Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomic nervous system in patients with type 2 diabetes.
Type 2 diabetes is associated with elevated oxidative stress and declines in antioxidant defense. The disease is also characterized by an imbalance in the ratio of cardiac sympathetic to parasympathetic tone. Antioxidants, vitamin E in particular, may have beneficial effects on the cardiac autonomic nervous system through a decline in oxidative stress. We investigated the possible effects of vitamin E on the cardiac autonomic nervous system, as assessed by analysis of heart rate variability, in patients with type 2 diabetes and cardiac autonomic neuropathy. In a double-blind randomized controlled trial, 50 patients with type 2 diabetes were assigned to treatment with vitamin E (600 mg/d) or placebo for 4 mo. The anthropometric characteristics of the patients remained unchanged throughout the study. Chronic vitamin E administration was associated with decreases in concentrations of glycated hemoglobin (P < 0.05), plasma insulin (P < 0.05), norepinephrine (P < 0.03), and epinephrine (P < 0.02); a lower homeostasis model assessment index (P < 0.05); and improved indexes of oxidative stress. Furthermore, vitamin E administration was associated with increases in the R-R interval (P < 0.05), total power (P < 0.05), and the high-frequency component of heart rate variability (HF; P < 0.05) and decreases in the low-frequency component (LF; P < 0.05) and the ratio of LF to HF (P < 0.05). Finally, change in the plasma vitamin E concentration was correlated with change in the LF-HF ratio (r = -0.43, P < 0.04) independently of changes in the homeostasis model assessment index and plasma catecholamines concentrations. Chronic vitamin E administration improves the ratio of cardiac sympathetic to parasympathetic tone in patients with type 2 diabetes. Such an effect might be mediated by a decline in oxidative stress.


Fetal damage after accidental polio vaccination of an immune mother.
Irreparable damage to the anterior horn cells of the cervical and thoracic cord was found in a 20-week-old fetus whose mother was immune to poliomyelitis before conceiving but who was inadvertently given oral polio vaccine at 18 weeks gestation. Polio neutralizing antibody titres in sera, taken before and after pregnancy, were identical and were at levels normally regarded as providing protection. Unsuccessful attempts were made to isolate poliovirus from extracts of fetal brain, lung, liver and placenta. Fluorescent antibody tests were performed on various levels of the central nervous system and on the left and right extensor forearm muscles. Specific positive fluorescence to poliovirus 2 and 3 antigens was detected at dorsal spinal cord level only. One positive result was seen with Coxsackie A9 antiserum and fresh guinea-pig complement in the inflammatory cells in the right extensor forearm muscles.This experience, as yet unexplained, underlines the importance of ensuring that women are not pregnant prior to oral polio vaccination.


Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial.
To determine the prognostic importance of p16 and human papillomavirus (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial. Patients with stage III or IV head and neck squamous cell cancer were randomly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine. In this substudy, analyses were restricted to patients with oropharyngeal cancer. p16 was detected by immunohistochemistry, and HPV was detected by in situ hybridization and polymerase chain reaction. Slides were available for p16 assay in 206 of 465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172 patients. One hundred six (57%) of 185 were p16-positive, and in patients evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also HPV-positive. Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group (ECOG) performance status. p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74; P = .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P = .003). p16 was a significant prognostic factor on multivariable analysis (HR, 0.45; 95% CI, 0.21 to 0.96; P = .04). p16-positive patients had lower rates of locoregional failure and deaths due to other causes. There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients (HR, 0.33; 95% CI, 0.09 to 1.24; P = .13). HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.


Vision and touch in relation to foraging and predator detection: insightful contrasts between a plover and a sandpiper.
Visual fields were determined in two species of shorebirds (Charadriiformes) whose foraging is guided primarily by different sources of information: red knots (Calidris canutus, tactile foragers) and European golden plovers (Pluvialis apricaria, visual foragers). The visual fields of both species showed features that are found in a wide range of birds whose foraging involves precision pecking or lunging at food items. Surprisingly, red knots did not show comprehensive panoramic vision as found in some other tactile feeders; they have a binocular field surrounding the bill and a substantial blind area behind the head. We argue that this is because knots switch to more visually guided foraging on their breeding grounds. However, this visual field topography leaves them vulnerable to predation, especially when using tactile foraging in non-breeding locations where predation by falcons is an important selection factor. Golden plovers use visually guided foraging throughout the year, and so it is not surprising that they have precision-pecking frontal visual fields. However, they often feed at night and this is associated with relatively large eyes. These are anchored in the skull by a wing of bone extending from the dorsal perimeter of each orbit; a skeletal structure previously unreported in birds and which we have named 'supraorbital aliform bone', Os supraorbitale aliforme. The larger eyes and their associated supraorbital wings result in a wide blind area above the head, which may leave these plovers particularly vulnerable to predation. Thus, in these two shorebirds, we see clear examples of the trade-off between the two key functions of visual fields: (i) the detection of predators remote from the animal and (ii) the control of accurate behaviours, such as the procurement of food items, at close quarters.


Endogenous concentrations, pharmacokinetics, and selected pharmacodynamic effects of a single dose of exogenous GABA in horses.
The anti-anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA-containing product. The mean (±SD) endogenous GABA level was 36.4 ± 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospinal fluid (n = 2) samples were collected at time 0 and at various times for up to 48 h and analyzed using LC-MS. Plasma clearance and volume of distribution was 155.6 and 147.6 L/h and 0.154 and 7.39 L for the central and peripheral compartments, respectively. Terminal elimination half-life was 22.1 (intravenous) and 25.1 (oral) min. Oral bioavailability was 9.81%. Urine GABA concentrations peaked rapidly returning to baseline levels by 3 h. Horses appeared behaviorally unaffected following oral administration, while sedative-like changes following intravenous administration were transient. Heart rate was increased for 1 h postintravenous administration, and gastrointestinal sounds decreased for approximately 30 min following both intravenous and oral administration. Based on a limited number of horses and time points, exogenously administered GABA does not appear to enter the CSF to an appreciable extent.


Activation of Pak1/Akt/eNOS signaling following sphingosine-1-phosphate release as part of a mechanism protecting cardiomyocytes against ischemic cell injury.
We investigated whether plasma long-chain sphingoid base (LCSB) concentrations are altered by transient cardiac ischemia during percutaneous coronary intervention (PCI) in humans and examined the signaling through the sphingosine-1-phosphate (S1P) cascade as a mechanism underlying the S1P cardioprotective effect in cardiac myocytes. Venous samples were collected from either the coronary sinus (n = 7) or femoral vein (n = 24) of 31 patients at 1 and 5 min and 12 h, following induction of transient myocardial ischemia during elective PCI. Coronary sinus levels of LCSB were increased by 1,072% at 1 min and 941% at 5 min (n = 7), while peripheral blood levels of LCSB were increased by 579% at 1 min, 617% at 5 min, and 436% at 12 h (n = 24). In cultured cardiac myocytes, S1P, sphingosine (SPH), and FTY720, a sphingolipid drug candidate, showed protective effects against CoCl induced hypoxia/ischemic cell injury by reducing lactate dehydrogenase activity. Twenty-five nanomolars of FTY720 significantly increased phospho-Pak1 and phospho-Akt levels by 56 and 65.6% in cells treated with this drug for 15 min. Further experiments demonstrated that FTY720 triggered nitric oxide release from cardiac myocytes is through pertussis toxin-sensitive phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase signaling. In ex vivo hearts, ischemic preconditioning was cardioprotective in wild-type control mice (Pak1(f/f)), but this protection appeared to be ineffective in cardiomyocyte-specific Pak1 knockout (Pak1(cko)) hearts. The present study provides the first direct evidence of the behavior of plasma sphingolipids following transient cardiac ischemia with dramatic and early increases in LCSB in humans. We also demonstrated that S1P, SPH, and FTY720 have protective effects against hypoxic/ischemic cell injury, likely a Pak1/Akt1 signaling cascade and nitric oxide release. Further study on a mouse model of cardiac specific deletion of Pak1 demonstrates a crucial role of Pak1 in cardiac protection against ischemia/reperfusion injury.


Light-controlled self-assembly of semiconductor nanoparticles into twisted ribbons.
The collective properties of nanoparticles manifest in their ability to self-organize into complex microscale structures. Slow oxidation of tellurium ions in cadmium telluride (CdTe) nanoparticles results in the assembly of 1- to 4-micrometer-long flat ribbons made of several layers of individual cadmium sulfide (CdS)/CdTe nanocrystals. Twisting of the ribbons with an equal distribution of left and right helices was induced by illumination with visible light. The pitch lengths (250 to 1500 nanometers) varied with illumination dose, and the twisting was associated with the relief of mechanical shear stress in assembled ribbons caused by photooxidation of CdS. Unusual shapes of multiparticle assemblies, such as ellipsoidal clouds, dog-bone agglomerates, and ribbon bunches, were observed as intermediate stages. Computer simulations revealed that the balance between attraction and electrostatic repulsion determines the resulting geometry and dimensionality of the nanoparticle assemblies.


Postoperative cataract surgery satisfaction in a rural Kenyan clinic.
To assess prospectively the factors influencing patient satisfaction following intracapsular cataract extraction (ICCE) surgery in a rural eye unit in Kenya. Nakuru Eye Unit, Rift Valley Provincial General Hospital, Nakuru, Kenya, and Johns Hopkins School of Public Health, Department of International Health, Baltimore, Maryland, USA. Starting in November 1992, 232 consecutive blind or visually impaired rural patients, over age 40, with simple senile cataract were offered free standard ICCE. Only 70% agreed to surgery. An interviewer-administered questionnaire and a brief interview were performed postoperatively on day 2, completing an extensive preoperative analysis that was part of the Kenya Rural Cataract Project. A satisfaction level indicator composed from the most important factors, applying a logistic regression model, is suggested as a predictive index for a patient to become a motivator in his or her community. Most patients were happy with their decision to have cataract surgery, even though 92% of the operations were done by clinical officers. Patients were overwhelmingly willing to have their fellow eye operated on or to recommend the operation to another "blind" friend (83.4%). The proposed model correctly classified 87.1% of operated patients, with high sensitivity (88.2%) and specificity (81.5%). Cultural differences are paramount in determining health behavior priorities and satisfaction. The post ICCE satisfaction in developing countries must be better evaluated to achieve higher self-referral of cataract-blind patients for surgery in Africa. Hospital conditions, although appreciated, did not play a major role in patients' satisfaction. The immediate surgical outcome was the key factor.


RPPAs for Cell Subpopulation Analysis.
Understanding cellular heterogeneity is a challenge for cell biology, particularly in the fields of stem cell and cancer biology. We recently established a reverse phase protein array (RPPA)-modified method, colony lysate array (CoLA), which enables proteomic profiling of individual subpopulations (i.e., colonies) derived from various cell proliferative conditions. Here we describe two independent CoLA assays for a functional subpopulation, drug-tolerant persisters (DTPs), which are considered to mimic the origin of chemotherapeutic cancer relapse. In the first study, we analyzed individual DTPs derived from different cell types grown in the presence of different drugs. A hierarchical clustering analysis of DTPs using CoLA revealed two types of clonal populations, including those that expressed stem cell-associated proteins as well as epithelium-associated proteins. Subsequent principal component analyses demonstrated that the DTPs clustered on the basis of their proteomic profiles, which could change in response to drugs and doses. Another study was designed to identify signaling pathways that may be associated with drug resistance using a pair of 5-fluorouracil-tolerant and parental gastric cancer cell lines. Although a hierarchical clustering analysis did not show any specific clusters for the tolerant line, a drug dose-response analysis revealed that phosphorylation of PI3K and AKT increased and decreased, respectively, specifically in the tolerant cell line. These frameworks that readily profile small subpopulations isolated from an external stresses may be applicable to a wide variety of heterogeneous cellular samples.


Tuned switching of surface waves by a liquid crystal cap layer in one-dimensional photonic crystals.
In this paper, we theoretically study the electromagnetic surface waves localized at the interface between a homogeneous dielectric medium and a semi-infinite, one-dimensional photonic crystal (1D PC). The semi-infinite 1D PC is made of alternative layers of right-handed (RH) and dispersive left-handed (LH) materials in the presence of a liquid crystal (LC) cap layer. In this structure, we derive the surface waves dispersion relation with tunable switching and localization by using an analytical direct matching procedure within the Kronig-Penny model. It is shown that, for both of layer arrangements, the variation of molecules orientation of the LC cap layer acts as an effective tool to tune the type (tuned switching) and localization of the surface waves and it also can create a surface mode with maximum localization in the first frequency bandgap.


Comparison of two computer-automated procedures for tinnitus pitch matching.
Clinical assessment of the perceptual characteristics of tinnitus usually includes an attempt to match the pitch of tinnitus to a pure tone. A standardized clinical protocol for tinnitus pitch matching does not yet exist, and there is a history of unsuccessful attempts to obtain such measures reliably. The present study was designed to evaluate new protocols for identifying the perceived pitch of tinnitus, with the objectives of reducing testing time and improving test-retest reliability. Two protocols ("Octave" and "Binary") were developed, each of which was patterned after the testing procedure previously developed at the Oregon Tinnitus Clinic and used to assess thousands of tinnitus patients. Both protocols use computer-automation to conduct testing; the protocols differ according to their specific testing algorithms. Twenty subjects with nonfluctuating tinnitus were each tested over two sessions. Results of testing revealed that both protocols could obtain pitch matches within 20 to 25 min. Reliability of responses was good for some subjects but not others, and the Binary protocol generally provided more reliable results.


Psychopharmacologic treatment of pediatric major depressive disorder.
The role of pharmacotherapy in the treatment of major depressive disorder (MDD) in youth has received much attention in recent years due to concerns of efficacy and safety of the antidepressants for the treatment of MDD in youth. This review describes the existing published and unpublished literature regarding the efficacy and short-term safety of the antidepressants and decision-making process required for the use of these medications for youth with MDD. In addition, current continuation and maintenance treatments are discussed. In general, nine depressed youth must be treated with an antidepressant to obtain one clinical response above that achieved with placebo. To date, fluoxetine has showed the most consistent positive treatment effects. Depressed youth had also acutely responded to other antidepressants, but the response to placebo has also been high. Overall, the antidepressants are well tolerated, but 1-3 children and adolescents of 100 taking antidepressants showed onset or worsening of suicidal ideation and, more rarely, suicide attempts. There is a positive risk-benefit ratio for the use of antidepressants in the acute treatment of depressed youth. First-line antidepressant treatment with-or without-specific types of psychotherapy is indicated for youth with MDD of at least moderate severity. All youth taking antidepressants must be closely monitored for suicidality and medication side effects. Many youth will likely require psychotherapy or additional medication treatments to address comorbid disorders. Treatments to prevent relapses and recurrences require further study.


Visual communication with retinex coding.
Visual communication with retinex coding seeks to suppress the spatial variation of the irradiance (e.g., shadows) across natural scenes and preserve only the spatial detail and the reflectance (or the lightness) of the surface itself. The separation of reflectance from irradiance begins with nonlinear retinex coding that sharply and clearly enhances edges and preserves their contrast, and it ends with a Wiener filter that restores images from this edge and contrast information. An approximate small-signal model of image gathering with retinex coding is found to consist of the familiar difference-of-Gaussian bandpass filter and a locally adaptive automatic-gain control. A linear representation of this model is used to develop expressions within the small-signal constraint for the information rate and the theoretical minimum data rate of the retinex-coded signal and for the maximum-realizable fidelity of the images restored from this signal. Extensive computations and simulations demonstrate that predictions based on these figures of merit correlate closely with perceptual and measured performance. Hence these predictions can serve as a general guide for the design of visual communication channels that produce images with a visual quality that consistently approaches the best possible sharpness, clarity, and reflectance constancy, even for nonuniform irradiances. The suppression of shadows in the restored image is found to be constrained inherently more by the sharpness of their penumbra than by their depth.


Genotoxic and cytotoxic effects of mobile phone use on the oral epithelium: a systematic review with meta-analysis.
The use of mobile phones is based on radiofrequency (RF) waves, and the devices act as transmitters and receivers of non-ionizing energy. The micronucleus test was developed to identify increases in the occurrence of mutations in cells exposed to various agents. This systematic review with meta-analysis adhered to the following protocol: defining the objective, outlining the search method (PICO model), conducting the search, identifying literature, selecting articles, and extracting data. The study aimed to answer the following research question: Does non-ionizing radiation emitted by mobile phones have genotoxic and/or cytotoxic effects on the oral epithelium? The search for evidence published 2009-2019 was conducted in the MEDLINE, PubMed, Scopus, LILACS, Google Scholar, PROSPERO, and Cochrane Library databases. The following inclusion criteria were defined: investigations of effects on the oral mucosa related to RF; investigations of cytotoxic and/or genotoxic effects; investigations involving humans; and investigations using cells exfoliated from the oral epithelium. Investigations related to the parotid gland were excluded. The search strategy found 464 articles; after application of the eligibility criteria, 358 abstracts were analyzed and 351 abstracts excluded. After 7 full texts were reviewed, 1 study was excluded. The 6 included studies were classified as level 5 quality of evidence (observational studies). The meta-analysis included 2 studies that compared the frequency of micronuclei on the side exposed to RF electromagnetic fields (RF-EMFs) to that on the unexposed side. The studies evaluated presented a low degree of evidence, but the meta- analysis indicated that no genotoxic effects are associated with mobile phone use. However, observations of other nuclear abnormalities in some studies suggest the occurrence of cytotoxic effects caused by exposure to the RF-EMFs emitted by mobile phones. More studies are necessary to prove or refute this association.


Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin.
Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least 11 complementation groups (A, B, C, D1, D2, E, F, G, I, J, and L), and eight FA genes have been cloned. The FANCD1 gene is identical to the breast cancer susceptibility gene, BRCA2. The FA proteins cooperate in a common pathway, but the function of BRCA2/FANCD1 in this pathway remains unknown. Here we show that monoubiquitination of FANCD2, which is activated by DNA damage, is required for targeting of FANCD2 to chromatin, where it interacts with BRCA2. FANCD2-Ub then promotes BRCA2 loading into a chromatin complex. FANCD2(-/-) cells are deficient in the assembly of DNA damage-inducible BRCA2 foci and in chromatin loading of BRCA2. Functional complementation with the FANCD2 cDNA restores BRCA2 foci and its chromatin loading following DNA damage. BRCA2(-/-) cells expressing a carboxy-terminal truncated BRCA2 protein form IR-inducible BRCA2 and FANCD2 foci, but these foci fail to colocalize. Functional complementation of these cells with wild-type BRCA2 restores the interaction of BRCA2 and FANCD2. The C terminus of BRCA2 is therefore required for the functional interaction of BRCA2 and FANCD2 in chromatin. Taken together, our results demonstrate that monoubiquitination of FANCD2, which is regulated by the FA pathway, promotes BRCA2 loading into chromatin complexes. These complexes appear to be required for normal homology-directed DNA repair.


Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines.
Protein thiols play a crucial role in redox signaling, in the regulation of enzymatic activity and protein function, and in maintaining redox homeostasis in living systems. The unique chemical reactivity of the thiol group makes protein cysteines susceptible to reactions with reactive oxygen and nitrogen species that form various reversible and irreversible post-translational modifications (PTMs). The reversible PTMs in particular are major components of redox signaling and are involved in the regulation of various cellular processes under physiological and pathological conditions. The biological significance of these redox PTMs in both healthy and disease states has been increasingly recognized. Herein, we review recent advances in quantitative proteomic approaches for investigating redox PTMs in complex biological systems, including general considerations of sample processing, chemical or affinity enrichment strategies, and quantitative approaches. We also highlight a number of redox proteomic approaches that enable effective profiling of redox PTMs for specific biological applications. Although technical limitations remain, redox proteomics is paving the way to a better understanding of redox signaling and regulation in both healthy and disease states.


Interactive multiple object tracking (iMOT).
We introduce a new task for exploring the relationship between action and attention. In this interactive multiple object tracking (iMOT) task, implemented as an iPad app, participants were presented with a display of multiple, visually identical disks which moved independently. The task was to prevent any collisions during a fixed duration. Participants could perturb object trajectories via the touchscreen. In Experiment 1, we used a staircase procedure to measure the ability to control moving objects. Object speed was set to 1°/s. On average participants could control 8.4 items without collision. Individual control strategies were quite variable, but did not predict overall performance. In Experiment 2, we compared iMOT with standard MOT performance using identical displays. Object speed was set to 2°/s. Participants could reliably control more objects (M = 6.6) than they could track (M = 4.0), but performance in the two tasks was positively correlated. In Experiment 3, we used a dual-task design. Compared to single-task baseline, iMOT performance decreased and MOT performance increased when the two tasks had to be completed together. Overall, these findings suggest: 1) There is a clear limit to the number of items that can be simultaneously controlled, for a given speed and display density; 2) participants can control more items than they can track; 3) task-relevant action appears not to disrupt MOT performance in the current experimental context.


Left ventricular strain analysis reveals better synchrony and diastolic function for septal versus apical right ventricular permanent pacing.
Left ventricular function and synchrony may be altered by right ventricular (RV) apical pacing. Septal pacing might be a better alternative. We compared effects on cardiac synchrony and function, between the 2 pacing sites, in chronically implanted patients. 40 pacing-dependent patients (74±9 years, 21 men), 20 paced at the apex, were studied 11±4 months after implantation (baseline); 32 of them were re-examined after 1 year. Systolic function was assessed from ejection fraction (EF), cardiac index (CI), mean longitudinal systolic strain (MLSS), and strain rate (MLSR); diastolic function from E/A, E/E', and E/Vp ratios. Intraventricular dyssynchrony from standard deviation (SSD) and maximal difference (MAXS) of the 12 LV myocardial systolic timings, and sum of all times from the aortic valve closure to peak strain (SUMTAVC) for those segments with post-systolic shortening; interventricular synchrony from the aorto-pulmonary delay (APD). Four patients died, all of them from the apical group. NYHA functional class was not different. Cardiac synchrony was not significantly different between the two pacing sites at baseline, and after 1 year follow-up. Although at baseline there was a greater dyssynchrony for the septal site, this did not progress at follow-up, whereas this increased for the apical site. Meanwhile, there was a higher LV filling pressure (E/E' ratio) for the apical site at 1 year (13±6 vs.18±6; p=0.04). Both septal and apical pacing sites affect negatively LV mechanical activation timings and synchrony. Apical, but not septal site, affects LV synchrony at 1 year, associated with increased filling pressure.


Trends in aircraft noise annoyance: the role of study and sample characteristics.
Recently, it has been suggested that the annoyance of residents at a given aircraft noise exposure level increases over the years. The objective of the present study was to verify the hypothesized trend and to identify its possible causes. To this end, the large database used to establish earlier exposure-response relationships on aircraft noise was updated with original data from several recent surveys, yielding a database with data from 34 separate airports. Multilevel grouped regression was used to determine the annoyance response per airport, after which meta-regression was used to investigate whether study characteristics could explain the heterogeneity in annoyance response between airports. A significant increase over the years was observed in annoyance at a given level of aircraft noise exposure. Furthermore, the type of annoyance scale, the type of contact, and the response percentage were found to be sources of heterogeneity. Of these, only the scale factor could statistically account for the trend, although other findings rule it out as a satisfactory explanation. No evidence was found for increased self-reported noise sensitivity. The results are of importance to the applicability of current exposure-annoyance relationships for aircraft noise and provide a basis for decisions on whether these need to be updated.


Dominant-side intracarotid amobarbital spares comprehension of word meaning.
Abolition of speech production after intracarotid amobarbital injection is generally considered evidence for language laterality. However, complex auditory comprehension may be preserved after injection of the dominant (left) side. The possibility that this sparing may be due to the intracarotid amobarbital injection not adequately deactivating some of the areas responsible for speech comprehension in the posterior part of the hemisphere was tested with a task known to be critically dependent on the left posterotemporal-inferoparietal region, one assessing visuo-verbal semantic relatedness. Even when the intracarotid injection of the left side produced marked deficits of speech production, comprehension of semantic relations was still intact in eight of 15 patients. Ten of these 15 patients also received right carotid injections, none of which affected comprehension of semantic relatedness. These data indicate that the intracarotid amobarbital injection cannot always specify the laterality of all language functions, an important concern when considering surgical procedures in the dominant posterotemporal-inferoparietal region.


On improving the credibility of candidate gene studies: A review of candidate gene studies published in Emotion.
The discovery of genetic variants associated with psychological traits deepens our knowledge about causes and consequences of individual differences. In psychology, the standard approach to identify these variants is the "candidate gene study." In a candidate gene study, a limited set of genetic variants is selected based on their hypothesized or known biological function, and these variants are tested for association with the psychological trait of interest. The successful replication of published candidate gene studies, however, is alarmingly scarce. In this article we describe the challenges to successfully identifying genetic associations, and review the candidate gene studies published in Emotion. We conclude that the implementation of 4 methodological guidelines developed by the Behavior Genetics Association for evaluating candidate gene studies will help to increase the credibility of candidate gene study findings.


An instrument to measure musculoskeletal symptoms among immigrant Hispanic farmworkers: validation in the nursery industry.
We report on the construction and psychometrics of a survey measure of musculoskeletal symptomatology for use with Spanish-speaking immigrant farmworkers. Survey development included focus groups with workers, forward and backward translations, and pilot testing. The final survey includes a body diagram and items about symptom severity, frequency, and duration and about self-treatment, medical care, and job tasks. We report on the initial test of the survey with 213 commercial nursery workers in Southern California. Fifty-five percent of the workers reported pain, with 30% reporting back pain, 21% reporting upper extremity pain, 19% reporting lower extremity pain, and 10% reporting neck and shoulder pain. A composite symptom score exhibited acceptable test-retest reliability (r = 0.41, p < 0.01) over the annual agricultural cycle. Greater symptomatology was associated with greater frequency of self-treatment (r = 0.42, p < 0.01), seeking professional health care (t = 2.49, p < 0.05), and exposure to high-risk jobs (OR = 2.1, p < 0.05, CI = 1.0 to 4.4), supporting the validity of composite score.


Real-time imaging of individual virion-triggered cortical actin dynamics for human immunodeficiency virus entry into resting CD4 T cells.
Real-time imaging of single virus particles allows the visualization of subtle dynamic events of virus-host interaction. During the human immunodeficiency virus (HIV) infection of resting CD4 T lymphocytes, overcoming cortical actin restriction is an essential step, but the dynamic process and mechanism remain to be characterized. Herein, by using quantum dot (QD) encapsulated fluorescent viral particles and single-virus tracking, we explored detailed scenarios of HIV dynamic entry and crossing the cortical actin barrier. The fine-scale temporal and spatial processes of single HIV virion interaction with the cortical actin were studied in depth during virus entry via plasma membrane fusion. Individual HIV virions modulate the subtle rearrangement of the cortical actin barrier to open a door to facilitate viral entry. The actin-binding protein, α-actinin, was found to be critical for actin dynamics during HIV entry. An α-actinin-derived peptide, actin-binding site 1 peptide (ABS1p), was developed to block HIV infection. Our findings reveal an α-actinin-mediated dynamic cortical actin rearrangement for HIV entry, and identify an antiviral target as well as a corresponding peptide inhibitor based on HIV interaction with the actin cytoskeleton.


Improved sensitivity for two-photon frequency-domain lifetime measurement.
We demonstrate a method to improve the measurement sensitivity of two-photon frequency-domain lifetime measurements in poor signal to background conditions. This technique uses sinusoidal modulation of the two-photon excitation source and detection of the second harmonic of the modulation frequency that appears in the emission. Additionally, we present the mathematical model which describes how the observed phase shift and amplitude demodulation factor of two-photon phosphorescence emission are related to the phosphorescence lifetime and modulation frequency. We demonstrate the validity of the model by showing the existence of new frequency terms in the phosphorescence emission generated from the quadratic nature of two-photon absorption and by showing that the phase shift and demodulation match theory for all frequency components.


Targeted delivery of antiglaucoma drugs to the supraciliary space using microneedles.
In this work, we tested the hypothesis that highly targeted delivery of antiglaucoma drugs to the supraciliary space by using a hollow microneedle allows dramatic dose sparing of the drug compared to topical eye drops. The supraciliary space is the most anterior portion of the suprachoroidal space, located below the sclera and above the choroid and ciliary body. A single, hollow 33-gauge microneedle, 700 to 800 μm in length, was inserted into the sclera and used to infuse antiglaucoma drugs into the supraciliary space of New Zealand white rabbits (N = 3-6 per group). Sulprostone, a prostaglandin analog, and brimonidine, an α₂-adrenergic agonist, were delivered via supraciliary and topical administration at various doses. The drugs were delivered unilaterally, and intraocular pressure (IOP) of both eyes was measured by rebound tonometry for 9 hours after injection to assess the pharmacodynamic responses. To assess safety of the supraciliary injection, IOP change immediately after intravitreal and supraciliary injection were compared. Supraciliary delivery of both sulprostone and brimonidine reduced IOP by as much as 3 mm Hg bilaterally in a dose-related response; comparison with topical administration at the conventional human dose showed approximately 100-fold dose sparing by supraciliary injection for both drugs. A safety study showed that the kinetics of IOP elevation immediately after supraciliary and intravitreal injection of placebo formulations were similar. This study introduced the use of targeted drug delivery to the supraciliary space by using a microneedle and demonstrated dramatic dose sparing of antiglaucoma therapeutic agents compared to topical eye drops. Targeted delivery in this way can increase safety by reducing side effects and could allow a single injection to contain enough drug for long-term sustained delivery.


Experts' Views on the Gaps in Public Health Emergency Preparedness in Israel: A Qualitative Case Study.
Despite the significant improvement in all components of preparedness in the past decade, there are still gaps between the guidelines and the reality on the ground. The purpose of this study is to explore how Israeli public health and emergency medicine experts perceive the demands for health organization emergency preparedness and the actual practice. Qualitative phenomenological research. We interviewed 22 Israeli public health and emergency medicine experts face-to-face and conducted a content analysis. The findings revealed barriers in the following areas: preparation and readiness of hospitals, preparedness and readiness in the community, connection between the community and the hospital, inter-agency coordination and interface, interdisciplinary integration, preparedness resources, postcrisis evaluation, assimilating smart technologies, information accessibility, and communication. To reduce the gap between theory and practice, retrospective research and evaluation must be included to learn in depth what strategies and resources should be used during a health crisis. Likewise, profiles should be constructed and the community should be segmented in order to design resilience programs and accommodate information to subpopulations.


Transcription of Staphylococcus aureus fibronectin binding protein genes is negatively regulated by agr and an agr-independent mechanism.
The production of cell surface proteins in Staphylococcus aureus is generally down-regulated in the postexponential growth phase by the global regulator agr. The effector of this regulation is the RNAIII molecule, which is encoded within the agr locus. RNAIII seems to regulate most target genes at the level of transcription, but it also has an effect on the translation of some genes. To study the role of agr on the expression of fibronectin binding proteins (FnBPs), we investigated the transcription and translation of fnb genes in agr mutant strain WA250 and its parent strain, 8325-4. The results show that fnb genes are negatively regulated by agr and also by an agr-independent mechanism that restricts fnb mRNA synthesis to the early exponential phase of growth. Transcription and Western blot analysis of cell-associated FnBPs demonstrated that synthesis of both FnBPA and FnBPB in the wild-type and agr mutant strains took place preferentially during the first hour of growth and rapidly decreased after the second hour. We also confirmed previous results showing that the agr mutant strain has an increased capacity to bind fibronectin compared to its parent agr+ strain. However, while the concentrations of fnb mRNAs and proteins differed by a factor of 16 between the strains, the difference in fibronectin binding was only twofold, indicating that the binding of fibronectin to the bacteria is not proportional to the amount of FnBPs on their surface.


An efficient and extensible format, library, and API for binary trajectory data from molecular simulations.
Molecular dynamics simulations is an important application in theoretical chemistry, and with the large high-performance computing resources available today the programs also generate huge amounts of output data. In particular in life sciences, with complex biomolecules such as proteins, simulation projects regularly deal with several terabytes of data. Apart from the need for more cost-efficient storage, it is increasingly important to be able to archive data, secure the integrity against disk or file transfer errors, to provide rapid access, and facilitate exchange of data through open interfaces. There is already a whole range of different formats used, but few if any of them (including our previous ones) fulfill all these goals. To address these shortcomings, we present "Trajectory Next Generation" (TNG)--a flexible but highly optimized and efficient file format designed with interoperability in mind. TNG both provides state-of-the-art multiframe compression as well as a container framework that will make it possible to extend it with new compression algorithms without modifications in programs using it. TNG will be the new file format in the next major release of the GROMACS package, but it has been implemented as a separate library and API with liberal licensing to enable wide adoption both in academic and commercial codes.


European Forum for Primary Care: Position Paper for Primary Care Mental Health.
There is a need for a paradigm shift across mental health in primary care to improve the lives of millions of Europeans. To contribute to this paradigm shift, the European Forum for Primary Care (EFPC-MH) working group for Mental Health, produced a Position Paper for Primary Care Mental Health outlining 14 themes that needed prioritizing. These themes were developed and discussed interactively during the EFPC conferences between 2012 and 2019. The Position Paper on Mental Health gives direction to the necessary improvements over the next ten years. The themes vary from preferable healthcare model to the social determinants highlighting issues such as inequalities. The Statement of Mental Health in Primary Care will be established in cooperation with fellow organizations.


Bee Venom Ameliorates Cognitive Dysfunction Caused by Neuroinflammation in an Animal Model of Vascular Dementia.
Vascular dementia (VaD) is caused by the reduction of blood supply by vessel occlusion and is characterized by progressive cognitive decline. VaD incidence has been growing due to the aging population, placing greater strain on social and economic resources. However, the pathological mechanisms underlying VaD remain unclear. Many studies have used the bilateral common carotid artery occlusion (BCCAO) animal model to investigate potential therapeutics for VaD. In this study, we investigated whether bee venom (BV) improves cognitive function and reduces neuroinflammation in the hippocampus of BCCAO animals. Animals were randomly divided into three groups: a sham group (n = 15), BCCAO control group (n = 15), and BV-treated BCCAO group (n = 15). BCCAO animals were treated with 0.1 μg/g BV at ST36 ("Joksamli" acupoint) four times every other day. In order to investigate the effect of BV treatment on cognitive function, we performed a Y-maze test. In order to uncover any potential relationship between these results and neuroinflammation, we also performed Western blotting in the BCCAO group. Animals that had been treated with BV showed an improved cognitive function and a reduced expression of neuroinflammatory proteins in the hippocampus, including Iba-1, TLR4, CD14, and TNF-α. Furthermore, we demonstrated that BV treatment increased pERK and BDNF in the hippocampus. The present study thus underlines the neuroprotective effect of BV treatment against BCCAO-induced cognitive impairment and neuroinflammation. Our findings suggest that BV may be an effective complementary treatment for VaD, as it may improve cognitive function and attenuate neuroinflammation associated with dementia.


Protein and Microbial Biomarkers in Sputum Discern Acute and Latent Tuberculosis in Investigation of Pastoral Ethiopian Cohort.
Differential diagnosis of tuberculosis (TB) and latent TB infection (LTBI) remains a public health priority in high TB burden countries. Pulmonary TB is diagnosed by sputum smear microscopy, chest X-rays, and PCR tests for distinct Mycobacterium tuberculosis (Mtb) genes. Clinical tests to diagnose LTBI rely on immune cell stimulation in blood plasma with TB-specific antigens followed by measurements of interferon-γ concentrations. The latter is an important cytokine for cellular immune responses against Mtb in infected lung tissues. Sputum smear microscopy and chest X-rays are not sufficiently sensitive while both PCR and interferon-γ release assays are expensive. Alternative biomarkers for the development of diagnostic tests to discern TB disease states are desirable. This study's objective was to discover sputum diagnostic biomarker candidates from the analysis of samples from 161 human subjects including TB patients, individuals with LTBI, negative community controls (NCC) from the province South Omo, a pastoral region in Ethiopia. We analyzed 16S rRNA gene-based bacterial taxonomies and proteomic profiles. The sputum microbiota did not reveal statistically significant differences in α-diversity comparing the cohorts. The genus Mycobacterium, representing Mtb, was only identified for the TB group which also featured reduced abundance of the genus Rothia in comparison with the LTBI and NCC groups. Rothia is a respiratory tract commensal and may be sensitive to the inflammatory milieu generated by infection with Mtb. Proteomic data supported innate immune responses against the pathogen in subjects with pulmonary TB. Ferritin, an iron storage protein released by damaged host cells, was markedly increased in abundance in TB sputum compared to the LTBI and NCC groups, along with the α-1-acid glycoproteins ORM1 and ORM2. These proteins are acute phase reactants and inhibit excessive neutrophil activation. Proteomic data highlight the effector roles of neutrophils in the anti-Mtb response which was not observed for LTBI cases. Less abundant in the sputum of the LTBI group, compared to the NCC group, were two immunomodulatory proteins, mitochondrial TSPO and the extracellular ribonuclease T2. If validated, these proteins are of interest as new biomarkers for diagnosis of LTBI.


Relative Radiosensitivities of Woody and Herbaceous Spermatophytes.
The sensitivities of several woody and herbaceous species to single acute exposures to cobalt-60 gamma rays have been determined. Within each group the sensitivity of each species is largely determined by its average interphase chromosome volume (interphase nuclear volume divided by chromosome number) of shoot apical meristem cells. On the basis of the calculated amounts of energy absorbed (in kiloelectron volts) per interphase chromosome at an exposure necessary to produce a given biological effect, woody species were approximately twice as sensitive as herbaceous species.


The Use and Effectiveness of an Online Diagnostic Support System for Blood Film Interpretation: Comparative Observational Study.
The recognition and interpretation of abnormal blood cell morphology is often the first step in diagnosing underlying serious systemic illness or leukemia. Supporting the staff who interpret blood film morphology is therefore essential for a safe laboratory service. This paper describes an open-access, web-based decision support tool, developed by the authors to support morphological diagnosis, arising from earlier studies identifying mechanisms of error in blood film reporting. The effectiveness of this intervention was assessed using the unique resource offered by the online digital morphology Continuing Professional Development scheme (DM scheme) offered by the UK National External Quality Assessment Service for Haematology, with more than 3000 registered users. This allowed the effectiveness of decision support to be tested within a defined user group, each of whom viewed and interpreted the morphology of identical digital blood films. The primary objective of the study was to test the effectiveness of the decision support system in supporting users to identify and interpret abnormal morphological features. The secondary objective was to determine the pattern and frequency of use of the system for different case types, and to determine how users perceived the support in terms of their confidence in decision-making. This was a comparative study of identical blood films evaluated either with or without decision support. Selected earlier cases from the DM scheme were rereleased as new cases but with decision support made available; this allowed a comparison of data sets for identical cases with or without decision support. To address the primary objectives, the study used quantitative evaluation and statistical comparisons of the identification and interpretation of morphological features between the two different case releases. To address the secondary objective, the use of decision support was assessed using web analytical tools, while a questionnaire was used to assess user perceptions of the system. Cases evaluated with the aid of decision support had significantly improved accuracy of identification for relevant morphological features (mean improvement 9.8%) and the interpretation of those features (mean improvement 11%). The improvement was particularly significant for cases with higher complexity or for rarer diagnoses. Analysis of website usage demonstrated a high frequency of access for web pages relevant to each case (mean 9298 for each case, range 2661-24,276). Users reported that the decision support website increased their confidence for feature identification (4.8/5) and interpretation (4.3/5), both within the context of training (4.6/5) and also in their wider laboratory practice (4.4/5). The findings of this study demonstrate that directed online decision support for blood morphology evaluation improves accuracy and confidence in the context of educational evaluation of digital films, with effectiveness potentially extending to wider laboratory use.


Drug metabolism alterations in nonalcoholic fatty liver disease.
Drug-metabolizing enzymes play a vital role in the elimination of the majority of therapeutic drugs. The major organ involved in drug metabolism is the liver. Chronic liver diseases have been identified as a potential source of significant interindividual variation in metabolism. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting between 60 and 90 million Americans, yet the vast majority of NAFLD patients are undiagnosed. NAFLD encompasses a spectrum of pathologies, ranging from steatosis to nonalcoholic steatohepatitis and fibrosis. Numerous animal studies have investigated the effects of NAFLD on hepatic gene expression, observing significant alterations in mRNA, protein, and activity levels. Information on the effects of NAFLD in human patients is limited, though several significant investigations have recently been published. Significant alterations in the activity of drug-metabolizing enzymes may affect the clearance of therapeutic drugs, with the potential to result in adverse drug reactions. With the enormous prevalence of NAFLD, it is conceivable that every drug currently on the market is being given to patients with NAFLD. The current review is intended to present the results from both animal models and human patients, summarizing the observed alterations in the expression and activity of the phase I and II drug-metabolizing enzymes.


Biochemical characterization of diverse Stat5b-binding enhancers that mediate growth hormone-activated insulin-like growth factor-I gene transcription.
Many of the biological effects of growth hormone (GH) are mediated by insulin-like growth factor I (IGF-I), a 70-amino acid secreted peptide whose gene expression is rapidly induced by GH via the Stat5b transcription factor. We previously identified multiple evolutionarily conserved GH-activated chromosomal binding domains for Stat5b within the rat Igf1 locus, and proposed that they could regulate IGF-I gene activity. Here we investigate the biochemical and functional characteristics of these putative long-range transcriptional enhancers. Each element contained 2 or 3 individual Stat5b recognition sequences that could bind Stat5b in vitro, but with affinities that varied over a >100-fold range. Full transcriptional responsiveness to GH required that all Stat5b sites be intact within an individual enhancer. Replacement of a single lower-affinity Stat5b sequence with a higher-affinity one increased in vitro binding of Stat5b, and boosted transcriptional potency of the entire element to GH. As enhanced transcriptional activity involved changes in only one or two nucleotides within an enhancer DNA segment, there appears to be remarkable specificity and sensitivity in the ability of Stat5b to transform DNA binding activity into transcriptional function. Stat5b was able to stimulate the transcriptional activity of two enhancers in the absence of GH, indicating that individual Stat5b-regulated elements possess distinct functional features. We conclude that combinatorial interplay among multiple Stat5b-binding response elements with distinguishable biochemical properties is responsible for highly regulated control of IGF-I gene activity by GH.


Evidence for intrinsic differences in the formation of chromatin domains in Drosophila melanogaster.
The results of an investigation into intrinsic differences in the formation of two different heterochromatic domains are presented. The study utilized two different position effect variegation mutants in Drosophila melanogaster for investigating the process of compacting different stretches of DNA into heterochromatin. Each stretch of DNA encodes for a gene that affects different aspects of bristle morphology. The expression of each gene is prevented when it is compacted into heterochromatin thus the genes serve as effective reporter systems to monitor the spread of heterochromatin. Both variegating mutants are scored in the same cell such that environmental and genetic background differences are unambiguously eliminated. Any differences observed in the repression of the two genes must therefore be the result of intrinsic differences in the heterochromatic compaction process for the two stretches of DNA. Studies of the effects different enhancers of variegation have upon the compaction of the two genes indicate each compaction event occurs independently of the other, and that different components are involved in the two processes. These results are discussed with regard to spreading heterochromatin and the role this process may play in regulating gene expression.


Effect of droplet-induced breakdown on CARS temperature measurements.
This research examines the potential for coherent anti-Stokes Raman scattering (CARS) to provide reliable gas temperature measurements in the presence of liquid droplets. The droplets cause dielectric breakdown by focusing the CARS laser beams. This breakdown produces a plasma that can disrupt or obscure the CARS signal. Specifically, we examine the influence of laser induced breakdown on the CARS signal, and we determine the importance of droplet position relative to the CARS focal volume and droplet concentration on the reliability of CARS temperature measurements in droplet-laden flows. In addition, we propose a reliable data reduction procedure to minimize the disruptive influence of laser induced breakdown on CARS temperatures.


Amyloidosis involving the respiratory system: 5-year's experience of a multi-disciplinary group's activity.
Amyloidosis may involve the respiratory system with different clinical-radiological-functional patterns which are not always easy to be recognized. A good level of knowledge of the disease, an active integration of the pulmonologist within a multidisciplinary setting and a high level of clinical suspicion are necessary for an early diagnosis of respiratory amyloidosis. The aim of this retrospective study was to evaluate the number and the patterns of amyloidosis involving the respiratory system. We searched the cases of amyloidosis among patients attending the multidisciplinary rare and diffuse lung disease outpatients' clinic of Pulmonology Unit of the Hospital of Arezzo from 2007 to 2012. Among the 298 patients evaluated during the study period, we identified three cases of amyloidosis with involvement of the respiratory system, associated or not with other extra-thoracic localizations, whose diagnosis was histo-pathologically confirmed after the pulmonologist, the radiologist, and the pathologist evaluation. Our experience of a multidisciplinary team confirms that intra-thoracic amyloidosis is an uncommon disorder, representing 1.0% of the cases of rare and diffuse lung diseases referred to our center. The diagnosis of the disease is not always easy and quick as the amyloidosis may involve different parts of the respiratory system (airways, pleura, parenchyma). It is therefore recommended to remind this orphan disease in the differential diagnosis of the wide clinical scenarios the pulmonologist may intercept in clinical practice.


Bubble-Driven Detachment of Bacteria from Confined Microgeometries.
Moving air-liquid interfaces, for example, bubbles, play a significant role in the detachment and transport of colloids and microorganisms in confined systems as well as unsaturated porous media. Moreover, they can effectively prevent and/or postpone the development of mature biofilms on surfaces that are colonized by bacteria. Here we demonstrate the dynamics and quantify the effectiveness of this bubble-driven detachment process for the bacterial strain Staphylococcus aureus. We investigate the effects of interface velocity and geometrical factors through microfluidic experiments that mimic some of the confinement features of pore-scale geometries. Depending on the bubble velocity U, at least three different flow regimes are found. These operating flow regimes not only affect the efficiency of the detachment process but also modify the final distribution of the bacteria on the surface. We organize our results according to the capillary number, [Formula: see text], where μ and γ are the viscosity and the surface tension, respectively. Bubbles at very low velocities, corresponding to capillary numbers Ca < 5 × 10-5, exhibit detachment efficiencies of up to 80% at the early stage of bacterial adhesion. In contrast, faster bubbles at capillary numbers Ca > 10-3, have lower detachment efficiencies and cause significant nonuniformities in the final distribution of the cells on the substrate. This effect is associated with the formation of a thin liquid film around the bubble at higher Ca. In general, at higher bubble velocities bacterial cells in the corners of the geometry are less influenced by the bubble passage compared to the central region.


Flowering Locus C's Lessons: Conserved Chromatin Switches Underpinning Developmental Timing and Adaptation.
Analysis of how seasonal cues influence the timing of the floral transition has revealed many important principles for how epigenetic regulation can integrate a variety of environmental cues with developmental signals. The study of the pathways that necessitate overwintering in plants and their ability to respond to prolonged cold (the vernalization requirement and response pathways) has elaborated different chromatin regulatory pathways and the involvement of noncoding RNAs. The major target of these vernalization pathways in Arabidopsis (Arabidopsis thaliana) is Flowering Locus C (FLC). A relatively simple picture of FLC regulation is emerging of a few core complexes and mechanisms that antagonize each other's actions. This balance provides a fine degree of control that has nevertheless permitted evolution of a wide range of natural variation in vernalization in Arabidopsis. Similar simple routes of adaptation may underlie life history variation between species.


Genetic parameters of calcium, phosphorus, magnesium, and potassium serum concentrations during the first 8 days after calving in Holstein cows.
Calcium, Mg, P, and K are of great importance for the health and productivity of dairy cows after calving. So far genetic studies have focused on clinical hypocalcemia, leaving the genetic parameters of these macroelements unstudied. Our objective was to estimate the genetic parameters of Ca, Mg, P, and K serum concentrations and their changes during the first 8d after calving. The study was conducted in 9 herds located in northern Greece, with 1,021 Holstein cows enrolled from November 2010 until November 2012. No herd used any kind of preventive measures for hypocalcemia. Pedigree information for all cows was available. A total of 35 cows were diagnosed and treated for periparturient paresis and, therefore, excluded from the study. The remaining 986 cows were included in genetic analysis. The distribution of cows across parities was 459 (parity 1), 234 (parity 2), 158 (parity 3), and 135 (parity ≥4). A sample of blood was taken from each cow on d1, 2, 4, and 8 after calving and serum concentrations of Ca, P, Mg, and K were measured in each sample. A final data set of 15,390 biochemical records was created consisting of 3,903 Ca, 3,902 P, 3,903Mg, and 3,682K measurements. Moreover, changes of these concentrations between d1 and 4 as well as 1 and 8 after calving were calculated and treated as different traits. Random regression models were used to analyze the data. Results showed that daily heritabilities of Ca, P, and Mg concentrations traits were moderate to high (0.20-0.43), whereas those of K were low to moderate (0.12-0.23). Regarding concentration changes, only Mg change between d1 and 8 after calving had a significant heritability of 0.18. Genetic correlations between Ca, P, Mg, and K concentrations and their concentration changes from d1 to 4 and 1 to 8 after calving were not significantly different from zero. Most phenotypic correlations among Ca, P, Mg, and K concentrations were positive and low (0.09-0.16), whereas the correlation between P and Mg was negative and low (-0.16). Phenotypic correlations among macromineral concentrations on d1 and their changes from d1 to 4 and 1 to 8 after calving varied for each macromineral. This study revealed that genetic selection for normal Ca, P, Mg, and K concentrations in the first week of lactation is possible and could facilitate the management of their deficiencies during the early stages of lactation.


Congenital coronary artery anomalies silent until geriatric age: non-invasive assessment, angiography tips, and treatment.
Coronary artery anomalies (CAAs) may be discovered more often as incidental findings during the normal diagnostic process for other cardiac diseases or less frequently on the basis of manifestations of myocardial ischemia. The cardiovascular professional may be involved in their angiographic diagnosis, functional assessment and eventual endovascular treatment. A complete angiographic definition is mandatory in order to understand the functional effects and plan any intervention in CAAs: computed tomography and magnetic resonance imaging are useful non-invasive tools to detect three-dimensional morphology of the anomalies and its relationships with contiguous cardiac structures, whereas coronary arteriography remains the gold standard for a definitive anatomic picture. A practical idea of the possible functional significance is mandatory for deciding how to manage CAAs: non-invasive stress tests and in particular the invasive pharmacological stress tests with or without intravascular ultrasound monitoring can assess correctly the functional significance of the most CAAs. Finally, the knowledge of the particular endovascular techniques and material is of paramount importance for achieving technical and clinical success. CAAs represent a complex issue, which rarely involve the cardiovascular professional at different levels. A timely practical knowledge of the main issues regarding CAAs is important in the management of such entities.


Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease.
Genome-wide linkage studies have defined a broad susceptibility region for late-onset Alzheimer's disease on chromosome 12, which contains the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) gene, a coreceptor for Wnt signaling. Here, we report the association between common LRP6 variants and late-onset Alzheimer's disease in a multicenter case-control series as well as in a large family-based series ascertained by the National Institute of Mental Health-National Institute on Aging Genetics Initiative. As shown in the genome-wide linkage studies, our association depends mainly on apolipoprotein E-epsilon4 (APOE-epsilon4) carrier status. Haplotype tagging single-nucleotide polymorphisms (SNPs) with a set of seven allelic variants of LRP6 identified a putative risk haplotype, which includes a highly conserved coding sequence SNP: Ile-1062 --> Val. Functional analyses revealed that the associated allele Val-1062, an allele previously linked to low bone mass, has decreased beta-catenin signaling in HEK293T cells. Our study unveils a genetic relationship between LRP6 and APOE and supports the hypothesis that altered Wnt/beta-catenin signaling may be involved in this neurodegenerative disease.


The provision of surgical care for children with cardiac disease: the Jamaican experience--an 18-year review.
The aim of this article is to review the local experience over the last 18 years (1994-2011) in providing surgical intervention for children with heart conditions in Jamaica. Eight hundred and sixty-three children received cardiac surgery during this period, 441 were done with the assistance of visiting overseas teams and 422 by the local surgical teams. The majority of cases receiving cardiac surgery were for congenital heart defects; however 3% of cases were for rheumatic heart disease. The overall survival rate was 94% for the period 1994 to 2008.


Aberrant promoter methylation and loss of suppressor of cytokine signalling-1 gene expression in the development of uterine cervical carcinogenesis.
Cervical cancer is a leading cause of cancer related deaths in women worldwide caused due to infection of high-risk human papillomaviruses. As JAK/STAT signalling pathway has been shown to play an important role during carcinogenesis, we studied the role of silencing of Suppressor of Cytokine Signalling-1 (SOCS-1) gene, a negative regulator of JAK/STAT pathway in cervical cancer. The expression pattern of SOCS-1 mRNA and protein was analyzed in different stages of cervical tumor biopsies while normal cervical tissues served as controls. RT-PCR, immunohistochemistry and methylation-specific PCR (MSP) were performed to assess the expression pattern and promoter methylation of SOCS-1 gene in a total of 120 fresh surgically resected cervical tissue specimens comprising precancer (n = 12), cancer (n = 78) and normal controls (n = 30). Compared with expression of SOCS-1 in normal tissues, 64% of the tumor tissues expressed either undetectable or reduced expression. Aberrant promoter methylation of SOCS-1 was found in 61% of the cervical tumor tissues. SOCS-1 expression and methylation were significantly associated with severity of the disease (p < 0.01). We demonstrate for the first time the transcriptional inactivation of SOCS-1 gene due to hypermethylation and synergism with HPV infection which may play an important role in cervical carcinoma.


Characterizing gibberellin flow in planta using photocaged gibberellins.
Gibberellins (GAs) are ubiquitous plant hormones that coordinate central developmental and adaptive growth processes in plants. Accurate movement of GAs throughout the plant from their sources to their destination sites is emerging to be a highly regulated and directed process. We report on the development of novel photocaged gibberellins that, in combination with a genetically encoded GA-response marker, provide a unique platform to study GA movement at high-resolution, in real time and in living, intact plants. By applying this platform to the Arabidopsis thaliana endogenous bioactive gibberellin GA4, we measure kinetic parameters of its flow, such as decay length and velocity, in vivo.


Exploring the conceptualization of program theories in Dutch community programs: a multiple case study.
Our objective was to evaluate whether the limited effectiveness of most community programs intended to prevent disease and promote health should be attributed to the quality of the conceptualization of their program theories. In a retrospective multiple case study we assessed the program theories of 16 community programs (cases) in the Netherlands (1990-2004). Methods were a document analysis, supplemented with member checks (insider information from representatives). We developed a community approach reference framework to guide us in reconstructing and evaluating the program theories. On the whole, programs did not clearly spell out the process theories (enabling the implementation of effective interventions), the program components (interventions) and/or the impact theories (describing pathways from interventions to ultimate effects). Program theories usually turned out to be neither specific nor entirely plausible (complete and valid). The limited effectiveness of most community programs should most probably be attributed to the limited conceptualization of program theories to begin with. Such a failure generally also precludes a thorough examination of the effectiveness of the community approach as such.


Pre- and postsynaptic actions of ATP on neurotransmission in rat submandibular ganglia.
The pre- and postsynaptic actions of exogenously applied ATP were investigated in intact and dissociated parasympathetic neurones of rat submandibular ganglia. Nerve-evoked excitatory postsynaptic potentials (EPSPs) were not inhibited by the purinergic receptor antagonists, suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), or the desensitising agonist, alpha,beta-methylene ATP. In contrast, EPSPs were abolished by the nicotinic acetylcholine receptor antagonists, hexamethonium and mecamylamine. Focal application of ATP (100 microM) had no effect on membrane potential of the postsynaptic neurone or on the amplitude of spontaneous EPSPs. Taken together, these results suggest the absence of functional purinergic (P2) receptors on the postganglionic neurone in situ. In contrast, focally applied ATP (100 microM) reversibly inhibited nerve-evoked EPSPs. Similarly, bath application of the non-hydrolysable analogue of ATP, ATP gamma S, reversibly depressed EPSPs amplitude. The inhibitory effects of ATP and ATP gamma S on nerve-evoked transmitter release were antagonised by bath application of either PPADS or suramin, suggesting ATP activates a presynaptic P2 purinoceptor to inhibit acetylcholine release from preganglionic nerves in the submandibular ganglia. In acutely dissociated postganglionic neurones from rat submandibular ganglia, focal application of ATP (100 microM) evoked an inward current and subsequent excitatory response and action potential firing, which was reversibly inhibited by PPADS (10 microM). The expression of P2X purinoceptors in wholemount and dissociated submandibular ganglion neurones was examined using polyclonal antibodies raised against the extracellular domain of six P2X purinoceptor subtypes (P2X(1-6)). In intact wholemount preparations, only the P2X(5) purinoceptor subtype was found to be expressed in the submandibular ganglion neurones and no P2X immunoreactivity was detected in the nerve fibres innervating the ganglion. Surprisingly, in dissociated submandibular ganglion neurones, high levels of P2X(2) and P2X(4) purinoceptors immunoreactivity were found on the cell surface. This increase in expression of P2X(2) and P2X(4) purinoceptors in dissociated submandibular neurones could explain the increased responsiveness of the neurones to exogenous ATP. We conclude that disruption of ganglionic transmission in vivo by either nerve damage or synaptic blockade may up-regulate P2X expression or availability and alter neuronal excitability.


Moisture retention extended enhanced bioelectrochemical remediation of unsaturated soil.
Bioelectrochemical systems (BESs) have demonstrated great promise in augmented biodegradation of petroleum hydrocarbons in water-saturated soils. However, bioremediation of unsaturated soil in vadose zone has been a challenge due to poor mass transfer and low conductivity. This study proposed a moisture retention layer (2 cm thickness) around the BES anodes to enhance soil remediation under unsaturated conditions. The active soil BESs (closed circuit) includes two reactors with anodic moisture-retaining layers of soil-polyacrylamide hydrogel (SHB) and graphite granule-polyacrylamide hydrogel (GHB) mixtures, and another reactor filled with only soil (SB) without moisture-retaining layer. An open circuit SB was served as a control to simulate natural attenuation. This study demonstrated for the first time that moisture retention layers around the BES anodes could significantly extend and enhance hydrocarbon degradation in vadose zone soil. Results showed that SHB reactor could maintain 43-100% longer duration for electricity generation than other reactors. Correspondingly, SHB showed the best removal (average 21-37%) of total petroleum hydrocarbon (TPH) in spatial distribution, which was ~91% and ~164% higher than other BESs and control, respectively. This study demonstrated that by using low-cost and environmentally friendly hydrogel, BESs could become a viable remediation method for vadose zone soil.


Magnesium status and attention deficit hyperactivity disorder (ADHD): A meta-analysis.
Current research suggests conflicting evidence surrounding the association between serum magnesium levels and the diagnosis of attention deficit hyperactivity disorder (ADHD). This systematic review and meta-analysis aims to explore, summarize and quantify the published literature addressing this topic. We conducted an exhaustive literature search on Scopus and PubMed for all the relevant observational studies published up to August 2018. A meta-analysis using a random-effects model was used to summarize the overall association between serum magnesium level and ADHD from the available data. We identified seven studies which reported the mean and standard deviation (SD) of magnesium concentration in both ADHD and control groups. The random-effects meta-analysis showed that subjects with ADHD had 0.105 mmol/l (95% CI: -0.188, -0.022; P < 0.013) lower serum magnesium levels compared with to their healthy controls. Moreover, we observed striking and statistically significant heterogeneity among the included studies (I2 = 96.2%, P = 0.0103). The evidence from this meta-analysis supports the theory that an inverse relationship between serum magnesium deficiency and ADHD exists. High heterogeneity amongst the included studies suggests that there is a residual need for observational and community-based studies to further investigate this issue.


Live-cell imaging to compare the transfection and gene silencing efficiency of calcium phosphate nanoparticles and a liposomal transfection agent.
The processing of DNA (for transfection) and short interfering RNA (siRNA; for gene silencing), introduced into HeLa cells by triple-shell calcium phosphate nanoparticles, was followed by live-cell imaging. For comparison, the commercial liposomal transfection agent Lipofectamine was used. The cells were incubated with these delivery systems, carrying either enhanced green fluorescent protein (eGFP)-encoding DNA or siRNA against eGFP. In the latter case, HeLa cells that stably expressed eGFP were used. The expression of eGFP started after 5 h in the case of nanoparticles and after 4 h in the case of Lipofectamine. The corresponding times for gene silencing were 5 h (nanoparticles) and immediately after incubation (Lipofectamine). The expression of eGFP was notably enhanced 2-3 h after cell division (mitosis). In general, the transfection and gene silencing efficiencies of the nanoparticles were lower than those of Lipofectamime, even at a substantially higher dose (factor 20) of nucleic acids. However, the cytotoxicity of the nanoparticles was lower than that of Lipofectamine, making them suitable vectors for in vivo application.


Expression profiling and gene discovery in the mouse lens.
Defects in the development and physiology of the lens can result in cataracts (opacification of the lens), which are currently treatable only by surgical removal. The lens is also an excellent system for understanding fundamental biological processes such as cellular differentiation and ageing. Here, microarrays have been used to gain insights into global patterns of gene expression in the mouse lens. Lens gene expression compared to non-lens tissues has been investigated in order to identify genes preferentially expressed in the lens and lenses of different ages have been compared to identify differentially regulated genes. Genes expressed in the lens were identified using mouse GeneFilters microarrays (GF400; ResGen). Each array comprises 5,184 mouse cDNAs representing sequence-verified known genes and uncharacterized ESTs spotted onto a nylon membrane. Target RNA (33P labeled) from lens and non-lens samples was hybridized to the arrays. The proportion of genes involved in various biological processes was investigated using Onto-Express to search for GeneOntology terms associated with them. Differential gene expression was investigated using K-means clustering analysis. Expression of known and uncharacterized genes selected from the arrays was investigated further using semi-quantitative RT-PCR. 1,668 genes were expressed in one or more of newborn, 7 day old, and adult mouse lenses at levels significantly above background. Raw data and bioinformatics data relating to these genes have been published herein. There were 543 (33%) known genes, 124 (7%) had some similarity to known genes, 400 (24%) were functionally uncharacterized, and the remaining 601 (36%) genes were novel (matching only existing ESTs). Onto-Express identified genes involved in various biological processes including several categories containing greater numbers of genes than would be expected by chance, such as transcription regulation and G-protein coupled receptor signaling genes. Semi-quantitative RT-PCR confirmed preferential expression of several genes in the lens compared to non-lens tissues and genes exhibiting significantly higher expression in the 7 day lens compared to either adult or newborn lenses. Expression in the lens of 10 genes involved in apoptosis was also confirmed and, intriguingly, expression of hemoglobin isoforms (Hba-a1, Hba-X, Hbb-b1, Hbb-b2, and Hbb-Y) was confirmed using isotype specific primers. Finally, we confirmed the expression in the lens of all additional novel, uncharacterized and known genes tested. The present work has provided insights into global patterns of gene expression in the lens and the expression of a significant number of genes has been confirmed using semi-quantitative RT-PCR. Genes preferentially expressed in the lens compared to non-lens tissues have been identified as well as genes differentially expressed between lenses at different ages. Gene expression profiling and gene discovery in the lens are essential prerequisites for future functional studies aimed at gaining insights into the potential roles of these genes in lens development, maturation, physiology, and pathogenesis (using targeted mutagenesis in mice, for instance).


Method Specific Calibration Corrects for DNA Extraction Method Effects on Relative Telomere Length Measurements by Quantitative PCR.
Telomere length (TL) is increasingly being used as a biomarker in epidemiological, biomedical and ecological studies. A wide range of DNA extraction techniques have been used in telomere experiments and recent quantitative PCR (qPCR) based studies suggest that the choice of DNA extraction method may influence average relative TL (RTL) measurements. Such extraction method effects may limit the use of historically collected DNA samples extracted with different methods. However, if extraction method effects are systematic an extraction method specific (MS) calibrator might be able to correct for them, because systematic effects would influence the calibrator sample in the same way as all other samples. In the present study we tested whether leukocyte RTL in blood samples from Holstein Friesian cattle and Soay sheep measured by qPCR was influenced by DNA extraction method and whether MS calibration could account for any observed differences. We compared two silica membrane-based DNA extraction kits and a salting out method. All extraction methods were optimized to yield enough high quality DNA for TL measurement. In both species we found that silica membrane-based DNA extraction methods produced shorter RTL measurements than the non-membrane-based method when calibrated against an identical calibrator. However, these differences were not statistically detectable when a MS calibrator was used to calculate RTL. This approach produced RTL measurements that were highly correlated across extraction methods (r > 0.76) and had coefficients of variation lower than 10% across plates of identical samples extracted by different methods. Our results are consistent with previous findings that popular membrane-based DNA extraction methods may lead to shorter RTL measurements than non-membrane-based methods. However, we also demonstrate that these differences can be accounted for by using an extraction method-specific calibrator, offering researchers a simple means of accounting for differences in RTL measurements from samples extracted by different DNA extraction methods within a study.


Linkage of protection against amyloid fibril formation in the mouse to a single, autosomal dominant gene.
Inbred strains of mice provide a model for studies of the pathogenesis of amyloid A (AA) amyloidosis. All susceptible strains of mice described to date codominantly express two serum amyloid A (apoSAA) isoforms, apoSAA1 and apoSAA2, of which only apoSAA2 serves as a precursor for amyloid fibrils. In previous studies, we have shown that the CE/J strain, which produces a single, novel apoSAA isoform, apoSAACE/J, is amyloid resistant. In the present study amyloid-resistant CE/J females were mated with amyloid-susceptible CBA/J males to produce F1 hybrid offspring which were then backcrossed to the parental CBA/J mouse strain. Amyloid susceptibility was determined in 30 backcrossed mice 72 h after injection of murine amyloid enhancing factor and silver nitrate. ApoSAA isoforms in plasma were separated by isoelectric focusing gel electrophoresis and visualized after immunoblotting with anti-AA antiserum. Amyloid A fibrils in spleen homogenates were denatured by formic acid and AA protein was quantified by ELISA using anti-mouse apoSAA antibodies. Values < 5 apoSAA equivalent units were considered negative. 13 mice expressed an apoSAA1 and apoSAA2 doublet characteristic of CBA/J mice, whereas 17 mice, expressed the apoSAACE/J isoform codominantly with apoSAA1 and apoSAA2. The correlation of amyloid resistance to expression of the apoSAACE/J isoform was absolute (17/17 were negative; mean score 2.6 +/- 0.17 [standard error of the mean] apoSAA equivalent units) and the correlation between amyloid susceptibility and the expression of apoSAA2/apoSAA1 was also striking (12/13 were amyloid positive; mean score 47.9 +/- 9.0 [standard error of the mean] apoSAA equivalent units (P < 0.001). This is not significantly different from the 50% segregation of apoSAA phenotypes expected for linkage to a single gene. These results indicate that a single gene governs apoSAACE/J expression and thus confers protection against amyloid deposition even in the presence of apoSAA1 and apoSAA2 isoforms and show for the first time that resistance to AA amyloidosis is a dominant trait governed by a single gene.


Cognitively-Based Compassion Training versus cancer health education to improve health-related quality of life in survivors of solid tumor cancers and their informal caregivers: study protocol for a randomized controlled pilot trial.
Cancer survivors and their informal caregivers (family members, close friends) often experience significant impairments in health-related quality of life (HRQOL), including disruptions in psychological, physical, social, and spiritual well-being both during and after primary cancer treatment. The purpose of this in-progress pilot trial is to determine acceptability and preliminary efficacy (as reflected by effect sizes) of CBCT® (Cognitively-Based Compassion Training) compared with a cancer health education (CHE) attention control to improve the primary outcome of depressive symptoms and secondary outcomes of other HRQOL domains (e.g., anxiety, fatigue), biomarkers of inflammation and diurnal cortisol rhythm, and healthcare utilization-related outcomes in both cancer survivors and informal caregivers. Forty dyads consisting of solid tumor survivors who have completed primary treatments (chemotherapy, radiation, surgery) and their informal caregivers, with at least one dyad member with ≥ mild depressive symptoms or anxiety, will be recruited from Tucson, Arizona, USA. Survivor-caregiver dyads will be randomized together to complete either CBCT or CHE. CBCT is a manualized, 8-week, group meditation-based intervention that starts with attention and mindfulness and builds to contemplative practices aimed at cultivating compassion to the self and others. The goal of CBCT is to challenge unexamined assumptions about feelings and behaviors, with a focus on generating spontaneous self-compassion and increased empathic responsiveness and compassion for others. CHE is an 8-week, manualized group intervention that provides cancer-specific education on various topics (e.g., cancer advocacy, survivorship wellness). Patient-reported HRQOL outcomes will be assessed before, immediately after (week 9), and 1 month after CBCT or CHE (week 13). At the same time points, stress-related biomarkers of inflammation (e.g., plasma interleukin-6) and saliva cortisol relevant for survivor and informal caregiver wellness and healthcare utilization will be measured. If CBCT shows acceptability, a larger trial will be warranted and appropriately powered to formally test the efficacy of this dyadic intervention. Interventions such as CBCT directed toward both survivors and caregivers may eventually fill a gap in supportive oncology care programs to improve HRQOL and healthcare utilization in both dyad members. Clinicaltrials.gov, NCT03459781 . Prospectively registered on 9 March 2018.


Tailoring shear-stiff, mica-like nanoplatelets.
This work introduces a novel facile method to produce shear-stiff, mica-like nanoplatelets by efficient exfoliation. The essence of this procedure is the nonreversible alteration of the interlamellar reactivity of a synthetic fluorohectorite by simple cation exchange. The possibility of switching from highly hydrated to collapsed interlayers permits a highly efficient exfoliation in the swollen state while providing shear-stiffness in the collapsed state. This method restricts cation exchange in the mica-like nanoplatelets to the outer surfaces, which represents a significant advantage for use in nanocomposites as compared to conventional organoclays which contain up to 40%/wt of organocations. It is expected that this new type of rigid, shear-stiff, clay-based nanoplatelets will be superior for reinforcement when used in composite materials like polymer layered silicate nanocomposites or artificial nacre.


Computing the Local Field Potential (LFP) from Integrate-and-Fire Network Models.
Leaky integrate-and-fire (LIF) network models are commonly used to study how the spiking dynamics of neural networks changes with stimuli, tasks or dynamic network states. However, neurophysiological studies in vivo often rather measure the mass activity of neuronal microcircuits with the local field potential (LFP). Given that LFPs are generated by spatially separated currents across the neuronal membrane, they cannot be computed directly from quantities defined in models of point-like LIF neurons. Here, we explore the best approximation for predicting the LFP based on standard output from point-neuron LIF networks. To search for this best "LFP proxy", we compared LFP predictions from candidate proxies based on LIF network output (e.g, firing rates, membrane potentials, synaptic currents) with "ground-truth" LFP obtained when the LIF network synaptic input currents were injected into an analogous three-dimensional (3D) network model of multi-compartmental neurons with realistic morphology, spatial distributions of somata and synapses. We found that a specific fixed linear combination of the LIF synaptic currents provided an accurate LFP proxy, accounting for most of the variance of the LFP time course observed in the 3D network for all recording locations. This proxy performed well over a broad set of conditions, including substantial variations of the neuronal morphologies. Our results provide a simple formula for estimating the time course of the LFP from LIF network simulations in cases where a single pyramidal population dominates the LFP generation, and thereby facilitate quantitative comparison between computational models and experimental LFP recordings in vivo.


Complementary foods in Jamaica: viscosity, energy density and feeding practices.
To develop and validate a field method for measuring the viscosity of small quantities of weaning porridges, to measure the viscosity and energy density of porridges fed in urban and rural environments, and to relate the findings to ingredients used and feeding practices. A new method for determining the viscosity of homogeneous, semi-solid weaning foods was developed. The viscosity and energy density of porridges fed to young children were measured, ingredients obtained by recall, and caregiver feeding behaviours observed. One urban and one rural community in Jamaica. A purposive random sample of 70 children aged 3 to 14 months. Most children (80%) were fed porridges with medium viscosity (1700-2900 mPa s) or thicker. The mean energy density was 3.18 +/- 0.92 kJ g(-1). Energy density was only moderately related to viscosity, being higher only in porridges > 4000 mPa s (analysis of variance (ANOVA), P < 0.05). Energy density was correlated (P < 0.05) with the amounts of sugar (r = 0.28) and milk powder (r = 0.24) used. Viscosity and energy density were lower in porridges fed by bottle than in those fed by spoon. Anthropometric status (weight-for-length and weight-for-age) was positively correlated with energy density of the porridge but not to the encouragement or persistence of the caregiver. Porridges of adequate energy density were prepared by caregivers in Jamaica without raising viscosity to levels that might constrain intakes. Improvements in porridge preparation and more varied weaning diets may have contributed to the decline in undernutrition in Jamaica.


Surgical repair of aorto-ventricular tunnel.
This report presents a trans-aortic trans-infundibular double-patch repair of an aorto-left ventricular tunnel in a 17-day old male child. It reviews the literature on aorto-ventricular tunnels and debates strategic and surgical options available to correct these defects. Diagnosis of the tunnel in the case described herein was made prenatally. The child was presented with left ventricular dilatation with early and progressive signs of congestive heart failure. Decision for early surgical correction was made considering the quantum of regurgitant jet, diastolic backflow in the aorta and consequent left ventricular dilatation. After establishing cardiopulmonary bypass and arresting the heart, the aorta was transversely opened above the sinotubular junction and the tunnel identified. Aortic valve morphology and the coronary ostia not involved in the tunnel were carefully investigated. Through a transverse infundibulotomy, the thinned outer wall of the tunnel abutting the posterior wall of the infundibular septum was slit open vertically, thus clearly defining the aortic and the left ventricular orifices. The distal tunnel orifice, now presenting as a subaortic Ventricular septal defect (VSD), was closed using a xenopericardial patch and running polypropylene 7-0 stitches. The aortic end of the tunnel was closed in a similar fashion through the aortotomy, remaining clear of the right coronary artery and respecting the aortic valve geometry. The marsupialized wall of the tunnel as seen through the infundibulotomy was sutured with polypropylene stitches. The aortotomy and right ventriculotomy were closed. The postoperative course was uneventful. A follow-up echocardiography at 2 years showed a perfect outcome with no residual tunnel, no aortic stenosis and trivial aortic regurgitation.


Critical Incident Techniques and Reflection in Nursing and Health Professions Education: Systematic Narrative Review.
The terms critical incident technique and reflection are widely used but often not fully explained, resulting in ambiguity. The aims of this review were to map and describe existing approaches to recording or using critical incidents and reflection in nursing and health professions literature over the last decade; identify challenges, facilitating factors, strengths, and weaknesses; and discuss relevance for nursing education. A systematic narrative review was undertaken. MEDLINE and the Cumulative Index to Nursing and Allied Health Literature were searched using MeSH terms, returning 223 articles (2006-2017). After exclusions, 41 were reviewed. Articles were categorized into 3 areas: descriptions of the development of an original tool or model, critical incidents or reflection on events used as a learning tool, and personal reflections on critical incidents. Benefits have been identified in all areas. More attention is needed to the pedagogy of reflection and the role of educators in reflection.


In vitro comparison of the new in-line monitor BMU 40 versus a conventional laboratory analyzer.
Reliable information about different blood parameters is essential in maintaining hemodynamics, perfusion, and gas exchange during cardiopulmonary bypass (CPB). For this purpose, a precise and continuous monitoring is needed. The objective of this in vitro study was to compare a novel continuous in-line blood parameter monitoring system versus a reference laboratory analyzer. The study was conducted as an in vitro prospective experimental study during a CPB simulation. The reliability of BMU 40 was tested in monitoring the pO2, oxygen saturation (SO2), and hematocrit (Hct) under physiological and extreme conditions with regards to temperature, oxygenation, and blood concentration. Four different tests were performed and conducted with five sensors each. Correlation analyses and Bland-Altman analyses were performed. A total of 350 measurement points were compared. All monitored values of blood parameters correlated highly with laboratory values (all r values >.90). Test 1: Biases of pO2 (act) varied from -3.24 mmHg (+/- 6.86 mmHg) up to 6.0 mmHg (+/- 17.89 mmHg). The biases of pO2 (37 degrees C) ranged from -3.52 mmHg (+/- 6.01 mmHg) up to 68.8 mmHg (+/- 67.82 mmHg). Test 2: The biases standard deviations (SD) for Hct ranged from -0.35% (+/- .79%) up to 2.35% (+/- .91%). The biases (SD) for SO2 varied from -.45% (+/- .86%) up to .85% (+/- 1.01%). Test 3: The biases (SD) of Hct ranged from -1.00% (+/- 1.84%) up to -.67% (+/- 1.49%). Test 4: The biases (SD) for SO2 varied from -.36% (+/- 1.60%) up to .48% (+/- .90%).The BMU 40 is a reliable device in measuring the partial oxygen pressure (pO2), SO2, and Hct under normal physiological and extreme conditions with regards to temperature, oxygenation, and blood concentration in simulation of CPB. The algorithm to calculate pO2 (37 degrees C) under hypothermic conditions needs to be adjusted. (Before the official market launch a new software version of the BMU 40 has been developed. The algorithm to calculate pO2 (37 degrees C) under hypothermic conditions has been improved and the miscalculation eliminated.)


Photonic-crystal-based cloaking device at optical wavelengths.
We present a photonic crystal cloaking device at optical wavelengths based on the association of two lattices working in different regimes, namely, stop band and negative refraction. The idea is to reconstruct in phase an incident cut Gaussian modulated plane wave by using the photonic crystal dispersion properties to ensure that no light penetrates in the core of the device. It is believed that such a cloaking device could become a building block for future generations of 3D integrated optical circuits.