Central and peripheral information source use among rural and remote Registered Nurses.
This paper reports a study examining the use of central (colleagues, inservice and newsletters) and peripheral information sources (Internet, library, journal subscriptions and continuing education) among a large sample of rural and remote nurses and explores the factors associated with the use of particular peripheral information sources. There have been few studies of the specific sources of information accessed by Registered Nurses, particularly rural or remote nurses, and the characteristics of nurses and their organizations that are associated with the use of particular information sources. A questionnaire survey was conducted with 3933 Registered Nurses from all regions of rural and remote Canada between October 2001 and July 2002. We used frequencies and cross-tabulations to describe rates of information use, and forward selection logistic regression with likelihood ratio selection to build the best-fitting model of the variables that affected the odds of using each peripheral information source. Nursing colleagues ranked as the information source most frequently used, and the Internet and library ranked lowest. On average, nurses used a statistically significantly greater number of central than peripheral sources. Peripheral information source use was higher among nurses who had access to current information, opportunities to share their knowledge with others, higher education levels, were in positions of authority and worked with healthcare students. The associations between age and geographical location varied according to the peripheral information source under consideration. The vast majority of rural and remote nurses used at least one peripheral information source to inform their practice. Increasing the number of research sources used by these nurses requires attention to issues of information access in these areas, as well as issues of staff recruitment and retention of staff in under-serviced rural and remote regions.


"Psychosis-predictive value of self-reported schizotypy in a clinical high-risk sample": Correction to Flückiger et al. (2016).
Reports an error in "Psychosis-Predictive Value of Self-Reported Schizotypy in a Clinical High-Risk Sample" by Rahel Flückiger, Stephan Ruhrmann, Martin Debbané, Chantal Michel, Daniela Hubl, Benno G. Schimmelmann, Joachim Klosterkötter and Frauke Schultze-Lutter (Journal of Abnormal Psychology, Advanced Online Publication, Sep 1, 2016, np). In the article, there was an error in the Author Note. The affiliation of Daniela Hubl was incorrectly listed as "University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern." It should have been listed as "University Hospital of Psychiatry and Psychotherapy, University of Bern." All versions of this article have been corrected. (The following abstract of the original article appeared in record 2016-41994-001.) Schizotypy is considered an indicator of psychosis-proneness and therefore, a precursor to schizophrenia-spectrum psychosis. In the early detection of psychosis, the widely used ultra high-risk criteria refer to the positive features of schizotypy and schizotypal personality disorders (SPD). In clinical high risk (CHR) samples, self-reported or clinically assessed SPD, notably the lack of close friends, has been suggested to facilitate the prediction of psychosis. In community samples, self-reported schizotypy has mainly been assessed psychometrically using the 4 Wisconsin Schizotypy Scales (WSS; Chapman, Chapman, Kwapil, Eckbald, & Zinser, 1994), and the positive schizotypy dimension was consistently predictive of psychosis (Debbané et al., 2015). However, psychometrically assessed schizotypy has not yet been studied as a potential predictor of psychosis in CHR samples. To bridge this gap, we studied the psychosis-predictive value of 3 of the WSSs and their association with CHR state in a clinical sample. One hundred 28 patients (23 ± 7 years; 81% considered CHR) from 2 early detection services were followed for 12 to 101 months. Within 48 months, 36 (28.1%) converted to psychosis. Only physical anhedonia was associated with CHR state, and high scores for physical anhedonia were predictive of conversion in conjunction with the CHR state. Physical anhedonia rather than positive schizotypy scales might separate future converters from nonconverters in clinical samples already presenting a phenomenologically more extreme range on the psychosis continuum. Given their reported psychosis-predictive value in nonclinical samples, psychometric schizotypy measures in general might be useful for the initial screening of psychosis-proneness in the community, whereas physical anhedonia might be particularly useful in CHR samples.


Characterization of spatial patterns in river water quality using chemometric pattern recognition techniques.
This study employed three chemometric data mining techniques (factor analysis (FA), cluster analysis (CA), and discriminant analysis (DA)) to identify the latent structure of a water quality (WQ) dataset pertaining to Kinta River (Malaysia) and to classify eight WQ monitoring stations along the river into groups of similar WQ characteristics. FA identified the WQ parameters responsible for variations in Kinta River's WQ and accentuated the roles of weathering and surface runoff in determining the river's WQ. CA grouped the monitoring locations into a cluster of low levels of water pollution (the two uppermost monitoring stations) and another of relatively high levels of river pollution (the mid-, and down-stream stations). DA confirmed these clusters and produced a discriminant function which can predict the cluster membership of new and/or unknown samples. These chemometric techniques highlight the potential for reasonably reducing the number of WQVs and monitoring stations for long-term monitoring purposes.


Topical application of yeast extract accelerates the wound healing of diabetic mice.
Alcoholic extracts of yeast have been used as the active ingredient in medications under names such as "tissue or skin respiratory factor," Biodyne (Sperti Drug Co, Cincinnati, Ohio--now defunct), and live yeast cell derivative (LYCD). Beneficial clinical results from the use of LYCD have been reported for the treatment of burns, wounds, and hemorrhoids. The medicinal effects of LYCD have recently been localized to a protein fraction containing a mixture of several peptides. The effects of topical application of the peptide mixture on wounds were examined in diabetic mice, an animal model in which the healing process is disrupted and delayed. Full-thickness wounds were created on the backs of diabetic (DB) and nondiabetic (non-DB) mice. Half of the DB and non-DB mice were treated with 0.05 mL of LYCD after wounding and for 4 successive days. All other mice received vehicle. Wound areas were measured at Day 0 and at 2-day intervals. Mice were sacrificed at 3, 7, 10, 21, and 28 days postinjury. Differences in the extent and quality of healing appeared between DB mice receiving LYCD and DB mice receiving vehicle by day 10 (P < .0001). By 24 days postinjury, DB mice receiving LYCD had achieved 100% wound closure, whereas DB mice receiving vehicle had achieved only 31.4% wound closure. Histologic examination of wounds reflected improved wound healing in DB mice receiving LYCD as compared with those receiving vehicle. A topically applied yeast extract peptide mixture significantly attenuates wound closure and the degree of cellular reorganization of full-thickness excisional wounds of DB mice.


Co-inertia multivariate approach for the evaluation of anthropogenic impact on two commercial fish along Tyrrhenian coasts.
Aliphatic hydrocarbon levels were determined by the GC/MS technique in fish livers of Engraulis encrasicolus (Ee) and Trachurus trachurus (Tt), collected from a particular area of the Mediterranean Sea, called GSA 10, which is located exactly in Tyrrhenian Sea between Campania coast and North Sicily coast. The aim was to evaluate their potential use as specific bioindicators towards this class of contaminants. Both Tt and Ee are considered to be pollution monitoring bioindicators, due to their dominance in marine communities and economic fishing interest. Ee showed a higher tendency to bioaccumulate TAHs, due to the lower quantity of fatty acids in liver tissues with respect to Tt. The area under study has been characterised a) chemically with the acquisition of temperature, oxygen and salinity profiles along the water column, and b) ecologically with the determination of amino acid contents in fish eyes, in order to gain information on the adaptation to environmental changes. Moreover, specific activities of two hydrolytic enzymes, such as alkaline phosphatase and peroxidase in fish epidermal mucus, together with lactate in blood plasma and cortisol levels, have been investigated for the first time, in order to obtain insights into the effects of hydrocarbons on animal welfare. A multiple co-inertia analysis was also applied to chemical and environmental parameters, in order to explore any possible correlation between different variables. The multivariate approach showed a clear spatial distribution between environmental and chemical variables in Ee, whilst there was an absence of a spatial trend in Tt. Moreover, the chemometric analysis showed a very high correlation between amino acid profiles and environmental variables for both species, confirming the possibility of being used as ecological welfare indices for short-term environmental variations.


V.A. Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: I. Design, methods, and baseline characteristics.
This report describes the experimental design, methods, and baseline characteristics of patients enrolled in a Veterans Administration Cooperative Study on the effect of aspirin (325 mg t.i.d.) and dipyridamole (75 mg t.i.d.) (110 patients), or placebo (121 patients) on major vascular outcome variables in noninsulin-dependent diabetic patients with either a recent amputation for gangrene (n = 207) or active gangrene (n = 24). It also describes the baseline characteristics of the patients. A total of 231 patients of 563 screened (41%) were enrolled at 11 participating V.A. Medical Centers during a 39 month period. The median age at entry was 60 years, the median duration of diabetes was 10 years, and weight was 110% of desirable. All patients were men. Sixty-eight percent were treated with insulin and 32% with diet alone. Only 42% were smokers at entry, 40% had retinopathy, 61% sensory neuropathy, 42% hypertension, and 29% had a history of myocardial infarction, angina, and/or congestive heart failure. Thirteen percent had a history of cerebrovascular disease. Despite randomization, the treatment group had an increased frequency of a history of cerebrovascular disease (p = 0.01), diagnosed as stroke (p = 0.03), a finding suggesting that the treatment group was at a slightly increased risk for vascular disease upon enrollment in the study. Other baseline variables did not differ significantly between the two groups. This study should provide definitive data on the efficacy of these doses of antiplatelet agents in preventing further vascular disease in diabetic men with gangrene or recent amputation for gangrene, using death due to vascular disease and subsequent amputation of the opposite extremity for gangrene as major outcome variables. It should also give useful information on the effect of antiplatelet therapy on vascular outcome variables such as same side amputations, myocardial infarction, stroke, transient ischemic attack, retinopathy, and renal failure. Finally, the study should provide useful data on the natural history and significance of risk factors in this patient population.


[Connective tissue function in diseases of the digestive organs (a review of the literature)].
Review of the literature presented deals with the state of connective tissue and some aspects of its metabolism in ulcer disease, chronic gastritis, chronic hepatitis, hepatic cirrhosis, acute and chronic pancreatitis. Disorders of synthesis and degradation of collagen, changes in metabolism of glycosaminoglycans, glycoproteins and aminoglycans are described, their pathogenetical role in development end exacerbation of diseases of digestive organs is demonstrated.


Meta-analysis in the assessment of treatment outcome.
Randomized clinical trials provide the most reliable estimates of the benefits and harms of treatments. Limited sample sizes restrict their power to allow informative analyses of secondary outcomes, or patient subgroups. The overall results of trials only apply to the average patient and clinical application ignores the individual patient differences.Meta-analysis in the context of a systematic review can produce more precise estimates of effect by combining the results of primary studies. This is particularly valuable for investigating rare, but important outcomes such as suicide. Variations between the trial-specific results can be investigated by meta-regression. Individual patient data meta-analyses (IPDMAs) are potentially much more powerful designs because they allow analysis of patient-level variables. As more genetic factors are identified that might account for treatment variability between individuals, IPDMAs offer a powerful strategy that can be used on existing trial data sets. Despite practical difficulties, IPDMAs are increasingly being conducted.


Unusual anal fin in a Devonian jawless vertebrate reveals complex origins of paired appendages.
Jawed vertebrates (gnathostomes) have undergone radical anatomical and developmental changes in comparison with their jawless cousins (cyclostomes). Key among these is paired appendages (fins, legs and wings), which first evolved at some point on the gnathostome stem. The anatomy of fossil stem gnathostomes is, therefore, fundamental to our understanding of the nature and timing of the origin of this complex innovation. Here, we show that Euphanerops, a fossil jawless fish from the Devonian, possessed paired anal-fin radials, but no pectoral or pelvic fins. This unique condition occurs at an early stage on the stem-gnathostome lineage. This condition, and comparison with the varied condition of paired fins in other ostracoderms, indicates that there was a large amount of developmental plasticity during this episode-rather than a gradual evolution of this complex feature. Apparently, a number of different clades were exploring morphospace or undergoing multiple losses.


Quantification of optic nerve blood flow changes using magnetic resonance imaging.
To evaluate the possibilities of magnetic resonance imaging (MRI) for quantification of pharmacologically induced changes in optic nerve microcirculation. T2-weighted MRI sequences were used to image the eye, optic nerve, and frontal cortex in rats. Two sets of control images before and one set during Gd (DTPA) infusion were recorded. Blood flow values for two regions of the optic nerve (an anterior part, including the optic nerve head, and a more posterior part) and the frontal cortex were calculated by image analysis from the change in signal intensity, as already reported for cerebral blood flow. For each rat, a control experiment before drug administration and a second experiment 30 minutes after subcutaneous injection of either placebo (n = 7), timolol (n = 7), or SDZ GLC-756, a dopamine D-1 antagonist and D-2 agonist (n = 7), were carried out in a double-blind fashion. Mean basal blood flow values were found between 29.4 and 45.6 ml/100 g per minute in the anterior part of the optic nerve, 38.3 and 42.9 ml/100 g per minute in the posterior part of the optic nerve, and 68.0 and 75.0 ml/100 g per minute in the frontal cortex. Placebo and timolol did not cause significant changes. SDZ GLC-756 significantly increased blood flow by 238% +/- 65% in the anterior part and by 87% +/- 40% in the posterior part of the optic nerve. These results suggest that MRI provides quantification of optic nerve blood flow and that dopaminergic substances increase optic nerve blood flow.


The Incidence of and Predictors for Severe Perineal Trauma and Intact Perineum in Women Having a Waterbirth in England: A Hospital-Based Study.
Background: To determine the incidence of and predictors for obstetric anal sphincter injuries (OASIS) and intact perineum in women giving birth in the water and compare with the general obstetric population. Materials and Methods: Data were retrospectively collected for women who had singleton cephalic presentation vaginal births in the water and the general obstetric population between August 2007 and December 2017. Results: We identified 1,007 women who had a waterbirth and 36,924 women from the general obstetric population. There was no significant difference in the incidence of OASIS between waterbirths and the general obstetric population (2.3% vs. 2.0%). Having a waterbirth was associated with a lower probability for an intact perineum (odds ratio [OR] = 0.83; confidence interval [95% CI]: 0.73-0.94) when compared with the general obstetric population (44.7% vs. 51.3%). Nulliparous women with a waterbirth when compared with multiparous women had an eightfold higher likelihood for the occurrence of OASIS (OR = 8.28; 95% CI: 2.64-25.86). The risk for a higher degree of OASIS was associated with increased maternal age in the total sample (OR = 1.08; 95% CI: 1.06-1.11) and with a lower body mass index (BMI) at booking in multiparous women (OR = 0.96; 95% CI: 0.92-0.99). The risk for any type of perineal trauma was associated with increased maternal age in the total sample (OR = 1.10; 95% CI: 1.07-1.13) and with a lower BMI at booking in multiparous women (OR = 0.95; 95% CI: 0.91-0.99). Conclusions: We found that giving birth in the water reduced the chance of having an intact perineum. We have also shown that nulliparity, increased maternal age in all women, and a lower BMI at booking in multiparous were associated with OASIS and lower rates of intact perineum in waterbirths.


Variational Bayesian approach to canonical correlation analysis.
As a dimension reduction algorithm, canonical correlation analysis (CCA) encounters the issue of selecting the number of canonical correlations. In this letter, we present a Bayesian model selection algorithm for CCA based on a probabilistic interpretation. A hierarchical Bayesian model is applied to probabilistic CCA and learned by variational approximation. This method not only estimates the model parameters, but also automatically determines the number of canonical correlations and avoids overfitting. Experiments show that it performs better compared with maximum likelihood and some other model selection methods.


The possibility of resistant hypertension during the treatment of hypertensive patients.
Patients with poorly controlled hypertension despite taking at least three different kinds of anti-hypertensive drugs, including diuretics, are considered to have resistant hypertension (RH). The prevalence of RH was reported to be 13% in the Japanese J-HOME study. The incidences of RH in younger and older Japanese individuals should be prospectively investigated in the near future. RH is associated with poor outcomes and various cardiovascular events. In addition, it is frequently associated with older age, obesity, sleep apnea, long-term hypertension, diabetes, dyslipidemia, reduced renal function, microalbuminuria and left ventricular hypertrophy. Some cases of RH exhibit high levels of aldosterone and cortisol, suggesting that endocrine hypertension should be ruled out among RH patients. Carotid baroreceptor activation and renal sympathetic denervation have recently been developed as treatments for RH. In conclusion, we should consider the possibility of RH during the treatment of hypertensive patients who do not achieve appropriate blood pressure control, in order to avoid the early onset of fatal cardiovascular events and reduce medical costs.


Shewanella gelidii sp. nov., isolated from the red algae Gelidium amansii, and emended description of Shewanella waksmanii.
A novel Gram-stain-negative, straight or slightly curved rod-shaped, non-spore-forming, facultatively anaerobic bacterium with a single polar flagellum, designated RZB5-4T, was isolated from a sample of the red algae Gelidium amansii collected from the coastal region of Rizhao, PR China (119.625° E 35.517° N). The organism grew optimally between 24 and 28 °C, at pH 7.0 and in the presence of 2-3 % (w/v) NaCl. The strain required seawater or artificial seawater for growth, and NaCl alone did not support growth. Strain RZB5-4T contained C16 : 1ω7c and/or C16 : 1ω6c, C16 : 0 and iso-C15 : 0 as the dominant fatty acids. The respiratory quinones detected in strain RZB5-4T were ubiquinone 7, ubiquinone 8, menaquinone 7 and methylmenaquinone 7. The polar lipids of strain RZB5-4T comprised phosphatidylethanolamine, phosphatidylglycerol, phosphatidylmonomethylethanolamine, one unidentified glycolipid, one unidentified phospholipid and one unknown lipid. The DNA G+C content of strain RZB5-4T was 47 mol %. Phylogenetic analysis based on 16S rRNA and gyrase B (gyrB) gene sequences showed that strain RZB5-4T belonged to the genus Shewanella, clustering with Shewanella waksmanii ATCC BAA-643T. Strain RZB5-4T exhibited the highest 16S rRNA gene sequence similarity value (96.6 %) and the highest gyrB gene sequence similarity value (80.7 %), respectively, to S. waksmanii ATCC BAA-643T. On the basis of polyphasic analyses, strain RZB5-4T represents a novel species of the genus Shewanella, for which the name Shewanella gelidii sp. nov. is proposed. The type strain is RZB5-4T (=JCM 30804T=KCTC 42663T=MCCC 1K00697T).


Effect of lesions of the superior portion of the glenoid labrum on glenohumeral translation.
Lesions of the superior portion of the glenoid labrum were created in seven cadaveric shoulders. The shoulders were mounted on a special apparatus attached to a servocontrolled hydraulic materials-testing device. Sequential fifty-newton anterior, posterior, superior, and inferior forces and a twenty-two-newton joint compressive load were applied to the shoulders. In addition, a fifty-five-newton force was applied to the tendon of the long head of the biceps brachii. The shoulders were tested in seven positions of glenohumeral elevation and rotation. An isolated lesion of the anterosuperior portion of the labrum, which did not involve the supraglenoid insertion of the biceps brachii, had no significant effect on anteroposterior or superoinferior glenohumeral translation, either with or without application of the fifty-five-newton force to the biceps brachii tendon. In contrast, a complete lesion of the superior portion of the labrum that destabilized the insertion of the biceps resulted in significant increases in anteroposterior and superoinferior glenohumeral translations. At 45 degrees of glenohumeral elevation, the complete lesion led to a 6.0-millimeter increase in anterior translation when the arm was in neutral rotation and to a 6.3-millimeter increase when the arm was in internal rotation; inferior translation also increased, by 1.9 to 2.5 millimeters. The increases in translation persisted despite application of a fifty-five-newton force to the long head of the biceps.


Biocontrol of Bacillus subtilis against infection of Arabidopsis roots by Pseudomonas syringae is facilitated by biofilm formation and surfactin production.
Relatively little is known about the exact mechanisms used by Bacillus subtilis in its behavior as a biocontrol agent on plants. Here, we report the development of a sensitive plant infection model demonstrating that the bacterial pathogen Pseudomonas syringae pv tomato DC3000 is capable of infecting Arabidopsis roots both in vitro and in soil. Using this infection model, we demonstrated the biocontrol ability of a wild-type B. subtilis strain 6051 against P. syringae. Arabidopsis root surfaces treated with B. subtilis were analyzed with confocal scanning laser microscopy to reveal a three-dimensional B. subtilis biofilm. It is known that formation of biofilms by B. subtilis is a complex process that includes secretion of surfactin, a lipopeptide antimicrobial agent. To determine the role of surfactin in biocontrol by B. subtilis, we tested a mutant strain, M1, with a deletion in a surfactin synthase gene and, thus, deficient in surfactin production. B. subtilis M1 was ineffective as a biocontrol agent against P. syringae infectivity in Arabidopsis and also failed to form robust biofilms on either roots or inert surfaces. The antibacterial activity of surfactin against P. syringae was determined in both broth and agar cultures and also by live-dead staining methods. Although the minimum inhibitory concentrations determined were relatively high (25 microg mL(-1)), the levels of the lipopeptide in roots colonized by B. subtilis are likely to be sufficient to kill P. syringae. Our results collectively indicate that upon root colonization, B. subtilis 6051 forms a stable, extensive biofilm and secretes surfactin, which act together to protect plants against attack by pathogenic bacteria.


Transgenic rice grains expressing a heterologous ρ-hydroxyphenylpyruvate dioxygenase shift tocopherol synthesis from the γ to the α isoform without increasing absolute tocopherol levels.
We generated transgenic rice plants overexpressing Arabidopsis thaliana ρ-hydroxyphenylpyruvate dioxygenase (HPPD), which catalyzes the first committed step in vitamin E biosynthesis. Transgenic grains accumulated marginally higher levels of total tocochromanols than controls, reflecting a small increase in absolute tocotrienol synthesis (but no change in the relative abundance of the α and γ isoforms). In contrast, there was no change in the absolute tocopherol level, but a significant shift from the γ to the α isoform. These data confirm HPPD is not rate limiting, and that increasing flux through the early pathway reveals downstream bottlenecks that act as metabolic tipping points.


Differential IgG4-Producing Plasma Cell Infiltration in Non- and Post-Transplant Plasma Cell Hepatitis.
Autoimmune hepatitis (AIH), post-transplant recurrent AIH (rAIH), and plasma cell-rich rejection (PCR) are clinical diagnoses with the shared histopathologic hallmark of plasma cell hepatitis (PCH). As these histologically and serologically indistinguishable diagnoses are differentiated by clinical context, it remains uncertain whether they represent distinct immunologic phenomena. Improved understanding of immunoglobulin subclass 4-producing plasma cells (IgG4-PC) has brought attention to IgG4 as an immunophenotypic biomarker. To date, degree and clinical significance of IgG4-PC infiltration in PCH remain elusive. This retrospective, single-center study assessed IgG4-PC infiltration in AIH, rAIH, and PCR via standardized immunohistochemistry analysis. Identified cases from 2005 to 2020 (n = 47) included AIH (treatment-naïve AIH (tnAIH): n = 15 and AIH-flare on treatment (fAIH); n = 10), rAIH (n = 8), and PCR (n = 14) were analyzed and correlated with clinical characteristics. IgG4-Positivity (# IgG4-PC/# pan-IgG-expressing cells) distribution was heterogenous and overlapping [tnAIH: 0.060 (IQR 0.040-0.079), fAIH: 0.000 (0.000-0.033), rAIH: 0.000 (0.000-0.035), PCR: 0.228 (0.039-0.558)]. IgG4-Positivity was inversely correlated with corticosteroid use (p < 0.001). IgG4-Positivity ≥0.500 was associated with rapid AST improvement (p = 0.03). The variable IgG4-Positivity of AIH, rAIH and PCR suggests diverse and overlapping immunopathologic mechanisms and that current diagnostic schemes inadequately capture PCH immunopathology. We propose incorporation of IgG4-Positivity to refine current PCH classification and treatment strategies.


Molecular Doping of a Naphthalene Diimide-Bithiophene Copolymer and SWCNTs for n-Type Thermoelectric Composites.
Molecular doping is a powerful tool to tune the thermoelectric (TE) properties of solution-processed semiconductors. In this work, we prepared a binary composite and effectively doped both of its constituents, that is, naphthalene diimide-bithiophene copolymers (PNDI2OD-T2) and single-walled carbon nanotubes (SWCNTs), by a 1H-benzimidazole derivative (N-DMBI). The doped composites show an n-type character and an in-plane TE figure of merit (ZT), exceeding the values obtained with the doped polymers. The use of SWCNTs consistently results in a higher σ with a maximum value above 102 S/cm, resulting in the highest power factor of 18.1 μW/mK2 for an SWCNT loading of 45.5 wt %. Furthermore, an SWCNT content up to 9 wt % does not compromise the low thermal conductivity of the polymer matrices, leading to a ZT value of 0.0045. The n-type composites show good solution processability and relatively stable Seebeck coefficients upon air exposure for 8 months.


A cationic cesium continuum in zeolite x.
A cesium continuum that fills the channels and cavities of zeolite X has been prepared, and its structure has been determined by single-crystal x-ray crystallography. The three-dimensional continuum is cationic to balance the negative charge of the zeolite framework. Its valence electrons, only 0.3 per Cs(+) ion, are widely delocalized over 95 percent of the cesium ions in the crystal. The continuum has a unit cell formula of (Cs(122))(86+) and contains Cs(13) and Cs(14) clusters (one per supercage) arranged like the atoms in diamond, with one Cs(2) appendix (in the sodalite cavity) per cluster.


Pulmonary complications of chronic neuromuscular diseases and their management.
Chronic neuromuscular diseases may affect all major respiratory muscles groups including inspiratory, expiratory, and bulbar, and respiratory complications are the major cause of morbidity and mortality. Untreated, many of these diseases lead inexorably to hypercapnic respiratory failure, precipitated in some cases by chronic aspiration and secretion retention or pneumonia, related to impairment of cough and swallowing mechanisms. Many measures are helpful including inhibition of salivation, cough-assist techniques, devices to enhance communication, and physical therapy. In addition, ventilatory assistance is an important part of disease management for patients with advanced neuromuscular disease. Because of its comfort, convenience, and portability advantages, noninvasive positive pressure ventilation (NPPV) has become the modality of first choice for most patients. Patients to receive NPPV should be selected using consensus guidelines, and initiation should be gradual to maximize the chances for success. Attention should be paid to individual preferences for interfaces and early identification of cough impairment that necessitates the use of cough-assist devices. For patients considered unsuitable for noninvasive ventilation, invasive mechanical ventilation should be considered, but only after a frank but compassionate discussion between the patient, family, physician, and other caregivers.


Metagenomic Analysis of Chicken Gut Microbiota for Improving Metabolism and Health of Chickens - A Review.
Chicken is a major food source for humans, hence it is important to understand the mechanisms involved in nutrient absorption in chicken. In the gastrointestinal tract (GIT), the microbiota plays a central role in enhancing nutrient absorption and strengthening the immune system, thereby affecting both growth and health of chicken. There is little information on the diversity and functions of chicken GIT microbiota, its impact on the host, and the interactions between the microbiota and host. Here, we review the recent metagenomic strategies to analyze the chicken GIT microbiota composition and its functions related to improving metabolism and health. We summarize methodology of metagenomics in order to obtain bacterial taxonomy and functional inferences of the GIT microbiota and suggest a set of indicator genes for monitoring and manipulating the microbiota to promote host health in future.


Structural and Chemical Properties of NiOx Thin Films: Oxygen Vacancy Formation in O2 Atmosphere.
NiOx films on Si(111) were put in contact with oxygen at elevated temperatures. During heating and cooling in oxygen atmosphere Near Ambient Pressure (NAP)-XPS and -XAS and work function (WF) measurements reveal the creation and replenishing of oxygen vacancies in dependence of temperature. Oxygen vacancies manifest themselves as a distinct O1s feature at 528.9 eV on the low binding energy side of the main NiO peak as well as by a distinct deviation of the Ni2p3/2 spectral features from the typical NiO spectra. DFT calculations reveal that the presence of oxygen vacancies leads to a charge redistribution and altered bond lengths of the atoms surrounding the vacancies causing the observed spectral changes. Furthermore, we observed that a broadening of the lowest energy peak in the O K-edge spectra can be attributed to oxygen vacancies. In the presence of oxygen vacancies, the WF is lowered by 0.1 eV.


Experimental evaluation of susceptibility to fractures of the orbital floor in patients with unilateral complete cleft palate.
We set out this study to verify a hypothesis that orbital floor fractures tend to affect wider areas in patients with unilateral complete cleft palate. Using a striking machine, the inferior orbital rims of eight normal skulls (intact skull group) and eight skulls with parts of the maxillas removed to simulate alveolar and palatal clefts (cleft skull group) were impacted. The fractured areas were compared. Models designed using a computer were produced to simulate the skulls of 12 normal people and 12 patients with left unilateral complete cleft palate, and were classified as the intact model group and the cleft model group, respectively. Computer simulation of applying external forces to the inferior orbital rim of each model was performed. Areas where stresses exceeded the bone-yielding threshold were compared. Actual fractured areas were significantly larger in the cleft skull group than in the intact skull group. Theoretical fracture areas were also significantly greater in the cleft model group than in the intact model group. We conclude that orbital floor fractures develop in wider areas in patients with unilateral complete cleft palates, because of the instability of the maxilla on the cleft side.


Combining electronic healthcare databases in Europe to allow for large-scale drug safety monitoring: the EU-ADR Project.
In this proof-of-concept paper we describe the framework, process, and preliminary results of combining data from European electronic healthcare record (EHR) databases for large-scale monitoring of drug safety. Aggregated demographic, clinical, and prescription data from eight databases in four countries (Denmark, Italy, Netherlands, the UK) were pooled using a distributed network approach by generation of common input data followed by local aggregation through custom-built software, Jerboa(©). Comparison of incidence rates of upper gastrointestinal bleeding (UGIB) and nonsteroidal anti-inflammatory drug (NSAID) utilization patterns were used to evaluate data harmonization and quality across databases. The known association of NSAIDs and UGIB was employed to demonstrate sensitivity of the system by comparing incidence rate ratios (IRRs) of UGIB during NSAID use to UGIB during all other person-time. The study population for this analysis comprised 19,647,445 individuals corresponding to 59,929,690 person-years of follow-up. 39,967 incident cases of UGIB were identified during the study period. Crude incidence rates varied between 38.8 and 109.5/100,000 person-years, depending on country and type of database, while age-standardized rates ranged from 25.1 to 65.4/100,000 person-years. NSAID use patterns were similar for databases within the same country but heterogeneous among different countries. A statistically significant age- and gender-adjusted association between use of any NSAID and increased risk for UGIB was confirmed in all databases, IRR from 2.0 (95%CI:1.7-2.2) to 4.3 (95%CI: 4.1-4.5). Combining data from EHR databases of different countries to identify drug-adverse event associations is feasible and can set the stage for changing and enlarging the scale for drug safety monitoring.


Pathogenesis and Inhibition of Flaviviruses from a Carbohydrate Perspective.
Flaviviruses are enveloped, positive single stranded ribonucleic acid (RNA) viruses with various routes of transmission. While the type and severity of symptoms caused by pathogenic flaviviruses vary from hemorrhagic fever to fetal abnormalities, their general mechanism of host cell entry is similar. All pathogenic flaviviruses, such as dengue virus, yellow fever virus, West Nile virus, Japanese encephalitis virus, and Zika virus, bind to glycosaminglycans (GAGs) through the putative GAG binding sites within their envelope proteins to gain access to the surface of host cells. GAGs are long, linear, anionic polysaccharides with a repeating disaccharide unit and are involved in many biological processes, such as cellular signaling, cell adhesion, and pathogenesis. Flavivirus envelope proteins are N-glycosylated surface proteins, which interact with C-type lectins, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) through their glycans. In this review, we discuss both host and viral surface receptors that have the carbohydrate components, focusing on the surface interactions in the early stage of flavivirus entry. GAG-flavivirus envelope protein interactions as well as interactions between flavivirus envelope proteins and DC-SIGN are discussed in detail. This review also examines natural and synthetic inhibitors of flaviviruses that are carbohydrate-based or carbohydrate-targeting. Both advantages and drawbacks of these inhibitors are explored, as are potential strategies to improve their efficacy to ultimately help eradicate flavivirus infections.


gamma-Aminobutyric acid type A receptor antagonists picrotoxin and bicuculline alter acetylcholine channel kinetics in cultured embryonic rat skeletal muscle.
The effects of the classical gamma-aminobutyric acid type A receptor antagonists picrotoxin and bicuculline on nicotinic acetylcholine receptors in cultured embryonic rat skeletal muscle were examined with whole-cell and cell-attached single-channel recording methods. Up to 600 microM picrotoxin had little or no effect on the amplitude of the whole-cell current, whereas bicuculline dose-dependently blocked it, with an IC50 value of 101.2 +/- 8.9 microM. Bicuculline reduced the maximum inducible acetylcholine current without changing the Kd value, suggesting that bicuculline uncompetitively blocked the binding of acetylcholine to its receptor. The elementary nicotinic acetylcholine receptor currents recorded in the cell-attached single-channel recording configuration exhibited properties typical of those recorded in embryonic muscle (approximately 36 pS and approximately 6 msec). Picrotoxin dramatically transformed individual channel openings into briefly interrupted bursts, so that the number of openings increased while the mean open time markedly decreased. Bicuculline decreased mean open time to a lesser but statistically significant degree. The dominant component of the closed time histogram in control recordings occurred at 17 msec, whereas that recorded with picrotoxin occurred at 0.5 msec. Bicuculline prolonged the closed time, with a dominant closed time component at 52 msec. Elementary conductance was not altered by either agent. In conclusion, we found that the gamma-aminobutyric acid type A channel antagonists picrotoxin and bicuculline were also blockers of embryonic nicotinic acetylcholine receptor channels in cultured rat muscle.


Monoacylglycerol lipase activity is a critical modulator of the tone and integrity of the endocannabinoid system.
Endocannabinoids are lipid molecules that serve as natural ligands for the cannabinoid receptors CB1 and CB2. They modulate a diverse set of physiological processes such as pain, cognition, appetite, and emotional states, and their levels and functions are tightly regulated by enzymatic biosynthesis and degradation. 2-Arachidonoylglycerol (2-AG) is the most abundant endocannabinoid in the brain and is believed to be hydrolyzed primarily by the serine hydrolase monoacylglycerol lipase (MAGL). Although 2-AG binds and activates cannabinoid receptors in vitro, when administered in vivo, it induces only transient cannabimimetic effects as a result of its rapid catabolism. Here we show using a mouse model with a targeted disruption of the MAGL gene that MAGL is the major modulator of 2-AG hydrolysis in vivo. Mice lacking MAGL exhibit dramatically reduced 2-AG hydrolase activity and highly elevated 2-AG levels in the nervous system. A lack of MAGL activity and subsequent long-term elevation of 2-AG levels lead to desensitization of brain CB1 receptors with a significant reduction of cannabimimetic effects of CB1 agonists. Also consistent with CB1 desensitization, MAGL-deficient mice do not show alterations in neuropathic and inflammatory pain sensitivity. These findings provide the first genetic in vivo evidence that MAGL is the major regulator of 2-AG levels and signaling and reveal a pivotal role for 2-AG in modulating CB1 receptor sensitization and endocannabinoid tone.


High prevalence of prior contact sports play and concussion among orthopedic and neurosurgical department chairs.
OBJECTIVE Increased understanding of the consequences of traumatic brain injury has heightened concerns about youth participation in contact sports. This study investigated the prevalence of high school and collegiate contact sports play and concussion history among surgical department chairs. METHODS A cross-sectional survey was administered to 107 orthopedic and 74 neurosurgery chairs. Responses were compared to published historical population norms for contact sports (high school 27.74%, collegiate 1.44%), football (high school 10.91%, collegiate 0.76%), and concussion prevalence (12%). One-proportion Z-tests, chi-square tests, and binary logistic regression were used to analyze differences. RESULTS High school contact sports participation was 2.35-fold higher (65.3%, p < 0.001) for orthopedic chairs and 1.73-fold higher (47.9%, p = 0.0018) for neurosurgery chairs than for their high school peers. Collegiate contact sports play was 31.0-fold higher (44.7%, p < 0.001) for orthopedic chairs and 15.1-fold higher (21.7%, p < 0.001) for neurosurgery chairs than for their college peers. Orthopedic chairs had a 4.30-fold higher rate of high school football participation (46.9%, p < 0.001) while neurosurgery chairs reported a 3.05-fold higher rate (33.3%, p < 0.001) than their high school peers. Orthopedic chairs reported a 28.1-fold higher rate of collegiate football participation (21.3%, p < 0.001) and neurosurgery chairs reported an 8.58-fold higher rate (6.5%, p < 0.001) compared to their college peers. The rate at which orthopedic (42.6%, p < 0.001) and neurosurgical (42.4%, p < 0.001) chairs reported having at least 1 concussion in their lifetime was significantly higher than the reported prevalence in the general population. After correction for worst possible ascertainment bias, all results except high school contact sports participation remained significant. CONCLUSIONS The high prevalence of youth contact sports play and concussion among surgical specialty chairs affirms that individuals in careers requiring high motor and cognitive function frequently played contact sports. The association highlights the need to further examine the relationships between contact sports and potential long-term benefits as well as risks of sport-related injury.


The virtual frame technique: ultrafast imaging with any camera.
Many phenomena of interest in nature and industry occur rapidly and are difficult and cost-prohibitive to visualize properly without specialized cameras. Here we describe in detail the virtual frame technique (VFT), a simple, useful, and accessible mode of imaging that increases the frame acquisition rate of any camera by several orders of magnitude by leveraging its dynamic range. The VFT is a powerful tool for capturing rapid phenomena where the dynamics facilitate a transition between two states, and are thus binary. The advantages of the VFT are demonstrated by examining such dynamics in five physical processes at unprecedented rates and spatial resolution: fracture of an elastic solid, wetting of a solid surface, rapid fingerprint reading, peeling of adhesive tape, and impact of an elastic hemisphere on a hard surface. We show that the performance of the VFT exceeds that of any commercial high-speed camera not only in rate of imaging but also in field of view, achieving a 65MHz frame rate at 4MPx resolution. Finally, we discuss the performance of the VFT with several commercially available conventional and high-speed cameras. In principle, modern cell phones can achieve imaging rates of over a million frames per second using the VFT.


Involvement of CD14 and toll-like receptor 4 in the acute phase response of serum amyloid A proteins and serum amyloid P component in the liver after burn injury.
Acute phase proteins such as serum amyloid A proteins (SAAs) and serum amyloid P component (SAP) are induced in the liver after various insults (e.g., infection, injury). The cellular and molecular mechanisms controlling the expression of these acute phase proteins may be specifically designed for different insults. The roles of two central molecules of the lipopolysaccharide (LPS)-mediated inflammation pathway (CD14 and toll-like receptor 4 [Tlr4]) were investigated for the regulation of SAAs and SAP in the liver of mice after an 18% total body surface area burn injury. RT-PCR analysis revealed a subtype- and time-dependent induction of SAA mRNAs between 3 h and 3 days, while there was a peak induction of SAP mRNA at day 1. Marked elevations of SAA and SAP protein levels at day 1 supported the mRNA data. Furthermore, a differential regulation of SAAs and SAP mRNAs was noted between CD14 knockout (KO) and their control mice after injury. SAA protein was induced to a lesser degree after injury in C3H/HeJ (Tlr4-defective) mice than in their control mice. In addition, in both CD14 KO and C3H/HeJ mice, the induction of SAP protein was significantly reduced compared with respective controls. These data provide evidence that CD14 and Tlr4 participate, at least in part, in a cascade of signaling events that control the immediate-early and differential induction of SAAs and SAP in the liver after injury. They also suggest that LPS may be one of the initial inducing agents associated with these acute phase responses in the liver after injury.


Smoke-free legislation: global reach, impact and remaining challenges.
Article 8 of the World Health Organization Framework Convention on Tobacco Control (2005) requires all signatory countries to adopt measures to protect people from tobacco smoke in indoor workplaces, indoor public places, public transport and other public places as appropriate. The aims of this symposium were to review progress across the world, to assess the evidence for the impact of legislation on health, and to identify the continuing challenges in making universal protection a reality. There was agreement that even in countries where strict legislation is enforced, many children continue to be dangerously exposed to parental second-hand smoke in the womb, the home and private cars. The importance of using accurate estimates of the burden of disease caused by second-hand smoke was agreed, in order to present an unassailable case for legislation and enforcement.


Using physician billing claims from the Ontario Health Insurance Plan to determine individual influenza vaccination status: an updated validation study.
Owing to the absence of a vaccination registry in Ontario, administrative data are currently the best available source to determine population-based individual-level influenza vaccination status. Our objective was to validate physician billing claims for influenza vaccination in the Ontario Health Insurance Plan database against the Canadian Community Health Survey. We used self-reported seasonal influenza vaccination status of Ontario residents surveyed between 2007 and 2009 as the reference standard. The survey responses were linked to physician claims database records to validate billing codes for influenza vaccination. We calculated sensitivity, specificity, positive predictive value and negative predictive value with 95% confidence intervals (CIs). We stratified the data by several covariates and comorbidities to determine stratum-specific performance characteristics. We used these estimates to adjust an estimate of influenza vaccine effectiveness for the 2010/11 influenza season. For the 47 301 patients included in the analysis, the sensitivity for the billing codes was 49.8% (95% CI 49.0%-50.5%), specificity was 95.7% (95% CI 95.5%-96.0%), positive predictive value was 88.4% (95% CI 87.8%-89.0%) and negative predictive value was 74.5% (95% CI 74.0%-74.9%). Performance measures were optimized in patients aged 65 years and older, particularly those with comorbidities. Although administrative data have limitations for determining influenza vaccination status, owing to the high positive predictive value, they are well suited for self-controlled study designs that are often used to assess vaccine safety. For studies of coverage and effectiveness, restricting the cohort to patients aged 65 years and older will minimize misclassification bias. Performance characteristics from this study can be used to mitigate misclassification bias.


Leveraging African American family connectors for Alzheimer's disease genomic studies.
The underrepresentation of African Americans (AAs) in Alzheimer's disease (AD) research may limit potential benefits from translational applications. This article describes an approach to recruit AA families into an AD genomic study and characteristics of seeds (family connectors) used to overcome recruitment barriers of AA families into AD research. A four-step outreach and snowball sampling approach relying on family connectors was used to recruit AA families. Descriptive statistics of a profile survey were gathered to understand the demographic and health characteristics of family connectors. Twenty-five AA families (117 participants) were enrolled in the study via family connectors. Most family connectors self-identified as female (88%), were 60 years of age or older (76%), and attained post-secondary education (77%). Community-engaged strategies were essential to recruit AA families. Relationships between study coordinators and family connectors build trust early in the research process among AA families. Community events were most effective for recruiting African American families. Family connectors were primarily female, in good health, and highly educated. Systematic efforts by researchers are necessary to "sell" a study to participants.


Biological activities of fusarochromanone: a potent anti-cancer agent.
Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity. Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50 ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells. Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101's molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery.


MicroRNA expression profile in patients with cystic echinococcosis and identification of possible cellular pathways.
Cystic echinococcosis (CE) is a neglected tropical disease, caused by metacestode (larval) form of the Echinococcus granulosus sensu lato (sl) in humans. MicroRNAs (miRNAs) are small, stable, tissue-specific RNA molecules encoded by the genome that are not translated into proteins. Circulating miRNA expression profiles vary in health and disease. The aim of this study is to determine the altered cellular pathways in CE by comparing the miRNA profiles of controls and CE patients with active or inactive cysts. Following abdominal ultrasonography (US) examination, 20 patients diagnosed with active CE (CE1, CE2, CE3a and CE3b) or inactive CE (CE4 and CE5) and three healthy controls were included in the study. The expression profiles of 372 biologically relevant human miRNAs were investigated in serum samples from CE patients and healthy controls with miScript miRNA HC PCR Array. Compared with the control group, expression of 6 miRNAs (hsa-miR-4659a-5p, hsa-miR-4518, hsa-miR-3977, hsa-miR-4692, hsa-miR-181b-3p, hsa-miR-4491) and one miRNA (hsa-miR-4687-5p) were found to be downregulated in CE patients with active and inactive cysts, respectively (p < 0.05). For downregulated miRNAs in this study, predicted targets were found to be associated mainly with cell proliferation, apoptosis, cell-cell interactions and cell cycle regulation. Further studies in this direction may elucidate the pathogenesis of human CE and the relationship between CE and other pathologies.


Structural insights into activation of phosphatidylinositol 4-kinase (Pik1) by yeast frequenin (Frq1).
Yeast frequenin (Frq1), a small N-myristoylated EF-hand protein, activates phosphatidylinositol 4-kinase Pik1. The NMR structure of Ca2+-bound Frq1 complexed to an N-terminal Pik1 fragment (residues 121-174) was determined. The Frq1 main chain is similar to that in free Frq1 and related proteins in the same branch of the calmodulin superfamily. The myristoyl group and first eight residues of Frq1 are solvent-exposed, and Ca2+ binds the second, third, and fourth EF-hands, which associate to create a groove with two pockets. The Pik1 peptide forms two helices (125-135 and 156-169) connected by a 20-residue loop. Side chains in the Pik1 N-terminal helix (Val-127, Ala-128, Val-131, Leu-132, and Leu-135) interact with solvent-exposed residues in the Frq1 C-terminal pocket (Leu-101, Trp-103, Val-125, Leu-138, Ile-152, and Leu-155); side chains in the Pik1 C-terminal helix (Ala-157, Ala-159, Leu-160, Val-161, Met-165, and Met-167) contact solvent-exposed residues in the Frq1 N-terminal pocket (Trp-30, Phe-34, Phe-48, Ile-51, Tyr-52, Phe-55, Phe-85, and Leu-89). This defined complex confirms that residues in Pik1 pinpointed as necessary for Frq1 binding by site-directed mutagenesis are indeed sufficient for binding. Removal of the Pik1 N-terminal region (residues 8-760) from its catalytic domain (residues 792-1066) abolishes lipid kinase activity, inconsistent with Frq1 binding simply relieving an autoinhibitory constraint. Deletion of the lipid kinase unique motif (residues 35-110) also eliminates Pik1 activity. In the complex, binding of Ca2+-bound Frq1 forces the Pik1 chain into a U-turn. Frq1 may activate Pik1 by facilitating membrane targeting via the exposed N-myristoyl group and by imposing a structural transition that promotes association of the lipid kinase unique motif with the kinase domain.


The role of vaginal brachytherapy in stage I endometrial serous cancer: a systematic review.
Serous adenocarcinoma (uterine serous carcinoma - USC) is a rare and aggressive histologic subtype of endometrial cancer, with a high-rate of recurrence and poor prognosis. The adjuvant treatment for stage I patients is unclear. The purpose of this study was to evaluate the outcomes of stage I USC treated exclusively with chemotherapy plus vaginal brachytherapy (VBT). A systematic research using PubMed, Scopus, and Cochrane library was conducted to identify full articles evaluating the efficacy of VBT in patients with stage I USC. A search in ClinicalTrials.gov was performed in order to detect ongoing or recently completed trials, and in PROSPERO for searching ongoing or recently completed systematic reviews. All studies were retrospective and 364 of evaluated patients were found. The average local control was 97.5% (range, 91-100%), the disease free-survival was 88% (range, 82-94%), the overall survival was 93% (range, 72-100%), the specific cancer survival was 89.4% (range, 84.8-94%), and the G3-G4 toxicity was 0-8%. These data support the concept that in adequately selected patients, VBT alone may be a suitable radiotherapy technique in women with stage I USC who underwent surgical staging and received adjuvant chemotherapy.


Socioeconomic factors and self-reported health outcomes in African Americans with rheumatoid arthritis from the Southeastern United States: the contribution of childhood socioeconomic status.
There is abundant evidence that low socioeconomic status (SES) is associated with worse health outcomes among people with Rheumatoid Arthritis (RA); however, the influence of socioeconomic disadvantage in early life has yet to be studied within that population. Data originated from the cross-sectional arm of the Consortium Evaluation of African-Americans with Rheumatoid Arthritis (CLEAR II), which recruited African-Americans with RA from six sites in the Southeastern United States. We used linear regression models to evaluate associations of parental homeownership status and educational level at participant time of birth with participant-reported fatigue (Visual Analog scale, cm), pain (Visual Analog scale, cm), disability (Health Assessment Questionnaire) and helplessness (Rheumatology Attitudes Index), independently of participant homeownership status and educational level. Models included random effects to account for intra-site correlations, and were adjusted for variables identified using backward selection, from: age, disease-duration, sex, medication use, body-mass index, smoking history. Our sample included 516 CLEAR II participants with full data on demographics and covariates. 89% of participants were women, the mean age was 54.7 years and mean disease duration was 10.8 years. In age adjusted models, parental non-homeownership was associated with greater fatigue (β = 0.75, 95% CI = 0.36-1.14), disability (β = 0.12, 95% CI = 0.04-0.19) and helplessness (β = 0.12, 95% CI = 0.03-0.21), independently of participant homeownership and education; parental education had a further small influence on self-reported fatigue (β = 0.20, 95% CI = 0.15-0.24). Parental homeownership, and to a small extent parental education, had modest but meaningful relationships with self-reported health among CLEAR II participants.


Mobile health technologies in the diagnosis and management of atrial fibrillation.
Atrial fibrillation is the most common sustained rhythm abnormality and is associated with stroke, heart failure, cognitive decline, and premature death. Digital health technologies using consumer-grade mobile technologies (i.e. mHealth) capable of recording heart rate and rhythm can now reliably detect atrial fibrillation using single lead or multilead ECG or photoplethysmography (PPG). This review will discuss how these developments are being used to detect and manage atrial fibrillation. Studies have established the accuracy of mHealth devices for atrial fibrillation detection. The feasibility of using mHealth technology to screen for atrial fibrillation has also been established, though the utility of screening is controversial. In addition to screening, key aspects of atrial fibrillation management can also be performed remotely and effectively using mHealth, though with some important limitations. mHealth technologies have proven disruptive in the diagnosis and management of atrial fibrillation. Healthcare providers can leverage these advances to better care for their atrial fibrillation patients whenever necessary.


Idiopathic esophagopleural fistula in the newborn. A review, with a case report.
Idiopathic rupture of the esophagus in the neonate is a rare event, probably related to the same mechanism of ischemic necrosis responsible for other "spontaneous" g.i. tract perforations in the newborn. The laceration is usually located on the right aspect of the distal esophagus and is complicated by esophagopleural fistula and hydropneumothorax. Plain chest film and esophagography are diagnostic. The condition is an emergency one and usually carries a bad prognosis without prompt surgical repair. A typical case is reported in a baby who survived without early surgery; a residual tiny blind pouch and a small hiatal hernia required surgery at 1 year of age.


Dichloroacetate does not speed phase-II pulmonary VO2 kinetics following the onset of heavy intensity cycle exercise.
We hypothesised that pharmacological activation of the pyruvate dehydrogenase enzyme complex (PDC) by dichloroacetate (DCA) would speed phase-II pulmonary O2 uptake (VO2) kinetics following the onset of high-intensity, sub-maximal exercise. Eight healthy males (aged 19-33 years) completed two "square-wave" transitions of 6 min duration from unloaded cycling to a work-rate equivalent to approximately 80% of peak VO2 either with or without prior i.v. infusion of DCA (50 mg kg(-1) body mass in 50 ml saline). Pulmonary VO2 was measured breath-by-breath throughout all tests, and VO2 kinetics were determined using non-linear regression techniques from the averaged individual response to each of the conditions. Infusion of DCA resulted in significantly lower blood [lactate] during the baseline cycling period (means+/-SEM: control 0.9+/-0.1, DCA 0.5+/-0.1 mM; P<0.01) consistent with successful activation of PDC. However, DCA had no discernible effect on the rate at which VO2 increased towards the initially anticipated steady state following the onset of exercise as reflected in the time constant of the fundamental VO2 response (control 26.7+/-4.1, DCA 27.7+/-2.8 s). These results indicate that the principal limitation to oxidative metabolism following the onset of high-intensity, sub-maximal cycle exercise lies downstream from PDC and/or that muscle O2 consumption is primarily under "feedback" control via the concentration of one or more of the reactants associated with ATP hydrolysis.


[Oncological patients in primary care : ruptures and transitions].
Patients with severe cancer go through a journey requiring the involvement of several healthcare providers. Several transitions of care occur: from the general practitioner to the oncologist, and then depending on the outcomes of treatment, the patient enters a palliative care phase, and eventually end of life care. Lack of coordination of the different actors can lead to repeated loss of the continuum of care. Each transition requires better communication between healthcare providers and also with the patient. Improving communication skills could improve the definition of care goals, support family caregivers, facilitate early contact with a palliative care team, and better respect patient choices.


Cortical Control of Spatial Resolution by VIP+ Interneurons.
Neuronal tuning, defined by the degree of selectivity to a specific stimulus, is a hallmark of cortical computation. Understanding the role of GABAergic interneurons in shaping cortical tuning is now possible with the ability to manipulate interneuron classes selectively. Here, we show that interneurons expressing vasoactive intestinal polypeptide (VIP+) regulate the spatial frequency (SF) tuning of pyramidal neurons in mouse visual cortex. Using two-photon calcium imaging and optogenetic manipulations of VIP+ cell activity, we found that activating VIP+ cells elicited a stronger network response to stimuli of higher SFs, whereas suppressing VIP+ cells resulted in a network response shift toward lower SFs. These results establish that cortical inhibition modulates the spatial resolution of visual processing and add further evidence demonstrating that feature selectivity depends, not only on the feedforward excitatory projections into the cortex, but also on dynamic intracortical modulations by specific forms of inhibition. We demonstrate that interneurons expressing vasoactive intestinal polypeptide (VIP+) play a causal role in regulating the spatial frequency (SF) tuning of neurons in mouse visual cortex. We show that optogenetic activation of VIP+ cells results in a shift in network preference toward higher SFs, whereas suppressing them shifts the network toward lower SFs. Several studies have shown that VIP+ cells are sensitive to neuromodulation and increase their firing during locomotion, whisking, and pupil dilation and are involved in spatially specific top-down modulation, reminiscent of the effects of top-down attention, and also that attention enhances spatial resolution. Our findings provide a bridge between these studies by establishing the inhibitory circuitry that regulates these fundamental modulations of SF in the cortex.


Synaptic Wnt/GSK3β Signaling Hub in Autism.
Hundreds of genes have been associated with autism spectrum disorders (ASDs) and the interaction of weak and de novo variants derive from distinct autistic phenotypes thus making up the "spectrum." The convergence of these variants in networks of genes associated with synaptic function warrants the study of cell signaling pathways involved in the regulation of the synapse. The Wnt/β-catenin signaling pathway plays a central role in the development and regulation of the central nervous system and several genes belonging to the cascade have been genetically associated with ASDs. In the present paper, we review basic information regarding the role of Wnt/β-catenin signaling in excitatory/inhibitory balance (E/I balance) through the regulation of pre- and postsynaptic compartments. Furthermore, we integrate information supporting the role of the glycogen synthase kinase 3β (GSK3β) in the onset/development of ASDs through direct modulation of Wnt/β-catenin signaling. Finally, given GSK3β activity as key modulator of synaptic plasticity, we explore the potential of this kinase as a therapeutic target for ASD.


Screening for Gaucher Disease Using Dried Blood Spot Tests: A Japanese Multicenter, Cross-sectional Survey.
Objective For patients with Gaucher disease (GD), a rare, inherited lysosomal storage disease, obtaining a definitive diagnosis is currently time-consuming and costly. A simplified screening method to measure the glucocerebrosidase (GBA) activity using dried blood spots (DBS) on filter paper has recently been developed. Using this newly developed screening method, we evaluated real-world GD screening in patients suspected of having GD. Methods This multicenter, cross-sectional, observational study with a diagnostic intervention component evaluated real-world screening in patients suspected of having GD based on their clinical symptoms and a platelet count <120,000/μL. The endpoint was the number of patients with low GBA activity determined using DBS. Results In 994 patients who underwent initial DBS screening, 77 had low GBA activity. The assay was not repeated in 1 patient who was diagnosed as having a high possibility of GD due to clinical symptoms, and a further 21 patients completed the study without undergoing the second assay. Of the remaining 55 patients who had 2 DBS assays performed, 11 had a low GBA activity in both assays. Overall, DBS screening identified 12 (1.2%) patients with a low GBA activity, a proportion consistent with prior screening studies. Conclusion These results suggest that the simplified DBS method was less burdensome to patients, was easily utilized by many physicians, and could be a useful first-tier screening assay for GD prior to initiating burdensome genetic testing.


Metal-organic frameworks catalyzed C-C and C-heteroatom coupling reactions.
Metal organic frameworks (MOFs) are porous crystalline solids whose structure is formed by metal ions or clusters of a few metal ions held in place by bi- or multipodal organic linkers. In some cases, the metal nodes in MOFs have exchangeable coordination positions that allow them to participate as active sites promoting organic reactions. There is much current interest in exploiting the advantages that MOFs offer as catalysts, including a large surface area, high metal content, flexibility in the design of the active sites in the framework, together with the easy synthesis of these materials. In the present review we describe the use of MOFs as catalysts to promote cross-coupling reactions involving organometallic reaction intermediates and catalysis by Lewis acid sites. These types of reactions are of large synthetic utility due to the high yields achieved, mild conditions and compatibility with other functional groups. The content includes C-C bond forming reactions, such as Suzuki-Miyaura, Mizoroki-Heck, Sonogashira, Stille and Ullmann, but also C-O and C-N cross-couplings. The final section summarizes our views on future developments and targets in these types of reactions. The core of the review is references that have appeared in 2010 or after, which give an idea of the novelty and current interest in this area.


Adaptation of the vestibulo-ocular reflex in amblyopia.
Adaptation of the vestibulo-ocular reflex (VOR) is demonstrated by changes in gain in response to discrepancies between visual and vestibular stimulation. The authors have investigated the effect of monocular asymmetries of OKN in amblyopia upon adapting the gain of the VOR. Adaptation was investigated by modifying the horizontal balance of the VOR. While monocularly fixating a head referenced spot for 2 min, subjects were sinusoidally oscillated on a chair inside an optokinetic drum that rotated in one direction (left or right) at the peak velocity of sinusoidal chair rotation. The VOR was then measured during continued sinusoidal body oscillation in darkness for 1 min. Imbalance of the horizontal VOR gain equalled the ratio of slow phase velocities in the rightward and leftward directions. After rotating the drum in the nasalward direction, an increase was observed in slow phase gain of the VOR in the nasalward direction for either eye of our amblyopes that was significantly greater than similar changes in gain for the normals. Increased VOR gains for the amblyopic group following temporalward stimulation were significantly less than the nasal aftereffect. Gain changes of the VOR in normals had similar magnitudes following nasal or temporal stimulation. These results suggest that disturbances of OKN in amblyopia are common to the pathways that modify the slow phase gain of the VOR.


Prevalence of SARS-CoV-2 in an area of unrestricted viral circulation: Mass seroepidemiological screening in Castiglione d'Adda, Italy.
Castiglione D'Adda is one of the municipalities more precociously and severely affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic in Lombardy. With our study we aimed to understand the diffusion of the infection by mass serological screening. We searched for SARS-CoV-2 IgGs in the entire population on a voluntary basis using lateral flow immunochromatographic tests (RICT) on capillary blood (rapid tests). We then performed chemioluminescent serological assays (CLIA) and naso-pharyngeal swabs (NPS) in a randomized representative sample and in each subject with a positive rapid test. Factors associated with RICT IgG positivity were assessed by uni- and multivariate logistic regression models. Out of the 4143 participants, 918 (22·2%) showed RICT IgG positivity. In multivariable analysis, IgG positivity increases with age, with a significant non-linear effect (p = 0·0404). We found 22 positive NPSs out of the 1330 performed. Albeit relevant, the IgG prevalence is lower than expected and suggests that a large part of the population remains susceptible to the infection. The observed differences in prevalence might reflect a different infection susceptibility by age group. A limited persistence of active infections could be found after several weeks after the epidemic peak in the area.


Eye-specific projections of retinogeniculate axons are altered in albino mice.
The divergence of retinal ganglion cell (RGC) axons into ipsilateral and contralateral projections at the optic chiasm and the subsequent segregation of retinal inputs into eye-specific domains in their target, the dorsal lateral geniculate nucleus (dLGN), are crucial for binocular vision. In albinism, affected individuals exhibit a lack or reduction of pigmentation in the eye and skin, a concomitant reduced ipsilateral projection, and diverse visual defects. Here we investigate how such altered decussation affects eye-specific retinogeniculate targeting in albino mice using the C57BL/6 Tyr(c-2J/c-2J) strain, in which tyrosinase, necessary for melanogenesis, is mutated. In albino mice, fewer RGCs from the ventrotemporal (VT) retina project ipsilaterally, reflected in a decrease in cells expressing ipsilateral markers. In addition, a population of RGCs from the VT retina projects contralaterally and, within the dLGN, their axons cluster into a patch separated from the contralateral termination area. Furthermore, eye-specific segregation is not complete in the albino dLGN and, upon perturbing postnatal retinal activity with epibatidine, the ipsilateral projection fragments and the aberrant contralateral patch disappears. These results suggest that the defects in afferent targeting and activity-dependent refinement in the albino dLGN arise from RGC misspecification together with potential perturbations of early activity patterns in the albino retina.


Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family.
The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. RV144 secondary immune correlate analysis demonstrated that the combination of low plasma anti-HIV-1 Env IgA antibodies and high levels of antibody-dependent cellular cytotoxicity (ADCC) inversely correlate with infection risk. One hypothesis is that the observed protection in RV144 is partially due to ADCC-mediating antibodies. We found that the majority (73 to 90%) of a representative group of vaccinees displayed plasma ADCC activity, usually (96.2%) blocked by competition with the C1 region-specific A32 Fab fragment. Using memory B-cell cultures and antigen-specific B-cell sorting, we isolated 23 ADCC-mediating nonclonally related antibodies from 6 vaccine recipients. These antibodies targeted A32-blockable conformational epitopes (n = 19), a non-A32-blockable conformational epitope (n = 1), and the gp120 Env variable loops (n = 3). Fourteen antibodies mediated cross-clade target cell killing. ADCC-mediating antibodies displayed modest levels of V-heavy (VH) chain somatic mutation (0.5 to 1.5%) and also displayed a disproportionate usage of VH1 family genes (74%), a phenomenon recently described for CD4-binding site broadly neutralizing antibodies (bNAbs). Maximal ADCC activity of VH1 antibodies correlated with mutation frequency. The polyclonality and low mutation frequency of these VH1 antibodies reveal fundamental differences in the regulation and maturation of these ADCC-mediating responses compared to VH1 bNAbs.


Effectiveness of mechanical separation for reducing ammonia loss from field-applied slurry: Assessment through literature review and model calculations.
To assess solid-liquid separation as a technology to reduce ammonia (NH3) emission from storage and field application of animal slurry, it is necessary to consider a possible higher NH3 loss from the solid fraction after application than from raw slurry, as well as losses during storage. A literature review was conducted, and a case study was developed for Denmark, including cattle slurry, pig slurry, and biogas digestate applied by trailing hose, trailing shoe, or open slot injection at five different periods of the year. Standard storage emission factors were used and emission factors after field application were estimated using the ALFAM2 model with input data for dry matter (DM), pH, total ammoniacal nitrogen (TAN), and separation efficiency all from the literature compilation. In general, a clear reduction in the emission factors after application of the liquid fraction was found relative to application of raw slurry in the literature data. Case study results provide some evidence that separation of cattle slurry or digestate, followed by storage and subsequent application by trailing hose or trailing shoe of the liquid fraction and broadcast application of the solid fraction reduces overall NH3 loss, with a higher reduction when the solid fraction is incorporated by plowing after 4 h. This effect was not present for pig slurry. For all slurry types when the raw slurry and liquid fraction is applied by open slot injection, the overall reduction in emission due to separation is not present or even negative.


Randomized prospective trial of cooled versus traditional radiofrequency ablation of the medial branch nerves for the treatment of lumbar facet joint pain.
No previous study has assessed the outcomes of cooled radiofrequency ablation (C-RFA) of the medial branch nerves (MBN) for the treatment of lumbar facet joint pain nor compared its effectiveness with traditional RFA (T-RFA). This study evaluated 6-month outcomes for pain, function, psychometrics, and medication usage in patients who underwent MBN C-RFA versus T-RFA for lumbar Z-joint pain. In this blinded, prospective trial, patients with positive diagnostic MBN blocks (>75% relief) were randomized to MBN C-RFA or T-RFA. The primary outcome was the proportion of 'responders' (≥50% Numeric Rating Scale (NRS) reduction) at 6 months. Secondary outcomes included NRS, Oswestry Disability Index (ODI), and Patient Global Impression of Change. Forty-three participants were randomized to MBN C-RFA (n=21) or T-RFA (n=22). There were no significant differences in demographic variables (p>0.05). A ≥50% NRS reduction was observed in 52% (95% CI 31% to 74%) and 44% (95% CI 22% to 69%) of participants in the C-RFA and T-RFA groups, respectively (p=0.75). A ≥15-point or ≥30% reduction in ODI score was observed in 62% (95% CI 38% to 82%) and 44% (95% CI 22% to 69%) of participants in the C-RFA and T-RFA groups, respectively (p=0.21). When using a single diagnostic block paradigm with a threshold of >75% pain reduction, both treatment with both C-RFA and T-RFA resulted in a success rate of approximately 50% when defined by both improvement in pain and physical function at 6-month follow-up. While the success rate was higher in the C-RFA group, this difference was not statistically significant. NCT02478437.


Insulin resistance, weight, and behavioral variables as determinants of brain reactivity to food cues: a Prevention of Diabetes through Lifestyle Intervention and Population Studies in Europe and around the World - a PREVIEW study.
Obesity and type 2 diabetes have been linked to alterations in food reward processing, which may be linked to insulin resistance. In this clinical study, we investigated the respective contribution of insulin resistance, anthropometric measurements, and behavioral factors to brain reward activation in response to visual stimuli. Food reward-related brain reward activation was assessed with functional magnetic resonance imaging in 39 overweight or obese individuals with impaired fasting glucose, impaired glucose tolerance, or both [22 women, 17 men; mean ± SD insulin sensitivity index (ISI): 2.7 ± 1.3; body mass index (BMI; kg/m2): 32.3 ± 3.7; body fat percentage: 40.5% ± 7.9%; fasting glucose: 6.3 ± 0.6 mmol/L]. Food and nonfood images were shown in a randomized block design. Brain activation (food compared with nonfood images) was correlated with anthropometric and behavioral variables. Behavioral variables included eating behavior [Three-Factor Eating Questionnaire (TFEQ)] and habitual physical activity (Baecke). Glucose and insulin concentrations, determined during an oral-glucose challenge, were used to assess the homeostatic model assessment for insulin resistance (HOMA-IR) and Matsuda ISI. Food compared with nonfood brain activation was positively associated with HOMA-IR in the nucleus accumbens, right and left insula, and right cingulate gyrus (P < 0.005, corrected for multiple comparisons). TFEQ factor 2 was positively related to food compared with nonfood brain activation in the supramarginal gyrus (P < 0.005, corrected for multiple comparisons). Habitual physical activity during leisure time was negatively associated with food compared with nonfood brain activation in multiple regions associated with the attention and reward network (P < 0.005, corrected for multiple comparisons). Individuals with increased insulin resistance and emotional eating or disinhibition showed higher brain reactivity to food cues, which may imply changes in food preference and hyperphagia. Individuals with higher habitual physical activity showed less food reward-related brain activation.


Acute management of stroke patients taking non-vitamin K antagonist oral anticoagulants Addressing Real-world Anticoagulant Management Issues in Stroke (ARAMIS) Registry: Design and rationale.
Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients. The ARAMIS Registry is a multicenter cohort study of acute stroke patients who were taking chronic anticoagulation therapy prior to admission and are admitted with either an acute ischemic stroke or intracerebral hemorrhage. Built upon the existing infrastructure of American Heart Association/American Stroke Association Get With the Guidelines Stroke, the ARAMIS Registry will enroll a total of approximately 10,000 patients (5000 with acute ischemic stroke who are taking a NOAC and 5000 with anticoagulation-related intracerebral hemorrhage who are on warfarin or a NOAC). The primary goals of the ARAMIS Registry are to provide a comprehensive picture of current treatment patterns and outcomes of acute ischemic stroke patients on NOACs, as well as anticoagulation-related intracerebral hemorrhage in patients on either warfarin or NOACs. Beyond characterizing the index hospitalization, up to 2500 patients (1250 ischemic stroke and 1250 intracerebral hemorrhage) who survive to discharge will be enrolled in an optional follow-up sub-study and interviewed at 3 and 6 months after discharge to assess longitudinal medication use, downstream care, functional status, and patient-reported outcomes. The ARAMIS Registry will document the current state of management of NOAC treated patients with acute ischemic stroke as well as contemporary care and outcome of anticoagulation-related intracerebral hemorrhage. These data will be used to better understand optimal strategies to care for these complex but increasingly common emergent real world clinical challenges.


Androgens regulate brain aromatase activity in adult male rats through a receptor mechanism.
We studied the regulation of aromatase activity in the hypothalamus-preoptic area ( HPOA ) of adult male rats using a sensitive in vitro assay which measures the amount of 3H2O formed by tissue homogenates during the conversion of [1 beta-3H]androstenedione to estrone. After castration, HPOA aromatase activity was decreased by 60% (P less than 0.05), seminal vesicle (SV) and ventral prostate (VP) weights were significantly decreased (P less than 0.05), and serum LH levels were elevated. We found that testosterone (T) or 5 alpha-dihydrotestosterone (DHT) administered in Silastic capsules for 7 days reversed the effects of castration. Testosterone and DHT stimulated HPOA aromatase activity 133% and 92%, respectively (P less than 0.05). Both steroids significantly increased SV and VP wet weights and suppressed serum levels of LH (P less than 0.05). Administration of either estradiol or progesterone did not reverse the effect of castration on HPOA aromatase activity or any other parameter measured. To determine the involvement of androgen receptors in the mechanism by which androgens affect brain aromatase, we administered the nonsteroidal antiandrogen flutamide to intact male rats (15 mg/day for 7 days). There was 42% less HPOA aromatase activity in treated rats than in oil-injected controls (P less than 0.05). Flutamide significantly decreased SV and VP wet weights, while serum LH levels were enhanced (P less than 0.05). Likewise, administration of flutamide to T-implanted castrated males blocked the T-induced increase in HPOA aromatase activity and accessory sexual organ wet weights, and prevented the T-induced suppression of serum LH. Flutamide given alone to castrated rats had no effect. Since both T and DHT stimulated HPOA aromatase activity and since the effects of T are blocked by the concomitant administration of the antiandrogen flutamide, we concluded that the control of HPOA aromatase activity by androgens is receptor mediated.


Pneumococcal type-associated variability in alternate complement pathway activation.
Opsonization of Streptococcus pneumoniae may be mediated by the alternate complement pathway. To study the importance of this interaction to human disease, complement consumption by pneumococci of various serotypes was measured in humwn serum chelated with ethyleneglycoltraacetic acid, a substance that blocks the classic but not the alternate complement pathwway. Serotype I, in contrast to all other types studied, lacked ability to consume complement in this system. The ability for serotypes III, IV, and VIII to activate the alternate pathway could be eliminated by prior serum absorption at O C with they type in question, a condition that would remove antibody but not complement. Types VII, XII, XIV, and XXV readily activated the alternate pathway in unabsorbed and absorbed sera. Differences could not be related to properties of the capsules. It was concluded that types I, III, IV, and VIII lack intrinsic ability to activate and thus be opsonized by the alternate complement pathway, although types III, IV, and VIII can do so in concert with specific antibody. The fact that these same types are especially prominent in human disease suggests that the ability to evade opsonization by the alternate complement pathway in pre-antibody phases of infection may be a virulence factor in pneumococci.


Experimental evidence that the Ornstein-Uhlenbeck model best describes the evolution of leaf litter decomposability.
Leaf litter decomposability is an important effect trait for ecosystem functioning. However, it is unknown how this effect trait evolved through plant history as a leaf 'afterlife' integrator of the evolution of multiple underlying traits upon which adaptive selection must have acted. Did decomposability evolve in a Brownian fashion without any constraints? Was evolution rapid at first and then slowed? Or was there an underlying mean-reverting process that makes the evolution of extreme trait values unlikely? Here, we test the hypothesis that the evolution of decomposability has undergone certain mean-reverting forces due to strong constraints and trade-offs in the leaf traits that have afterlife effects on litter quality to decomposers. In order to test this, we examined the leaf litter decomposability and seven key leaf traits of 48 tree species in the temperate area of China and fitted them to three evolutionary models: Brownian motion model (BM), Early burst model (EB), and Ornstein-Uhlenbeck model (OU). The OU model, which does not allow unlimited trait divergence through time, was the best fit model for leaf litter decomposability and all seven leaf traits. These results support the hypothesis that neither decomposability nor the underlying traits has been able to diverge toward progressively extreme values through evolutionary time. These results have reinforced our understanding of the relationships between leaf litter decomposability and leaf traits in an evolutionary perspective and may be a helpful step toward reconstructing deep-time carbon cycling based on taxonomic composition with more confidence.


Isoflurane produces marked and nonlinear decreases in the vasoconstriction and shivering thresholds.
Desflurane decreases the vasoconstriction and shivering thresholds disproportionately at high anesthetic concentrations. This result contrasts with the authors' previous report that isoflurane decreases the vasoconstriction threshold linearly. It is surprising that the basic shape of the concentration-response curve should differ with these two otherwise similar anesthetics. Therefore, the hypothesis that isoflurane produces a nonlinear reduction in the vasoconstriction threshold was tested. Because the effect of isoflurane on shivering remains unknown, the extent to which isoflurane reduces the shivering threshold also was determined. Eight men volunteered to be studied on four randomly ordered days: (1) a target end-tidal isoflurane concentration of 0.55%, (2) a target concentration of 0.7%, (3) control (no anesthesia) and a target end-tidal concentration of 0.85%, and (4) a target end-tidal concentration of 1.0%. Volunteers were surface-cooled until peripheral vasoconstriction and shivering were observed. We arithmetically compensated for changes in skin temperature using the established linear cutaneous contributions to control for each response. From the calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C), the concentration-response relation was determined. Isoflurane administration produced a dose-dependent reduction in the vasoconstriction and shivering thresholds, decreasing each approximately 4.6 degrees C at an end-tidal concentration of 1%. Residual analysis indicated that the vasoconstriction and shivering thresholds were decreased in a nonlinear fashion during isoflurane administration. The vasoconstriction-to-shivering range was 1.5 +/- 0.8 degree C without isoflurane, and did not change significantly during isoflurane administration. The vasoconstriction-to-shivering range remained unchanged by isoflurane administration. In this regard, the effects of isoflurane are similar to those of desflurane, propofol, and alfentanil. The current data differ from the authors' previous report, in that the dose-dependence for vasoconstriction was nonlinear, with isoflurane reducing the threshold disproportionately at higher anesthetic concentrations. Differing dose-dependence in the two studies may result either because the current study's volunteers were not exposed to surgical stimulation and were given less isoflurane, or because of design limitations in the previous protocol.


Prediction of COVID-19-related Mortality and 30-Day and 60-Day Survival Probabilities Using a Nomogram.
Prediction of mortality in patients with coronavirus disease 2019 (COVID-19) is a key to improving the clinical outcomes, considering that the COVID-19 pandemic has led to the collapse of healthcare systems in many regions worldwide. This study aimed to identify the factors associated with COVID-19 mortality and to develop a nomogram for predicting mortality using clinical parameters and underlying diseases. This study was performed in 5,626 patients with confirmed COVID-19 between February 1 and April 30, 2020 in South Korea. A Cox proportional hazards model and logistic regression model were used to construct a nomogram for predicting 30-day and 60-day survival probabilities and overall mortality, respectively in the train set. Calibration and discrimination were performed to validate the nomograms in the test set. Age ≥ 70 years, male, presence of fever and dyspnea at the time of COVID-19 diagnosis, and diabetes mellitus, cancer, or dementia as underling diseases were significantly related to 30-day and 60-day survival and mortality in COVID-19 patients. The nomogram showed good calibration for survival probabilities and mortality. In the train set, the areas under the curve (AUCs) for 30-day and 60-day survival was 0.914 and 0.954, respectively; the AUC for mortality of 0.959. In the test set, AUCs for 30-day and 60-day survival was 0.876 and 0.660, respectively, and that for mortality was 0.926. The online calculators can be found at https://koreastat.shinyapps.io/RiskofCOVID19/. The prediction model could accurately predict COVID-19-related mortality; thus, it would be helpful for identifying the risk of mortality and establishing medical policies during the pandemic to improve the clinical outcomes.


Current diagnosis and treatment of chronic subdural haematomas.
A developed society is usually also characterized by an elderly population, which has a continuous percentage growth. This population frequently presents a cumulus of medical pathologies. With the development of the medication and surgical treatment of different affections, the life span has increased and the pathology of an old patient has diversified as far as the cumulus of various pathological diseases in the same person is concerned. Chronic subdural pathologies represent an affection frequently met in neurosurgery practice. Any neurosurgeon, neurologist and not only, has to be aware of the possibility of the existence of a chronic subdural haematoma, especially when the patient is old and is subjected to an anticoagulant or antiaggregant treatment, these 2 causes being by far the etiological factors most frequently met in chronic subdural haematomas. With an adequate diagnosis and treatment, usually surgical, the prognosis is favorable. Although the surgical treatment presents a categorical indication in most of the cases, the fact that there are many surgical techniques, a great relapse rate, as well as the numerous studies, which try to highlight the efficiency of a technique as compared to another, demonstrate that the treatment of these haematomas is far from reaching a consensus among the neurosurgeons. The latest conservatory treatment directions are still being studied and need many years to be confirmed. CT = computerized tomography, MRI = magnetic resonance imaging.


Tip-Enhanced Infrared Difference-Nanospectroscopy of the Proton Pump Activity of Bacteriorhodopsin in Single Purple Membrane Patches.
Photosensitive proteins embedded in the cell membrane (about 5 nm thickness) act as photoactivated proton pumps, ion gates, enzymes, or more generally, as initiators of stimuli for the cell activity. They are composed of a protein backbone and a covalently bound cofactor (e.g. the retinal chromophore in bacteriorhodopsin (BR), channelrhodopsin, and other opsins). The light-induced conformational changes of both the cofactor and the protein are at the basis of the physiological functions of photosensitive proteins. Despite the dramatic development of microscopy techniques, investigating conformational changes of proteins at the membrane monolayer level is still a big challenge. Techniques based on atomic force microscopy (AFM) can detect electric currents through protein monolayers and even molecular binding forces in single-protein molecules but not the conformational changes. For the latter, Fourier-transform infrared spectroscopy (FTIR) using difference-spectroscopy mode is typically employed, but it is performed on macroscopic liquid suspensions or thick films containing large amounts of purified photosensitive proteins. In this work, we develop AFM-assisted, tip-enhanced infrared difference-nanospectroscopy to investigate light-induced conformational changes of the bacteriorhodopsin mutant D96N in single submicrometric native purple membrane patches. We obtain a significant improvement compared with the signal-to-noise ratio of standard IR nanospectroscopy techniques by exploiting the field enhancement in the plasmonic nanogap that forms between a gold-coated AFM probe tip and an ultraflat gold surface, as further supported by electromagnetic and thermal simulations. IR difference-spectra in the 1450-1800 cm-1 range are recorded from individual patches as thin as 10 nm, with a diameter of less than 500 nm, well beyond the diffraction limit for FTIR microspectroscopy. We find clear spectroscopic evidence of a branching of the photocycle for BR molecules in direct contact with the gold surfaces, with equal amounts of proteins either following the standard proton-pump photocycle or being trapped in an intermediate state not directly contributing to light-induced proton transport. Our results are particularly relevant for BR-based optoelectronic and energy-harvesting devices, where BR molecular monolayers are put in contact with metal surfaces, and, more generally, for AFM-based IR spectroscopy studies of conformational changes of proteins embedded in intrinsically heterogeneous native cell membranes.