Use of snus and smoking tobacco among pregnant women in the Agder counties.
The use of snus during pregnancy increases the risk of stillbirths, premature delivery and reduced birthweight. People have been warned against smoking during pregnancy, but less so against the use of snus. We have investigated the use of snus and smoking tobacco among pregnant women in the Agder counties. Data on pregnant women and 10 583 births for the years 2012, 2013 and 2014 were retrieved from the electronic birth records of Sørlandet Hospital. In the three-year period 2012 – 2014, altogether 5 % used snus and 19 % used smoking tobacco before pregnancy and 2 % and 8 % respectively at the end of pregnancy. The use of snus before pregnancy increased from 3.6 % in 2012 to 6.8 % in 2014. The equivalent figures for the first trimester were 1.7 % and 3.4 %, and for the last trimester 1.2 % and 2.1 %. The use of smoking tobacco declined by 2 % over the three-year period. In the age group 16 – 24 years, a total of 12 % used snus before pregnancy and 5 % at the end. Of 522 women who used snus before their pregnancy, altogether 57.5 % had quit during the first trimester and 71.4 % during the third trimester. The corresponding figures for those 2 015 women who used smoking tobacco before their pregnancy were 45.2 % and 58.0 % (p < 0.001). The use of snus before and during pregnancy doubled over the three-year period 2012 – 2014. The use was especially widespread in the youngest age groups. The proportion of women who quit using snus during their pregnancy was significantly higher than the proportion that quit smoking.


Estimating updraft velocity components over large spatial scales: contrasting migration strategies of golden eagles and turkey vultures.
Soaring birds migrate in massive numbers worldwide. These migrations are complex and dynamic phenomena, strongly influenced by meteorological conditions that produce thermal and orographic uplift as the birds traverse the landscape. Herein we report on how methods were developed to estimate the strength of thermal and orographic uplift using publicly available digital weather and topography datasets at continental scale. We apply these methods to contrast flight strategies of two morphologically similar but behaviourally different species: golden eagle, Aquila chrysaetos, and turkey vulture, Cathartes aura, during autumn migration across eastern North America tracked using GPS tags. We show that turkey vultures nearly exclusively used thermal lift, whereas golden eagles primarily use orographic lift during migration. It has not been shown previously that migration tracks are affected by species-specific specialisation to a particular uplift mode. The methods introduced herein to estimate uplift components and test for differences in weather use can be applied to study movement of any soaring species.


Effects on breathing of medullary bicuculline microinjections in immature opossums.
The role of medullary gamma-aminobutyric acid A (GABAA)-receptor activation in the expression of breathing was studied in suckling opossums (Didelphis virginiana) from 4 to 8 wk of age. Animals were anesthetized with a thiobarbiturate, and the ventral medulla was exposed so that drugs could be microinjected into the medulla with a two-barrel glass micropipette. The GABAA antagonist bicuculline at approximately 1-3 pmol total dose was injected in volumes < 1 nl; injections of saline with pontamine sky blue dye were used as controls and to mark location. Breathing pattern was assessed using diaphragm electromyography (EMG). Effective sites for bicuculline microinjection were obtained in the ventrolateral medulla, with both lateral reticular and inferior olive nuclei present as rostrocaudal markers. Responses among 18 tested animals included increased duration of breaths (Ttot) and duration of inspiration (Ti). Peak amplitude of the diaphragm EMG and peak amplitude of the diaphragm/Ti were not consistently affected. Transient apnea, lasting at least 8 s, occurred in five of the animals. Control solutions did not elicit respiratory responses. These results suggest that neural circuitry in the medulla, using the neurotransmitter GABA, can have an early role in the modulation of breathing pattern.


Cephalexin in lower respiratory tract infections.
Cephalexin has had 12 years of extensive clinical usage in the management of respiratory tract and other infections. It is reliably absorbed from the gastrointestinal tract and reaches therapeutic levels in serum and tissues. Toxicity and adverse side effects are minimal. The antimicrobial spectrum includes a majority of the pathogens usually associated with community-acquired lower respiratory tract infections with the significant exception of Haemophilus influenzae. Resistance of H. influenzae strains reduces the uses of cephalexin in the paediatric population and may limit its effectiveness in some patients with acute exacerbations of chronic bronchitis. In contrast, it is inordinately effective in managing most adult patients with lower respiratory tract infections, either as a primary agent, as a substitute for penicillins or other antimicrobial agents in patients unable to receive these, or for continuation of therapy in individuals who no longer require parenteral compounds. As with other cephalosporins, caution should be exercised to exclude meningitis when treating patients with respiratory tract infections since the majority of these compounds, including cephalexin, produce little or no cerebrospinal fluid levels.


Genetics of floral traits influencing reproductive isolation between Aquilegia formosa and Aquilegia pubescens.
Abstract: Reproductive isolation between Aquilegia formosa and Aquilegia pubescens is influenced by differences in their flowers through their effects on pollinator visitation and pollen transfer. Here, we investigate the genetic basis of floral characters differentiating these species. We found that in addition to the effects of flower orientation and the length of nectar spurs previously described, other characters such as flower color or odor affect hawkmoth visitation. Repeatability of measurements in an F2 population ranged from 0.53 to 0.83 among five floral traits, indicating that using the means of multiple measures per plant will substantially increase the power of a quantitative trait locus (QTL) analysis. Integration of floral traits was indicated by significant correlations among traits in an F2 population. In a separate F2 population we found that QTL for different floral traits were often closely associated, indicating that linkage or pleiotropy cause at least some of this integration. In addition, we found QTL for all floral traits examined. Because Aquilegia species are largely interfertile and vary extensively in both floral morphology and ecology, they offer the opportunity for QTL studies of a wide range of characters affecting reproductive isolation.


Enzyme immunoassays for bromocriptine and its metabolites.
We have developed two bromocriptine enzyme immunoassays with different specificities for applications in human and animal pharmacokinetic studies. The first assay uses antibodies directed against the cyclopeptide structure of bromocriptine, and is specific for untransformed bromocriptine. The second assay uses antibodies directed against the bromolysergic part of the molecule and allows the measurement of both bromocriptine and its metabolites. Enzymatic tracers were obtained by covalent coupling of bromocriptine analogs to acetylcholinesterase from the electric eel Electrophorus electricus. Both assays have a limit of detection of 10 pg/ml and a limit of quantification of 50 pg/ml. The specificity of the assays was determined following fractionation by high-performance liquid chromatography of rat samples obtained after administration of bromocriptine.


Chorismate mutase/prephenate dehydratase from Escherichia coli K12. 2. Evidence for identical subunits catalysing the two activities.
On the basis of amino acid composition, tryptic fingerprints and the determination of amino acid sequences around the four cysteine residues, it can be concluded that chorismate mutase/prephenate dehydratase from Escherichia coli K12 consists of identical, or closely similar subunits. It follows from this that the mutase and dehydratase activities of the enzyme are probably catalysed on the one subunit.


Immunoadsorption against two distinct epitopes on human type XVII collagen abolishes dermal-epidermal separation induced in vitro by autoantibodies from pemphigoid gestationis patients.
Pemphigoid gestationis (PG) is a subepidermal autoimmune blistering disease characterized by self-reactive T and B cells specific for the transmembrane hemidesmosomal protein type XVII collagen/BP180. Major T and B cell epitopes are located within the immunodominant 16th non-collagenous domain A (NC16A) of type XVII collagen. The aim of the present study was to map the pathogenically relevant epitopes targeted by blister-inducing patients' autoantibodies. For this purpose, we used an in vitro model of autoantibody-induced leukocyte-dependent dermal-epidermal separation. Pre-adsorption against a recombinant form of the NC16A region abolished the blister-inducing potential of autoantibodies from all PG patients. Using overlapping synthetic peptides, we demonstrated that PG autoantibodies bind to two defined epitopes within the NC16A region (aa 500-514 and aa 511-523). Importantly, pre-adsorption using an affinity matrix containing these epitopes completely abolished dermal-epidermal separation induced by PG autoantibodies. This study identifies the epitopes relevant for blister induction in PG and should facilitate the development of an antigen-specific immunoadsorption therapy for this disease.


Nationwide Survey of Knowledge and Health Beliefs regarding Human Papillomavirus among HPV-Vaccinated Female Students in Malaysia.
The National HPV Immunization Programme, which offers free human papillomavirus (HPV) vaccines to teenaged female students, was launched in Malaysia in 2010. HPV vaccination paired with adequate knowledge about HPV infection provides the best protection against cervical cancer. To identify the level of knowledge and the health beliefs towards HPV and the HPV vaccine among HPV-vaccinated female students in Malaysia. A nationwide cross-sectional survey among 14 years old female students who had received three doses of the HPV vaccine was conducted in 32 randomly selected schools from 13 states and 3 federal territories in Malaysia between February 2013 and April 2013. Among 2482 respondents, knowledge about HPV infection and the HPV vaccine was extremely poor. The mean total knowledge score was only 3.56 (SD ± 1.76), out of a possible score of 10. The majority of respondents were unaware that vaccinating boys with HPV can help protect girls against HPV infection (91.6%), HPV cannot be cured (81.6%) and that HPV is a sexually transmitted infection (70.3%). Most of the respondents had the misconception that only females get HPV (95.1%), and that the HPV vaccine eliminates the need for Pap smear tests (68.3%). Most respondents (91.6%) believed that they would not get an HPV infection. Almost half of the respondents (42.9%) held the misconception that HPV infection could not lead to serious illness. Findings revealed poor knowledge about both HPV and the HPV vaccine, low perceived susceptibility to HPV infection and misinformation about HPV infection among HPV-vaccinated girls. Therefore, it is essential to increase the knowledge and awareness of health risks regarding HPV infection among teenaged girls who have received the HPV vaccine.


Interferon-γ release assay in HIV-infected patients with active tuberculosis: impact of antituberculous drugs on host immune response.
The objective of the study was to: 1) investigate the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) in HIV-infected patients with active tuberculosis (TB); 2) evaluate the sequential changes in QFT-GIT assay during the treatment response; 3) investigate the direct in vitro effects of antituberculous drugs on both secretion of IFN-g and apoptosis of T cells. Forty-four HIV-patients with active TB were enrolled and tested with QFT-GIT. Thirteen of them were followed longitudinally by QFT-GIT, performed at baseline and six and nine months after TB-treatment onset. For in vitro experiments, cells from healthy donors and HIV-naive subjects were pretreated with four antituberculous-drugs, and then examined for IFN-g secretion and apoptosis of T-cells. The QFT-GIT was positive in 66%, negative in 11.3% and indeterminate in 22.7%. Longitudinal analysis in 13 HIV-TB subjects showed that at therapy completion a reversion to negative response was found only in 38.4% of patients, but in 30.7% the QFT-GIT remained positive. Overall, during the anti-TB treatment no significant decrease in average IFN-g response was observed in these patients (p<0.001). In vitro experiments showed that the four antituberculous- drugs, within the range of therapeutically achievable concentrations, did not exert any down-regulatory effect on IFN-g production and did not have any effect on apoptosis of T cells from HIV naïve subjects. Despite the high rate of indeterminate results, QFT-GIT assay may represent a good tool in the diagnostic workup for active TB in HIV-patients. Although the antituberculous drugs do not have any direct effect on host immune response to mycobacterial antigen, changes in longitudinal IGRA response have been found during in vivo anti-TB treatment.


Mapping the literature of physical therapy.
Physical therapy is a fast growing profession because of the aging population, medical advances, and the public's interest in health promotion. This study is part of the Medical Library Association (MLA) Nursing and Allied Health Resources Section's project to map the allied health literature. It identifies the core journals in physical therapy by analyzing the cited references of articles in two established physical therapy journals, Physical Therapy and Archives of Physical Medicine and Rehabilitation, during the period 1991 through 1993. This bibliometric analysis also determines the extent to which these journals are covered by the primary indexing sources, Allied and Alternative Medicine (AMED), the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and MEDLINE. In this study, fourteen journals were found to supply one-third of all references studied. Ninety-five journals provided an additional third of the references. MEDLINE rated the highest as the indexing tool of choice for these 109 journals. The study results can assist in collection development decisions, advise physical therapists as to the best access to their core literature, and influence database producers to increase their coverage of the literature important to physical therapy.


High prevalence of jumper's knee and sonographic changes in Swedish elite junior volleyball players compared to matched controls.
Jumper's knee is a common and troublesome condition among senior volleyball players, but its prevalence among elite junior players compared to matched non-sports active controls is not known. To clinically, and by sonography, examine the patellar tendons in elite junior volleyball players (15-19 years) at the Swedish National Centre for volleyball and in matched controls. The patellar tendons in the 57 students at the Swedish National Centre for high school volleyball and in 55 age, height, and weight matched not regularly sports active controls were evaluated clinically and by grey scale ultrasonography (US) and power Doppler (PD) sonography. There were no significant differences in mean age, height, and weight between the volleyball players and the controls. In the volleyball group, jumper's knee was diagnosed clinically and by US in 12 patellar tendons (10 male and two female). In 12/12 tendons, PD sonography demonstrated a neovascularisation in the area with structural tendon changes. In another 10 pain free tendons, there were structural tendon changes and neovessels. In the control group, no individual had a clinical diagnosis of jumper's knee. US demonstrated structural tendon changes in 11 tendons, but there was no neovascularisation on PD sonography. A clinical diagnosis of jumper's knee, together with structural tendon changes and neovascularisation visualised with sonography, was seen among Swedish elite junior volleyball players but not in matched not regularly sports active controls. Structural tendon change alone was seen in 10% of the control tendons.


Applying unsupervised machine learning approaches to characterize autologous breast reconstruction patient subgroups: an NSQIP analysis of 14,274 patients.
Autologous breast reconstruction is composed of diverse techniques and results in a variety of outcome trajectories. We propose employing an unsupervised machine learning method to characterize such heterogeneous patterns in large-scale datasets. A retrospective cohort study of autologous breast reconstruction patients was conducted through the National Surgical Quality Improvement Program database. Patient characteristics, intraoperative variables, and occurrences of acute postoperative complications were collected. The cohort was classified into patient subgroups via the K-means clustering algorithm, a similarity-based unsupervised learning approach. The characteristics of each cluster were compared for differences from the complementary sample (p < 2 ×10-4) and validated with a test set. A total of 14,274 female patients were included in the final study cohort. Clustering identified seven optimal subgroups, ordered by increasing rate of postoperative complication. Cluster 1 (2027 patients) featured breast reconstruction with free flaps (50%) and latissimus dorsi flaps (40%). In addition to its low rate of complications (14%, p < 2 ×10-4), its patient population was younger and with lower comorbidities when compared with the whole cohort. In the other extreme, cluster 7 (1112 patients) almost exclusively featured breast reconstruction with free flaps (94%) and possessed the highest rates of unplanned reoperations, readmissions, and dehiscence (p < 2 ×10-4). The reoperation profile of cluster 3 was also significantly different from the general cohort and featured lower proportions of vascular repair procedures (p < 8 ×10-4). This study presents a novel, generalizable application of an unsupervised learning model to organize patient subgroups with associations between comorbidities, modality of breast reconstruction, and postoperative outcomes.


Porphyrins in photodynamic therapy - a search for ideal photosensitizers.
The utility of light as a therapeutic agent can be traced back over thousands of years when it was used in Ancient Egypt, India and China to treat a variety of skin diseases like psoriasis, vitiligo, rickets, cancer and psychosis. The isolation of porphyrins and their inherent tumor localizing properties coupled with its ability to generate reactive singlet oxygen when activated by light of particular wavelength which in turn results in cytotoxicity led to the emergence of a new modality namely, photodynamic therapy (PDT) as a therapeutic tool. The higher degree of selectivity offered by this modality and fewer side effects when compared to chemotherapy and radiotherapy has prompted the researchers around the globe to generate new photosensitizers. Porphyrins and expanded porphyrins are one class of molecules under intense investigation due to their photosensitizing ability for PDT application. Expanded porphyrins result from the expansion of the phi electron conjugation by increasing the number of heterocyclic rings or bridging carbons of the existing porphyrin framework. These chromophores show strong absorptions in the red region (650-800 nm) compared to that of normal 18phi porphyrins. The strong absorption of light by a water soluble nontoxic photosensitizing molecule in the therapeutic window resulting in maximum penetration of light into the tissues coupled with high singlet oxygen production will conceptualize an ideal photosensitizer. This review highlights various porphyrinoid sensitizers reported till date and their photosensitizing ability both in vitro and in vivo studies. Furthermore, the urgent need for developing ideal photosensitizer for PDT will also be highlighted.


[Current problems of the pathological anatomy of ischemic (coronary) heart disease].
Original and reported data are reviewed with respect to the development, from childhood onwards, of coronary arterial atherosclerosis. The leading contribution of coronary arterial thrombosis to myocardial infarction is demonstrated, as is high incidence of excentric atherosclerotic patches in coronary arteries, which are prone to spasm in the presence of such patches; the course and complications of left ventricular and right atrial or right ventricular infarction are described. Data on "incomplete", stable and unstable myocardial infarction are presented.


Safety of a Rapidly Dissolving Buprenorphine/Naloxone Sublingual Tablet (BNX-RDT) for Treatment of Opioid Dependence: A Multicenter, Open-label Extension Study.
To assess the safety of rapidly dissolving buprenorphine/naloxone sublingual tablets (BNX-RDT) in opioid-dependent patients. This open-label, 24-week extension study enrolled patients who completed primary trials of BNX-RDT. Daily tablet doses ranged from 5.7 to 17.1 mg. The primary endpoint was safety; secondary assessments included opioid cravings, addiction severity, health-related quality of life (QOL), and workplace productivity at screening (final day of the primary trials) through study end, with changes measured from baseline of the primary trials. In all, 665 patients received treatment; 292 (43.9%) completed the study. A total of 258 patients (38.8%) reported 557 treatment-emergent adverse events, most commonly headache (3.2%) and constipation (3.0%). Craving scores showed continued improvement on 100-mm visual analog scale (mean change from primary trial baseline, -52.8 at screening; mean change from extension trial baseline, -60.5 at week 24). Reductions in addiction severity from baseline of both the primary and extension trial were maintained through week 24 on multiple assessments, as were improvements in QOL on Short Form 36. Employment increased by 15% and mean (SD) hours worked per week increased by 4.6 (20.1) from baseline to study end. Mean (SD) scores for impact of opioid dependence on work productivity improved from 4.7 (3.0) at baseline to 0.9 (1.8) at study end (11-point scale). Extended treatment with BNX-RDT demonstrated a safety profile similar to other BNX formulations, reduced opioid cravings, and improved both QOL and work productivity. Continued treatment may enable patients to advance in recovery and return to normal functioning.


Rural general practice patients' coping with hazards and harm: an interview study.
The aim of this study is to identify and analyse rural general practice patients' experiences of hazards and harm that comprise adverse events, and their strategies for coping with them. Interview study using systematic text condensation and coping strategy theory in an abductive analysis process. Nine rural general practice clinics in Norway. Twenty participants, aged 21-79 years, all presenting with recent onset of somatic and/or psychiatric complaints. Participating rural general practice patients described their experiences of a variety of hazards and harms. Their three most discussed cognitive and behavioural coping strategies were: (1) to accept the events; (2) to confront them and (3) to engage in planful problem-solving. While the participants demonstrated a tendency toward accepting hazards and harm that their regular general practitioner created, they were often willing to confront those that locum (ie, substitute) general practitioners created. Participants used planful problem-solving in situations they deemed hazardous, such as breaches of confidentiality or not being taken seriously, as well as during potential/actual emergencies. Patients at rural general practice clinics actively identify and respond to hazards and harm, applying three coping strategies. Thus, patients themselves may serve as an important safety barrier against hazards and harm; their potential contributions to improving patient safety must be appreciated accordingly and reflected in future research as well as in everyday clinical practice.


Isolation and characterization of canine placenta-derived mesenchymal stromal cells for the treatment of neurological disorders in dogs.
Spinal cord injury (SCI) is a devastating disorder that affects humans and dogs. The prognosis of SCI depends on the severity of the injury and can include varying levels of motor and sensory deficits including devastating paraplegia and quadriplegia. Placental mesenchymal stromal cells (PMSCs) have been shown to improve wound healing and possess neuroprotective and immunomodulatory capabilities, but have not yet been clinically tested for the treatment of SCI. This study established a protocol to isolate fetal PMSCs from canine placentas and characterized their paracrine secretion profile and ability to stimulate neurons in vitro to assess their potential as a treatment option for neurological disorders in dogs. Canine PMSCs (cPMSCs) were plastic adherent and capable of trilineage differentiation. cPMSCs expressed typical MSC markers and did not express hematopoietic or endothelial cell markers. Genotyping of cPMSCs revealed fetal rather than maternal origin of the cells. cPMSCs were viable and mitotically expansive in a collagen hydrogel delivery vehicle, and they secreted the immunomodulatory and neurotrophic paracrine factors interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), and vascular endothelial growth factor (VEGF). cPMSCs also stimulated the growth of complex neural networks when co-cultured with SH-SY5Y cells, a neuroblastoma cell line used to model neuron growth in vitro. cPMSCs are analogous to human PMSCs. They meet the criteria to be defined as MSCs and represent a potential regenerative therapy option for neurological disorders in dogs with their robust growth in collagen hydrogel, stimulation of neural network formation, and secretion of potent paracrine factors. © 2017 International Society for Advancement of Cytometry.


Human pro-B-type natriuretic peptide is processed in the circulation in a rat model.
The appearance of B-type natriuretic peptide (BNP) in the blood is ultimately caused by proteolytic processing of its precursor, proBNP. The mechanisms leading to the high plasma concentration of unprocessed proBNP are still poorly understood. The goals of the present study were to examine whether processing of proBNP takes place in the circulation and to evaluate the clearance rate of proBNP and proBNP-derived peptides. We studied the processing of human proBNP in the circulation and the clearance rate of proBNP and proBNP-derived peptides (BNP and N-terminal fragment of proBNP, NT-proBNP) in rats by injecting the corresponding peptides and analyzing immunoreactivity at specific time points. Glycosylated and nonglycosylated proBNP and NT-proBNP were used in the experiments. We applied immunoassays, gel filtration, and mass spectrometry (MS) techniques to analyze the circulation-mediated processing of proBNP. ProBNP was effectively processed in the circulation into BNP (1-32) and various truncated BNP forms as confirmed by gel filtration and MS analysis. Glycosylation of proBNP close to the cleavage-site region suppressed its processing in the circulation. The terminal half-life for human glycosylated proBNP was 9.0 (0.5) min compared with 6.4 (0.5) min for BNP. For NT-proBNP, the terminal half-lives were 15.7 (1.4) min and 15.5 (1.3) min for glycosylated and nonglycosylated forms, respectively. In rats, processing of human proBNP to active BNP occurs in the circulation. The clearance rate of proBNP is quite similar to that of BNP. These observations suggest that peripheral proBNP processing may be an important regulatory step rather than mere degradation.


The application of thermoelastic analysis to study stresses in human teeth.
The aims of this investigation were to use a full-field thermoelastic technique to study the stress distribution on human teeth subjected to dynamic loads and derive a value for the thermoelastic constant for human enamel. Surface stresses were observed on extracted intact human molar teeth subjected to a load of 200 N cycled at 20 Hz. Measurements were repeated for the same teeth following mesio-occluso-distal cavity preparation and restoration with amalgam and adhesively bonded composite restorations. A value for the thermoelastic constant for human enamel (Km) of 2.25 X 10(-12)m2/N was calculated from physical coefficients in the literature. Unprepared specimens exhibited a comparable magnitude and distribution of stresses to those seen when teeth were restored with adhesively bonded composite restorations. Higher stresses were observed on prepared teeth and there was little change following restoration with amalgam. It can be concluded that a full-field thermoelastic stress analysis technique can be successfully applied to study teeth subjected to axial dynamic loads in vitro and that the resultant stresses are greater in prepared teeth than those restored with bonded composite materials.


Polypoid metastatic hepatocellular carcinoma of the esophagus occurring after endoscopic variceal band ligation.
This report describes a rare case of metastatic hepatocellular carcinoma (HCC) presenting as a polypoid mass in the lower esophagus after endoscopic variceal band ligation (EVL). A 56-year-old man underwent EVL for variceal bleeding in September 1993. He presented with dysphagia and tarry stool in December 1993. An endoscopic examination revealed a semipedunculated polypoid mass at the lower part of the esophagus, where EVL had been performed 3 months previously. The histologic examination at autopsy revealed that the polypoid mass consisted of metastatic HCC that had spread via the retrograde portal flow.


The diagnostic utility of intraoperative cytology in the management of ovarian tumours.
The present study was done to evaluate the status of intraoperative cytology as a diagnostic and supportive investigation for ovarian tumours. The present study was conducted in the Department of Pathology, Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India during a time span of 13 months (June 2011 to June 2012). A prospective investigation was performed on 50 cases of suspected ovarian neoplasms. Imprint smears were made intraoperatively from fresh samples from various representative areas, and they were immediately fixed in 95% ethyl alcohol and stained with the haematoxylin and eosin stain. The results were compared with the final histopathological diagnoses in each case. There were 20 benign lesions, 4 borderline epithelial neoplasms and 26 malignant tumours according to the final histopathological diagnosis. The overall diagnostic accuracy of imprint cytology has been satisfactory, with those of 90% of the cases correlating with the final diagnoses. Characteristic cytological patterns were noted in various surface epithelial, sex cord stromal and germ cell tumours. Imprint cytology can be used as an adjunct to histopathology for a rapid and an early diagnosis in the operation theatre, particularly in developing countries like ours, where the facility of frozen sections is often not available, since a rapid preliminary diagnosis may help in the surgical management planning.


Long-term efficacy and safety of erenumab in migraine prevention: Results from a 5-year, open-label treatment phase of a randomized clinical trial.
Although erenumab has demonstrated significant reduction in migraine frequency and improved quality of life in studies lasting 3 to 12 months, little is known about long-term therapy. This study was an open-label, 5-year treatment phase following a 12-week, double-blind, placebo-controlled trial in adults with episodic migraine. Patients initially received open-label erenumab 70 mg, which increased to 140 mg following a protocol amendment. Efficacy analyses included change from baseline in monthly migraine days (MMDs), monthly acute migraine-specific medication (AMSM) days, and health-related quality of life. Of 383 patients enrolled, 250 switched to 140 mg; 215 (56.1%) completed open-label treatment. Mean (standard error) change in MMDs from baseline of 8.7 (0.2) days was -5.3 (0.3) days; an average reduction of 62.3% at year 5. Among patients using AMSM at baseline (6.3 [2.8] treatment days), mean change in monthly AMSM days was -4.4 (0.3) days at the end of 5 years. Patient-reported outcomes indicated stable improvements in disability, headache impact, and migraine-specific quality of life. Exposure-adjusted patient incidence rates of adverse events (AEs) were 123.0/100 patient-years; AEs were most frequently nasopharyngitis, upper respiratory tract infection, and influenza. Serious AEs (SAEs) reported by 49 patients (3.8/100 patient-years) were mostly single occurrence. Two fatal adverse events were reported. There were no increases in incidence of AEs, SAEs, or AEs leading to treatment discontinuation over 5 years of exposure. Treatment with erenumab was associated with reductions in migraine frequency and improvements in health-related quality of life that were maintained for at least 5 years. No new safety signals were observed.


Patellofemoral overstuff and its relationship to flexion after total knee arthroplasty.
Flexion is an important outcome variable after total knee arthroplasty. Traditionally, matched implant-bone resections of the distal and posterior aspects of the femur are used to prevent loss of knee flexion or extension. However, given limited implant sizes, resection of these portions of the femur may affect the shape of the knee. Variations in the anterior aspects of the femur along with implant size constraints may increase trochlear groove height in the anterior compartment, increase the arc that the extensor mechanism must travel, and thereby decrease passive flexion. We determined the trochlear groove height change in 55 patients after primary total knee arthroplasties. The thickness of the replaced lateral and medial anterior flanges increased by 1.1 +/- 2.6 mm and 0.5 +/- 2.2 mm, respectively, whereas the change in trochlear groove thickness was 0 +/- 1.1 mm. We examined varying amounts of patellofemoral buildup in a cadaver model to observe the effect on passive range of motion of the knee. A 2-mm and 4-mm buildup of the anterior cortex resulted in flexion loss of 1.8 degrees and 4.4 degrees, respectively. The change in the shape of the anterior aspect of the femur may have small effects on flexion but they may not be clinically important.


HV1 acts as a sodium sensor and promotes superoxide production in medullary thick ascending limb of Dahl salt-sensitive rats.
We previously characterized a H(+) transport pathway in medullary thick ascending limb nephron segments that when activated stimulated the production of superoxide by nicotinamide adenine dinucleotide phosphate oxidase. Importantly, the activity of this pathway was greater in Dahl salt-sensitive rats than salt-resistant (SS.13(BN)) rats, and superoxide production was enhanced in low Na(+) media. The goal of this study was to determine the molecular identity of this pathway and its relationship to Na(+). We hypothesized that the voltage-gated proton channel, HV1, was the source of superoxide-stimulating H(+) currents. To test this hypothesis, we developed HV1(-/-) null mutant rats on the Dahl salt-sensitive rat genetic background using zinc-finger nuclease gene targeting. HV1 could be detected in medullary thick limb from wild-type rats. Intracellular acidification using an NH4Cl prepulse in 0 sodium/BaCl2 containing media resulted in superoxide production in thick limb from wild-type but not HV1(-/-) rats (P<0.05) and more rapid recovery of intracellular pH in wild-type rats (ΔpHI 0.005 versus 0.002 U/s, P=0.046, respectively). Superoxide production was enhanced by low intracellular sodium (<10 mmol/L) in both thick limb and peritoneal macrophages only when HV1 was present. When fed a high-salt diet, blood pressure, outer medullary renal injury (tubular casts), and oxidative stress (4-hydroxynonenal staining) were significantly reduced in HV1(-/-) rats compared with wild-type Dahl salt-sensitive rats. We conclude that HV1 is expressed in medullary thick ascending limb and promotes superoxide production in this segment when intracellular Na(+) is low. HV1 contributes to the development of hypertension and renal disease in Dahl salt-sensitive rats.


A rapid review of mental and physical health effects of working at home: how do we optimise health?
The coronavirus (COVID-19) pandemic has resulted in changes to the working arrangements of millions of employees who are now based at home and may continue to work at home, in some capacity, for the foreseeable future. Decisions on how to promote employees' health whilst working at home (WAH) need to be based on the best available evidence to optimise worker outcomes. The aim of this rapid review was to review the impact of WAH on individual workers' mental and physical health, and determine any gender difference, to develop recommendations for employers and employees to optimise workers' health. A search was undertaken in three databases, PsychInfo, ProQuest, and Web of Science, from 2007 to May 2020. Selection criteria included studies which involved employees who regularly worked at home, and specifically reported on physical or mental health-related outcomes. Two review authors independently screened studies for inclusion, one author extracted data and conducted risk of bias assessments with review by a second author. Twenty-three papers meet the selection criteria for this review. Ten health outcomes were reported: pain, self-reported health, safety, well-being, stress, depression, fatigue, quality of life, strain and happiness. The impact on health outcomes was strongly influenced by the degree of organisational support available to employees, colleague support, social connectedness (outside of work), and levels of work to family conflict. Overall, women were less likely to experience improved health outcomes when WAH. This review identified several health outcomes affected by WAH. The health/work relationship is complex and requires consideration of broader system factors to optimise the effects of WAH on workers' health. It is likely mandated WAH will continue to some degree for the foreseeable future; organisations will need to implement formalised WAH policies that consider work-home boundary management support, role clarity, workload, performance indicators, technical support, facilitation of co-worker networking, and training for managers.


Exploring Substance Use and HIV Treatment Factors Associated with Neurocognitive Impairment among People Living with HIV/AIDS.
Neurocognitive (NC) impairment remains prevalent among people living with HIV (PLWH) and may be exacerbated by alcohol and drug use. This cross-sectional study assesses the degree to which alcohol and other drug use, time from HIV diagnosis to treatment, and years living with HIV affect three areas of NC functioning among HIV-seropositive adults. NC functioning in 370 PLWH living in Miami, FL was assessed using the Auditory Verbal Learning Test, the Short Category Test, Booklet Format, and the Color Trails Test 2 (CTT2). Participants reported the number of days using alcohol, marijuana, and cocaine over the previous 3 months, the number of known years living with HIV and length of time from HIV diagnosis to seeking care. Bivariate linear regression and multivariate linear regression were used to test associations between independent and dependent variables. Mean scores on NC measures were significantly lower than published norms; 39% of participants scored ≥1 standard deviation below normative sample means on >2 NC tests. No significant associations were found between alcohol or cocaine use and any NC measure. Years living with HIV was associated with CTT2 in the bivariate analysis (β = 1.031; p = 0.007). In multivariate analysis, each day of marijuana use and years living with HIV were associated with a 0.32 (p = 0.05) point and 1.18 (p = 0.03) points poorer performance score on the CTT2, respectively. Results suggest that both marijuana use and duration of HIV infection may affect cognitive functioning among PLWH in ways that may impair their ability to follow important treatment guidance.


[Ultrastructural images of nuclear extrusions in cutaneous lymphomas (author's transl)].
In 10 cases of cutaneous lymphomas, outflow of nuclear material into the cytoplasm of tumoral cells was observed ultrastructurally. Various stages of this phenomenon could be visualized. These observations were made in various types of epidermotropic and on epidermotropic cutaneous lymphomas but they are particularly evident in Crosti's reticulosis. These nuclear abnormalities were observed prior to any treatment; they are unrelated with tissue preparation and are very different from the well-known nuclear degeneration processes. They have been observed in various but exceptional physiological or pathological conditions, but have apparently not been noticed in earlier works on cutaneous lymphomas, except in 1 case of Crosti's reticulosis. No prognosis implication of these images was found. Their significance is not clear, but could be related with mitotic disorders.


Diagnostic Error in Medicine: Implications for Clinical Laboratory Scientists.
The recent interest in diagnostic error in medicine was preceded almost fifty years ago by a focus on the problem-solving strategies of the experts of that time. This focus also extended to include the development of computer-based decision support systems to aid clinicians in diagnosis. Interest in medical errors was heightened with the publication of the Institute of Medicine report To Err is Human in 2000; however, there was still a relative neglect of the problem that diagnostic error presents. This article discusses the extent and types of diagnostic error in medicine, the challenges of studying diagnostic error, and strategies to address these errors. The role of the clinical laboratory in regard to diagnostic errors in medicine is also highlighted.


WOMENtorship: The #WomenInMedicine perspective.
Mentorship is essential for career development, personal development, and job satisfaction for physicians in academic medicine. Women in academic medicine face unique challenges including significant gender disparities in positions of leadership as well as difficulty finding mentors. As leaders in academic medicine, we have collated several structured recommendations for physicians of both genders seeking to be better mentors to female trainees and early career physicians. We discuss each of these recommendations in detail including the following: acknowledging your own strengths and limitations as a mentor, addressing issues of work-life integration, helping your mentee set long-term career goals, and acting as a sponsor as well as a mentor. We hope these suggestions are helpful for current and aspiring mentors and provide a platform to improve career development for female physicians and reduce gender inequities in academic medicine.


Generalization of appetitive conditioned responses.
A stimulus (conditioned stimulus, CS) associated with an appetitive unconditioned stimulus (US) acquires positive properties and elicits appetitive conditioned responses (CR). Such associative learning has been examined extensively in animals with food as the US, and results are used to explain psychopathologies (e.g., substance-related disorders or obesity). Human studies on appetitive conditioning exist, too, but we still know little about generalization processes. Understanding these processes may explain why stimuli not associated with a drug, for instance, can elicit craving. Forty-seven hungry participants underwent an appetitive conditioning protocol during which one of two circles with different diameters (CS+) became associated with an appetitive US (chocolate or salty pretzel, according to participants' preference) but never the other circle (CS-). During generalization, US were delivered twice and the two CS were presented again plus four circles (generalization stimuli, GS) with gradually increasing diameters from CS- to CS+. We found successful appetitive conditioning as reflected in appetitive subjective ratings (positive valence, higher contingency) and physiological responses (startle attenuation and larger skin conductance responses) to CS+ versus CS-, and, importantly, both measures confirmed generalization as indicated by generalization gradients. Small changes in CS-US contingency during generalization may have weakened generalization processes on the physiological level. Considering that appetitive conditioned responses can be generalized to non-US-associated stimuli, a next important step would be to investigate risk factors that mediate overgeneralization.


Tight junction-related human diseases.
Tight junctions are intercellular junctions adjacent to the apical ends of paracellular spaces. They have two classical functions, the barrier function and the fence function. The former regulates the passage of ions, water and various molecules through paracellular spaces, and is thus related to edema, jaundice, diarrhea and blood-borne metastasis. The latter function maintains cell polarity by forming a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell properties in terms of loss of cell polarity. Recently, two novel aspects of tight junctions have been reported. One is their involvement in signal transduction. The other is that fact that tight junctions are considered to be a crucial component of innate immunity. In addition, since some proteins comprising tight junctions work as receptors for viruses and extracellular stimuli, pathogenic bacteria and viruses target and affect the tight junction functions, leading to diseases. In this review, the relationship between tight junctions and human diseases will be described.


Implementing the Affordable Care Act: state action on the 2014 market reforms.
The Affordable Care Act includes numerous consumer protections designed to improve the accessibility, adequacy, and affordability of private health insurance. Because states are the primary regulators of health insurance, this issue brief examines new state action on a subset of protections--such as guaranteed access to coverage and a ban on preexisting condition exclusions--that go into effect in 2014. The analysis finds that, to date, only one state passed new legislation on all of these protections, and an additional 10 states and the District of Columbia passed new legislation or issued a new regulation on at least one protection. The analysis also finds that--without new legislation--some states face limitations in fully enforcing these reforms. These findings suggest an acute need for states to take action in 2013 to help ensure that consumers are fully protected by and benefit from the Affordable Care Act's most significant reforms.


Treatment of the primary lesion in melanoma.
The routine wide sacrifice of skin, fat and fascia for the treatment of all melanomas is clearly ill-advised. For the low risk primary lesion, conservative excision is sufficient. For the high risk lesion, individualized therapy should be the rule.


Altered Peripheral B-Lymphocyte Subsets in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults.
B lymphocytes play an important role in the immunopathogenesis of autoimmune diabetes. We hypothesized that the altered B-cell subset phenotype is associated with autoimmune diabetes. Patients with type 1 diabetes (T1D) (n = 81), latent autoimmune diabetes in adults (LADA) (n = 82), or type 2 diabetes (T2D) (n = 95) and healthy control subjects (n = 218) with normal glucose tolerance (NGT) were recruited. We determined the percentage of circulating B-lymphocyte subsets, including CD19(+)CD23(-)CD21(+) (marginal zone B [MZB]), CD19(+)CD23(+)CD21(-) (follicular B [FoB]), and CD19(+)CD5(+)CD1d(hi) (interleukin-10-producing regulatory B [B10]) cells by flow cytometry. Patients with T1D or LADA had increased percentages of MZB cells and decreased percentages of FoB cells compared with healthy control subjects with NGT and patients with T2D. Moreover, patients with T1D showed the lowest frequency of B10 cells compared with patients with LADA or T2D, whereas healthy control subjects expressed the highest frequency of B10 cells. Of note, the frequency of MZB cells was negatively associated and the frequency of FoB cells was positively associated with fasting C-peptide (FCP). The frequency of B10 cells was positively correlated with FCP and negatively correlated with hemoglobin A(1c). The data show that patients with T1D or LADA express an altered frequency of B-cell subsets, which is associated with islet function and glycemia. These findings suggest that B lymphocytes may be involved in loss of self-tolerance and β-cell destruction and could be used as a biomarker and potential target for immunological intervention.


Analysis of B-cell antigens in normal reactive lymphoid tissue using four B-cell monoclonal antibodies.
Lymph nodes from 13 cases of reactive hyperplasia were examined with four different monoclonal antibodies to B cells. B-1 recognizes an antigen of 30,000 daltons on B cells. CB-2 was prepared with normal spleen and binds to a glycolipid. BA-1 labels surface immunoglobulin-positive cells, but not T lymphocytes or monocytes. B-532 recognizes an antigenic determinant of 45,000 daltons. Using the immunoperoxidase method on frozen sections of reactive lymph nodes, the staining patterns of these four unique antibodies showed dramatic differences. B-1 labeled 80%-90% of the germinal center cells and 10%-50% of the mantle region. Few interfollicular cells were positive. CB-2 stained predominantly in the mantle area (50%-90% positive cells), with moderate staining in the germinal center as well and less than 1% positive cells in the diffuse cortex. BA-1 exhibited predominant labeling in the mantle (50%-90%), with little staining in the germinal center. A large number of cells in the interfollicular, subcapsular, and medullary regions expressed the BA-1 antigen. The B-5 antibody demonstrated intense staining in the follicle (50%-95%). This staining often appeared to be polarized within the germinal center. The mantle zone demonstrated staining of 30%-50% of the cells. The different staining patterns of the B-cell antibodies, as demonstrated by the in situ distribution of positive cells within the lymph node, may reflect stages of development or activation of the B-cell population.


Impacts on work performance; what matters 6 months on?
Presenteeism often precedes and follows a period of work absence. Cross-sectional analysis of a workforce survey highlighted health, psychosocial and work characteristics as being particularly important in understanding current work performance, but it is unclear whether these variables predict future work performance. To establish whether self-reported health, perceptions of work and objective characteristics of work measured at baseline can predict performance at 6 months follow-up. Self-completed questionnaires to assess health, objective characteristics of work and perceptions of work were completed at two public sector organizations. Follow-up questionnaires were completed at 6 months to assess workplace performance using a visual analogue scale for self-rated performance and the Stanford Presenteeism Scale 6 (SPS6). Five hundred and five employees completed questionnaires at baseline and 310 (61%) of these completed follow-up questionnaires. Psychological distress as measured with the General Health Questionnaire and perceptions of work predicted both self-rated performance and SPS6 score. Objective characteristics of work were relatively unimportant in the prediction of future performance. This study has provided an initial indication of the factors that may predict performance at follow-up in the population studied. These findings may be used to generate hypotheses for future studies and highlights the need to assess a range of factors in relation to an individual's performance at work including health and perceptions of work.


Impact of soybean aging conditions on tofu sensory characteristics and acceptance.
Tofu from aged soybeans is of poor quality, mainly with respect to texture. Texture defects described in the literature are contradictory. No study has investigated all sensory properties simultaneously. The objective of the present study was to evaluate the effect of soybean aging conditions [natural: ambient temperature and RH, 18 months, and accelerated: 30 °C, 84% relative humidity (RH), 6 months] on all of the sensory characteristics and the acceptance of tofu. Texture and color were also evaluated via an instrumental method. The control condition was -20 °C and 47% RH. Coodetec 214 and BRS 267 cultivars were studied. The effect of soybean accelerated aging on tofu sensory characteristics and acceptance was more pronounced compared to the natural condition. The two cultivars had a similar behavior. Tofu control exhibited a light, uniform and bright color, cohesive appearance, sweet aroma and flavor, as well as a firm and elastic texture. Tofu made from both aged cultivars showed a gray color with dark spots, a rough appearance, fermented aroma, rancid flavor, an astringent and bitter taste, a fracturable texture and adherence to the oral cavity after chewing. These characteristics of tofu from aged soybeans implied a low acceptance by consumers. Tofu from natural and accelerated aged soybeans has sensory attributes of appearance, as well as aroma, flavor and damaged texture, that are unacceptable by consumers. © 2017 Society of Chemical Industry.


[Establishment and validation of nomogram prediction model for complicated acute appendicitis].
Objective: To establish and internally validate a nomogram model for predicting complicated acute appendicitis (CA). Methods: The clinical data from 663 acute appendicitis patients from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from October 2015 to October 2022 were retrospectively analyzed. There were 411 males and 252 females, aged (M (IQR)) 41 (22) years (range: 18 to 84 years). There were 516 cases of CA and 147 cases of uncomplicated acute appendicitis. The minimum absolute contraction and selection operator regression model was used to screen the potential relative factors of CA, and the screened factors were included in the Logistic regression model for multivariate analysis. Software R was used to establish a preoperative CA nomogram prediction model, the receiver operating characteristic curve of the model was drawn, and the value of area under the curve (AUC) was compared to evaluate its identification ability, and the Bootstrap method was used for internal verification. Result: The elderly (age≥60 years) (OR=2.428, 95%CI: 1.295 to 4.549), abdominal pain time (every rise of 1 hour) (OR=1.089, 95%CI: 1.072 to 1.107), high fever (body temperature≥39 ℃) (OR=1.122, 95%CI: 1.078 to 1.168), total bilirubin (every rise of 1 μmol/L) (OR=2.629, 95%CI: 1.227 to 5.635) were independent relative factors of CA (all P<0.05). The AUC of this model was 0.935 (95%CI: 0.915 to 0.956). After internal verification using the Bootstrap method, the model still had a high discrimination ability (AUC=0.933), and the predicted CA curve was still in good agreement with the actual clinical CA curve. Conclusion: The clinical prediction model based on the elderly (age≥60 years), prolonged abdominal pain time, high fever (body temperature≥39 ℃), and increased total bilirubin can help clinicians effectively identify CA.


The role of domain knowledge in automating medical text report classification.
To analyze the effect of expert knowledge on the inductive learning process in creating classifiers for medical text reports. The authors converted medical text reports to a structured form through natural language processing. They then inductively created classifiers for medical text reports using varying degrees and types of expert knowledge and different inductive learning algorithms. The authors measured performance of the different classifiers as well as the costs to induce classifiers and acquire expert knowledge. The measurements used were classifier performance, training-set size efficiency, and classifier creation cost. Expert knowledge was shown to be the most significant factor affecting inductive learning performance, outweighing differences in learning algorithms. The use of expert knowledge can affect comparisons between learning algorithms. This expert knowledge may be obtained and represented separately as knowledge about the clinical task or about the data representation used. The benefit of the expert knowledge is more than that of inductive learning itself, with less cost to obtain. For medical text report classification, expert knowledge acquisition is more significant to performance and more cost-effective to obtain than knowledge discovery. Building classifiers should therefore focus more on acquiring knowledge from experts than trying to learn this knowledge inductively.


Myopathy and spontaneous Pasteurella pneumotropica-induced abscess formation in an HIV-1 transgenic mouse model.
In an effort to augment human immunodeficiency virus type 1 (HIV-1) gene expression in transgenic mice, an infectious proviral DNA clone was modified by deleting the two NF kappa B binding sites and some adjacent upstream LTR sequences and replacing them with the core enhancer of Moloney murine leukemia virus (MLV). Two independent lines of MLV/HIV transgenic mice were established that expressed HIV-1-specific RNA in lymphoid tissue, striated skeletal muscle, and the eye lens. Heterozygous animals from each transgenic line spontaneously developed an inflammatory disease of the eye associated with the production of copious amounts of purulent lacrimal secretions beginning at 2 weeks of age. Periorbital abscess formation became grossly apparent by 2 months of age and Pasteurella pneumotropica was cultured from the harderian glands and conjunctival surfaces of many of the MLV/HIV animals but not their nontransgenic, cohabiting littermates. This gram-negative commensal bacterium has been previously associated with a similar disease phenotype in immunocompromised (e.g., nude mice) rodent colonies. MLV/HIV mice developed normally until 15 weeks of age, when weight loss and wasting occurred, culminating in premature death (as earlier as 6 months of age). The cachexia was associated with an initially focal and subsequently progressive myopathy, coinciding with age-related increases of HIV gene expression in muscle.


Pharmacosomes: an emerging novel vesicular drug delivery system for poorly soluble synthetic and herbal drugs.
In the arena of solubility enhancement, several problems are encountered. A novel approach based on lipid drug delivery system has evolved, pharmacosomes. Pharmacosomes are colloidal, nanometric size micelles, vesicles or may be in the form of hexagonal assembly of colloidal drug dispersions attached covalently to the phospholipid. They act as befitting carrier for delivery of drugs quite precisely owing to their unique properties like small size, amphiphilicity, active drug loading, high entrapment efficiency, and stability. They help in controlled release of drug at the site of action as well as in reduction in cost of therapy, drug leakage and toxicity, increased bioavailability of poorly soluble drugs, and restorative effects. There has been advancement in the scope of this delivery system for a number of drugs used for inflammation, heart diseases, cancer, and protein delivery along with a large number of herbal drugs. Hence, pharmacosomes open new challenges and opportunities for improved novel vesicular drug delivery system.


Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies.
Although the precise pathogenesis of schizophrenia is unknown, genetic, biomarker and imaging studies suggest involvement of the immune system. In this study, we performed a systematic review and meta-analysis of studies investigating factors related to the immune system in postmortem brains of schizophrenia patients and healthy controls. Forty-one studies were included, reporting on 783 patients and 762 controls. We divided these studies into those investigating histological alterations of cellular composition and those assessing molecular parameters; meta-analyses were performed on both categories. Our pooled estimate on cellular level showed a significant increase in the density of microglia (P=0.0028) in the brains of schizophrenia patients compared with controls, albeit with substantial heterogeneity between studies. Meta-regression on brain regions demonstrated this increase was most consistently observed in the temporal cortex. Densities of macroglia (astrocytes and oligodendrocytes) did not differ significantly between schizophrenia patients and healthy controls. The results of postmortem histology are paralleled on the molecular level, where we observed an overall increase in expression of proinflammatory genes on transcript and protein level (P=0.0052) in patients, while anti-inflammatory gene expression levels were not different between schizophrenia and controls. The results of this meta-analysis strengthen the hypothesis that components of the immune system are involved in the pathogenesis of schizophrenia.


Upscaling the Surveillance of Tick-borne Pathogens in the French Caribbean Islands.
Despite the high burden of vector-borne disease in (sub)tropical areas, few information are available regarding the diversity of tick and tick-borne pathogens circulating in the Caribbean. Management and control of vector-borne disease require actual epidemiological data to better assess and anticipate the risk of (re)emergence of tick-borne diseases in the region. To simplify and reduce the costs of such large-scale surveys, we implemented a high-throughput microfluidic real-time PCR system suitable for the screening of the main bacterial and parasitic genera involved in tick-borne disease and potentially circulating in the area. We used the new screening tool to perform an exploratory epidemiological study on 132 adult specimens of Amblyomma variegatum and 446 of Rhipicephalus microplus collected in Guadeloupe and Martinique. Not only the system was able to detect the main pathogens of the area-Ehrlichia ruminantium, Rickettsia africae, Anaplasma marginale, Babesia bigemina and Babesia bovis-but the system also provided evidence of unsuspected microorganisms in Caribbean ticks, belonging to the Anaplasma, Ehrlichia, Borrelia and Leishmania genera. Our study demonstrated how high-throughput microfluidic real-time PCR technology can assist large-scale epidemiological studies, providing a rapid overview of tick-borne pathogen and microorganism diversity, and opening up new research perspectives for the epidemiology of tick-borne pathogens.


Effect of Vitamin D Level on Clinical Outcomes in Patients Undergoing Left Ventricular Assist Device Implantation.
Vitamin D is an important hormone that regulates cardiac myocyte function. Low levels contribute to the development of cardiovascular disease and have been implicated in immune function and the inflammatory cascade. Patients who undergo left ventricular assist device (LVAD) implantation are at risk for driveline infection, stroke, and gastrointestinal (GI) bleeding. We investigated whether serum 25-hydroxy (25-OH) vitamin D levels affect clinical outcomes after LVAD. 212 patients who underwent LVAD implantation between 2010 and 2015 were included. We measured preoperative 25-OH vitamin D level and postoperative adverse events during the first year. Vitamin D level was classified into 3 categories: normal (>30 ng/mL), insufficient (20-30 ng/mL), and deficient (<20 ng/mL). Clinical outcomes in both insufficient and deficient categories were compared with the normal category. The odds ratio (OR) of being admitted ≥2 times was 2.46 (95% confidence interval [CI]: 1.067-5.769) for deficiency and 2.5 (95% CI: 0.970-6.443) for insufficiency. The OR of driveline infection was 6.185 (95% CI: 0.80-49.2; P = .07) for insufficiency and 11.467 (95% CI: 1.204-109.26; P = .03) for deficiency. Vitamin D levels were not associated with GI bleeding, length of stay, or stroke. In patients with LVAD, both deficiency and insufficiency of 25-OH vitamin D levels are independently associated with increased postoperative driveline infection risk and higher rate of readmission. Further trials are needed to confirm whether a repletion regimen could be a promising means of decreasing the risk for these postoperative adverse events.


Acceptance of COVID-19 Vaccine Among Refugees in the United States.
Little is known about COVID-19 vaccination intentions among refugee communities in the United States. The objective of this study was to measure COVID-19 vaccination intentions among a sample of refugees in the United States and the reasons for their vaccine acceptance or hesitancy. From December 2020 through January 2021, we emailed or text messaged anonymous online surveys to 12 bilingual leaders in the Afghan, Bhutanese, Somali, South Sudanese, and Burmese refugee communities in the United States. We asked community leaders to complete the survey and share the link with community members who met the inclusion criteria (arrived in the United States as refugees, were aged ≥18, and currently lived in the United States). We compared the characteristics of respondents who intended to receive the COVID-19 vaccine with those of respondents who did not intend to receive the vaccine or were unsure. We then conducted crude and adjusted logistic regression analysis to measure the association between employment as an essential worker and COVID-19 vaccine acceptance. Of 435 respondents, 306 (70.3%) indicated that they planned to receive a COVID-19 vaccine. Being an essential worker (adjusted odds ratio [aOR] = 2.37; 95% CI, 1.44-3.90) and male sex (aOR = 1.87; 95% CI, 1.12-3.12) were significantly associated with higher odds of intending to receive a COVID-19 vaccine. Among respondents who intended to receive a COVID-19 vaccine, wanting to protect themselves (68.6%), family members (65.0%), and other people (54.3%) were the main reasons. Many refugees who responded to the survey, especially those who worked in essential industries, intended to receive a COVID-19 vaccine. Community organizations, health care providers, and public health agencies should work together to ensure that vaccine registration and vaccination sites are accessible to refugees.


Uranyl acetate causes DNA single strand breaks in vitro in the presence of ascorbate (vitamin C).
Uranium is a radioactive heavy metal with isotopes that decay on the geological time scale. People are exposed to uranium through uranium mining, processing, the resulting mine tailings, and the use of depleted uranium in the military. Acute exposures to uranium are chemically toxic to the kidney; however, little is known about chronic exposures, for example, if there is a direct chemical genotoxicity of uranium. The hypothesis that is being tested in the current work is that hexavalent uranium, as uranyl ion, may have a chemical genotoxicity similar to that of hexavalent chromium. In the current study, reactions of uranyl acetate (UA) and ascorbate (vitamin C) were observed to produce plasmid relaxation in pBluescript DNA. DNA strand breaks increased with increasing concentrations of a 1:1 reaction of UA and ascorbate but were not affected by increasing the ratio of ascorbate. Plasmid relaxation was inhibited by coincubation of reactions with catalase but not by coincubation with the radical scavengers mannitol, sodium azide, or 5,5-dimethyl-1-pyrroline-N-oxide. Reactions of UA and ascorbate monitored by (1)H NMR spectroscopy showed formation of a uranyl ascorbate complex, with no evidence of a dehydroascorbate product. A previous study inferred that hydroxyl radical formation was responsible for oxidative DNA damage in the presence of reactions of uranyl ion, hydrogen peroxide, and ascorbate [Miller et al. (2002) J. Bioinorg. Chem. 91, 246-252]. Current results, in the absence of added hydrogen peroxide, were not completely consistent with the interpretation that strand breaks were produced by a Fenton type generation of reactive oxygen species. Data were also consistent with the interpretation that a uranyl ascorbate complex was catalyzing hydrolysis of the DNA-phosphate backbone, in a manner similar to that known for the lanthanides. These data suggest that uranium may be directly genotoxic and may, like chromium, react with DNA by more than one pathway.


The expression of human papillomavirus type 18 E6 protein in bacteria and the production of anti-E6 antibodies.
Human papillomavirus type 18 (HPV-18) has recently been closely linked with human malignant cervical lesions. The early region of the genome of the related bovine papillomavirus (BPV) has been shown to be important for the production of the transformed phenotype. BPV E6 has been shown to be a transforming protein. We report the primary structure of the HPV-18 E6 open reading frame and its predicted amino acid sequence. Both E6 protein and E6-beta-galactosidase fusion protein were synthesized in bacteria. Antisera were raised against the E6-beta-galactosidase fusion protein and against an E6 N-terminal peptide which was 14 amino acids long. We show that these antisera reacted on Western blots against E6 synthesized in bacteria. The HPV E6 antigen and antibodies described here will be useful in understanding HPV expression and its association with human malignancies and may also be diagnostically useful.


[Health research and health technology assessment in Chile].
Health research is considered an essential element for the improvement of population health and it has been recommended that a share of the national health budget should be allocated to develop this field. Chile has undertaken efforts in the last decades in order to improve the governmental structure created to promote the development of health research, which has increased human resources and funding opportunities. On the other hand, the sustained economic growth of Chile in the last decades suggests that the health expenditure will maintain its increasing trend in the following years. This additional funding could be used to improve coverage of current activities performed in the health system, but also to address the incorporation of new strategies. More recently, health technology assessment (HTA) has been proposed as a process to support decisions about allocation of resources based on scientific evidence. This paper examines the relationship between the development of health research and the HTA process. First, it presents a brief diagnosis of the situation of health research in Chile. Second, it reviews the conceptual basis and the methods that account for the relationship between a HTA process and the development of health research. In particular, it emphasizes the relevance of identifying information gaps where funding additional research can be considered a good use of public resources. Finally, it discusses the challenges and possible courses of action that Chile could take in order to guarantee the continuous improvement of an articulated structure for health research and HTA.


Opsin gene sequence variation across phylogenetic and population histories in Mysis (Crustacea: Mysida) does not match current light environments or visual-pigment absorbance spectra.
The hypothesis that selection on the opsin gene is efficient in tuning vision to the ambient light environment of an organism was assessed in 49 populations of 12 Mysis crustacean species, inhabiting arctic marine waters, coastal littoral habitats, freshwater lakes ('glacial relicts') and the deep Caspian Sea. Extensive sequence variation was found within and among taxa, but its patterns did not match expectations based on light environments, spectral sensitivity of the visual pigment measured by microspectrophotometry or the history of species and populations. The main split in the opsin gene tree was between lineages I and II, differing in six amino acids. Lineage I was present in marine and Caspian Sea species and in the North American freshwater Mysis diluviana, whereas lineage II was found in the European and circumarctic fresh- and brackish-water Mysis relicta, Mysis salemaai and Mysis segerstralei. Both lineages were present in some populations of M. salemaai and M. segerstralei. Absorbance spectra of the visual pigment in nine populations of the latter three species showed a dichotomy between lake (λ(max) =554-562 nm) and brackish-water (Baltic Sea) populations (λ(max) = 521-535 nm). Judged by the shape of spectra, this difference was not because of different chromophores (A2 vs. A1), but neither did it coincide with the split in the opsin tree (lineages I/II), species identity or current light environments. In all, adaptive evolution of the opsin gene in Mysis could not be demonstrated, but its sequence variation did not conform to a neutral expectation either, suggesting evolutionary constraints and/or unidentified mechanisms of spectral tuning.


Perpetration and Victimization of Intimate Partner Aggression Among Rural Mothers.
Intimate partner aggression is a leading cause of injury among women of child-bearing age. Research suggests that pregnancy and the postpartum period are times of increased vulnerability to aggression. Since rural women are at an increased risk of intimate partner aggression, research is needed to examine the role of pregnancy and the presence of children on intimate partner aggression among this vulnerable population. The purpose of this study is to examine the association between young children and intimate partner aggression victimization and perpetration among a rural sample. This analysis utilized data from biologic females of child-bearing age from the Keokuk County Rural Health Study, a cohort study of over 1,000 rural families conducted from 1994 to 2011. Crude and adjusted logistic regression was used to determine the relationship between having a young child and experiencing four forms of intimate partner aggression: verbal aggression perpetration, verbal aggression victimization, physical aggression perpetration, and physical aggression victimization. Having young children was significantly associated with increased odds of perpetrating verbal aggression but not victimization of verbal aggression or perpetration and victimization of physical aggression. This significant relationship persisted after adjustment for education, employment, or location of residence but not age or marital status. The increased odds of perpetrating verbal aggression among mothers in a rural area highlight the need for interventions designed for rural parents. One method of reducing intimate partner aggression may be to incorporate intimate partner aggression prevention activities into existing child abuse intervention activities.


Comparative efficacy of the generalized anxiety disorder 7-item scale and the Edinburgh Postnatal Depression Scale as screening tools for generalized anxiety disorder in pregnancy and the postpartum period.
About 24.1% of pregnant women suffer from at least 1 anxiety disorder, 8.5% of whom suffer specifically from generalized anxiety disorder (GAD). GAD is often associated with major depressive disorder (MDD). During the perinatal period, the presence of physical and somatic symptoms often makes differentiation between depression and anxiety more challenging. To date, no screening tools have been developed to detect GAD in the perinatal population. We investigated the psychometric properties of the GAD 7-item Scale (GAD-7) as a screening tool for GAD in pregnant and postpartum women. Two hundred and forty perinatal women (n = 155 pregnant and n = 85 postpartum) referred for psychiatric consultation were enrolled. On the day of initial assessment, all women completed the GAD-7 and the Edinburgh Postnatal Depression Scale (EPDS). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-based diagnoses were made by experienced psychiatrists. Scores from the GAD-7 and EPDS were compared with the clinical diagnoses to evaluate the psychometric properties of the GAD-7 and EPDS when used as a screening tool for GAD. The GAD-7 yielded a sensitivity of 61.3% and specificity of 72.7% at an optimal cut-off score of 13. Compared with the EPDS and the EPDS-3A subscale, the GAD-7 displayed greater accuracy and specificity over a greater range of cut-off scores and more accurately identified GAD in patients with comorbid MDD. Our findings suggest that the GAD-7 represents a clinically useful scale for the detection of GAD in perinatal women.


Gout and the risk of type 2 diabetes among men with a high cardiovascular risk profile.
Our objective was to evaluate the independent relation between a history of gout and the future risk of type 2 diabetes among men with a high cardiovascular risk profile. We prospectively examined over a 6-yr period the relation between gout and the risk of incident type 2 diabetes in 11 351 male participants from the Multiple Risk Factor Intervention Trial (MRFIT). Incident diabetes was defined based on the American Diabetes Association (ADA) criteria for epidemiological studies. Cox proportional hazards regression was used to adjust for potential confounders. We documented 1215 new cases of type 2 diabetes. After adjusting for age, BMI, smoking, family history of type 2 diabetes, alcohol intake, dietary factors and presence of individual components of the metabolic syndrome, the multivariate relative risk (RR) for incident type 2 diabetes among men with gout at baseline, as compared with men without gout, was 1.34 (95% CI 1.09, 1.64). When we further adjusted for serum uric acid levels, the association remained significant (RR 1.26; 95% CI 1.02, 1.54). When we updated the status of gout annually during follow-up as a time-varying covariate, the association remained similar. The association also remained similar in our subgroup analyses by major covariates (P-values for interaction >0.16). These findings from men with a high cardiovascular risk profile suggest that men with gout are at a higher future risk of type 2 diabetes independent of other known risk factors. These data expand on well-established, cross-sectional associations between hyperuricaemia, gout and the metabolic syndrome, and extend the link to the future risk of type 2 diabetes.


Do potential patients prefer tissue plasminogen activator (TPA) over streptokinase (SK)? An evaluation of the risks and benefits of TPA from the patient's perspective.
In patients with acute myocardial infarction, TPA (compared to SK), has been shown to reduce the 30-day mortality rate at the expense of an increased rate of stroke. The assumption in the literature is that were it not for cost issues, all patients presenting with a myocardial infarction would choose TPA. Our hypothesis is that, for many informed individuals, regardless of cost, the increased risk of stroke may deter them from selecting TPA over SK. To assess which thrombolytic drug informed patients would prefer and to explore the clinical and economic implications of such preferences. Prospective survey. Tertiary care hospital. 120 hospitalized patients with cardiac disease who would be "at risk" for a myocardial infarction. Face-to-face interviews utilizing a decision instrument. To minimize bias in soliciting patients' preferences and to standardize the presentation of information we developed a decision instrument which portrays a case scenario of a myocardial infarction, describes treatment outcomes (survival and stroke rate), and displays the likelihood of these outcomes with SK and TPA using three scenarios: a base stroke risk (all patients data), a lower stroke risk (<75 years old data), a higher stroke risk (>75 years old data). Outcome data were derived from the published literature (GUSTO study). When presented the overall results of the GUSTO study, 60/120 (50%) expressed a preference for SK. When presented the outcome data for the subgroups of patients <75 years old (lower stroke rate), 37/120 (31%) preferred SK. When presented the subgroup data for patients >75 years old (higher stroke risk), 67/120 (56%) preferred SK. Regardless of the scenario that individuals were presented with, a substantial proportion of individuals (31-56%) who could potentially require thrombolytic therapy chose SK over TPA. This study should be repeated in other settings to establish the generalizability of our results. Assuming that these results will be consistent, considering the patient's perspective has significant implications on clinical decision making as well as from an economic perspective.


Development of acetophenone ligands as potential neuroimaging agents for cholinesterases.
Association of cholinesterase with β-amyloid plaques and tau neurofibrillary tangles in Alzheimer's disease offers an opportunity to detect disease pathology during life. Achieving this requires development of radiolabelled cholinesterase ligands with high enzyme affinity. Various fluorinated acetophenone derivatives bind to acetylcholinesterase with high affinity, including 2,2,2-trifluoro-1-(3-dimethylaminophenyl)ethanone (1) and 1-(3-tert-butylphenyl)-2,2,2-trifluoroethanone (2). Such compounds also offer potential for incorporation of radioactive fluorine (18F) for Positron Emission Tomography (PET) imaging of cholinesterases in association with Alzheimer's disease pathology in the living brain. Here we describe the synthesis of two meta-substituted chlorodifluoroacetophenones using a Weinreb amide strategy and their rapid conversion to the corresponding trifluoro derivatives through nucleophilic substitution by fluoride ion, in a reaction amenable to incorporating 18F for PET imaging. In vitro kinetic analysis indicates tight binding of the trifluoro derivatives to cholinesterases. Compound 1 has a Ki value of 7nM for acetylcholinesterase and 1300nM for butyrylcholinesterase while for compound 2 these values are 0.4nM and 26nM, respectively. Tight binding of these compounds to cholinesterase encourages their development for PET imaging detection of cholinesterase associated with Alzheimer's disease pathology.


Characterization of activating signal cointegrator-2 as a novel transcriptional coactivator of the xenobiotic nuclear receptor constitutive androstane receptor.
Activating signal cointegrator-2 (ASC-2) is a recently isolated transcriptional coactivator protein for a variety of different transcription factors, including many members of the nuclear receptor superfamily. In this report, we demonstrate that ASC-2 also serves as a coactivator of the xenobiotic nuclear receptor constitutive androstane receptor (CAR). First, transcriptional activation by CAR was enhanced by cotransfected ASC-2 in CV-1 and HeLa cells. In contrast, CAR transactivation was significantly impaired in HepG2 cells stably expressing specific small interfering RNA directed against ASC-2. Consistent with these results, chromatin immunoprecipitation experiments revealed that ASC-2 is recruited to the known CAR target genes in a ligand-dependent manner. Secondly, CAR specifically interacted with the first LXXLL motif of ASC-2, and these interactions were stimulated by CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene and repressed by CAR inverse agonist androstanol, suggesting that this motif may mediate the interactions of ASC-2 and CAR in vivo. In support of this idea, DN1, a fragment of ASC-2 encompassing the first LXXLL motif, suppressed CAR transactivation, and coexpressed ASC-2 but not other LXXLL-type coactivators such as thyroid hormone receptor-associated protein 220 reversed this repression. Finally, CAR was recently found to play a pivotal role in effecting the severe acetaminophen-induced liver damage. Interestingly, transgenic mice expressing DN1 were resistant to the acetaminophen-induced hepatotoxicity and expression of a series of the known CAR target genes was specifically repressed in these transgenic mice. Taken together, these results strongly suggest that ASC-2 is a bona fide coactivator of the xenobiotic nuclear receptor CAR and mediate the specific xenobiotic response by CAR in vivo.


Assessment of iron stores in anemic geriatric patients.
Of patients referred to a geriatric service, 66 were identified who were clearly anemic (hemoglobin less than 12 g in men, less than 11 g in women) but whose cause of anemia was not readily identifiable by noninvasive measures. The difficulty in distinguishing iron deficiency from chronic disease as a cause of anemia by noninvasive means (serum iron, total iron binding capacity, transferrin saturation ratio, and serum ferritin), is highlighted by the poor power of these investigations when compared with bone marrow iron stores. A transferrin saturation ratio of less than 11% and a serum ferritin of less than 45 pg/L serve better than currently accepted values to identify iron deficiency in this population.


CIRCUS: a package for Circos display of structural genome variations from paired-end and mate-pair sequencing data.
Detection of large genomic rearrangements, such as large indels, duplications or translocations is now commonly achieved by next generation sequencing (NGS) approaches. Recently, several tools have been developed to analyze NGS data but the resulting files are difficult to interpret without an additional visualization step. Circos (Genome Res, 19:1639-1645, 2009), a Perl script, is a powerful visualization software that requires setting up numerous configuration files with a large number of parameters to handle. R packages like RCircos (BMC Bioinformatics, 14:244, 2013) or ggbio (Genome Biol, 13:R77, 2012) provide functions to display genomic data as circular Circos-like plots. However, these tools are very general and lack the functions needed to filter, format and adjust specific input genomic data. We implemented an R package called CIRCUS to analyze genomic structural variations. It generates both data and configuration files necessary for Circos, to produce graphs. Only few R pre-requisites are necessary. Options are available to deal with heterogeneous data, various chromosome numbers and multi-scale analysis. CIRCUS allows fast and versatile analysis of genomic structural variants with Circos plots for users with limited coding skills.


Provision of arts therapies for people with severe mental illness.
Arts therapies are still inadequately regulated throughout the world despite a 100-year-long tradition, a vast number of academically trained therapists and importance in treating psychiatric patients. It is essential that more evidence-based studies are undertaken. Current international guidelines focus on the efficacy and effectiveness of arts therapies. New international evidence-based studies reporting clear-cut therapeutic effects of art therapy, music therapy and dance movement therapy are described here, with a focus on developments in Australia, Egypt and the United States. Further effort must be put into the development of evidence-based treatment programmes for all arts therapies, and effort needs to go into the establishment of arts therapists as a profession, with appropriate training standards.


Minimally invasive mitral valve surgery without aortic cross-clamping and with femoral cannulation is not associated with increased risk of stroke compared with traditional mitral valve surgery: a propensity score-matched analysis.
Open-heart surgery with fibrillatory arrest has been reported to be associated with an increased risk of stroke. We examined whether minimally invasive mitral valve surgery with fibrillatory arrest conferred a higher risk of stroke/transient ischaemic attack (TIA) and other major complications compared with median sternotomy and cardioplegic arrest. Data were collected prospectively for 387 patients who had mitral valve surgery; 239 had a minimally invasive surgical approach and 148 had median sternotomy. All minimally invasive surgeries were performed by surgeons who were experienced in minimally invasive techniques. The effect of operative approach on risk of stroke/TIA and major morbidity was examined. After propensity score matching (PSM) was conducted between the two groups, 76 patients remained in each group. Before matching, the incidence of stroke/TIA did not differ between patients who had minimally invasive surgery (0.5%, n = 1) and those who had median sternotomy (1.4%, n = 2; P = 0.56). Patients who had minimally invasive surgery had a lower incidence of other major morbidity (0.8%, n = 2) than patients who had median sternotomy (6.1%, n = 9; P = 0.004). After adjustment for age and Society of Thoracic Surgeons predicted risk, there was no effect of operative approach on the odds for stroke/TIA (odds ratio [OR] = 0.41, P = 0.49) or other major morbidity (OR = 0.40, P = 0.31). After PSM, patients were balanced on preoperative characteristics. No patient in either matched group experienced permanent stroke/TIA, and major morbidity did not differ between the two groups (minimally invasive, 1.3%, n = 1; median sternotomy, 1.3%, n = 1; P > 0.99). A minimally invasive approach for mitral valve surgery on a fibrillating heart was not associated with a greater incidence of stroke/TIA than was median sternotomy. When performed by highly experienced surgeons, the minimally invasive approach with fibrillatory arrest did not increase the risk of perioperative stroke.


[The toxin-containing filtrates from the culture broths of clinical strains of Corynebacterium diphtheriae].
Composition as well as toxicity and antigenicity of toxin-including filtrates of 6 circulating strains of Corynebacterium diphtheriae, isolated in 1992-1994 in the city of Kharkiv have been studied as compared with production strain PW-8. It is shown that toxicity of filtrates of circulating strains was analogous of toxicity of the strain PW-8 (100 dlm) or lower (45 dlm). Antigenicity of four strains which was expressed in if units proved to be higher than that of the production strains and it was considerably higher in two strains isolated from adults who died from diphtheria. The methods of gel-filtration and immunoprecipitation were used to establish differences between strains in their capacity to preferential accumulation of different molecular forms of toxin under stationary cultivation.


Arabidopsis heterotrimeric G protein β subunit, AGB1, regulates brassinosteroid signalling independently of BZR1.
The Arabidopsis thaliana heterotrimeric G protein β subunit, AGB1, is involved in both abscisic acid (ABA) signalling and brassinosteroid (BR) signalling, but it is unclear how AGB1 regulates these signalling pathways. A key transcription factor downstream of BR, BZR1, and its gain-of-function mutant, bzr1-1, were overexpressed in an AGB1-null mutant, agb1-1, to examine their effects on the BR hyposensitivity and the ABA hypersensitivity of agb1-1, and to examine whether AGB1 regulates the functions of BZR1. Because the amino acid sequence of AGB1 contains 17 putative modification motifs of glycogen synthase kinase 3/SHAGGY-like protein kinases (GSKs), which are known components of BR signalling, the interaction between AGB1 and one of the Arabidopsis GSKs, BIN2, was examined. Expression of bzr1-1 alleviated the effects of a BR biosynthesis inhibitor, brassinazole, in both the wild type and agb1-1, and overexpression of BZR1 alleviated the effects of ABA in both the wild type and agb1-1. AGB1 did not affect the phosphorylation state of BZR1 in vivo. AGB1 interacted with BIN2 in vitro, but did not affect the phosphorylation state of BIN2. The results suggest that AGB1 interacts with BIN2, but regulates the BR signalling in a BZR1-independent manner.


On-line continuous potentiometric measurement of potassium concentration in whole blood during open-heart surgery.
We describe a flow-through system with an ion-selective electrode for measurement of blood potassium ion concentration, continuously and on-line off the extracorporeal blood circulation in an operating theater during human open-heart surgery. Comparison measurements were made with the SMA flame photometer (blood plasma) and an Orion SS 30 sodium/potassium analyzer (whole blood). The potassium concentration values obtained with the flow-through system agree well with the ones determined with the flame photometer. The time delay of the measurement with the flow-through system was relatively long (2 min) but delays of only 10--20 s seem feasible. Short time delays can deepen insight and simplify rational treatment under surgery conditions.


The Production of Subject Anaphoric Expressions in Italian and Mexican Spanish: A Forced-Choice Experimental Study.
We compare the production of anaphoric expressions in Spanish and Italian. In two sentence completion tasks, Spanish and Italian-speaking participants complete sentence fragments where we manipulate the location of the antecedents (in a main or subordinate clause), the gender of the antecedents (similar or different) and the referent of the anaphoric expression (subject or object antecedent). Our results show a weaker subject bias for null pronouns and a weaker object bias for overt pronouns in Spanish compared to Italian. In addition, a thetic interpretation of the initial (subordinate) clause decreases the accessibility of the subject antecedent, leading to an increased use of noun phrases when there is gender-similarity between antecedents. By including gender dissimilar antecedents, we further observe an increase in speakers' production of overt pronouns when reference to an object antecedent is expected.


Imaging the C black formation by acetylene pyrolysis with molecular reactive force field simulations.
C black is a class of substantial materials with a long history of applications. However, apart from some descriptions of primary reactions, subsequent processes leading up to the final formation mechanism remain unclear. This mechanism is also crucial for understanding the formation of other carbonaceous materials. In this work, we visualize C black formation by acetylene pyrolysis using molecular dynamics simulations with a molecular reactive force field named ReaxFF. We find that the formation undergoes four stages: (1) chain elongation by H abstraction and polymerization of small C species, (2) chain branching, (3) cyclization and ring densification, and (4) condensed ring folding. The simulated C black particle possesses a structure of folded graphite layers, which is in good accordance with experimental observations. Cyclization and condensation are derived from fusion between neighboring chains, significantly varying from common experimental observations at relatively low temperatures that abide by the mechanism of H abstraction and C2H2 addition. Moreover, polyyne and polyene are usually found during acetylene pyrolysis, suggesting that the pyrolysis of acetylene and other hydrocarbons may be a feasible method of obtaining carbyne, a novel carbonaceous material with a high value.


A glucose-starvation response regulates the diffusion of macromolecules.
The organization and biophysical properties of the cytosol implicitly govern molecular interactions within cells. However, little is known about mechanisms by which cells regulate cytosolic properties and intracellular diffusion rates. Here, we demonstrate that the intracellular environment of budding yeast undertakes a startling transition upon glucose starvation in which macromolecular mobility is dramatically restricted, reducing the movement of both chromatin in the nucleus and mRNPs in the cytoplasm. This confinement cannot be explained by an ATP decrease or the physiological drop in intracellular pH. Rather, our results suggest that the regulation of diffusional mobility is induced by a reduction in cell volume and subsequent increase in molecular crowding which severely alters the biophysical properties of the intracellular environment. A similar response can be observed in fission yeast and bacteria. This reveals a novel mechanism by which cells globally alter their properties to establish a unique homeostasis during starvation.


Acute Traumatic Quadriplegia in Adults: Predictors of Acute in-Hospital Mortality.
To assess the in-hospital mortality rate in adult patients suffering acute traumatic complete quadriplegia and determine the possible predictors of mortality in these patients. A review of all complete quadriplegics treated from January 1996 through March 2004 in a regional spine injuries unit measuring in-hospital mortality and other factors that might contribute to increased mortality. Multivariate logistic regression analysis was performed to explore these possible predictors of mortality. We identified 126 cases of cervical spinal cord injury treated at our hospital from January 1996 to March 2004 and identified only 62 cases of complete quadriplegia. Of 62 patients, 11 (17.7%) died in the hospital. Age, gender, injury mechanism and medical co-morbidity showed only trends towards a higher mortality. Age and pre-injury medical co-morbidity were found to be significant independent predicting factors for mortality. Gender, mechanism of injury, neurological level and injury severity score were not the predictors of mortality in these patients. Despite the limitations of the current evidence, advanced age and pre-existing medical co-morbidity are likely predictors of hospital mortality in the traumatic quadriplegia population.