Functional activation and neural networks in women with posttraumatic stress disorder related to intimate partner violence.
Intimate partner violence (IPV) is one of the most common causes of posttraumatic stress disorder (PTSD) in women. Victims of IPV are often preoccupied by the anticipation of impending harm. This investigation tested the hypothesis that IPV-related PTSD individuals show exaggerated insula reactivity to the anticipation of aversive stimuli. Fifteen women with a history of IPV and consequent PTSD (IPV-PTSD) and 15 non-traumatized control (NTC) women performed a task involving cued anticipation to images of positive and negative events during functional magnetic resonance imaging. Both groups showed increased activation of bilateral anterior insula during anticipation of negative images minus anticipation of positive images. Activation in right anterior/middle insula was significantly greater in the IPV-PTSD relative to the NTC group. Functional connectivity analysis revealed that changes in activation in right middle insula and bilateral anterior insula were more strongly associated with amygdala activation changes in NTC than in IPV-PTSD subjects. This study revealed increased activation in the anterior/middle insula during negative anticipation in women with IPV-related PTSD. These findings in women with IPV could be a consequence of the IPV exposure, reflect pre-existing differences in insular function, or be due to the development of PTSD. Thus, future longitudinal studies need to examine these possibilities.


Bladder electromyography: response to electric stimulation and to terbutaline.
Four patients with traumatic spinal cord injuries and paraplegia received electric stimulation of the conus medullaris. An additional 5 patients with traumatic spinal cord injuries and paraplegia received terbutaline for asthma. All 9 patients were studied with bladder and external urethral sphincter electromyography (EMG). Bladder pressures were recorded in the electric stimulation group and cystometry in the terbutaline group. The electric impulses were recorded without attenuation, and bladder and external urethral sphincter contractility increased. Terbutaline reduced the bladder's electric activity and pressure at capacity without affecting external urethral sphincter function. More evaluations of terbutaline's effect on the bladder are necessary to determine its applicability to incontinence problems.


Monitoring eukaryotic and bacterial UDG repair activity with DNA-multifluorophore sensors.
We report the development of simple fluorogenic probes that report on the activity of both bacterial and mammalian uracil-DNA glycosylase (UDG) enzymes. The probes are built from short, modified single-stranded oligonucleotides containing natural and unnatural bases. The combination of multiple fluorescent pyrene and/or quinacridone nucleobases yields fluorescence at 480 and 540 nm (excitation 340 nm), with large Stokes shifts of 140-200 nm, considerably greater than previous probes. They are strongly quenched by uracil bases incorporated into the sequence, and they yield light-up signals of up to 40-fold, or ratiometric signals with ratio changes of 82-fold, on enzymatic removal of these quenching uracils. We find that the probes are efficient reporters of bacterial UDG, human UNG2, and human SMUG1 enzymes in vitro, yielding complete signals in minutes. Further experiments establish that a probe can be used to image UDG activity by laser confocal microscopy in bacterial cells and in a human cell line, and that signals from a probe signalling UDG activity in human cells can be quantified by flow cytometry. Such probes may prove generally useful both in basic studies of these enzymes and in biomedical applications as well.


The emerging role of 3D printing in water desalination.
Unmatched flexibility in terms of material selection, design and scalability, along with gradually decreasing cost, has led 3D printing to gain significant attention in various water treatment and desalination applications. In desalination, 3D printing has been applied to improve the energy efficiency of existing technologies. For thermal desalination, this involves the use of 3D printed components that enhance water evaporation and energy harvesting with new materials and designs. For membrane-based desalination, 3D printing offers membranes and other module components with customized materials and geometries for better fouling resistance and productivity. This review highlights the current status, advances and challenges associated with 3D printing in both thermal and membrane-based desalination technologies. Other unique benefits offered by 3D printing for water desalination along with the associated challenges are also discussed in this review. Finally, the future prospects and research directions are highlighted related to the application of 3D printing in the water desalination industry.


Effects of cocaine and morphine on IgG production by human peripheral blood lymphocytes in vitro.
Elevated serum levels of IgG are amongst the immunological abnormalities exhibited by intravenous drug addicts. We therefore addressed the hypothesis that cocaine and morphine (the major metabolite of heroin) exert a direct effect on human B cell function in vitro. Human peripheral blood mononuclear cells from normal individuals were incubated for 7 days with the T cell-dependent B cell activator pokeweed mitogen (PWM) and serial dilutions of either cocaine or morphine. At the end of this time total IgG was measured by use of a sandwich ELISA incorporating a biotin-labelled affinity-purified anti-IgG and streptavidin peroxidase. At concentrations relevant to those found in plasma, morphine and cocaine did not affect PWM-stimulated IgG synthesis in vitro. We suggest that these drugs of abuse do not directly influence human B cells, but in vivo exert immune modulatory effects via indirect mechanisms.


Opportunities for shared decision-making about major surgery with high-risk patients: a multi-method qualitative study.
Little is known about the opportunities for shared decision-making when older high-risk patients are offered major surgery. This study examines how, when, and why clinicians and patients can share decision-making about major surgery. This was a multi-method qualitative study, combining video recordings of preoperative consultations, interviews, and focus groups (33 patients, 19 relatives, 36 clinicians), with observations and documentary analysis in clinics in five hospitals in the UK undertaking major orthopaedic, colorectal, and/or cardiac surgery. Three opportunities for shared decision-making about major surgery were identified. Resolution-focused consultations (cardiac/colorectal) resulted in a single agreed preferred option related to a potentially life-threatening problem, with limited opportunities for shared decision-making. Evaluative and deliberative consultations offered more opportunity. The former focused on assessing the likelihood of benefits of surgery for a presenting problem that was not a threat to life for the patient (e.g., orthopaedic consultations) and the latter (largely colorectal) involved discussion of a range of options while also considering significant comorbidities and patient preferences. The extent to which opportunities for shared decision-making were available, and taken up by surgeons, was influenced by the nature of the presenting problem, clinical pathway, and patient trajectory. Decisions about major surgery were not always shared between patients and doctors. The nature of the presenting problem, comorbidities, clinical pathways, and patient trajectories all informed the type of consultation and opportunities for sharing decision-making. Our findings have implications for clinicians, with shared decision-making about major surgery most feasible when the focus is on life-enhancing treatment.


Cardiac xenotransplantation: progress and challenges.
Cardiac xenotransplantation (CXTx) remains a promising approach to alleviate the chronic shortage of donor hearts. This review summarizes recent results of heterotopic and orthotopic CXTx, highlights the role of non-Gal antibody in xenograft rejection, and discusses challenges to clinical orthotopic CXTx. Pigs mutated in the α 1,3 galactosyltransferase gene (GTKO pigs) are devoid of the galactose α1,3 galactose (αGal) carbohydrate antigen. This situation effectively eliminates any role for anti-Gal antibody in GTKO cardiac xenograft rejection. Survival of heterotopic GTKO cardiac xenografts in nonhuman primates continues to increase. GTKO graft rejection commonly involves vascular antibody deposition and variable complement deposition. Non-Gal antibody responses to porcine antigens associated with inflammation, complement, and hemostatic regulation and to new carbohydrate antigens have been identified. Their contribution to rejection remains under investigation. Orthotopic CXTx is limited by early perioperative cardiac xenograft dysfunction (PCXD). However, hearts affected by PCXD recover full cardiac function and orthotopic survival up to 2 months without rejection has been reported. CXTx remains a promising technology for treating end-stage cardiac failure. Genetic modification of the donor and refinement of immunosuppressive regimens have extended heterotopic cardiac xenograft survival from minutes to in excess of 8 months.


Interferon: cellular executioner or white knight?
Interferons (IFNs) are a family of pleiotropic cytokines that typically exhibit antiviral, antiproliferative, antitumor, and immunomodulatory properties. While their complex mechanisms of action remain unclear, IFNs are used clinically in the treatment of viral infections, such as hepatitis B and hepatitis C, and remain the primary treatment for a limited number of malignancies, such as melanoma, hairy cell leukemia, and non-Hodgkin's lymphoma and in autoimmune diseases such as multiple sclerosis. IFNs not only regulate somatic cell growth and division but also influence cell survival through the modulation of apoptosis. Paradoxically, IFNs are described to be both pro- and anti-apoptotic in nature. The biological effects of IFNs are primarily mediated via activation of the JAK/STAT pathway, formation of the ISGF3 and STAT1:STAT1 protein complexes, and the subsequent induction of IFN-stimulated genes. However, the activation of JAK/STAT-independent signal transduction pathways also contribute to IFN-mediated responses. To further demonstrate the complexity of the downstream events following stimulation, oligonucleotide microarray studies have shown that in excess of 300 genes are induced following treatment with IFN, some of which are crucial to the induction of apoptosis and cell growth control. In this review we describe the recent advances made in elucidating the various signaling pathways that are activated by IFNs and how these diverse signals contribute to the regulation of cell growth and apoptosis and inhibition of viral replication. Furthermore, we highlight the role of specific signaling molecules and the function(s) of particular IFN-stimulated genes that have been implicated in determining cell fate in response to IFN, as well as the clinical experience of IFN immunotherapy.


Factors associated with treatment failure of direct-acting antivirals for chronic hepatitis C: A real-world nationwide hepatitis C virus registry programme in Taiwan.
Direct-acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)-infected patients. The real-world treatment outcome in Taiwanese patients on a nationwide basis is elusive. The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end-of-treatment). A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype-1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment-naïve noncirrhotic, treatment-naïve cirrhotic, treatment-experienced noncirrhotic and treatment-experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment-experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment-naïve noncirrhotic patients (94.8%) and treatment-experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence < 60% ( adjusted odds ratio [aOR]/95% confidence interval [CI]: 117.1/52.4-261.3, P < .001), followed by GT3/GT2 (aOR/CI: 5.78/2.25-14.9, P = .0003 and aOR/CI: 1.55/1.05-2.29, P = .03, compared with GT1), active hepatocellular carcinoma (aOR/CI: 4.29/2.57-7.16, P < .001), the use of sofosbuvir/ribavirin (aOR/CI: 2.51/1.67-3.77, P < .001) and daclatasvir/asunaprevir (aOR/CI: 3.29/1.94-5.58, P < .001), decompensated liver cirrhosis (aOR/CI: 2.50/1.20-5.22, P = .02) and high HCV viral loads (aOR/CI: 2.16/1.57-2.97, P < .001). DAAs are highly effective in treating Taiwanese HCV patients in the real-world setting. Maintaining DAA adherence and selecting highly efficacious regimens are keys to ensure treatment success.


Measuring Spinal Mobility Using an Inertial Measurement Unit System: A Validation Study in Axial Spondyloarthritis.
Portable inertial measurement units (IMUs) are beginning to be used in human motion analysis. These devices can be useful for the evaluation of spinal mobility in individuals with axial spondyloarthritis (axSpA). The objectives of this study were to assess (a) concurrent criterion validity in individuals with axSpA by comparing spinal mobility measured by an IMU sensor-based system vs. optical motion capture as the reference standard; (b) discriminant validity comparing mobility with healthy volunteers; (c) construct validity by comparing mobility results with relevant outcome measures. A total of 70 participants with axSpA and 20 healthy controls were included. Individuals with axSpA completed function and activity questionnaires, and their mobility was measured using conventional metrology for axSpA, an optical motion capture system, and an IMU sensor-based system. The UCOASMI, a metrology index based on measures obtained by motion capture, and the IUCOASMI, the same index using IMU measures, were also calculated. Descriptive and inferential analyses were conducted to show the relationships between outcome measures. There was excellent agreement (ICC > 0.90) between both systems and a significant correlation between the IUCOASMI and conventional metrology (r = 0.91), activity (r = 0.40), function (r = 0.62), quality of life (r = 0.55) and structural change (r = 0.76). This study demonstrates the validity of an IMU system to evaluate spinal mobility in axSpA. These systems are more feasible than optical motion capture systems, and they could be useful in clinical practice.


Transcriptome analysis in primary neural stem cells using a tag cDNA amplification method.
Neural stem cells (NSCs) can be isolated from the adult mammalian brain and expanded in culture, in the form of cellular aggregates called neurospheres. Neurospheres provide an in vitro model for studying NSC behaviour and give information on the factors and mechanisms that govern their proliferation and differentiation. They are also a promising source for cell replacement therapies of the central nervous system. Neurospheres are complex structures consisting of several cell types of varying degrees of differentiation. One way of characterising neurospheres is to analyse their gene expression profiles. The value of such studies is however uncertain since they are heterogeneous structures and different populations of neurospheres may vary significantly in their gene expression. To address this issue, we have used cDNA microarrays and a recently reported tag cDNA amplification method to analyse the gene expression profiles of neurospheres originating from separate isolations of the lateral ventricle wall of adult mice and passaged to varying degrees. Separate isolations as well as consecutive passages yield a high variability in gene expression while parallel cultures yield the lowest variability. We demonstrate a low technical amplification variability using the employed amplification strategy and conclude that neurospheres from the same isolation and passage are sufficiently similar to be used for comparative gene expression analysis.


The role of FACT in making and breaking nucleosomes.
FACT is a roughly 180kDa heterodimeric protein complex important for managing the properties of chromatin in eukaryotic cells. Chromatin is a repressive barrier that plays an important role in protecting genomic DNA and regulating access to it. This barrier must be temporarily removed during transcription, replication, and repair, but it also must be rapidly restored to the original state afterwards. Further, the properties of chromatin are dynamic and must be adjusted as conditions dictate. FACT was identified as a factor that destabilizes nucleosomes in vitro, but it has now also been implicated as a central factor in the deposition of histones to form nucleosomes, as an exchange factor that swaps the histones within existing nucleosomes for variant forms, and as a tether that prevents histones from being displaced by the passage of RNA polymerases during transcription. FACT therefore plays central roles in building, maintaining, adjusting, and overcoming the chromatin barrier. This review summarizes recent results that have begun to reveal how FACT can promote what appear to be contradictory goals, using a simple set of binding activities to both enhance and diminish the stability of nucleosomes. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.


Clinical status and cardiovascular risk profile of adults with a history of juvenile dermatomyositis.
A pilot study of adults who had onset of juvenile dermatomyositis (JDM) in childhood, before current therapeutic approaches, to characterize JDM symptoms and subclinical cardiovascular disease. Eight adults who had JDM assessed for disease activity and 8 healthy adults (cardiovascular disease controls) were tested for carotid intima media thickness and brachial arterial reactivity. Adults who had JDM and 16 age-, sex-, and body mass index-matched healthy metabolic controls were evaluated for body composition, blood pressure, fasting glucose, lipids, insulin resistance, leptin, adiponectin, proinflammatory oxidized high-density lipoprotein (HDL), and nail-fold capillary end row loops. Adults with a history of JDM, median age 38 years (24-44 years) enrolled a median 29 years (9-38 years) after disease onset, had elevated disease activity scores, skin (7/8), muscle (4/8), and creatine phosphokinase (2/8). Compared with cardiovascular disease controls, adults who had JDM were younger, had lower body mass index and HDL cholesterol (P = .002), and increased intima media thickness (P = .015) and their brachial arterial reactivity suggested impairment of endothelial cell function. Compared with metabolic controls, adults who had JDM had higher systolic and diastolic blood pressure, P = .048, P = .002, respectively; lower adiponectin (P = .03); less upper arm fat (P = .008); HDL associated with end row loops loss (r = -0.838, P = .009); and increased proinflammatory oxidized HDL (P = .0037). Adults who had JDM, 29 years after disease onset, had progressive disease and increased cardiovascular risk factors.


Clinical features of Wilms' tumor and treatment results.
We retrospectively reviewed 34 children treated for Wilms' tumors at Chang-Gung Memorial Hospital from September 1979 to April 1992. The clinical data were analyzed. Patients were treated with standard multimodal therapy; three patients received preoperative chemotherapy. The survival and relapse-free survival curves were calculated for the overall group and compared with prognostic variables. Patients included 20 boys and 14 girls; the median age at diagnosis was 2 years 1 month. Congenital anomalies, hypertension and gross hematuria were found in 11.8%, 17.9% and 17.9%, respectively. The tumors were on the right side in 19 patients, on the left side in 13, and bilateral in two. Tumor weights ranged from 95 g (following preoperative chemotherapy) to 3500 g. The tumor was histologically favorable in 29 cases (85.3%), anaplastic in two and clear cell sarcoma in three. The clinical stages of these patients were: stage 1, 10; stage II, five; stage III, 15, stage IV, two; and stage V, two. The median follow-up duration was 26 months (range, eight weeks to 12 years 10 months). Eight patients had a poor outcome and four patients died of disease. The probability of survival was 83.6% and the relapse-free survival was 69.4% at five years. Tumor histology and clinical stage were associated with statistically significant differences in outcome. The complications and patterns of relapse are discussed. The annual incidence rate of Wilms' tumor in Taiwan is estimated to be 2.7 per million children under the age of 15 years.


Enhancement of pyrimidine nucleoside uptake into K562 and YAC-1 cells by cadeguomycin.
Cadeguomycin markedly stimulated the uptake of thymidine, deoxycytidine and uridine into the acid-insoluble fraction of K562 human leukemic cells, but did not significantly affect adenosine incorporation. The enhancement of pyrimidine nucleoside uptake was 6 approximately 17 fold over the control. Aspartate incorporation into nucleic acid was not significantly blocked by the antibiotic, suggesting that the stimulation of pyrimidine nucleoside incorporation is not due to the inhibition of de novo pyrimidine nucleotide synthesis. Net DNA and RNA syntheses, observed by [32P]phosphate uptake, were not significantly affected by cadeguomycin. The enzymatic activity of thymidine, deoxycytidine and uridine kinases was higher in cadeguomycin-treated cells than in untreated cells, suggesting that the enhancement of pyrimidine nucleoside uptake occurs in the phosphorylation process. The stimulatory activity of cadeguomycin of thymidine uptake was reversed by guanosine and deoxyguanosine, but not by adenosine and deoxyadenosine, suggesting that intracellular metabolism and/or action of cadeguomycin is related to that of guanosine and deoxyguanosine. The stimulation of pyrimidine nucleoside incorporation by cadeguomycin was also found with YAC-1 cells, but not with the other cell lines. The enhancement effect of the antibiotic seems to be not directly related to its cytotoxicity.


Febrile exudative tonsillitis: viral or streptococcal?
A prospective 1-year study of acute febrile exudative tonsillitis in 110 children was carried out. Viral infection was associated with 42% of the cases, beta-hemolytic streptococci with 31% (12% group A), Mycoplasma pneumoniae with 5%, and unknown cause with 35%. More than one agent was implicated in 14% of the cases. Adenovirus was the viral agent most frequently (19%) recorded. Other viruses involved were Epstein-Barr virus, parainfluenza, influenza A, herpes simplex, and respiratory syncytial viruses. The responsible agent was found by rapid viral antigen detection in 20% of all cases and by rapid test for group A streptococcal antigen detection in 10%. Age was the most important factor in predicting the causative agent. Viral tonsillitis was most common in children younger than 3 years of age and group A beta-hemolytic streptococci tonsillitis in children 6 years of age or more. Clinical analysis of the illness, WBC count, and ESR did not reveal differences that could help in differentiating bacterial from viral tonsillitis. All patients were treated with a regimen of oral penicillin. Fever associated with group A beta-hemolytic streptococci tonsillitis responded to penicillin therapy significantly more rapidly than fever associated with viral infections. These observations demonstrate the prominent role of viruses in the etiology of febrile exudative tonsillitis, especially in young children, and reinforce the benefit of rapid tests before antibiotic therapy is started.


Smoking during pregnancy among immigrants to Sweden, 1992-2008: the effects of secular trends and time since migration.
Smoking during pregnancy has been declining in the past decades in high-income countries, including Sweden. Paradoxically, increasing trends associated with duration of residence have been reported among immigrants. We aimed to clarify how these two contrasting trends have shaped smoking patterns among immigrants. We conducted a population-based study of 1 598 433 pregnancies in Sweden in the period 1992-2008. We used multinomial logistic regression to estimate the odds of mild and heavy smoking relative to no smoking associated with year of delivery, years since migration, maternal region of birth and their interaction, after controlling for potential confounders. The prevalence of smoking decreased for the Swedish-born and for immigrants during the study period. Among immigrants, duration of residence was independently associated with increases in smoking and varied according to maternal region of birth (P-value for interaction <0.001). The odds ratio associated with a 10-year increase in duration of residence was weakest for mild smoking among former Yugoslav women (adjusted odds ratio; 95% confidence interval: 1.10; 1.04-1.17) and those from other Nordic countries (1.22; 1.17-1.26) and strongest for heavy smoking among East African (4.46; 3.23-6.16) and sub-Saharan African (3.56; 2.68-4.72) women. The association between duration of residence and smoking was attenuated after stratifying by cohorts of arrival among European but not among non-European immigrants. Declines in smoking during pregnancy among immigrants from various regions of the world were differentially affected by opposite increasing trends throughout their residence in Sweden.


Duration of exclusive breastfeeding may be related to eating behaviour and dietary intake in obesity prone normal weight young children.
Infants who are breastfed are introduced to a variety of flavours from the maternal milk, and thus the transition from maternal milk to complementary foods may be easier for these children. The aim of this study was to investigate if duration of exclusive breastfeeding was associated with pickiness or dietary intake of vegetables, fruit, starchy foods or sugar sweetened beverages among obesity prone normal weight children aged 2-6 years. This cohort study was based on data from the Healthy Start primary intervention study, the Danish Medical Birth registry and the Danish Health Visitor's Child Health Database. Infant feeding was registered by health nurses while home-visiting the mother and child up to four times within the first year. Information on eating behaviour and diet intake at age 2-6 years was obtained by parents. Crude and adjusted logistic and general linear regression models were used to investigate associations. A total of 236 children had complete information on all variables. Data showed lower odds of picky eating behaviour when exclusively breastfed until age 4-5 months compared to exclusively breastfed for 0-1 months (OR = 0.35, 95CI = 0.16;0.76, p = 0.008). In the crude analysis only, exclusively breastfed until age 6-10 months was associated with a higher daily intake of vegetables (p = 0.04). This study suggests that exclusive breastfeeding duration seems to influence pickiness and may contribute to facilitate the consumption of more vegetables in later childhood in obesity prone normal weight children.


Analysis and control of multi-zone sound field reproduction using modal-domain approach.
Multi-zone sound control aims to reproduce multiple sound fields independently and simultaneously over different spatial regions within the same space. This paper investigates the multi-zone sound control problem formulated in the modal domain using the Lagrange cost function and provides a modal-domain analysis of the problem. The Lagrange cost function is formulated to represent a quadratic objective of reproducing a desired sound field within the bright zone and with constraints on sound energy in the dark zone and global region. A fundamental problem in multi-zone reproduction is interzone sound interference, where based on the geometry of the sound zones and the desired sound field within the bright zone the achievable reproduction performance is limited. The modal-domain Lagrangian solution demonstrates the intrinsic ill-posedness of the problem, based on which a parameter, the coefficient of realisability, is developed to evaluate the reproduction limitation. The proposed reproduction method is based on controlling the interference between sound zones and sound leakage outside the sound zones, resulting in a suitable compromise between good bright zone performance and satisfactory dark zone performance. The performance of the proposed design is demonstrated through numerical simulations of two-zone reproduction in free-field and in reverberant environments.


Level of acculturation and hypertension among Dallas County Hispanics: findings from the Dallas Heart Study.
The purpose of this study is to examine whether the prevalence of hypertension differs by acculturation status among Hispanics in Dallas County, Texas. The authors test the hypothesis that compared with those of low acculturation, those of mid- and high-level acculturation will be at greater risk for having hypertension. Conducted from July 2000 through October 2002, the Dallas Heart Study (DHS) is a general population cross-sectional study of cardiovascular risk factors among Dallas County residents. These analyses focus on the 1163 DHS participants who self-reported Hispanic ethnicity, completed a household interview, and had blood pressures measured. Acculturation was assessed with a validated 12-item scale that measured the following dimensions of cultural adaptation: language; media preference; social interaction; and ease of relationships with those of other ethnicities. The majority of participants were born in Mexico (57.5%) and ranged in age from 18 to 65 years (mean age 33 years). Women made up just under half of the sample (47.81%). The unadjusted prevalence of hypertension was 9.78%. When age-adjusted for the 2000 US Standard Population, the prevalence was 17.27%. The chi(2) analysis showed that those of low acculturation were significantly less likely to have hypertension (6.05%) than those of mid- and high-level acculturation (10.78% and 12.80%, respectively). After controlling for the effects of possible confounders (i.e., sociodemographic factors, health care access and utilization, health behaviors, and health status), logistic regression showed that when compared with Hispanics of low acculturation, those of middle and high acculturation were at greater risk of having hypertension (OR=3.04, 95% CI, 1.27, 7.29 and OR=2.62, 95% CI, 1.04, 6.59, respectively). These findings demonstrate that acculturation is significantly associated with hypertensive status.


Virtual street-crossing performance in persons with multiple sclerosis: Feasibility and task performance characteristics.
Multiple sclerosis (MS) is a neurological disease that commonly results in physical and cognitive dysfunction. Accordingly, MS might impact the ability to safely cross the street. The purpose of this study was to examine the feasibility of a simulated street-crossing task in persons with MS and to determine differences in street-crossing performance between persons with MS and non-MS controls. 26 participants with MS (median Expanded Disability Status Scale [EDSS] score = 3.5) and 19 controls completed 40 trials of a virtual street-crossing task. There were 2 crossing conditions (i.e., no distraction and phone conversation), and participants performed 20 trials per condition. Participants were instructed that the goal of the task was to cross the street successfully (i.e., without being hit be a vehicle). The primary outcome was task feasibility, assessed as completion and adverse events. Secondary outcomes were measures of street-crossing performance. Overall, the simulated street-crossing task was feasible (i.e., 90% completion, no adverse events) in participants with MS. Participants with MS waited longer and were less attentive to traffic before entering the street compared with controls (all P < .05). Participants with MS also took longer to cross the street and were closer to oncoming vehicles when exiting the street compared to controls (all P < .05). When distracted, all participants took longer to initiate crossing, took longer to cross the street, and made more head turns while crossing (all P < .05). There were no significant group by condition interaction effects (all P > .05). A virtual street-crossing task is feasible for studying street-crossing behavior in persons with mild MS and most individuals with moderate MS. Virtual street-crossing performance is impaired in persons with MS compared to controls; however, persons with MS do not appear to be more vulnerable to a distracting condition. The virtual reality environment presents a safe and useful setting for understanding pedestrian behavior in persons with MS.


[Stress on the ligamentum transversum acetabuli in physiological stress on the hip joint].
We investigated the strain on the transverse acetabular ligament (TAL) and the labrum close to the anterior and posterior horn of the lunate surface using Omega strain gauges [5] while increasing loads were applied to the hip joint. Two fresh hip joint specimens and four specimens fixed in 3.7% formalin were examined. The two components of the joint were disarticulated and soaked in physiological saline and then placed in a material-testing machine (Zwick) in the neutral position of the joint. The strain on the TAL and the labrum was measured at loads of 10 N, 350 N, 700 N, 1050 N, 1400 N, 2100 N and 2800 N. Finally, the contact areas were measured at a load of 350 N using a polyether casting method. Depending on load, the length of the TAL increased by up to about 3.2% at a load of 2800 N, but the length of the labrum increased by only 0.5% at the same load. Following rotation of the femoral head to positions corresponding to 15 degrees extension and 15 degrees and 30 degrees flexion, only slight differences of about 0.2% for the TAL and even less for the labrum were measured. The contact areas are all located in the anterior and posterior horn of the lunate surface. The measured changes in strain on the TAL confirm the widening of the acetabular notch and a subsequent stretching of the TAL as the load on the hip joint increases.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthetic Biology of Cannabinoids and Cannabinoid Glucosides in Nicotiana benthamiana and Saccharomyces cerevisiae.
Phytocannabinoids are a group of plant-derived metabolites that display a wide range of psychoactive as well as health-promoting effects. The production of pharmaceutically relevant cannabinoids relies on extraction and purification from cannabis (Cannabis sativa) plants yielding the major constituents, Δ9-tetrahydrocannabinol and cannabidiol. Heterologous biosynthesis of cannabinoids in Nicotiana benthamiana or Saccharomyces cerevisiae may provide cost-efficient and rapid future production platforms to acquire pure and high quantities of both the major and the rare cannabinoids as well as novel derivatives. Here, we used a meta-transcriptomic analysis of cannabis to identify genes for aromatic prenyltransferases of the UbiA superfamily and chalcone isomerase-like (CHIL) proteins. Among the aromatic prenyltransferases, CsaPT4 showed CBGAS activity in both N. benthamiana and S. cerevisiae. Coexpression of selected CsaPT pairs and of CHIL proteins encoding genes with CsaPT4 did not affect CBGAS catalytic efficiency. In a screen of different plant UDP-glycosyltransferases, Stevia rebaudiana SrUGT71E1 and Oryza sativa OsUGT5 were found to glucosylate olivetolic acid, cannabigerolic acid, and Δ9-tetrahydrocannabinolic acid. Metabolic engineering of N. benthamiana for production of cannabinoids revealed intrinsic glucosylation of olivetolic acid and cannabigerolic acid. S. cerevisiae was engineered to produce olivetolic acid glucoside and cannabigerolic acid glucoside.


[Correlation of neurodevelopmental disorders in schizophrenia].
Contemporary aetiopathogenetic considerations, based on neuro-imaging, genetic and developmental neurobiology studies, suggest neurodevelopmental origin of schizophrenia. Several lines of evidence including structural abnormalities on in vivo brain imaging, the excess of prenatal and obstetric complications and the association of congenital and minor physical anomalies with schizophrenia, strongly indicate the neurodevelopmental pathogenesis of schizophrenia. On the other hand, controversial concept of psychotic continuum suggests schizophrenia and depression sharing the same genetic contribution to the pathogenesis. If this would be the case, depression could also be considered as neurodevelopmental disorder. The aims of the study were to investigate the association between: a) pregnancy and birth complications (PBC), and b) minor physical anomalies (MPA) and schizophrenia or depression. Experimental groups consisted of 60 schizophrenic, 28 major depression patients and 30 healthy controls. All patients were diagnosed according to DSM-IV. Schizophrenic group was divided with regard to PANSS score into positive (n = 32) and negative form (n = 28) subgroups. PBC informations were gathered from maternal recall while MPA were examined by using Waldrop scale for adults. The results showed that negative and positive schizophrenic subgroups had significantly more PBC than depressive group (p < 0.05), as well than controls (p < 0.001; p < 0.05; respectively). There was nonsignificant trend for more PBC in negative than in positive subgroup. All schizophrenic patients had higher rates of MPA than depressives (p < 0.05). This trend for more MPA was not significant in comparison with healthy controls. These findings suggest that schizophrenia, especially its negative forms, could be considered as a member of the spectrum of neurodevelopmental disorders, which does not seem to be the case with depression. PBC and MPA could also be valuable in evaluation of risks for schizophrenia and possible predictive indicators of its development.


A novel landmark for endonasal surgery of the pterygopalatine fossa and inferior orbital fissure: The orbito-pterygo-sphenoidal ligament.
The pterygopalatine fossa contains a dense and complex array of neurovascular structures vulnerable to accidental surgical injury. This study aims to describe a novel landmark, the orbito-pterygo-sphenoidal ligament (OPSL), and implications of this structure for surgery in the pterygopalatine fossa and the inferior orbital fissure. Six cadaveric specimens (12 sides) were dissected using an endonasal approach to expose the periosteal layers associated with the pterygopalatine fossa and orbit. The thickened triangular-shaped ligament at their confluence was termed the OPSL. Dimensions of its lateral, inferior, and medial borders were measured, and their anatomical relationships defined. The pterygopalatine ganglion and the maxillary nerve lie immediately inferior and deep into the OPSL. The superior aspect of the posterior nasoseptal artery and nerve are covered by the medial OPSL. The lateral and inferior borders of the OPSL are contiguous with the periorbita and the periosteum of the pterygopalatine fossa, respectively. Along the medial border of the ligament, the openings of the palatovaginal fissure, vidian canal, and foramen rotundum were sequentially identified in a medial to lateral trajectory. The length of the lateral, inferior, and medial borders of the triangular OPSL were 13.25 ± 0.62, 14.25 ± 0.45, and 12.08 ± 0.90 mm, respectively. The OPSL is a thick, triangular-shaped fascial confluence, which may serve as a landmark for procedures within the pterygopalatine fossa and the inferior orbital fissure.


Quality of life in children surviving cancer: a personality and multi-informant perspective.
To describe quality of life (QoL) of children surviving cancer in relation to their personality, using self- and maternal reports and examining differences with healthy referents. Sixty-seven children who survived childhood cancer were compared with eighty-one healthy children on QoL and personality characteristics. Children who survived cancer reported higher QoL than healthy children, whereas there were no differences for personality. Two main effects emerged for informant with children rating themselves as less neurotic and more conscientious than their mothers. The correspondence between mothers and children was substantially higher for survivors for QoL and personality ratings. QoL and trait measures share substantial variance, and personality traits significantly predict QoL. Parental personality ratings explained child QoL beyond children's personality ratings. Personality traits contribute to quality of life, indicating that personality significantly influences child's quality of life beyond the experience of a negative life event such as surviving cancer and its treatment. From a diagnostic perspective, parental trait ratings are informative in addition to children's ratings of personality to understand children's QoL.


Factors Influencing COVID-19 Vaccination Intentions Among College Students: A Cross-Sectional Study in India.
Background: Students act as messengers in delivering effective messages for better uptake of health-promoting behavior. Understanding their knowledge about coronavirus disease 2019 (COVID-19), intentions to use the COVID-19 vaccine, and its associated factors will help develop promising strategies in vaccine promotion concerning the current COVID-19 pandemic. Methods: A cross-sectional online survey was carried out among students in the healthcare and non-healthcare sectors to assess their intentions to get vaccinated against the COVID-19. A non-probability snowball sampling technique was used to recruit study participants (N = 655) through social media platforms and emails. Study participants were recruited across the country, including six major geographical regions (Eastern, Western, Northern, Southern, North-east, and Central) in India between November 2020 and January 2021 before the introduction of the COVID-19 vaccine. Descriptive statistics were used to present the sociodemographic, and vaccine-related behaviors of the study participants. Key determinants that likely predict vaccine acceptance among students were modeled using logistic regression analysis. For each analysis, p < 0.05 was considered significant. Results: A total of 655 students were recruited, 323 from healthcare and 332 from non-healthcare sectors, to assess their intentions to receive the COVID-19 vaccine. Of the 655 students, 63.8% expressed intentions to receive the COVID-19 vaccine. The acceptance was higher among non-healthcare students (54.07 vs. 45.93%). At the time of the study, 27.8% of the students indicated that they had been exposed to a confirmed COVID-19 patient. A vast majority (93.4%) of the students knew about the COVID-19 virus, and most (89.3%) of them were aware of the development of a COVID-19 vaccine. The history of vaccine hesitancy was found to be low (17.1%). Only one-third (33.4%) of the students showed concern about contracting COVID-19. Trust in the healthcare system [adjusted odds ratio (aOR): 4.13; (95% CI: 2.83-6.04), p < 0.00] and trust in domestic vaccines [aOR: 1.46; (95% CI: 1.02-2.08), p < 0.05] emerged as the significant predictors of student's intention to get vaccinated. Higher acceptance for vaccine was observed among students in the non-healthcare [aOR: 1.982; 95% CI: 1.334-2.946, p < 0.00]. Conclusion: This study shows that the Indian college students had relatively high levels of positive intentions to receive COVID-19 vaccines, although about one-third were not sure or unwilling to receive the vaccine, highlighting possible vaccine hesitancy. Informational campaigns and other strategies to address vaccine hesitancy are needed to promote uptake of COVID-19 vaccines.


High-quality, high-throughput, early whole-body bone scanning.
99mTc-IDP allows for high-quality, high-throughput and early whole-body bone scanning. Whole-body bone scans obtained at 30 min after intravenous administration of the tracer were compared with the standard and delayed 180 min p.i images. A subtraction technique allowed for the anlysis of the 30 min scans and it was found that in both types of investigation the same clinical information was present. This procedure will therefore increase considerably the throughput of whole-body bone scans in a busy department of nuclear medicine. It is however inadequate for detailed analysis of the skeleton (evaluation of benign bone disease).


Granulocyte colony-stimulating factor (G-CSF) production and G-CSF receptor structure in patients with congenital neutropenia.
Congenital neutropenia (Kostmann's syndrome [KS]) is an autosomal recessive syndrome that is characterized by profound neutropenia, resulting in major clinical infections and death. Since the neutropenia and symptoms in KS improve in response to exogenous administration of granulocyte colony-stimulating factor (G-CSF), we studied bone marrow cytokine (G-CSF, granulocyte-macrophage CSF [GM-CSF], and interleukin-6) production under both basal and stimulated conditions. No differences in G-CSF, GM-CSF, or IL-6 gene expression were found in bone marrow stromal cells between normal controls and KS patients, and all three cytokines were detected by enzyme-linked immunosorbent assay (ELISA) in medium conditioned by bone marrow stromal cells from normal donors and patients with KS. Each KS patient tested had detectable, functional G-CSF in their own serum before exogenous G-CSF administration. Since G-CSF production appeared normal in KS patients, we then asked whether we could detect structural defects in the signaling portion of G-CSF receptor genes. Polymerase chain reaction (PCR) amplification of the G-CSF receptor transmembrane region alone, and of the transmembrane plus cytosolic portions of the receptor, yielded the size products predicted from the sequences of the normal G-CSF receptor. Single-strand conformational polymorphism (SSCP) analysis of G-CSF receptor PCR products demonstrated no variance in structural conformation between KS patients and normal subjects. These results demonstrate that bone marrow stromal cells in patients with KS secrete normal concentrations of functional G-CSF and suggest that the neutropenia in KS patients is caused by an inability of neutrophilic progenitor and precursor cells to respond to normal, physiologic levels of G-CSF. Such a defect, clinically responsive to pharmacologic doses of G-CSF, might be caused by defects in the post-G-CSF receptor signal transduction pathway.


Predictors of severe hypoxemia among COVID-19 patients in Burkina Faso (West Africa): Findings from hospital based cross-sectional study.
COVID-19 is one of the world's major health crises. The objective of this study was to determine the predictive factors of severe hypoxemia in patients hospitalized in COVID-19 health facilities in Burkina Faso. This study was a hospital-based cross-sectional study. The data collected relate to the period of the first wave of the epidemic (March 9 to June 30, 2020). All patients hospitalized for COVID-19 in the requisitioned health facilities of Ouagadougou were included in this study. Predictors of severe hypoxemia were identified using a multivariate logistic regression model. During the study period, 442 patients were included, representing 45.7% of the total number of positive patients in the entire country. The most common co-morbidities were diabetes (55; 12.4%) and arterial hypertension (97; 21.9%). Severe hypoxemia (SpO2 < 90%) was observed in 64 patients (14.5%). Age over 65 years (OR = 8.24; 95% CI: 2.83-24.01) and diabetes (OR = 2.43; 95% CI: 1.17-5.06) were the predictors for occurrence of severe hypoxemia in multivariate analysis. The predictive factors of COVID-19 are similar in African and Caucasian populations. The surveillance of COVID-19 in risk groups should be strengthened to reduce their morbidity and mortality.


Urinary AASA excretion is elevated in patients with molybdenum cofactor deficiency and isolated sulphite oxidase deficiency.
Analysis of α-aminoadipic semialdehyde is an important tool in the diagnosis of antiquitin deficiency (pyridoxine-dependent epilepsy). However continuing use of this test has revealed that elevated urinary excretion of α-aminoadipic semialdehyde is not only found in patients with pyridoxine-dependent epilepsy but is also seen in patients with molybdenum cofactor deficiency and isolated sulphite oxidase deficiency. This should be taken into account when interpreting the laboratory data. Sulphite was shown to inhibit α-aminoadipic semialdehyde dehydrogenase in vitro.


Effects of nonionic monomeric and dimeric contrast media on the twitching reaction of the rat. Importance of osmolality and electrolyte content.
The authors established a rat model of the twitching reaction to contrast media in striated muscle and investigated the influence of nonionic contrast medium on the twitching reaction regarding the nonionic dimer iodixanol compared with the monomer iohexol and the dimer iotrolan. The authors also studied the influences from the electrolyte additions of iodixanol. The interval from start of contrast medium injection to start of head movement was compared for iohexol (140 and 350 mg iodine/mL), iodixanol (150 and 320 mg iodine/mL), and iotrolan (300 mg iodine/mL). Comparison was made with mannitol and mannitol containing the same electrolyte concentrations as iodixanol (150 and 320 mg iodine/mL). No differences in latency period were found between iohexol 140 mg iodine/mL (isotonic) and 350 mg iodine/mL (880 mOsm/kg). Iodixanol caused a lesser effect on the twitching reaction than the iohexol solutions and iotrolan. When the electrolytes of iodixanol were added to mannitol (300 mOsm/kg), there was a later onset of the twitching reaction than with electrolyte-free mannitol. Differences in latency period caused by a change in osmolality were not found. The interval for a twitching reaction was longer with iodixanol than with iohexol, iotrolan, and iso-osmolar mannitol. The weak effect of the iodixanol solution was probably partially caused by the electrolyte content.


Alliance rupture and repair in conjoint family therapy: an exploratory study.
In this article, we introduce a methodology for studying alliance rupture and repair in conjoint family therapy. Using the System for Observing Family Therapy Alliances (Friedlander, Escudero, & Heatherington, 2006), we identified rupture markers and repair interventions in a session with a single mother and her 16-year-old "rebellious" daughter. The session was selected for analysis because a severe rupture was clinically evident; however, by the end of the session, there was an emotional turnaround, which was sustained in the following session and continued until the successful, mutually agreed upon termination. The first rupture occurred when the psychotherapist suggested that the mother explore, in an individual session, how her "personal stress" may be affecting her daughter. The observational analysis showed repeated rupture markers, that is, confrontation and withdrawal behavior, hostile within-family interactions, and a seriously "split" alliance in family members' expressed feelings toward the psychotherapist. The time-stamped behavioral stream showed that the psychotherapist focused first on safety, then on enhancing his emotional connection with each client, and finally on helping mother and daughter understand each other's behavior and recognize their shared isolation.


A sensitive human thyroglobulin RIA to define clearly the presence or absence of functioning thyroid tissue.
This paper describes a practical procedure to establish a sensitive radioimmunoassay for the measurement of human thyroglobulin (HTg) in serum. The assay enables a clear distinction to be made between levels of HTg indicating the presence or absence of functioning thyroid tissue. It compares the use of HTg serum levels with the conventional I-131 scintigram as a marker for recurrent thyroid cancer. In addition, a simple and sensitive radioimmunologic assay is described for the determination of serum antithyroglobulin autoantibodies, the presence of which may give falsely elevated HTg levels.


Inhibition of dopamine-induced release of growth hormone by thyrotropin-releasing hormone.
The effects of thyrotropin-releasing hormone (TRH) and dopamine (DA) on serum growth hormone (GH) levels were examined in the adolescent male baboon. Intravenously administered DA (40 microgram/kg-min-1 for 20 min) raised serum GH and glucose and lowered serum insulin concentrations but caused no increase in blood pressure. Concomitant intravenous infusion of TRH at 2 doses (96 ng/kg-min-1 and 40 microgram/kg-min-1 for 20 min) blocked the DA-induced increase in serum GH. The relatively low effective doses of TRH used to suppress the DA-induced GH increase suggest an interaction with catecholamines at the hypothalamic and/or pituitary to influence GH release.


Indirect effect of conjugate vaccine on adult carriage of Streptococcus pneumoniae: an explanation of trends in invasive pneumococcal disease.
Use of heptavalent protein-polysaccharide pneumococcal conjugate vaccine (PCV7) has been associated with decreases in PCV7-type invasive pneumococcal disease and nasopharyngeal (NP) carriage in children. Vaccine use has also indirectly decreased the rate of invasive disease in adults, presumably through decreased transmission of pneumococci from vaccinated children to adults. We conducted NP carriage surveys in 8 villages in Alaska in 1998-2004. Streptococcus pneumoniae isolates were characterized by serotype and antimicrobial susceptibility. We analyzed trends in serotype distribution, antibiotic resistance, and factors associated with adult carriage of PCV7-serotype pneumococci before and after the introduction of PCV7 in 2001. We collected 15,598 NP swabs; overall, 52% of adults living in the villages surveyed participated in the colonization study. The proportion of adult carriers with PCV7-type pneumococcal carriage decreased from 28% of carriers in 1998-2000 to 4.5% of carriers in 2004 (P<.0001). Among adults, the proportion of colonizing isolates that were resistant to penicillin decreased from 13% in 1998-2000 to 6% in 2004 (P=.05), whereas the percentage of isolates with intermediate susceptibility to penicillin increased from 12% in 1998-2000 to 19% in 2004 (P<.01). Adults were more likely to carry PCV7-type pneumococci if they lived with a child <5 years old or if they lived with a child who had not been age-appropriately vaccinated with PCV7. Pediatric vaccination with PCV7 has resulted in decreased PCV7-type pneumococcal carriage among adults and helps to explain recent decreases in the rate of PCV7-type invasive pneumococcal disease among adults.


Can athletes be tough yet compassionate to themselves? Practical implications for NCAA mental health best practice no. 4.
Recent tragic events and data from official NCAA reports suggest student-athletes' well-being is compromised by symptoms of mental health (MH) disorders. Self-compassion (SC) and mental toughness (MT) are two psychological constructs that have been shown effective against stressors associated with sports. The purpose of this study was to investigate SC, MT, and MH in a NCAA environment for the first time and provide practical suggestions for MH best practice No.4. In total, 542 student-athletes participated across Divisions (Mage = 19.84, SD = 1.7). Data were collected through Mental Toughness Index, Self-Compassion Scale, and Mental Health Continuum-Short Form. MT, SC (including mindfulness), and MH were positively correlated. Males scored higher than females on all three scales. No differences were found between divisions. SC partially mediated the MT-MH relationship, but moderation was not significant. Working towards NCAA MH best practice should include training athletes in both MT and SC skills (via mindfulness).


An experimental design approach to the chemical characterisation of pectin polysaccharides extracted from Cucumis melo Inodorus.
Extracted pectins have been utilised in a number of applications in both the food and pharmaceutical industries where they are generally used as gelling agents, thickeners and stabilisers, although a number of pectins have been shown to be bioactive. These functional properties will depend upon extraction conditions. A statistical experimental design approach was used to study the effects of extraction conditions pH, time and temperature on pectins extracted from Cucumis melo Inodorus. The results show that the chemical composition is very sensitive to these conditions and that this has a great influence on for example the degree of branching. Higher temperatures, lower pHs and longer extraction times lead to a loss of the more acid labile arabinofuranose residues present on the pectin side chain. The fitting of regression equations relating yield and composition to extraction conditions can therefore lead to tailor-made pectins for specific properties and/or applications.


Fat embolism: a rare cause of perioperative renal transplant dysfunction.
Fat embolism is a recognised complication of bony injury and orthopaedic surgery, commonly involving the long bones and pelvis. We report on the case of a 68-year-old renal transplant recipient who developed acute kidney injury following surgical stabilisation of metastatic carcinoma of the acetabulum and replacement of the proximal femur. A CT renal angiogram demonstrated a large fat embolus in the inferior vena cava (IVC) and left iliac veins below the level of IVC filter, with impaired renal perfusion. The risks of open or endovascular lipothrombectomy were felt to outweigh the potential benefits. The patient was managed with systemic anticoagulation and prepared for transplant failure. Subsequently, there was spontaneous improvement in urine output and 4 months postoperatively her transplant function had returned to her baseline level and this has remained stable at 1 year postsurgery.


Resource utilization in patients with schizophrenia who initiated risperidone long-acting therapy: results from the Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation (SOURCE).
Schizophrenia is a chronic mental health disorder associated with increased hospital admissions and excessive utilization of outpatient services and long-term care. This analysis examined health care resource utilization from a 24-month observational study of patients with schizophrenia initiated on risperidone long-acting therapy (RLAT). Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation (SOURCE) was a 24-month observational study designed to examine real-world treatment outcomes by prospectively following patients with schizophrenia initiated on RLAT. At baseline visit, prior hospitalization and ER visit dates were obtained for the previous 12 months and subsequent hospitalization visit dates were obtained at 3-month visits, if available. The health care resource utilization outcomes measures observed in this analysis were hospitalizations for any reason, psychiatric-related hospitalizations, and emergency room (ER) visits. Incidence density analysis was used to assess pre-event and postevent rates per person-year (PY). The primary medical resource utilization analysis included 435 patients who had a baseline visit, ≥1 postbaseline visits after RLAT initiation, and valid hospitalization dates. The number of hospitalizations and ER visits per PY declined significantly (p < .0001) after initiation with RLAT. A 41% decrease (difference of -0.29 hospitalizations per PY [95% CI: -0.39 to -0.18] from baseline) in hospitalizations for any reason, a 56% decrease (a difference of -0.35 hospitalizations per PY [95% CI: -0.44 to -0.26] from baseline) in psychiatric-related hospitalizations, and a 40% decrease (-0.26 hospitalizations per PY [95% CI: -0.44 to -0.10] from baseline) in ER visits were observed after the baseline period. The percentage of psychiatric-related hospitalizations decreased significantly after RLAT initiation, and patients had fewer inpatient hospitalizations and ER visits (all p < .0001). The results suggest that treatment with RLAT may result in decreased hospitalizations for patients with schizophrenia. ClinicalTrials.gov: NCT00246194.


Determinants of early follicular phase gonadotrophin and estradiol concentrations in women of late reproductive age.
FSH and estradiol measured during the menstrual (basal) phase of cycles predict the success of infertility treatment; but the role of these hormones as markers for ovarian reserve in normal populations needs further study. From a cohort study of depressed and non-depressed women, a subset of 406 non-depressed women between the ages of 36 and 45 years with spontaneous periods were selected and their concentrations and determinants of basal hormones measured at study entry, 6 and 12 months later were described. FSH and LH increased significantly over the 12 months of observation (P <or= 0.001), but considerable variation was noted in FSH and estradiol in some women monitored over the three cycles. Concentrations often varied between a pattern of low FSH, high estradiol in one cycle and high FSH, low estradiol in another. In multivariate models focusing on the maximum observed hormone concentration, significant predictors included: increasing age (P < 0.0001), smoking (P = 0.04), and shorter cycle length (P < 0.0001) during adolescence (P < 0.0001) associated with higher FSH; increasing age (P < 0.0266) and lower body mass index (P < 0.0289) associated with higher LH; and a greater number of estimated ovulatory cycles associated with higher estradiol (P < 0.0425). Early reproductive landmarks, smoking, body weight, and factors that determine number of ovulatory cycles impact on ovarian/pituitary physiology in late reproductive life.


Association of host protein VARICOSE with HCPro within a multiprotein complex is crucial for RNA silencing suppression, translation, encapsidation and systemic spread of potato virus A infection.
In this study, we investigated the significance of a conserved five-amino acid motif 'AELPR' in the C-terminal region of helper component-proteinase (HCPro) for potato virus A (PVA; genus Potyvirus) infection. This motif is a putative interaction site for WD40 domain-containing proteins, including VARICOSE (VCS). We abolished the interaction site in HCPro by replacing glutamic acid (E) and arginine (R) with alanines (A) to generate HCProWD. These mutations partially eliminated HCPro-VCS co-localization in cells. We have earlier described potyvirus-induced RNA granules (PGs) in which HCPro and VCS co-localize and proposed that they have a role in RNA silencing suppression. We now demonstrate that the ability of HCProWD to induce PGs, introduce VCS into PGs, and suppress RNA silencing was impaired. Accordingly, PVA carrying HCProWD (PVAWD) infected Nicotiana benthamiana less efficiently than wild-type PVA (PVAWT) and HCProWD complemented the lack of HCPro in PVA gene expression only partially. HCPro was purified from PVA-infected leaves as part of high molecular weight (HMW) ribonucleoprotein (RNP) complexes. These complexes were more stable when associated with wild-type HCPro than with HCProWD. Moreover, VCS and two viral components of the HMW-complexes, viral protein genome-linked and cylindrical inclusion protein were specifically decreased in HCProWD-containing HMW-complexes. A VPg-mediated boost in translation of replication-deficient PVA (PVAΔGDD) was observed only if viral RNA expressed wild-type HCPro. The role of VCS-VPg-HCPro coordination in PVA translation was further supported by results from VCS silencing and overexpression experiments and by significantly elevated PVA-derived Renilla luciferase vs PVA RNA ratio upon VPg-VCS co-expression. Finally, we found that PVAWD was unable to form virus particles or to spread systemically in the infected plant. We highlight the role of HCPro-VCS containing multiprotein assemblies associated with PVA RNA in protecting it from degradation, ensuring efficient translation, formation of stable virions and establishment of systemic infection.


Posttraumatic mental health establishment of the Tsunami survivors in Thailand.
The natural disaster known as "the Tsunami" occurred in Andaman coast of Thailand in December 2004, and there had been questions whether it could cause PTSD amongst the population who lives in the affected area and how to avoid PTSD condition to occur.The purpose of this study is to establish statistical results of psychosocial factors, and their correlation to PTSD and other mental disorders in order to generate the PTSD database. Cross sectional community surveys had been conducted in two phases from the same sampling group, the first phase is concerned with prevalence of PTSD, depression and related factors. Results were collected from 3,133 samples and shows that 33.6% suffered from PTSD, 14.27% with depression and 11.27% suffered from both. The second phase is focused on chronic PTSD and other mental disorders 2,573 samples were collected and only 21.6% were diagnosed with chronic PTSD.The statistical analysis has identified risks factors that could cause PTSD, and protective actions which could help to prevent PTSD.


Microsurgery for Vestibular Schwannoma via Retrosigmoid Transmeatal Approach with Intraoperative Monitoring Techniques.
Functional preservation of cranial nerves remains an issue in surgical treatment of vestibular schwannoma. To explore the functional outcomes of vestibular schwannoma removed by microsurgery via a retrosigmoid transmeatal approach with intraoperative monitoring techniques. A retrospective cross-sectional study was conducted on a group of patients with vestibular schwannoma operated by microsurgery. The outcomes, including the extent of tumor removal, the anatomic positions of the facial nerve, and postoperative Karnofsky performance status score, facial nerve function, and hearing function were reviewed and were statistically compared among tumor sizes (small, medium, and giant) and intraoperative monitoring types [electrophysiological monitoring only (E), electrophysiological monitoring + intraoperative imaging examination (E+I), and electrophysiological monitoring + neuronavigation (E+N)]. A total of 436 patients with VS received microsurgery. The position of the facial nerve was anterior in 85.5% of cases with small vestibular schwannoma. Other position patterns, especially anterior- superior and anterior-inferior, increased in tumors > 2.0 cm. Total resections were performed in all patients with small vestibular schwannoma. A total of 98.1% and 84.8% of patients with medium and giant vestibular schwannoma, respectively, had total resections. More than 90% of patients in all of the 3 monitoring groups had total resections. More than 80% of patients had excellent Karnofsky performance status score regardless of tumor size and monitoring type. After surgery, 100%, 84.4%, and 59.8% of patients with small-, medium-, and giant-sized vestibular schwannoma, respectively, had good facial nerve function. More than 70% of patients in all of the 3 monitoring groups had good facial nerve function postoperatively. The hearing preservation rate was 26.7% and 7.7% in small- and medium-sized vestibular schwannoma, respectively, and was 21.6% and 27.3% in the E group and the E+N group, respectively. The statistical analyses showed that tumor size was significantly associated with the extent of tumor resection, facial nerve localization, complications, postoperative Karnofsky performance status score, facial nerve function, and hearing function (all P ≤ .001). Monitoring type was significantly associated with the extent of resection (P ≤ .001). Additionally, patients in the E+N group had higher total resection rates than those in the E group (P ≤ .001). No cerebrospinal fluid leakage and surgery-related death occurred. In vestibular schwannoma microsurgery, tumor size is an important parameter that affects the localization of the facial nerve, the extent of resection, postoperative outcomes and complications. Intraoperative electrophysiological techniques combined with neuronavigation may be helpful to improve the extent of resection.


Roles of patch characteristics, drought frequency, and restoration in long-term trends of a widespread amphibian.
Despite the high profile of amphibian declines and the increasing threat of drought and fragmentation to aquatic ecosystems, few studies have examined long-term rates of change for a single species across a large geographic area. We analyzed growth in annual egg-mass counts of the Columbia spotted frog (Rana luteiventris) across the northwestern United States, an area encompassing 3 genetic clades. On the basis of data collected by multiple partners from 98 water bodies between 1991 and 2011, we used state-space and linear-regression models to measure effects of patch characteristics, frequency of summer drought, and wetland restoration on population growth. Abundance increased in the 2 clades with greatest decline history, but declined where populations are considered most secure. Population growth was negatively associated with temporary hydroperiods and landscape modification (measured by the human footprint index), but was similar in modified and natural water bodies. The effect of drought was mediated by the size of the water body: populations in large water bodies maintained positive growth despite drought, whereas drought magnified declines in small water bodies. Rapid growth in restored wetlands in areas of historical population declines provided strong evidence of successful management. Our results highlight the importance of maintaining large areas of habitat and underscore the greater vulnerability of small areas of habitat to environmental stochasticity. Similar long-term growth rates in modified and natural water bodies and rapid, positive responses to restoration suggest pond construction and other forms of management can effectively increase population growth. These tools are likely to become increasingly important to mitigate effects of increased drought expected from global climate change. Papeles de las Características del Fragmento, Frecuencia de Sequía y Restauración en las Tendencias a Largo Plazo de un Anfibio Ampliamente Distribuido.


Equipoise and the ethics of clinical research.
The ethics of clinical research requires equipoise--a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial. Should the investigator discover that one treatment is of superior therapeutic merit, he or she is ethically obliged to offer that treatment. The current understanding of this requirement, which entails that the investigator have no "treatment preference" throughout the course of the trial, presents nearly insuperable obstacles to the ethical commencement or completion of a controlled trial and may also contribute to the termination of trials because of the failure to enroll enough patients. I suggest an alternative concept of equipoise, which would be based on present or imminent controversy in the clinical community over the preferred treatment. According to this concept of "clinical equipoise," the requirement is satisfied if there is genuine uncertainty within the expert medical community--not necessarily on the part of the individual investigator--about the preferred treatment.


Optically-pumped dilute nitride spin-VCSEL.
We report the first room temperature optical spin-injection of a dilute nitride 1300 nm vertical-cavity surface-emitting laser (VCSEL) under continuous-wave optical pumping. We also present a novel experimental protocol for the investigation of optical spin-injection with a fiber setup. The experimental results indicate that the VCSEL polarization can be controlled by the pump polarization, and the measured behavior is in excellent agreement with theoretical predictions using the spin flip model. The ability to control the polarization of a long-wavelength VCSEL at room temperature emitting at the wavelength of 1.3 µm opens up a new exciting research avenue for novel uses in disparate fields of technology ranging from spintronics to optical telecommunication networks.


[Intramural hemorrhage of the thoracic aorta].
Intramural hemorrhage (IMH) of the aorta is considered to be a possible preliminary stage to dissection. We report on our experience with MRI, CT, and TEE in the diagnosis as well as in the correct evaluation of the extent of an IMH. Between 1983 and 1997 a total of 26 patients were examined using MRI (n = 13) and/or contrast enhanced CT (n = 18) or TEE. The validation was effected in 17 cases through intraoperative or postmortem inspection and in the remaining cases either through continuous clinical or radiological monitoring (n = 6) or through the depiction of the results in 2 different imaging procedures (n = 3). The correct diagnosis of an IMH was made on all examined patients with all imaging modalities. In all cases, MRI enabled the correct identification of the affected aortic segments. Using CT the affected descending aorta was overlooked in one out of 15 cases; TEE failed in one out of two cases of intramural hemorrhage in the aortic arch. A false positive diagnosis was made with CT in one out of 9 cases in the ascending aorta, and using sonography, this occurred in two out of 3 cases in the area of the aortic arch. According to our experience, magnetic resonance imaging is the most accurate method for the diagnosis of an IMH.


Rheumatoid arthritis and the alpha-chemokine IP-10.
Interferon(IFN)-gamma-induced protein 10 (IP-10) and its receptor, CXCR3, appear to contribute to the pathogenesis of rheumatoid arthritis (RA). IP-10 has been detected in sera, synovial fluid (SF), and synovial tissue in RA patients. IP-10 is mainly expressed by infiltrating macrophage-like cells and fibroblast-like synoviocytes in RA synovium. The elevated expression of CXCR3 on T cells from SF has been associated with high levels of IFN-gamma, which suggest a preferential Th1 phenotype. A human phase II clinical trial using an anti-IP-10 monoclonal antibody (MDX-1100) for RA patients who had an inadequate response to methotrexate treatment has shown that blocking IP-10 significantly increased response rate compared to the placebo group, suggesting a possible therapeutic use in humans.


Behaviour of breast cancer molecular subtypes through tumour progression.
INTRODUCTION Breast cancer (BC) becomes more aggressive throughout disease progression. Clinical stage is correlated with patient outcome. We hypothesised that BC molecular subtypes are associated with a poor prognosis in advanced clinical stages. We analysed the distribution and behaviour of molecular subtypes at different BC tumour size and variation of molecular subtype in recurrent lesions. We studied 1647 consecutive patients with non-metastatic invasive and microinvasive (Tmi) BC treated from January 1997 to December 2007. Patients were categorised by tumour size and molecular subtype. A chi-square method was used for multiple group comparisons. Kaplan-Meier product limit method was used to calculate overall survival and disease-free survival. Median follow-up was 7.2 years. For patients with invasive BC the median age was 56 years. Four hundred and fifteen patients recurred and 225 died. Larger tumours were more frequently of triple-negative (TN) subtype than small ones or Tmi lesions. Any molecular subtype change from primary tumour to recurrent lesions is more likely to happen from a good prognosis to a subtype of worse prognosis than the opposite. Larger tumours of luminal A, luminal B and TN, but not HER2 subtype, are more likely to carry aggressive markers and to have worse outcomes than small ones. We found accumulation of TN subtype, migration to a poor prognosis subtype and increasing aggressiveness of luminal and TN subtypes throughout tumour progression. Tumours belonging to the HER2 subtype behave aggressively regardless of the primary size.


The incidence and pattern of copollinator diversification in dioecious and monoecious figs.
Differences in breeding system are associated with correlated ecological and morphological changes in plants. In Ficus, dioecy and monoecy are strongly associated with different suites of traits (tree height, population density, fruiting frequency, pollinator dispersal ecology). Although approximately 30% of fig species are pollinated by multiple species of fig-pollinating wasps, it has been suggested that copollinators are rare in dioecious figs. Here, we test whether there is a connection between the fig breeding system and copollinator incidence and diversification by conducting a meta-analysis of molecular data from pollinators of 119 fig species that includes new data from 15 Asian fig species. We find that the incidence of copollinators is not significantly different between monoecious and dioecious Ficus. Surprisingly, while all copollinators in dioecious figs are sister taxa, only 32.1% in monoecious figs are sister taxa. We present hypotheses to explain those patterns and discuss their consequences on the evolution of this mutualism.


Metabolic abnormalities are present in adults with elevated serum cystatin C.
Although metabolic anomalies are often seen in advanced chronic kidney disease (CKD), their presence in more mild states is unknown. We studied 6722 participants in the Third National Health and Nutrition Examination Survey, dividing them into three mutually exclusive groups consisting of those having a normal or mildly reduced estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease (MDRD) formula), those with normal or elevated serum cystatin C, and those with clinically relevant moderate or severely reduced eGFR (stage 3 or 4 of CKD). The prevalence of several metabolic abnormalities associated with moderate to advanced CKD was determined after standardization for age, race-ethnicity, and gender. In the absence of stage 3 or 4 CKD, patients with elevated serum cystatin C had a higher prevalence of low hemoglobin and elevated uric acid, homocysteine, phosphorus, fibrinogen, and C-reactive protein than patients with a normal serum cystatin C. Our results show that in adults with normal or mildly reduced eGFR, elevated serum cystatin C is associated with an increased prevalence of metabolic abnormalities traditionally found in moderate or severe CKD. Elevated serum cystatin C may identify patients with 'preclinical' kidney disease not detected by traditional serum creatinine measurements.


Regulatory role of RsgI in sigI expression in Bacillus subtilis.
The sigma gene, sigI, of Bacillus subtilis belongs to the group IV heat-shock response genes and has many orthologues in the bacterial phylum Firmicutes. The B. subtilis sigI gene is considered to constitute an operon with rsgI (regulation of sigI, formerly ykrI). As little is known about either the structure and function of the sigI-rsgI operon or the SigI regulons, the role of RsgI in heat-inducible transcription of the sigI-rsgI operon was investigated, using Northern analysis and a heat-stable beta-galactosidase reporter assay. Heat-inducible, SigI-dependent transcription of the sigI-rsgI operon was stimulated greatly by disrupting rsgI. Yeast two-hybrid analysis showed direct interaction between the N-terminal portion of the presumed RsgI protein and SigI. Without RsgI function, induction of transcription of the sigI-rsgI operon upon transient heat stress depended on dnaK activity. However, transcription of the operon was induced during growth at prolonged higher temperature even without DnaK function. Without RsgI function, sigI-rsgI operon transcription was induced after the end of growth independent of any temperature shift in a sporulation medium and toward the end of growth in a rich complex medium. Furthermore, glucose addition resulted in a strong suppression of sigI-rsgI transcription. Therefore it is hypothesized that transcription of the sigI-rsgI operon of B. subtilis is negatively regulated by the putative transmembrane protein RsgI, which moderates SigI's sensitivity to heat shock or nutritional stress.


Purification and characterization of an outer membrane-bound protein involved in long-chain fatty acid transport in Escherichia coli.
We report the purification and localization of the fadL gene product (FLP), an essential component of the long-chain fatty acid transport machinery in Escherichia coli. FLP was extracted from total membranes by differential extraction with the nonionic detergents Tween 20 and Triton X-100. This protein was further purified from a Tween 20-insoluble-Triton X-100-soluble extract by salt fractionation, gel filtration chromatography, and hydrophobic interaction chromatography. This regime results in a 95-fold purification of FLP from total membranes. The purified protein preparation was homogeneous based on silver staining and gave the characteristic behavior established for the fadL gene product in the presence of sodium dodecyl sulfate at different temperatures prior to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Mr of 33,000 when heated at 25 degrees C and Mr of 43,000 when heated at 100 degrees C) and on two-dimensional polyacrylamide gels (pI of 4.6 and a Mr of 33,000). Purified FLP was rich in hydrophobic residues accounting for approximately 45% of the total amino acid composition. To localize FLP, antisera were raised against the purified protein and were used to probe differentially fractionated membranes by Western immunoblotting. This procedure demonstrated the presence of this protein only in the outer membrane fraction of fadL+ strains. We confirmed the outer membrane localization of FLP by measuring long-chain fatty acid transport in fadL+ and fadL strains treated with EDTA to alter outer membrane permeability and in spheroplasts generated from fadL+ and fadL strains. Both EDTA-treated cells and spheroplasts transported long-chain fatty acids at essentially the same rate regardless of whether they contained a wild-type or mutant fadL gene. These data imply that FLP is a protein in the outer membrane which is specifically involved in long-chain fatty acid transport.


Arthroscopy Up to Date: Hip Femoroacetabular Impingement.
To provide a comprehensive review and summary of the research published in Arthroscopy: The Journal of Arthroscopic and Related Surgery and The American Journal of Sports Medicine (AJSM) related to hip arthroscopy for femoroacetabular impingement (FAI). A comprehensive review was conducted in duplicate of Arthroscopy and AJSM from February 2012 to February 2015 for all articles related to FAI, and a quality assessment was completed for all included studies. Clinical outcomes were dichotomized into short-term (<6 months) and midterm (<24 months) outcomes, and values were pooled when possible. We identified 60 studies in Arthroscopy and 44 studies in AJSM, primarily from North America (78.8%), that predominantly assessed clinical outcomes after arthroscopic hip surgery (46.1%). Seventy-one percent of Arthroscopy studies and 20.5% of AJSM studies were Level IV evidence. The modified Harris Hip Score (mHHS) was used by 81.5% of included studies. Pooled weighted mean mHHS values after arthroscopic surgery for FAI showed improvements at the midterm from 60.5 points (range, 56.6 to 83.6 points) to 80.5 points (range, 72.1 to 98.0 points) out of a possible 100 points. Pooled weighted outcomes for labral repair showed mean mHHS improvements from 63.8 points (range, 62.5 to 69.0 points) preoperatively to 86.9 points (range, 85.5 to 89.9 points) up to 24 months postoperatively. This comprehensive review of research published in Arthroscopy and AJSM over the past 3 years identified a number of key findings. Arthroscopic intervention results in improvements in functional outcomes at both the short-term and midterm for patients with symptomatic FAI in the absence of significant existing degenerative changes. Labral repair may result in improvements over labral debridement. The most commonly used outcome score was the mHHS for objective assessment of surgical success. There is a need for continued focus on improvement of methodologic quality and reporting of research pertaining to FAI. Level IV, systematic review of Level IV studies.


The association between road traffic noise and depressed mood among different ethnic and socioeconomic groups. The HELIUS study.
Although there is growing evidence that depressed mood is affected by road traffic noise, previous results are not fully consistent. Furthermore, to our knowledge, no previous research has assessed ethnic and socioeconomic inequalities in the association of noise exposure with depressed mood. To investigate the association between road traffic noise with depressed mood and to determine to what extent this association varies between ethnic and socioeconomic groups. We investigated cross-sectional data collected between 2011 and 2015 from 23,293 HELIUS participants (18-70 years) living in Amsterdam. Our study included five different ethnic groups (Dutch, Moroccan, Turkish, South-Asian Surinamese and African Surinamese origin). All respondents were linked by their residential postal code to geographic data on road traffic noise levels (24 h noise average in A-weighted decibels [dB(A)]). Noise was categorized into five categories (45-54 dB(A), 55-59 dB(A), 60-64 dB(A), 65-69 dB(A), ≥70 dB(A)) and high noise exposure was defined as noise levels ≥65 dB(A). Depressed mood was defined as a sum-score of ≥10 on the 9-item Patient Health Questionnaire (PHQ-9). Logistic regression was performed to assess the relationship between road traffic noise and depressed mood. Multilevel analyses were used to take into account the clustering of observations within neighbourhoods. Lastly, logistic regression analyses were applied to estimate relative risks for depressed mood per different ethnic and socioeconomic groups exposed to high noise exposure ≥65 dB(A) compared to <65 dB(A). Analyses were adjusted for individual- and neighbourhood-level confounders. Exposure to ≥70 dB(A) compared to the reference group of 45-54 dB(A) showed a significant positive association with depressed mood (OR: 1.65, 95% CI 1.10, 2.48). Participants exposed to 60-64 dB(A) showed a significantly lower odds ratio of 0.82 (95% CI 0.70, 0.97) compared to the reference group. We observed no differences between ethnic groups in the association of high noise exposure ≥65 dB(A) with depressed mood. Regarding socioeconomic groups, results were different for the medium-low educated group and unemployed group only. This study adds new evidence regarding a positive association between high road traffic noise exposure and depressed mood in residential settings. We found no evidence for systematic ethnic or socioeconomic inequalities regarding this association.


Digital and analogical reality in proteomics investigation.
Are protein functions continuous or discretized? Proteomics investigations are starting to address this non-trivial awesome question focusing upon determining the nature of biological molecular relationships. In the following editorial we present a number of experimental studies published in this themed Proteomics Issue demonstrating the development of a new analogical vision for the interpretation of genotype-phenotype relationships. New metrics and languages are evolving, which may complement the insufficiency based on a binary digital interpretation of biological phenomena, providing new tools for the interpretation of large scale-experimental studies.


Spatio-temporal modeling of nanoparticle delivery to multicellular tumor spheroids.
The inefficiency of nanoparticle penetration in tissues limits the therapeutic efficacy of such formulations for cancer applications. Recent work has indicated that modulation of tissue architecture with enzymes such as collagenase significantly increases macromolecule delivery. In this study we developed a mathematical model of nanoparticle penetration into multicellular spheroids that accounts for radially dependent changes in tumor architecture, as represented by the volume fraction of tissue accessible to nanoparticle diffusion. Parameters such as nanoparticle binding, internalization rate constants, and accessible volume fraction were determined experimentally. Unknown parameters of nanoparticle binding sites per cell in the spheroid and pore shape factor were determined by fitting to experimental data. The model was correlated with experimental studies of the penetration of 40 nm nanoparticles in SiHa multicellular spheroids with and without collagenase treatment and was able to accurately predict concentration profiles of nanoparticles within spheroids. The model was also used to investigate the effects of nanoparticle size. This model contributes toward the understanding of the role of tumor architecture on nanoparticle delivery efficiency.


Molecular pharmacology of histamine H4 receptors.
The histamine H4 receptor (H4R) is the youngest member of the histamine receptor family. Based on its predominant expression pattern in hematopoietic cells, the H4R is considered to be an interesting drug target for inflammatory disorders such as allergy and asthma. Since the identification and cloning of the H4R in 2000, drug discovery programs boosted the development of various H4R (specific) ligands. Differences between H4R orthologs in combination with available three-dimensional G protein-coupled receptor (GPCR) models have guided site-directed mutagenesis studies to gain insight in ligand binding and receptor activation. In addition, ongoing characterization of H4R-mediated signaling in transfected and native cells contributes to further unravel the (patho-) physiological functions of H4Rs.


Impact of an education campaign on management in pregnancy of women infected with a blood-borne virus.
To assess obstetricians' antenatal screening practice for blood-borne viruses (HIV, hepatitis B and C viruses [HBV and HCV]) and knowledge about management during labour and risk of transmission via breastfeeding for infected women after an educational intervention, Australia. Cohort study, with surveys before and after an educational intervention. Survey 1 was mailed in 2002-2003 to all 767 Fellows registered with the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), and Survey 2 was mailed in 2004 to the 743 of these Fellows who were still practising. Multifaceted intervention with mail-out of survey results and a summary of recommended management, publication of two review articles in the RANZCOG journal, and an oral presentation at the RANZCOG annual scientific meeting. Self-reported frequency of antenatal screening for blood-borne viruses, change in practice based on a woman's infection status, and advice given about risk of virus transmission via breastfeeding in Survey 2, compared with Survey 1. Survey 2 (response rate, 68%) found increases from the previous survey in the proportion of respondents reporting they always offered antenatal screening for HIV, from 51% to 59%, and for HCV, from 60% to 69% (P = 0.001 for both). For women with HIV infection, the proportion of respondents always recommending elective caesarean section increased from 37% to 49% (P = 0.001) and always avoiding rupture of membranes increased from 33% to 49% (P < 0.001). The proportion who reported advising (incorrectly) that breastfeeding is associated with increased risk of transmission to the infant decreased from 34% to 25% for HBV (P = 0.01) and from 47% to 39% for HCV (P = 0.03). The frequency of antenatal testing for HIV and HCV is increasing in Australia. Knowledge about interventions to reduce mother-to-child transmission of HIV and knowledge of the risk of HBV and HCV transmission via breastfeeding improved after a relatively simple educational intervention.


Finger Force Matching and Verbal Reports: Testing Predictions of the Iso-Perceptual Manifold Concept.
We used force matching and verbal reports of finger force to explore a prediction of the iso-perceptual manifold concept, which assumes that stable percepts are associated with a manifold in the afferent-efferent space. Young subjects produced various force magnitudes with the index finger, middle finger, or both fingers together. Further, they reported the force level using a verbal scale and by matching the force with fingers of the contralateral hand. Force matching, but not verbal reports, showed larger variable errors for individual fingers in the two-finger task compared to the single-finger tasks. We discuss possible differences in afferent and efferent contributions to force perception at low and high forces based on the idea of motor control with referent coordinates for the effectors. The differences between the force matching and verbal reports are possibly related to neural circuitry differences between perceiving without action and perceiving-to-act.


Observation of a structural gradient in Winsor-III microemulsion systems.
We demonstrate here for the first time via small-angle neutron scattering (SANS) that the middle, bicontinuous microemulsion (BμE) phase of Winsor-III systems undergoes a gradual change of structure and composition in the vertical direction, contrary to the commonly held belief of uniform structure and composition. A vertical stage was deployed to enable precise alignment of a custom-designed rectangular cell containing the WIII system with respect to the neutron beam, allowing for several different vertical positions to be analyzed. For the water/AOT/CK-2,13 (two-tailed alkyl ethoxylate containing a 1,3-dioxolane linkage)/heptane Winsor-III system, the quasi-periodic repeat distance (d) and correlation length (ξ), obtained from the Teubner-Strey model applied to the SANS data, decreased and the surface area per volume of the surfactant monolayer (via Porod analysis) increased in the downward direction, trends that reflect an increase of surfactant concentration, consistent with the ultralow interfacial tension that often occurs for the lower liquid-liquid interface of many WIII systems. The water/sodium dodecyl sulfate (SDS)/1-pentanol/dodecane system shared the same trend with regard to d as observed for AOT/CK-2,13. In contrast, for SDS/pentanol, ξ increased and the amphiphilicity factor (fa) decreased in the downward direction, trends consistent with a decrease of cosurfactant (pentanol) concentration in the downward direction. Non-uniformity in the vertical direction has implications in the transport of solutes between WIII phases during the extractive purification of proteins or the removal of heavy metals and pollutants from wastewater, or the deposition of BμEs onto hydrophilic vs. hydrophobic surfaces as thin coatings.


A Systematic Review of Nurses' Experiences With Unintended Consequences When Using the Electronic Health Record.
In response to unprecedented financial government incentives, electronic health record (EHR) adoption has tripled since 2009. While EHR benefits are emphasized, research demonstrates that adoption may result in unintended consequences that nurse administrators can anticipate and mitigate. Unintended consequences are defined as unplanned effects, whether positive or negative. Little is known about nursing perceptions and experience of unintended consequences arising from EHR implementation, and nursing studies are minimal in comparison with research on experience among their interprofessional colleagues. The purpose of this article is to present the state of the science on nurses' experiences with unintended consequences of EHRs derived from a systematic review that includes 4 original studies. Findings demonstrate that nurses experience changes to workflow, must continually adapt to meet patient's needs in the context of imperfect EHR systems, and have difficulty accessing the information they need to make patient care decisions. Even so, most state they would not revert to paper records if given the choice. Implications for nurse administrators include the need for continual engagement with nurses along the continuum of EHR design, as well as the need to encourage nurses to speak up and acknowledge workflow changes that threaten patient safety or do not support work efficiency.


Paediatric outcomes and timing of admission.
Studies of adult patients have demonstrated that weekend admissions compared with weekday admissions had a significantly higher hospital mortality rate. We have reviewed the literature to determine if the timing of admission, for example, weekend or weekday, influenced mortality and morbidity in children. Seventeen studies reported the effect of timing of admission on mortality, and only four studies demonstrated an increase in those admitted at the weekend. Meta-analysis of the results of 15 of the studies demonstrated there was no significant weekend effect. There was, however, considerable heterogeneity in the studies. There were two large UK studies: one reported an increased mortality only for planned weekend admissions likely explained by planned admissions for complex conditions and the other showed no significant weekend effect. Two studies, one of which was large (n=2913), reported more surgical complications in infants undergoing weekend oesophageal atresia and trachea-oesophageal repair. Medication errors have also been reported to be more common at weekends. Five studies reported the effect of length of stay, meta-analysis demonstrated a significantly increased length of stay following a weekend admission, the mean difference was approximately 1 day. Those data, however, should be interpreted with the caveat that there was no adjustment in all of the studies for differences in disease severity. We conclude that weekend admission overall does not increase mortality but may be associated with a longer length of stay and, in certain conditions, with greater morbidity.