Complex N-linked glycans serve as a determinant for exosome/microvesicle cargo recruitment.
Exosomes, also known as microvesicles (EMVs), are nano-sized membranous particles secreted from nearly all mammalian cell types. These nanoparticles play critical roles in many physiological processes including cell-cell signaling, immune activation, and suppression and are associated with disease states such as tumor progression. The biological functions of EMVs are highly dependent on their protein composition, which can dictate pathogenicity. Although some mechanisms have been proposed for the regulation of EMV protein trafficking, little attention has been paid to N-linked glycosylation as a potential sorting signal. Previous work from our laboratory found a conserved glycan signature for EMVs, which differed from that of the parent cell membranes, suggesting a potential role for glycosylation in EMV biogenesis. In this study, we further explore the role of glycosylation in EMV protein trafficking. We identify EMV glycoproteins and demonstrate alteration of their recruitment as a function of their glycosylation status upon pharmacological manipulation. Furthermore, we show that genetic manipulation of the glycosylation levels of a specific EMV glycoprotein, EWI-2, directly impacts its recruitment as a function of N-linked glycan sites. Taken together, our data provide strong evidence that N-linked glycosylation directs glycoprotein sorting into EMVs.


[The vocation of orthodontics].
For Angle, the goal of orthodontic treatment was to correct malocclusions. Then, the raison d'être seemed to be to restore normality as described through an increasing number of measurements and in seeking an average value. But 95.5% of variations were in fact normal and didn't need to be brought into a normal range. In addition, conforming to average dimensions was not an appealing goal for prospective patients. It is not divergence from the average that justifies treatment; it is instead the disturbances that these divergences engender. What are needed in the future are fewer measurements and more applications of clinical treatment. It is towards this route that the definitions of orthodontics and dento-facial orthopedics adopted by the SFODF direct us.


A novel method for finding non-small cell lung cancer diagnosis biomarkers.
One of the most common causes of worldwide cancer premature death is non-small cell lung carcinoma (NSCLC) with a very low survival rate of 8%-15%. Since patients with an early stage diagnosis can have up to four times the survival rate, discovering cost-effective biological markers that can be used to improve the diagnosis and prognosis of the disease is an important clinical challenge.In the last few years, significant progress has been made to address this challenge with identified biomarkers ranging from 5-gene signatures to 133-gene signatures. However, A typical molecular sub-classification method for lung carcinomas would have a low predictive accuracy of 68%-71% because datasets of gene-expression profiles typically have tens of thousands of genes for just few hundreds of patients. This type of datasets create many technical challenges impacting the accuracy of the diagnostic prediction. We discovered that a small set of nine gene-signatures (JAG1, MET, CDH5, ABCC3, DSP, ABCD3, PECAM1, MAPRE2 and PDF5) from the dataset of 12,600 gene-expression profiles of NSCLC acts like an inference basis for NSCLC lung carcinoma and hence can be used as genetic markers. This very small and previously unknown set of biological markers gives an almost perfect predictive accuracy (99.75%) for the diagnosis of the disease the sub-type of cancer. Furthermore, we present a novel method that finds genetic markers for sub-classification of NSCLC. We use generalized Lorenz curves and Gini ratios to overcome many challenges arose from datasets of gene-expression profiles. Our method discovers novel genetic changes that occur in lung tumors using gene-expression profiles. While proteins encoded by some of these gene-signatures (e.g., JAG1 and MAPRE2) have been showed to involve in the signal transduction of cells and proliferation control of normal cells, specific functions of proteins encoded by other gene-signatures have not yet been determined. Hence, this work opens new questions for structural and molecular biologists about the role of these gene-signatures for the disease.


Peripheral serum metabolomic profiles inform central cognitive impairment.
The incidence of Alzheimer's disease (AD) increases with age and is becoming a significant cause of worldwide morbidity and mortality. However, the metabolic perturbation behind the onset of AD remains unclear. In this study, we performed metabolite profiling in both brain (n = 109) and matching serum samples (n = 566) to identify differentially expressed metabolites and metabolic pathways associated with neuropathology and cognitive performance and to identify individuals at high risk of developing cognitive impairment. The abundances of 6 metabolites, glycolithocholate (GLCA), petroselinic acid, linoleic acid, myristic acid, palmitic acid, palmitoleic acid and the deoxycholate/cholate (DCA/CA) ratio, along with the dysregulation scores of 3 metabolic pathways, primary bile acid biosynthesis, fatty acid biosynthesis, and biosynthesis of unsaturated fatty acids showed significant differences across both brain and serum diagnostic groups (P-value < 0.05). Significant associations were observed between the levels of differential metabolites/pathways and cognitive performance, neurofibrillary tangles, and neuritic plaque burden. Metabolites abundances and personalized metabolic pathways scores were used to derive machine learning models, respectively, that could be used to differentiate cognitively impaired persons from those without cognitive impairment (median area under the receiver operating characteristic curve (AUC) = 0.772 for the metabolite level model; median AUC = 0.731 for the pathway level model). Utilizing these two models on the entire baseline control group, we identified those who experienced cognitive decline in the later years (AUC = 0.804, sensitivity = 0.722, specificity = 0.749 for the metabolite level model; AUC = 0.778, sensitivity = 0.633, specificity = 0.825 for the pathway level model) and demonstrated their pre-AD onset prediction potentials. Our study provides a proof-of-concept that it is possible to discriminate antecedent cognitive impairment in older adults before the onset of overt clinical symptoms using metabolomics. Our findings, if validated in future studies, could enable the earlier detection and intervention of cognitive impairment that may halt its progression.


Effect of terbutaline on peripheral lymph flow, protein concentration and transport, and edema formation after thermal injury in rabbits.
In the rabbit, intraarterial infusion of 5 micrograms/min of terbutaline within the first two hours after moderate thermal injury prevents edema and reduces augmented lymph flow, lymphatic protein transport, and tissue fluid protein concentration. Terbutaline, however, fails to prevent edema 4 hours after thermal injury although the increase of leg volume (24%) is less than in the untreated, burned control leg (56%). A higher dose of terbutaline (15 micrograms/min) also fails to block edema 4 hours after burning and its effect on leg volume, lymph flow, and lymphatic protein concentration is similar to that of 5 micrograms/min infusion. Terbutaline does not alter the extent of tissue injury after burning as the increase in tissue fluid lactic dehydrogenase and potassium are similar with "treated" and "untreated" burns.


Illusory movements induced by tendon vibration in right- and left-handed people.
Frequency-specific vibratory stimulation of peripheral tendons induces an illusion of limb movement that may be useful for restoring proprioceptive information in people with sensorimotor disability. This potential application may be limited by inter- and intra-subject variability in the susceptibility to such an illusion, which may depend on a variety of factors. To explore the influence of stimulation parameters and participants' handedness on the movement illusion, we vibrated the right and left tendon of the biceps brachii in a group of right- and left-handed people with five stimulation frequencies (from 40 to 120 Hz in step of 20 Hz). We found that all participants reported the expected illusion of elbow extension, especially after 40 and 60 Hz. Left-handers exhibited less variability in reporting the illusion compared to right-handers across the different stimulation frequencies. Moreover, the stimulation of the non-dominant arm elicited a more vivid illusion with faster onset relative to the stimulation of the dominant arm, an effect that was independent from participants' handedness. Overall, our data show that stimulation frequency, handedness and arm dominance influence the tendon vibration movement illusion. The results are discussed in reference to their relevance in linking motor awareness, improving current devices for motor ability recovery after brain or spinal damage and developing prosthetics and virtual embodiment systems.


Machine Learning Based Diagnosis of Vertigo using Video Head Impulse Test.
This work utilises the strength of state space based dynamic modelling and the ability of machine learning based segmentation of SRM standard descriptors to reach superior diagnostic capabilities. Dynamic modelling ensured vHIT input-output characteristics generated SRM standard descriptors, which were consequently used in formation of ML classification models.The best ML model was Linear SVM when built on left and right sided data with the SRM standard descriptors: rise time, settling time, settling minimum, settling maximum, overshoot and undershoot. The model was able to classify individuals to patient or control groups with an accuracy of 100% and a sensitivity and specificity of 1.Clinical Relevance- Dizziness is one of the most common presentations to family physicians and emergency departments. It is associated with significant medical complications such as falls as well as economic costs to both the individual and the community. Vestibular diseases comprise the bulk of dizzy disorders and are often associated with dysfunction of the vestibular or inner ear balance apparatus. This is most commonly the result of hypo-function of the semi-circular canals. Clinically, the most commonly employed objective test of semicircular function is the video Head Impulse Test (vHIT). Here we provide a machine learning approach to a more comprehensible and accurate interpretation of the results obtained by the vHIT to more robustly establish the presence and severity of VOR dysfunction, and ultimately aid in the diagnosis of vestibular disorders.


Depressive symptoms in Chinese family caregivers of patients with heart failure: A cross-sectional study.
Depressive symptoms are related to negative health outcomes in caregivers of patients with HF. Understanding the factors that are associated with depressive symptoms among caregivers is essential to providing appropriate interventions. Little is known about which status and factors are related to depressive symptoms among Chinese caregivers of patients with heart failure. This study aimed to investigate the status of depressive symptoms and to identify the factors that are associated with depressive symptoms in family caregivers of patients with heart failure in China.A cross-sectional design and a convenience sample were used. Participants (N = 134) from 1 hospital in Chengdu were recruited from June 2013 to June 2014. The following measurement tools were used in this study: Center for Epidemiologic Studies Depression Scale, Hospital Anxiety and Depression Scale, Coping Strategies Simplified Coping Style Questionnaire, and Zarit Burden Interview. A hierarchical multiple linear regression analysis was used to determine which factors were associated with depressive symptoms.The results showed that 31% of the caregivers experienced depressive symptoms. The type of payment for treatment (b = -0.312, P < 0.01), readmissions within the last 3 months (b = 0.397, P < 0.01), duration of caregiving (b = -0.213, P < 0.05), caregiver burden (b = 0.299, P < 0.05), active coping (b = -0.235, P < 0.01), and negative coping (b = 0.245, P < 0.05) were related to caregivers' depressive symptoms. Fifty-four percent of the variance in caregivers' depressive symptoms was explained by these factors.The caregiver depressive symptoms in China were higher than those reported in studies that were conducted in Western countries. Caregiver depressive symptoms can be improved by providing support for new caregivers (with a caregiving duration of less than 1 year), reducing readmissions, easing caregiver burden, and promoting their coping strategies.


Implementation of a competency assessment tool for agency nurses working in an acute paediatric setting.
This paper reports on the implementation of a competency assessment tool for registered general agency nurses working in an acute paediatric setting, using a change management framework. The increased number of registered general agency nurses working in an acute children's hospital alerted concerns around their competency in working with children. These concerns were initially raised via informal complaints about 'near misses', parental dissatisfaction, perceived competency weaknesses and rising cost associated with their use. [Young's (2009) Journal of Organisational Change, 22, 524-548] nine-stage change framework was used to guide the implementation of the competency assessment tool within a paediatric acute care setting. The ongoing success of the initiative, from a nurse manager's perspective, relies on structured communication with the agency provider before employing competent agency nurses. Sustainability of the change will depend on nurse managers' persistence in attending the concerns of those resisting the change while simultaneously supporting those championing the change. These key communication and supporting roles highlight the pivotal role held by nurse managers, as gate keepers, in safe-guarding children while in hospital. Leadership qualities of nurse managers will also be challenged in continuing to manage and drive the change where resistance might prevail.


Gynecologic and urodynamic evaluation of women with urinary incontinence.
One hundred women with urinary incontinence were evaluated at the urodynamic investigation unit. Sixty-seven percent of the patients in this series were found to have significant gynecologic disease underscoring the importance of simultaneous gynecologic and urologic investigation. Incontinence surgery was determined to be indicated in 44 of the 87 patients who had the symptom of stress urinary incontinence, suggesting that accurate evaluation of the lower urinary tract in women complaining of incontinence does allow a careful selection of patients for surgical therapy. Discussion is given regarding the determination of the amount of patient evaluation necessary before instituting therapy.


Fatigue of systemic lupus erythematosus in China: contributors and effects on the quality of life.
Fatigue is a very common symptom of systemic lupus erythematosus (SLE), which significantly impairs patients' quality of life. The purpose of this study is to evaluate contributors of fatigue and effects of fatigue on the quality of life in Chinese SLE patients. A survey of 119 SLE patients using the Fatigue Severity Scale (FSS) to assess the severity of fatigue was carried out. SLE patients completed the Systemic Lupus Erythematosus Disease Activity Index, the Hospital Anxiety and Depression Scale, the Short Form 36 health survey and the Pittsburgh Sleep Quality Index. Meanwhile, 105 healthy individuals completed FSS, the Hospital Anxiety and Depression Scale and Short Form 36 health survey. We used chi-squared analysis, independent samples t-tests and logistic regression models to analyze data. Our results found that the FSS score of patients with SLE was higher than that of healthy controls. The disease duration, anxiety, depression, subjective sleep quality and sleep disorders significantly correlated with fatigue in SLE patients. Moreover, logistic regression models showed depression and sleep disorders as predictors of fatigue. In SLE patients, fatigued patients had lower quality of life than those who were non-fatigued. This is the first time to explore contributors of fatigue and the influence of fatigue on SLE patients' quality of life in China. Our study showed that depression and sleep disorders were predictors of fatigue, and fatigue seriously damaged SLE patients' quality of life. The results indicate that it is necessary to conduct holistic assessment and effective intervention, such as systemic psychiatric screening, psychological care and practical sleep guidance, to relieve symptoms of fatigue and finally improve their quality of life in SLE patients.


Influence of isoflavones on cadmium-induced adverse effects in vascular endothelial cells (ECV 304).
To study the possible intervention of isoflavones in cytotoxicity induced by cadmium in vascular endothelial cells. An ECV 304 cell line derived from human umbilical vein endothelial cells was adopted. Genistein/daidzein was added prior to or simultaneously with CdCl2, cell viability was determined by MTT assay, and metallothionein mRNA expression was monitored by RT-PCR method. Cell viability was higher in isoflavone and CdCl2 co-treated groups than that in CdCl2 treated group, with CdCl2 concentration at 10, 20, 40, and 80 micromol/L, respectively. However this increase was not observed in the group treated with CdCl2 at a concentration of 60 micromol/L. Isoflavones (10(-10) mol/L to 10(-5) mol/L) were added 24 h before cells were challenged with 80 micromol/L CdCl2 for 24 h or simultaneously with 80 micromol/L CdCl2. Genistein increased cell viability only at 10(-5) mol/L, while daidzein caused a dose-dependent increase from 10(-10) mol/L to 10(-5) mol/L in co-treatment with CdCl2. In pre-treatment, genistein (10(-7) to 10(-5) mol/L) increased cell viability whereas only 10(-5) mol/L of daidzein exerted protection. Apparent protection could be found when the cells were pre-treated with 10(-5) mol/L isoflavones for over 12 h, whereas 24 h incubation was required in such a co-treatment, with the exception of daidzein that had a significant protection in only 3 h. Isoflavones (10(-6) mol/L) incubated for 3 h to 24 h, increased MT IIA and MT IF mRNA expression, but the induction could not last for more than 24 h. Co-treatment with isoflavones could induce an additional induction of MT IIA mRNA expression in cells exposed to cadmium. However, the additional induction of MT IIA and MT IF mRNA was not seen when pre-treatment was carried out with isoflavones, with the exception of an increase in MT IIA mRNA expression in the daidzein pre-treated group. Genistein/daidzein could reverse the cytotoxicity of cadmium either in pre-treatment or in co-treatment. The protection is the strongest in 10(-5) mol/L of isoflavones with a dose-dependent pattern. There are differences between genistein and daidzein in their protective effects. Whether the protection of isoflavones is related to their capacity of inducing MT mRNA expression remains to be elucidated.


Segregation of sex chromosomes in human lymphocytes.
Centromeric FISH was used to investigate the segregation of sex chromosomes in human lymphocytes. The aim of the study was to evaluate the effects of cell culture, cytokinesis block, age and sex on segregation and to compare the behaviour of the X and Y chromosomes. In uncultured T lymphocytes of five elderly women, the mean frequencies of nuclei hyperdiploid and hypodiploid for the X chromosome were not significantly affected by culturing the cells or by cytokinesis block. In cultured binucleate lymphocytes of two age groups of men, the X chromosome showed significantly higher mean frequencies of hyperdiploidy, hypodiploidy and reciprocal gain and loss than the Y chromosome. Reciprocal gain and loss of the Y chromosome was statistically significantly higher in the older than the younger men. In four women, studied in the same series, the rates of X chromosome aneuploidy did not significantly differ from those obtained in men. In conclusion, malsegregation of the X chromosome is common in lymphocytes of both men and women and more frequent than Y chromosome malsegregation. However, there is no clear sex difference for X chromosome reciprocal gain and loss. This would suggest that the high loss of the X chromosome in women, documented in metaphase studies, is due to micronucleation.


Vascular endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells.
Vascular endothelial growth factor (VEGF) stimulated the tyrosine phosphorylation of multiple components in confluent human umbilical vein endothelial cells (HUVECs) including bands of Mr 205,000, corresponding to the VEGF receptors Flt-1 and KDR, and Mr 145,000, 120,000, 97,000, and 65,000-70,000. VEGF caused a striking and transient increase in mitogen-activated protein (MAP) kinase activity and stimulated phospholipase C-gamma tyrosine phosphorylation, but it had no effect on phosphatidylinositol 3'-kinase activity. VEGF caused a marked increase in tyrosine phosphorylation of p125 focal adhesion kinase (p125(FAK)), which was both rapid and concentration-dependent. VEGF produced similar effects on p125(FAK) in the endothelial cell line ECV.304. VEGF stimulated tyrosine phosphorylation of the 68-kDa focal adhesion-associated component, paxillin, with similar kinetics and concentration dependence to that for p125(FAK). Thrombin and the phorbol ester, phorbol 12-myristate 13-acetate, also increased p125(FAK) tyrosine phosphorylation in HUVECs. The effect of VEGF on p125(FAK) tyrosine phosphorylation was completely inhibited by the actin filament-disrupting agent cytochalasin D and was partially inhibited by the protein kinase C inhibitor GF109203X. Inhibition of the MAP kinase pathway using a specific inhibitor of MAP kinase kinase had no effect on p125(FAK) tyrosine phosphorylation. VEGF stimulated migration and actin stress fiber formation in confluent HUVEC, and VEGF-induced p125(FAK)/paxillin tyrosine phosphorylation was accompanied by increased immunofluorescent staining of p125(FAK), paxillin, and phosphotyrosine in focal adhesions in confluent cultures of HUVECs. These findings identify p125(FAK) and paxillin as components in a VEGF-stimulated signaling pathway and suggest a novel mechanism for VEGF regulation of endothelial cell functions.


Normal B cells express ZAP70 in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation?
ZAP70 has a prognostic value in chronic lymphocytic leukemia (CLL), through altered B-cell receptor signaling, which is important in CLL pathogenesis. A good correlation between ZAP70 expression in CLL cells and the occurrence of autoimmune phenomena has been reported. Yet, the great majority of CLL-associated autoimmune cytopenia is due to polyclonal immunoglobulin (Ig) G synthesized by nonmalignant B cells, and this phenomenon is poorly understood. Here, we show, using flow cytometry, that a substantial percentage of CD5- nonmalignant B cells from CLL patients expresses ZAP70 compared with CD5- B cells from healthy subjects. This ZAP70 expression in normal B cells from CLL patients was also evidenced by the detection of ZAP70 mRNA at single-cell level with polyclonal Ig heavy- and light-chain gene transcripts. ZAP70+ normal B cells belong to various B-cell subsets and their presence in the naïve B-cell subset suggests that ZAP70 expression may occur during early B-cell development in CLL patients and potentially before malignant transformation. The presence of ZAP70+ normal B cells is associated with autoimmune cytopenia in CLL patients in our cohort of patients, and recombinant antibodies produced from these ZAP70+ nonmalignant B cells were frequently autoreactive including anti-platelet reactivity. These results provide a better understanding of the implication of ZAP70 in CLL leukemogenesis and the mechanisms of autoimmune complications of CLL.


BPI-ANCA is found in reactive arthritis caused by Yersinia and Salmonella infection and recognise exclusively the C-terminal part of the BPI molecule.
To examine the prevalence, binding sites and functional interactions of antineutrophil cytoplasmic autoantibodies (ANCA) against the bactericidal/permeability increasing protein (BPI) in reactive arthritis (ReA). Sera were analysed for the occurrence of ANCA by indirect immunofluorescence microscopy (IIF) and ELISA. Binding sites were determined using BPI, lipopolysaccharid binding protein (LBP), and fusion proteins of both proteins in ELISA. In addition, the effect of antibodies on the antibiotic activity of BPI was examined. BPI-ANCA was found in patients with Yersinia- and Salmonella-triggered ReA and directed against the C-terminal portion of BPI. Goat anti BPI antibodies recognising this part inhibited the antibiotic activity of BPI in vitro. BPI-ANCA was associated with ReA triggered by Salmonella and Yersinia infection. Directed against the C-terminal part of BPI, it can potentially inhibit its antibiotic activity and might be useful to identify patients with infectious bowel disease prone to extraintestinal sequelae.


Na+-inhibitory sites of the Na+/H+ exchanger are Li+ substrate sites.
Amiloride-inhibitable Li+ influx in dog red blood cells is mediated by the Na+/H+ exchanger, NHE. However, there are substantial differences between the properties of Li+ transport and Na+ transport through the NHE. Li+ influx is activated by cell shrinkage, and Na+ influx is not, as we reported previously (Dunham PB, Kelley SJ, and Logue PJ. Am J Physiol Cell Physiol 287: C336-C344, 2004). Li+ influx is a sigmoidal function of its concentration, and Na+ activation is linear at low Na+ concentrations. Li+ does not inhibit its own influx; in contrast, Na+ inhibits Na+ influx. Li+ prevents this inhibition by Na+. Na+ is a mixed or noncompetitive inhibitor of Li+ influx, implying that both a Na+ and a Li+ can be bound at the same time. In contrast, Li+ is a competitive inhibitor of Na+ influx, suggesting Li+ binding at one class of sites on the transporter. Because the properties of Li+ transport and Na+ transport are different, a simple explanation is that Na+ and Li+ are transported by separate sites. The similarities of the properties of Li+ transport and the inhibition of Na+ transport by Na+ suggest that Li+ is transported by the Na+-inhibitory sites.


Adaptive differentiations of the skin of the head in a subterranean rodent, Spalax ehrenbergi.
The skin of macroscopically distinct regions (hairy skin, vibrissal fields, buccal ridge, and rhinarium) of the head of the blind mole-rat, Spalax ehrenbergi, was studied by routine histological methods. Few guard and several soft vellus hairs are organized into tufts that grow from a group of hair follicles localized in an invaginated compound cavity. We suggest that this hair arrangement may be a burrowing adaptation to match frictional resistance. The follicles and the compound cavity possess either well developed complex striated musculature or errector pili muscles. There are no structural specializations (sweat glands, glomus bodies) to enhance thermoregulatory (heat dissipative) capacities in the hairy skin of the head. Vibrissae penetrate the epidermal surface as single hairs. They are microscopically normally developed and arranged in vibrissal fields according to a basal mammalian pattern. Most of them are, however, relatively short and inconspicuous. The mystacial vibrissal field is horizontally divided by a prominent buccal ridge which is probably involved in bulldozing. The hairs in the ridge leave the compound cavity singularly. The follicles of guard hairs and bristles are equipped with well developed pilo-Ruffini complexes indicating that the buccal ridge may serve also as a tactile organ. The glabrous skin of the rhinarium has a highly interdigitated dermal-epidermal interface. The dermal papillae possess simple lamellated and/or simple Meissner's corpuscles and few Merkel cell-axon-complexes indicating that the skin of the rhinarium may be particularly sensitive to perception of vibrations.


Increasing polyunsaturation of milk fats by feeding formaldehyde protected sunflower-soybean supplement.
A practical means of protecting fats of a feed concentrate containing high polyunsaturated fatty acids is described. A ground mixture of 30% soybeans and 70% sunflower seeds was treated with 1% formaldehyde to protect the unsaturated lipids from microbial hydrogenation in the rumen. This was fed as a supplement to two Holstein cows in amounts that were doubled weekly. These ranged from 524 to 8384 g/day and provided successively increasing intakes of 100, 200, 400, 800, and 1600 g of linoleic acid daily. Percent milk fat increased by more than one, and linoleic acid (C18:2) of milk fat increased from 2.5 to 20% with compensatory declines in myristic (C14:0) and palmitic (C16:0) acids. Cholesterol and vitamin E of plasma both doubled at the highest supplementation. Milk yield, solids-not-fat, protein and milk cholesterol were unaltered. Fat in feces doubled from about 3 to 6%. Daily linoleic acid content of feces increased from 25 g to 120 g, indicating a dietary loss of 7 to 10% of this polyunsaturated acid. These cheaper feed ingredients elevated the polyunsaturated fats in milk as effectively as the expensive purified casein and safflower oil supplements in previous experiments.


Biochemical Responses to the Long-Term Impact of Copper Sulfate (CuSO4) in Tobacco Plants.
Metabolic changes under stress are often studied in short-term experiments, revealing rapid responses in gene expression, enzyme activity, and the amount of antioxidants. In a long-term experiment, it is possible to identify adaptive changes in both primary and secondary metabolism. In this study, we characterized the physiological state of tobacco plants and assessed the amount and spectrum of phenolic compounds and the lignification of axial organs under excess copper stress in a long-term experiment (40 days). Plants were treated with 100 and 300 μM CuSO4, as well as a control (Knop solution). Copper accumulation, the size and anatomical structure of organs, stress markers, and the activity of antioxidant enzymes were studied. Lignin content was determined with the cysteine-assisted sulfuric method (CASA), and the metabolite profile and phenolic spectrum were determined with UHPLC-MS and thin-layer chromatography (TLC). Cu2+ mainly accumulated in the roots and, to a lesser extent, in the shoots. Copper sulfate (100 μM) slightly stimulated stem and leaf growth. A higher concentration (300 μM) caused oxidative stress; H2O2 content, superoxide dismutase (SOD), and guaiacol peroxidase (GPOX) activity increased in roots, and malondialdehyde (MDA) increased in all organs. The deposition of lignin increased in the roots and stems compared with the control. The content of free phenolics, which could be used as substrates for lignification, declined. The proportions of ferulic, cinnamic, and p-coumaric acids in the hydrolysate of bound phenolics were higher, and they tended toward additional lignification. The metabolic profile changed in both roots and stems at both concentrations, and changed in leaves only at a concentration of 300 μM. Thus, changes in the phenolic spectrum and the enhanced lignification of cell walls in the metaxylem of axial (root and stem) organs in tobacco can be considered important metabolic responses to stress caused by excess CuSO4.


Evidence-based selection of environmental factors and datasets for measuring multiple environmental deprivation in epidemiological research.
This Environment and Human Health project aims to develop a health-based summary measure of multiple physical environmental deprivation for the UK, akin to the measures of multiple socioeconomic deprivation that are widely used in epidemiology. Here we describe the first stage of the project, in which we aimed to identify health-relevant dimensions of physical environmental deprivation and acquire suitable environmental datasets to represent population exposure to these dimensions at the small-area level. We present the results of this process: an evidence-based list of environmental dimensions with population health relevance for the UK, and the spatial datasets we obtained and processed to represent these dimensions. This stage laid the foundations for the rest of the project, which will be reported elsewhere.


High-Sensitivity C-Reactive Protein Is Associated With Incident Type 2 Diabetes Among African Americans: The Jackson Heart Study.
Previous studies on the association between hs-CRP and incident type 2 diabetes among African Americans have been inconclusive. We examined the association between hs-CRP and incident diabetes in a large African American cohort (Jackson Heart Study). hs-CRP was measured in 3,340 participants. Incident diabetes was defined by fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes drugs, or A1C ≥6.5% (48 mmol/mol) at follow-up. Cox regression was used to estimate hazard ratios (HRs) for incident diabetes, adjusting for age, sex, education, diabetes family history, alcohol, HDL, triglycerides, hypertension status, hypertension medications, physical activity, BMI, HOMA-insulin resistance (HOMAIR), and waist circumference. Participants (63% women) were aged 53.3 ± 12.5 years. During a median follow-up of 7.5 years, 17.4% developed diabetes (23.1/1,000 person-years, 95% CI 21.3-25.1). After adjustment, the HR (hs-CRP third vs. first tertile) was 1.64 (95% CI 1.26-2.13). In separate models, further adjustment for BMI and waist circumference attenuated this association (HR 1.28 [95% CI 0.97-1.69] and 1.35 [95% CI 1.03-1.78, P < 0.05 for trend], respectively). Upon adding HOMAIR in the models, the association was no longer significant. In adjusted HOMAIR-stratified analysis, the hs-CRP-diabetes association appeared stronger in participants with HOMAIR <3.0 compared with HOMAIR ≥3.0 (P < 0.0001 for interaction). The association was also stronger among nonobese participants, although not significant when adjusted for HOMAIR. Low-grade inflammation, as measured by hs-CRP level, may have an important role in the development of diabetes among African Americans with a lesser degree of insulin resistance.


[In situ time-resolved FTIR studies of HCOOH oxidation on Pt(100)/Sb electrodes].
The electrocatalytic oxidation of formic acid on Pt(100)/Sb electrodes of different coverage of Sb was investigated by using electrochemical techniques and in situ time-resolve FTIRS. The results demonstrated that the dissociative adsorption of formic acid was inhibited by the presence of Sbad on Pt(100) surface, as a consequence HCOOH can be oxidized directly into CO2 via reactive intermediates. The rate of oxidation of formic acid varied with the coverage of Sbad. It was revealed that at a Sbad coverage of 0.24 the Pt(100)/Sb electrode exhibited the highest electrocatalytic activity for HCOOH oxidation.


Analysis of nevirapine resistance mutations in cloned HIV type 1 variants from HIV-infected Ugandan infants using a single-step amplification-sequencing method (AmpliSeq).
We analyzed the genetic linkage of nevirapine (NVP) resistance mutations and the genetic complexity of HIV-1 variants in Ugandan infants who were HIV infected despite single dose (SD) prophylaxis. Plasma samples were obtained from six HIV-infected infants who had two or more NVP resistance mutations detected by population sequencing (ViroSeq). ViroSeq PCR products were cloned and transformed, and a single-step amplification-sequencing reaction (AmpliSeq) was used to analyze NVP resistance mutations in cloned HIV-1 variants directly from bacterial colonies. Fifty clones were analyzed for each infant sample. This analysis revealed numerous NVP resistance mutations not detected by population sequencing, genetically linked NVP resistance mutations, and a high degree of genetic complexity at codons that influence NVP susceptibility.


Handgrip strength shows no improvements in geriatric patients with persistent inflammation during hospitalization.
Hospital-associated deconditioning due to a combination of illness and inactivity is a serious problem for elderly adults. Here we investigate whether persistence in inflammatory status affects changes in physical function during short-term hospitalization. This was a prospective observational study in elderly medical patients at a geriatric department. Measurements were obtained at admission and one week after admission and included de Morton Mobility Index (DEMMI) test, 30-second chair stand test (30-s CST), 4-m gait speed (4-m GST) test, handgrip strength, activity levels determined with ActivPALs, and concentrations of circulating C-reactive protein (CRP) from blood samples. Only patients with inflammation (C-reactive protein levels ≥10mg·L-1) at admission were included in this study. They were divided into those with continued inflammation (CI: CRP remained ≥10mg·L-1) and those that became non-inflammatory (BN: CRP decreased to <10mg·L-1) after one week of admission. On admission 214 patients (67% female) with a median (IQR) age of 86 (81-91) years were categorized as inflammatory. There were no baseline differences in physical function between CI (n=138, 67% female) and BN (n=76, 68% female). DEMMI-score increased similarly in both groups (P<0.05). When normalized to days between tests, only changes in handgrip strength were significantly different between the CI- and BN-group (-0.05 [-0.27-0.28] vs. 0.16 [-0.10-0.41] kg·day-1, respectively, P<0.01). There was a positive association between changes in CRP and length of hospital stay (rs=0.30, P<0.001). Hospitalized geriatric patients admitted with inflammation showed only moderate improvement of general mobility during hospital stay, regardless of changes in their inflammatory status. However, handgrip strength increased only in those patients who became non-inflammatory during hospitalization.


[The formation and significance of antibodies to interferon beta during immunomodulating treatment of multiple sclerosis].
Patients with multiple sclerosis receiving interferon beta (IFN) may develop neutralizing anti-interferon beta antibodies (NABs). The importance of NABs has not been completely explained, however it is generally reckoned that they might be one of the factors diminishing treatment efficacy. This paper presents the consequences of NABs formation during IFN therapy. Differences of immunogenicity between the interferon beta products with regard to their structure, formulation, dose, route of administration were presented and the influence of NABs on the biological and clinical activity of IFN beta therapy was shown.


Base of the skull morphology and Class III malocclusion in patients with unilateral cleft lip and palate.
The aim of the present study was to determine the morphological differences in the base of the skull of individuals with cleft lip and palate and Class III malocclusion in comparison to control groups with Class I and Class III malocclusion. A total of 89 individuals (males and females) aged between 5 and 27 years old (Class I, n = 32; Class III, n = 29; and Class III individuals with unilateral cleft lip and palate, n = 28) attending PUC-MG Dental Center and Cleft Lip/Palate Care Center of Baleia Hospital and PUC-MG (CENTRARE) were selected. Linear and angular measurements of the base of the skull, maxilla and mandible were performed and assessed by a single calibrated examiner by means of cephalometric radiographs. Statistical analysis involved ANCOVA and Bonferroni correction. No significant differences with regard to the base of the skull were found between the control group (Class I) and individuals with cleft lip and palate (P > 0.017). The cleft lip/palate group differed from the Class III group only with regard to CI.Sp.Ba (P = 0.015). Individuals with cleft lip and palate had a significantly shorter maxillary length (Co-A) in comparison to the control group (P < 0.001). No significant differences were found in the mandible (Co-Gn) of the control group and individuals with cleft lip and palate (P = 1.000). The present findings suggest that there are no significant differences in the base of the skull of individuals Class I or Class III and individuals with cleft lip and palate and Class III malocclusion.


Pathogen transmission from vaccinated hosts can cause dose-dependent reduction in virulence.
Many livestock and human vaccines are leaky because they block symptoms but do not prevent infection or onward transmission. This leakiness is concerning because it increases vaccination coverage required to prevent disease spread and can promote evolution of increased pathogen virulence. Despite leakiness, vaccination may reduce pathogen load, affecting disease transmission dynamics. However, the impacts on post-transmission disease development and infectiousness in contact individuals are unknown. Here, we use transmission experiments involving Marek disease virus (MDV) in chickens to show that vaccination with a leaky vaccine substantially reduces viral load in both vaccinated individuals and unvaccinated contact individuals they infect. Consequently, contact birds are less likely to develop disease symptoms or die, show less severe symptoms, and shed less infectious virus themselves, when infected by vaccinated birds. These results highlight that even partial vaccination with a leaky vaccine can have unforeseen positive consequences in controlling the spread and symptoms of disease.


SAP and partners: IS-H and IS-H* MED.
The Styrian Hospital Organization with 21 hospitals including the Graz University Hospital, and the Heidelberg University Hospital implemented a new HIS based on SAP/R3, ISH, ISH* MED with the objective to have an integrated system to support patient administration and management, patient care, clinical documentation, research etc. Heidelberg University Hospital chose a step by step method for the introduction of the system, beginning with patient administration (ISH) and proceeding with clinical functions (ISH* MED). In Styria, the full functionality was implemented--as part of the selection process--in one peripheral hospital and in the Ear, Nose and Throat (ENT) Department of the Graz University Hospital, including special documents to support the processes in the highly specialized ENTunits. The standard modules are performant, stable and basically well accepted. Particularly in Graz, it has been shown that the requirements of highly specialized departments for work flow management, documentation and integration of subsystems and data from different sources can be fulfilled by special documents and programs--although at the expense of additional workload particularly in the initial phases of such a project.


Magnetic resonance arthrography of the acetabular labrum. Macroscopic and histological correlation in 20 cadavers.
We studied the sensitivity and specificity of magnetic resonance arthrography (MRa) for the diagnosis of lesions of the acetabular labrum in 20 cadaver hips. The MRa results were compared with macroscopic and histological findings. We found that the labrum could be satisfactorily delineated by MRa and that large detachments could be identified satisfactorily. The diagnosis of small detachments and degeneration of the labrum was less reliable.


OVOL2 antagonizes TGF-β signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis.
Great progress has been achieved in the study of the role of TGF-β signaling in triggering epithelial-mesenchymal transition (EMT) in a variety of cancers; however, the regulation of TGF-β signaling during EMT in mammary tumor metastasis has not been completely defined. In the present study, we demonstrated that OVOL2, a zinc finger transcription factor, inhibits TGF-β signaling-induced EMT in mouse and human mammary tumor cells, as well as in mouse tumor models. Data from the Oncomine databases indicated a strong negative relationship between OVOL2 expression and breast cancer progression. Moreover, our experiments revealed that OVOL2 inhibits TGF-β signaling at multiple levels, including inhibiting Smad4 mRNA expression and inducing Smad7 mRNA expression, blocking the binding between Smad4 and target DNA, and interfering with complex formation between Smad4 and Smad2/3. These findings reveal a novel mechanism that controls the TGF-β signaling output level in vitro and in vivo. The modulation of these molecular processes may represent a strategy for inhibiting breast cancer invasion by restoring OVOL2 expression.


Palladium-catalyzed diastereo- and enantioselective allylic alkylation of oxazolones with 1,3-dienes under base-free conditions.
Herein, we report a highly diastereo- and enantioselective allylic alkylation of oxazolones with 1,3-dienes by palladium-hydride catalyst under base-free conditions. With DTBM-SEGPHOS as the chiral ligand, a series of enantioenriched oxazolones bearing tertiary carbon centers were synthesized from substituted 1,3-dienes via exclusive 1,2-addition with moderate to good diastereoselectivities and high enantioselectivities. When simple 1,3-butadiene was used as the allyl precursor under this base-free catalytic system, 1,4-addition products were obtained in good yields with high regioselectivities.


Differences in the early cognitive development of children and great apes.
There is very little research comparing great ape and human cognition developmentally. In the current studies we compared a cross-sectional sample of 2- to 4-year-old human children (n=48) with a large sample of chimpanzees and bonobos in the same age range (n=42, hereafter: apes) on a broad array of cognitive tasks. We then followed a group of juvenile apes (n=44) longitudinally over 3 years to track their cognitive development in greater detail. In skills of physical cognition (space, causality, quantities), children and apes performed comparably at 2 years of age, but by 4 years of age children were more advanced (whereas apes stayed at their 2-year-old performance levels). In skills of social cognition (communication, social learning, theory of mind), children out-performed apes already at 2 years, and increased this difference even more by 4 years. Patterns of development differed more between children and apes in the social domain than the physical domain, with support for these patterns present in both the cross-sectional and longitudinal ape data sets. These results indicate key differences in the pattern and pace of cognitive development between humans and other apes, particularly in the early emergence of specific social cognitive capacities in humans.


[Clinical semeiology of the perforating veins in essential varicosis in the postphlebitic syndrome].
After a reminder of the anatomy of the perforating veins of the lower extremities and their physiopathology, various clinical aspects are presented. In the essential form of varicose veins disease, long saphenous refluxes are, at the beginning, responsible for stasis in the superficial venous system. During the course of the disease, it seems that the perforators become incontinent. In the post-phlebitic syndrome, the manifestations are different and there are numerous perforators, the topography of which depends on the location of the thrombosis. A well conducted clinical examination is absolutely necessary in order to demonstrate the origin of the long or short reflux, before the start of any treatment. In case of failure or recurrence, phlebography or varicography must be performed.


Whole brain inhomogeneous magnetization transfer (ihMT) imaging: Sensitivity enhancement within a steady-state gradient echo sequence.
To implement, characterize, and optimize an interleaved inhomogeneous magnetization transfer (ihMT) gradient echo sequence allowing for whole-brain imaging within a clinically compatible scan time. A general framework for ihMT modelling was developed based on the Provotorov theory of radiofrequency saturation, which accounts for the dipolar order underpinning the ihMT effect. Experimental studies and numerical simulations were performed to characterize and optimize the ihMT-gradient echo dependency with sequence timings, saturation power, and offset frequency. The protocol was optimized in terms of maximum signal intensity and the reproducibility assessed for a nominal resolution of 1.5 mm isotropic. All experiments were performed on healthy volunteers at 1.5T. An important mechanism driving signal optimization and leading to strong ihMT signal enhancement that relies on the dynamics of radiofrequency energy deposition has been identified. By taking advantage of the delay allowed for readout between ihMT pulse bursts, it was possible to boost the ihMT signal by almost 2-fold compared to previous implementation. Reproducibility of the optimal protocol was very good, with an intra-individual error < 2%. The proposed sensitivity-boosted and time-efficient steady-state ihMT-gradient echo sequence, implemented and optimized at 1.5T, allowed robust high-resolution 3D ihMT imaging of the whole brain within a clinically compatible scan time. Magn Reson Med 79:2607-2619, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


High-affinity binding of the basement membrane proteins collagen type IV and laminin to the gastric pathogen Helicobacter pylori.
The ability of 16 isolates of the human gastroduodenal pathogen Helicobacter pylori to bind 125I-radiolabelled tissue proteins was quantitated by liquid-phase assay. While capable of binding generally low levels of collagen types I and II, vitronectin, and fibronectin (average binding, 8%; highest binding, 23%), the various H. pylori isolates were good binders of the basement membrane proteins collagen type IV and laminin (average binding, 27%; highest binding, 60%). Campylobacter species tested bound lower levels of collagen type IV and laminin (average binding, 12%; highest binding, 17%). Trypsin and proteinase K treatment of H. pylori cells markedly reduced the binding of collagen type IV and laminin, as did heat treatment, suggesting that the binding of basement membrane proteins is mediated by bacterial surface proteins. Binding of both basement membrane proteins was rapid and saturable. 125I-collagen type IV binding to H. pylori 915 was inhibited by preincubation with unlabelled collagen type IV but was not inhibited by laminin or a number of other proteins. Once bound, radiolabelled collagen type IV but was not displaced by an excess of unlabelled collagen type IV, indicating that the binding interaction was of high affinity. Binding of laminin was partially reversible, and analysis in a solid-phase nonradiolabel assay showed that the interaction was of high affinity, with a Kd of 7.9 nM. This interaction was affected by salt, indicating the presence of a hydrophobic component in the ability of H. pylori to bind laminin.


Copulating with multiple mates enhances female fecundity but not egg-to-adult survival in the bruchid beetle Callosobruchus maculatus.
Postcopulatory sexual selection theory has come a long way since the evolutionary implications of sperm competition were first spelled out by Parker (1970). However, one of the most enduring questions remains: why do females copulate with multiple males? Here we show that females copulating with multiple males lay more eggs than those copulating repeatedly with the same male. We also show egg-to-adult survival to be more variable when females copulate multiply with different males and less variable when they copulate multiply with the same male. This supports the notion that egg-to-adult survival may depend on the genetic compatibility of males and females. However, pre-adult survival was highest when females copulated repeatedly with the same male rather than with different males. Thus, it would appear that polyandry in this species does not function to reduce the risk of embryo failure resulting from fertilization by genetically incompatible sperm.


Multiple, disseminated cutaneous metastases of vulvar squamous cell carcinoma.
Cutaneous metastases of vulvar carcinoma are extremely rare and have been reported in six patients so far. Our patient, who is the seventh one, is a 38-year-old woman with a history of diabetes mellitus. After detecting stage III squamous cell carcinoma of the vulva, she underwent radical vulvectomy and bilateral inguinal lymphadenectomy. She received 6000 cGy external beam radiation for positive margins. Six months later, she came back with multiple advanced skin lesions. Biopsy was performed and lesions were confirmed as cutaneous metastases. For her palliation, some chemotherapy drugs were prescribed. She is on her sixth chemotherapy cycle, but these skin lesions are somewhat a preterminal event and there is no well-established treatment for this phase of disease.


Loose interaction between glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase revealed by fluorescence resonance energy transfer-fluorescence lifetime imaging microscopy in living cells.
Loose interaction between the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoglycerate kinase (PGK) was visualized in living CHO-K1 cells by fluorescence resonance energy transfer (FRET), using time-domain fluorescence lifetime imaging microscopy. FRET between active tetrameric subunits of GAPDH linked to cerulean or citrine was observed, and this FRET signal was significantly attenuated by coexpression of PGK. Also, direct interaction between GAPDH-citrine and PGK-cerulean was observed by FRET. The strength of FRET signals between them was dependent on linkers that connect GAPDH to citrine and PGK to cerulean. A coimmunoprecipitation assay using hemagglutinin-tagged GAPDH and FLAG-tagged PGK coexpressed in CHO-K1 cells supported the FRET observation. Taken together, these results demonstrate that a complex of GAPDH and PGK is formed in the cytoplasm of living cells.


Improving management of student clinical placements: insights from activity theory.
An approach to improve management of student clinical placements, the Building Teams for Quality Learning project, was trialed in three different health services. In a previous paper the authors explored in some detail the factors associated with considerable success of this approach at one of these services. In this paper, the authors extend this work with further analysis to determine if the more limited outcomes observed with participants at the other two services could be explained by application of activity theory and in particular the expansive learning cycle. Staff at three health services participated in the Building Teams for Quality Learning project: a dental clinic, a community aged care facility and a rural hospital. At each site a team of seven multi-disciplinary staff completed the project over 9 to 12 months (total 21 participants). Evaluation data were collected through interviews, focus groups and direct observation of staff and students. Following initial thematic analysis, further analysis was conducted to compare the processes and outcomes at each participating health service drawing on activity theory and the expansive learning cycle. Fifty-one interview transcripts, 33 h of workplace observation and 31 sets of workshop field notes (from 36 h of workshops) were generated. All participants were individually supportive of, and committed to, high quality student learning experiences. As was observed with staff at the dental clinic, a number of potentially effective strategies were discussed at the aged care facility and the rural hospital workshops. However, participants in these two health services could not develop a successful implementation plan. The expansive learning cycle element of modeling and testing new solutions was not achieved and participants were unable, collectively to reassess and reinterpret the object of their activities. The application of activity theory and the expansive learning cycle assisted a deeper understanding of the differences in outcomes observed across the three groups of participants. This included identifying specific points in the expansive learning cycle at which the three groups diverged. These findings support some practical recommendations for health services that host student clinical placements.


Effect of maurotoxin, a four disulfide-bridged toxin from the chactoid scorpion Scorpio maurus, on Shaker K+ channels.
Maurotoxin is a 34-residue toxin isolated from the venom of the Tunisian chactoid scorpion Scorpio maurus palmatus and contains four disulfide bridges that are normally found in long-chain toxins of 60-70 amino acid residues, which affect voltage-gated sodium channels. However, despite the unconventional disulfide-bridge pattern of maurotoxin, the conformation of this toxin remains similar to that of other toxins acting on potassium channels. Here, we analyzed the effects of synthetic maurotoxin on voltage-gated Shaker potassium channels (ShB) expressed in Xenopus oocytes. Maurotoxin produces a strong, but reversible, inhibition of the ShB K+ current with an IC50 of 2 nM. Increasing concentrations of the toxin induce a progressively higher block at saturating concentrations. At nonsaturating concentrations of the toxin (5-20 nM), the channel block appears slightly more pronounced at threshold potentials suggesting that the toxin may have a higher affinity for the closed state of the channel. At the single channel level, the toxin does not modify the unitary current amplitude, but decreases ensemble currents by increasing the number of depolarizing epochs that failed to elicit any opening. A point mutation of Lys23 to alanine in maurotoxin produces a 1000-fold reduction in the IC50 of block by the toxin suggesting the importance of this charged residue for the interaction with the channel. Maurotoxin does not affect K+ currents carried by Kir2.3 channels in oocytes or Na+ currents carried by the alphaIIa channel expressed in CHO cells.


Resveratrol Improves Growth Performance, Intestinal Morphology, and Microbiota Composition and Metabolism in Mice.
Resveratrol (RSV) plays a vital role in alleviating various stresses and improving intestinal health. The current study was conducted to explore whether RSV alleviates weaning stress through improving gut health in a weaning mouse model. Forty 21-day-old weaned mice were randomly assigned to a control group without RSV treatment and three treatment groups with 10, 20, and 50 mg/kg RSV for 28 days. The results showed that RSV at a dose of 20 mg/kg improved total body weight, intestinal morphology (villus length and the ratio of villus length to crypt depth), and the levels of intestinal barrier proteins (claudin-1 and occludin), but had little effect on the food intake, crypt depth, and serum free amino acids of mice. Compared with the control group, mice supplemented with RSV had decreased mRNA expression of genes related to inflammatory cytokines (IL-6 and IL-1β), but increased mRNA expression of genes related to host defense peptides (Defa3, Defa5, Defa20, and Lyz) and short-chain fatty acids (SCFAs) production (propionic acid, isobutyric acid, butyric acid, and isovaleric acid). In addition, 16S rRNA sequencing results showed that RSV supplementation increased the richness indices of intestinal microbiota (Chao, ACE) and shaped the composition of intestinal microbiota (e.g., increased β-diversity of intestinal microbiota community). Meanwhile, RSV supplementation increased genes of Butyricicoccus, Ruminococcus_1, and Roseburia, which are producers of SCFAs. Furthermore, RSV supplementation significantly influenced the metabolism of intestinal microbiota, namely, amino acids metabolism, lipid metabolism, and defense mechanisms. RSV can improve growth performance and intestinal morphology in weaning mice, possibly through improving gut immune response and microbiota function.


An unusual organoyttrium alkyl complex containing a [C5HMe3(η(3)-CH2)-C5H4N-κ]- ligand and an elusive cyclopentadienide-based scandium tuck-over zwitterion obtained by C-H bond activation.
The acid-base reaction between Y(CH(2)SiMe(3))(3)(thf)(2) and the pyridyl-functionalized cyclopentadienyl (Cp) ligand C(5)Me(4)H-C(5)H(4)N (1 equiv) at 0 °C afforded a mixture of two products: (η(5):κ-C(5)Me(4)-C(5)H(4)N)Y(CH(2)SiMe(3))(2)(thf) (1 a) and (η(5):κ-C(5)Me(4)-C(5)H(4)N)(2)YCH(2)SiMe(3) (1 b), in a 5:2 ratio. Addition of the same ligand (2 equiv) to Y(CH(2)SiMe(3))(3)(thf)(2), however, generated 1 b together with the novel complex 1 c, the first well defined yttrium mono(alkyl) complex (η(5):κ-C(5)Me(4)-C(5)H(4)N)[C(5)HMe(3)(η(3)-CH(2))-C(5)H(4)N-κ]Y(CH(2)SiMe(3)) containing a rare κ/η(3)-allylic coordination mode in which the C-H bond activation occurs unexpectedly with the allylic methyl group rather than conventionally on Cp ring. If the central metal was changed to lutetium, the equimolar reaction between Lu(CH(2)SiMe(3))(3)(thf)(2) and C(5)Me(4)H-C(5)H(4)N exclusively afforded the bis(alkyl) product (η(5):κ-C(5)Me(4)-C(5)H(4)N)Lu(CH(2)SiMe(3))(2)(thf) (2 a). Similarly, the reaction between the ligand (2 equiv) and Lu(CH(2)SiMe(3))(3)(thf)(2) gave the mono(alkyl) complex (η(5):κ-C(5)Me(4)-C(5)H(4)N)(2)LuCH(2)SiMe(3) (2 b), in which no ligand redistribution was observed. Strikingly, treatment of Sc(CH(2)SiMe(3))(3)(thf)(2) with C(5)Me(4)H-C(5)H(4)N in either 1:1 or 1:2 ratio at 0 °C generated the first cyclopentadienide-based scandium zwitterionic "tuck-over" complex 3, (η(5):κ-C(5)Me(4)-C(5)H(4)N)Sc(thf)[μ-η(5):η(1):κ-C(5)Me(3)(CH(2))-C(5)H(4)N]Sc(CH(2)SiMe(3))(3). In the zwitterion, the dianionic ligand [C(5)Me(3)(CH(2))-C(5)H(4)N](2-) binds both to Sc1(3+) and to Sc2(3+), in η(5) and η(1)/κ modes. In addition, the reaction chemistry, the molecular structures, and the mechanism are also discussed in detail.


The prevention of inadvertent hypothermia during fetal surgery: an ovine model.
The effect of application of a reflective thermoblanket was compared with varying degrees of partial removal of the ovine fetus from the uterus. The thermoblanket reduced heat loss by a 53.3% slower fall in rectal temperature when compared to exposed fetuses during the same surgery (Welch t statistic = 3.68, d.f. = 26.08, P less than 0.001). This was further reduced by limiting the area of fetal exposure without thermoblanket application.


Potential of entomopathogenic nematodes for biological control of Acalymma vittatum (Coleoptera: Chrysomelidae) in cucumbers grown in conventional and organic soil management systems.
Acalymma vittatum (F.) is the primary insect pest of fresh-market cucumber and melon crops in much of the eastern United States because of their herbivory and interactions with several diseases, most notably bacterial wilt. A study was conducted to determine how soil management affects viability and infectivity of an entomopathogenic nematode that may be used for the control of A. vittatum. Dose-mortality curves under laboratory conditions suggested several Steinernema spp. as potential biocontrol agents. Field injections combined with soil bioassays showed that Steinernema riobravis Cabanillas, Poinar & Raulston (Rhabditus: Steinernematidae) longevity exceeded A. vittatum immature development time in both conventional and organic soil management systems. Mean root length densities of cucumbers increased in both soil management systems with the inclusion of nematodes. Soil management alone also influenced A. vittatum larval survivorship, with higher survival rates in the organic compared with the conventional soil management system. A 50% reduction in A. vittatum larval survival rates in both soil management systems, as determined by adult A. vittatum emergence, demonstrated the potential of incorporation of entomopathogenic nematodes for integrated pest management of diabroticites in commercial cucumber production.


Comparative molecular analyses of Borrelia burgdorferi sensu stricto strains B31 and N40D10/E9 and determination of their pathogenicity.
Lyme disease in the United States is caused primarily by B. burgdorferi sensu stricto while other species are also prevalent in Europe. Genetic techniques have identified several chromosomal and plasmid-borne regulatory and virulence factors involved in Lyme pathogenesis. B31 and N40 are two widely studied strains of B. burgdorferi, which belong to two different 16 S-23 S rRNA spacer types (RST) and outer surface protein C (OspC) allelic groups. However, the presence of several known virulence factors in N40 has not been investigated. This is the first comprehensive study that compared these two strains both in vitro and using the mouse model of infection. Phylogenetic analyses predict B31 to be more infectious. However, our studies here indicate that N40D10/E9 is more infectious than the B31 strain at lower doses of inoculation in the susceptible C3H mice. Based-upon a careful analyses of known adhesins of these strains, it is predicted that the absence of a known fibronectin-glycosaminoglycan binding adhesin, bbk32, in the N40 strain could at least partially be responsible for reduction in its binding to Vero cells in vitro. Nevertheless, this difference does not affect the infectivity of N40D10/E9 strain. The genes encoding known regulatory and virulence factors critical for pathogenesis were detected in both strains. Differences in the protein profiles of these B. burgdorferi strains in vitro suggest that the novel, differentially expressed molecules may affect infectivity of B. burgdorferi. Further exacerbation of these molecular differences in vivo could affect the pathogenesis of spirochete strains. Based upon the studies here, it can be predicted that N40D10/E9 disseminated infection at lower doses may be enhanced by its lower binding to epithelial cells at the site of inoculation due to the absence of BBK32. We suggest that complete molecular analyses of virulence factors followed by their evaluation using the mouse infection model should form the basis of determining infectivity and pathogenicity of different strains rather than simple phylogenetic group analyses. This study further emphasizes a need to investigate multiple invasive strains of B. burgdorferi to fully appreciate the pathogenic mechanisms that contribute to Lyme disease manifestations.


Housing and health in Ghana: the psychosocial impacts of renting a home.
This paper reports the findings of a qualitative study investigating the impacts of renting a home on the psychosocial health of tenants in the Accra Metropolitan Area (AMA) in Ghana. In-depth interviews (n = 33) were conducted with private renters in Adabraka, Accra. The findings show that private renters in the AMA face serious problems in finding appropriate and affordable rental units, as well as a persistent threat of eviction by homeowners. These challenges tend to predispose renters to psychosocial distress and diminishing ontological security. Findings are relevant to a range of pluralistic policy options that emphasize both formal and informal housing provision, together with the reorganization and decentralization of the Rent Control Board to the district level to facilitate easy access by the citizenry.


Optic neuropathy secondary to perhexiline and amiodarone.
Bilateral optic disc swelling is an important clinical sign for potentially life-threatening and sight-threatening conditions, with the most common being raised intracranial pressure and pseudopapillitis. Perhexiline-related and amiodarone-related optic disc swellings are diagnoses of exclusion. This report describes the diagnosis of a man with perhexiline-induced and amiodarone-induced optic neuropathy after extensive investigation consisting of full ophthalmic examination, biochemical screen, temporal artery biopsy, CT, MRI, positron emission tomography and lumbar puncture. There was partial to complete resolution of optic neuropathy following cessation of the causative medication. We postulate that the underlying mechanism of perhexiline toxicity could be mitochondrial dysfunction related. Our case demonstrates that patients treated with perhexiline and amiodarone should be monitored closely for ocular side effects.


Trans-radial versus trans-femoral intervention for the treatment of coronary bifurcations: results from Coronary Bifurcation Stenting Registry.
Trans-radial (TR) approach is increasingly recognized as an alternative to the routine use of trans-femoral (TF) approach. However, there are limited data comparing the outcomes of these two approaches for the treatment of coronary bifurcation lesions. We evaluated outcomes of TR and TF percutaneous coronary interventions (PCI) in this complex lesion. Procedural outcomes and clinical events were compared in 1,668 patients who underwent PCI for non-left main bifurcation lesions, according to the vascular approach, either TR (n = 503) or TF (n = 1,165). The primary outcome was major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR) in all patients and in 424 propensity-score matched pairs of patients. There were no significant differences between TR and TF approaches for procedural success in the main vessel (99.6% vs 98.6%, P = 0.08) and side branches (62.6% vs 66.7%, P = 0.11). Over a mean follow-up of 22 months, cardiac death or MI (1.8% vs 2.2%, P = 0.45), TLR (4.0% vs 5.2%, P = 0.22), and MACE (5.2% vs 7.0%, P = 0.11) did not significantly differ between TR and TF groups, respectively. These results were consistent after propensity score-matched analysis. In conclusion, TR PCI is a feasible alternative approach to conventional TF approaches for bifurcation PCI (clinicaltrials.gov number: NCT00851526).


'Taking care' in the age of AIDS: older rural South Africans' strategies for surviving the HIV epidemic.
Older adults have been largely overlooked in community studies of HIV in highly endemic African countries. In our rural study site in Mpumalanga Province, South Africa, HIV prevalence among those aged 50 and older is 16.5%, suggesting that older adults are at risk of both acquiring and transmitting HIV. This paper utilises community-based focus-group interviews with older rural South African men and women to better understand the normative environment in which they come to understand and make decisions about their health as they age in an HIV endemic setting. We analyse the dimensions of an inductively emerging theme: ku ti hlayisa (to take care of yourself). For older adults, 'taking care' in an age of AIDS represented: (1) an individualised pathway to achieving old-age respectability through the taking up of responsibilities and behaviours that characterise being an older person, (2) a set of gendered norms and strategies for reducing one's HIV risk, and (3) a shared responsibility for attenuating the impact of the HIV epidemic in the local community. Findings reflect the individual, interdependent and communal ways in which older rural South Africans understand HIV risk and prevention, ways that also map onto current epidemiological thinking for improving HIV-related outcomes in high-prevalence settings.


Biological markers of neonatal calf performance: the relationship of insulin-like growth factor-I, zinc, and copper to poor neonatal growth.
Raising a heifer calf to reproductive age represents an enormous cost to the producer. Poor neonatal growth exacerbates the costs incurred for rearing, and use of blood variables that may be associated with poorly growing calves may offer predictive value for growth and performance. Thus, the principal objective of the present study was to describe changes in serum IGF-I, zinc, and copper from birth to 90 d in Holstein calves, while accounting for sex and twin status, in poorly growing calves and calves growing well. A second objective was to test the hypothesis that an association exists between these serum variables and morphometric indicators of growth. Measurements of BW, length, and height were recorded at birth and at 30, 60, and 90 d of age. Jugular blood (12 mL) was collected from each calf on d 1 to determine serum total protein, serum IgG, packed cell volume, serum zinc, serum copper, serum IGF-I, and CD18 genotype for bovine leukocyte adhesion deficiency; serum zinc, serum copper, and serum IGF-I (predictor variables) were also determined for each calf on d 2 through 10 and on d 30, 60, and 90. Stepwise multiple regression and logistic regression analyses were used to examine the relationships between the predictor variables and the dependent variables (BW, height, and length at d 30, 60, and 90 of life). Birth weight, sex, serum IGF-I (at all ages), serum copper, and the serum copper-to-zinc ratio were associated, to varying degrees, with the dependent growth variables. Birth weight was consistently the dominant predictor. In conclusion, these results suggest that lighter birth weight, reduced serum IGF-I, and inflammation may be important causes of poor growth in neonatal Holstein dairy calves.


Determining epithelial contribution to in vivo mesenchymal tumour expression signature using species-specific microarray profiling analysis of xenografts.
Gene expression profiling using microarrays and xenograft transplants of human cancer cell lines are both popular tools to investigate human cancer. However, the undefined degree of cross hybridization between the mouse and human genomes hinders the use of microarrays to characterize gene expression of both the host and the cancer cell within the xenograft. Since an increasingly recognized aspect of cancer is the host response (or cancer-stroma interaction), we describe here a bioinformatic manipulation of the Affymetrix profiling that allows interrogation of the gene expression of both the mouse host and the human tumour. Evidence of microenvironmental regulation of epithelial mesenchymal transition of the tumour component in vivo is resolved against a background of mesenchymal gene expression. This tool could allow deeper insight to the mechanism of action of anti-cancer drugs, as typically novel drug efficacy is being tested in xenograft systems.


Synthesis of some new pyridyl-ethylated benzoxazolinones with analgesic and anti-inflammatory activities.
Twelve new 3-[2-(2- and/or 4-pyridyl)ethyl]benzoxazolinone derivatives have been synthesized by reacting 2- and/or 4-vinylpyridine and appropriate benzoxazolinones. Their chemical structures have been proven by IR, 1H-NMR and elemental analysis. Analgesic activities of these compounds were investigated by a modified Koster and constant temperature hot-plate test. Test results revealed that most of the compounds at 100 mg/kg dose level showed significant analgesic activities when compared to acetylsalicylic acid and morphine. Therefore the compounds were screened for their anti-inflammatory activities using the carrageenan hind paw edema test. Compounds 3-8 were found more active than indometacin. In gastric ulceration studies, any of the compounds showed no gastrointestinal bleeding at 100 mg/kg dose level.


A Holistic Approach to Risk for Early Kidney Injury in Indigenous Youth With Type 2 Diabetes: A Proof of Concept Paper From the iCARE Cohort.
Indigenous youth with type 2 diabetes (T2D) are disproportionately affected by early onset albuminuria and are at high risk of kidney failure in early adulthood. Traditional biological approaches have failed to fully explain the renal morbidity seen in this population. The improving renal Complications in Adolescents with type 2 diabetes through REsearch cohort (iCARE) study was therefore designed in collaboration with patients, to more holistically evaluate risk factors for renal morbidity. We hypothesize that both biological factors and mental health influence renal outcomes, mediated via inflammatory pathways. The objective of this study was to evaluate the iCARE analytic framework which evaluates relationships between biological factors, mental health, inflammation, and albuminuria utilizing a structural equation modeling (SEM) approach. The first 187 youth with T2D (10-25 years) from the Manitoba iCARE cohort are presented here to evaluate our theoretical and analytic framework. An SEM was chosen to evaluate the statistical significance of proposed associations. The primary outcome was a nonorthostatic urine albumin:creatinine ratio ≥2 mg/mmol. Main exposures (ie, latent factors) included psychological health (distress, perceived stress, positive mental health and resilience), hypertension (24 hour monitored), and inflammatory markers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], fibrinogen). Hemoglobin A1c (HbA1c) and duration of diabetes were covariates. Within the initial cohort (median age = 15 years, duration of diabetes = 2.3 years, 66.8% female), 30.5% (n = 57) had nonorthostatic albuminuria (ALB), and the majority of ALB was persistent (confirmed in 2/3 samples over a 6-month period; n = 47). Youth with ALB had higher HbA1c (10.9% vs 8.9%; P < .001), more hypertension (94.2% vs 78·2%; P = .02), longer duration of diabetes (3.4 vs 2.4 years; P = .01), higher distress (9.2 vs 7.3; P = .02), and stress scores (28.7 vs 26.4; P = .03), and elevated inflammatory markers (CRP: 4.9 vs 3.1 mg/L; P = .01, fibrinogen: 3.7 vs 3.3 µmol/L; P = .02). Factors directly associated with ALB in the SEM were hypertension (0.28; P = .001), inflammation (0.41; P < .001), and HbA1c (0.50; P < .001). Psychological health was independently associated with inflammation (-0.20; P < .001) but not directly associated with ALB. Albuminuria is highly prevalent in Indigenous youth with T2D. This preliminary analysis supports a theoretical framework linking glycemic control, hypertension, and inflammation, potentially mediated by psychological factors with albuminuria. These data support the need for more holistic models of evaluation and care for youth with T2D and multifactorial interventions to prevent complications.


Oncogenic Role of SET/I2PP2A for Gynecologic Cancers.
SET (SE translocation, SET) is an evolutionarily conserved gene broadly expressed in various human tissues, especially in the gonadal and neural system. As a multitasking protein, SET is involved in essential cell processes such as histone modification, chromatin remodeling, DNA repair, gene transcription, and androgen synthesis. Recent studies showed that SET is overexpressed in breast cancers, ovary cancers and a variety of other malignancies. The strong correlation between SET expression levels and survival of ovarian cancer patients, and SET-mediated activation of androgen synthesis, strongly indicated that this factor may play a significant role in gynecologic cancers. Here, we summarized data pertaining to the pathological implications of SET in tumorigenesis and cancer progression. We analyzed how SET, through the PP2A-dependent and PP2A-independent pathways, may regulate different cell functions. Potential interactions among these pathways and future studies on SET's oncogenic activities are also discussed.


Simultaneous external subretinal fluid drainage and intravitreal gas injection.
Simultaneous external subretinal fluid drainage and intravitreal gas injection was performed in 12 patients requiring a large or near-total internal gas tamponade (eight eyes with proliferative vitreo-retinopathy following vitrectomy and four eyes without proliferative vitreoretinopathy that had not undergone vitrectomy). None of the patients had a preexisting or intentional posterior retinal break. The retina was attached six or more months postoperatively in nine of the 12 patients. In one patient, an iatrogenic retinal break occurred without retinal incarceration. In selected cases, this procedure is an alternative to internal fluid-gas exchange through a posterior retinal break, thus avoiding the necessary postoperative facedown position, which is difficult for some patients to maintain. This method may also be used for preventing "fish-mouthed" retinal breaks in selected cases.


Decomposition of Phenolic Impregnated Carbon Ablator (PICA) as a Function of Temperature and Heating Rate.
Material response models for phenolic-based thermal protection systems (TPSs) for atmospheric entry are limited by the lack of knowledge of the nonequilibrium processes that may govern the decomposition pathways of phenolic resin at heating rates up to tens of degrees Celsius per second. We have investigated the pyrolysis of phenolic impregnated carbon ablator (PICA) by measuring the molar yields of the volatile decomposition products as a function of temperature at four nominal heating rates of 3.1, 6.1, 12.7, and 25 °C s-1, over the temperature range of 100-1200 °C. A mass spectrometer was used to probe the 14 significant gaseous products directly as PICA samples were heated resistively in vacuum. Four products, H2, CH4, H2O, and CO, overwhelmingly dominated the molar yields. However, in terms of mass yield, phenol and its methylated derivatives, cresol and dimethyl phenol, were significant. The temperature-dependent molar yields of the observed products exhibited a marked dependence on heating rate. The heating-rate-dependent behavior of the molar yields has been attributed to two main competing decomposition processes that occur as the temperature passes from roughly 300 to 500 °C: (1) cross-linking reactions that produce ether functional groups and carbon-carbon bonds and eliminate H2O and (2) breakdown of the polymer backbone through scission of methylene bridges and liberation of phenol and its methylated derivatives. The latter process competes more effectively with the former as the heating rate increases. The relative rates of these processes appear to have a significant effect on the molar yields of volatile products from subsequent decomposition processes as the temperature is increased further. Thus, the heating rate strongly affects the pathways taken during the pyrolysis of the phenolic resin in PICA. The new data may be used to test nonequilibrium models that are designed to simulate the response of TPS materials during atmospheric entry of spacecraft.


Randomized comparison of prophylactic antidiarrheal treatment versus no prophylactic antidiarrheal treatment in patients receiving CPT-11 (irinotecan) for advanced 5-FU-resistant colorectal cancer: an open-label multicenter phase II study.
Delayed diarrhea is the main toxicity of irinotecan at the currently recommended dose of 350 mg/m2 30-minute intravenous infusion, once every 3 weeks. This phase II, multicenter, open-label, randomized study was primarily designed to evaluate the effect of a 15-day Tiorfan (racecadotril) treatment on the incidence and severity of irinotecan-induced delayed diarrhea. One hundred thirty-six patients with metastatic colorectal cancer who failed to respond to a 5-fluorouracil-based treatment received 714 cycles of irinotecan. The patients were randomly allocated either to group A (68 patients) and received Tiorfan (300 mg/day) from D0 to D15 or to group B (68 patients) with no prophylactic treatment. Delayed diarrhea occurred in 197 of 355 cycles (55%) in Group A and 203 of 344 cycles (59%) in Group B. grade III-IV diarrhea was reported in 17 of 40 compliant patients (42%) in group A and 31 of 68 evaluable patients (45%) in group B. No difference was observed between the two groups for delayed diarrhea characteristics, incidence, or severity. The response rate in 99 evaluable patients was 12.1% (6.4%-20.2%). This study has shown that Tiorfan given prophylactically at 300 mg/day has no effect on delayed diarrhea.


Noise Induced Hearing Loss in Iran: (1997-2012): Systematic Review Article.
Noise-induced hearing loss, which is one of the 10 leading occupational diseases, is a debilitating and irreversible disease. During the recent 15-years period (1997-2012), several studies have investigated the association between noise, hearing damage and other side effects of noise in Iran. The aim of this study was to review systematically the relevant literature related to noise-induced hearing loss, lead to developing noise exposure limits. In this systematic review, two researchers independently extracted the data from 31 past studies that had considered noise-induced hearing loss (including hearing loss, temporary and permanent hearing threshold shift and auditory trauma). The data were then recorded in a modified form and Statistical analyses were performed using SPSS, version 16.0. In analyzed studies the weighted average equivalent sound pressure level [L Aeq ] was 90.29 dB(A) and average hearing loss was 26.44 dB(A). The Highest degree of hearing loss in the right ear was associated at 4000 Hz, and the highest degree of hearing loss in the left ear was associated to 1000 and 4000 Hz. The majority of the reviewed studies have confirmed that exposure to a noise level above 85 dB (A) can lead to an increased chance of hearing loss. Furthermore, the results of the present review indicated that as L Aeq increased up to 85 dB(A), so did the severity of the hearing loss.


Breakfast habits among school children in selected communities in the eastern region of Ghana.
Breakfast is considered the most important meal of the day, yet many people skip breakfast. Studies indicate that school age children who regularly skip breakfast are not likely to concentrate in class, thus affecting school performance. This study determined the breakfast habits and nutrient contributions of the breakfast meal to the days' nutrient intake. A cross sectional study was conducted among school children (n=359) between the ages of 6-19 years in Manya Krobo in the Eastern Region of Ghana. Questionnaires were used to collect information on background characteristics and breakfast consumption habits. The 24-hour dietary recall method was used to obtain information on the children's food intake. T-test was used to compare differences between means of variables of breakfast consumers and skippers. About 85.5% of the children had breakfast on the day of interview. More boys (87.8%) consumed breakfast compared to the girls (83.1%). For those who skipped breakfast, lack of food at home or lack of no money (36.5%) was the main reason. Breakfast consumers had significantly higher energy and nutrient intakes than those who skipped breakfast (energy 2259 verses 1360 kcal, p-0.039; vitamin A 1534 verses 662 ug/RE, p=0.001; iron 22.9 verses 13.9 mg, p=0.017, zinc 9.9 verses 5.6 mg, p=0.034). The breakfast meal contributed between 32-41% of the day's energy intake, and between 30-47% of micronutrient intake. Encouraging breakfast consumption among school children is a way to ensure that they meet their daily nutrient and energy intakes.


[Algorithm for the coproscopic diagnosis of human intestinal parasites].
The purpose of the study was to elaborate a detection algorithm for human intestinal helminth eggs. There is a broad spectrum ofcoproscopic methods recommended for the detection of Opisthorchis eggs in man and animals; these include Fulleborn's method, formalin-ether method, Goryachev's, Katoh's, Kalantaryan's, Shcherbovich's, and Kotelnikov-Varenichev methods. Combined coproscopic methods are significantly more effective in detecting the causative agents of enteric parasitoses than is Katoh's method. Among the considered coproscopic techniques for the diagnosis of human ascariasis, it is most rational to use a combined method for fecal examination, the basis for which is a multicomponent flotation system (such as the author's one). The Kotelnikov-Varenichev method is optimal for diagnosing opisthorchiasis. It is optimal to use 2-3 methods of different groups simultaneously for the screening diagnosis of intestinal parasitoses.


Just a fad? Gamification in health and fitness apps.
Gamification has been a predominant focus of the health app industry in recent years. However, to our knowledge, there has yet to be a review of gamification elements in relation to health behavior constructs, or insight into the true proliferation of gamification in health apps. The objective of this study was to identify the extent to which gamification is used in health apps, and analyze gamification of health and fitness apps as a potential component of influence on a consumer's health behavior. An analysis of health and fitness apps related to physical activity and diet was conducted among apps in the Apple App Store in the winter of 2014. This analysis reviewed a sample of 132 apps for the 10 effective game elements, the 6 core components of health gamification, and 13 core health behavior constructs. A regression analysis was conducted in order to measure the correlation between health behavior constructs, gamification components, and effective game elements. This review of the most popular apps showed widespread use of gamification principles, but low adherence to any professional guidelines or industry standard. Regression analysis showed that game elements were associated with gamification (P<.001). Behavioral theory was associated with gamification (P<.05), but not game elements, and upon further analysis gamification was only associated with composite motivational behavior scores (P<.001), and not capacity or opportunity/trigger. This research, to our knowledge, represents the first comprehensive review of gamification use in health and fitness apps, and the potential to impact health behavior. The results show that use of gamification in health and fitness apps has become immensely popular, as evidenced by the number of apps found in the Apple App Store containing at least some components of gamification. This shows a lack of integrating important elements of behavioral theory from the app industry, which can potentially impact the efficacy of gamification apps to change behavior. Apps represent a very promising, burgeoning market and landscape in which to disseminate health behavior change interventions. Initial results show an abundant use of gamification in health and fitness apps, which necessitates the in-depth study and evaluation of the potential of gamification to change health behaviors.


Pazopanib in Patients with Osteosarcoma Metastatic to the Lung: Phase 2 Study Results and the Lessons for Tumor Measurement.
This single-arm, multicenter, phase 2 study evaluated the safety and antitumor activity of pazopanib in patients with unresectable, pulmonary metastatic osteosarcoma. Patients and Methods. Patients with pulmonary metastatic osteosarcoma unresponsive to chemotherapy were eligible. Patients who received prior tyrosine kinase inhibitor therapy were excluded. Pazopanib at 800 mg once daily was administered for 28-day cycles. Tumor responses were evaluated by local radiology assessment 1 month prior to and after initiation of treatment to calculate tumor doubling time and after every even numbered cycle. The primary endpoints were progression-free survival at 4 months, concomitant with a demonstrated 30% increase in tumor doubling time relative to the pretreatment growth rate. 12 patients (7 female) were enrolled. The study was terminated prematurely due to withdrawal of financial support by the sponsor. 8 subjects were eligible for the primary analysis, whereas 4 patients were in a predefined exploratory "slow-growing" cohort. In the "fast-growing" cohort, 3 of the 8 patients (37.5%) eligible for first-stage analysis were deemed "success" by the preplanned criteria, adequate to proceed to second-stage accrual. In addition, 1 of the 4 patients in the "slow-growing" cohort experienced a partial remission. Grade 1-2 diarrhea was the most common adverse event, and grade 3 events were infrequent. This study illustrates a novel method of demonstrating positive drug activity in osteosarcoma by increasing tumor doubling time, and this is further supported by a partial response in a patient with "slow-growing" disease. This trial is registered with NCT01759303.


Hepatic Fat in Participants With and Without Incident Diabetes in the Diabetes Prevention Program Outcome Study.
There is little information about fatty liver in prediabetes as it transitions to early diabetes. This study is aimed at evaluating the prevalence and determinants of fatty liver in the Diabetes Prevention Program (DPP). We measured liver fat as liver attenuation (LA) in Hounsfield units (HU) in 1876 participants at ~14 years following randomization into the DPP, which tested the effects of lifestyle or metformin interventions versus standard care to prevent diabetes. LA was compared among intervention groups and in those with versus without diabetes, and associations with baseline and follow-up measurements of anthropometric and metabolic covariates were assessed. There were no differences in liver fat between treatment groups at 14 years of follow-up. Participants with diabetes had lower LA (mean ± SD: 46 ± 16 vs 51 ± 14 HU; P < 0.001) and a greater prevalence of fatty liver (LA < 40 HU) (34% vs 17%; P < 0.001). Severity of metabolic abnormalities at the time of LA evaluation was associated with lower LA categories in a graded manner and more strongly in those with diabetes. Averaged annual fasting insulin (an index of insulin resistance [OR, 95% CI 1.76, 1.41-2.20]) waist circumference (1.63, 1.17-2.26), and triglyceride (1.42, 1.13-1.78), but not glucose, were independently associated with LA < 40 HU prevalence. Fatty liver is common in the early phases of diabetes development. The association of LA with insulin resistance, waist circumference, and triglyceride levels emphasizes the importance of these markers for hepatic steatosis in this population and that assessment of hepatic fat in early diabetes development is warranted.


Analyzing receptor assemblies in the cell membrane using fluorescence anisotropy imaging with TIRF microscopy.
Signaling within and between animal cells is controlled by the many receptor proteins in their membrane. They variously operate as trans-membrane monomers and homo- or hetero-dimers, and may assemble with ion-channels: analyses thereof are needed in studies of receptor actions in tissue physiology and pathology. Interactions between membrane proteins are detectable when pre-labeled with fluorophores, but a much fuller analysis is achievable via advanced optical techniques on living cells. In this context, the measurement of polarization anisotropy in the emitted fluorescence has been the least exploited. Here we demonstrate its methodology and particular advantages in the study of receptor protein assembly. Through excitation in both TIRF and EPI fluorescence illumination modes we are able to quantify and suppress contributions to the signal from extraneous intra-cellular fluorescence, and we show that the loss of fluorescence-polarization measured in membrane proteins reports on receptor protein assembly in real time. Receptor monomers and homo-dimers in the cell membrane can be analyzed quantitatively and for homo-dimers only a single fluorescent marker is needed, thus suppressing ambiguities that arise in alternative assays, which require multiple label moieties and which are thus subject to stoichiometric uncertainty.


Ion microprobe analysis of bone surface elements: effects of 1,25(OH)2D3.
When neonatal mouse calvariae are incubated with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] there is net calcium efflux from the bone into the medium. The effect of this enhanced cell-mediated Ca efflux on the relative concentrations of mineral 23Na, 39K, and 40Ca has not previously been studied. We used an imaging scanning ion microprobe, utilizing secondary ion mass spectrometry, to compare the relative ion concentrations of Na, K, and Ca on the surface, subsurface, and cross-section of cultured bone incubated in the presence of 1,25(OH)2D3 with the ion concentrations in similar regions of bone incubated in unaltered control medium. Changes in mineral ion concentration were correlated with net fluxes of Na, K, and Ca relative to bone. Calvariae incubated in control medium (24 h at pH approximately 7.40) have abundant surface Na and K relative to Ca (Na/Ca, 85 and K/Ca, 68), whereas the subsurface has less Na/Ca (21) and K/Ca (23), and on cross section the ratios of both Na/Ca (2.0) and K/Ca (1.9) decrease further. After incubation with 10(-8) M 1,25(OH)2D3, there is a significant increase in bone surface Na/Ca (154) and K/Ca (141) without a change in these ratios on the subsurface and a small fall in both ratios on cross section. The linear relationship between Na/Ca and K/Ca across the three regions of bone observed in control calvariae did not change with 1,25(OH)2D3 treatment. As determined by flux measurements there is a net efflux of Ca but not Na or K from bone.(ABSTRACT TRUNCATED AT 250 WORDS)


Using point-of-care C-reactive protein to guide antibiotic prescribing for lower respiratory tract infections in elderly nursing home residents (UPCARE): study design of a cluster randomized controlled trial.
Antibiotics are over-prescribed for lower respiratory tract infections (LRTI) in nursing home residents due to diagnostic uncertainty. Inappropriate antibiotic use is undesirable both on patient level, considering their exposure to side effects and drug interactions, and on societal level, given the development of antibiotic resistance. C-reactive protein (CRP) point-of-care testing (POCT) may be a promising diagnostic tool to reduce antibiotic prescribing for LRTI in nursing homes. The UPCARE study will evaluate whether the use of CRP POCT for suspected LRTI is (cost-) effective in reducing antibiotic prescribing in the nursing home setting. A cluster randomized controlled trial will be conducted in eleven nursing homes in the Netherlands, with the nursing home as the unit of randomization. Residents with suspected LRTI who reside at a psychogeriatric, somatic, or geriatric rehabilitation ward are eligible for study participation. Nursing homes in the intervention group will provide care as usual with the possibility to use CRP POCT, and the control group will provide care as usual without CRP POCT for residents with (suspected) LRTI. Data will be collected from September 2018 for approximately 1.5 year, using case report forms that are integrated in the electronic patient record system. The primary study outcome is antibiotic prescribing for suspected LRTI at index consultation (yes/no). This is the first randomised trial to evaluate the effect of nursing home access to and training in the use of CRP POCT on antibiotic prescribing for LRTI, yielding high-level evidence and contributing to antibiotic stewardship in the nursing home setting. The relatively broad inclusion criteria and the pragmatic study design add to the applicability and generalizability of the study results. Netherlands Trial Register, Trial NL5054. Registered 29 August 2018.