Translation and validation of the Comfort Behaviors Checklist in hospitalized children with chronic diseases.
Different tools have been developed to measure patients' comfort. This study aims to translate, validate, and apply the Comfort Behaviors Checklist to hospitalized children with chronic diseases. Validity and reliability are assessed using face and content validity, construct validity (known-groups technique and Principal Component Analysis), internal consistency, and inter-rater reliability. The study takes place in a children's hospital in Iran, involving 220 children aged 4 to 6. The Comfort Behaviors Checklist demonstrates acceptable face and content validity. Construct validity is supported by the lack of correlation between behavioral comfort scores in known groups. The Principal Component analysis results in five components, explaining 70.39% of the total variation. The checklist exhibits acceptable reliability, with a total Cronbach's alpha coefficient of 0.86 and an intraclass correlation coefficient of 0.835. The Comfort Behavior Checklist is a valid and reliable tool for assessing the level of comfort in Iranian children with chronic diseases.


No change in health behavior, BMI or self-rated health after a psychosocial cancer rehabilitation: Results of a randomized trial.
The aim of cancer rehabilitation is to enable patients to attain and maintain optimal physical, psychological and social functioning. We evaluated the effect on health behavior, BMI and self-rated health of a residential psychosocial rehabilitation course for cancer patients. Patients with a primary cancer of the breast, prostate, colon or rectum were randomized to either a six-day multi-focus psychosocial residential rehabilitation intervention that included lectures, discussions and peer group discussions on issues related to treatment and life with cancer or to usual care. The end points were changes in smoking, alcohol consumption, physical activity, body mass index and self-rated health between baseline and follow-up after one and six months. The primary analyses included all participants who received their allocated condition. The two follow-up times were analyzed separately in general linear and logistic regression models for continuous and dichotomous outcomes, respectively. The analyses were adjusted for baseline outcome score, cancer site, time since diagnosis, age and education. Of the 507 participants who were randomly assigned, 452 were included in the analysis, of whom 404 completed the one month and 394 completed the six month assessment. The intervention group showed slightly more positive changes in health behavior, BMI and self-rated health than the usual care group, but the differences between the groups were small and not significant. Participation in a six-day cancer rehabilitation course did not significantly influence health behavior, BMI or self-rated health among cancer patients.


Lower baseline autoantibody levels are associated with immune-related adverse events from immune checkpoint inhibition.
Immune checkpoint inhibitors (ICI) are a novel cancer therapeutic that have been successful in treating advanced malignancies; however, they also cause immune-related adverse events (irAE). Given that some irAE are clinically similar to traditional autoimmune diseases, autoantibodies have been suggested as possible biomarkers of irAE. However, there are very little data on autoantibody investigation prior to ICI. Our aim was to determine if specific baseline autoantibodies were associated with irAE and see if changes in autoantibody concentration corresponded with irAE development. This study used data from an oncologic clinical trial of adaptive dosing combination ICI therapy in patients with advanced melanoma. Plasma was collected at baseline and 6 weeks after ICI initiation and tested in a microarray of 120 autoantigens commonly associated with autoimmune disease, as well as antinuclear antibody (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibody (anti-CCP). Autoantibody concentrations were compared between patients experiencing an organ-specific event versus not. Heatmaps, volcano plots and hierarchical clustering were used to determine autoantibody concentration differences among irAE patient clusters as defined by signal intensity of autoantibodies. Kaplan-Meier curves were created and a log-rank test was performed to assess differences in survival. The microarray analysis demonstrated that patients who experienced specific irAE had fewer differentially expressed autoantibodies at baseline than those that did not have those specific irAE, and a greater fold change (FC) in antibody concentration from baseline to 6 weeks corresponded with specific irAE development. However, no autoantibodies were identified as being predictive of specific events. Time to first irAE was less than 6 weeks in 69% of patients, and these patients had less autoantibodies at baseline. Considering ANA, RF and CCP autoantibodies, there were no significant differences between the seropositive and seronegative patients in irAE development, severity, timing or survival. Patients with low autoantibody concentrations at baseline as well as a greater FC in autoantibody concentration over 6 weeks developed more distinct organ-specific irAE. This may suggest differences in the balance of cellular immunity and humoral pathways that are relevant in the pathogenesis of irAE, though further investigation is needed.


"Why Aren't You Breastfeeding?": How Mothers Living With HIV Talk About Infant Feeding in a "Breast Is Best" World.
Infant feeding raises unique concerns for mothers living with HIV in Canada, where they are recommended to avoid breastfeeding yet live in a social context of "breast is best." In narrative interviews with HIV-positive mothers from Ontario, Canada, a range of feelings regarding not breastfeeding was expressed, balancing feelings of loss and self-blame with the view of responsibility and "good mothering" under the current Canadian guidelines. Acknowledging responsibility to put their child's health first, participants revealed that their choices were influenced by variations in social and cultural norms, messaging, and guidelines regarding breastfeeding across geographical contexts. This qualitative study raises key questions about the impact of breastfeeding messaging and guidelines for HIV-positive women in Canada.


Models to crack the code of organ regeneration.
In recent years, there has been a growing, widespread interest in tissue regeneration, with all its medical and social implications, such as, for example, the recovery from illness and wellbeing of humans. Yet, some of the most noticeable features of regeneration were discovered using a purely biological perspective with experimental biology on animal models. We are proud to introduce this Special Issue of The International Journal of Developmental Biology (Int. J. Dev. Biol.) on Regeneration Biology, which is devoted to the different animal models currently used to study regeneration. We also have tailored this Special Issue to include the different achievements that are today the state-of-the art in tissue and organ regeneration. The animal model perspective allows us to identify common and specific traits, summarize the most relevant advances, establish knowledge for the new "kids-on-the-block" and provide a framework to explore the open questions that researchers in the field are pursuing.


Stochastic disturbance regimes alter patterns of ecosystem variability and recovery.
Altered ecosystem variability is an important ecological response to disturbance yet understanding of how various attributes of disturbance regimes affect ecosystem variability is limited. To improve the framework for understanding the disturbance regime attributes that affect ecosystem variability, we examine how the introduction of stochasticity to disturbance parameters (frequency, severity and extent) alters simulated recovery when compared to deterministic outcomes from a spatially explicit simulation model. We also examine the agreement between results from empirical studies and deterministic and stochastic configurations of the model. We find that stochasticity in disturbance frequency and spatial extent leads to the greatest increase in the variance of simulated dynamics, although stochastic severity also contributes to departures from the deterministic case. The incorporation of stochasticity in disturbance attributes improves agreement between empirical and simulated responses, with 71% of empirical responses correctly classified by stochastic configurations of the model as compared to 47% using the purely deterministic model. By comparison, only 2% of empirical responses were correctly classified by the deterministic model and misclassified by stochastic configurations of the model. These results indicate that stochasticity in the attributes of a disturbance regime alters the patterns and classification of ecosystem variability, suggesting altered recovery dynamics. Incorporating stochastic disturbance processes into models may thus be critical for anticipating the ecological resilience of ecosystems.


Addition, deletion, and substitution of long nonhomologous deoxyribonucleic acid segments by genetic transformation of Haemophilus influenzae.
A complete EcoRI digest of Haemophilus influenzae phage HP1 deoxyribonucleic acid (DNA) was mixed with incomplete digests of various H. influenzae R plasmids, sealed with T4 ligase, and transformed into an HP1 lysogen. Most of the chloramphenicol- and tetracycline-resistant transformants did not produce phage although they possessed all the phage genes examined. They also did not transfer antibiotic resistance by conjugation. DNA lysates from them transformed other lysogens to resistance and to loss of phage production at different but quite high frequencies (addition of long DNA segments). They themselves could be transformed efficiently to strains with a wild prophage (deletion of long DNA segments). It was concluded that lysogenic cultures had been constructed with various DNA inserts in their prophages carrying antibiotic resistance genes from the R plasmids. The site of insertion was determined by genetic crosses. DNAs with inserts that transferred with lower efficiency were more sensitive to ultraviolet radiation. This supports the view that insert transfer efficiencies reflect the sizes of the insert.


Pimecrolimus -- an anti-inflammatory drug targeting the skin.
Pimecrolimus is the most recent member of calcineurin inhibitors available for the therapy for inflammatory skin diseases. It targets T-cells and mast cells and inhibits the production and release of cytokines and other inflammatory mediators, as well as the expression of signals essential for the activation of inflammatory T-lymphocytes. Pimecrolimus has a cell-selective mode of action. In contrast to corticosteroids, it does not affect, e.g., Langerhans'cells/dendritic cells (LC/DC), as demonstrated in vitro with human monocyte-derived DC and in vivo with epidermal LC in mice, nor human primary fibroblasts. As shown in vitro with human skin and by comparison of clinical pharmacokinetic data from patients with atopic dermatitis, pimecrolimus permeates less through skin than tacrolimus and much less than corticosteroids. It, thus, has a lower potential for transcutaneous resorption after topical administration, resulting in a lower risk of systemic effects. Pimecrolimus has high anti-inflammatory activity in animal models of skin inflammation, including a model reflecting neurogenic inflammation, but a more favourable balance of anti-inflammatory vs. immunosuppressive activity than tacrolimus. Pimecrolimus does not affect sensitization in a murine model of allergic contact dermatitis and has a lower potency in various models of immunosuppression after systemic administration, compared to tacrolimus. In conclusion, the results of preclinical studies show that pimecrolimus has a selective pharmacological profile, suited for effective and safe treatment for inflammatory skin diseases.


Endothelial L-selectin ligands in sinus mucosa during chronic maxillary rhinosinusitis.
Chronic rhinosinusitis is characterized by persistent inflammation of the nasal and paranasal mucosa with numerous emigrated leukocytes. L-selectin on leukocytes and its endothelial glycosylated ligands initiate organ-specific leukocyte infiltration into inflamed tissues. The purpose of this study was to evaluate the endothelial expression of functionally active endothelial L-selectin ligands, sulfated sialyl Lewis x, in maxillary sinus mucosa from patients with chronic rhinosinusitis and from normal control subjects. Maxillary sinus mucosa specimens (116) were obtained surgically and immunohistochemically stained with monoclonal antibodies detecting sialyl Lewis x or sulfated extended core 1 lactosamines. The severity of the inflammation was determined by intraoperative endoscopic findings, computed tomography scans, and histopathologic assessment of the specimens. The percentage of vessels expressing endothelial sulfated sialyl Lewis x epitopes increased during chronic rhinosinusitis compared with uninflamed control tissue, especially in patients with additional allergic rhinitis, and decreased in specimens from aspirin-intolerant patients with preoperative oral corticosteroid treatment. In addition, the expression level of endothelial sulfated sialyl Lewis x epitopes and the number of mucosal eosinophils correlated with the severity of the inflammation, and decreased in specimens taken 9 months postoperatively compared with intraoperative samples, especially in patients with intranasal corticosteroid treatment. Our results suggest that functionally active L-selectin ligands might guide leukocyte traffic into maxillary sinus mucosa preferentially in patients with severe findings of chronic maxillary rhinosinusitis, thus leading to aggravation of the inflammation.


New tetrahydroisoquinoline-based P-glycoprotein modulators: decoration of the biphenyl core gives selective ligands.
P-glycoprotein (P-gp, MDR1) is a membrane transporter expressed in several regions of our body. It plays a crucial defense role as it mediates the efflux of hundreds of potentially toxic substances. However, P-gp is one of the main causes of failure in cancer chemotherapy, as a number of chemotherapeutic agents are P-gp substrates. Another interesting implication concerns the correlation between P-gp expression impairment and the onset of several central nervous system pathologies such as Alzheimer's and Parkinson's diseases. In view of these considerations, in the present study, a new series of P-gp modulators have been designed, synthesized and evaluated for their activity towards P-gp and two other sister proteins (BCRP and MRP1). The compounds, structurally correlated to the potent but non-selective P-gp inhibitor MC70 [4'-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-ylmethyl)biphenyl-4-ol], proved fairly selective towards P-gp, with a potency in the micromolar range. Compounds 5a, 5d and 12d proved capable of restoring doxorubicin toxicity in resistant cancer cells.


Evidence that Dot-dependent and -independent factors isolate the Legionella pneumophila phagosome from the endocytic network in mouse macrophages.
Legionella pneumophila survives within macrophages by evading phagosome-lysosome fusion. To determine whether L. pneumophila resides in an intermediate endosomal compartment or is isolated from the endosomal pathway and to investigate what bacterial factors contribute to establishment of its vacuole, we applied a series of fluorescence microscopy assays. The majority of vacuoles, aged 2.5 min to 4 h containing post-exponential phase (PE) L. pneumophila, appeared to be separate from the endosomal pathway, as judged by the absence of transferrin receptor, LAMP-1, cathepsin D and each of four fluorescent probes used to label the endocytic pathway either before or after infection. In contrast, more than 70% of phagosomes that contained Escherichia coli, polystyrene beads, or exponential phase (E) L. pneumophila matured to phagolysosomes, as judged by co-localization with LAMP-1, cathepsin D and fluorescent endosomal probes. Surprisingly, neither bacterial viability nor the putative Dot/Icm transport complex was absolutely required for vacuole isolation; although phagosomes containing either formalin-killed PE wild-type or live PE dotA or dotB mutant L. pneumophila rapidly accumulated LAMP-1, less than 20% acquired lysosomal cathepsin D or fluorescent endosomal probes. Therefore, a Dot-dependent factor(s) isolates the L. pneumophila phagosome from a LAMP-1-containing compartment, and a formalin-resistant Dot-independent activity inhibits vacuolar accumulation of endocytosed material and delivery to the degradative lysosomes.


Proteolysis of recombinant proteins in bioengineered plant cells.
Plants are increasingly used as alternative expression hosts for the production of recombinant proteins offering many advantages including higher biomass and the ability to perform post-translational modifications on complex proteins. Key challenges for optimized accumulation of recombinant proteins in a plant system still remain, including endogenous plant proteolytic activity, which may severely compromise recombinant protein stability. Several strategies have recently been applied to improve protein stability by limiting protease action such as recombinant protein production in various sub-cellular compartments or application of protease inhibitors to limit protease action. A short update on the current strategies applied is provided here, with particular focus on sub-cellular sites previously selected for recombinant protein production and the co-expression of protease inhibitors to limit protease activity.


Motion analysis in the hemicochlea.
Optical flow techniques are often used to estimate velocity fields to represent motion in successive video images. Usually the method is mathematically ill-posed, because the single scalar equation representing the conservation of local intensity contains more than one unknown velocity component. Instead of regularizing the problem using optimization techniques, we formulate a well-posed problem for the gerbil hemicochlea preparation by introducing an in-plane incompressibility constraint, and then show that local brightness is also conserved. We solve the resulting system using a Lagrangian description of the conservation equations. With this approach, the displacement of isointensity contours on sequential images determines the normal component of velocity of an area element, while the tangential component is computed from the local constant area constraint. We have validated our method using pairs of images generated from our calculations of the vibrational deformation in a cross section of the organ of Corti and tectorial membrane in the mammalian cochlea, and quantified the superior performance of our method when complex artificial motion is applied to a noisy image obtained from the hemicochlea preparation. The micromechanics of the organ of Corti and the tectorial membrane is then analyzed by our new method.


Infrared scanning images: an archeological application.
Aerial infrared scanner images of an area near the Little Colorado River in north-central Arizona disclosed the existence of scattered clusters of parallel linear features in the ashfall area of Sunset Crater. The features are not obvious in conventional aerial photographs, and only one cluster could be recognized on the ground. Soil and pollen analyses reveal that they are prehistoric agricultural plots.


Cholescintigraphy in the diagnosis of intrahepatic cholestasis. How specific is it?
Previous results from tests on a limited number of patients suggested that the combination of relatively normal hepatocyte clearance, prolonged parenchymal transit time, and eventual passage of radiotracer into the intestine or gallbladder without evidence of biliary tract dilatation were relatively specific for intrahepatic cholestasis. We reevaluated the specificity of cholescintigraphy for the diagnosis of intrahepatic cholestasis in an unselected group of patients from a general hospital. Sixteen patients had the cholescintigraphic findings of intrahepatic cholestasis and an established diagnosis of biliary tract dilatation or nondilatation by ultrasound, ERCP, or intraoperative cholangiography. Using 6 mm as the upper limits of normal for the diameter of the common hepatic duct by ultrasonography resulted in a specificity of 63% (10 correct out of 16); using 6 mm plus 1 mm for for every decade over 60 years of age gave a specificity of 75% (12 correct out of 16); and using the more liberal criterion of 8 mm as the upper limits of normal increased the specificity to 81% (13 out of 16). The data suggest that cholescintigraphy alone is unreliable in differentiating intrahepatic cholestasis from extrahepatic obstruction, even when the obstruction is partial and radiotracer eventually passes through the extrahepatic biliary tract.


Thin-walled cysts as a pathognomonic CT finding in cystic mesothelioma.
Cystic mesothelioma is a rare disease that results in abdominal distention and poorly defined abdominal pain. Diagnosis has always been made by tissue biopsy rather than by radiologic studies. Our experience with 7 patients with cystic mesothelioma includes 4 patients who had not had prior surgery before the performance of a high resolution CT scan. A special review of the radiology of these cases was performed in order to identify any pathognomonic signs of this disease. In all patients who did not have a distortion of the radiologic images (as a result of surgical interventions) prior to the performance of a high resolution CT scan at our institution, a pathognomonic thin-wall cystic structure located within the gelatinous appearing mass was observed. These thin-walled cysts were of variable size and preferentially located within the greater omentum, pelvis and beneath the right hemidiaphragm. Cystic mesothelioma can be diagnosed preoperatively by a high resolution abdominal and pelvic CT. The thin-walled cysts with great variation in size are located beneath the right hemidiaphragm, within the greater omentum and in the pelvis. No other disease with these radiologic findings has been identified.


Diet and esophageal cancer risk in the Eastern Cape Province of South Africa.
A multicenter hospital-based case-control study comprising 670 incident cases of esophageal cancer (EC) and 1188 controls, frequency-matched for age and sex, was conducted to evaluate the role of diet on EC development in the Eastern Cape Province, South Africa. A locally relevant lifestyle and dietary questionnaire was used. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional multivariable logistic regression. Individually, maize or sorghum consumption vs. never or rare consumption were not associated with EC (P > 0.1). Males and females consuming green leafy vegetables 5-7 days/wk had 38% (P = 0.04) and 50% (P = 0.007) reduced odds of developing EC, respectively, compared with consumption ≤1 day/wk. A similar reduction in odds was observed with fruit consumption. Principal component factor analysis revealed 3 distinct dietary patterns. In females, high vs. low consumption of Pattern 1 (sorghum, green leafy vegetables, green legumes, fruits, meat) was inversely associated with EC development (OR = 0.54; 95% CI: 0.34-0.89), whereas for Pattern 2 (maize, wild greens-imifino, dry beans) the odds were elevated (OR = 1.67; 95% CI: 1.04-2.67). Compared with low adherence, high adherence to Pattern 3 (wheat-based products) reduced the odds by 35% for both sexes. This study provides further evidence on the role of diet in minimizing EC risk in this population.


A comparison of adherence by four strains of Staphylococcus intermedius and Staphylococcus hominis to canine corneocytes collected from normal dogs and dogs suffering from atopic dermatitis.
The aim of this study was to compare the adherence of four strains of Staphylococcus intermedius and a single strain of Staphylococcus hominis to corneocytes from both normal dogs and dogs suffering from atopic dermatitis. Cells from the skin surface, corneocytes, were collected from 10 normal dogs and 10 dogs suffering from atopic dermatitis. Four strains of S. intermedius, three isolated from canine pyoderma skin lesions (strains A, B and C), and one isolated form from canine synovial membrane sample from a case of septic arthritis (strain D) were compared. S. hominis, which is not normally associated with canine disease, was also evaluated for its ability to adhere to canine corneocytes. S. hominis did not adhere to canine corneocytes. All four strains of S. intermedius adhered well to canine corneocytes collected from both normal and atopic dogs. All strains of S. intermedius showed statistically greater adherence to corneocytes collected from atopic dogs compared with those collected from normal dogs. It was concluded that the adherence assay employed here showed that S. hominis does not adhere to canine corneocytes, S. intermedius adheres preferentially to atopic corneocytes.


Associations between body mass index and height during childhood and adolescence and the risk of coronary heart disease in adulthood: A systematic review and meta-analysis.
Body mass index (BMI) at child and adolescent ages is positively associated with adult coronary heart disease (CHD) whereas height at these ages may be inversely associated with CHD. However, potential effects of age, sex, and socioeconomic status on associations between BMI and CHD are less investigated. We conducted a systematic review and meta-analysis of BMI and height at ages 2-19 years in relation to adult CHD and examined effects of age, sex, socioeconomic status, and other factors. Twenty-two studies on BMI and five on height were included, comprising 5,538,319 individuals and 69,830 CHD events. Random effects meta-analyses were conducted. Child and adolescent BMI were positively associated with CHD (hazard ratio = 1.12; 95% confidence interval [CI] [1.01, 1.25] per standard deviation [SD]), and categorical analyses supported these findings. The associations did not significantly differ by age, sex, or by adjustment for socioeconomic status. Child and adolescent height were inversely associated with CHD (hazard ratio = 0.87; 95% CI [0.81, 0.93] per SD), and categorical analyses agreed. Insufficient studies on height precluded subgroup analyses. Heterogeneity was generally high in all analyses. We found that BMI in youth is positively associated with adult CHD regardless of sex or adjustment for socioeconomic status whereas height is inversely associated with later risk of CHD.


Thermal inactivation and reactivation of an enzyme in vivo. Pantothenate hydrolase of Pseudomonas fluorescens.
Thermal inactivation and reactivation of pantothenate hydrolase were studied in whole cells of Pseudomonas fluorescens. The enzyme is susceptible to thermal inactivation in whole cells at 37-40 degrees C, and is reactivated when the temperature is lowered again. Chloramphenicol does not prevent reactivation. The activation energy of enzyme inactivation in vivo is about 540kJ/mol. This activation energy is 220kJ/mol in vitro, but it is increased to 550-630kJ/mol by several metabolites, such as succinate, glyoxylate and oxalate. Generally, good carbon sources, causing rapid growth, protect the enzyme from thermal inactivation in vivo, and enable reactivation to occur at a fast rate. The enzyme is also inactivated below 35 degrees C, showing an activation energy of about 35kJ/mol. Good carbon sources prevent this inactivation as well, and cause slight reactivation. Glycine, although not utilized for growth, protects the enzyme well from this inactivation but not from inactivation at 37-40 degrees C, and prevents reactivation totally. From the activation energies of inactivation and the effects of the various carbon sources, it appears possible that changes in the concentrations of intracellular metabolites may be responsible for the changes in inactivation and reactivation.


Alcohol interventions, alcohol policy and intimate partner violence: a systematic review.
Intimate partner violence (IPV) is a significant global public health issue. The consistent evidence that alcohol use by one or both partners contributes to the risk and severity of IPV suggests that interventions that reduce alcohol consumption may also reduce IPV. This study sought to review the evidence for effects on IPV of alcohol interventions at the population, community, relationship and individual levels using the World Health Organization ecological framework for violence. Eleven databases including Medline, PsycINFO, CINAHL and EMBASE were searched for English-language studies and grey literature published 1 January 1992 - 1 March 2013 investigating whether alcohol interventions/policies were associated with IPV reduction within adult (≥ 18) intimate relationships. Eleven studies meeting design criteria for attributing effects to the intervention and ten studies showing mediation of alcohol consumption were included in the review. The heterogeneity of study designs precluded quantitative meta analysis; therefore, a critical narrative approach was used. Population-level pricing and taxation studies found weak or no evidence for alcohol price changes influencing IPV. Studies of community-level policies or interventions (e.g., hours of sale, alcohol outlet density) showed weak evidence of an association with IPV. Couples-based and individual alcohol treatment studies found a relationship between reductions in alcohol consumption and reductions in IPV but their designs precluded attributing changes to treatment. Randomized controlled trials of combined alcohol and violence treatment programs found some positive effects of brief alcohol intervention as an adjunct to batterer treatment for hazardous drinking IPV perpetrators, and of brief interventions with non-dependent younger populations, but effects were often not sustained. Despite evidence associating problematic alcohol use with IPV, the potential for alcohol interventions to reduce IPV has not been adequately tested, possibly because studies have not focused on those most at risk of alcohol-related IPV. Research using rigorous designs should target young adult populations among whom IPV and drinking is highly prevalent. Combining alcohol and IPV intervention/policy approaches at the population, community, relationship and individual-level may provide the best opportunity for effective intervention.


beta-Adrenergic activity and cardiovascular response to severe respiratory acidosis.
The mechanism responsible for the depressive myocardial effects of severe respiratory acidosis is unclear; however, sympathetic stimulation and catecholamines are known to be involved. The influence of beta-adrenergic receptor activity on the myocardial response to severe respiratory acidosis was studied in 18 anesthetized, mechanically ventilated dogs. Arterial CO2 tension (PaCO2) was raised by increasing the inspired CO2 fraction in O2. In control animals, as PaCO2 increased, heart rate (HR) decreased (PaCO2 approximately 110 mmHg), then returned to control (PaCO2 approximately 220 mmHg), whereas arterial blood pressure (Pa) and cardiac output (Q) remained unchanged from prehypercapnia levels. At PaCO2 greater than 350 mmHg, Pa, HR, and Q decreased and left ventricular function (LVF) curves were depressed. Death occurred at a PaCO2 of 404 +/- 25 mmHg (pH 6.48 +/- 0.02). In a second group of animals, administration of isoproterenol during the increase in PaCO2 did not result in depression of myocardial function, and death did not occur even at a significantly higher PaCO2 (PaCO2 496 +/- 12 mmHg; pH 6.39 +/- 0.02) than in the control group. Administration of propranolol to a third group of animals as PaCO2 increased did not change Pa, HR, and Q; however, LVF curves indicated a more rapid and severe depression of myocardial performance than in control, and death occurred at a significantly lower PaCO2 (PaCO2 220 +/- 25 mmHg; pH 6.65 +/- 0.02). We conclude that beta-adrenergic receptor stimulation can prevent hypercapnic heart failure and that beta-adrenergic receptor activity is involved in the mechanism responsible for this failure.


Pulmonary artery banding in dilative cardiomyopathy of young children: review and protocol based on the current knowledge.
Dilated cardiomyopathy (DCM) is a leading cause of cardiac death in children. Current therapeutic strategies are focused on improving symptoms of congestive heart failure (CHF); the potentials of cardiac regeneration especially in infants and young children are neglected in particular when DCM is classified as "end-stage". Heart transplantation (HTx) serves as the only life-saving option, despite is palliative character with limited survival time. Therapeutic alternatives are strongly needed, but already existing though less used; presupposed, that cardiac dysfunction and its treatment are not reduced to the four components of heart rate (rhythm), myocardial contractility, preload and afterload. A paradigm shift in the treatment of pediatric heart failure can be achieved by modifying ventricular afterload with improving contra-lateral ventricular function. Adverse ventricular-ventricular interactions (VVI) have the potential to harness them for therapeutic benefit. Surgical placement of a pulmonary artery banding (PAB) utilized in infants and young children with LV-DCM and preserved RV function are able to improve LV function via VVI; it is hypothesized, that functional recovery can be achieved in almost 80% especially of infants with LV-DCM despite criteria for listing to orthotopic HTx. The review summarizes details of the current perioperative treatment enabling each pediatric heart center to utilize rPAB as a strategy for functional recovery, even in centers without the option for Htx. Of course, future studies are needed to delineate the geometrical, temporal and molecular mechanisms of PA-banding-induced ventricular crosstalk and to examine their potential modulation through mechanical, electrophysiological and pharmacological interventions, but our patients are born, now.


No exploitation of temporal sequence context during visual search.
The human visual system can rapidly extract regularities from our visual environment, generating predictive context. It has been shown that spatial predictive context can be used during visual search. We set out to see whether observers can additionally exploit temporal predictive context based on sequence order, using an extended version of a contextual cueing paradigm. Though we replicated the contextual cueing effect, repeating search scenes in a structured order versus a random order yielded no additional behavioural benefit. This was also true when we looked specifically at participants who revealed a sensitivity to spatial predictive context. We argue that spatial predictive context during visual search is more readily learned and subsequently exploited than temporal predictive context, potentially rendering the latter redundant. In conclusion, unlike spatial context, temporal context is not automatically extracted and used during visual search.


Deriving motion from megavoltage localization cone beam computed tomography scans.
Cone beam computed tomography (CBCT) projection data consist of views of a moving point (e.g. diaphragm apex). The point is selected in identification views of extreme motion (two inhale, two exhale). The room coordinates of the extreme points are determined by source-to-view ray tracing intersections. Projected to other views, these points become opposite corners of a motion-bounding box. The view coordinates of the point, relative to the box, are used to interpolate between extreme room coordinates. Along with the views' time stamps, this provides the point's room coordinates as a function of time. CBCT-derived trajectories of a tungsten pin, moving 3 cm cranio-caudally and 1 cm elsewhere, deviate from expected ones by at most 1.06 mm. When deviations from the ideal imaging geometry are considered, mean errors are less than 0.2 mm. While CBCT-derived cranio-caudal positions are insensitive to the choice of identification views, the bounding box determination requires view separations between 15 and 163 degrees . Inhale views with the two largest amplitudes should be used, though corrections can account for different amplitudes. The information could be used to calibrate motion surrogates, adaptively define phase triggers immediately before gated radiotherapy and provide phase and amplitude sorting for 4D CBCT.


Cost analysis of breast cancer: a comparison between private and public hospitals in Iran.
Breast cancer is the most prevalent cancer among women. Breast cancer imposes a considerable economic burden on the health system. This study aimed to compare the cost of breast cancer among patients who referred to private and public hospitals in Iran (2017). This was a prevalence-based cost of illness study. A total of 179 patients were selected from private and public hospitals using the census method. The researcher-constructed checklist was used for data collection. Data were analyzed using SPSS software version 22. The estimated total mean (SD) direct cost of patients who referred to the private hospital and the public hospital was $10,050 (19,480) and $3960 (6780), respectively. Further, the total mean indirect cost of patients who referred to the private hospital was lower than those referring to the public hospital at $1870 (15 % of total costs) and $22,350 (85 % of total costs), respectively. These differences were statistically significant (P < 0.05). Breast cancer imposes a substantial cost on patients, health insurance organizations and the whole society in Iran. Therefore, the adoption of effective measures for the prevention and early diagnosis of breast cancer is urgently needed.


The fatty acid content of the Bordetella pertussis endotoxin.
The fatty acid content of Bordetella pertussis endotoxin has been estimated by several methods. Expressed as 3-hydroxytetradecanoic acid, it was 0.74 mumol (mg lyophilized material)-1, 0.38 mumol being ester-bound, and 0.32 mumol in amide linkage. Reported molar ratios of ester-bound to amide-bound fatty acids in endotoxins of various bacterial species range from 2.4 to 2 in B. pertussis, to 5 to 2 in Salmonella minnesota; according to these figures large differences must exist in the degree of substitution, and the substitution pattern of the glucosaminyl-beta-1,6-glucosamine unit present in the hydrophobic region of endotoxins. When fatty acids, released by acid and alkaline hydrolyses of the B. pertussis endotoxin, were extracted into chloroform, unidentified chromogenic substances appearing in the extract interfered with their colorimetric estimation; no interference was observed when hexane was used instead of chloroform.


Chronic Stress and Latent Virus Reactivation: Effects on Immune Aging, Chronic Disease Morbidity, and Mortality.
Social stress has been shown to affect immune functioning. Past research has found that chronic social stress and latent viral infections accelerate immune aging, leading to chronic disease morbidity and mortality. Chronic stress may also reactivate latent viral infections, like cytomegalovirus (CMV), accelerating the aging of the immune system. Utilizing panel survey data from 8,995 U.S. adults aged 56 or older from the Health and Retirement Study, this study investigates whether chronic stress interacts with CMV positivity to drive aging of the immune system, multimorbidity, and mortality. Results of moderated mediation analysis indicate that the effect of CMV positivity on morbidity and mortality as mediated by immune aging indicators is amplified by chronic stress. These findings suggest that immune aging is a biological pathway underlying the stress process and help explain past findings in the literature on stress and health.


Characterizing Patients after Opioid Taper in a VA Medical Center.
To identify potential areas for intervention and gain insight on current practice in patients who are tapered to zero morphine equivalent daily doses (MEDD) through the Pharmacy Pain E-Consult at a Veterans Healthcare System. This was done by describing the types of follow-up care and resources utilized by patients. This project is a retrospective chart review of Veterans with non-cancer pain on chronic-opioid therapy consulted to the pharmacy e-consult service and tapered to 0 MEDD. Descriptive statistics are collected one year pre-taper and one year post-taper. One year post-taper, approximately one-third of the patients were re-started on opioid therapy. However, average MEDD overall was significantly decreased one year post-taper compared to pre-taper. Average pain scores were not significantly different pre-taper compared to post-taper. Non-opioid medications generally increased post-taper. Follow-up with mental health and pain management clinical pharmacy specialists decreased post-taper. Tapering to zero MEDD did not lead to a significant increase in pain one-year post-taper; however, approximately 33% of patients were re-started on opioids within one year post-taper. Average MEDD scores decreased post-taper as expected but with effects on mental health being largely unknown, we believe that further study in this area will help us better support patients.


Effect of Lactobacillus casei Shirota supplementation on trimethylamine-N-oxide levels in patients with metabolic syndrome: An open-label, randomized study.
Recent studies in animal models have shown a link between ingestion of dietary phosphatidylcholine (PC), choline, l-carnitine and cardiovascular risk. Intestinal microbiota-dependent metabolism of PC and l-carnitine is involved in formation of trimethylamine (TMA), which is further metabolized to the proatherogenic compound trimethylamine-N-oxide (TMAO). It has been suggested that changes in gut microbiota by supplementation of probiotic drinks might alter TMAO levels. Hence, the aim of this analysis was to investigate the impact of Lactobacillus casei Shirota (LcS) on formation of TMAO in subjects with metabolic syndrome. In a single-center, prospective, randomized-controlled study 30 subjects with metabolic syndrome were randomized to receive either 3 times daily 6.5 × 10(9) CFU (colony-forming units) LcS (probiotic group) or not (standard therapy group) for 12 weeks. TMAO plasma levels were quantified by means of liquid chromatography and tandem mass spectrometry. Thirteen patients in the probiotic group and 15 in the standard therapy group finished the study. Mean age was 52 ± 11 and 55 ± 9 years, respectively. TMAO levels decreased during the intervention period in both groups (from 4.66 ± 2.66 μM to 4.31 ± 2.04 μM in the probiotic group and from 4.64 ± 2.75 μM to 4.40 ± 2.14 μM in the control group). Changes in TMAO between subjects receiving LcS (-0.25 ± 2.39 μM) and controls (-0.34 ± 2.23 μM) were not significantly different (p = 0.510). In conclusion, intake of LcS for 12 weeks did not affect levels of TMAO in patients with metabolic syndrome.


[Applications of 3D printing in medicine; 5 years later].
5 years ago, we described the emergence of 3D printing in medicine. It was about 3D printing of anatomical structures, patient-specific drilling guides, cutting templates and implants and printing of living cells, growth factors and biomaterials ('bioprinting'). Surgeons are increasingly making use of 3D printing possibilities in preparation of surgeries on patients with complicated anatomies. Using tangible 3D models, it is easier for surgeons to prepare for surgeries and discussions with patients. They can also use 3D models as a tool to help with the training of young surgeons. Permanent titanium implants are increasingly being printed. Bioprinting is still in its infancy and there are no direct clinical applications yet. As we already predicted 5 years ago, many hurdles still have to be taken before broad clinical application of bioprinted products will become a reality.


[Dermatoglyphic studies in parents of children with Down's syndrome. I. Digital patterns].
Finger prints of 34 groups of parents with a child affected of Down's syndrome by regular trisomy were studied and then compared with 34 groups of parents with two or more normal children without family antecedents of genetic alterations. The separate study of the distribution of the pattern types in each of the fingers and the latter comparison of the two groups shows: Different distribution of the pattern types in the two groups. The groups of parents of children affected of Down's syndrome occupies an intermediate position between the group of parents of normal children and a group of subjects affected of Down's syndrome. The total sum of pattern types in each group were also compared using a table of contingency, indicating a difference (SD p less than 0.05) between both groups.


The planar cell polarity protein VANG-1/Vangl negatively regulates Wnt/β-catenin signaling through a Dvl dependent mechanism.
Van Gogh-like (Vangl) and Prickle (Pk) are core components of the non-canonical Wnt planar cell polarity pathway that controls epithelial polarity and cell migration. Studies in vertebrate model systems have suggested that Vangl and Pk may also inhibit signaling through the canonical Wnt/β-catenin pathway, but the functional significance of this potential cross-talk is unclear. In the nematode C. elegans, the Q neuroblasts and their descendants migrate in opposite directions along the anteroposterior body axis. The direction of these migrations is specified by Wnt signaling, with activation of canonical Wnt signaling driving posterior migration, and non-canonical Wnt signaling anterior migration. Here, we show that the Vangl ortholog VANG-1 influences the Wnt signaling response of the Q neuroblasts by negatively regulating canonical Wnt signaling. This inhibitory activity depends on a carboxy-terminal PDZ binding motif in VANG-1 and the Dishevelled ortholog MIG-5, but is independent of the Pk ortholog PRKL-1. Moreover, using Vangl1 and Vangl2 double mutant cells, we show that a similar mechanism acts in mammalian cells. We conclude that cross-talk between VANG-1/Vangl and the canonical Wnt pathway is an evolutionarily conserved mechanism that ensures robust specification of Wnt signaling responses.