The Microtubule-Associated Protein IQ67 DOMAIN5 Modulates Microtubule Dynamics and Pavement Cell Shape.
The dynamic arrangement of cortical microtubules (MTs) plays a pivotal role in controlling cell growth and shape formation in plants, but the mechanisms by which cortical MTs are organized to regulate these processes are not well characterized. In particular, the dynamic behavior of cortical MTs is critical for their spatial organization, yet the molecular mechanisms controlling MT dynamics remain poorly understood. In this study, we used the puzzle piece-shaped pavement cells of Arabidopsis (Arabidopsis thaliana) leaves as a model system in which to study cortical MT organization. We isolated an ethyl methanesulfonate mutant with reduced interdigitation of pavement cells in cotyledons. This line carried a mutation in IQ67 DOMAIN5 (IQD5), which encodes a member of the plant-specific IQ motif protein family. Live-cell imaging and biochemical analyses demonstrated that IQD5 binds to MTs and promotes MT assembly. MT-depolymerizing drug treatment and in vivo MT dynamics assays suggested that IQD5 functions to stabilize MTs. Hence, our findings provide genetic, cell biological, and biochemical evidence that IQD5 regulates MT dynamics that affect MT organization and subsequent cell shape formation.


Using a Facebook Forum to Cope With Narcolepsy After Pandemrix Vaccination: Infodemiology Study.
In 2010, newly diagnosed narcolepsy cases among children and adolescents were seen in several European countries as a consequence of comprehensive national vaccination campaigns with Pandemrix against H1N1 influenza. Since then, a large number of people have had to live with narcolepsy and its consequences in daily life, such as effects on school life, social relationships, and activities. Initially, the adverse effects were not well understood and there was uncertainty about whether there would be any financial compensation. The situation remained unresolved until 2016, and during these years affected people sought various ways to join forces to handle the many issues involved, including setting up a social media forum. Our aim was to examine how information was shared, and how opinions and beliefs about narcolepsy as a consequence of Pandemrix vaccination were formed through discussions on social media. We used quantitative and qualitative methods to investigate a series of messages posted in a social media forum for people affected by narcolepsy after vaccination. Group activity was high throughout the years 2010 to 2016, with peaks corresponding to major narcolepsy-related events, such as the appearance of the first cases in 2010, the first payment of compensation in 2011, and passage of a law on compensation in July 2016. Unusually, most (462/774, 59.7%) of the group took part in discussions and only 312 of 774 (40.3%) were lurkers (compared with the usual 90% rule of thumb for participation in an online community). The conversation in the group was largely factual and had a civil tone, even though there was a long struggle for the link between the vaccine and narcolepsy to be acknowledged and regarding the compensation issue. Radical, nonscientific views, such as those expounded by the antivaccination movement, did not shape the discussions in the group but were being actively expressed elsewhere on the internet. At the outset of the pandemic, there were 18 active Swedish discussion groups on the topic, but most dissolved quickly and only one Facebook group remained active throughout the period. The group studied is a good example of social media use for self-help through a difficult situation among people affected by illness and disease. This shows that social media do not by themselves induce trench warfare but, given a good group composition, can provide a necessary forum for managing an emergency situation where health care and government have failed or are mistrusted, and patients have to organize themselves so as to cope.


The effects of obesity on the first stage of labor.
To estimate the effects of obesity on the duration and progression of the first stage of labor in a predominantly obese population and estimate the dose-effect with increasing classes of obesity. We performed a retrospective cohort study of labor progression among 5,204 consecutive parturients with singleton term pregnancies (37 weeks of gestation or more) and vertex presentation who completed the first stage of labor. Two comparison groups were defined by body mass index (BMI) less than 30 (n=2,413) or 30 or more (n=2,791). Repeated-measures analysis with polynomial modeling was used to construct labor curves. The duration and progression among women with BMIs less than 30 and BMIs of 30 or more were compared in a multivariable interval-censored regression model adjusting for parity, type of labor onset, race, and birth weight more than 4,000 g. The labor curves indicate longer duration and slower progression of the first stage of labor among women with BMIs of 30 or more for both nulliparous and multiparous women. Multivariable interval-censored regression analysis confirmed significantly longer duration (4-10 cm: 4.7 compared with 4.1 hours, P<.01) and slower progression of cervical dilation from 4 to 6 cm (2.2 compared with 1.9 hours, P<.01 with a range of 0.5-10.0 hours) among women with BMIs of 30 or more after adjusting for confounders. The overall duration is longer and progression of the early part of the first stage of labor is slower in obese women. This suggests that obesity should be considered in defining norms for management of labor, particularly in the early part of the first stage.


The interactions between anticonvulsants and non-vitamin K antagonist oral anticoagulant agents: A systematic review.
Use of non-vitamin K antagonist oral anticoagulants (NOACs), including dabigatran etexilate, rivaroxaban, apixaban, edoxaban or betrixaban provides a safe and convenient alternative to the traditional anticoagulation with vitamin K antagonists or heparin derivatives. Many patients receiving long-term seizure prophylaxis with antiepileptic drugs (AEDs) may require anticoagulation with NOACs. Providers caring for these patients need to be informed about potential interactions between AEDs and NOACs and the relevant clinical consequences. A systematic review of the existing literature was conducted to elucidate current knowledge on the clinically relevant interactions between AEDs and NOACs and highlight areas in which further research is needed. The systematic review protocol was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Ovid MEDLINE, Embase, The Cochrane Library and SciFinder were searched. Of the 630 non-duplicate items identified by the search, 13 met eligibility criteria. These 13 items included 8 case reports, 2 letters to the editor and 3 nonrandomized studies. The majority of pharmacokinetic interactions between NOACs and first generation AEDs occurred via the induction of the hepatic enzyme system and competition for the P-glycoprotein transporter and lead to decreased NOAC plasma levels and consequent thrombotic events. Only one article, a case report, was identified that focused on interactions between the second generation AED and a NOAC. At the present time, the limited evidence suggests that enzyme-inducing or inhibiting AEDs reduce the effectiveness of anticoagulation produced by several NOACs. This information may help providers anticipate possible interactions and guide therapy appropriately.


Initial Impact and Operational Responses to the COVID-19 Pandemic by American Radiation Oncology Practices.
In February 2020, the COVID-19 pandemic reached the United States. The impact of the pandemic on the US radiation oncology field remains unknown. The American Society for Radiation Oncology surveyed US radiation oncology practice leaders to gauge initial impact and immediate operational responses to the pandemic. From April 16 to April 30, 2020, the American Society for Radiation Oncology surveyed US radiation oncology practice leaders by email to gauge initial impact and immediate operational responses to the COVID-19 pandemic. Two hundred twenty-two (43%) of 517 leaders responded from community and academic practices (62% and 34%, respectively), hospital-based and free-standing centers (69% and 29%), and metro and rural locations (88% and 12%). Practices reported treating an average of 1086 patients per year in 2019 (range, 0-7900) with an average daily treatment volume of 70 patients (range, 5-400). All practices reported uninterrupted operation. On average, practices were treating 68% of their typical volume (range, 10%-95%), with 92% implementing planned treatment postponement for lower risk patients. An estimated revenue decrease of 20% or more was experienced by 71% of practices. Confirmed COVID-19 patient cases were treated by 39% of practices. Seventy percent experienced staff shortages. Almost all (98%) practices implemented formal operational procedures to protect patients and staff, although personal protective equipment/infection control supply shortages were reported by 78% of practices. Seventy-four percent used telemedicine for virtual follow-up surveillance, and 15% leveraged telemedicine for on-treatment assessment. The clinical and financial impacts of the COVID-19 pandemic on US radiation oncology were deep and broad. Despite reported shortages in personal protective equipment, declines in revenue, and reduced patient volumes, practices adapted quickly by refining standard processes of care, implementing recommended safety measures, and employing telemedicine to facilitate treatment continuity. Patients with higher risk disease experienced uninterrupted access to care. We plan to continue regular surveying across the lifespan of the pandemic to document the geographic and temporal impact of COVID-19 on the field and its patients.


Somatic symptom disorder, a new DSM-5 diagnosis of an old clinical challenge.
Somatic symptom disorder (SSD) is characterised by a dysfunctional preoccupation with one or more physical symptoms. Patients with SSD often pursue excessive and unnecessary investigations, hospitalisations and treatments that significantly affect quality of life and drain healthcare resources. Thus, appropriate diagnosis and careful management are required to mitigate the patient's distress and to reduce the burden to the healthcare system. SSD is a new disorder defined in the Diagnostic and Statistical Manual Fifth Edition (DSM-5), replacing somatoform and related disorders in the DSM-4-Text Revision with diagnostic criteria that are inclusive of a broad array of presentations. This report presents a detailed clinical case of an elderly man with a history of frequent hospital visits presenting with SSD. We discuss diagnostic challenges and evidence-based management in acute inpatient as well as in outpatient settings. We also review data on healthcare utilisation associated with SSD.


Near-future ocean warming and acidification alter foraging behaviour, locomotion, and metabolic rate in a keystone marine mollusc.
Environmentally-induced changes in fitness are mediated by direct effects on physiology and behaviour, which are tightly linked. We investigated how predicted ocean warming (OW) and acidification (OA) affect key ecological behaviours (locomotion speed and foraging success) and metabolic rate of a keystone marine mollusc, the sea hare Stylocheilus striatus, a specialist grazer of the toxic cyanobacterium Lyngbya majuscula. We acclimated sea hares to OW and/or OA across three developmental stages (metamorphic, juvenile, and adult) or as adults only, and compare these to sea hares maintained under current-day conditions. Generally, locomotion speed and time to locate food were reduced ~1.5- to 2-fold when the stressors (OW or OA) were experienced in isolation, but reduced ~3-fold when combined. Decision-making was also severely altered, with correct foraging choice nearly 40% lower under combined stressors. Metabolic rate appeared to acclimate to the stressors in isolation, but was significantly elevated under combined stressors. Overall, sea hares that developed under OW and/or OA exhibited a less severe impact, indicating beneficial phenotypic plasticity. Reduced foraging success coupled with increased metabolic demands may impact fitness in this species and highlight potentially large ecological consequences under unabated OW and OA, namely in regulating toxic cyanobacteria blooms on coral reefs.


A comparative carbon footprint analysis of disposable and reusable vaginal specula.
Healthcare systems in the United States have increasingly turned toward the use of disposable medical equipment in an attempt to save time, lower costs, and reduce the transmission of infections. However, the use of disposable instruments is associated with increased solid waste production and may have negative impacts on the environment, such as increased greenhouse gas emissions. The purpose of this study was to inform this discussion; we applied life cycle assessment methods to evaluate the carbon footprints of 3 vaginal specula: a single-use acrylic model and 2 reusable stainless steel models. The functional unit of the study was defined as the completion of 20 gynecologic examinations by either type of speculum. The greenhouse gas emissions (eg, carbon dioxide, methane, nitrous oxide) across all life cycle stages, which includes material production and manufacturing, transportation, use and reprocessing, and end-of-life, were analyzed with the use of SimaPro life cycle assessment software and converted into carbon dioxide equivalents. The reusable stainless steel grade 304 speculum was found to have a lesser carbon footprint over multiple model scenarios (different reprocessing techniques, autoclave loading/efficiency, and number of uses) than either the reusable stainless steel grade 316 or the disposable acrylic specula. The material production and manufacturing phase contributed most heavily to the total life cycle carbon footprint of the acrylic speculum, whereas the use and reprocessing phase contributed most to the carbon footprints of both stainless steel specula. The use of disposable vaginal specula is associated with increased greenhouse gas equivalents compared with reusable alternatives with no significant difference in clinical utility. These findings can be used to inform decision-making by healthcare systems, because they weigh a wide range of considerations in making final purchase decisions; similar analytic methods can and should be applied to other components of health systems' waste streams.


Discovery of diverse thyroid hormone receptor antagonists by high-throughput docking.
Treatment of hyperthyroidism, a common clinical condition that can have serious manifestations in the elderly, has remained essentially unchanged for >30 years. Directly antagonizing the effect of the thyroid hormone at the receptor level may be a significant improvement for the treatment of hyperthyroid patients. We built a computer model of the thyroid hormone receptor (TR) ligand-binding domain in its predicted antagonist-bound conformation and used a virtual screening algorithm to select 100 TR antagonist candidates out of a library of >250,000 compounds. We were able to obtain 75 of the compounds selected in silico and studied their ability to act as antagonists by using cultured cells that express TR. Fourteen of these compounds were found to antagonize the effect of T3 on TR with IC50s ranging from 1.5 to 30 microM. A small virtual library of compounds, derived from the highest affinity antagonist (1-850) that could be rapidly synthesized, was generated. A second round of virtual screening identified new compounds with predicted increased antagonist activity. These second generation compounds were synthesized, and their ability to act as TR antagonists was confirmed by transfection and receptor binding experiments. The extreme structural diversity of the antagonist compounds shows how receptor-based virtual screening can identify diverse chemistries that comply with the structural rules of TR antagonism.


Convolutional neural networks (CNNs): concepts and applications in pharmacogenomics.
Convolutional neural networks (CNNs) have been used to extract information from various datasets of different dimensions. This approach has led to accurate interpretations in several subfields of biological research, like pharmacogenomics, addressing issues previously faced by other computational methods. With the rising attention for personalized and precision medicine, scientists and clinicians have now turned to artificial intelligence systems to provide them with solutions for therapeutics development. CNNs have already provided valuable insights into biological data transformation. Due to the rise of interest in precision and personalized medicine, in this review, we have provided a brief overview of the possibilities of implementing CNNs as an effective tool for analyzing one-dimensional biological data, such as nucleotide and protein sequences, as well as small molecular data, e.g., simplified molecular-input line-entry specification, InChI, binary fingerprints, etc., to categorize the models based on their objective and also highlight various challenges. The review is organized into specific research domains that participate in pharmacogenomics for a more comprehensive understanding. Furthermore, the future intentions of deep learning are outlined.


A new semi-automated method for fetal volume measurements with three-dimensional ultrasound: preliminary results.
Complications in pregnancy are suggested to be the result of intrauterine conditions in the first trimester of pregnancy. Three-dimensional ultrasound volume measurements might give more information, compared with two-dimensional measurements. Commonly available methods for volume measurements are not suited for daily practice. This is a report of preliminary results of a promising, more practical semi-automated method for volume calculations with three-dimensional ultrasound. Volume datasets of 16 objects (10.2-41.5 cm(3) ) were obtained. Euclidean shortening flow and Perona and Malik were used as image enhancement techniques. The image gradient was calculated. The points of interest were detected by the iso-intensity and the edge-detection technique. Volume measurements with Volume Computer-aided AnaLysis (VOCAL) are used as a reference. A volume dataset of a first trimester fetus was acquired to test this method in vivo. The mathematical calculations with iso-intensity (Perona and Malik: average= -1.57 cm(3) , SD=4.05; and Euclidean shortening flow: average= -1.38 cm(3) , SD=2.47) showed results comparable with the VOCAL method (average= +1.28 cm(3) , SD=2.07). We also succeeded in detecting all voxels in the whole contour of a 12-week fetus. Mathematical volume calculations are possible with the semi-automated method. We were able to apply this new method on a first trimester fetus. This new method is promising for future use in the daily practice.


Cigarette tax and public health: what are the implications of financially stressed smokers for the effects of price increases on smoking prevalence?
This paper models the predicted impact of tobacco price increases proposed in the United States and Australia during 2009 on smoking prevalence in 2010 while taking account of the effects of financial stress among smokers on cessation rates. Two models of smoking prevalence were developed for each country. In model 1, prevalence rates were determined by price elasticity estimates. In model 2 price elasticity was moderated by financial stress. Each model was used to estimate smoking prevalence in 2010 in Australia and the United States. Proposed price increases resulted in a 1.89% and 7.84% decrease in smoking participation among low socio-economic status (SES) groups in the United States and Australia, respectively. Model 1 overestimated the number of individuals expected to quit in both the United States (0.13% of smokers) and Australia (0.36% of smokers) by failing to take account of the differential effects of the tax on financially stressed smokers. The proportion of low-income smokers under financial stress increased in both countries in 2010 (by 1.06% in the United States and 3.75% in Australia). The inclusion of financial stress when modelling the impact of price on smoking prevalence suggests that the population health returns of increased cigarette price will diminish over time. As it is likely that the proportion of low-income smokers under financial stress will also increase in 2010, future population-based approaches to reducing smoking will need to address this factor.


Cloud, Aerosol, and Radiative Properties Over the Western North Atlantic Ocean.
This study examines the atmospheric properties of weather states (WSs) derived from the International Satellite Cloud Climatology Project over the Western North Atlantic Ocean. In particular, radiation and aerosol data corresponding to two sites in the study domain, Pennsylvania State University and Bermuda, were examined to characterize the atmospheric properties of the various satellite-derived WSs. At both sites, the fair weather WS was most prevalent, followed by the cirrus WS. Differences in the seasonality of the various WSs were observed at the two sites. Fractional sky cover and effective shortwave cloud transmissivity derived from ground-based radiation measurements were able to capture differences among the satellite-derived WSs. Speciated aerosol optical thicknesses (AOT) from the Modern-Era Retrospective Analysis for Research and Applications, version 2 were used to investigate potential differences in aerosol properties among the WSs. The clear sky WS exhibited below-average seasonal values of AOT at both sites year-round, as well as relatively high rates of occurrence with low AOT events. In addition, the clear sky WS showed above-average contributions from dust and black carbon to the total AOT year-round. Finally, transitions between various WSs were examined under low, high, and midrange AOT conditions. The most common pathway was for the WSs to remain in the same state after a 3 h interval. Some WSs, such as mid latitude storms, deep convection, middle top, and shallow cumulus, were more prevalent as ending states under high AOT conditions. This work motivates examining differences in aerosol properties between WSs in other regions.


A migration signature and plasma biomarker panel for pancreatic adenocarcinoma.
Pancreatic ductal adenocarcinoma is a disease of extremely poor prognosis for which there are no reliable markers of asymptomatic disease. To identify pancreatic cancer biomarkers, we focused on a genomic interval proximal to the most common fragile site in the human genome, chromosome 3p12, which undergoes smoking-related breakage, loss of heterozygosity, and homozygous deletion as an early event in many epithelial tumors, including pancreatic cancers. Using a functional genomic approach, we identified a seven-gene panel (TNC, TFPI, TGFBI, SEL-1L, L1CAM, WWTR1, and CDC42BPA) that was differentially expressed across three different expression platforms, including pancreatic tumor/normal samples. In addition, Ingenuity Pathways Analysis (IPA) and literature searches indicated that this seven-gene panel functions in one network associated with cellular movement/morphology/development, indicative of a "migration signature" of the 3p pathway. We tested whether two secreted proteins from this panel, tenascin C (TNC) and tissue factor pathway inhibitor (TFPI), could serve as plasma biomarkers. Plasma ELISA assays for TFPI/TNC resulted in a combined area under the curve (AUC) of 0.88 and, with addition of CA19-9, a combined AUC for the three-gene panel (TNC/TFPI/CA19-9), of 0.99 with 100% specificity at 90% sensitivity and 97.22% sensitivity at 90% specificity. Validation studies using TFPI only in a blinded sample set increased the performance of CA19-9 from an AUC of 0.84 to 0.94 with the two-gene panel. Results identify a novel 3p pathway-associated migration signature and plasma biomarker panel that has utility for discrimination of pancreatic cancer from normal controls and promise for clinical application.


HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression.
Type 1 diabetes (T1D) is characterized by T cell-mediated destruction of the insulin-producing β cells of the pancreatic islets. Among the loci associated with T1D risk, those most predisposing are found in the MHC region. HLA-B*39:06 is the most predisposing class I MHC allele and is associated with an early age of onset. To establish an NOD mouse model for the study of HLA-B*39:06, we expressed it in the absence of murine class I MHC. HLA-B*39:06 was able to mediate the development of CD8 T cells, support lymphocytic infiltration of the islets, and confer T1D susceptibility. Because reduced thymic insulin expression is associated with impaired immunological tolerance to insulin and increased T1D risk in patients, we incorporated this in our model as well, finding that HLA-B*39:06-transgenic NOD mice with reduced thymic insulin expression have an earlier age of disease onset and a higher overall prevalence as compared with littermates with typical thymic insulin expression. This was despite virtually indistinguishable blood insulin levels, T cell subset percentages, and TCR Vβ family usage, confirming that reduced thymic insulin expression does not impact T cell development on a global scale. Rather, it will facilitate the thymic escape of insulin-reactive HLA-B*39:06-restricted T cells, which participate in β cell destruction. We also found that in mice expressing either HLA-B*39:06 or HLA-A*02:01 in the absence of murine class I MHC, HLA transgene identity alters TCR Vβ usage by CD8 T cells, demonstrating that some TCR Vβ families have a preference for particular class I MHC alleles.


Supplementation of Mice with Specific Nondigestible Oligosaccharides during Pregnancy or Lactation Leads to Diminished Sensitization and Allergy in the Female Offspring.
The maternal environment and early life exposure affect immune development in offspring. We investigated whether development of food allergy in offspring is affected by supplementing pregnant or lactating sensitized or nonsensitized mice with a mixture of nondigestible oligosaccharides. Dams were sensitized intragastrically with ovalbumin before mating, with use of cholera toxin (CT) as an adjuvant. Nonsensitized dams received CT only. Dams were fed a control diet or a diet supplemented with short-chain galacto oligosaccharides (scGOSs), long-chain fructo oligosaccharides (lcFOSs), and pectin-derived acidic oligosaccharides (pAOSs) in a ratio of 9:1:2 at a dose of 2% during pregnancy or lactation, resulting in 7 experimental groups. After weaning, offspring were fed a control diet and ovalbumin-CT sensitized. Acute allergic skin responses (ASRs), shock symptoms, body temperature, and specific plasma immunoglobulins were measured upon intradermal ovalbumin challenge. Th2/Th1- and regulatory T cells were analyzed with use of quantitative polymerase chain reaction and flow cytometric analysis in spleen, mesenteric lymph nodes, and blood. Supplementing sensitized pregnant or lactating dams with scGOS/lcFOS/pAOS resulted in lower ASRs in the offspring [offspring of sensitized female mice fed experimental diet during pregnancy (S-Preg): 48 ± 2.1 μm; offspring of sensitized female mice fed experimental diet during lactation (S-Lact): 60 ± 6.2 μm] compared with the sensitized control group (119 ± 13.9 μm). In the S-Lact group, this coincided with an absence of shock symptoms compared with the offspring of sensitized female mice fed control food during pregnancy and lactation (S-Con) and S-Preg groups, and lower ovalbumin-IgG1 [S-Con: 3.8 ± 0.1 arbitrary units (AUs); S-Preg: 3.3 ± 0.1 AUs; S-Lact: 2.4 ± 0.1 AUs] and higher ovalbumin-IgG2a concentrations (S-Con: 1.1 ± 0.1 AUs; S-Preg: 0.8 ± 0.1 AUs; S-Lact: 2.0 ± 0.1 AUs). Supplementing nonsensitized pregnant or lactating dams with scGOS/lcFOS/pAOS resulted in lower plasma ovalbumin-IgE [offspring of nonsensitized female mice fed experimental diet during pregnancy (NS-Preg): 1.6 ± 0.4 AUs; offspring of nonsensitized female mice fed experimental diet during lactation (NS-Lact): 0.3 ± 0.1 AUs vs. offspring of nonsensitized female mice fed control food during pregnancy and lactation (NS-Con): 3.1 ± 0.6 AUs] and ovalbumin-IgG1 (NS-Lact: 2.3 ± 0.3 AUs vs. NS-Con: 3.4 ± 0.3 AUs) concentrations in offspring. Ovalbumin-IgG2a plasma concentrations were higher in offspring of scGOS/lcFOS/pAOS-supplemented dams (NS-Preg: 1.1 ± 0.1 AUs; NS-Lact: 1.1 ± 0.1 AUs) than in those of unsupplemented, nonsensitized controls (0.4 ± 0.0 AUs). These data show impaired sensitization in offspring of scGOS/lcFOS/pAOS-supplemented mice. A number of the analyzed variables are differentially affected by whether supplementation occurs during pregnancy or lactation, and the outcome of dietary supplementation is affected by whether the mother has been sensitized to ovalbumin and CT.


De novo design of a picomolar nonbasic 5-HT(1B) receptor antagonist.
We describe herein the discovery of novel, de novo designed, 5-HT(1B) receptor antagonists that lack a basic moiety and that provide improved hERG and in vitro phospholipidosis profiles. We used a known 5-HT(1B) antagonist template as our starting point and focused on replacing the piperazine moiety. Pyrazole-based ideas were designed and synthesized among a small library of piperazine replacements. To our knowledge, these are the first potent, nonbasic, functionally active antagonists of the 5-HT(1B) receptor.


A pilot study measuring the impact of yoga on the trait of mindfulness.
The current study examined whether yoga would increase levels of mindfulness in a healthy population. Forty-six participants were randomly assigned to an 8-week yoga intervention group or a wait-list control group. Mindfulness was assessed pre and post yoga, using the Freiburg Mindfulness Inventory (FMI). Results indicate that the yoga group experienced a significant increase in Overall mindfulness, and in three mindfulness subscales; Attention to the present moment, Accepting and open attitudes toward experience, and Insightful understanding (p < .01). The control group experienced a significant increase in overall mindfulness (p < .02) and insightful understanding (p < .01). Findings suggest that a yoga intervention may be a viable method for increasing levels of trait mindfulness in a healthy population, potentially implicating yoga as a preventive method for the later development of negative emotional mood states (i.e. anxiety and depression). The control group also experienced moderate elevations of mindfulness at the second assessment.


Recognition by macrophages and liver cells of opsonized phospholipid vesicles and phospholipid headgroups.
The interaction of liposomes with blood proteins is believed to play a critical role in the clearance pharmacokinetics and tissue distribution of intravenously injected liposomes. In this article we have focused our discussion on the interaction of liposomes with key blood proteins, which include immunoglobulins, complement proteins, apolipoproteins, fetuin, von Willebrand factor, and thrombospondin, and their role in liposome recognition by professional phagocytes and nonmacrophage hepatic cells. Alternatively, macrophages as well as hepatocytes and liver endothelial cells may phagocytose/endocytose liposomes via direct recognition of phospholipid headgroups. A number of plasma membrane receptors such as lectin receptors, CD14, various classes of scavenger receptors (e.g., classes A, B, and D), Fc-gammaRI and FcgammaRII-B2 may participate in phospholipid recognition. These concepts are also discussed.


The context of uncertainty modulates the subcortical response to predictability.
Implicit motor learning tasks typically involve comparisons of subject responses during a sequence versus a random condition. In neuroimaging, brain regions that are correlated with a sequence are described, but the temporal relationship of sequence versus nonsequence conditions is often not explored. We present a functional magnetic resonance imaging (fMRI) study describing activation related to sequential predictability in an implicit sensorimotor learning task and the history (context) dependence of these effects. Participants regarded four squares displayed horizontally across a screen and pressed a button when any one of the four targets was illuminated in a particular color. A repeating spatial sequence with varying levels of predictability was embedded within a random color presentation. Both the right dorsolateral prefrontal cortex (R DLPFC) and right caudate displayed a positive correlation to increasing predictability, whereas the left posterior parietal cortex (L PPC) displayed a negative correlation. However, the activation changes within the caudate were significant when transitioning from high predictability to low predictability but not for the reverse case, suggesting a sensitivity not only to predictability but to order effects as well. These results support the hypothesized relationship between basal ganglia and visuomotor sequential learning, but demonstrate the importance of context upon sequence learning.


Rb and p16INK4a expression in resected non-small cell lung tumors.
Inactivation of the cyclin-dependent kinase inhibitor p16INK4a (CDKN2/MTS1) is documented in a wide variety of cancer cell lines and tumors. We have shown that loss of p16INK4a protein expression is a common event in early stage non-small cell lung cancer (NSCLC), correlates with a significantly worse survival, and is more common in higher stage disease. One hundred NSCLC tumors from patients undergoing definitive thoracotomies at a single institution were examined for p16INK4a and retinoblastoma protein (pRB) expression. Abnormal pRB staining was identified in 15% of the tumors, whereas 51% possessed aberrant p16INK4a protein expression. Tumors with aberrant expression of p16INK4a by immunohistochemistry were associated with a significantly worse survival (P=0.04). Additionally, the inverse correlation of pRB and p16INK4a expression previously noted in lung cancer cell lines and tumors was confirmed in this large cohort of patients, with 65% of the tumors demonstrating inverse expression of pRB and p16INK4a (p=0.00019). A statistically significant increase in aberrant p16INK4a expression, as well as inverse expression of p16INK4a and pRB, was seen with increasing pathological stage of disease. These findings establish the prognostic significance (of the absence of p16INK4, in resected NSCLC and confirm the critical importance of disrupting the pathway of cyclin-dependent kinase-mediated phosphorylation of pRB in the molecular oncogenesis and progression of NSCLC.


Neighbor of Brca1 gene (Nbr1) functions as a negative regulator of postnatal osteoblastic bone formation and p38 MAPK activity.
The neighbor of Brca1 gene (Nbr1) functions as an autophagy receptor involved in targeting ubiquitinated proteins for degradation. It also has a dual role as a scaffold protein to regulate growth-factor receptor and downstream signaling pathways. We show that genetic truncation of murine Nbr1 leads to an age-dependent increase in bone mass and bone mineral density through increased osteoblast differentiation and activity. At 6 mo of age, despite normal body size, homozygous mutant animals (Nbr1(tr/tr)) have approximately 50% more bone than littermate controls. Truncated Nbr1 (trNbr1) co-localizes with p62, a structurally similar interacting scaffold protein, and the autophagosome marker LC3 in osteoblasts, but unlike the full-length protein, trNbr1 fails to complex with activated p38 MAPK. Nbr1(tr/tr) osteoblasts and osteoclasts show increased activation of p38 MAPK, and significantly, pharmacological inhibition of the p38 MAPK pathway in vitro abrogates the increased osteoblast differentiation of Nbr1(tr/tr) cells. Nbr1 truncation also leads to increased p62 protein expression. We show a role for Nbr1 in bone remodeling, where loss of function leads to perturbation of p62 levels and hyperactivation of p38 MAPK that favors osteoblastogenesis.


[Reduction of automobile traffic: urgent health promotion policy].
During the last few decades, traffic injuries have become one of the leading causes of death and disability in the world. In urban areas, traffic congestion, noise, and emissions from motor vehicles produce subjective disturbances and detectable pathological effects. More than one billion people are exposed to harmful levels of environmental pollution. Because its combustion engine generates carbon dioxide (CO2), the automobile is one of the chief sources of the gases that are causing the greenhouse effect. The latter has already caused a rise in the average ambient temperature, and over the next decades it will predictable cause significant climatic changes whose consequences, though uncertain, are likely to be harmful and possibly catastrophic. Aside from the greenhouse effect, the relentless growth of parking zones, traffic, and the roadway infrastructure in urban and rural areas is currently one of the leading causes of environmental degradation. Urban development, which is nearly always "planned" around traffic instead of people, leads to a significant deterioration in the quality of life, while it also destroys the social fabric. Unlike the private automobile, public transportation, bicycles, and walking help reduce pollution, congestion, and traffic volume, as well as the morbidity and mortality resulting from injuries and ailments related to pollution. Non-automobile transportation also encourages physical activity--with its positive effect on general health--and helps reduce the greenhouse effect. The drop in traffic volume and the increased use of alternate means of transportation are thus an integrated health promotion policy which should become an inherent part of the movement for the promotion of healthy cities and of transportation policies and economic policy in general.


Computer simulation of uranyl uptake by the rough lipopolysaccharide membrane of Pseudomonas aeruginosa.
Heavy metal environmental contaminants cannot be destroyed but require containment, preferably in concentrated form, in a solid or immobile form for recycling or final disposal. Microorganisms are able to take up and deposit high levels of contaminant metals, including radioactive metals such as uranium and plutonium, into their cell wall. Consequently, these microbial systems are of great interest as the basis for potential environmental bioremediation technologies. The outer membranes of Gram-negative microbes are highly nonsymmetric and exhibit a significant electrostatic potential gradient across the membrane. This gradient has a significant effect on the uptake and transport of charged and dipolar compounds. However, the effectiveness of microbial systems for environmental remediation will depend strongly on specific properties that determine the uptake of targeted contaminants by a particular cell wall. To aid in the design of microbial remediation technologies, knowledge of the factors that determine the affinity of a particular bacterial outer membrane for the most common ionic species found in contaminated soils and groundwater is of great importance. Using our previously developed model for the lipopolysaccharide (LPS) membrane of Pseudomonas aeruginosa, this work presents the potentials of mean force as the estimate of the free energy profile for uptake of sodium, calcium, chloride, uranyl ions, and a water molecule by the bacterial LPS membrane. A compatible classical parameter set for uranyl has been developed and validated. Results show that the uptake of uranyl is energetically a favorable process relative to the other ions studied. At neutral pH, this nuclide is shown to be retained on the surface of the LPS membrane through chelation with the carboxyl and hydroxyl groups located in the outer core.


Ozone: A Multifaceted Molecule with Unexpected Therapeutic Activity.
A comprehensive outline for understanding and recommending the therapeutic use of ozone in combination with established therapy in diseases characterized by a chronic oxidative stress is currently available. The view of the absolute ozone toxicity is incorrect, because it has been based either on lung or on studies performed in artificial environments that do not correspond to the real antioxidant capacity of body compartments. In fact, ozone exerts either a potent toxic activity or it can stimulate biological responses of vital importance, analogously to gases with prospective therapeutic value such as NO, CO, H2S, H2, as well as O2 itself. Such a crucial difference has increasingly become evident during the last decade. The purpose of this review is to explain the aspects still poorly understood, highlighting the divergent activity of ozone on the various biological districts. It will be clarified that such a dual effect does not depend only upon the final gas concentration, but also on the particular biological system where ozone acts. The real significance of ozone as adjuvant therapeutic treatment concerns severe chronic pathologies among which are cardiovascular diseases, chronic obstructive pulmonary diseases, multiple sclerosis, and the dry form of age-related macular degeneration. It is time for a full insertion of ozone therapy within pharmaceutical sciences, responding to all the requirements of quality, efficacy and safety, rather than as either an alternative or an esoteric approach.


Alternative therapeutics for self-limiting infections-An indirect approach to the antibiotic resistance challenge.
Alternative therapeutics for infectious diseases is a top priority, but what infections should be the primary targets? At present there is a focus on therapies for severe infections, for which effective treatment is most needed, but these infections are hard to manage, and progress has been limited. Here, we explore a different approach. Applying an evolutionary perspective to a review of antibiotic prescription studies, we identify infections that likely make a large contribution to resistance evolution across multiple taxa but are clinically mild and thus present easier targets for therapeutics development. Alternative therapeutics for these infections, we argue, would save lives indirectly by preserving the high efficacy of existing antibiotics for the patients who need them the most.


Dropped head syndrome due to myogenic atrophy - a case report of surgical treatment.
We report a case of a 69-year-old man with dropped head syndrome associated with isolated neck extensor myopathy (INEM). Over a period of 2 years, he exhibited progressive inability to lift his chin off his chest, resulting in the dropped head position that impaired his activities of daily living. He had a disturbed gait with severe imbalance of spinal alignment. Computed tomography revealed osseous contracture of cervical vertebral bodies in flexed position. Anterior combined posterior reconstruction surgery yielded a successful outcome in his activities of daily living, including his walking balance of spinal alignment. Pathologic study confirmed myogenic atrophy in the cervical extensor muscles. We suggest that consideration for surgical management should be given to dropped head syndrome especially due to INEM.


Depression, smoking, physical inactivity and season independently associated with midnight salivary cortisol in type 1 diabetes.
Disturbances of the circadian rhythm of cortisol secretion are associated with depression, coronary calcification, and higher all-cause and cardiovascular mortality.The primary aim of this study was to test the associations between midnight salivary cortisol (MSC), depression and HbA1c, and control for behavioural, environmental and intra individual factors with possible impact on cortisol secretion, like smoking, physical inactivity, season, medication, diabetes duration, severe hypoglycemia episodes, age and gender in patients with type 1 diabetes. Secondary aims were to present MSC levels for a reference group of non-depressed type 1 diabetes patients with a healthy life style (physically active and non-smoking), and to explore seasonal variations. A cross-sectional population based study of 196 patients (54% men and 46% women) aged 18-59 years that participated in a randomized controlled trial targeting depression in type 1 diabetes. Depression was assessed by the Hospital Anxiety and Depression Scale-depression subscale. MSC, HbA1c, serum-lipids, blood pressure, waist circumference and data from medical records and the Swedish National Diabetes Registry were collected. Thirty four patients (17%) had MSC ≥9.3 nmol/L, which was associated with smoking (AOR 5.5), spring season (AOR 4.3), physical inactivity (AOR 3.9), self-reported depression (AOR 3.1), and older age (per year) (AOR 1.08). HbA1c >70 mmol/mol (>8.6%) (AOR 4.2) and MSC ≥9.3 nmol/L (AOR 4.4) were independently linked to self-reported depression. Season was strongly associated with MSC levels and no other variables studied showed seasonal variations. In a reference group of 137 non-depressed patients with a healthy life style (physically active, non-smoking) the median MSC level was 4.6 nmol/L (range 1.9-23.0). In this study of patients with type 1 diabetes high MSC was linked to smoking, physical inactivity, depression, season and older age. Thus a high cortisol value identified three major targets for treatment in type 1 diabetes.


Who will win the race in childrens' oral cavities? Streptococcus mutans or beneficial lactic acid bacteria?
Adhesion to oral soft and hard tissue is crucial for bacterial colonisation in the mouth. The aim of this work was to select strains of oral lactic acid bacteria that could be used as probiotics for oral health. To this end, the adhesive properties of some lactic acid bacteria were investigated. Seventeen lactic acid bacteria including two Streptococcus mutans strains were isolated from the oral cavity of healthy children, while other strains were isolated from fermented meat products. The bacterial strains were applied to teeth surfaces covered with saliva or without saliva. A significant diversity in adhesion capacity to teeth surfaces among the lactic acid bacteria was observed. Lactic acid bacteria isolated from the oral cavity adhered the best to teeth surfaces covered with saliva, whereas lactic acid bacteria isolated from fermented meat samples adhered the best to tooth surface without saliva. All strains of lactic acid bacteria were able to reduce the number of S. mutans cells, in particular on saliva-coated tooth surface. Therefore, they might have potential as probiotics for the oral cavity.


Antroquinonol Attenuated Abdominal and Hepatic Fat Accumulation in Rats Fed an Obesogenic Diet.
An imbalance of energy intake and expenditure leads to fat accumulation and metabolic disorders. The aim of the study was to investigate the effects of antroquinonol on diet-induced obesity. Thirty-two rats were divided into a control group (C), an obesogenic group (OB), and two experimental groups consuming 25 (OB-AQ25) and 50 mg/kg (OB-AQ50) antroquinonol (n = 8). After a 12-week experimental period, we collected blood, liver, abdominal fat, and gastrocnemius muscle tissue for analysis. The obesogenic diet induced greater weight gain and fat accumulation, and increased hepatic lipids, and tumor necrosis factor-α and interleukin-1β concentrations in rats. Antroquinonol consumption reduced epididymal and hepatic lipids and inflammatory cytokines. We found that antroquinonol upregulated hepatic adenosine monophosphate-activated protein kinase and downregulated sterol regulatory element-binding protein-1 protein expressions and downregulated fatty acid synthase mRNA expression. In addition, gastrocnemius fibronectin type III domain containing 5 protein expression was also higher in the B group. In conclusion, our results suggested that consuming antroquinonol may ameliorate diet-induced abdominal and hepatic fat accumulation. PRACTICAL APPLICATION: Antroquinonol is a bioactive compound derived from Antrodia camphorate which is traditionally used in Chinese medicinal cuisine, and is used for developing functional foods in Taiwan. This is the first study investigating the possible effects of antroquinonol on obesity and we found that antroquinonol can ameliorate diet-induced obesity, and therefore may be used in further studies and functional food development.


Differential Effects of 2 Rehabilitation Programs Following Anterior Cruciate Ligament Reconstruction.
The muscular function restoration related to the type of physical rehabilitation followed after anterior cruciate ligament reconstruction (ACLR) using autologous hamstring tendon graft in terms of strength and cross-sectional area (CSA) remain controversial. To analyze the CSA and force output of quadriceps and hamstring muscles in subjects following either an Objective Criteria-Based Rehabilitation (OCBR) algorithm or the usual care (UCR) for ACL rehabilitation in Spain, before and 1 year after undergoing an ACLR. Longitudinal clinical double-blinded randomized controlled trial. Sports-medicine research center. 40 recreational athletes (30 male, 10 female [24 ± 6.9 y, 176.55 ± 6.6 cm, 73.58 ± 12.3 kg]). Both groups conducted differentiated rehabilitation procedures after ACLR. Those belonging to OCBR group were guided in their recovery according to the current evidence-based principles. UCR group followed the national conventional approach for ACL rehabilitation. Concentric isokinetic knee joint flexor-extension torque assessments at 180°/s and Magnetic Resonance Imaging (MRI) evaluations were performed before and 12 months after ACLR. Anatomical muscle CSA (mm2) was assessed, in Quadriceps, Biceps femoris, Semitendinous, Semimembranosus, and Gracilis muscles at 50% and 70% femur length. Reduced muscle CSA was observed in both treatment groups for Semitendinosus and Gracilis 1 year after ACLR. At 1-year follow-up, subjects allocated to the OCBR demonstrated greater knee flexor and extensor peak torque values in their reconstructed limbs in comparison with patients treated by UCR. Objective atrophy of Semitendinosus and Gracilis muscles related to surgical ACLR was found to persist in both rehabilitation groups. However, OCBR after ACLR lead to substantial gains on maximal knee flexor strength and ensured more symmetrical anterior-posterior laxity levels at the knee joint.


Analyzing Empowerment Processes Among Cancer Patients in an Online Community: A Text Mining Approach.
Peer-to-peer online support groups and the discussion forums in these groups can help patients by providing opportunities for increasing their empowerment. Most previous research on online empowerment and online social support uses qualitative methods or questionnaires to gain insight into the dynamics of online empowerment processes. The overall goal of this study was to analyze the presence of the empowerment processes in the online peer-to-peer communication of people affected by cancer, using text mining techniques. Use of these relatively new methods enables us to study social processes such as empowerment on a large scale and with unsolicited data. The sample consisted of 5534 messages in 1708 threads, written by 2071 users of a forum for cancer patients and their relatives. We labeled the posts in our sample with 2 types of labels: labels referring to empowerment processes and labels denoting psychological processes. The latter were identified using the Linguistic Inquiry and Word Count (LIWC) method. Both groups of labels were automatically assigned to posts. Automatic labeling of the empowerment processes was done by text classifiers trained on a manually labeled subsample. For the automatic labeling of the LIWC categories, we used the Dutch version of the LIWC consisting of a total of 66 word categories that are assigned to text based on occurrences of words in the text. After the automatic labeling with both types of labels, we investigated (1) the relationship between empowerment processes and the intensity of online participation, (2) the relationship between empowerment processes and the LIWC categories, and (3) the differences between patients with different types of cancer. The precision of the automatic labeling was 85.6%, which we considered to be sufficient for automatically labeling the complete corpus and doing further analyses on the labeled data. Overall, 62.94% (3482/5532) of the messages contained a narrative, 23.83% (1318/5532) a question, and 27.49% (1521/5532) informational support. Emotional support and references to external sources were less frequent. Users with more posts more often referred to an external source and more often provided informational support and emotional support (Kendall τ>0.2; P<.001) and less often shared narratives (Kendall τ=-0.297; P<.001). A number of LIWC categories are significant predictors for the empowerment processes: words expressing assent (ok and yes) and emotional processes (expressions of feelings) are significant positive predictors for emotional support (P=.002). The differences between patients with different types of cancer are small. Empowerment processes are associated with the intensity of online use. The relationship between linguistic analyses and empowerment processes indicates that empowerment processes can be identified from the occurrences of specific linguistic cues denoting psychological processes.


Sudden infant death syndrome and inherited cardiac conditions.
Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality in developed countries, characterized by the death of infants for no obvious reason and without prior warning. The complex interaction of multiple factors in the pathogenesis of SIDS is illustrated by the 'triple risk hypothesis', which proposed that SIDS results from a convergence of three overlapping risk factors: a critical developmental period, an exogenous stressor, and underlying genetic and/or nongenetic vulnerability in the infant. Rare variants in genes associated with inherited arrhythmia syndromes and cardiomyopathies have been proposed as the substrate for an infant's critical vulnerability in a small subset of SIDS cases. Given the potential risk of inherited cardiac disease, current guidelines recommend post-mortem genetic testing (molecular autopsy) and cardiological investigation of the surviving family, complemented by targeted genetic testing if appropriate. In this Review, we highlight the latest developments in understanding the spectrum and prevalence of cardiac-mediated SIDS, and discuss the clinical implications of SIDS in the surviving family and the general population.


The cytoskeletal and contractile apparatus of smooth muscle: contraction bands and segmentation of the contractile elements.
Confocal laser scanning microscopy of isolated and antibody-labeled avian gizzard smooth muscle cells has revealed the global organization of the contractile and cytoskeletal elements. The cytoskeleton, marked by antibodies to desmin and filamin is composed of a mainly longitudinal, meandering and branched system of fibrils that contrasts with the plait-like, interdigitating arrangement of linear fibrils of the contractile apparatus, labeled with antibodies to myosin and tropomyosin. Although desmin and filamin were colocalized in the body of the cell, filamin antibodies labeled additionally the vinculin-containing surface plaques. In confocal optical sections the contractile fibrils showed a continuous label for myosin for at least 5 microns along their length: there was no obvious or regular interruption of label as might be expected for registered myosin filaments. The cytoplasmic dense bodies, labeled with antibodies to alpha-actinin exhibited a regular, diagonal arrangement in both extended cells and in cells shortened in solution to one-fifth of their extended length: after the same shortening, the fibrils of the cytoskeleton that showed colocalization with the dense bodies in extended cells became crumpled and disordered. It is concluded that the dense bodies serve as coupling elements between the cytoskeletal and contractile systems. After extraction with Triton X-100, isolated cells bound so firmly to a glass substrate that they were unable to shorten as a whole when exposed to exogenous Mg ATP. Instead, they contracted internally, producing integral of 10 regularly spaced contraction nodes along their length. On the basis of differences of actin distribution two types of nodes could be distinguished: actin-positive nodes, in which actin straddled the node, and actin-negative nodes, characterized by an actin-free center flanked by actin fringes of 4.5 microns minimum length on either side. Myosin was concentrated in the center of the node in both cases. The differences in node morphology could be correlated with different degrees of coupling of the contractile with the cytoskeletal elements, effected by a preparation-dependent variability of proteolysis of the cells. The nodes were shown to be closely related to the supercontracted cell fragments shown in the accompanying paper (Small et al., 1990) and furnished further evidence for long actin filaments in smooth muscle. Further, the segmentation of the contractile elements pointed to a hierarchial organization of the myofilaments governed by as yet undetected elements.


A new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities.
The Clinical Research Center for Dementia of South Korea (CREDOS) group developed a new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities (WMHs). In this study, we aimed to evaluate the validity of the CREDOS ischemia classification system. A total of 352 patients with cognitive impairments were included. Their WMH scores were rated using the CREDOS WMH visual rating scale. These patients were divided into 3 groups according to the CREDOS ischemia classification system. The volume of WMH was also automatically measured. The number of lacunes and microbleeds (MBs) were counted. The CREDOS ischemia classification system was revised with factor analysis using vascular risk factors and cerebrovascular disease (CVD) markers (WMH volume, lacunes, and MBs). External validation was performed in another group of patients with cognitive impairment using multinomial logistic regression analysis. The CREDOS WMH visual rating scale showed excellent correlation with the automatically measured volume of WMH. The factor analysis showed that the severe group was expanded to D3P1 and D3P2 in the revised CREDOS ischemia classification system. In the validation group, the presence of vascular risk factors and the severity of CVD markers could be distinguished according to the revised CREDOS ischemia classification. We validated a newly developed classification system for ischemia. This simple visual classification system was capable of providing information on vascular risk factors and CVD markers by simply rating WMH on magnetic resonance imaging.


[Generation of skin-derived iPSCs from an Osteogenesis imperfecta patient carrying WNT1c.677C>T mutation].
To obtain skin-derived induced pluripotent stem cells (iPSCs) from an Osteogenesis imperfecta (OI) patient carrying WNT1c.677C>T mutation in order to provide a new cell model for investigating the underlying molecular mechanism and stem cell therapy for OI. The pathogenic variant of the patient was identified by Sanger sequencing. With informed consent from the patient, skin tissue was biopsied, and primary skin fibroblasts were cultured. Skin fibroblasts were induced into iPSCs using Sendai virus-mediated non-genomic integration reprogramming method. The iPSC cell lines were characterized for pluripotency, differentiation capacity, and karyotyping assay. The patient was found to carry homozygous missense c.677C>T (p.Ser226Leu) mutation of the WNT1 gene. The established iPSC lines possessed self-renewal and capacity for in vitro differentiation. It also has a diploid karyotype (46,XX). A patient-specific WNT1 gene mutation (WNT1c.677C>T) iPSC line was established, which can provide a cell model for the study of OI caused by the mutation.


Reproducibility of diabetic macular edema estimates from SD-OCT is affected by the choice of image analysis algorithm.
To evaluate the intersession repeatability of retinal thickness measurements in patients with diabetic macular edema (DME) using the Heidelberg Spectralis optical coherence tomography (OCT) algorithm and a publicly available, three-dimensional graph search-based multilayer OCT segmentation algorithm, the Iowa Reference Algorithm. Thirty eyes from 21 patients diagnosed with clinically significant DME were included and underwent consecutive, registered macula-centered spectral-domain optical coherence scans (Heidelberg Spectralis). The OCT scans were segmented into separate surfaces, and the average thickness between internal limiting membrane and outer retinal pigment epithelium complex surfaces was determined using the Iowa Reference Algorithm. Variability between paired scans was analyzed and compared with the retinal thickness obtained from the manufacturer-supplied Spectralis software. The coefficient of repeatability (variation) for central macular thickness using the Iowa Reference Algorithm was 5.26 μm (0.62% [95% confidence interval (CI), 0.43-0.71]), while for the Spectralis algorithm this was 6.84 μm (0.81% [95% CI, 0.55-0.92]). When the central 3 mm was analyzed, the coefficient of repeatability (variation) was 2.46 μm (0.31% [95% CI, 0.23-0.38]) for the Iowa Reference Algorithm and 4.23 μm (0.53% [95% CI, 0.39-0.65]) for the Spectralis software. The Iowa Reference Algorithm and the Spectralis software provide excellent reproducibility between serial scans in patients with clinically significant DME. The publicly available Iowa Reference Algorithm may have lower between-measurement variation than the manufacturer-supplied Spectralis software for the central 3 mm subfield. These findings have significant implications for the management of patients with DME.


Evaluation of a fully absorbable poly-4-hydroxybutyrate/absorbable barrier composite mesh in a porcine model of ventral hernia repair.
The objective of this study was to evaluate the mechanical and histological properties of a fully absorbable poly-4-hydroxybutyrate/absorbable barrier composite mesh (Phasix™ ST) compared to partially absorbable (Ventralight™ ST), fully absorbable (Phasix™), and biologically derived (Strattice™) meshes in a porcine model of ventral hernia repair. Bilateral abdominal surgical defects were created in twenty-four Yucatan pigs, repaired with intraperitoneal (Phasix™ ST, Ventralight™ ST) or retromuscular (Phasix™, Strattice™) mesh, and evaluated at 12 and 24 weeks (n = 6 mesh/group/time point). Prior to implantation, Strattice™ demonstrated significantly higher (p < 0.001) strength (636.6 ± 192.1 N) compared to Ventralight™ ST (324.3 ± 37.1 N), Phasix™ ST (206.9 ± 11.3 N), and Phasix™ (200.6 ± 25.2 N). At 12 and 24 weeks, mesh/repair strength was significantly greater than NAW (p < 0.01 in all cases), and no significant changes in strength were observed for any meshes between 12 and 24 weeks (p > 0.05). Phasix™ mesh/repair strength was significantly greater than Strattice™ (p < 0.001) at 12 and 24 weeks, and Ventralight™ ST mesh/repair strength was significantly greater than Phasix™ ST mesh (p < 0.05) at 24 weeks. At 12 and 24 weeks, Phasix™ ST and Ventralight™ ST were associated with mild inflammation and minimal-mild fibrosis/neovascularization, with no significant differences between groups. At both time points, Phasix™ was associated with minimal-mild inflammation/fibrosis and mild neovascularization. Strattice™ was associated with minimal inflammation/fibrosis, with minimal neovascularization at 12 weeks, which increased to mild by 24 weeks. Strattice™ exhibited significantly less neovascularization than Phasix™ at 12 weeks and significantly greater inflammation at 24 weeks due to remodeling. Phasix™ ST demonstrated mechanical and histological properties comparable to partially absorbable (Ventralight™ ST) and fully resorbable (Phasix™) meshes at 12 and 24 weeks in this model. Data also suggest that fully absorbable meshes with longer-term resorption profiles may provide improved mechanical and histological properties compared to biologically derived scaffolds.


Induction of antitumor immunity ex vivo using dendritic cells transduced with fowl pox vector expressing MUC1, CEA, and a triad of costimulatory molecules (rF-PANVAC).
The fowl pox vector expressing the tumor-associated antigens, mucin-1 and carcinoembryonic antigen in the context of costimulatory molecules (rF-PANVAC) has shown promise as a tumor vaccine. However, vaccine-mediated expansion of suppressor T-cell populations may blunt clinical efficacy. We characterized the cellular immune response induced by ex vivo dendritic cells (DCs) transduced with (rF)-PANVAC. Consistent with the functional characteristics of potent antigen-presenting cells, rF-PANVAC-DCs demonstrated strong expression of mucin-1 and carcinoembryonic antigen and costimulatory molecules, CD80, CD86, and CD83; decreased levels of phosphorylated STAT3, and increased levels of Tyk2, Janus kinase 2, and STAT1. rF-PANVAC-DCs stimulated expansion of tumor antigen-specific T cells with potent cytolytic capacity. However, rF-PANVAC-transduced DCs also induced the concurrent expansion of FOXP3 expressing CD4CD25 regulatory T cells (Tregs) that inhibited T-cell activation. Moreover, Tregs expressed high levels of Th2 cytokines [interleukin (IL)-10, IL-4, IL-5, and IL-13] together with phosphorylated STAT3 and STAT6. In contrast, the vaccine-expanded Treg population expressed high levels of Th1 cytokines IL-2 and interferon-γ and the proinflammatory receptor-related orphan receptor γt (RORγt) and IL-17A suggesting that these cells may share effector functions with conventional TH17 T cells. These data suggest that Tregs expanded by rF-PANVAC-DCs, exhibit immunosuppressive properties potentially mediated by Th2 cytokines, but simultaneous expression of Th1 and Th17-associated factors suggests a high degree of plasticity.


Socio-cognitive constraints and opportunities for sustainable intensification in South Asia: insights from fuzzy cognitive mapping in coastal Bangladesh.
Appreciating and dealing with the plurality of farmers' perceptions and their contextual knowledge and perspectives of the functioning and performance of their agroecosystems-in other words, their 'mental models'-is central for appropriate and sustainable agricultural development. In this respect, the sustainable development goals (SDGs) aim to eradicate poverty and food insecurity by 2030 by envisioning social inclusivity that incorporates the preferences and knowledge of key stakeholders, including farmers. Agricultural development interventions and policies directed at sustainable intensification (SI), however, do not sufficiently account for farmers' perceptions, beliefs, priorities, or interests. Considering two contrasting agroecological systems in coastal Bangladesh, we used a fuzzy cognitive mapping (FCM)-based simulation and sensitivity analysis of mental models of respondents of different farm types from 240 farm households. The employed FCM mental models were able to (1) capture farmers' perception of farming system concepts and relationships for each farm type and (2) assess the impact of external interventions (drivers) on cropping intensification and food security. We decomposed the FCM models' variance into the first-order sensitivity index (SVI) and total sensitivity index (TSI) using a winding stairs algorithm. Both within and outside polder areas, the highest TSIs (35-68%) were observed for effects of agricultural extension on changes in other concepts in the map, particularly food security and income (SI indicators), indicating the importance of extension programs for SI. Outside polders, drainage and micro-credit were also influential; within polders, the availability of micro-credit appears to affect farmer perceptions of SI indicators more than drainage. This study demonstrated the importance of reflection on the differing perspectives of farmers both within and outside polders to identify entry points for development interventions. In addition, the study underscores the need for micro-farming systems-level research to assess the context-based feasibility of introduced interventions as perceived by farmers of different farm types. The online version contains supplementary material available at 10.1007/s10668-021-01342-y.


Crab regulation of cross-ecosystem resource transfer by marine foraging fire ants.
Permeability of boundaries in biological systems is regulated by biotic and/or abiotic factors. Despite this knowledge, the role of biotic factors in regulating resource transfer across ecosystem boundaries has received little study. Additionally, little is known about how cross-ecosystem resource transfer affects source populations. We used experiments, observations and stable isotopes, to evaluate: (1) the proportion of intertidal-foraging black fire ant (Solenopsis richteri) diet derived from marine sources, (2) how black fire ant cross-ecosystem resource transfer is altered by the dominant bioengineer in the intertidal, a burrowing crab (Neohelice granulata), (3) the top-down impact of these terrestrial ants on a marine resource, and (4) the effect of marine resources on recipient black fire ants. We found that more than 85% of the black fire ant diet is derived from marine sources, the number of intertidal foraging ants doubles in the absence of crab burrows, and that ants cause a 50% reduction in intertidal polychaetes. Also, ant mound density is three times greater adjacent to marine systems. This study reveals that cross-ecosystem foraging terrestrial ants can clearly have strong impacts on marine resources. Furthermore, ecosystem engineers that modify and occupy habitat in these ecosystem boundaries can strongly regulate the degree of cross-ecosystem resource transfer and resultant top down impacts.


Factors associated with poor outcomes of continuous renal replacement therapy.
Continuous renal replacement therapy (CRRT) is one of the dialysis modalities for critically ill patients. Despite intensive dialysis care, a high mortality rate is found in these patients. Our objective was to investigate the factors associated with poor outcomes in these patients. We conducted a retrospective cohort study using the National Health Insurance Research Database. Records of critically ill patients who received CRRT between 2007 and 2011 were retrieved, and the patients were categorized into two groups: those with acute kidney injury (AKI) and those with history of end-stage renal disease (ESRD). Our primary and secondary outcomes were in-hospital mortality and long-term survival and non-renal recovery (long-term dialysis dependence), respectively, in the AKI group. We enrolled 15,453 patients, with 13,204 and 2249 in the AKI and ESRD groups, respectively. Overall, 66.5% patients died during hospitalization. In-hospital mortality did not differ significantly between groups (adjusted odds ratio, 0.93; 95% CI, 0.84-1.02). Age, chronic liver disease, and cancer history were identified as independent risk factors for in-hospital mortality in both groups. Hypertension was associated with higher risk of in-hospital mortality in patients with AKI. Age, coronary artery disease, and admission to the medical intensive care unit (MICU) were risk factors for long-term dialysis dependence in patients with AKI. Patients with AKI and ESRD have similarly poor outcomes after CRRT. Older age and presence of chronic liver disease and cancer were associated with higher mortality. Older age, presence of coronary artery disease, and admission to MICU were associated with lower renal recovery rate in patients with AKI.


Nitrous oxide and ammonia fluxes in a soybean field irrigated with swine effluent.
In the United States, swine (Sus scrofa) operations produce more than 14 Tg of manure each year. About 30% of this manure is stored in anaerobic lagoons before application to land. While land application of manure supplies nutrients for crop production, it may lead to gaseous emissions of ammonia (NH3) and nitrous oxide (N2O). Our objectives were to quantify gaseous fluxes of NH3 and N2O from effluent applications under field conditions. Three applications of swine effluent were applied to soybean [Glycine max (L.) Merr. 'Brim'] and gaseous fluxes were determined from gas concentration profiles and the flux-gradient gas transport technique. About 12% of ammonium (NH4-N) in the effluent was lost through drift or secondary volatilization of NH3 during irrigation. An additional 23% was volatilized within 48 h of application. Under conditions of low windspeed and with the wind blowing from the lagoon to the field, atmospheric concentrations of NH3 increased and the crop absorbed NH3 at the rate of 1.2 kg NH3 ha(-1) d(-1), which was 22 to 33% of the NH3 emitted from the lagoon during these periods. Nitrous oxide emissions were low before effluent applications (0.016 g N2O-N ha(-1) d(-1)) and increased to 25 to 38 g N2O-N ha(-1) d(-1) after irrigation. Total N2O emissions during the measurement period were 4.1 kg N2O-N ha(-1), which was about 1.5% of total N applied. The large losses of NH3 and N2O illustrate the difficulty of basing effluent irrigation schedules on N concentrations and that NH3 emissions can significantly contribute to N enrichment of the environment.


Cumulative-genetic plasticity, parenting and adolescent self-regulation.
The capacity to control or regulate one's emotions, cognitions and behavior is central to competent functioning, with limitations in these abilities associated with developmental problems. Parenting appears to influence such self-regulation. Here the differential-susceptibility hypothesis is tested that the more putative 'plasticity alleles' adolescents carry, the more positively and negatively influenced they will be by, respectively, supportive and unsupportive parenting. One thousand, five hundred and eighty-six (1586) adolescents (n = 754 males; n = 832 females) enrolled in the American Add Health project were scored in terms of how many of 5 putative 'plasticity alleles' they carried - the 10R allele of DAT1, the A1 allele of DRD2, the 7R allele of DRD4, the short allele of 5HTTLPR, and the 2R/3R alleles of MAOA. Then the effect of the resultant index (ranging from 0 to 5) of cumulative-genetic plasticity in moderating effects of parenting on adolescent self-regulation was evaluated. Consistent with differential susceptibility, the more plasticity alleles males (but not females) carried, the more and less self-regulation they manifested under, respectively, supportive and unsupportive parenting conditions. Adolescent males appear to vary for genetic reasons in their susceptibility to parenting vis-à-vis self-regulation, perhaps due to epistatic and/or epigenetic processes. G×E research may benefit from compositing candidate genes. To afford comparative evaluation of differential-susceptibility vs. diathesis-stress models of environmental action, future G×E work should focus on positive as well as negative environmental conditions and developmental outcomes.


Fabry International Prognostic Index: a predictive severity score for Anderson-Fabry disease.
Anderson-Fabry disease (AFD) is a disorder of glycosphingolipid metabolism resulting from deficiency of α-galactosidase A and accumulation of globotriaosylceramide. Presentation is heterogeneous and, despite guidelines for initiation of therapy, there is no basis for defining subgroups that will progress more rapidly, whether treated or not. The authors of this study used clinical and pathological data recorded on 1483 patients in the Fabry Outcome Survey, a large international registry, to develop a prognostic severity score. Parameters relevant to disease progression or outcome were initially selected, using variables that are readily available in clinical practice. Individual end points for renal, cardiac, neurological disease, and death were selected, and a composite end point developed. Potential prognostic variables were correlated with each end point, before multivariate analysis. Variables retaining significance were then used to construct organ specific and composite prognostic scores. Kaplan-Meier (KM) analysis, according to score, was performed for each end point. Analysis demonstrated that it is possible to differentiate groups of patients with different outcome probabilities. Cardiac, renal and neurological end points could each be categorised into three separate groups. The 80% event-free survival for these groups differed by approximately 10 years. The overall composite score, the Fabry International Prognostic Index (FIPI), distinguished two distinct groups where the 50% event-free survival differed by 10 years. A prognostic scoring system for AFD has been developed and retrospective validation performed. The FIPI should prove to be a valuable tool in the counselling and management of AFD patients, and in comparative analyses of outcome using different therapies.


The impact of obesity on short- and long-term outcomes after lumbar fusion.
Retrospective cohort study. To compare short- and long-term outcomes in obese versus nonobese patients undergoing instrumented posterolateral fusion of the lumbar spine. Obesity is an important public health issue due to the negative effects on quality of life. Some studies have shown an association between obesity and higher rates of complications and unfavorable outcomes after spine surgery. We retrospectively reviewed medical records for all adult patients undergoing 1- to 3-level posterolateral fusion for degenerative spine disease between 1992 and 2012 at a single institution. Patients were divided into obese (body mass index > 30 kg/m) and nonobese cohorts to compare complications, reoperation rates, and symptom resolution at the last follow-up. A regression model was used to estimate relative risk ratios. During the study period, 732 patients underwent lumbar fusion, with 662 (90.44%) nonobese patients and 70 (9.56%) obese patients in the cohort. Obese patients had significantly higher blood loss intraoperatively (P = 0.002) and a longer average length of stay (P = 0.022). Moreover, obesity was independently associated with a significantly increased risk of developing a postoperative complication (risk ratio 2.14; 95% confidence interval, 1.10-4.16) and surgical site infection (risk ratio 3.11; 95% confidence interval, 1.48-6.52). At the last follow-up, a higher proportion of obese patients had radiculopathy (P = 0.018), motor deficits (P = 0.006), sensory deficits (P = 0.008), and bowel or bladder dysfunction (P = 0.006) than nonobese patients. In this study, obese patients undergoing lumbar fusion had higher blood loss, longer lengths of stay, higher complication rates, and worse functional outcomes at the last follow-up than nonobese patients. These findings suggest that both surgeons and patients should acknowledge the significantly increased morbidity profile of obese patients after lumbar fusion.


Doctoral training in Uganda: evaluation of mentoring best practices at Makerere university college of health sciences.
Good mentoring is a key variable for determining success in completing a doctoral program. We identified prevailing mentoring practices among doctoral students and their mentors, identified common challenges facing doctoral training, and proposed some solutions to enhance the quality of the doctoral training experience for both candidates and mentors at Makerere University College of Health Sciences (MakCHS). This cross-sectional qualitative evaluation was part of the monitoring and evaluation program for doctoral training. All doctoral students and their mentors were invited for a half-day workshop through the MakCHS mailing list. Prevailing doctoral supervision and mentoring guidelines were summarised in a one-hour presentation. Participants were split into two homogenous students' (mentees') and mentors' groups to discuss specific issues using a focus group discussion (FGD) guide, that highlighted four main themes in regard to the doctoral training experience; what was going well, what was not going well, proposed solutions to current challenges and perceived high priority areas for improvement. The two groups came together again and the note-takers from each group presented their data and discussions were recorded by a note-taker. Twelve out of 36 invited mentors (33%) and 22 out of 40 invited mentees (55%) attended the workshop. Mentors and mentees noted increasing numbers of doctoral students and mentors, which provided opportunities for peer mentorship. Delays in procurement and research regulatory processes subsequently delayed students' projects. Similarly, mentees mentioned challenges of limited; 1) infrastructure and mentors to support basic science research projects, 2) physical office space for doctoral students and their mentors, 3) skills in budgeting and finance management and 4) communication skills including conflict resolution. As solutions, the team proposed skills' training, induction courses for doctoral students-mentor teams, and a Frequently Asked Questions' document, to better inform mentors', mentees' expectations and experiences. Systemic and infrastructural limitations affect the quality of the doctoral training experience at MaKCHS. Clinical and biomedical research infrastructure, in addition to training in research regulatory processes, procurement and finance management, communication skills and information technology, were highlighted as high priority areas for strategic interventions to improve mentoring within doctoral training of clinician scientists.


Homoleptic and heteroleptic N-alkylimidazole zinc(ii)-containing ionic liquids for high current density electrodeposition.
New homoleptic and heteroleptic zinc(ii)-containing liquid metal salts with N-alkylimidazole (AlkIm) ligands and bis(trifluoromethylsulfonyl)imide (Tf2N(-)) anions are described. The general formulae of the complexes are [Zn(AlkIm)6][Tf2N]2 and [Zn(AlkIm)6-x(AlkIm')x][Tf2N]2. Single-crystal X-ray diffraction revealed that, in the solid state, the cations consist of octahedral zinc(ii) centres. The heteroleptic complexes contain two different N-alkylimidazole ligands. The melting points of the liquid metal salts are below or slightly above room temperature. The dependence of the melting points, viscosity and crystal structure on the alkyl chain length of the N-alkylimidazole ligand for the homoleptic complexes and on the ratio of the two N-alkylimidazole ligands AlkIm and AlkIm' for the heteroleptic compounds is discussed. The possibility of incongruent melting and the presence of a mixture of the four-coordinate zinc(ii) centre and neutral ligands is discussed. The new zinc(ii)-containing liquid metal salts have been used as non-aqueous electrolytes for electrodeposition of zinc. A highly reversible deposition-stripping behaviour was found. Zinc electroplating was possible at very high current densities of more than -200 mA cm(-2) in unstirred solutions. Compact and highly crystalline zinc deposits were obtained.


The utility of screening for perinatal depression in the second trimester among Chinese: a three-wave prospective longitudinal study.
This paper aims to study the pattern of perinatal depressive symptomatology and determine the predictive power of second trimester perinatal depressive symptoms for future perinatal periods. A population-based sample of 2,178 women completed the Edinburgh Postnatal Depression Scale (EPDS) in the second and third trimesters and at 6 weeks postpartum. Repeated measures ANOVAs were used to determine the EPDS scores across three stages. The predictive power of the second trimester EPDS score in identifying women with an elevated EPDS score in the third trimester and at 6 weeks postpartum were determined. The predictive power of the second trimester EPDS score was further assessed using stepwise logistic regression and receiver operator characteristic curves. EPDS scores differed significantly across three stages. The rates were 9.9%, 7.8%, and 8.7% for an EPDS score of >14 in the second and third trimesters and at 6 weeks postpartum, respectively. Using a cut-off of 14/15, the second trimester EPDS score accurately classified 89.6% of women in the third trimester and 87.2% of those at 6 weeks postpartum with or without perinatal depressive symptomatology. Women with a second trimester EPDS score >14 were 11.78 times more likely in the third trimester and 7.15 times more likely at 6 weeks postpartum to exhibit perinatal depressive symptomatology after adjustment of sociodemographic variables. The area under the curve for perinatal depressive symptomatology was 0.85 in the third trimester and 0.77 at 6 weeks postpartum. To identify women at high risk for postpartum depression, healthcare professionals could consider screening all pregnant women in the second trimester so that secondary preventive intervention may be implemented.


The spirited, the observant, and the disheartened: social concepts of optimism, realism, and pessimism.
The social concepts of optimism, pessimism, and realism were investigated by assessing the prototypical acts (thoughts, feelings, goals, and actions) that laypersons assign to optimists, pessimists, and realists responding to a controllable and an uncontrollable situation. Optimists and realists, but not pessimists, were seen as adjusting their behavior to the situation. However, whereas optimists were characterized by flexibility in thoughts and feelings but invariance in goals and actions (i.e., they pursued their goals in both controllable and uncontrollable situations), the act profiles assigned to realists varied on all of these dimensions. The profile assigned to pessimists was characterized by cognitive, affective, motivational, and behavioral invariance, encompassing negative construals of the situation, giving up, and a focus on distress.


FoxO1 Inhibitors: The Future Medicine for Metabolic Disorders?
FoxO1, one of the most widely expressed sub-families of the winged helix forkhead factors, is biologically 'omni-functional' owing to its far-flung roles in metabolism, cell cycle, tissue differentiation and development and oxidative stress response. The knowledge of involvement of FoxO1 in metabolic disorders has long been there, but the potential target remained underutilized due to unavailability of specific and potent inhibitors. The review provides an insight into the role of FoxO1 in orchestrating metabolic diseases' pathogenesis (including diabetes, its secondary complications and obesity) and compiles the literature on FoxO1 inhibitors. The emergence of various natural molecules and synthesized small molecules like AS1842856 as FoxO1 inhibitors urges us to think further and decide the future course of drug development for the management of metabolic disorders.


Islet amyloid: phase partitioning and secondary nucleation are central to the mechanism of fibrillogenesis.
Islet amyloid polypeptide (IAPP) contributes to the pathogenesis of type II diabetes by depositing as cytotoxic amyloid fibers in the endocrine pancreas. Fiber formation occurs with a marked conformational change from an unstructured precursor. Using real-time quantitative kinetic methods, fibrillogenesis was characterized as a function of protein, denaturant, and seed concentration. Several observations are in sharp contrast to the expectations for nucleation-dependent polymerization. First, the half-time of conversion for both de novo and seeded kinetics were found to be independent of protein concentration. Second, while elongation kinetics scale linearly with protein concentration, they are relatively insensitive to changes in the total seed concentration. Third, seeded bypass of de novo fiber formation kinetics shows a lag phase. The seeded lag phase is eliminated by a time delay before the introduction of seed to a de novo reaction. Last, conversion is highly cooperative, with the time required for 10-90% conversion occurring much faster than the lag time. At a minimum, four kinetic steps are required to describe these observations: activation, fiber independent nucleation, fiber-dependent nucleation, and elongation. Furthermore, we invoke a phase transition in which protein initially forms an off-pathway dispersion. This single construct allows us to model both the concentration independence of the de novo reaction time and the first-order concentration dependence of the elongation kinetics. Marked acceleration of this reaction by hexafluoro-2-propanol reinforces this view by altering the relative solubility of the two phases and/or by stabilizing hydrogen-bonded structures in the transition states of the reaction pathway.


Schizophrenia and suicide: systematic review of risk factors.
Suicide risk is greatly increased in schizophrenia. Detection of those at risk is clinically important. To identify risk factors for suicide in schizophrenia. The international literature on case-control and cohort studies of patients with schizophrenia or related conditions in which suicide was reported as an outcome was systematically reviewed. Studies were identified through searching electronic databases and reference lists, and by consulting experts. Twenty-nine eligible studies were identified. Factors with robust evidence of increased risk of suicide were previous depressive disorders (OR=3.03, 95% CI 2.06-4.46), previous suicide attempts (OR=4.09, 95% CI 2.79-6.01), drug misuse (OR=3.21, 95% CI 1.99-5.17), agitation or motor restlessness (OR=2.61, 95% CI 1.54-4.41), fear of mental disintegration (OR=12.1, 95% CI 1.89-81.3), poor adherence to treatment (OR=3.75, 95% CI 2.20-6.37) and recent loss (OR=4.03, 95% CI 1.37-11.8). Reduced risk was associated with hallucinations (OR=0.50, 95% CI 0.35-0.71). Prevention of suicide in schizophrenia is likely to result from treatment of affective symptoms, improving adherence to treatment, and maintaining special vigilance in patients with risk factors, especially after losses.


Application of the video head impulse test to detect vertical semicircular canal dysfunction.
The video head impulse test (vHIT) is a useful clinical tool to detect semicircular canal dysfunction. However, so far, vHIT has been limited to measurement of the function of the horizontal semicircular canals. The goal of this study was to determine if vHIT can detect vertical semicircular canal dysfunction. Horizontal and vertical eye movements were recorded in response to abrupt, passive, unpredictable head turns (head impulses) in the planes of the vertical semicircular canals by high-speed video (250-Hz sampling rate) together with measures of the head movement. Head impulses were delivered diagonally in the plane of the vertical semicircular canals, whereas gaze was directed along the same plane. Patients with known vestibular loss as shown by previous scleral search coil recording were tested to identify if the vHIT testing could detect the loss. The results of patients with unilateral, bilateral, and individual semicircular canal dysfunction were compared with the results of a healthy control subject. The patient with bilateral vestibular loss had no compensatory slow eye movements in any direction. The patient with unilateral vestibular loss showed reduced response for head impulses activating the canals in their affected right ear (right anterior, right posterior, and right horizontal head impulses). The patient with isolated canal loss showed reduced response for head impulses activating the affected right posterior canal. vHIT detects peripheral deficits of both vertical and horizontal semicircular canal function and is a new tool for measuring dysfunction of individual semicircular canals in vestibular patients.


Synergetic Enhancement of Thermoelectric Performance by Selective Charge Anderson Localization-Delocalization Transition in n-Type Bi-Doped PbTe/Ag2Te Nanocomposite.
Considerable efforts have been devoted to enhancing thermoelectric performance, by employing phonon scattering from nanostructural architecture, and material design using phonon-glass and electron-crystal concepts. The nanostructural approach helps to lower thermal conductivity but has limited effect on the power factor. Here, we demonstrate selective charge Anderson localization as a route to maximize the Seebeck coefficient while simultaneously preserving high electrical conductivity and lowering the lattice thermal conductivity. We confirm the viability of interface potential modification in an n-type Bi-doped PbTe/Ag2Te nanocomposite and the resulting enhancement in thermoelectric figure-of-merit ZT. The introduction of random potentials via Ag2Te nanoparticle distribution using extrinsic phase mixing was determined using scanning tunneling spectroscopy measurements. When the Ag2Te undergoes a structural phase transition ( T > 420 K) from monoclinic β-Ag2Te to cubic α-Ag2Te, the band gap in the α-Ag2Te increases due to the p -d hybridization. This results in a decrease in the potential barrier height, which gives rise to partial delocalization of the electrons, while wave packets of the holes are still in a localized state. Using this strategic approach, we achieved an exceptionally high thermoelectric figure-of-merit in n-type PbTe materials, a ZT greater than 2.0, suitable for waste heat power generation.


Influence of electric potential on the apparent viscosity of an ionic liquid: facts and artifacts.
According to recent findings, the steady shear viscosity of the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Emim][Tf2N]) decreases significantly under the influence of electric potential. This implies a causal connection between nanoscale ordering at the electrified interface and a macroscopic change of transport properties. To study this phenomenon in more detail, we reproduced the above-mentioned measurements; however, we find no evidence that the viscosity of [Emim][Tf2N] is a function of electric potential. Additionally, our results show that steady shear measurements can lead to artifacts that, at first glance, may appear to be potential-induced changes in viscosity. We demonstrate that the artifacts result from a sliding electrical contact at the working electrode of the electrochemical cell and we suggest to consider our findings for future viscosity measurements of ionic liquids.


Elemental geochemistry of sedimentary rocks at Yellowknife Bay, Gale crater, Mars.
Sedimentary rocks examined by the Curiosity rover at Yellowknife Bay, Mars, were derived from sources that evolved from an approximately average martian crustal composition to one influenced by alkaline basalts. No evidence of chemical weathering is preserved, indicating arid, possibly cold, paleoclimates and rapid erosion and deposition. The absence of predicted geochemical variations indicates that magnetite and phyllosilicates formed by diagenesis under low-temperature, circumneutral pH, rock-dominated aqueous conditions. Analyses of diagenetic features (including concretions, raised ridges, and fractures) at high spatial resolution indicate that they are composed of iron- and halogen-rich components, magnesium-iron-chlorine-rich components, and hydrated calcium sulfates, respectively. Composition of a cross-cutting dike-like feature is consistent with sedimentary intrusion. The geochemistry of these sedimentary rocks provides further evidence for diverse depositional and diagenetic sedimentary environments during the early history of Mars.


Determinants of persistent asthma in young adults.
Objective: The aim of the study was to evaluate determinants for the prognosis of asthma in a population-based cohort of young adults. Design: The study was a nine-year clinical follow up of 239 asthmatic subjects from an enriched population-based sample of 1,191 young adults, aged 20-44 years, who participated in an interviewer-administered questionnaire and clinical examination at baseline in 2003-2006. From the interview, an asthma score was generated as the simple sum of affirmative answers to five main asthma-like symptoms in order to analyse symptoms of asthma as a continuum. The clinical examination comprised spirometry, bronchial challenge or bronchodilation, and skin prick test. Results: Among the 239 individuals with asthma at baseline 164 (69%) had persistent asthma at follow up, while 68 (28%) achieved remission of asthma and seven (3%) were diagnosed with COPD solely. Determinants for persistent asthma were use of medication for breathing within the last 12 months: Short-acting beta-adrenoceptor agonists (SABA) only (OR 3.39; 95%CI: 1.47-7.82) and inhaled corticosteroids (ICS) and/or long-acting beta-adrenoceptor agonists (LABA) (8.95; 3.87-20.69). Stratified by age of onset determinants for persistence in individuals with early-onset asthma (age less than 16 years) were FEV₁ below predicted (7.12; 1.61-31.50), asthma score at baseline (2.06; 1.15-3.68) and use of ICS and/or LABA within 12 months (9.87; 1.95-49.98). In individuals with late-onset asthma the determinant was use of ICS and/or LABA within 12 months (6.84; 2.09-22.37). Conclusions: Pulmonary function below predicted, severity of disease expressed by asthma score and use of ICS and/or LABA were all determinants for persistent early-onset asthma, whereas only use of ICS and/or LABA was a determinant in late-onset asthma. A high asthma score indicated insufficient disease control in a substantial proportion of these young adults.