Fine mapping of the major histocompatibility complex (MHC) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggests involvement of both HLA class I and class II loci.
The etiology of myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is unknown, but involvement of the immune system is one of the proposed underlying mechanisms. Human leukocyte antigen (HLA) associations are hallmarks of immune-mediated and autoimmune diseases. We have previously performed high resolution HLA genotyping and detected associations between ME/CFS and certain HLA class I and class II alleles. However, the HLA complex harbors numerous genes of immunological importance, and there is extensive and complex linkage disequilibrium across the region. In the current study, we aimed to fine map the association signals in the HLA complex by genotyping five additional classical HLA loci and 5,342 SNPs in 427 Norwegian ME/CFS patients, diagnosed according to the Canadian Consensus Criteria, and 480 healthy Norwegian controls. SNP association analysis revealed two distinct and independent association signals (p ≤ 0.001) tagged by rs4711249 in the HLA class I region and rs9275582 in the HLA class II region. Furthermore, the primary association signal in the HLA class II region was located within the HLA-DQ gene region, most likely due to HLA-DQB1, particularly the amino acid position 57 (aspartic acid/alanine) in the peptide binding groove, or an intergenic SNP upstream of HLA-DQB1. In the HLA class I region, the putative causal locus might map outside the classical HLA genes as the association signal spans several genes (DDR1, GTF2H4, VARS2, SFTA2 and DPCR1) with expression levels influenced by the ME/CFS associated SNP genotype. Taken together, our results implicate the involvement of the MHC, and in particular the HLA-DQB1 gene, in ME/CFS. These findings should be replicated in larger cohorts, particularly to verify the putative involvement of HLA-DQB1, a gene important for antigen-presentation to T cells and known to harbor alleles providing the largest risk for well-established autoimmune diseases.


Ascorbato(1,2-diaminocyclohexane):platinum(II) complexes, a new series of water-soluble antitumor drugs.
Dichloro-1,2-diaminocyclohexane (DACH):platinum(II), the prototype DACH:platinum complex, had good antitumor activity, was not cross-resistant with cis-dichlorodiammineplatinum(II) (DDP), but was, unfortunately, virtually insoluble in water and was, therefore, not evaluated clinically. This paper summarizes some of the chemical and biological attributes of a series of cis-bisascorbato-DACH:platinum(II) complexes (DAP). Although the primary emphasis has been placed on the DAP complex consisting of the isomeric mixture DACH, a series of complexes using the isomers of either DACH or ascorbic acid have also been synthesized. The synthetic procedure entailed reacting the water-soluble sulfato-DACH:platinum(II) with barium ascorbate, and the water-soluble product DAP was removed from the BaSO4 precipitate by filtration. Based upon elemental analysis, all the complexes had stoichiometric composition of one DACH:one platinum and two ascorbate monoanions. High-pressure liquid chromatography of cis-bisascorbato (mixed-isomer DACH):platinum revealed a series of platinum-containing, ultraviolet-absorbing peaks. All the DAP complexes had significant in vitro cytotoxicity against L1210 leukemia cells (L1210/0) with 50%-inhibitory dose values ranging from 2 to 5 micrograms/ml. None of the complexes was cross-resistant with DDP when tested in vitro against L1210 cells 50-fold resistant to DDP (L1210/DDP). The cis-bisascorbato (mixed-isomer DACH):platinum (DAP-1) was administered i.p. to C57BL X DBA/2 F1 mice inoculated i.p. with 10(6) L1210/0 cells. When administered on Days 1, 5, and 9, the DAP-1 complex consistently produced treated:control values in excess of 200% with several long-term survivors (alive 60 days after tumor inoculation). Further, the DAP-1 complex was totally non-cross-resistant with DDP when tested in vivo against a DDP-resistant L1210 line. Toxicological investigations revealed that DAP-1 was relatively nonnephrotoxic but did cause the expected bone marrow and gastrointestinal toxicity. In summary, the DAP complexes are highly water-soluble, nonnephrotoxic platinum complexes with sufficient antitumor activity to warrant further pharmacological, biochemical, and chemical investigations.


Perceived knowledge on the ICNP© in undergraduate nursing students: the development of a scale.
To develop and validate an instrument to assess nursing students' perceived knowledge on the International Classification for Nursing Practice. The study design is an initial development of a scale by a longitudinal, prospective, monocentric study. An instrument, including a final pool of 6 items, was developed and through a Content Validity approved by experts. Cronbach's alpha coefficient, Exploratory Factor Analysis and Confirmatory Factor Analysis were calculated in a sample of nursing students. The instrument demonstrated a CVI of 1.0. Cronbach's alpha coefficient was 0.879. Exploratory Factor Analysis indicated one component, with a saturation of items in the range between 0.594 and 0.856. Confirmatory Factor Analysis confirmed the structure. Although further studies are needed, the preliminary analyses of the instrument suggest satisfaction in terms of content validity, factorial structure, and reliability. This instrument may rise interest in international nursing educational context.


The Development of Representations of Pretend Object Substitutions.
Many theories of how pretense is mentally represented have been posited, but none have been effectually empirically tested to date. This research is the first to explore how children and adults mentally process simple pretend actions, specifically pretend object substitutions, and whether this representation changes with age. Preschoolers, older children, and undergraduates heard or read about a variety of pretend object substitutions, and their reaction time to name an image related to the object's real identity, pretend identity, or an unrelated image was measured. To test what is unique to pretense, these reaction times were compared to those from participants who responded to the same images after reading about nonpretend versions of the same actions. Results suggest that preschoolers inhibit reality when representing a pretend action, older children activate an object's real and pretend identities equally, and adults activate the object's real identity more than the pretend one. Implications for current theories of pretense representation are discussed.


Startling sweet temptations: hedonic chocolate deprivation modulates experience, eating behavior, and eyeblink startle.
Many individuals restrict their food intake to prevent weight gain. This restriction has both homeostatic and hedonic effects but their relative contribution is currently unclear. To isolate hedonic effects of food restriction, we exposed regular chocolate eaters to one week of chocolate deprivation but otherwise regular eating. Before and after this hedonic deprivation, participants viewed images of chocolate and images of high-calorie but non-chocolate containing foods, while experiential, behavioral and eyeblink startle responses were measured. Compared to satiety, hedonic deprivation triggered increased chocolate wanting, liking, and chocolate consumption but also feelings of frustration and startle potentiation during the intertrial intervals. Deprivation was further characterized by startle inhibition during both chocolate and food images relative to the intertrial intervals. Individuals who responded with frustration to the manipulation and those who scored high on a questionnaire of impulsivity showed more relative startle inhibition. The results reveal the profound effects of hedonic deprivation on experiential, behavioral and attentional/appetitive response systems and underscore the role of individual differences and state variables for startle modulation. Implications for dieting research and practice as well as for eating and weight disorders are discussed.


Learning from deaths: Parents' Active Role and ENgagement in The review of their Stillbirth/perinatal death (the PARENTS 1 study).
Following a perinatal death, a formal standardised multi-disciplinary review should take place, to learn from the death of a baby and facilitate improvements in future care. It has been recommended that bereaved parents should be offered the opportunity to give feedback on the care they have received and integrate this feedback into the perinatal mortality review process. However, the MBRRACE-UK Perinatal Confidential Enquiry (2015) found that only one in 20 cases parental concerns were included in the review. Although guidance suggests parental opinion should be sought, little evidence exists on how this may be incorporated into the perinatal mortality review process. The purpose of the PARENTS study was to investigate bereaved parents' views on involvement in the perinatal mortality review process. A semi-structured focus group of 11 bereaved parents was conducted in South West England. A purposive sampling technique was utilised to recruit a diverse sample of women and their partners who had experienced a perinatal death more than 6 months prior to the study. A six-stage thematic analysis was followed to explore parental perceptions and expectations of the perinatal mortality review process. Four over-arching themes emerged from the analysis: transparency; flexibility combined with specificity; inclusivity; and a positive approach. It was evident that the majority of parents were supportive of their involvement in the perinatal mortality review process and they wanted to know the outcome of the meeting. It emerged that an individualised approach should be taken to allow flexibility on when and how they could contribute to the process. The emotional aspects of care should be considered as well as the clinical care. Parents identified that the whole care pathway should be examined during the review including antenatal, postnatal, and neonatal and community based care. They agreed that there should be an opportunity for parents to give feedback on both good and poor aspects of their care. Parents were unaware that a review of their baby's death took place in the hospital. Parental involvement in the perinatal mortality review process would promote an open culture in the healthcare system and learning from adverse events including deaths. Further research should focus on designing and evaluating a perinatal mortality review process where parental feedback will be integral.


Computational modeling of the mechanical behavior of the cerebrospinal fluid system.
A computational fluid dynamics (CFD) model of the cerebrospinal fluid system was constructed based on a simplified geometry of the brain ventricles and their connecting pathways. The flow is driven by a prescribed sinusoidal motion of the third ventricle lateral walls, with all other boundaries being rigid. The pressure propagation between the third and lateral ventricles was examined and compared to data obtained from a similar geometry with a stenosed aqueduct. It could be shown that the pressure amplitude in the lateral ventricles increases in the presence of aqueduct stenosis. No difference in phase shift between the motion of the third ventricle walls and the pressure in the lateral ventricles because of the aqueduct stenosis could be observed. It is deduced that CFD can be used to analyze the pressure propagation and its phase shift relative to the ventricle wall motion. It is further deduced that only models that take into account the coupling between ventricles, which feature a representation of the original geometry that is as accurate as possible and which represent the ventricle boundary motion realistically, should be used to make quantitative statements on flow and pressure in the ventricular space.


Multiple Sclerosis vision questionnaire (MSVQ-7): Reliability, validity, precision and discrimination.
Visual dysfunction is common in people with Multiple Sclerosis (pwMS), associated with a variety of visual symptoms. Capturing the patient experience of these complex patterns of visual pathology is challenging. A valid and reliable patient reported measure, capable of detecting clinically significant change, would have considerable research and clinical benefits. We examined the properties of the MS Vision Questionnaire (MSVQ-7) in a large MS population. Data were collected from participants in the UK-wide Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study: MS subtype and Expanded Disability Status Scale (EDSS) band from the clinical team, as well as serial packs including the MSVQ-7 and questionnaires on depression, anxiety and stigma. A calibration sample of 1000 pwMS contributing several years of follow-up were split into training and validation samples for a Confirmatory Factor Analysis and Rasch analysis. The Minimal Detectable Change (MDC) was computed as well as the Minimal Clinically Important Change (MIC), by an anchor-based method, for different MS subtypes. The MSVQ-7 is unidimensional and can be fit to the Rasch model with a solution discarding 3% of variance. Providing all 7 items are answered, the total can be converted to an interval-level metric for calculation of change scores and other parametric analyses. The % of missing values did not exceed 1.7%. Among 5478 pwMS, 80% reported visual problems. MSVQ-7 scores were categorised as mild for 36.1%, moderate for 33.6% and severe for 10.3%, and varied by MS subtype. In the follow-up sample of 2227 pwMS, 42.5% changed MSVQ-7 category between baseline and first follow-up (mean 22.6 months). The MIC exceeded the MDC so clinically significant change exceeds measurement error. While MDC was identical for relapsing and progressive MS, MIC varied by MS subtype, with smaller MIC in relapsing MS. Over one-quarter of the follow-up sample reported a clinically significant change in MSVQ-7: 12.2% improved and 13.5% deteriorated. For pwMS recruited within 2 years of diagnosis, 17.3% reported significant change on follow-up, all improving. MSVQ-7 scores showed strong associations with anxiety, depression and stigma (effect sizes>0.8). Duration, EDSS band and MS subtype all had effect sizes 0.2-0.49. A multinomial logistic regression exploring vision disturbance and depression, adjusted for age, gender, MS subtype, duration and disability, showed vision is the strongest significant predictor of depression. Each unit increase in interval MSVQ-7 increases risk by 10% of 'possible' and by 17% of 'probable' depression. The MSVQ-7 is a brief self-report measure of visual problems for pwMS. It can easily be converted to interval-level measurement for change scores or power calculations and has good precision and discrimination. Visual problems were reported by 80% of pwMS and changed over time, evidencing the need for regular monitoring. MIC varied by MS subtype, indicating that perception of impact changes over the disease course. Visual dysfunction significantly affects depression risk and perceived stigma, highlighting the importance of routine assessment of visual problems in comprehensive care. The MSVQ-7 has strong psychometric properties for adoption as a measure for vision in clinical and research settings.


Improving methodology in heart rate variability analysis for the premature infants: Impact of the time length.
Heart rate variability (HRV) has been emerging in neonatal medicine. It may help for the early diagnosis of pathology and estimation of autonomous maturation. There is a lack of standardization and automation in the selection of the sequences to analyze and some features have not been explored in this specific population. The main objective of this study was to analyze the impact of the time length of the sequences on the estimation of linear and non-linear HRV features, including horizontal visibility graphs (HVG). HRV features were repeatedly measured with linear and non-linear methods on 2-, 5-, 10-minute sequences selected from the longest 15-min sequence and recorded on a weekly basis in 39 infants less than 31 weeks at birth. The associations between HRV measurements were analyzed through principal component analysis and k-means clustering. The effects of the time lengths on HRV measurements and post-menstrual age (PMA) were analyzed by linear mixed effect model for repeated measures. The domains of analysis were concordant for their descriptive parameters of short (rMSSD, SD1 and HF) and long-term (SD, SD2 and LF) variability. α1 was correlated with the LF/HF and SD2/SD1. DC and AC were correlated with short-term variability estimates and significantly increased with GA and PMA. Shortening the windows of analysis increased the random measurement error for all the features and increased the bias for all but short term features and HVGs. The linear and non-linear measurements of HRV are correlated each other. Shortening the windows of analysis increased the random error for all the features and increased the bias for all but short term features and HVGs. Short-term HRV can be an index for evaluating the maturation in whatever sequence length.


Comparison of PET template-based and MRI-based image processing in the quantitative analysis of C11-raclopride PET.
Quantitative measures of 11C-raclopride receptor binding can be used as a correlate of postsynaptic D2 receptor density in the striatum, allowing 11C-raclopride positron emission tomography (PET) to be used for the differentiation of Parkinson's disease from atypical parkinsonian syndromes. Comparison with reference values is recommended to establish a reliable diagnosis. A PET template specific to raclopride may facilitate direct computation of parametric maps without the need for an additional MR scan, aiding automated image analysis. Sixteen healthy volunteers underwent a dynamic 11C-raclopride PET and a high-resolution T1-weighted MR scan of the brain. PET data from eight healthy subjects was processed to generate a raclopride-specific PET template normalized to standard space. Subsequently, the data processing based on the PET template was validated against the standard magnetic resonance imaging (MRI)-based method in 8 healthy subjects and 20 patients with suspected parkinsonian syndrome. Semi-quantitative image analysis was performed in Montreal Neurological Institute (MNI) and in original image space (OIS) using VOIs derived from a probabilistic brain atlas previously validated by Hammers et al. (Hum Brain Mapp, 15:165-174, 2002). The striatal-to-cerebellar ratio (SCR) of 11C-raclopride uptake obtained using the PET template was in good agreement with the MRI-based image processing method, yielding a Lin's concordance coefficient of 0.87. Bland-Altman analysis showed that all measurements were within the ±1.96 standard deviation range. In all 20 patients, the PET template-based processing was successful and manual volume of interest optimization had no further impact on the diagnosis of PD in this patient group. A maximal difference of <5% was found between the measured SCR in MNI space and OIS. The PET template-based method for automated quantification of postsynaptic D2 receptor density is simple to implement and facilitates rapid, robust and reliable image analysis. There was no significant difference between the SCR values obtained with either PET- or MRI-based image processing. The method presented alleviates the clinical workflow and facilitates automated image analysis.


Chronic inflammation is associated with low physical function in older adults across multiple comorbidities.
Chronic subclinical inflammation may contribute to impaired physical function in older adults; however, more data are needed to determine whether inflammation is a common mechanism for functional decline, independent of disease or health status. We examined associations between physical function and inflammatory biomarkers in 542 older men and women enrolled in four clinical studies at Wake Forest University between 2001 and 2006. All participants were at least 55 years and had chronic obstructive pulmonary disease, congestive heart failure, high cardiovascular risk, or self-reported physical disability. Uniform clinical assessments were used across studies, including grip strength; a Short Physical Performance Battery (SPPB; includes balance, 4-m walk, and repeated chair stands); inflammatory biomarker assays for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP); and anthropometric measures. Higher levels of CRP and IL-6, but not TNF-alpha, were associated with lower grip strength and SPPB scores and longer times to complete the 4-m walk and repeated chair stands tests, independent of age, gender, and race. More importantly, these relationships were generally independent of disease status. Further adjustment for fat mass, lean mass, or percent body fat altered some of these relationships but did not significantly change the overall results. Elevated CRP and IL-6 levels are associated with poorer physical function in older adults with various comorbidities, as assessed by a common battery of clinical assessments. Chronic subclinical inflammation may be a marker of functional limitations in older persons across several diseases/health conditions.


Predicting episodic and spatial memory performance from hippocampal resting-state functional connectivity: Evidence for an anterior-posterior division of function.
fMRI studies have identified distinct resting-state functional connectivity (RSFC) networks associated with the anterior and posterior hippocampus. However, the functional relevance of these two networks is still largely unknown. Hippocampal lesion studies and task-related fMRI point to a role for the anterior hippocampus in nonspatial episodic memory and the posterior hippocampus in spatial memory. We used Relevance Vector Regression (RVR), a machine-learning method that enables predictions of continuous outcome measures from multivariate patterns of brain imaging data, to test the hypothesis that patterns of whole-brain RSFC associated with the anterior hippocampus predict episodic memory performance, while patterns of whole-brain RSFC associated with the posterior hippocampus predict spatial memory performance. Magnetic resonance imaging and memory assessment took place at two separate occasions. The anterior and posterior RSFC largely corresponded with previous findings, and showed no effect of laterality. Supporting the hypothesis, RVR produced accurate predictions of episodic performance from anterior, but not posterior, RSFC, and accurate predictions of spatial performance from posterior, but not anterior, RSFC. In contrast, a univariate approach could not predict performance from resting-state connectivity. This supports a functional dissociation between the anterior and posterior hippocampus, and indicates a multivariate relationship between intrinsic functional networks and cognitive performance within specific domains, that is relatively stable over time.


Electrolyte-induced aggregation of zein protein nanoparticles in aqueous dispersions.
Ion specific effects on the charging and aggregation features of zein nanoparticles (ZNP) were studied in aqueous suspensions by electrophoretic and time-resolved dynamic light scattering techniques. The influence of mono- and multivalent counterions on the colloidal stability was investigated for positively and negatively charged particles at pH values below and above the isoelectric point, respectively. The sequence of the destabilization power of monovalent salts followed the prediction of the indirect Hofmeister series for positively charged particles, while the direct Hofmeister series for negatively charged ones assumed a hydrophobic character for their surface. The multivalent ions destabilized the oppositely charged ZNPs more effectively and the aggregation process followed the Schulze-Hardy rule. For some multivalent ions, strong adsorption led to charge reversal resulting in restabilization of the suspensions. The experimental critical coagulation concentrations (CCCs) could be well-predicted with the theory developed by Derjaguin, Landau, Verwey and Overbeek indicating that the aggregation processes were mainly driven by electrical double layer repulsion and van der Waals attraction. The ion specific dependence of the CCCs is owing to the modification of the surface charge through ion adsorption at different extents. These results are crucial for drug delivery applications, where inorganic electrolytes are present in ZNP samples.


Plasmonically Enhanced Ultrasensitive Epitope-Specific Serologic Assay for COVID-19.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread and resulted in the global pandemic of COVID-19. Although IgM/IgG serology assay has been widely used, with the entire spike or nucleocapsid antigens, they only indicate the presence or absence of antibodies against these proteins but are not specific to the neutralization antibodies, therefore providing only generic information about infection stage and possible future immune protection. Novel technologies enabling easy-to-use and sensitive detection of multiple specific antibodies simultaneously will facilitate precise diagnosis of infection stage, prediction of clinical outcomes, and evaluation of future immune protection upon viral exposure or vaccination. Here, we demonstrate a rapid and ultrasensitive quantification method for epitope-specific antibodies, including different isotypes and subclasses, in a multiplexed manner. Using an ultrabright fluorescent nanolabel, plasmonic-fluor, this novel assay can be completed in 20 min and more importantly, the limit of detection of the plasmon-enhanced immunoassay for SARS-CoV-2 antibodies is as much as 100-fold lower compared to the assays relying on enzymatic amplification of colorimetric signals. Using convalescent patient plasma, we demonstrate that this biodetection method reveals the patient-to-patient variability in immune response as evidenced by the variations in whole protein and epitope-specific antibodies. This cost-effective, rapid, and ultrasensitive plasmonically enhanced multiplexed epitope-specific serological assay has the potential to be broadly employed in the detection of specific antibodies, which may benefit the advanced epidemiology studies and enable improvement of the clinical outcomes and prediction of the future protection against the SARS-CoV-2.


What does the modularity of morals have to do with ethics? Four moral sprouts plus or minus a few.
Flanagan (1991) was the first contemporary philosopher to suggest that a modularity of morals hypothesis (MMH) was worth consideration by cognitive science. There is now a serious empirically informed proposal that moral competence is best explained in terms of moral modules-evolutionarily ancient, fast-acting, automatic reactions to particular sociomoral experiences (Haidt & Joseph, 2007). MMH fleshes out an idea nascent in Aristotle, Mencius, and Darwin. We discuss the evidence for MMH, specifically an ancient version, "Mencian Moral Modularity," which claims four innate modules, and "Social Intuitionist Modularity," which claims five innate modules. We compare these two moral modularity models, discuss whether the postulated modules are best conceived as perceptual/Fodorian or emotional/Darwinian, and consider whether assuming MMH true has any normative ethical consequences whatsoever. The discussion of MMH reconnects cognitive science with normative ethics in a way that involves the reassertion of the "is-ought" problem. We explain in a new way what this problem is and why it would not yield. The reason does not involve the logic of "ought," but rather the plasticity of human nature and the realistic options to "grow" and "do" human nature in multifarious legitimate ways.


Preservation of autophagy should not direct nutritional therapy.
Recent reports in the literature have proposed that forced mandatory feeding should be avoided in the first week of critical illness to preserve autophagy, in order to maximize responses to oxidative stress, preserve organ function, and improve outcomes. Autophagy is a well recognized physiologic process that serves a housekeeping role for the cell to eliminate large protein aggregates and as a survival mechanism in starvation for generating energy (ATP) and promoting protein synthesis to maintain cell structure. In the critical care setting, autophagy may have important roles in modulating immune function, fighting infection, and preventing organ failure. The effect of feeding on autophagy is complex, poorly understood, and difficult to predict. The argument to withhold feeding to preserve autophagy is poorly substantiated and should not interfere with the delivery of early enteral nutrition to the critically ill patient in that first week following admission to the ICU.


Pediatric multicenter evaluation of the Verigene gram-negative blood culture test for rapid detection of inpatient bacteremia involving gram-negative organisms, extended-spectrum beta-lactamases, and carbapenemases.
We evaluated the investigational use only (IUO) version of the rapid Verigene Gram-negative blood culture test (BC-GN), a microarray that detects 9 genus/species targets (Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli/Shigella spp., Klebsiella oxytoca, Klebsiella pneumoniae, Proteus spp., Pseudomonas aeruginosa, and Serratia marcescens) and 6 antimicrobial resistance determinants (blaCTX-M, blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA) directly from positive blood cultures. BC-GN was performed on positive BacT/Alert Pediatric FAN and Bactec Peds Plus blood cultures with Gram-negative organisms at two tertiary pediatric centers. Vitek MS (bioMérieux, Durham, NC) was used to assign gold standard organism identification. The Check MDR CT-102 microarray (Check Points B.V., Wageningen, Netherlands) was used as an alternative method for detecting resistance determinants. In total, 104 organisms were isolated from 97 clinical blood cultures. BC-GN correctly detected 26/26 cultures with Acinetobacter spp., P. aeruginosa, and S. marcescens, 5/6 with Citrobacter spp., 13/14 with Enterobacter spp., 23/24 with E. coli, 2/3 with K. oxytoca, 16/17 with K. pneumoniae, and 0/1 with Proteus spp. BC-GN appropriately reported negative BC-GN results in 8/13 blood cultures that grew organisms that were not represented on the microarray but failed to detect targets in 3/5 cultures that grew multiple Gram-negative organisms. BC-GN detected 5/5 and 1/1 clinical blood cultures with blaCTX-M and blaVIM. All 6 results were corroborated by Check MDR CT-102 microarray testing. The Verigene BC-GN test has the potential to expedite therapeutic decision making in pediatric patients with Gram-negative bacteremia. Sensitivity was satisfactory but may be suboptimal in mixed Gram-negative blood cultures.


ESCAPE: database for integrating high-content published data collected from human and mouse embryonic stem cells.
High content studies that profile mouse and human embryonic stem cells (m/hESCs) using various genome-wide technologies such as transcriptomics and proteomics are constantly being published. However, efforts to integrate such data to obtain a global view of the molecular circuitry in m/hESCs are lagging behind. Here, we present an m/hESC-centered database called Embryonic Stem Cell Atlas from Pluripotency Evidence integrating data from many recent diverse high-throughput studies including chromatin immunoprecipitation followed by deep sequencing, genome-wide inhibitory RNA screens, gene expression microarrays or RNA-seq after knockdown (KD) or overexpression of critical factors, immunoprecipitation followed by mass spectrometry proteomics and phosphoproteomics. The database provides web-based interactive search and visualization tools that can be used to build subnetworks and to identify known and novel regulatory interactions across various regulatory layers. The web-interface also includes tools to predict the effects of combinatorial KDs by additive effects controlled by sliders, or through simulation software implemented in MATLAB. Overall, the Embryonic Stem Cell Atlas from Pluripotency Evidence database is a comprehensive resource for the stem cell systems biology community. Database URL: http://www.maayanlab.net/ESCAPE


Red cell genetic abnormalities and environmental interactions: a study in Tehamat Aseer.
In a study conducted in the lowland areas of Tehamat Aseer and low mountainous areas of Al-Hepatah in the South Western Province of Saudi Arabia, different villages were screened for parasite infestation, anaemia prevalence and frequency of sickle cell (HbS) gene. The prevalence of alpha- and beta-thalassaemias and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were also investigated. The prevalence of anaemia was found to range between 3.5% and 9.1% in the different villages, while parasite infestation ranged from 0 to 36.4%. Sickle cell gene frequency was similar in the different villages, ranging between 0.06% and 0.11%. G-6-PD deficiency ranged from 8% to 14%, alpha-thalassaemia from 20% to 30% and beta-thalassaemia from 10% to 15%. Parasite infestation was found to be a major cause of anaemia in these populations.


Electrotonic interactions between aggregates of chick embryo cardiac pacemaker cells.
Synchronization of spontaneously active heart cell aggregates occurs shortly after they are brought into contact. The synchronous rate is determined by pacemaker phase resetting and passive subthreshold electrotonic interactions. To further study the effects of passive electrical interactions, we have used 150-microns diameter aggregates prepared from cells of 4d (4-day ventricle + 1 day in vitro), 7d, and 14d embryonic chick ventricle as models of primary, latent, and nonpacemaker tissues, respectively. Coupling of 4d and 7d aggregates (4d/7d pairs) leads to intermediate synchronous rates. We show here that elevating external K+ from 1.3 to 2.8 mM, which has no effect on 4d/4d pairs but selectively reduces the beat rate of 7d/7d pairs by 42%, slows the synchronous beat rate of 4d/7d pairs by 23%. Increases in electrical coupling in newly joined 4d/14d pairs cause the 4d rate to slow to a minimum value (16 +/- 13 beats/min, n = 16) just prior to the onset of synchronous activity. The rate slowly recovers to a final value of 40 +/- 12 beat/min. We conclude that the spontaneous beat rate of a primary pacemaker is modulated by both active and passive interactions with latent or nonpacemaker tissues.


Functionalized halloysite nanotube by chitosan grafting for drug delivery of curcumin to achieve enhanced anticancer efficacy.
Halloysite nanotubes (HNTs) have a unique tubular structure in nanoscale, and have shown potential as novel carriers for various drugs. Coating the nanotubes with a hydrophilic polymer shell can significantly decrease the toxicity and provide colloidal stability during blood circulation. Here, we synthesized chitosan grafted HNTs (HNTs-g-CS) and investigated their potential as a nano-formulation for the anticancer drug curcumin. The structure and properties of HNTs-g-CS were characterized using water contact angle, zeta-potential, Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) techniques. HNTs-g-CS exhibit a maximum 90.8% entrapment efficiency and 3.4% loading capacity of curcumin, which are higher than those of raw HNTs. HNTs-g-CS also show no obvious hemolytic phenomenon and good stability in serum. The cumulative release ratio of curcumin from HNTs-g-CS/curcumin at cell lysate after 48 hours is 84.2%. The curcumin loaded HNTs-g-CS show specific toxicity to various cancer cell lines, including HepG2, MCF-7, SV-HUC-1, EJ, Caski and HeLa, and demonstrate an inhibition concentration of IC50 at 5.3-192 μM as assessed by cytotoxicity studies. The anticancer activity of this nanoformulation is extremely high in EJ cells compared with the other cancer cell lines. The cell uptake of HNTs-g-CS is confirmed by fluorescence microscopy. Flow cytometric analysis of curcumin loaded HNTs-g-CS shows that curcumin loaded HNTs-g-CS increase apoptosis on EJ cells. The content of ROS created by HNTs-g-CS/curcumin is more than that of free curcumin. All these results suggest that HNTs-g-CS are potential nanovehicles for anticancer drug delivery in cancer therapy.


Facial recognition using simulated prosthetic pixelized vision.
To evaluate a model of simulated pixelized prosthetic vision using noncontiguous circular phosphenes, to test the effects of phosphene and grid parameters on facial recognition. A video headset was used to view a reference set of four faces, followed by a partially averted image of one of those faces viewed through a square pixelizing grid that contained 10x10 to 32x32 dots separated by gaps. The grid size, dot size, gap width, dot dropout rate, and gray-scale resolution were varied separately about a standard test condition, for a total of 16 conditions. All tests were first performed at 99% contrast and then repeated at 12.5% contrast. Discrimination speed and performance were influenced by all stimulus parameters. The subjects achieved highly significant facial recognition accuracy for all high-contrast tests except for grids with 70% random dot dropout and two gray levels. In low-contrast tests, significant facial recognition accuracy was achieved for all but the most adverse grid parameters: total grid area less than 17% of the target image, 70% dropout, four or fewer gray levels, and a gap of 40.5 arcmin. For difficult test conditions, a pronounced learning effect was noticed during high-contrast trials, and a more subtle practice effect on timing was evident during subsequent low-contrast trials. These findings suggest that reliable face recognition with crude pixelized grids can be learned and may be possible, even with a crude visual prosthesis.


Low dose interferon-alpha2b combined with PUVA is an effective treatment of early stage mycosis fungoides: results of a multicenter study. Cutaneous-T Cell Lymphoma Multicenter Study Group.
The early stages of mycosis fungoides (MF) can be treated but not cured by photochemotherapy (PUVA) alone; some recent studies of the effect of a combination of human interferon-alpha (IFN(alpha)) and PUVA reported a high degree of response. The aim of our study was to evaluate the activity of a low dose of IFN-alpha2b combined with PUVA. Twenty-five patients were included: 16 men and 9 women aged between 23-80 years; 19 patients ahd stage I and 6 stage II disease. In the induction phase, the dose of IFNalpha was gradually raised over 6-8 weeks to the target dose of 18 MU/week; in the maintenance phase, the combination with PUVA allowed IFNalpha to be reduced to a maximum dose of 6 MU/week; in this way the cumulative administration of IFNalpha and PUVA was considerably lower than in similar combination protocols. Treatment success was analyzed in terms of freedom from treatment failure (FFTF). After the induction phase 9/25 patients (36%) achieved complete remission (CR) and 15/25 (56%) achieved partial remission (PR). One to five months from the beginning of the maintenance phase, a CR was recorded in 19/25 patients (76%) and a PR in 5/25 patients (20%) accounting for an overall response rate of 96%. The median of FFTF was not reached; probability of FFTF was 82% at 12 months and 62% at 24 months. Disease free survival projected to 48 months was 75%. Even with low doses of IFNalpha plus PUVA it is possible to achieve excellent clinical responses,many of which are long-lasting, in patients with early MF.


Cellular, pharmacokinetic, and pharmacodynamic aspects of response to camptothecins: can we improve it?
The camptothecins provide a novel class of effective anticancer agents that exert their action against DNA topoisomerase I. Members of the camptothecins include topotecan, irinotecan, 9-aminocamptothecin, and 9-nitrocamptothecin, which are analogs of the plant alkaloid 20(S)-camptothecin. These agents vary in their antitumor efficacy and toxicity. Several pharmacokinetic and pharmacodynamic factors including cellular efflux, modulation of topoisomerases I and II, lactone stability, alterations in metabolism, and drug-drug interactions, influence the antitumor response and toxicity of these agents. Preclinical studies suggest that protracted schedules of administration produce greater antitumor effect than bolus administration. However, the optimal treatment regimens and administration schedules of these agents have yet to be established in clinical studies.


Evaluation of the snowing-like ultrasonographic features of intraosseous jaw pathologies.
Aim of the study: Ultrasonographic examination of intraosseous jaw pathologies may reveal interesting incidental, mobile hyperechoic particles ("snowflakes") in anechoic areas. Purpose of this study is to explain and discuss this snowing-like ultrasonographic feature of intraosseous jaw pathologies. Material and methods: This study included 113 patients admitted to our clinic for examination: 43 (38.05%) males and 70 (61.9%) females with a mean age of 34.9 ± 17.2 years (range: 6-72 years). A total of 120 intraosseous lesions were evaluated prior to surgery using ultrasonography; these included non-neoplastic, odontogenic, and non-odontogenic lesions. Results: In total, 5 (4.1%) of the 120 lesions exhibited snowing-like feature on ultrasonography, including 2 (1.6% of total) of 3 incisive canal cysts, 2 (1.6% of total) of 7 dentigerous cysts, and 1 (0.8% of total) of 19 odontogenic keratocysts. Conclusions: Snowflakes evident on ultrasonography of intraosseous jaw lesions may be specific to certain pathologies. Future studies correlating radiologic and pathologic features of intraosseous jaw lesions should focus on ultrasonographic snowing-like appearance in different types of lesions and explore why they occur.


DNA methylation induces subtle mechanical alteration but significant chiral selectivity.
DNA methylation is a major epigenetic modification that is closely related to human health. Many experimental techniques as well as theoretical methods have been used to detect the modified nucleotides and identify their effects on molecular binding. It remains challenging to resolve the effect of few methylations of nucleic acids. Using super-resolution force spectroscopy, we firstly revealed that single cytosine methylation increases the mechanical stability of the DNA duplex by 1.9 ± 0.3 pN. Methylation also induces significant chiral selectivity towards drug molecules such as d,l-tetrahydropalmatine. Our results precisely quantify the mechanical effect of methylation and suggest that drug design should take methylation into consideration for enhanced selectivity.


[Semeiology, examination and diagnosis of lesions of the oral mucosa].
Tracking down the oral mucosa lesions require precise interrogation and cervico-facial, buccal and general examination. Diagnosis needs more often biopsy if not contra-indicated. The opportunity of further examinations and tests is discussed.


[Molecular-genetic status of the adolescents living in the condition of the constant influense of low dose radiation].
In the present investigation the analysis of the cytogenetic status and some blood characteristics of the adolescents from the contaminated area of Vulka-2 in Belarus has been done. The obtained data testifed that patients living in the condition of chronic radiation influence had essentially increased general frequency of all types of chromosome aberrations. First of all the elevated level of radiation markers is marked (0.54 +/- 0.11 and 0.11 +/- 0.05% in control. group, p < 0.05), the growth of double fragments (1.27 +/- 0.17 and 0.40 +/- 0.09% in control group, p < 0.05). The Spearmen correlation alalysis has revealed statistically significant increase of apoptosis level on the background of increased level of micronuclei (R = 0.832, p < 0.01). Thus our data testify that the degree of the biological homeostasis violation is intimately connected with the level of genome destabilization.


Preoperative pain treatment in acute abdomen in Osogbo, Nigeria: a randomized double-blind placebo-controlled study.
Withholding analgesics in acute abdomen for fear of masking clinical features and impairing diagnosis and decision-making is still being practiced despite recent evidence to the contrary. This study assesses the effect of preoperative analgesia on clinical findings, clinical diagnosis, and decision-making in patients with non-trauma acute abdomen. This is a randomized, double-blind, placebo-controlled study using Tramal, a brand of tramadol, at the ED of LAUTECH Teaching Hospital Osogbo, Nigeria. Ninety-five patients between 18-60 years received Tramal (n = 46) or placebo (n = 49). The pain score, clinical findings, provisional diagnosis, and treatment plan were noted before and 15-20 min after administration of the analgesic or placebo. The final diagnosis arrived at after adequate investigation or operation was considered the gold standard. The pain scores, diagnosis, treatment plan, and decision between the two groups were compared. Statistical analysis was by SPSS 16. Results were considered statistically significant at p < 0.05. Demography and case distribution were similar in both groups. The improvement in pain was greater in the Tramal group (p = 0.001). The abdominal palpation findings were also better in the Tramal group (p = 0.02). There were more changes in the diagnosis after use of Tramal (p = 0.01). There were more changes in the decision in the Tramal group (p = 0.03). Most of the changes in diagnosis and decision in the Tramal group were for the better. The preoperative use of Tramal in acute abdomen improved the experience of pain and did not adversely affect the accuracy of the diagnosis or decision-making.


[The morphological response of the pineal gland of old animals on course of melatonin injections].
On the old (18-20 months) male rats of Wistar population the influence of the 10 days evening melatonin injections in physiological rang doses on morphological state pineal gland, was studied. It has been shown, that the course of melatonin injections to old rats brings appearance of histological pattern of pineal gland activation: increasing of area of pinealocytes nuclear and density of nuclear and cytoplasm with stein by hallocyanine on total nucleic acid that means stimulation to material both indole, and peptide nature production. Using of melatonin in dose 0.05 mg/kg mass of the body is sparing for pinealocytes of the old rats and slows the apoptosis processes on background of polyploidization. Using of melatonin in dose 0,5 mg/kg mass of the body causes cell's overstrain and induces the forced apoptosis. It's possible to suppose that the geroprotective effect of the evening injections of melatonin is increased due to stimulation of the biosynthesis of neuropeptides in pineal gland.


Antimicrobial and antiseptic strategies in wound management.
Wounds, especially chronic wounds, represent a global problem costing millions of dollars per year in developed countries and are characterised by microbial complications including local or overt infection, delayed healing and spread of multiresistant germs. Therefore, antimicrobial wound management is a major challenge that continues to require new solutions against microbes and their biofilms. As systemic antibiotics can barely penetrate into wound biofilms and topically applied ones can easily lead to sensitisation, antisepsis is the method of choice to treat germs in wounds. This brief review discusses the role of antiseptics in reducing bioburden in chronic wounds. Balancing antimicrobial potency and tolerability of antiseptic procedures is critical in wound therapy. However, antiseptics alone may not be able to achieve wound healing without addressing other factors regarding the patient's general health or the wound's physical environment. Although the precise role of bioburden in chronic wounds remains to be evaluated, planktonic as well as biofilm-bound microbes are indications for antiseptic intervention. Octenidine dihydrochloride and polyhexanide are the most effective, as well as best tolerated, antiseptics in wound management today, and new strategies to reduce bacterial wound burden and support the body's immune response are being developed.


The Altered Functions of Shelterin Components in ALT Cells.
Telomeres are nucleoprotein complexes that cap the ends of eukaryotic linear chromosomes. Telomeric DNA is bound by shelterin protein complex to prevent telomeric chromosome ends from being recognized as damaged sites for abnormal repair. To overcome the end replication problem, cancer cells mostly preserve their telomeres by reactivating telomerase, but a minority (10-15%) of cancer cells use a homologous recombination-based pathway called alternative lengthening of telomeres (ALT). Recent studies have found that shelterin components play an important role in the ALT mechanism. The binding of TRF1, TRF2, and RAP1 to telomeres attenuates ALT activation, while the maintenance of ALT telomere requires TRF1 and TRF2. POT1 and TPP1 can also influence the occurrence of ALT. The elucidation of how shelterin regulates the initiation of ALT remains elusive. This review presents a comprehensive overview of the current findings on the regulation of ALT by shelterin components, aiming to enhance the insight into the altered functions of shelterin components in ALT cells and to identify potential targets for the treatment of ALT tumor cells.


Calcium pump activity of sarcoplasmic reticulum in diabetic rat skeletal muscle.
Ca2+ pump activity of skeletal muscle microsomes containing fragments of sarcoplasmic reticulum was examined in rats 8 wk after the induction of chronic diabetes by an intravenous injection of streptozotocin (65 mg/kg). In comparison with the control values, both ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase activities were increased in the microsomal fraction from diabetic rats. These changes were seen as early as 7 days after streptozotocin injection and were apparent at various times of incubation (1-10 min) as well as at different concentrations of free Ca2+ (10(-7)-5 X 10(-5) M Ca2+). Insulin administration to diabetic animals for 2 wk reversed Ca2+ uptake and ATPase activities to control levels. The increase in microsomal ATPase activity of the diabetic preparation due to cAMP-dependent protein kinase or calmodulin was greater than in the control microsomes and the depression by a specific inhibitor of protein kinase, but not of calmodulin, was greater in diabetic muscle. The enhanced Ca2+ pump activity was associated with altered phospholipid composition and protein profile of the diabetic preparations. The rate of Ca2+ release from microsomal vesicles was unaffected by the diabetic condition. Isometric contractile force development as well as positive dF/dt and negative dF/dt of the skeletal muscle from diabetic animals were higher at different pulse strengths (0.5-100 V) and at different Ca2+ concentrations (0.25-2.5 mM). These results suggest that diabetes is associated with enhanced sarcoplasmic reticular Ca2+ pump activity, and this may account for the hyperfunction of skeletal muscle in this disease.


Forelimb and hindlimb ground reaction forces of walking cats: assessment and comparison with walking dogs.
The primary aim of this study was to assess the potential of force plate analysis for describing the stride cycle of the cat. The secondary aim was to define differences in feline and canine locomotion based on force plate characteristics. Ground reaction forces of 24 healthy cats were measured and compared with ground reaction forces of 24 healthy dogs. Force-time waveforms in cats generated by force plate analysis were consistent, as reflected by intra-class correlation coefficients for peak vertical force, peak propulsive force and peak braking force (0.94-0.95, 0.85-0.89 and 0.89-0.90, respectively). Compared with dogs, cats had a higher peak vertical force during the propulsion phase (cat, 3.89 ± 0.19 N/kg; dog, 3.03 ± 0.16 N/kg), and a higher hindlimb propulsive force (cat, -1.08 ± 0.13 N/kg; dog, (-0.87 ± 0.13 N/kg) and hindlimb impulse (cat, -0.18 ± 0.03 N/kg; dog, -0.14 ± 0.02 N/kg). Force plate analysis is a valuable tool for the assessment of locomotion in cats, because it can be applied in the clinical setting and provides a non-invasive and objective measurement of locomotion characteristics with high repeatability in cats, as well as information about kinetic characteristics. Differences in force-time waveforms between cats and dogs can be explained by the more crouched position of cats during stance and their more compliant gait compared with dogs. Feline waveforms of the medio-lateral ground reaction forces also differ between cats and dogs and this can be explained by differences in paw supination-pronation.


Environmental correlates of abundances of mosquito species and stages in discarded vehicle tires.
Discarded vehicle tires are a common habitat for container mosquito larvae, although the environmental factors that may control their presence or abundance within a tire are largely unknown. We sampled discarded vehicle tires in six sites located within four counties of central Illinois during the spring and summer of 2006 to determine associations between a suite of environmental factors and community composition of container mosquitoes. Our goal was to find patterns of association between environmental factors and abundances of early and late instars. We hypothesized that environmental factors correlated with early instars would be indicative of oviposition cues, whereas environmental factors correlated with late instars would be those important for larval survival. We collected 13 species of mosquitoes, with six species (Culex restuans, Cx. pipiens, Aedes albopictus, Cx. salinarius, Ae. atropalpus, and Ae. triseriatus) accounting for r95% of all larvae. There were similar associations between congenerics and environmental factors, with Aedes associated with detritus type (fine detritus, leaves, seeds) and Culex associated with factors related to the surrounding habitat (human population density, canopy cover, tire size) or microorganisms (bacteria, protozoans). Although there was some consistency in factors that were important for early and late instar abundance, there were few significant associations between early and late instars for individual species. Lack of correspondence between factors that explain variation in early versus late instars, most notable for Culex, suggests a difference between environmental determinants of oviposition and survival within tires. Environmental factors associated with discarded tires are important for accurate predictions of mosquito occurrence at the generic level.


Oral care as a life course project: A qualitative grounded theory study.
To report on a theory to explain the oral health of older people over the life course. The study of ageing has burgeoned into a complex interdisciplinary field of research, yet there are few studies in oral health from the perspective of older people that bridge the gap between sociology and oral health related research. A grounded theory study involving a convenience sample of 15 men and 28 women aged between 65 and 91 years across different levels of education. Data were subjected to grounded theory analysis using QSR NVivo 11.0 and where relevant phenomenological theory. Participants conceived of oral care as a life course project that resulted from an active plan to keep one's teeth into older age. This involved accessing the social world of dentistry, holding appropriate values, understanding the associated personality types, social practices, goals and outcomes. The life course project is a social project supported by social institutions. It involves ideas about appropriate ageing including how oral health is to be managed at different stages in the life course. The degree to which individuals are able to participate in this project is determined by both individual and social factors. The theory explains why the loss of a single tooth might be experienced as traumatic but also why older people adapt to their changing oral health. Oral health in older age represented a lifetime's investment in oral care. Future health policies should consider this lifetime investment when considering care for older people.


A path toward the clinical translation of nano-based imaging contrast agents.
Recently, nanoparticles have evolved ubiquitously in therapeutic applications to treat a range of diseases. Despite their regular use as therapeutic agents in the clinic, we have yet to see much progress in their clinical translation as diagnostic imaging agents. Several clinical and preclinical studies support their use as imaging contrast agents, but their use in the clinical setting has been limited to off-label imaging procedures (i.e., Feraheme). Since diagnostic imaging has been historically used as an exploratory tool to rule out disease or to screen patients for various cancers, nanoparticle toxicity remains a concern, especially when introducing exogenous contrast agents into a potentially healthy patient population, perhaps rationalizing why several nano-based therapeutic agents have been clinically translated before nano-based imaging agents. Another potential hindrance toward their clinical translation could be their market potential, as most therapeutic drugs have higher earning potential than small-molecule imaging contrast agents. With these considerations in mind, perhaps a clinical path forward for nano-based imaging contrast agents is to help guide/manage therapy. Several studies have demonstrated the ability of nanoparticles to produce more accurate imaging preoperatively, intraoperatively, and postoperatively. These applications illustrate a more reliable method of cancer detection and treatment that can prevent incomplete tumor resection and incorrect assessment of tumor progression following treatment. The aim of this review is to highlight the research that supports the use of nanoparticles in biomedical imaging applications and offer a new perspective to illustrate how nano-based imaging agents have the potential to better inform therapeutic decisions. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.


Specificity of P2 primary alkylsulphohydrolase induction in the detergent-degrading bacterium Pseudomonas C12B. Effects of alkanesulphonates, alkyl sulphates and other related compounds.
Primary alkanesulphonates were shown to serve as non-metabolizable (gratuitous) inducers of the P2 primary alkylsulphohydrolase enzyme in resting cell suspensions of Pseudomonas C12B. The effects of increasing concentrations of inducer on the production of enzyme were complex and suggestive of a multiphasic phenomenon. However, it was possible to determine Kinducer constants (analogous to Km or Ki) for alkanesulphonates of chain length from C7 to c12. these decreased with increasing chain length in a manner characteristic of an homologous series. Primary alkyl sulphates also served as good inducers of alkylsulphohydrolase, but valid kinetic values could not be obtained because these esters are good substrates for the enzyme and are therefore appreciably hydrolysed during the induction period. Small amounts of enzyme were also produced when cyprinol sulphate, dodecyltriethoxy sulphate C12H23-[O-CH2-CH2]3-O-SO3-Na+), Crag herbicide and some secondary alkyl sulphates were tested as inducers.


Adult age-differences in subjective impression of emotional faces are reflected in emotion-related attention and memory tasks.
Although younger and older adults appear to attend to and remember emotional faces differently, less is known about age-related differences in the subjective emotional impression (arousal, potency, and valence) of emotional faces and how these differences, in turn, are reflected in age differences in various emotional tasks. In the current study, we used the same facial emotional stimuli (angry and happy faces) in four tasks: emotional rating, attention, categorical perception, and visual short-term memory (VSTM). The aim of this study was to investigate effects of age on the subjective emotional impression of angry and happy faces and to examine whether any age differences were mirrored in measures of emotional behavior (attention, categorical perception, and memory). In addition, regression analyses were used to further study impression-behavior associations. Forty younger adults (range 20-30 years) and thirty-nine older adults (range 65-75 years) participated in the experiment. The emotional rating task showed that older adults perceived less arousal, potency, and valence than younger adults and that the difference was more pronounced for angry than happy faces. Similarly, the results of the attention and memory tasks demonstrated interaction effects between emotion and age, and age differences on these measures were larger for angry than for happy faces. Regression analyses confirmed that in both age groups, higher potency ratings predicted both visual search and VSTM efficiency. Future studies should consider the possibility that age differences in the subjective emotional impression of facial emotional stimuli may explain age differences in attention to and memory of such stimuli.


MIG in psoriatic arthritis.
Monokine induced by interferon (IFN)-γ (MIG) / chemokine (C-X-C motif) ligand 9 (CXCL)9 is involved in the pathogenesis of psoriatic arthritis (PsA). It was demonstrated that both blood plasma-derived dendritic cells (pDCs) and pDCs isolated from rheumatoid arthritis (RA) and PsA synovial fluid (SF), expressed CXC receptor (R) 3 and CXCR4, and that the chemotaxis of blood-derived pDCs is stimulated by MIG, (IFN)-γ-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T-cell α chemoattractant (I-TAC) )/CXCL11 and stromal cell-derived factor 1 (SDF-1)/ CXCL12, present in RA and PsA SF. In PsA patients have been found a Th1 immune predominance at early stage of disease, while a reduction of these chemokines has been observed in long lasting PsA, with a significant increase of monocyte chemoattractant protein-1/IP-10 ratio. This suggest a shift from Th1 to the Th2 immune response in long lasting PsA. High levels of MIG has been found in patients with PsA and autoimmune thyroiditis too. This chemokine has been proposed as a useful marker to monitor the activity as well the progression of PsA. Efforts have been made to modulate or prevent the production of MIG in PsA aiming to alter the course of the disease.


Phylogeny of 33 ribosomal and six other proteins encoded in an ancient gene cluster that is conserved across prokaryotic genomes: influence of excluding poorly alignable sites from analysis.
Thirty-nine proteins encoded in a large gene cluster that is well-conserved in gene content and gene order across 18 sequenced prokaryotic genomes were extracted, aligned and subjected to phylogenetic analysis. In individual analyses of the alignments, only two probable examples of lateral gene transfer between archaea and eubacteria were detected, involving the genes for ribosomal protein Rpl23 and adenylate kinase. Amino acid sequences for 35 of the 39 proteins were concatenated to yield a data set of 9087 amino acid positions per genome. Many of these proteins, 33 of which are ribosomal proteins, are not highly conserved across distantly related organisms and thus contain many regions that are difficult to align. Phylogenetic analyses were performed with subsets of the concatenated data from which the most highly variable sites had been iteratively removed, using the number of different amino acids that occur at a given site as a criterion of variability. Glycine, which has a strong influence on protein structure, tended to be more frequent at the most conserved (least polymorphic) sites. With most subsets of the data, the proteins from the cyanobacterium Synechocystis tended to branch with their homologues from gram-positive bacteria. The results indicate that excluding only a few percentage of poorly alignable sites from phylogenetic analysis can have a severe impact upon the phylogeny inferred and that bootstrap support for branches can fluctuate substantially, depending upon which sites are excluded.


Association between TGFβ1 Levels in Cord Blood and Weight Progress in the First Year of Life.
Transforming growth factor beta-1 (TGFβ1) is an adipokine secreted from adipose tissue, placental tissue and immune cells with a role in cell proliferation, cell apoptosis and angiogenic proliferation. The role of TGFβ1 in pregnancy and child growth and the source of cord TGFβ1 are yet unknown. In this study, we sought to clarify the correlation of TGFβ1 levels with parameters of intrauterine growth and child growth during the first year of life, and to determine whether their source is primarily of fetal or maternal origin. Serum samples and anthropometric measurements were obtained from the LIFE Child cohort of 79 healthy mother-child pairs. Measurements were conducted using enzyme-linked immunosorbent assays. Statistical analyses including Mann-Whitney U-test, correlation analyses and linear regression analyses were performed using GraphPad Prism and R. TGFβ1 levels were significantly higher in cord than in maternal serum, suggesting a fetal origin. Multivariate regression analyses revealed strong positive associations between cord TGFβ1 levels at birth and child weight at U6. Furthermore, cord TGFβ1 was significantly correlated with child weight at approximately one year of age. An increase of 10,000 pg/mL in cord TGFβ1 concentrations at birth was associated with a higher body weight of 201 g at roughly one year of age when adjusted for sex.


Conserved NDR/LATS kinase controls RAS GTPase activity to regulate cell growth and chronological lifespan.
Adaptation to the nutritional environment is critical for all cells. RAS GTPase is a highly conserved GTP-binding protein with crucial functions for cell growth and differentiation in response to environmental conditions. Here, we describe a novel mechanism connecting RAS GTPase to nutrient availability in fission yeast. We report that the conserved NDR/LATS kinase Orb6 responds to nutritional cues and regulates Ras1 GTPase activity. Orb6 increases the protein levels of an Ras1 GTPase activator, the guanine nucleotide exchange factor Efc25, by phosphorylating Sts5, a protein bound to efc25 mRNA. By manipulating the extent of Orb6-mediated Sts5 assembly into RNP granules, we can modulate Efc25 protein levels, Ras1 GTPase activity, and, as a result, cell growth and cell survival. Thus, we conclude that the Orb6-Sts5-Ras1 regulatory axis plays a crucial role in promoting cell adaptation, balancing the opposing demands of promoting cell growth and extending chronological lifespan.


Flexible Organic Tribotronic Transistor for Pressure and Magnetic Sensing.
Flexible electronics has attracted enormous interest in wearable electronics and human-machine interfacing. Here, a flexible organic tribotronic transistor (FOTT) without a top gate electrode has been demonstrated. The FOTT is fabricated on a flexible polyethylene terephthalate film using the p-type pentacene and poly(methyl methacrylate)/Cytop composites as the conductive channel and dielectric layer, respectively. The charge carriers can be modulated by the contact electrification between the dielectric layer and a mobile triboelectric layer. Based on the fabricated FOTT, pressure and magnetic sensors have been developed, respectively, that exhibit great sensitivity, fast response time, and excellent stability. The FOTT in this simple structure shows bright potentials of tribotronics in human-machine interaction, electronic skins, wearable electronics, intelligent sensing, and so on.


Effects of detector wobble motion on image noise in positron emission tomography.
The effects of detector wobble motion on image variance is described analytically and verified by simulation studies. Simulation results in the form of variance images are presented for various phantoms, sampled under both uniform and wobble-motion conditions. It is shown that under most measurement conditions in a typical PET study, the image precision is degraded due to the nonuniform projection variance introduced by the wobble motion. Using the wobble parameters of the UBC-TRIUMF development of PETT VI, the rms noise is found to be increased by 9 percent due to wobbling.


Plummer Vinson Syndrome: A Rare Syndrome in Male with Review of the Literature.
Plummer Vinson syndrome also known as Paterson Brown-Kelly syndrome is a syndrome associated with the triad of symptoms comprising microcytic hypochromic anemia, oesophageal strictures, and dysphagia. PVS is commonly found in women of middle age especially in the fourth and fifth decade of life and is rarely reported in males. The authors report a case of 43-year-old male patient who presented with the classic symptoms of Plummer Vinson syndrome. Dentists have to be familiar with symptoms of PVS and a thorough clinical examination of the patient is necessary for early diagnosis and treatment. As PVS is a precancerous condition with high malignant potential, early diagnosis is of utmost importance for better prognosis. Mutual interaction of systemic and oral health has largely been underestimated by many patients in the developing countries and hence this report includes a note on importance of adequate medical history taking and its relevance to the dental health and treatment.


[A case of peritoneal carcinomatosis due to recurrence of primary adenocarcinoma of the ureter treated with weekly paclitaxel].
This report describes the case of a patient with peritoneal carcinomatosis due to recurrent adenocarcinoma of the ureter who was chemo-sensitive to weekly paclitaxel. A 73-year-old man was admitted to our hospital for pain in the right back in September 2009. Drip infusion pyelography(DIP)showed right hydronephrosis. Cytologic examination of the urine revealed many carcinoma cells in the urothelial tract. The patient underwent right nephroureterectomy, and examination of the resected specimen revealed a primary enteric-type adenocarcinoma of the ureter. Six months after surgery, he visited our hospital because of abdominal pain and distension. Abdominal computed tomography(CT)showed massive ascites. Cytologic examination of the ascitic fluid revealed many adenocarcinoma cells resembling those of the primary lesion. The patient received chemotherapy with S-1 as first-line treatment; however, he experienced severe anorexia and diarrhea. Subsequently, the patient received chemotherapy with uracil/tegafur(UFT)but abdominal distension worsened. Next, he received chemotherapy with weekly paclitaxel(80mg/m2 on days 1, 8, and 15, every 4 weeks). Thereafter, the ascitic fluid disappeared rapidly. After 6 courses of treatment with paclitaxel, abdominal CT revealed no ascitic fluid collection. The treatment was discontinued because of sensory neuropathy. Approximately 10 months later, the patient experienced massive ascites again. At 25 months after recurrence, he died of peritoneal carcinomatosis.


[Nosocomial pneumonia].
Nosocomial pneumonia (hospital-acquired pneumonia - HAP) is the form of pneumonia the symptoms of which present after more than 2 days (> 48 hours) of admission to hospital or as late as 14 days of discharge from hospital. The HAP pneumonias represent 13-18 % of all nosocomial infections. Incidence of HAP is the most frequent in mechanically ventilated patients. The type and representation of HAP agents primarily depends on the length of a patients stay in hospital and on their condition and character of treatment. Diagnosing of pneumonia is based on anamnesis, physical and X-ray findings, results of examination of microbiological samples from the respiratory tract, hemoculture, the pleural effusion test, serological, hematological and biochemical tests. Antibiotic treatment is key to the comprehensive treatment of HAP. The HAP treatment always requires the dosing of antibiotics near the upper limit of the possible range. A precondition for successful avoidance of HAP pneumonias is the creation of a preventive programme with active engagement of medical staff.Key words: diagnostics - HAP pneumonia - treatment - ventilator-associated pneumonia.


Avoidable claims in the liability experience of Virginia FPs insured by the reciprocal.
In response to the threat of litigation, physicians practice defensive medicine. A more effective means of reducing malpractice liability and improving the quality of patient care is to practice defensible medicine, i.e., those practice patterns that reduce the potential for claims and increase the likelihood that when claims do arise, they can be successfully defended. Unlike hospital-based specialists, family physicians can directly influence a significant portion of their risk of suit. By focusing management time and attention on the factors in their office practices that are linked to malpractice claims activity, family physicians can reduce the likelihood of being involved in claims.


Impact of exercise on muscle and nonmuscle organs.
Exercise is known to prevent and treat metabolic diseases such as diabetes. However, the underlying mechanisms are not fully understood, and there is currently much focus on detailing such pathways. Traditionally, much emphasis has been placed on skeletal muscle; however, recently, nonmuscle organs such as adipose tissue have been highlighted in mediating protective actions after training. Moreover, novel paracrine- and endocrine-signaling molecules have been shown to trigger important responses in nonmuscle organs after exercise. This is exciting because, when administered exogenously, such signals have obvious therapeutic potential. In this review, the authors have described some general and historical aspects of training and disease protection. The authors have also highlighted some of the current knowledge on how exercise impacts nonmuscle organs.


iSUMOK-PseAAC: prediction of lysine sumoylation sites using statistical moments and Chou's PseAAC.
Sumoylation is the post-translational modification that is involved in the adaption of the cells and the functional properties of a large number of proteins. Sumoylation has key importance in subcellular concentration, transcriptional synchronization, chromatin remodeling, response to stress, and regulation of mitosis. Sumoylation is associated with developmental defects in many human diseases such as cancer, Huntington's, Alzheimer's, Parkinson's, Spin cerebellar ataxia 1, and amyotrophic lateral sclerosis. The covalent bonding of Sumoylation is essential to inheriting part of the operative characteristics of some other proteins. For that reason, the prediction of the Sumoylation site has significance in the scientific community. A novel and efficient technique is proposed to predict the Sumoylation sites in proteins by incorporating Chou's Pseudo Amino Acid Composition (PseAAC) with statistical moments-based features. The outcomes from the proposed system using 10 fold cross-validation testing are 94.51%, 94.24%, 94.79% and 0.8903% accuracy, sensitivity, specificity and MCC, respectively. The performance of the proposed system is so far the best in comparison to the other state-of-the-art methods. The codes for the current study are available on the GitHub repository using the link: https://github.com/csbioinfopk/iSumoK-PseAAC.


Stability study for 53 antibiotics in solution and in fortified biological matrixes by LC/MS/MS.
This study was performed in order to determine the stability of antibiotics belonging to eight families in solution or biological matrix. Knowledge of the stability of antibiotics has to be demonstrated during method development or validation. The stability of stock standard solutions of 53 antibiotics was assessed after determining the appropriate conditions of dissolution and storage. The stability of the same 53 antibiotics after addition to negative control cow milk or pork muscle tissue stored at -18 and -70 degrees C was also assessed. Our concern was to obtain information concerning the stability of antibiotic residues in fortified biological matrixes in order to make easier the implementation of a routine screening method for antibiotic residues within the framework of the French monitoring program. Antibiotic solutions and fortified samples were analyzed using an LC/MS/MS method previously validated for screening purposes and for which it was checked that all pertinent criteria to obtain interpretable stability results were fulfilled. The design for testing the stability of antibiotics in solutions and matrix samples is described, as well as the rules of decision that were observed. Term periods for the stability study ranged from 1 month to 1 year, depending on the class of compounds. The results presented in this article will be useful and time-saving for many reference and field laboratories because LC/MS/MS methods are more and more commonly used for screening purposes.


Prolyl-leucyl-glycinamide shares some effects with oxytocin but decreases oxytocin levels.
Oxytocin treatment in rats induces long-lasting antistress and growth promoting effects. This study investigated whether prolyl-leucyl-glycinamide (PLG) (the c-terminal tripeptide of oxytocin) or tocinoic acid (the ring structure of oxytocin) could induce some of these effects in male rats. For this purpose, PLG (2 or 10 mg/kg, s.c.) or tocinoic acid (1 mg/kg, s.c.) was administered to rats once a day for 3 or 5 days. Blood pressure, heart rate, spontaneous motor activity, nociceptive thresholds, and the survival of ischaemic musculocutaneous flaps were measured. In addition, endogenous oxytocin levels and plasma levels of some hormones known to be influenced by oxytocin were determined. PLG (2 mg/kg, s.c., but not 10 mg/kg, s.c.) decreased diastolic blood pressure (p<0.05) and locomotor activity (p<0.05). PLG (10 mg/kg, s.c.) decreased gastrin (p<0.05) and endogenous oxytocin levels in plasma (p<0.01). Tocinoic acid decreased locomotor activity (p<0.05), but did not affect any of the other parameters measured. In conclusion, this study showed that both PLG and tocinoic acid decrease locomotor activity. In addition, PLG also induced some other effects similar to those induced by oxytocin treatment but when administered in high doses it decreased oxytocin levels.


Community-based screening for childhood lead poisoning. Identification of risk factors and susceptible populations in Duluth.
The purpose of this matched case-controlled study was to identify local risk factors and susceptible populations for childhood lead poisoning in Duluth, Minnesota. We mailed questionnaires to the parents of 20 children with known elevated capillary lead levels > or = 10 micrograms/dL; 76 age-matched controls had capillary lead levels < 10 micrograms/dL. The study identified these risk factors for elevated capillary lead levels in children: not attending daycare, having nonwhite parents, living in rental property in central Duluth, and moving with family three or more times in the previous five years. We conclude that these risk factors are related to socioeconomics. Minority children and children living in poverty in the Duluth area should be screened for lead poisoning according to the Centers for Disease Control and Prevention screening guidelines for high-risk lead exposure.


Extracorporeal irradiation of blood: dosimetry corrected for shortened erythrocyte lifespans.
The amount of radiation delivered to erythrocytes during extracorporeal irradiation of blood (ECIB) has been described using Poisson distribution statistics. The Poisson expression for erythrocyte radiation dose distribution was simplified by considering the slight dilution of blood with fluid that is initially in the extracorporeal tubing. An algorithm was devised that allows curtailed lifespans of irradiated erythrocytes to be taken into account in a short computer program of radiation dosimetry for ECIB. Radiation doses to erythrocytes with and without lifespan corrections are compared.


Colorectal and rectocolonic reflexes in canines: involvement of tone, compliance, and anal sphincter relaxation.
Distention of the proximal colon may have inhibitory or excitatory effects on the rectum and vice versa. The reflexes between the proximal colon and the rectum have not been well studied due to difficulties in accessing the proximal colon. The aim of this study was to investigate the reflex responses and their mechanisms between the proximal colon and the rectum in consideration of distention-related changes in tone and compliance of these regions as well as anal sphincter relaxation in a canine model. Proximal colon/rectal tone, compliance, and anal sphincter relaxation were investigated in six dogs chronically implanted with a proximal colon cannula while in the fasting state and during proximal colon distention or rectal distention. It was found that: 1) both rectal distention and proximal colon distention significantly and substantially decreased the compliance of the opposite regions, and guanethidine abolished proximal colon distention-induced changes in rectal compliance; 2) rectal/proximal colon distension decreased proximal colonic/rectal tone, and guanethidine abolished both of these inhibitory effects; 3) the anal sphincter was more sensitive to rectal distention than proximal colon distention; and 4) the minimal distention pressure required to induce anal inhibitory reflex was lower for rectal distention than proximal colon distention. It was concluded that distention-related changes in tone and compliance suggest the long inhibitory reflexes between the proximal colon and the rectum with the sympathetic involvement in rectal responses. The anal sphincter is more sensitive to the distention of the rectum than that of the proximal colon.


Interactions between SIRT1 and AP-1 reveal a mechanistic insight into the growth promoting properties of alumina (Al2O3) nanoparticles in mouse skin epithelial cells.
The physicochemical properties of nanomaterials differ from those of the bulk material of the same composition. However, little is known about the underlying effects of these particles in carcinogenesis. The purpose of this study was to determine the mechanisms involved in the carcinogenic properties of nanoparticles using aluminum oxide (Al(2)O(3)/alumina) nanoparticles as the prototype. Well-established mouse epithelial JB6 cells, sensitive to neoplastic transformation, were used as the experimental model. We demonstrate that alumina was internalized and maintained its physicochemical composition inside the cells. Alumina increased cell proliferation (53%), proliferating cell nuclear antigen (PCNA) levels, cell viability and growth in soft agar. The level of manganese superoxide dismutase, a key mitochondrial antioxidant enzyme, was elevated, suggesting a redox signaling event. In addition, the levels of reactive oxygen species and the activities of the redox sensitive transcription factor activator protein-1 (AP-1) and a longevity-related protein, sirtuin 1 (SIRT1), were increased. SIRT1 knockdown reduces DNA synthesis, cell viability, PCNA levels, AP-1 transcriptional activity and protein levels of its targets, JunD, c-Jun and BcL-xl, more than controls do. Immunoprecipitation studies revealed that SIRT1 interacts with the AP-1 components c-Jun and JunD but not with c-Fos. The results identify SIRT1 as an AP-1 modulator and suggest a novel mechanism by which alumina nanoparticles may function as a potential carcinogen.


Lonely drinking fountains and comforting coolers: paradoxes of water value and ironies of water use.
This article focuses ethnographically on Americans and technologies of drinking water, as tokens of and vehicles for health, agency, and surprising kinds of community. Journalists and water scholars have argued that bottled water is a material concomitant of privatization and alienation in U.S. society. But, engaging Latour, this research shows that water technologies and the groups they assemble, are plural. Attention to everyday entwining of workplace lives with drinking fountains, single-serve bottles, and spring water coolers shows us several different quests, some individualized, some alienated, but some seeking health via public, collective care, acknowledgment of stakeholding, and community organizing. Focused on water practices on a college campus, in the roaring 1990s and increasingly sober 2000s in the context of earlier U.S. water histories of inclusion and exclusion, I draw on ethnographic research from the two years that led up to the recession and the presidential election of 2008. I argue for understanding of water value through attention to water use, focusing both on the social construction of water and the use of water for social construction.


Mouse models of genomic syndromes as tools for understanding the basis of complex traits: an example with the smith-magenis and the potocki-lupski syndromes.
Each human's genome is distinguished by extra and missing DNA that can be "benign" or powerfully impact everything from development to disease. In the case of genomic disorders DNA rearrangements, such as deletions or duplications, correlate with a clinical specific phenotype. The clinical presentations of genomic disorders were thought to result from altered gene copy number of physically linked dosage sensitive genes. Genomic disorders are frequent diseases (~1 per 1,000 births). Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are genomic disorders, associated with a deletion and a duplication, of 3.7 Mb respectively, within chromosome 17 band p11.2. This region includes 23 genes. Both syndromes have complex and distinctive phenotypes including multiple congenital and neurobehavioral abnormalities. Human chromosome 17p11.2 is syntenic to the 32-34 cM region of murine chromosome 11. The number and order of the genes are highly conserved. In this review, we will exemplify how genomic disorders can be modeled in mice and the advantages that such models can give in the study of genomic disorders in particular and gene copy number variation (CNV) in general. The contributions of the SMS and PTLS animal models in several aspects ranging from more specific ones, as the definition of the clinical aspects of the human clinical spectrum, the identification of dosage sensitive genes related to the human syndromes, to the more general contributions as the definition of genetic locus impacting obesity and behavior and the elucidation of general mechanisms related to the pathogenesis of gene CNV are discussed.


Isolated Adrenal Metastases of Castration-Resistant Prostate Cancer: Excellent Response to 177 Lu-PSMA With No Adrenal Insufficiency.
We present isolated bilateral adrenal metastases successfully treated with 177 Lu-PSMA in a 66-year-old man diagnosed with castration-resistant prostate cancer. The patient had progression under chemotherapy as depicted by 68 Ga-PSMA PET/CT showing intense bilateral PSMA uptake in the adrenal masses, and metastasis-directed therapies were considered as the first option for improving survival because the patient was oligometastatic. However, surgery and radiotherapy were not justifiable options due to the high risk of definitive adrenal insufficiency; therefore, the patient received 4 cycles of 177 Lu-PSMA treatment. 68 Ga-PSMA PET/CT showed near-complete response in bilateral adrenal metastases, and no sign of adrenal insufficiency was observed during follow-up.


Outcome of glansectomy and skin grafting in the management of penile cancer.
Purpose. To report outcome data for patients with penile cancer treated surgically with glansectomy and skin grafting. Materials and Methods. We retrospectively reviewed data on all patients undergoing surgical management of penile cancer by a single surgeon between 1998 and 2008. Outcomes in patients who underwent glansectomy and skin grafting were analysed. Results. Between 1998 and 2008 a total of 25 patients with a mean age 60 (39-83) underwent glansectomy and skin grafting. Six patients had carcinoma in situ (CIS); the stage in the remaining patients ranged from T1G1 to T3G3. Mean followup for patients was 28 months (range 6-66). Disease specific survival was 92% with 2 patients who had positive nodes at lymph node dissection developing groin recurrence. One patient developed a local recurrence requiring a partial penectomy. Conclusions. Penile preserving surgery with glansectomy and skin grafting is a successful technique with minimal complications for local control of penile carcinoma arising on the glans. Careful followup to exclude local recurrence is required.


Effects of timing of grazing on arthropod communities in semi-natural grasslands.
Arthropod communities were investigated in two Swedish semi-natural grasslands, each subject to two types of grazing regime: conventional grazing from May to September (continuous grazing) and traditional late management from mid-July (late grazing). Pitfall traps were used to investigate abundance of carabids, spiders, and ants over the grazing season. Ant abundance was also measured by mapping nest density during three successive years. Small spiders, carabids and ants (Myrmica spp.) were more abundant in continuous grazing than in late grazing while larger spiders, carabids, and ants (Formica spp.) were more abundant in late grazing. The overall abundance of carabids was higher in continuous grazing in the early summer but higher in late grazing in the late summer. The switch of preference from continuous to late grazing coincided with the time for larvae hibernating species replacing adult hibernating. We discuss possible explanations for the observed responses in terms of effects of grazing season on a number of habitat variables for example temperature, food resources, structure of vegetation, litter layer, competition, and disturbance.


A provider intervention to improve colorectal cancer screening in county health centers.
Publicly-funded health centers serve disadvantaged populations who underuse colorectal cancer screening (CRC). Because physicians play a key role in patient adherence to screening, provider interventions within health center practices could improve the delivery/utilization of CRC screening. A 2-group study design was used with 4 pairs of health centers randomized to the intervention or control condition. The provider intervention featured academic detailing of the small practice groups, followed by a strategic planning session with the entire health center staff using SWOT analysis. The outcome measure of provider endoscopy referral/fecal occult blood test dispensing and/or completion of CRC screening was determined by medical record audit (n = 2224). The intervention effect was evaluated using generalized estimating equations. Pre-post intervention patient surveys (n = 281) were conducted. Chart audits of the 1 year period before and after the intervention revealed a 16% increase from baseline in CRC screening referral/dispensing/completion among intervention centers, compared with a 4% increase among controls, odds ratio (OR) = 2.25 (1.67-3.04) P < 0.001. Intervention versus control health center patient self-reports of lack of physician recommendation as a reason for not having CRC screening declined from baseline to follow-up (P = 0.04). Provider referrals/dispensing/completion of CRC screening within health centers was significantly improved and barriers reduced through a provider intervention combining continuing medical education with a team building strategic planning exercise.


An artificial intelligence-derived tool proposal to ease disordered eating screening in people with obesity.
In people with obesity, food addiction (FA) tends to be associated with poorer outcomes. Its diagnosis can be challenging in primary care. Based on the SCOFF example, we aim to determine whether a quicker and simpler screening tool for FA in people with obesity could be developed, using artificial intelligence (machine learning). The first step was to look for the most discriminating items, among 152 different ones, to differentiate between FA-positive and FA-negative populations of patients with obesity. Items were ranked using the Fast Correlation-Based Filter (FCBF). Retained items were used to test the performance of nine different predictive algorithms. Then, the construction of a graphic tool was proposed. Data were available for 176 patients. Only three items had a FCBF score > 0.1: "I eat to forget my problems"; "I eat more when I'm alone"; and "I eat sweets or comfort foods". Naive Bayes classification obtained best predictive performance. Then, we created a 3-item nomogram to predict a positive scoring on the YFAS. A simple and fast screening tool for detecting high-disordered eating risk is proposed. The next step will be a validation study of the FAST nomogram to ensure its relevance for emotional eating diagnosis. Level V, cross-sectional descriptive study. NCT02857179 at clinicaltrials.gov.


Use of mass spectrometry fingerprinting to identify urinary metabolites after consumption of specific foods.
The lack of robust biological markers of dietary exposure hinders the quantitative understanding of causal relations between diet and health. We aimed to develop an efficient procedure to discover metabolites in urine that may have future potential as biomarkers of acute exposure to foods of high public health importance. Twenty-four participants were provided with a test breakfast in which the cereal component of a standardized breakfast was replaced by 1 of 4 foods of high public health importance; 1.5-, 3-, and 4.5-h postprandial urine samples were collected. Flow infusion electrospray-ionization mass spectrometry followed by supervised multivariate data analysis was used to discover signals resulting from consumption of each test food. Fasted-state urine samples provided a universal comparator for food biomarker lead discovery in postprandial urine. The filtering of data features associated with consumption of the common components of the standardized breakfast improved discrimination models and readily identified metabolites that showed consumption of specific test foods. A combination of trimethylamine-N-oxide and 1-methylhistidine was associated with salmon consumption. Novel ascorbate derivatives were discovered in urine after consumption of either broccoli or raspberries. Sulphonated caffeic acid and sulphonated methyl-epicatechin concentrations increased dramatically after consumption of raspberries. This biomarker lead discovery strategy can identify urinary metabolites associated with acute exposure to individual foods. Future studies are required to validate the specificity and utility of potential biomarkers in an epidemiologic context.


The effect of pentoxifylline on red cell deformability in cerebrovascular accidents.
A study was carried out in 49 recent cerebrovascular accident (CVA) patients to compare red cell deformability in this group with that in 65 healthy controls. Deformability was determined using a standard technique for measuring blood filtration time through a micropore filter. Filtration time was shown to be significantly reduced in the CVA patients. All patients had ACTH treatment, 28 of them receiving in addition 600 mg pentoxifylline per day, either by intravenous infusion or by intramuscular injection. After 2-weeks' treatment, red cell deformability was increased in the patients treated with pentoxifylline and ACTH and was unchanged in the 21 patients receiving only ACTH (p less than 0.001). The authors discuss the role of increased red cell deformability in the clinical prognosis of the patients.


Parent's perceived responsibility for children's problems.
Beliefs about parents' influence on their children's behaviour have developed over the last 300 years. During this century multiple socio-economic, ideological and technological changes have combined to leave expert and lay person alike in a sea of confusion and ambiguity about optimal parent-child relationships. While fashions in child rearing change, the mother is usually accorded responsibility for the child's behaviour and social skills. In this study parents attending a multidisciplinary pediatric clinic were asked their opinion of the source of their child's emotional or behavioural problem. Describing confusion and conflicting advice, most parents had concluded that the problem had multiple roots. Between male and female parents, however, a marked difference was evident in the attribution of responsibility to themselves or their spouses and in their formulation of the nature of parental deficiencies.