Clinical presentation and risk factors of inflammatory bowel disease in Sri Lanka.
There have been very few studies on inflammatory bowel disease (IBD) in Sri Lanka. This study was undertaken to determine the clinical presentation and whether a western style diet or infection with geo-helminths were associated with the condition. Three questionnaires were given to the patients: one relating to diet, one relating to clinical presentation and one relating to quality of life. The disease was confirmed endoscopically and histologically. Faeces were examined for parasites. Forty four patients were enrolled (43-ulcerative colitis; 1-Crohn's Disease). All but one had ulcerative colitis. Most had no family history of disease. The peak age of onset was 21-40 y and 63% gave a history of more than 6 months symptoms prior to diagnosis. Clinical presentation was similar to cases in western countries although milder with less severe life-events. None of them had undergone surgery. All patients ate a rice-based diet and none ate bread made of refined flour. Only 2 patient was infected with a geo-helminth. Eating bread made of refined flour is not related to development of IBD in these patients. The prevalence of geo-helminths in the study population corresponded to the general population average. Delay in diagnosis occurs because of an initial assumption that the cause of symptoms is infective. A National Register of non-infectious gastrointestinal disease would aid the epidemiology and allocation of funding to this inflammatory condition.


Demographic analysis of an Israeli Carpobrotus population.
Carpobrotus species are harmful invaders to coastal areas throughout the world, particularly in Mediterranean habitats. Demographic models are ideally suited to identify and understand population processes and stages in the life cycle of the species that could be most effectively targeted with management. However, parameterizing these models has been limited by the difficulty in accessing the cliff-side locations where its populations are typically found, as well as accurately measuring the growth and spread of individuals, which form large, dense mats. This study uses small unmanned aerial vehicles (drones) to collect demographic data and parameterize an Integral Projection Model of an Israeli Carpobrotus population. We validated our data set with ground targets of known size. Through the analysis of asymptotic growth rates and population sensitivities and elasticities, we demonstrate that the population at the study site is demographically stable, and that reducing the survival and growth of the largest individuals would have the greatest effect on reducing overall population growth rate. Our results provide a first evaluation of the demography of Carpobrotus, a species of conservation and economic concern, and provide the first structured population model of a representative of the Aizoaceae family, thus contributing to our global knowledge on plant population dynamics. In addition, we demonstrate the advantages of using drones for collecting demographic data in understudied habitats such as coastal ecosystems.


Susceptibility to trypanosomosis of three Bos indicus cattle breeds in areas of differing tsetse fly challenge.
Studies to assess the differences in susceptibility to trypanosomosis among Bos indicus cattle breeds (Maasai Zebu, Orma Boran and Galana Boran) were conducted under conditions of varying tsetse fly challenge at the Nguruman escarpment in south-western Kenya, for a period of 1 year. It was found that under tsetse challenge quantified as high, Maasai Zebu and Orma Boran were less susceptible than Galana Boran to trypanosome infections, as judged by the significantly lower incidence of infection, development of less severe anaemia, fewer requirements for trypanocidal drug treatments, higher growth rates and fewer mortalities. In the area where tsetse challenge was considered low as a result of a tsetse fly control operation using odour-baited traps, only the Maasai Zebu and Orma Boran were compared. No significant differences in the incidence of infection, degree of anaemia or growth rates were observed between the two breeds, but all were significantly different from their counterparts in the high tsetse challenge area. These results suggest that there is variation in resistance to trypanosomosis among Bos indicus cattle breeds that could be exploited as part of the integrated trypanosomosis control programmes in East Africa.


Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid.
Dehydroascorbic acid (DHA) is rapidly taken up by cells and reduced to ascorbic acid (AA). Using the Xenopus laevis oocyte expression system we examined transport of DHA and AA via glucose transporter isoforms GLUT1-5 and SGLT1. The apparent Km of DHA transport via GLUT1 and GLUT3 was 1.1 +/- 0.2 and 1.7 +/- 0.3 mM, respectively. High performance liquid chromatography analysis confirmed 100% reduction of DHA to AA within oocytes. GLUT4 transport of DHA was only 2-4-fold above control and transport kinetics could not be calculated. GLUT2, GLUT5, and SGLT1 did not transport DHA and none of the isoforms transported AA. Radiolabeled sugar transport confirmed transporter function and identity of all cDNA clones was confirmed by restriction fragment mapping. GLUT1 and GLUT3 cDNA were further verified by polymerase chain reaction. DHA transport activity in both GLUT1 and GLUT3 was inhibited by 2-deoxyglucose, D-glucose, and 3-O-methylglucose among other hexoses while fructose and L-glucose showed no inhibition. Inhibition by the endofacial inhibitor, cytochalasin B, was non-competitive and inhibition by the exofacial inhibitor, 4,6-O-ethylidene-alpha-glucose, was competitive. Expressed mutant constructs of GLUT1 and GLUT3 did not transport DHA. DHA and 2-deoxyglucose uptake by Chinese hamster ovary cells overexpressing either GLUT1 or GLUT3 was increased 2-8-fold over control cells. These studies suggest GLUT1 and GLUT3 isoforms are the specific glucose transporter isoforms which mediate DHA transport and subsequent accumulation of AA.


Fetal megacystis: a lot more than LUTO.
Fetal megacystis presents a challenge in terms of counseling and management because of its varied etiology and evolution. The aim of this study was to present a comprehensive overview of the underlying etiologies and structural anomalies associated with fetal megacystis. This was a retrospective multicenter study of cases referred to the fetal medicine unit of one of the eight academic hospitals in The Netherlands with a diagnosis of fetal megacystis. For each case, data on and measurements of fetal urinary tract and associated structural anomalies were collected. All available postmortem examinations and postnatal investigations were reviewed in order to establish the final diagnosis. In the first trimester, fetal megacystis was defined as longitudinal bladder diameter (LBD) ≥ 7 mm, and in the second and third trimesters as an enlarged bladder failing to empty during an extended ultrasound examination lasting at least 40 min. Of the 541 pregnancies with fetal megacystis, it was isolated (or solely accompanied by other signs of lower urinary tract obstruction (LUTO)) in 360 (67%) cases and associated with other abnormal ultrasound findings in 181 (33%) cases. The most common associated ultrasound anomaly was an increased nuchal translucency thickness (22%), followed by single umbilical artery (10%) and cardiac defect (10%). A final diagnosis was established in 418 cases, including 222 (53%) cases with isolated LUTO and 60 (14%) infants with normal micturition or minor isolated urological anomalies. In the remaining 136 (33%) cases, concomitant developmental or chromosomal abnormality or genetic syndrome was diagnosed. Overall, 40 chromosomal abnormalities were diagnosed, including trisomy 18 (n = 24), trisomy 21 (n = 5), Turner syndrome (n = 5), trisomy 13 (n = 3) and 22q11 deletion (n = 3). Thirty-two cases presented with anorectal malformations involving the anus, rectum and urogenital tract. In cases with confirmed urethral and anal atresia, megacystis occurred early in pregnancy and the bladder appeared severely distended (the LBD (in mm) was equal to or greater than twice the gestational age (in weeks)). Fetal macrosomia was detected in six cases and an overgrowth syndrome was detected in four cases, comprising two infants with Beckwith-Wiedemann syndrome and two with Sotos syndrome. Megacystis-microcolon-intestinal hypoperistalsis syndrome was diagnosed in five (1%) cases and prenatally suspected only in one case. Although the main cause of fetal megacystis is LUTO, an enlarged fetal bladder can also be present as a concomitant finding of miscellaneous genetic syndromes, developmental disturbances and chromosomal abnormalities. We provide an overview of the structural anomalies and congenital disorders associated with fetal megacystis and propose a practical guide for the differential diagnosis of genetic syndromes and chromosomal and developmental abnormalities in pregnancies presenting with fetal megacystis, focusing on the morphological examination of the fetus. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.


How Well Do Raters Agree on the Development Stage of Caenorhabditis elegans?
The assessment of inter-rater reliability is a topic that is infrequently addressed in Caenorhabditis elegans research, despite the existence of sophisticated statistical methods and the strong interest in the field in obtaining reliable and accurate data. This study applies statistical modeling as a robust means of analyzing the performance of worm researchers measuring the stage of worm development in terms of the two independent factors that comprise "agreement", which are (1) accuracy, representing trueness, a lack of systematic differences, or lack of bias, and (2) precision, representing reliability or the extent to which random differences are small. In our study, multiple raters assessed the same sample of worms to determine the developmental stage of each animal, and we collected data linking each scorer with their assessment for each worm. To describe the agreement of the raters, we developed a structural equation model with latent variables and thresholds, which assumes that all the raters are jointly scoring each worm. This common factor model separately quantifies the two aspects of agreement. The stage-specific thresholds examine accuracy and characterize the relative biases of each rater during the scoring process. The factor loadings for each rater examine the precision and characterizes the random error of the rater. Within our group, we found that the overall agreement was good, while certain adjustments in particular raters would have decreased systematic differences. Hence, the use of developmental stage as an experimental outcome can be both accurate and precise.


Two distinct modes for propagation of histone PTMs across the cell cycle.
Epigenetic states defined by chromatin can be maintained through mitotic cell division. However, it remains unknown how histone-based information is transmitted. Here we combine nascent chromatin capture (NCC) and triple-SILAC (stable isotope labeling with amino acids in cell culture) labeling to track histone modifications and histone variants during DNA replication and across the cell cycle. We show that post-translational modifications (PTMs) are transmitted with parental histones to newly replicated DNA. Di- and trimethylation marks are diluted twofold upon DNA replication, as a consequence of new histone deposition. Importantly, within one cell cycle, all PTMs are restored. In general, new histones are modified to mirror the parental histones. However, H3K9 trimethylation (H3K9me3) and H3K27me3 are propagated by continuous modification of parental and new histones because the establishment of these marks extends over several cell generations. Together, our results reveal how histone marks propagate and demonstrate that chromatin states oscillate within the cell cycle.


Induction of apoplastic invertase of Chenopodium rubrum by D-glucose and a glucose analog and tissue-specific expression suggest a role in sink-source regulation.
Photoautotrophic suspension-culture cells of Chenopodium rubrum that were shifted to mixotrophic growth by adding glucose were used as model system to investigate the influence of the source-sink transition in higher plants on the expression and enzyme activities of intracellular and extracellular invertases. The complete cDNA coding for an extracellular invertase was cloned and sequenced from C. rubrum, and its identity has been proven by heterologous expression in Saccharomyces cerevisiae. The higher activity of extracellular invertase after preincubation in the presence of glucose was paralleled by an increased expression of the corresponding gene. The induction by glucose could be mimicked by the nonmetabolizable glucose analog 6-deoxyglucose. Both enzyme activity and mRNA level of extracellular invertase showed a sink-tissue-specific distribution in plants. The activity of neutral and acidic intracellular invertases were not affected by preincubation of autotrophic tissue cultures with sugars, nor did they show a tissue-specific distribution in plants. The data suggest that apoplastic invertase not only has an important function in phloem unloading and carbohydrate partitioning between source and sink tissues but may also have a role in establishing metabolic sinks.


Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis.
MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration.


Point-of-care testing in the overcrowded emergency department--can it make a difference?
Emergency departments (EDs) face several challenges in maintaining consistent quality care in the face of steadily increasing public demand. Improvements in the survival rate of critically ill patients in the ED are directly related to the advancement of early recognition and treatment. Frequent episodes of overcrowding and prolonged waiting times force EDs to operate beyond their capacity and threaten to impact upon patient care. The objectives of this review are as follows: (a) to establish overcrowding as a threat to patient outcomes, person-centered care, and public safety in the ED; (b) to describe scenarios in which point-of-care testing (POCT) has been found to ameliorate factors thought to contribute to overcrowding; and (c) to discuss how POCT can be used directly, and indirectly, to expedite patient care and improve outcomes. Various studies have shown that overcrowding in the ED has profound effects on operational efficiency and patient care. Several reports have quantified overcrowding in the ED and have described a relationship between heightened periods of overcrowding and delays in treatment, increased incidence of adverse events, and an even greater probability of mortality. In certain scenarios, POCT has been found to increase the number of patients discharged in a timely manner, expedite triage of urgent but non-emergency patients, and decrease delays to treatment initiation. This review concludes that POCT, when used effectively, may alleviate the negative impacts of overcrowding on the safety, effectiveness, and person-centeredness of care in the ED.


Supported microfiber loops for optical sensing.
We demonstrate refractive-index sensors based on copper-rod- supported microfiber loops. Due to the robustness of the supported loop structure and the flexibility of obtaining critical coupling within a broad spectral range, these microfiber loops show high sensitivity and high stability for sensing in both low- and high-concentration solutions with estimated sensitivity of refractive-index measurement up to 1.8 x 10(-5).


A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica.
Urine is a metabolite-rich biofluid that reflects the body's effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. For illustration of the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses, 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum disorder (NMO-SD) patients and analyzed with NMR, multivariate statistics, one-way ANOVA, and univariate statistics. Urine from MS patients exhibited a statistically distinct metabolic signature from healthy and NMO-SD controls. A total of 27 metabolites were differentially altered in the urine from MS and NMO-SD patients and were associated with synthesis and degradation of ketone bodies, amino acids, propionate and pyruvate metabolism, tricarboxylic acid cycle, and glycolysis. Metabolites altered in urine from MS patients were shown to be related to known pathogenic processes relevant to MS, including alterations in energy and fatty acid metabolism, mitochondrial activity, and the gut microbiota.


Successful nonsurgical transfer of bovine elongating conceptuses and its application to sexing.
The objectives of the present study were to establish a nonsurgical transfer method for elongating bovine conceptuses and to combine this method with biopsy and sexing. Bovine conceptuses were recovered from donor cows on days 13-14 of the estrus cycle. In experiment 1, day 13 conceptuses were transferred to recipient cows using a standard day 7 embryo transfer (ET) method. The pregnancy rate of day 13 conceptus transfer (CT) is comparable to that of day 7 ET. In experiment 2, day 14 conceptuses were transferred using modified methods (balloon catheters or ET guns with modified sheaths). Using the standard ET method, no pregnancies were obtained; however, when balloon catheters or ET guns with modified sheaths were used, the pregnancy rates after CT were 48.0% and 44.8%, respectively. In experiment 3, day 14 conceptuses were biopsied without a micromanipulator, sexed using the loop-mediated isothermal amplification method and transferred to recipient cows. The pregnancy rate of biopsied conceptuses was 46.2% and did not differ significantly from that of unbiopsied conceptuses. Moreover, all pregnant cows transferred conceptuses following biopsy and sexing delivered calves with the expected sexes. These results suggested that the nonsurgical bovine CT method was comparable to day 7 ET and that this technique enables biopsy and sexing without expensive equipment such as a micromanipulator or specialized skills.


Neighborhood matters: the impact of Hispanic ethnic density on future depressive symptoms 1-year following an ACS event among Hispanic patients.
The Ethnic Density hypothesis posits that living around others from similar ethnic backgrounds reduces the risk of adverse mental health outcomes such as depression. Contrary to this hypothesis, previous work has shown that Hispanic ethnic density is cross-sectionally associated with increased depressive symptom severity among patients hospitalized with an acute coronary syndrome (ACS; myocardial infarction or unstable angina pectoris). To date, no study has examined the prospective association of Hispanic ethnic density on long-term depressive symptom severity following an acute medical event. We prospectively assessed the impact of Hispanic ethnic density on depressive symptoms, 1-year following an ACS event, among Hispanic adult patients. We tested the non-linear association between ethnic density and depressive symptoms to account for inconsistent findings on the ethnic density hypothesis. At the time of an index ACS event (i.e., baseline, N = 326) and 1-year later (N = 252), Hispanic patients from the Prescription Usage, Lifestyle, and Stress Evaluation prospective cohort study completed the Beck Depression Inventory as a measure of depressive symptom severity. Hispanic ethnic density was defined by the percentage of Hispanic residents within each patient's census tract using data extracted from the American Community Survey Census (2010-2013). Covariates included baseline demographic factors (age, gender, English fluency, education, nativity status), cardiovascular factors (Charlson comorbidity index, left ventricular ejection fraction, Global Registry of Acute Coronary Events 6-month prognostic risk score), and neighborhood factors (residential density, income, and percentage of households receiving public assistance). In an adjusted multivariable linear regression analysis there was a significant curvilinear association between Hispanic ethnic density and depressive symptom severity at 1 year. As Hispanic ethnic density increased from low to moderate density, there was an increase in depressive symptoms, but depressive symptoms slightly declined in census tracts with the highest density of Hispanics. Furthermore, gender significantly moderated the relation between Hispanic ethnic density and 1-year depressive symptom severity, such that Hispanic ethnic density was significantly associated with increased depressive symptom severity for female Hispanic patients with ACS, but not for male Hispanic patients. Previous research suggests that ethnic density may be protective against depression in Hispanic enclaves; however, our findings suggest a non-linear ethnic density effect and an overall more complex association between ethnic density and depression. These data add to a growing body of literature on the effects of sociodemographic and contextual factors on health.


Association between caffeine consumption and nonalcoholic fatty liver disease: a systemic review and meta-analysis.
Caffeine consumption is reported to be associated with reduced hepatic fibrosis in patients with chronic liver diseases. We performed a systematic review and meta-analysis to assess the association between caffeine consumption and prevalence or hepatic fibrosis of nonalcoholic fatty liver disease (NAFLD) in observational studies. We searched the literature of all languages from PubMed, EMBASE, and the Cochrane library from 1 January 1980 through 10 January 2015. Total caffeine consumption was defined as the daily intake of caffeine (mg/day) from all caffeine-containing products. Combined and subgroup analyses stratified by study designs, study locations, and type of caffeine intake were performed. Four cross-sectional and two case control studies with a total of 20,064 subjects were included in the meta-analysis. Among these, three studies with 18,990 subjects were included in the analysis for prevalence of NAFLD while the other three studies with 1074 subjects were for hepatic fibrosis. Total caffeine consumption (mg/day) was not significantly associated with either the prevalence [pooled mean difference (MD) 2.36; 95% confidence interval (CI) -35.92 to 40.64] or hepatic fibrosis (higher versus lower stages; pooled MD -39.95; 95% CI -132.72 to 52.82) of NAFLD. Subgroup analyses stratified by study designs and locations were also not significant. However, after stratifying by type of caffeine intake, regular coffee caffeine intake (mg/day) was significantly associated with reduced hepatic fibrosis of NAFLD (pooled MD -91.35; 95% CI -139.42 to -43.27; n = 2 studies). Although total caffeine intake is not associated with the prevalence or hepatic fibrosis of NAFLD, regular coffee caffeine consumption may significantly reduce hepatic fibrosis in patients with NAFLD.


Identifying possible indicators of systematic overuse of health care procedures with claims data.
Health care quality is frequently described with measures representing the overall performance of a health care system. Despite the growing attention to overuse of health care resources, there is little experience with aggregate measures of overuse. To identify a set of possible indicators of overuse that can be operationalized with claims data and to describe variation in these indicators across the hospital referral regions (HRRs). Using an environmental scan, we identified published descriptions of overused procedures. We assessed each procedure's feasibility for measurement with claims and developed algorithms for occurrences of procedures in patients unlikely to benefit. Using a 5% sample of Medicare claims from 2008, we calculated summary statistics to illustrate variance in the use across HRRs. A total of 613 procedures were identified as overused; 20 had abundant frequency and variance to be possible measures of systematic overuse. These included 13 diagnostic tests, 2 tests for screening, 1 for monitoring, and 4 therapeutic procedures. The usage varied markedly across HRRs. For illustration, 1 HRR used computed tomography for rhinosinusitis diagnosis in 80 of 1000 beneficiaries (mean usage across HRRs was 14/1000). Among 1,451,142 beneficiaries, 14% had at least one overuse event (range, 8.4%-27%). We identified a set of overused procedures that may be used as measures of overuse and that demonstrate significant variance in their usage. The implication is that an index of overuse might be built from these indicators that would reveal systematic patterns of overuse within regions. Alternatively, these indicators may be valuable in the quality improvement efforts.


Medical implications of understanding complex disease traits.
The application of genetic mapping to human disease gene identification has led to the definition of many linkages and a few disease genes in complex traits over the past two years. Its application has also increased to include aspects of pharmacogenetics relating to pharmacokinetics and pharmacodynamics.


Evaluating the Impact of Neighborhood Characteristics on Differences between Residential and Mobility-Based Exposures to Outdoor Air Pollution.
Epidemiological studies often assign outdoor air pollution concentrations to residential locations without accounting for mobility patterns. In this study, we examined how neighborhood characteristics may influence differences in exposure assessments between outdoor residential concentrations and mobility-based exposures. To do this, we linked residential location and mobility data to exposure surfaces for NO2, PM2.5, and ultrafine particles in Montreal, Canada for 5452 people in 2016. Mobility data were collected using the MTL Trajet smartphone application (mean: 16 days/subject). Generalized additive models were used to identify important neighborhood predictors of differences between residential and mobility-based exposures and included residential distances to highways, traffic counts within 500 m of the residence, neighborhood walkability, median income, and unemployment rate. Final models including these parameters provided unbiased estimates of differences between residential and mobility-based exposures with small root-mean-square error values in 10-fold cross validation samples. In general, our findings suggest that differences between residential and mobility-based exposures are not evenly distributed across cities and are greater for pollutants with higher spatial variability like NO2. It may be possible to use neighborhood characteristics to predict the magnitude and direction of this error to better understand its likely impact on risk estimates in epidemiological analyses.


Neuroreductionism about Sex and Love.
"Neuroreductionism" is the tendency to reduce complex mental phenomena to brain states, confusing correlation for physical causation. In this paper, we illustrate the dangers of this popular neuro-fallacy, by looking at an example drawn from the media: a story about "hypoactive sexual desire disorder" in women. We discuss the role of folk dualism in perpetuating such a confusion, and draw some conclusions about the role of "brain scans" in our understanding of romantic love.


The radioprotective effect of N-acetylcysteine against x-radiation-induced renal injury in rats.
The purpose of this study was therefore to investigate the effects of radiotherapy on the kidney and the potential use of agents such as N-acetylcysteine (NAC) in developing a future therapeutic protocol for radiation-induced nephrotoxicity at the histopathological and biochemical levels. Our study consisted of three groups: control (oral saline solution only; group 1), irradiation (IR; group 2), and NAC + IR (group 3). The irradiation groups received a single dose of whole-body 6-Gy x-irradiation. The NAC group received 300 mg/kg by the oral route for 7 days, from 5 days before irradiation to 2 days after. All subjects were sacrificed under anesthesia 2 days after irradiation. IR increased tubular necrosis scores (TNS), MDA, and caspase-3 expression, while reducing renal tissue GSH levels. We also observed dilation in renal corpuscles and tubules. Capillary congestion was present in the intertubular spaces. NAC reduced the levels of TNS, MDA, and caspase-3 expression, but increased the levels of renal tissue GSH. ROS-scavenging antioxidants may represent a promising means of preventing renal injury in patients undergoing radiotherapy.


Phytosterols, Cholesterol Control, and Cardiovascular Disease.
The use of phytosterols (or plant sterols) for the control of plasma cholesterol concentrations has recently gained traction because their efficacy is acknowledged by scientific authorities and leading guidelines. Phytosterols, marketed as supplements or functional foods, are formally classified as food in the European Union, are freely available for purchase, and are frequently used without any health professional advice; therefore, they are often self-prescribed, either inappropriately or in situations in which no significant advantage can be obtained. For this reason, a panel of experts with diverse medical and scientific backgrounds was convened by NFI-Nutrition Foundation of Italy-to critically evaluate and summarize the literature available on the topic, with the goal of providing medical doctors and all health professionals useful information to actively govern the use of phytosterols in the context of plasma cholesterol control. Some practical indications to help professionals identify subjects who will most likely benefit from the use of these products, optimizing the therapeutic outcomes, are also provided. The panel concluded that the use of phytosterols as supplements or functional foods to control Low Density Lipoprotein (LDL) cholesterol levels should be preceded by the assessment of some relevant individual characteristics: cardiovascular risk, lipid profile, correct understanding of how to use these products, and willingness to pay for the treatment.


Organic solvent tolerance and antibiotic resistance increased by overexpression of marA in Escherichia coli.
We previously reported that overexpression of the soxS or robA gene causes in several Escherichia coli strains the acquisition of higher organic solvent tolerance and also increased resistance to a number of antibiotics (H. Nakajima, K. Kobayashi, M. Kobayashi, H. Asako, and R. Aono, Appl. Environ. Microbiol. 61:2302-2307, 1995). Most E. coli strains cannot grow in the presence of cyclohexane. We isolated the marRAB genes from a Kohara lambda phage clone and cyclohexane-tolerant mutant strain OST3408. We found a substitution of serine for arginine at position 73 in the coding region of marR of OST3408 and designated the gene marR08. Our genetic analysis revealed that marR08 is responsible for the cyclohexane-tolerant phenotype. We observed that the marA gene on high-copy-number plasmids increased the organic solvent tolerance of E. coli strains. Furthermore, exposure of E. coli cells to salicylate, which activates the mar regulon genes, also raised organic solvent tolerance. Overexpression of the marA, soxS, or robA gene increased resistance to numerous antibiotics but not to hydrophilic aminoglycosides.


Lyme arthritis: a comparison of presentation, synovial fluid analysis, and treatment course in children and adults.
This case series examines differences in the presentation, management, and outcome of Lyme arthritis between the pediatric and adult population. We reviewed charts of pediatric and adult patients evaluated for Lyme arthritis by rheumatologists and pediatric infectious disease specialists in Portland, Maine between January 2002 and July 2008. Patients included for analysis had documented joint swelling and positive Lyme serology. Data on clinical presentation, synovial fluid and peripheral blood results, treatment, and clinical course were analyzed. Twenty-nine adults and 52 children met case criteria for Lyme arthritis. Children were more likely than adults to present acutely (P < 0.0001) and also had higher mean peripheral blood (P = 0.05) and synovial fluid white blood cell counts (P < 0.0001). Lyme arthritis was more frequently suspected in children at presentation (P = 0.04). There was no difference between children and adults with respect to suspicion for septic arthritis, hospitalization, or surgical intervention. Adults received more antibiotic courses (P = 0.007) and were more likely to have intravenous antibiotics in subsequent treatment courses (P = 0.006). Children were more likely to have normal function within 4 weeks of initiating antibiotic treatment (P < 0.0001). Children with Lyme arthritis were more likely to present acutely with higher synovial white cell counts than adults. We did not, however, observe a significant difference in hospitalization or surgical management. Children had more prompt resolution of their joint swelling and received less treatment overall.


Effects of the oral angiotensin-converting enzyme inhibitor MK-421 in human hypertension.
1. The effects of the new oral angiotensin-converting enzyme (ACE) inhibitor MK-421 on blood pressure, plasma renin activity, angiotensin-II, aldosterone and converting enzyme activity were assessed in 16 hypertensive patients followed for 6--18 weeks. 2. After an initial titration period, maintenance doses of 2.5--40 mg once daily produced satisfactory blood pressure control in 11 and a partial but significant decrease in the remainder. 3. Treatment was associated with no change in heart rate and no orthostatic hypotension. At 24 h after the first effective dose, blood pressure was still decreased, plasma ACE was suppressed to 16% of the baseline, plasma angiotensin to 58%, aldosterone to 42%, and plasma renin activity was elevated to 228% of the baseline. 4. Magnitude of blood pressure fall was significantly correlated with the height of pretreatment blood pressure but not with baseline levels of plasma renin activity.


In situ measurement of dissolved methane and carbon dioxide in freshwater ecosystems by off-axis integrated cavity output spectroscopy.
A novel low-cost method for the combined, real-time, and in situ determination of dissolved methane and carbon dioxide concentrations in freshwater ecosystems was designed and developed. This method is based on the continuous sampling of water from a freshwater ecosystem to a gas/liquid exchange membrane. Dissolved gas is transferred through the membrane to a continuous flow of high purity nitrogen, which is then measured by an off-axis integrated cavity output spectrometer (OA-ICOS). This method, called M-ICOS, was carefully tested in a laboratory and was subsequently applied to four lakes in Mexico and Alaska with contrasting climates, ecologies, and morphologies. The M-ICOS method allowed for the determination of dissolved methane and carbon dioxide concentrations with a frequency of 1 Hz and with a method detection limit of 2.76 × 10(-10) mol L(-1) for methane and 1.5 × 10(-7) mol L(-1) for carbon dioxide. These detection limits are below saturated concentrations with respect to the atmosphere and significantly lower than the minimum concentrations previously reported in lakes. The method is easily operable by a single person from a small boat, and the small size of the suction probe allows the determination of dissolved gases with a minimized impact on shallow freshwater ecosystems.


The state and fate of Himalayan glaciers.
Himalayan glaciers are a focus of public and scientific debate. Prevailing uncertainties are of major concern because some projections of their future have serious implications for water resources. Most Himalayan glaciers are losing mass at rates similar to glaciers elsewhere, except for emerging indications of stability or mass gain in the Karakoram. A poor understanding of the processes affecting them, combined with the diversity of climatic conditions and the extremes of topographical relief within the region, makes projections speculative. Nevertheless, it is unlikely that dramatic changes in total runoff will occur soon, although continuing shrinkage outside the Karakoram will increase the seasonality of runoff, affect irrigation and hydropower, and alter hazards.


Purification of native surfactant protein SP-A from pooled amniotic fluid and bronchoalveolar lavage.
Surfactant protein SP-A is a hydrophilic glycoprotein, similar to SP-D, which plays an important role in pulmonary surfactant homeostasis and innate immunity. SP-A is actively expressed in the alveolar type II cells and Clara cells. Their basic structure consists of triple-helical collagen region and a C-terminal carbohydrate recognition domain (CRD). By binding to the infectious microbes, SP-A (like SP-D) are involved in pathogen opsonization and agglutination and subsequent clearance of the microorganism, via recruitment of phagocytic cells via receptors for the collagen region. SP-A has also been localized at extra-pulmonary sites such as salivary epithelium, amniotic fluid, prostate glands, and semen. The presence of SP-A in fetal and maternal tissue and amniotic fluid suggests it is involved in pregnancy and labor. Native SP-A can be purified from amniotic fluid and bronchiolar lavage fluid (BALF) via affinity chromatography. In addition, we also report here a procedure to express and purify a recombinant form of trimeric CRD in Escherichia coli. The availability of highly pure native SP-A and CRD region can be central to studies that examine the diverse roles that SP-A play in surfactant homeostasis, pulmonary infection and inflammation and pregnancy.


Identification and deconvolution of cross-resistance signals from antimalarial compounds using multidrug-resistant Plasmodium falciparum strains.
Plasmodium falciparum, the most deadly agent of malaria, displays a wide variety of resistance mechanisms in the field. The ability of antimalarial compounds in development to overcome these must therefore be carefully evaluated to ensure uncompromised activity against real-life parasites. We report here on the selection and phenotypic as well as genotypic characterization of a panel of sensitive and multidrug-resistant P. falciparum strains that can be used to optimally identify and deconvolute the cross-resistance signals from an extended panel of investigational antimalarials. As a case study, the effectiveness of the selected panel of strains was demonstrated using the 1,2,4-oxadiazole series, a newly identified antimalarial series of compounds with in vitro activity against P. falciparum at nanomolar concentrations. This series of compounds was to be found inactive against several multidrug-resistant strains, and the deconvolution of this signal implicated pfcrt, the genetic determinant of chloroquine resistance. Targeted mode-of-action studies further suggested that this new chemical series might act as falcipain 2 inhibitors, substantiating the suggestion that these compounds have a site of action similar to that of chloroquine but a distinct mode of action. New antimalarials must overcome existing resistance and, ideally, prevent its de novo appearance. The panel of strains reported here, which includes recently collected as well as standard laboratory-adapted field isolates, is able to efficiently detect and precisely characterize cross-resistance and, as such, can contribute to the faster development of new, effective antimalarial drugs.


Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2.
Mitochondria underpin metabolism, bioenergetics, signalling, development and cell death in eukaryotes. Most of the ~1,000 yeast mitochondrial proteins are encoded in the nucleus and synthesised as precursors in the cytosol, with mitochondrial import facilitated by molecular chaperones. Here, we focus on the Hsp40 chaperone Ydj1 in the fungal pathogen Candida albicans, finding that it is localised to both the cytosol and outer mitochondrial membrane, and is required for cellular stress responses and for filamentation, a key virulence trait. Mapping the Ydj1 protein interaction network highlighted connections with co-chaperones and regulators of filamentation. Furthermore, the mitochondrial processing peptidases Mas1 and Mas2 were highly enriched for interaction with Ydj1. Additional analysis demonstrated that loss of MAS1, MAS2 or YDJ1 perturbs mitochondrial morphology and function. Deletion of YDJ1 impairs import of Su9, a protein that is cleaved to a mature form by Mas1 and Mas2. Thus, we highlight a novel role for Ydj1 in cellular morphogenesis, stress responses, and mitochondrial import in the fungal kingdom.


Human body-segment tilts induced by galvanic stimulation: a vestibularly driven balance protection mechanism.
1. We have studied the effects of changes in posture on the motor response to galvanic vestibular stimulation (GVS). The purpose of the experiments was to investigate whether the function of the GVS-evoked response is to stabilize the body or the head in space. Subjects faced forwards with eyes closed standing with various stance widths and sitting. In all cases the GVS-evoked response consisted of a sway of the body towards the anodal ear. 2. In the first set of experiments the response was measured from changes in (i) electromyographic activity of hip and ankle muscles, (ii) the lateral ground reaction force, and (iii) lateral motion of the body at the level of the neck (C7). For all measurements the response became smaller as the feet were placed further apart. 3. In the second set of experiments we measured the GVS-evoked tilts of the head, torso and pelvis. The basic response consisted of a tilt in space (anodal ear down) of all three segments. The head tilted more than the trunk and the trunk tilted more than the pelvis producing a leaning and bending of the body towards the anodal ear. This change in posture was sustained for the duration of the stimulus. 4. The tilt of all three segments was reduced by increasing the stance width. This was due to a reduction in evoked tilt of the pelvis, the bending of the upper body remaining relatively unchanged. Changing from a standing to a sitting posture produced additional reductions in tilt by reducing the degree of upper body bending. 5. The results indicate that the response is organized to stabilize the body rather than the head in space. We suggest that GVS produces a vestibular input akin to that experienced on an inclined support surface and that the function of the response is to counter any threat to balance by keeping the centre of mass of the body within safe limits.


Photothermal cellular stimulation in functional bio-polymer interfaces.
Hybrid interfaces between organic semiconductors and living tissues represent a new tool for in-vitro and in-vivo applications, bearing a huge potential, from basic researches to clinical applications. In particular, light sensitive conjugated polymers can be exploited as a new approach for optical modulation of cellular activity. In this work we focus on light-induced changes in the membrane potential of Human Embryonic Kidney (HEK-293) cells grown on top of a poly(3-hexylthiophene) (P3HT) thin film. On top of a capacitive charging of the polymer interface, we identify and fully characterize two concomitant mechanisms, leading to membrane depolarization and hyperpolarisation, both mediated by a thermal effect. Our results can be usefully exploited in the creation of a new platform for light-controlled cell manipulation, with possible applications in neuroscience and medicine.


Can the AGE/RAGE/ERK signalling pathway and the epithelial-to-mesenchymal transition interact in the pathogenesis of chronic rhinosinusitis with nasal polyps?
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent sinonasal mucosa inflammatory disease with still unclear pathophysiologic mechanisms that imply events of tissue repair and structural remodelling. Several cascades seem to have a considerable role in the onset and progression of mucosa hyperproliferation in nasal polyps including transforming growth factor β/Small mother against decapentaplegic (TGFβ/Smads), mitogenactivated protein kinases (MAPKs), advanced glycosylation end-products (AGEs) together with epithelial-tomesenchymal transition (EMT). Since many inflammatory mediators are reported to play important roles in the development of nasal polyps (NP) disease, this study aimed to analyse the correlation between the AGEs/receptor of advanced glycosylation end-products (RAGE)/extracellular signal-regulated kinase (ERK) signalling pathway and the main markers of EMT to better understand the influence that they exert on the remodelling of nasal mucous membranes in patients affected by CRSwNP vs normal controls. A total of 30 patients were enrolled in this study. Immunohistochemical analysis, using AGE, RAGE, p-ERK, MMP-3, TGF-β1, Smad2/3, Collagen I-III, α-SMA, E-cadherin, IL-6 and Vimentin antibodies, was performed. AGE, RAGE, ERK, p-ERK and MMP3 were also evaluated using western blot analysis. We observed an overexpression of the AGE/RAGE/p-ERK and the main mesenchymal markers of EMT (Vimentin and IL-6) in CRSwNP vs controls whereas the TGF-β/Smad3 pathway did not show any significant differences between the two groups of patients. These observations suggest a complex network of processes in the pathogenesis of NP, and the AGE/RAGE/ERK pathway and EMT might work together in promoting tissue remodelling in the formation of CRSwNP.


Perceived barriers to the provision of preventive care among Iranian dentists.
The aim of this study was to examine the perceived barriers to preventive dental practice among Iranian dentists. A questionnaire survey was performed among the dentists who participated in two annual dental meetings (conducted in December 2004 and in July 2005) in Tehran, Iran. The dentists who attended the meeting completed the self-administered questionnaire anonymously. The questionnaire included 12 statements with answer alternatives rated on a 5-point scale to which the dentists were asked to indicate how much each of the 12 items, later classified as three barriers (practice-, dentist- and patient-related), impedes them from practising preventive care. The sum of the scores of the four items in each barrier served as an indicator of each dentist's perception of the strength of each barrier. The background data included dentists' personal and professional characteristics. In total, 1033 dentists completed the questionnaire, of whom 980 (64% men) were eligible. Statistical evaluation was performed using analysis of variance, t test and Pearson's correlation coefficient. Of the respondents, 29% to 66% rated the items of the practice-related barrier as very strong impediments. Corresponding figures for the dentist- and the patient-related barriers were 20% to 54% and 70% to 77%, respectively. The highest mean of the score sum was for the patient-related barrier (11.9) and the lowest mean was for the dentist-related barrier (7.9). For both practice- and dentist-related barriers, male dentists reported significantly higher scores than the female dentists (P < 0.001). The perceived barriers to the provision of preventive care should be meticulously explored and tackled to enhance oral health in Iran.


Modeling the Sensitivity of Aquatic Macroinvertebrates to Chemicals Using Traits.
In this study, a trait-based macroinvertebrate sensitivity modeling tool is presented that provides two main outcomes: (1) it constructs a macroinvertebrate sensitivity ranking and, subsequently, a predictive trait model for each one of a diverse set of predefined Modes of Action (MOAs) and (2) it reveals data gaps and restrictions, helping with the direction of future research. Besides revealing taxonomic patterns of species sensitivity, we find that there was not one genus, family, or class which was most sensitive to all MOAs and that common test taxa were often not the most sensitive at all. Traits like life cycle duration and feeding mode were identified as important in explaining species sensitivity. For 71% of the species, no or incomplete trait data were available, making the lack of trait data the main obstacle in model construction. Research focus should therefore be on completing trait databases and enhancing them with finer morphological traits, focusing on the toxicodynamics of the chemical (e.g., target site distribution). Further improved sensitivity models can help with the creation of ecological scenarios by predicting the sensitivity of untested species. Through this development, our approach can help reduce animal testing and contribute toward a new predictive ecotoxicology framework.


A methylaspartate cycle in haloarchaea.
Access to novel ecological niches often requires adaptation of metabolic pathways to cope with new environments. For conversion to cellular building blocks, many substrates enter central carbon metabolism via acetyl-coenzyme A (acetyl-CoA). Until now, only two such pathways have been identified: the glyoxylate cycle and the ethylmalonyl-CoA pathway. Prokaryotes in the haloarchaea use a third pathway by which acetyl-CoA is oxidized to glyoxylate via the key intermediate methylaspartate. Glyoxylate condensation with another acetyl-CoA molecule yields malate, the final assimilation product. This cycle combines reactions that originally belonged to different metabolic processes in different groups of prokaryotes, which suggests lateral gene transfer and evolutionary tinkering of acetate assimilation. Moreover, it requires elevated intracellular glutamate concentrations, as well as coupling carbon assimilation with nitrogen metabolism.


Effects of sieving, storage, and incubation temperature on the phospholipid Fatty Acid profile of a soil microbial community.
Disturbances typically associated with the study of soil microbial communities, i.e., sieving, storage, and subsequent incubation at elevated temperatures, were investigated with phospholipid fatty acid (PLFA) analyses. Treatment effects were quantified by statistical analyses of the mole percentage distribution of the individual fatty acids. Changes in the concentrations of individual fatty acids over a 7-week storage period at 4.5 degrees C were generally not statistically significant. Sieving effects (mesh size, 4 or 2 mm) on CO(2) evolution and the PLFA profile were monitored over 3 weeks; the physical disturbance had only minor effects, although some damage to fungal hyphae by the first sieving (<4 mm) was suggested by a decrease in the signature fatty acid 18:2 omega6c. Temperature effects were investigated by incubating soil for up to 3 weeks at 4.5, 10, or 25 degrees C. Principal component analyses demonstrated a significant shift in the PLFA composition at 25 degrees C over the first 2 weeks, while changes at the other two temperatures were minor. Several of the changes observed at 25 degrees C could be explained with reference to mechanisms of temperature adaptation or as a response to conditions of stress, including a decrease in the degree of unsaturation, an increased production of cyclopropyl fatty acids, and increased ratios of the branched-chain fatty acids iso-15:0 and iso-17:0 over anteiso-15:0 and anteiso-17:0, respectively. A decrease in the total amount of PLFA was also indicated.


Endothelin-1 transgenic mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension.
The human endothelin-1 (ET-1) gene under the control of its natural promoter was transferred into the germline of mice. The transgene was expressed predominantly in the brain, lung, and kidney. Transgene expression was associated with a pathological phenotype manifested by signs such as age-dependent development of renal cysts, interstitial fibrosis of the kidneys, and glomerulosclerosis leading to a progressive decrease in glomerular filtration rate. This pathology developed in spite of only slightly elevated plasma and tissue ET-1 concentrations. Blood pressure was not affected even after the development of an impaired glomerular filtration rate. Therefore, these transgenic lines provide a new blood pressure-independent animal model of ET-1-induced renal pathology leading to renal fibrosis and fatal kidney disease.


A corpus for mining drug-related knowledge from Twitter chatter: Language models and their utilities.
In this data article, we present to the data science, natural language processing and public heath communities an unlabeled corpus and a set of language models. We collected the data from Twitter using drug names as keywords, including their common misspelled forms. Using this data, which is rich in drug-related chatter, we developed language models to aid the development of data mining tools and methods in this domain. We generated several models that capture (i) distributed word representations and (ii) probabilities of n-gram sequences. The data set we are releasing consists of 267,215 Twitter posts made during the four-month period-November, 2014 to February, 2015. The posts mention over 250 drug-related keywords. The language models encapsulate semantic and sequential properties of the texts.


Field assessment of reproduction-related traits of chironomids using a newly developed emergence platform (E-Board).
Further progress in the development of reliable biomonitoring strategies requires to better link effects in aquatic ecological systems to ambient concentrations of chemical contaminants. Among existing tools, in situ bioassays using caging method represent an interesting way to achieve this challenge. However, elaboration of adapted exposure chambers and suitable operating procedures is still required, particularly to assess ecological relevant traits such as those related to the reproduction. In such context, we developed a new device (Emergence board - E-Board) which allows assessing in rivers the development of the Chironomus riparius species from the early fourth instar larvae to the adult stage. The system acts as a suspended matter trap floating in the subsurface of the water equipped of an emergence trap for catching adults. The system was tested in actual field conditions. Its easy handling allowed obtaining data which demonstrated its applicability for assessing the development of the chironomids. Moreover, by adapting energy-based models (DEB) specifically developed in the laboratory for the species C. riparius, we were able to predict the growth pattern and the emergence of chironomids in real environmental conditions. The E-Board represents thus a promising new in situ tool in perspective of evaluation of the quality of the ecosystems.


A novel, highly stable fold of the immunoglobulin binding domain of streptococcal protein G.
The high-resolution three-dimensional structure of a single immunoglobulin binding domain (B1, which comprises 56 residues including the NH2-terminal Met) of protein G from group G Streptococcus has been determined in solution by nuclear magnetic resonance spectroscopy on the basis of 1058 experimental restraints. The average atomic root-mean-square distribution about the mean coordinate positions is 0.27 angstrom (A) for the backbone atoms, 0.65 A for all atoms, and 0.39 A for atoms excluding disordered surface side chains. The structure has no disulfide bridges and is composed of a four-stranded beta sheet, on top of which lies a long helix. The central two strands (beta 1 and beta 4), comprising the NH2- and COOH-termini, are parallel, and the outer two strands (beta 2 and beta 3) are connected by the helix in a +3x crossover. This novel topology (-1, +3x, -1), coupled with an extensive hydrogen-bonding network and a tightly packed and buried hydrophobic core, is probably responsible for the extreme thermal stability of this small domain (reversible melting at 87 degrees C).


Embolization of cerebral arteriovenous malformations with silk: histopathologic changes and hemorrhagic complications.
To evaluate the safety of silk as an embolic agent for preoperative embolization of cerebral arteriovenous malformations (AVMs) by assessing the histopathologic changes and hemorrhagic complications associated with its use. Histopathologic specimens, medical records, and radiologic records of 73 patients with AVMs embolized with silk (alone or in combination with other agents) were reviewed retrospectively. Forty-eight histologic specimens obtained at surgery were analyzed for inflammatory responses and compared with the time interval between embolization and surgery. Postembolization angiograms were assessed for vasculitis and CT scans were reviewed for evidence of hemorrhage after embolization. There was no angiographic evidence of vasculitis. Histologic evidence of vasculitis was absent or mild in 92% of cases and histologic evidence of perivascular inflammation was absent or mild in 73% of cases. The frequency of histologic changes associated with vasculitis, perivascular inflammation, and vessel necrosis varied with the time interval between embolization and AVM resection. Intracranial hemorrhage, as a direct complication of silk use, occurred in one patient. Another patient had subarachnoid hemorrhage 24 hours after embolization, caused by rupture of a posteroinferior cerebellar artery aneurysm. Intraventricular high-density material appeared on routine postembolization CT scans in two other patients who had intraventricular AVM extension. This high-density material was thought to be contrast extravasation from intrinsically leaky AVM nidus vessels and not frank hemorrhage. Embolization of AVMs with silk does not result in marked inflammation or increased hemorrhagic complications as compared with other agents.


[DNA polymerases beta and lambda, and their roles in the DNA replication and repair].
One of the key stages of life of a cell is genome duplication. The main enzymes which lead this process are DNA-dependent DNA polymerases. At the moment, 19 DNA polymerases with striking properties are listed in the eukaryotic cells. Mitochondrial DNA polymerase gamma from A family and most of the nuclear enzymes from B family are high fidelity DNA polymerases which are participate in genome DNA replication process as well as in DNA repair. Among the other 1 5 proteins, the D N A polymerases belonging to the X and Y families have a special place. They participate in a different repair processes such as base excision repair and non-homologous end joining. Moreover, some of them play a specific role in the replication of the damaged DNA templates. This process is referred as translesion synthesis or TLS. The DNA polymerases beta and lambda members of X family are enclosed in polyfunctional enzymes, and their properties and functions will be discussed in this review.


CAM use in dermatology. Is there a potential role for honey, green tea, and vitamin C?
Complementary and alternative medicine (CAM) is a group of non-traditional medical practices that includes natural products, manipulations, and mind and body medicine. CAM use has grown and become popular among patients. In dermatology, honey, green tea, and vitamin C have been used as topical treatments for a variety of diseases. We performed a systematic review to explore the cutaneous effects of each of these three products. Honey's unique antibacterial, anti-inflammatory, and antioxidant properties were shown to contribute to wound healing, especially in ulcers and burns. Green tea, among many health benefits, demonstrated protection from ultraviolet-induced events, such as photoimmunosuppression and skin cancer growth. Vitamin C, known for its antioxidant properties and key role in collagen production, has been shown to produce positive effects on skin hyperpigmentation and aging. Future large well-designed clinical trials are needed in order to further investigate the potential of these agents as dermatological therapies.


Reduced electronic spaces for modeling donor/acceptor interactions.
Diabatic states for donor (D) and acceptor (A) interactions in electron transfer (ET) processes are formulated and evaluated, along with coupling elements (H(DA)) and effective D/A separation distances (r(DA)), for reduced electronic spaces of variable size, using the generalized Mulliken Hush model (GMH), applicable to an arbitrary state space and nuclear configuration, and encompassing Robin-Day class III and as well as class II situations. Once the electronic state space is selected (a set of n ≥ 2 adiabatic states approximated by an orbital space based on an effective 1-electron (1-e) Hamiltonian), the charge-localized GMH diabatic states are obtained as the eigenstates of the dipole moment operator, with rotations to yield locally adiabatic states for sites with multiple states. The 1-e states and energies are expressed in terms of Kohn-Sham orbitals and orbital energies. Addressing questions as to whether the estimate of H(DA) "improves" as one increases n, and in what sense the GMH approach "converges" with n, we carry out calculations for three mixed-valence binuclear Ru complexes, from which we conclude that the 2-state (2-st) model gives the most appropriate estimate of the effective coupling, similar (to within a rms deviation of ≤15%) to coupling elements obtained by superexchange correction of H(DA) values based on larger spaces (n = 3-6), and thus yielding a quasi-invariant value for H(DA) over the range explored in the calculations (n = 2-6). An analysis of the coupling and associated D and A states shows that the 2-st coupling involves crucial mixing with intervening bridge states (D and A "tails"), while increasingly larger state spaces for the same system yield increasingly more localized D and A states (and weaker coupling), with H(DA) tending to approach the limit of "bare" or "through space" coupling. These results help to reconcile seemingly contradictory assertions in the recent literature regarding the proper role of multistate frameworks in the formulation of coupling for both intra- and intermolecular ET systems.The present results are compared in detail with other reported results.


Religiosity may help preserve the cortisol rhythm in women with stress-related illness.
Fibromyalgia has been characterized as a basic disorder of endocrine stress responses in which psychological stress has been linked both with etiology and symptom severity. This study investigated associations of religiosity and spirituality with psychological and physiological (endocrine) measures of stress in a sample of women with fibromyalgia. Ninety-one participants provided self-reports of religiosity and spirituality using the Duke University Religion Index (DUREL) and the Index of Core Spiritual Experiences (INSPIRIT). Psychological outcomes were measured with the Perceived Stress Scale (PSS), and diurnal salivary cortisol profiles were measured as an indicator of neuroendocrine regulation. Hierarchal regression analyses controlling for age and medications likely to affect cortisol levels revealed significant associations of nonorganizational religiosity and intrinsic religiosity with the diurnal cortisol rhythm. Patients reporting medium or high religiosity had rhythmic cortisol profiles characterized by high morning and low evening levels. In contrast, cortisol rhythms of those reporting low religiosity appeared flattened. The association between intrinsic religiosity and cortisol rhythm persisted after controlling for social support. No significant effects of religiosity or spirituality on perceived stress were observed. These data suggest that religiosity may have a protective effect on the physiological effects of stress among women with fibromyalgia.


Visualization of species pairwise associations: a case study of surrogacy in bird assemblages.
Quantifying and visualizing species associations are important to many areas of ecology and conservation biology. Species networks are one way to analyze species associations, with a growing number of applications such as food webs, nesting webs, plant-animal mutualisms, and interlinked extinctions. We present a new method for assessing and visualizing patterns of co-occurrence of species. The method depicts interactions and associations in an analogous way with existing network diagrams for studying pollination and trophic interactions, but adds the assessment of sign, strength, and direction of the associations. This provides a distinct advantage over existing methods of quantifying and visualizing co-occurrence. We demonstrate the utility of our new approach by showing differences in associations among woodland bird species found in different habitats and by illustrating the way these can be interpreted in terms of underlying ecological mechanisms. Our new method is computationally feasible for large assemblages and provides readily interpretable effects with standard errors. It has wide applications for quantifying species associations within ecological communities, examining questions about particular species that occur with others, and how their associations can determine the structure and composition of communities.


The effects of cryopreservation on the expression of canine regulatory T-cell markers.
Regulatory T (Treg) cells have been described as key regulators in various immunological processes and are of growing interest in veterinary allergy. Cryopreservation of immune cells is performed routinely in human basic science research and in clinical studies. As such, it allows batch testing of collected samples at a single time point, resulting in a significant reduction in sample variability. Data which describe the effects of cryopreservation on Treg cell frequency and functionality in the canine species are important to inform future research. The purpose of this study was to establish a robust freeze/thaw procedure and flow cytometric staining protocol for canine Treg cells, and to compare the frequencies of different canine Treg cell phenotypes before and after cryopreservation. Nine privately owned dogs. Peripheral blood mononuclear cells were isolated and Treg cells stained and analysed by flow cytometry, before and after three months of cryopreservation. The recovery percentages and the corresponding correlations (fresh versus cryopreserved) for CD4+ CD25+ , CD4+ FOXP3+ and CD4+ CD25+ FOXP3+ cell populations were calculated. A high recovery rate of 97.2 (r = 0.94, P < 0.0001), 93.9 (r = 0.77, P < 0.01) and 101.7% (r = 0.99, P < 0.0001) for CD4+ CD25+ , CD4+ FOXP3+ and CD4+ CD25+ FOXP3+ cell populations, respectively, was observed. This study demonstrates an optimized protocol for freezing, thawing and quantifying canine Treg cells. These results indicate that cryopreservation does not substantially affect the expression of surface and intracellular markers of canine Treg cells; however, additional studies will be necessary to assess whether functionality of the cells is also maintained.


A biomechanical model of the inner ear: numerical simulation of the caloric test.
Whether two vertical semicircular canals can receive thermal stimuli remains controversial. This study examined the caloric response in the three semicircular canals to the clinical hot caloric test using the finite element method. The results of the developed model showed the horizontal canal (HC) cupula maximally deflected to the utricle side by approximately 3 μm during the hot supine test. The anterior canal cupula began to receive the caloric stimuli about 20 s after the HC cupula, and it maximally deflected to the canal side by 0.55 μm. The posterior canal cupula did not receive caloric stimuli until approximately 40 s after the HC cupula, and it maximally deflected to the canal side by 0.34 μm. Although the endolymph flow and the cupular deformation change with respect to the head position during the test, the supine test ensures the maximal caloric response in the HC, but no substantial improvement for the responses of the two vertical canals was observed. In conclusion, while the usual supine test is the optimum test for evaluating the functions of the inner ear, more irrigation time is needed in order to effectively clinically examine the vertical canals.


The health of people in Australian immigration detention centres.
To determine the health status of people in Australian immigration detention centres and the effect of time in, and reason for, detention. An analysis of the health records of 720 of the 7375 people in detention in the financial year 1 July 2005-30 June 2006, with oversampling of those detained for > 3 months. Health encounters and health condition categories; estimated incidence rates of new health conditions, new mental health conditions, and new injuries for each cohort (defined by time in, and reason for, detention). People in detention had an estimated 1.2 (95% CI, 1.18-1.27) health encounters per person-week. Those detained for > 24 months had particularly poor health, both mental and physical. Asylum seekers had more health problems than other people in detention. The main health problems varied depending on the length of time in detention, but included dental, mental health, and musculoskeletal problems, and lacerations. Both time in, and reason for, detention were significantly related to the rate of new mental health problems (P = 0.018 and P < 0.001, respectively). The relationship between these variables and the incidence rates of physical health problems was more complex. People in immigration detention are frequent users of health services, and there is a clear association between time in detention and rates of mental illness. Government policies internationally should be informed by evidence from studies of the health of this marginalised and often traumatised group.


Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA.
DNMT2 is a human protein that displays strong sequence similarities to DNA (cytosine-5)-methyltransferases (m(5)C MTases) of both prokaryotes and eukaryotes. DNMT2 contains all 10 sequence motifs that are conserved among m(5)C MTases, including the consensus S:-adenosyl-L-methionine-binding motifs and the active site ProCys dipeptide. DNMT2 has close homologs in plants, insects and Schizosaccharomyces pombe, but no related sequence can be found in the genomes of Saccharomyces cerevisiae or Caenorhabditis elegans. The crystal structure of a deletion mutant of DNMT2 complexed with S-adenosyl-L-homocysteine (AdoHcy) has been determined at 1.8 A resolution. The structure of the large domain that contains the sequence motifs involved in catalysis is remarkably similar to that of M.HHAI, a confirmed bacterial m(5)C MTase, and the smaller target recognition domains of DNMT2 and M.HHAI are also closely related in overall structure. The small domain of DNMT2 contains three short helices that are not present in M.HHAI. DNMT2 binds AdoHcy in the same conformation as confirmed m(5)C MTases and, while DNMT2 shares all sequence and structural features with m(5)C MTases, it has failed to demonstrate detectable transmethylase activity. We show here that homologs of DNMT2, which are present in some organisms that are not known to methylate their genomes, contain a specific target-recognizing sequence motif including an invariant CysPheThr tripeptide. DNMT2 binds DNA to form a denaturant-resistant complex in vitro. While the biological function of DNMT2 is not yet known, the strong binding to DNA suggests that DNMT2 may mark specific sequences in the genome by binding to DNA through the specific target-recognizing motif.


Quantitative genetics of sex ratio traits in the parasitic wasp, Nasonia vitripennis.
We detected significant parent-offspring regressions for the first sex ratio (the sex ratio produced by a female in a fresh host) and the second sex ratio (the sex ratio produced by a female in a previously parasitized host) in the parasitic wasp, Nasonia vitripennis. For both traits, estimates of the narrow-sense heritability range from approximately 0.05 to approximately 0.15 (depending on how the data are analyzed). The study population was derived from isofemale strains created from wasps captured in a single bird nest. The same population exhibited no significant parent-offspring regression for the brood sizes associated with the first and second sex ratios. There may be a significant negative parent-offspring regression for diapause proportion in the first sex ratio broods. The estimates of the genetic correlations between first and second sex ratios are positive although almost all are not significantly different from 0.0. To our knowledge, this study is the first "fine-scale" analysis of genetic variation for sex ratio traits in any species of insect. Such studies are an essential part of the assessment of the validity of claims that sex ratio traits are locally optimal.


Sex differences in autoimmune disorders of the central nervous system.
Stronger adaptive immune responses in females can be observed in different mammals, resulting in better control of infections compared to males. However, this presumably evolutionary difference likely also drives higher incidence of autoimmune diseases observed in humans. Here, we summarize sex differences in the most common autoimmune diseases of the central nervous system (CNS) and discuss recent advances in the understanding of possible underlying immunological and CNS intrinsic mechanisms. In multiple sclerosis (MS), the most common inflammatory disease of the CNS, but also in rarer conditions, such as neuromyelitis optica spectrum disorders (NMOSD) or neuronal autoantibody-mediated autoimmune encephalitis (AE), sex is one of the top risk factors, with women being more often affected than men. Immunological mechanisms driving the sex bias in autoimmune CNS diseases are complex and include hormonal as well as genetic and epigenetic effects, which could also be exerted indirectly via modulation of the microbiome. Furthermore, CNS intrinsic differences could underlie the sex bias in autoimmunity by differential responses to injury. The strong effects of sex on incidence and possibly also activity and progression of autoimmune CNS disorders suggest that treatments need to be tailored to each sex to optimize efficacy. To date, however, due to a lack of systematic studies on treatment responses in males versus females, evidence in this area is still sparse. We argue that studies taking sex differences into account could pave the way for sex-specific and therefore personalized treatment.


Superior early diagnostic performance of a sensitive cardiac troponin assay as compared to a standard troponin test in the diagnosis of acute myocardial infarction.
New generation cardiac troponin assays have sufficient precision to detect and quantify plasma troponin concentrations below the lower threshold of detection of the currently employed troponin tests. However, diagnostic performance of the newer generation assays in daily clinical practice is not well established. To evaluate the diagnostic performance of a sensitive assay as compared to a standard assay in a single reading at admission in the diagnosis of acute myocardial infarction (AMI) in patients presenting to the Emergency Department with chest pain. The study comprised 187 consecutive patients admitted to the Institute of Cardiology in Warsaw in June and July 2010 with chest pain in whom the attending physician ordered troponin assay to rule AMI in or out. In all of these patients, in addition to the standard Dimension Flex Troponin I (Siemens Healthcare Diagnostics, Inc.) the sensitive Architect Stat Troponin I (Abbott Diagnostics) test was assayed. The triage of patients as well as all diagnostic and treatment decisions were left to the discretion of the attending physician who was blinded to the sensitive troponin test readings. The final diagnosis was adjudicated by a team of two cardiologists on the basis of all the available medical records except for sensitive troponin test results. Mean age of the study cohort (n = 187) was 64.3 ± 13.9 years and 119 (63.6%) were males. The final diagnosis of AMI was adjudicated in 84 (44.9%) patients (mean age 67.5 ± 12.9 years; 119 [63.6%] males). Receiver operating characteristic (ROC) analysis showed greater area under the curve (AUC) for the sensitive cardiac troponin assay compared to the standard assay (AUC = 0.916, 95% CI = 0.866-0.951 vs AUC = 0.863, 95% CI = 0.806-0.909, respectively; p = 0.02) in a single reading at admission. Sensitive assay was characterised by higher sensitivity (87%), specificity (88%), positive (86%) and negative (89%) predictive values in the detection of AMI compared to the standard troponin test (82%, 81%, 78%, and 85% respectively). The newer generation sensitive cardiac troponin assay presented superior diagnostic accuracy in the diagnosis of AMI compared to the standard troponin test in a single reading at admission with improved sensitivity and specificity. The sensitive troponin assay has the potential to improve early detection and/or exclusion of AMI.


Efficacy and safety of recombinant human C1-inhibitor for the treatment of attacks of hereditary angioedema: European open-label extension study.
Hereditary angioedema (HAE) owing to C1 inhibitor deficiency is an autosomal dominant disorder, characterized by recurrent, potentially life-threatening, localized attacks of tissue swelling. Current treatment involves the infusion of C1 inhibitor protein (C1-INH) isolated from human plasma. This open-label extension to a European, Israeli and Argentinean randomized study (NCT00262301) aimed to investigate the efficacy and safety of recombinant human C1 inhibitor (rhC1-INH) as a first-line treatment following an HAE attack, together with its effect on subsequent attacks. An HAE-specific visual analogue scale (VAS) 0-100 mm was used by patients to assess the severity of attack at four anatomical locations. Patients were treated with one, single-vial, fixed-dose of rhC1-INH (2100 U), followed by up to two further vials at the investigators discretion. The primary end-point was the time from first rhC1-INH injection to first onset of relief of symptoms (≥ 20 mm decrease on VAS). Response to treatment was defined as the onset of relief within 4 h. A total of 57 patients were treated for 194 HAE attacks. Overall, sustained relief of symptoms was achieved in 87% of rhC1-INH-treated patients within 4 h of treatment, with 57% of attacks requiring only one vial of rhC1-INH. When categorized by successive attacks experienced by individual patients, the response rate to rhC1-INH treatment was 96%, 83%, 87%, 80% and 80% for attacks 1-5 respectively. Treatment with rhC1-INH was well tolerated, with no discontinuations owing to treatment-emergent adverse events and no adverse events relating to immunogenicity. Treatment with rhC1-INH provides fast-onset relief for an HAE attack, with a high rate of therapeutic response maintained throughout subsequent attacks.


The facilitator effect: results from a four-year follow-up of children with asthma.
A long-term evaluation of the process and outcomes of primary and secondary care is required to establish whether audit facilitators can improve the care of childhood asthma. To examine the long-term effect of an intervention by an audit facilitator on the management of children with asthma, and to investigate the implications for health service costs. A 4-year follow up was conducted of an intervention and control group totalling 2557 children aged 1-15 years from 12 general practices in the Tayside region. Primary care consultations, prescriptions, hospital contacts and health service costs 1 year before and 3 years after a facilitator visited practices were recorded. The facilitator encouraged the diagnosis and treatment of childhood asthma in the intervention group. Favourable changes in consultation patterns, prescriptions and reduced hospital admissions seen during the intervention year did not persist in subsequent years. Two and three years after the facilitator visit the process and outcome of care was similar in both groups. The reduction in health service costs seen in the intervention group was equivalent to the cost of employing a facilitator. The effect of a facilitator lasts only for the period of intervention. Enthusiasts will say that improving patient care without increasing health service costs justifies the widespread deployment of facilitators. Others more interested in long-term outcomes may disagree.


Donor-derived transmission events in 2013: a report of the Organ Procurement Transplant Network Ad Hoc Disease Transmission Advisory Committee.
The Organ Procurement Transplant Network Disease Transmission Advisory Committee (DTAC), a multidisciplinary committee, evaluates potential donor-derived transmission events (PDDTE), including infections and malignancies, to assess for donor transmitted events. Reports of unexpected PDDTE to Organ Procurement Transplant Network in 2013 were fully reviewed by DTAC. A standardized algorithm was used to assess each PDDTE from a given donor and to classify each individual recipient from that donor. Of 443 total PDDTE submitted, 159 were triaged and not sent out to the full DTAC. Of 284 fully evaluated reports, 32 (11.3%) resulted in a proven/probable (P/P) transmission of infection, malignancy or other conditions to 42 recipients. Of 204 infection events, 24 were classified as P/P affecting 30 recipients, with four deaths. Bacteria were the most frequently reported type of infection, accounting for 99 reports but only 12 recipients from 11 donors experienced P/P transmission. There were 65 donors reported with potential malignancy events and 5 were classified as P/P transmissions with 8 affected recipients and 2 deaths. Additionally, there were 16 noninfection, nonmalignancy reports resulting in 3 P/P transmissions to 4 recipients and 1 death. There was a 43% increase in the number of PDDTE reported and reviewed in 2013 over 2012. However, the percent with P/P transmission remains low, affecting recipients from 32 donors especially when compared with the more than 14,000 donors recovered annually in the United States. The continued use of the new standard algorithm and triaging process will enhance the reproducibility of DTAC assessments and allow more robust analysis of our aggregate DTAC experience.


Global analysis of gene expression during development and ripening of citrus fruit flesh. A proposed mechanism for citric Acid utilization.
Microarrays of cDNA have been used to examine expression changes of 7000 genes during development and ripening of the fruit flesh of self-incompatible Citrus clementina, a non-climateric species. The data indicated that 2243 putative unigenes showed significant expression changes. Functional classification revealed that genes encoding for regulatory proteins were significantly overrepresented in the up-regulated gene clusters. The transcriptomic study together with the analyses of selected metabolites highlighted key physiological processes occurring during citrus fruit development and ripening such as water accumulation, carbohydrate build-up, acid reduction, pigment substitutions (carotenoid accumulation and chlorophyll decreases) and ascorbic acid diminution. Often, the combined analyses strongly suggested prevalence of specific metabolic alternatives. This observation has been exemplified with the proposal for a mechanism for citrate utilization, a process of much importance in citrus industry. Microarray data validated by real-time RT-PCR suggested that citrate was sequentially metabolyzed to isocitrate, 2-oxoglutarate and glutamate. Thereafter, glutamate was both utilized for glutamine production and catabolyzed through the gamma-aminobutirate (GABA) shunt (GABA --> succinate semialdehyde --> succinate). This last observation appears to be of special relevance since it links the proton consuming reaction glutamate + H(+)--> GABA + CO(2) with high acid levels. GG-MS determinations showed that glutamate was constant while GABA levels decreased at ripening in agreement with a feasible activation of the GABA shunt during acid catabolism. This suggestion provides a convincing explanation for the strong reduction of both citrate and cytoplasmatic acidity that takes place in citrus fruit flesh during development and ripening.


Porphyrins Containing a Triphenylamine Donor and up to Eight Alkoxy Chains for Dye-Sensitized Solar Cells: A High Efficiency of 10.9%.
Porphyrins are promising DSSC sensitizers due to their structural similarity to chlorophylls as well as their tunable strong absorption. Herein, a novel D-π-A porphyrin dye XW14 containing a strongly electron-donating triphenylamine moiety as the electron donor was designed and synthesized. To avoid undesirably decreased Voc caused by dye aggregation effect, two methoxy or hexyloxy chains were introduced to the para positions of the triphenylamine moiety to afford XW15 and XW16, respectively. To further extend the absorption to a longer wavelength, a benzothiadiazole unit was introduced as an auxiliary acceptor to furnish XW17. Compared with XW14, the introduction of additional methoxy or hexyloxy groups in XW15 and XW16 red-shift the onset wavelengths from 760 to 780 and 790 nm, respectively. More impressively, XW17 has a more extended π-conjugation framework, and thus, it exhibits a much broader IPCE spectrum with an extremely red-shifted onset wavelength of 830 nm, resulting in the highest Jsc (18.79 mA cm(-2)). On the other hand, the hexyloxy chains are favorable for suppressing the dye aggregation effect, and thus XW16 shows the highest Voc of 734 mV. As a result, XW16 and XW17 demonstrate photovoltaic efficiencies of 9.1 and 9.5%, respectively, higher than those of XW14 (8.6%) and XW15 (8.7%), and obviously higher than that of 7.94% for our previously reported dye, XW4. On the basis of optimized porphyrin dye XW17, we used a nonporphyrin dye with a high Voc and strong absorption around 500 nm (WS-5) as the cosensitizer to improve the Voc from 700 to 748 mV, with synergistical Jsc enhancement from 18.79 to 20.30 mA cm(-2). Thus, the efficiency was dramatically enhanced to 10.9%, which is among the highest efficiencies obtained for the DSSCs based on traditional iodine electrolyte. In addition, the DSSCs based on XW17 + WS-5 exhibit good photostability, which is beneficial for practical applications.


Towards (99m)Tc-based imaging agents with effective doxorubicin mimetics: a molecular and cellular study.
Doxorubicin is a clinical benchmark drug, which is applied in the treatment of numerous cancers. Known for its accumulation in the nucleus and ability to intercalate into DNA, it targets quickly dividing i.e. hypermitotic cells. Through this mechanism, it could be an ideal structural motif for a new class of imaging agents, given that the new entity approximates the in vitro profile of the parent drug. Here we describe design, synthesis and biological activity of a small array of Doxorubicin-metalloconjugates (M = (99m)Tc, Re). We demonstrate that the conjugates preferably accumulate in the nuclear compartment, tightly bind to DNA and retain an appreciable cytotoxicity. Moreover, the Re conjugates effectively act as inhibitors of the human Topoisomerase II enzyme, which is the widely accepted mechanism of action of the parent drug. Since the conjugates effectively mimic the in vitro behavior of native Doxorubicin, the (99m)Tc compounds are prospective imaging agents.


Embossing of a screw thread and TCP granules enhances the fixation strength of compressed ACL grafts with interference screws.
Fixation of soft tissue grafts with interference screws relies on the friction of the graft between the screw and the bone tunnel. The goal of this study was to precondition such grafts by mechanical compression in order to reduce anticipated and undesired viscoelastic adaptation of the graft to screw pressure. Further, the otherwise slippery graft surface was modified with impressed tricalcium phosphate granules (TCP) to improve friction and mechanical hold. Fresh flexor digitorum tendons from young bovines were used to create bundles with a diameter of 8-9 mm and were divided into 10 groups to compare the pullout strength and bone damage in a variety of construct scenarios. Specifically, the effects of graft precompression to reduce preimplantation graft diameter were investigated. Further the effects of impressing TCP granules and/or a screw thread into the tendon surface during the compression process were studied. In sawbone tests, radial graft compression allowed for a smaller bone tunnel (7 mm), but resulted in a significantly lower pullout strength of 174 N (95% CI: 97, 250), compared with controls [315 N (204, 426)]. In contrast, TCP coated [402 N (243, 561)], screw embossed grafts [458 N (302, 614)], and the combination of TCP and embossing [409 N (274, 543)] achieved higher pullout strengths when compared to the standard technique. In porcine bone, untreated grafts using an 8 mm screw pulled out at 694 ± 93 N, significantly higher loads were required to pullout compressed grafts with or without TCP coating (870 ± 74 and 878 ± 131 N), yet fixed with a 7 mm screw. Modification of the tendon graft surface has a large influence on the biomechanical performance of interference screw fixation and results in less bone damage inflicted during insertion to a smaller tunnel diameter, while simultaneously achieving superior pullout strength.


The effects of hearing impairment in older adults on communication partners: a systematic review.
Hearing impairment is highly prevalent in older adults and can affect the daily activities of a person who is hard of hearing (HOH). The impact of hearing impairment may also have collateral effects on the primary communication partner (CP; e.g., spouse, close family member, or caregiver) of the person who is HOH. We aimed to characterize the impact of hearing loss in a person who is HOH on his or her CP. We conducted a systematic review of manuscripts examining the consequences of hearing loss in a person who is HOH on the CP. We searched PubMed, Embase, Scopus, PyscINFO, CINAHL Plus with full text, and Web of Science for peer-reviewed articles using a predefined search string and hand-searched reference lists of relevant articles. We initially screened abstracts blinded for author and journal to eliminate irrelevant and duplicate articles. Descriptive information on study populations, hearing assessments, outcome metrics, and study findings were extracted from full-length manuscripts. Of the 1,047 abstracts retrieved from database searching and 5 hand-searched articles, 24 articles met inclusion criteria. These articles included observational clinical studies, randomized clinical trials, and epidemiologic studies. Overall, CPs experienced a restricted social life, increased burden of communication, and poorer quality of life (QOL) and relationship satisfaction. Effects of hearing impairment on a CP's mental health were unclear. Treatment of hearing loss in the person who is HOH tended to improve QOL, communication, feelings toward the person who is HOH, and activity participation of the CP. This review highlights the broad effects of hearing impairment and the importance of involving CPs in hearing loss treatment decisions.


What becomes of patients one year after the intragastric balloon has been removed?
The BioEnterics Intragastric Balloon (BIB) is a saline-filled balloon recommended to remain in the gastric cavity for a maximum of 6 months. Is this short period sufficient to change patients' lifestyle and eating practices to maintain weight reduction after BIB removal? 100 patients who received a BIB were included in this prospective study and followed for 1 year after BIB removal. The post-implantation follow-up visits took place monthly, during which the patient was seen by the surgeon, dietitian, and if necessary, psychologist. At BIB removal, mean weight loss for the group was 12.0 kg. Mean percent excess weight loss (%EWL) was 39.8%. 12 months after removal of the BIB, mean weight loss was 8.6 kg and mean %EWL was 26.8% for the group as a whole. The results 1 year after removal of the BIB were encouraging. Because the BIB is a temporary non-surgical and non-pharmaceutical treatment for obesity that is reversible and repeatable, we recommend it to patients who have previously failed traditional methods of weight reduction. Careful patient follow-up is of primary importance in avoiding complications and supporting efficacy of the treatment. Although 1 year follow-up cannot be considered long term, these results are encouraging. Concurrent behavior modification is needed for durable weight loss.


Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine.
The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms. However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control. Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T(EM)) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV(MAC239) infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (≥1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8(+) T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated T(EM) responses might significantly contribute to an efficacious HIV/AIDS vaccine.


Regulation of interferon production by RIG-I and LGP2: a lesson in self-control.
The cytoplasmic CARD-containing DExD/H box RNA helicases RIG-I and MDA5 act as sensors of viral infections through recognition of viral double-stranded (ds) RNAs. They both associate with the mitochondrial adaptor IPS-1 (also referred to as MAVS, VISA, and CARDIF) through homotypic CARD-CARD interactions. IPS-1, in turn, triggers signaling pathways, including activation of the protein kinases TBK1 and IKKepsilon, responsible for the phosphorylation of IRF3, a key transcription factor involved in interferon (IFN) synthesis, one essential element of the innate immune response. RIG-I remains in an autoinhibited state in the absence of dsRNA, through an internal repressor domain (RD) that binds within both its CARD and its RNA helicase domains and therefore acts in cis to control its multimerization and interaction with IPS-1. Ectopic expression of the RD prevents signaling and increases cell permissiveness to viruses, including hepatitis C virus. LGP2, which is another DExD/H RNA helicase of the RIG-I and MDA5 family and which is devoid of CARD domain, negatively controls IFN induction at different levels: by sequestering dsRNA, by blocking RIG-I's multimerization in trans through a domain analogous to the RIG-I RD, and by competing with the protein kinase IKKepsilon for a common interaction site on IPS-1. The ability of RIG-I and LGP2 to exert such a feedback control at the earliest steps of IFN synthesis allows the cells to exert a tight regulation of the induction of the innate immune response.


Variable effects on growth and defense traits for plant ecotypic differentiation and phenotypic plasticity along elevation gradients.
Along ecological gradients, phenotypic differentiation can arise through natural selection on trait diversity and magnitude, and environment-driven plastic changes. The magnitude of ecotypic differentiation versus phenotypic plasticity can vary depending on the traits under study. Using reciprocal transplant-common gardens along steep elevation gradients, we evaluated patterns of ecotypic differentiation and phenotypic plasticity of several growth and defense-related traits for two coexisting but unrelated plant species, Cardamine pratensis and Plantago major. For both species, we observed ecotypic differentiation accompanied by plasticity in growth-related traits. Plants grew faster and produced more biomass when placed at low elevation. In contrast, we observed fixed ecotypic differentiation for defense and resistance traits. Generally, low-elevation ecotypes produced higher chemical defenses regardless of the growing elevation. Yet, some plasticity was observed for specific compounds, such as indole glucosinolates. The results of this study may suggest that ecotypic differentiation in defense traits is maintained by costs of chemical defense production, while plasticity in growth traits is regulated by temperature-driven growth response maximization.