New type of osmoregulated solute transporter identified in halophilic members of the bacteria domain: TRAP transporter TeaABC mediates uptake of ectoine and hydroxyectoine in Halomonas elongata DSM 2581(T).
The halophilic bacterium Halomonas elongata synthesizes as its main compatible solute the aspartate derivative ectoine. We constructed a deletion mutant of H. elongata, KB1, defective in ectoine synthesis and tolerating elevated salt concentrations only in the presence of external compatible solutes. The dependency of KB1 on solute uptake for growth in high-salt medium was exploited to select insertion mutants unable to accumulate external solutes via osmoregulated transporters. One insertion mutant out of 7,200 failed to accumulate the osmoprotectants ectoine and hydroxyectoine. Genetic analysis of the insertion site proved that the mutation affected an open reading frame (ORF) of 1,281 bp (teaC). The nucleotide sequence upstream of teaC was determined, and two further ORFs of 603 bp (teaB) and 1,023 bp (teaA) were identified. Deletion of teaA and teaB proved that all three genes are mandatory for ectoine uptake. Sequence comparison showed significant identity of TeaA, TeaB, and TeaC to the transport proteins of the recently identified tripartite ATP-independent periplasmic transporter family (TRAP-T). The affinity of the cells for ectoines was determined (K(s) = 21.7 microM), suggesting that the transporter TeaABC exhibits high affinity for ectoines. An elevation of the external osmolarity resulted in a strong increase in ectoine uptake via TeaABC, demonstrating that this transporter is osmoregulated. Deletion of teaC and teaBC in the wild-type strain led to mutants which excreted significant amounts of ectoine into the medium when cultivated at high salt concentrations. Therefore, the physiological role of TeaABC may be primarily to recover ectoine leaking through the cytoplasmic membrane.


Serum of Behçet's disease enhances superoxide production of normal neutrophils.
Using an MCLA-dependent chemiluminescence technique, we evaluated superoxide production by neutrophils isolated from 7 patients with Behçet's disease. After stimulation by phorbol myristate acetate, N-formyl-methionyl-leucyl-phenylalanine or opsonized zymosan, neutrophils from the patients produced significantly more superoxide than those from 20 controls. Pretreatment of control neutrophils with serum prominently enhanced superoxide production, and serum from Behçet's disease patients had a significantly greater effect than that from controls. These findings suggest that serum from patients with Behçet disease contains the priming factor(s) that can enhance enhanced superoxide production by neutrophils in response to stimulation.


Irony comprehension and context processing in schizophrenia during remission--a functional MRI study.
Schizophrenic patients have Theory of Mind (ToM) deficits even during remission, but it is yet unknown whether this could be influenced. We examined the neural correlates of irony understanding in schizophrenic patients, as an indicator of ToM capacity, and evaluated how linguistic help inserted into the context phase could affect irony comprehension. Schizophrenic patients in remission and healthy controls were subjected to event-related functional MRI scanning while performing irony, 'irony with linguistic help', and control tasks. Patients understood irony significantly worse than healthy controls. The patients showed stronger brain activity in the parietal and frontal areas in the early phase of irony task, however the healthy controls exhibited higher activation in frontal, temporal and parietal regions in the latter phase of the irony task. Interestingly the linguistic help not only improved the patients' ToM performance, but it also evoked similar activation pattern to healthy controls.


Effects of cyclin D1 (CCND1) polymorphism on susceptibility to lung cancer in a North Indian population.
Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the transition from G1 to S phase of the cell cycle. The CCND1 gene has a G-->A polymorphism in exon 4 that increases the frequency of alternate splicing. We analyzed the potential role of CCND1 gene polymorphisms in lung cancer patients (n = 151) and in a matched control population (n = 151). DNA was isolated from blood samples, and exon 4 of CCND1 was amplified by polymerase chain reaction. After digestion with MspI, common CCND1 polymorphic alleles were analyzed by means of agarose gel electrophoresis. The data obtained were analyzed using multiple logistic regression. After adjustment for age, sex, and smoking status, the AG genotype was associated with an increased risk for overall lung cancer (odds ratio OR = 1.7, 95% confidence interval CI = 0.92-3.14). No association was found between AA genotype and risk of lung cancer. In smokers, the combined AG+AA genotypes of CCND1 were found to be significant (OR = 1.9, 95% CI = 1.03-3.71, P = 0.03). No positive association was found between CCND1 genotypes in nonsmokers. The results suggest that the CCND1 A870G gene polymorphisms may increase the risk of lung cancer in smokers from north India.


Pooled testing of traced contacts under superspreading dynamics.
Testing is recommended for all close contacts of confirmed COVID-19 patients. However, existing pooled testing methods are oblivious to the circumstances of contagion provided by contact tracing. Here, we build upon a well-known semi-adaptive pooled testing method, Dorfman's method with imperfect tests, and derive a simple pooled testing method based on dynamic programming that is specifically designed to use information provided by contact tracing. Experiments using a variety of reproduction numbers and dispersion levels, including those estimated in the context of the COVID-19 pandemic, show that the pools found using our method result in a significantly lower number of tests than those found using Dorfman's method. Our method provides the greatest competitive advantage when the number of contacts of an infected individual is small, or the distribution of secondary infections is highly overdispersed. Moreover, it maintains this competitive advantage under imperfect contact tracing and significant levels of dilution.


Reliability of submaximal stimulation for the train-of-four test using acceleromyography and electromyography with individualized stimulation currents.
The supramaximal stimulation (SMS) of the TOF test causes uncomfortable sensations in patients. We aimed to determine whether the submaximal stimulation would be reliable in TOF tests with reduced painful sensation. The accelomyography (AMG) and electromyography (EMG) monitor was applied at each arm and general anesthesia was induced and maintained by total intravenous anesthesia. At extubation, we conducted TOF test three times at each of four different currents: SMS, 70% SMS, 50% SMS, and 30% SMS. The same procedure was performed in the postanesthesia care unit (PACU) only with EMG, and the pain scores on the numerical rating scale (NRS) during the tests were recorded. A total of 36 patients were enrolled. At extubation, TOF ratios with SMS in AMG and EMG were 112.0 ± 13.1% and 93.7 ± 8.9%, respectively. There were no significant differences in TOF ratios between the SMS and lower stimulation intensities. However, 30% and 50% SMS showed significantly higher rates of the unmeasurable results of tests in the PACU. In terms of the stimulation pain, NRS showed a downward pattern as the current decreased and was significantly lower at 50% and 30% SMS than the NRS at SMS. The TOF test with submaximal stimulation is still reliable and can reduce stimulation pain. Considering the importance of the TOF results in determining extubation, the authors suggest the minimal current for the TOF test as 70% SMS.


Federal sector equal employment opportunity. Final rule.
The Equal Employment Opportunity Commission is publishing this final rule to implement the amendment of section 501 of the Rehabilitation Act, under the Rehabilitation Act Amendments of 1992. This rule continues the movement towards full integration of individuals with disabilities into the Federal workforce.


Validation of potential inhibitors for SrtA against Bacillus anthracis by combined approach of ligand-based and molecular dynamics simulation.
The development of SrtA inhibitors targeting the biothreat organism namely Bacillus anthracis was achieved by the combined approach of pharmacophore modeling, binding interactions, electron transferring capacity, ADME, and Molecular dynamics studies. In this study, experimentally reported Ba-SrtA inhibitors (pyridazinone and pyrazolethione derivatives) were considered for the development of enhanced pharmacophoric model. The obtained AAAHR hypothesis was a pure theoretical concept that accounts for common molecular interaction network present in experimentally active pyridazinone and pyrazolethione derivatives. Pharmacophore-based screening of AAAHR hypothesis provides several new compounds, and those compounds were treated with four phases of docking protocols with combined Glide-QPLD docking approach. In this approach, scoring and charge accuracy variations were seen to be dominated by QM/MM approach through the allocation of partial charges. Finally, we reported the best compounds from binding db, Chembridge db, and Toslab based on scoring values, energy parameters, electron transfer reaction, ADME, and cell adhesion inhibition activity. The dynamic state of interaction and binding energy assess that new compounds are more active inside the binding pocket and these compounds on experimental validations will survive as better inhibitors for targeting the cell adhesion mechanism of Ba-SrtA.


Influence of Left Atrial Function on Exercise Capacity and Left Ventricular Function in Patients With Heart Failure and Preserved Ejection Fraction.
Although left atrial (LA) dysfunction is common in heart failure with preserved ejection fraction (HFpEF), its functional implications beyond the reflection of left ventricular (LV) pathology are not well understood. The aim of this study was to further characterize LA function in HFpEF patients. We performed cardiac magnetic resonance myocardial feature tracking in 22 patients with HFpEF and 12 patients without HFpEF. LA reservoir strain, LA conduit strain, and LA booster pump strain were quantified. Peak oxygen uptake (VO2max) was determined. Invasive pressure-volume loops were obtained to evaluate LV diastolic properties. LV early filling was determined from LV volume-time curves as derived from cardiac magnetic resonance. LA reservoir and conduit strain were significantly lower in HFpEF (LA reservoir strain, 22±7% versus 29±6%, P=0.04; LA conduit strain, -9±5% versus -15±4%, P<0.01). Patients with HFpEF showed lower oxygen uptake (17±6 versus 29±8 mL/(kg min); P<0.01). Strain measurement for LA conduit function was strongly associated with VO2max (r=0.80; P<0.01). On multivariable regression analysis, LA conduit strain emerged as strongest predictor for VO2max even after inclusion of LV stiffness and relaxation time (β=0.80; P<0.01). LA conduit strain correlated with the volume of early ventricular filling (r=0.67; P<0.01), but not LV stiffness constant β (-0.34; P=0.051) or relaxation constant τ (r=-0.33; P=0.06). Cardiac magnetic resonance myocardial feature tracking-derived conduit strain is significantly impaired in HFpEF and associated with exercise intolerance. Impaired conduit function is associated with impaired early ventricular filling, as potential mechanism leading to impaired oxygen uptake. Our results propose that impaired LA conduit function represents a distinct feature of HFpEF, independent of LV stiffness and relaxation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02459626.


Ascorbate biosynthesis during early fruit development is the main reason for its accumulation in kiwi.
Ascorbic acid (AsA) is a unique antioxidant as well as an enzyme cofactor. Although it has multiple roles in plants, it is unclear how its accumulation is controlled at the expression level, especially in sink tissues. Kiwifruit (Actinidia) is well-known for its high ascorbate content. Our objective was to determine whether AsA accumulates in the fruits primarily through biosynthesis or because it is imported from the foliage. We systematically investigated AsA levels, biosynthetic capacity, and mRNA expression of genes involved in AsA biosynthesis in kiwi (A. deliciosa cv. Qinmei). Recycling and AsA localization were also monitored during fruit development and among different tissue types. Over time, the amount of AsA, with its capacity for higher biosynthesis and lower recycling, peaked at 30 days after anthesis (DAA), and then decreased markedly up to 60 DAA before declining more slowly. Expression of key genes showed similar patterns of change, except for L-galactono-1,4-lactone dehydrogenase and L-galactose-1-phosphate phosphatase (GPP). However, GPP had good correlation with the rate of AsA accumulation. The expression of these genes could be detected in phloem of stem as well as petiole of leaf and fruit. Additionally, fruit petioles had greater ascorbate amounts, although that was the site of lowest expression by most genes. Fruit microtubule tissues also had higher AsA. However, exogenous applications of AsA to those petioles did not lead to its transport into fruits, and distribution of ascorbate was cell-specific in the fruits, with more accumulation occurring in larger cells. These results suggest that AsA biosynthesis in kiwi during early fruit development is the main reason for its accumulation in the fruits. We also postulate here that GPP is a good candidate for regulating AsA biosynthesis whereas GDP-L-galactose-1-phosphate phosphorylase is not.


Chronic demyelinating polyneuropathy in graft-versus-host disease following allogeneic bone marrow transplantation.
In recent years a novel problem has arisen in organ transplantation medicine, namely GVHD. The nervous system has been involved mainly at the level of the CNS and this can lead to a serious outcome for the patient. In rare cases, peripheral nerves may be affected and show acute or chronic polyneuropathy. Here a case is reported of polyneuropathy associated with chronic GVHD. A 32-year-old man, suffering from chronic GVHD following an allogeneic bone marrow transplantation (BMT) for malignant lymphoma at the age of 25, developed a motor dominant polyneuropathy 5 years later. Electrophysiologic studies demonstrated the demyelinating type of polyneuropathy. Biopsy specimens from skin and skeletal muscle disclosed perivascular lymphocytic infiltrates expressing T-cell markers. The sural nerve showed a loss of myelinated nerve fibers with epineurial fibrosis and rare occurrence of T cells, but without obvious vasculitic changes. The present case suggested that polyneuropathy could develop in association with chronic GVHD in some patients with a long-standing disease course.


Immobilization of cobalt in collapsed non-irradiated and gamma-irradiated X zeolites.
Cobalt exchanged X zeolites were gamma irradiated and heated until the zeolite structure collapsed. Heating destroys the zeolite network as found by X-ray-diffraction and 29Si, 27Al MAS NMR spectroscopy. Gamma irradiation treatment diminished the collapsing temperature of zeolite. Cobalt leaching from crystalline and amorphized zeolites was verified by ion exchange with NaCl solution. Results show that cobalt is not released from the amorphous materials. Furthermore adsorption of xenon and 129Xe NMR spectroscopy reveal that cobalt ions are heterogeneously distributed in the non irradiated amorphous materials. Gamma irradiation causes the mobility of cobalt in the amorphous materials resulting then in a more homogeneous distribution. Cobalt is, thus, retained safely in the amorphous materials.


Network Medicine: A Mandatory Next Step for Inflammatory Bowel Disease.
Despite unquestionable progress in the management of inflammatory bowel disease (IBD) and the much improved clinical results achievable today in Crohn's disease (CD) and ulcerative colitis (UC) patients, the overall therapeutic outcome remains far from optimal. The main reason of this partial success is that all current medications only block individual components of a highly complex disease process that results from the integration of multiple and incompletely identified pathogenic components. Thus, if further progress is to be achieved in IBD therapeutics and we want to move from the current success rate to nearly 100%, bold new ideas must be entertained and new approaches put into practice. Both are necessary because in IBD we are dealing with a prototypical complex disease superimposed to the background of the extreme biological diversity of humans in response to injury. An unresolved challenge mandates the adoption of new solutions specifically designed to address the unique features of that challenge. Translated to a disease condition, and IBD in particular, the unresolved challenges of CD and UC demand bold new thinking leading to the conception and implementation of totally innovative therapies. In this article, we propose that one such new thinking is the notion of network medicine for IBD, and that the development of brand new treatments should be based on the identification of the molecular structure of the IBD interactome with the purpose of targeting its controlling elements (central nodes or hubs). This specific targeting of the underlying molecular disease modules will lead to the disruption of the IBD interactome and foster the resolution of intestinal inflammatory process.


Signal transduction during oxidative stress.
As an unfortunate consequence of aerobic life, active oxygen species (AOS) are formed by partial reduction of molecular oxygen. Plants possess a complex battery of enzymatic and non-enzymatic antioxidants that can protect cells from oxidative damage by scavenging AOS. It is becoming evident that AOS, which are generated during pathogen attack and abiotic stress situations, are recognized by plants as a signal for triggering defence responses. An overview of the literature is presented on the signalling role of AOS in plant defence responses, cell death, and development. Special attention is given to AOS and redox-regulated gene expression and the role of kinases and phosphatases in redox signal transduction.


Evaluating the top electrode material for achieving an equivalent oxide thickness smaller than 0.4 nm from an Al-doped TiO₂ film.
The effects of Pt and RuO2 top electrodes on the electrical properties of capacitors with Al-doped TiO2 (ATO) films grown on the RuO2 bottom electrode by an atomic layer deposition method were examined. The rutile phase ATO films with high bulk dielectric constant (>80) were well-grown because of the local epitaxial relationship with the rutile structured RuO2 bottom electrode. However, the interface between top electrode and ATO was damaged during the sputtering process of the top electrode, resulting in the decrease in the dielectric constant. Postmetallization annealing at 400 °C was performed to mitigate the sputtering damage. During the postmetallization annealing, the ATO layer near the RuO2 top electrode/ATO interface was well-crystallized because of the structural compatibility between RuO2 and rutile ATO, while the ATO layer near the Pt top electrode/ATO interface still exhibited an amorphous-like structure. Despite the same thickness of the ATO films, therefore, the capacitors with RuO2 top electrodes showed higher capacitance compared to the capacitors with Pt top electrodes. Eventually, an extremely low equivalent oxide thickness of 0.37 nm with low enough leakage current density (<1 × 10(-7) A/cm(2) at 0.8 V) and physical thickness of 8.7 nm for the next-generation dynamic random access memory was achieved from ATO films with RuO2 top electrodes.


Kisspeptin: a new marker for human pre-ovulation.
Kisspeptin is a polypeptide that plays an important role in reproductive endocrine regulation. The aim of present study was to investigate the dynamic trend of kisspeptin levels during the menstrual cycle and to elucidate the relationship between kisspeptin ovulation. First, 15 female volunteers with regular menstrual cycles were recruited to detect the change in serum and urine kisspeptin levels over one menstrual cycle within each individual. Subsequently, 114 serum samples and 79 urine samples from 114 individuals were randomly collected at the outpatient department to better ascertain the results. Kisspeptin levels showed a distinctive stage-specific pattern during the normal menstrual cycle in both serum and urine. It was low during the first 5 days, while the first surge appeared on the 11th day (the diameter of the dominant follicle was approximately 1.2 cm). Later, a second smaller surge appeared around the 14th day and the same changes were identified in serum and urine. Furthermore, serum kisspeptin levels were positively related to 17-β estradiol (E2) level increase. Thus, kisspeptin surge in serum and urine may be used as a marker for dominant follicle development and pre-ovulation. Moreover, kisspeptin may also play a vital role in female reproduction through regulating hormonal state.


Intelligent polyelectrolytes and gels in oral drug delivery.
The present review concerns smart, or intelligent polymers for oral administration that change conformation in aqueous solutions in response to external stimuli such as pH or temperature. We concentrate on charged polymers and gels with polyelectrolyte properties. Because of the ionization at a certain pH or in response to changes in the ionic composition of the solution, a polyelectrolyte has better chances of displaying smart properties than a neutral polymer. When such smart polyelectrolyte is cross-linked by covalent or hydrogen bonding and/or physical aggregation or is entangled, it forms an environmentally sensitive gel capable of swelling and collapse in an aqueous medium. Varying pH, temperature, and microbial flora are found in the gastrointestinal tract, and thus pH- sensitive polymers and gels that can be degraded by specific enzymes and/or inhibit proteolytic enzymes can be tailored for the efficient site-specific therapy. Smart polymers wield a lot of promise in the targeted, site-specific administration where they can provide advantages in loading of sensitive drugs such as proteins and peptides, while releasing the drug at a specific pH or in response to the presence of certain microbial flora.


Computational studies of CXCR1, the receptor of IL-8/CXCL8, using molecular dynamics and electrostatics.
The three-dimensional structure of IL-8/CXCL8 has been previously determined using NMR spectroscopy and X-ray crystallography, but the structure of the receptors for this chemokine has not been determined experimentally. We present here the development of a model for the structure of the IL-8/CXCL8 receptor CXCR1, using a combination of homology modeling and a molecular dynamics simulation. Based on this model, we discuss the analysis of structural, dynamic, and physicochemical properties of CXCR1. We focused on the role of pairwise ionic interactions in local structural stability of CXCR1 and the role of electrostatic potentials in recognition of CXCR1 with IL-8/CXCL8. We have performed theoretical mutations of six charged amino acids in CXCR1, which abolish binding as suggested by earlier experimental data, to shed light on the effect of charge on association ability. We propose that the observed loss of binding in the six CXCR1 mutants is owed to loss of local structural stability, rather than hindrance of the recognition process because of changes in the overall electrostatic properties of the receptor. Based on further structural analysis, we propose some mutations of charged residues involving ion pairs in different elements of transmembrane helices and extracellular loops, which are expected to alter the local structure and possibly affect binding.


Extrinsic feedback and upper limb motor skill learning in typically-developing children and children with cerebral palsy: Review.
Improvment of upper limb motor skills occurs through motor learning that can be enhanced by providing extrinsic feedback. Different types and frequencies of feedback are discussed but specific guidelines for use of feedback for motor learning in typically-developing (TD) children and children with Cerebral Palsy (CP) are not available. Identify the most effective modalities and frequencies of feedback for improving upper limb motor skills in TD children and children with CP. Ovid MEDLINE, Cochrane, PEDro and PubMed-NCBI were searched from 1950 to December 2015 to identify English-language articles addressing the role of extrinsic feedback on upper limb motor learning in TD children and children with CP. Nine studies were selected with a total of 243 TD children and 102 children with CP. Study quality was evaluated using the Downs and Black scale and levels of evidence were determined with Sackett's quality ratings. There was a lack of consistency in the modalities and frequencies of feedback delivery used to improve motor learning in TD children and in children with CP. Moreover, the complexity of the task to be learned influenced the degree of motor learning achieved. A better understanding of the influence of feedback on motor learning is needed to optimize motor skill acquisition in children with CP.


Development and optimization of a cell-associated challenge model for Mycoplasma hyorhinis in 7-week-old cesarean-derived, colostrum-deprived pigs.
Mycoplasma hyorhinis (MHR) causes polyserositis and lameness in grower pigs. While herd-specific vaccines for this bacterium are being marketed, there are currently no licensed, commercially available vaccines for MHR. The objective of this study was to develop a challenge model in cesarean-derived, colostrum-deprived (CDCD) pigs using cell-associated MHR that results in both severe pericarditis and lameness, in order to evaluate suitable vaccine candidates. We investigated administering MHR to 7-week-old pigs over 3 d using 3 different routes compared to administering MHR on a single day using 1 of 3 routes. Pigs were monitored for 21 d for signs of lameness and well-being. At the end of the study, pigs were examined for evidence of polyserositis and arthritis associated with Mycoplasma. Results indicate that clinical manifestation of disease depended more on the route of administration than on the total dose given. A single intravenous (IV) administration of MHR resulted in extensive polyserositis, while a single intranasal (IN) administration showed little to no signs of disease. A single intraperitoneal (IP) administration did not induce the same level of polyserositis as observed in the IV group, but did result in an increased incidence of lameness. Furthermore, pigs administered MHR by IP (Day 0), IV (Day 1), and IN (Day 2) on 3 consecutive days showed a more robust disease manifestation, which resulted in both polyserositis and lameness. Optimization of this group showed that elimination of the 3rd-day IN challenge had no detrimental effect on clinical outcomes. The consecutive day administration of cell-associated MHR will allow polyserositis and lameness to be simultaneously evaluated in future vaccine trials.


Lysine: arginine ratio of a protein influences cholesterol metabolism. Part 1--Studies on sesame protein having low lysine: arginine ratio.
The effect of globulin fraction with a lysine: arginine (lys:arg) ratio 0.67, isolated from sesame (Sesamum Indicum) seeds on cholesterol metabolism was studied in rats fed cholesterol free and cholesterol containing diet and compared with casein (lys:arg ratio-2.0). Rats fed sesame seed globulin showed significantly lower concentrations of cholesterol in the serum and aorta. The decrease in serum was manifested in both HDL and LDL + VLDL fractions. There was increased cholesterogenesis in the liver as was evident from increased incorporation of labeled acetate into cholesterol and increased activity of 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Increased hepatic diversion of cholesterol to bile acid synthesis and increased fecal excretion of bile acids and sterols were also observed in rats fed sesame seed globulins. Rats fed sesame globulins also showed significantly higher activity of lipoprotein lipase in the heart and adipose tissue and that of plasma Lecithin: cholesterol acyltransferase (LCAT). These studies suggest that low lysine: arginine ratios of a protein exert hypocholesterolemic effects.


Ionizing radiation-induced cell death.
Selected aspects of radiation-induced cell death, connected with signal transduction pathways are reviewed. Cell death is defined as insufficiency of the cellular signal transducing system to maintain the cell's physiological functions. The insufficiency may be due to impaired signal reception and/or transduction, lack or erroneous transcription activation, and eventual cellular 'misexpression' of the signal. The molecular basis of this insufficiency would be damage to genomic (but also other cellular) structures and closing of specific signalling pathways or opening of others (like those leading to apoptosis). I describe experimental data that suggest an important role of RAS/NF1 and p53/p105 Rb proteins in cell cycle control-coupled responses to DNA damage.


General and specific consciousness: a first-order representationalist approach.
It is widely acknowledged that a complete theory of consciousness should explain general consciousness (what makes a state conscious at all) and specific consciousness (what gives a conscious state its particular phenomenal quality). We defend first-order representationalism, which argues that consciousness consists of sensory representations directly available to the subject for action selection, belief formation, planning, etc. We provide a neuroscientific framework for this primarily philosophical theory, according to which neural correlates of general consciousness include prefrontal cortex, posterior parietal cortex, and non-specific thalamic nuclei, while neural correlates of specific consciousness include sensory cortex and specific thalamic nuclei. We suggest that recent data support first-order representationalism over biological theory, higher-order representationalism, recurrent processing theory, information integration theory, and global workspace theory.


Actinomyces species, streptococci, and Enterococcus faecalis in primary root canal infections.
The purpose of this study was to evaluate the prevalence of Actinomyces species, streptococci, and Enterococcus faecalis in primary root canal infections by using a molecular genetic method. Samples were obtained from 53 infected teeth, of which 27 cases were diagnosed as acute periradicular abscesses. DNA was extracted to evaluate the occurrence of 13 bacterial species by using whole genomic DNA probes and checkerboard DNA-DNA hybridization. Polymerase chain reaction using an ubiquitous bacterial primer was undertaken to check the presence of bacterial DNA in clinical samples. All root canal samples contained bacteria as demonstrated by polymerase chain reaction. The checkerboard DNA-DNA hybridization assay allowed the detection of streptococci in 22.6% of the samples, Actinomyces species in 9.4%, and E. faecalis in 7.5%. The most prevalent species were members of the Streptococcus anginosus group. With regard to the asymptomatic lesions, the most prevalent species were S. intermedius (11.5% of the cases), E. faecalis (11.5%), and S. anginosus (7.7%). S. constellatus was the most prevalent species in pus samples (25.9% of the cases). The other most prevalent species in abscessed teeth were A. gerencseriae (14.8%), S. gordonii (11.1%), S. intermedius (11.1%), A. israelii (7.4%), S. anginosus (7.4%), and S. sanguis (7.4%). S. constellatus was the only species positively associated with acute periradicular abscess (p < 0.01).


Tyramine-induced contractions in the rabbit ear and basilar arteries.
This study examined in vitro tyramine (TY)-induced contractions of the isolated ring segments of the rabbit basilar and ear arteries in relation to their sympathetic innervations. The TY dose--response relationship in the basilar artery was not affected by cocaine, chronic sympathectomy, or reserpine pretreatment. However, these treatments shifted the TY dose--response relationship in the ear arteries significantly to the right. These results indicate that the TY-induced contraction in the basilar artery is due solely to its direct stimulation of the postsynaptic alpha-receptors, but in the ear artery it is due both to its indirect [release of norepinephrine (NE)] and direct actions. The failure of TY to induce contraction in the basilar artery by the indirect mechanism is probably in part due to a wide synaptic cleft distance and the reported insensitivity of alpha-receptors of this artery. These results suggest that the endogenous NE releasable from the sympathetic nerve in the basilar artery is insufficient to bring about vasoconstriction. This is turn favors our previous hypothesis that transmural-nerve-stimulation (TNS)-induced constriction of this artery is to a transmitter other than NE. It further suggests that the functional significance of the sympathetic innervations to different regions of the vessels is highly variable even when they are of the same ganglionic origin.


[Cardiac scintigraphy-Pharmacological stress and appropriate management of pediatric radiopharmaceutical administration in patients after Kawasaki disease].
Cardiac scintigraphy accounted for 2.5 % of all 3,884 patients based on a survey ques- tionnaire of pediatric nuclear medicine examinations performed at 14 Japanese institutes in 2011. Myocardial perfusion imaging, classified as cardiac scintigraphy, is essential to detect myocardial ischemia in patients after Kawasaki disease (KD), although its less frequent performance is reported. Adenosine is widely noticed as a medication for pharma- cological stress testing in coronary arterial lesions after KD. We describe characteristics of adenosine including newly-devised administration protocol and pathway making of intravenous injection for stress testing. We comment on optimal radiopharmaceutical administered doses proposed in Japanese consensus guidelines for pediatric nuclear medi- cine. Their proposal doses approximate that calculated by Pediatric Dosage Card of Euro- pean Association of Nuclear Medicine. We hope myocardial perfusion imaging is performed under appropriate management of pediatric radiopharmaceutical administration.


Incidence of and factors associated with SARS-CoV-2 infection among people living with HIV in Southern Spain after one year of pandemic.
Whether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of associated factors with and the clinical outcome of SARS-CoV-2 infection in PLWH in Southern Spain. This prospective cohort study included PLWH from a Tertiary University Hospital in Southern Spain. Patients were enrolled in the study if (1) they had attended as outpatients our Unit from 1 August 2019 to 8 February 2020 and (2) had two subsequent evaluations from 9 February 2020 to 4 March 2021. SARS-CoV-2 infections were diagnosed by PCR, antigen detection or serology. Seven hundred and nine PLWH were included in the study. Of them, 55 [7.8%, 95% confidence interval (95% CI) 5.9%-9.9%] patients developed SARS-CoV-2 infection. Between 18 May and 29 November 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%-9.0%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%-2.6%) for PLWH in this study (p = .001). After multivariable analysis, adjusted by age, sex, and risk factors for HIV infection, active tobacco use and CDC stage, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection [Incidence rate ratio: 0.29 (95% CI 0.16-0.55) p < .001]. In conclusion, the incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area.


Near- and Extended-Edge X-Ray-Absorption Fine-Structure Spectroscopy Using Ultrafast Coherent High-Order Harmonic Supercontinua.
Recent advances in high-order harmonic generation have made it possible to use a tabletop-scale setup to produce spatially and temporally coherent beams of light with bandwidth spanning 12 octaves, from the ultraviolet up to x-ray photon energies >1.6 keV. Here we demonstrate the use of this light for x-ray-absorption spectroscopy at the K- and L-absorption edges of solids at photon energies near 1 keV. We also report x-ray-absorption spectroscopy in the water window spectral region (284-543 eV) using a high flux high-order harmonic generation x-ray supercontinuum with 10^{9} photons/s in 1% bandwidth, 3 orders of magnitude larger than has previously been possible using tabletop sources. Since this x-ray radiation emerges as a single attosecond-to-femtosecond pulse with peak brightness exceeding 10^{26} photons/s/mrad^{2}/mm^{2}/1% bandwidth, these novel coherent x-ray sources are ideal for probing the fastest molecular and materials processes on femtosecond-to-attosecond time scales and picometer length scales.


TAR RNA recognition by a cyclic peptidomimetic of Tat protein.
The search for new antiviral drugs that repress HIV viral replication by blocking transactivation of viral RNA transcription has long been advocated as an approach to novel antiviral therapy. However, research in this area has so far failed to yield attractive lead compounds because of the insufficient development of RNA-based medicinal chemistry. One difficulty in efforts to inhibit protein-RNA interactions using small druglike molecules is the large surface areas typically found at these interfaces. To overcome this problem, we sought to identify constrained peptidomimetic inhibitors that would provide potential new drug leads. We previously reported the discovery of a cyclic peptide mimic of the RNA-binding domain of BIV Tat protein based on a designed beta-hairpin scaffold. We demonstrated that the cyclic peptide bound BIV TAR RNA with an affinity comparable to that of the RNA-binding domain of the Tat protein and inhibited protein binding to the RNA. In this study, we report the structure of the complex of the cyclic peptide bound to BIV TAR RNA determined using heteronuclear NMR methods. The structure reveals a beta-hairpin conformation in the bound peptide, which adopts an unexpected orientation in the major groove of the RNA opposite those observed for peptides derived from the Tat protein. This structure suggests many ways in which to optimize the compound and enhance its activity and pharmacological potential and represents a further step in the rational design of a new class of HIV-1 virus replication inhibitors based on peptidomimetic chemistry.


Review of the surgical management of recurrent hiatal hernia: 5-year follow-up.
Symptoms in patients with hiatal hernia often respond to treatment consisting of diet and medication. Operative procedures, designed to control gastroesophageal reflux and avoid surgically induced problems, are reserved for those with intractable symptoms. When these operative procedures fail, reoperation may be necessary. The reoperative procedure is often technically complex because of esophageal and gastric scar fixation. The authors reviewed the surgical management of recurrent hiatal hernia in 168 patients followed up to 5 years or more; 43 of them had undergone gastric surgery previously.Radiologically, 97% patients studied (142 of 146) had no evidence of anatomic recurrence or reflux post operatively. Manometric studies postoperatively in 114 patients showed that the mean tone of the high pressure zone was within the normal range and lower esophageal disordered motor activity was decreased by 34.5% from the preoperative level. Symptoms of recurrent hiatal hernia were abolished by operation in 88% of the patients; only 4.8% had serious or recurrent symptoms.


Correction: Dynamical self-assembly of dipolar active Brownian particles in two dimensions.
Correction for 'Dynamical self-assembly of dipolar active Brownian particles in two dimensions' by Guo-Jun Liao et al., Soft Matter, 2020, 16, 2208-2223, DOI: .


Ab initio anharmonic force field and rotational analyses of infrared bands of perchloryl fluoride.
Perchloryl fluoride, FClO(3), has been studied both experimentally and theoretically, using high-resolution Fourier transform spectroscopy and high-level ab initio methods. The geometry, dipole moment, and anharmonic force field of the molecule have been calculated ab initio, using the coupled-cluster with single, double, and perturbative triple excitations [CCSD(T)] level of theory. The infrared spectra of monoisotopic species have been recorded. The nu(1) + nu(2) bands of F(35)Cl(16)O(3), F(37)Cl(16)O(3), F(35)Cl(18)O(3), and F(37)Cl(18)O(3), the nu(2) + nu(3) and nu(2) + nu(3) - nu(3) bands of F(35)Cl(16)O(3) and F(37)Cl(16)O(3), and the 2nu(3) - nu(3) band of F(37)Cl(16)O(3) have been analyzed. The spectroscopic parameters obtained from these and from previous analyses have been compared with the theoretical results.


[Epidemiology of rheumatoid arthritis].
Although arthritis is a common disease in adults, only one in five new cases of arthritides is classifiable as rheumatoid arthritis (RA). The annual incidence of adult RA is about 0.05 per cent, and is ten times higher among women over fifty than among men under 50. The prevalence increases with age up to 70 years, after which it declines due to premature mortality. The high or low prevalences characteristic of certain populations may be explained by ethnic differences in genetic susceptibility.


Perfluoro-15-crown-5-ether labelled macrophages in adoptive transfer experimental allergic encephalomyelitis.
In this serial in vivo study, macrophages labelled with perfluoro-15-crown-5-ether (15C5) were monitored in rats after inducing adoptive transfer experimental allergic encephalomyelitis (AT-EAE). AT-EAE is an animal model of multiple sclerosis and is characterized by inflammatory infiltrates in the central nervous system (CNS) and breakdown of the blood-brain-barrier. A particular feature of AT-EAE are macrophage infiltrates. Purpose of this study was to monitor the invasive and evasive phase of the macrophages in AT-EAE by using 3-dimensional 19F magnetic resonance imaging (3D 19F-MRI). In the early stage of the disease, a much stronger 19F-signal intensity was observed in AT-EAE-rats than in healthy control rats in the tissue adjacent to CNS regions severely affected by inflammatory infiltrates, and thereafter the 19F-signal intensity was decreasing over the time. However, no 19F-signal could be observed in the CNS itself neither in AT-EAE-rats nor in control rats. According to these findings it is assumed that we monitored the evasion of the macrophages from the region of inflammation.


[2 cases of post-measles myelitis].
Two cases of a very rare complication of rubella i.e. a strictly spinal cord lesion developing during the course of the viral infection, are reported. In the first case, there was a flaccid paraplegia which incompletely regressed after two months. In the second case there were only sensory disorders and sphincter disturbances and recovery was complete after one month. The post-eruption encephalomyelitis lesions are of uncertain paphogenesis but the most common hypothesis suggested is that of a delayed hypersensitivity mechanism involving a cell-mediated immunologic reaction. The prognosis of these post-injection neurologic manifestations is difficult to assess, but spinal cord lesions could have a good prognosis.


Dengue fever and dengue haemorrhagic fever in adolescents and adults.
Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a paediatric disease, the age distribution of dengue has been rising and more cases have been observed in adolescents and adults. Furthermore, the development of tourism in the tropics has led to an increase in the number of tourists who become infected, most of whom are adults. Symptoms and risk factors for dengue haemorrhagic fever (DHF) and severe dengue differ between children and adults, with co-morbidities and incidence in more elderly patients associated with greater risk of mortality. Treatment options for DF and DHF in adults, as for children, centre round fluid replacement (either orally or intravenously, depending on severity) and antipyretics. Further data are needed on the optimal treatment of adult patients.


Regional pharmacokinetics of 5-fluorouracil in dogs: role of the liver, gastrointestinal tract, and lungs.
The purpose of this study was to determine the presence and extent of pulmonary elimination for 5-fluorouracil (FUra). A secondary aim was to characterize the relative importance of the liver, gastrointestinal tract, splanchnic region, and lungs toward the overall elimination of FUra. A total of 10 mixed-breed male and female dogs were used in these acute studies in which FUra was administered through a cephalic vein. Six dogs were studied at sequentially escalated dose rates of 0.125, 0.250, 0.500, 0.750, and 1.00 micromol/min/kg (8-fold range); four dogs were studied at sequentially escalated dose rates of 0.0625, 0.250, 0.750, 1.50, and 2.00 micromol/min/kg (32-fold range). Each infusion lasted 2 h, at which time steady-state plasma concentrations were obtained (i.e., portal vein, carotid artery, hepatic vein, and pulmonary artery), perfusion rates were measured (hepatic artery, portal vein, and cardiac output), and pharmacokinetic parameters were directly assessed. Pulmonary elimination of FUra was conclusively demonstrated. Although only 17% of the drug was extracted by the lungs at the lowest dose rate, pulmonary clearance (16.0 ml/min/kg) was on the order of splanchnic clearance (13.5 ml/min/kg), or larger. As the dose rate increased, pulmonary clearance was more easily saturated than splanchnic clearance. Thus, it appears that at increasing dose rates, the splanchnic region becomes a more significant pathway, whereas the lungs have a reduced role in the overall elimination of FUra.


rs187960998 polymorphism in miR-211 prevents development of human colon cancer by deregulation of 3'UTR in CHD5.
Previous research indicated that overexpression of miRNA-211 could promote colorectal cancer cell growth by targeting tumor suppressive gene Chromodomain-helicase-DNA-binding protein 5 (CHD5) in human colon cancer (CC). Moreover, the function of the single-nucleotide polymorphism (SNP) located in the mature region of miR-211 has not been investigated. In this study, we found that SNP of rs187960998 in miR-211 was involved in the occurrence of CC by acting as a tumor suppressor by mal-regulation of its target gene CHD5. The genotype of total 685 CC patients was detected by real-time PCR, the proliferation of CC cell lines with different genotypes of miR-211 was determined by Cell Counting Kit-8, cell invasion evaluated by transwell and the activity of the CHD5 promoter in CC cell lines transfected with different miR-211 was determined by luciferase assay. The expression of CHD5 in CC patients was determined by the immunohistochemistry, and the relapse-free survival rate was analyzed by Kaplan-Meier analysis. C/T SNP of miR-211 could inhibit CC cell proliferation and invasion by upregulation of CHD5. And SNP in rs187960998 of miR-211 was associated with tumor size, metastasis and tumor differentiation in CC patients. Patients with CC genotype have significantly low CHD5 expression than the T-carrier, while no significant expression difference in miR-211 expression among different genotype subsets. Patients with CC genotype have significantly shorter postsurgery survival rate compared to the T-carrier. rs187960998 in miR-211 was highly associated with a decreased risk of CC in the Chinese population by deregulating a tumor suppressive gene CHD5.


Zeroth order regular approximation approach to electric dipole moment interactions of the electron.
A quasi-relativistic two-component approach for an efficient calculation of P,T-odd interactions caused by a permanent electric dipole moment of the electron (eEDM) is presented. The approach uses a (two-component) complex generalized Hartree-Fock and a complex generalized Kohn-Sham scheme within the zeroth order regular approximation. In applications to select heavy-elemental polar diatomic molecular radicals, which are promising candidates for an eEDM experiment, the method is compared to relativistic four-component electron-correlation calculations and confirms values for the effective electric field acting on the unpaired electron for RaF, BaF, YbF, and HgF. The calculations show that purely relativistic effects, involving only the lower component of the Dirac bi-spinor, are well described by treating only the upper component explicitly.


[A resected case of metastatic pancreatic cancer from cecal carcinoma].
A 64-year-old woman underwent an ileocecectomy in July 2002 for ruptured cecal carcinoma, which was a well-differentiated adenocarcinoma, stage II, ss, ly0, v0, n (-). In August 2005, abdominal CT revealed a tumor 20mm in diameter in the pancreatic tail, therefore, a distal pancreatectomy and splenectomy were performed. The pancreatic tumor resembled the moderately differentiated cecal adenocarcinoma, both having p53 and k-ras point mutations in common, and it was diagnosed as a metastasis of the cecal carcinoma.


Intracavitary brachytherapy for carcinoma of the esophagus.
Local control of unresectable esophageal carcinomas remains a significant problem in spite of aggressive treatments. External beam radiation therapy, chemotherapy, and combined modality treatment have all been employed with limited success. Here we review the existing literature and our own experience with external beam radiation followed by low-dose-rate or high-dose-rate intracavitary radiation for carcinoma of esophagus. The addition of intracavitary brachytherapy to external beam irradiation is well tolerated, causes no significant toxicity, and improves local control. Low-dose-rate intracavitary boost compared to high-dose-rate intracavitary boost has the advantage of a greater margin of safety, requires a single application, does not require highly sophisticated computerized technology, and is accompanied with fewer high-grade toxicities. Combined modality therapy consisting of concomitant infusional chemotherapy, external beam irradiation, and low-dose-rate intracavitary boost needs to be investigated.


A novel method for enhancement of T independent responses.
Bacterial capsular polysaccharides are the major targets for vaccination against encapsulated bacteria but present problems when used for immunisation as they are T cell independent antigens (TI-II). TI-II antigens do not induce a memory response, but induce an antibody response which is of low magnitude and is predominantly IgM, with little or no isotype switching to IgG isotypes. This is because TI-II antigens do not induce T cell help. Such T cell help to B cells is mediated through up regulation of the CD40 ligand (CD154) on the activated T cell, which binds to CD40 inducing B cell activation, proliferation and isotype switching in conjunction with cytokines produced by the T cell. We have successfully mimicked this T cell help and induced very strong, isotype switched antibody responses to TI-II antigens by the simple addition of agonistic anti-CD40 antibodies to pneumococcal polysaccharides before immunisation.


Purification and molecular properties of mouse alcohol dehydrogenase isozymes.
Alcohol dehydrogenase isozymes from mouse liver (A2 and B2) and stomach (C2) tissues have been purified to homogeneity using triazine-dye affinity chromatography. The enzymes are dimers with similar but distinct subunit sizes, as determined by SDS/polyacrylamide gel electrophoresis: A, 43000; B, 39000, and C, 47000. Zinc analyses and 1,10-phenanthroline inhibition studies indicated that the A and C subunits each contained two atoms of zinc, with at least one being involved catalytically, whereas the B subunit probably contained a single non-catalytic zinc atom. The isozymes exhibited widely divergent kinetic characteristics. A2 exhibited a Km value for ethanol of 0.15 mM and a broad substrate specificity, with Km values decreasing dramatically with an increase in chain length; C2 also exhibited this broad specificity for alcohols but showed a Km value of 232 mM for ethanol. These isozymes also showed broad substrate specificities as aldehyde reductases. In contrast, B2 showed no detectable activity as an aldehyde reductase for the aldehydes examined, and used ethanol as substrate only at very high concentrations (greater than 0.5 M). The isozyme exhibited low Km and high Vmax values, however, with medium-chain alcohols. Immunological studies showed that A2 was immunologically distinct from the B2 and C2 isozymes. In vitro molecular hybridization studies gave no evidence for association between the alcohol dehydrogenase subunits. The results confirm genetic analyses [Holmes, Albanese, Whitehead and Duley (1981) J. Exp. Zool. 215, 151-157] which are consistent with at least three structural genes encoding alcohol dehydrogenase in the mouse and confirm the role of the major liver isozyme (A2) in ethanol metabolism.


Nutritionally-induced elevation of serum proteinase inhibitors and reduced 3-methylhistidine excretion in the rat.
One group of growing rats was fed ad libitum a low protein and energy diet (PER). A second group was fed a low protein diet (PR). Both these groups showed a gain in weight below that of the control group. A third group was fed a very low protein and energy diet (VPER). A weight gain could also be observed in this group but this gain was lower than those observed in the first two groups. A fourth group that was on a very low protein diet (VPR) gained almost no weight. After 6 weeks a significant reduction in 3-methylhistidine excretion in urine was observed in all the experimental animals with lowest values found in the VPER and VPR groups. Total serum protein levels declined to a certain extent because of the protein and energy restrictions but albumin and transferrin remained largely unaffected. Significantly lower serum concentrations were found only in the VPR group. The rat serum proteinase inhibitors alpha 1-macroglobulin and alpha 1-inhibitor3 decreased when protein and energy were restricted and alpha 1-proteinase inhibitor decreased only in the VPER and VPR groups. alpha 2-macroglobulin and alpha 1-cysteine proteinase inhibitor concentrations increased considerably in the serum of the experimental groups. The results are discussed in relation to the probable role of the latter two inhibitors in the adaptation process when protein and energy were restricted and compared to similar observations recorded in man.


Anatomical study of the maxillary artery at the pterygomaxillary fissure in a Thai population: its relationship to maxillary osteotomy.
The maxillary artery (MA) and its terminal branches are commonly damaged in the maxillary osteotomy, especially during separation of the pterygomaxillary junction (PMJ). To evaluate the positional relationship between the MA at the pterygomaxillary fissure (PMF) and the PMJ in Thais, as well as to measure the diameter of the MA as it enters the pterygopalatine fossa (PPF) and the heights of PMJ, maxillary tuberosity and posterior maxilla. Both sides of 100 Thai adult cadavers (50 males and 50 females) were examined The mean age of the subjects was 64.5 +/- 12.8 years. With the lateral infratemporal approach, the branches from the third part of the MA, PMJ and posterolateral maxilla were dissected. Measurements taken included the following: First, the distance from the most inferior point of the PMJ to the most inferior position of the MA as it entered the PPF; second, the external diameter of the MA as it entered the PPF; third, vertical heights of the PMJ, maxillary tuberosity and posterior maxilla. Means, standard deviations and ranges were determined and statistical differences were calculated between sides and genders at p < 0. 05. The MA entered the PPF at a mean distance of 23.5 +/- 2.5 mm above the most inferior point of the PMJ. The mean external diameter of the MA as it entered the PPF was 2.8 +/- 0.6 mm. The mean heights of the PMJ, maxillary tuberosity and posterior maxilla were 19.5 +/- 2.3 mm, 6.1 +/- 2.7 mm, and 25.6 +/- 3.3 mm, respectively. There were no differences with respect to side and gender, except that the distance from the most inferior point of the PMJ to the most inferior position of the MA as it entered the PPF was longer in males than in females (p < 0.05). The mean location of the MA was 23.5 mm apart from the most inferior point of the PMJ, therefore, dysjunction of the PMJ using an osteotome with a 15-mm cutting edge may be conducted without damaging to the MA. When properly placed, the margin of safety from the superior cutting edge of the osteotome to the MA is approximately 8 mm in adults.


Progression of pre-eclampsia to eclampsia under spinal anaesthesia.
Eclampsia remains a problem in the developing countries despite improvements in antenatal care and emergency obstetric facilities. It is an important cause of maternal morbidity and mortality in Nigeria. A 26-year-old primipara, residing in an urban city in Nigeria with antenatal care facilities, booked for antenatal care at 36 weeks of gestation and was then diagnosed with severe pre-eclampsia. She initially refused therapy and was later booked for an emergency cesarean section. She had eclamptic fits during cesarean section under spinal anesthesia, and the seizure was aborted with intravenous diazepam. The postoperative period was uneventful. Progression of pre-eclampsia to eclampsia during cesarean section under spinal anesthesia is rare, but it can occur. Early booking for antenatal care to enable an early diagnosis and treatment are necessary to prevent the progression of pre-eclampsia to eclampsia. There is need to educate the populace on the importance of ante natal care so as to improve its utilization.


Case report on the use of canakinumab for treatment of recurrent fevers and proteinuria in refractory systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic multiorgan autoimmune disease with a wide range of clinical manifestations and a characteristic renal involvement leading to proteinuria. There remains an unmet need in SLE disease management as standard treatments including anti-inflammatory drugs, corticosteroids, antimalarial agents, and immunosuppressant therapies are not always effective in moderating disease activity. We report a 41-year-old Caucasian female patient with a 12-year history of SLE complicated by debilitating nocturnal fevers and WHO Class IV lupus nephritis who for years was refractory to standard therapies but improved dramatically with canakinumab, an interleukin-1β (IL-1β)antagonist. This is the first case of the use of canakinumab in SLE. The standard interventions demonstrated no significant impact on her proteinuria (>3 g/24 h), joint complaints, and nocturnal fevers. Additionally, her anti-dsDNA levels remained elevated, and her kidney function did not improve significantly. In contrast, the introduction of canakinumab provided a rapid reduction in nocturnal fevers within 6 weeks (i.e. decreased in frequency by 90%). Her proteinuria has also dropped from 3.5 g/24 h to 0.274 g/24 h, and her prednisone has been tapered and discontinued. In addition, her renal function has improved with an average glomerular filtration rate (GFR) level of 84.14 ± 7.56. There has also been a significant decrease in both erythrocyte sedimentation rate (ESR) and anti-dsDNA levels compared with the previous treatments. We report that canakinumab could potentially represent the next step in SLE patients' treatment who have failed conventional therapies or who are intolerant to them. In this case, the addition of canakinumab facilitated the tapering and ultimately discontinuing of corticosteroids. This case represents the first successful use of canakinumab in the treatment of refractory fevers and diffuse proliferative glomerulonephritis in SLE.


Psychological problem areas of pregnant women diagnosed with abortus imminens as a result of assisted reproductive techniques: A comparative study.
The study was to evaluate the anxiety, depressive symptoms, hopelessness, and perceived social support of women who became pregnant using assisted reproductive techniques and who were both diagnosed or not diagnosed with threatened miscarriage (TM). This comparative and descriptive study was carried out with 194 pregnant women with-TM (96) and non-TM (98). The study data were collected using the Pregnant-Women-Information-Form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Beck Hopelessness Scale (BHS) and Multidimensional Scale of Perceived Social Support (MSPSS). Women in the TM group were found to have higher mean scores from the BDI, BAI, and BHS, and a lower mean score from the MSPSS compared to the non-TM group (The group with TM had higher levels of anxiety, depression, and hopelessness than the group without TM, and the level of perceived social support by this group was lower). It was found that there was a strongly significant positive correlation in both groups between the BDI and BAI, and between the BDI and BHS. A strongly significant negative correlation was found between the BDI, BAI, BHS, and MSPSS in the TM group, whereas there was a moderately significant negative correlation in the non-TM group. It was found that there was a statistically significant difference between the mean BDI, BAI, BHS, and MSPSS scores according to age group, educational status, number of interventional in vitro fertilization attempts, and history of depression. In addition, there was a statistically significant difference between the mean BDI, BAI, and BHS scores according to previous abortion and family history of depression in the TM group. Monitoring symptoms of depression, anxiety, and hopelessness in women diagnosed with TM who have become pregnant after infertility treatment, intervening due to the risk factors involved, may prevent possible mental problems and have a positive impact on the healthy continuation of the pregnancy.


Facial aesthetics: achieving the natural, relaxed look.
When patients undergoing nonsurgical facial rejuvenation procedures are asked to state their expectations in terms of outcomes, the achievement of a "natural, relaxed look" usually emerges as the paramount goal. The importance to clinicians of delivering on this patient desire is becoming increasingly clear. After all, patient satisfaction is the ultimate treatment goal. This article explores aspects of what defines the natural, relaxed look and what patients are seeking when they undergo nonsurgical facial rejuvenation procedures and is based on the clinical experience of the authors. The article also offers suggestions intended to help clinicians provide each patient with appropriate outcomes and satisfaction.


Genetic-Algorithm-Based Inverse Optimization Identification Method for Hot-Temperature Constitutive Model Parameters of Ti6Al4V Alloy.
A precise constitutive model is the foundation and key to finite element simulation in material volume forming and the optimization of the hot working process. Hence, to build a precise constitutive model, a method based on a genetic algorithm (GA) for the inverse optimization identification of parameters is presented in this paper. The idea of this method is to continuously adjust the model parameters through GA until the objective function reaches the minimum value. In this study, hot compression experiments were performed on the Gleeble-1500D thermal simulator at temperatures ranging from 800 °C to 1000 °C and strain rates of 0.01 s-1 to 1 s-1. The Arrhenius-type (A-T) model considering strain compensation and the Johnson-Cook (JC) model considering the coupling effects of strain, temperature and strain rate were constructed, respectively, by using the regression method and the parameter inverse optimization identification method. For the purposes of comparing and verifying the reliability of the predictions of the two established constitutive models, the correlation coefficient (R), average absolute relative error (AARE), and relative error (RE) were adopted. The results show that both the optimized A-T model and the optimized JC model have high prediction accuracy. Compared to the optimized JC model, the optimized A-T model demonstrated a higher correlation coefficient, by 0.003, and a lower average absolute relative error, by 1.43%. Furthermore, the relative error distribution of the optimized A-T model was found to be more concentrated than that of the optimized JC model. These results suggest that the A-T model is more appropriate than the JC model for characterizing the high-temperature deformation behavior of Ti6Al4V alloy.


Probing Transient Valence Orbital Changes with Picosecond Valence-to-Core X-ray Emission Spectroscopy.
We probe the dynamics of valence electrons in photoexcited [Fe(terpy)2]2+ in solution to gain deeper insight into the Fe-ligand bond changes. We use hard X-ray emission spectroscopy (XES), which combines element specificity and high penetration with sensitivity to orbital structure, making it a powerful technique for molecular studies in a wide variety of environments. A picosecond-time-resolved measurement of the complete 1s X-ray emission spectrum captures the transient photoinduced changes and includes the weak valence-to-core (vtc) emission lines that correspond to transitions from occupied valence orbitals to the nascent core-hole. Vtc-XES offers particular insight into the molecular orbitals directly involved in the light-driven dynamics; a change in the metal-ligand orbital overlap results in an intensity reduction and a blue energy shift in agreement with our theoretical calculations and more subtle features at the highest energies reflect changes in the frontier orbital populations.


Comparative effectiveness of oral antidiabetic drugs in preventing cardiovascular mortality and morbidity: A network meta-analysis.
In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. We assessed the differences in the risks of all-cause mortality, cardiovascular-related mortality, acute coronary syndrome (ACS), and myocardial infarction (MI) among antidiabetic drugs with fixed effect models for direct pairwise comparisons and Bayesian network meta-analyses to integrate direct and indirect comparisons. Of the 101,183 patients in 73 randomized controlled trials, 3,434 (3.4%) died. The relative risks of all-cause mortality with SGLT2 inhibitor use were 0.68 (95% credible interval: 0.57-0.80), 0.74 (0.49-1.10), 0.63 (0.46-0.87), 0.71 (0.55-0.90), and 0.65 (0.54-0.78), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of cardiovascular-related mortality with SGLT2 inhibitor use were 0.61 (0.50-0.76), 0.81(0.36-1.90), 0.52(0.31-0.88), 0.66(0.49-0.91), and 0.61(0.48-0.77), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of ACS with SGLT2 inhibitor use was consistent with that of all-cause mortality. SGLT2 inhibitor use was associated with a lower risk of ACS than the other OADs and placebo. The relative risks of MI with SGLT2 inhibitor use were 0.77 (0.63-0.93) and 0.75 (0.60-0.94), compared with placebo and DPP4 inhibitor, respectively. The currently available data provide the evidence of cardiovascular benefit from use of SGLT2 inhibitors to patients with type 2 diabetes, although additional results from ongoing studies will be pivotal.


[Effects of adenovirus-delivered angiopoietin-1 siRNA on expression of matrix metalloproteinases in rats with acute lung injury induced by phosgene].
To investigate the effects of adenovirus-delivered angiopoietin-1 siRNA (Ad. Ang-1siRNA) on the expression of matrix metalloproteinase-2, 9 (MMP-2, 9) and tissue inhibitor of metallopro-teinase-1 (TIMP-1) in rats with acute lung injury (ALI) induced by phosgene (Psg). We first established a rat model of Psg-induced acute lung injury (ALI). The rats were randomly divided into 6 groups: air control group with exposure to air, air+adenovirus (air+Ad) group with caudal vein injection of 1×10(8) pfu/ml adenovirus 1 h after air exposure, air+Ad/Ang1 group with caudal vein injection of 1×10(8) pfu/ml Ad.Ang-1siRNA 1 h after air exposure, Psg group with exposure to 8.33 mg/L Psg (purity 100%, of the same volume as the inhaled air in the air control group) for 5 min, Psg+Ad group with caudal vein injection of 1×10(8) pfu/ml adenovirus 1 h after exposure to the same dose of Psg, and Psg+Ad/Ang1 group with caudal vein injection of 1×10(8) pfu/ml Ad.Ang-1siRNA 1 h after exposure to the same dose of Psg. Serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected 36 h after exposure. The protein expression of Ang-1, MMP-2, 9, and TIMP-1 in serum and BALF was determined by double-antibody sandwich ELISA. RT-PCR was used to determine the mRNA levels of Ang-1, MMP-2, 9, and TIMP-1 in lung tissue. The protein expression of MMP-2, 9 and TIMP-1 in lung tissue was determined by Western blot. A rat model of Psg-induced ALI was successfully established. The levels of MMP-2, 9 in serum, BALF, and lung tissue were significantly increased in the Psg group and Psg+Ad/Ang1 group as compared with the control group (P<0.01); no significant change was observed in serum TIMP-1 protein expression (P>0.05); interestingly, TIMP-1 protein expression in BALF and lung tissue was significantly increased (P<0.01). Compared with the Psg group, the Psg+Ad/Ang1 group showed a significant decrease in MMP-2, 9 expression in BALF, serum, and lung tissue (P<0.05), but no significant change in protein expression of TIMP-1 was discovered (P>0.05). Ad.Ang-1siRNA has a potential beneficial effect in rats with Psg-induced ALI through inhibition of MMP-2, 9 expression, but has no significant effect on the expression of TIMP-1.


Replication fork bypass of a pyrimidine dimer blocking leading strand DNA synthesis.
We constructed a double-stranded plasmid containing a single cis, syn-cyclobutane thymine dimer (T[c,s]T) 385 base pairs from the center of the SV40 origin of replication. This circular DNA was replicated in vitro by extracts from several types of human cells. The dimer was placed on the leading strand template of the first replication fork to encounter the lesion. Two-dimensional gel electrophoresis of replication intermediates documented the transient arrest of the replication fork by the dimer. Movement of the replication fork beyond the dimer was recognized by the appearance of a single fork arc in DNA sequences located between the T[c,s]T and the half-way point around the circular template (180 degrees from the origin). Upon completion of plasmid replication, the T[c,s]T was detected by T4 endonuclease V in about one-half (46 +/- 9%) of the closed circular daughter molecules. Our results demonstrate that extracts prepared from HeLa cells and SV40-transformed human fibroblasts (SV80, IDH4), including a cell line defective in nucleotide-excision repair (XPA), were competent for leading strand DNA synthesis opposite the pyrimidine dimer and replication fork bypass. In contrast, dimer bypass was severely impaired in otherwise replication-competent extracts from two different xeroderma pigmentosum variant cell lines.


Public awareness and use of direct-to-consumer personal genomic tests from four state population-based surveys, and implications for clinical and public health practice.
Direct-to-consumer personal genomic tests are widely available, but population-based data are limited on awareness and use of these tests among the general public in the United States. We assessed awareness and use of direct-to-consumer personal genomic tests in Connecticut, Michigan, Oregon, and Utah using the 2009 Behavioral Risk Factor Surveillance System and compared the state results to the 2008 national HealthStyles survey results. Awareness was the highest in Oregon (29.1%) and the lowest in Michigan (15.8%). Factors associated with awareness across all states and nationally were higher education, higher income, and increasing age, except among those 75 years or older. Less than 1% of respondents had used the tests, with about one-half to three-quarters of those sharing the results with a health-care provider. Awareness of direct-to-consumer genetic tests is greater in this study as compared with a related study conducted in 2006, whereas use is similarly low in both studies. The few respondents who reported using the tests often reported sharing their results with their health-care provider, indicating an important opportunity for health-care providers to offer patient education regarding these tests. Public health agencies have important roles in surveillance, education, and policy development on direct-to-consumer genomic tests.


Traditional Arabic & Islamic medicine: validation and empirical assessment of a conceptual model in Qatar.
Evidence indicates traditional medicine is no longer only used for the healthcare of the poor, its prevalence is also increasing in countries where allopathic medicine is predominant in the healthcare system. While these healing practices have been utilized for thousands of years in the Arabian Gulf, only recently has a theoretical model been developed illustrating the linkages and components of such practices articulated as Traditional Arabic & Islamic Medicine (TAIM). Despite previous theoretical work presenting development of the TAIM model, empirical support has been lacking. The objective of this research is to provide empirical support for the TAIM model and illustrate real world applicability. Using an ethnographic approach, we recruited 84 individuals (43 women and 41 men) who were speakers of one of four common languages in Qatar; Arabic, English, Hindi, and Urdu, Through in-depth interviews, we sought confirming and disconfirming evidence of the model components, namely, health practices, beliefs and philosophy to treat, diagnose, and prevent illnesses and/or maintain well-being, as well as patterns of communication about their TAIM practices with their allopathic providers. Based on our analysis, we find empirical support for all elements of the TAIM model. Participants in this research, visitors to major healthcare centers, mentioned using all elements of the TAIM model: herbal medicines, spiritual therapies, dietary practices, mind-body methods, and manual techniques, applied singularly or in combination. Participants had varying levels of comfort sharing information about TAIM practices with allopathic practitioners. These findings confirm an empirical basis for the elements of the TAIM model. Three elements, namely, spiritual healing, herbal medicine, and dietary practices, were most commonly found. Future research should examine the prevalence of TAIM element use, how it differs among various populations, and its impact on health.


Whole-gut irrigation as antiendotoxinaemic therapy in inflammatory bowel disease.
Marked endotoxaemia was found in 12 patients suffering from severe relapse of chronic inflammatory bowel disease. These patients did not respond satisfactorily to conservative treatment. Whole gut irrigation was employed to reduce drastically the absorbable endotoxin pool in the gut. Following the lavage the condition of all the patients thus treated improved. Plasma endotoxins dropped rapidly, serum iron increased, and in 7 febrile patients body temperature normalized. The results obtained suggest a beneficial use of whole gut irrigation as a therapeutic means in endotoxaemia associated with inflammatory bowel disease.


Risk factors for pancreatitis in patients with anomalous union of pancreatobiliary duct.
The clinical features of pancreatitis in patients with an anomalous union of the pancreatobiliary duct (AUPBD) are unclear. This study analyzed the clinical features, pathogenic mechanisms, risk factors, and clinical courses after treatment in AUPBD patients. The medical records and cholangiopancreatograms of 58 patients with AUPBD and a choledochal cyst diagnosed between 1982 and 2001 were retrospectively reviewed. Sixteen (27.6%) out of the 58 AUPBD patients experienced pancreatitis. The incidence of pancreatitis was significantly higher in those patients with a long (>21mm) and wide (>5mm) common channel, a wide diameter of the proximal pancreatic duct (>2.5mm), the presence of a filling defect in the common channel, and the presence of a pancreatic duct anomaly (p<0.05). A bile duct diversion from the pancreatic duct by a choledochal cyst excision prevented the recurrence of pancreatitis in most cases. A duodenopancreatectomy was required in some cases. The morphological characteristics of the common channel and pancreatic duct contribute to the development pancreatitis in AUPBD patients and bile reflux into the pancreatic duct might be the main mechanism of pancreatitis in these patients.


Survival Rates of Concurrent Chemo-Radiation versus Radiation Alone in Locally Advanced, Unresectable Head and Neck Cancers: A Retrospective Cohort Study.
To compare survival rates of concurrent chemo-radiation (CRT) and radiation (RT) alone in locally, advanced unresectable head and neck cancers and to assess factors associated with survival. A retrospective cohort study was conducted of 165 patients treated for locally advanced unresectable head and neck cancers (Stage III, IV) at the Department of Radiation Oncology, Rajavithi Hospital, from 1 January 2011 to 31 December 2013. Patients were divided into two groups: in the first group, 68 patients received CRT and in the second, 97 patients received RT alone. The Cox proportional hazards model was used to assess the factors which had an impact on survival while controlling for known prognostic factors. The ethics committee of Rajavithi Hospital reviewed and approved this study. There was an overall survival (OS) rate of 1 year (1 year OS) in 27% of cases, and 2 years (2 years OS) in 15.4% of cases with a median overall survival rate of 7.63 months (7.63 OS) (95% CI 6.99-8.2 7). The mean follow-up time was 7.34 months with maximal follow-up time of 41.77 months and minimal follow-up time of 0.2 months (6 days). Patients who received chemotherapy had better overall survival rates than those who had no chemotherapy with 1 year OS of 52% vs. 9.5%, 2 years OS of 36.7% vs. 1.5%, and median OS of 13.17 vs. 5.4 months, p < 0.001. However, no significant difference for median survival was observed among three different chemotherapy regimens with median OS of 11-13 months but chemotherapy group had significant difference from no chemotherapy group with median OS of 5.40 months (4.59-6.21). Concurrent chemo-radiation (CRT) should be used as the standard treatment in patients who are medically fit. A Cisplatin or Carboplatin weekly regimen can be used as an alternative to a Cisplatin three-weekly regimen. Site of primary tumor N-stage, recurrent tumor, low RT dose (below 70 Gy), and co-morbidity (with impaired renal or liver function) are significant predictors of overall survival.


Motion generated in the unstable cervical spine during the application and removal of cervical immobilization collars.
Many studies have compared the restriction of motion that immobilization collars provide to the injured victim. No previous investigation has assessed the amount of motion that is generated during the fitting and removal process. The purpose of this study was to compare the three-dimensional motion generated when one-piece and two-piece cervical collars are applied and removed from cadavers intact and with unstable cervical spine injuries. Five fresh, lightly embalmed cadavers were tested three times each with either a one-piece or two-piece cervical collar in the supine position. Testing was performed in the intact state, following creation of a global ligamentous instability at C5-C6. The amount of angular motion resulting from the collar application and removal was measured using a Fastrak, three-dimensional, electromagnetic motion analysis device (Polhemus Inc., Colchester, VT). The measurements recorded in this investigation included maximum values for flexion/extension, axial rotation, medial/lateral flexion, anterior/posterior displacement, axial distraction, and medial/lateral displacement at the level of instability. There was statistically more motion observed with application or removal of either collar following the creation of a global instability. During application, there was a statistically significant difference in flexion/extension between the one-piece (1.8 degrees) and two-piece (2.6 degrees) collars, p = 0.009. There was also a statistically significant difference in anterior/posterior translation between the one-piece (3.6 mm) and two-piece (3.4 mm) collars, p = 0.015. The maximum angulation and displacement during the application of either collar was 3.4 degrees and 4.4 mm. Statistical analysis revealed no significant differences between the one-piece and two-piece collars during the removal process. The maximum angulation and displacement during removal of either collar type was 1.6 degrees and 2.9 mm. There were statistically significant differences in motion between the one-piece and two-piece collars during the application process, but it was only 1.2 degrees in flexion/extension and 0.2 mm in anterior/posterior translation. Overall, the greatest amount of angulation and displacement observed during collar application was 3.4 degrees and 4.4 mm. Although the exact amount of motion that could be deleterious to a cervical spine-injured patient is unknown, collars can be placed and removed with manual in-line stabilization without large displacements. Only trained practitioners should do so and with great care given that some motion in all planes does occur during the process.


Analysis of historical data suggests long-lasting protective effects of smallpox vaccination.
More than half of the US population has received the smallpox vaccine, but it is unknown what fraction is still protected against infection and disease. Residual protection and age-dependent case-fatality ratios have therefore been widely neglected in the current bioterrorism debate. The author analyzed 1902-1903 data from Liverpool, United Kingdom, and from reintroductions of the disease to Europe in 1950-1971 to estimate to what degree vaccinated cases were protected against developing severe or fatal disease and how quickly this protection waned over time. Protection against severe and fatal disease was lost at the rate of 1.41% per year, corresponding to a half-life of 49.2 years (95% confidence interval: 42.0, 57.3), and protection against fatal disease alone declined 0.363% per year. Thus, even 70 years after primary vaccination, 77.6% of cases were still protected (95% confidence interval: 66.6, 85.4). Protection against severe disease should therefore extend for many decades after a single vaccination, and protection against death from smallpox may even be lifelong for the majority of vaccinees. This protection should greatly reduce the number of severe and fatal cases of disease expected in a bioterrorist attack, but residual protection may also increase the risk that some previously vaccinated cases who develop mild disease may remain unrecognized longer, while moving around freely and disseminating the infection.


Accumulative effects of 2 weeks' exposure to a 2-G hypergravity state and estrogen treatment upon intact and fractured radii of young female birds.
Female birds were subjected to closed fractured of the right radius at 2 weeks post-hatching and allowed to heal for 14 d. The animals were maintained at either earth gravity or a 2-G hypergravity state with control and 2000 and 4000 IU Estrone-(estrogen) injected groups. Intact and fractured radii were measured for length, weight, average epiphysial-diaphysial diameters, and length, width and weight of fracture callus. Animals receiving 2000 IU estrogen treatment showed decreased intact and fractured bone weight, as well as smaller diaphysial diameters. Fractured, but not intact, bone length was decreased by the two estrogen levels without affecting the callus parameters. Bone weight and average epiphysial diameters of both intact and fractured radii were decreased by the hypergravity state. Intact bone diaphysis and fractured bone length were similarly affected. Large, 4000 IU, estrogen levels potentiated the hypergravity state and reduced distal epiphysial diameter of intact radii.


Anaerobic comma-shaped bacteria recovered from the human genital tract. A review.
The present survey reviews the current knowledge on comma-shaped anaerobic rods that can be isolated from the human genital tract. It summarizes bacterial characteristics such as morphology, biochemical activities, gas chromatographic patterns and differential diagnostic tests. In particular the existence of two variants of such rods is stressed. These variants differ in length, number of flagella, certain biochemical activities and susceptibility to nitroimidazoles. The occurrence of comma-shaped rods in relation to clinical findings is also discussed.


Nievergelt-Pearlman syndrome with impairment of hearing. Report of three cases in a family.
Three cases of the Nievergelt-Pearlman syndrome occurring in a family are presented. In addition to the major features of the syndrome (symphalangism, carpal fusion, atypical club foot with massive tarsal fusion, and congenital dislocation of the head of the radius), all three patients exhibited conductive deafness, which had not been recorded in previous reports. The clinical findings strongly suggested that the loss of hearing was due to fusion of the ossicles of the middle ear.


[Surgical tactics at "difficult" perforative duodenal ulcers].
Bacteriological research of abdominal cavities exsudate is conducted to 264 patients on perforative duodenal ulcers and the dynamics of peritonitis motion is studied in a postoperative period. It is set that already hour-long after the perforation of duodenal ulcer, according to information of peritoneal maintenance pH-metry and it's bacteriologic research, the optimum conditions for progress of inflammatory and infectious factors are created in an abdominal cavity. Therefore a formal term from the moment of perforation can not be the index of degree of inflammation (bacterial contamination) of peritoneum. The methods of duodenoplasty are improved at the giant perforative ulcers of duodenum and ulcers, combined with tubular stenosis of duodenum, allowed to avoid development of purulent-septic postoperative complications through insolvency of stitches and severe motor function disturbances.


Use of Tuberosity Tissue Block for Tunneling Reconstruction of Class III Sockets With Simultaneous Implant Placement: A Case Report.
Immediate implant placement in the anterior maxilla remains a complex procedure, particularly when the cortical bone plate of the socket is not intact and a gingival recession is present. The reconstruction of both hard and soft tissues increases the complexity of these clinical scenarios. This case report describes a novel, minimally invasive technique to reconstruct class III sockets with simultaneous implant placement. Four incisions are made with a scalpel blade to create, or "draw," a square outline instead of raising a flap at the tuberosity to harvest a hard- and soft-tissue block. In addition, a tunneling approach is described to graft the site while preserving the recipient area's vascularity. Harvesting a hard- and soft-tissue block from the tuberosity in a minimally invasive manner preserves the donor site and helps to reconstruct a class III alveolus in one single appointment, thereby reducing morbidity, costs, and treatment time.


Effects of cytosine methylation on DNA morphology: An atomic force microscopy study.
Methylation is one of the most important epigenetic mechanisms in eukaryotes. As a consequence of cytosine methylation, the binding of proteins that are implicated in transcription to gene promoters is severely hindered, which results in gene regulation and, eventually, gene silencing. To date, the mechanisms by which methylation biases the binding affinities of proteins to DNA are not fully understood; however, it has been proposed that changes in double-strand conformations, such as stretching, bending, and over-twisting, as well as local variations in DNA stiffness/flexibility may play a role. The present work investigates, at the single molecule level, the morphological consequences of DNA methylation in vitro. By tracking the atomic force microscopy images of single DNA molecules, we characterize DNA conformations pertaining to two different degrees of methylation. In particular, we observe that methylation induces no relevant variations in DNA contour lengths, but produces measurable incremental changes in persistence lengths. Furthermore, we observe that for the methylated chains, the statistical distribution of angles along the DNA coordinate length is characterized by a double exponential decay, in agreement with what is predicted for polyelectrolytes. The results reported herein support the claim that the biological consequences of the methylation process, specifically difficulties in protein-DNA binding, are at least partially due to DNA conformation modifications.


Spectroscopic and hydrodynamic studies reveal structural differences in normal and transforming H-ras gene products.
We have recorded the circular dichroism spectra of the cellular and the viral H-ras gene products both in the absence and in the presence of guanine nucleotides and analyzed these spectra in terms of the secondary structure composition of these proteins. It is shown that the GTP complex of the ras proteins has a different secondary structure composition than the GDP complex and, furthermore, that there are differences in the secondary structure of the viral ras protein and the cellular ras protein. We have also recorded and analyzed the circular dichroism spectrum of the isolated guanine nucleotide binding domain of the Escherichia coli elongation factor Tu (EF-Tu), which has been considered as a model for the tertiary structure of the ras proteins [McCormick, F., Clark, B. F. C., LaCour, T. F. M., Kjeldgaard, M., Norskov-Lauritsen, L., & Nyborg, J. (1985) Science (Washington, D.C.) 230, 78-82]. Our data show that the guanine nucleotide binding domain of EF-Tu (30% alpha-helix and 16% beta-pleated sheet for the GDP complex) has quite a different secondary structure composition than the ras proteins (e.g., the cellular ras protein has 47% alpha-helix and 22% beta-pleated sheet for the GDP complex), indicating that the protein core comprising the guanine nucleotide binding site might be similar but that major structural differences must exist at the portion outside this core. Normal and transforming ras proteins also differ slightly in their hydrodynamic properties as shown by sedimentation velocity runs in the analytical ultracentrifuge.(ABSTRACT TRUNCATED AT 250 WORDS)


The behavior of mentally disordered criminals in civil mental hospitals.
Because of changes in Ohio mental health legislation in 1978, mentally disordered criminal offenders can now be turned over to the civil probate court for civil commitment procedures. In part because many officials in the civil hospital system fear the admission of dangerous criminals into their hospitals, the authors conducted a statewide research project to compare civil and criminal patients on demographic, diagnostic, and behavioral variables. There were no differences between the two groups on some indices of dangerousness, but on other variables the two groups differed. Sometimes it was not the forensic but the civil patients who appeared more threatening. In all, the forensic patients did not constitute a unique class of patients who are clearly and categorically more dangerous than civil patients. The findings suggest a more open-door policy toward forensic clients in the civil mental health system.


Dentin bonding as a function of dentin structure.
The traditional principles of operative dentistry have been challenged since Dr. Buonocore introduced the aid-etch technique in 1955. In spite of the numerous changes in clinical protocols and adhesive techniques, adhesion to dentin remains difficult. The importance of micromechanical bonding to dentin has been recognized over the last decade. Researchers now believe that dentin adhesion relies primarily on the penetration of adhesive monomers into the filigree of collagen fibers left exposed by acid etching. Two main strategies are currently in use for bonding to enamel and dentin: the self-etch technique and the total-etch technique. The efficiency of either bonding strategy depends very much on the dentin substrate used for bonding. Laboratory tests use ideal dentin from extracted teeth, which does not reflect the clinical reality. Clinical studies are the ultimate test for any dental adhesive material.


Serotonin triggers a transient epigenetic mechanism that reinstates adult visual cortex plasticity in rats.
Cortical circuitries are highly sensitive to experience during early life but this phase of heightened plasticity decreases with development. We recently demonstrated that fluoxetine reinstates a juvenile-like form of plasticity in the adult visual system. Here we explored cellular and molecular mechanisms that underlie the occurrence of these plastic phenomena. Adult rats were intracortically treated with serotonin (5-HT) whereas long-term fluoxetine-treated rats were infused with the 5-HT(1A) -receptor antagonist WAY-100635, brain-derived neurotrophic factor (BDNF) scavenger trkB-IgG or the mitogen-activated protein kinase inhibitor U0126. Plasticity was assessed as variations of visual cortex responsiveness after unilateral eyelid suture and reverse occlusion by using an electrophysiological approach. Real-time PCR and chromatin immunoprecipitation analysis were then used to explore alterations in gene expression and modifications of chromatin structure associated with the plastic outcome caused by fluoxetine in the visual system. Local infusion of 5-HT into visual cortex restored susceptibility to monocular deprivation in adulthood whereas infusion of WAY-100635, trkB-IgG or U0126 prevented the process of plasticity reactivation in fluoxetine-treated animals. Long-term fluoxetine treatment promoted a transient increase of Bdnf expression in the visual cortex, which was paralleled by an increased histone acetylation status at Bdnf promoter regions and by decreased expression of Hdac5. Accordingly, enhancing histone acetylation levels by systemic treatment with Trichostatin-A reactivated plasticity in the adult while WAY-100635-infusion prevented epigenetic modifications in Bdnf promoter areas. The data suggest a key role for 5-HT(1A) receptor and BDNF-trkB signalling in driving a transitory epigenetic remodelling of chromatin structure that underlies the reactivation of plasticity in the visual system.


Prenatal diagnosis of cystic fibrosis: ultrasonographic appearance of meconium ileus in the fetus.
Four of ten fetuses carrying a risk of 1:4 for cystic fibrosis were found to have low levels of microvillar enzymes in the amniotic fluid obtained between 17 and 18 weeks' gestational age. On sonography performed prior to the amniocentesis, three fetuses showed enlarged bowel loops. At autopsy, meconium ileus was detected. Enlarged bowel loops are a sign which has not been described previously so early in pregnancies.


Racial differences in glucose control among patients with type 2 diabetes: a survey on dietary temptations, coping, and trust in physicians.
A quantitative evaluation of self-care behaviors, psychosocial stressors, and patient relationships to health care to better understand racial disparities in these domains. A cross-sectional study of adult patients with type 2 diabetes in University of Pennsylvania Healthcare System who had a HbA1c test within one month of survey administration. The survey instrument included among other items, the Dieter's Inventory of Eating Temptations Self-Efficacy instrument (DIET-SE), the Jalowiec Coping Scale (JCS), and the Trust in Physician (TIP) scale. 332 individuals completed the survey. Poor glucose control was significantly associated with Black race, lower income level, other demographic variables, non-perfect medication adherence, and poorer diet quality. It was also associated with lower self-efficacy to resist social dietary temptations, and among White patients it was associated was decreased use of a confrontive coping style. However, these factors did not explain the racial differences in glucose control between Blacks and Whites. Interventions aimed at dietary temptations, coping styles, or trust in physicians may not reduce racial disparities in glucose control. However, interventions that focus on dietary temptations may positively affect all diabetic patients.