Implementation of an institutional program to improve clinical and financial outcomes of mechanically ventilated patients: one-year outcomes and lessons learned.
To determine the effect of an institutional approach to the care of patients requiring mechanical ventilation for longer than three consecutive days in five adult intensive care units (ICU) on clinical and financial outcomes. A multidisciplinary team was selected from five adult ICUs to design the approach. Planning occurred from August 1999 to September 2000. The process was called outcomes management (OM) and included an evidence-based clinical pathway, protocols for weaning and sedation use, and the selection of four advanced practice nurses (called outcomes managers) to manage and monitor the program. The project was completed in a 550-bed mid-Atlantic academic medical center. The ICUs included the following: coronary care, medical ICU, neuroscience ICU, surgical trauma ICU, and thoracic cardiovascular ICU. The sample included 595 pre-OM patients and 510 post-OM patients mechanically ventilated for greater than three consecutive days. Full implementation of the OM approach occurred in March 2001. Retrospective baseline (18 months pre-OM) and prospective (12 months OM) clinical and financial data were compared. Statistically significant differences in clinical outcomes were demonstrated in the managed patients compared with those managed before the institutional approach. Outcomes include ventilator duration (median days declined from ten to nine; p =.0001), ICU length of stay (median days declined from 15 to 12; p =.0008), hospital length of stay (median days declined from 22 to 20; p =.0001), and mortality rate (declined from 38% to 31%, p =.02). More than 3,000,000 US dollars cost savings were realized in the OM group. This institutional approach to the care of patients ventilated >3 days improved all clinical and financial outcomes of interest. To date, few similar initiatives have demonstrated similar results. The approach and lessons learned in this process improvement project may be helpful to other institutions attempting to improve outcomes in this vulnerable population.


The concept of mixed organic ligands in metal-organic frameworks: design, tuning and functions.
The research on metal-organic frameworks (MOFs) has been developing at an extraordinary pace in its two decades of existence, as judged by the exponential growth of novel structures and the constant expansion of its applicability and research scope. A major part of the research and its success are due to the vital role of the concept of mixed organic ligands in the design, tuning and functions. This perspective, therefore, reviews the recent advances in MOFs based on this concept, which is generally based on employing a small polydentate ligand (here labelled as "nodal ligand") to form either clusters, rods or layers, which are then connected by a second ditopic linker ligand to form the framework. The structures of the materials can be grouped into the following three categories: layer-spacer (usually known as pillared-layer), rod-spacer, and cluster-spacer based MOFs. Depending on the size and geometry of the spacer ligands, interpenetrations of frameworks are occasionally found. These MOFs show a wide range of properties such as (a) crystal-to-crystal transformations upon solvent modifications, post-synthetic metal exchange or ligand reactions, (b) gas sorption, solvent selectivity and purification, (c) specific catalysis, (d) optical properties including colour change, luminescence, non-linear optic, (e) short- and long range magnetic ordering, metamagnetism and reversible ground-state modifications and (f) drug and iodine carriers with controlled release. In the following, we will highlight the importance of the above concept in the design, tuning, and functions of a selection of existing MOFs having mixed organic ligands and their associated structures and properties. The results obtained so far using this concept look very promising for fine-tuning the pore size and shape for selective adsorption and specificity in catalytic reactions, which appears to be one way to propel the advances in the application and commercialization of MOFs.


Towards a phenome-wide catalog of human clinical traits impacted by genetic ancestry.
Racial/ethnic differences for commonly measured clinical variables are well documented, and it has been postulated that population-specific genetic factors may play a role. The genetic heterogeneity of admixed populations, such as African Americans, provides a unique opportunity to identify genomic regions and variants associated with the clinical variability observed for diseases and traits across populations. To begin a systematic search for these population-specific genomic regions at the phenome-wide scale, we determined the relationship between global genetic ancestry, specifically European and African ancestry, and clinical variables measured in a population of African Americans from BioVU, Vanderbilt University's biorepository linked to de-identified electronic medical records (EMRs) as part of the Epidemiologic Architecture using Genomics and Epidemiology (EAGLE) study. Through billing (ICD-9) codes, procedure codes, labs, and clinical notes, 36 common clinical and laboratory variables were mined from the EMR, including body mass index (BMI), kidney traits, lipid levels, blood pressure, and electrocardiographic measurements. A total of 15,863 DNA samples from non-European Americans were genotyped on the Illumina Metabochip containing ~200,000 variants, of which 11,166 were from African Americans. Tests of association were performed to examine associations between global ancestry and the phenotype of interest. Increased European ancestry, and conversely decreased African ancestry, was most strongly correlated with an increase in QRS duration, consistent with previous observations that African Americans tend to have shorter a QRS duration compared with European Americans. Despite known racial/ethnic disparities in blood pressure, European and African ancestry was neither associated with diastolic nor systolic blood pressure measurements. Collectively, these results suggest that this clinical population can be used to identify traits in which population differences may be due, in part, to population-specific genetics.


Predictors of use of complementary and alternative medicine by non-hodgkin lymphoma survivors and relationship to quality of life.
This study hypothesized that non-Hodgkin lymphoma (NHL) patients who used complementary and alternative medicine (CAM) would have higher health-related quality of life (HRQOL) and a greater perceived sense of control than nonusers. However, since CAM may predict HRQOL, and perceived control may be both associated with CAM use as well as being an independent predictor of HRQOL, the authors also sought to test whether perceived control mediated the relationship between CAM use and HRQOL. This was a cross-sectional study design. NHL survivors diagnosed between June 1, 1998 and August 31, 2001 were selected from the population-based SEER (Surveillance, Epidemiology, and End Results) cancer registry for Los Angeles County and were mailed a survey in 2003 that assessed CAM use and predictors of CAM use. The response rate was 54.8%; 319 provided complete data for analysis. Categories of CAM were defined according to the National Center for Complementary and Alternative Medicine guidelines. The authors measured survivors' cancer-related control using the Perceived Personal Control scale, a 4-question scale that was adapted from previously validated scales. HRQOL was measured using the mental component summary and physical component summary scores from the SF-36 v2.0. Bivariate and multivariable logistic and linear regression models were used to assess factors associated with CAM use and the association of CAM use with psychosocial health outcomes, respectively. Sixty-one percent of respondents reported using at least one CAM modality within the past 4 weeks, and 40% did so after excluding personal prayer and support groups. Younger age and higher education were significantly associated with greater CAM use as were higher perception of cancer-related control (P = .004) and more positive mental functioning (P = .016). Perception of control significantly mediated the association between CAM use and mental functioning (P < .001). CAM use may be related to more positive mental health-related quality of life by increasing patients' perception of perceived control over their health; however, cause and effect cannot be determined. Physicians should be aware that cancer survivors have a need to take an active role in improving their health.


An Outbreak of Gummosis of Mango Trees Caused by Lasiodiplodia theobromae in Guangxi, South China.
Mango (Mangifera indica L.) is an economically important fruit in southern provinces of China. In May 2012, field surveys including 2,250 mango trees were done in nine orchards of five different counties in Guangxi Province. An outbreak of gummosis was observed in the province involving over 30,000 ha with an average of 50% disease incidence (DI) and a maximum of 70% in some orchards. Until then, gummosis had been considered a common but not serious disease. In 2012, high temperatures in April and extensive rain in May favored increased disease development. Infected plants showed abundant gum secretion from branches, stems, and main trunks. Some branches died from the disease. During the early stages of infection, branches or stems turned brown followed by xylem necrosis and exudation of a milky sap. The sap turned yellow and finally formed amber gum within several days. Initially, the gum appeared as small droplets, increasing in number, and covering most of the branches and the trunk with bark cracking under severe conditions. On potato dextrose agar (PDA), isolates with similar morphology were consistently recovered from symptomatic plant tissues after surface sterilization in 75% ethanol for 30 seconds and then in 0.1% mercuric chloride for 1 min. Five single-spore isolates from five different locations in Guangxi Province were used to evaluate characteristics of the pathogen. On PDA, cultures were gray with an irregularly distributed, fast-growing, and fluffy aerial mycelium, showing a dark underside as the colony changed from greenish to black after 5 days at 28°C. After 1 month, cultures produced globose pycnidia. Conidia were elliptical and hyaline when immature, becoming dark brown and one-septate, longitudinally striate when mature, and ranged from 20.0 to 28.0 × 10.5 to 16.0 μm (average 23.3 × 13.7 μm). Paraphyses produced within the tissues of pycnidia were hyaline, cylindrical, nonseptate, and up to 61 μm long. The fungus was identified as Lasiodiplodia theobromae (Pat.) Griffon & Maubl. (=Botryosphaeria rhodina (Cooke) Arx) based on morphological and cultural characteristics (1,2). The rDNA internal transcribed spacer region of one isolate showed 100% identity to L. theobromae (GenBank HM346876.2) and was deposited in GenBank (JX982240). Pathogenicity of the five isolates was tested in the field on healthy tissues in June 2012. Five green twigs and five 3-year-old branches were used. Three wounds were made on each twig or branch with a sterilized needle. Mycelial plugs were placed on wounds and covered with Parafilm. Uncolonized PDA plugs were used as controls. Two weeks later, typical brown lesions were observed on inoculated branches, and gum exuded from infected wounds. No symptoms were seen on the controls. Koch's postulates were fulfilled by reisolation of L. theobromae from diseased branches. L. theobromae is well documented as a pathogen of mango. In China, the disease was observed in the 1990s in Hainan Province, and the causal agents were identified as L. theobromae and Colletotrichum gloeosporioides Penz. & Sacc based on morphological observation (3). To our knowledge, this is the most severe outbreak reported from China. References: (1) V. S. de Oliveira Costa et al. Eur. J. Plant Pathol. 127:509, 2010. (2) F. Wang et al. Plant Dis. 95:1378, 2011. (3) Q. C. Xiao et al. Tropical Crops Research (in Chinese) 2:25, 1995.


Gamma band activity in an auditory oddball paradigm studied with the wavelet transform.
To examine the characteristics of evoked and induced gamma band oscillatory responses occurring during P300 development in an auditory oddball paradigm. A time-frequency analysis method was applied to an auditory oddball paradigm in 7 healthy subjects. This method combines a multiresolution wavelet algorithm for signal extraction and the Gabor transform to represent the temporal evolution of the selected frequency components. Phase-locked or evoked activity and also non-phase-locked activity were computed for both standard and target stimuli. The gamma band frequency components differed between target and non-target stimuli processing. The study showed an early and mainly phase-locked oscillatory response appearing around 26--28 ms after both standard and target stimuli onset. This response showed a spectral peak around 44 Hz for both stimuli. A late oscillatory activity peaking at 37 Hz with a latency around 360 ms was observed appearing only for target stimuli. The latency of this late oscillatory activity had a high correlation (P=0.002) to the latency of the P300 wave. EEG signal analysis with wavelet transform allows the identification of an early oscillatory cortical response in the gamma frequency range, as well as a late P300-related response.


A red palm oil diet can reduce the effects of oxidative stress on rat spermatozoa.
Male Wistar rats (n = 54) received daily supplementation of red palm oil (RPO: 0, 2, 4 ml). Subgroups were subsequently injected with saline, cumene hydroperoxide (cHP, 10 μm) or t-butyl hydroperoxide (tbHP, 20 μm) over a 60-day period after which animals were sacrificed. Epididymal sperm motility, concentration, reactive oxygen species (ROS), lipid peroxidation and enzymes were measured. Sperm concentration, motility, superoxide dismutase (SOD) concentration, glutathione (GSH) and catalase (CAT) activities were significantly lower, while dichlorofluorescein (DCF) and malondialdehyde (MDA) were higher in sperm of hydroperoxide-treated animals compared to controls (P < 0.05). DCF and MDA levels were significantly lower, while SOD, CAT and GSH were significantly higher in the sperm of rats supplemented with RPO in combination with hydroperoxide treatment when compared to those receiving hydroperoxide and no RPO supplementation (P < 0.05). Moreover, the DCF, SOD, CAT and GSH levels in the RPO hydroperoxide groups did not differ from control values (P > 0.05). RPO supplementation can successfully attenuate the oxidative stress-induced sperm damage due to organic hydroperoxide exposure. We therefore propose that a daily intake of RPO supplement to the diet might be helpful in protecting males against the adverse effects of high ROS in sperm function and help preserve fertility.


Segmenting CT prostate images using population and patient-specific statistics for radiotherapy.
In the segmentation of sequential treatment-time CT prostate images acquired in image-guided radiotherapy, accurately capturing the intrapatient variation of the patient under therapy is more important than capturing interpatient variation. However, using the traditional deformable-model-based segmentation methods, it is difficult to capture intrapatient variation when the number of samples from the same patient is limited. This article presents a new deformable model, designed specifically for segmenting sequential CT images of the prostate, which leverages both population and patient-specific statistics to accurately capture the intrapatient variation of the patient under therapy. The novelty of the proposed method is twofold: First, a weighted combination of gradient and probability distribution function (PDF) features is used to build the appearance model to guide model deformation. The strengths of each feature type are emphasized by dynamically adjusting the weight between the profile-based gradient features and the local-region-based PDF features during the optimization process. An additional novel aspect of the gradient-based features is that, to alleviate the effect of feature inconsistency in the regions of gas and bone adjacent to the prostate, the optimal profile length at each landmark is calculated by statistically investigating the intensity profile in the training set. The resulting gradient-PDF combined feature produces more accurate and robust segmentations than general gradient features. Second, an online learning mechanism is used to build shape and appearance statistics for accurately capturing intrapatient variation. The performance of the proposed method was evaluated on 306 images of the 24 patients. Compared to traditional gradient features, the proposed gradient-PDF combination features brought 5.2% increment in the success ratio of segmentation (from 94.1% to 99.3%). To evaluate the effectiveness of online learning mechanism, the authors carried out a comparison between partial online update strategy and full online update strategy. Using the full online update strategy, the mean DSC was improved from 86.6% to 89.3% with 2.8% gain. On the basis of full online update strategy, the manual modification before online update strategy was introduced and tested, the best performance was obtained; here, the mean DSC and the mean ASD achieved 92.4% and 1.47 mm, respectively. The proposed prostate segmentation method provided accurate and robust segmentation results for CT images even under the situation where the samples of patient under radiotherapy were limited. A conclusion that the proposed method is suitable for clinical application can be drawn.


Context-specific drinking and social anxiety: The roles of anticipatory anxiety and post-event processing.
Individuals with clinically elevated social anxiety are especially vulnerable to alcohol-related problems, despite not drinking more than those with less anxiety. It is therefore important to identify contexts in which socially anxious persons drink more to inform intervention efforts. This study tested whether social anxiety was related to greater drinking before, during, or after a social event and whether such drinking was related to the psychosocial factors anticipatory anxiety or post-event processing (PEP; review of the social event). Among past-month drinkers, those with clinically elevated or higher social anxiety (HSA; n = 212) reported more anticipatory anxiety, more pre-event drinking to manage anxiety, and PEP than those with normative or lower social anxiety (LSA; n = 365). There was a significant indirect effect of social anxiety on pre-drinking via anticipatory anxiety. Social anxiety was related to more drinking during the event indirectly via the serial effects of anticipatory anxiety and pre-drinking. Unexpectedly, PEP did not mediate or moderate the relation between social anxiety and post-event drinking. In sum, anticipatory anxiety was related to more drinking before, during, and after a social event and HSA drinkers were especially vulnerable to drinking more to manage this anxiety, which increased drinking before and during the event. This effect was specific to anticipatory anxiety and not evident for another social anxiety-specific risk factor, PEP. Thus, anticipatory anxiety may be an important therapeutic target for drinkers generally and may be especially important among HSA drinkers.


CXCR4/SDF1 interaction inhibits the primordial to primary follicle transition in the neonatal mouse ovary.
The molecular mechanisms behind the entry of the primordial follicle into the growing follicle pool remain poorly understood. To investigate this process further, a microarray-based comparison was undertaken between 2-day postpartum mouse ovaries consisting of primordial follicles/naked oocytes only and those with both primordial follicles and newly activated follicles (7-day postpartum). Gene candidates identified included the chemoattractive cytokine stromal derived factor-1 (SDF1) and its receptor CXCR4. SDF1 and CXCR4 have been implicated in a variety of physiological processes including the migration of embryonic germ cells to the gonads. SDF1-alpha expression increased with the developmental stage of the follicle. Embryonic expression was found to be dichotomous post-germ cell migration, with low expression in the female. Immunohistochemical studies nonetheless indicate that the autocrine pattern of expression ligand and receptor begins during embryonic life. Addition of recombinant SDF1-alpha to neonatal mouse ovaries in vitro resulted in significantly higher follicle densities than for control ovaries. TUNEL analysis indicated no detectable difference in populations of apoptotic cells of treated or control ovaries. Treated ovaries also contained a significantly lower percentage of activated follicles as determined by measurement of oocyte diameter and morphological analysis. Treatment of cultured ovaries with an inhibitor of SDF1-alpha, AMD3100, ablated the effect of SDF1-alpha. By retaining follicles in an unactivated state, SDF1/CXCR4 signaling may play an important role in maintaining the size and longevity of the primordial follicle pool.


The varieties of contemplative experience: A mixed-methods study of meditation-related challenges in Western Buddhists.
Buddhist-derived meditation practices are currently being employed as a popular form of health promotion. While meditation programs draw inspiration from Buddhist textual sources for the benefits of meditation, these sources also acknowledge a wide range of other effects beyond health-related outcomes. The Varieties of Contemplative Experience study investigates meditation-related experiences that are typically underreported, particularly experiences that are described as challenging, difficult, distressing, functionally impairing, and/or requiring additional support. A mixed-methods approach featured qualitative interviews with Western Buddhist meditation practitioners and experts in Theravāda, Zen, and Tibetan traditions. Interview questions probed meditation experiences and influencing factors, including interpretations and management strategies. A follow-up survey provided quantitative assessments of causality, impairment and other demographic and practice-related variables. The content-driven thematic analysis of interviews yielded a taxonomy of 59 meditation-related experiences across 7 domains: cognitive, perceptual, affective, somatic, conative, sense of self, and social. Even in cases where the phenomenology was similar across participants, interpretations of and responses to the experiences differed considerably. The associated valence ranged from very positive to very negative, and the associated level of distress and functional impairment ranged from minimal and transient to severe and enduring. In order to determine what factors may influence the valence, impact, and response to any given experience, the study also identified 26 categories of influencing factors across 4 domains: practitioner-level factors, practice-level factors, relationships, and health behaviors. By identifying a broader range of experiences associated with meditation, along with the factors that contribute to the presence and management of experiences reported as challenging, difficult, distressing or functionally impairing, this study aims to increase our understanding of the effects of contemplative practices and to provide resources for mediators, clinicians, meditation researchers, and meditation teachers.


Managing nitrogen to restore water quality in China.
The nitrogen cycle has been radically changed by human activities1. China consumes nearly one third of the world's nitrogen fertilizers. The excessive application of fertilizers2,3 and increased nitrogen discharge from livestock, domestic and industrial sources have resulted in pervasive water pollution. Quantifying a nitrogen 'boundary'4 in heterogeneous environments is important for the effective management of local water quality. Here we use a combination of water-quality observations and simulated nitrogen discharge from agricultural and other sources to estimate spatial patterns of nitrogen discharge into water bodies across China from 1955 to 2014. We find that the critical surface-water quality standard (1.0 milligrams of nitrogen per litre) was being exceeded in most provinces by the mid-1980s, and that current rates of anthropogenic nitrogen discharge (14.5 ± 3.1 megatonnes of nitrogen per year) to fresh water are about 2.7 times the estimated 'safe' nitrogen discharge threshold (5.2 ± 0.7 megatonnes of nitrogen per year). Current efforts to reduce pollution through wastewater treatment and by improving cropland nitrogen management can partially remedy this situation. Domestic wastewater treatment has helped to reduce net discharge by 0.7 ± 0.1 megatonnes in 2014, but at high monetary and energy costs. Improved cropland nitrogen management could remove another 2.3 ± 0.3 megatonnes of nitrogen per year-about 25 per cent of the excess discharge to fresh water. Successfully restoring a clean water environment in China will further require transformational changes to boost the national nutrient recycling rate from its current average of 36 per cent to about 87 per cent, which is a level typical of traditional Chinese agriculture. Although ambitious, such a high level of nitrogen recycling is technologically achievable at an estimated capital cost of approximately 100 billion US dollars and operating costs of 18-29 billion US dollars per year, and could provide co-benefits such as recycled wastewater for crop irrigation and improved environmental quality and ecosystem services.


Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy.
The common form of myotonic dystrophy (DM1) is associated with the expression of expanded CTG DNA repeats as RNA (CUG(exp) RNA). To test whether CUG(exp) RNA creates a global splicing defect, we compared the skeletal muscle of two mouse models of DM1, one expressing a CTG(exp) transgene and another homozygous for a defective muscleblind 1 (Mbnl1) gene. Strong correlation in splicing changes for approximately 100 new Mbnl1-regulated exons indicates that loss of Mbnl1 explains >80% of the splicing pathology due to CUG(exp) RNA. In contrast, only about half of mRNA-level changes can be attributed to loss of Mbnl1, indicating that CUG(exp) RNA has Mbnl1-independent effects, particularly on mRNAs for extracellular matrix proteins. We propose that CUG(exp) RNA causes two separate effects: loss of Mbnl1 function (disrupting splicing) and loss of another function that disrupts extracellular matrix mRNA regulation, possibly mediated by Mbnl2. These findings reveal unanticipated similarities between DM1 and other muscular dystrophies.


Design for human factors (DfHF): a grounded theory for integrating human factors into production design processes.
The 'design for human factors' grounded theory explains 'how' human factors (HF) went from a reactive, after-injury programme in safety, to being proactively integrated into each step of the production design process. In this longitudinal case study collaboration with engineers and HF Specialists in a large electronics manufacturer, qualitative data (e.g. meetings, interviews, observations and reflections) were analysed using a grounded theory methodology. The central tenet in the theory is that when HF Specialists acclimated to the engineering process, language and tools, and strategically aligned HF to the design and business goals of the organisation, HF became a means to improve business performance. This led to engineers 'pulling' HF Specialists onto their team. HF targets were adopted into engineering tools to communicate HF concerns quantitatively, drive continuous improvement, visibly demonstrate change and lead to benchmarking. Senior management held engineers accountable for HF as a key performance indicator, thus integrating HF into the production design process. Practitioner Summary: Research and practice lack explanations about how HF can be integrated early in design of production systems. This three-year case study and the theory derived demonstrate how ergonomists changed their focus to align with design and business goals to integrate HF into the design process.


Auditory event-related potential (ERP) and difference-wave topography in schizophrenic patients with/without active hallucinations and delusions: a comparison with young obsessive-compulsive disorder (OCD) and healthy subjects.
Event-related potentials (ERPS) in schizophrenics have been reported to show a reduced P3 on the left and less frontal mismatch negativity (MMN). But the specificity of such findings to component, its locus, the type of eliciting event and patient group remains uncertain. Hence, we examined ERP topography for P3, N2 and 3 precursor peaks according to stimulus (3-tone oddball), attention condition (diffuse/focused) and four types of difference-waves. We contrasted 24 healthy and 13 OCD subjects with schizophrenic patients with high versus low ratings of active delusions and hallucinations (12 paranoid-hallucinatory, PH; 12 nonparanoid, NP). P3 peaks were delayed and reduced in NP and PH groups. Midline peaks were usual in focused attention and a right bias in diffuse attention. P3 responses to irrelevant standards remained lateral in NP and small in OCD patients. All showed a small left and anterior bias in the P3-like peak in difference-waves. Mismatch negativity waveform (MMN) peaks shifted to the right in OCD, to both sides in PH and posteriorly in NP patients. Frontal processing negativity was biased to the left (early) in NP and to the right (late) in PH groups. Early peak topography reflected some later changes (e.g. PH and NP groups; P1-like peak, right bias absent; N1-like peak depressed and widely distributed; NP group, P2-like peak smaller on the left). In OCD patients, peak latencies were topographically undifferentiated (P1, P2) or delayed (N2). The OCD group showed an unusual regional allocation of processing effort. Before 200 ms frontocentral activity was more widespread in Ph and NP groups. Lateralization of negativity in target- and nontarget-derived difference-waves may reflect differential disruption of the frontal-temporal dialogue in registering important vs unimportant features. NP patients, in particular, treated irrelevant stimuli anomalously.


Longitudinal influence of musculo-skeletal injuries and extra physical education on physical fitness in schoolchildren.
The aims of this study were to investigate if (A) injuries and (B) increased physical education (PE) influenced the development of physical fitness in schoolchildren. Simultaneously, to investigate if a possible PE effect was modified by sport participation outside school hours. This was a longitudinal controlled school-based study. Six schools with 270 min of PE (extra PE) and four schools with 90 min of PE were followed up for 2.5 years. In total, 1054 children were included for analysis (normal PE = 443, extra PE = 611). Development in fitness was analyzed using composite z-scores from six fitness tests measured four times. Information of injury and sport was derived from weekly automated mobile phone text messages surveying the presence of musculo-skeletal pain and organized sport participation. Injury and extra PE both influenced the development of physical fitness. Injury decreased development of physical fitness with -1.01 composite z-score units (95% CI: -1.57; -0.45). Extra PE increased physical fitness development with 0.80 (95% CI: 0.49; 1.10) composite z-score units. The influence of injury was not dependent on extra PE. No modifying effect was found by mean weekly sport participation outside school hours. In conclusion, extra PE had a positive effect, whereas injuries had a negative effect on physical fitness development in schoolchildren.


Determination of nanoparticle size distribution together with density or molecular weight by 2D analytical ultracentrifugation.
Nanoparticles are finding many research and industrial applications, yet their characterization remains a challenge. Their cores are often polydisperse and coated by a stabilizing shell that varies in size and composition. No single technique can characterize both the size distribution and the nature of the shell. Advances in analytical ultracentrifugation allow for the extraction of the sedimentation (s) and diffusion coefficients (D). Here we report an approach to transform the s and D distributions of nanoparticles in solution into precise molecular weight (M), density (ρ(P)) and particle diameter (d(p)) distributions. M for mixtures of discrete nanocrystals is found within 4% of the known quantities. The accuracy and the density information we achieve on nanoparticles are unparalleled. A single experimental run is sufficient for full nanoparticle characterization, without the need for standards or other auxiliary measurements. We believe that our method is of general applicability and we discuss its limitations.


Influence of age on deterioration of the remnant kidney in uninephrectomized rats.
To investigate the influence of age on the remnant kidney, unilateral nephrectomy was performed in rats at 1 day (group N-0), 2 weeks (group N-2), 4 weeks (group N-4) or 8 weeks (group N-8) of age. Serial changes in urinary protein during 48 weeks after the uninephrectomy and blood chemistries and renal histology at week 48 were compared between the groups. The increase in proteinuria was significantly greater in groups N-0, N-2 and N-4 than in group N-8 from week 32 to week 48 after the uninephrectomy. There was no significant difference in urinary protein between groups N-0, N-2 and N-4. Hypoproteinaemia and hypoalbuminaemia were also more severe in groups N-0, N-2 and N-4 than in group N-8 at week 48. A compensatory renal growth in groups N-0 and N-4 was significantly greater than that in group N-8 at week 48 after the uninephrectomy. Focal and segmental glomerular sclerosis, a characteristic finding in the uninephrectomy groups, was significantly more marked in groups N-0, N-2 and N-4 than in group N-8 at week 48. We conclude that uninephrectomy at young ages leads to increased incidence of glomerular sclerosis in rats compared with uninephrectomy in the adult.


Associations between physical activity, sedentary behavior, and glycemic control in a large cohort of adolescents with type 1 diabetes: the Hvidoere Study Group on Childhood Diabetes.
The Hvidoere Study Group on Childhood Diabetes has demonstrated persistent differences in metabolic outcomes between pediatric diabetes centers. These differences cannot be accounted for by differences in demographic, medical, or treatment variables. Therefore, we sought to explore whether differences in physical activity or sedentary behavior could explain the variation in metabolic outcomes between centers. An observational cross-sectional international study in 21 centers, with demographic and clinical data obtained by questionnaire from participants. Hemoglobin A1c (HbA1c) levels were assayed in one central laboratory. All individuals with diabetes aged 11-18 yr (49.4% female), with duration of diabetes of at least 1 yr, were invited to participate. Individuals completed a self-reported measure of quality of life (Diabetes Quality of Life - Short Form [DQOL-SF]), with well-being and leisure time activity assessed using measures developed by Health Behaviour in School Children WHO Project. Older participants (p < 0.001) and females (p < 0.001) reported less physical activity. Physical activity was associated with positive health perception (p < 0.001) but not with glycemic control, body mass index, frequency of hypoglycemia, or diabetic ketoacidosis. The more time spent on the computer (r = 0.06; p < 0.05) and less time spent doing school homework (r = -0.09; p < 0.001) were associated with higher HbA1c. Between centers, there were significant differences in reported physical activity (p < 0.001) and sedentary behavior (p < 0.001), but these differences did not account for center differences in metabolic control. Physical activity is strongly associated with psychological well-being but has weak associations with metabolic control. Leisure time activity is associated with individual differences in HbA1c but not with intercenter differences.


The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology.
Observational studies indicate that psychologic factors strongly influence the course of coronary artery disease (CAD). In this review, we examine new epidemiologic evidence for the association between psychosocial risk factors and CAD, identify pathologic mechanisms that may be responsible for this association, and describe a paradigm for studying positive psychologic factors that may act as a buffer. Because psychosocial risk factors are highly prevalent and are associated with unhealthy lifestyles, we describe the potential role of cardiologists in managing such factors. Management approaches include routinely screening for psychosocial risk factors, referring patients with severe psychologic distress to behavioral specialists, and directly treating patients with milder forms of psychologic distress with brief targeted interventions. A number of behavioral interventions have been evaluated for their ability to reduce adverse cardiac events among patients presenting with psychosocial risk factors. Although the efficacy of stand-alone psychosocial interventions remains unclear, both exercise and multifactorial cardiac rehabilitation with psychosocial interventions have demonstrated a reduction in cardiac events. Furthermore, recent data suggest that psychopharmacologic interventions may also be effective. Despite these promising findings, clinical practice guidelines for managing psychosocial risk factors in cardiac practice are lacking. Thus, we review new approaches to improve the delivery of behavioral services and patient adherence to behavioral recommendations. These efforts are part of an emerging field of behavioral cardiology, which is based on the understanding that psychosocial and behavioral risk factors for CAD are not only highly interrelated, but also require a sophisticated health care delivery system to optimize their effectiveness.


Holographic sol-gel monoliths: optical properties and application for humidity sensing.
Sol-gel monoliths based on SiO2, TiO2 and ZrO2 with holographic colourful diffraction on their surfaces were obtained via a sol-gel synthesis and soft lithography combined method. The production was carried out without any additional equipment at near room temperature and atmospheric pressure. The accurately replicated wavy structure with nanoscale size of material particles yields holographic effect and its visibility strongly depends on refractive index (RI) of materials. Addition of multi-walled carbon nanotubes (MWCNTs) in systems increases their RI and lends absorbing properties due to extremely high light absorption constant. Further prospective and intriguing applications based on the most successful samples, MWCNTs-doped titania, were investigated as reversible optical humidity sensor. Owing to such property as reversible resuspension of TiO2 nanoparticles while interacting with water, it was proved that holographic xerogels can repeatedly act as humidity sensors. Materials which can be applied as humidity sensors in dependence on holographic response were discovered for the first time.


Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer.
Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). Here, we report a role for the NAD+-dependent histone deacetylase SIRT1 in the control of anti-bacterial defense. Mice with an intestinal specific Sirt1 deficiency (Sirt1int-/-) have more Paneth and goblet cells with a consequent rearrangement of the gut microbiota. From a mechanistic point of view, the effects on mouse intestinal cell maturation are mediated by SIRT1-dependent changes in the acetylation status of SPDEF, a master regulator of Paneth and goblet cells. Our results suggest that targeting SIRT1 may be of interest in the management of IBD and CAC.


Plant defense responses in opium poppy cell cultures revealed by liquid chromatography-tandem mass spectrometry proteomics.
Opium poppy (Papaver somniferum) produces a diverse array of bioactive benzylisoquinoline alkaloids, including the narcotic analgesic morphine and the antimicrobial agent sanguinarine. In contrast to the plant, cell cultures of opium poppy do not accumulate alkaloids constitutively but produce sanguinarine in response to treatment with certain fungal-derived elicitors. The induction of sanguinarine biosynthesis provides a model platform to characterize the regulation of benzylisoquinoline alkaloid pathways and other defense responses. Proteome analysis of elicitor-treated opium poppy cell cultures by two-dimensional denaturing-polyacrylamide gel electrophoresis coupled with liquid chromatography-tandem mass spectrometry facilitated the identification of 219 of 340 protein spots based on peptide fragment fingerprint searches of a combination of databases. Of the 219 hits, 129 were identified through pre-existing plant proteome databases, 63 were identified by matching predicted translation products in opium poppy-expressed sequence tag databases, and the remainder shared evidence from both databases. Metabolic enzymes represented the largest category of proteins and included S-adenosylmethionine synthetase, several glycolytic, and a nearly complete set of tricarboxylic acid cycle enzymes, one alkaloid, and several other secondary metabolic enzymes. The abundance of chaperones, heat shock proteins, protein degradation factors, and pathogenesis-related proteins provided a comprehensive proteomics view on the coordination of plant defense responses. Qualitative comparison of protein abundance in control and elicitor-treated cell cultures allowed the separation of induced and constitutive or suppressed proteins. DNA microarrays were used to corroborate increases in protein abundance with a corresponding induction in cognate transcript levels.


An outer segment localization signal at the C terminus of the photoreceptor-specific retinol dehydrogenase.
Photoreceptor retinol dehydrogenase (prRDH) is a membrane-associated cytosolic protein that localizes to the outer segments (OS) of rods and cones. Here, we demonstrate that the C-terminal 16 amino acids of prRDH confer membrane association as well as cone and rod OS targeting on a linked green fluorescent protein. Membrane association in transfected 293 cells and in transgenic Xenopus photoreceptors is mediated by fatty acylation at one or more evolutionarily conserved cysteines within the prRDH C-terminal tail. In bovine OS, native prRDH is similarly acylated, and hydrolysis of this linkage releases the protein from the membrane. Efficient OS localization requires both membrane association and the prRDH sequence. (V/I)XPX at the extreme C terminus, which closely resembles the C-terminal sequence that targets opsin/rhodopsin to the OS. Taken together, these data imply that the C-terminal. (V/I)XPX sequence is a general OS localization signal that can function in the context of both integral and peripheral membrane proteins. This strategy for OS localization resembles those used for protein localization to mitochondria, peroxisomes, endosomes, and endoplasmic reticulum; in each case, a short N- or C-terminal sequence is shared among structurally diverse proteins that are targeted to the same subcellular destination.


Immunological tolerance. Dissociation between in vivo and in vitro reactivity in parabiosed mice.
Although most mouse strain combinations succumb to a lethal wasting disease when parabiosed across a strong histocompatibility (H-2) barrier, a high proportion of DBA mice parabiosed to DBA/C3H F(1) hybrids survive and appear healthy. DBA mice accept C3H skin grafts following parabiosis, and may therefore be considered operationally tolerant of C3H antigens. Nonetheless, spleen cells from long-term DBA and F(1) parabionts give normal and enhanced responses, respectively, to C3H antigens in mixed lymphocyte culture (MLC). This indicates that the tolerance mechanism can distinguish between MLC recognition reactivity and in vivo effector reactivity, and that the former can therefore exist in the absence of the latter.


Effect of postactivation potentiation on swimming starts in international sprint swimmers.
The aim of this study was to investigate the effects of postactivation potentiation (PAP) on swim start performance (time to 15 m) in a group of international sprint swimmers. Nine international sprint swimmers (7 men and 2 women) volunteered and gave informed consent for this study, which was approved by the university ethics committee. Initially, swimmers performed a countermovement jump (CMJ) on a portable force platform (FP) at baseline and at the following time points ∼15 seconds, 4, 8, 12, and 16 minutes after a PAP stimulus (1 set of 3 repetitions at 87% 1 repetition maximum [RM]) to individually determine the recovery time required to observe enhanced muscle performance. On 2 additional days, swimmers performed a swim start to 15 m under 50-m freestyle race conditions, which was preceded by either their individualized race specific warm-up or a PAP stimulus (1 set of 3 repetitions at 87% 1RM). Both trials were recorded on 2 cameras operating at 50 Hz with camera 1 located at the start and camera 2 at the 15-m mark. Peak vertical force (PVF) and peak horizontal force (PHF) were measured during all swim starts from a portable FP placed on top of the swim block. A repeated measures analysis of variance revealed a significant time effect with regard to power output (PO) (F = 20.963, p < 0.01) and jump height (JH) (F = 14.634, p < 0.01) with a paired comparison indicating a significant increase in PO and JH after 8 minutes of recovery from the PAP stimulus. There was a significant increase in both PHF and PVF after the PAP stimulus compared to the swim-specific warm-up during the swim start (PHF 770 ± 228 vs. 814 ± 263 N, p = 0.018; PVF: 1,462 ± 280 vs. 1,518 ± 311 N, p = 0.038); however, time to 15 m was the same when both starts were compared (7.1 ± 0.8 vs. 7.1 ± 0.8 seconds, p = 0.447). The results from this study indicate that muscle performance during a CMJ is enhanced after a PAP stimulus providing adequate recovery (∼8 minutes) is given between the 2 activities. In addition, this study demonstrated that swimmers performed equally well in terms of time to 15 m when a PAP stimulus was compared to their individualized race specific warm-up and indicates that PAP may be a useful addition to a warm-up protocol before races. However, more research is required to fully understand the role PAP plays in swim performance.


Salient, Irrelevant Sounds Reflexively Induce Alpha Rhythm Desynchronization in Parallel with Slow Potential Shifts in Visual Cortex.
Recent findings suggest that a salient, irrelevant sound attracts attention to its location involuntarily and facilitates processing of a colocalized visual event [McDonald, J. J., Störmer, V. S., Martinez, A., Feng, W. F., & Hillyard, S. A. Salient sounds activate human visual cortex automatically. Journal of Neuroscience, 33, 9194-9201, 2013]. Associated with this cross-modal facilitation is a sound-evoked slow potential over the contralateral visual cortex termed the auditory-evoked contralateral occipital positivity (ACOP). Here, we further tested the hypothesis that a salient sound captures visual attention involuntarily by examining sound-evoked modulations of the occipital alpha rhythm, which has been strongly associated with visual attention. In two purely auditory experiments, lateralized irrelevant sounds triggered a bilateral desynchronization of occipital alpha-band activity (10-14 Hz) that was more pronounced in the hemisphere contralateral to the sound's location. The timing of the contralateral alpha-band desynchronization overlapped with that of the ACOP (∼240-400 msec), and both measures of neural activity were estimated to arise from neural generators in the ventral-occipital cortex. The magnitude of the lateralized alpha desynchronization was correlated with ACOP amplitude on a trial-by-trial basis and between participants, suggesting that they arise from or are dependent on a common neural mechanism. These results support the hypothesis that the sound-induced alpha desynchronization and ACOP both reflect the involuntary cross-modal orienting of spatial attention to the sound's location.


Population study of 1311 C/T polymorphism of Glucose 6 Phosphate Dehydrogenase gene in Pakistan - an analysis of 715 X-chromosomes.
Nucleotide 1311 polymorphism at exon 11 of G6PD gene is widely prevalent in various populations of the world. The aim of the study was to evaluate 1311 polymorphism in subjects carrying G6PD Mediterranean gene and in general population living in Pakistan. Patients already known to be G6PD deficient were tested for 563C-T (G6PD Mediterranean) and 1311 C-T mutation through RFLP based PCR and gene sequencing. A control group not known to be G6PD deficient was tested for 1311C/T only.C-T transition at nt 1311 was detected in 60/234 X-chromosomes with 563 C-T mutation (gene frequency of 0.26) while in 130 of normal 402 X-chromosomes (gene frequency of 0.32). We conclude that 1311 T is a frequent polymorphism both in general populations and in subjects with G6PD Mediterranean gene in Pakistan. The prevalence is higher compared to most of the populations of the world. The present study will help in understanding genetic basis of G6PD deficiency in Pakistani population and in developing ancestral links of its various ethnic groups.


The paradox of non-evidence based, publicly funded complementary alternative medicine in the English National Health Service: An explanation.
Despite the unproven effectiveness of many practices that are under the umbrella term 'complementary alternative medicine' (CAM), there is provision of CAM within the English National Health Service (NHS). Moreover, although the National Institute for Health and Care Excellence was established to promote scientifically validated medicine in the NHS, the paradox of publicly funded, non-evidence based CAM can be explained as linked with government policy of patient choice and specifically patient treatment choice. Patient choice is useful in the political and policy discourse as it is open to different interpretations and can be justified by policy-makers who rely on the traditional NHS values of equity and universality. Treatment choice finds expression in the policy of personalised healthcare linked with patient responsibilisation which finds resonance in the emphasis CAM places on self-care and self-management. More importantly, however, policy-makers also use patient choice and treatment choice as a policy initiative with the objective of encouraging destabilisation of the entrenched healthcare institutions and practices considered resistant to change. This political strategy of system reform has the unintended, paradoxical consequence of allowing for the emergence of non-evidence based, publicly funded CAM in the NHS. The political and policy discourse of patient choice thus trumps evidence based medicine, with patients that demand access to CAM becoming the unwitting beneficiaries.


Questioning the dichotomy: A Latent profile analysis of ecological management practices in Swedish agriculture.
Currently, farmers who are not certified according to organic certification schemes are considered to be conventional farmers. Discussions in the farming sector reveal a view that the current organic classification system is too narrow and does not account for the full heterogeneity of the ecological practices that are prevalent in the agricultural sector. The failure to recognise practices within conventional farming, such as low-input farming or conservation agriculture, may therefore undermine efforts to adopt ecological practices. This study investigates heterogeneity in farmer uptake of management practices using factor analysis for dimension reduction and Latent Profile Analysis (LPA) for identification of farmer segments. The findings reveal four farmer profiles with a varying degree of use of chemicals and ecological, alternative, or mixed management approaches. Using seemingly unrelated regression, we find that being certified according to the Swedish organic certification scheme KRAV, or the EU organic label, does not have an impact on a farmer's profile, suggesting that the data do not support the organic/conventional dichotomy. Instead, age, farming income and geographical location are to a greater degree the key factors in determining the larger farmer profile compared with the smaller, more diversified farmer profiles.


Evolution of External Health Costs of Electricity Generation in the Baltic States.
Implementation of strict policies for mitigating climate change has a direct impact on public health as far as the external health costs of electricity generation can be reduced, thanks to the reduction of emission of typical pollutants by switching to cleaner low carbon fuels and achieving energy efficiency improvements. Renewables have lower external health costs due to the lower life cycle emission of typical air pollutants linked to electricity generation, such as SO2, NOx, particulate matter, NH3, or NMVOC (Non-methane volatile organic compounds), which all appear to have serious negative effects on human health. Our case study performed in the Baltic States analyzed the dynamics of external health costs in parallel with the dynamics of the main health indicators in these countries: life expectancy at birth, mortality rates, healthy life years, self-perceived health, and illness indicators. We employed the data for external health costs retrieved from the CASES database, as well as the health statistics data compiled from the EUROSTAT database. The time range of the study was 2010-2018 due to the availability of consistent health indicators for the EU Member States. Our results show that the decrease of external health costs had a positive impact on the increase of the self-perceived good health and reduction of long-standing illness as well as the decrease of infant death rate. Our conclusions might be useful for other countries as well as for understanding the additional benefits of climate change mitigation policies and tracking their positive health impacts. The cooperation initiatives on clean energy and climate change mitigation between countries like One Belt One Road initiative by the Chinese government can also yield additional benefits linked to the public health improvements.


Teen parties: who has parties, what predicts whether there is alcohol and who supplies the alcohol?
This study explores which youth are more likely to have parties at home, what factors are associated with the presence of alcohol at parties, and who supplies the alcohol. We collected data in 2011 and 2012 through telephone interviews with 1,121 teens living in 50 mid-sized California cities. Overall, about a quarter of teens reported having had a party at their house in the past 12 months, of whom 39 % reported that there was alcohol at their last party. Multiple sources supplied alcohol for most parties. Seventy-two percent of those having a party stated that at least one of their parents knew about their last party, and 64 % reported that a parent was home at least part of the time. Seventy percent of youth who hosted a party with alcohol said that their parent(s) definitely knew that there was alcohol at the party, 24 % replied that their parent(s) probably knew, and only 5 % said that their parent(s) did not know that there was alcohol at the party. Logistic regression analyses indicated that youth with parents who host parties at home are themselves more likely to host parties at home. Having alcohol at a party was positively related to the age of the teen and the number of guests attending, and was negatively related to parents' awareness of the party. However, we found no relationship between whether a parent was at home at the time of the party and whether it included alcohol. These findings suggest that teens who have parties with alcohol at home have parents who know that there is alcohol at the party, even though only a small number of parents provided alcohol for the party.


Characterization of stanniocalcin 1 binding and signaling in gill cells of Japanese eels.
Stanniocalcin 1 (STC1) is a hypocalcemic hormone that is known to play an important role in calcium metabolism in teleost fish. An increase in blood Ca(2) (+) levels stimulates its synthesis and release. The biological action of STC1 inhibits gill Ca(2) (+) transport (GCAT), but we as yet have no clear understanding of how STC1 inhibits GCAT. In the present study, we characterized the binding, signaling, and action of STC1 on gill cells. Treatment of gill cell cultures with the extracts of corpuscles of Stannius or recombinant STC1 proteins (STC1-V5) led to an increase in cytosolic cAMP levels. Using in situ ligand-binding assays, we demonstrated that STC1-V5 binds to both lamellar and inter-lamellar regions of gill sections. The binding sites were significantly increased in gill sections obtained from fish adapted to high-Ca(2) (+) (2 mM) freshwater (FW) as compared with those from fish adapted to low-Ca(2) (+) (0.2 mM) FW. Receptor-binding assays illustrated specific binding of STC1-alkaline phosphatase to plasma membrane (Kd of 0.36 nM), mitochondria (Kd of 0.41 nM), and nuclear (Kd of 0.71 nM) preparations from gill cells. STC1 binding capacity was significantly greater in the plasma membrane preparations of gills obtained from fish adapted to high-Ca(2) (+) FW. Using isolated pavement cells and mitochondria-rich cells in cAMP assays, we obtained results indicating that both cell types responded to STC1. To illustrate the biological action of STC1, we conducted Ca(2) (+) imaging experiments to demonstrate the effects of STC1 on thapsigargin-induced elevation of cytosolic Ca(2) (+). Our results indicated that STC1 exerted its inhibitory action via a cAMP pathway to lower intracellular Ca(2) (+) levels. Intriguingly, we were able to block the action of STC1 using an inhibitor, NS-398, of cyclooxygenase-2 (COX-2), which is known to stimulate the activity of sarcoplasmic and endoplasmic reticulum Ca(2) (+)-ATPase (SERCA). A follow-up experiment in which gill cells were incubated with STC1 revealed a downregulation of the epithelial Ca(2) (+) channel (ecacl) but an upregulation of cox-2 expression. The ECaCl is a gatekeeper for Ca(2) (+) entry, whereas COX-2 mediates an activation of SERCA. Taking these results together, the present study is, to our knowledge, the first to provide evidence of STC1 binding and signaling as well as the first to decipher the mechanism of the effect of STC1 on fish gills.


Segmenting cardiac-related data using sleep stages increases separation between normal subjects and apnoeic patients.
Inter-patient comparisons of cardiovascular metrics indicative of patient health have been shown to be successful in differentiating patients on a group rather than an individual level. This is in part due to the range of mental (as well as physical) activity-based variations for each patient and the difficulty assessing physical and mental activity during conscious states. In order to provide an objective scale for measuring central nervous system activity during sleep, the heart rate (RR) interval time series is divided into coarse sleep stage segments in which the LF/HF-ratio (the relative balance between low and high frequency power) is estimated for age and sex-matched populations of apnoeic and healthy subjects. Activity-based noise is therefore reduced and a more useful comparison of heart rate variability can be made. Additionally, the spectral estimation performances of the FFT and the Lomb-Scargle periodogram (LSP), a Fourier-based technique for unevenly sampled time series are compared. Separation of patients according to condition is shown to be more pronounced when using the LSP than the FFT. Furthermore, separation is found to be most marked in slow wave sleep.


Husbands' involvement in delivery care utilization in rural Bangladesh: A qualitative study.
A primary cause of high maternal mortality in Bangladesh is lack of access to professional delivery care. Examining the role of the family, particularly the husband, during pregnancy and childbirth is important to understanding women's access to and utilization of professional maternal health services that can prevent maternal mortality. This qualitative study examines husbands' involvement during childbirth and professional delivery care utilization in a rural sub-district of Netrokona district, Bangladesh. Using purposive sampling, ten households utilizing a skilled attendant during the birth of the youngest child were selected and matched with ten households utilizing an untrained traditional birth attendant, or dhatri. Households were selected based on a set of inclusion criteria, such as approximate household income, ethnicity, and distance to the nearest hospital. Twenty semi-structured interviews were conducted in Bangla with husbands in these households in June 2010. Interviews were transcribed, translated into English, and analyzed using NVivo 9.0. By purposefully selecting households that differed on the type of provider utilized during delivery, common themes--high costs, poor transportation, and long distances to health facilities--were eliminated as sufficient barriers to the utilization of professional delivery care. Divergent themes, namely husbands' social support and perceived social norms, were identified as underlying factors associated with delivery care utilization. We found that husbands whose wives utilized professional delivery care provided emotional, instrumental and informational support to their wives during delivery and believed that medical intervention was necessary. By contrast, husbands whose wives utilized an untrained dhatri at home were uninvolved during delivery and believed childbirth should take place at home according to local traditions. This study provides novel evidence about male involvement during childbirth in rural Bangladesh. These findings have important implications for program planners, who should pursue culturally sensitive ways to involve husbands in maternal health interventions and assess the effectiveness of education strategies targeted at husbands.


TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics.
Millions of patients suffer from major depressive disorder (MDD), but many do not respond to selective serotonin reuptake inhibitor (SSRI) therapy. We used a pharmacometabolomics-informed pharmacogenomics research strategy to identify genes associated with metabolites that were related to SSRI response. Specifically, 306 MDD patients were treated with citalopram or escitalopram and blood was drawn at baseline, 4 and 8 weeks for blood drug levels, genome-wide single nucleotide polymorphism (SNP) genotyping and metabolomic analyses. SSRI treatment decreased plasma serotonin concentrations (P<0.0001). Baseline and plasma serotonin concentration changes were associated with clinical outcomes (P<0.05). Therefore, baseline and serotonin concentration changes were used as phenotypes for genome-wide association studies (GWAS). GWAS for baseline plasma serotonin concentrations revealed a genome-wide significant (P=7.84E-09) SNP cluster on chromosome four 5' of TSPAN5 and a cluster across ERICH3 on chromosome one (P=9.28E-08) that were also observed during GWAS for change in serotonin at 4 (P=5.6E-08 and P=7.54E-07, respectively) and 8 weeks (P=1.25E-06 and P=3.99E-07, respectively). The SNPs on chromosome four were expression quantitative trait loci for TSPAN5. Knockdown (KD) and overexpression (OE) of TSPAN5 in a neuroblastoma cell line significantly altered the expression of serotonin pathway genes (TPH1, TPH2, DDC and MAOA). Chromosome one SNPs included two ERICH3 nonsynonymous SNPs that resulted in accelerated proteasome-mediated degradation. In addition, ERICH3 and TSPAN5 KD and OE altered media serotonin concentrations. Application of a pharmacometabolomics-informed pharmacogenomic research strategy, followed by functional validation, indicated that TSPAN5 and ERICH3 are associated with plasma serotonin concentrations and may have a role in SSRI treatment outcomes.


Olanzapine-divalproex combination versus divalproex monotherapy in the treatment of bipolar mixed episodes: a double-blind, placebo-controlled study.
This 6-week, randomized, double-blind, placebo-controlled trial used simultaneous depression and mania criteria to compare a single mood stabilizer, divalproex, with and without adjunctive olanzapine in patients with bipolar I disorder experiencing acute mixed episodes. Two hundred two adults, aged 18 to 60 years, who met DSM-IV-TR criteria for bipolar disorder with a current mixed episode and had been taking divalproex for >or=14 days at levels of 75 to 125 microg/mL with inadequate efficacy (21-item Hamilton Depression Rating Scale [HDRS-21] and Young Mania Rating Scale [YMRS] scores >or=16) were randomly assigned to olanzapine 5 to 20 mg/d versus placebo augmentation. HDRS-21, YMRS, Clinical Global Impressions for Bipolar Disorder (CGI-BP), hospitalizations, concomitant medications, and adverse events were assessed. Comparisons included changes in both HDRS-21 and YMRS (primary outcome measure), time to partial response and time to response, CGI-BP improvement, hospitalizations, and safety (secondary outcome measures). The study was conducted from December 2006 to February 2008. Mean (SD) baseline HDRS-21 and YMRS scores were 22.2 (4.5) and 20.9 (4.4), respectively, with 59% female and 51% white subjects. Mean +/- SE score changes from baseline across the 6-week treatment period for adjunctive olanzapine (n = 100) versus adjunctive placebo (n = 101) arms, respectively, were -9.37 +/- 0.55 versus -7.69 +/- 0.54, P = .022, on the HDRS-21 and -10.15 +/- 0.44 versus -7.68 +/- 0.44 P < .001, on the YMRS. Mean +/- SE score changes from baseline to last observation carried forward for CGI-BP measures were -1.34 +/- 0.11 for adjunctive olanzapine versus -1.06 +/- 0.11 for adjunctive placebo, P = .056. Time to partial response (>or=25% HDRS-21 and YMRS decreases, median 7 versus 14 days) and time to response (>or=50% HDRS-21 and YMRS decreases, median 25 versus 49 days) were significantly shorter with adjunctive olanzapine. Increases in weight (total and >or=7%) and fasting blood glucose were significantly greater with adjunctive olanzapine. Adjunctive olanzapine yielded greater and earlier reduction of manic and depressive symptoms in mixed-episode patients with inadequate response to at least 2 weeks of divalproex. clinicaltrials.gov Identifier: NCT00402324.


Clinical, Histologic, and Molecular Characteristics of Anaplastic Lymphoma Kinase-positive Primary Cutaneous Anaplastic Large Cell Lymphoma.
Unlike systemic anaplastic large cell lymphoma, the vast majority of primary cutaneous anaplastic large cell lymphomas (C-ALCL) do not carry translocations involving the ALK gene and do not express ALK. Expression of ALK protein therefore strongly suggests secondary cutaneous involvement of a systemic anaplastic large cell lymphoma. Recent studies described a small subgroup of ALK-positive C-ALCL, but information on frequency, prognosis, and translocation partners is virtually lacking. A total of 6/309 (2%) C-ALCL patients included in the Dutch registry for cutaneous lymphomas between 1993 and 2019 showed immunohistochemical ALK expression. Clinical and histopathologic characteristics, immunophenotype and disease course were evaluated. Underlying ALK translocations were analyzed with anchored multiplex polymerase chain reaction-based targeted next-generation sequencing. Median age at diagnosis was 39 years (range: 16 to 53 y). All patients presented with a solitary lesion. Treatment with radiotherapy (n=5) or anthracycline-based chemotherapy (n=1) resulted in complete responses in all 6 patients. Three patients developed a relapse, of whom 2 extracutaneous. After a median follow-up of 41 months, 5 patients were alive without disease and 1 patient died of lymphoma. Immunohistochemically, 3 cases (50%) showed combined nuclear and cytoplasmic ALK expression with underlying NPM1-ALK fusions, while 3 cases (50%) showed solely cytoplasmic ALK expression with variant ALK fusion partners (TRAF1, ATIC, TPM3). ALK-positive C-ALCL is extremely uncommon, has a comparable favorable prognosis to ALK-negative C-ALCL, and should be treated in the same way with radiotherapy as first-line treatment.


Telehealth at UC Davis--a 20-year experience.
Telehealth at the University of California Health System began as a telefetal monitoring connection with a rural hospital in 1992 and evolved to become the Center for Health and Technology (CHT) in 2000. The Center supports the vision of the University of California Davis (UC Davis) Health System-a healthier world through bold innovation. The CHT focuses on the four pillars of the academic health center: clinical services, research and scholarly work, education, and public service. Since 1996, the Center has provided more than 33,000 telemedicine consultation (excluding teleradiology, telepathology, and phone consultations) in over 30 clinical specialties and at more than 90 locations across California. Research and continuous evaluation have played an integral role in shaping the telehealth program, as well as strategic collaborations and partnerships. In an effort to expand the field of telehealth the CHT provides telehealth training for health professionals, technical specialists, and administrators. Furthermore, it also plays an integral role in workforce development through the education of the next generation of community primary care physicians through Rural Programs In Medical Education (Rural PRIME) and continuing educational programs for working health professionals through videoconferencing and Web-based modalities. The Center is supported through a variety of funding sources, and its sustainability comes from a mix of fee-for-service payment, contracts, grants, gifts, and institutional funding. Together with key partners, UC Davis has educated and informed initiatives resulting in legislation and policies that advance telehealth. Looking toward the future, UC Davis is focused on technology-enabled healthcare and supporting synergy among electronic health records, health information exchange, mobile health, informatics, and telehealth.


Methionine restriction alters bone morphology and affects osteoblast differentiation.
Methionine restriction (MR) extends the lifespan of a wide variety of species, including rodents, drosophila, nematodes, and yeasts. MR has also been demonstrated to affect the overall growth of mice and rats. The objective of this study was to evaluate the effect of MR on bone structure in young and aged male and female C57BL/6J mice. This study indicated that MR affected the growth rates of males and young females, but not aged females. MR reduced volumetric bone mass density (vBMD) and bone mineral content (BMC), while bone microarchitecture parameters were decreased in males and young females, but not in aged females compared to control-fed (CF) mice. However, when adjusted for bodyweight, the effect of MR in reducing vBMD, BMC and microarchitecture measurements was either attenuated or reversed suggesting that the smaller bones in MR mice is appropriate for its body size. In addition, CF and MR mice had similar intrinsic strength properties as measured by nanoindentation. Plasma biomarkers suggested that the low bone mass in MR mice could be due to increased collagen degradation, which may be influenced by leptin, IGF-1, adiponectin and FGF21 hormone levels. Mouse preosteoblast cell line cultured under low sulfur amino acid growth media attenuated gene expression levels of Col1al, Runx2, Bglap, Alpl and Spp1 suggesting delayed collagen formation and bone differentiation. Collectively, our studies revealed that MR altered bone morphology which could be mediated by delays in osteoblast differentiation.


Folic acid modified gelatine coated quantum dots as potential reagents for in vitro cancer diagnostics.
Gelatine coating was previously shown to effectively reduce the cytotoxicity of CdTe Quantum Dots (QDs) which was a first step towards utilising them for biomedical applications. To be useful they also need to be target-specific which can be achieved by conjugating them with Folic Acid (FA). The modification of QDs with FA via an original "one-pot" synthetic route was proved successful by a range of characterisation techniques including UV-visible absorption spectroscopy, Photoluminescence (PL) emission spectroscopy, fluorescence life-time measurements, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The resulting nanocomposites were tested in Caco-2 cell cultures which over-express FA receptors. The presence of FA on the surface of QDs significantly improved the uptake by targeted cells. The modification with folic acid enabled to achieve a significant cellular uptake and cytotoxicity towards a selected cancer cell lines (Caco-2) of gelatine-coated TGA-CdTe quantum dots, which demonstrated good potential for in vitro cancer diagnostics.


Are pedophiles with aggressive tendencies more sexually violent?
Pedophiles use varying degrees of persuasion, coercion, and physical force in their sexual assaults. Pedophiles may also display aggressiveness and characteristics of hostility in nonsexual areas of their behavior. This study (N = 263) investigates the relationship between pedophiles with aggressive tendencies and the degree of sexual violence in their pedophilic acts. The degree of sexual violence was rated subjectively after a comprehensive psychiatric and psycho-sexual assessment and obtaining collateral information from police reports and witness statements. The degree of sexual violence was also rated more objectively using the penile plethysmography. Strict DSM-IV pedophilic disorder criteria were adopted for this study. The authors discuss whether sexual violence in a pedophilic population is focused to sexual areas or tends to be more generalized in other physically aggressive and hostile areas.


Micelle-induced folding of spinach thylakoid soluble phosphoprotein of 9 kDa and its functional implications.
Thylakoid soluble phosphoprotein of 9 kDa (TSP9) has been identified as a plant-specific protein in the photosynthetic thylakoid membrane (Carlberg et al. (2003) Proc. Natl. Acad. Sci. 100, 757-762). Nonphosphorylated TSP9 is associated with the membrane, whereas, after light-induced phosphorylation, a fraction of the phosphorylated TSP9 is released into the aqueous stroma. By NMR spectroscopy, we have determined the structural features of nonphosphorylated TSP9 both in aqueous solution and in membrane mimetic micelles. The results show that both wild type nonphosphorylated TSP9 and a triple-mutant (T46E + T53E + T60E) mimic of the triphosphorylated form of TSP9 are disordered under aqueous conditions, but adopt an ordered conformation in the presence of detergent micelles. The micelle-induced structural features, which are similar in micelles either of SDS or dodecylphosphocholine (DPC), consist of an N-terminal alpha-helix, which may represent the primary site of interaction between TSP9 and binding partners, and a less structured helical turn near the C-terminus. These structured elements contain mainly hydrophobic residues. NMR relaxation data for nonphosphorylated TSP9 in SDS micelles indicated that the molecule is highly flexible with the highest order in the N-terminal alpha-helix. Intermolecular NOE signals, as well as spin probe-induced broadening of NMR signals, demonstrated that the SDS micelles contact both the structured and a portion of the unstructured regions of TSP9, in particular, those containing the three phosphorylation sites (T46, T53, and T60). This interaction may explain the selective dissociation of phosphorylated TSP9 from the membrane. Our study presents a structural model for the role played by the structured and unstructured regions of TSP9 in its membrane association and biological function.


Intergenerational Continuity of Intimate Partner Violence Perpetration: An Investigation of Possible Mechanisms.
Intimate partner violence (IPV) is a continuum of abuse that is associated with a number of negative outcomes including substance misuse, depression, and suicidal ideation. This study aims to investigate the intergenerational transmission of IPV perpetration and the mechanisms involved. Intergenerational transmission was investigated using information from two generations of the Cambridge Study in Delinquent Development which is a prospective longitudinal study of 411 males from an inner London area in the UK who have been followed up over a period of 50 years. Information with regard to IPV perpetration, specifically physical violence, was garnered from self-reports by the male at age 32, from their female partner at age 48, and from their male and female children in early adulthood. Regression analyses were used to investigate intergenerational transmission and examine whether psychosocial risk factors could be identified as potential intergenerational pathways. Having a father who was a perpetrator of IPV significantly increased the odds of daughters being perpetrators by 2 times. It did not significantly increase the odds for sons. The intergenerational transmission of IPV perpetration remains between fathers and their daughters over and above a series of psychosocial factors such as accommodation problems and alcohol misuse. Identification of factors associated with the intergenerational transmission of IPV perpetration will inform practitioners and policymakers. Information garnered from studies such as this may contribute to the development of prevention and intervention strategies for those at risk.


Nanoarchitectonics for carbon-material-based sensors.
Recently, the nanoarchitectonics concept has been proposed to fabricate functional materials on the basis of concerted harmonization actions to control materials organization. In this review, we introduce recent several sensor designs from viewpoints of nanoarchitectonics that are classified into three categories: (i) inside nanoarchitectonics, (ii) outside nanoarchitectonics, and (iii) hierarchic nanoarchitectonics. In addition, various nanocarbons, such as carbon nanotubes, graphene derivatives, fullerene assemblies and nanoporous carbons, are selected as standard materials. In the first section, design and fabrication of mesoporous or nanoporous materials for enhanced sensing are especially exemplified as inside nanoarchitectonics. In the next section, recent examples of layer-by-layer nanoarchitectures for sensor fabrications are explained for outside nanoarchitectonics. Finally, their combined strategies for hierarchic carbon nanoarchitectonics are introduced as advanced sensor materials designs.


Unicompartmental knee arthroplasty: is the glass half full or half empty?
There is a large amount of evidence available about the relative merits of unicompartmental and total knee arthroplasty (UKA and TKA). Based on the same evidence, different people draw different conclusions and as a result, there is great variability in the usage of UKA. The revision rate of UKA is much higher than TKA and so some surgeons conclude that UKA should not be performed. Other surgeons believe that the main reason for the high revision rate is that UKA is easy to revise and, therefore, the threshold for revision is low. They also believe that UKA has many advantages over TKA such as a faster recovery, lower morbidity and mortality and better function. They therefore conclude that UKA should be undertaken whenever appropriate. The solution to this argument is to minimise the revision rate of UKA, thereby addressing the main disadvantage of UKA. The evidence suggests that this will be achieved if surgeons use UKA for at least 20% of their knee arthroplasties and use implants that are appropriate for these broad indications.


Investigation of computer-generated diffractive beam shapers for flattening of single-modal CO(2) laser beams.
A full cycle was realized of the photolithographic development and detailed testing of a diffractive optical element that transforms the diverging Gaussian beams of CO(2) lasers into a uniformly filled-in rectangle. The zone feature size of the beam shaper, the diffractive efficiency and accuracy, the focus depth, and the stability with respect to the size and the divergence of incident Gaussian beams are studied by computer modeling. Calculated flattop intensity distributions are presented in the same form of gray-level pictures and three-dimensional plots as the corresponding results measured by an IR camera.


Tobacco smoking among school children in Colombo district, Sri Lanka.
Tobacco smoking is an important problem among schoolchildren. The authors studied the patterns of tobacco smoking among schoolchildren in Colombo, Sri Lanka, using a self-administered questionnaire. Multistaged stratified random sampling was used to select 6000 students. Response rate was 90.7% (5446), out of which 53.4% were males. Prevalence rates for males and females, respectively, were as follows: having smoked at least 1 complete cigarette: 27.0% and 13.3%, smoked more than 100 cigarettes: 2.3% and 0.3%, daily smoking: 1.8% and 0.2%. Mean age of starting to smoke was 14.16 years. The tobacco products most used were cigarettes (91.5%) and bidis (3.8%). In univariate analysis, male gender, parental smoking, studying non-science subjects, peer smoking, and participating in sports were significantly associated with smoking of at least 1 complete cigarette (P < .05). In multivariate analysis, the most significant correlates were having close friends (odds ratio = 3.29, confidence interval = 2.47-4.37) or parents who smoked (odds ratio = 1.86, confidence interval = 1.28-2.71). Female smoking has increased from previously reported values. These high-risk groups can be targets for preventive programs.


The Regulatory Status Adopted by Lymph Node Dendritic Cells and T Cells During Healthy Aging Is Maintained During Cancer and May Contribute to Reduced Responses to Immunotherapy.
Aging is associated with an increased incidence of cancer. One contributing factor could be modulation of immune cells responsible for anti-tumor responses, such as dendritic cells (DCs) and T cells. These immunological changes may also impact the efficacy of cancer immunotherapies in the elderly. The effects of healthy aging on DCs and T cells, and their impact on anti-mesothelioma immune responses, had not been reported. This study examined DCs and T cells in young (2-5 months; equivalent to 16-26 human years) and elderly (20-24 months; equivalent to 60-70 human years) healthy and mesothelioma-bearing C57BL/6J mice. During healthy aging, elderly lymph nodes adopted a regulatory profile, characterized by: (i) increased plasmacytoid DCs, (ii) increased expression of the adenosine-producing enzyme CD73 on CD11c+ cells, and (iii) increased expression of multiple regulatory markers (including CD73, the adenosine A2B receptor, CTLA-4, PD-1, ICOS, LAG-3, and IL-10) on CD8+ and CD4+ T cells, compared to lymph nodes from young mice. Although mesotheliomas grew faster in elderly mice, the increased regulatory status observed in healthy elderly lymph node DCs and T cells was not further exacerbated. However, elderly tumor-bearing mice demonstrated reduced MHC-I, MHC-II and CD80 on CD11c+ cells, and decreased IFN-γ by CD8+ and CD4+ T cells within tumors, compared to young counterparts, implying loss of function. An agonist CD40 antibody based immunotherapy was less efficient at promoting tumor regression in elderly mice, which may be due to: (i) failure of elderly CD8+ T cells to up-regulate perforin, and (ii) increased expression of multiple regulatory markers on CD11c+ cells and T cells in elderly tumor-draining lymph nodes (including CD73, PD-1, ICOS, LAG-3, and TGF-β). Our findings suggest that checkpoint blockade may improve responses to immunotherapy in elderly hosts with mesothelioma, and warrants further investigation.


Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women.
Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection. We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe. Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups. A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .).


Short report: efficient oral infection of Culex pipiens quinquefasciatus by Rift Valley fever virus using a cotton stick support.
Transmission experiments are essential to assess vector competence. In an attempt to study Rift Valley fever virus (RVFV) transmission in its arthropod vector, disseminated infection rates were measured in Culex pipiens quinquefasciatus exposed to Clone 13, an avirulent variant of RVFV. We compared the classic system of glass feeders covered with different membranes (0-1%) with an alternative system in which a cotton stick is used as a support of a blood meal. The latter system showed the highest successful feeding rate (80%). Using this system, we optimized two parameters to obtain the highest numbers of engorged females and thus the highest numbers of females with disseminated infection: 1) use of freshly collected washed erythrocytes and 2) duration of the extrinsic incubation period of at least 14 days after infection.


Thrombotic Complications of Nose and Toe Associated With Mycoplasma pneumoniae Infection.
Thrombosis is a very rare complication of Mycoplasma pneumoniae (M. pneumoniae) infection. We report a case of a woman who has thrombotic complications associated with mycoplasma infection in distal body parts. A 79-year-old female patient applied to the emergency department with complaints of the pain and discoloration at the nose tip and distal toes of the feet. Those symptoms have occurred in 10 days after the onset of the respiratory problems. The venous obstruction was diagnosed by venous Doppler ultrasound related to the distal part of the toes. The occurrence of the thrombosis associated with M. pneumoniae could be explained with some reaction of the inflammatory products in the blood circulation.


Anisotropy and multiple scattering in thick mammalian tissues.
A dual-channel Mach-Zehnder interferometer using heterodyne detection allowed us to measure simultaneously parallel and perpendicular polarization components through various mammalian tissues at a wavelength of lambda = 633 nm. By contrast with liver tissue, squeletic muscles of a few millimeters thickness exhibit strong anisotropic properties that change the direction of the linear polarization of the light. This rotation of the initial plane of polarization is to be distinguished from the depolarization that is due to the multiple light scattering that goes along with large temporal fluctuations. Complementary photos under linearly polarized light illustrate the behavior difference between liver (isotropic medium) and muscle (anisotropic medium).


A Narrative Review of Motor Competence in Children and Adolescents: What We Know and What We Need to Find Out.
Lack of physical activity is a global public health problem causing not only morbidity and premature mortality, but it is also a major economic burden worldwide. One of the cornerstones of a physically active lifestyle is Motor Competence (MC). MC is a complex biocultural attribute and therefore, its study requires a multi-sectoral, multi-, inter- and transdisciplinary approach. MC is a growing area of research, especially in children and adolescents due to its positive association with a plethora of health and developmental outcomes. Many questions, however, remain to be answered in this field of research, with regard to: (i) Health and Developmental-related Associations of MC; (ii) Assessment of MC; (iii) Prevalence and Trends of MC; (iv) Correlates and Determinants of MC; (v) MC Interventions, and (vi) Translating MC Research into Practice and Policy. This paper presents a narrative review of the literature, summarizing current knowledge, identifying key research gaps and presenting questions for future investigation on MC in children and adolescents. This is a collaborative effort from the International Motor Competence Network (IMCNetwork) a network of academics and researchers aiming to promote international collaborative research and knowledge translation in the expansive field of MC. The knowledge and deliverables generated by addressing and answering the aforementioned research questions on MC presented in this review have the potential to shape the ways in which researchers and practitioners promote MC and physical activity in children and adolescents across the world.


Effect of a platelet activating factor antagonist, WEB 2086, on allergen induced asthmatic responses.
Platelet activating factor (PAF) has been implicated in the pathogenesis of airway hyperresponsiveness in asthma. The purpose of this study was to evaluate the effects of a selective PAF antagonist (WEB 2086), given in doses known to antagonise the effects of inhaled PAF in human subjects, on allergen induced early and late asthmatic responses and on airway hyperresponsiveness. Eight atopic, mildly asthmatic subjects were studied during a screening period and two treatment periods. During the screening period subjects inhaled an allergen to which they were known to be sensitised and the response was measured as the fall in the forced expired volume in one second (FEV1) to show the presence of early (0-1 h) and late (3-7 h) asthmatic responses. On another day the subjects inhaled allergen diluent. During the treatment periods subjects inhaled allergen after one week's pretreatment with WEB 2086 (100 mg three times a day) or placebo administered in a randomised, double blind, crossover fashion. Histamine airway responsiveness was measured 24 hours before and 24 hours after allergen and the results were expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). The maximal early asthmatic response after allergen with placebo treatment was 18.4% (SE 4.4%) and with WEB 2086 18.9% (4.4%). The maximal late response with placebo treatment was 21.7% (5.3%) and with WEB 2086 21.2% (3.0%). The log difference (before and after allergen) in histamine PC20 was 0.35 (0.06) after placebo treatment and 0.30 (0.1) after WEB 2086. These results indicate that one week of treatment with an orally administered PAF antagonist (WEB 2086) does not attenuate allergen induced early or late responses or airway hyperresponsiveness.


Eating behavior and obesity at Chinese buffets.
The aim of this study was to investigate whether the eating behaviors of people at all-you-can-eat Chinese buffets differs depending upon their body mass. The resulting findings could confirm or disconfirm previous laboratory research that has been criticized for being artificial. Trained observers recorded the height, weight, sex, age, and behavior of 213 patrons at Chinese all-you-can-eat restaurants. Various seating, serving, and eating behaviors were then compared across BMI levels. Patrons with higher levels of BMI were more likely to be associated with using larger plates vs. smaller plates (OR 1.16, P < 0.01) and facing the buffet vs. side or back (OR 1.10, P < 0.001). Patrons with higher levels of BMI were less likely to be associated with using chopsticks vs. forks (OR 0.90,P < 0.05), browsing the buffet before eating vs. serving themselves immediately (OR 0.92, P < 0.001), and having a napkin on their lap vs. not having a napkin on their lap (OR 0.92, P < 0.01). Patrons with lower BMIs left more food on their plates (10.6% vs. 6.0%, P < 0.05) and chewed more per bite of food (14.8 vs. 11.9, P < 0.001). These observational findings of real-world behavior provide support for laboratory studies that have otherwise been dismissed as artificial.


Protein tyrosine phosphatase 1B interacts with the activated insulin receptor.
Protein tyrosine phosphatase 1B (PTP1B) is a protein tyrosine phosphatase of unknown function, although increasing evidence supports a role for this phosphatase in insulin action. We have investigated the interaction of PTP1B with the insulin receptor using a PTP1B glutathione S-transferase (GST) fusion protein with a point mutation in the enzyme's catalytic domain. This fusion protein is catalytically inactive, but the phosphatase's phosphotyrosine binding site is maintained. The activated insulin receptor was precipitated from purified receptor preparations and whole-cell lysates by the inactive PTP1B-GST, demonstrating a direct association between the insulin receptor and PTP1B. A p120 of unknown identity was also precipitated from whole-cell lysates by the PTP1B fusion protein, but IRS-1 (pp185) was not. A catalytically inactive [35S]PTP1B-fusion protein bound directly to immobilized insulin receptor kinase domains and was displaced in a concentration-dependent manner. Finally, tyrosine-phosphorylated PTP1B was precipitated from whole-cell lysates by an anti-insulin receptor antibody after insulin stimulation. The site of interaction between PTP1B and the insulin receptor was studied using phosphopeptides modeled after the receptor's kinase domain, the NPXY domain, and the COOH-terminal. Each phosphopeptide inhibited the PTP1B-GST:insulin receptor interaction. Study of mutant insulin receptors demonstrated that activation of the kinase domain is necessary for the PTP1B:insulin receptor interaction, but receptors with deletion of the NPXY domain or of the COOH-terminal can still bind to the PTP1B-GST. We conclude that PTP1B can associate directly with the activated insulin receptor at multiple different phosphotyrosine sites and that dephosphorylation by PTP1B may play a significant role in insulin receptor signal transduction.


Computational design of proteins targeting the conserved stem region of influenza hemagglutinin.
We describe a general computational method for designing proteins that bind a surface patch of interest on a target macromolecule. Favorable interactions between disembodied amino acid residues and the target surface are identified and used to anchor de novo designed interfaces. The method was used to design proteins that bind a conserved surface patch on the stem of the influenza hemagglutinin (HA) from the 1918 H1N1 pandemic virus. After affinity maturation, two of the designed proteins, HB36 and HB80, bind H1 and H5 HAs with low nanomolar affinity. Further, HB80 inhibits the HA fusogenic conformational changes induced at low pH. The crystal structure of HB36 in complex with 1918/H1 HA revealed that the actual binding interface is nearly identical to that in the computational design model. Such designed binding proteins may be useful for both diagnostics and therapeutics.


Receptor specific, stimuli responsive and subcellular targeted approaches for effective therapy of Alzheimer: Role of surface engineered nanocarriers.
The present review deals in-depth with the current application of nanotechnology in targeting the major pathological hallmarks of Alzheimer's disease. This review further focuses on the surface modification of the nanocarriers using antibody, aptamers, proteins and peptides for specific targeting in the brain by overcoming the biological barriers such as blood brain barrier. The stimuli responsive/pulsatile drug delivery nanoplatforms using stimuli such as pH, temperature, photo-thermal, reactive oxygen species, ultrasonic stimulation and electrical stimulation, which help to create a micro-environment to either trigger the site-specific drug release from the nanoplatform or to reduce the disease burden in the brain, have been discussed. The targeting of nanoplatforms to sub-cellular compartments such as mitochondria, nuclei, endoplasmic reticulum, golgi apparatus and lysosomes along with receptor specific interactions such as such folate, lactoferrin, transferrin, insulin and low-density lipoprotein (LDL) receptors has been included to give reader an idea about strategies to enhance cellular co-localization and receptor based targeting of nanoparticles to enhance efficacy of delivery platform. This article describes the various type of nanoplatforms which include lipidic nanoplatforms, polymeric nanoplatforms, inorganic nanoplatforms (metallic nanocarriers, quantum dots, ceramic based nanocarriers), carbon based nanocarriers and cell derived or biomimetic (exosomes and virus based) nanoplatforms, to either deliver the active ingredient or to themselves target the Alzheimer's disease pathology. Thus the review gives a detailed insight of all the recent research studies carried out using nanotechnology in the field of Alzheimer's disease.