Care Arrangements in Dementia Care Networks: Findings From the DemNet-D Study Baseline and 1-Year Follow-Up.
This study was conducted to describe care arrangements for persons with dementia (PwDs) who are living at home with the support of a dementia care network (DCN). Data on the utilization of formal and informal support were collected in face-to-face interviews at baseline and 1-year follow-up with PwDs and caregivers receiving support from 1 of 13 DCNs. Men with dementia were supported by twice as many informal caregivers as women (2 vs. 1, respectively, p < .001). Regional differences were found in home-care nursing services, social care groups, companion home services, and day care. The care situations were considered stable by most caregivers. DCNs appear to contribute to a high degree of perceived stability in care situations. Future research should investigate possible gender differences in informal support networks. DCNs should continue their efforts in making low-threshold services in rural areas available and accessible.


Understanding the impact of mannitol on physical stability and aerosolization of spray-dried protein powders for inhalation.
Pulmonary delivery of protein-based therapeutics, including antibodies, is a promising option for treating respiratory diseases. Spray drying is a widely used method for producing dry powder formulations with mannitol being a commonly used excipient for these inhalation formulations. There is limited research available concerning the utilization of mannitol as an excipient in the spray drying of proteins and its impact on aerosol performance. This study highlights the importance to understand mannitol's potential role and impact in this context. To investigate the impact of mannitol on physical stability and aerosolization of spray-dried protein formulations, Bovine Serum Albumin (BSA) was employed as a model protein and formulated with different concentrations of mannitol via spray drying. The spray-dried solids were characterized for their particle size using Malvern Mastersizer and aerodynamic particle size using Next Generation Impactor (NGI). Additionally, the solids were characterized with solid-state Fourier-transform infrared spectroscopy (ssFTIR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and ssNMR to analyze the change in their secondary structure, crystallinity, particle morphology, and protein-excipient interaction, respectively. Size exclusion chromatography (SEC) was used to investigate changes in monomer content resulting from storage under the stressed condition of 40°C. Protein formulations containing more than 33% mannitol by weight showed crystallization tendency, causing an increase in monomer loss over time. ssNMR data also showed mixing heterogeneity of BSA and mannitol in the formulations with high mannitol contents. Fine Particle Fraction (FPF) was also found to decrease over time for the formulations containing BSA: Mannitol in the ratios of 2:1, 1:2, and 1:5, due to particle agglomeration induced by crystallization of mannitol. This study underscores the significant influence of excipients such as mannitol on the aerosol performance and storage stability of spray-dried protein formulations.


Growth performance and root transcriptome remodeling of Arabidopsis in response to Mars-like levels of magnesium sulfate.
Martian regolith (unconsolidated surface material) is a potential medium for plant growth in bioregenerative life support systems during manned missions on Mars. However, hydrated magnesium sulfate mineral levels in the regolith of Mars can reach as high as 10 wt%, and would be expected to be highly inhibitory to plant growth. Disabling ion transporters AtMRS2-10 and AtSULTR1;2, which are plasma membrane localized in peripheral root cells, is not an effective way to confer tolerance to magnesium sulfate soils. Arabidopsis mrs2-10 and sel1-10 knockout lines do not mitigate the growth inhibiting impacts of high MgSO(4).7H(2)O concentrations observed with wildtype plants. A global approach was used to identify novel genes with potential to enhance tolerance to high MgSO(4).7H(2)O (magnesium sulfate) stress. The early Arabidopsis root transcriptome response to elevated concentrations of magnesium sulfate was characterized in Col-0, and also between Col-0 and the mutant line cax1-1, which was confirmed to be relatively tolerant of high levels of MgSO(4).7H(2)O in soil solution. Differentially expressed genes in Col-0 treated for 45 min. encode enzymes primarily involved in hormone metabolism, transcription factors, calcium-binding proteins, kinases, cell wall related proteins and membrane-based transporters. Over 200 genes encoding transporters were differentially expressed in Col-0 up to 180 min. of exposure, and one of the first down-regulated genes was CAX1. The importance of this early response in wildtype Arabidopsis is exemplified in the fact that only four transcripts were differentially expressed between Col-0 and cax1-1 at 180 min. after initiation of treatment. The results provide a solid basis for the understanding of the metabolic response of plants to elevated magnesium sulfate soils; it is the first transcriptome analysis of plants in this environment. The results foster the development of Mars soil-compatible plants by showing that cax1 mutants exhibit partial tolerance to magnesium sulfate, and by elucidating a small subset (500 vs. >10,000) of candidate genes for mutation or metabolic engineering that will enhance tolerance to magnesium sulfate soils.


Renal Protection Mediated by Hypoxia Inducible Factor-1α Depends on Proangiogenesis Function of miR-21 by Targeting Thrombospondin 1.
Angiogenesis contributes to the repair process after renal ischemia/reperfusion (I/R) injury. In the present study, we tested the role of miR-21 in the angiogenesis induced by hypoxia inducible factor (HIF)-1α through inhibiting a predicted target gene thrombospondin 1 (TSP-1). To stabilize HIF-1α, hypoxia (1% O2 for 24 hours) was performed in human umbilical vein endothelial cells and cobalt chloride (CoCl2) was pretreated intraperitoneally 24 hours before renal I/R in mice. Locked nucleic acid modified anti-miR-21 and scrambled control was transfected with hypoxic cells or delivered into the mice via tail vein 1 hour before CoCl2 injection. The kidneys and blood were collected at 24 hours after reperfusion. HIF-1α induced by hypoxia and CoCl2 upregulated vascular endothelial growth factor and miR-21, and increased angiogenesis. It was found that expression of TSP-1 was inversely related with miR-21 in vitro and in vivo. Targeting of TSP-1 by miR-21 was further confirmed in vitro. Furthermore, HIF-1α improved renal function, accompanied with increased angiogenesis after I/R injury in mice. The protective effect of HIF-1α was attenuated by inhibition of miR-21. HIF-1α induced angiogenesis by upregulating not only vascular endothelial growth factor but also miR-21 via inhibiting a novel target gene TSP-1. Both of them may contribute to the protective effect of HIF-1α on renal I/R injury.


Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment.
Cardiac autonomic neuropathy (CAN) is a frequent chronic complication of diabetes mellitus with potentially life-threatening outcomes. CAN is caused by the impairment of the autonomic nerve fibers regulating heart rate, cardiac output, myocardial contractility, cardiac electrophysiology and blood vessel constriction and dilatation. It causes a wide range of cardiac disorders, including resting tachycardia, arrhythmias, intraoperative cardiovascular instability, asymptomatic myocardial ischemia and infarction and increased rate of mortality after myocardial infarction. Etiological factors associated with autonomic neuropathy include insufficient glycemic control, a longer period since the onset of diabetes, increased age, female sex and greater body mass index. The most commonly used methods for the diagnosis of CAN are based upon the assessment of heart rate variability (the physiological variation in the time interval between heartbeats), as it is one of the first findings in both clinically asymptomatic and symptomatic patients. Clinical symptoms associated with CAN generally occur late in the disease process and include early fatigue and exhaustion during exercise, orthostatic hypotension, dizziness, presyncope and syncope. Treatment is based on early diagnosis, life style changes, optimization of glycemic control and management of cardiovascular risk factors. Medical therapies, including aldose reductase inhibitors, angiotensin-converting enzyme inhibitors, prostoglandin analogs and alpha-lipoic acid, have been found to be effective in randomized controlled trials. The following article includes the epidemiology, clinical findings and cardiovascular consequences, diagnosis, and approaches to prevention and treatment of CAN.


[Laser therapy and famotidine in complex restorative treatment of primary chronic gastroduodenitis].
Primary chronic gastroduodenitis (PCG) is one of the most frequent diseases of the gastrointestinal tract. Timely and efficient treatment of patients with PCG promotes ulcer prevention. In this connection, an urgent problem of restorative medicine is to develop medical programs with active introduction of pharmacophysiotherapeutic complexes, in particular, laser therapy and anti-secretory preparation (famotidine) that increase therapeutic efficacy of treatment of this disease. To this end, we give results of treatment of 50 patients with primary chronic gastroduodenitis (26 having undergone laser therapy only, and 24 having had a combination of laser therapy and famotidine), which demonstrated that the complex action method has a more adequate effect on pathogenetic components in this disease than monotherapy.


Central sleep apnea and associated Chiari malformation in children with syndromic craniosynostosis: treatment and outcome data from a supraregional national craniofacial center.
The association of Chiari malformation Type I (CM-I) with syndromic craniosynostosis (SC) in children is well established. Central sleep apnea (CSA) may subsequently occur. However, sleep studies performed in these patients have been focused mainly on assessing the severity of obstructive sleep apnea. Therefore, the incidence and management of CSA in these patients remains poorly defined. Authors of this study aimed to assess the efficacy of foramen magnum decompression (FMD) in resolving CSA, initially detected incidentally, in a small cohort of patients with CM-I and SC. The clinical data for 5 children who underwent FMD for CSA at Alder Hey Children's Hospital between December 2007 and December 2009 were retrospectively analyzed. Outcomes were evaluated with respect to FMDs by utilizing pre- and postdecompression sleep studies. Of the 5 patients, 2 had Crouzon syndrome and 3 had Pfeiffer syndrome. Patient age at the time of surgery ranged from 1.1 to 12.6 years (median 4.1 years). The median postoperative follow-up was 3.6 years. Sleep studies revealed that 2 children experienced a > 80% reduction in CSAs at 1.5 and 21 months after decompression. The remaining 3 children experienced a > 60% reduction in CSAs when reevaluated between 2 and 10 months after decompression. The associated central apnea index improved for all patients. Findings suggested that FMD is an effective treatment modality for improving CSA in patients with SC and associated CM-I. The use of multimodal polysomnography technology may improve the evaluation and management of these patients.


[Megaloblastic anemia: rapid and economical study].
The diagnosis of megaloblastic anaemias caused by cobalamine or folate deficiency are still difficult. The dosage of these two substances help to differenciate between both carencies, but it is not determinant of any of them and is an expensive method. Homocisteinuria (HC), methylmalonuria (MMA) and formiminoglutamic acid (FIGLU) are cheap tests which could help in the differential diagnosis, if they are used properly. We report 62 patients to whom we made these test simultaneously. All of the patients received 10 micrograms of vit B12 and after 72 hours, 1 mg/day of folic acid (for 3 days). In both cases waiting for the increase of reticulocytyes up to 150 x 10(9)/L as a form of therapeutic test of diagnosis. By this simple way we have detected 97.9% of specificity for cobalamin deficiency of the MMA test, and only 4.2% for HC. This last test had increased its specificity up to 91.6% in association with the negative FIGLU test. We have also found a high specificity (92.3%) for FIGLU due to the detection of folate deficiency, in opposition with other authors who had described it as low as 50%. We have also compared the costs of the 3 tests with the dosage of cobalamine and folate, and we have found that the formers are 11 times less expensive than the last ones.


Consensus on acute behavioural disturbance in the UK: a multidisciplinary modified Delphi study to determine what it is and how it should be managed.
Acute behavioural disturbance (ABD) is a term used in law enforcement and healthcare, but there is a lack of clarity regarding its meaning. Common language should be used across staff groups to support the identification, prioritisation and delivery of care to this group of patients. The terminology currently used is inconsistent and confusing. This study aimed to reach a consensus on the criteria for identification and management of ABD, and to agree when other care pathways or guidelines might be more appropriately used. A modified Delphi study with participation from stakeholder organisation representatives was conducted in January-April 2023 online. In round 1, statements were generated by participants in response to broad questions. Participants then rated their level of agreement with statements in subsequent rounds, with statements achieving a consensus removed for inclusion in the final derived consensus statement. Non-consensus statement responses were assessed for stability. Of 430 unique statements presented for rating, 266 achieved a consensus among 30 participants representing eight stakeholder organisations. A derived consensus statement was generated from these statements. The median group response to statements which failed to achieve a consensus was reliable (Krippendorff's alpha=0·67). There is a consensus across stakeholder organisations that ABD is not a separate entity to agitation, and guidance should instead be altered to address the full range of presentations of agitation. While the features of concern in this severely agitated group of patients can be described, the advice for recognition may vary depending on staff group. Criteria for recognition are provided and potential new terminology is described.


Protection motivation theory in predicting intention to receive cervical cancer screening in rural Chinese women.
Despite the significance of cervical cancer screening, motivating more women to participate remains a challenge in resource-limited settings. In this study, we tested the protection motivation theory (PMT) in predicting screening intentions. Participants were women from Wufeng, a typical rural county in China. Participants (n = 3000) with no cervical cancer history were recruited from 10 randomly selected villages. As mediating variables, 6 PMT constructs (Perceived Risk, Fear Arousal, Perceived Severity, Response Efficacy, Response Cost, and Self-Efficacy) were measured using the standardized questionnaire. Structural equation modeling (SEM) method was employed to test PMT-based prediction models. Of the total sample, 57.77% believed that regular screening may reduce cervical cancer risk, and 45.26% agreed that women should be screened regularly. Our data fit the PMT model well (GFI = 0.95, AGFI = 0.93, CFI = 0.90, RMSEA = 0.06, SRMR = 0.04, Chi-square/df = 2.47). Knowledge of screening was directly and positively associated with screening intention. Age, annual income, and awareness of and prior experience with screening were significantly associated with screening intention by enhancing cervical cancer risk perception and by reducing response cost (P<0.05 for both). PMT can be used as guidance to investigate cervical cancer screening intentions among rural women in China with focus on cancer knowledge, some demographic factors, and awareness of and previous experience with screening. These findings, if verified with longitudinal data, can be used for intervention program development.


Sensitive High-Resolution Melting Analysis for Screening of KRAS and BRAF Mutations in Iranian Human Metastatic Colorectal Cancers
Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes.


Sedentary behavior and physical function: objective evidence from the Osteoarthritis Initiative.
Investigate the relationship between sedentary behavior and physical function in adults with knee osteoarthritis (OA), controlling for moderate-vigorous physical activity (MVPA) levels. Sedentary behavior was objectively measured by accelerometer on 1,168 participants ages 49-83 years in the Osteoarthritis Initiative with radiographic knee OA at the 48-month clinic visit. Physical function was assessed using 20-meter walk and chair stand testing. Sedentary behavior was identified by accelerometer activity counts/minute <100. The cross-sectional association between sedentary quartiles and physical function was examined by multiple linear regression, adjusting for demographic factors (age, sex, race/ethnicity, education level), health factors (comorbidity, body mass index, knee pain, knee OA severity, presence of knee symptoms), and average daily MVPA minutes. Adults with knee OA spent two-thirds of their daily time in sedentary behavior. The average gait speed among the most sedentary quartile was 3.88 feet/second, which was significantly slower than the speed of the less sedentary groups (4.23, 4.33, and 4.33 feet/second, respectively). The average chair stand rate among the most sedentary group was significantly lower (25.9 stands/minute) than the rates of the less sedentary behavior groups (28.9, 29.1, and 31.1 stands/minute, respectively). These trends remained significant in multivariable analyses adjusted for demographic factors, health factors, and average daily MVPA minutes. Being less sedentary was related to better physical function in adults with knee OA independent of MVPA time. These findings support guidelines to encourage adults with knee OA to decrease time spent in sedentary behavior in order to improve physical function.


Estimation of metabolic pathway systems from different data sources.
Parameter estimation is the main bottleneck of metabolic pathway modelling. It may be addressed from the bottom up, using information on metabolites, enzymes and modulators, or from the top down, using metabolic time series data, which have become more prevalent in recent years. The authors propose here that it is useful to combine the two strategies and to complement time-series analysis with kinetic information. In particular, the authors investigate how the recent method of dynamic flux estimation (DFE) may be supplemented with other types of estimation. Using the glycolytic pathway in Lactococcus lactis as an illustration example, the authors demonstrate some strategies of such supplementation.


Synergistic action of neuropeptide Y and adrenaline in the eel atrium.
To investigate the influence of neuropeptide Y (NPY) on heart function in a relatively simple model system, the effects of eel NPY (eNPY) on the eel atrium were examined. Eel NPY enhanced the contractile force of the isolated atrium in a dose-dependent manner, without altering the rate of contraction. Although adrenaline also exerts a positive inotropic effect, the effect of eNPY was not blocked by the beta 1-adrenoceptor antagonist betaxolol, indicating that eNPY does not act via adrenaline release. When eNPY and adrenaline were applied simultaneously, their effects were additive at lower concentrations but not at higher concentrations. The plateau reached at high concentrations suggests that these two regulators act through a common signal transduction process. One candidate for this is an elevation of the concentration of intracellular free Ca2+ ([Ca2+]i), since treatment with eNPY or adrenaline enhanced [Ca2+]i, as assessed by fluorescence of Calcium Green-1. The increase in [Ca2+]i after eNPY and adrenaline treatment is presumably due to Ca2+ influx from the external medium, since the effect was greatly reduced in Ca(2+)-free Ringer's solution and after treatment with verapamil, a Ca2+ channel blocker. Although both eNPY and adrenaline enhanced the atrial contractile force, the time courses were different, with the effect of eNPY being gradual and long-lasting, and that of adrenaline being immediate and transient. It is plausible, therefore, that eNPY and catecholamine(s) act synergistically to cause a long-lasting enhancement of contraction force if the two regulators arrive at the atrium simultaneously. The present study also demonstrates that the eel heart contains eNPY.


Invasive ecosystem engineer selects for different phenotypes of an associated native species.
Invasive habitat-forming ecosystem engineers modify the abiotic environment and thus represent a major perturbation to many ecosystems. Because native species often persist in these invaded habitats but have no shared history with the ecosystem engineer, the engineer may impose novel selective pressure on native species. In this study, we used a phenotypic selection framework to determine whether an invasive habitat-forming ecosystem engineer (the seaweed Caulerpa taxifolia) selects for different phenotypes of a common co-occurring native species (the bivalve Anadara trapezia). Compared to unvegetated habitat, Caulerpa habitat has lower water flow, lower dissolved oxygen, and sediments are more silty and anoxic. We determined the performance consequences of variation in key functional traits that may be affected by these abiotic changes (shell morphology, gill mass, and palp mass) for Anadara transplanted into Caulerpa and unvegetated habitat. Both linear and nonlinear performance gradients in Anadara differed between habitats, and these gradients were stronger in Caulerpa compared to unvegetated sediment. Moreover, in Caulerpa alternate phenotypes performed well, and these phenotypes were different from the dominant phenotype in unvegetated sediment. By demonstrating that phenotype-performance gradients differ between habitats, we have highlighted a role for Caulerpa as an agent of selection on native species.


Evidence that ATP-dependent Ca2+ transport in rat parotid microsomal membranes requires charge compensation.
ATP-dependent Ca2+ transport was investigated in a rat parotid microsomal-membrane preparation enriched in endoplasmic reticulum. Ca2+ uptake, in KCl medium, was rapid, linear with time up to 20 s, and unaffected by the mitochondrial inhibitors NaN3 and oligomycin. This Ca2+ uptake followed Michaelis-Menten kinetics, and was of high affinity (Km approximately 38 nM) and high capacity (approximately 30 nmol/min per mg of protein). In the presence of oxalate, Ca2+ uptake continued to increase for at least 5 min, reaching an intravesicular accumulation approx. 10 times higher than without oxalate. Ca2+ uptake was dependent on univalent cations in the order K+ = Na+ greater than trimethylammonium+ greater than mannitol and univalent anions in the order Cl- greater than acetate- greater than Br- = gluconate- = NO3- greater than SCN-. Ca2+ uptake was not elevated if membranes were incubated in the presence of a lipophilic anion (NO3-) and carbonyl cyanide p-trifluoromethoxyphenylhydrazone. Ca2+ transport was altered by changes in the K+-diffusion potential of the membranes. A relatively negative K+-diffusion potential increased the initial rate of Ca2+ accumulation, whereas a relatively positive potential decreased Ca2+ accumulation. In the presence of an outwardly directed K+ gradient, nigericin had no effect on Ca2+ uptake. In aggregate, these studies suggest that the ATP-dependent Ca2+-transport mechanism present in rat parotid microsomal membranes exhibits an electrogenic Ca2+ flux which requires the movement of other ions for charge compensation.


Importance of Hydrodynamic Interactions in the Stepping Kinetics of Kinesin.
Conventional kinesin walks by a hand-over-hand mechanism on the microtubule (MT) by taking ∼8 nm discrete steps and consumes one ATP molecule per step. The time needed to complete a single step is on the order of 20 μs. We show, using simulations of a coarse-grained model of the complex containing the two motor heads, the MT and the coiled coil, that to obtain quantitative agreement with experiments for the stepping kinetics hydrodynamic interactions (HIs) have to be included. In simulations without hydrodynamic interactions, spanning nearly 20 μs, not a single step was completed in one hundred trajectories. In sharp contrast, nearly 14% of the steps reached the target binding site within 6 μs when HIs were included. Somewhat surprisingly, there are qualitative differences in the diffusion pathways in simulations with and without HI. The extent of movement of the trailing head of kinesin on the MT during the diffusion stage of stepping is considerably greater in simulations with HI than in those without HI. It is likely that inclusion of HI is crucial in the accurate description of motility of other motors as well.


Snail defence responses to parasite infection: The Lymnaea stagnalis-Trichobilharzia szidati model.
Lymnaea stagnalis is a common freshwater gastropod. Importantly, the snail serves as the intermediate host for more than one hundred species of digenetic trematodes, including the avian schistosome Trichobilharzia szidati, a causative agent of cercarial dermatitis in humans. Infection of L. stagnalis by T. szidati initiates a dynamic confrontation between the host and the parasite that culminates in immunocompatibility ensuring survival and development of larvae. Unfortunately, the molecular mechanisms determining this immunocompatibility remain poorly characterised. By employing a variety of immune elicitors, including chemical compounds, PAMPs and bacteria, research in the last two decades has elucidated some of the molecular processes that regulate the snail internal defence response such as haemocyte signalling pathways. These discoveries provide a framework for future studies of molecular interactions between T. szidati and L. stagnalis to help elucidate factors and mechanisms enabling transmission of schistosome parasites. Moreover, support from recently available next generation sequence data and CRISPR-enabled functional genomics should further enable L. stagnalis as an important model for comparative immunology and contribute to a more comprehensive understanding of immune functions in gastropod molluscs.


Global small bowel motility: assessment with dynamic MR imaging.
To assess the repeatability in human volunteers of software-quantified small bowel motility captured with magnetic resonance (MR) imaging and to test the ability to detect changes in motility induced by pharmacologic agents. The study was approved by the Royal Free Research Ethics Committee, and all subjects gave full written informed consent. Twenty-one healthy volunteers (14 men, seven women; mean age, 28 years) underwent cine MR imaging with a three-dimensional balanced turbo field-echo sequence to capture small bowel motility. Volume blocks (15 cm thick) were acquired every second during a 20-second breath hold. A randomized, blinded, placebo-controlled crossover study of either 0.5 mg neostigmine or saline (n = 11) or 20 mg intravenous butylscopolamine or saline (n = 10) was performed with motility MR imaging at baseline and repeated at a mean of 4 weeks (range, 2-7 weeks). Two readers independently drew regions of interest around the small bowel, and motility was quantified by using a registration algorithm that provided a global motility metric in arbitrary units. Repeatability of the motility measurements at baseline was assessed by using Bland-Altman and within-subject coefficient of variation measures. Changes in mean motility measurements after drug administration were compared with those after placebo administration by using paired t testing. The repeatability between baseline measurements of motility was high; the Bland-Altman mean difference was -0.0025 (range, 0.28-0.4), the 95% limit of agreement was ±0.044 arbitrary units (au), and the within-subject coefficient of variation was 4.9%. Measured motility with neostigmine (mean, 0.39 au) was significantly higher than that with placebo (mean, 0.34 au; P < .001), whereas that with butylscopolamine (mean, 0.13 au) was significantly lower than that with placebo (mean, 0.30 au; P < .001). Quantification of small bowel motility with use of MR imaging in healthy volunteers is repeatable and sensitive to changes induced by means of pharmacologic manipulation. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130151/-/DC1.


Angiogenic Host Defense Peptide AG-30/5C and Bradykinin B2 Receptor Antagonist Icatibant Are G Protein Biased Agonists for MRGPRX2 in Mast Cells.
AG-30/5C is an angiogenic host defense peptide that activates human mast cells (MC) via an unknown mechanism. Using short hairpin RNA-silenced human MC line LAD2 and stably transfected RBL-2H3 cells, we demonstrate that AG-30/5C induces MC degranulation via Mas-related G protein-coupled receptor X2 (MRGPRX2). Most G protein-coupled receptors signal via parallel and independent pathways mediated by G proteins and β-arrestins. AG-30/5C and compound 48/80 induced similar maximal MC degranulation via MRGPRX2, which was abolished by pertussis toxin. However, compound 48/80 induced a robust β-arrestin activation as determined by transcriptional activation following arrestin translocation (Tango), but AG-30/5C did not. Overnight culture of MC with compound 48/80 resulted in reduced cell surface MRGPRX2 expression, and this was associated with a significant decrease in subsequent MC degranulation in response to compound 48/80 or AG-30/5C. However, AG-30/5C pretreatment had no effect on cell surface MRGPRX2 expression or degranulation in response to compound 48/80 or AG-30/5C. Icatibant, a bradykinin B2 receptor antagonist, promotes MC degranulation via MRGPRX2 and causes pseudoallergic drug reaction. Icatibant caused MC degranulation via a pertussis toxin-sensitive G protein but did not activate β-arrestin. A screen of the National Institutes of Health Clinical Collection library led to the identification of resveratrol as an inhibitor of MRGPRX2. Resveratrol inhibited compound 48/80-induced Tango and MC degranulation in response to compound 48/80, AG-30/5C, and Icatibant. This study demonstrates the novel finding that AG-30/5C and Icatibant serve as G protein-biased agonists for MRGPRX2, but compound 48/80 signals via both G protein and β-arrestin with distinct differences in receptor regulation.


Insomnia and hypersomnia in major depressive episode: Prevalence, sociodemographic characteristics and psychiatric comorbidity in a population-based study.
To examine (i) the frequency of different sleep complaints (early wake-up, trouble falling asleep, hypersomnia) and their co-occurrence and (ii) the sociodemographic characteristics and psychiatric comorbidity associated with each type of sleep profiles. Data were drawn from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative survey of the US adult population (wave 1, 2001-2002; wave 2, 2004-2005). The primary analyses were limited to 3573 participants who had a DSM-IV-TR diagnosis of major depressive episode (MDE) between the two waves. We used a multiple regression model to estimate the strength of independent associations between self-reported sleep complaints, sociodemographic characteristics and lifetime psychiatric comorbidity. Most of participants with MDE (92%) reported significant sleep complaints, from whom 85.2% had insomnia and 47.5% hypersomnia symptoms. The prevalence rates were for insomnia "only" of 48.5%, hypersomnia "only" of 13.7%, and their co-occurrence of 30.2%. We found that several sociodemographic characteristics (gender, age, education, individual and familial income, marital status) and psychiatric disorders (bipolar disorders, post-traumatic disorders and panic disorder) were significantly and independently associated with different sleep profiles. The co-occurrence of insomnia (especially early wake-up) and hypersomnia presented with a two-/three- fold increase risk of bipolar disorders. Definitions of sleep complaints were qualitative and subjective. Sleep complaints are prevalent and heterogeneous in expression during MDE. Sleep disturbance profiles are associated with specific patterns of comorbidity. Our findings highlight the importance of continued research on sleep complaints during MDE while taking into account psychiatric comorbidity.


Giant posterior fossa cavernous malformations in 2 infants with familial cerebral cavernomatosis: the case for early screening.
The author reports the details in 2 cases of infants with familial cerebral cavernomatosis who presented in dire condition from hemorrhagic posterior fossa cavernous malformations. In Case 1, a 4-month-old boy presented with opisthotonos, gaze palsy, and lethargy. Magnetic resonance imaging revealed a multilobulated cavernous malformation in the fourth ventricle with evidence of bleeding and obstructive hydrocephalus. In Case 2, a 7-month-old girl presented with lethargy, followed by rapid neurological decline. Imaging demonstrated a large lesion involving both the brainstem and cerebellum, with obstructive hydrocephalus. Both patients required immediate surgical intervention, and external ventricular drainage and posterior fossa craniotomies were performed. Both patients made excellent recoveries. These cases suggest that infants in families with suspected or confirmed familial cerebral cavernomatosis should be screened at an early age.


Sentinel lymph node biopsy mapped with methylene blue dye alone in patients with breast cancer: A systematic review and meta-analysis.
Methylene blue dye is easy to obtain in developing countries and can be used in sentinel lymph node mapping for breast cancer. However, the accuracy of methylene blue alone for sentinel lymph node mapping in breast cancer has not been well defined. In this study, we collected data to assess the feasibility and accuracy of sentinel lymph node biopsy mapped with methylene blue alone in patients with breast cancer. We searched the PubMed, EMBASE, and Cochrane Library databases from January 1, 1993, to March 31, 2018. Selected studies had to have a defined group of patients with breast cancer in which MBD alone was used as the mapping technique for SNB. 18 studies were included in this study. The combined identification rate was 91% [95% confidence interval (CI): 88%-94%, I2 = 68.3%], and the false negative rate was 13% (95% CI: 9%-18%, I2 = 36.7%). The pooled sensitivity, negative predictive value, and accuracy rate were 87% (95% CI: 82%-91%, I2 = 37.5%), 91% (95% CI: 87%-93%, I2 = 32.4%) and 94% (95% CI: 92%-96%, I2 = 29%), respectively. This meta-analysis found that mapping sentinel lymph node locations with methylene blue dye alone results in an acceptable identification rate but an excessive false negative rate according to the American Society of Breast Surgeons' recommendations. Caution is warranted when using methylene blue dye alone as the mapping method for sentinel lymph node biopsy.


Glycogen synthase kinase 3 β activity is essential for Polo-like kinase 2- and Leucine-rich repeat kinase 2-mediated regulation of α-synuclein.
Parkinson's disease (PD) is a currently incurable disease and the number of patients is expected to increase due to the extended human lifespan. α-Synuclein is a pathological hallmark of PD and variations and triplications of the gene encoding α-synuclein are strongly correlated with the risk of developing PD. Decreasing α-synuclein is therefore a promising therapeutic strategy for the treatment of PD. We have previously demonstrated that Polo-like kinase 2 (PLK-2) regulates α-synuclein protein levels by modulating the expression of α-synuclein mRNA. In this study, we further expand the knowledge on this pathway and show that it depends on down-stream modulation of Glycogen-synthase kinase 3 β (GSK-3β). We show that PLK-2 inhibition only increases α-synuclein levels in the presence of active GSK-3β in both cell lines and primary neuronal cultures. Furthermore, direct inhibition of GSK-3β decreases α-synuclein protein and mRNA levels in our cell model and overexpression of Leucine-rich repeat kinase 2, known to activate GSK-3β, increases α-synuclein levels. Finally, we show an increase in endogenous α-synuclein in primary neurons when increasing GSK-3β activity. Our findings demonstrate a not previously described role of endogenous GSK-3β activity in the PLK-2 mediated regulation of α-synuclein levels. This finding opens up the possibility of GSK-3β as a novel target for decreasing α-synuclein levels by the use of small molecule compounds, hereby serving as a disease modulating strategy.


Technique for measuring laser beam propagation direction fluctuations.
A technique has been developed for the measurement of a component of the position of a small target within a laser beam and used to measure atmospherically induced beam-pointing fluctuations. A modulation is impressed on the beam in a manner such that the modulation phase varies with position across the beam, so the relative modulation phase of the signal returned from a remote retroreflector is indicative of the position of the retroreflector within the beam. The far-field modulation phase distribution is shown to be relatively unaffected by turbulence, and results are given for a series of experimental measurements of beam-pointing fluctuations.


Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.
The antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to achieve steady-state dose, variations in INR, and allelic variance. Results were compared with those previously reported in the literature for 637 patients. The relationships between allelic variants and warfarin sensitivity found in our study of Mayo Clinic patients are fundamentally the same as in those reported by others. The Mayo Clinic population is predominantly white and shows considerable allelic variability in CYP2C9 and VKORC1. Certain of these alleles are associated with increased sensitivity to warfarin. Polymorphisms in CYP2C9 and VKORC1 have a considerable effect on warfarin dose in white people. A correlation between steady-state warfarin dose and allelic variants of CYP2C9 and VKORC1 has been demonstrated by many previous reports and is reconfirmed in this report. The allelic variants found to most affect warfarin sensitivity are CYP2C9*1*1-VKORC1BB (less warfarin sensitivity than typical); CYP2C9*1*1-VKORC1AA (considerable variance in INR throughout initiation); CYP2C9*1*2-VKORC1AB (more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*2-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AA (much more sensitivity to warfarin than typical); and CYP2C9*2*2-VKORC1AB (much more sensitivity to warfarin than typical). Although we were unable to show an association between allelic variants and initial warfarin dose or dose escalation, an association was seen between allelic variant and steady-state warfarin dose. White people show considerable variance in CYP2C9 allele types, whereas people of Asian or African descent infrequently carry CYP2C9 allelic variants. The VKORC1AA allele associated with high warfarin sensitivity predominates in those of Asian descent, whereas white people and those of African descent show diversity, carrying either the VKORC1BB, an allele associated with low warfarin sensitivity, or VKORC1AB or VKORC1AA, alleles associated with moderate and high warfarin sensitivity, respectively.


Cross chromosomal similarity for DNA sequence compression.
Current DNA compression algorithms work by finding similar repeated regions within the DNA sequence and then encoding these regions together to achieve compression. Our study on chromosome sequence similarity reveals that the length of similar repeated regions within one chromosome is about 4.5% of the total sequence length. The compression gain is often not high because of these short lengths. It is well known that similarity exist among different regions of chromosome sequences. This implies that similar repeated sequences are found among different regions of chromosome sequences. Here, we study cross-chromosomal similarity for DNA sequence compression. The length and location of similar repeated regions among the sixteen chromosomes of S. cerevisiae are studied. It is found that the average percentage of similar subsequences found between two chromosome sequences is about 10% in which 8% comes from cross-chromosomal prediction and 2% from self-chromosomal prediction. The percentage of similar subsquences is about 18% in which only 1.2% comes from self-chromosomal prediction while the rest is from cross-chromosomal prediction among the 16 chromosomes studied. This suggests the importance of cross-chromosomal similarities in addition to self-chromosomal similarities in DNA sequence compression. An additional 23% of storage space could be reduced on average using self-chromosomal and cross-chromosomal predictions in compressing the 16 chromosomes of S. cerevisiae.


Structural and evolutionary analysis of an orangutan foamy virus.
The full-length proviral genome of a foamy virus infecting a Bornean orangutan was amplified, and its sequence was analyzed. Although the genome showed a clear resemblance to other published foamy virus genomes from apes and monkeys, phylogenetic analysis revealed that simian foamy virus SFVora was evolutionarily equidistant from foamy viruses from other hominoids and from those from Old World monkeys. This finding suggests an independent evolution within its host over a long period of time.


Approaches to vital pulp therapies.
Tooth decay, which leads to pulpal inflammation due to the pulp's response to bacterial components and byproducts is the most common infectious disease. The main goals of clinical management are to eliminate sources of infection, to facilitate healing by regulating inflammation indental tissue, and to replace lost tissues. A variety of novel approaches from tissue engineering based on stem cells, bioactive molecules, and extracellular matrix-like scaffold structures to therapeutic applications, or a combination of all these are present in the literature. Shortcomings of existing conventional materials for pulp capping and the novel approches aiming to preserve pulp vitality highligted the need for developing new targeted dental materials. This review looks at the novel approches for vital pulp treatments after briefly addresing the conventional vital pulp treatment as well as the regenerative and self defense capabilities of the pulp. A narrative review focusing on the current and future approaches for pulp preservation was performed after surveying the relevant papers on vital pulp therapies including pulp capping, pulpotomy, and potential approaches for facilitating dentin-pulp complex regeneration in PubMed, Medline, and Scopus databases.


Clinical Predictors of Extrapyramidal Symptoms Associated With Aripiprazole Augmentation for the Treatment of Late-Life Depression in a Randomized Controlled Trial.
Augmentation with aripiprazole is an effective pharmacotherapy for treatment-resistant late-life depression (LLD). However, aripiprazole can cause extrapyramidal symptoms (EPS) such as akathisia and parkinsonism; these symptoms are distressing and can contribute to treatment discontinuation. We investigated the clinical trajectories and predictors of akathisia and parkinsonism in older patients receiving aripiprazole augmentation for treatment-resistant LLD. Between 2009 and 2013, depressed older adults who did not remit with venlafaxine were randomized to aripiprazole or placebo in a 12-week trial. Participants were 60 years or older and met DSM-IV-TR criteria for major depressive episode with at least moderate symptoms. The presence of akathisia and parkinsonism was measured at each visit using the Barnes Akathisia Scale (BAS) and Simpson-Angus Scale (SAS), respectively. In an exploratory analysis, we examined a broad set of potential clinical predictors and correlates: age, sex, ethnicity, weight, medical comorbidity, baseline anxiety severity, depression severity, concomitant medications including rescue medications, and aripiprazole dosage. Twenty-four (26.7%) of 90 participants randomized to aripiprazole and who had akathisia scores available developed akathisia compared to 11 (12.2%) of 90 randomized to placebo. Greater depression severity was the main predictor of treatment-emergent akathisia. Most participants who developed akathisia improved over time, especially with reductions in dosage. Fifteen (16.5%) of 91 participants taking aripiprazole and who had parkinsonism scores available developed parkinsonism, but no clinical predictors or correlates were identified. Akathisia is a common side effect of aripiprazole, but it is typically mild and responds to dose reduction. Patients with greater baseline depression may warrant closer monitoring for akathisia. More research is needed to understand the course and predictors of treatment-emergent EPS with antipsychotic augmentation for treatment-resistant LLD. ClinicalTrials.gov identifier: NCT00892047.


Reliable Reference Genes for Gene Expression Assessment in Tendon-Derived Cells under Inflammatory and Pro-Fibrotic/Healing Stimuli.
Tendon cells (TCs) are important for homeostatic maintenance in the healthy tendon and to promote tissue healing after injury. Further, resident and rare populations of tendon stem/progenitor cells, located at various sites within the tendon, contribute to tendon recovery by differentiating into repairing TCs. Gene expression analysis, through quantitative reverse-transcription polymerase chain reaction (qRT-PCR), constitutes a useful tool to study cellular responses, including the transition from initial inflammation to healing processes. A critical step required for data normalization is the choice of reliable reference genes (RGs), a process highly underestimated in tendon biology. In this study, the suitability of five commonly used RGs (ACTB, B2M, GAPDH, HPRT1, and RPLP0) was evaluated using TCs samples cultured in both standard and progenitor-enriching conditions, as well as under either inflammatory (IFNγ + TNFα) or pro-fibrotic/healing (CTGF) stimulation. The stability of the candidate RGs was computationally determined using NormFinder, geNorm, BestKeeper, and DeltaCt applets. Overall, ACTB resulted as the most stable RG on the basis of the integration of each gene weight, whereas B2M and RPLP0 performed poorly. To further validate ACTB's optimal performance, we evaluated the expression of ICAM1, coding for an immune-related cell surface glycoprotein, and COL1A1, encoding collagen type I that is the main component of the tendon extracellular matrix (ECM), both known to be modulated by inflammation. The expression of both genes was heavily affected by the RGs used. Consequently, when analyzing gene expression in tendon-derived cells subjected to various stimulatory protocols, the use of a suitable RG should be considered carefully. On the basis of our results, ACTB can be reliably used when analyzing different TC types exposed to pathological conditions.


Gallium-indium nanoparticles as phase change material additives for tunable thermal fluids.
One of the most critical limitations for high-power electronics today is thermal management and routing thermal energy efficiently away from thermally sensitive components. A potential solution to this problem is the integration of cooling channels in close proximity to thermally sensitive materials for increased heat removal efficiency. These channels typically use single phase fluids (liquid), dual phase fluids (vapor-liquid), or suspended organic/polymer phase change material particles in a fluid (PCM slurry). Expanding upon the latter, this work demonstrates the use of inorganic Ga-In alloy nanoparticles (NPs) suspended in a traditional thermal transport fluid to simultaneously (1) increase the overall thermal diffusivity of the fluid and (2) serve as a cyclable solid-liquid PCM slurry which provides a thermal sink that is definable over a wide range of relevant temperatures for power electronics. Herein, the relationship between particle size, composition, and volume fraction are explored as they relate to the PCM slurry optimum working temperature, total energy absorption, and rheological properties. A mere 0.10 volume fraction of Ga-In NPs is reported to increase the overall thermal conductivity by nearly 50% and can be optimized to melt at temperatures as low as -46 °C. Based on thermal measurements, it was observed that these nanoparticle systems lack the preference to form αGa and have a large thermal hysteresis due to exhibiting extreme undercooling, with crystallization temperatures near -130 °C, enabling opportunities within extreme environments such as space applications or low temperature imaging systems.


GGT levels in type II diabetic patients with acute coronary syndrome (does diabetes have any effect on GGT levels in acute coronary syndrome?).
Elevated gamma-glutamyltransferase (GGT) level is independently correlated with conditions associated with increased atherosclerosis, such as obesity, elevated serum cholesterol, high blood pressure and myocardial infarction. It is demonstrated that serum GGT activity is an independent risk factor for myocardial infarction and cardiac death in patients with coronary artery disease. Diabetes is also a well-known cardiovascular risk factor and an equivalent of coronary artery disease. Although the relationship between GGT and coronary artery disease has been reported, there are limited data exploring the changes of GGT in acute coronary syndromes, especially in patients with diabetes. So, this study aimed to determine changes in GGT level in diabetic and non-diabetic acute coronary syndromes. This trial was carried out at Kosuyolu Cardiovascular Training and Research Hospital and Van Yuksek Ihtisas Hospital, Turkey. A total of 219 patients (177 men and 42 women) presenting with acute coronary syndrome) and 51 control subjects between September 2007 and September 2008 were included in the study. Serum γ-glutamyltransferase and serum lipoprotein levels were determined. The resuls indicated that serum GGT levels were higher in acute coronary syndrome patients compared with control. In subgroup analyses, there was no difference between diabetic and non-diabetic subgroups. There was also weak correlation between GGT and blood glucose levels. There was no correlation between GGT and serum lipoprotein levels. In conclusion, serum GGT levels were higher in acute coronary syndrome patients. In subgroup analyses, There was no difference between diabetic and non diabetic subgroup.


Multinuclear NMR studies of single lipid bilayers supported in cylindrical aluminum oxide nanopores.
Lipid bilayers were deposited inside the 0.2 microm pores of anodic aluminum oxide (AAO) filters by extrusion of multilamellar liposomes and their properties studied by 2H, 31P, and 1H solid-state NMR. Only the first bilayer adhered strongly to the inner surface of the pores. Additional layers were washed out easily by a flow of water as demonstrated by 1H magic angle spinning NMR experiments with addition of Pr3+ ions to shift accessible lipid headgroup resonances. A 13 mm diameter Anopore filter of 60 microm thickness oriented approximately 2.5 x 10(-7) mol of lipid as a single bilayer, corresponding to a total membrane area of about 500 cm2. The 2H NMR spectra of chain deuterated POPC are consistent with adsorption of wavy, tubular bilayers to the inner pore surface. By NMR diffusion experiments, we determined the average length of those lipid tubules to be approximately 0.4 microm. There is evidence for a thick water layer between lipid tubules and the pore surface. The ends of tubules are well sealed against the pore such that Pr3+ ions cannot penetrate into the water underneath the bilayers. We successfully trapped poly(ethylene glycol) (PEG) with a molecular weight of 8000 in this water layer. From the quantity of trapped PEG, we calculated an average water layer thickness of 3 nm. Lipid order parameters and motional properties are unperturbed by the solid support, in agreement with existence of a water layer. Such unperturbed, solid supported membranes are ideal for incorporation of membrane-spanning proteins with large intra- and extracellular domains. The experiments suggest the promise of such porous filters as membrane support in biosensors.


[Rehabilitation of patients with stroke].
Stroke is one of the most frequent causes of death and disability. 14,000 to 15,000 individuals are hit by stroke in Norway annually, and the incidence is expected to rise. Optimal organization of rehabilitation for stroke patients has been extensively documented during the last 10 years. It is established that a larger reduction of disability and mortality for stroke patients is obtained by treatment and rehabilitation in stroke units than in general medical wards. WHO Region Europe recommends that all stroke patients are treated in stroke units in the acute phase. Additional reduction in mortality and disability is achieved through home-based rehabilitation, coordination by a multidisciplinary ambulatory team and by emphasizing cooperation between different levels of healthcare. Strategies for organising rehabilitation for different stroke patients must be based on scientific evidence; more knowledge is needed and much research is currently ongoing. The field of neuroscience has developed quickly during the last years, and evidence of brain plasticity gives reason to believe that an increase in the amount and intensity of training is important for an optimal effect. There is a need for more systematized knowledge, and further research will hopefully define a more specific and optimal strategy for stroke rehabilitation within a few years.


Deriving semantic structure from category fluency: clustering techniques and their pitfalls.
Assessing verbal output in category fluency tasks provides a sensitive indicator of cortical dysfunction. The most common metrics are the overall number of words produced and the number of errors. Two main observations have been made about the structure of the output, first that there is a temporal component to it with words being generated in spurts, and second that the clustering pattern may reflect a search for meanings such that the 'clustering' is attributable to the activation of a specific semantic field in memory. A number of sophisticated approaches to examining the structure of this clustering have been developed, and a core theme is that the similarity relations between category members will reveal the mental semantic structure of the category underlying an individual's responses, which can then be visualized by a number of algorithms, such as MDS, hierarchical clustering, ADDTREE, ADCLUS or SVD. Such approaches have been applied to a variety of neurological and psychiatric populations, and the general conclusion has been that the clinical condition systematically distorts the semantic structure in the patients, as compared to the healthy controls. In the present paper we explore this approach to understanding semantic structure using category fluency data. On the basis of a large pool of patients with schizophrenia (n = 204) and healthy control participants (n = 204), we find that the methods are problematic and unreliable to the extent that it is not possible to conclude that any putative difference reflects a systematic difference between the semantic representations in patients and controls. Moreover, taking into account the unreliability of the methods, we find that the most probable conclusion to be made is that no difference in underlying semantic representation exists. The consequences of these findings to understanding semantic structure, and the use of category fluency data, in cortical dysfunction are discussed.


Optimal Number of Message Transmissions forProbabilistic Guarantee of Latency in the IoT.
The Internet of Things (IoT) is now experiencing its first phase of industrialization. Industrial companies are completing proofs of concept and many of them plan to invest in automation, flexibility and quality of production in their plants. Their use of a wireless network is conditioned upon its ability to meet three Key Performance Indicators (KPIs), namely a maximum acceptable end-to-end latency L, a targeted end-to-end reliability R and a minimum network lifetime T. The IoT network has to guarantee that at least R % of messages generated by sensor nodes are delivered to the sink with a latency ≤L, whereas the network lifetime is at least equal to T. In this paper, we show how to provide the targeted end-to-end reliability R by means of retransmissions to cope with the unreliability of wireless links. We present two methods to compute the maximum number of transmissions per message required to achieve R. M F a i r is very easy to compute, whereas M O p t minimizes the total number of transmissions necessary for a message to reach the sink. M F a i r and M O p t are then integrated into a TSCH network with a load-based scheduler to evaluate the three KPIs on a generic data-gathering application. We first consider a toy example with eight nodes where the maximum number of transmissions M a x T r a n s is tuned per link and per flow. Finally, a network of 50 nodes, representative of real network deployments, is evaluated assuming M a x T r a n s is fixed. For both TSCH networks, we show that M O p t provides a better reliability and a longer lifetime than M F a i r , which provides a shorter average end-to-end latency. M O p t provides more predictable end-to-end performances than Kausa, a KPI-aware, state-of-the-art scheduler.


Characterization of the sea-urchin egg microtubule-activated ATPase.
We have found that cytoplasmic extracts from unfertilized sea-urchin eggs contain a prominent microtubule-activated ATPase activity. This activity is induced by polymeric tubulin, but not by tubulin subunits. The activity cosediments with taxol-stabilized microtubules in an ATP-independent manner. We have separated the ATPase from cytoplasmic dynein and other ATPases on sucrose gradients. The sedimentation, enzymic and microtubule-binding properties of the microtubule-activated species show it to be distinct from cytoplasmic dynein, myosin and kinesin. Since the major function of microtubules in the early sea-urchin embryo is in mitosis, this enzyme represents a new candidate for a role in spindle motility.


The failure of long-term feeding of raw soy flour, in the presence or absence of azaserine, to induce carcinogenic changes in the mouse pancreas.
The effects of feeding mice raw or heated soy flours or casein in the presence and absence of injected azaserine were investigated over a period of 18 months. Although the feeding of raw soy flour (compared with heated soy flour or casein) caused a significant inhibition of growth and an enlargement of the pancreas, there was no macroscopic evidence of pancreatic nodules in any of the six experimental groups. Microscopic examination of the pancreas revealed a somewhat higher (not significant) incidence of atypical acinar cell nodules in all animals injected with azaserine, but this difference was little influenced by the diets themselves. We concluded that raw soy flour itself has no carcinogenic effect on the mouse pancreas and does not enhance the sensitivity of the mouse pancreas to azaserine. Thus, it cannot be assumed that the appearance of pancreatic nodules constitutes an obligatory sequela of pancreatic hypertrophy and/or hyperplasia in all species of animals.


Contralaterally Enhanced Networks for Thoracic Disease Detection.
Identifying and locating diseases in chest X-rays are very challenging, due to the low visual contrast between normal and abnormal regions, and distortions caused by other overlapping tissues. An interesting phenomenon is that there exist many similar structures in the left and right parts of the chest, such as ribs, lung fields and bronchial tubes. This kind of similarities can be used to identify diseases in chest X-rays, according to the experience of broad-certificated radiologists. Aimed at improving the performance of existing detection methods, we propose a deep end-to-end module to exploit the contralateral context information for enhancing feature representations of disease proposals. First of all, under the guidance of the spine line, the spatial transformer network is employed to extract local contralateral patches, which can provide valuable context information for disease proposals. Then, we build up a specific module, based on both additive and subtractive operations, to fuse the features of the disease proposal and the contralateral patch. Our method can be integrated into both fully and weakly supervised disease detection frameworks. It achieves 33.17 AP50 on a carefully annotated private chest X-ray dataset which contains 31,000 images. Experiments on the NIH chest X-ray dataset indicate that our method achieves state-of-the-art performance in weakly-supervised disease localization.


Effect of poly herbal formulation, EuMil, on neurochemical perturbations induced by chronic stress.
EuMil, a polyherbal formulation consisting of standardised extracts of Withania somnifera (L) Dunal, Ocimum sanctum L, Asparagus racemosus Wilid and Emblica officinalis Gaertn., is used as an anti-stress agent to attenuate the various aspects of stress related disorders. In the present study, the neurochemical mechanisms underlying the anti-stress activity of EuMil were evaluated by measuring the rat brain monoamine neurotransmitter levels and tribulin activity. Chronic electroshock stress (14 days) significantly decreased the nor-adrenaline (NA) and dopamine (DA) levels in frontal Cortex, pons-medulla, hypothalamus, hippocampus and striatal, hypothalamal region, respectively, and increased the 5-hydroxytryptamine (5HT) level in frontal cortex, pons medulla, hypothalamus and hippocampus. Chronic stress, also increased the rat brain tribulin activity. EuMil (100 mg/kg, p.o., 14 days) treatment normalized the perturbed regional NA, DA, 5HT concentrations, induced by chronic stress. EuMil also significantly attenuated the stress-induced increase in the rat brain tribulin activity. The amelioration of chronic stress-induced neurochemical perturbations by EuMil explains the neurochemical mechanisms underlying the observed putative anti-stress activity of the product.


A method for the analysis of butyltin chlorides in air by gas chromatography with atomic emission detection.
An initial screening test compared the use of tropolone (2-hydroxy-2,4-6-cycloheptatrienone) in acetic acid with sodium diethyldithiocarbamate (NaDDC) as chelating agents for the extraction of butyltin chlorides from glass fiber filters and XAD-2 resin tube. NaDDC was chosen for subsequent analyses. Mono-, di-, and tributyltin chloride were spiked onto glass fiber filters and XAD-2 resin, extracted in toluene with NaDDC and derivatized with pentylmagnesium bromide. Derivatized butyltin species were determined by gas chromatography with plasma atomic emission detection. Glass fiber filters and XAD-2 resin were found to provide high retention of butyltin compounds during sampling and efficient recovery of butyltin compounds by extraction with NaDDC.


Early Mucosal Healing Predicts Favorable Outcomes in Patients With Moderate to Severe Ulcerative Colitis Treated With Golimumab: Data From the Real-life BE-SMART Cohort.
Golimumab (GOL) is registered for moderate to severely active ulcerative colitis (UC). Data on the use of GOL in daily clinical practice are limited. Currently, it is unclear which factors are predictive of a favorable outcome. The goals of this study were to evaluate the mid-term outcome of GOL (week 26) in patients with moderate to severe UC and to determine predictors of favorable outcome. Patients included in the SMART study (NCT02155335) were evaluated for their mid-term outcome. Demographic data, disease characteristics, and medical history were recorded retrospectively. Data on disease activity based on total Mayo score, previous and concomitant medication, GOL dosing, mucosal healing (Mayo 0 or 1), adverse events (colectomy, hospitalization), and biomarkers (C-reactive protein, fecal calprotectin, hemoglobin, and albumin) were collected at baseline and weeks 2, 6, 14, 26, and 52. GOL was dosed at 200 and 100 mg at weeks 0 and 2, respectively, and 50 mg (<80 kg body weight) or 100 mg (≥80 kg body weight) every 4 weeks thereafter. The primary end point was steroid-free GOL continuation at week 26. From the 91 evaluable patients (42% female; median age, 42 years; median disease duration, 5 years), 4% were active smokers, 25% had extensive colitis, and 38% had an endoscopic Mayo score of 3 at baseline. The median (interquartile range [IQR]) baseline Mayo score was 9 (8-10). Although 75% of patients had previously failed immunomodulators (IMMs), the majority (87%) were anti-tumor necrosis factor (TNF) naïve. GOL was started in combination with IMM in 40% and steroids in 64%. The median (IQR) duration of GOL therapy during follow-up was 35.7 (11.4-105.7) weeks. Twenty-six weeks after GOL induction, 37 patients (41%) were steroid-free and still on GOL, of whom 8 (21.6%) required GOL dose optimization. Short-term mucosal healing (STMH) at week 14 was evaluated in 60% of the patients. Considering the whole cohort, only 40% achieved STMH. No predictors could be retained of short-term treatment outcome. In multivariate analysis, STMH was predictive of steroid-free GOL continuation at week 26 (odds ratio [OR], 5.56; 95% confidence interval [CI], 1.90-16.29; P = 0.002) and week 52 (OR, 9.38; 95% CI, 2.68-32.84; P < 0.001). In patients continuing GOL after week 14, STMH was predictive of intervention-free survival (OR, 2.05; 95% CI, 1.09-3.86; P = 0.026) and discontinuation-free survival (OR, 3.47; 95% CI, 1.58-7.58; P = 0.002). During follow-up, 78% needed an intervention, 68% discontinued GOL, and 3 patients needed a colectomy. Real-life data confirm the moderate effectiveness of GOL on the mid-term in active UC, but therapeutic interventions are frequently needed. Short-term mucosal healing predicts a favorable outcome. 10.1093/ibd/izy219_video1izy219.video15798038438001.


Effects of thermodynamic ensembles and mineral surfaces on interfacial water structure.
While performing molecular dynamics simulations of water or aqueous solutions in a slab geometry, such as at mineral surfaces, it is important to match bulk water density in the diffuse region of the model system with that expected for the appropriate experimental conditions. Typically, a slab geometry represents parallel surfaces with a variable region of confined water (this region can range in size from a few Ångstroms to many tens of Ångstroms). While constant-pressure simulations usually result in appropriate density values in the bulk diffuse region removed from either surface, constant-volume simulations have also been widely used, sometimes without careful consideration of the method for determining water content. Simulations using two thermodynamic ensembles as well as two methods for calculating the water-accessible volume have been investigated for two distinct silicate surfaces-hydrophilic cristobalite (111) and hydrophobic pyrophyllite (001). In cases where NPT simulations are not feasible, a simple geometry-based treatment of the accessible volume can be sufficient to replicate bulk water density far from the surface. However, the use of the Connolly method can be more appropriate in cases where a surface is less well-defined. Specific water-surface interactions (e.g., hydrophobic repulsion) also play a role in determining water content in a confined water simulation. While reported here for planar surfaces, these results can be extended to an interface with any solvent, or to other types of surfaces and geometries.


Changing climate and the altitudinal range of avian malaria in the Hawaiian Islands - an ongoing conservation crisis on the island of Kaua'i.
Transmission of avian malaria in the Hawaiian Islands varies across altitudinal gradients and is greatest at elevations below 1500 m where both temperature and moisture are favorable for the sole mosquito vector, Culex quinquefasciatus, and extrinsic sporogonic development of the parasite, Plasmodium relictum. Potential consequences of global warming on this system have been recognized for over a decade with concerns that increases in mean temperatures could lead to expansion of malaria into habitats where cool temperatures currently limit transmission to highly susceptible endemic forest birds. Recent declines in two endangered species on the island of Kaua'i, the 'Akikiki (Oreomystis bairdi) and 'Akeke'e (Loxops caeruleirostris), and retreat of more common native honeycreepers to the last remaining high elevation habitat on the Alaka'i Plateau suggest that predicted changes in disease transmission may be occurring. We compared prevalence of malarial infections in forest birds that were sampled at three locations on the Plateau during 1994-1997 and again during 2007-2013, and also evaluated changes in the occurrence of mosquito larvae in available aquatic habitats during the same time periods. Prevalence of infection increased significantly at the lower (1100 m, 10.3% to 28.2%), middle (1250 m, 8.4% to 12.2%), and upper ends of the Plateau (1350 m, 2.0% to 19.3%). A concurrent increase in detections of Culex larvae in aquatic habitats associated with stream margins indicates that populations of the vector are also increasing. These increases are at least in part due to local transmission because overall prevalence in Kaua'i 'Elepaio (Chasiempis sclateri), a sedentary native species, has increased from 17.2% to 27.0%. Increasing mean air temperatures, declining precipitation, and changes in streamflow that have taken place over the past 20 years are creating environmental conditions throughout major portions of the Alaka'i Plateau that support increased transmission of avian malaria.


Platelet and HIV Interactions and Their Contribution to Non-AIDS Comorbidities.
Platelets are anucleate cytoplasmic cell fragments that circulate in the blood, where they are involved in regulating hemostasis. Beyond their normal physiologic role, platelets have emerged as versatile effectors of immune response. During an infection, cell surface receptors enable platelets to recognize viruses, resulting in their activation. Activated platelets release biologically active molecules that further trigger host immune responses to protect the body against infection. Their impact on the immune response is also associated with the recruitment of circulating leukocytes to the site of infection. They can also aggregate with leukocytes, including lymphocytes, monocytes, and neutrophils, to immobilize pathogens and prevent viral dissemination. Despite their host protective role, platelets have also been shown to be associated with various pathophysiological processes. In this review, we will summarize platelet and HIV interactions during infection. We will also highlight and discuss platelet and platelet-derived mediators, how they interact with immune cells, and the multifaceted responsibilities of platelets in HIV infection. Furthermore, we will give an overview of non-AIDS comorbidities linked to platelet dysfunction and the impact of antiretroviral therapy on platelet function.


[Modulation of molecular signaling mechanisms in excitable cells by toxins and bacterial substances].
The mechanisms of bacterial substances (protein A, peptidoglican Staphylococcus aureus), bacterium toxins (St. aureus, Corynebacterium diphtheriae, Shigella dysenteriae, Clostridium botulinum, Clostridium tetani, Vibrio choleral), transfer factor of immune reactivity to Staphylococcus aureus upon the key link (acetylcholine-, ATP-, inositol-1,4,5-triphosphate-, ryanodin-sensitive receptors, G-proteins, Ca2+, K(+)-transporting systems, second messengers) in the chain of signal conduction of excitatory and inhibitory agonists in excitable cells were examined. The action of these immune-active substances upon contractile proteins ATP-ase activity and protein synthesis was also discussed.


Image registration: Maximum likelihood, minimum entropy and deep learning.
In this work, we propose a theoretical framework based on maximum profile likelihood for pairwise and groupwise registration. By an asymptotic analysis, we demonstrate that maximum profile likelihood registration minimizes an upper bound on the joint entropy of the distribution that generates the joint image data. Further, we derive the congealing method for groupwise registration by optimizing the profile likelihood in closed form, and using coordinate ascent, or iterative model refinement. We also describe a method for feature based registration in the same framework and demonstrate it on groupwise tractographic registration. In the second part of the article, we propose an approach to deep metric registration that implements maximum likelihood registration using deep discriminative classifiers. We show further that this approach can be used for maximum profile likelihood registration to discharge the need for well-registered training data, using iterative model refinement. We demonstrate that the method succeeds on a challenging registration problem where the standard mutual information approach does not perform well.


Ethanol and the gamma-aminobutyric acid-benzodiazepine receptor complex.
Ethanol appears to enhance gamma-aminobutyric acid (GABA)-mediated synaptic transmission. Using radioligand binding techniques, we investigated the possibility that the GABA-benzodiazepine receptor complex is the site responsible for this effect. Ethanol at concentrations up to 100 mM failed to alter binding of [3H]flunitrazepam (FNZ), [3H]Ro 15-1788, or [3H]methyl-beta-carboline-3-carboxylate (MBCC) to benzodiazepine receptors, or of [3H]muscimol to GABA receptors in rat brain membranes. Scatchard analyses of the binding of these radioligands at 4 degrees C and 37 degrees C revealed no significant effects of 100 mM ethanol on receptor affinity or number. A variety of drugs as well as chloride ion increased binding of [3H]FNZ and/or [3H]muscimol, but these influences were not modified by ethanol. These findings indicate that ethanol probably potentiates GABAergic neurotransmission at a signal transduction site beyond the GABA-benzodiazepine receptor complex.


Virolysis of feline calicivirus and human GII.4 norovirus following chlorine exposure under standardized light soil disinfection conditions.
The relationship between the infectivity of the feline calicivirus (FCV) vaccine strain F-9 and capsid destruction (virolysis) in response to available chlorine was investigated under standardized light soil disinfection conditions. Virolysis was measured using RNase pretreatment (in order to destroy exposed RNA following chlorine treatment) and quantitative reverse transcription PCR. A comparison between the results of plaque assays and virolysis following exposure of FCV F-9 grown in tissue culture to different concentrations of available chlorine showed a similar log-linear relationship, with >4-log reductions occurring at 48 and 66 ppm, respectively. Three non-epidemiologically linked human GII.4 noroviruses (NoVs) present in dilute clinical samples showed behavior similar to each other and were 10 times more resistant to virolysis than cultured FCV F-9. FCV F-9 when present in dilute human GII.4 samples acquired increased resistance to virolysis approaching that of human NoVs. This study represents a direct comparison between the virolysis of a surrogate virus (FCV F-9) and that of human GII.4 NoVs within the same matrix in response to available chlorine. The results support the view that matrix effects have a significant effect on virus survival.


A Case of Shingles Following Auricular Acupuncture.
This is a case report of an occurrence of shingles (herpes zoster [HZ]) following auricular acupuncture. The patient developed acute reactivation HZ in the V1 distribution of the right trigeminal nerve involving the forehead, scalp, and medial upper eyelid 13 days after being treated with auricular acupuncture for chronic low-back pain. The lesions were initially painless, but they clustered and became painful within 2 days. The patient was treated with oral valacyclovir 1000 mg, 3 times daily for 7 days, and ibuprofen as needed. The lesions resolved without sequelae.


An electronic checklist improves transfer and retention of critical information at intraoperative handoff of care.
Communication failures are a significant cause of preventable medical errors, and poor-quality handoffs are associated with adverse events. We developed and implemented a simple checklist to improve communication during intraoperative transfer of patient care. A prospective observational assessment was performed to compare relay and retention of critical patient information between the outgoing and incoming anesthesiologist before and after introduction of an electronic handoff checklist. Secondary measurements included checklist usage and clinician satisfaction. Sixty-nine handoffs were observed (39 with and 30 without the checklist). Significant improvements in the frequency of information relay occurred with checklist use, most notably related to administration of vasopressors and antiemetics (85% vs 44%, P = 0.008; 46% vs 15%, P = 0.015, respectively); estimated blood loss and urine output (85% vs 57%, P = 0.014; 85% vs 52%, P = 0.006, respectively); communication about potential areas of concern (92% vs 57%, P = 0.001), postoperative planning (92% vs 43%, P < 0.001), and introduction of the relieving anesthesiologist to the operating team (51% vs 3%, P < 0.001). When queried after the handoff, relieving anesthesiologists more frequently knew the antibiotic (97% vs 75%, P = 0.020), muscle relaxant (97% vs 63%, P = 0.003), and amount of fluid administered (97% vs 72%, P = 0.008) when the checklist was used. Voluntary use of the checklist occurred in 60% of the handoffs by the end of the observation period (99% control limits: 58%-75%.). Clinicians who reported using the checklist in at least two-thirds of their handoffs reported higher satisfaction with quality of communication at handoff (P = 0.003). An electronic checklist improved relay and retention of critical patient information and clinician communication at intraoperative handoff of care.


Actinomycete Metabolome Induction/Suppression with N-Acetylglucosamine.
The metabolite profiles of three sponge-derived actinomycetes, namely, Micromonospora sp. RV43, Rhodococcus sp. RV157, and Actinokineospora sp. EG49 were investigated after elicitation with N-acetyl-d-glucosamine. 1H NMR fingerprint methodology was utilized to study the differences in the metabolic profiles of the bacterial extracts before and after elicitation. Our study found that the addition of N-acetyl-d-glucosamine modified the secondary metabolite profiles of the three investigated actinomycete isolates. N-Acetyl-d-glucosamine induced the production of 3-formylindole (11) and guaymasol (12) in Micromonospora sp. RV43, the siderophore bacillibactin 16, and surfactin antibiotic 17 in Rhodococcus sp. RV157 and increased the production of minor metabolites actinosporins E-H (21-24) in Actinokineospora sp. EG49. These results highlight the use of NMR fingerprinting to detect changes in metabolism following addition of N-acetyl-d-glucosamine. N-Acetyl-d-glucosamine was shown to have multiple effects including suppression of metabolites, induction of new metabolites, and increased production of minor compounds.


Potential Diagnostic and Prognostic Value of Lymphocytic Mitochondrial DNA Deletion in Relation to Folic Acid Status in HCV-Related Hepatocellular Carcinoma
Objective: We assessed the possibility of using mitochondrial (mt) DNA deletion as a molecular biomarker for disease progression in HCV-related hepatocellular carcinoma (HCC) and to identify its association with folic acid status. Methods: Serum folic acid and lymphocytic mtDNA deletions were assessed in 90 patients; 50 with HCC, 20 with liver cirrhosis (LC), and 20 with chronic hepatitis C (CHC) compared to 10 healthy control subjects. The diagnostic accuracy of mtDNA deletions frequency was evaluated using receiver-operating characteristic (ROC) curve analysis Survival analysis was performed using the Kaplan-Meier method. Differences in the survival rates were compared using log-rank test. Result: Our data revealed a significant elevation of mtDNA deletions frequency in the HCC group compared to the other groups (P-value <0.01). Also, our data showed a significant correlation between folate deficiency and high frequency of mtDNA deletions in patients with HCV-related HCC when compared to the other groups (r= -0.094 and P-value <0.05). Moreover, the size of the hepatic focal lesion in the HCC patients was positively correlated with mtDNA deletions (r= 0.09 and P-value <0.01). The median survival time for the HCC patients with high frequency of mtDNA deletions (ΔCt ≥3.9; 5.7+ 0.6 months) was significantly shorter than those with low mtDNA deletions frequency (ΔCt < 3.9; 11.9+ 0.04 months, P-value <0.01). Conclusion: Our data provided an evidence that lymphocytic mtDNA deletion could be used as non-invasive biomarker for disease progression and patients' survival in HCV-related HCC. Also, our findings implied a causal relationship between the folate deficiency and the high mtDNA deletions frequency among Egyptian patients with HCV related HCC.


[Clinical aspects and treatment of spontaneous carotid artery-cavernous sinus fistula].
21 patients, who fulfilled the clinical and angiographic criteria of a spontaneous carotid cavernous fistula (CCF), were studied at the Alfried Krupp Hospital, Essen, Germany, between 1980 and 1988. Of these patients, 4 had direct shunts between the internal carotid artery and the cavernous sinus and 17 patients had unilateral or bilateral dural shunts between meningeal branches of the internal and/or external carotid artery and the cavernous sinus. The most common initial symptoms were eye redness, bruit and headache. 6 of 12 patients with double vision had mechanical disorders of eye movement. A rapid irreversible loss of vision occurred in 2 patients. In 9 of 21 patients either progressive visual deterioration, proptosis or severe orbital pain necessitated prompt institution of treatment. All direct fistulas could be occluded by the use of the detachable balloon technique. 5 patients with dural CCF were successfully treated with particle embolization of the external carotid artery blood supply. In dural CCF not requiring emergent treatment, combined carotid artery and jugular vein compression was preferred and resulted in complete cure or sufficient improvement in all but one patient. We recommend this method as the first stage of treatment in dural CCF with uncomplicated course.


Comparison of therapist implemented and iPad-assisted interventions for children with autism.
This study compares intervention delivered by a therapist to intervention delivered using an iPad for two children with autism. Further, this study evaluates the influence of choice between the conditions. Time on-task, challenging behaviour, session duration and correct responses were compared across conditions in an alternating treatment design. The effect of choice was evaluated in an ABAB design. The iPad was associated with shorter intervention sessions, more time on-task and less challenging behaviour for one participant. There was no difference between conditions for the second participant. Both participants selected the iPad when given the choice and, although the effect of choice was modest, choosing was associated with more time on-task and less challenging behaviour. These data suggest that iPad-assisted intervention can be as effective as therapist-implemented intervention. Further, even for children for whom no differences between the interventions exist, offering a choice may be beneficial.


Objective survey of the prescription of occlusion therapy for amblyopia.
To identify the variation within and consistency amongst orthoptists when prescribing occlusion therapy for amblyopia in an objective survey. A questionnaire was designed with five case examples of amblyopic children and distributed at annual meetings of orthoptists in The Netherlands and Germany. It was filled in simultaneously within 15 min in complete silence to avoid any exchange of opinions between orthoptists that would reduce variability. For each case the orthoptists were asked to give their prescription of hours or days of occlusion. The questionnaire was filled in by 177 Dutch orthoptists and 227 German orthoptists. Their prescriptions of occlusion therapy were classified into five main regimens: part-time; part-time not every day; full-time; also occluding the amblyopic eye; alternating; and no occlusion therapy. The variation was large: the standard deviation was half the average prescribed hours of occlusion for each regimen in each of the five cases. All orthoptists were assigned a rank number for each of the five cases depending on whether their prescription was above or below average. These five rank numbers were not consistently above or consistently below average value per case. The number of prescribed hours of occlusion varied widely per regimen per case. Orthoptists were not consistently strict or lenient in their prescription of occlusion therapy.


Pediatric ATV Injuries in a Statewide Sample: 2004 to 2014.
To establish the incidence, mortality rate, and fracture location of pediatric patients injured while using an all-terrain vehicle (ATV) over an 11-year period. A retrospective study using a state trauma database for patients ages 0 to 17 years who sustained injuries while using an ATV. Thirty-two pediatric and adult trauma centers within the state were evaluated from January 1, 2004, to December 31, 2014. The inclusion criteria were met by 1912 patients. The estimated mean annual incidence during the period of the study was 6.2 patients per 100 000 children in the pediatric population <18 years of age. There was a decrease of 13.4% in the mean incidence when comparing the first 5 years of the study with the last 6 years. The median age of patients was 14 years. The median hospital length of stay and injury severity score were 3 days and 9, respectively. There were 28 fatalities (1.5%). The mean mortality incidence was 0.09 deaths per 100 000 children and remained relatively constant. The majority of patients (55.4%) sustained at least 1 bone fracture at or below the cervical spine. The femur and tibia were more commonly fractured (21.6% and 17.7% of the patients, respectively). Despite current guidelines by the American Academy of Pediatrics, patients younger than 16 years of age remain victims of ATV injuries. Although there was a 13.4% reduction in the incidence of ATV-related injuries in recent years, continued preventive guidelines are still necessary to avert these injuries in children and adolescents.


Therapeutic Interventions and Risk Factors of Bleeding During Extracorporeal Membrane Oxygenation.
Bleeding is the most common complication during extracorporeal membrane oxygenation (ECMO). It is associated with an increased mortality and represents the most frequent cause of preliminary ECMO termination. We performed a retrospective analysis in a single ECMO referral center delineating the risk factors and therapeutic interventions of bleeding during adult ECMO in a total of 59 patients. The median length of ECMO support was 158 hours, with an all-cause mortality of 41%. Bleeding occurred on 40% of the days. On multivariate analysis, fungal pneumonia was the only significant factor associated with the occurrence of a bleeding event. The most common bleeding locations were the ECMO cannulation sites. Termination of ECMO support was the most successful therapeutic intervention, followed by the administration of tranexamic acid, replacement of the membrane oxygenator or the ECMO system, administration of factor VIIa, and repositioning of at least one ECMO cannula. Moreover, the transfusion of platelets was a successful mean, as well as the utilization of desmopressin to enhance platelet function. As such, further delineation of the coagulation disorders during ECMO support to provide a sophisticated pharmacotherapy may stop this serious adverse event.


[Time trends in cancer incidence in Navarra and Zaragoza, spain].
The knowledge of time-related changes occurring in cancer incidence and mortality is an essential element for cancer control. This paper aims to describe the time trends of the more important cancer sites in Navarra and Zaragoza. The influence of age, diagnosis period and birth cohort on the observed time trend cancer incidence in Navarre and Zaragoza was assessed using a log-linear model. Results are showed graphically, for the different tumour sites by sex and each registry. Among males, a considerable rise in the incidence of lung cancer (5% per year), prostate cancer (> 2% per year) and non-Hodgkin's lymphomas was found. Among females, the highest increases corresponded to non-Hodgkin's lymphomas, with a yearly rise greater than 7%, and ovarian cancer (4% per year). Breast cancer in women increased in both registries (3.5% per year in Navarre and 0.9% per year in Zaragoza), part of the increment in Navarra being explained by a higher case detection rate. Finally, the incidence of colorectal, bladder and kidney cancer rose more than a 3% per year in both registries and sexes. For most types of tumours, cancer risk increased with subsequent generations. The substantial cancer increment observed points out the inefficacy of primary prevention policies, the importance of studying cancer incidence for long time periods and the need to increase the population coverage of Spanish cancer registries.


Comprehensive validation of a real-time quantitative bcr-abl assay for clinical laboratory use.
We developed and extensively validated a real-time PCR assay for the quantitation of bcr-abl to determine residual disease in patients with chronic myelogenous leukemia. This method quantitates the p210 and the p190 bcr-abl RNA fusion transcripts with results normalized to a housekeeping gene, using the 5'-exonuclease technique and the ABI PRISM 7700 Sequence Detection System (Applied Biosystems, Foster City, CA). We parallel tested 372 clinical specimens and 50 peripheral blood samples from patients not known to have any myeloproliferative disorders. The results were 100% specific. Sensitivity studies showed that this method can detect bcr-abl in cell lines diluted to 0.0001% and can detect a single bcr-abl plasmid spiked into negative RNA. The between-run reproducibility showed a coefficient of variance (CV) of 12.3%, and within-run reproducibility showed a CV of 13.8%. This method can be used to reliably monitor the disease load in patients with bcr-abl-positive diseases.


The sarcolemma of Aplysia smooth muscle in freeze-fracture preparations.
Smooth muscle cells in the sheath covering the visceral ganglion of Aplysia californica were examined with the techniques of freeze-fracture and conventional electron microscopy. The sarcolemma of these muscle cell invaginates to form myriad caveolae that have an intrinsic marker within their membrane. This intrinsic structure of the caveolar membrane is revealed by freeze-fracture and consists of rows of large particles in the outer half and matching grooves on the complementary inner half of the membrane. In thin plastic sections, parallel striations or shelves within the caveolar membrane appear to be the equivalent of the particles and grooves of the fractured membrane. Physical fixation of some specimens by rapid freezing in super-cooled liquid nitrogen or in liquid helium suggests that in their natural state, the caveolar ostia are not uniform in size and that at any given moment a number of caveolae are flattened. When segments of the connective nerves which link the visceral ganglion to the cephalic ganglia are stretched in vitro two to three times their in situ length, the caveolae lose their invaginated shape and are fully exposed to the extracellular space. The caveolar membrane, so stretched, is pulled into the line of fracture with the result that the large particles rather than the ostia appear on the cleaved surface. This flattening of the caveolae is reversible and suggests that they might serve as miniature stretch-receptors within the membrane of the smooth muscle cells. The caveolae are accessible to extracellular horseradish peroxidase but do not appear to pinocytose the protein.


Group-specific polymerase chain reaction for DNA-based analysis of species diversity and identity in dietary samples.
Unique DNA sequences are present in all species and can be used as biomarkers for the detection of cells from that species. These DNA sequences can most easily be detected using the polymerase chain reaction (PCR), which allows very small quantities of target DNA sequence to be amplified even when the target is mixed with large amounts of nontarget DNA. PCR amplification of DNA markers that are present in a wide range of species has proven very useful for studies of species diversity in environmental samples. The taxonomic range of species to be identified from environmental samples may often need to be restricted to simplify downstream analyses and to ensure that less abundant sequences are amplified. Group-specific PCR primer sets are one means of specifying the range of taxa that produce an amplicon in a PCR. We have developed a range of group-specific PCR primers for studying the prey diversity found in predator stomach contents and scats. These primers, their design and their application to studying prey diversity and identity in predator diet are described.


A controllable double-well magneto-optical trap for Rb and Cs atoms.
We experimentally demonstrate a novel scheme to simultaneously confine two atomic species of (87)Rb and (133)Cs with adjustable spatial separation by a controllable double-well magneto-optic trap. Using a single-loop wire and a magnetic bias field, the two clouds, each containing more than 1 x 10(6) atoms, are spatially separated above and below the wire center of the double-well MOT. The cloud interdistance can be controlled by independently varying the wire current and external bias field. This allows to load the double-well magnetic trap, and to study the dynamics of cold collisions between two-species atoms.


Case #7. Residual cyst.
A 26-year-old male visited a general dentist for his annual check-up. Radiographic examination revealed a small radiolucent lesions in the anterior mandible.