A competing risks model in early screening for preeclampsia.
It was the aim of this study to develop models for the prediction of preeclampsia (PE) based on maternal characteristics and biophysical markers at 11-13 weeks' gestation in which gestation at the time of delivery for PE is treated as a continuous variable. This was a screening study of singleton pregnancies at 11-13 weeks including 1,426 (2.4%) cases that subsequently developed PE and 57,458 cases that were unaffected by PE. We developed a survival time model for the time of delivery for PE in which Bayes' theorem was used to combine the prior information from maternal characteristics with the uterine artery pulsatility index (PI) and the mean arterial pressure (MAP), using multiple of the median values. The risk for PE increased with maternal age, weight, Afro-Caribbean and South Asian racial origin, previous pregnancy with PE, conception by in vitro fertilization and a medical history of chronic hypertension, type 2 diabetes mellitus as well as systemic lupus erythematosus or antiphospholipid syndrome. In pregnancies with PE, there was an inverse correlation between multiple of the median values of the uterine artery PI and MAP with gestational age at delivery. Screening by maternal characteristics, uterine artery PI and MAP detected 90% of PE cases requiring delivery before 34 weeks and 57% of all PE cases at a fixed false-positive rate of 10%. A new model has been developed for effective first-trimester screening for PE.


Variability of Skin Pharmacokinetic Data: Insights from a Topical Bioequivalence Study Using Dermal Open Flow Microperfusion.
Dermal open flow microperfusion (dOFM) has previously demonstrated its utility to assess the bioequivalence (BE) of topical drug products in a clinical study. We aimed to characterize the sources of variability in the dermal pharmacokinetic data from that study. Exploratory statistical analyses were performed with multivariate data from a clinical dOFM-study in 20 healthy adults evaluating the BE, or lack thereof, of Austrian test (T) and U.S. reference (R) acyclovir cream, 5% products. The overall variability of logAUC values (CV: 39% for R and 45% for T) was dominated by inter-subject variability (R: 82%, T: 91%) which correlated best with the subject's skin conductance. Intra-subject variability was 18% (R) and 9% (T) of the overall variability; skin treatment sites or methodological factors did not significantly contribute to that variability. Inter-subject variability was the major component of overall variability for acyclovir, and treatment site location did not significantly influence intra-subject variability. These results support a dOFM BE study design with T and R products assessed simultaneously on the same subject, where T and R treatment sites do not necessarily need to be next to each other. Localized variation in skin microstructure may be primarily responsible for intra-subject variability.


Physician preferences for bone metastasis drug therapy in Canada.
Currently in Canada, several bone-targeted agents (btas) with varying characteristics are available for the prevention of skeletal-related events (sres) in patients with bone metastasis secondary to solid tumours. In the present study, we evaluated the preferences of physicians in Canada for the various attributes of the available btas. Physicians treating patients with bone metastasis from solid tumours were invited to complete an online discrete-choice experiment. Respondents were asked to choose between pairs of hypothetical medications for virtual patients. Each hypothetical medication was described based on predefined key attributes: time until first sre, time until worsening of pain, medication-related annual risk of osteonecrosis of the jaw (onj), medication-related annual risk of renal impairment, and mode of administration. A random-parameters logit model was used to analyze the choices between hypothetical medications and thus infer physician preferences for medication attributes. Responses from the 200 physicians who completed the discrete-choice experiment suggested that months until first sre, risk of renal impairment, and months until worsening of pain were considered the most important attributes affecting choice of bta. The annual risk of onj was considered the least important attribute. When making treatment decisions about the choice of bta for patients with bone metastasis from solid tumours, delaying sres and worsening of pain, and reducing the risk of renal impairment are primary considerations for physicians in Canada.


Evidence of impact of maternal HIV infection on immunoglobulin levels in HIV-exposed uninfected children.
HIV infection affects B cell function and is associated with increased immunoglobulin levels, including in HIV-infected pregnant women. It is unknown if maternal HIV infection affects immunoglobulins in their uninfected children. We investigated this using prospective longitudinal data from children born to HIV-infected women enrolled in the European Collaborative Study (ECS). Data from children enrolled in the European Paediatric Hepatitis C Virus Network (EPHN) were used as a comparison group. Associations between infant and maternal factors and child log(10) total IgG, IgM, and IgA levels were quantified in linear regression analyses. A total of 1751 HIV-uninfected (ECS) and 167 HCV-uninfected children (EPHN) were included. HIV-uninfected children had significantly higher IgG, IgM, and IgA levels than HCV-uninfected children up to at least 24 months. Among HIV-exposed uninfected children, IgG levels from birth until 5 years of age were correlated with increased maternal IgG levels. ART exposure in fetal and early neonatal life was associated with lower IgG. These findings indicate alterations in immunoglobulin levels in uninfected children born to HIV-infected women, suggesting that fetal exposure to a chronically activated maternal immune system is associated with an altered humoral response.


The Impact of Shame, Self-Criticism and Social Rank on Eating Behaviours in Overweight and Obese Women Participating in a Weight Management Programme.
Recent research has suggested that obesity is a stigmatised condition. Concerns with personal inferiority (social rank), shame and self-criticism may impact on weight management behaviours. The current study examined associations between social comparison (shame, self-criticism), negative affect and eating behaviours in women attending a community based weight management programme focused on behaviour change. 2,236 participants of the programme completed an online survey using measures of shame, self-criticism, social comparison, and weight-related affect, which were adapted to specifically address eating behaviour, weight and body shape perceptions. Correlation analyses showed that shame, self-criticism and social comparison were associated with negative affect. All of these variables were related to eating regulation and weight control (p < 0.001). Path analysis revealed that the association of shame, hated-self, and low self-reassurance on disinhibition and susceptibility to hunger was fully mediated by weight-related negative affect, even when controlling for the effect of depressive symptoms (p < 0.050 to p < 0.010). In addition, feelings of inadequacy and unfavourable social comparisons were associated with higher disinhibition and susceptibility to hunger, partially mediated through weight-related negative affect (p = 0.001). These variables were negatively associated with extent of weight loss during programme attendance prior to the survey, while self-reassurance and positive social comparisons were positively associated with the extent of weight loss prior to the survey (p < .050). Shame, self-criticism, and perceptions of inferiority may play a significant role in self-regulation of eating behaviour in overweight people trying to manage their weight.


Evidence for Use of Cannabinoids in Mood Disorders, Anxiety Disorders, and PTSD: A Systematic Review.
Two primary compounds of the cannabis plant (Cannabis sativa), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), differentially and dose-dependently affect mood and anxiety. In this systematic review, the authors summarize the design and results of controlled trials assessing the effects of THC and CBD on affective disorders, anxiety disorders, and posttraumatic stress disorder (PTSD). A keyword search of eight online literature databases identified eight randomized controlled trials of defined CBD or THC doses for the target populations. A 1-month trial of daily THC (up to 3 mg per day) for DSM-II anxiety disorder reduced anxiety symptoms, but symptoms were very low throughout the study. Another trial of sequential, single-day, low-dose THC in social anxiety disorder found no symptom changes. Two studies reported that single-dose CBD pretreatment reduced anxiety in laboratory paradigms among individuals with social anxiety disorder. A study of daily CBD for 4 weeks among adolescents with social anxiety disorder indicated modest symptom improvements. One crossover trial involving 10 patients with PTSD showed that THC added to standard pharmacotherapy reduced self-reported nightmares. Two small studies of THC for hospitalized patients with unipolar or bipolar depression found no improvement of depression; instead, anxiety and psychotic symptoms emerged in >50% of patients. With only eight very small studies, insufficient evidence was found for efficacy of CBD and THC to manage affective disorders, anxiety disorders, or PTSD. Therefore, medical cannabis should not be recommended for treating patients with these disorders. Further research should investigate the safety and efficacy of managing psychiatric disorders with cannabinoids.


Non-compartmental estimation of pharmacokinetic parameters in serial sampling designs.
Pharmacokinetic studies are commonly analyzed using a two-stage approach where the first stage involves estimation of pharmacokinetic parameters for each subject separately and the second stage uses the individual parameter estimates for statistical inference. This two-stage approach is not applicable in sparse sampling situations where only one sample is available per subject. Nonlinear models are often applied to analyze pharmacokinetic data assessed in such serial sampling designs. Modelling approaches are suitable provided that the form of the true model is known, which is rarely the case in early stages of drug development. This paper presents an alternative approach to estimate pharmacokinetic parameters based on non-compartmental and asymptotic theories in the case of serial sampling when a drug is given as an intravenous bolus. The statistical properties of estimators of the pharmacokinetic parameters are investigated and evaluated using Monte Carlo simulations.


Release of Enterococcus mundtii Bacteriocin ST4SA from Self-Setting Brushite Bone Cement.
Maxillofacial and craniofacial surgery is on the increase, which exposes more patients at risk of acquiring microbial infections. The use of antibiotic-loaded calcium phosphate bone cements has been shown to reduce the incidence of infection. A marked increase in antibiotic-resistant pathogens, including multidrug-resistant pathogens, has been reported. This has led to the investigation of various compounds as alternatives to conventional treatments. In this paper, we report on the incorporation and release of a broad-spectrum class II antimicrobial peptide, bacteriocin ST4SA produced by Enterococcus mundtii, into a calcium orthophosphate-based bone cement. Our results suggest class II bacteriocins may be incorporated into self-setting bone cements to produce implants with antimicrobial activity over extended periods of time.


Hepatic resection for hepatocellular carcinoma: do contemporary morbidity and mortality rates demand a transition to ablation as first-line treatment?
Despite the rising incidence of hepatocellular carcinoma (HCC), challenges and controversy persist in optimizing treatment. As recent randomized trials suggest that ablation can have oncologic equivalence compared with resection for early HCC, the relative morbidity of the 2 approaches is a central issue in treatment decisions. Although excellent contemporary perioperative outcomes have been reported by a few hepatobiliary units, it is not clear that they can be replicated in broader practice. Our objective was to help inform this treatment dilemma by defining perioperative outcomes in a broader set of patients as represented in NSQIP-participating institutions. Mortality and morbidity data were extracted from the 2005-2010 NSQIP Participant Use Data Files based on Current Procedural Terminology (hepatectomy and ablation) and ICD-9 (HCC). Perioperative outcomes were reviewed, and factors associated with morbidity and mortality were identified with multivariable logistic regression. Eight hundred and thirty-seven (52%) underwent minor hepatectomy, 444 (28%) underwent major hepatectomy, and 323 (20%) underwent surgical ablation. Mortality rates were 3.4% for minor hepatectomy, 3.7% for ablation, and 8.3% for major hepatectomy (p < 0.01). Major complication rates were 21.3% for minor hepatectomy, 9.3% for ablation, and 35.1% for major hepatectomy (p < 0.01). When controlling for confounders, ablation was associated with decreased mortality (adjusted odds ratio = 0.20; 95% CI, 0.04-0.97; p = 0.046) and major complications (adjusted odds ratio = 0.34; 95% CI, 0.22-0.52; p < 0.001). Exceedingly high complication rates after major hepatectomy for HCC exist in the broader NSQIP treatment environment. These data strongly support the use of parenchymal-sparing minor resections or ablation over major hepatectomy for early HCC when feasible.


Effect of Rhamnolipid (Biosurfactant) Structure on Solubilization and Biodegradation of n-Alkanes.
A study to quantify the effect of rhamnolipid biosurfactant structure on the degradation of alkanes by a variety of Pseudomonas isolates was conducted. Two dirhamnolipids were studied, a methyl ester form (dR-Me) and an acid form (dR-A). These rhamnolipids have different properties with respect to interfacial tension, solubility, and charge. For example, the interfacial tension between hexadecane and water was decreased to <0.1 dyne/cm by the dR-Me but was only decreased to 5 dyne/cm by the dR-A. Solubilization and biodegradation of two alkanes in different physical states, liquid and solid, were determined at dirhamnolipid concentrations ranging from 0.01 to 0.1 mM (7 to 70 mg/liter). The dR-Me markedly enhanced hexadecane (liquid) and octadecane (solid) degradation by seven different Pseudomonas strains. For an eighth strain tested, which exhibited extremely high cell surface hydrophobicity, hexadecane degradation was enhanced but octadecane degradation was inhibited. The dR-A also enhanced hexadecane degradation by all degraders but did so more modestly than the dR-Me. For octadecane, the dR-A only enhanced degradation by strains with low cell surface hydrophobicity.


Recognizing and treating anal cancer: training medical students and physicians in Puerto Rico.
This training activity aimed at increasing the knowledge of anal cancer screening, diagnostic and treatment options in medical students and physicians, to determine the interest of these individuals in receiving training in the diagnosis and treatment of anal cancer, and to explore any previous training and/or experience with both anal cancer and clinical trials that these individuals might have. An educational activity (1.5 contact hours) was attended by a group of medical students, residents and several faculty members, all from the Medical Sciences Campus of the University of Puerto Rico (n = 50). A demographic survey and a 6-item pre- and post-test on anal cancer were given to assess knowledge change. Thirty-four participants (68%) answered the survey. Mean age was 29.6 +/- 6.6 years; 78.8% had not received training in anal cancer screening, 93.9% reported being interested in receiving anal cancer training, and 75.8% expressed an interest in leading or conducting a clinical trial. A significant increase in the test scores was observed after the educational activity (pre-test: 3.4 +/- 1.2; post-test: 4.7 +/- 0.71). Three of the items showed an increase in knowledge by the time the post-test was taken. The first of these items assessed the participants' knowledge regarding the existence of any guidelines for the screening/treatment of patients with human papillomavirus (HPV)-related anal disease. The second of these items attempted to determine whether the participants recognized that anal intraepithelial neoplasia (AIN) 2 is considered to be a high-grade neoplasia. The last of the 3 items was aimed at ascertaining whether or not the participants were aware that warty growths in the anus are not necessarily a manifestation of high-grade AIN. This educational activity increased the participants' knowledge of anal cancer and revealed, as well, that most of the participants were interested in future training and in collaborating in a clinical trial. Training physicians from Puerto Rico on anal cancer clinical trials is essential to encourage recruitment of Hispanic patients in these studies now that the guidelines in anal cancer screening and treatment are on their way to be defined.


Dynamic regulation of barrier integrity of the corneal endothelium.
The corneal endothelium maintains stromal deturgescence, which is a prerequisite for corneal transparency. The principal challenge to stromal deturgescence is the swelling pressure associated with the hydrophilic glycosaminoglycans in the stroma. This negative pressure induces fluid leak into the stroma from the anterior chamber, but the rate of leak is restrained by the tight junctions of the endothelium. This role of the endothelium represents its barrier function. In healthy cornea, the fluid leak is counterbalanced by an active fluid pump mechanism associated with the endothelium itself. Although this pump-leak hypothesis was postulated several decades ago, the mechanisms underlying regulation of the balance between the pump and leak functions remain largely unknown. In the last couple of decades, the ion transport systems that support the fluid pump activity have been discovered. In contrast, despite significant evidence for corneal edema secondary to endothelial barrier dysfunction, the molecular aspects underlying its regulation are relatively unknown. Recent findings in our laboratory, however, indicate that barrier integrity (i.e., structural and functional integrity of the tight junctions) of the endothelium is sensitive to remodeling of its peri-junctional actomyosin ring, which is located at the apical junctional complex. This review provides a focused perspective on dynamic regulation of the barrier integrity of endothelium vis-à-vis plasticity of the peri-junctional actomyosin ring and its association with cell signaling downstream of small GTPases of the Rho family. Based on findings to date, it appears that development of specific pharmacological strategies to treat corneal edema in response to inflammatory stress would be possible in the near future.


Electrochemical imaging of cells and tissues.
The technological and experimental progress in electrochemical imaging of biological specimens is discussed with a view on potential applications for skin cancer diagnostics, reproductive medicine and microbial testing. The electrochemical analysis of single cell activity inside cell cultures, 3D cellular aggregates and microtissues is based on the selective detection of electroactive species involved in biological functions. Electrochemical imaging strategies, based on nano/micrometric probes scanning over the sample and sensor array chips, respectively, can be made sensitive and selective without being affected by optical interference as many other microscopy techniques. The recent developments in microfabrication, electronics and cell culturing/tissue engineering have evolved in affordable and fast-sampling electrochemical imaging platforms. We believe that the topics discussed herein demonstrate the applicability of electrochemical imaging devices in many areas related to cellular functions.


SALON: Simplified Sensing System for Activity of Daily Living in Ordinary Home.
As aging populations continue to grow, primarily in developed countries, there are increasing demands for the system that monitors the activities of elderly people while continuing to allow them to pursue their individual, healthy, and independent lifestyles. Therefore, it is required to develop the activity of daily living (ADL) sensing systems that are based on high-performance sensors and information technologies. However, most of the systems that have been proposed to date have only been investigated and/or evaluated in experimental environments. When considering the spread of such systems to typical homes inhabited by elderly people, it is clear that such sensing systems will need to meet the following five requirements: (1) be inexpensive; (2) provide robustness; (3) protect privacy; (4) be maintenance-free; and, (5) work with a simple user interface. In this paper, we propose a novel senior-friendly ADL sensing system that can fulfill these requirements. More specifically, we achieve an easy collection of ADL data from elderly people while using a proposed system that consists of a small number of inexpensive energy harvesting sensors and simple annotation buttons, without the need for privacy-invasive cameras or microphones. In order to evaluate the practicality of our proposed system, we installed it in ten typical homes with elderly residents and collected the ADL data over a two-month period. We then visualized the collected data and performed activity recognition using a long short-term memory (LSTM) model. From the collected results, we confirmed that our proposed system, which is inexpensive and non-invasive, can correctly collect resident ADL data and could recognize activities from the collected data with a high recall rate of 72.3% on average. This result shows a high potential of our proposed system for application to services for elderly people.


Organization of visual inputs to the inferior temporal and posterior parietal cortex in macaques.
It has been proposed that visual information in the extrastriate cortex is conveyed along 2 major processing pathways, a "dorsal" pathway directed to the posterior parietal cortex, underlying spatial vision, and a "ventral" pathway directed to the inferior temporal cortex, underlying object vision. To determine the relative distributions of cells projecting to the 2 pathways, we injected the posterior parietal and inferior temporal cortex with different fluorescent tracers in 5 rhesus monkeys. The parietal injections included the ventral intraparietal (VIP) and lateral intraparietal (LIP) areas, and the temporal injections included the lateral portions of cytoarchitectonic areas TE and TEO. There was a remarkable segregation of cells projecting to the 2 systems. Inputs to the parietal cortex tended to arise either from areas that have been implicated in spatial or motion analysis or from peripheral field representations in the prestriate cortex. By contrast, inputs to the temporal cortex tended to arise from areas that have been implicated in form and color analysis or from central field representations. Cells projecting to the parietal cortex were found in visual area 2 (V2), but only in the far peripheral representations of both the upper and lower visual field. Likewise, labeled cells found in visual areas 3 (V3) and 4 (V4) were densest in their peripheral representations. Heavy accumulations of labeled cells were found in the dorsal parieto-occipital cortex, including the parieto-occipital (PO) area, part A of V3 (V3A), and the dorsal prelunate area (DP). In the superior temporal sulcus, cells were found within several motion-sensitive areas, including the middle temporal area (MT), the medial superior temporal area (MST), the fundus of the superior temporal area (FST), and the superior temporal polysensory area (STP), as well as within anterior portions of the sulcus whose organization is as yet poorly defined. Cells projecting to areas TE and TEO in the temporal cortex were located within cytoarchitectonic area TG at the temporal pole and cytoarchitectonic areas TF and TH on the parahippocampal gyrus, as well as in noninjected portions of area TE buried within the superior temporal sulcus. In the prestriate cortex, labeled cells were found in V2, V3, and V4, but, in contrast to the loci labeled after parietal injections, those labeled after temporal injections were concentrated in the foveal or central field representations. Although few double-labeled cells were seen, 2 regions containing intermingled parietal- and temporal-projection cells were area V4 and the cortex at the bottom of the anterior superior temporal sulcus.(ABSTRACT TRUNCATED AT 400 WORDS)


Impact of SARS-CoV-2 on training and mental well-being of surgical gynecological oncology trainees.
The SARS-CoV-2 global pandemic has caused a crisis disrupting health systems worldwide. While efforts are being made to determine the extent of the disruption, the impact on gynecological oncology trainees/training has not been explored. We conducted an international survey of the impact of SARS-CoV-2 on clinical practice, medical education, and mental well-being of surgical gynecological oncology trainees. In our cross-sectional study, a customized web-based survey was circulated to surgical gynecological oncology trainees from national/international organizations from May to November 2020. Validated questionnaires assessed mental well-being. The Wilcoxon rank-sum test and Fisher's exact test were used to analyse differences in means and proportions. Multiple linear regression was used to evaluate the effect of variables on psychological/mental well-being outcomes. Outcomes included clinical practice, medical education, anxiety and depression, distress, and mental well-being. A total of 127 trainees from 34 countries responded. Of these, 52% (66/127) were from countries with national training programs (UK/USA/Netherlands/Canada/Australia) and 48% (61/127) from countries with no national training programs. Altogether, 28% (35/125) had suspected/confirmed COVID-19, 28% (35/125) experienced a fall in household income, 20% (18/90) were self-isolated from households, 45% (57/126) had to re-use personal protective equipment, and 22% (28/126) purchased their own. In total, 32.3% (41/127) of trainees (16.6% (11/66) from countries with a national training program vs 49.1% (30/61) from countries with no national training program, p=0.02) perceived they would require additional time to complete their training fellowship. The additional training time anticipated did not differ between trainees from countries with or without national training programs (p=0.11) or trainees at the beginning or end of their fellowship (p=0.12). Surgical exposure was reduced for 50% of trainees. Departmental teaching continued throughout the pandemic for 69% (87/126) of trainees, although at reduced frequency for 16.1% (14/87), and virtually for 88.5% (77/87). Trainees reporting adequate pastoral support (defined as allocation of a dedicated mentor/access to occupational health support services) had better mental well-being with lower levels of anxiety/depression (p=0.02) and distress (p<0.001). Trainees from countries with a national training program experienced higher levels of distress (p=0.01). Mean (SD) pre-pandemic mental well-being scores were significantly higher than post-pandemic scores (8.3 (1.6) vs 7 (1.8); p<0.01). SARS-CoV-2 has negatively impacted the surgical training, household income, and psychological/mental well-being of surgical gynecological oncology trainees. The overall clinical impact was worse for trainees in countries with no national training program than for those in countries with a national training program, although national training program trainees reported greater distress. COVID-19 sickness increased anxiety/depression. The recovery phase must focus on improving mental well-being and addressing lost training opportunities.


Environmental effects of offshore produced water discharges: A review focused on the Norwegian continental shelf.
Produced water (PW), a large byproduct of offshore oil and gas extraction, is reinjected to formations or discharged to the sea after treatment. The discharges contain dispersed crude oil, polycyclic aromatic hydrocarbons (PAHs), alkylphenols (APs), metals, and many other constituents of environmental relevance. Risk-based regulation, greener offshore chemicals and improved cleaning systems have reduced environmental risks of PW discharges, but PW is still the largest operational source of oil pollution to the sea from the offshore petroleum industry. Monitoring surveys find detectable exposures in caged mussel and fish several km downstream from PW outfalls, but biomarkers indicate only mild acute effects in these sentinels. On the other hand, increased concentrations of DNA adducts are found repeatedly in benthic fish populations, especially in haddock. It is uncertain whether increased adducts could be a long-term effect of sediment contamination due to ongoing PW discharges, or earlier discharges of oil-containing drilling waste. Another concern is uncertainty regarding the possible effect of PW discharges in the sub-Arctic Southern Barents Sea. So far, research suggests that sub-arctic species are largely comparable to temperate species in their sensitivity to PW exposure. Larval deformities and cardiac toxicity in fish early life stages are among the biomarkers and adverse outcome pathways that currently receive much attention in PW effect research. Herein, we summarize the accumulated ecotoxicological knowledge of offshore PW discharges and highlight some key remaining knowledge needs.


Interactions of parental feeding characteristics and adolescent emotional eating in relation to unhealthful food and sugar-sweetened beverage intake among adolescents.
The purpose of the current study was to examine main and interaction effects of parental feeding characteristics and adolescent emotional eating in relation to adolescents' unhealthful food and sugar-sweetened beverage intake. Data was used from the Family Life, Activity, Sun, Health, and Eating (FLASHE) study, which is an internet-administered cross-sectional study of adolescent-parent dyads. There were 1573 dyads who completed all study questionnaires. Adolescents completed measures of their emotional eating and dietary intake and parents completed items of parental feeding practices and legitimacy of parental authority. Adolescents with parents who reported higher instrumental feeding, higher limiting and legitimacy of authority, and lower role modeling and stimulus control had greater unhealthful eating and sugar-sweetened beverage intake. Elevated adolescent emotional eating strengthened the positive association between parental instrumental feeding and adolescent unhealthful food and sugar-sweetened beverage intake. Elevated adolescent emotional eating weakened the negative association between parental role modeling and stimulus control and adolescent sugar-sweetened beverage consumption. There was no interaction between parental role modeling and stimulus control and adolescent emotional eating for unhealthful food intake and no interaction between parental limiting and legitimacy of authority and adolescent emotional eating for unhealthful food or sugar-sweetened beverage intake. Given these findings, adolescent obesity and nutrition interventions and preventions should target both parental feeding characteristics and adolescent emotional eating.


Benefits of glass fibers in solar fiber optic lighting systems.
The transmission properties and coupling of solar light have been studied for glass core multimode fibers in order to verify their benefits for a solar fiber optic lighting system. The light transportation distance can be extended from 20 m with plastic fibers to over 100 m with the kind of glass fibers studied here. A high luminous flux, full visible spectrum, as well as an outstanding color rendering index (98) and correlated color temperature similar to the direct sun light outside have been obtained. Thus the outstanding quality of solar light transmitted through these fibers would improve the visibility of all kinds of objects compared to fluorescent and other artificial lighting. Annual relative lighting energy savings of 36% in Uppsala, Sweden, and 76% in Dubai were estimated in an office environment. The absolute savings can be doubled by using glass optical fibers, and are estimated to be in the order of 550 kWh/year in Sweden and 1160 kWh/year in Dubai for one system of only 0.159 m(2) total light collecting area. The savings are dependent on the fiber length, the daily usage time of the interior, the type of artificial lighting substituted, the system light output flux, and the available time of sunny weather at the geographic location.


2-D modeling of laterally acoustically coupled thin film bulk acoustic wave resonator filters.
A 2-D model is developed for calculating lateral acoustical coupling between adjacent thin film BAW resonators forming an electrical N-port. The model is based on solution and superposition of lateral eigenmodes and eigenfrequencies in a structure consisting of adjacent regions with known plate wave dispersion properties. Mechanical and electrical response of the device are calculated as a superposition of eigenmodes according to voltage drive at one electrical port at a time while extracting current induced in the other ports, leading to a full Y-parameter description of the device. Exemplary cases are simulated to show the usefulness of the model in the study of the basic design rules of laterally coupled thin film BAW resonator filters. Model predictions are compared to an experimental 1.9-GHz band-pass filter based on aluminum nitride thin film technology and lateral acoustical coupling. Good agreement is obtained in prediction of passband behavior. The eigenmode-based model forms a useful tool for fast simulation of laterally coupled acoustic devices. It allows one to gain insight into basic device physics in a very intuitive fashion compared with more detailed but heavier finite element method. Shortcomings of this model and possible improvements are discussed.


Parental monitoring trajectories and gambling among a longitudinal cohort of urban youth.
To test the strength of the association between parental monitoring trajectories throughout early adolescence (ages 11-14) and gambling behaviours by young adulthood (age 22). Longitudinal cohort design. Baltimore, Maryland. The sample of 514 participants with gambling data between ages 16-22 and parental monitoring data between ages 11-14 were predominantly African American and received subsidized lunches at age 6. The South Oaks Gambling Screen and South Oaks Gambling Screen-Revised for Adolescents collected self-reports on annual gambling and gambling problems between ages 16-22. The Parental Monitoring Subscale of the Structured Interview of Parent Management Skills and Practices-Youth Version collected self-reports on annual parental monitoring between ages 11-14. General growth mixture modelling identified two parental monitoring trajectories: (i) 'stable' class (84.9%) began with a high level of parental monitoring at age 11 that remained steady to age 14; (ii) 'declining' class (15.1%) began with a significantly lower level of parental monitoring at age 11 and experienced a significant to through age 14. The declining class had increased significantly unadjusted (OR = 1.91; 95% CI = 1.59, 2.23; P ≤ 0.001) and adjusted (aOR = 1.57; 95% CI = 1.24, 1.99; P = 0.01) odds of problem gambling compared with non-gambling. Low and/or declining parental monitoring of children between the ages of 11 and 14 is associated significantly with problem gambling when those children reach young adulthood.


Myopia: precedents for research in the twenty-first century.
The myopic eye is generally considered to be a vulnerable eye and, at levels greater than 6 D, one that is especially susceptible to a range of ocular pathologies. There is concern therefore that the prevalence of myopia in young adolescent eyes has increased substantially over recent decades and is now approaching 10-25% and 60-80%, respectively, in industrialized societies of the West and East. Whereas it is clear that the major structural correlate of myopia is longitudinal elongation of the posterior vitreous chamber, other potential correlates include profiles of lenticular and corneal power, the relationship between longitudinal and transverse vitreous chamber dimensions and ocular volume. The most potent predictors for juvenile-onset myopia continue to be a refractive error </=+0.50 D at 5 years of age and family history. Significant and continuing progress is being made on the genetic characteristics of high myopia with at least four chromosomes currently identified. Twin studies and genetic modelling have computed a heritability index of at least 80% across the whole ametropic continuum. The high index does not, however, preclude an environmental precursor, sustained near work with high cognitive demand being the most likely. The significance of associations between accommodation, oculomotor dysfunction and human myopia is equivocal despite animal models that have demonstrated that sustained hyperopic defocus can induce vitreous chamber growth. Recent optical and pharmaceutical approaches to the reduction of myopia progression in children are likely precedents for future research, for example progressive addition spectacle lens trials and the use of the topical M1 muscarinic antagonist pirenzepine.


Cys34 Adductomes Differ between Patients with Chronic Lung or Heart Disease and Healthy Controls in Central London.
Oxidative stress generates reactive species that modify proteins, deplete antioxidant defenses, and contribute to chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD). To determine whether protein modifications differ between COPD or IHD patients and healthy subjects, we performed untargeted analysis of adducts at the Cys34 locus of human serum albumin (HSA). Biospecimens were obtained from nonsmoking participants from London, U.K., including healthy subjects (n = 20) and patients with COPD (n = 20) or IHD (n = 10). Serum samples were digested with trypsin and analyzed by liquid chromatography-high resolution mass spectrometry. Effects of air pollution on adduct levels were also investigated based on estimated residential exposures to PM2.5, O3 and NO2. For the 39 adducts with sufficient data, levels were essentially identical in blood samples collected from the same subjects on two consecutive days, consistent with the 28 day residence time of HSA. Multivariate linear regression revealed 21 significant associations, mainly with the underlying diseases but also with air-pollution exposures (p-value < 0.05). Interestingly, most of the associations indicated that adduct levels decreased with the presence of disease or increased pollutant concentrations. Negative associations of COPD and IHD with the Cys34 disulfide of glutathione and two Cys34 sulfoxidations, were consistent with previous results from smoking and nonsmoking volunteers and nonsmoking women exposed to indoor combustion of coal and wood.


Peripheral neuromodulation for the treatment of refractory trigeminal neuralgia.
Trigeminal neuralgia is a type of orofacial pain that is diagnosed in 150,000 individuals each year, with an incidence of 12.6 per 100,000 person-years and a prevalence of 155 cases per 1,000,000 in the United States. Trigeminal neuralgia pain is characterized by sudden, severe, brief, stabbing or lancinating, recurrent episodes of pain in the distribution of one or more branches of the trigeminal nerve, which can cause significant suffering for the affected patient population. In many patients, a combination of medication and interventional treatments can be therapeutic, but is not always successful. Peripheral nerve stimulation has gained popularity as a simple and effective neuromodulation technique for the treatment of many pain conditions, including chronic headache disorders. Specifically in trigeminal neuralgia, neurostimulation of the supraorbital and infraorbital nerves may serve to provide relief of neuropathic pain by targeting the distal nerves that supply sensation to the areas of the face where the pain attacks occur, producing a field of paresthesia within the peripheral distribution of pain through the creation of an electric field in the vicinity of the leads. The purpose of the present case report is to introduce a new, less-invasive interventional technique, and to describe the authors' first experience with supraorbital and infraorbital neurostimulation therapy for the treatment of trigeminal neuralgia in a patient who had failed previous conservative management.


A Temperature-Based Bioimpedance Correction for Water Loss Estimation During Sports.
The amount of total body water (TBW) can be estimated based on bioimpedance measurements of the human body. In sports, TBW estimations are of importance because mild water losses can impair muscular strength and aerobic endurance. Severe water losses can even be life threatening. TBW estimations based on bioimpedance, however, fail during sports because the increased body temperature corrupts bioimpedance measurements. Therefore, this paper proposes a machine learning method that eliminates the effects of increased temperature on bioimpedance and, consequently, reveals the changes in bioimpedance that are due to TBW loss. This is facilitated by utilizing changes in skin and core temperature. The method was evaluated in a study in which bioimpedance, temperature, and TBW loss were recorded every 15 min during a 2-h running workout. The evaluation demonstrated that the proposed method is able to reduce the error of TBW loss estimation by up to 71%, compared to the state of art. In the future, the proposed method in combination with portable bioimpedance devices might facilitate the development of wearable systems for continuous and noninvasive TBW loss monitoring during sports.


A robust comparison of dynamical scenarios in a glass-forming liquid.
We use Bayesian inference methods to provide fresh insights into the sub-nanosecond dynamics of glycerol, a prototypical glass-forming liquid. To this end, quasielastic neutron scattering data as a function of temperature have been analyzed using a minimal set of underlying physical assumptions. On the basis of this analysis, we establish the unambiguous presence of three distinct dynamical processes in glycerol, namely, translational diffusion of the molecular centre of mass and two additional localized and temperature-independent modes. The neutron data also provide access to the characteristic length scales associated with these motions in a model-independent manner, from which we conclude that the faster (slower) localized motions probe longer (shorter) length scales. Careful Bayesian analysis of the entire scattering law favors a heterogeneous scenario for the microscopic dynamics of glycerol, where molecules undergo either the faster and longer or the slower and shorter localized motions.


The Role of Parenting Practices in the Home Environment among Underserved Youth.
The home environment, which includes parenting practices, is an important setting in which children develop their health behaviors. We examined the role of parenting practices in the home environment among underserved youth. We examined baseline data of a family-focused pediatric obesity intervention. Parenting practices (monitoring, discipline, limit setting of soda/snacks [SS] and screen media [SM], pressure to eat, and reinforcement) and availability of fruits/vegetables (FV) and sugar-sweetened beverages (SSBs), family meals, television (TV) watching during meals, TVs in the home, owning active video games/sports equipment, and household food security were assessed in 301 parent/caregivers of overweight/obese children (ages 7-12 years; BMI≥85th percentile). Associations were evaluated using Spearman's rank correlation coefficients and logistic regression models adjusted for potential confounders. Parents/caregivers (ages 22-67 years) were largely Hispanic/Latino (74.1%), female (92.4%), and reported high levels of limit setting SS and low levels of pressure to eat. Parent age, gender, country of birth, and years living in the United States accounted for differences among several parenting practices. Adjusted logistic regression models identified several statistically significant associations, including: Monitoring was positively associated with availability FV (odds ratio [OR]=2.19; 95% confidence interval [CI], 1.25, 3.82); limit setting SS was inversely associated with availability of SSBs (OR=0.40; 95% CI, 0.21, 0.75); and limit setting SM was inversely associated with TV viewing during family meals (OR=0.51; 95% CI, 0.31, 0.85). Nearly 40% of our population was food insecure, and food insecurity was positively associated with pressure to eat (OR=1.77; 95% CI, 1.01, 3.15). Parenting practices play an important role in the home environment, and longitudinal studies are needed to examine these associations in the context of family-focused pediatric obesity interventions.


CSE database: extended annotations and new recommendations for ECG software testing.
Nowadays, cardiovascular diseases represent the most common cause of death in western countries. Among various examination techniques, electrocardiography (ECG) is still a highly valuable tool used for the diagnosis of many cardiovascular disorders. In order to diagnose a person based on ECG, cardiologists can use automatic diagnostic algorithms. Research in this area is still necessary. In order to compare various algorithms correctly, it is necessary to test them on standard annotated databases, such as the Common Standards for Quantitative Electrocardiography (CSE) database. According to Scopus, the CSE database is the second most cited standard database. There were two main objectives in this work. First, new diagnoses were added to the CSE database, which extended its original annotations. Second, new recommendations for diagnostic software quality estimation were established. The ECG recordings were diagnosed by five new cardiologists independently, and in total, 59 different diagnoses were found. Such a large number of diagnoses is unique, even in terms of standard databases. Based on the cardiologists' diagnoses, a four-round consensus (4R consensus) was established. Such a 4R consensus means a correct final diagnosis, which should ideally be the output of any tested classification software. The accuracy of the cardiologists' diagnoses compared with the 4R consensus was the basis for the establishment of accuracy recommendations. The accuracy was determined in terms of sensitivity = 79.20-86.81%, positive predictive value = 79.10-87.11%, and the Jaccard coefficient = 72.21-81.14%, respectively. Within these ranges, the accuracy of the software is comparable with the accuracy of cardiologists. The accuracy quantification of the correct classification is unique. Diagnostic software developers can objectively evaluate the success of their algorithm and promote its further development. The annotations and recommendations proposed in this work will allow for faster development and testing of classification software. As a result, this might facilitate cardiologists' work and lead to faster diagnoses and earlier treatment.


Synergistic suppression of t(8;21)-positive leukemia cell growth by combining oridonin and MAPK1/ERK2 inhibitors.
One of the most common chromosomal translocations in acute myeloid leukemia is t(8;21)(q22;q22), which results in the appearance of abnormal transcripts encoding for the fusion protein RUNX1-ETO. Therefore, this oncoprotein is considered to be a pertinent and promising target for treating t(8;21) leukemia. Previously, we have shown that downregulation of RUNX1-ETO leads to activation of intracellular signaling pathways enhancing cell survival and determined that the protein ERK2 can mediate activation of most of these pathways. Here we used a combination of oridonin (natural tetracycline diterpenoid), which has been shown to exhibit anti-RUNX1-ETO activity, and ERK2 kinase inhibitors. We found that treatment of leukemic t(8;21)-positive Kasumi-1 cells with oridonin cause decrease of phosphorylated ERK1/2. Treatment of these cells with ERK2 inhibitors makes them more sensitive to RUNX1-ETO inhibition with oridonin. Therefore we postulate that simultaneous inhibition of RUNX1-ETO and ERK2 cause synergistic effect on survival of leukemic cells.


Radiology Education in the 21st Century: Threats and Opportunities.
Over the past 25 years, radiology has seen tremendous growth in interpretive demands, including increasing imaging volumes and shorter turnaround times, as well as increased noninterpretive demands often targeting value-adding opportunities. These mounting pressures have led to increased burnout among radiologists nationwide and, in the academic setting, have begun to threaten the core educational mission. Despite these threats, radiology has also proven itself over the years to be a leader when it comes to innovation, and as such, no other field is better suited to confront these challenges with innovative solutions. This article explores the impact these workload trends have had on radiology education and educators, as well as opportunities to confront these challenges.


Presence of double-strand breaks with single-base 3' overhangs in cells undergoing apoptosis but not necrosis.
Apoptotic cells in rat thymus were labeled in situ in paraffin-embedded and frozen tissue sections by ligation of double-stranded DNA fragments containing digoxigenin or Texas red. Two forms of double-stranded DNA fragments were prepared using the polymerase chain reaction: one was synthesized using Taq polymerase, which yields products with single-base 3' overhangs, and one using Pfu polymerase, which produces blunt-ended products. Both types of fragment could be ligated to apoptotic nuclei in thymus, indicating the presence in such nuclei of DNA double-strand breaks with single-base 3' overhangs as well as blunt ends. However, in nuclei with DNA damage resulting from a variety of nonapoptotic processes (necrosis, in vitro autolysis, peroxide damage, and heating) single-base 3' overhangs were either nondetectable or present at much lower concentrations than in apoptotic cells. Blunt DNA ends were present in such tissues, but at lower concentrations than in apoptotic cells. In contrast, in all of these forms of DNA damage, nuclei contained abundant 3'-hydroxyls accessible to labeling with terminal deoxynucleotidyl transferase. Thus, although single-base 3' overhangs and blunt ends are present in apoptotic nuclei, the specificity of the in situ ligation of 3'-overhang fragments to apoptotic nuclei indicates that apoptotic cells labeled in this way can readily be distinguished from cells with nonapoptotic DNA damage. These data are consistent with the involvement of an endonuclease similar to DNase I in apoptosis, which is predicted to leave short 3' overhangs as well as blunt ends in digestion of chromatin.


SIPP, a Novel Mitochondrial Phosphate Carrier, Mediates in Self-Incompatibility.
In Solanaceae, the S-specific interaction between the pistil S-RNase and the pollen S-Locus F-box protein controls self-incompatibility (SI). Although this interaction defines the specificity of the pollen rejection response, the identification of three pistil essential modifier genes unlinked to the S-locus (HT-B, 120K, and NaStEP) unveils a higher degree of complexity in the pollen rejection pathway. We showed previously that NaStEP, a stigma protein with homology with Kunitz-type protease inhibitors, is essential to SI in Nicotiana spp. During pollination, NaStEP is taken up by pollen tubes, where potential interactions with pollen tube proteins might underlie its function. Here, we identified NaSIPP, a mitochondrial protein with phosphate transporter activity, as a novel NaStEP-interacting protein. Coexpression of NaStEP and NaSIPP in pollen tubes showed interaction in the mitochondria, although when expressed alone, NaStEP remains mostly cytosolic, implicating NaSIPP-mediated translocation of NaStEP into the organelle. The NaSIPP transcript is detected specifically in mature pollen of Nicotiana spp.; however, in self-compatible plants, this gene has accumulated mutations, so its coding region is unlikely to produce a functional protein. RNA interference suppression of NaSIPP in Nicotiana spp. pollen grains disrupts the SI by preventing pollen tube inhibition. Taken together, our results are consistent with a model whereby the NaStEP and NaSIPP interaction, in incompatible pollen tubes, might destabilize the mitochondria and contribute to arrest pollen tube growth.


Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome.
Exome sequencing of an individual with congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis, all typical symptoms of Sengers syndrome, discovered two nonsense mutations in the gene encoding mitochondrial acylglycerol kinase (AGK). Mutation screening of AGK in further individuals with congenital cataracts and cardiomyopathy identified numerous loss-of-function mutations in an additional eight families, confirming the causal nature of AGK deficiency in Sengers syndrome. The loss of AGK led to a decrease of the adenine nucleotide translocator in the inner mitochondrial membrane in muscle, consistent with a role of AGK in driving the assembly of the translocator as a result of its effects on phospholipid metabolism in mitochondria.


Specialist Perspectives on Delivering High-Quality Telemedicine for Diabetes: A Mixed Methods Survey Study.
Recent recommendations guiding appropriate use of telemedicine for endocrinology care have largely relied on expert opinion due to limited evidence on factors that increase quality of telemedicine care. In this study, we assessed the perspectives of front-line specialists on factors and strategies perceived to increase quality of diabetes care delivered via telemedicine after more than 2 years of widespread use. Adult diabetes specialists in 2 academic health systems who recently used video-based telemedicine to provide diabetes care were invited to participate in an online survey study between March and April 2022. Likert-style questions, followed by related open-ended questions, assessed perspectives on availability of key resources, factors affecting quality, and anticipated benefits from telemedicine for diabetes. Response rate was 52% (56/111). More than half (54%) of participants reported better overall quality of diabetes care with face-to-face care vs telemedicine. Participants reported clinical data supporting high-quality care, such as home blood glucose readings and vital signs, were often not available with telemedicine. Patient factors, including comorbidities and communication barriers, reduced anticipated benefit from telemedicine, while geographic and mobility barriers increased expected benefit. Providers described multiple health care setting resources that could promote high-quality telemedicine diabetes care, including greater support for sharing patient-generated health data and coordinating multidisciplinary care. After 2 years of sustained use, diabetes specialists identified telemedicine as an important way to enhance access to care. However, specialists identified additional supports needed to increase appropriate use and delivery of high-quality telemedicine care for patients with complex clinical needs.


Q fever cases in the Northern Territory of Australia from 1991 to 2006.
Q fever (infection with Coxiella burnetii) has been uncommon in Australia's Northern Territory, with no reported cases until 2002. Since then, twelve cases of Q fever have been reported, representing a much lower notification rate than in surrounding Australian states. Three cases were identified in Central Australia during 2006, prompting this review of clinical and epidemiological features of all notified Northern Territory cases. Three patients required Intensive Care admission, 1 died, 5 had moderately severe illness, 2 were treated as outpatients and 2 were excluded as unlikely Q fever cases on clinical grounds. Hospital stays were long (median length of stay 9.5 days), and diagnosis and definitive therapy were generally delayed. Although macrolides and quinolones have some reported efficacy against C. burnetii, 2 patients experienced prolonged fever (5 and 9 days respectively) despite azithromycin, and the fatality occurred in a patient treated with multiple antibiotics including ciprofloxacin. Four patients were Aboriginal, 3 were tested for HTLV-1 and 2 were positive. The patient who died was diabetic. None of acute and chronic manifestations of Q fever is required in the Northern Territory. Early institution of doxycyline in suspected cases is recommended, and more rapid diagnostic methods including polymerase chain reaction testing should be considered. Host risk factors for chronicity, which may be of particular importance in Indigenous patients, merit attention. Given the lack of occupational exposure in these cases, there seems little reason to change the current Northern Territory policy of opting out of the National Q Fever Vaccination Program. Recognised alternative exposures, such as non-occupational livestock and domestic animal contact, require consideration as local Q fever sources.


Evaluation of Polyphenol Anthocyanin-Enriched Extracts of Blackberry, Black Raspberry, Blueberry, Cranberry, Red Raspberry, and Strawberry for Free Radical Scavenging, Reactive Carbonyl Species Trapping, Anti-Glycation, Anti-β-Amyloid Aggregation, and Microglial Neuroprotective Effects.
Glycation is associated with several neurodegenerative disorders, including Alzheimer's disease (AD), where it potentiates the aggregation and toxicity of proteins such as β-amyloid (Aβ). Published studies support the anti-glycation and neuroprotective effects of several polyphenol-rich fruits, including berries, which are rich in anthocyanins. Herein, blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts were evaluated for: (1) total phenolic and anthocyanins contents, (2) free radical (DPPH) scavenging and reactive carbonyl species (methylglyoxal; MGO) trapping, (3) anti-glycation (using BSA-fructose and BSA-MGO models), (4) anti-Aβ aggregation (using thermal- and MGO-induced fibrillation models), and, (5) murine microglia (BV-2) neuroprotective properties. Berry crude extracts (CE) were fractionated to yield anthocyanins-free (ACF) and anthocyanins-enriched (ACE) extracts. The berry ACEs (at 100 μg/mL) showed superior free radical scavenging, reactive carbonyl species trapping, and anti-glycation effects compared to their respective ACFs. The berry ACEs (at 100 μg/mL) inhibited both thermal- and MGO-induced Aβ fibrillation. In addition, the berry ACEs (at 20 μg/mL) reduced H₂O₂-induced reactive oxygen species production, and lipopolysaccharide-induced nitric oxide species in BV-2 microglia as well as decreased H₂O₂-induced cytotoxicity and caspase-3/7 activity in BV-2 microglia. The free radical scavenging, reactive carbonyl trapping, anti-glycation, anti-Aβ fibrillation, and microglial neuroprotective effects of these berry extracts warrant further in vivo studies to evaluate their potential neuroprotective effects against AD.


Infant-Guided, Co-Regulated Feeding in the Neonatal Intensive Care Unit. Part I: Theoretical Underpinnings for Neuroprotection and Safety.
The rapid progress in medical and technical innovations in the neonatal intensive care unit (NICU) has been accompanied by concern for outcomes of NICU graduates. Although advances in neonatal care have led to significant changes in survival rates of very small and extremely preterm neonates, early feeding difficulties with the transition from tube feeding to oral feeding are prominent and often persist beyond discharge to home. Progress in learning to feed in the NICU and continued growth in feeding skills after the NICU may be closely tied to fostering neuroprotection and safety. The experience of learning to feed in the NICU may predispose preterm neonates to feeding problems that persist. Neonatal feeding as an area of specialized clinical practice has grown considerably in the last decade. This article is the first in a two-part series devoted to neonatal feeding. Part 1 explores factors in NICU feeding experiences that may serve to constrain or promote feeding skill development, not only in the NICU but long after discharge to home. Part II describes approaches to intervention that support neuroprotection and safety.


The cross-sectional relationship of hemoglobin levels and functional outcomes in women with self-reported osteoarthritis: results from the Women's Health Initiative.
Gastrointestinal blood loss is a recognized complication of the use of nonsteroidal anti-inflammatory drugs (NSAIDS) in patients with arthritis. We examined the cross-sectional relationship of patient-reported outcomes of overall health, physical function, vitality, and quality of life to hemoglobin (hgb) levels in postmenopausal women with self-reported osteoarthritis to determine whether hgb levels as potential markers of chronic blood loss were associated with these functional outcomes. Postmenopausal women (N = 64,850) with self-reported osteoarthritis (srOA) at baseline in the Women's Health Initiative study, excluding participants with chronic or hemolytic diseases associated with anemia, had hgb levels measured and completed Short-Form Health Surveys. General linear models analysis adjusting for potential confounders was performed. A nonlinear plateauing relationship between hgb levels and functional outcomes was found. Participants with srOA had statistically significantly worse overall health, physical function, and vitality, but not quality of life, for each gram of hgb below 14 g/dL, compared with those with hgb 14 g/dL (P < 0.001). Participants with srOA taking NSAIDS had worse functional outcomes for each level of hgb compared with those not reporting NSAIDS use. In cross-sectional analyses of postmenopausal women with srOA, differences in hgb levels are related to differences in functional outcomes of overall health, physical function, and vitality at clinically important levels. Prospective studies evaluating whether changes in hgb levels result in changes in functional outcomes in participants with osteoarthritis are needed to confirm of our findings and before any changes in therapeutics based on hemoglogin levels are considered in the care of patients with osteoarthritis.


Graphene-based plasmonic waveguides for photonic integrated circuits.
We perform experimental investigations on the characteristics of graphene-based plasmonic waveguides for development of photonic integrated circuits. By embedding chemical vapor deposited graphene strip in a photoactive UV curable perfluorinated acrylate polymer with a low refractive index and material loss, the two-dimensional metal-like plasmonic waveguide demonstrated as a light signal guiding medium for high-speed optical data transmission. The fabricated graphene-based plasmonic waveguide supports the transverse-magnetic (TM) polarization modes with the averaged extinction ratio of 19 dB at a wavelength of 1.31 µm. The 2.5 Gbps optical signals were successfully transmitted via 6 mm-long graphene plasmonic waveguides. The proposed graphene-based plasmonic waveguides can be exploited further for development of next-generation photonic integrated circuit and devices.


Yogurt inhibits intestinal barrier dysfunction in Caco-2 cells by increasing tight junctions.
Chronic inflammation disrupts intestinal barrier function and may contribute to the pathology of obesity and other diseases. The goal of this study was to determine the mechanism by which yogurt improves intestinal barrier function. Caco-2 cells were differentiated on Transwell inserts and used as a model of intestinal barrier permeability. Transepithelial electrical resistance (TEER) and flux of 4 kDa fluorescein isothiocyanate-dextran (FD) and lucifer yellow (LY) were used as indicators of monolayer integrity and paracellular permeability. Immunofluorescence microscopy and real time quantitative polymerase chain were used to assess the localization and expression of tight junction proteins known to regulate intestinal permeability. Differentiated cells were treated with a vehicle control (C), inflammatory stimulus (I) (interleukin-1β, tumor necrosis factor-α, interferon-γ, and lipopolysaccharide), or I and 0.03 g mL-1 yogurt (IY). After 48 h, I reduced Caco-2 TEER by 46%, while IY reduced TEER by only 27% (P < 0.0001). FD and LY flux reflected TEER measurements, with IY having significantly lower permeability than I (P < 0.05). Yogurt also improved localization of occludin and zona occludens protein 1 (ZO-1) at tight junctions of differentiated Caco-2 cells. IY increased Caco-2 claudin-1, ZO-1, and occludin mRNA relative to I (P < 0.05). In a simulated digestion, the barrier-improving bioactivity of yogurt was maintained through the gastric phase, but was reduced to the level of I after intestinal digestion (P < 0.05). Therefore, yogurt improved inflammation-disrupted intestinal barrier function in a Caco-2 model by increasing tight junctions, but the beneficial effect on barrier function was reduced at latter stages of digestion.


The kinetics of the B cyclin p56cdc13 and the phosphatase p80cdc25 during the cell cycle of the fission yeast Schizosaccharomyces pombe.
The levels of the B cyclin p56cdc13 and the phosphatase p80cdc25 have been followed in selection-synchronised cultures of Schizosaccharomyces pombe wild-type and wee1 mutant cells. p56cdc13 has also been followed in induction-synchronised cells of the mutant cdc2-33. The main conclusions are: (1) cdc13 levels in wild-type cells start to rise from base line at about mid-G2, reach a peak before mitosis and then fall slowly through G1. Cells exit mitosis with appreciable levels of cdc13. (2) cdc13 levels in wee1 cells fall to zero in interphase. They also start to rise at the beginning of G2, which may be related to the absence of a mitotic size control. (3) cdc25 starts to rise later and reaches a peak after mitosis. This is not what would be expected from a simple mitotic inducer and suggests that cdc25 has an important function at the end of mitosis. (4) An upper (heavier) band of cdc25 peaks at the same time as the main band but rises and falls more rapidly. If this is a hyperphosphorylated form, its timing shows that it is most unlikely to function in the ways shown for such a form in eggs and mammalian cells. (5) Experiments with the mutant cdc10-129 and with hydroxyurea show that the initial signal to begin synthesis of cdc13 originates at Start. (6) In induction synchrony, where G2 spans across cell division, there is evidence that some events in one cycle cannot start in the previous one. (7) Revised timings are given for the times of mitosis in these cultures.


A recombinant protein containing highly conserved hemagglutinin residues 81-122 of influenza H5N1 induces strong humoral and mucosal immune responses.
Influenza has long been considered a serious global health threat. The highly pathogenic avian influenza A virus (IAV) H5N1, particularly the currently identified IAV/H7N9 in humans in China, illustrates that influenza is still a significant public health problem. Due to the high mortality of H5N1, development of safe and effective vaccines against divergent strains of H5N1 influenza virus, especially the one capable of inducing both strong systemic and local immune responses in the vaccinated targets, is a challenge of immediate importance. In the present study, we designed two recombinant proteins containing highly conserved hemagglutinin (HA) residues 81-122 of H5N1 fused with Fc of human IgG (HA-81-122-Fc) and/or foldon (Fd) trimeric motif (HA-81-122-Fdc), and identified their immunogenicity in vaccinated mice. We found that HA-81-122-Fc and HA-81-122-Fdc proteins formed high molecular weight dimer and oligomer, respectively, and induced potent IgG antibodies in vaccinated mouse sera and lung wash. Stronger IgG1 (Th2-associated) and IgG2 (Th1-associated) antibody responses could be raised in the sera of mice following last vaccination of HA-81-122-Fdc than those raised by HA-81-122-Fc vaccination. Importantly, HA-81-122-Fdc is able to elicit high titers of IgA antibodies in vaccinated mouse lung wash and sera through the parenteral immunization pathway. Our data demonstrated that the recombinant protein containing highly conserved HA residues 81-122 of H5N1 fused with Fd and Fc could induce strong local mucosal and systemic humoral immune responses in the vaccinated animals, revealing the possibility of developing an effective Fc-mediated mucosal influenza vaccine.


Non-linear integration of crowded orientation signals.
Crowding of oriented signals has been explained as linear, compulsory averaging of the signals from target and flankers [Parkes, L., Lund, J., Angelucci, A., Solomon, J. A., & Morgan, M. (2001). Compulsory averaging of crowded orientation signals in human vision. Nature Neuroscience, 4(7), 739-744]. On the other hand, a comparable search task with sparse stimuli is well modeled by a 'Signed-Max' rule that integrates non-linearly local tilt estimates [Baldassi, S., & Verghese, P. (2002). Comparing integration rules in visual search. Journal of Vision, 2(8), 559-570], as reflected by the bimodality of the distributions of reported tilts in a magnitude matching task [Baldassi, S., Megna, N., & Burr, D. C. (2006). Visual clutter causes high-magnitude errors. PLoS Biology, 4(3), e56]. This study compares the two models in the context of crowding by using a magnitude matching task, to measure distributions of perceived target angles and a localization task, to probe the degree of access to local information. Response distributions were bimodal, implying uncertainty, only in the presence of abutting flankers. Localization of the target is relatively preserved but it quantitatively falls in between the predictions of the two models, possibly suggesting local averaging followed by a max operation. This challenges the notion of global averaging and suggests some conscious access to local orientation estimates.


Genetic signs of connectivity in Primula vulgaris (Primulaceae) in a hedgerow network landscape.
The effects of landscape configuration on the genetic connectivity of the heterostylous species Primula vulgaris Huds. (Primulaceae) were studied using AFLP markers. Isolation by distance pattern was shown by spatial autocorrelation analysis; moreover, hedgerow network distances were found to contribute less than Euclidian distances to spatial genetic structure. Pollen flow is probably the main factor shaping the spatial genetic structure rather than seed dispersal, which is limited in this myrmecochorous species. Detailed analysis on the genetic similarity between neighborhoods and differentiation rates showed that density of hedgerow networks impede gene flow. We therefore concluded that a high degree of habitat contiguity does not necessarily promote genetic connectivity.


Circulating Selenium Concentration Is Inversely Associated With the Prevalence of Stroke: Results From the Canadian Health Measures Survey and the National Health and Nutrition Examination Survey.
Background Observational studies have suggested that selenium (Se) may have beneficial effects against certain cardiovascular outcomes, with a possible U-shaped association. We assessed the hypothesis that blood Se concentration might be inversely associated with the prevalence of stroke and the relationship would be nonlinear. Methods and Results Data collected from adult participants (aged ≥20 years) in the Canadian Health Measures Survey ( CHMS 2007-2011, n=7065) and the US National Health and Nutrition Examination Survey ( NHANES 2011-2012, n=5030) were analyzed. A total of 82 (1.16%) and 202 (4.02%) stroke cases were identified in CHMS and NHANES . Respondents with stroke had lower Se levels than those without stroke, with a mean difference of 16 μg/L and 12 μg/L for CHMS and NHANES , respectively. Respondents with high blood Se concentration (tertile 3) had a lower prevalence of stroke compared with those with low Se concentration (tertile 1). The adjusted odds ratios were 0.38 (95% CI : 0.15, 0.92) and 0.57 (95% CI : 0.31, 1.03) for CHMS and NHANES , respectively. A continuous decreasing trend of stroke with whole blood selenium was observed in CHMS , whereas the curve plateaued starting at 190 μg/L for NHANES , based on the cubic restricted spline regression. Sensitivity analysis using the serum and urinary Se concentrations demonstrates that our results were consistent across different selenium biomarkers. Conclusions We observed inverse cross-sectional associations between whole blood Se and the prevalence of stroke in representative samples of the Canadian and the US population.


Finite element analysis of knee injury risks in car-to-pedestrian impacts.
In vehicle-pedestrian collisions, lower extremities of pedestrians are frequently injured by vehicle front structures. In this study, a finite element (FE) model of THUMS (total human model for safety) was modified in order to assess injuries to a pedestrian lower extremity. Dynamic impact responses of the knee joint of the FE model were validated on the basis of data from the literature. Since in real-world accidents, the vehicle bumper can impact the lower extremities in various situations, the relations between lower extremity injury risk and impact conditions, such as between impact location, angle, and impactor stiffness, were analyzed. The FE simulation demonstrated that the motion of the lower extremity may be classified into a contact effect of the impactor and an inertia effect from a thigh or leg. In the contact phase, the stress of the bone is high in the area contacted by the impactor, which can cause fracture. Thus, in this phase the impactor stiffness affects the fracture risk of bone. In the inertia phase, the behavior of the lower extremity depends on the impact locations and angles, and the knee ligament forces become high according to the lower extremity behavior. The force of the collateral ligament is high compared with other knee ligaments, due to knee valgus motions in vehicle-pedestrian collisions.


Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness.
There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).


Interventions with family caregivers of cancer patients: meta-analysis of randomized trials.
Family caregivers of cancer patients receive little preparation, information, or support to perform their caregiving role. However, their psychosocial needs must be addressed so they can maintain their own health and provide the best possible care to the patient. The purpose of this article is to analyze the types of interventions offered to family caregivers of cancer patients, and to determine the effect of these interventions on various caregiver outcomes. Meta-analysis was used to analyze data obtained from 29 randomized clinical trials published from 1983 through March 2009. Three types of interventions were offered to caregivers: psychoeducational, skills training, and therapeutic counseling. Most interventions were delivered jointly to patients and caregivers, but they varied considerably with regard to dose and duration. The majority of caregivers were female (64%) and Caucasian (84%), and ranged in age from 18 to 92 years (mean age, 55 years). Meta-analysis indicated that although these interventions had small to medium effects, they significantly reduced caregiver burden, improved caregivers' ability to cope, increased their self-efficacy, and improved aspects of their quality of life. Various intervention characteristics were also examined as potential moderators. Clinicians need to deliver research-tested interventions to help caregivers and patients cope effectively and maintain their quality of life.


Producer survey of herd-level risk factors for nursing beef calf respiratory disease.
To identify herd-level risk factors for bovine respiratory disease (BRD) in nursing beef calves. Population-based cross-sectional survey. 2,600 US cow-calf producers in 3 Eastern and 3 Plains states. The associations of herd characteristics with BRD detection in calves and cumulative BRD treatment incidence were determined. 459 (177%) surveys were returned and met the inclusion criteria; 48% and 52% of these surveys were completed by producers in Plains and Eastern states, respectively. Mean (95% confidence interval) number of animals in herds in Plains and Eastern states were 102 (77 to 126) and 48 (40 to 56), respectively. Bovine respiratory disease had been detected in ≥ 1 calf in 21% of operations; ≥ 1 calf was treated for BRD and ≥ 1 calf died because of BRD in 89.2% and 46.4% of operations in which calf BRD was detected, respectively. Detection of BRD in calves was significantly associated with large herd size, detection of BRD in cows, and diarrhea in calves. Calving season length was associated with BRD in calves in Plains states but not Eastern states. Cumulative incidence of BRD treatment was negatively associated with large herd size and examination of cows to detect pregnancy and positively associated with calving during the winter, introduction of calves from an outside source, offering supplemental feed to calves, and use of an estrous cycle synchronization program for cows. Results of this study indicated factors associated with calf BRD risk; modification of these factors could potentially decrease the incidence of BRD in nursing calves.


Rethinking schizophrenia in the context of normal neurodevelopment.
The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood, or adolescent periods. To place schizophrenia neuropathology in a neurodevelopmental context requires solid, scrutinized evidence of changes occurring during normal development of the human brain, particularly in the cortex; however, too often data on normative developmental change are selectively referenced. This paper focuses on the development of the prefrontal cortex and charts major molecular, cellular, and behavioral events on a similar time line. We first consider the time at which human cognitive abilities such as selective attention, working memory, and inhibitory control mature, emphasizing that attainment of full adult potential is a process requiring decades. We review the timing of neurogenesis, neuronal migration, white matter changes (myelination), and synapse development. We consider how molecular changes in neurotransmitter signaling pathways are altered throughout life and how they may be concomitant with cellular and cognitive changes. We end with a consideration of how the response to drugs of abuse changes with age. We conclude that the concepts around the timing of cortical neuronal migration, interneuron maturation, and synaptic regression in humans may need revision and include greater emphasis on the protracted and dynamic changes occurring in adolescence. Updating our current understanding of post-natal neurodevelopment should aid researchers in interpreting gray matter changes and derailed neurodevelopmental processes that could underlie emergence of psychosis.


Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias.
It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusion-dependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism. The efficacy and safety of deferasirox (Exjade®) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10-30 mg/kg/d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias. Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells/kg/d), mean deferasirox dosing (19.3 vs. 19.0 mg/kg/d) and baseline median serum ferritin (2926 vs. 2682 ng/mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng/mL were attained, respectively (-26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (< 0.4 μm) subsequently. The most common drug-related, investigator-assessed adverse events were diarrhoea (n = 16) and nausea (n = 12). At matched transfusional iron-loading rates, the responses of rare transfusion-dependent anaemias to deferasirox are similar at 1 yr, irrespective of the underlying pathogenic mechanism.


Improving the quality of STI care by private general practitioners: a South African case study.
Evaluation of an intervention to improve quality of sexually transmitted infections (STI) care among 64 private general practitioners (GPs) working in two urban districts in Gauteng Province, South Africa. We implemented a multifaceted intervention, the core of which were four interactive continuing medical education seminars. Changes in STI treatment practices were evaluated through record reviews before and after the continuing medical education intervention in 17 randomly selected practices in the intervention districts and in nine randomly selected practices from a reference GP group (n = 34). There were statistically significant improvements in the quality of drug treatment for urethral discharge but not pelvic inflammatory disease among both intervention and reference GPs. Improvements in STI quality were possibly the result of a background secular trend rather than the intervention itself. Further research is needed on financial and other incentives to improved quality of STI care in the private sector environment.


Disorder-induced transition from grain boundary to bulk dominated ionic diffusion in pyrochlores.
We use molecular dynamics simulations to investigate the role of grain boundaries (GBs) on ionic diffusion in pyrochlores, as a function of the GB type, chemistry of the compound, and level of cation disorder. We observe that the presence of GBs promotes oxygen transport in ordered and low-disordered systems, as the GBs are found to have a higher concentration of mobile carriers with higher mobilities than in the bulk. Thus, in ordered samples, the ionic diffusion is 2D, localized along the grain boundary. When cation disorder is introduced, bulk carriers begin to contribute to the overall diffusion, while the GB contribution is only slightly enhanced. In highly disordered samples, the diffusive behavior at the GBs is bulk-like, and the two contributions (bulk vs. GB) can no longer be distinguished. There is thus a transition from 2D/GB dominated oxygen diffusivity to 3D/bulk dominated diffusivity versus disorder in pyrochlores. These results provide new insights into the possibility of using internal interfaces to enhance ionic conductivity in nanostructured complex oxides.


Unconventional superconductivity in Y5Rh6Sn18 probed by muon spin relaxation.
Conventional superconductors are robust diamagnets that expel magnetic fields through the Meissner effect. It would therefore be unexpected if a superconducting ground state would support spontaneous magnetics fields. Such broken time-reversal symmetry states have been suggested for the high-temperature superconductors, but their identification remains experimentally controversial. We present magnetization, heat capacity, zero field and transverse field muon spin relaxation experiments on the recently discovered caged type superconductor Y5Rh6Sn18 ( TC= 3.0 K). The electronic heat capacity of Y5Rh6Sn18 shows a T(3) dependence below Tc indicating an anisotropic superconducting gap with a point node. This result is in sharp contrast to that observed in the isostructural Lu5Rh6Sn18 which is a strong coupling s-wave superconductor. The temperature dependence of the deduced superfluid in density Y5Rh6Sn18 is consistent with a BCS s-wave gap function, while the zero-field muon spin relaxation measurements strongly evidences unconventional superconductivity through a spontaneous appearance of an internal magnetic field below the superconducting transition temperature, signifying that the superconducting state is categorized by the broken time-reversal symmetry.


Vitrectomy for epiretinal membranes with good visual acuity.
To evaluate the visual results of vitrectomy for epiretinal membrane in eyes with a preoperative visual acuity of 20/50 or better. The visual results and complications were analyzed following vitrectomy for idiopathic epiretinal membranes and epiretinal membranes secondary to retinal tears. This study was a retrospective, consecutive case series of 40 eyes of 40 patients treated by a single surgeon. The mean preoperative visual acuity was 20/50 +2 (range, 20/30 +1 to 20/50 -3). The mean visual acuity improved to 20/40 +2 (P = .02) by the final examination at a mean of 2.4 years following surgery. The status of the lens at the final examination was correlated with the visual results of surgery. Twenty-one eyes were phakic preoperatively, and 14 of these eyes had cataracts removed by the final examination. The mean preoperative visual acuity in seven eyes that were still phakic at the final examination was 20/50, and this decreased to 20/50 -2 (P = .82). The mean preoperative visual acuity was 20/50 +2 in 33 eyes that were pseudophakic by the final examination, and this improved to 20/32 -2 (P = .005). The visual acuity improved by 2 or more Snellen lines in only one in seven eyes (14%) that were still phakic on the final examination and in 14 of 33 eyes (42.4%) that were pseudophakic by the final examination. There were no serious surgical complications. Vitrectomy for epiretinal membranes is beneficial in eyes with relatively good preoperative visual acuities, but cataract surgery is necessary in phakic eyes to achieve long-term visual acuity improvement.


Validation of a Food Frequency Questionnaire for the indigenous Épera-Siapidara people in Ecuador.
A Food Frequency Questionnaire (FFQ) must be designed and validated in the local environment to ensure that the method is adapted to the objectives of the study and the population. The aim of this study was to validate an FFQ to evaluate the food consumption pattern of the Épera-Siapidara population of Ecuador. One hundred and fourindividuals (54% men and 46% women), aged between 2 and 84, took part in the study. The validity of this tool was assessed by comparing the relationship between the average daily nutrient intake estimated by the FFQ and the intake estimated in the three non-consecutive 24 h dietary recalls (24hR). The existing correlations were evaluated by Pearson's or Spearman's correlation, the inter-class correlation coefficient, Lin's concordance correlation coefficient and a Bland-Altman plot. The values estimated by the FFQ were significantly higher for minerals and vitamins. The relative correlation coefficients ranged from 0.71 to 0.23 for Na and Ca, respectively, while the inter-class correlation coefficient ranged from 0.84 to 0.33 for Na and cholesterol, respectively. Lin's concordance correlation coefficient was higher for macronutrients, with values ranging from between 0.35 for lipids to 0.51 for energy. Only 6% of the participants were wrongly classified. The Bland-Altman plots showed an overestimation of macronutrient and calcium intake by the FFQ compared with the 24hR, and an underestimation of fiber intake. The FFQ demonstrated a good external consistency, which makes it a suitable instrument for correctly identifying the food and nutrient intake of the Épera-Siapidara population.


Differential actions of the endocytic collagen receptor uPARAP/Endo180 and the collagenase MMP-2 in bone homeostasis.
A well-coordinated remodeling of uncalcified collagen matrices is a pre-requisite for bone development and homeostasis. Collagen turnover proceeds through different pathways, either involving extracellular reactions exclusively, or being dependent on endocytic processes. Extracellular collagen degradation requires the action of secreted or membrane attached collagenolytic proteases, whereas the alternative collagen degradation pathway proceeds intracellularly after receptor-mediated uptake and delivery to the lysosomes. In this study we have examined the functional interplay between the extracellular collagenase, MMP-2, and the endocytic collagen receptor, uPARAP, by generating mice with combined deficiency of both components. In both uPARAP-deficient and MMP-2-deficient adult mice the length of the tibia and femur was decreased, along with a reduced bone mineral density and trabecular bone quality. An additional decrease in bone length was observed when combining the two deficiencies, pointing to both components being important for the remodeling processes in long bone growth. In agreement with results found by others, a different effect of MMP-2 deficiency was observed in the distinct bone structures of the calvaria. These membranous bones were found to be thickened in MMP-2-deficient mice, an effect likely to be related to an accompanying defect in the canalicular system. Surprisingly, both of the latter defects in MMP-2-deficient mice were counteracted by concurrent uPARAP deficiency, demonstrating that the collagen receptor does not support the same matrix remodeling processes as the MMP in the growth of the skull. We conclude that both uPARAP and MMP-2 take part in matrix turnover processes important for bone growth. However, in some physiological situations, these two components do not support the same step in the growth process.


Distinct viral sequence elements are necessary for expression of Tomato golden mosaic virus complementary sense transcripts that direct AL2 and AL3 gene expression.
Transient expression studies using Nicotiana benthamiana protoplasts and plants have identified sequences important for transcription of complementary sense RNAs derived from Tomato golden mosaic virus (TGMV) DNA component A that direct expression of AL2 and AL3. Transcription of two complementary sense RNAs, initiating at nucleotides 1,935 (AL1935) and 1,629 (AL1629), is directed by unique sequences located upstream of each transcription initiation site. One element is located between 28 and 124 nucleotides (nt) upstream of the AL1935 transcription start site, which differs from a second element located 150 nt downstream, between 129 and 184 nt upstream of the AL1629 transcription start site. Transcription initiation at nucleotide 1,935 is lower than that at nucleotide 1,629 as determined by run-on transcription assays, and the resulting transcript is only capable of expressing AL3. The transcript initiating at nucleotide 1,629 is capable of directing expression of both AL2 and AL3, although expression of AL3 is up to fourfold greater than that for AL2. Nuclear factors purified from tobacco suspension cells bind to sequences upstream of both AL1935 and AL1629, correlating with the ability of these sequences to direct gene expression. Thus, in tobacco, regulatory sequences direct transcription of two unique TGMV messenger RNAs that differentially express AL2 and AL3.


Perfluorinated alkylated substances and brominated flame retardants in serum of the Czech adult population.
Persistent organic pollutants, such as perfluorinated alkylated substances (PFASs) and brominated flame retardants (BFRs) are widespread in the environment and most of them are bioaccumulated in wildlife and humans. The present study is the first investigation to reveal the PFAS and BFR levels of serum samples in the adult population of the Czech Republic. Altogether, 300 serum samples from blood donors in four cities were examined. In all samples 19 PFASs and 33 BFRs, including some of their metabolites, were targeted. The analyses were performed using ultra high performance liquid chromatography coupled with tandem mass spectrometry or gas chromatography with mass spectrometry (according to the type of analyte). PFASs, with the carbon chain length C6 and higher, dominated in all samples. Perfluorooctanesulfonate (PFOS; median: 2.43ng/mL), perfluorooctanoic acid (PFOA; median: 0.756ng/mL), perfluorodecanoic acid (PFDA; median: 0.145ng/mL) and perfluorohexanesulfonate (PFHxS; median: 0.184ng/mL) were detected in 100% of samples. Perfluorononanoic acid (PFNA; median: 0.325ng/mL) and perfluoroundecanoic acid (PFUdA; median: 0.058ng/mL) in 99.7% and 96.0% of samples, respectively. We observed statistically significant associations (p<0.05) between selected PFAS concentrations and the locality, gender, age of donors and education level. None of the BFRs was detected above the LOQ in more than 9% of the samples. The most frequently detected representatives of this group were congeners of polybrominated diphenyl ethers, namely BDE-47 (in 8.7%; range: 0.496-5.44ng/g lipid weight (l.w.)), BDE-99 (in 6.0%; range: 0.706-9.46ng/g l.w.), BDE-153 (in 7.3%; range: 0.736-6.44ng/g l.w.) and BDE-209 (in 7.0%; range: 13.7-2693ng/g l.w.).


Expression of Ixodes scapularis antifreeze glycoprotein enhances cold tolerance in Drosophila melanogaster.
Drosophila melanogaster experience cold shock injury and die when exposed to low non-freezing temperatures. In this study, we generated transgenic D. melanogaster that express putative Ixodes scapularis antifreeze glycoprotein (IAFGP) and show that the presence of IAFGP increases the ability of flies to survive in the cold. Male and female adult iafgp-expressing D. melanogaster exhibited higher survival rates compared with controls when placed at non-freezing temperatures. Increased hatching rates were evident in embryos expressing IAFGP when exposed to the cold. The TUNEL assay showed that flight muscles from iafgp-expressing female adult flies exhibited less apoptotic damage upon exposure to non-freezing temperatures in comparison to control flies. Collectively, these data suggest that expression of iafgp increases cold tolerance in flies by preventing apoptosis. This study defines a molecular basis for the role of an antifreeze protein in cryoprotection of flies.