Preventing and managing exacerbations in COPD--critical appraisal of the role of tiotropium.
The course of COPD is punctuated by acute exacerbations that are associated with an increase in the morbidity and mortality related to this chronic disease and may contribute to its rate of progression. Therefore, preventing and treating exacerbations are major goals of COPD management. The role of tiotropium in the prevention of exacerbations has been investigated in several placebo-controlled randomized clinical trials varying in duration from 3 months to 4 years in patients with moderate to very severe COPD. In all of these trials, tiotropium has uniformly reduced the proportion of patients experiencing at least one exacerbation and delayed the time to the first exacerbation compared with placebo. In the longer trials (> or =6 months' duration) tiotropium has also reduced the exposure-adjusted incidence rate of exacerbations. In trials of at least 1 year in duration, tiotropium either significantly reduced the risk of hospitalization for an exacerbation and/or the proportion of patients with an exacerbation-related hospitalization. In a meta-analysis that included 15 trials of tiotropium vs either placebo (n = 13) and/or a long-acting beta-agonist (LABA; n = 4), tiotropium significantly reduced the odds of experiencing an exacerbation compared to placebo as well as a LABA. The potential additive benefits of tiotropium to those of a LABA and/or inhaled corticosteroid in reducing exacerbations require further investigation. The mechanism whereby tiotropium reduces exacerbations is not due to an anti-inflammatory effect but more likely relates to its property of causing a sustained increase in airway patency and reduction in hyperinflation, thereby counteracting the tendency for respiratory insults to worsen airflow obstruction and hyperinflation. For the management of acute exacerbations, an increase in short-acting inhaled bronchodilators is recommended as needed, while the potential role of long-acting bronchodilators, such as tiotropium, in conjunction with short-acting agents, is unclear and warrants further study.


Silver ion coordination countercurrent chromatography: Separation of β-elemene from the volatile oil of Curcumae Rhizoma.
In this work, the antitumor constituent β-elemene was selectively separated from the volatile oil of the Curcumae Rhizoma by countercurrent chromatography with silver nitrate as selective reagent based on the formation of coordination complexes. A biphasic solvent system composed of n-hexane/methanol/water (2:1.5:0.5, v/v/v) was selected, in which 0.15 mol/L of silver nitrate was added to the aqueous phase. The aqueous phase was used as the stationary phase for separation of β-elemene by countercurrent chromatography after it was partially purified from the volatile oil by silica gel column chromatography. An enriched β-elemene fraction was obtained by silica gel column chromatography to improve the percentage of β-elemene from 16.5 to 46.1%. Subsequently, β-elemene was further purified from 445 mg of the partially purified sample of volatile oil by countercurrent chromatography with silver nitrate as a selective reagent, yielding 145 mg of β-elemene with greater than 99% purity, as determined by gas chromatography mass spectrometry. The recovery of β-elemene from the crude volatile oil through two steps was around 63.6%.


Inhibition of Factor Xa : a potential target for the development of new anticoagulants.
Anticoagulant therapy plays an important role in the prevention and treatment of pathologic arterial and venous thrombosis. There is increasing enthusiasm in the inhibition of Factor Xa as a target to achieve therapeutic anticoagulation because of its central and 'upstream' position in the coagulation process. The indirect, selective, parenteral Factor Xa inhibitor fondaparinux sodium (synthetic pentasaccharide) has been studied extensively in the prevention and treatment of venous thromboembolism. In an overview of four studies in patients undergoing major orthopedic surgery, fondaparinux sodium was associated with a 55% reduction in recurrent thromboembolism, albeit with a modest increase in bleeding. Preliminary results from phase II studies of fondaparinux sodium in patients with ST-elevation and non-ST-elevation acute coronary syndromes have been promising and have led to the initiation of two large phase III trials, which are currently underway. Idraparinux sodium, a long-acting synthetic pentasaccharide, is currently being investigated as a once-weekly alternative to other long-term anticoagulants. DX-9065a and razaxaban are two of many direct selective Factor Xa inhibitors currently in development. DX-9065a has been studied in phase II trials in patients undergoing percutaneous coronary intervention and in those with non-ST-elevation acute coronary syndromes. Razaxaban has been studied in a phase II trial in patients who have undergone orthopedic surgery. Data from these trials, although preliminary and based on small numbers of patients, suggest that direct selective Factor Xa inhibition may provide effective anticoagulation, perhaps without excessive bleeding. Inhibition of Factor Xa is a promising target for the prevention and treatment of thrombosis in both the venous and arterial circulation. Ongoing investigation with numerous oral and parenteral inhibitors of Factor Xa will establish the potential of Factor Xa as a target for therapeutic anticoagulation.


Cl-Loss Dynamics of Vinyl Chloride Cations in the B2A″ State: Role of the C2A' State.
The dissociative photoionization of vinyl chloride (C2H3Cl) in the 11.0-14.2 eV photon energy range was investigated using threshold photoelectron photoion coincidence (TPEPICO) velocity map imaging. Three electronic states, namely, A2A', B2A″, and C2A', of the C2H3Cl+ cation were prepared, and their dissociation dynamics were investigated. A unique fragment ion, C2H3+, was observed within the excitation energy range. TPEPICO three-dimensional time-sliced velocity map images of C2H3+ provided the kinetic energy release distributions (KERD) and anisotropy parameters in dissociation of internal-energy-selected C2H3Cl+ cations. At 13.14 eV, the total KERD showed a bimodal distribution consisting of Boltzmann- and Gaussian-type components, indicating a competition between statistical and non-statistical dissociation mechanisms. An additional Gaussian-type component was found in the KERD at 13.65 eV, a center of which was located at a lower kinetic energy. The overall dissociative photoionization mechanisms of C2H3Cl+ in the B2A″ and C2A' states are proposed based on time-dependent density functional theory calculations of the Cl-loss potential energy curves. Our results highlight the inconsistency of previous conclusions on the dissociation mechanism of C2H3Cl+.


Addressing gaps in physician knowledge regarding transgender health and healthcare through medical education.
Transgender people (those people whose sex at birth does not "match" their felt gender identity) are a priority group for healthcare as they experience high rates of discrimination and related illnesses. Despite this, there is a trend of poor healthcare access for trans people due, in large part, to the denial of care on the part of physicians. A small body of literature is beginning to suggest that this denial of care may be due to a lack of physician knowledge as well as, in some cases, to transphobia. There is a dearth of research in Canada, however, exploring whether and/or how knowledge gaps create barriers to quality care, and whether medical education can attend to these gaps while and through addressing gender normativity. To fill these gaps in the literature, we undertook a qualitative study with 30 trans identified people and 11 physicians (N=41) in Winnipeg, Manitoba. Methods included semi-structured individual interviews and focus groups. Data were transcribed and analyzed with NVivo qualitative data software using iterative methods. An overwhelming finding of this study was a lack of physician knowledge, as reported both by trans people and by physicians, that resulted in a denial of trans-specific care and also impacted general care. Transphobia was also identified as a barrier to quality care by both trans people and physicians. Physicians were open to learning more about trans health and healthcare. The findings suggest a pressing need for better medical education that exposes students to basic skills in trans health so that they can become competent in providing care to trans people. This learning must take place alongside anti-transphobia education. Based on these findings, we suggest key recommendations at the close of the paper for providing quality trans health curriculum in medical education.


Intravenous lipid emulsions in pediatric patients with intestinal failure.
The incidence of cholestatic liver disease (CLD) in pediatric patients suffering intestinal failure (IF) is not well established. Due to persistent portal inflammation, about 20% of these patients will progress to end-stage intestinal failure associated liver disease (IFALD) leading to liver transplant or death. Premature babies as well as infants with short bowel syndrome (SBS) and repeated sepsis (catheter or small intestinal bacterial overgrowth related) are at risk of developing CLD. Clinical data in SBS infants focused on intravenous lipid emulsion (ILE) as an important factor of CLD. Compared to the last generation of composite ILE containing fish oil (FO), soybean oil (SO) based ILE, have marked differences in term of oil source, omega-3 fatty acids (FAs) composition, vitamin E (α-tocopherols) and plant sterols contents, that may explain CLD and CLD reversal. Randomized controlled trials and meta-analysis allow the following recommendations. In pediatric patients with developing or established CLD or IFALD, potential causes should be explored and pure SO ILE should be avoided. A reduction of the ILE dosage and/or the use of the new composite FO based ILE, may be recommended along with the treatment and management of other risk factors. The 10% pure FO ILE should not be used as a sole provision of IV lipids in paediatric patients on total PN but can only serve as a short-term rescue treatment.


Effect of Obesity on the Expression of Genes Associated with Severe Asthma-A Pilot Study.
Asthma is a complex condition resulting from the interaction of genes and environment. Obesity is a risk factor to develop asthma and contributes to poor response to asthma therapy and severity. The aim of the study was to evaluate the effect of obesity on the expression levels of genes previously associated with severe asthma. Three groups of subjects were studied: non-obese asthmatics (NOA), obese asthma patients (OA), and non-asthmatic obese subjects (O). Previously reported overexpressed (IL-10, MSR1, PHLDA1, SERPINB2, and CD86) and underexpressed genes (CHI3L1, CPA3, IL-8, and PI3) in severe asthma were analyzed by RT-qPCR in peripheral blood mononuclear cells (PBMCs). In the overexpressed genes, obesity significantly decreased the expression of MSR1 and PHLDA1 and had no effects on CD86, IL-10, and SERPINB2. In underexpressed genes, obesity did not affect PI3, CHI3L1, and IL-8 and significantly reduced CPA3 expression. The results of this study show that obesity should be included among the known factors that can contribute toward modifying the expression of genes associated with asthma and, in particular, severe asthma.


Translating Research on Myoelectric Control into Clinics-Are the Performance Assessment Methods Adequate?
Missing an upper limb dramatically impairs daily-life activities. Efforts in overcoming the issues arising from this disability have been made in both academia and industry, although their clinical outcome is still limited. Translation of prosthetic research into clinics has been challenging because of the difficulties in meeting the necessary requirements of the market. In this perspective article, we suggest that one relevant factor determining the relatively small clinical impact of myocontrol algorithms for upper limb prostheses is the limit of commonly used laboratory performance metrics. The laboratory conditions, in which the majority of the solutions are being evaluated, fail to sufficiently replicate real-life challenges. We qualitatively support this argument with representative data from seven transradial amputees. Their ability to control a myoelectric prosthesis was tested by measuring the accuracy of offline EMG signal classification, as a typical laboratory performance metrics, as well as by clinical scores when performing standard tests of daily living. Despite all subjects reaching relatively high classification accuracy offline, their clinical scores varied greatly and were not strongly predicted by classification accuracy. We therefore support the suggestion to test myocontrol systems using clinical tests on amputees, fully fitted with sockets and prostheses highly resembling the systems they would use in daily living, as evaluation benchmark. Agreement on this level of testing for systems developed in research laboratories would facilitate clinically relevant progresses in this field.


A mutant with bilateral whisker to barrel inputs unveils somatosensory mapping rules in the cerebral cortex.
In mammals, tactile information is mapped topographically onto the contralateral side of the brain in the primary somatosensory cortex (S1). In this study, we describe Robo3 mouse mutants in which a sizeable fraction of the trigemino-thalamic inputs project ipsilaterally rather than contralaterally. The resulting mixture of crossed and uncrossed sensory inputs creates bilateral whisker maps in the thalamus and cortex. Surprisingly, these maps are segregated resulting in duplication of whisker representations and doubling of the number of barrels without changes in the size of S1. Sensory deprivation shows competitive interactions between the ipsi/contralateral whisker maps. This study reveals that the somatosensory system can form a somatotopic map to integrate bilateral sensory inputs, but organizes the maps in a different way from that in the visual or auditory systems. Therefore, while molecular pre-patterning constrains their orientation and position, preservation of the continuity of inputs defines the layout of the somatosensory maps.


Interpreting interrater reliability coefficients of the Braden scale: a discussion paper.
There are many studies investigating psychometric properties of the Braden scale, a scale that predicts the risk for pressure ulcers. The main focus of these studies is validity as opposed to reliability. In order to estimate the degree of interrater reliability a literature review revealed that numerous statistical approaches and coefficients were used (Pearson's product-moment correlation, Cohen's kappa, overall percentage of agreement, intraclass correlation). These coefficients were calculated for the individual items and the overall Braden score and were used inconsistently. The advantages and limitations of every coefficient are discussed and it is concluded that most of them are inappropriate measures. Therefore, estimating the degree of the Braden scale interrater reliability is limited to a certain extent. It is shown that the intraclass correlation coefficient is an appropriate statistical approach for calculating the interrater reliability of the Braden scale. It is recommended to present intraclass correlation coefficients in combination with the overall percentage of agreement.


Comparison of the effect of orally versus submucosally administered meperidine on the behavior of pediatric dental patients: a retrospective study.
The purpose of this study was to compare the effect of oral versus submucosal meperidine on the behavior of pediatric dental patients. Twenty charts (10 in each group) were retrospectively reviewed. The groups were matched for age and weight. Presedation and postsedation behavior was rated. No difference was found in the increase in cooperation between the oral and the submucosal meperidine groups. While no difference was found between the 2 groups, a larger prospective study is needed to confirm these findings.


Thoracic paravertebral block for postoperative pain management after renal surgery: A randomised controlled trial.
Thoracic paravertebral block (ThPVB) combined with general anaesthesia is used in thoracic and general surgery. It provides effective analgesia, reduces surgical stress response and the incidence of chronic postoperative pain. To assess the efficacy of ThPVB in reducing opioid requirements and decreasing the intensity of pain after renal surgery. A randomised, open label study. A single university hospital. Study conducted from August 2013 to February 2014. In total, 68 patients scheduled for elective renal surgery (open nephrectomy or open nephron-sparing surgery). Preoperative ThPVB with 0.5% bupivacaine combined with general anaesthesia, followed by postoperative oxycodone combined with nonopioid analgesics as rescue drugs. Follow-up period: 48 h. Total dose of postoperative oxycodone required, pain intensity, occurrence of opioid related adverse events, ThPVB-related adverse events and patient satisfaction. A total of 68 patients were randomised into two groups and, of these, 10 were subsequently excluded from analysis. Patients in group paravertebral block (PVB; n = 27) had general anaesthesia and ThPVB, and those in group general (anaesthesia) (GEN) (n = 31) formed a control group receiving general anaesthesia only. Compared with patients in group GEN, patients who received ThPVB required 39% less i.v. oxycodone over the first 48 h and had less pain at rest (P < 0.01) throughout the first 24 h. Group PVB patients also experienced fewer opioid-related adverse events and were less sedated during the first 12 postoperative hours. Patients in the PVB group had higher satisfaction scores at 48 h compared with the control group. There were no serious adverse events. In our study, preoperative ThPVB was an effective part of a multimodal analgesia regimen for reducing opioid consumption and pain intensity. Methods and drugs used in both groups were well tolerated with no serious adverse events. Compared with the control group, patients in the ThPVB group reported increased satisfaction. Clinical Trials NCT02840526.


[Methods of studying genes and gene function].
In several fields, such as immunology, biochemistry, and structural biology, but particularly in molecular genetics, modern methods enable genes and their protein products to be analysed and described. The tools are now available to study any physiological process or disease at the molecular level. As a result, genetic diseases and viral infections can be better identified and understood. Basic cellular and physiological mechanisms are beginning to be elucidated, the disturbance of which is a factor involved in cancerogenesis, for instance, or the development of hypercholesterolaemia. The article is intended as a brief review of current methods of studying genes and their function. The isolation and characterisation of genes by means of recombinant DNA technology, the identification of defective genes, and the analysis of gene function, both in vitro and in vivo are presented.


Constructing explicit magnetic analogies for the dynamics of glass forming liquids.
By defining a spatially varying replica overlap parameter for a supercooled liquid referenced to an ensemble of fiducial liquid state configurations, we explicitly construct a constrained replica free energy functional that maps directly onto an Ising Hamiltonian with both random fields and random interactions whose statistics depend on the liquid structure. Renormalization group results for random magnets when combined with these statistics for the Lennard-Jones glass suggest that discontinuous replica symmetry breaking would occur if a liquid with short range interactions could be equilibrated at a sufficiently low temperature where its mean field configurational entropy would vanish, even though the system strictly retains a finite configurational entropy.


A case of resected hepatocellular carcinoma after drug-eluting bead transarterial chemoembolization.
We report a case of resected hepatocellular carcinomas (HCCs) after drug-eluting bead transarterial chemoembolization (DEB-TACE). A 67-year-old man with alcoholic liver disease was diagnosed with HCCs. Serological markers for hepatitis B and C viruses were negative. Among tumor markers, alpha-fetoprotein was 2.7ng/mL, and protein induced by vitamin K absence II was 868mAU/mL. Two HCCs were detected using dynamic computed tomography: one was 9cm in diameter in S8 and the other was 2cm in diameter in S4. We performed DEB-TACE using HepaSphere(®) and epirubicin. DEB-TACE was repeated three times in three months. Severe postembolization syndrome was not seen with any treatment. Four weeks after the last DEB-TACE, we performed surgical resection. Histopathological study revealed dense distribution of numerous bead particles in necrotic tumor tissue. Otherwise, in non-cancerous tissue, some beads were in portal areas, without necrotic change. Granulomas from foreign body reaction with giant cells were present around the beads. There were no necrotic changes in the smaller HCC, the intrahepatic metastatic nodules, or the microscopic invasion to the portal vein. In conclusion, DEB-TACE would be a useful treatment for huge HCCs; however, patients should be monitored for early recurrence from residual tumor tissue. This study will be helpful to perform DEB-TACE in the future.


Never smokers and lung cancer risk: a case-control study of epidemiological factors.
We performed an analysis of potential epidemiological risk factors for lung cancer using data from 280 cases and 242 hospital-based controls, all lifetime never smokers (those who had smoked <100 cigarettes in their lifetimes) and frequency matched on age, gender and ethnicity. The data on demographic characteristics, medical history of respiratory diseases (asthma, emphysema, pneumonia and hay fever), weight and height, family history, female characteristics and environmental tobacco smoke (ETS) and dust exposure were derived from personal interviews. We performed a logistic regression analysis of these variables adjusting for age, gender, ethnicity, income and years of education. Exposure to ETS (OR = 2.08, 95% CI [1.25-3.43]) and dusts (OR = 2.43, 95% CI [1.53-3.88]) were associated with significantly increased risk. In the analysis for joint effects, exposure to both ETS and dusts conferred a higher risk (OR = 3.25, 95% CI [1.58-6.70]) than exposure to either alone. Family history of any cancer with onset before age 50 in at least 1 first degree relative was a significant risk predictor (OR = 1.70, 95% CI [1.10-2.64]). Individuals with a self-reported physician-diagnosed history of hay fever, but not asthma, had a decreased lung cancer risk (OR = 0.57, 95% CI [0.35-0.92]). In the multivariate analysis, exposure to ETS and dusts, and family history of cancer with onset before age 50 were significant risk factors, while a history of hay fever (occurring without asthma) was significantly protective.


[Doctors' alcohol problems].
An overusing and an addiction to alcoholic drinks are important problems in a medical society. The studies made in the United States had documented that about 8-12% doctors were addicted to alcohol. In many cases the doctors are able to keep their problem as a secret and their activity is satisfied up to the moment when a decrease is noticed. Some factors--such as a high level of stress--predispose doctors to alcoholic problems especially surgeons. Alcohol problems should be identified as early as possible, and therapy ought to be given as well. There is no reason to hide the problem.


A solution for removal of resin from epoxy sections.
Development of a resin-dissolving solution for use at low alkali concentrations is described. Crown ether dissolved in dimethyl-sulfoxide produces a superbasic alkoxide anion. A five minute treatment resulted in complete resin removal from kidney biopsy specimens embedded in Epon 812. Specimens were well stained by Loeffler's methylene blue. Periodic acid-methenamine silver and Giemsa stains yielded good results. Application of PAS reaction and subsequent hematoxylin counterstaining was practicable for diagnosis.


Prevention of Bacterial Colonization on Catheters by a One-Step Coating Process Involving an Antibiofouling Polymer in Water.
As reports of multidrug resistant pathogens have increased, patients with implanted medical catheters increasingly need alternative solutions to antibiotic treatments. As most catheter-related infections are directly associated with biofilm formation on the catheter surface, which, once formed, is difficult to eliminate, a promising approach to biofilm prevention involves inhibiting the initial adhesion of bacteria to the surface. In this study, we report an amphiphilic, antifouling polymer, poly(DMA-mPEGMA-AA) that can facilely coat the surfaces of commercially available catheter materials in water and prevent bacterial adhesion to and subsequent colonization of the surface, giving rise to an antibiofilm surface. The antifouling coating layer was formed simply by dipping a model substrate (polystyrene, PET, PDMS, or silicon-based urinary catheter) in water containing poly(DMA-mPEGMA-AA), followed by characterization by X-ray photoelectron spectroscopy (XPS). The antibacterial adhesion properties of the polymer-coated surface were assessed for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) growth under static (incubation in the presence of a bacterial suspension) and dynamic (bacteria suspended in a solution under flow) conditions. Regardless of the conditions, the polymer-coated surface displayed significantly reduced attachment of the bacteria (antiadhesion effect > ∼8-fold) compared to the bare noncoated substrates. Treatment of the implanted catheters with S. aureus in vivo further confirmed that the polymer-coated silicon urinary catheters could significantly reduce bacterial adhesion and biofilm formation in a bacterial infection animal model. Furthermore, the polymer-coated catheters did not induce hemolysis and were resistant to the adhesion of blood-circulating cells, indicative of high biocompatibility. Collectively, the present amphiphilic antifouling polymer is potentially useful as a coating platform that renders existing medical devices resistant to biofilm formation.


[Research on the mechanism of ginsenoside Rh2 reversing the resistance of lung adenocarcinoma cells to cisplatin].
To explore the mechanism of ginsenoside Rh2 in reversing the resistance of lung adenocarcinoma cells to cisplatin. In the Rh2, DDP and DDP + Rh2 group A549DDP cells were treated with Rh2, cisplatin, cisplatin + Rh2 respectively for 48 hours. In the control group the A549DDP cells were not treated with any kind of drugs. The state of mitochondrial permeability transition pore (PTP) was evaluated by ultra violate spectrofluorometer. Concentration of calcium in cells, membrane potential of mitochondrion and apoptosis cells were determined by flow cytometry. The expression of cyt-c and Caspase-3 was estimated by Western blots. Cellular shapes were observed by fluorescent microscopy. The concentrations of calcium were similar among the former three groups, but was obviously increased in the Rh2 + DDP group (t = 22.47, P < 0.01). A(540) of mitochondrion among the former three groups were not different, but decreased significantly in the Rh2 + DDP group (t = 8.21, P < 0.01). The membrane potentials of mitochondrion showed no difference in the former groups, that was remarkably lower in the Rh2 + DDP group than in the control group (chi(2) = 46.01, P < 0.01). There was little expression of cty-c and Caspase-3 in the former groups, but high expression of those in the Rh2 + DDP group. Fluorescence was distributed equally on the cells nucleus in the former groups. In the Rh2 + DDP group many cell nucleus shrank or were distorted. The apoptosis rate of the cells was 6.32%, 7.24%, 7.41% and 21.96% in the four groups respectively. Which in Rh2 + DDP group was higher than that in the control group (t = 10.92, P < 0.05). The effect of ginsenoside Rh2 reversing resistance of lung adenocarcinoma A549DDP cells to cisplatin can be performed by apoptotic mitochondria pathway.


Interhemispheric transfer in children with early-treated phenylketonuria.
Phenylketonuria (PKU) is a genetic disorder of amino acid metabolism that is associated with brain catecholamine depletion and deficient myelination. Although neuropsychological deficits have been documented in children with early-treated PKU (ETPKU), no study to date has examined possible effects of impaired myelination in this population. In the present study, interhemispheric transfer time was assessed for 14 children with ETPKU, 22 children with attention deficit-hyperactivity disorder, and 48 normal children, using a manual reaction time paradigm previously validated with callosal agenesis patients (Milner, 1982). Children with ETPKU demonstrated slowed interhemispheric transfer from the left to the right hemisphere as compared with the two other groups. The magnitude of slowing was correlated with age and phenylalanine levels at birth. Results support the hypothesis that abnormal myelination disrupts the development of interhemispheric connections in ETPKU, and suggest that left hemisphere projections may be particularly susceptible to such disruption.


The usefulness of a Trauma Registry and the role of the general surgeon in the multidisciplinary approach to trauma patients: 3-year experience at Sant'Andrea University Hospital in Rome.
The purpose of this study is to verify the usefulness of a multidisciplinary Trauma Registry in the evaluation of trauma, particularly in relation to the number of specialists involved, and to analyze the effective role of the general trauma surgeon in an integrated trauma care system. The present study was performed by analyzing data from the Trauma Registry of the University Hospital Sant'Andrea in Rome, which was set up in March 2006. Data recorded between March 2006 and March 2009 was considered for the present study. The severity of trauma was categorized by dividing patients into 4 subgroups based on the value of ISS: minor injuries (ISS 1-8), moderate (ISS 9-15), severe (ISS 16-24) and very severe (ISS> 24). Patients who had an ISS greater than 9 were taken into account for further analysis and comparison. To evaluate the significance of the multidisciplinarity the patients were stratified in subgroups considering the number of specialists involved in relation to the anatomic location of injuries. In the 1386 trauma patients entered in the registry, the mean and median ISS value were 10.7 ± 8.4 and 9 respectively. The overall mortality and morbidity were 4.1% and 7.4% respectively. There was a statistically significant linear relationship between the number of specialists involved and the ISS (multidisciplinarity / ISS r = 0.493, p <0.001). Patients with ISS greater than 9 were 358, 25.8% of all cases. The mean ISS was 21.4 ± 10.3. Mortality and morbidity rates were 9.8% (35 patients) and 22.1% (79 patients) respectively. The average number of specialists involved was 2.4 ± 1.1, median 2 (range 1- 6). Results confirmed the significance of the multidisciplinary treatment for patients with trauma and the central role played by the general surgeon.


Synthesis and characterization of the first carbene derivative of a polyoxometalate.
Reaction of the Keggin-type polyanion [PW11O39]7- with the tetrakis-carbene ruthenium precursor [RuLMe4Cl2] (LMe = 1,3-dimethylimidazolidine-2-ylidene), in water, results in the formation of Na4K9[(PW9O34)2(cis-WO2)(cis-RuLMe2)].23H2O, which is the first carbene derivative of a polyoxometalate. The oxidation state of the ruthenium is confirmed by XANES experiments.


Levetiracetam Treatment-Associated Acute Rhabdomyolysis in an Adolescent.
Etiology of rhabdomyolysis includes hereditary muscle enzyme deficiencies, trauma, viral infections, excessive exercise, hypothyroidism, and medications such as colchicine, lithium, and statins. Several studies have reported that various antiepileptic drugs may induce rhabdomyolysis. Levetiracetam is one of the antiepileptic drugs implicated in the etiology of rhabdomyolysis. Herein, we present a case of rhabdomyolysis in an adolescent treated with levetiracetam. We wanted to draw attention to the increasing trend of levetiracetam-associated rhabdomyolysis frequency in pediatric patients.


Topographic organization of the olivocochlear projections from the lateral and medial zones of the superior olivary complex.
By anterograde tracing using autoradiography, we have found topographic organizations in the projections of both medial and lateral olivocochlear (OC) systems in the cat. Lateral-zone injections show an ipsilateral cochleotopic projection pattern with more medial injections projecting more basally in the cochlea. In the contralateral cochlea, in contrast, the projections from all of the lateral-zone injections were predominantly to the apex. However, detailed analysis suggests the possibility that the contralateral lateral-zone projections may have the same cochleotopic organization as the ipsilateral projections but with a heavy bias toward the apex. Medial-zone injections show a pattern in which more dorsal regions project more basally in both cochleas. The ipsilateral projections of lateral OC neurons appear to connect regions with similar best frequencies but the projections of medial OC neurons do not. Summation of data from all of the injections in each zone indicates that lateral OC projections are relatively evenly distributed throughout the ipsilateral cochlea but are predominantly to the apex in the contralateral cochlea. Medial OC projections are predominantly to the middle and basal parts of the cochlea on both sides with contralateral projections somewhat more basal than ipsilateral projections.


Identifying Lynch syndrome in patients with endometrial carcinoma: shortcomings of morphologic and clinical schemas.
It has been suggested that reflex testing for Lynch syndrome (LS) using mismatch repair immunohistochemistry and/or microsatellite instability analysis in newly diagnosed colorectal carcinoma (CRC) patients is an emerging standard of care in the United States. The risk of gynecologic malignancy in women with LS approaches and even exceeds that of CRC. Furthermore, gynecologic malignancies are often the sentinel cancers in these patients. There is significant variation in practice, but some groups have similarly recommended deployment of reflex testing strategies in patients presenting with endometrial cancer (EC). The College of American Pathologists has stated that pathologists should recognize the histologic and clinical features that should prompt at least a recommendation for mismatch repair testing. Morphologic and clinical schemas in EC to identify microsatellite unstable/LS tumors are less refined than the colon-centric schemas (Amsterdam, Bethesda, and MsPath). Studies of LS EC are few and interpretation is limited by recruitment strategies and the myriad of definitions and study designs used. Although serous cell type is used to triage ovarian cancer patients for BRCA screening, cell type correlation in LS is less certain but seems to involve a spectrum of cell types. We review the morphologic and clinical features/schemas in LS EC and highlight limitations of restrictive aged-based screening strategies, uncertainty in current clinical schemas and equivocal results of morphologic studies of LS EC. With uncertainty of histologic and clinical schemas, and following developments in CRC, reflex testing of all/vast majority of newly diagnosed EC for LS should be considered.


Health plan choice in the Netherlands: restrictive health plans preferred by young and healthy individuals.
In a health care system based on managed competition, health insurers negotiate on quality and price with care providers and are allowed to offer restrictive health plans. It is crucial that enrolees who need care choose restrictive health plans, as otherwise health insurers cannot channel patients to contracted providers and they will lose their bargaining power in negotiations with providers. We aim to explain enrolees' choice of a restrictive health plan in exchange for a lower premium. In 2014 an online survey with an experimental design was conducted on members of an access panel (response 78%; n=3,417). Results showed 37.4% of respondents willing to choose a restrictive health plan in exchange for a lower premium. This fell to 22% when the restrictive health plan also included a longer travelling time. Enrolees who choose a restrictive health plan are younger and healthier, or on lower incomes, than those preferring a non-restrictive one. This means that enrolees who use care will be unlikely to choose a restrictive health plan and, therefore, health insurers will not be able to channel them to contracted care providers. This undermines the goals of the health care system based on managed competition.


A Herbal Medicine, Gongjindan, in Subjects with Chronic Dizziness (GOODNESS Study): Study Protocol for a Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Clinical Trial for Effectiveness, Safety, and Cost-Effectiveness.
This study protocol aims to explore the effectiveness, safety, and cost-effectiveness of a herbal medication, Gongjindan (GJD), in patients with chronic dizziness. This will be a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group, clinical trial. Seventy-eight patients diagnosed with Meniere's disease, psychogenic dizziness, or dizziness of unknown cause will be randomized and allocated to either a GJD or a placebo group in a 1 : 1 ratio. Participants will be orally given 3.75 g GJD or placebo in pill form once a day for 56 days. The primary outcome measure will be the Dizziness Handicap Inventory score. Secondary outcome measures will be as follows: severity (mean vertigo scale and visual analogue scale) and frequency of dizziness, balance function (Berg Balance Scale), fatigue (Fatigue Severity Scale) and deficiency pattern/syndrome (qi blood yin yang-deficiency questionnaire) levels, and depression (Korean version of Beck's Depression Inventory) and anxiety (State-Trait Anxiety Inventory) levels. To assess safety, adverse events, including laboratory test results, will be monitored. Further, the incremental cost-effectiveness ratio will be calculated based on quality-adjusted life years (from the EuroQoL five dimensions' questionnaire) and medical expenses. Data will be statistically analyzed at a significance level of 0.05 (two-sided). This trial is registered with ClinicalTrials.gov NCT03219515, in July 2017.


Fatal bilateral pneumonitis after locoregional thoracic chemoradiation in a transplanted patient under immunosuppressive therapy.
After thoracic radiotherapy a pneumonitis may occur, mostly confined to the irradiated volume of the lung. In general, it resolves spontaneously without long-term effects. A 68-year-old man was diagnosed with a stage IIIA adenocarcinoma of the lung and was treated with sequential chemoradiation. He had a heart and kidney transplant for which an immunosuppressant was taken. During the fourth week of radiotherapy, he developed a bilateral interstitial pneumonia. Despite antibiotics and steroids, the patient died twelve days after the onset of complaints due to respiratory failure. Autopsy showed in all pulmonary lobes extensive diffuse alveolar damage, probably leading to respiratory insufficiency and death. Literature and Conclusion: Bilateral pneumonitis after radiotherapy is thought to be an immunologically-mediated response, which usually resolves without long-term effects. Since in radiation pneumonitis an increase in T-cells is described, the suppression of these cells by an immunosuppressant might have exaggerated the pulmonary toxicity.


Effect of protein kinase C inhibitor (H-7) and calmodulin antagonist (W-7) on pertussis toxin-induced IL-1 production by human adherent monocytes. Comparison with lipopolysaccharide as a stimulator of IL-1 production.
Human adherent monocytes stimulated with 1 microgram/ml pertussis toxin (PT) produced interleukin-1 (IL-1), as measured by thymocyte co-stimulation assay and enzyme-linked immunosorbent assay (ELISA), specific for IL-1 alpha and IL-1 beta. To clarify the role of protein kinase C (PKC) and calmodulin in IL-1 production, we investigated the effects of a PKC inhibitor, H-7, and a calmodulin antagonist, W-7 on PT- and lipopolysaccharide (LPS)-induced IL-1 production by monocytes. Addition of 10 microM and 20 microM H-7 to the culture medium markedly suppressed both PT- and LPS-induced IL-1 production. PT-induced IL-1 production was significantly suppressed by 5 microM and 10 microM W-7. However, LPS-induced IL-1 production was not suppressed by W-7 at the concentrations tested. When monocytes were labelled with Quin 2/AM, IL-1 production by monocytes stimulated with PT and LPS was markedly suppressed. These results indicate that different pathways are involved in the IL-1 production by PT and LPS; both calmodulin- and PKC-dependent processes are necessary for the IL-1 production induced by PT, whereas LPS-induced IL-1 production is dependent on the PKC. Inhibition of IL-1 production by interfering with intracellular Ca2+ trafficking in Quin 2/AM-loaded monocytes may be associated with the inhibition of PKC and calmodulin activity.


A study on age- and gender-dependent differences in distance and angle between the internal carotid artery and basilar artery.
Variations or malformation of the internal carotid artery (ICA) and basilar artery (BA) can be risk factors during simple surgery. So medically the focus has been on information about the positional relationship between the blood vessels based on the distance and angle between the ICA and BA. This study measured the distance and angle between the ICA and BA in 188 healthy Korean male and female subjects in their 20s and 40s and analyzed the differences in terms of age and gender. Magnetic resonance images were obtained; the distance between the right ICA and BA was defined as R1 [cm], the distance between the left ICA and BA was defined as L2 [cm], and the distance between the right ICA and left ICA was defined as M3 [cm]. The angles between the right and left ICA and BA were defined as AR1 [degree] and AR2 [degree], respectively. With increasing age, R1 and M3 became shorter in both men and women, and L2 became shorter only in women. The results of this study provide data on the average distance and angle between the ICA and BA of healthy Korean men and women in their 20s and 40s, which may later be used to support the diagnosis of relevant brain diseases and simple routine surgical procedures.


COVID-19 anti-Asian racism: A tripartite model of collective psychosocial resilience.
Anti-Asian racism has spiked since the outbreak of the coronavirus 2019 (COVID-19) pandemic, creating compounded threats to Asian Americans' psychological wellbeing on top of other pandemic stressors (e.g., fears of infection, financial insecurity, or quarantine isolation). COVID-19 anti-Asian racism signifies the relevance of race and racism during public health crises and highlights the importance of examining the psychological impacts of racialized stress and avenues for resilience during a pandemic. This article describes a conceptual model that emphasizes the importance of rechanneling the experience of COVID-19 anti-Asian racism toward resilience. Specifically, the proposed model identifies a tripartite process of collective psychosocial resilience, comprised of (a) critical consciousness of discrimination as a common fate, (b) critical consciousness-informed racial/ethnic identity, and (c) advocacy, for empowering Asian Americans and protecting them against the harmful effects of COVID-19 anti-Asian racism during and beyond the pandemic. Theoretical and empirical underpinnings of the proposed tripartite process for cultivating resilience against COVID-19 anti-Asian racism are delineated. Practice implications and future research directions, as informed and revealed by the conceptual model, are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Dynamic migration and cell-cell interactions of early reprogramming revealed by high-resolution time-lapse imaging.
Discovery of the cellular and molecular mechanisms of induced pluripotency has been hampered by its low efficiency and slow kinetics. Here, we report an experimental system with multicolor time-lapse microscopy that permits direct observation of pluripotency induction at single cell resolution, with temporal intervals as short as 5 minutes. Using granulocyte-monocyte progenitors as source cells, we visualized nascent pluripotent cells that emerge from a hematopoietic state. We engineered a suite of image processing and analysis software to annotate the behaviors of the reprogramming cells, which revealed the highly dynamic cell-cell interactions associated with early reprogramming. We observed frequent cell migration, which can lead to sister colonies, satellite colonies, and colonies of mixed genetic makeup. In addition, we discovered a previously unknown morphologically distinct two-cell intermediate of reprogramming, which occurs prior to other reprogramming landmarks. By directly visualizing the reprogramming process with E-cadherin inhibition, we demonstrate that E-cadherin is required for proper cellular interactions from an early stage of reprogramming, including the two-cell intermediate. The detailed cell-cell interactions revealed by this imaging platform shed light on previously unappreciated early reprogramming dynamics. This experimental system could serve as a powerful tool to dissect the complex mechanisms of early reprogramming by focusing on the relevant but rare cells with superb temporal and spatial resolution.


Subsyndromal Delirium.
The authors sought to determine whether subsyndromal delirium is a qualitatively distinct clinical entity or a spectrum of cognitive and behavioral abnormalities. They conducted a prospective, longitudinal study on 325 patients in an acute care hospital with 3- and 6-month follow-ups. Patients were classified into one of three groups: those meeting full DSM criteria for delirium, those with subsyndromal delirium, and those with no symptoms of delirium. There were no differences in risk factors between those developing DSM-defined delirium or subsyndromal delirium. Number of independent risk factors was a significant predictor of delirium. Patients with subsyndromal delirium fall on a continuum between those with DSM-defined delirium and those with no symptoms of delirium. These data suggest that delirium does represent a spectrum of neurobehavioral impairment. Patients with symptoms of subsyndromal delirium are at risk for considerable morbidity; therefore clinicians should attempt to reduce and treat the onset of occurrence of subsyndromal delirium.


HD Therapeutics - CHDI Fifth Annual Conference.
The CHDI Fifth Annual HD Therapeutics Conference, held in Palm Springs, CA, included topics covering new therapeutic developments in the field of Huntington's disease (HD). This conference report highlights presentations on biomarkers in HD; emerging topics in drug targeting, such as the lysosomal degradation pathway and target prediction by network-based modeling; understanding phenotype and neuronal circuit dysfunction in animal models; regulation of huntingtin protein expression and function; RNAi and antisense technology to deplete the mutant huntingtin protein; and small-molecule drugs that are progressing quickly through the clinic. Investigational drugs discussed include ALN-HTT (Alnylam Pharmaceuticals Inc/Medtronic Inc), EPI-743 (Edison Pharmaceuticals Inc), LNK-754 (Link Medicine Corp) and pridopidine (NeuroSearch A/S).


Activity of exporters of Escherichia coli in Corynebacterium glutamicum, and their use to increase L-threonine production.
L-Threonine is an important biotechnological product and Corynebacterium glutamicum is able to synthesize and accumulate this amino acid to high intracellular levels. We here use four exporters of Escherichia coli and show that three of them operate in C. glutamicum, with RhtA and RhtC being the most effective. Whereas RhtA was unspecific, resulting in L-homoserine together with L-threonine excretion, this was not the case with RhtC. Expression of rhtC reduced the intracellular L-threonine concentration from 140 to 11 mM and resulted in maximal excretion rates of 11.2 nmol min(-1) mg(-1) as compared to 2.3 nmol min(-1) mg(-1) obtained without rhtC expression. In combination with an ilvA mutation generated and introduced into the chromosome, an accumulation of up to 54 mM L-threonine was achieved as compared to 21 mM obtained with the ancestor strain. This shows that expression of rhtC is the pivotal point for industrial relevant L-threonine production with C. glutamicum, and might encourage in general the use of heterologous exporters in the field of white biotechnology to make full use of biosynthesis pathways.


Inhibitors of Src-family tyrosine kinases favour Th2 differentiation.
Two potent pyrazolo-pyrimidine inhibitors of Src-family kinases were found to enhance interleukin 4 (IL-4) and reduce interferon gamma(IFN-gamma) production in cultures of splenocytes from ovalbumin-specific TCR-transgenic BALB/c mice. The effect was increased by addition of a monoclonal antibody binding to domains 3/4 of CD4, while other antibodies binding to domain 1 had the opposite effect. The inhibitors suppressed CD40 ligand (CD40L) expression on activated CD4 T cells, which may explain this Th2 differentiating effect. More generally, the effect fits within the overall framework of signal attenuation in T cells driving this form of differentiation. The inhibitors did not revert previously induced Th1 differentiation in serial cultures of the TCR-transgenic cells. Drugs with this activity are of obvious interest as probes and potential therapeutic agents in autoimmune disease.


[Experiences and feelings of nursing professionals in caring of the dead patient].
This study aimed to understand the experiences and feelings of ten professional nurses related to the dead patient, in a private hospital of the metropolitan area of Porto Alegre-RS, Brazil. We used a qualitative approach, descriptive, exploratory, with data collected in July 2009, through interviews with semi-structured questionnaire. The results were grouped into the categories: feelings about the patient's death, reactions to the death and preparing the patient's body. It was concluded that the most remarkable experiences were related to the first contact with the death, the presence of emotional bonding with patients and families and the patients' age at death. The latter two are considered hindering elements of care offered to patients without life.


Immunologic properties differ in preterm infants fed olive oil vs soy-based lipid emulsions during parenteral nutrition.
In the first period of life, premature infants need parenteral nutrition. Lipid emulsions (LEs), which are a part of parenteral nutrition, are known as potent immunological modulators and may therefore influence the immune status of parenterally fed infants. The aim of the study was to compare tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 production in the peripheral blood mononuclear cells (PBMCs) of premature infants parenterally fed with 2 LEs: olive oil (OO) and soybean oil (SO). Premature infants born at <32 weeks' gestation and with a birth weight <1500 g were randomized in a double-blind method within the first 48 hours of life to receive 1 of 2 LEs: OO based or SO based. At baseline and after 14 days, blood samples were collected, and PBMCs were isolated and then cultured for 48 hours in medium only and in the presence of anti-CD3 antibodies. Of 44 recruited infants, 38 completed the study, 18 in the OO group and 20 in the SO group. The cytokine synthesis profile before the LE introduction was the same in both groups (nonstimulated and anti-CD3-induced PBMC). In the succeeding 14 days of parenteral nutrition, TNF-alpha, IL-6, and IL-10 levels in nonstimulated PBMCs remained unchanged in both groups. In contrast, IL-6 production was significantly higher in the SO group. SO-based LE may promote an excess of IL-6 production, especially in the T cell-dependent way of PBMC activation (via anti-CD3). OO emulsion seems to be immunologically more neutral than SO emulsion.


Diagnostic strategies and clinical management of lipodystrophy.
Introduction: Lipodystrophy is a heterogeneous group of rare diseases characterized by various degrees of fat loss which leads to serious morbidity due to metabolic abnormalities associated with insulin resistance and subtype-specific clinical features associated with underlying molecular etiology.Areas covered: This article aims to help physicians address challenges in diagnosing and managing lipodystrophy. We systematically reviewed the literature on PubMed and Google Scholar databases to summarize the current knowledge in lipodystrophy management.Expert opinion: Adipose tissue is a highly active endocrine organ that regulates metabolic homeostasis in the human body through a comprehensive communication network with other organ systems such as the central nervous system, liver, digestive system, and the immune system. The adipose tissue is capable of producing and secreting numerous factors with important endocrine functions such as leptin that regulates energy homeostasis. Recent developments in the field have helped to solve some of the mysteries behind lipodystrophy that allowed us to get a better understanding of adipocyte function and differentiation. From a clinical standpoint, physicians who suspect lipodystrophy should distinguish the disease from several others that may present with similar clinical features. It is also important for physicians to carefully interpret clinical features, laboratory, and imaging results before moving to more sophisticated tests and making decisions about therapy.


Rapid Synthesis of Cobalt Nitride Nanowires: Highly Efficient and Low-Cost Catalysts for Oxygen Evolution.
Electrochemical splitting of water to produce hydrogen and oxygen is an important process for many energy storage and conversion devices. Developing efficient, durable, low-cost, and earth-abundant electrocatalysts for the oxygen evolution reaction (OER) is of great urgency. To achieve the rapid synthesis of transition-metal nitride nanostructures and improve their electrocatalytic performance, a new strategy has been developed to convert cobalt oxide precursors into cobalt nitride nanowires through N2 radio frequency plasma treatment. This method requires significantly shorter reaction times (about 1 min) at room temperature compared to conventional high-temperature NH3 annealing which requires a few hours. The plasma treatment significantly enhances the OER activity, as evidenced by a low overpotential of 290 mV to reach a current density of 10 mA cm(-2) , a small Tafel slope, and long-term durability in an alkaline electrolyte.


Erythropoietin receptor in myelodysplastic syndrome and leukemia.
Erythropoietin (Epo) is one of the main regulators of growth and differentiation of hematopoietic cells. In normal bone marrow cells, the amount of erythropoietin receptor (EpoR) was highest in the CD34+ CD38- subset, and decreased on lineage committed progenitor cells expressing CD38 antigens. Among the erythroid cells expressing GpA antigens, CD34-positive fractions expressed more EpoR than CD34-negative fractions. Although the amounts of EpoR of bone marrow cells from patients with refractory anemia (RA) were less than those of normal bone marrow cells in all phenotypes examined, there was no statistical significant difference. EpoR was detected on leukemia cells from 60% of acute myeloblastic leukemia (AML) cases and 29% of acute lymphoblastic leukemia (ALL) cases, and distributed widely among all FAB-subtypes. In spite of the presence of EpoR, in vitro proliferative response to Epo was not observed in a large proportion of AML. And there was no correlation between the amount of EpoR and the in vitro response to EPO. Patients with both EpoR expression and in vitro response to Epo had shorter remission duration than those without EpoR.


Signal-averaged ECG abnormalities in haemodialysis patients. Role of dialysis.
Late potentials (LP) on the signal-averaged electrocardiogram (SAECG) are predictive of malignant ventricular arrhythmias and sudden cardiac death in patients with ischaemic and non-ischaemic cardiomyopathy. Cardiac dysfunction, both regional and global, as well as supraventricular and ventricular arrhythmias are reported in a high percentage of patients with end-stage renal failure (ESRF). The aim of the study was to assess the prevalence of LP and the effects of haemodialysis on the SAECG of ESRF patients. SAECG was recorded immediately before and within 30 min after the end of dialysis in 48 patients in sinus rhythm, free of conduction disturbances on ECG and of signs of congestive heart failure. Serum electrolytes were sampled together with the SAECG recordings. An echo-Doppler exam was performed within 2 weeks of the study. SAECGs were adequate for analysis in 45/48 patients. LP were present when at least two of the following criteria were fulfilled: QRS duration < or = 115 ms, LAS40 < or = 38 ms, RMS40 > or = 38 microV at 40 Hz high pass bidirectional filter, and noise <0.7 microV. LP were detected in 12/45 patients (25%) on the SAECG before dialysis; of these 12 patients, seven had a history of a previous myocardial infarction and two had documented coronary artery disease (CAD). A significant greater wall motion score index--calculated on a 16 segment model--was reported in patients with LP (1.20+/-0.20 vs 1.01+/-0.03, P<0.01), while left ventricular mass was comparable in the two groups of patients. At the end of dialysis, a significant prolongation of fQRS duration was found both at 25 and 40 Hz filters (from 98+/-11 to 106+/-16 ms and from 97+/-12 s to 102+/-13 ms, respectively, P<0.001). A significant inverse relationship was seen between the percentage of dialysis-induced serum potassium reduction and fQRS changes at 40 Hz (r=-0.68, P<0.001). LP were detected in a significant proportion of dialysis patients, probably related to underlying CAD with left ventricular dysfunction. Prolongation of fQRS after dialysis could be explained by the acute reduction in serum potassium levels.


What types of epilepsy are preceded by febrile seizures? A population-based study of children.
In a population of 850,000, the authors studied afebrile seizures that follow febrile seizures. Review of all paediatric EEGs identified 504 children with epilepsy beginning between 1977 and 1985. Follow-up averaged 85 months. 14.9 per cent had preceding febrile seizures: 13 per cent complex partial, 13 per cent partial/secondary generalized and 22 per cent generalized tonic-clonic. The rate of preceding febrile seizures did not vary with the cause of epilepsy. Prolonged febrile seizures were not associated with any particular afebrile seizure type. Of 17 with preceding prolonged febrile seizures, seven developed intractable epilepsy: 17.9 per cent of the total intractable cases. Only two developed idiopathic intractable complex partial seizures after prolonged febrile seizures. The authors conclude that febrile seizures most often precede generalized tonic-clonic afebrile seizures. Prolonged febrile seizures rarely precede idiopathic intractable complex partial seizures. The febrile seizure tendency may be a fundamental marker of an individual's seizure threshold.


Experimentation Management in the Co-Created Smart-City: Incentivization and Citizen Engagement.
Under the smart city paradigm, cities are changing at a rapid pace. In this context, it is necessary to develop tools that allow service providers to perform rapid deployments of novel solutions that can be validated by citizens. In this sense, the OrganiCity experimentation-as-a-service platform brings about a unique solution to experiment with new urban services in a co-creative way, among all the involved stakeholders. On top of this, it is also necessary to ensure that users are engaged in the experimentation process, so as to guarantee that the resulting services actually fulfill their needs. In this work, we present the engagement monitoring framework that has been developed within the OrganiCity platform. This framework permits the tailored definition of metrics according to the experiment characteristics and provides valuable information about how citizens react to service modifications and incentivization campaigns.


Surface immobilized antibody orientation determined using ToF-SIMS and multivariate analysis.
Antibody orientation at solid phase interfaces plays a critical role in the sensitive detection of biomolecules during immunoassays. Correctly oriented antibodies with solution-facing antigen binding regions have improved antigen capture as compared to their randomly oriented counterparts. Direct characterization of oriented proteins with surface analysis methods still remains a challenge however surface sensitive techniques such as Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) provide information-rich data that can be used to probe antibody orientation. Diethylene glycol dimethyl ether plasma polymers (DGpp) functionalized with chromium (DGpp+Cr) have improved immunoassay performance that is indicative of preferential antibody orientation. Herein, ToF-SIMS data from proteolytic fragments of anti-EGFR antibody bound to DGpp and DGpp+Cr are used to construct artificial neural network (ANN) and principal component analysis (PCA) models indicative of correctly oriented systems. Whole antibody samples (IgG) test against each of the models indicated preferential antibody orientation on DGpp+Cr. Cross-reference between ANN and PCA models yield 20 mass fragments associated with F(ab')2 region representing correct orientation, and 23 mass fragments associated with the Fc region representing incorrect orientation. Mass fragments were then compared to amino acid fragments and amino acid composition in F(ab')2 and Fc regions. A ratio of the sum of the ToF-SIMS ion intensities from the F(ab')2 fragments to the Fc fragments demonstrated a 50% increase in intensity for IgG on DGpp+Cr as compared to DGpp. The systematic data analysis methodology employed herein offers a new approach for the investigation of antibody orientation applicable to a range of substrates. Controlled orientation of antibodies at solid phases is critical for maximizing antigen detection in biosensors and immunoassays. Surface-sensitive techniques (such as ToF-SIMS), capable of direct characterization of surface immobilized and oriented antibodies, are under-utilized in current practice. Selection of a small number of mass fragments for analysis, typically pertaining to amino acids, is commonplace in literature, leaving the majority of the information-rich spectra unanalyzed. The novelty of this work is the utilization of a comprehensive, unbiased mass fragment list and the employment of principal component analysis (PCA) and artificial neural network (ANN) models in a unique methodology to prove antibody orientation. This methodology is of significant and broad interest to the scientific community as it is applicable to a range of substrates and allows for direct, label-free characterization of surface bound proteins.


Validation of Perceptual Strain Index to Evaluate the Thermal Strain in Experimental Hot Conditions.
The incidence of heat stress is one of the most common problems in workplaces and industries. Many heat stress indices have been developed, and these indices have some disadvantages. The purpose of this study is to validate the perceptual strain index (PeSI) in experimental hot conditions. This study is of cross-sectional carried out on 15 men at five different thermal conditions (35°C, 30°C, 27°C, 24°C, and 21°C) in a climate chamber and on a treadmill at three levels of light (2.4 kph), medium (4.8 kph) and heavy activity (6.3 kph). Heart rate and oral temperature were respectively measured to calculate the physiological strain index. Also, thermal sensation and rate perceive exertion were respectively measured to calculate the PeSI. Finally, the correlation between the indices was analyzed using Pearson correlation test and regression analysis. Pearson correlation test showed a high correlation (r = 0.94) between the PeSI and physiological strain index (P = 0/001). It was also observed a high correlation between the PeSI and the oral temperature (r = 0.78, P = 0/001) and the heart rate (r = 0.90, P = 0/001). In addition, there was found a moderate correlation (r = 0.71) between the PeSI and the wet bulb glob temperature (P = 0/001). However, there was no correlation between the PeSI and the body mass index (r = 0.0009, P = 0.79). The research findings showed when there is no access to other forms of methods to evaluate the heat stress, it can be used the PeSI in evaluating the strain because of its favorable correlation with the thermal strain.


Diagnosis of fanconi anemia: chromosomal breakage analysis.
Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked. Cells derived from FA patients are-by definition-hypersensitive to DNA cross-linking agents, such as mitomycin C, diepoxybutane, or cisplatinum, which becomes manifest as excessive growth inhibition, cell cycle arrest, and chromosomal breakage upon cellular exposure to these drugs. Here we provide a detailed laboratory protocol for the accurate assessment of the FA diagnosis as based on mitomycin C-induced chromosomal breakage analysis in whole-blood cultures. The method also enables a quantitative estimate of the degree of mosaicism in the lymphocyte compartment of the patient.


First record of Viminella sp. (Anthozoa: Alcyonacea: Ellisellidae) in the Persian Gulf.
This paper presents the first record of Viminella Gray 1870 from the Persian Gulf. This genus has a global distribution and its largest distribution is in the Indo-Pacific region. A single specimen was collected by a local fisherman from south Hengam Island (the north Persian Gulf) from 60-70 m depth. Colony morphology characteristics were examined by stereomicroscope and optical microscope. Descriptions of the colony and other taxonomic characteristics are provided. The colony is unbranched with a height of 12 cm and its basal diameter is approximately 1.63 mm. The sclerites of the coenenchyme comprise a variety of symmetrical double heads and capstan-like forms (0.05-0.11 mm). In the wall of calyces, slightly elongated double heads, capstans and spindles (about 0.08-0.19 mm) are present. Our finding extends the known geographical distribution of this genus in the Indo-Pacific region to the Persian Gulf.


Scopolamine induces recovery of shuttle box avoidance behavior after frontal cortex ablation.
The learning and reversal of shuttle box active avoidance behavior in animals with a bilateral frontal cortex ablation was investigated during and after scopolamine or pilocarpine treatment. Scopolamine facilitated the performance of the avoidance task in normal animals and in those with frontal cortex lesions and also increased the number of intertrial responses, while pilocarpine increased the deleterious effects of the lesions. Furthermore, in the absence of scopolamine, the animals previously treated with the drug showed that its beneficial effects persisted while the number of intertrial responses were no longer increased. The results indicate that the beneficial effects of scopolamine treatment on active avoidance behavior are independent from the effects observed on intertrial activity since only the former are observed after drug withdrawal. Therefore, scopolamine treatment seems to induce a long lasting recovery process in frontal cortex ablated animals.


Engineered cystine-knot peptides that bind alpha(v)beta(3) integrin with antibody-like affinities.
The alpha(v)beta(3) integrin receptor is an important cancer target due to its overexpression on many solid tumors and the tumor neovasculature and its role in metastasis and angiogenesis. We used a truncated form of the Agouti-related protein (AgRP), a 4-kDa cystine-knot peptide with four disulfide bonds and four solvent-exposed loops, as a scaffold for engineering peptides that bound to alpha(v)beta(3) integrins with high affinity and specificity. A yeast-displayed cystine-knot peptide library was generated by substituting a six amino acid loop of AgRP with a nine amino acid loop containing the Arg-Gly-Asp integrin recognition motif and randomized flanking residues. Mutant cystine-knot peptides were screened in a high-throughput manner by fluorescence-activated cell sorting to identify clones with high affinity to detergent-solubilized alpha(v)beta(3) integrin receptor. Select integrin-binding peptides were expressed recombinantly in Pichia pastoris and were tested for their ability to bind to human cancer cells expressing various integrin receptors. These studies showed that the engineered AgRP peptides bound to cells expressing alpha(v)beta(3) integrins with affinities ranging from 15 nM to 780 pM. Furthermore, the engineered peptides were shown to bind specifically to alpha(v)beta(3) integrins and had only minimal or no binding to alpha(v)beta(5), alpha(5)beta(1), and alpha(iib)beta(3) integrins. The engineered AgRP peptides were also shown to inhibit cell adhesion to the extracellular matrix protein vitronectin, which is a naturally occurring ligand for alpha(v)beta(3) and other integrins. Next, to evaluate whether the other three loops of AgRP could modulate integrin specificity, we made second-generation libraries by individually randomizing these loops in one of the high-affinity integrin-binding variants. Screening of these loop-randomized libraries against alpha(v)beta(3) integrins resulted in peptides that retained high affinities for alpha(v)beta(3) and had increased specificities for alpha(v)beta(3) over alpha(iib)beta(3) integrins. Collectively, these data validate AgRP as a scaffold for protein engineering and demonstrate that modification of a single loop can lead to AgRP-based peptides with antibody-like affinities for their target.


Evaluation of use of a new chromogenic agar in detection of urinary tract pathogens.
CHROMagar Orientation, a new chromogenic medium, was evaluated for the detection and differentiation of gram-positive and gram-negative pathogenic microorganisms in 900 urine samples from hospitalized patients. Performance characteristics of the medium were evaluated in comparison to those of 5% sheep blood and MacConkey agars by direct inoculation of the urine samples on the three media. Four gram-negative and two gram-positive strains as well as one yeast control strain from the American Type Culture Collection were used to ensure quality control. CHROMagar Orientation succeeded in detecting all the urine pathogens that were detected by the reference media, including gram-negative bacilli, staphylococci, streptococci, and yeasts. Colony color and morphology on CHROMagar Orientation accurately differentiated Escherichia coli, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, and Acinetobacter spp. Owing to the similarity in the pigmentation produced by Klebsiella, Enterobacter, and Citrobacter isolates, the medium failed to distinguish among them; however, these isolates were easily recognized as coliforms because of their metallic blue coloration. Staphylococci were clearly perceptible: S. aureus and S. epidermidis grow in regular-size colonies that range from opaque white to yellowish, and S. saprophyticus produces opaque pink colonies. All streptococcus strains, including those from groups B and C, were detected. They grow as undifferentiated flat dry diffused colonies, and additional tests were required for identification. Enterococci were easily discriminated by their strong turquoise pigmentation and their typical growth on the agar's surface. Yeast grow in typical creamy wet convex colonies. The accuracy of antibiotic susceptibility determinations according to standard methods was also tested by picking isolates directly from CHROMagar Orientation. The results showed excellent correlation with those obtained with microorganisms picked from reference media. Owing to the ease in differentiating mixed flora on CHROMagar Orientation, antimicrobic susceptibility tests were performed directly from primary isolates in all cases without the need for subcultures.


Meta-Analysis of Matrix Metalloproteinases in the Risk of Cardiovascular and Neurodegenerative Diseases.
To investigate the risk of cardiovascular and neurodegenerative diseases induced by matrix metalloproteinases (MMPs) by meta-analysis. Relevant literature was searched from Wanfang Medical Center, CNQI, VIP, PubMed, and other domestic and foreign literature databases for the research direction, and the risk of cardiovascular and neurodegenerative diseases induced by MMPs was meta-analyzed using the fixed-effect model and random-effect model. MMP-1 and MMP-9 were risk factors for cardiovascular diseases by fixed and random-effect model analysis, respectively, while MMP-2 and MMP-9 were risk factors for increased neurodegenerative diseases by random-effect model analysis. MMP-1 and MMP-9 are risk factors for cardiovascular diseases, and MMP-2 and MMP-9 are major factors for increased risk of neurodegenerative diseases. MMP-1, MMP-2, and MMP-9 can be used as new targets for clinical diagnosis, treatment, and research of subsequent cardiovascular and neurodegenerative diseases.


Changes in bone in a model of spinal cord injury.
Bone calcium, histomorphometry, and mechanical strength were evaluated in a model of spinal cord injury. Cortical bone area and rates of formation and apposition at the tibiofibular junction (TFJ) and midshaft of the humerus were measured at 35-42, 42-77, and 77-94 days after transection of the spinal cord. All comparisons were between the animals with a spinal lesion and control animals. A 0.34% difference in the length of the tibia of the two groups of animals was observed, the dry weight of the tibia was 28.4% less in rats with a lesion, and there was no significant difference in the amount of calcium per milligram of bone. At 35 days after surgery, the cortical area in the midshaft of the humerus was slightly less (11%) in rats with a lesion, but by 94 days there was no difference in cortical or medullary area. The final (day 94) cortical area at the TFJ in rats with a lesion was less than that in the controls. Bone formation at the TFJ was similar in both groups in the period of 35-42 days and was similar at 77-94 days in the animals with a lesion, and rates of formation and apposition were greater in the humerus of rats with a lesion; the rates did not differ significantly between groups at either site. At 94 days, trabecular bone area in the tibial metaphysis was 41% less in rats with a lesion. Mechanical parameters were significantly less in the femora, but not the humeri, of rats with a lesion.


Enzymatic properties of human cytosolic phospholipase A(2)gamma.
The enzymatic properties of cytosolic phospholipase A(2)gamma (cPLA(2)gamma), an isoform of 85-kDa group IV cPLA(2)alpha (cPLA(2)alpha) were studied in vitro and when the enzyme was expressed in cells. cPLA(2)gamma expressed in Sf9 cells is associated with membrane. Membranes isolated from [(3)H]arachidonic acid-labeled Sf9 cells expressing cPLA(2)gamma, constitutively release [(3)H]arachidonic acid. The membrane-associated activity is inhibited by the group IV PLA(2) inhibitor methylarachidonyl fluorophosphonate, but not effectively by the group VI PLA(2) inhibitor (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one. cPLA(2)gamma has higher lysophospholipase activity than PLA(2) activity. Purified His-cPLA(2)gamma does not exhibit phospholipase A(1) activity, but sequentially hydrolyzes fatty acid from the sn-2 and sn-1 positions of phosphatidylcholine. cPLA(2)gamma overexpressed in HEK293 cells is constitutively active in isolated membranes, releasing large amounts of oleic, arachidonic, palmitic, and stearic acids; however, basal fatty acid release from intact cells is not increased. cPLA(2)gamma overexpressed in lung fibroblasts from cPLA(2)alpha-deficient mice is activated by mouse serum resulting in release of arachidonic, oleic, and palmitic acids, whereas overexpression of cPLA(2)alpha results primarily in arachidonic acid release.


The transcription factor FOXN3 inhibits cell proliferation by downregulating E2F5 expression in hepatocellular carcinoma cells.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and the mechanisms underlying the development of HCC remain to be elucidated. Forkhead box N3 (FOXN3) is an important member of the FOX family of transcription factors that plays an essential role in several cancers but has not been investigated in HCC. In this study, we demonstrate that FOXN3 is downregulated in human primary HCC tissues compared with their matched adjacent liver tissues. Functional tests of FOXN3 demonstrated that FOXN3 inhibits the proliferation of HCC cells in vitro and in vivo. Additionally, FOXN3 repressed the mRNA and protein expression of E2F5, a reported potential oncogene, by inhibiting the promoter activity of E2F5. Collectively, our findings indicate that FOXN3 functions as a tumor suppressor in HCC by downregulating the expression of E2F5.


Drinking-water quality, sanitation, and breast-feeding: their interactive effects on infant health.
The promotion of proper infant feeding practices and the improvement of environmental sanitation have been two important strategies in the effort to reduce diarrhoeal morbidity among infants. Breast-feeding protects infants by decreasing their exposure to water- and foodborne pathogens and by improving their resistance to infection; good sanitation isolates faecal material from the human environment, reducing exposures to enteric pathogens. Taken together, breast-feeding and good sanitation form a set of sequential barriers that protect infants from diarrhoeal pathogens. As a result, breast-feeding may be most important if the sanitation barrier is not in place. This issue is explored using data from a prospective study of 2355 urban Filipino infants during the first 6 months of life. Longitudinal multivariate analyses are used to estimate the effects of full breast-feeding and mixed feeding on diarrhoeal disease at different levels of sanitation. Breast-feeding provides significant protection against diarrhoeal disease for infants in all environments. Administration of even small portions of contaminated water supplements to fully breast-fed infants nearly doubles their risk of diarrhoea. Mixed-fed and weaned infants consume much greater quantities of supplemental liquids, and as a result, the protective effect of full breast-feeding is greatest when drinking-water is contaminated. Similarly, full breast-feeding has stronger protective effects among infants living in crowded, highly contaminated settings.


Impact of Zika virus for infertility specialists: current literature, guidelines, and resources.
In the past 2 years, Zika virus has emerged from obscurity onto the world stage-traversing and transcending clinical specialties, basic science disciplines, and public health efforts. The spread of Zika virus has serious implications for the specialty of reproductive endocrinology and infertility. Our patients, practices, and labs-worldwide and specifically in the USA-have been impacted by this teratogenic, sexually transmitted, largely asymptomatic virus. While the World Health Organization's Public Emergency of International Concern designation has lapsed as major epidemics have subsided and understanding of risks is in part clarified, the acute and long-term threat to pregnant patients is not over. The risk of wider spread in the USA is not insignificant, the subtler and long-ranging consequences beyond microcephaly are not fully known, large geographic areas of risk still contain naïve populations, and whether Zika will continue to be an intermittent risk in endemic areas is uncertain. Staying up to date with the burgeoning research on Zika virus is an important objective for the infertility specialist. Here, we review in detail the most relevant recent developments, discuss applicable guidelines, and propose strategies for contributing to a reduction in the risk and burden of Zika virus.


[Percutaneous thrombus aspiration and thrombolysis for the treatment of acute portal vein thrombosis in a 5-year-old child].
Early portal vein thrombosis is a frequent and severe complication following pediatric liver transplantation. The clinical presentation is characterized by signs and symptoms of portal hypertension such as ascites and digestive hemorrhage. Primary treatment consists of heparin therapy. In the case of persistent or progressive thrombosis or symptoms, surgical thrombectomy or retransplantation should be considered. However, surgical intervention is associated with significant morbidity and mortality. We report on successful minimally invasive percutaneous thrombus aspiration and thrombolysis for the treatment of acute portal vein thrombosis in a 5-year-old child post liver transplantation.


A biologically active lectin of enteroaggregative Escherichia coli.
The pathogenesis of enteroaggregative Escherichia coli, a major contributor to paediatric diarrhoea, is still not clearly understood. A complex carbohydrate specific lectin was identified from the culture supernatant of an enteroaggregative E. coli strain. The lectin was purified to 660-fold by a combination of sequential saturated ammonium sulphate precipitation and gel filtration chromatography in the FPLC system. The homogeneity of the purified lectin was established by analytical isoelectrofocusing [pI 6.75]. Hemagglutination of rabbit erythrocytes by the purified lectin was best inhibited by fetuin. The N-terminal sequence of the 41.7 kDa subunit showed homology to the outermembrane porins and the 23.4 kDa subunit showed homology to a hypothetical protein of Yersinia pestis and secreted Hcp protein. This protein could induce extensive morphological changes in HEp-2 cells and significant amount of fluid accumulation in rabbit ileal loop. GM1 showed maximum binding to the lectin among all other gangliosides. This purified protein showed cross-reactivity to the binding subunit of cholera toxin in western immunoblot. The presence of this toxin in some of the clinical isolates of enteroaggregative E. coli was also observed. The structural and functional characteristics of the toxin revealed that it is a novel virulence determinant of aggregative E. coli.


Active reactions of the rabbit ear artery to distension.
Changes in the external diameter of active arteries, excised from the rabbit ear, were recorded following jumps in pressure within the arteries. The arteries were either spontaneously active or were constricted with noradrenaline. Active arteries dilated when the transmural pressure was jumped from 60 to 100 mmHg, but the dilatation was largely, sometimes completely, overcome by compensatory constriction within 1-2 min. Varying the constriction from 15 to 80% of the maximal constriction had no effect on the ability of the arteries to counteract distension. An average of 90 +/- 2% of the distension was overcome in 2 min and this was achieved against increases in stress (force/wall cross-sectional area) on the muscle of not less than 74%. Jumps in pressure rarely enhanced constriction and then only when constriction was slight (less than 15% of maximal). Restoring the transmural pressure to 60 from 100 mmHg produced a transient constriction when the initial constriction was less than 50% of the maximal constriction. The sequence of counteraction of distension and transient constriction on reversing the pressure jump was reproducible for many hours. Increasing constriction of the arteries first decreased and then, at maximal constriction, suppressed all transient changes in diameter. Smaller jumps in pressure produced less dilatation which was more readily prevented by increasing constriction. These results show that the wall of the ear artery possesses a pressure-sensitive, negative feed-back mechanism which minimized changes in diameter following jumps in pressure.


Tears of Joy as an Emotional Expression of the Meaning of Life.
This article describes a research project in which a qualitative research was carried out consisting of 24 semi-structured interviews and a subsequent data analysis using the MAXQDA software in order to investigate a particular dimorphic emotional expression: tears of joy (TOJ). The working hypothesis is that TOJ are not only an atypical expression due to a "super joy," or that they are only an attempt by the organism to self-regulate the excess of joyful emotion through the expression of the opposite emotion (sadness), but that it is an emotional experience in its own right-not entirely overlapping with joy-with a specific adaptive function. Through the interviews, conducted in a cross-cultural context (mainly in India and Japan), we explored the following possibility: what if the adaptive function of crying for joy were to signal, to those experiencing it, the meaning of their life; the most important direction given to their existence? The material collected provided positive support for this interpretation.


The correlation between increased reactivity of the bronchi and of mediator releasing cells in asthma.
The hypothesis that increased reactivity in asthma is not always limited to the bronchi but also exists in the mediator releasing system was investigated in forty-five asthmatic children, approximately half of whom had exercise-induced bronchoconstriction (EIB). The bronchial threshold to histamine was measured as an indicator of the reactivity of the bronchi and the histamine release from leucocytes without adding allergen (spontaneous histamine release) was considered as an indicator of the reactivity of the basophil leucocytes. There was a significant correlation between the histamine threshold and spontaneous histamine release and between these and EIB. These findings support the hypothesis.


[Chronic allograft dysfunction: role of immunosuppressive treatment].
Renal transplantation is the treatment of choice for patients with end-stage renal disease. In recent years a major improvement has been observed in short-term graft survival, but there has been no corresponding improvement in long-term survival. Chronic allograft dysfunction (CAD) is an anatomical and clinical alteration that can lead to the loss of the transplanted organ without any specific cause. The pathogenesis of CAD, which still remains to be fully clarified, involves both immunological factors (acute rejection, subclincial rejection, HLA mismatches between donor and recipient, noncompliance, etc) and non-immunological factors (marginal donor ischemia/reperfusion injury, infection, cardiovascular risk factors, nephrotoxicity, etc). Immunosuppressive therapy represents one of the strategies for the prevention of CAD. The introduction into clinical practice of novel immunosuppressive agents with no or lower nephrotoxicity, like mycophenolate mofetile, rapamycin and everolimus, will make therapeutic strategies aimed at decreasing the incidence of CAD feasible.


Larger genetic differences within africans than between Africans and Eurasians.
The worldwide pattern of single nucleotide polymorphism (SNP) variation is of great interest to human geneticists, population geneticists, and evolutionists, but remains incompletely understood. We studied the pattern in noncoding regions, because they are less affected by natural selection than are coding regions. Thus, it can reflect better the history of human evolution and can serve as a baseline for understanding the maintenance of SNPs in human populations. We sequenced 50 noncoding DNA segments each approximately 500 bp long in 10 Africans, 10 Europeans, and 10 Asians. An analysis of the data suggests that the sampling scheme is adequate for our purpose. The average nucleotide diversity (pi) for the 50 segments is only 0.061% +/- 0.010% among Asians and 0.064% +/- 0.011% among Europeans but almost twice as high (0.115% +/- 0.016%) among Africans. The African diversity estimate is even higher than that between Africans and Eurasians (0.096% +/- 0.012%). From available data for noncoding autosomal regions (total length = 47,038 bp) and X-linked regions (47,421 bp), we estimated the pi-values for autosomal regions to be 0.105, 0.070, 0.069, and 0.097% for Africans, Asians, Europeans, and between Africans and Eurasians, and the corresponding values for X-linked regions to be 0.088, 0.042, 0.053, and 0.082%. Thus, Africans differ from one another slightly more than from Eurasians, and the genetic diversity in Eurasians is largely a subset of that in Africans, supporting the out of Africa model of human evolution. Clearly, one must specify the geographic origins of the individuals sampled when studying pi or SNP density.


Apparent Interfacial Tension Effects in Protein Stabilized Emulsions Prepared with Microstructured Systems.
Proteins are mostly used to stabilize food emulsions; however, production of protein containing emulsions is notoriously difficult to capture in scaling relations due to the complex behavior of proteins in interfaces, in combination with the dynamic nature of the emulsification process. Here, we investigate premix membrane emulsification and use the Ohnesorge number to derive a scaling relation for emulsions prepared with whey protein, bovine serum albumin (BSA), and a standard emulsifier Tween 20, at various concentrations (0.1%, 0.5%, 1.25% and 2%). In the Ohnesorge number, viscous, inertia, and interfacial tension forces are captured, and most of the parameters can be measured with great accuracy, with the exception of the interfacial tension. We used microfluidic Y-junctions to estimate the apparent interfacial tension at throughputs comparable to those in premix emulsification, and found a unifying relation. We next used this relation to plot the Ohnesorge number versus P-ratio defined as the applied pressure over the Laplace pressure of the premix droplet. The measured values all showed a decreasing Ohnesorge number at increasing P-ratio; the differences between regular surfactants and proteins being systematic. The surfactants were more efficient in droplet size reduction, and it is expected that the differences were caused by the complex behavior of proteins in the interface (visco-elastic film formation). The differences between BSA and whey protein were relatively small, and their behavior coincided with that of low Tween concentration (0.1%), which deviated from the behavior at higher concentrations.


High-Performance Cathode Based on Microporous Mo-V-Bi Oxide for Li Battery and Investigation by Operando X-ray Absorption Fine Structure.
The development of cathode-active material of Li battery is important for the current emerging energy transferring and saving problems. A stable crystalline microporous complex metal oxide based on Mo, V, and Bi is an active and suitable material for Li battery. High capacity (380 Ah/kg) and stable cycle performance are achieved. X-ray absorption near-edge structure analyses demonstrate that the original Mo6+ and V4+ ions are reduced to Mo4+ and V3+ in the discharging process, respectively, which results in a 70-electron reduction per formula. The reduced metal ions can be reoxidized reversibly in the next charging process. Furthermore, extended X-ray absorption fine structure analyses reveal that the Mo-O bonds in the material are lengthened in the discharging process probably due to interaction with Li+ without change of the basic structure.


Reduced expression of somatostatin in GABAergic interneurons derived from induced pluripotent stem cells of patients with parkin mutations.
Parkinson's disease (PD) is associated with both motor and non-motor symptoms, including constipation, sensory neuropathy, depression, dementia and sleep disorder. Somatostatin (SST) is considered to be a modulator of GABAergic inhibitory transmission, and its levels are reduced in cerebrospinal fluid of PD patients. In the present study, we evaluated the changes in the expression of SST in GABAergic neurons derived from induced pluripotent stem cells (iPSCs) of PD patients. Neural cells were co-treated with the Wnt antagonist IWP-2 and Shh during neurosphere formation to induce GABA-positive forebrain interneurons. Quantitative analyses showed no significant differences, but slight decreases, in the potency of differentiation into GABAergic neurons derived from iPSCs between healthy control and patients with PARK2 mutations, who have been classified as a type of early-onset familial PD due to mutations in the parkin gene. Under this condition, the mRNA level of SST in GABAergic interneurons derived from iPSCs of PARK2-specific PD patients significantly decreased as neural maturation progressed. We also found that SST-positive GABAergic neurons were clearly reduced in GABAergic neurons derived from iPSCs of patients with PARK2 mutations. These findings suggest that the reduction in the expression level of SST in GABAergic interneurons of PD may, at least partly, lead to complex PD-induced symptoms.


Acoustic myography in the assessment of human masseter muscle.
The feasibility of examining electro-mechanical activity of the human masseter muscles using non-invasive recording techniques was examined in six healthy dentate adults (aged 34-57 years). Electrical activity of the muscle was examined by surface electromyography (EMG) and the mechanical activity, in the form of muscle sounds, was examined by acoustic myography (AMG). Bilateral recordings of EMG and AMG were made simultaneously using composite probes which were placed on the skin over the masseter muscles. A standardized pressure was applied to the probes via adjustable rods attached to a safety helmet. Pressures were monitored by strain gauges placed between the ends of the rods and the probes. With the subject seated, recordings of AMG and EMG were obtained during maximal jaw clenching for 4 s and the raw signals were stored on a computer. Of three maximal contractions performed, the last two were used in the analysis. The raw amplified signals underwent frequency analysis by fast Fourier Transform. Total activity was also assessed after amplification, full-wave rectification and integration, and repeatability of the results was assessed. The AMG frequency range was 6-15 Hz and was similar to values for other human skeletal muscles. The integrated values for EMG and AMG were repeatable on both sides of the face (IEMG, right r = 0.99, left r = 0.99; IAMG right r = 0.70, left r = 0.71). Simultaneous recordings of AMG and EMG from the masseter muscles may be useful for assessing electro-mechanical muscle function but further validation studies are required before the technique can be used clinically.


Antibiotic-resistant Pseudomonas aeruginosa infection in patients with bronchiectasis: prevalence, risk factors and prognostic implications.
Pseudomonas aeruginosa (PA) is the most common pathogen in bronchiectasis and frequently develops resistance to multiple classes of antibiotics, but little is known about the clinical impacts of PA-resistant (PA-R) isolates on bronchiectasis. We, therefore, investigated the prevalence, risk factors and prognostic implications of PA-R isolates in hospitalized bronchiectasis patients. Between June 2011 and July 2016, data from adult bronchiectasis patients isolated with PA at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. PA was classified as PA-R in case antibiogram demonstrated resistance on at least one occasion. Seven hundred forty-seven bronchiectasis patients were assessed. Of these, 147 (19.7%) had PA isolate in the sputum or bronchoscopic culture. PA-R and PA-sensitive accounted for 88 (59.9%) and 59 (31.1%) patients, respectively. In multivariate model, factors associated with PA-R isolate in bronchiectasis included prior exposure to antibiotics (odds ratio [OR] =6.18), three or more exacerbations in the previous year (OR =2.81), higher modified Medical Research Council dyspnea scores (OR =1.93) and greater radiologic severity (OR =1.15). During follow-up (median: 26 months; interquartile range: 6-59 months), 36 patients died, of whom 24 (66.7%) had PA-R isolate at baseline. However, PA-R isolate was not associated with greater all-cause mortality in bronchiectasis. PA-R infection is common among bronchiectasis patients, mainly determined by prior exposure to antibiotics, frequent exacerbations, more pronounced dyspnea and more severe radiologic involvement. However, PA-R isolate is not an independent risk factor for all-cause mortality in bronchiectasis.


Ciliary beat frequency in transplanted lungs.
Patients with lung transplantation are prone to respiratory infections. Generally this is attributable to the effects of immunosuppressive drugs but mucociliary clearance has been found to be impaired in these subjects. A study was performed to determine whether this finding is accompanied by a reduction in ciliary beat frequency (CBF). Six patients who had undergone single lung transplantation for fibrosing lung disease were investigated. CBF was measured in mucosal samples from native and transplanted bronchi by a videophotometry method. The CBF was reduced in the transplanted bronchi in all cases when both fastest and slowest beating cilia were examined. The fastest beating cilia on the native side had a mean (SD) CBF of 12.1 (1.3) Hz compared with 9.6 (2.0) Hz on the transplanted side. The slowest beating cilia also had reduced CBF on the transplanted side. In patients with fibrotic lung disease, CBF is reduced in transplanted bronchi in comparison with native bronchi.