants (diagnosed by a breath test, histopathology and/or culture) of the Aklavik H. pylori project were randomised to standard-of-care or sequential treatment. We ascertained adherence by interviewing participants using a structured questionnaire. We estimated adherence frequencies as the proportion of participants who reported taking either 100% of doses (perfect adherence) or ≥80% of doses (good adherence). To compare the proportion with perfect or good adherence in subgroups, we report proportion differences and 95% confidence intervals (CI). Of 87 participants who were interviewed, 64% reported perfect adherence and 80% reported good adherence. We observed more frequent perfect adherence for: standard therapy (67%) versus sequential (62%); males (76%) versus females (52%); participants 40-77 years (79%) versus 17-39 (50%). Proportion differences were 5% (CI: -15, 25) for standard versus sequential therapy; 23% (CI: 4, 43) for male versus female; and 29% (CI: 10, 48) for 40-77 versus 15-39 years for perfect adherence. Of the 29 participants who reported poor adherence (<80% of doses taken), the following barriers to treatment were reported: changed mind about taking treatment (24%), consumption of alcoholic beverages (18%), nausea (18%), forgetfulness (12%), stomach pain (12%), difficulty in swallowing pills (6%), no reason (6%) or bad taste of the pills (6%). This analysis suggests that adherence to treatment for eliminating H. pyori infection may vary by regimen and may be influenced by socio-demographic factors. These findings add to the small body of evidence pertaining to adherence to H. pylori treatment in Arctic Aboriginal communities. On-going research in additional northern Canadian communities will accumulate data for developing recommendations to improve adherence for treatment to eliminate H. pylori infection.


Distributed chemical computing using ChemStar: an open source java remote method invocation architecture applied to large scale molecular data from PubChem.
We present the application of a Java remote method invocation (RMI) based open source architecture to distributed chemical computing. This architecture was previously employed for distributed data harvesting of chemical information from the Internet via the Google application programming interface (API; ChemXtreme). Due to its open source character and its flexibility, the underlying server/client framework can be quickly adopted to virtually every computational task that can be parallelized. Here, we present the server/client communication framework as well as an application to distributed computing of chemical properties on a large scale (currently the size of PubChem; about 18 million compounds), using both the Marvin toolkit as well as the open source JOELib package. As an application, for this set of compounds, the agreement of log P and TPSA between the packages was compared. Outliers were found to be mostly non-druglike compounds and differences could usually be explained by differences in the underlying algorithms. ChemStar is the first open source distributed chemical computing environment built on Java RMI, which is also easily adaptable to user demands due to its "plug-in architecture". The complete source codes as well as calculated properties along with links to PubChem resources are available on the Internet via a graphical user interface at http://moltable.ncl.res.in/chemstar/.