Pinhole imaging of 131I-metaiodobenzylguanidine (131I-MIBG) in an animal model of neuroblastoma.
To evaluate (131)I-MIBG scintigraphic localization of xenotransplanted and spontaneously arising neuroblastomas in murine models of high-risk neuroblastoma. Neuroblastoma xenografts were created by inoculation of human neuroblastoma cell suspensions into the subcutaneous flanks of athymic nude mice. In addition, spontaneous paraspinal neuroblastomas were detected by direct palpation in MYCN transgenic mice. After measured tumor volumes exceeded 200 mm(3), each mouse received an intraperitoneal injection of 18 muCi/g (131)I-metaiodobenzylguanidine ((131)I-MIBG). Pinhole scintigraphy was performed to evaluate the MIBG biodistribution and to attempt to visualize the tumors. Each mouse was imaged on a gamma camera equipped with a 3-mm pinhole on one head and an HEGP collimator on the other. Images demonstrated absorption of radiolabeled MIBG and visualization of tumors. Analysis of the images allowed for quantification of relative MIBG uptake and for determination of linear and area measurements of the tumors. High-energy pinhole imaging effectively demonstrates uptake of radiolabeled MIBG by human neuroblastoma tumors in murine laboratory models. This technique allows for in vivo assessment of tumor burden. In the future, we plan to use this method to evaluate sensitivity for detecting metastatic spread as well as investigating the therapeutic efficacy of high-dose (131)I-MIBG in combination with radiosensitizing agents.


Sex determination systems in reptiles are related to ambient temperature but not to the level of climatic fluctuation.
Vertebrates exhibit diverse sex determination systems and reptiles stand out by having highly variable sex determinations that include temperature-dependent and genotypic sex determination (TSD and GSD, respectively). Theory predicts that populations living in either highly variable or cold climatic conditions should evolve genotypic sex determination to buffer the populations from extreme sex ratios, yet these fundamental predictions have not been tested across a wide range of taxa. Here, we use phylogenetic analyses of 213 reptile species representing 38 families (TSD = 101 species, GSD = 112 species) and climatic data to compare breeding environments between reptiles with GSD versus TSD. We show that GSD and TSD are confronted with the same level of climatic fluctuation during breeding seasons. However, TSD reptiles are significantly associated with warmer climates. We found a strong selection on the breeding season length that minimises exposure to cold and fluctuating climate. Phylogenetic path analyses comparing competing evolutionary hypotheses support that transitions in sex determination systems influenced the ambient temperature at which the species reproduces and nests. In turn, this interaction affects other variables such as the duration of the breeding season and life-history traits. Taken together, our results challenge long-standing hypotheses about the association between sex determination and climate variability. We also show that ambient temperature is important during breeding seasons and it helps explain the effects of sex determination systems on the geographic distribution of extant reptile species.


Lupus nephritis with corticosteroid responsiveness: molecular changes of CD46-mediated type 1 regulatory T cells.
The engagement of the complement regulatory proteins CD46 and CD3 in human CD4+ T cells induces the type 1 regulatory T cells (Tr1) and interleukin-10 (IL-10) secretion. This study aimed to elucidate the molecular changes of Tr1 cells through CD46 cytoplasmic Cyt1 tail in lupus nephritis (LN) respond to intravenous methylprednisolone (ivMP) therapy. We enrolled 40 pediatric patients with LN and 30 healthy controls. Clinical characteristics and peripheral blood mononuclear cells were collected before and 3 days after the administration of ivMP. Kidney specimens were taken from five LN and five minimal-change nephrotic syndrome patients. We found that defective CD46-mediated T-helper type 1 contraction (IL-10 switching) is present in active LN patients. The ivMP therapy enhanced LN remission, restored the production of IL-10, increased the CD46-Cyt1/Cyt2 ratio, AKT, and cAMP-responsive element-binding protein phosphorylation, and induced migration with the expression of chemokine receptor molecules CCR4, CCR6, and CCR7 of CD3/CD46-activated Tr1 cells. Pharmacologic interventions that alter the patterns of CD46-Cyt1/Cyt2 expression and the secretion of IL-10 by CD3/CD46-activated Tr1 cells can be used in patients with active LN. In patients with LN, ivMP was associated with increased IL-10 production and increased CD46-Cyt1/Cyt2 ratio and AKT phosphorylation by Tr1 cells, with enhanced potential to migration in response to CCL17. These results suggest that expression levels of CD46 isoforms Cyt1 and Cyt2 in CD4 + CD46 + Tr1 cells differ in patients with active LN but can be corrected by corticosteroid treatment. Enhancing the expression of functional CD4 + CD46 + Tr1 cells may be a useful therapeutic approach for LN.


A new analysis of allogeneic interactions.
Allogeneic reactions have conventionally been considered as typical immune responses by one population of cells to antigens present on the other. This view is inadequate, since it does not explain many features of these reactions, among which are: (1) reactivity is much higher between different strains within a species than between species, in spite of the much greater antigenic disparity in the second case; (2) a very high proportion of cells may respond to allogeneic stimuli; (3) major histocompatibility differences are not essential for vigorous allogeneic reactions; (4) the responding population need not be immunologically competent to respond to antigens of the stimulating population; (5) the stimulating population must be both metabolically active and immunocompetent. We have tried to produce a model of cell interaction which will account for these and other anomalies, which at the same time explaining both normal antigenic stimulation (through cell-cell cooperation) and allogeneic interactions as examples of the same basic mechanisms. The model is based on the Bretscher-Cohn scheme of cell interaction. An allogeneic reaction is seen as having two stages: (1) Cells come together when antibody receptors on cells of one population combine with antigens on cells of the other. To this extent, our model is the same as the conventional one. It need not be the responding population which has the receptors, however. (2) A species-specific proliferation signal passes between the cells. This is the same signal as is involved in normal antibody induction. Even antigen-receptor bonds which are very weak may result in effective stimulation of one or both partners because of enhancing effect of this signal, and because the antigens involved are probably repeated over the cell surface, enabling multipoint binding. This explains the very proportions of cells which proliferate. The exact outcome of any allogeneic interaction will depend on which of the two populations have antibody receptors for antigens on the other, which can produce the proliferative stimulus, and which can respond to either the proliferative signal alone or to this stimulus plus antigen.


Assessment of shunt volumes in children with ventricular septal defects: comparative quantification of MR flow measurements and invasive oximetry.
The aim of this study was to compare the results of magnetic resonance based shunt volume measurements with the results of the invasive method by the principle of Fick. In 14 children (median age: 16.5 months) with ventricular septal defects the shunt volume was quantified by magnetic resonance flow measurements under spontaneous breathing conditions as well as with invasive angiography during one sedation. A good correlation between both methods was observed (r(2) = 0.8, p <0.0001, CI(95%) = 0.62-1.22). A tendency towards higher values in the noninvasive technique was found in the Bland-Altman plot (bias = 3.79). Magnetic resonance based shunt measurements are a reliable alternative to the invasive shunt measurement by cardiac catheterization.


Nerve Sheath Tumors in Neurofibromatosis Type 1: Assessment of Whole-Body Metabolic Tumor Burden Using F-18-FDG PET/CT.
To determine the metabolically active whole-body tumor volume (WB-MTV) on F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) in individuals with neurofibromatosis type 1 (NF1) using a three-dimensional (3D) segmentation and computerized volumetry technique, and to compare PET WB-MTV between patients with benign and malignant peripheral nerve sheath tumors (PNSTs). Thirty-six NF1 patients (18 patients with malignant PNSTs and 18 age- and sex-matched controls with benign PNSTs) were examined by F-18-FDG PET/CT. WB-MTV, whole-body total lesion glycolysis (WB-TLG) and a set of semi-quantitative imaging-based parameters were analyzed both on a per-patient and a per-lesion basis. On a per-lesion basis, malignant PNSTs demonstrated both a significantly higher MTV and TLG than benign PNSTs (p < 0.0001). On a per-patient basis, WB-MTV and WB-TLG were significantly higher in patients with malignant PNSTs compared to patients with benign PNSTs (p < 0.001). ROC analysis showed that MTV and TLG could be used to differentiate between benign and malignant tumors. WB-MTV and WB-TLG may identify malignant change and may have the potential to provide a basis for investigating molecular biomarkers that correlate with metabolically active disease manifestations. Further evaluation will determine the potential clinical impact of these PET-based parameters in NF1.


Opposite effects of smoking and nicotine intake on cognition.
Our main purpose was to investigate how smoking and nicotine interacted with specific aspects of cognitive functioning. The research was conducted in two parts: (i) an investigation of cognition in heavy smokers and healthy nonsmokers, and (ii) an investigation of cognition in healthy nonsmokers enrolled in a clinical trial involving administration of nicotine gum. Results indicated that the relationship between smoking and nicotine was characterized by an inverted U-shaped effect. On the one hand, cognitive test performance of the heavy smokers group was reduced on all of the cognitive tasks used here. On the other hand, healthy nonsmokers who used 2-mg of nicotine gum performed better, whilst the 4-mg group performed worse than the 2-mg and the placebo group. Demographic data were not related to the cognitive tasks. These data suggest that small doses of nicotine can have an activating function that leads to improved cognition, while heavy smoking on a chronic (and possibly acute) basis leads to cognitive impairment.


Lubricant for reducing perineal trauma: A systematic review and meta-analysis of randomized controlled trials.
To assess the effect of lubricants on reducing perineal trauma during vaginal delivery. PubMed, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, China Biology Medicine disc, WanFang databases, and ClinicalTrials.gov, were searched for literature up to 25 June 2021. Randomized controlled trials published in English or Chinese that compared the vaginal application of lubricant with standard care for women were included. Two reviewers independently performed study screening, data extraction, risk of bias assessment, and certainty of evidence assessment. Pooled effect sizes and corresponding 95% confidence intervals (CI) were calculated using meta-analysis. Nineteen trials enrolling 5445 pregnant women were included. Compared with standard care, women using lubricants had a lower incidence of perineal trauma (risk ratio [RR] 0.84, 95% CI 0.76-0.93; low certainty evidence), second-degree perineal laceration (RR 0.72, 95% CI 0.64-0.82; moderate certainty evidence) and episiotomy (RR 0.77, 95% CI 0.62-0.96; very low certainty evidence), and had a shorter duration of the second-stage labor (MD -13.72 min, 95% CI -22.68 to -4.77; very low certainty evidence). Lubricants might reduce the incidence of perineal trauma, especially second-degree perineal laceration, and shorten the duration of the second-stage labor. More well-designed studies will continue developing high-quality evidence in this field.


Pharmacokinetics and clinical efficacy of oral morphine solution and controlled-release morphine tablets in cancer patients.
Twenty-three adult patients with chronic pain due to cancer completed a double-blind, randomized, two-phase crossover trial comparing plasma morphine concentrations and analgesic efficacy of oral morphine sulfate solution (MSS) and controlled-release morphine sulfate tablets (MS Contin [MSC], Purdue Frederick, Inc., Toronto, Ontario, Canada). MS Contin was given every 12 hours to all patients except those whose daily morphine dose could not be equally divided into two 12-hour doses with the tablet strengths available. MSS was given every 4 hours. Patients received both of the test drugs for at least 5 days, and, on the final day of each phase, peripheral venous blood samples for morphine analysis were obtained. Eighteen patients received MSC every 12 hours, and five received it every 8 hours. The same total daily morphine dose was given in both phases. In the 18 patients who received MSC every 12 hours, the daily morphine dose was 183.9 +/- 140.0 mg (mean +/- SD). In this group, the mean area under the curve (AUC) with MSC was 443.6 +/- 348.4 ng/ml/hour, compared with 406.8 +/- 259.7 ng/ml/hour for MSS (P greater than 0.20). Mean maximum morphine concentrations (Cmax) for MSC and MSS were 67.9 +/- 42.1 and 58.8 +/- 30.3 ng/ml, respectively (P greater than 0.05). Mean minimum morphine concentrations (Cmin) were 17.0 +/- 17.7 and 18.3 +/- 15.0, respectively (P greater than 0.30). There was a significant difference (P less than 0.001) between the two drugs in time required to reach maximum morphine concentration (Tmax). Mean Tmax after MSC occurred at 3.6 +/- 2.3 hours. After MSS, it occurred at 1.3 +/- 0.4 hours. In the five patients who received MSC every 8 hours, the findings paralleled those in the principal group, with no significant differences between MSC and MSS in Cmax or Cmin and a highly significant difference between the two in Tmax. However, in this small group of patients, the AUC with MSC was significantly (P = 0.04) greater than that with MSS. All patients had very good pain control throughout the study and both formulations were well tolerated. There were no significant differences between MSC and MSS in pain scores or side effects. Under the conditions of this study there was no clinically significant difference in bioavailability between MSC and oral MSS. When given on a 12-hourly basis in individually titrated doses, the MSC provided therapeutic plasma morphine concentrations throughout the dosing interval.


Probing the interaction between vesicular stomatitis virus and phosphatidylserine.
The entry of enveloped animal viruses into their host cells always depends on membrane fusion triggered by conformational changes in viral envelope glycoproteins. Vesicular stomatitis virus (VSV) infection is mediated by virus spike glycoprotein G, which induces membrane fusion between the viral envelope and the endosomal membrane at the acidic environment of this compartment. In this work, we evaluated VSV interactions with membranes of different phospholipid compositions, at neutral and acidic pH, using atomic force microscopy (AFM) operating in the force spectroscopy mode, isothermal calorimetry (ITC) and molecular dynamics simulation. We found that the binding forces differed dramatically depending on the membrane phospholipid composition, revealing a high specificity of G protein binding to membranes containing phosphatidylserine (PS). In a previous work, we showed that the sequence corresponding amino acid 164 of VSV G protein was as efficient as the virus in catalyzing membrane fusion at pH 6.0. Here, we used this sequence to explore VSV-PS interaction using ITC. We found that peptide binding to membranes was exothermic, suggesting the participation of electrostatic interactions. Peptide-membrane interaction at pH 7.5 was shown to be specific to PS and dependent on the presence of His residues in the fusion peptide. The application of the simplified continuum Gouy-Chapman theory to our system predicted a pH of 5.0 at membrane surface, suggesting that the His residues should be protonated when located close to the membrane. Molecular dynamics simulations suggested that the peptide interacts with the lipid bilayer through its N-terminal residues, especially Val(145) and His(148).


Knocking Down DUX4 in Immortalized Facioscapulohumeral Muscular Dystrophy Patient-Derived Muscle Cells.
The third most common muscular dystrophy in the world, facioscapulohumeral muscular dystrophy (FSHD), is an inherited disorder characterized by distinct asymmetric, progressive skeletal muscle weakness that begins in the upper body and spreads to other regions with age. It is caused by mutations that induce aberrant expression of the DUX4 gene in skeletal muscle. DUX4 is highly cytotoxic in skeletal muscle, dysregulating numerous signaling pathways as a result of its transcription factor activity. A promising set of approaches being developed to treat FSHD uses antisense oligonucleotides (AOs) to inhibit DUX4 transcript expression. Both steric-blocking and gapmer AOs have been shown to induce efficient DUX4 transcript knockdown in vitro and in vivo. Here, we describe a protocol that allows reliable screening of DUX4-targeting AOs through the evaluation of DUX4 transcript expression by quantitative real-time polymerase chain reaction. We also describe methods to assess the efficacy of these AOs by looking at their effect on the expression of DUX4 downstream target and potential off-target genes, as well as on the amelioration of in vitro muscle cell phenotypes.


Drug-drug interaction signals between loop diuretics and teicoplanin during acute kidney injury evaluated using Japanese spontaneous adverse drug event reports.
Teicoplanin can cause acute kidney injury, but little is known about the risk of acute kidney injury when teicoplanin is co-administered with loop diuretics (a powerful diuresis), which can alter renal hemodynamics and glomerular filtration rate. We performed a signal detection analysis using a Japanese adverse event database to determine the additive impact of loop diuretics on acute kidney injury associated with teicoplanin. The dataset originated between April 2004 and August 2022. Disproportionality analysis was performed to detect the signals for acute kidney injury (the Standardized MedDRA Query) when co-administered teicoplanin or vancomycin (a positive control) with individual diuretics, including loop diuretics. Multivariate logistic regression analysis was tested to estimate the adjusted reporting odds ratio (aROR) and 95% confidence interval (95% CI). There were 147 and 515 events of acute kidney injury associated with teicoplanin and vancomycin, respectively. A significant positive signal for acute kidney injury when teicoplanin was co-administered with loop diuretics was present (aROR 4.83, 95% CI 3.52-6.61, p < 0.0001). Contrastingly, no significant signals were observed when vancomycin was co-administered with any diuretics. These findings suggest that co-administered loop diuretics may have an unfavorable effect on acute kidney injury while undertaking teicoplanin but not vancomycin.


Patient safety in interventional pain procedures.
The objective of this article was to present a systematic review of the safety issues encountered in interventional pain management. Patient safety is an important consideration in the practice of interventional pain management. Although there is a paucity of scientific articles addressing this topic, the authors have reviewed the literature and present a review of the topic, as well as strategies to minimize the risk to patients undergoing interventional spine procedures.


Mistrust in public health institutions is a stronger predictor of vaccine hesitancy and uptake than Trust in Trump.
This study examines the sources of COVID-19 vaccine hesitancy and refusal in Americans by decomposing different forms of government trust/mistrust including trust in Trump and mistrust in public health institutions. Using linear panel regression models with data from 5,446 US adults (37,761 responses) from the Understanding America Survey, the likelihoods of vaccine hesitancy, uptake, and trust in various information sources were examined. We find that the likelihoods of hesitancy and having negative perceptions of COVID-19 vaccines were consistently much higher among PHI mistrusters, showing even a stronger hesitancy than Trump trusters. This tendency has persisted over time, resulting in only 49% of PHI mistrusters having been vaccinated in the most recent survey wave. However, a large portion of PHI mistrusters still trusted physicians, family, and friends. These findings suggest that mistrust in PHIs is a salient predictor of vaccine hesitancy and reduced uptake on its own, which is compounded by trust in Trump.


Structure formation of supercooled polymers in confined geometries--a molecular-dynamics simulation study.
Molecular-dynamics simulations of thin polymer films are performed with a recently introduced coarse-grained model. This model reproduces many features of polymer crystallization from the melt. In this work, we show how confining walls influence the structure formation depending on the degree of supercooling. Already in the melt at high temperature a preorder is induced near the walls. On lowering the temperature, crystalline order nucleates at the walls, from which it propagates into the film. We show how this growth can be influenced by prestructuring the wall.


Mineral profiling of local pig-feeds and pigs reared under resource driven production system to reduce porcine mineral deficiency in subtropical hill ecosystem of Northeastern India.
The present study assessed the mineral status of pigs fed with local feed resources. The commonly used plants for feeding pigs and blood serum samples from Hampshire, Large White Yorkshire and indigenous pigs were analyzed for total protein, albumin and cholesterol levels. Processed plant and serum samples were also analyzed for calcium, phosphorus, magnesium, sodium, potassium, copper, cobalt, manganese, iron and zinc. The incidence and extent of mineral deficiency in pigs was quantified. No significant difference was observed in total protein and albumin levels between any two breed/types of pigs, however the Indigenous pigs showed significantly (P < 0.05) higher cholesterol level compared to other two breeds. Among different plants, Spilanthus sp had majority of macro and micro nutrients in high levels. Regarding incidence of mineral deficiency in pigs, it was observed that 90, 67.1, 61.4, 48.6, 95.7% of the pigs were deficient in calcium, phosphorus, sodium, magnesium and potassium. An interesting finding was that all the pigs (100%) utilized in the study were deficient in zinc. From this study, it was inferred that there are good numbers of potential source of mineral that might be used more economically to improve the mineral availability to pigs.


Oxidative stress in a phenylketonuria animal model.
Oxidative stress is seen in various metabolic disorders for unknown reasons. Oxidative stress is defined as an imbalance between pro-oxidant and antioxidant status in favor of the former. This study investigated whether oxidative stress exists in phenylketonuria (PKU) using the BTBR-Pah(enu2) animal model for PKU. Animals (14-24 weeks old) were sacrificed and brain and red blood cells (RBCs) were obtained aseptically. The lipid peroxidation by-product, evaluated as malondialdehyde (MDA), was significantly higher in the brains and RBCs of PKU animals (n = 6) than in controls (n = 6). Glutathione/glutathione disulfide, a good indicator for tissue thiol status, was significantly decreased both in the brains and RBCs. Some antioxidant enzymes were also analyzed in RBCs, including glucose-6-phosphate dehydrogenase (G6PD), which provides the RBC's main reducing power, reduced nicotinamide adenine dinucleotide phosphate (NADPH), and catalase detoxifies H2O2 by catalyzing its reduction to O2 and H2O. Both catalase and G6PD were significantly increased in the RBCs of PKU animals.


[Role of the spleen in the regulation of the calcium content of the blood plasma in health and in stress].
Splenectomy is found to be followed by an increase of the calcium level in blood. Administration of the spleen extract (splenin) decreases the calcium concentration in blood plasma of splenectomized animals. The normalizing splenin effect is observed in the presence of stress when the concentration of the studied trace element sharply increases as well. It is supposed that the humoral spleen factors participate in maintenance of the constant calcium level in blood preventing its elimination from tissues.


High expression of GLO1 indicates unfavorable clinical outcomes in glioma patients.
Glyoxalase I (GLO1), a ubiquitous enzyme involved in the process of detoxification of methylglyoxal in the cellular glycolysis pathway, was reported to be highly expressed in human tumor. It has also been found that GLO1 is associated with tumor cell survival and proliferation in some types of cancer, such as pancreatic cancer, hepatocellular carcinoma and gastric cancer. However, the role of GLO1 in glioma has not been clarified. The purpose of the present study was to explore the expression pattern of GLO1 and whether the expression level of GLO1 is associated with the unfavorable clinical outcomes of patients with glioma. Quantitative RT-PCR and immunohistochemistry staining were used to investigate the mRNA and protein level of GLO1 in glioma tissues together with normal brain tissues. The prognostic role of GLO1 in glioma patients was assessed using univariate and multivariate analyses. Clinical outcomes were estimated by using the Kaplan-Meier analysis and the log-rank test. The function of GLO1 in glioma cell lines were investigated by in-vitro experiments. Expression level of GLO1 was higher in glioma tissues than that in normal brain tissues. High GLO1 expression was significantly correlated with WHO grade and the poor overall survival time in glioma patients. Moreover, GLO1 was also defined as an unfavorable prognosis factor. Overexpression of GLO1 in the glioma cell line U87 can enhance the tumor cell proliferation, migration and invasion. Whereas knockdown of GLO1 can suppress those abilities. Our studies demonstrated that GLO1 was highly expressed in glioma tissues and significantly correlated with the poor prognosis of glioma patients. It indicated that GLO1 might serve as a new prognostic predictor and therapeutic target for glioma treatment.


Driver performance modelling and its practical application to railway safety.
This paper reports on the development and main features of a model of driver information processing. The work was conducted on behalf of Network Rail to meet a requirement to understand and manage the driver's interaction with the infrastructure through lineside reminder appliances. The model utilises cognitive theory and modelling techniques to describe driver performance in relation to infrastructure features and operational conditions. The model is capable of predicting the performance time, workload and error consequences of different operational conditions. The utility of the model is demonstrated through reports of its application to the following studies: Research on the effect of line speed on driver interaction with signals and signs. Calculation of minimum reading times for signals. Development of a human factors signals passed at danger (SPAD) hazard checklist, and a method to resolve conflicts between signal sighting solutions. Research on the demands imposed on drivers by European train control system (ETCS) driving in a UK context. The paper also reports on a validation of the model's utility as a tool for assessing cab and infrastructure drivability.


Disparities in use of disciplinary solitary confinement by mental health diagnosis, race, sexual orientation and sex: Results from a national survey in the United States of America.
Solitary confinement is still used in prisons in the USA, despite its links to poor health. Past research suggests that there may be disparities by race, ethnicity, sex and mental disorders regarding who is placed in solitary confinement, although nationwide studies have been sparse. To explore possible disparities by race, ethnicity, sex, sexual orientation, adverse childhood experiences and mental disorders in solitary confinement as a disciplinary action for adults incarcerated in USA prisons. Data come from a recently released national survey of 24,848 adults incarcerated in the USA-the 2016 Survey of Prison Inmates. Logistic regression models were used to identify disparities in the use of disciplinary action and solitary confinement as a disciplinary action, while controlling for type of rule violation. After controlling for rule violation type, solitary confinement was used as a disciplinary action at higher rates for people who: were multiracial, as compared to white (aOR = 1.30), male, as compared to female (aOR = 1.46), bisexual, as compared to heterosexual (aOR = 1.64), had multiple mental disorders, as compared to none (aOR = 1.22) or had more adverse childhood experiences (aOR = 1.13). Findings highlight demographic and health disparities in the use of solitary confinement, which may further widen health disparities. More effective implementation of policies to reduce the use of solitary confinement are still needed. Mental health professionals should have an active role in advising on measures when mental disorder is a factor and must ensure adequate treatment of disorders in prison or transfer to health facilities.


Medicago truncatula dihydrodipicolinate synthase (DHDPS) enzymes display novel regulatory properties.
Lysine biosynthesis in plants is tightly regulated by feedback inhibition of the end product on the first enzyme of the lysine-specific branch, dihydrodipicolinate synthase (DHDPS). Three complete DHDPS coding sequences and one partial sequence were obtained in Medicago truncatula via inverse PCR. Analysis of the MtDHDPS sequences indicated the presence of isozymes (MtDHDPS2 and MtDHDPS3) with multiple amino acid substitutions on positions previously shown to be involved in feedback inhibition and of residues important for catalytic activity, possibly affecting the enzymatic properties of these isoforms. Sequences similar to MtDHDPS2 and 3 are present in Lotus japonicus and Glycine max, suggesting the existence of a specific conserved class of DHDPS genes within the Fabaceae family. The MtDHDPS genes were found by quantitative RT-PCR analysis to be expressed in an organ-specific manner in M. truncatula. All four MtDHDPS enzymes were expressed separately in Escherichia coli, revealing a strongly reduced sensitivity of the MtDHDPS2 protein to lysine feedback inhibition and a severely reduced activity of the MtDHDPS3 protein. Remarkably, MtDHDPS3 expression in Arabidopsis thaliana produced transgenic plants with a significantly increased threonine level, suggesting a dominant DHDPS inhibiting role of this isoform. This is supported by co-expression experiments in E. coli which indicate that AtDHDPS and MtDHDPS3 interact and may form hetero-oligomers with strongly reduced enzymatic activity. In conclusion, analysis of DHDPS in M. truncatula revealed the presence of unique isozymes displaying novel regulatory properties.


Cell-Based Therapies for Lumbar Discogenic Low Back Pain: Systematic Review and Single-Arm Meta-analysis.
A systematic review and single-arm meta-analysis of clinical trials. To assess the efficacy of mesenchymal stem cells or chondrocyte in patients with discogenic low back pain. There is no previous review evaluated the efficacy of mesenchymal stem cell or chondrocyte therapy in adults with discogenic low back pain. A comprehensive literature search was conducted on PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO, and Web of Science from database inception through on September 10th, 2015. We included clinical trials that evaluated stem cells or chondrocyte-based therapy in patients with discogenic back pain. The primary outcomes of interest were pain score and Oswestry Disability Index (ODI). We performed random-effects model meta-analyses to assess net changes in the same outcome variables. Heterogeneity between studies was estimated by I statistic. The initial search identified 1393 articles, of which 6 studies were eligible for this review. The pooled mean difference in pain score from baseline to follow-up points was 44.2 points decreased (95% CI: -61.8 to -26.5, P < 0.001, I = 99.4%). Meanwhile, the pooled mean difference in ODI from baseline to follow-up points was 32.2 points decreased (95% CI: -41.6 to -22.9, P < 0.001, I = 99.5%). No related adverse effects were reported by the included studies. Cell-based therapy is for patients who have discogenic low back pain associated with improved pain relief and ODI. More stringently designed randomized double-blind clinical trials with appropriately determined sample sizes will be needed to confirm its clinical efficacy and safety. 4.


IL-27R-mediated regulation of IL-17 controls the development of respiratory syncytial virus-associated pathogenesis.
IL-27 is a heterodimeric cytokine composed of the subunits p28 and Epstein-Barr virus induced gene (EBI)-3 and is known for its effects on T-cell function and differentiation. IL-27 signals through the widely expressed IL-27 receptor (IL-27R), composed of the ligand-specific IL-27Rα chain and gp130. Engagement of the IL-27R activates STAT1 signaling, induces the expression of the type 1 helper T-cell (Th1) cytokine, interferon γ, and suppresses the differentiation of Th2 and Th17 cells. This study investigates the role of IL-27 signaling in respiratory syncytial virus (RSV) infection using IL-27Rα-deficient mice (IL-27rKO). Analysis of lungs from RSV-infected IL-27rKO mice showed exacerbation of mucus secretion compared with wild type, as well as enhanced expression of Muc5ac and Gob5 mRNA, markers of goblet cell metaplasia/hyperplasia. When compared with wild-type mice, RSV-challenged IL-27rKO mice had enhanced expression of Th17-associated cytokine IL-17a and an imbalance between Th1 and Th2 cytokine levels. Neutralization of IL-17 in RSV-infected IL-27rKO mice resulted in a significant decrease in the pulmonary mucus response and inhibition of the Th2-associated cytokines. Interestingly, IL-17 blockage led to an increase in the expression of IL-27 subunits p28 and EBI-3 in the lungs and lymph nodes of RSV-infected mice. Thus, IL-27 functions as a regulatory cytokine during RSV pathogenesis by suppressing the development of Th17 cells, but it also appears to be regulated by IL-17 induced by the virus.


Initiation of rivaroxaban in patients with nonvalvular atrial fibrillation at the primary care level: the Swiss Therapy in Atrial Fibrillation for the Regulation of Coagulation (STAR) Study.
Rivaroxaban has become an alternative to vitamin-K antagonists (VKA) for stroke prevention in non-valvular atrial fibrillation (AF) patients due to its favourable risk-benefit profile in the restrictive setting of a large randomized trial. However in the primary care setting, physician's motivation to begin with rivaroxaban, treatment satisfaction and the clinical event rate after the initiation of rivaroxaban are not known. Prospective data collection by 115 primary care physicians in Switzerland on consecutive nonvalvular AF patients with newly established rivaroxaban anticoagulation with 3-month follow-up. We enrolled 537 patients (73±11years, 57% men) with mean CHADS2 and HAS-BLED-scores of 2.2±1.3 and 2.4±1.1, respectively: 301(56%) were switched from VKA to rivaroxaban (STR-group) and 236(44%) were VKA-naïve (VN-group). Absence of routine coagulation monitoring (68%) and fixed-dose once-daily treatment (58%) were the most frequent criteria for physicians to initiate rivaroxaban. In the STR-group, patient's satisfaction increased from 3.6±1.4 under VKA to 5.5±0.8 points (P<0.001), and overall physician satisfaction from 3.9±1.3 to 5.4±0.9 points (P<0.001) at 3months of rivaroxaban therapy (score from 1 to 6 with higher scores indicating greater satisfaction). In the VN-group, both patient's (5.4±0.9) and physician's satisfaction (5.5±0.7) at follow-up were comparable to the STR-group. During follow-up, 1(0.19%; 95%CI, 0.01-1.03%) ischemic stroke, 2(0.37%; 95%CI, 0.05-1.34%) major non-fatal bleeding and 11(2.05%; 95%CI, 1.03-3.64%) minor bleeding complications occurred. Rivaroxaban was stopped in 30(5.6%) patients, with side effects being the most frequent reason. Initiation of rivaroxaban for patients with nonvalvular AF by primary care physicians was associated with a low clinical event rate and with high overall patient's and physician's satisfaction.


Heterointerface Engineering of ZnO/CdS Heterostructures through ZnS Layers for Photocatalytic Water Splitting.
Solar-driven water splitting to produce clean and renewable hydrogen offers a green strategy to address the energy crisis and environmental pollution. Heterostructure catalysts are receiving increasing attention for photocatalytic hydrogen generation. ZnO/ZnS/CdS and ZnO/CdS heterostructures have been successfully designed and prepared according to two different strategies. By introducing a heterointerface layer of ZnS between ZnO and CdS, a Z scheme charge-transfer channel was promoted and achieved superior photocatalytic performance. A highest hydrogen generation rate of 156.7 μmol g-1 h-1 was achieved by precise control of the thickness of the heterointerface layer and of the CdS shell. These findings demonstrated that heterostructures are promising catalysts for solar-driven water splitting, and that heterointerface engineering is an effective way to improve the photocatalytic properties of heterostructures.


Why are so few patients with epilepsy treated surgically? A United Kingdom perspective.
The reasons why many patients with drug resistant complex partial epilepsy who might benefit from surgery are not appropriately assessed are examined, and include the attitudes and prejudices of Neurologists, Neurophysiologists, Neuroradiologists, Neurosurgeons and the patients themselves. Finally, the implications of provision of the necessary resources in the United Kingdom are presented.


Dexmedetomidine: current role in anesthesia and intensive care.
To update and review the application of dexmedetomidine in anesthesia and intensive care. This study is a comprehensive review of clinical uses, pharmacology, pharmacokinetics, mechanism of action and adverse effects of dexmedetomidine. The effective use of sedative-hypnotic agents and analgesics is an integral part of comfort and safety of patients. Dexmedetomidine is a potent and highly selective α-2 adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties, which has been described as a useful and safe adjunct in many clinical applications. It provides a unique "conscious sedation", analgesia, without respiratory depression. The current reviewed uses include sedation at Intensive Care Unit-ICU (both adult and pediatric), emergency department, regional and general anesthesia, neurosurgery, sedation for pediatric procedures, awake fiber-optic intubation, cardiac surgery and bariatric surgery. Dexmedetomidine offers a unique ability of providing both sedation and analgesia without respiratory depression. It is a new agent with a wide safety margin, excellent sedative capacity and moderate analgesic properties. Although its wide use is currently in patients of surgical and non-surgical intensive care units, dexmedetomidine seems to have promising future applications in neuroprotection, cardioprotection and renoprotection. More detailed studies are required to define its role as sedative in critical, neurosurgical and pediatric patients, as anesthesia adjunct and sedative during procedures.


Optimal controls for a model with pharmacokinetics maximizing bone marrow in cancer chemotherapy.
A mathematical model for the depletion of bone marrow under cancer chemotherapy is analyzed as an optimal control problem. The control represents the drug dosage of a single chemotherapeutic agent and pharmacokinetic equations which model its plasma concentration are included. The drug dosages enter the objective linearly. It is shown that optimal controls are bang-bang, i.e. alternate the drug dosages at full dose with rest-periods in between, and that singular controls which correspond to treatment schedules with varying dosages at less than maximum rate are not optimal. Numerical simulations are given to illustrate the effect of the pharmacokinetic equations on the dosages.


Organocatalytic asymmetric aldol reaction of hydroxyacetone with β,γ-unsaturated α-keto esters: facile access to chiral tertiary alcohols.
An efficient direct asymmetric aldol reaction between hydroxyacetone and β,γ-unsaturated α-keto esters has been successfully developed. In the presence of 9-amino-9-deoxy-epi-cinchonine and trifluoroacetic acid, the direct aldol reaction of O-protected hydroxyacetone proceeded in a highly enantioselective manner, affording the desired adducts containing a chiral tertiary alcohol in high yields and with excellent enantioselectivities. The aldol products obtained are valuable precursors for the synthesis of 2-substituted glycerol derivatives.


Chondroblastoma and clear cell chondrosarcoma: radiological and MRI characteristics with histopathological correlation.
To analyze and compare the radiological and magnetic resonance imaging (MRI) appearances of chondroblastoma and clear cell chondrosarcoma with histopathological correlation. Twelve patients with histologically proven chondroblastoma and of another four patients with clear cell chondrosarcoma were investigated by radiographs and MRI (T1-, T2-weighted sequences, intravenous gadolinium application). Additionally, the clinical and radiologic data of seven cases of clear cell chondrosarcoma without available MRI were considered. The localization, calcification of tumor matrix, periosteal reaction, cortical bone and patterns of bone destruction were analyzed according to the Lodwick radiological grading system (LRGS). The signal intensity on T1- and T2-weighted sequences, characteristics of contrast enhancement, associated bone marrow edema, soft tissue reaction and joint involvement were evaluated. Histopathological specimens were available in all cases. The age of patients with chondroblastoma (range 15-59 years, mean 22.3 years) was lower than that of those with clear cell chondrosarcoma (range 19-61 years, mean 36.6 years), and the lesions were smaller in the chondroblastoma group (range 1-4 cm, mean 2.3 cm) than in patients with clear cell chondrosarcoma (range 3-7.5 cm, mean 5.2 cm). The chondroblastomas were more confined to the epiphysis (10/12) than the clear cell chondrosarcomas. All chondroblastomas and clear cell chondrosarcomas except one were classified as grade 1A or 1B according to the LRGS; one clear cell chondrosarcoma was judged as grade 2. Signal intensity of the tumors on MRI was very heterogeneous in both groups. High signal intensity on T2-weighted MR images in chondroblastoma mostly corresponded to areas with aneurysmal bone cyst components and in clear cell chondrosarcoma to islands of hyaline cartilage. Contrast enhancement occurred in all tumors and tended to be more intense with clear cell chondrosarcoma. Chondroblastoma was more frequently associated with bone marrow edema (11/12), periosteal reaction (10/12), soft tissue reaction (7/12) and synovitis (3/12). Chondroblastoma occurs in younger patients, is smaller than clear cell chondrosarcoma and is more confined to the epiphysis. The overlap of signal intensity and contrast enhancement patterns does not allow a reliable differentiation of the two tumors by MRI. Chondroblastomas are typically associated with bone marrow edema, periosteal reaction and soft tissue reaction.


Reperfusion with nifedipine: improved functional recovery after cold cardioplegic arrest.
Nifedipine, an antagonist of myocardial calcium uptake, given after a period of a cold, cardioplegic arrest (150 min, 18 degrees C, St Thomas' cardioplegic solution) improved contractile recovery of the isolated working rat heart model of cardiopulmonary bypass. The hearts were reperfused with various concentrations of nifedipine in Krebs-Henseleit buffer (37 degrees C, 100 cm H2O) and their functional recoveries were compared with the control series reperfused without nifedipine. A bell-shaped dose/response curve was produced by the drug, and optimal protection observed with 0.1 mumol/l of nifedipine which improved the post-ischaemic recovery of the aortic flow from 56.8% +/- 3.7% to 80.1% +/- 3.2% (P less than 0.001). The importance of careful dose adjustment is stressed since it was noted that higher concentrations inhibit both functional and metabolic performance. This study supports the hypothesis that at the end of a cold cardioplegic arrest there are still reversibly injured cells which could restore their function if the cellular ingress of Ca++ during reperfusion is reduced by nifedipine.


Diagnostic workup for neuromuscular diseases.
Clinical symptoms of neuromuscular diseases vary according to age and type of primary involvement (spinal motor neuron, nerve, neuromuscular junction or muscle). Tools at our disposal for diagnostic purposes are graduated based on the age of the patient and diagnostic suspicions generated by the clinical workup. Seven clinical presentations can be identified that all require technical facilities specifically dedicated to pediatric neuromuscular diseases: congenital hypomobility and arthrogryposis, paralytic hypotonia in infancy, motor delay and chronic walking difficulties after the age of 18 months, progressive walking difficulties after the age of 3 years, effort intolerance and acute rhabdomyolysis, acute motor symptoms or fatigability, and variability of symptoms. Electrophysiological investigation, particularly electromyography, is a valuable tool where neurogenic involvement or neuromuscular block is suspected. However, the technique is difficult to perform in children. Muscle biopsy is generally the key investigation and can be performed at any age. Molecular biology helps to improve diagnostic strategy. Muscle MRI, in combination with clinical evaluation, assists the selection of appropriate genetic tests and more generally the identification of genetically distinct forms of neuromuscular disorder. None of these are by any means routine investigations, and only a specialized multidisciplinary clinical approach can permit correct diagnosis and proper follow-up.


Development of a solubility parameter calculation-based method as a complementary tool to traditional techniques for indoor dust microplastic determination and risk assessment.
Herein, a method based on solubility parameter calculation was first used to analyze microplastics in indoor dust. The limit of quantification (LOQ) reached 0.2 mg/g, and the result of reference material SRM 2585 (n = 3) was 14.8 mg/g ± 1.8 %, suggesting satisfying sensitivity and precision. Recoveries of spiking experiments were > 80 % with no obvious matrix interferences observed, except ethylene propylene diene monomer (EPDM) MPs. Further, 69 indoor dust samples were analyzed to verify the method and to assess exposure scenarios for graduate students in Tianjin, China. EPDM was identified in an indoor environment for the first time as the second most widely detected type after PET in this work. The mass-based result is complementary to the outcomes from thermogravimetric analysis-gas chromatography-mass spectrometry and laser direct infrared imaging. Significant correlations were found between total organic carbon (TOC), microplastics, and BDE-209 concentrations, indicating microplastics important contaminant vectors in indoor dust. Dormitory stays and PET contributed the most to health risks among the three exposure scenarios and detected four polymers, respectively. This work provides an approach with the potential for the standardized determination of microplastics in complex environmental matrices and reveals exposure characteristics of indoor dust microplastics.


The relationship between elevated plasma zonulin levels and Hashimoto's thyroiditis.
Hashimoto thyroiditis (HT) is one of the most prevalent autoimmune diseases. The intestine microbiota is strongly associated with autoimmune diseases. Zonulin, a modulator of tight junctions that controls the selective permeability of the intestine can induce an elevation in gut permeability. We aimed to investigate the association of plasma zonulin levels with HT. We compared 77 HT patients with 66 age-gender and BMI-matched healthy individuals in the case of plasma zonulin levels. Plasma zonulin levels were measured by ELISA. The statistical analyses were performed using Student's t-test and chi-square tests. The predictive power was investigated using univariate and multivariate logistic regression analysis. We found that the increase in plasma zonulin levels in the HT group was statistically significant compared to the control group (p < 0.001). The regression analysis showed that urea, anti-thyroid peroxidase, aspartate aminotransferase, thyroid-stimulating hormone, free T3, and serum zonulin levels were found to be associated with HT in both univariate and multivariate models (p < 0.05). Zonulin is a possible biomarker candidate that may link intestinal permeability with the etiology of autoimmune diseases.


"The problem is that our culture is just so messed up about aging." Recruiting older men who have sex with men (MSM) into research studies: an example from a study of aging, HIV, and anal HPV.
Anal human papillomavirus (HPV) disproportionately affects men who have sex with men (MSM), particularly those who are older and those living with HIV. After experiencing difficulty recruiting older MSM into a study on aging and anal HPV, we conducted a sub-study to gain feedback on our recruitment methods and explore barriers and facilitators to participating in anal HPV research. We conducted focus groups with 30 men who have sex with men (MSM), both HIV-negative and MSM living with HIV, ages 50-75. We identified multiple themes that were barriers to participation including: (1) lack of knowledge about human papillomavirus and anal cancer; (2) research focused on anal cancer or discomfort with topics or procedures concerning the anus; (3) stigma including stigma associated with being men who have sex with men, being out, being a receptive partner, and being considered "older" in the gay community; and (4) confidentiality concerns including a fear of breach of confidentiality. Facilitators to participation were also identified; these motivational factors include altruism, wanting recommendations from a doctor, and desire to receive the best available care. Researchers seeking to enroll older men who have sex with men should be aware of these barriers and facilitators to participation in order to maximize recruitment.


Low Contrast Volume Protocol in Routine Chest CT Amid the Global Contrast Shortage: A Single Institution Experience.
To assess the effectiveness of low contrast volume (LCV) chest CT performed with multiple contrast agents on multivendor CT with varying scanning techniques. The study included 361 patients (65 ± 15 years; M: F 173:188) who underwent LCV chest CT on one of the six 64-256 detector-row CT scanners using single-energy (SECT) or dual-energy (DECT) modes. All patients were scanned with either a fixed-LCV (LCVf, n = 103) or weight-based LCV (LCVw, n = 258) protocol. Two thoracic radiologists independently assessed all LCV CT and patients' prior standard contrast volume (SCV, n = 263) chest CT for optimality of contrast enhancement in thoracic vasculature, cardiac chambers, and in pleuro-parenchymal and mediastinal abnormalities. CT attenuations were recorded in the main pulmonary trunk, ascending, and descending thoracic aorta. To assess the interobserver agreement, pulmonary arterial enhancement was divided into two groups: optimal or suboptimal. There was no significant difference among patients' BMI (p = 0.883) in the three groups. DECT had a significantly higher aortic arterial enhancement (250 ± 99HU vs 228 ± 76 HU for SECT, p < 0.001). Optimal enhancement was present in 558 of 624 chest CT (89.4%), whereas 66 of 624 chest CT with suboptimal enhancement was noted in 48 of 258 LCVw (18.6%) and 14 of 103 LCVf (13.6%). Most patients with suboptimal enhancement with LCVw injection protocol were overweight/obese (30/48; 62.5%), (p < 0.001). LCV chest CT can be performed across complex multivendor, multicontrast media, multiscanner, and multiprotocol CT practices. However, LCV chest CT examinations can result in suboptimal contrast enhancement in patients with larger body habitus.


Towards a Field-Portable Real-Time Organic and Elemental Carbon Monitor.
Diesel particulate matter (DPM) has been classified as a carcinogen to humans by the International Agency for Research on Cancer. As a result of its potential carcinogenic nature, DPM exposure is regulated by the Mine Safety and Health Administration. Currently, diesel emissions in the workplace are monitored by collecting the aerosol onto filters, which are then sent to a laboratory for thermal-optical analysis using the NIOSH method 5040. This process can take days or even weeks, and workers can potentially be exposed to excessive levels of DPM before the problem is identified. Moreover, the delay involved in getting the loaded filter to the lab inevitably means the loss of some of the more volatile organic carbon. To remedy this delay, researchers from the National Institute for Occupational Safety and Health are seeking to develop a field-portable, real-time method for measuring elemental and organic carbons in DPM aerosols. In the current study, the use of mid-infrared spectrometry was investigated. It is believed that mid-infrared spectroscopy is more suitable for use in a real-time field-portable device than thermo-optical analysis methods. This article presents a method for measuring organic carbon (OC) and elemental carbon (EC) in DPM for a broad range of OC/EC ratios. The method has been successfully applied to laboratory-generated and mine samples.


The calcium-binding property of equine lysozyme.
It was found that equine lysozyme binds one Ca2+. It was eluted with equimolar Ca2+ from a Bio-Gel P-4 column. Human lysozyme did not behave similarly. Equine lysozyme is concluded to be a calcium metallo-protein like alpha-lactalbumin, which is a homologue of hen egg white lysozyme.


Farming Practices Influence Antibiotic Resistance and Biogenic Amine Capacity of Staphylococci from Bulk Tank Ewe's Milk.
Staphylococci are one of the main microorganisms responsible for intramammary infections in sheep, causing important economic losses for farmers and eventually health problems in humans, especially by the consumption of dairy products made with raw milk containing toxic compounds, such as biogenic amines or antibiotic resistant bacteria. This study aimed to check the presence and safety of staphylococci in bulk tank ewe's milk from different farms, and to determine the relationship between the presence of these staphylococci and farming practices, by applying nonlinear canonical correlation models (OVERALS). Two-hundred and fifty-nine staphylococci from milk samples from eighteen farms were genotyped and representative isolates of the major clusters were identified as belonging to Staphylococcus (S.) aureus, S. epidermidis, S. arlettae, S. lentus, S. simulans, and S. chromogenes species. Identified isolates were assayed in terms of their safety, by evaluating resistance to antimicrobial drugs and the aminobiogenic capacity, using both phenotypic and genetic assays. Antibiotic resistance phenotypic assay revealed that 82.9% were resistant to some antibiotics, although in the genotypic assay only the genes tetM, ermB, ermC, and grlA were detected. Fifty-three percent were high biogenic amine (BA) producers, being putrescine the most produced amine. A lowered risk of finding antibiotic-resistant and BA-producing staphylococci is related to some farming methods such as enrolling in a breeding program, use of good farming practices, postdipping teat disinfection, hygienic livestock housing, or periodic check of the milking machine.


Bacillus licheniformis variant DY proteinase: specificity in relation to the geometry of the substrate recognition site.
S1-S4 specificity of the Bacillus licheniformis variant DY proteinase (subtilisin DY) was determined by a series of peptide nitroanilides. The broad S1 specificity is due to the relative flexibility of the binding loop, which exhibits a preference for phenylalanine and accepts poorly the side chains of alanine, valine, lysine, and especially that of glutamic acid, due probably to a steric repulsion by Asn 155 and the narrow entrance of the "pocket." Alanine in position P2 of the substrate is more favorable for the catalysis than glycine. S3 is located on the protein surface. It is more open than the other subsites and can accept a variety of residues. S4 exhibits an extremely high affinity for the aromatic group of phenylalanine. Evidently, hydrophobic forces predominate in the S4--P4 interactions. The results characterize subtilisin DY as a bacterial proteinase with a broad specificity due to the specific geometry and flexibility of the substrate recognition site, which can accommodate different types of amino acid side chains.


Frequency & factors associated with apparent resistant hypertension among Ghanaians in a multicenter study.
Apparent resistant hypertension (ARH) is rife among people living with hypertension and is associated with significant morbidity and mortality. There is however paucity of data from sub-Saharan Africa on the burden of ARH. We sought to report on the frequency and factors associated with ARH among a cohort of Ghanaians with hypertension. A cross-sectional study involving 2912 participants with hypertension enrolled at five health facilities in Ghana. ARH was defined as either office BP ≥ 140/90 mm Hg on 3 or more antihypertensive medications or on 4 or more antihypertensive medications regardless of BP. Factors associated with ARH were evaluated in a multivariate logistic regression model. We found 550 out of 2,912 (18.9%) of study participants had ARH. Out of these 550 subjects, 511 (92.9%) were on 3 or more antihypertensive medications with BP ≥ 140/90 mm Hg and 39 (7.1%) were on 4 or more antihypertensive medications with BP ≥ 140/90 mm Hg. The prevalence of ARH was 15.5% among elderly aged 75 + years (n = 341), 20.7% among 65-74 years (n = 588), and 18.9% among those ≤ 64 years (n = 1983). The adjusted odds ratio (95% CI) of factors independently associated with ARH was duration of hypertension, 1.05 (1.03-1.06) for each year rise; eGFR < 60 mL/min, 1.73 (1.33-2.25); and diabetes mellitus, 0.59 (0.46-0.76). Attaining secondary level education and residence in a peri-urban setting were significantly associated with ARH though not in a dose-dependent manner. ARH is rife among Ghanaians and may negatively impact on cardiovascular outcomes in the long term.


Patients With a High Femoroepiphyseal Roof With Concomitant Borderline Hip Dysplasia and Femoroacetabular Impingement Syndrome Do Not Demonstrate Inferior Outcomes Following Arthroscopic Hip Surgery.
The purpose of this study was to compare outcomes after hip arthroscopy for femoroacetabular impingement syndrome (FAIS) in patients with borderline hip dysplasia and hip instability defined radiographically using the femoroepiphyseal acetabular roof (FEAR) index and in patients without radiographic evidence of hip instability. Data from consecutive patients with borderline hip dysplasia (lateral center edge angle between 18˚-25˚) who underwent primary hip arthroscopy between April 2012 and June 2017 for the treatment of FAIS were analyzed. Baseline demographic data, radiographic parameters, preoperative, and 2-year postoperative patient-reported outcome measures were collected. The FEAR index was measured by 3 different observers. Patients with an average FEAR index ≥2˚ were categorized as having radiographic evidence of instability as previously published. The analysis was powered to detect a minimal clinically important difference (MCID) for each outcome score. Statistical analysis was performed as appropriate to compare patients with FEAR index ≥2 and <2°. A total of 140 patients met the inclusion criteria. The average age and body mass index of included patients was 31.7 ± 13.2 (P < .325) years and 25.1 ± 5.6 kg/m2 (P < .862). There were no statistically significant demographic differences between the groups. Nineteen (13.0%) patients were found to have a FEAR index of over 2˚. The FEAR index <2° and FEAR index ≥2° groups had a mean preoperative FEAR index (standard deviation, range) of -7.0 (5.2, -26.8 to 1.9) and 4.8 (2.5, 2.0-11.8), respectively. The interrater intraclass correlation coefficient was 0.96. Postoperative patient-reported outcomes and rates of MCID and patient-acceptable symptomatic state achievement were not statistically different between the radiographically stable and unstable groups. (p>0.05 for all). Patients with borderline hip dysplasia and radiographic evidence of hip instability, as measured by the FEAR index (≥2°), achieve similar improvement in 2-year outcomes compared to those with radiographically stable hips after arthroscopic treatment of FAIS. Retrospective Level III cohort study.


Corrigendum: Spjut R, Simon A, Guissard M, Magain N, Sérusiaux E (2020) The fruticose genera in the Ramalinaceae (Ascomycota, Lecanoromycetes): their diversity and evolutionary history. MycoKeys 73: 1-68. https://doi.org/10.3897/mycokeys.73.47287.
[This corrects the article DOI: 10.3897/mycokeys.73.47287.].


Thermoelectric Transport in a Three-Dimensional HgTe Topological Insulator.
The thermoelectric response of 80 nm-thick strained HgTe films of a three-dimensional topological insulator (3D TI) has been studied experimentally. An ambipolar thermopower is observed where the Fermi energy moves from conducting to the valence bulk band. The comparison between theory and experiment shows that the thermopower is mostly due to the phonon drag contribution. In the region where the 2D Dirac electrons coexist with bulk hole states, the Seebeck coefficient is modified due to 2D electron-3D hole scattering.


Do desert locust hoppers develop gregarious characteristics by watching a video?
Various sensory stimuli have been suggested to induce gregarious body coloration in locusts, but most previous studies ignored the importance of substrate color. This study tested the effects of visual, olfactory and tactile stimuli from other locusts on the induction of gregarious body coloration in single (isolated-reared) Schistocerca gregaria nymphs housed in yellow-green cups. Odor from gregarious (crowd-reared) locusts, which is believed to induce black patterns in single locusts, had little effect when applied to visually isolated nymphs at the 2nd stadium onward, and all test nymphs remained green without black patterns at the last stadium, as in controls reared without odor and visual stimuli. Visual stimuli alone induced black patterns when a single solitarious nymph was allowed to see other locusts in another cup. The degree of black patterns increased as the number of locusts shown increased, and some test nymphs developed body coloration typically observed in gregarious forms. A classical morphometric ratio (hind femur length/head width) shifted toward the value typical of gregarious forms when the single nymphs were allowed to see 5 or 10 locusts. Single nymphs also developed black patterns when presented green conspecific nymphs and adults of two hemipteran species kept in another cup. No synergetic effects of visual and odor stimuli were detected. Movies of locusts, crickets and tadpoles were found effective in inducing black patterns in single locusts. Ontogenetic variation in the sensitivity to crowding and experimental methodology might be responsible for some discrepancies in the conclusions among different researchers.


Two-step pressure injection-assisted online enrichment of herbicides from foods with affinity micelle sweeping by micellar electrokinetic chromatography.
A novel online two-step pressure injection-assisted stacking preconcentration method, which involves sweeping and affinity micelles in micellar electrokinetic chromatography was developed to simultaneously measure various organic anions. The micellar solution was a mixed solution that contained 0.3 mM didodecyldimethylammonium bromide and 20 mM borax. After the micellar solution was injected for 60 s, the tested analytes prepared in 20 mM borax were introduced into the capillary for 150 s. The key experimental factors that influenced the separation and sensitivity were investigated and optimized, including the concentration and injection time of the micellar solution, the concentration of borax in the sample solution, the concentration of sodium dodecyl sulfate and borax in the background electrolyte (BGE), the content of acetonitrile in the BGE and the injection time of the sample solution. Compared with typical injection methods, this method achieved sensitivity enhancement factors ranging from 85 to 97 under optimized conditions. Good linearity for matrix-matched calibration was established for all analytes with R2 values of 0.9986-0.9996. The intraday (n = 6) and interday (n = 6) precisions of the method were less than 2.85% when expressed as relative standard deviations. When the method was applied to analyze rice and dried ginger samples, analyte recoveries ranged from 85.81% to 106.59%. Through sweeping and affinity micelles, stacking preconcentration method was successfully employed to analyze trace amounts of fenoprop and 2,4-dichlorophenoxyacetic acid in rice and dried ginger samples.


Unravelling the adsorption and electroreduction performance of CO2 and N2 over defective and B, P, Si-doped C3Ns: a DFT study.
Two-dimensional carbon-based materials have great potential for electrocatalysis. Herein, we screen 12 defective and doped C3N nanosheets by evaluating their CO2RR and NRR activity and selectivity vs. the HER based on density functional theory calculations. The calculation results suggest that all 12 C3Ns can enhance CO2 adsorption and activation. And PN-VC-C3N is the best electrocatalyst for the CO2RR towards HCOOH with UL = -0.17 V, which is much more positive than most of the reported values. BN-C3N and PN-C3N are also good electrocatalysts that promote the CO2RR towards HCOOH (UL = -0.38 V and -0.46 V). Moreover, we find that SiC-C3N can reduce CO2 to CH3OH, adding an alternative option to the limited catalysts available for the CO2RR to CH3OH. Furthermore, BC-VC-C3N, BC-VN-C3N, and SiC-VN-C3N are promising electrocatalysts for the HER with |ΔGH*| ≤ 0.30 eV. However, only three C3Ns of BC-VC-C3N, SiC-VN-C3N, and SiC-VC-C3N can slightly improve N2 adsorption. And none of the 12 C3Ns are found to be suitable for the electrocatalytic NRR because all the ΔeNNH* values are larger than the corresponding ΔGH* values. The high performance of C3Ns in the CO2RR stems from the altered structure and electronic properties, which result from the introduction of vacancies and doping elements into C3N. This work identifies suitable defective and doped C3Ns for excellent performance in the electrocatalytic CO2RR, which will inspire relevant experimental studies to further explore C3Ns for electrocatalysis.


Asymmetric Dimethylarginine Levels and Its Correlation to Cerebral Blood Flow in Children with Sickle Cell Anemia.
Asymmetric dimethylarginine (ADMA) level may play a role in the pathogenesis of cerebrovascular stroke in Children with Sickle Cell Anemia (SCA). To assess the plasma level of ADMA in children with SCA and its correlation to cerebral blood flow. This is a cross sectional study was carried out on 30 children with homozygous SCA under follow up in the Out Patients Clinic, Pediatric Department at Tanta University Hospital and 30 healthy children as a control group. Both groups had undergone the following investigations: Complete blood count, lactate dehydrogenase enzyme, and plasma level of ADMA by a commercial ADMA ELISA Kit. Trans-cranial Doppler were done for both groups. ADMA plasma level was significantly higher in-patient group in comparison to the control group (p < 0.001), with a mean value 1.43 ± 0.20 μmol/l, 0.48 ± 0.16 μmol/l respectively. The time-averaged mean maximum velocities for middle cerebral artery, anterior cerebral artery, inferior cerebral artery and posterior cerebral artery were significantly different between patient and control group, p < 0.05. Trans-cranial Doppler data revealed that, 86.7% of patients have low velocity (< 70 cm/s) and 13.3% having very low velocity (< 10 cm/s) while control group have normal velocity. There was a significant negative correlation between ADMA plasma levels and cerebral blood flow. Elevated ADMA levels may have a role in the pathogenesis of the decreased cerebral blood flow in children with SCA.


Driver obesity and the risk of fatal injury during traffic collisions.
Few studies have looked at how obesity affects injury outcomes among vehicle occupants involved in traffic collisions. To estimate the association of obesity with death risk among drivers of passenger vehicles aged ≥16 and to examine effect modification by driver sex, driver seat belt use, vehicle type and collision type. We conducted a matched-pair cohort study using data from the Fatality Analysis Reporting System. WHO body mass index (BMI) categories were calculated. Data were analysed using conditional Poisson regression. Estimated risk ratios (RRs) were slightly raised for underweight drivers (RR=1.19, 95% CI 0.86 to 1.63). RR increased with higher BMI categories and were 1.21 (0.98 to 1.49) for BMI 30-34.9, 1.51 (1.10 to 2.08) for BMI 35-39.9 and 1.80 (1.15 to 2.84) for BMI ≥40. Estimated BMI effects varied by gender. We found no meaningful variation across levels of vehicle type, collision type or seat belt use. Findings from this study suggest that obese vehicle drivers are more likely to die from traffic collision-related injuries than non-obese occupants involved in the same collision. Education is needed to improve seat belt use among obese people, as is research to understand the potential role of comorbidities in injury outcomes.


Heightened blood pressure and drinking responsiveness to intracerebroventricularly applied angiotensins in the spontaneously hypertensive rat.
The effects of bolus intracerebroventricular (i.c.v.) injections of angiotensin II (AII) and angiotensin III (AIII) on blood pressure and water consumption were investigated in Okamoto-Aoki spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive controls. Heightened sensitivity to i.c.v. administered AII and AIII was observed in the SHR as compared with WKY and SD strains for both pressor and drinking responses. The results are consistent with the notion that the SHR has a genetic defect that directly perturbs central angiotensinergic transmission. Two types of defects appear plausible, an alteration in the central angiotensin receptor and its associated transduction system and/or a decrease in the efficiency of signal termination. The present results are interpreted to primarily support the second possibility that a dysfunction in central aminopeptidase activity results in an extended life expectancy of angiotensin, and perhaps other peptides, that contribute to the hypersensitivity seen in the SHR.


The association between the CC chemokine ligand 5 -28C>G gene polymorphism and tuberculosis susceptibility.
To assess the association between chemotactic chemokine (C-C motif) ligand 5 (CCL5) -28C>G polymorphism and tuberculosis (TB) risk. PubMed, Web of Science, and WanFang were searched up to April 2015 for eligible studies on CCL5 -28C>G polymorphism. Data was extracted, and pooled odd ratios (ORs) as well as 95% confidence intervals (95% CI) were calculated. Eight case-control studies were extracted from 8 articles on the polymorphism involving 1852 TB cases and 2068 controls. The results of meta-analysis showed that significant reduced risks were found for the polymorphism with the risk of TB in Asians and Arabs as follows: OR=0.12, 95% CI=0.06-0.26, p=0.000 for mutant homozygous (GG) versus wild-type homozygous (CC) for Asian descent, OR=0.14, 95% CI=0.07-0.28, p=0.000 for GG versus CC in the Arab descent. Our findings demonstrated that CCL5 gene -28C>G polymorphism might be a protective factor for the development of TB.


Basal rate of metabolism and temperature regulation of two desert herbivorous octodontid rodents: Octomys mimax and Tympanoctomys barrerae.
We studied the energetics of two herbivorous desert rodents from South America. The two species had slightly lower basal metabolic rates, lower thermal conductances, and higher temperature differentials than those expected from their body mass. Mass-independent basal rates of metabolism were higher than those reported for seed-eating desert rodents from North America. Our observations support the hypothesis that desert rodents that eat foods with high water content have higher mass-independent metabolic rates than seed-eating desert rodents.


Core temperature measurement: a comparison of rectal, axillary and pulmonary artery blood temperature.
This research study was undertaken to determine the relationship between pulmonary artery (PA) blood temperature, rectal temperature and axillary temperature for adult patients admitted to an intensive care unit (ICU). 31 adults had their temperatures monitored. Simultaneous recordings of PA blood temperature, rectal temperature and axillary temperature were taken every 4h for up to 7 days. The mean difference between rectal and axillary temperature for all 31 patients was 0.32 degree C. Of the 16 patients who had their PA blood temperature monitored mean rectal temperature was 0.1 degree C above PA blood temperature and mean axillary temperature was 0.19 degree C below PA blood temperature. Very high statistical correlations were obtained which demonstrate the strength of the relationships between the three sites (rectal-axillary temperature difference R = 0.97; PA blood-rectal temperature difference R = 0.99; PA blood-axilla temperature difference R = 0.97). The linear relationship between the three sites studied was not found to be affected by age, gender, number of temperature samples taken, post/non-operative admission or peripheral temperature.


From dogs to frogs: how pets, laboratory animals, and wildlife aided in elucidating harmful effects arising from a hazardous dumpsite.
The medical literature contains many examples of cases in which serendipitous observations have led to important findings. In the example described in this article, laboratory and field observations conducted at the Mohawk Nation Community of Akwesasne led to the important and unexpected finding that frogs once plentiful in the area were no longer observed. Laboratory tests comparing river sediments from Akwesasne to pristine sediment from Ithaca, NewYork, indicated multiple adverse health effects on developing frogs. Some of the behavioral changes observed in the laboratory were similar to those described by residents of Akwesasne before the onset of amphibian decline. The magnitude of changes paralleled frog body burden of polychlorinated biphenyls acquired from the Akwesasne sediment. The impact of these findings on the identification of a hazardous waste site and global amphibian decline are discussed.


Understanding individual differences in vulnerability to cigarette smoking is enhanced by attention to the intersection of common risk factors.
While smoking prevalence in the U.S. and other industrialized countries has decreased substantially, this change has been unevenly distributed, with dramatic decreases in certain subpopulations but little change or even increases in others. Accordingly, considerable attention has been fruitfully devoted to identifying important risk factors for smoking (e.g., mental illness, other substance use disorders). However, there has been little research on the intersection of these risk factors. As risk factors rarely occur in isolation, it is important to examine risk-factor profiles as is commonly done in studying other chronic conditions (e.g., cardiovascular disease). The purpose of this Commentary is to encourage greater interest in the intersection of multiple risk factors using cigarette smoking as an exemplar. We focus on the intersection of eight well-established risk factors for smoking (age, gender, race/ethnicity, educational attainment, poverty, drug abuse/dependence, alcohol abuse/dependence, mental illness). Studying the intersection of risk factors is likely to require use of innovative data-analytic methods. We illustrate, using years 2011-2016 of the US National Household Survey on Drug Use and Health, how Classification and Regression Tree (CART) analysis can be an effective tool for identifying risk profiles for smoking. Examination of the intersection of these risk factors elucidates a series of risk profiles with associated, orderly gradations in vulnerability to current smoking, including the striking and reliable strength of a college education as a stand-alone profile predicting low risk for current smoking, and illustrating the potentially increasing importance of drug abuse/dependence as a risk factor.


Ranking potential impacts of priority and emerging pollutants in urban wastewater through life cycle impact assessment.
Life cycle impact assessment (LCIA), a feature of the Life cycle assessment (LCA) methodology, is used in this work outside the LCA framework, as a means to quantify the potential environmental impacts on ecotoxicity and human toxicity of wastewater containing priority and emerging pollutants. In order to do this, so-called characterisation factors are obtained for 98 frequently detected pollutants, using two characterisation models, EDIP97 and USES-LCA. The applicability of this methodology is shown in a case study in which wastewater influent and effluent samples from a Spanish wastewater treatment plant located in the Mediterranean coast were analysed. Characterisation factors were applied to the average concentration of each pollutant, obtaining impact scores for different scenarios: discharging wastewater to aquatic recipient, and using it for crop irrigation. The results show that treated wastewater involves a substantially lower environmental impact when compared to the influent, and pharmaceuticals and personal care products (PPCPs) are very important contributors to toxicity in this wastewater. Ciprofloxacin, fluoxetine, and nicotine constitute the main PPCPs of concern in this case study, while 2,3,7,8-TCDD, Nickel, and hexachlorobenzene are the priority pollutants with highest contribution. Nevertheless, it must be stressed that the new characterisation factors are based on very limited data, especially with regard to toxicology, and therefore they must be seen as a first screening to be improved in the future when more and higher quality data is available.


Using global gene expression patterns to characterize Annexin V positive and negative human monocytes in culture.
To investigate the early apoptosis that may be detected by Annexin V binding to phosphatidylserine and propidium iodide (PI) exclusion in human monocytes. When studying monocytes in culture, less than 40 % of these cells survive after 7 days. In the first 4 h, 24 % of monocytes in culture develop into Annexin V(+)/PI(-) cells. Human monocytes were investigated at 0 h and sorted into Annexin V(+) and Annexin V(-) by FACS after 4 h. Gene expression was examined by microarray analyses. At 4 h, Annexin V(+) monocytes versus Annexin V(-) cells showed 1220 differentially expressed genes. Ingenuity Pathway Analysis disclosed 153 genes related to cell death. Among these were caspase activators, caspase 6, Apaf 2 and FAS, as well as the autophagy gene ATG5. In addition, examination of the most up-regulated or down-regulated genes among the 1220 revealed genes involved in other biological processes, as well as genes not yet annotated. These included the non-annotated genes LOC28480 (fold change: 82) and 225767-at (fold change: 68) and the transcription factor SOX 4 (fold change: 24). conclusions: We suggest that apoptosis in cultured monocytes, as evidenced by Annexin V(+), operates through genes well known in apoptosis, but that the process also involves additional genes not commonly associated with apoptosis.


Cu2+-regulated one-pot wet-chemical synthesis of uniform PdCu nanostars for electrocatalytic oxidation of ethylene glycol and glycerol.
The fabrication of effective and stable electrocatalysts is crucial for practical applications of direct alcohol fuel cells (DAFCs). In this study, bimetallic PdCu nanostars (PdCu NSs) were fabricated by a Cu2+-modulated one-pot wet-chemical method, where cetyltrimethyl ammonium bromide (CTAB) worked as a structure-regulating reagent. The morphology, compositions, crystal structures and formation mechanism of the as-prepared PdCu NSs were investigated by a series of techniques. The unique architectures created abundant active sites, which resulted in a large electrochemical active surface area (9.5 m2 g-1). The PdCu NSs showed negative shifts in the onset potentials and large forward peak current densities by contrast with those of commercial Pd black for the catalytic ethylene glycol oxidation reaction (EGOR) and glycerol oxidation reaction (GOR). It revealed that the PdCu NSs outperformed Pd black in the similar surroundings. This work provides a constructive strategy for fabrication of high-efficiency electrocatalysts for alcohol fuel cells.


Use of a modified N-nitrosoproline test to show intragastric nitrosation in patients at risk of gastric cancer.
Intragastric nitrosation has been implicated in the pathogenesis of gastric cancer and in precancerous conditions such as pernicious anaemia and the post-gastrectomy state. Intragastric nitrosation was assessed in at-risk patients by N-nitrosoproline (NPRO) excretion using both a conventional and a modified test. Twenty-four hour urinary excretion of NPRO was measured after oral administration of sodium nitrate (300 mg) and L-proline (500 mg) as an indirect indicator of intragastric nitrosation. In the conventional test no differences in intragastric nitrosation were found between at-risk patients and controls. In the modified test the loading dose of sodium nitrate was omitted and urinary NPRO levels were found to be significantly increased in Polya partial gastrectomy patients (P = 0.003) and post-vagotomy patients (P = 0.03) compared to controls. In pernicious anaemia patients NPRO levels were also higher than in controls but just failed to reach statistical significance. This study has confirmed that hypochlorhydria results in increased intragastric nitrosation, thus facilitating the formation of potentially carcinogenic N-nitroso compounds.


Single cell RNA-seq in phytohormone signaling: a promising future.
Phytohormone signaling regulates plant growth and development. Single cell RNA sequencing (scRNA-seq) provides unprecedented opportunities to decipher hormone-mediated spatiotemporal gene regulatory networks. In a recent study, Nolan et al. used time-series scRNA-seq to identify the cortex as a key site for brassinosteroid (BR)-mediated gene expression and revealed a signaling network during cell phase transition.


Plasma antithrombin-III values in healthy horses: effect of sex and/or breed.
Plasma antithrombin-III (AT-III) values were determined in 74 healthy horses by an automated spectrophotometric assay. The mean plasma AT-III value was 218% +/- 18% of normal human plasma. Plasma AT-III values did not differ significantly (P less than 0.05) among Thoroughbred, Standardbred, Quarter Horse, and other breeds or among mares, geldings, or stallions.


Fluorescent assay for alkaline phosphatase by integrating strand displacement amplification with DNAzyme-catalytic recycling cleavage of molecular beacons.
A fluorescence sensing method for the quantification of alkaline phosphatase (ALP) was developed by integrating the strand displacement amplification with DNAzyme-catalytic recycling cleavage of molecular beacons. ALP can hydrolyze a 3'-phosphoralated primer into a 3'-hydroxy primer which can initiate the strand displacement amplification to produce the Mg2+-dependent DNAzyme. The DNAzyme can then catalyze the cleavage of the DNA molecular beacon labeled with FAM fluorophore at its 5'-end and BHQ1 quencher at its 3'-end, turning on the fluorescence of FAM fluorophore. The content of ALP in a sample can be deduced from the measured fluorescence intensity. Due to the cascading nature of its amplification strategy, the proposed method achieved sensitive and specific ALP detection in human serum samples. Its results were in good consistent with the corresponding values obtained by a commercial ALP detection kit. The limit of detection of the proposed method for ALP is about 0.015 U/L, lower than some methods recently reported in literature, demonstrating its potential for ALP detection in biomedical research and clinical diagnosis.


Thermally activated Cu/Cu2S/ZnO nanoarchitectures with surface-plasmon-enhanced Raman scattering.
Hierarchical Cu/Cu2S/ZnO nanoarchitectures were fabricated via an electroplated ZnO nanorod array in the first step, followed by the growth of Cu2S nanostructures for the application of surface-enhanced Raman scattering (SERS) detection. The Cu/Cu2S nanostructures as grown were thermally treated at 150-300°C under a nitrogen atmosphere to improve the crystalline quality, and, unexpectedly, to induce plasmonic Cu nanoshells on the surface of Cu2S. With 4-aminothiophenol (4-ATP) as probing molecules, SERS experiments showed that the thermally treated Cu/Cu2S/ZnO nanostructures exhibit excellent detection performance, so that they can serve as active and cost-effective SERS substrates for ultrasensitive detection. The enhancement is attributed to the coupling between Cu2S and plasmonic Cu, as confirmed by electromagnetic field simulations. This novel hierarchical substrate shows satisfactory reproducibility and a linear dependence of intensity on analyte concentration, revealing an advantage of this method for easily scaled production.


Outcome after disarticulation of the hip for sarcomas.
To review the oncological and functional outcome in 80 patients who underwent disarticulation of the hip as part of their treatment. Eighty patients had disarticulation, of whom 46 had a bone sarcoma and 34 a soft tissue sarcoma. In 42 patients the operation was done as the first definitive surgical procedure for that patient. In 38 patients the disarticulation followed local recurrence after unsuccessful limb salvage, three of these patients had palliative amputations already having metastatic disease. All patients had adjuvant therapy when appropriate. The overall survival of the patients following the amputation was 56% at 1 year, 39% at 2 years, 27% at 5 years and 21% at 10 years. The 5-year survival of patients having the amputation as a primary procedure was 32%, for those with local recurrence it was 25% whilst for those with a palliative amputation it was nil. Local recurrence developed in 10 patients following the amputation, and was related to close margins of excision; all of these patients subsequently died. Function was on the whole poor, with only one surviving patient regularly using an artificial limb. Disarticulation of the hip remains a disabling procedure usually carried out for high grade sarcomas with extensive involvement of bone and soft tissues in the thigh. Long term survival is possible if wide margins of excision can be achieved.


Reoperation following Adult Tonsillectomy: Review of the American College of Surgeons National Surgical Quality Improvement Program.
Tonsillectomy remains a common procedure in adults; however, there are few population-level data evaluating risk factors for reoperation. Retrospective review of national database. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), 2005-2013. The ACS-NSQIP was queried for patients undergoing tonsillectomy ± adenoidectomy as their primary procedure (CPT 42821 or 42826). Demographic information and indications were reviewed along with complications and reoperation rates. In total, 12,542 cases met inclusion criteria. Patients were predominantly female (66.4%) and white (70.8%), with mean age of 30 ± 12 years (range: 16-90+). Thirty-day mortality was 0.03%, and 4.8% of patients experienced at least 1 complication, including reoperation (3.6%). Risk of complications was associated with male sex (P < .0001; odds ratio [OR], 1.7), diabetes (P = .0002; OR, 2.1), and presence of a bleeding disorder (P = .002; OR, 3.2). Risk factors for reoperation were similar, in addition to older age (P = .002; OR, 0.986). Complications other than reoperation were correlated with older age (P = .001; OR, 1.02) and diabetes (P = .001; OR, 2.59). Procedures were done mostly for infectious/inflammatory (70.4%) versus hypertrophic (16.4%) indications. Indication had no significant effect on the rate of reoperation. Most reoperations occurred after postoperative day 1 (86%; mean, 6.4 ± 4.2 days). This review of a large validated surgical database provides an overview of the rates of, and risk factors for, complications and reoperations following tonsillectomy in the adult population.


Comparative study of pre- and postauricular flaps for external auditory canal defect reconstruction.
Malignancies involving the external auditory canal deserve critical evaluation due to this area's aesthetic and functional importance. Flaps can be very useful for the restoration of the external auditory canal. A variety of flaps available for the surgical treatment of external acoustic meatus defects exist, depending on the precise location and size. Our study aimed to compare aesthetic and functional results in the postoncological reconstruction of external auditory canal defects using a preauricular flap and postauricular revolving door flap. Sixteen patients treated at our plastic surgery unit for defects involving the external auditory canal between January 2014 and December 2020 were included in the study. All defects were the result of a primary or secondary skin cancer excision. Patients were divided into two groups, one receiving the preauricular flap technique and the other the postauricular revolving door flap technique. Three separate visual analog scales reported excellent scores for the two procedures, though the postauricular revolving door flap had slightly better results. Both preauricular flap and postauricular revolving door flap reconstructive techniques showed good options for external auditory canal reconstruction in postexcision skin cancer patients. From an aesthetic point of view, the revolving door flap appeared to be a more elegant surgical approach in this type of reconstruction because the scar was hidden in the postauricular sulcus. Reconstruction with a postauricular revolving door flap allowed for a more natural movement with no external pedicle. IV.


Brainstem vascular stroke anatomy.
Brainstem infarcts comprise approximately 10% of all first ischemic brain strokes. The extrinsic vascular supply to the stem is complex. The intrinsic vascularization of the stem may be conceptualized in terms of four relatively constant and distinct vascular territories designated anteromedial, anterolateral, lateral, and dorsal (or dorsolateral). The anatomic structures found within each intrinsic territory determine the symptomatology associated with infarction of that territory. This territorial anatomy permits the knowledgeable physician to plan an MR imaging examination tailored to the patient's history and to predict the patient's neurologic deficits from the MR imaging findings.


[Some problems in health status of residents of the Russian Federation].
This paper sums up the effect of socio-economic crisis developing in the country in the nineties on the population health. Based on analysis of the status and time course of medico-demographic processes, morbidity, and physical development, the author demonstrates the staged pattern in the formation of these values: each new exacerbation of the socio-economic situation augmented the negative changes in comparison with the previous high level.


A case of Ménétrier's disease localized to the gastric antrum without helicobacter infection or hypoalbuminemia.
Ménétrier's disease (MD) is a rare gastric disorder closely associated with Helicobacter pylori infection characterized by enlarged gastric mucosal folds and hyperplasia of surface mucus-secreting cells classically localized to the gastric body. This disease has significant morbidity and mortality secondary to hypoproteinemia, gastric obstruction, hemorrhage, and increased risk of adenocarcinoma. We report a 53-year-old female who presented with severe epigastric pain, anorexia, weight loss, and prandial vomiting with serum albumin and chloride levels in the normal range. After serial upper endoscopy with biopsy identified nonspecific inflammatory changes in the absence of H. pylori, surgical exploration was performed with intraoperative tissue samples revealing nondysplastic, foveolar hyperplasia. Gastric antrectomy was performed with gross and microscopic examination verifying the diagnosis of MD. The unusual presentation of this case differentiates it from other known cases due to the rare localization of the disease to the gastric antrum, the absence of H. pylori infection, and the uncharacteristically normal serum albumin level on presentation. This case may represent an unreported subset of MD where limited surgical resection is demonstrated to offer an exceptional outcome.


The Role of the Neonatal Registered Dietitian Nutritionist: Past, Present, and Future.
Neonatal registered dietitian nutritionists (RDNs) are critical members of the neonatal intensive care unit (NICU) team due to their unique skillset of growth assessment, nutrition evaluation, and implementation of nutrition best practices. There is a paucity of data on appropriate staffing of neonatal RDNs in NICUs to promote improved patient outcomes. Here, the authors describe current neonatal RDN staffing and responsibilities in the US NICUs.


Field-scale decentralized domestic wastewater treatment system: Effect of dynamic loading conditions on the removal of organic carbon and nitrogen.
The field-scale decentralized wastewater treatment system (DWTS) was developed with an anaerobic baffled reactor (ABR) and a newly configured hybrid constructed wetland (HCW) vegetated with Typha angustifolia and Canna indica to treat 42 kLd of domestic wastewater. Biorack baffled constructed wetland (BBCW) and baffled vertical flow constructed wetland (BVFCW) were used in the first and second stage of HCW respectively. DWTS was assessed for its efficiency to remove COD, BOD and TKN under high (varying flow and varying COD) and moderate (constant flow and varying COD) dynamic loading conditions. The tracer study and pertinent computation showed the good performance of DWTS in its hydraulic efficiency. COD of raw wastewater was the treatment-limiting step in ABR. BBCW sustained larger fluctuations in loading rates [hydraulic (0.43-10.29 m3/m2.d) and organic (0.08-2.30 kgCOD/m2.d)]. The draining (unsaturated) conditions enhanced COD and BOD removal in BVFCW. DWTS was found to be efficient for the average removal of COD (70-90%) and TKN (40-65%). HCW contributed 50-60% and 70-80% to COD and TKN removal respectively. The quantification of impacts on treatment efficiency and sustainability of DWTS was demonstrated at field-scale under high and moderate dynamic conditions.


Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins.
Protein segments that form amphipathic alpha-helices in their native state have periodic variation in the hydrophobicity values of the residues along the segment, with a 3.6 residue per cycle period characteristic of the alpha-helix. The assignment of hydrophobicity values to amino acids (hydrophobicity scale) affects the display of periodicity. Thirty-eight published hydrophobicity scales are compared for their ability to identify the characteristic period of alpha-helices, and an optimum scale for this purpose is computed using a new eigenvector method. Two of the published scales are also characterized by eigenvectors. We compare the usual method for detecting periodicity based on the discrete Fourier transform with a method based on a least-squares fit of a harmonic sequence to a sequence of hydrophobicity values. The two become equivalent for very long sequences, but, for shorter sequences with lengths commonly found in alpha-helices, the least-squares procedure gives a more reliable estimate of the period. The analog to the usual Fourier transform power spectrum is the "least-squares power spectrum", the sum of squares accounted for in fitting a sinusoid of given frequency to a sequence of hydrophobicity values. The sum of the spectra of the alpha-helices in our data base peaks at 97.5 degrees, and approximately 50% of the helices can account for this peak. Thus, approximately 50% of the alpha-helices appear to be amphipathic, and, of those that are, the dominant frequency at 97.5 degrees rather than 100 degrees indicates that the helix is slightly more open than previously thought, with the number of residues per turn closer to 3.7 than 3.6. The extra openness is examined in crystallographic data, and is shown to be associated with the C terminus of the helix. The alpha amphipathic index, the key quantity in our analysis, measures the fraction of the total spectral area that is under the 97.5 degrees peak, and is a characteristic of hydrophobicity scales that is consistent for different sets of helices. Our optimized scale maximizes the amphipathic index and has a correlation of 0.85 or higher with nine previously published scales. The most surprising feature of the optimized scale is that arginine tends to behave as if it were hydrophobic; i.e. in the crystallographic data base it has a tendency to be on the hydrophobic face of teh amphipathic helix. Although the scale is optimal only for predicting alpha-amphipathicity, it also ranks high in identifying beta-amphipathicity and in distinguishing interior from exterior residues in a protein.(ABSTRACT TRUNCATED AT 400 WORDS)