Estimation of passive and active properties in the human heart using 3D tagged MRI.
Advances in medical imaging and image processing are paving the way for personalised cardiac biomechanical modelling. Models provide the capacity to relate kinematics to dynamics and-through patient-specific modelling-derived material parameters to underlying cardiac muscle pathologies. However, for clinical utility to be achieved, model-based analyses mandate robust model selection and parameterisation. In this paper, we introduce a patient-specific biomechanical model for the left ventricle aiming to balance model fidelity with parameter identifiability. Using non-invasive data and common clinical surrogates, we illustrate unique identifiability of passive and active parameters over the full cardiac cycle. Identifiability and accuracy of the estimates in the presence of controlled noise are verified with a number of in silico datasets. Unique parametrisation is then obtained for three datasets acquired in vivo. The model predictions show good agreement with the data extracted from the images providing a pipeline for personalised biomechanical analysis.


Positive effects of thyroid replacement therapy on assisted reproductive technology outcomes in women with subclinical hypothyroidism with positive thyroid peroxidase autoantibodies.
To study the beneficial effects of thyroid replacement therapy (TRT) on pregnancy outcomes in patients with subclinical hypothyroidism (SCl hypoT) with respect to thyroid peroxidase (TPO) autoantibodies. Retrospective study of 706 patients. Not applicable. The study evaluated 706 patients, who were divided into 3 cohorts: euthyroid patients, with pre-in vitro fertilization thyroid-stimulating hormone levels of <2.5 μIU/mL; patients with SCl hypoT, defined as thyroid-stimulating hormone levels of >2.5 μIU/mL and <4 μIU/mL, who were not treated; and patients with SCl hypoT who received TRT. The 3 cohorts were further subclassified into 2 groups, each based on TPO antibody levels. The cohorts were compared for the effects of TRT on pregnancy outcomes. Identification of effects of TRT on assisted reproductive technology outcomes. Patients with SCl hypoT had significantly fewer positive pregnancy outcomes than euthyroid patients. Importantly, low-dose TRT was found to be beneficial in improving IVF success and pregnancy outcomes in patients with SCl hypoT. The original cohort of patients, further classified into 2 subgroups on the basis of antithyroid (TPO) antibodies, showed that low-dose TRT was associated with improved pregnancy outcomes in women with SCl hypoT and TPO-positive antibodies. Our findings demonstrate that low-dose TRT may be beneficial in improving in vitro fertilization success and pregnancy outcomes in women with SCl hypoT and TPO-positive antibodies.


The role of fibronectin fragments and cell-attached transamidase on the binding of soluble fibrin to macrophages.
Proteolytic fragments from the N-terminus of the fibronectin subunit chains were shown to mediate the binding of 125-I-fibrin to macrophages. With increasing molecular weight of the fragments, binding activity decreased and intact plasma fibronectin was inactive. Fibrin binding to macrophages was a time dependent reaction and proceeded considerably faster than binding of fibrinogen. The binding reaction was inhibited by putrescine suggesting the involvement of a transamidase. Pericellular transamidase was demonstrated on macrophages by incorporation of 14-C-putrescine into fibronectin 30 kD-fragment. Expression of this enzyme appeared to be rate-limiting for the binding reaction which was accelerated after loading the cells with placental transamidase.


The increasing incidence of congenital penile anomalies in the United States.
Epidemiologic studies have suggested that the incidence of congenital penile anomalies (CPA), particularly hypospadias, is increasing. This phenomenon has significant biological and socioeconomic implications. We sought further confirmation of the reported trends using a large national database. The Nationwide Inpatient Sample is a 20% sample of United States hospitals containing data on 5 to 7 million hospital inpatient stays per year. We identified male newborns, used ICD-9 codes to identify newborns with CPA, determined nationally weighted incidence over time and performed multivariate analyses to identify factors associated with CPA. Of the 4.84 million male newborns in the Nationwide Inpatient Sample we identified 37,577 with CPA (weighted incidence rate 7.8/1000 newborns). The weighted incidence increased from 7.0/1000 newborns in 1988 to 1991 to 8.3/1000 in 1997 to 2000 (p <0.0001). The most common diagnosis was hypospadias (68.3%), followed by chordee (8.6%) and hypospadias plus chordee (5%). Unspecified genital or penile anomalies were reported for 14% of the cases. The highest incidence of CPA was in white newborns (9.2/1000), followed by black newborns (7.5/1000), Asians (5.0/1000) and Hispanics (4.7/1000) (p <0.0001). Socioeconomic status (SES) was strongly associated with CPA, with CPA odds 19% higher for the highest SES category versus the lowest (OR 1.18, 95% CI 1.16-1.20). Increasing incidence of CPA over time was observed even after adjusting for race/ethnicity, geographic region, insurance status and SES. These nationally representative, weighted analyses reveal a significant increase in the incidence of CPA, with striking variation by race, region and SES. Further research into potential causes, as well as the observed disparities in incidence, is needed.


Kronic hysteria: exploring the intersection between Australian synthetic cannabis legislation, the media, and drug-related harm.
Having first appeared in Europe, synthetic cannabis emerged as a drug of concern in Australia during 2011. Kronic is the most well-known brand of synthetic cannabis in Australia and received significant media attention. Policy responses were reactive and piecemeal between state and federal governments. In this paper we explore the relationship between media reports, policy responses, and drug-related harm. Google search engine applications were used to produce time-trend graphs detailing the volume of media stories being published online about synthetic cannabis and Kronic, and also the amount of traffic searching for these terms. A discursive analysis was then conducted on those media reports that were identified by Google as 'key stories'. The timing of related media stories was also compared with self-reported awareness and month of first use, using previously unpublished data from a purposive sample of Australian synthetic cannabis users. Between April and June 2011, mentions of Kronic in the media increased. The number of media stories published online connected strongly with Google searches for the term Kronic. These stories were necessarily framed within dominant discourses that served to construct synthetic cannabis as pathogenic and created a 'moral panic'. Australian state and federal governments reacted to this moral panic by banning individual synthetic cannabinoid agonists. Manufacturers subsequently released new synthetic blends that they claimed contained new unscheduled chemicals. Policies implemented within in the context of 'moral panic', while well-intended, can result in increased awareness of the banned product and the use of new yet-to-be-scheduled drugs with unknown potential for harm. Consideration of regulatory models should be based on careful examination of the likely intended and unintended consequences. Such deliberation might be limited by the discursive landscape.


Effects of safety belt laws on safety belt use by American High School Seniors, 1986-2000.
This manuscript evaluates the effects of enactment of state laws that required safety belt use in various U.S. states between 1986 and 2000. Safety belt use was assessed using nationally representative cross-sectional samples of high school seniors; evaluation of the effects of laws used data from over 2,000 high school seniors before and about 3,300 after the laws took effect in 20 states. Belt use was found to increase significantly between 1986 and 2000, and the laws contributed significantly to that increase. Increases were similar for students differing by gender, race/ethnicity, parent education, grades, truancy, evenings out per week, miles driven per week, and an index of illicit drug use. The data show that although the laws have increased belt use, use is not universal and continued efforts are needed. This study shows that many teenagers fail to use belts when there is a secondary use law; an implication is that primary laws would be more efficacious in increasing use among this vulnerable population.


Child safety in cars: An observational study on the use of child restraint systems in The Netherlands.
To minimize children's injuries due to car accidents, children must be transported in approved child restraint systems (CRS). The European Union optimized child protection by implementing R129 legislation for CRS in 2013. However, compliance with CRS recommendations after introduction of this newer standard has been scarcely evaluated. The main objectives of this study were to determine the prevalence of various types of CRS misuse and to investigate the use of ISOFIX and i-Size seats and parental knowledge regarding safe transportation of children in cars 5 years after the introduction of the newer R129 standard. During a cross-sectional observational study in the summer of 2018, parking lots of sites in the Netherlands were visited by researchers. Arriving or departing Dutch drivers who transported children under 9 years old were interviewed by means of a questionnaire and the misuse of CRS was directly observed using a checklist. Misuse was defined as CRS inappropriate for the child (based on height and weight) and/or CRS wrongly installed in the car and/or child improperly restrained in CRS. In total, 392 drivers and 470 children were included in the study. Results showed that 83% of the children were transported with at least 1 misuse of their CRS: 7% of the CRS were inappropriate for the child, 49% of the CRS were wrongly installed in the car, and 59% of the children were improperly restrained in a CRS. Most CRS were installed using the seat belt (88%) compared to ISOFIX (12%). ISOFIX usage did not result in less CRS installation misuse (P = .338). The number of observed i-Size CRS was low (n = 13, 3%). Most drivers were familiar with ISOFIX (76%), but only 13% of the drivers had heard of i-Size. For 9 out of 10 children, CRS misuse was observed. Many children were transported in an appropriate CRS, but various mistakes were made when installing the CRS in the car and restraining children in the CRS. Moreover, ISOFIX usage did not result in statistically significant less CRS installation misuse compared to traditional seat belt usage, and i-Size CRS are still rather unknown 5 years after their introduction.


Has selenium a beneficial role in human exposure to inorganic mercury?
Laboratory experiments have indicated that selenium acts as a powerful antagonist to mercury intoxication. The literature is reviewed and from this it is concluded that mercury and selenium react in various ways. 1) The mercuric ion binds to selenium to form a biologically inert complex leading to increased body burden of both elements. This reaction seems to take place only when a threshold of mercury exposure is exceeded. 2) Selenium influences the oxidation rate of elemental mercury and as such the distribution pattern. This reaction is influenced by the nature of the antioxidative system. In species with low glutathione peroxidase activity, mercury oxidation seems decreased which can lead to an increased brain uptake. In this process there is no threshold. 3) Selenium can, as part of the antioxidative defence system, counteract mercury induced lipid peroxidation. Other antioxidants e.g. vitamin E might be just as effective. Based upon the literature it is hypothesised that to man selenium is of no benefit in cases of exposure to mercury either as mercuric mercury or as vapours. The only protection against mercury will still be a low exposure level.


Cardiopathia fantastica and arteritis factitia as manifestations of Munchausen syndrome.
We describe three patients, each with a cardiovascular presentation of Munchausen's syndrome. Two patients' symptoms masqueraded as unstable angina (cardiopathia fantastica); one required intra-aortic balloon counterpulsation, while repeated cardiac catheterizations revealed normal coronary arteries. The third patient, with at least 27 documented hospital admissions, first presented as the cardiopathia fantastica variety and progressed to recurrent thromboembolism and limb amputations as a result of iatrogenic complications induced by angiographic and surgical procedures (arteritis factitia).


Outcomes of septorhinoplasty: a new approach comparing functional and aesthetic results.
The aim of this study was to compare objective and subjective functional results of septorhinoplasty with subjective aesthetic results. A prospective study was performed including global and subgroup analyses (primary versus secondary septorhinoplasty). Three instruments were used to evaluate pre- and postoperative results: rhinomanometry for the objective functional analysis, the Nasal Symptom Obstruction Evaluation (NOSE) scale for the subjective functional analysis, and the Rhinoplasty Outcome Evaluation (ROE) scale for the subjective aesthetic analysis. A septorhinoplasty was performed in all cases. Thirty-five patients were included (22 female), of whom 74% underwent primary septorhinoplasty. The correlation between rhinomanometry, NOSE and ROE scores was analysed. Mean resistance of the two nasal cavities was 4.9 (standard deviation (SD) 8.35) sPa/ml before surgery and 0.8 (SD 0.7) sPa/ml after surgery. NOSE and ROE scores were, respectively, 72.5/100 (SD 21.7) and 7.5/24 (SD 11.3) before surgery and 22/100 (SD 20.6) and 18/24 (SD 17.3) after surgery. Patients complaining of postoperative nasal obstruction had a worse aesthetic evaluation. Correction of the functional disease appears to be as important as aesthetic correction. This study comparing functional and aesthetic results after septorhinoplasty could provide a basis for future studies.


M-mode echocardiograms for determination of optimal left atrial timing in patients with dual chamber pacemakers.
To determine if the A wave of the mitral valve echocardiogram can be used as a marker for left atrial (LA) activity and assist in the programming of dual chamber pacemakers, 156 echocardiograms with the mitral A wave present were obtained from 23 patients with dual chamber pacemakers, all of whom had bipolar esophageal recordings of LA depolarization. Twelve of these patients also underwent hemodynamic study with cardiac function determined at 5 different pacemaker settings: ventricular demand pacing and dual chamber sequential pacing at 0 or 25, 150, 200 and 250 ms programming atrioventricular (AV) delay. The time delay from right atrial pacing artifact to onset and peak of mitral A wave was linearly related to the time from atrial pacing artifact to LA depolarization on the esophageal lead (p less than 0.001). As pacing mode changed from dual chamber sequential pacing (DVI) mode to atrial synchronous-ventricular pacing (VDD), the A wave came earlier relative to the ventricular pacing spike, linearly related to the LA to ventricular extension with mode change determined with the esophageal lead (r = 0.94, p less than 0.001). The time from atrial pacing to peak of A wave was shorter in patients whose optimal programmed AV delay was 150 ms compared with those whose optimal AV delay was 200 or 250 ms (p less than 0.02). At the optimal programmed delay for cardiac output, the peak of the A wave was an average of 13 +/- 36 ms after the ventricular pacing spike.(ABSTRACT TRUNCATED AT 250 WORDS)


Colleters, osmophores, and nectaries in the species Ceropegia lenewtonii: a sapromyiophilous stapeliad (Asclepiadoideae, Apocynaceae).
Ceropegia lenewtonii (Plowes) Bruyns (=Huernia keniensis), currently belonging to the Huernia section of the genus Ceropegia, is a stapeliad species distributed in Africa and the Arabian Peninsula; but it is widely cultivated as ornamental in most parts of the world. This species of stapeliad presents "carrion flowers" associated with a sapromyophilous pollination syndrome since the flowers emit an unpleasant odor. In this work, we describe the floral morphology and anatomy of the calyx, corolla, and corona of this species based on bright-field and scanning electron microscope techniques. We detected the presence of diverse floral secretor tissues, and based on different histochemical tests, the principal component of the secreted substance was identified. We interpret the functions of the glands and compare with other related species of stapeliads. Our results indicate that flowers of C. lenewtonii present colleters in sepals, osmophores in corolla, and primary and secondary nectaries in corona. All these floral glands have specific functions that involve the processes of pollination and reproduction of this species, as well as protection and defense mechanisms.


Acute anxiety during the COVID-19 pandemic was associated with higher levels of everyday altruism.
Prior laboratory research has suggested that humans may become more prosocial in stressful or threatening situations, but it is unknown whether the link between prosociality and defense generalizes to real-life. Here, we examined the association between defensive responses to a real-world threat (the COVID-19 pandemic) and everyday altruism. Four independent samples of 150 (N = 600) US residents were recruited online at 4 different timepoints, and self-report measures of perceived COVID-19 threat, defensive emotions (e.g., stress and anxiety), and everyday altruism were collected. Our operationalization of defensive emotions was inspired by the threat imminence framework, an ecological model of how humans and animals respond to varying levels of threat. We found that perceived COVID-19 threat was associated with higher levels of everyday altruism (assessed by the Self-report Altruism scale). Importantly, there was a robust association between experiencing acute anxiety and high physiological arousal during the pandemic (responses typically characteristic of higher perceived threat imminence), and propensity to engage in everyday altruism. Non-significant or negative associations were found with less acute defensive responses like stress. These findings support a real-life relation between defensive and altruistic motivation in humans, which may be modulated by perceived threat imminence.


Generation of a catR deficient mutant of P. putida KT2440 that produces cis, cis-muconate from benzoate at high rate and yield.
Pseudomonas putida KT2440-JD1 was derived from P. putida KT2440 after N-methyl-N'-nitro-N-nitrosoguanidine (NTG)-mutagenesis and exposure to 3-fluorobenzoate (3-FB). The mutant was no longer able to grow using benzoate as a sole carbon source, but co-metabolized benzoate to cis, cis-muconate during growth on glucose, which accumulated in the growth medium. The specific production rate (q(pm)) was 0.18±0.03 g cis, cis-muconate/(g(DCW) h) in continuous cultures, and increased to 1.4 g cis, cis-muconate/(g(DCW) h) during wash-out cultivation. Transcriptome analysis showed that the cat operon was not induced in P. putida KT2440-JD1 in the presence of 5mM benzoate, due to a point mutation in the highly conserved DNA binding domain of the transcriptional regulator (catR) of the cat operon. The ben operon was highly expressed in the presence of benzoate in the mutant and its parental strain. This operon contains PP_3166 (catA2), which was shown to be a second catechol 1,2-dioxygenase besides catA. P. putida KT2440-JD1 is the first cis, cis-muconate-accumulating mutant that was characterized at the genetic level. The specific production rate achieved is at least eight times higher than those reported for other cis, cis-muconate-producing strains.


Validity of nerve conduction velocity studies after anterior transposition of the ulnar nerve.
To determine which anatomic position and marking techniques are valid for postoperative electrodiagnostic testing, ten patients were studied during anterior transposition of the ulnar nerve. Variables included skin and ulnar nerve distances measured anterior and posterior to the medial humeral epicondyle, and ulnar nerve conduction velocities over these distances, with the elbow flexed and extended, and with the ulnar nerve in the pretransposition and posttransposition location. The results of the study confirm that ulnar nerve conduction velocity is recorded as faster with elbow flexion preoperatively and elbow extension postoperatively when the skin measurement used for the distance is kept constant. Postoperatively, the most valid measurement of ulnar nerve conduction velocity was a skin distance that was posterior to the medial humeral epicondyle with the elbow extended.


Clinical efficacy of upper limb robotic therapy in people with tetraplegia: a pilot randomized controlled trial.
A pilot randomized controlled trial. To evaluate the clinical efficacy of upper limb robotic therapy in people with tetraplegia. Inpatient rehabilitation hospital in Seoul, Korea. Participants were randomly allocated to a robotic therapy (RT) or occupational therapy (OT) group. Both groups received usual care plus 30 min of additional therapy per day for 4 weeks. The additional therapy provided to the OT group was OT, and the additional therapy provided to RT group was RT using the Armeo Power. Primary outcomes were the Medical Research Council scale of each key muscle and Upper Extremity Motor Score (UEMS) for the trained arm. Secondary outcomes were the Spinal Cord Independence Measurement version III (SCIM-III) subscale and total score. Evaluations were performed at baseline and 4 weeks. A total of 34 individuals with tetraplegia were included; 17 in each group. At 4 weeks, the median (IQR) change in UEMS in the RT group was 1/25 (0 to 3) points compared with 0/25 (-1 to 1) points in the OT group (p = 0.03). The median (IQR) change in total SCIM-III score in the RT group was 7/100 (1.5 to 11) points compared with 0/100 (-8 to 4) points in the OT group (p < 0.01). There were small improvements in motor strength and SCIM-III scores in the RT group, but there were no statistically significant differences between the groups. Further studies are required for a better understanding of the effects of RT for people with tetraplegia.


Radiogenic responses of normal tissue induced by fractionated irradiation--a simulation study. I. Acute effects.
Based on control theory, the attempt is made in this paper to construct a computer model which describes the time course of fast proliferating normal tissue after irradiation treatment. Subsequently, different clinical irradiation schemes are compared in regard to their radiogenic acute effects. A cybernetic model of a cell renewal system consisting of stem-, transit- and functional cells has been developed and transferred into a computer model. The radiation effects are considered by characteristic cell parameters as well as by the linear-quadratic model. Three kinds of tissue (thick epidermis of man, thin epidermis of the mouse and jejunum of the mouse) have been irradiated in the model in accordance with different clinical irradiation schemes (standard-, super-, hyperfractionation and a single high dose per week). The simulation studies demonstrate that the acute reaction of normal tissue to hyperfractionation (3 times 1.5 Gy per day) is particularly severe. Furthermore, the radiation damage of the jejunum and of the thin epidermis of the mouse depends on the specific irradiation scheme and is only partially compensated. A comparison of the simulation results with clinical experience (and practice) demonstrates that the clinical reality can in quality be successfully represented by the model. This opens the door for connecting the side effects of irradiation to normal tissue with the corresponding tumor effectiveness (see our previous papers about irradiation of tumor spheroids.


Proteinuria and hypertension with tyrosine kinase inhibitors.
Tyrosine kinases are important for the development of pathological angiogenesis, a critical factor for survival and proliferation of tumor cells. Inhibition of tyrosine kinases either through targeted binding of its ligands or inhibition of its receptor has led to significant hindrance in angiogenesis and has improved survival for several cancers. Several of these antibodies or small molecules have been approved for treatment of recurrent and resistant cancers over the last decade. Although generally well tolerated, tyrosine kinase inhibitors have been linked with development of hypertension and proteinuria. We review the literature for incidence and severity of hypertension and proteinuria among several tyrosine kinase inhibitors, their pathophysiologic mechanisms, and provide a guide for screening and management.


Diversity of Volatile Compounds in Raw Milk with Different n-6 to n-3 Fatty Acid Ratio.
Fatty acid profiles may affect the flavor of milk. The diversity of volatile compounds in raw milk with different ratios of n-6 to n-3 fatty acids (8:1, 4:1, and 3:1) was studied. Gas chromatography-ion mobility spectroscopy (GC-IMS) is a promising technology for the accurate characterization and detection of volatile organic compounds in agricultural products, but its application in milk is rare or even unavailable. In this experiment, GC-IMS fingerprints along with principal component analysis (PCA) were used to study the flavor fingerprints of fresh milk samples with different percentages. Thirty-four typical target compounds were identified in total. A diversity of flavor compounds in raw milk with different n-6/n-3 was observed. After reduction of the proportion, the concentrations of volatile compounds, such as hexanoic acid (dimer and monomer), ethyl acetate, and 2-methylpropanoic acid (dimer and monomer) decreased, while those of 4-methyl-2-pentanone, pentanal, and acetone increased. We carried out PCA according to the signal strength of the identified volatile compounds, and the examination showed that it could precisely make a distinction among the samples in a comparative space. In conclusion, the results show that the volatile compounds are different as the proportion is different. The volatile compounds in raw milk are mainly hexanoic acid, ethyl acetate, and 2-methylpropanoic acid. After adjustment of the ratio, the flavor substances of the medium-ratio (MR) group were mainly ketones, while those of the low-ratio (LR) group were aldehydes. Therefore, in production, reducing the impact on volatile substances while adjusting the proportion of n-6 and n-3 fatty acids to obtain functional dairy products should be taken into consideration.


Integrated Metabolomics and Network Pharmacology to Reveal the Mechanisms of Gandouling Tablets Against Copper-Overload-Induced Neuronal Injury in Rats with Wilson's Disease.
Gandouling Tablets (GDL), a proprietary Chinese medicine, have shown a preventive effect against Wilson's disease (WD)-induced neuronal damage in previous studies. However, the potential mechanisms need additional investigation. Combining metabonomics and network pharmacology revealed the GDL pathway against WD-induced neuronal damage. The WD rat model with a high copper load was developed, and nerve damage was assessed. Total metabonomics was used to identify distinct hippocampus metabolites and enriched metabolic pathways in MetaboAnalyst. The GDL's possible targets against WD neuron damage were then determined by network pharmacology. Cytoscape constructed compound metabonomics and pharmacology networks. Moreover, molecular docking and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) validated key targets. GDL reduced WD-induced neuronal injury. Twenty-nine GDL-induced metabolites may protect against WD neuron injury. According to network pharmacology, we identified three essential gene clusters, of which genes in cluster 2 had the most significant impact on the metabolic pathway. A comprehensive investigation identified six crucial targets, including UGT1A1, CYP3A4, CYP2E1, CYP1A2, PIK3CB, and LPL, and their associated core metabolites and processes. Four targets reacted strongly with GDL active components. GDL therapy improved five targets' expression. This collaborative effort revealed the mechanisms of GDL against WD neuron damage and a way to investigate the potential pharmacological mechanisms of other Traditional Chinese Medicine (TCM).


The opioid epidemic: A worldwide exploratory study using the WHO pharmacovigilance database.
The current opioid epidemic in the United States began 20 years ago and has become the leading cause of accidental deaths in the country. This crisis prompted us to explore trends in opioid abuse and dependence worldwide. We sought to identify other countries at high-risk of opioid use disorders, using the World Health Organization's (WHO) pharmacovigilance database. We performed a disproportionality analysis using VigiBase, the WHO Global Individual Case Safety Report (ICSR) database. Five opioids used worldwide were included: oxycodone, fentanyl, morphine, tramadol, and codeine. We extracted all ICSRs associated with the drugs of interest, considered as suspect medication and recorded up until 5 June 2021, using the narrow Standardised MedDRA Query (SMQ) for drug abuse and dependence. Countries with at least one ICSR for each of the five opioids were retained. The relationship between the use of a drug (i.e. an opioid) and the occurrence of an adverse drug reaction (i.e. drug abuse and dependence) for each country was assessed by calculating the information component (IC) and its 99.9% CI [IC0005 ; IC9995 ], using a quasi-Bayesian confidence propagation neural network (BCPNN). A hierarchical cluster analysis (Ward's method) of the IC0005 value for each of the five opioids was performed to identify subgroups of countries with similar reported risks of opioid abuse and dependence. Among 21 countries, the optimal number of clusters was calculated to be four, each with a Jaccard index >0.5 (0.95, 0.78, 0.65 and 0.75, respectively). Six countries with the highest signals of drug abuse and dependence were identified in cluster 1, with significant CIs for the five opioids of interest (IC0005 > 0), ranging from 0.9 to 5.8 for the lower endpoint. There appear to be four distinct clusters of countries with similar opioid abuse and dependence profiles. The group with the highest reported risk for the opioids oxycodone, fentanyl, morphine, tramadol and codeine includes Australia, Canada, France, Germans, the United Kingdom and the United States.


Binding characteristics of the 5-HT2A receptor antagonists altanserin and MDL 100907.
To study the 5-HT(2A) receptors in the living human brain, using positron emission tomography (PET), two selective radiotracers are currently in use: [(18)F]altanserin and [(11)C]MDL 100907. It is, however, currently unknown to what extent data obtained with either tracer are directly comparable. The aim of this study was to compare binding characteristics of these two radiotracers in rat brain with respect to affinity (K(d)), receptor binding density (B(max)), binding potential (BP), and nonspecific binding. Further, binding kinetics, sensitivity towards competition with the endogenous transmitter serotonin, and the competitive/noncompetitive interaction between the two radioligands were evaluated. In addition, the selectivity of [(18)F]altanserin for the 5-HT(2A) receptor was assessed. The K(d) value of [(18)F]altanserin and [(3)H]MDL 100907 was in the order of 0.3 nM. B(max) in frontal cortex was 523 and 527 fmol/mg protein, respectively. The binding of [(18)F]altanserin was not influenced by blocking either the 5-HT(2B/2C) or the alpha(1)-adrenergic receptors. At 37 degrees C the association t(1/2) was 2.8 and 2.7 min and the dissociation t(1/2) was 11 and 13.5 min for [(18)F]altanserin and [(3)H]MDL 100907, respectively. Both radioligands were displaced by 5-HT, only at high concentrations; the K(i) value of 5-HT ranging between 650 and 3,300 nM. This indicates that binding of both radioligands in PET studies is not directly influenced by changes in endogenous 5-HT.Overall, the binding of [(18)F]altanserin and [(3)H]MDL 100907 to the 5-HT(2A) receptor was very comparable, showing selective high affinity binding in the subnanomolar range.


Production of biodiesel from coastal macroalgae (Chara vulgaris) and optimization of process parameters using Box-Behnken design.
Renewable biodiesels are needed as an alternative to petroleum-derived transport fuels, which contribute to global warming and are of limited availability. Algae biomass, are a potential source of renewable energy, and they can be converted into energy such as biofuels. This study introduces an integrated method for the production of biodiesel from Chara vulgaris algae collected from the coastal region of Bangladesh. The Box-Behnken design based on response surface methods (RSM) used as the statistical tool to optimize three variables for predicting the best performing conditions (calorific value and yield) of algae biodiesel. The three parameters for production condition were chloroform (X1), sodium chloride concentration (X2) and temperature (X3). Optimal conditions were estimated by the aid of statistical regression analysis and surface plot chart. The optimal condition of biodiesel production parameter for 12 g of dry algae biomass was observed to be 198 ml chloroform with 0.75 % sodium chloride at 65 °C temperature, where the calorific value of biodiesel is 9255.106 kcal/kg and yield 3.6 ml.


Formaldehyde and methanol biodegradation with the methylotrophic yeast Hansenula polymorpha. An application to real wastewater treatment.
The application of methylotrophic yeast Hansenula polymorpha to the treatment of methanol and formaldehydecontaining wastewater was experimentally verified. A variety of real wastewater samples originating from chemical industry effluent were examined. The yeast cell culture could grow in the wastewater environment, revealing low trophic requirements and a very high adaptation potential to poor cultivation conditions. The proliferation of cells was accompanied by a concomitant xenobiotic biodegradation. Grown, preadapted cellular suspension at a density of about 1 x 10(7) cells/ml proved to be able to utilize formaldehyde present in wastewater at concentrations up to 1750 mg/l, levels toxic to most microorganisms. The biological waste treatment method presented shows the enhanced potential by means of specific enzymatic activities of monocarbonic compound oxidations through methylotrophic pathway reactions. The need to obtain mutants highly resistant to formaldehyde has also been rationalized.


Larger regional white matter volume is associated with executive function deficit in remitted geriatric depression: an optimized voxel-based morphometry study.
We aimed to investigate structural abnormalities in first-episode remitted geriatric depression (RGD) using optimized voxel-based morphometry (VBM) in closely matched patients and healthy controls, and examining the relationship of performances on neuropsychological tests with regional white matter volumes. Forty subjects with first-episode RGD and 36 well-matched healthy controls were recruited for this study and neuropsychological tests and magnetic resonance imaging (MRI) were conducted on the subjects. The differences in regional white matter volume were determined between these two groups by optimized VBM. The white matter volumes of left inferior parietal lobule and right inferior frontal gyrus were significantly larger in patients with RGD relative to healthy controls. RGD patients performed significantly worse in the delayed recall of RAVLT, Trail Making Test A and B (seconds), and Symbol Digit Modalities Test when compared with the control group (all P<0.01). And there was a significant positive correlation between white matter volume of right inferior frontal gyrus and Trail Making Test A (r=0.319, P=0.045) in patients with RGD. This study is cross-sectional, therefore it cannot determine whether increased white matter volume is a state marker or trait marker of RGD. These results reveal that RGD is associated with larger white matter volumes of left inferior parietal lobule and right inferior frontal gyrus, and the right inferior frontal gyrus may thus be involved in the pathophysiology of executive function in RGD.


Effects of 4-nonylphenol on oxidant/antioxidant balance system inducing hepatic steatosis in male rat.
An emerging literature suggests that early life exposure to 4-nonylphenol (4-NP), a widespread endocrine disrupting chemical, may increase the risk of metabolic syndrome. In this study, we investigated the hypothesis that intraperitoneal administration of 4-NP induces hepatic steatosis in rat. 24 male Sprague-Dawley rats were administered with 4-NP (0, 2, 10 and 50 mg/kg b.wt) in corn oil for 30 days. Liver histology, biochemical analysis and gene expression profiling were examined. After treatment, abnormal liver morphology and function were observed in the 4-NP-treated rat, and significant changes in gene expression an indicator of hepatic steatosis and apoptosis were observed compared with controls. Up-regulated genes involved in apoptosis, hepatotoxity and oxidative stress, increased ROS and decrease of antioxidant enzyme were observed in the 4-NP exposed rat. Extensive fatty accumulation in liver section and elevated serum GOT, GPT, LDH and γ-GT were also observed. Incidence and severity of liver steatosis was scored and taken into consideration (steatosis, ballooning and lobular inflammation). Hepatocytes apoptosis could promote NAFLD progression; Fas/FasL, TNF-α and Caspase-9 mRNA activation were important contributing factors to hepatic steatosis. These findings provide the first evidence that 4-NP affects the gene expression related to liver hepatotoxicity, which is correlated with hepatic steatosis.


The prevalence and influencing factors for compassion fatigue among nurses in Fangcang shelter hospitals: A cross-sectional study.
We aim to investigate the prevalence and associated factors for compassion fatigue among nurses in Fangcang Shelter Hospitals in Wuhan. Studies have shown that compassion fatigue was more common among nurses than other health-care providers, and its predictors were also different. In recent years, most studies have investigated compassion fatigue in emergency and oncology nurses, whereas there is little information on compassion fatigue among nurses from the frontline of Fangcang Shelter Hospitals during the COVID-19 pandemic. A descriptive, cross-sectional design was used in this study. An online survey was conducted among nurses (n = 972) of five Fangcang Shelter Hospitals in Wuhan, Hubei province, China, from 6 March to 10 March 2020. A self-administered questionnaire including demographic information, work-related information, General Health Questionnaire, Perceived Stress Scale and Compassion Fatigue Scale was used. The prevalence of compassion fatigue among nurses in Fangcang Shelter Hospitals was moderate, and most cases were mild. There was a significant relationship between compassion fatigue and work-related factors, mental health and perceived stress among nurses working in Fangcang Shelter Hospitals. Various factors contribute to compassion fatigue, including lower job satisfaction and job adaptability, less praise from patients, more fear of infection and more perceived stress. A good working atmosphere, organizational support and psychological consultation are essential to alleviate nurses' compassion fatigue during the anti-epidemic period.


Morphologic and cell kinetic investigations of the spleen after repeated in situ freezing of liver and kidney.
In order to evaluate a possible primary or secondary immunologic response of the spleen after single or repeated in situ freezing of parenchymal organs such as liver and kidney within a four week period, light microscopic and cell kinetic investigations with tritiated thymidine were performed on spleens of non-germfree rats. Sham operations served as controls. The sham operations did not induce any significant morphological or cell kinetic changes in the splenic white pulp. After cryolesions were produced in the liver and kidney, the percentages of activated germinal centers, labeled germinal center cells, and cells in the perifollicular area of the lymphatic mantle and marginal zones increased, with maxima during the first 3 days. The investigations show that the cellular reaction of the spleen starts earlier and is more prominent after repeated in situ freezing than after a single cryolesion. These findings point to an immunologic response of the anamnestic type, and correspond to results after repeated freezing of normal and malignant tissue of the urogenital tract. These cell kinetic results are important in the evaluation of further immunologic studies involving the cryotherapy of malignant tissues.


Effect of the age and sex on growth performance and feather quality of 13 to 25-weeks-old White Roman geese.
This study aimed to determine the effect of age and sex in weeks on growth, carcass performances, and feather quality of White Roman geese and analyze the relative effect of age and sex in weeks on feather characteristics in geese. In animal experiments, 120 White Roman geese aged 13 wk were randomly distributed among 12 pens and fed grower diet ad libitum during the growing period, with each pen containing 10 males or 10 females, depending on a completely random design. Ten geese each in their 13, 15, 17, 19, 21, 23, and 25 wk of age were sacrificed. The results showed that the age had no significant effect on the body weight (BW) of geese (P > 0.05). The chest girth was significantly longer in 21 to 25 wk old than in 13- to 19-wk-old geese (P < 0.05). The results reveal no significant change in carcass weight of grower geese among 13- to 25-wk age groups (P > 0.05). The down percentage of the 25-wk-old age group was significantly higher than that of the 13-, 15-, and 17-wk age groups (P < 0.05). The male geese had a higher dry feather weight than the females (P < 0.05). Similarly, the 18-h feed-deprived body weight (18-h FDBW) and 4 to 10 cm feather weight were significantly negatively correlated in grower geese (-0.42). This provides the feather industry an opportunity for the better utilization of grower geese by-products. In conclusion, the age has no influence on BW among 13- to 25-wk-old geese, and a good down percentage and dry weight were observed at 25 wk of age. The 18-h FDBW and down percentage had a significantly negative correlation (-0.55) in grower geese.


[Postmenopausal osteoporosis: its epidemiology, prevention and treatment].
Postmenopausal osteoporosis is a burden both to the society and to its victims. Many factors concur to make this burden heavier. Yet the means of prophylaxis are available. Curative therapy, once the disease is established, is at hand, but much remains to be done in this area.


Isoprenylation of an inhibitory G protein alpha subunit occurs only upon mutagenesis of the carboxyl terminus.
We transfected COS cells with expression vectors for the wild-type G protein alpha i1 subunit (pWT) and for mutated alpha i1 subunits, including the nonmyristylated glycine 2 to alanine mutant (pGA) and mutants in which the carboxyl termini of pWT and pGA were changed from CGLF to CVLS (pCVLS and pGA-CVLS, respectively). Immunoblot analysis of transfected COS cells with an antibody to residues 159-168 of the alpha i1 protein indicated that all four proteins were expressed. Unlike the WT and GA proteins, both CVLS mutant proteins failed to react with an antibody specific for the carboxyl terminus and failed to undergo pertussis toxin-catalyzed ADP-ribosylation. Analysis of COS cell lysates after [3H]mevalonic acid labeling indicated that specific incorporation of radioactivity occurred only in the alpha i1 subunits with the CVLS mutation. Immuno-precipitation of COS cell fractions after labeling with [35S]methionine indicated that both WT and CVLS mutant proteins were localized predominantly in the particulate fraction, whereas GA and GA-CVLS mutant proteins were found primarily in the soluble fraction. These results directly demonstrate that the carboxyl-terminal sequence, CGLF, is incapable of leading to isoprenylation but that alteration of two residues (glycine to valine, phenylalanine to serine) is sufficient to promote isoprenylation.


Implementation of clinical practice guidelines for pediatric weight management.
To evaluate the effect of computer-assisted decision tools that standardize pediatric weight management in a large, integrated health care system for the diagnosis and management of child and adolescent obesity. This was a large scale implementation study to document the impact of the Kaiser Permanente Southern California Pediatric Weight Management Initiative. An average of 739, 816 outpatient visits per year in children and adolescents from 2007 to 2010 were analyzed. Height, weight, evidence of exercise and nutrition counseling, and diagnoses of overweight and obesity were extracted from electronic medical records. Before the initiative, 66% of all children and adolescents had height and weight measured. This increased to 94% in 2010 after 3 years of the initiative (P < .001). In children and adolescents who were overweight or obese, diagnosis of overweight or obesity increased significantly from 12% in 2007 to 61% in 2010 (P < .001), and documented counseling rates for exercise and nutrition increased significantly from 1% in 2007 to 50% in 2010 (P < .001). Computer-assisted decision tools to standardize pediatric weight management with concurrent education of pediatricians can substantially improve the identification, diagnosis, and counseling for overweight or obese children and adolescents.


Monocled Cobra (Naja kaouthia) Envenomations Requiring Mechanical Ventilation.
Bites from nonnative snakes are uncommon, accounting for 1.1% of envenomations reported to poison centers between 2015 and 2018. Here we discuss two monocled cobra (Naja kaouthia) envenomations resulting in respiratory failure. A 30-year-old man and a 40-year-old man were bitten by their captive monocled cobras. At the first hospital, the first patient was mildly hypotensive, transiently bradycardic, and confused. He was intubated for respiratory distress. He was hypertensive to 211/119 mm Hg upon arrival to the second hospital. In the Emergency Department, cobra antivenom was administered. He was admitted to the medical intensive care unit (MICU) and had an additional bradycardic episode that corrected with atropine. He was extubated after 35 h. He was observed for an additional 9 h prior to going home, where he recovered without incident. The second patient developed abdominal pain, blurry vision, and dyspnea within 90 min of the bite. He was intubated at the first hospital. At the second hospital he received cobra antivenom and was admitted to the MICU. He was extubated after 9 h and discharged the following day with no further symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Envenomations after N. kaouthia bites are characterized by local tissue injury and various neurotoxic effects. Nonspecific signs and symptoms are common. Hematologic toxicity and cardiovascular manifestations are uncommon. Antivenom is the specific treatment for snake envenomation, but only certain antivenoms are indicated for N. kaouthia. Cholinesterase inhibitors may reduce toxicity from postsynaptic alpha toxins by increasing acetylcholine concentrations.


Provocative testing with prolonged hyperventilation and ergometrine in patients suspected of coronary artery spasm: a comparative study.
We induced coronary vasoconstriction by hyperventilation for 6 minutes (arterial pH = 7.6 +/- 0.06) and ergometrine (0.4 mg) in 24 patients suspected of coronary vasospasm. ST deviation greater than or equal to 1 mm was induced in 12 patients by hyperventilation and in 10 by ergometrine. Using spontaneous ST deviation as the independent reference the sensitivity of hyperventilation was 86% and the sensitivity of ergometrine 77%. Ergometrine caused sinus bradycardia and hypotension in 3 patients; hyperventilation caused no untoward reactions. In 12 of the patients coronary angiogram and wedge pressure were obtained during provocative testing. A computer-assisted analysis of coronary diameters in 43 arterial segments (3-4 per patient) showed a 16 +/- 12.6% and 14 +/- 16.7% reduction after hyperventilation and ergometrine, respectively. The maximal coronary diameter reduction induced by hyperventilation and ergometrine was 26 +/- 13.9% and 28 +/- 15.0%, respectively, and showed a significant correlation between the two tests (r = 0.77, N = 12, P less than 0.01). The wedge pressure increase induced by hyperventilation correlated to the maximal coronary diameter reduction (r = 0.63, N = 12, P less than 0.05), while no such correlation was found by ergometrine testing. We conclude that hyperventilation leading to arterial pH about 7.6 has essentially the same potency as 0.4 mg ergometrine, but the hyperventilation test appears to be safer.


The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children.
Cardiopulmonary bypass management in infants and children involves extensive alterations in temperature, hemodilution, and perfusion pressure, with occasional periods of circulatory arrest. Despite the use of these biologic extremes of temperature and perfusion, their effects on cerebral blood flow are unknown. This study was designed to examine the relationship of mean arterial pressure and nasopharyngeal temperature to cerebral blood flow during deep hypothermic cardiopulmonary bypass (18 degrees to 22 degrees C) with and without periods of total circulatory arrest. Cerebral blood flow was measured before, during, and after deep hypothermic cardiopulmonary bypass using xenon clearance techniques in 25 children, aged 2 days to 60 months. Fourteen patients underwent repair with circulatory arrest. There was a highly significant correlation of cerebral blood flow with temperature during cardiopulmonary bypass (p = 0.007). During deep hypothermic bypass there was a significant association between cerebral blood flow and mean arterial pressure (p = 0.027). In infants undergoing repair with deep hypothermia alone, cerebral blood flow returned to prebypass levels in the rewarming phase of bypass. However, in patients undergoing repair with circulatory arrest, no significant increase in cerebral blood flow during rewarming or even after bypass was observed (p = 0.01). These data show that deep hypothermic cardiopulmonary bypass significantly decreases cerebral blood flow because of temperature reduction. Under conditions of deep hypothermia, cerebral pressure-flow autoregulation is lost. This study also demonstrates that cerebral reperfusion after deep hypothermia is impaired if the patient is exposed to a period of total circulatory arrest.


Host defense against opportunist microorganisms following trauma. I. Studies to determine the association between changes in humoral components of host defense and septicemia in burned patients.
Total hemolytic complement (CH(50)), conversion of C3 by inulin, and immunochemical levels of Clq, C4, C2, C3, C5, factor B, C3b inactivator (KAF), and properdin were measured in the sera of 15 patients with severe thermal injury during nine weeks postburn. Five of the 15 patients had multiple episodes of septicemia as documented by positive blood cultures and clinical findings. Decrease in CH(50), Clq, C4, C2, C3, and C5 occurred prior to and during septic episodes in these patients. Although conversion of C3 by inulin was often reduced during septic episodes, levels of factor B and KAF were generally normal or elevated. In only one patient did consumption of complement occurring during septicemia decrease the opsonic capacity of the patient's sera for the patient's infecting microorganism, an isolate of E. coli; sera from the same patient opsonized her infecting strain of S. aureus normally. The microorganisms isolated from the other septic patients, which were opsonized normally by the patients' sera despite complement consumption, were also with one exception strains of Staphylococci. In the nonseptic burned patients, decrease in properdin and C3 conversion by inulin, and increase in C3, factor B and KAF were demonstrated as we have previously reported. The results indicate that the classical complement pathway was activated during septicemia in burned patients and that activation of this pathway occurred preferentially due to inhibition of the alternative pathway. In addition, the data show that complement consumption may reduce the opsonic capacity of a patient's sera for certain microorganisms and not for others.


Fluorimetric determination of some antibiotics in raw material and dosage forms through ternary complex formation with terbium (Tb(3+)).
A highly sensitive and specific fluorimetric method was developed for the determination of cefazolin sodium I, cefoperazone sodium II, ceftriaxone sodium III, and cefixime IV. The proposed method involves the formation of ternary complex with Tb(3+) in the presence of Tris buffer. The quenching of the terbium fluorescence due to the complex formation was quantitative for the four studied drugs. The effect of pH, concentration of Tris buffer and terbium were studied. The formation of the complex was highly dependent on the pH. The optimum pH was found to be pH 8 for cefazolin sodium I, ceftriaxone sodium III, cefixime IV and pH 10 for cefoperazone sodium II. The optimum concentration for Tb(3+) was found 1 ml of 10(-4) M solution and for Tris buffer 1 ml of the prepared solution. Under the described conditions, the proposed method was applicable over the concentration range 8.79 x 10(-6)-7.91 x 10(-5), 9.7 x 10(-6)-4.49 x 10(-)5, 6.10 x 10(-6)-2.50 x 10(-5), and 4.92 x 10(-6)-2.95 x 10(-5) mol with mean percentage accuracy of 99.79+/-0.24, 98.97+/-1.25, 100.05+/-0.79, and 100.15+/-0.54 for I, II, III, and IV, respectively. The proposed method was applied successfully for the determination of studied drugs in bulk powder and in pharmaceutical formulations. The results obtained by applying the described method were statistically analyzed and compared with those obtained by applying the official method. The proposed method was used as stability indicating method for the determination of the studied drugs in the presence of their degradation products.


4-Sulfonyloxy/alkoxy benzoxazolone derivatives with high anti-inflammatory activities: Synthesis, biological evaluation, and mechanims of action via p38/ERK-NF-κB/iNOS pathway.
In an effort to discover new agents with high anti-inflammatory activity, 22 new 4-sulfonyloxy/alkoxy benzoxazolone derivatives were synthesized, characterized, and evaluated for their anti-inflammatory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production and TNF-α expression in RAW 264.7 cells in vitro. Most of these compounds displayed greater inhibitory ability against NO production than the lead compound 4-o-methyl-benzenesulfonyl benzoxazolone, and the most active compound 2h exhibited the strongest inhibitory activity against NO, IL-1β, and IL-6 production with IC50 values 17.67, 20.07, and 8.61 μΜ, respectively. The effects of 2h were comparable or stronger than those of the positive control celecoxib. Compound 2h also displayed higher activity in vivo than celecoxib in a mouse model of xylene-induced ear edema, based on their inhibitory rates of 42.69% and 30.87%, respectively. Further molecular analysis revealed that compound 2h significantly reduced the iNOS levels in cell supernatant and suppressed the protein expression of iNOS, p-p38, p-ERK, and nuclear NF-κB. The results indicated that the anti-inflammatory effect of 2h might be realized through the regulation of ERK- and p38-mediated mitogen-activated protein kinase (MAPK)-NF-κB/iNOS signaling, thereby reducing the excessive release of NO, IL-1β, and IL-6. Our findings demonstrated that compound 2h, a new benzoxazolone derivative, could inhibit activation of the MAPK-NF-κB/iNOS pathway, supporting its potential as a novel anti-inflammatory agent.


Spontaneous electrochemical removal of aqueous sulfide.
Most of the existing sulfide removal processes from wastewaters and waste gases require substantial amounts of energy inputs. Here we present an electrochemical method by means of a fuel cell that removes sulfide while producing energy. A lab scale fuel cell was operated at ambient temperature and neutral pH, which was capable of removing aqueous sulfide continuously for 2 months at a rate of 0.62+/-0.1 kg S m(-3)d(-1) of net anodic compartment (NAC) (0.28+/-0.05 kg S m(-3)d(-1) of total anodic compartment, TAC). During continuous operation, on average, the power generated was 12+/-2 W m(-3) NAC (5+/-1 W m(-3) TAC), with a maximum capacity of the cell of 166 W m(-3) NAC (74 W m(-3) TAC). Potassium ferricyanide was used as cathodic electron acceptor. Elemental sulfur was identified as the predominant final oxidation product that was deposited on the anode. In this abiotic fuel cell, the sulfide oxidation rate was not diminished by the presence of an organic electron donor (acetate) during batch experiments while the acetate concentration remained unchanged. This is particularly important for selective sulfide removal from wastewater where organics are essential for downstream nutrient removal. Elemental sulfur deposited on the anode appeared to limit the operation of the fuel cell after 3 months of operation, necessitating periodic removal of the accumulated sulfur from the electrode.


HIV testing in emergency departments: a recommendation with missed opportunities.
The purpose of this study was to determine the effective use of the 2001 Centers for Disease Control and Prevention (CDC) HIV testing recommendations in emergency department settings. A postal questionnaire was distributed to health care providers in emergency departments across the United States to evaluate the rate HIV tests are routinely offered to individuals presenting to emergency departments for care. A total of 223 emergency department providers responded. Results indicated that health care providers generally were not aware that their institutions were located in areas with high HIV seroprevalence rates. Only 3% of the health care providers surveyed claimed they routinely offered an HIV test to everyone who sought care in their emergency department regardless of patients' presentation to care. The conclusion was that, in 2004, testing for HIV in emergency departments was not a priority for those providing care. In general, despite the fact that the CDC 2001 HIV testing guidelines were less universal than the 2006 recommendations, many had not implemented routine HIV testing programs in their emergency departments. The number of patients who use emergency departments for routine care is on the rise, and missed opportunities for offering HIV tests have detrimental effects for the individual as well as for the public health.


[Prostate carcinosarcoma.]
To report a new case of prostatic carcinosarcoma, an uncommon and locally and distance aggressive tumor. We analyzed one case diagnosed in our Center, from clinical and pathological diagnosis to death, describing the treatments received. Patient presented a huge pelvic mass and a pulmonary metastasis that was treated with cystoprostatectomy and bilateral cutaneous ureterostomy with the diagnosis of carcinosarcoma of the prostate. He received 8 cycles of Docetaxel with bone progression and then 3 cycles of doxorubicin, suspending treatment due to progression. The survival was 18 months. Prostate carcinosarcoma is a very aggressive neoplasia that does not respond to the usual treatments of prostate cancer.


Basic protein in brain myelin is phosphorylated by endogenous phospholipid-sensitive Ca2+-dependent protein kinase.
Phosphorylation of myelin basic protein (MBP) in rat or rabbit brain myelin was markedly stimulated by Ca2+, and this reaction was not essentially augmented by exogenous phosphatidylserine or calmodulin or both. Solubilization of myelin with 0.4% Triton X-100 plus 4 mM EGTA, with or without further fractionation, showed that Ca2+-dependent phosphorylation of MBP required phosphatidylserine, but not calmodulin. DEAE-cellulose chromatography of solubilized myelin revealed a pronounced peak of protein kinase activity stimulated by a combination of Ca2+ and phosphatidylserine; a protein kinase stimulated by Ca2+ plus calmodulin was not detected. These findings clearly indicate an involvement of phospholipid-sensitive Ca2+-dependent protein kinase in phosphorylation of brain MBP, although a possible role for the calmodulin-sensitive species of Ca2+-dependent protein kinase in this reaction could not be excluded or established. Phosphorylation of MBP in solubilized rat myelin catalyzed by the phospholipid-sensitive enzyme was inhibited by adriamycin, palmitoylcarnitine, trifluoperazine, melittin, polymyxin B, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7).


Probabilistic analysis of the influence of the bonding degree of the stem-cement interface in the performance of cemented hip prostheses.
The long-term behavior of the stem-cement interface is one of the most frequent topics of discussion in the design of cemented total hip replacements, especially with regards to the process of damage accumulation in the cement layer. This effect is analyzed here comparing two different situations of the interface: completely bonded and debonded with friction. This comparative analysis is performed using a probabilistic computational approach that considers the variability and uncertainty of determinant factors that directly compromise the damage accumulation in the cement mantle. This stochastic technique is based on the combination of probabilistic finite elements (PFEM) and a cumulative damage approach known as B-model. Three random variables were considered: muscle and joint contact forces at the hip (both for walking and stair climbing), cement damage and fatigue properties of the cement. The results predicted that the regions with higher failure probability in the bulk cement are completely different depending on the stem-cement interface characteristics. In a bonded interface, critical sites appeared at the distal and medial parts of the cement, while for debonded interfaces, the critical regions were found distally and proximally. In bonded interfaces, the failure probability was higher than in debonded ones. The same conclusion may be established for stair climbing in comparison with walking activity.


Clinical significance of condylar chondromalacia after arthroscopic resection of flap-tears of the medial meniscus. A prospective study of 93 cases.
We describe the results after arthroscopic resection of flap-tears of the medial meniscus posterior horn in 93 patients with (40) or without (53) chondromalacia of the adjacent condylar cartilage at the time of operation. These were 93 consecutive patients presenting with medial flap-tears during the period 1988-1990 in our departments. The follow-up averaged 42 (range 26-50) months. There was a significant difference in the functional results at review depending on the presence or absence of condylar chondromalacia at arthroscopy. Among the 40 patients with chondromalacia, the Lysholm score was significantly lower (P < 0.004), and only about half the patients reported a satisfactory result. There was a significant increase in the presence of chondromalacia with age (P < 0.001). In conclusion, the presence of minor degenerative changes in the articular cartilage adjacent to meniscal flap-tears correlated with a less favourable outcome.


Referral quality and the cooperation between hospital physicians and general practice: the role of physician and primary care factors.
It has been shown that referral letters from GPs often are of poor quality, but research in this field is scarce, and few efforts have been made to investigate the factors that may help explain the variation in referral quality. Combining a survey among 1298 Norwegian hospital physicians (response rate: 52%) with information on the hospitals and the communities they are serving, this study investigates how they view the general quality of patient referrals received from GPs, and the extent to which insufficient information in referrals and inappropriate referrals is considered a problem for cooperation with GPs. Only 15.6% of the hospital physicians perceived the quality of the referrals to be "usually good", and both lack of information in referrals and inappropriate referrals are seen as important barriers to cooperation with GPs. Of the individual factors, former GP practice is associated with a positive view on referral quality, while regular meetings between hospital physicians and GPs seem to reduce the problems of inappropriate and incomplete referrals. Furthermore, both average number of patients on GPs' lists and lack of free capacity in nursing and care institutions in the hospital catchment area was found to be negatively associated with perceived referral quality. There is a need to increase the knowledge on how contextual, institutional and professional factors affect coordination of care. The main contribution of this study lies in the attempt to address the macro and micro barriers of obtaining good referral care.


Management and Restoration of an Implant With Irreversibly Damaged Internal Threads: A Clinical Report.
This report describes a method to restore an implant with irreversibly damaged internal threads. The remaining fractured post from the previous restoration was removed using a combination of an impression coping and an end-cutting bur. An elastomeric impression of the internal surface of the damaged implant, as well as the position of the adjacent implant, was made for fabrication of a new cast post and core and an implant supported 2-unit ceramometal splinted prosthesis.


Ionization and electron excitation of C60 in a carbon nanotube: A variable temperature/voltage transmission electron microscopic study.
There is increasing attention to chemical applications of transmission electron microscopy, which is often plagued by radiation damage. The damage in organic matter predominantly occurs via radiolysis. Although radiolysis is highly important, previous studies on radiolysis have largely been descriptive and qualitative, lacking in such fundamental information as the product structure, the influence of the energy of the electrons, and the reaction kinetics. We need a chemically well-defined system to obtain such data and have chosen as a model a variable-temperature and variable-voltage (VT/VV) study of the [2 + 2] dimerization of a van der Waals dimer [60]fullerene (C60) to C120 in a carbon nanotube (CNT), as studied for several hundred individual reaction events at atomic resolution. We report here the identification of five reaction pathways that serve as mechanistic models of radiolysis damage. Two of them occur via a radical cation of the specimen generated by specimen ionization, and three involve singlet or triplet excited states of the specimen, as initiated by electron excitation of the CNT, followed by energy transfer to the specimen. The [2 + 2] product was identified by measuring the distance between the two C60 moieties, and the mechanisms were distinguished by the pre-exponential factor and the Arrhenius activation energy—the standard protocol of chemical kinetic studies. The results illustrate the importance of VT/VV kinetic analysis in the studies of radiation damage and show that chemical ionization and electron excitation are inseparable, but different, mechanisms of radiation damage, which has so far been classified loosely under the single term "ionization."


3EZ,20Ac-ingenol, a catalytic inhibitor of topoisomerases, downregulates p-Akt and induces DSBs and apoptosis of DT40 cells.
We have previously reported that many ingenol compounds derived from Euphorbia kansui exhibit topoisomerase (topo) II inhibitory activity. Of these compounds, 3EZ,20Ac-ingenol inhibited topo I activity. Camptothecin, which inhibits the religation activity of topo I without interfering with the binding of topo I to DNA and induces topo I-mediated DNA cleavage, was used as a positive control. In this study, we found that 3EZ,20Ac-ingenol did not hamper the binding of topo I to DNA in the same manner as camptothecin but affected the inhibition of cleavage of one DNA strand. 3EZ,20Ac-ingenol inhibited cell proliferation by blocking cell cycle progression in the G2/M phase. To define the mechanism of inhibition of DT40 cell proliferation, the change in Akt activity was observed because Akt activity is regulated in response to DNA damage. Western blot analysis revealed that 3EZ,20Ac-ingenol downregulated the expression of p-Akt, and apoptosis was detected by the presence of DNA double-strand breaks and caspase 3 activation.


Characterization of cDNA encoding a human sperm membrane protein sharing homology with Huntington protein.
In our earlier study, we have reported the identification and characterization of a 57-kDa sperm membrane protein from human spermatozoa. The protein was found to be localized on the acrosome in acrosome intact spermatozoa and shifted to equatorial region after acrosomal induction. Further, we demonstrated that it plays a critical role in sperm--egg binding and fusion. Since the protein was found to be either absent or poorly expressed on the spermatozoa from infertile men, we designated it as Fertility Associated Sperm Antigen (FASA). A human epididymal cDNA library in Lambda-ZAP vector was screened with a polyclonal antibody raised against FASA. A clone was obtained with an insert of approximately 1.9 kb cDNA. The sequence showed 99% homology with a part of the human chromosome 11. EST database showed that a portion of 1.9 kb gene has 87% homology to gene encoding Huntington disease protein (HDP). The mutated form of this protein is responsible for Huntington's disease (HD) and is found in the brain cells of HD patients.


Hippocampus, hippocampal sclerosis and epilepsy.
Hippocampal sclerosis (HS) is considered one of the major pathogenic factors of drug-resistant temporal lobe epilepsy. HS is characterized by selective loss of pyramidal neurons - especially of sectors CA1 and CA3 of the hippocampus - pathological proliferation of interneuron networks, and severe glia reaction. These changes occur in the course of long-term and complex epileptogenesis. The authors, on the basis of a review of the literature and own experience, present the pathomechanisms leading to hippocampal sclerosis and epileptogenesis, including various morphological and functional elements of this structure of the brain and pharmacological possibilities of preventing these processes.


Ventricular Tachycardia in Granulomatous Myocarditis: Role of Catheter Ablation.
Granulomatous myocarditis is an inflammatory disease of the myocardium, characterized by lymphocytic infiltration with characteristic granuloma formation. Although a host of disease processes can elicit myocardial granulomas, two common entities are cardiac sarcoidosis and cardiac tuberculosis. Cardiac arrhythmias in this condition are frequent and management of ventricular arrhythmias can be challenging, especially in those with drug-refractory ventricular tachycardia and electrical storm. In this review, we highlight the role of catheter ablation for ventricular tachycardia and optimal patient selection for catheter ablation, based on cardiac imaging.


Hyperthyroidism as a latent complication of autologous hematopoietic stem cell transplantation.
Thyroid dysfunction after hematopoietic stem cell transplantation has been investigated in many studies. Most post-transplant thyroid disorders such as hypothyroidism are recognized as a late complication whilst hyperthyroidism is infrequent and transient, and usually happens early at the onset after transplant. Here, we report two rare hyperthyroid cases, developing more than 2 years after autologous stem cell transplant. We suggest that hyperthyroidism be alerted in the post-transplant care, and special attention be paid to any latent events.


Purification and partial characterization of a nonprimate growth hormone receptor.
Pregnant rabbit liver membranes have been shown to possess two types of receptors by displacement analysis, a growth hormone (GH) receptor which binds bovine growth hormone with an affinity constant (KA) of 3 x 10(9) M-1 and ovine prolactin with a KA of 3 x 10(8) M-1, and a prolactin (Prl)-specific receptor which binds ovine prolactin with a KA of 5 x 10(9) M-1. The prolactin-specific receptor when solubilized with Triton exhibits a 4-fold increase in the its KA while the KA of the growth hormone receptor decreases slightly to 2 x 10(9) M-1 after solubilization. The 10-fold difference in affinity which results has been exploited to facilitate the separation of these two receptors by differential affinity chromatography on human growth hormone (hGH) affinity gels. The growth hormone receptor is eluted from the gel with 4 M urea while 5 M MgCl2 is required to elute the prolactin receptor. Conditions of affinity chromatography have been optimized, and further purification of the GH receptor by preparative isoelectric focusing and Sepharose 6B gel filtration resulted in a more than 8000-fold purification of the receptor. This material had a Stokes radius of 62 A, consistent with a molecular weight of 300,000 and gave one main band (75,000 to 80,000) and two minor bands on sodium dodecyl sulfate (SDS) polyacrylamide gels, which could be interpreted as indicating a tetrameric receptor. The GH receptor was shown to be a sialoglycoprotein (or closely associated with sialoglycoprotein) by analytical isoelectric focusing with an isoelectric point of 4.6. Specificity studies with the highly purified receptor confirmed the initial hypothesis that this receptor is capable of binding bovine growth hormone (bGH) with high affinity and ovine prolactin (oPrl) with low affinity, in contrast to the prolactin-specific receptor.


The dynamic nature of the reconsolidation process and its boundary conditions: Evidence based on human tests.
The reconsolidation process is the mechanism by which the strength and/or content of consolidated memories are updated. This process is triggered by the presentation of a reminder (training cues). It is not always possible to trigger the reconsolidation process. For example, memory age and strength are boundary conditions for the reconsolidation process. Here, we investigated the dynamic changes in these conditions. We propose that the boundary conditions of the reconsolidation process are not fixed and vary as a consequence of the interaction between memory features and reminder characteristics. To modify memory properties, participants received a threatening social protocol that improves memory acquisition or a control condition (fake, without social interaction) prior to learning pairs of meaningless syllables. To determine whether a strong young or old declarative memory undergoes the reconsolidation process, we used an interference task (a second list of pairs of meaningless syllables) to disrupt memory re-stabilization. To assess whether the older memory could be strengthened, we repeated the triggering of reconsolidation. Strong young or old memories modulated by a threatening experience could be interfered during reconsolidation and updated (strengthened) by reconsolidation. Rather than being fixed, boundary conditions vary according to the memory features (strong memory), which indicates the dynamic nature of the reconsolidation process. Our findings demonstrate that it is possible to modify these limits by recruiting the reconsolidation process and making it functionally operative again. This novel scenario opens the possibility to new therapeutically approaches that take into account the reconsolidation process.


Spectrophotometric investigation of the binding of vitamin E to water-containing reversed micelles.
The distribution constants of vitamin E partitioned between apolar organic phase and water-containing reversed micelles of sodium bis (2-ethylhexyl) sulfosuccinate (AOT), didodecyldimethylammonium bromide (DDAB), soybean phosphatidylcholine (lecithin) and tetraethylene glycol monododecyl ether (C12E4) have been evaluated by a spectrophotometric method. The results suggest that in the presence of domains from apolar organic solvent to surfactant and to water, vitamin E is partitioned between the micellar palisade layer and the organic solvent and also that its binding strength to reversed micelles depends mainly by specific interactions between the head group of vitamin E and that of the surfactant. Moreover, in addition to the advantageous interactions between vitamin E and water, the dependence of the distribution constants upon the molar ratio R (R=[water]/[surfactant]) indicates a competition between water and vitamin E for the binding sites at the water/surfactant interface. The biological implications of the preferential location and confinement of vitamin E in water-containing reversed micelles are discussed.


Minimization of the Risk of Diabetic Microangiopathy in Rats by Nigella sativa.
Microangiopathy is a chronic diabetic complication resulting from metabolic derangements, oxidative stress, and increased pro-inflammatory cytokine production. Nigella sativa Linn. is used as an herbal medicine that exerts hypoglycemic, antilipidemic, anti-inflammatory, and antioxidant effects. To examine the effects of N. sativa extract on cutaneous microvascular changes in diabetic rats. Sprague-Dawley rats were randomly assigned into the following four groups: Untreated and N. sativa-treated normal controls and untreated and N. sativa-treated rats with streptozotocin-induced diabetes. A cold-pressed N. sativa extract was then orally administered (1000 mg/kg/day). After 8 weeks of treatment, the glucose, glycosylated hemoglobin (HbA1c), tumor necrosis factor-alpha (TNF-α), insulin levels, and lipid profile were determined in cardiac blood. Dermal capillary wall thickness was measured in tail skin sections stained with periodic acid-Schiff. Endothelial apoptosis was morphologically evaluated by hematoxylin and eosin staining. Diabetes significantly reduced the circulating insulin and low-density lipoprotein levels and caused elevations in the glucose, HbA1c, and triglyceride levels, accompanied by a slight increase in total cholesterol levels and no change in the high-density lipoprotein and TNF-α levels. Capillary basement membrane thickening and a decreased capillary luminal diameter despite no evidence of endothelial cell apoptosis were also observed. N. sativa treatment of diabetic rats reduced the mean HbA1c concentration by 1.4%, enlarged the capillary lumens, and tended to attenuate dermal capillary basement membrane thickening without affecting the lipid profile or TNF-α level. Our results indicate that N. sativa may be used to minimize the risk of diabetic microangiopathy, potentially due in part to its glycemic control activity. Diabetes causes dermal capillary basement membrane thickening and a decreased capillary luminal diameterNigella sativa treatment of diabetic rats enlarged the capillary lumens and tended to attenuate dermal capillary basement membrane thickeningN. sativa treatment of diabetic rats reduced the mean glycosylated hemoglobin concentration by 1.4%, which exceeds the necessary reduction previously described to decrease the risk of diabetic microangiopathy, without affecting the lipid profile or tumor necrosis factor-alpha levelN. sativa improves rat diabetic microangiopathy, potentially due in part to its glycemic control activity. Abbreviations used: H and E: Hematoxylin and eosin, HbA1c: Glycosylated hemoglobin, HDL-C: High-density lipoprotein cholesterol, LDL-C: Low-density lipoprotein cholesterol, PAS: Periodic acid-Schiff, STZ: Streptozotocin.


Predicting Bleeding Risk by Platelet Function Testing in Patients Undergoing Heart Surgery.
Predicting bleeding events in patients with coronary artery bypass grafting (CABG) represents an unmet medical need that may improve CABG outcomes. To assess the potential link between platelet function testing and bleeding risk in patients undergoing CABG. Platelet aggregation and clinical outcomes in 478 patients treated with aspirin and/or clopidogrel were retrospectively analyzed. Platelet activity was assessed prior to CABG with arachidonic acid (ASPI Test), and adenosine diphosphate(ADP Test) utilizing multiple-electrode aggregometry. In the study group of 478 patients, mean age was 65.2±15.2 years; 138 were women. The majority of patients (n = 198) underwent on-pump surgery, with 162 undergoing off-pump and 30 undergoing minimally invasive surgery. Forty-eight patients received artificial valve implantation alone, and 40 received valve implantation in combination with CABG. The analysis of the entire pool revealed that an ASPI test value <407 area under curve per minute (AUC*min) may be useful in predicting postoperative drainage. In CABG patients only, an ASPI test value <271 AUC*min predicted the need for red blood cell concentrate transfusion following surgery. In patients who stopped clopidogrel for up to 5 days before surgery, the ADP test failed to exhibit prognostic utility for predicting bleeding risk. In patients undergoing heart surgery, an ASPI test value <407 AUC*min may predict higher postoperative drainage, whereas <271 AUC*min may be linked to postoperative use of red blood cell concentrate.


Ultrasonic evaluation of fetal body movements over twenty-four hours in the human fetus at twenty-four to twenty-eight weeks' gestation.
Continuous 24-hour observations of fetal gross body movements were performed in 20 women between 24 and 28 weeks of gestation by means of real-time ultrasound examination. At 24 to 26 weeks, fetuses moved 13.1% +/- 0.3% of the time, which was not significantly different from the incidence of 12.4% +/- 0.8% at 26 to 28 weeks' gestation. An examination of the number of movements per hour demonstrated that fetuses at 24 to 26 weeks' gestation moved on the average 53.4 +/- 1.6 times/hr, which was significantly different from 26 to 28 weeks' gestation when fetuses made 46.2 +/- 1.4 movements/hr. When examined on an hourly basis, fetuses in both age groups demonstrated a significant increase in the number of movements overnight from 2300 to 0800 hours. Intermovement intervals were also examined. Ninety-nine percent of intervals less than 6 minutes in both age groups contained movement. The longest observed quiescent interval was 24 minutes in both age groups. These data suggest that the incidence of fetal body movements is different than that observed in fetuses during the last 10 weeks of gestation. Fetuses at 24 to 28 weeks' gestation exhibit a diurnal pattern of fetal movement and move more frequently than do older fetuses. However, these movements are of a sporadic nature and relatively short duration. Thus these fetuses do not appear to have well-defined periods of rest and activity.


Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.
Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it.


Randomized clinical trial comparing affect regulation and supportive group therapies for victimization-related PTSD with incarcerated women.
Traumatic victimization and associated problems with posttraumatic stress disorder (PTSD) and affect dysregulation are prevalent among incarcerated women, but there is limited evidence to support psychotherapeutic interventions for these problems in this underserved population. A group psychotherapy designed to enhance affect regulation without trauma memory processing-Trauma Affect Regulation: Guide for Education and Therapy (TARGET)-was compared to a supportive group therapy (SGT) in a randomized clinical trial with 72 incarcerated women with full or partial PTSD. Both interventions achieved statistically significant reductions in PTSD and associated symptom severity and increased self-efficacy. Dropout rates for both interventions were low (<5%). TARGET was more effective than SGT in increasing sense of forgiveness toward others who have caused harm in the past. Group therapy that teaches affect regulation may enhance incarcerated women's ability to achieve affective resolution (forgiveness) while also reducing their victimization-related PTSD and associated symptoms. Experiential-focused supportive group therapy also may reduce victimization-related PTSD and associated symptoms. Both group therapy approaches warrant further study with this vulnerable population.


Comparative performances of eggs and embryos of sea urchin (Paracentrotus lividus) in toxicity bioassays used for assessment of marine sediment quality.
The potential toxicity of sediments from various ports was assessed by means of two different liquid-phase toxicity bioassays (acute and chronic) with embryos and eggs of sea urchin Paracentrotus lividus. Performances of embryos and eggs of P. lividus in these bioassays were compared for their interchangeable applicability in integrated sediment quality assessment. The obtained endpoints (percentages of normally developed plutei and fertilized eggs) were linked to physical and chemical properties of sediments and demonstrated dependence on sediment contamination. The endpoints in the two bioassays were strongly correlated and generally exhibited similar tendency throughout the samples. Therein, embryos demonstrated higher sensitivity to elutriate exposure, compared to eggs. It was concluded that these tests could be used interchangeably for testing toxicity of marine sediments. Preferential use of any of the bioassays can be determined by the discriminatory capacity of the test or vulnerability consideration of the test subject to the surrounding conditions.


Evidence for the existence of a substance P-containing pathway from the nucleus laterodorsalis tegmenti (Castaldi) to the medial frontal cortex of the rat.
A long ascending substance P (SP)-containing pathway from the nucleus laterodorsalis tegmenti (TLD) to the medial frontal cortex (MFC) has been demonstrated by means of experimental immunohistochemical procedures. The unilateral destruction of the TLD, which contains numerous SP-like immunoreactive (SPLI) cells, resulted in a marked ipsilateral decrease in the SPLI fibers in the MFC.


The increasing burden of diabetes and variations among the states of India: the Global Burden of Disease Study 1990-2016.
The burden of diabetes is increasing rapidly in India but a systematic understanding of its distribution and time trends is not available for every state of India. We present a comprehensive analysis of the time trends and heterogeneity in the distribution of diabetes burden across all states of India between 1990 and 2016. We analysed the prevalence and disability-adjusted life-years (DALYs) of diabetes in the states of India from 1990 to 2016 using all available data sources that could be accessed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, and assessed heterogeneity across the states. The states were placed in four groups based on epidemiological transition level (ETL), defined on the basis of the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa. We assessed the contribution of risk factors to diabetes DALYs and the relation of overweight (body-mass index 25 kg/m2 or more) with diabetes prevalence. We calculated 95% uncertainty intervals (UIs) for the point estimates. The number of people with diabetes in India increased from 26·0 million (95% UI 23·4-28·6) in 1990 to 65·0 million (58·7-71·1) in 2016. The prevalence of diabetes in adults aged 20 years or older in India increased from 5·5% (4·9-6·1) in 1990 to 7·7% (6·9-8·4) in 2016. The prevalence in 2016 was highest in Tamil Nadu and Kerala (high ETL) and Delhi (higher-middle ETL), followed by Punjab and Goa (high ETL) and Karnataka (higher-middle ETL). The age-standardised DALY rate for diabetes increased in India by 39·6% (32·1-46·7) from 1990 to 2016, which was the highest increase among major non-communicable diseases. The age-standardised diabetes prevalence and DALYs increased in every state, with the percentage increase among the highest in several states in the low and lower-middle ETL state groups. The most important risk factor for diabetes in India was overweight to which 36·0% (22·6-49·2) of the diabetes DALYs in 2016 could be attributed. The prevalence of overweight in adults in India increased from 9·0% (8·7-9·3) in 1990 to 20·4% (19·9-20·8) in 2016; this prevalence increased in every state of the country. For every 100 overweight adults aged 20 years or older in India, there were 38 adults (34-42) with diabetes, compared with the global average of 19 adults (17-21) in 2016. The increase in health loss from diabetes since 1990 in India is the highest among major non-communicable diseases. With this increase observed in every state of the country, and the relative rate of increase highest in several less developed low ETL states, policy action that takes these state-level differences into account is needed urgently to control this potentially explosive public health situation. Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.


Identification of epigenetically active L1 promoters in the human brain and their relationship with psychiatric disorders.
Long interspersed nuclear element-1 (LINE-1, L1) affects the transcriptome landscape in multiple ways. Promoter activity within its 5'UTR plays a critical role in regulating diverse L1 activities. However, the epigenetic status of L1 promoters in adult brain cells and their relationship with psychiatric disorders remain poorly understood. Here, we examined DNA methylation and hydroxymethylation of the full-length L1s in neurons and nonneurons and identified "epigenetically active" L1s. Notably, some of epigenetically active L1s were retrotransposition competent, which even had chimeric transcripts from the antisense promoters at their 5'UTRs. We also identified differentially methylated L1s in the prefrontal cortices of patients with psychiatric disorders. In nonneurons of bipolar disorder patients, one L1 was significantly hypomethylated and showed an inverse correlation with the expression level of the overlapping gene NREP. Finally, we observed that altered DNA methylation levels of L1 in patients with psychiatric disorders were not affected by the surrounding genomic regions but originated from the L1 sequences. These results suggested that altered epigenetic regulation of the L1 5'UTR in the brain was involved in the pathophysiology of psychiatric disorders.


Multimodal postcesarean delivery analgesia.
Cesarean deliveries can be associated with moderate to severe postoperative pain. Appropriate management of pain is important because it results in better patient satisfaction, earlier mobilization, and improved maternal-infant bonding. There are many individual options for treatment of pain; however, multimodal analgesic therapy has become the mainstay of treatment. In this article, the epidemiology of postcesarean delivery pain, pain mechanisms, and the multiple options available to providers for treatment of postoperative pain are discussed.


Stabilization of the peripheral-type benzodiazepine acceptor by specific phospholipids.
The peripheral-type benzodiazepine acceptor from rat adrenal gland was solubilized with Triton X-100. The soluble acceptor exhibited isoquinoline carboxamide and benzodiazepine binding activity only when supplemented with lipid. Phosphatidylserine and phosphatidylinositol were especially efficacious. Such selectivity may reflect a specific structural requirement for acceptor activity. The requirement for lipid for acceptor activity in fractions subsequent to solubilization was demonstrated. This stabilization of acceptor activity by the phospholipids promises to facilitate purification of the functional acceptor.


Leber's hereditary optic neuropathy: a multifactorial disease.
Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease characterized by acute or subacute visual loss predominantly affecting young men. The majority of LHON cases are caused by one of the three primary mitochondrial DNA (mtDNA) mutations: G3460A/ND1, G11778A/ND4, or T14484C/ND6. Although the primary etiological factor of LHON is a mtDNA mutation, the presence of a primary mtDNA mutation does not necessarily lead to visual loss. The pathogenesis of LHON remains unclear. The marked incomplete penetrance and gender bias indicate that additional genetic (nuclear or mitochondrial) and epigenetic factors may also be involved. Deficiency in respiratory chain function and reactive oxygen species (ROS) are believed to play a pivotal role in the pathophysiology of the disease.


Paraxial mesodermal progenitors derived from mouse embryonic stem cells contribute to muscle regeneration via differentiation into muscle satellite cells.
Pluripotent embryonic stem (ES) cells hold great potential for cell-based therapies. Although several recent studies have reported the potential of ES cell-derived progenitors for skeletal muscle regeneration, how the cells contribute to reconstitution of the damaged myofibers has remained elusive. Here, we demonstrated the process of injured muscle regeneration by the engraftment of ES cell-derived mesodermal progenitors. Mesodermal progenitor cells were induced by a conventional differentiation system and isolated by flow cytometer of platelet-derived growth factor receptor-alpha (PDGFR-alpha), a marker of paraxial mesoderm, and vascular endothelial growth factor receptor-2 (VEGFR-2), a marker of lateral mesoderm. The PDGFR-alpha(+) population that represented the paraxial mesodermal character demonstrated significant engraftment when transplanted into the injured muscle of immunodeficient mouse. Moreover, the PDGFR-alpha(+) population could differentiate into the muscle satellite cells that were the stem cells of adult muscle and characterized by the expression of Pax7 and CD34. These ES cell-derived satellite cells could form functional mature myofibers in vitro and generate myofibers fused with the damaged host myofibers in vivo. On the other hand, the PDGFR-alpha(-)VEGFR-2(+) population that showed lateral mesodermal character exhibited restricted potential to differentiate into the satellite cells in injured muscle. Our results show the potential of ES cell-derived paraxial mesodermal progenitor cells to generate functional muscle stem cells in vivo without inducing or suppressing gene manipulation. This knowledge could be used to form the foundation of the development of stem cell therapies to repair diseased and damaged muscles.


TRA-418, a novel compound having both thromboxane A(2) receptor antagonistic and prostaglandin I(2) receptor agonistic activities: its antiplatelet effects in human and animal platelets.
TRA-418 is a novel compound that has been found in our screening for compounds having both thromboxane A2 (TP) receptor antagonistic and prostaglandin I2 (IP) receptor agonistic activities. In the binding assays, TRA-418 showed a 10-fold higher affinity to TP-receptors than IP-receptors. TRA-418 inhibited platelet aggregation induced by the TP-receptor agonist, U-46619 and by arachidonic acid at concentrations lower than those required for inhibition of ADP-induced aggregations. Furthermore, TRA-418 inhibited not only platelet aggregation induced by ADP alone, but also that induced by ADP in the presence of the TP-receptor antagonist, SQ-29548. When the IC50 values of TRA-418 for platelet aggregation were estimated in platelet preparations from monkeys, dogs, cats, and rats using ADP and arachidonic acid as the platelet stimulating agents, it was found that the values estimated in monkey platelets were quite similar to those estimated in human platelets. In ex vivo platelet aggregation in monkeys, TRA-418 exhibited significant inhibitory effects on arachidonic acid-induced aggregation in platelet preparations from monkeys treated at 3 micro g kg min-1 or higher doses, where neither a significant decrease in blood pressure nor a significant increase in heart rate was observed. These results are consistent with the fact that TRA-418 has a relatively potent TP-receptor antagonistic activity together with a relatively weak IP-receptor agonistic activity.


[Basal metabolism in patients with a maxillofacial injury and disordered masticatory function].
In 31 patients (males, aged 21 to 50) with maxillary fractures basal metabolism was investigated during 24 days by the method of gas exchange. From the moment of the injury and up to the 18th day its level is shown to be by 19.9--30.6 per cent higher than in healthy persons and later on falls down to the normal value.