Different EPHX1 methylation levels in promoter area between carbamazepine-resistant epilepsy group and carbamazepine-sensitive epilepsy group in Chinese population.
Epigenetics underlying refractory epilepsy is poorly understood. DNA methylation may affect gene expression in epilepsy patients without affecting DNA sequences. Herein, we investigated the association between Carbamazepine-resistant (CBZ-resistant) epilepsy and EPHX1 methylation in a northern Han Chinese population, and conducted an analysis of clinical risk factors for CBZ-resistant epilepsy. Seventy-five northern Han Chinese patients participated in this research. 25 cases were CBZ-resistant epilepsy, 25 cases were CBZ-sensitive epilepsy and the remaining 25 cases were controls. Using a CpG searcher was to make a prediction of CpG islands; bisulfite sequencing PCR (BSP) was applied to test the methylation of EPHX1. We then did statistical analysis between clinical parameters and EPHX1 methylation. There was no difference between CBZ-resistant patients, CBZ-sensitive patients and healthy controls in matched age and gender. However, a significant difference of methylation levels located in NC_000001.11 (225,806,929.....225807108) of the EPHX1 promoter was found in CBZ-resistant patients, which was much higher than CBZ-sensitive and controls. Additionally, there was a significant positive correlation between seizure frequency, disease course and EPHX1 methylation in CBZ-resistant group. Methylation levels in EPHX1 promoter associated with CBZ-resistant epilepsy significantly. EPHX1 methylation may be the potential marker for CBZ resistance prior to the CBZ therapy and potential target for treatments.


Prediction of Pathological Tremor Signals Using Long Short-Term Memory Neural Networks.
Previous implementations of closed-loop peripheral electrical stimulation (PES) strategies have provided evidence about the effect of the stimulation timing on tremor reduction. However, these strategies have used traditional signal processing techniques that only consider phase prediction and might not model the non-stationary behavior of tremor. Here, we tested the use of long short-term memory (LSTM) neural networks to predict tremor signals using kinematic data recorded from Essential Tremor (ET) patients. A dataset comprising wrist flexion-extension data from 12 ET patients was pre-processed to feed the predictors. A total of 180 models resulting from the combination of network (neurons and layers of the LSTM networks, length of the input sequence and prediction horizon) and training parameters (learning rate) were trained, validated and tested. Predicted tremor signals using LSTM-based models presented high correlation values (from 0.709 to 0.998) with the expected values, with a phase delay between the predicted and real signals below 15 ms, which corresponds approximately to 7.5% of a tremor cycle. The prediction horizon was the parameter with a higher impact on the prediction performance. The proposed LSTM-based models were capable of predicting both phase and amplitude of tremor signals outperforming results from previous studies (32--56% decreased phase prediction error compared to the out-of-phase method), which might provide a more robust PES-based closed-loop control applied to PES-based tremor reduction.


Founder population-specific HapMap panel increases power in GWA studies through improved imputation accuracy and CNV tagging.
The combining of genome-wide association (GWA) data across populations represents a major challenge for massive global meta-analyses. Genotype imputation using densely genotyped reference samples facilitates the combination of data across different genotyping platforms. HapMap data is typically used as a reference for single nucleotide polymorphism (SNP) imputation and tagging copy number polymorphisms (CNPs). However, the advantage of having population-specific reference panels for founder populations has not been evaluated. We looked at the properties and impact of adding 81 individuals from a founder population to HapMap3 reference data on imputation quality, CNP tagging, and power to detect association in simulations and in an independent cohort of 2138 individuals. The gain in SNP imputation accuracy was highest among low-frequency markers (minor allele frequency [MAF] < 5%), for which adding the population-specific samples to the reference set increased the median R(2) between imputed and genotyped SNPs from 0.90 to 0.94. Accuracy also increased in regions with high recombination rates. Similarly, a reference set with population-specific extension facilitated the identification of better tag-SNPs for a subset of CNPs; for 4% of CNPs the R(2) between SNP genotypes and CNP intensity in the independent population cohort was at least twice as high as without the extension. We conclude that even a relatively small population-specific reference set yields considerable benefits in SNP imputation, CNP tagging accuracy, and the power to detect associations in founder populations and population isolates in particular.


Functional Neuroplasticity in the Nucleus Tractus Solitarius and Increased Risk of Sudden Death in Mice with Acquired Temporal Lobe Epilepsy.
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in individuals with refractory acquired epilepsy. Cardiorespiratory failure is the most likely cause in most cases, and central autonomic dysfunction has been implicated as a contributing factor to SUDEP. Neurons of the nucleus tractus solitarius (NTS) in the brainstem vagal complex receive and integrate vagally mediated information regarding cardiorespiratory and other autonomic functions, and GABAergic inhibitory NTS neurons play an essential role in modulating autonomic output. We assessed the activity of GABAergic NTS neurons as a function of epilepsy development in the pilocarpine-induced status epilepticus (SE) model of temporal lobe epilepsy (TLE). Compared with age-matched controls, mice that survived SE had significantly lower survival rates by 150 d post-SE. GABAergic NTS neurons from mice that survived SE displayed a glutamate-dependent increase in spontaneous action potential firing rate by 12 wks post-SE. Increased spontaneous EPSC frequency was also detected, but vagal afferent synaptic release properties were unaltered, suggesting that an increase in glutamate release from central neurons developed in the NTS after SE. Our results indicate that long-term changes in glutamate release and activity of GABAergic neurons emerge in the NTS in association with epileptogenesis. These changes might contribute to increased risk of cardiorespiratory dysfunction and sudden death in this model of TLE.


[Novel method for dynamic monitoring and early-warning on wild resources of traditional Chinese medicines based on price ratio between drug and foodstuff].
To probe into the new idea along with establishment of a novel method for dynamic monitoring and early-warning on the wild resources of traditional Chinese medicines (TCMs). The alterations of wild traditional Chinese medicinal resources were assessed through the price ratio between drug and foodstuff (PRDF) indicating the balance between supply and demand of the specific TCMs, referred to the price ration between pork to foodstuff which is used in national monitoring to the balance between pork supply and demand. Since the price of rice was tightly controlled by government, it was selected as a relatively stable reference to build the PRDF in order to take away the non-marketing influence to TCMs price such as CPI and inflation rate. The modified relative alteration trend of TCMs price had been researched through comparing different formulae to build PRDF, including absolute average month price of TCMs, month average price ratio of TCMs to foodstuff (rice) , month-on-month change of TCMs to rice, year-on-year change of TCMs to rice, and difference in value of period-on-period change (DVPPC). In the research, Cordyceps, Glycyrrhiza and totally five herbs were selected as model drugs and the price data were collected from 2002 to 2008. The results showed that DVPPC calculated of relative long time window was more sensitive and stable to reflect the relative alteration trend of TCMs price. For instance, the DVPPC of Ligustici showed continuously increase trend in recent years. This suggested appearance of unbalance between supply and demand of Ligustici, and forced policy intervention to maintain reasonable and continuable utilization of Ligustici resource. The proposed method and the formula of DVPPC revealed some useful guidance for dynamic monitoring the wild resources of TCMs.


Exceptional aerobic scope and cardiovascular performance of pink salmon (Oncorhynchus gorbuscha) may underlie resilience in a warming climate.
Little is known of the physiological mechanisms underlying the effects of climate change on animals, yet it is clear that some species appear more resilient than others. As pink salmon (Oncorhynchus gorbuscha) in British Columbia, Canada, have flourished in the current era of climate warming in contrast to other Pacific salmonids in the same watershed, this study investigated whether the continuing success of pink salmon may be linked with exceptional cardiorespiratory adaptations and thermal tolerance of adult fish during their spawning migration. Sex-specific differences existed in minimum and maximum oxygen consumption rates (M(O2,min) and M(O2,max), respectively) across the temperature range of 8 to 28°C, reflected in a higher aerobic scope (M(O2,max)-M(O2,min)) for males. Nevertheless, the aerobic scope of both sexes was optimal at 21°C (T(opt)) and was elevated across the entire temperature range in comparison with other Pacific salmonids. As T(opt) for aerobic scope of this pink salmon population is higher than in other Pacific salmonids, and historic river temperature data reveal that this population rarely encounters temperatures exceeding T(opt), these findings offer a physiological explanation for the continuing success of this species throughout the current climate-warming period. Despite this, declining cardiac output was evident above 17°C, and maximum attainable swimming speed was impaired above ∼23°C, suggesting negative implications under prolonged thermal exposure. While forecasted summer river temperatures over the next century are likely to negatively impact all Pacific salmonids, we suggest that the cardiorespiratory capacity of pink salmon may confer a selective advantage over other species.


Illness Expectations Assessment in People with Asthma: A Tool for Explicit and Implicit Beliefs.
Illness expectations are cognitive schemas, both explicit and implicit, describing how symptoms are expected to be in the future. They can be particularly relevant to disease in a mind/body framework. Asthma is a condition in which the psychological aspects can highly influence the body, but no study has directly explored these specific expectations, and no dedicated assessment tools are available. We developed a questionnaire to assess the illness expectations, together with an ad hoc version of the Implicit Association Test (IAT). We tested its factorial structure, and the internal and test-retest validity, recruiting a sample of 183 asthmatic people. We also explored the convergent validity and the correlations with objective and subjective clinical assessments. Data suggested a three-factorial structure of the questionnaire into expectations about future symptoms, change in current health status, and rigidity of these expectations. The questionnaire showed good psychometric properties and strong associations with the other considered outcomes, including implicit expectations. The implicit evaluation, however, lacked test-retest reliability. The questionnaire is a valid tool to assess illness expectations in people with asthma. The two expectation scales are highly related, and the implicit expectations are moderately associated with the explicit ones. The lack of stability related to IAT results may reflect a lack of stability of the implicit expectations. The implications for the mind/body framework still need to be fully explored.


The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease.
This article is part of a Special Issue "SBN 2014". Sex hormones are physiological factors that promote neurogenesis during embryonic and fetal development. During childhood and adulthood these hormones support the maintenance of brain structure and function via neurogenesis and the formation of dendritic spines, axons and synapses required for the capture, processing and retrieval of information (memories). Not surprisingly, changes in these reproductive hormones that occur with menopause and during andropause are strongly correlated with neurodegeneration and cognitive decline. In this connection, much evidence now indicates that Alzheimer's disease (AD) involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Intriguingly, a recent animal study has demonstrated that induction of adult neurogenesis results in the loss of previously encoded memories while decreasing neurogenesis after memory formation during infancy mitigated forgetting. Here we review the biochemical, epidemiological and clinical evidence that alterations in sex hormone signaling associated with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle that leads to neurite retraction, neuron dysfunction and neuron death. When the reproductive axis is in balance, gonadotropins such as luteinizing hormone (LH), and its fetal homolog, human chorionic gonadotropin (hCG), promote pluripotent human and totipotent murine embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the LH:sex steroid ratio as driving aberrant mitotic events. These include the upregulation of tumor necrosis factor; amyloid-β precursor protein processing towards the production of mitogenic Aβ; and the activation of Cdk5, a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and neurodegeneration). Cognitive and biochemical studies confirm the negative consequences of a high LH:sex steroid ratio on dendritic spine density and human cognitive performance. Prospective epidemiological and clinical evidence in humans supports the premise that rebalancing the ratio of circulating gonadotropins:sex steroids reduces the incidence of AD. Together, these data support endocrine dyscrasia and the subsequent loss of cell cycle control as an important etiological event in the development of neurodegenerative diseases including AD, stroke and Parkinson's disease.


[Not Available].
A patient's personal experience of an illness is as important as the illness itself. A patient-centred approach focuses on the patient's views and feelings concerning his health problem or illness, i.e., his beliefs, fears, his expectations, and the impact that the problem or illness is having on his life. A review of the literature by a group of researchers at the University of Western Ontario suggests that this approach results in improved patient satisfaction, observance and results. This approach can be used on a daily basis in almost all clinical situations. The results of a study on strategies used by clinicians with experience in family medicine to detect the "functional" patient are also presented.


Functional polymorphisms in Benzo(a)Pyrene-induced toxicity pathways associated with the risk on laryngeal squamous cell carcinoma.
Benzo(a)Pyrene (BaP) is a well-known environmental carcinogen that poses a significant risk to human health. The pivotal genes and toxicity pathways have been identified as key events to construct the mode of action (MOA) of BaP. In this study, we focused on evaluating the association between genetic variants in BaP-disturbed toxicity pathways and the susceptibility of laryngeal squamous cell carcinoma (LSCC), based on the data of our previous genome-wide association analysis (GWAS). In addition, we investigated the biological roles of these significant polymorphisms by integrating bioinformatic annotation and experimental validation. Our findings revealed that 15 functional polymorphisms in AHR signaling, p53 signaling, NRF2 signaling, TGF-β signaling, STAT3 signaling, and IL-8 signaling pathways were significantly associated with susceptibility to LSCC. Our study provides a novel approach for identifying novel risk genetic loci utilizing GWAS data, and suggests potential targets for early detection of LSCC in the future.


Controlling Bi-Provoked Nanostructure Formation in GaAs/GaAsBi Core-Shell Nanowires.
We control the formation of Bi-induced nanostructures on the growth of GaAs/GaAsBi core-shell nanowires (NWs). Bi serves as not only a constituent but also a surfactant and nanowire growth catalyst. Thus, we paved a way to achieve unexplored III-V nanostructures employing the characteristic supersaturation of catalyst droplets, structural modifications induced by strain, and incorporation into the host GaAs matrix correlated with crystalline defects and orientations. When Ga is deficient during growth, Bi accumulates on the vertex of core GaAs NWs and serves as a nanowire growth catalyst for the branched structures to azimuthal <112>. We find a strong correlation between Bi accumulation and stacking faults. Furthermore, Bi is preferentially incorporated on the GaAs (112)B surface, leading to spatially selective Bi incorporation into a confined area that has a Bi concentration of over 7%. The obtained GaAs/GaAsBi/GaAs heterostructure with an interface defined by the crystalline twin defects in a zinc-blende structure can be potentially applied to a quantum confined structure. Our finding provides a rational design concept for the creation of GaAsBi based nanostructures and the control of Bi incorporation beyond the fundamental limit.


A systematic nomenclature for codifying engineered nanostructures.
Nanotechnology's growing applications are fueled by the synthesis and engineering of a myriad nanostructures, yet there is no systematic naming or classification scheme for such materials. This lack of a coherent nomenclature is confusing the interpretation of data sets and threatens to hamper the pace of progress and risk assessment. A systematic nomenclature that encodes the overall composition, size, shape, core and ligand chemistry, and solubility of nanostructures is presented. A typographic string of minimalist field codes facilitates digital archiving and searches for desired properties. This nomenclature system could also be used for nanomaterial hazard labeling.


Four-Body Scale in Universal Few-Boson Systems.
The role of an intrinsic four-body scale in universal few-boson systems is the subject of active debate. We study these systems within the framework of effective field theory. For systems of up to six bosons we establish that no four-body scale appears at leading order (LO). However, we find that at next-to-leading order (NLO) a four-body force is needed to obtain renormalized results for binding energies. With the associated parameter fixed to the binding energy of the four-boson system, this force is shown to renormalize the five- and six-body systems as well. We present an original ansatz for the short-distance limit of the bosonic A-body wave function from which we conjecture that new A-body scales appear at N^{A-3} LO. As a specific example, calculations are presented for clusters of helium atoms. Our results apply more generally to other few-body systems governed by a large scattering length, such as light nuclei and halo states, the low-energy properties of which are independent of the detailed internal structure of the constituents.


IRAK4 is essential for TLR9-induced suppression of Epstein-Barr virus BZLF1 transcription in Akata Burkitt's lymphoma cells.
Burkitt's lymphoma (BL) is the most common childhood cancer in equatorial Africa, and is endemic to areas where people are chronically co-infected with Epstein-Barr virus (EBV) and the malaria pathogen Plasmodium falciparum. The contribution of these pathogens in the oncogenic process remains poorly understood. We showed earlier that the activation of Toll-like receptor (TLR) 9 by hemozoin, a disposal product formed from the digestion of blood by P. falciparum, suppresses the lytic reactivation of EBV in BL cells. EBV lytic reactivation is regulated by the expression of transcription factor Zta (ZEBRA), encoded by the EBV gene BZLF1. Here, we explore in the BL cell line Akata, the mechanism involved in repression by TLR9 of expression of BZLF1. We show that BZLF1 repression is mediated upon TLR9 engagement by a mechanism that is largely independent of de novo protein synthesis. By CRISPR/Cas9-induced inactivation of TLR9, MyD88, IRAK4 and IRAK1 we confirm that BZLF1 repression is dependent on functional TLR9 and MyD88 signaling, and identify IRAK4 as an essential element for TLR9-induced repression of BZLF1 expression upon BCR cross-linking. Our results unprecedentedly show that TLR9-mediated inhibition of lytic EBV is largely independent of new protein synthesis and demonstrate the central roles of MyD88 and IRAK4 in this process contributing to EBV's persistence in the host's B-cell pool.


Religiosity, dietary habit, intake of fruit and vegetable, and vegetarian status among Seventh-Day Adventists in West Malaysia.
Religion has been shown to be salutary on health, and a possible link between religion and positive health outcomes is diet. Research has shown that religiosity is associated with better diet but most studies were conducted in a multi-denominational context, which might be confounded with theological differences. This study examined the relationship between religiosity and diet within a homogenous group of believers. Data from survey of 574 Seventh-Day Adventists residing in West Malaysia, aged 18-80, were analyzed using multiple regressions. While none of the religious variables were significantly associated with fruit and vegetable intake, a higher level of religiosity was associated with a better dietary habit and vegetarian status. The mixed relationship between religiosity and diet suggest that further research is needed to explore how religion might influence the diet of adherents.


[Electron spin resonance of phosphorylating and non-phosphorylating submitochondrial particles].
Paramagnetic centres related with the work of ATP-synthetase, found earlier on mitochondria were studied on phosphorylating and non-phosphorylating submitochondrial particles (SMP). A complex doublet signal with half-width 38 . 10(-4) T was shown to be recorded only on actively phosphorylating and oligomycin-inhibited SMP. It was found that the signal components were conditioned by different paramagnetic centres, one of which (g = 2.03) seemed to be the metal centre, more probable non-hemeiron. The nature of the second signal characterized by evenly saturating doublet components with g = 2.03 and g = 2.00 is unclear. Studies of flavin signal saturation have also shown that it consists of two components: one of them--saturating, specific for non-phosphorylating SMP, another--non-saturating, mostly observed in phosphorylating SMP, probably conditioned by flavin--the constituent of ATP-synthetase.


Nutritional status and muscle dysfunction in chronic respiratory diseases: stable phase versus acute exacerbations.
Nutritional abnormalities are frequent in different chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis (CF), interstitial fibrosis and lung cancer, having important clinical consequences. However, nutritional abnormalities often remained underdiagnosed due to the relative lack of awareness of health professionals. Therefore, systematic anthropometry or even better, assessment of body composition, should be performed in all patients with chronic respiratory conditions, especially following exacerbation periods when malnutrition becomes more accentuated. Nutritional abnormalities very often include the loss of muscle mass, which is an important factor for the occurrence of muscle dysfunction. The latter can be easily detected with the specific assessment of muscle strength and endurance, and also negatively influences patients' quality of life and prognosis. Both nutritional abnormalities and muscle dysfunction result from the interaction of several factors, including tobacco smoking, low physical activity-sedentarism, systemic inflammation and the imbalance between energy supply and requirements, which essentially lead to a negative balance between protein breakdown and synthesis. Therapeutic approaches include improvements in lifestyle, nutritional supplementation and training. Anabolic drugs may be administered in some cases.


Memory for media: investigation of false memories for negatively and positively charged public events.
Despite a large body of false memory research, little has addressed the potential influence of an event's emotional content on susceptibility to false recollections. The Paradoxical Negative Emotion (PNE) hypothesis predicts that negative emotion generally facilitates memory but also heightens susceptibility to false memories. Participants were asked whether they could recall 20 "widely publicised" public events (half fictitious) ranging in emotional valence, with or without visual cues. Participants recalled a greater number of true negative events (M=3.31/5) than true positive (M=2.61/5) events. Nearly everyone (95%) came to recall at least one false event (M=2.15 false events recalled). Further, more than twice as many participants recalled any false negative (90%) compared to false positive (41.7%) events. Negative events, in general, were associated with more detailed memories and false negative event memories were more detailed than false positive event memories. Higher dissociation scores were associated with false recollections of negative events, specifically.


Sublingual Microcirculatory Evaluation of Extracorporeal Hemoadsorption with CytoSorb® in Abdominal Sepsis: A Case Report.
Cytokemia is associated with microcirculatory alterations often with persistent loss of coherence between the micro- and macrocirculation, linked to organ failure and poor outcome of septic patients. Addition of a hemoadsorbant filter to an extracorporeal circuit next to conventional treatment of septic shock results in the hematological clearance of cytokines, hypothetically leading to normalization of the microcirculation and thus organ perfusion. Bedside sublingual microcirculatory assessment using handheld vital microscopy allows real-time direct visualization of the microcirculation and its response to therapy. This is demonstrated in the present case report of an 83-year-old man admitted to our intensive care unit after surgical repair of a colonic perforation for fecal soiling after a low anterior resection for a rectum carcinoma, with leakage of bowel content at the resection site. The clinical course of this patient can be described as having undergone adequate surgical treatment taking away the source of the disease, followed by optimal support including antibiotic treatment in the ICU. However, during the course of his stay in the ICU, his condition deteriorated with symptoms consistent with septic shock. Our report shows that the addition of a hemoadsorbent (CytoSorb) to the continuous renal replacement therapy circuit was associated with an improvement in the condition of our severely ill patient with abdominal sepsis. Parallel to the clinical improvement of our patient, the functional parameters of the microcirculation also showed improvement suggesting that such a noninvasive real-time evaluation of the status of the microcirculation may be a sensitive diagnostic tool to monitor the effectiveness of hemoadsorbent therapy.


Clinical and genetic features of 3 patients with familial chylomicronemia due to mutations in GPIHBP1 gene.
Familial chylomicronemia is a recessive disorder that may be due to mutations in lipoprotein lipase (LPL) and in other proteins such as apolipoprotein C-II and apolipoprotein A-V (activators of LPL), GPIHBP1 (the molecular platform required for LPL activity on endothelial surface), and LMF1 (a factor required for intracellular formation of active LPL). We sequenced the familial chylomicronemia candidate genes in 2 adult females presenting long-standing hypertriglyceridemia and a history of acute pancreatitis. Both probands had plasma triglyceride >10 mmol/L but no mutations in the LPL gene. The sequence of the other candidate genes showed that one patient was homozygous for a novel missense mutation p.(Cys83Arg), and the other was homozygous for a previously reported nonsense mutation p.(Cys 89*), respectively, in GPIHBP1. Family screening showed that the hypertriglyceridemic brother of the p.(Cys83Arg) homozygote was also homozygous for this mutation. He had no history of pancreatitis. The p.(Cys83Arg) heterozygous carriers had normal triglyceride levels. The substitution of a cysteine residue in the Ly6 domain of GPIHBP1 is predicted to abolish one of the disulfide bridges required to maintain the structure of GPIHBP1. The p.(Cys89*) mutation results in a truncated protein devoid of function. Both mutant GPIHBP1 proteins are expected to be incapable of transferring LPL from the subendothelial space to the endothelial surface.


Nociceptive primary afferents: they have a mind of their own.
Nociceptive primary afferents have three surprising properties: they are highly complex in their expression of neurotransmitters and receptors and most probably participate in autocrine and paracrine interactions; they are capable of exerting tonic and activity-dependent inhibitory control over incoming nociceptive input; they can generate signals in the form of dorsal root reflexes that are transmitted antidromically out to the periphery and these signals can result in neurogenic inflammation in the innervated tissue. Thus, nociceptive primary afferents are highly complicated structures, capable of modifying input before it is ever transmitted to the central nervous system and capable of altering the tissue they innervate.


Nursing experiences in specialized services in child and adolescent mental health: a systematic review of qualitative studies.
to synthesize evidence from qualitative studies on nursing experiences regarding child and adolescent mental health care in specialized services. a systematic review with meta-synthesis of qualitative studies according to JBI guidelines. CINAHL, EMBASE, MEDLINE, LILACS, PSYCinfo, Scopus and Web of Science databases were used. The findings were classified according to the level of reliability and credibility and categorized by similarity between contents. 229 articles were identified, and five were included in the final sample and organized into the categories: Emotional impact; and Understanding nursing role. The level of evidence found was moderate. nursing experiences are permeated by emotional exhaustion, feelings of frustration and difficulty in understanding their professional role. The need for training spaces that qualify this care is highlighted.


DNA-binding specificity of AdpA, a transcriptional activator in the A-factor regulatory cascade in Streptomyces griseus.
AdpA, belonging to the AraC/XylS family, is the key transcriptional activator for a number of genes of various functions in the A-factor regulatory cascade in Streptomyces griseus. It consists of a ThiJ/PfpI/DJ-1-like dimerization domain at its N-terminal portion and a DNA-binding domain with two helix-turn-helix motifs at its C-terminal portion, representing a large subgroup of the AraC/XylS family. Uracil interference assay and missing T and GA interference assays on several AdpA binding sites, followed by gel mobility shift assays on systematically mutated binding sites, revealed a consensus AdpA-binding sequence, 5'-TGGCSNGWWY-3' (S: G or C; W: A or T; Y: T or C; N: any nucleotide). A dimer of AdpA bound a site including the two consensus sequences, with a space of 13-14 bp, as an inverted repeat (type I) at various positions, for example more than 200 bp upstream (-200) and 25 bp downstream (+25) from the transcriptional start point of the target gene. In addition, AdpA also bound a site including the consensus sequence in a single copy (type II) at positions, in most cases, from -40 to -50 and from -50 to -60. For transcriptional activation, some genes required simultaneous binding of a dimer of AdpA to type I and II sites, but others required only a single type I or type II site. AdpA bound mutated type I sites with various distances between the two consensus sequences with significant affinities, although the optimal distances for AdpA to bind were 13-14 bp and 2 bp. The DNA-binding domain is therefore connected to the ThiJ/PfpI/DJ-1-like dimerization domain with a flexible linker. The DNA-binding specificity of AdpA in conjunction with that of other AraC/XylS family members is discussed.


Identification of cross talk between SUMOylation and ubiquitylation using a sequential peptide immunopurification approach.
Ubiquitin and ubiquitin-like modifiers (UBLs) such as small ubiquitin-like modifier (SUMO) can act as antagonists to one another by competing to occupy similar residues in the proteome. In addition, SUMO and ubiquitin can be coupled to each other at key lysine residues to form highly branched protein networks. The interplay between these modifications governs important biological processes such as double-strand break repair and meiotic recombination. We recently developed an approach that permits the identification of proteins that are modified by both SUMOylation and ubiquitylation. This protocol requires cells that express a mutant 6×His-SUMO3m protein that has had its C terminus modified from QQQTGG to RNQTGG, enabling the purification of SUMOylated peptides and their identification by tandem mass spectrometry (MS/MS). Cells are lysed under denaturing conditions, and the SUMOylated proteins are purified on nickel-nitrilotriacetic acid (Ni-NTA) resin via the 6×His on the SUMO3m construct. After on-bead digestion using trypsin, ubiquitylated peptides are enriched by immunoprecipitation, and the flow-through from this step is subjected to anti-SUMO immunoprecipitation. The SUMOylated peptides are fractionated on strong cation exchange (SCX) StageTips to enhance the coverage of the SUMO proteome. The ubiquitylated and SUMOylated peptides are analyzed separately by liquid chromatography (LC)-MS/MS and identified with MaxQuant. We demonstrate how this approach can be used to identify temporal changes in SUMOylated and ubiquitylated proteins in response to, for instance, heat shock and proteasome inhibition. The procedure requires 3 d when starting from cell pellets and yields >8,000 SUMO sites and >3,500 ubiquitin sites from 16 mg of cell extract.


In defense of sugar: a critical analysis of rhetorical strategies used in The Sugar Association's award-winning 1976 public relations campaign.
In 1976, the U.S. Sugar Association (SA), a globally networked trade organization representing the cane and beet sugar industry, won the Public Relations Society of America's (PRSA) Silver Anvil Award for a crisis communication campaign. Their campaign successfully limited the diffusion of sugar restriction policies to control obesity, heart disease, diabetes, and dental caries, and marked the beginning of the modern-day SA. The sugar industry continues to resist measures to reduce sugar consumption, therefore understanding and addressing industry opposition is crucial to achieving global targets to reduce non-communicable disease. We critically analyze common crisis management rhetorical strategies used by SA to defend itself from perceived wrongdoing, and sugar from perceptions of harm using a thematic content analysis based on Hearit's Corporate Apologia theory. Data sources were internal SA documents related to the 1976 Silver Anvil Award in 1) PRSA records, 2) Great Western Sugar Company records, and 3) William Jefferson Darby Papers. SA, using prototypical apologia stances (counterattack, differentiation, apology, and corrective action) and rhetorical dissociation strategies (appearance/reality, opinion/knowledge, and act/essence) constructed a persuasive narrative to successfully defend sugar from a product safety crisis, and the sugar industry from a social legitimacy crisis. SA's overarching narrative was that restricting sugar, which it claimed was a valuable food that makes healthy foods more palatable, would cause harm and that claims to the contrary were made by opportunists, pseudoscientists, food-faddists, lay nutritionists or those who had been misled by them. SA's apologia does not meet criteria for truthfulness or sincerity. Corporate apologia theory provides an accessible way of understanding sugar industry crisis communication strategies. It enables public health actors to recognize and predict industry corporate apologia in response to ongoing product safety and social legitimacy challenges. Industry counterarguments can be examined for truthfulness and sincerity (or the lack thereof), and explained to policymakers considering sugar restriction policies, and to the public, thereby decreasing the effectiveness of illegitimate industry communication efforts to oppose regulation and legislation.


Patterns of chronic disease management and health outcomes in a population-based cohort of Black women with breast cancer.
Diabetes and hypertension are two common comorbidities that affect breast cancer patients, particularly Black women. Disruption of chronic disease management during cancer treatment has been speculated. Therefore, this study examined the implementation of clinical practice guidelines and health outcomes for these comorbidities before and during cancer treatment. We used a population-based, prospective cohort of Black women diagnosed with breast cancer (2012-2016) in New Jersey (n = 563). Chronic disease management for diabetes and hypertension was examined 12 months before and after breast cancer diagnosis and compared using McNemar's test for matched paired and paired t tests. Among this cohort, 18.1% had a co-diagnosis of diabetes and 47.2% had a co-diagnosis of hypertension. Implementation of clinical practice guidelines and health outcomes that differed in the 12 months before and after cancer diagnosis included lipid screening (64.5% before versus 50.0% after diagnosis; p = 0.004), glucose screening (72.7% versus 90.7%; p < 0.001), and blood pressure control < 140/90 mmHg (57.6% versus 71.5%; p = 0.004) among patients with hypertension-only. For patients with diabetes, eye and foot care were low (< 35%) and optimal HbA1c < 8.0% was achieved for less than 50% of patients in both time periods. Chronic disease management continued during cancer treatment; however, eye and foot exams for patients with diabetes and lipid screening for patients with hypertension-only were inadequate. Given that comorbidities may account for half of the Black-White breast cancer survival disparity, strategies are needed to improve chronic disease management during cancer, especially for Black women who bear a disproportionate burden of chronic diseases.


Methylation of Septin9, SRSF1, and PAX8 in Early Screening of Colorectal Cancer in the Population Undergoing Physical Examinations.
The aim was to investigate the value of blood Septin9, SRSF1, and PAX8 gene methylation detection techniques in early screening of colorectal cancer (CRC). A prospective cohort study enrolled 3,000 participants undergoing routine physical examination at Shizong County People's Hospital Health Management Center from December 2021 through November 2022, including 1,512 males and 1,488 females, ranging in age from 20 to 90 years, with a median age of 49 years. Fresh blood samples were collected and tested for Septin9, SRSF1, and PAX8 gene methylation. Positive or negative results were reported. Colonoscopy was recommended for positive results and telephone follow-up for negative results. A chi-squared test analyzed the positive rate of initial screening, colonoscopy compliance, and the detection rate of colorectal lesions. Finally, combined with the follow-up data, the screening effect of Septin9, SRSF1, and PAX8 methylation detection on CRC was evaluated. Among 3,000 cases, 215 cases were preliminarily positive, with a positive rate of 7.1% (215/3,000). The positive rate of Septin9 gene methylation was the highest (6%, 180/3000), followed by SRSF1 (4.1%, 124/3000) and PAX8 (3.6%, 108/3000). The sensitivity of combined detection of Septin9, SRSF1, and PAX8 methylation in the diagnosis of CRC was higher than that of the three alone, and the specificity, positive predictive value, and negative predictive value of combined detection were higher than that of the single detection of blood Septin9, SRSF1, and PAX8 DNA methylation. In addition, the positive rate of initial screening increased with age (χ2 = 32.135, p < 0.001). A total of 150 cases underwent further colonoscopy, and the colonoscopy compliance rate was 69.8% (150/215). Among 150 cases who completed colonoscopy, 5 cases of CRC (3.4%), 25 cases of advanced adenoma (16.0%), 78 cases of non-advanced adenoma (52.0%), and 24 cases of non-adenomatous polyps (22.7%) were detected. The positive predictive value of Septin9, SRSF1, and PAX8 methylation was 94% (141/150) for all colorectal lesions, and 70.0% (105/150) for colorectal cancer and precancerous lesions. Blood Septin9, SRSF1, and PAX8 gene methylation detection, combined with colonoscopy, can effectively detect colorectal cancer and precancerous lesions. This strategy may be an effective way to carry out large-scale colorectal cancer screening in the general risk population. Combined detection of the three genes can improve the detection rate of colorectal cancer, but Septin9 methylation is the most sensitive, which can be used for screening and efficacy evaluation of CRC.


Microfluidics for electronic paper-like displays.
Displays are ubiquitous in modern life, and there is a growing need to develop active, full color, video-rate reflective displays that perform well in high-light conditions. The core of display technology is to generate or manipulate light in the visible wavelength. Colored fluids or fluids with particles can be used to tune the light intensity (greyscale) or wavelength (colors) of reflective displays by different actuation methods. Microfluidic technology plays an increasing role in fluidic manipulation in microscale devices used in display areas. In this article, we will review microfluidic technologies based on different actuation methods used for display applications: pressure-driven flow, electrophoresis, electroosmosis, electrowetting, magnetic-driven flow, and cell-actuation principles.


Distinct Effects of Adipose-Derived Stem Cells and Adipocytes on Normal and Cancer Cell Hierarchy.
Adipose-derived stem cells (ASC) have received considerable attention in oncology because of the known direct link between obesity and cancer as well as the use of ASCs in reconstructive surgery after tumor ablation. Previous studies have documented how cancer cells commandeer ASCs to support their survival by altering extracellular matrix composition and stiffness, migration, and metastasis. This study focused on delineating the effects of ASCs and adipocytes on the self-renewal of stem/progenitor cells and hierarchy of breast epithelial cells. The immortalized breast epithelial cell line MCF10A, ductal carcinoma in situ (DCIS) cell lines MCF10DCIS.com and SUM225, and MCF10A-overexpressing SRC oncogene were examined using a mammosphere assay and flow cytometry for the effects of ASCs on their self-renewal and stem-luminal progenitor-differentiated cell surface marker profiles. Interestingly, ASCs promoted the self-renewal of all cell types except SUM225. ASC coculture or treatment with ASC conditioned media altered the number of CD49f(high)/EpCAM(low) basal/stem-like and CD49f(medium)/EpCAM(medium) luminal progenitor cells. Among multiple factors secreted by ASCs, IFNγ and hepatocyte growth factor (HGF) displayed unique actions on epithelial cell hierarchy. IFNγ increased stem/progenitor-like cells while simultaneously reducing the size of mammospheres, whereas HGF increased the size of mammospheres with an accompanying increase in luminal progenitor cells. ASCs expressed higher levels of HGF, whereas adipocytes expressed higher levels of IFNγ. As luminal progenitor cells are believed to be prone for transformation, IFNγ and HGF expression status of ASCs may influence susceptibility for developing breast cancer as well as on outcomes of autologous fat transplantation on residual/dormant tumor cells. This study suggests that the ratio of ASCs to adipocytes influences cancer cell hierarchy, which may impact incidence and progression. Mol Cancer Res; 14(7); 660-71. ©2016 AACR.


Sexual Consent Capacity: Ethical Issues and Challenges in Long-Term Care.
More than two million Americans live in nursing homes and other long-term care facilities. Available research suggests that the majority of older nursing home residents, including those with some degree of cognitive impairment, place significant value upon a variety of sexual activities. With nearly half of all residents suffering from dementia, psychologists and other mental health professionals often face significant challenges in the assessment of their patients' sexual consent capacity. A primary ethical issue is to balance an individual resident's rights to autonomy and privacy with a facility's need to protect residents from harm. Sexual consent capacity functions on a continuum across time and behavior. It also cannot be predetermined by proxy, in which an individual prepares legal documents ahead of time to identify a surrogate decision maker; sexual consent capacity must be determined by information obtained in the present moment. In this paper, an approach to the assessment of residents' sexual consent capacity, encompassing knowledge, reasoning, and voluntariness, along with a brief overview of sexual activity among long-term care residents, will be presented. A case example is offered to illustrate complex clinical dilemmas involving staff attitudes, residents' rights, and family dynamics.


Collaborative Multidisciplinary Incident Command at Seattle Children's Hospital for Rapid Preparatory Pediatric Surgery Countermeasures to the COVID-19 Pandemic.
Washington was the first US state to have a patient test positive for COVID-19. Before this, our children's hospital proactively implemented an incident command structure that allowed for collaborative creation of safety measures, policies, and procedures for patients, families, staff, and providers. Although the treatment and protective standards are continuously evolving, this commentary shares our thoughts on how an institution, and specifically, surgical services, may develop collaborative process improvement to accommodate for rapid and ongoing change. Specific changes outlined include early establishment of incident command; personal protective equipment conservation; workforce safety; surgical and ambulatory patient triage; and optimization of trainee education. Please note that the contents of this manuscript are shared in the interest of providing collaborative information and are under continuous development as our regional situation changes. We recognize the limitations of this commentary and do not suggest that our approaches represent validated best practices.


Galanin immunoreactive neurons in the human hypothalamus: colocalization with vasopressin-containing neurons.
Galanin (GA) is a recently described neuropeptide that has been demonstrated to be widely distributed in the hypothalamus of experimental animals. So far there is no immunohistochemical description of GA in the human hypothalamus and, in particular, no studies of the colocalization of this neuropeptide with other transmitter candidates in the human hypothalamus. We have now investigated this question immunohistochemically by using human brains fixed by vascular perfusion within 24 hours of death. Nerve cell bodies and fibers stained for GA were observed throughout the hypothalamus. Major populations of GA-ir cell bodies were found in the suprachiasmatic, intermediate, supraoptic, paraventricular, arcuate, tuberomammillary, and supramammillary nuclei. Scattered positive neurons were found in the periventricular preoptic area, the posterior hypothalamic nucleus, the lateral hypothalamic area, and zona incerta. A few positive cells were located in the dorsomedial and ventromedial hypothalamic nuclei. The number of GA-ir neurons estimated from three brains was 11,100 +/- 2,400 for the intermediate nucleus, 57,800 +/- 9,100 for the supraoptic nucleus and 47,400 +/- 13,900 for the paraventricular nucleus. GA-ir fibers were widely distributed in the hypothalamus. They were more dense in the periventricular and medial hypothalamic zones, whereas the lateral tuberal nuclei and the dorsolateral part of the supraoptic nucleus contained sparse positive fibers. The mammillary complex contained almost no GA-ir fibers. In the ventromedial tuberal region, GA-ir axons formed bundles travelling down in the infundibular stem. In the median eminence the vascular plexus was wrapped by GA-ir fiber networks. The coexistence of GA with arginine vasopressin (AVP), oxytocin (OXY), and tyrosine hydroxylase (TH) was examined in the supraoptic, paraventricular, and suprachiasmatic nuclei in adjacent paraffin sections. Neurons containing both GA and AVP were very common in the supraoptic nucleus and also occurred in the paraventricular and suprachiasmatic nuclei. The supraoptic and paraventricular nuclei also contained some neurons immunoreactive for both GA and OXY. Neurons positive for GA and TH were rare. The topographic distribution of GA-ir neuronal structures in the hypothalamus and the colocalization of GA, principally with AVP and to a lesser extent with OXY, in some hypothalamic nuclei constitute anatomical evidence that this neuropeptide may be involved in the regulation of endocrine, autonomic, and behavioural homeostatic responses.


[Local prevention with interferon of "epidemic" conjunctivitis caused by a currently unidentifiable virus].
Topical Interferon application did effectively interrupt the further clinical spread of a highly contagious viral keratoconjunctivitis. A total of 130 endangered inpatients, still free from symptoms, were treated with one drop per eye daily for a period of 12 days. 123 patients stood free from any further infection. Only during the first two days after the beginning of the Interferon prophylaxis 7 inpatients showed an acute viral keratoconjunctivitis still. Obviously these patients were infected prior to the prophylactic therapy and were just in the incubation period. We conclude that Interferon eye drops (one drop per eye daily) may offer a reliable protection from exogenous viral infection. Certainly this protection comes too late if the patient's incubation period has already started.


Sequential binding of calcium leads to dimerization in neural cadherin.
Neural cadherin (N-cadherin) is a calcium-dependent homophilic cell-adhesive molecule and critical for synaptogenesis and synapse maintenance. The extracellular region plays an important role in cadherin-mediated cell adhesion and has five tandemly repeated ectodomains (EC1-EC5) with three calcium-binding sites situated between each of these domains. Adhesive dimer formation is significantly dependent on binding of calcium such that mutations in the calcium-binding sites adversely affect cell adhesion. To investigate the relative significance of the calcium-binding sites at the EC1-EC2 interface in calcium-induced dimerization, we mutated three important amino acids, D134, D136, and D103, in NCAD12, a construct containing EC1 and EC2. Spectroscopic and chromatographic experiments showed that all three mutations affected calcium binding and dimerization. Mutation of D134, a bidentate chelator in site 3, severely impaired the binding of calcium to all three sites. These findings confirm that binding to site 3 is required for binding to occur at site 2 and site 1. Interestingly, while the D103A mutation diminished only the affinity for calcium, it completely eliminated dimerization. Equilibrium dialysis experiments showed a stoichiometry of 3 at 2 mM calcium for D103A, but no dimerization was apparent even at 10 mM calcium. These results indicate that calcium binding alone is not sufficient for dimerization but requires cooperativity between calcium-binding sites. In summary, our findings confirm that the calcium-binding sites are occupied sequentially in the order of site 3, then site 2 and site 1, and that cooperativity between site 2 and site 1 is essential for formation of adhesive dimers by N-cadherin.


Evaluation of Clinical Characteristics and Outcomes of Chest Trauma Patients with COVID-19 Infection Undergoing Emergency Surgeries.
This study aims to examine the clinical characteristics and prognosis of patients with chest trauma who were infected with COVID-19 and underwent emergency surgery. In light of the COVID-19 pandemic, this research investigates the impact of COVID-19 on patients with chest trauma who underwent emergency surgery. This retrospective cohort study was conducted on 56 patients with chest trauma in two groups with COVID-19, and no covid who underwent surgery in Shahid Madani Hospital. Among the trauma patients, 21 were infected with COVID-19, and 35 were not. The predominant causes of trauma were car and motorcycle accidents. Among COVID-19 patients, 3.3% exhibited symptoms of fever, chills, cough, shortness of breath, and gastrointestinal symptoms, while 5.9% had severe lung involvement confirmed by CT scan. Following surgery, 1.57% (12 individuals) of COVID-19 patients were transferred to the ICU, with an average hospitalization duration of 1.11 days. In contrast, the average hospitalization duration for non-COVID-19 chest trauma patients was 1.9 days (p =0.015). Patients with chest trauma who underwent surgery and were infected with COVID-19 demonstrated significant differences in average length of stay, ICU admissions, and pneumonia incidence. However, there was no significant distinction in the mortality rate between the two groups.


Self-alignment of dye molecules in micelles and lamellae for three-dimensional imaging of lyotropic liquid crystals.
We report alignment of anisotropic amphiphilic dye molecules within oblate and prolate anisotropic micelles and lamellae, the basic building blocks of surfactant-based lyotropic liquid crystals. Absorption and fluorescence transition dipole moments of these dye molecules orient either parallel or orthogonal to the liquid crystal director. This alignment enables three-dimensional visualization of director structures and defects in different lyotropic mesophases by means of fluorescence confocal polarizing microscopy and two-photon excitation fluorescence polarizing microscopy. The studied structures include nematic tactoids, Schlieren texture with disclinations in the calamitic nematic phase, oily streaks in the lamellar phase, developable domains in the columnar hexagonal phase, and various types of line defects in the discotic cholesteric phase. Orientational three-dimensional imaging of structures in the lyotropic cholesterics reveals large Burgers vector dislocations in cholesteric layering with singular disclinations in the dislocation cores that are not common for their thermotropic counterparts.


Gastrointestinal symptoms in patients with liver cirrhosis are linked to impaired quality of life and psychological distress.
The factors that lead to an impaired quality of life (QoL) in patients with liver cirrhosis are incompletely understood. Gastrointestinal (GI) symptoms are frequent in liver cirrhosis and are known to reduce QoL in GI and non-GI diseases. To study the possible association of GI symptoms with QoL and psychological distress in patients with liver cirrhosis. Seventy-five consecutive outpatients with liver cirrhosis received validated questionnaires to assess GI symptoms, QoL, anxiety, depression, and neuroticism. GI symptoms were considered as relevant when they occurred often over the last 12 months (more than 3 months total), were at least moderately severe and/or led to consultation of a physician. An association of GI symptoms with QoL and psychological scores was ascertained by logistic regression analysis before and after adjusting for age and sex. Eighty percent of patients had one or more relevant GI symptoms. Physical component of QoL correlated negatively with Child-Pugh scores (P<0.01), whereas no association between mental component of QoL and Child-Pugh scores was detectable (P=0.4). Both dimensions of QoL decreased significantly with increasing numbers of GI symptoms reported by the patients (physical component: P<0.001; mental component: P<0.01). Number of GI symptoms was also significantly related to poorer anxiety, depression, and neuroticism scores. GI symptoms are linked to QoL and psychological distress in patients with liver cirrhosis.


Mechanics and Buckling of Biopolymeric Shells and Cell Nuclei.
We study a Brownian dynamics simulation model of a biopolymeric shell deformed by axial forces exerted at opposing poles. The model exhibits two distinct, linear force-extension regimes, with the response to small tensions governed by linear elasticity and the response to large tensions governed by an effective spring constant that scales with radius as R-0.25. When extended beyond the initial linear elastic regime, the shell undergoes a hysteretic, temperature-dependent buckling transition. We experimentally observe this buckling transition by stretching and imaging the lamina of isolated cell nuclei. Furthermore, the interior contents of the shell can alter mechanical response and buckling, which we show by simulating a model for the nucleus that quantitatively agrees with our micromanipulation experiments stretching individual nuclei.


Migration patterns of pathogenic and nonpathogenic Naegleria spp.
Four species of Naegleria were tested for their ability to migrate under agarose. Pathogenic N. fowleri strains exhibited rapid locomotion at 37 degrees C. Environmental isolates of N. fowleri moved faster than clinical isolates which had been kept in axenic culture for longer periods, and this result was confirmed by using the 84-2205-7 strain kept in axenic culture for 1 or 5 months. Nonpathogenic N. gruberi strains migrated actively at 28 degrees C but not at 37 degrees C; moreover, even at 28 degrees C, active amoebae constituted only a small proportion of the whole. The temperature-tolerant, nonpathogenic species N. lovaniensis moved more slowly than N. fowleri at 37 degrees C. In contrast, N. australiensis, which is temperature tolerant as well as pathogenic for mice, migrated at a rate comparable to that of N. fowleri. There appears to be a direct correlation between the locomotive ability of free-living amoebae and their pathogenic potential.


Effect of cell cycle position on thermotolerance in Saccharomyces cerevisiae.
We showed that the heat killing curve for exponentially growing Saccharomyces cerevisiae was biphasic. This suggests two populations of cells with different thermal killing characteristics. When exponentially growing cells separated into cell cycle-specific fractions via centrifugal elutriation were heat shocked, the fractions enriched in small unbudded cells showed greater resistance to heat killing than did other cell cycle fractions. Cells arrested as unbudded cells fell into two groups on the basis of thermotolerance. Sulfur-starved cells and the temperature-sensitive mutants cdc25, cdc33, and cdc35 arrested as unbudded cells were in a thermotolerant state. Alpha-factor-treated cells arrested in a thermosensitive state, as did the temperature-sensitive mutant cdc36 when grown at the restrictive temperature. cdc7, which arrested at the G1-S boundary, arrested in a thermosensitive state. Our results suggest that there is a subpopulation of unbudded cells in exponentially growing cultures that is in G0 and not in G1 and that some but not all methods which cause arrest as unbudded cells lead to arrest in G0 as opposed to G1. It has been shown previously that yeast cells acquire thermotolerance to a subsequent challenge at an otherwise lethal temperature during a preincubation at 36 degrees C. We showed that this acquisition of thermotolerance was corrected temporally with a transient increase in the percentage of unbudded cells during the preincubation at 36 degrees C. The results suggest a relationship between the heat shock phenomenon and the cell cycle in S. cerevisiae and relate thermotolerance to transient as well as to more prolonged residence in the G0 state.


Engaging Leadership: How to Promote Work Engagement?
This paper introduces the notion of engaging leadership and reviews the empirical work done so far. Engaging leadership is defined as leadership behavior that facilitates, strengthens, connects and inspires employees in order to increase their work engagement. It can be measured with a reliable and valid self-report scale. As predicted by Self-Determination Theory, on which the concept of engaging leadership is based, basic need satisfaction mediates the relationship between engaging leadership and work engagement. This is true both for individual employees as well as the team level. In addition, job characteristics (job demands and job resources) seem to play a similar mediating role, just as personal resources. Furthermore, research shows that engaging leadership has a beneficial effect on individual and team performance which illustrates its relevance for organizations. Future research should focus, amongst others, on the opposite of engaging leadership (i.e., disengaging leadership) and interventions to foster engaging leadership. Moreover, alternative affective, cognitive and behavioral pathways should be explored that might play a role in addition to the motivational (through need fulfillment) and material (through job characteristics) pathways that have been investigated so far.


[Comparative evaluation of bicycle ergometry and coronary radiography results in stenocardia as a function of the ECG ST segment reaction during physical loading].
The authors undertook a comparative study of the results of bicycle ergometry and angiocardiography in two clinically homogeneous groups of patients with angina pectoris: without ischemic displacement (group I, 83 patients) and with displacement (group II, 85 patients) of the S--T segment on the ECG during an anginal attack induced by physical exercise. It is shown that the considerable diminution of functional reserves of coronary circulation in all patients revealed in bicycle ergometry was combined with marked coronary atherosclerosis. Affection of two or three arteries was encountered in 96.4% of patients in group I and in 88.2% of patients in group II. In group I patients the attacks of angina pectoris develop with lower values of double production, while the intercoronary collaterals on the coronarograms are more pronounced. The authors substantiate the reliability of a typical anginal attack induced by physical exertion as a criterion of positive bicycle ergometry test irrespective of the concomitant reaction of the S--T segment on the ECG.


Homogeneity test of rate ratios in stratified matched-pair studies.
This paper investigates homogeneity test of rate ratios in stratified matched-pair studies on the basis of asymptotic and bootstrap-resampling methods. Based on the efficient score approach, we develop a simple and computationally tractable score test statistic. Several other homogeneity test statistics are also proposed on the basis of the weighted least-squares estimate and logarithmic transformation. Sample size formulae are derived to guarantee a pre-specified power for the proposed tests at the pre-given significance level. Empirical results confirm that (i) the modified score statistic based on the bootstrap-resampling method performs better in the sense that its empirical type I error rate is much closer to the pre-specified nominal level than those of other tests and its power is greater than those of other tests, and is hence recommended, whilst the statistics based on the weighted least-squares estimate and logarithmic transformation are slightly conservative under some of the considered settings; (ii) the derived sample size formulae are rather accurate in the sense that their empirical powers obtained from the estimated sample sizes are very close to the pre-specified nominal powers. A real example is used to illustrate the proposed methodologies.


Four-week training involving ankle mobilization with movement versus static muscle stretching in patients with chronic stroke: a randomized controlled trial.
Patients with stroke generally have diminished balance and gait. Mobilization with movement (MWM) can be used with manual force applied by a therapist to enhance talus gliding movement. Furthermore, the weight-bearing position during the lunge may enhance the stretch force. This study aimed to compare the effects of a 4-week program of MWM training with those of static muscle stretching (SMS). Ankle dorsiflexion passive range of motion (DF-PROM), static balance ability (SBA), the Berg balance scale (BBS), and gait parameters (gait speed and cadence) were measured in patients with chronic stroke. Twenty patients with chronic stroke participated in this study. Participants were randomized to either the MWM (n = 10) or the SMS (n = 10) group. Patients in both groups underwent standard rehabilitation therapy for 30 min per session. In addition, MWM and SMS techniques were performed three times per week for 4 weeks. Ankle DF-PROM, SBA, BBS score, and gait parameters were measured after 4 weeks of training. After 4 weeks of training, the MWM group showed significant improvement in all outcome measures compared with baseline (p < 0.05). Furthermore, SBA, BBS, and cadence showed greater improvement in the MWM group compared to the SMS group (p < 0.05). This study demonstrated that MWM training, combined with standard rehabilitation, improved ankle DF-PROM, SBA, BBS scores, and gait speed and cadence. Thus, MWM may be an effective treatment for patients with chronic stroke.


How cells tiptoe on adhesive surfaces before sticking.
Cell membranes are studded with protrusions that were thoroughly analyzed with electron microscopy. However, the nanometer-scale three-dimensional motions generated by cell membranes to fit the topography of foreign surfaces and initiate adhesion remain poorly understood. Here, we describe the dynamics of surface deformations displayed by monocytic cells bumping against fibronectin-coated surfaces. We observed membrane undulations with typically 5 nm amplitude and 5-10 s lifetime. Cell membranes behaved as independent units of micrometer size. Cells detected the presence of foreign surfaces at 50 nm separation, resulting in time-dependent amplification of membrane undulations. Molecular contact then ensued with apparent cell-membrane separation of 30-40 nm, and this distance steadily decreased during the following tens of seconds. Contact maturation was associated with in-plane egress of bulky molecules and robust membrane fluctuations. Thus, membrane undulations may be the major determinant of cell sensitivity to substrate topography, outcome of interaction, and initial kinetics of contact extension.


Francisella sp., an emerging pathogen of tilapia, Oreochromis niloticus (L.), in Costa Rica.
Francisella sp. is an emergent bacterial pathogen that causes acute to chronic disease in warm and cold water cultured and wild fish species. During the past 3 years, the bacterium has been detected in tilapia, Oreochromis niloticus, cultured in Costa Rica. Infected fish presented non-specific clinical signs, such as erratic swimming, anorexia, anaemia, exophthalmia and high mortality. Upon macroscopic and microscopic examination, several internal organs (mainly spleen and kidney) were enlarged and contained white nodules. Histological examination revealed the presence of multifocal granulomatous lesions, with the presence of numerous small, pleomorphic, cocco-bacilli. The bacteria were isolated from infected tilapia on selective media and grown on several media with and without antibiotics. Specific PCR primers to the Francisella genus were used to confirm the preliminary diagnoses. In comparison with several bacterial 16S rRNA sequences, our isolate was found to share 99% identity with other Fransicella spp. isolated from fish, and more than 97% identity to the human pathogen Francisella tularensis. Koch's postulates were fulfilled after experimental intraperitoneal and gill exposure challenges.


Identification of a Ca(2+)-pectate binding site on an apoplastic peroxidase.
An apoplastic isoperoxidase from zucchini (APRX) was shown to bind strongly to polygalacturonic acid in their Ca(2)+-induced conformation. By homology modeling, we were able to identify a motif of four clustered arginines (positions 117, 262, 268, and 271) that could be responsible for this binding. To verify the role of these arginine residues in the binding process, we prepared three mutants of APRX (M1, R117S; M2, R262Q/R268S; and M3, R262Q/R268S/R271Q). APRX and the three mutants were expressed as recombinant glycoproteins by the baculovirus-insect cell system. This procedure yielded four active enzymes with similar molecular masses that were tested for their ability to bind Ca(2)+-pectate. Recombinant wild-type APRX exhibited an affinity for the pectic structure comparable to that of the native plant isoperoxidase. The mutations impaired binding depending on the number of arginine residues that were replaced. M1 and M2 showed intermediate affinities, whereas M3 did not bind at all. This was demonstrated using an in vitro binding test and on cell walls of hypocotyl cross-sections. It can be concluded that APRX bears a Ca(2)+-pectate binding site formed by four clustered arginines. This site could ensure that APRX is properly positioned in cell walls, using unesterified domains of pectins as a scaffold.


Characterization of 5-hydroxytryptamine receptors in rat stomach fundus.
1-Arylpiperazines (MK-212, quipazine, m-chlorophenylpiperazine and m-trifluoromethylphenylpiperazine) caused a serotonin (5-HT) receptor-mediated contraction of rat fundic strips. m-chlorophenylpiperazine and m-trifluoromethylphenylpiperazine had high affinity for the receptor but little efficacy, whereas quipazine and MK-212 had lesser affinity and much greater efficacy. 5-HT itself was the most potent (EC50 = 6-9 nM) agonist and possessed the greatest affinity (KA = 9.7 nM). Assessment of receptor occupancy vs. functional response (as well as receptor alkylation studies) demonstrated a very small, if any, receptor reserve in this tissue. Several arylquinolizines were found to be competitive antagonists of 5-HT-induced contraction, the most potent being L-653,267 and rauwolscine (KB values = 1.9 and 3.8 nM). Clozapine, trazodone and propranolol were identified as less potent, competitive antagonists, whereas various ergolines (including LY 53857), L-646,462 (cyproheptadine analog) and mianserin were noncompetitive. Potent 5-HT2 receptor antagonists (pirenpirone and ketanserin) antagonized only weakly or were without effect against 5-HT, indicating that the fundic 5-HT receptor is not of the 5-HT2 subtype. Because the fundic receptor has high affinity for 5-HT (as does the 5-HT1 binding site in brain tissue), the possible correspondence of the fundic 5-HT receptor with the 5-HT1 recognition site in rat brain cortex was considered. 5-HT, the nonindole agonists (1-arylpiperazines) and the competitive antagonists all competed with [3H]-5-HT for the 5-HT1 site. However, all compounds except 5-HT had Hill slopes significantly less than 1.0, precluding a valid comparison with dissociation constants derived pharmacologically in the fundus. With respect to having a high affinity for 5-HT, the 5-HT receptor mediating contraction of fundic smooth muscle resembles the 5-HT1 recognition site (as defined in brain tissue by radioligand binding), but identity remains unproven.


Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides. The purification and properties of an endogenous activator of the enzyme.
1. A low-molecular-weight activator of 5-aminolaevulinate synthetase was detected in extracts of Rhodopseudomonas spheroides. The compound activates the enzyme extracted from oxygenated semi-anaerobically grown organisms by a factor of 6-8. 2. The activator was extensively purified, but owing to the exceedingly small amounts that could be extracted in the active form its structure was not determined. 3. The activator contains an acetylatable amino group; it is more stable at acid than at alkaline pH values; it is stable to treatment with I(2)-KI or potassium ferricyanide, but irreversibly inactivated by Na(2)S(2)O(4) or NaBH(4). 4. The chromatographic, electrophoretic, chemical and stability properties of the activator are similar to those of pteridines; purified activator preparations contain pteridines, as shown by their fluorescence spectrum. This does not, however, constitute an identification of the activator. 5. The activator enhances the activity of crude and partially purified enzyme and does not appear to require other endogenous factors or a supply of air to produce activation. Activation of the purified enzyme, however, requires the presence of either pyridoxal phosphate or sodium succinate. In the absence of both these factors the activator produces a time- and temperature-dependent decay of activity.


Analysis of the best available techniques for wastewaters from a denim manufacturing textile mill.
The present study was undertaken as the first plant scale application and evaluation of Best Available Techniques (BAT) within the context of the Integrated Pollution Prevention and Control/Industrial Emissions Directive to a textile mill in Turkey. A "best practice example" was developed for the textile sector; and within this context, BAT requirements for one of the World's leading denim manufacturing textile mills were determined. In order to achieve a sustainable wastewater management; firstly, a detailed wastewater characterization study was conducted and the possible candidate wastewaters to be reused within the mill were identified. A wastewater management strategy was adopted to investigate the possible reuse opportunities for the dyeing and finishing process wastewaters along with the composite mill effluent. In line with this strategy, production processes were analysed in depth in accordance with the BAT Reference Document not only to treat the generated wastewaters for their possible reuse, but also to reduce the amount of water consumed and wastewater generated. As a result, several applicable BAT options and strategies were determined such as reuse of dyeing wastewaters after treatment, recovery of caustic from alkaline finishing wastewaters, reuse of biologically treated composite mill effluent after membrane processes, minimization of wash water consumption in the water softening plant, reuse of concentrate stream from reverse osmosis plant, reducing water consumption by adoption of counter-current washing in the dyeing and finishing processes. The adoption of the selected in-process BAT options for the minimization of water use provided a 30% reduction in the total specific water consumption of the mill. The treatability studies adopted for both segregated and composite wastewaters indicated that nanofiltration is satisfactory in meeting the reuse criteria for all the wastewater streams considered.


Phosphoryl-Transfer Reaction in RNA under Alkaline Conditions.
The phosphoryl-transfer reaction in RNA under alkaline conditions by exploring the influence of several solvents theoretically was studied. The calculations were carried out by using the M06-2X functional and the solvents were taken as a continuum by using the solvent model density (SMD) method. The main findings show that the O2'-P-O5' angle in the reactants, the free activation energies, and the reaction mechanism are clearly dependent on the dielectric constant of the environment, thus showing that the electrostatic term is the determining factor for this chemical system with two negative charges. Our study seems to indicate that water, the solvent with the greatest dielectric constant, would be the solvent that increases the reaction rate the most. As this outcome was not the case in enzymatic catalysis, one has to conclude that, in the case of proteins as well as for ribozymes, the enzymatic catalysis is not mainly due to the solvent reaction field, but to local electrical fields as a result of enzyme preorganization.


Optically induced periodic structures in smectic-C liquid crystals.
We explore periodic structures of smectic-C (SmC) liquid crystals, induced optically by a polarization grating. The studied cells contain a passive surface of rubbed polyimide and an active photosensitive substrate of azo-dye doped polyimide. In a nematic phase the director field can be periodic independent of the angle between the grating vector and the rubbing direction. In the SmA phase periodic structure can be induced only by layer undulations. The SmC behaves similarly to the nematic phase, but the director can rotate only on a cone, which results in a more complex geometry. The periodic pattern is superimposed with four different director and layer structures. In spite of the coexistence of the nonuniform structures the diffraction efficiency is better in the SmC, than in the nematic phase.


Reptiles, amphibians, and human Salmonella infection: a population-based, case-control study.
To estimate the burden of reptile- and amphibian-associated Salmonella infections, we conducted 2 case-control studies of human salmonellosis occurring during 1996-1997. The studies took place at 5 Foodborne Diseases Active Surveillance Network (FoodNet) surveillance areas: all of Minnesota and Oregon and selected counties in California, Connecticut, and Georgia. The first study included 463 patients with serogroup B or D Salmonella infection and 7618 population-based controls. The second study involved 38 patients with non-serogroup B or D Salmonella infection and 1429 controls from California only. Patients and controls were interviewed about contact with reptiles and amphibians. Reptile and amphibian contact was associated both with infection with serogroup B or D Salmonella (multivariable odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2; P<.009) and with infection with non-serogroup B or D Salmonella (OR, 4.2; CI, 1.8-9.7; P<.001). The population attributable fraction for reptile or amphibian contact was 6% for all sporadic Salmonella infections and 11% among persons <21 years old. These data suggest that reptile and amphibian exposure is associated with approximately 74,000 Salmonella infections annually in the United States.


Related clones containing SCCmec type IV predominate among clinically significant Staphylococcus epidermidis isolates.
SCCmec is a mobile genetic element that carries the gene (mecA) mediating methicillin resistance in staphylococci. For Staphylococcus aureus, four SCCmec types have been described, one (type IV) of which has been associated with newly identified community-acquired methicillin-resistant S. aureus. However, the distribution of SCCmec types among S. epidermidis is not known. SCCmec typing of a collection of 44 methicillin-resistant Staphylococcus epidermidis (MRSE) isolates recovered between 1973 and 1983 from the blood of patients with prosthetic valve endocarditis (PVE) was performed by PCR amplification of key genetic elements (mecA, mecI, IS1272, and ccrAB). Of the 44 isolates, 1 (2%) harbored SCCmec type I, 15 (34%) harbored type II, 12 (28%) harbored type III, and 16 (36%) harbored type IV. The complete nucleotide sequence of SCCmec type IV was determined for 16 isolates and found to be identical in size (24 kb) and 98% homologous to DNA sequences published for S. aureus. Type IV SCCmec was also common (5 of 10 isolates) among a geographically dispersed collection of 10 recent (1998 to 2001) S. epidermidis bloodstream isolates. Multilocus sequence typing (MLST) (using the same seven genes presently employed for S. aureus MLST) of these MRSE isolates and of 10 additional recent geographically dispersed methicillin-susceptible isolates demonstrated that all 16 PVE isolates and 2 of 5 recent isolates harboring type IV SCCmec were in three related clonal groups. All three MSSE PVE isolates recovered from patients between 1976 and 1979 were in the same clonal groups as type IV SCCmec MRSE isolates. These data support the hypothesis of intra- and interspecies transfer of type IV SCCmec and suggest that there are clonal associations in S. epidermidis that correlate with SCCmec type.


Sociodemographic and Psychosocial Predictors of VIP Attendance in Smart Beginnings Through 6 Months: Effectively Targeting At-Risk Mothers in Early Visits.
Past research on predictors of participation in early childhood parenting programs suggest that families experiencing higher levels of sociodemographic adversity (e.g., younger maternal age, single parenthood, lower income or education) are less likely to participate in parenting programs. This is significant, as it may indicate that those most in need of additional support are the least likely to receive it. Data from a randomized control trial (RCT) of Smart Beginnings, an integrated, tiered model for school readiness, were used to explore predictors of attendance in Video Interaction Project (VIP) through 6 months. VIP is a primary preventive intervention delivered in tandem with pediatric well-child visits, aimed at reducing income-based disparities in early child development through promotion of responsive parent-child interactions. Using Poisson distribution models (N = 403; treatment arm, n = 201), we find that demographic, socioeconomic status (SES), and psychosocial variables are associated with program attendance but not always in the expected direction. While analyses show that first-time mothers have higher levels of program attendance as expected, we find that less-educated mothers and those with lower parenting self-efficacy have higher levels of attendance as well. The latter findings may imply that the VIP intervention is, by some indicators, effectively targeting families who are more challenging to engage and retain. Implications for pediatric-based interventions with population-level accessibility are discussed.


Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation.
Erythropoiesis is marked by progressive changes in morphological, biochemical and mechanical properties of erythroid precursors to generate red blood cells (RBC). The earliest enucleated forms derived in this process, known as reticulocytes, are multi-lobular and spherical. As reticulocytes mature, they undergo a series of dynamic cytoskeletal re-arrangements and the expulsion of residual organelles, resulting in highly deformable biconcave RBCs (normocytes). To understand the significant, yet neglected proteome-wide changes associated with reticulocyte maturation, we undertook a quantitative proteomics approach. Immature reticulocytes (marked by the presence of surface transferrin receptor, CD71) and mature RBCs (devoid of CD71) were isolated from human cord blood using a magnetic separation procedure. After sub-fractionation into triton-extracted membrane proteins and luminal samples (isobaric tags for relative and absolute quantitation), quantitative mass spectrometry was conducted to identify more than 1800 proteins with good confidence and coverage. While most structural proteins (such as Spectrins, Ankyrin and Band 3) as well as surface glycoproteins were conserved, proteins associated with microtubule structures, such as Talin-1/2 and ß-Tubulin, were detected only in immature reticulocytes. Atomic force microscopy (AFM)-based imaging revealed an extended network of spectrin filaments in reticulocytes (with an average length of 48 nm), which shortened during reticulocyte maturation (average spectrin length of 41 nm in normocytes). The extended nature of cytoskeletal network may partly account for increased deformability and shape changes, as reticulocytes transform to normocytes.


Maladaptive daydreaming, emotional dysregulation, affect and internalized stigma in persons with borderline personality disorder and depression disorder: A network analysis.
Maladaptive daydreaming (MD) manifests through experiences of excessive, long-lasting daydreaming resulting in significant suffering, including isolation, distress and shame. Considering that one of its functions is a distraction from painful feelings, it is linked with escapism and plays a significant role in disorders associated with emotional dysregulation, maintaining negative symptoms, including internalized stigmatization and social withdrawal. The current study aimed to examine cognitive (internalized stigma), affective (affect, anhedonia, emotional dysregulation) and behavioural (escapism) aspects of MD in borderline personality disorder (BPD) and depression groups. The sample consisted of 188 persons, including 102 individuals with BPD. The results showed higher scores in emotional dysregulation, internalized stigma and escapism in the BPD group compared to the depression group; the subgroups did not vary in MD rates. The network analysis revealed significant differences between groups in variables dynamics, with links between MD and self-suppression escapism, negative affect in the BPD group and MD with self-suppression escapism and social withdrawal in the depression group. Emotionally dysregulation and internalized stigma factors posed as the most robust expected influence components in both networks, suggesting that the cognitive and affective factors, not strictly behavioural, are pivotal for one's functioning and regulation strategies in the groups studied. The current study allows for clinical implications in interventions focused on persons developing MD and emotional dysregulation symptoms, including persons with BPD and depression.


Acute Subdural Hematoma in Infants with Abusive Head Trauma: A Literature Review.
The number of cases with child abuse is increasing in Japan, and abusive head trauma (AHT) is a major cause of death in abused children. Child abuse has been recognized by the late 19th century, and widely accepted as battered child syndrome in the middle of the 20th century. As terms, there had been considerable mechanistic controversies between shaken-baby and -impact syndrome until the beginning of the 21st century. In recent years, AHT has been utilized as a less mechanistic term. Most of the characteristics of AHT in Japan have been similar to those in the United States as follows: infant is the most common victim, acute subdural hematoma (SDH) is the most common intracranial lesion, and retinal hemorrhage is often complicated. On the other hand, several characteristics have been different as follows: mother is the most common perpetrators, impact is a more common mechanism of trauma than shaking, and external trauma is more common reflecting the existence of impact. Since AHT as well as child abuse is a social pathological phenomenon influenced by victims, perpetrators, socioeconomic circumstances, and so on, various aspects of AHT as well as child abuse can be changed with times. Actually, a recent paper suggests such changes in infants with acute SDH due to AHT. In this review article, AHT, abusive infantile acute SDH in particular, are reviewed from the aspect of neurosurgical perspectives, including its mechanisms of trauma, biomechanics, clinical features, management, and prognosis, to update the trend in Japan.


Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: efficacy and mechanism.
Distal skin ischemic necrosis is a common complication in skin flap surgery. The pathogenesis of skin flap ischemic necrosis is unclear, and there is no clinical treatment available. Here, we used the 4 x 10 cm rat dorsal skin flap model to test our hypothesis that subcutaneous injection of vascular endothelial growth factor 165 (VEGF165) in skin flaps at the time of surgery is effective in augmentation of skin flap viability, which is associated with an increase in nitric oxide (NO) production, and the mechanism involves 1) an increase in skin flap blood flow in the early stage after surgery and 2) enhanced angiogenesis subsequently to sustain increased skin flap blood flow and viability. We observed that subcutaneous injection of VEGF165 in skin flaps at the time of surgery increased skin flap viability in a dose-dependent manner. Subcutaneous injection of VEGF165 at the dose of 2 microg/flap increased skin flap viability by 28% (P < 0.05; n = 8). Over 80% of this effect was blocked by intramuscular injection of the NO synthase (NOS) inhibitor Nomega-nitro-L-arginine (13 mg/kg) 45 min before surgery (P < 0.05; n = 8). The VEGF165 treatment also increased skin flap blood flow (2.68 +/- 0.63 ml x min(-1) x 100 g(-1)) compared with the control (1.26 +/- 0.10 ml x min(-1) x 100 g(-1); P < 0.05, n = 6) assessed 6 h postoperatively. There was no change in skin flap capillary density at this time point. VEGF165-induced increase in capillary density (32.2 +/- 1.1 capillaries/mm2; P < 0.05, n = 7) compared with control (24.6 +/- 1.4 capillaries/mm2) was seen 7 days postoperatively. There was also evidence to indicate that VEGF165-induced NO production in skin flaps was stimulated by activation of NOS activity followed by upregulation of NOS protein expression. These observations support our hypothesis and for the first time provide an important insight into the mechanism of acute local VEGF165 protein therapy in mitigation of skin flap ischemic necrosis.


SpidermiR: An R/Bioconductor Package for Integrative Analysis with miRNA Data.
Gene Regulatory Networks (GRNs) control many biological systems, but how such network coordination is shaped is still unknown. GRNs can be subdivided into basic connections that describe how the network members interact e.g., co-expression, physical interaction, co-localization, genetic influence, pathways, and shared protein domains. The important regulatory mechanisms of these networks involve miRNAs. We developed an R/Bioconductor package, namely SpidermiR, which offers an easy access to both GRNs and miRNAs to the end user, and integrates this information with differentially expressed genes obtained from The Cancer Genome Atlas. Specifically, SpidermiR allows the users to: (i) query and download GRNs and miRNAs from validated and predicted repositories; (ii) integrate miRNAs with GRNs in order to obtain miRNA-gene-gene and miRNA-protein-protein interactions, and to analyze miRNA GRNs in order to identify miRNA-gene communities; and (iii) graphically visualize the results of the analyses. These analyses can be performed through a single interface and without the need for any downloads. The full data sets are then rapidly integrated and processed locally.


Assignment of several epitopes to cyanogen bromide peptides of bovine retinal S-antigen by immunoblotting with peptide-specific antibodies.
Peptide fragments of bovine S-antigen, an immunopathogenic retinal autoantigen which mediates experimental autoimmune uveoretinitis, were produced by cyanogen bromide cleavage and used to study antibody-defined epitopes, primarily those defined by antibodies from Lewis rats immunized with the intact antigen or various peptide fragments purified from the digests by HPLC. Antibodies from the sera have been affinity-purified on several of the peptides and examined by western blot analysis and enzyme-linked immunosorbent assay on S-antigen, digests and purified fragments. By immunoblotting it could be shown that five of the purified peptides, CB46, CB47, CB67, CB74 and CB123 were immunogenic, eliciting antibodies which recognized the peptides to which they were prepared; all, except for CB67, elicited antibodies which also bound intact S-antigen. Two more peptides, CB14 and CB27 were not immunogenic and did not contain epitopes. An epitope was also found in CB35, a previously uncharacterized peptide. Using these procedures together with amino acid sequence and composition data, we have been able to determine the origins of the peptides which contain antibody epitopes, including those which we have previously determined to possess epitopes recognized by class II MHC-restricted T cell lines raised to S-antigen and several of the peptides. A T cell line specific for the non-uveitogenic CB47 peptide was unable to transfer the disease.


Fast and robust Fourier ptychographic microscopy with position misalignment correction.
Fourier ptychographic microscopy (FPM) is a new, developing computational imaging technology. It can realize the quantitative phase imaging of a wide field of view and high-resolution (HR) simultaneously by means of multi-angle illumination via a light emitting diode (LED) array, combined with a phase recovery algorithm and the synthetic aperture principle. However, in the FPM reconstruction process, LED position misalignment affects the quality of the reconstructed image, and the reconstruction efficiency of the existing LED position correction algorithms needs to be improved. This study aims to improve the FPM correction method based on simulated annealing (SA) and proposes a position misalignment correction method (AA-C algorithm) using an improved phase recovery strategy. The spectrum function update strategy was optimized by adding an adaptive control factor, and the reconstruction efficiency of the algorithm was improved. The experimental results show that the proposed method is effective and robust for position misalignment correction of LED arrays in FPM, and the convergence speed can be improved by 21.2% and 54.9% compared with SC-FPM and PC-FPM, respectively. These results can reduce the requirement of the FPM system for LED array accuracy and improve robustness.


Talking while walking: Cognitive loading and injurious falls in Parkinson's disease.
Multitasking has become a way of life, from operating multiple software packages simultaneously on a computer, to carrying on a conversation on a cell phone while driving. Perhaps one of the most common dual tasks performed is talking while walking. In isolation, neither task would be considered difficult to perform, yet when coupled, the relative ease of each task may change. This paper details significant problems that result from injurious falls, and points out the vulnerability of those who have been diagnosed with Parkinson's disease. In addition, it provides an illustrative study that demonstrates the potential danger of talking while walking, especially when the cognitive-linguistic complexity of verbal tasks is manipulated. In this investigation, 25 participants with Parkinson's disease and 13 participants without neurological compromise completed gait tasks while conducting tasks of low (counting by ones), middle (serial subtraction of threes), and high load (alpha-numeric sequencing). The results indicated that cognitive-linguistic demand had an impact on gait, the effects of which were demonstrated in individuals without neurological compromise as well as those with Parkinson's disease. One finding, altered double-support time, distinguished the Parkinson group from the control participants. These results suggest that it might be prudent for healthcare professionals and caregivers to alter expectations and monitor the cognitive-linguistic demands placed on elderly individuals, particularly those with neurological compromise who might be at greater risk for injurious falls.


Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers.
Exposure of macrophages to asbestos fibers resulted in enhancement of the production of oxygen radicals, determined by a lucigenin enhanced chemiluminescence (LEC) assay, a formation of thiobarbituric acid reactive substances (TBARS), a LDH release into the incubation mixture, and a rapid lysis of the cells. Rutin (Rut) and quercetin (Qr) were effective in inhibiting LEC, TBARS formation, and reducing peritoneal macrophages injury caused by asbestos. The concentrations pre-treatment of antioxidants that were required to prevent the injury of peritoneal macrophages caused by asbestos by 50% (IC50) were 90 microM and 290 microM for Qr and Rut, respectively. Both flavonoids were found to be oxidized during exposure of peritoneal macrophages to asbestos and the oxidation was SOD sensitive. The efficacy of flavonoids as antioxidant agents as well as superoxide ion scavengers was also evaluated using appropriate model systems, and both quercetin and rutin were found to be effective in scavenging O2.-. These findings indicate that flavonoids are able to prevent the respiratory burst in rat peritoneal macrophages exposed to asbestos at the stage of activated oxygen species generation, mainly as superoxide scavengers. On the basis of this study it was concluded that natural flavonoids quercetin and rutin would be promising drug candidates for a prophylactic asbestos-induced disease.