Favorable patient reported outcomes after penile plication for wide array of peyronie disease abnormalities.
We present patient reported outcomes from our 5-year experience using penile plication to correct a wide variety of Peyronie disease malformations. We reviewed the records of all men who underwent penile plication for Peyronie disease, as performed by one of us (AFM). All patients were treated with tunical plication without penile degloving via a 2 cm longitudinal penile incision regardless of curvature severity or erectile function. A concomitant inflatable penile prosthesis was placed in men with refractory erectile dysfunction. A questionnaire was administered to assess the patient perception of postoperative penile curvature, length, rigidity and adequacy for intercourse. Of 154 treated patients 78 (51%) and 65 (42%) had simple (less than 60 degrees) and complex (biplanar curvature, or curvature 60 degrees or greater) malformation, respectively, while 11 (7%) underwent plication plus inflatable penile prosthesis placement. A total of 132 patients responded to the questionnaire a mean 14 months after surgery. Overall, 96% of patients reported curvature improvement after penile plication, 93% reported erection adequate for sexual intercourse and 95% considered that the overall condition improved after surgery. Despite a significant difference in the number of plication sutures (mean 10 vs 7) and curvature angle correction (mean 57 vs 30 degrees, each p <0.005), self-reported outcomes of complex cases were equivalent to those of simple cases. While 84% of patients had no measureable decrease in stretched penile length, 103 of 154 (78%) reported a perceived penile length reduction after surgery. Penile plication without degloving is effective for correcting a wide variety of Peyronie disease malformations. It can be safely combined with inflatable penile prosthesis placement.


Lifelong genetic minipumps.
Most physiologists working with animals are familiar with osmotic minipumps. These surgically implanted devices can, for a limited period, administer a reagent at a constant predetermined rate that is unaffected by concurrent procedures. The investigator can then test the physiological effects of other treatments knowing that the animals' homeostatic responses will not be able to alter the dose of the pumped reagent. To develop the genetic equivalent of a lifelong minipump, simply inherited as an autosomal dominant, we here combine three of our previously described strategies, genetic clamping, single-copy chosen-site integration, and modification of untranslated regions (UTRs). As a test of the procedure, we have generated a series of intrinsically useful animals having genetic minipumps secreting renin ectopically from the liver at levels controlled by the investigator but not subject to homeostatic changes. To achieve the different dosage levels of these genetic minipumps, we altered the UTRs of a renin transgene driven by an albumin promoter and inserted it into the genome as a single copy at the ApoA1/ApoC3 locus, a locus that is strongly expressed in the liver. The resulting mice express plasma renin over ranges from near physiological to eightfold wild type and develop graded cardiovascular and kidney disease consequent to their different levels of ectopically secreted renin. The procedure and DNA constructs we describe can be used to generate genetic minipumps for controlling plasma levels of a wide variety of secreted protein products.


Elevated amylase in plasma represents an adverse prognostic marker in patients with metastatic pancreatic cancer : A retrospective analysis.
The aim of this study was to investigate the prognostic relevance of plasma amylase and lipase concerning survival of patients suffering from metastatic pancreatic cancer (PC). This retrospective study included 351 patients with metastatic PC, who were treated in a single academic institution. Cancer-specific survival (CSS) was analyzed using the Kaplan-Meier method. To further evaluate the prognostic significance of lipase and amylase, univariate and multivariate values were calculated using Cox proportional models. In univariate analysis, an increased amylase level was associated with shorter CSS in PC patients (hazard ratio HR = 1.258; 95% confidence interval CI = 1.011-1.566; p = 0.039). In multivariate analysis, including gender, age, CA19-9 and administration of chemotherapy, increased amylase levels prevailed as an independent prognostic factor for CSS (HR = 1.373; 95%CI = 1.004-1.878; p = 0.047). Plasma amylase was found to be an independent prognostic factor in patients with metastatic PC. The results indicate that amylase might represent a novel and useful marker for better patient stratification in PC management.


Erythropoietin inhibits osteoblast function in myelodysplastic syndromes via the canonical Wnt pathway.
The effects of erythropoietin on osteoblasts and bone formation are controversial. Since patients with myelodysplastic syndromes often display excessively high erythropoietin levels, we aimed to analyze the effect of erythropoietin on osteoblast function in myelodysplastic syndromes and define the role of Wnt signaling in this process. Expression of osteoblast-specific genes and subsequent osteoblast mineralization was increased in mesenchymal stromal cells from healthy young donors by in vitro erythropoietin treatment. However, erythropoietin failed to increase osteoblast mineralization in old healthy donors and in patients with myelodysplasia, whereas the basal differentiation potential of the latter was already significantly reduced compared to that of age-matched controls (P<0.01). This was accompanied by a significantly reduced expression of genes of the canonical Wnt pathway. Treatment of these cells with erythropoietin further inhibited the canonical Wnt pathway. Exposure of murine cells (C2C12) to erythropoietin also produced a dose-dependent inhibition of TCF/LEF promoter activity (maximum at 500 IU/mL, -2.8-fold; P<0.01). The decreased differentiation capacity of erythropoietin-pretreated mesenchymal stromal cells from patients with myelodysplasia could be restored by activating the Wnt pathway using lithium chloride or parathyroid hormone. Its hematopoiesis-supporting capacity was reduced, while reactivation of the canonical Wnt pathway in mesenchymal stromal cells could reverse this effect. Thus, these data demonstrate that erythropoietin modulates components of the osteo-hematopoietic niche in a context-dependent manner being anabolic in young, but catabolic in mature bone cells. Targeting the Wnt pathway in patients with myelodysplastic syndromes may be an appealing strategy to promote the functional capacity of the osteo-hematopoietic niche.


Computed tomographic characteristics of intrapelvic masses in dogs.
In people, the computed tomography (CT) characteristics of intrapelvic masses can be used to distinguish a malignant from a benign mass. As prognosis varies greatly between malignant and benign intrapelvic masses, knowledge of their biological behavior can aid treatment planning before surgery. The purpose of this study was to determine if CT characteristics exist to help differentiate benign from malignant intrapelvic masses in dogs. The CT images of 14 dogs with a histopathologically confirmed intrapelvic mass were evaluated. Postcontrast internal heterogeneity of the mass was the only characteristic significantly associated with malignancy (P = 0.005). Preoperative CT examination of intrapelvic masses in dogs can provide prognostic information before invasive surgical treatment.


Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up.
To report 5-year treatment outcomes in the Tube Versus Trabeculectomy (TVT) Study. Multicenter randomized clinical trial. Seventeen clinical centers. Patients 18 to 85 years of age who had previous trabeculectomy and/or cataract extraction with intraocular lens implantation and uncontrolled glaucoma with intraocular pressure (IOP) ≥18 mm Hg and ≤40 mm Hg on maximum tolerated medical therapy. Tube shunt (350-mm(2) Baerveldt glaucoma implant) or trabeculectomy with mitomycin C ([MMC]; 0.4 mg/mL for 4 minutes). IOP, visual acuity, use of supplemental medical therapy, and failure (IOP >21 mm Hg or not reduced by 20%, IOP ≤5 mm Hg, reoperation for glaucoma, or loss of light perception vision). A total of 212 eyes of 212 patients were enrolled, including 107 in the tube group and 105 in the trabeculectomy group. At 5 years, IOP (mean ± SD) was 14.4 ± 6.9 mm Hg in the tube group and 12.6 ± 5.9 mm Hg in the trabeculectomy group (P = .12). The number of glaucoma medications (mean ± SD) was 1.4 ± 1.3 in the tube group and 1.2 ± 1.5 in the trabeculectomy group (P = .23). The cumulative probability of failure during 5 years of follow-up was 29.8% in the tube group and 46.9% in the trabeculectomy group (P = .002; hazard ratio = 2.15; 95% confidence interval = 1.30 to 3.56). The rate of reoperation for glaucoma was 9% in the tube group and 29% in the trabeculectomy group (P = .025). Tube shunt surgery had a higher success rate compared to trabeculectomy with MMC during 5 years of follow-up in the TVT Study. Both procedures were associated with similar IOP reduction and use of supplemental medical therapy at 5 years. Additional glaucoma surgery was needed more frequently after trabeculectomy with MMC than tube shunt placement.


Interventions to prevent HIV and Hepatitis C in people who inject drugs: a review of reviews to assess evidence of effectiveness.
Injecting drug use is a major risk factor for the acquisition and transmission of HIV and Hepatitis C virus (HCV). Prevention of these infections among people who inject drugs (PWID) is critical to reduce ongoing transmission, morbidity and mortality. A review of reviews was undertaken involving systematic literature searches of Medline, Embase, CINAHL, PsychINFO, IBSS and the Cochrane Library (2000-2011) to identify English language reviews regarding the effectiveness of harm reduction interventions in relation to HIV transmission, HCV transmission and injecting risk behaviour (IRB). Interventions included needle and syringe programmes (NSP); the provision of injection paraphernalia; opiate substitution treatment (OST); information, education and counselling (IEC); and supervised injecting facilities (SIFs). Reviews were classified into 'core' or 'supplementary' using critical appraisal criteria, and the strength of review-level evidence was assessed. Twelve core and thirteen supplementary reviews were included. From these reviews we identified: (i) for NSP: tentative review-level evidence to support effectiveness in reducing HIV transmission, insufficient review-level evidence relating to HCV transmission, but sufficient review-level evidence in relation to IRB; (ii) for OST: sufficient review-level evidence of effectiveness in relation to HIV transmission and IRB, but tentative review-level evidence in relation to HCV transmission; (iii) for IEC, the provision of injection paraphernalia and SIFs: tentative review-level evidence of effectiveness in reducing IRB; and either insufficient or no review-level evidence for these interventions in relation to HIV or HCV transmission. Review-level evidence indicates that harm reduction interventions can reduce IRB, with evidence strongest for OST and NSP. However, there is comparatively little review-level evidence regarding the effectiveness of these interventions in preventing HCV transmission among PWID. Further studies are needed to assess the effectiveness and impact of scaling up comprehensive packages of harm reduction interventions to minimise HIV and HCV transmission among PWID.


Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer.
Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix-loop-helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis.


Association of Fasciola gigantica Co-infection With Bovine Tuberculosis Infection and Diagnosis in a Naturally Infected Cattle Population in Africa.
Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a major livestock and public health problem in both high and low-income countries. With the current absence of an effective vaccine, control in cattle populations is reliant on regular testing and removal of positive animals. However, surveillance and control are hampered by imperfect diagnostic tests that have poorly described properties in naturally infected populations. Recent research in cattle co-infected with the temperate liver fluke, Fasciola hepatica, has raised concerns about the performance of the intradermal skin test in high fluke incidence areas. Further, recent studies of parasitic co-infections have demonstrated their impact on Th1 and Th2 responses, concurrent disease pathology and susceptibility to mycobacterial infections. Here we report for the first time the association of co-infection with the tropical liver fluke, Fasciola gigantica, with the presence of bTB-like lesions and the IFN-γ response in naturally infected African cattle. After adjusting for age and sex we observed a complex interaction between fluke status and breed. Fulani cattle had a higher risk of having bTB-like lesions than the mixed breed group. The risk of bTB-like lesions increased in the mixed breed group if they had concurrent evidence of fluke pathology but was less clear in the coinfected Fulani breed. Further, we observed a slight decline in the IFN-γ levels in fluke infected animals. Finally we explored factors associated with IFN-γ false negative results compared to the presence of bTB-like lesions. Fulani cattle had a higher risk of having a false negative result compared to the mixed breed group. Further, the mixed breed cattle had an increased risk of being false negative if also co-infected with fluke. Interesting, as with the risk of bTB-like lesions, this association was less clear in the Fulani cattle with weak evidence of a slight decrease in risk of having a false negative test result when fluke pathology positive. This interesting interaction where different breeds appear to have different responses to co-infections is intriguing but further work is needed to confirm and understand more clearly the possible confounding effects of different other co-infections not measured here, breed, management or exposure risks.


Survey of pharmacist-managed primary care clinics using healthcare failure mode and effect analysis.
The primary objective was to expand upon results of a previously piloted patient perception survey with Healthcare Failure Mode and Effect Analysis (HFMEA), to identify areas within pharmacist-managed clinics needing improvement. The survey was adapted for use in pharmacist-managed clinics. Patients completed the survey following regularly scheduled pharmacist appointments. Data were analyzed with a method adapted from HFMEA. Product scores could range from five to 25. A product of five indicates that pharmacists are doing a good job on the items that patients place the most value on, while a product score of 25 indicates that pharmacists are doing a poor job. A score greater than or equal to ten was used to identify areas for improvement. Seventy-one patients completed surveys. Thirteen components were assessed and no item achieved a mean product greater than or equal to ten. The survey item with the highest mean product pertained to discussion of potential medication side effects (mean: 7.06; interquartile range: 5-10). Analysis of each survey item found that all survey items had multiple individual responses that provided a product score of greater than or equal to ten. The survey items most frequently listed in the overall population as being most valued were "Told you the name of each of your medicines and what they are used for", "Answered your questions fully," and "Explained what your medicines do". Educational components provided during pharmacist-managed clinic appointments are aligned with patients' needs and are successfully incorporating the components that patients value highly in a patient-healthcare provider interaction. The HFMEA model can be an important teaching tool to identify specific processes in need of improvement and to help enhance pharmacists' self-efficacy, which may further improve patient care.


Involving men to improve maternal and newborn health: A systematic review of the effectiveness of interventions.
Emerging evidence and program experience indicate that engaging men in maternal and newborn health can have considerable health benefits for women and children in low- and middle-income countries. Previous reviews have identified male involvement as a promising intervention, but with a complex evidence base and limited direct evidence of effectiveness for mortality and morbidity outcomes. To determine the effect of interventions to engage men during pregnancy, childbirth and infancy on mortality and morbidity, as well as effects on mechanisms by which male involvement is hypothesised to influence mortality and morbidity outcomes: home care practices, care-seeking, and couple relationships. Using a comprehensive, highly sensitive mapping of maternal health intervention studies conducted in low- and middle-income countries between 2000 and 2012, we identified interventions that have engaged men to improve maternal and newborn health. Primary outcomes were care-seeking for essential services, mortality and morbidity, and home care practices. Secondary outcomes relating to couple relationships were extracted from included studies. Thirteen studies from nine countries were included. Interventions to engage men were associated with improved antenatal care attendance, skilled birth attendance, facility birth, postpartum care, birth and complications preparedness and maternal nutrition. The impact of interventions on mortality, morbidity and breastfeeding was less clear. Included interventions improved male partner support for women and increased couple communication and joint decision-making, with ambiguous effects on women's autonomy. Interventions to engage men in maternal and newborn health can increase care-seeking, improve home care practices, and support more equitable couple communication and decision-making for maternal and newborn health. These findings support engaging men as a health promotion strategy, although evidence gaps remain around effects on mortality and morbidity. Findings also indicate that interventions to increase male involvement should be carefully designed and implemented to mitigate potential harmful effects on couple relationship dynamics.


New molecular insights into peripheral T cell lymphomas.
Peripheral T cell lymphomas (PTCLs) are heterogeneous neoplasms and represent about 12% of all lymphoid malignancies. They are often regarded as "orphan diseases," a designation that does not reflect their real incidence but rather signifies the difficulties encountered in their classification, diagnosis, and treatment. Here we revise the current understanding of the pathobiological characteristics of the most common nodal PTCLs by focusing on the contribution given by high-throughput technologies and the identification of potential therapeutic targets proposed by translational studies.


Baohuoside-I suppresses cell proliferation and migration by up-regulating miR-144 in melanoma.
Baohuoside-I was reported to induce apoptosis in non-small-cell lung cancer and inhibit the growth of multiple myeloma cells. The antitumour potential of baohuoside-I has not been demonstrated in melanoma yet. To investigate the potential antitumour activity of baohuoside-I against melanoma and elucidate its underlying molecular mechanism. Cell viability was evaluated by MTT assay. The malignant invasion capacity was measured with trans-well assay. The relative expression change of microRNAs was profiled with microarray. TargetScan was utilized for prediction of target gene of miR-144. Regulatory effect of miR-144 on SMAD1 was determined by dual luciferase reporter assay. Endogenous SMAD1 protein in response to ectopic expression of miR-144 was determined by immunoblotting. Xenograft mice were employed to evaluate antitumour potential of baohuoside-I (25 mg/kg by tail intravenous injection every two days) in vivo. Baohuoside-I significantly inhibited proliferation (45 ± 4% reduction in M14 and 35 ± 3% reduction in MV3 at 24 h) and migration (70 ± 4% reduction in M14 and 72 ± 3% reduction in MV3) in melanoma cells. Mechanistically, baohuoside-I up-regulated miR-144 expression levels (3 ± 0.2-fold). Silence of miR-144 reversed the inhibition of baohuoside-I in melanoma. We have identified that SMAD1 was the novel target of miR-144. Moreover, baohuoside-I suppressed melanoma in vivo (52 ± 8% reduction in xenograft tumour size at day 20). Our data suggested significant antitumour potential of baohuoside-I against melanoma both in vitro and in vivo, which warrants further laboratory investigation and clinical trial.


Preoperative medical therapy before surgery for uterine fibroids.
Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive.Fibroid growth is stimulated by oestrogen. Gonadotropin-hormone releasing analogues (GnRHa) induce a state of hypo-oestrogenism that shrinks fibroids , but has unacceptable side effects if used long-term. Other potential hormonal treatments, include progestins and selective progesterone-receptor modulators (SPRMs).This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low-quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD -175 mL, 95% CI -219.0 to -131.7; 13 studies; 858 participants; I² = 67%; low-quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate-quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate-quality evidence).Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (-9.59 minutes, 95% CI 15.9 to -3.28; 6 studies; 617 participants; I² = 57%; low-quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate-quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low-quality evidence).GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low-quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low-quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (-47% with GnRHa compared to -20% and -22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low-quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate-quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate-quality evidence) or haemoglobin levels (MD -0.2, 95% CI -0.6 to 0.2; 188 participants; moderate-quality evidence).There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI -5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low-quality evidence).The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB-2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high-quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low-quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low-quality evidence; asoprisnil: MD -166.9 mL; 95% CI -277.6 to -56.2; 1 study; 22 participants; low-quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid-related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost-effectiveness and distinguish between groups of women with fibroids who would most benefit.


Characterization of embryonic surface ectoderm cell protrusions.
During embryonic development, complex changes in cell behavior generate the final form of the tissues. Extension of cell protrusions have been described as an important component in this process. Cellular protrusions have been associated with generation of traction, intercellular communication or establishment of signaling gradients. Here, we describe and compare in detail from live imaging data the dynamics of protrusions in the surface ectoderm of chick and mouse embryos. In particular, we explore the differences between cells surrounding the lens placode and other regions of the head. Our results showed that protrusions from the eye region in mouse embryos are longer than those in chick embryos. In addition, protrusions from regions where there are no significant changes in tissue shape are longer and more stable than protrusions that surround the invaginating lens placode. We did not find a clear directionality to the protrusions in any region. Finally, we observed intercellular trafficking of membrane puncta in the protrusions of both embryos in all the regions analyzed. In summary, the results presented here suggest that the dynamics of these protrusions adapt to their surroundings and possibly contribute to intercellular communication in embryonic cephalic epithelia.


Overproduction of CcmABCDEFGH restores cytochrome c maturation in a DsbD deletion strain of E. coli: another route for reductant?
The multidomain transmembrane protein DsbD is essential for cytochrome c maturation (Ccm) in Escherichia coli and transports reductant to the otherwise oxidising environment of the bacterial periplasm. The Ccm proteins ABCDEFGH are also essential and we show that the overproduction of these proteins can unexpectedly complement for the absence of DsbD in a deletion strain by partially restoring the production of an exogenous c-type cytochrome under aerobic and anaerobic conditions. This suggests that one or more of the Ccm proteins can provide reductant to the periplasm. The Ccm proteins do not, however, restore the normal disulfide mis-isomerisation phenotype of the deletion strain, as shown by assay of the multidisulfide-bonded enzyme urokinase.


Semantic prioritization of novel causative genomic variants.
Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.


Short-term effects of high-intensity laser therapy on frozen shoulder: A prospective randomized control study.
Frozen shoulder, which is characterized by shoulder pain and limitation of the range of motion (ROM), is a common disorder. High-intensity laser therapy (HILT) was recently introduced in the musculoskeletal therapeutic field. The objective of this study is to evaluate the clinical efficacy of HILT in patients with frozen shoulder. A prospective randomized controlled study. Patients with frozen shoulder were randomly divided into 2 groups: a HILT group (n = 33) and a placebo group (n = 33). The treatment was administered 3 times per week on alternate days for 3 weeks. For all patients, the visual analog scale (VAS) for pain, VAS for satisfaction, and passive ROM were measured at baseline and 3, 8, and 12 weeks after the treatment. The HILT group had a lower pain VAS score at 3 weeks (3.2 ± 1.7 vs. 4.3 ± 2.2, p = 0.033) and 8 weeks (2.2 ± 2.0 vs. 3.4 ± 2.7, p = 0.042), however, no statistically significant difference in the pain VAS was observed between the two groups at the final follow-up (12 weeks). No statistical difference in the ROM and the satisfaction VAS was observed between the 2 groups at serial follow-ups. In management of frozen shoulder, HILT provided significant pain relief at 3 and 8 weeks, but not at the final follow-up time point. HILT is a noninvasive adjuvant treatment that can reduce pain in frozen shoulders. Further study is needed in order to optimize the dose and duration of HILT.


Evolution of acoustic and visual signals in Asian barbets.
The study of animal communication systems is an important step towards gaining greater understanding of the processes influencing diversification because signals often play an important role in mate choice and can lead to reproductive isolation. Signal evolution can be influenced by a diversity of factors such as biophysical constraints on the emitter, the signalling environment, or selection to avoid heterospecific matings. Furthermore, because signals can be costly to produce, trade-offs may exist between different types of signals. Here, we apply phylogenetic comparative analyses to study the evolution of acoustic and visual signals in Asian barbets, a clade of non-Passerine, forest-dependent birds. Our results suggest that evolution of acoustic and visual signals in barbets is influenced by diverse factors, such as morphology and signalling environment, suggesting a potential effect of sensory drive. We found no trade-offs between visual and acoustic signals. Quite to the contrary, more colourful species sing significantly longer songs. Song characteristics presented distinct patterns of evolution. Song frequency diverged early on and the rate of evolution of this trait appears to be constrained by body size. On the other hand, characteristics associated with length of the song presented evidence for more recent divergence. Finally, our results indicate that there is a spatial component to the evolution of visual signals, and that visual signals are more divergent between closely related taxa than acoustic signals. Hence, visual signals in these species could play a role in speciation or reinforcement of reproductive isolation following secondary contacts.


Characteristics and medical management of patients with rheumatoid arthritis and ankylosing spondylitis.
Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic, progressive, systemic inflammatory rheumatic diseases that lead to serious disability. The objective of this study was to investigate the demographic and clinical characteristics of the patients with RA and AS who were treated in tertiary hospitals in Turkey and to analyze their current medical management. A total of 562 RA and 216 AS patients were evaluated. The mean age of RA patients was 52.1 +/- 12.6 years. The female to male ratio was 3.7:1. Of the RA patients, 72.2% had positive rheumatoid factor (RF), 62.9% had high C-reactive protein, and 75.2% had radiological erosion. The ratio of patients with Disease Activity Score (DAS) 28 >3.2 was 73.9% and of those with Health Assessment Questionnaire (HAQ) > or =1.5 was 20.9%. There was a statistically significant increase in RF positivity and HAQ scores in the group with higher DAS 28 score. Frequency of extraarticular manifestations was 22.4%. The ratio of the patients receiving disease modifying antirheumatic drugs (DMARD) was 93.1%, and 6.9% of the patients were using anti-tumor necrosis factor (TNF) blocking agents. In AS, the mean age of the patients was 38.1 +/- 10.6, and the female to male ratio was 1:2.5. The time elapsed between the first symptom and diagnosis was 4.3 years. The ratio of peripheral joint involvement was 29.4%. Major histocompatibility complex, class I, B 27 was investigated in 31.1% of patients and the rate of positivity was 91%. In 52.4% of the patients, Bath AS Disease Activity Index (BASDAI) was > or =4. The erythrocyte sedimentation rate, Bath AS Functional Index, and peripheral involvement were significantly higher in the group with BASDAI > or =4. Frequency of extraarticular involvement was 21.2% in AS patients. In the treatment schedule, 77.5% of AS patients were receiving sulphasalazine, 15% methotrexate, and 9.9% anti-TNF agents. Despite widespread use of DMARD, we observed high disease activity in more than half of the RA and AS patients. These results may be due to relatively insufficient usage of anti-TNF agents in our patients and therefore these results mostly reflect the traditional treatments. In conclusion, analysis of disease characteristics will inform us about the disease severity and activity in RA and AS patients and could help in selecting candidate patients for biological treatments.


Ultrasound anatomy of the fingers: flexor and extensor system with emphasis on variations and anatomical detail.
Many anatomical details and variants occur in the finger tendons and soft tissue structures. These may lead to misdiagnosis if the radiologist is not well aware of them. We discuss the midhand extensor tendons, dorsal hood, junctura tendinea, conjoint tendons, transverse retinacular ligament, triangular ligament as well as central and distal slip anatomy and ultrasound correlation. The dorsal hood is an important structure to center the tendons at the midportion of the MCP heads, and the sagittal bands are its main components. Two tendons are present at the second digit, and two or more at the fifth digit. The extensor mechanism is anatomically interrelated with the palmar lumbricals and interosseous tendons. At the palmar side, the flexor superficialis and profundus tendons show varying relationships along the finger. The flexor profundus passes through an opening in the flexor superficialis. We also discuss the chiasma crurale, ridges at the flexor superficialis insertions and bifid flexor profundus tendon. Although a typical distribution of annular pulleys can be observed, many variants may be present of which we address some. The volar plate is a midline fibro-cartilaginous meniscus attached proximally to the well-identifiable checkrein ligaments and distally to the base of the phalanges. Knowledge of these details and variations allows for better understanding of the finger and hand ultrasound. Many anatomical details and variants occur in the finger tendons and soft tissue structures. These may lead to misdiagnosis if the radiologist is not well aware of them. We discuss the midhand extensor tendons, dorsal hood, junctura tendinea, conjoint tendons, transverse retinacular ligament, triangular ligament as well as central and distal slip anatomy and ultrasound correlation. The dorsal hood is an important structure to center the tendons at the midportion of the MCP heads, and the sagittal bands are its main components. Two tendons are present at the second digit, and two or more at the fifth digit. The extensor mechanism is anatomically interrelated with the palmar lumbricals and interosseous tendons. At the palmar side, the flexor superficialis and profundus tendons show varying relationships along the finger. The flexor profundus passes through an opening in the flexor superficialis. We also discuss the chiasma crurale, ridges at the flexor superficialis insertions and bifid flexor profundus tendon. Although a typical distribution of annular pulleys can be observed, many variants may be present of which we address some. The volar plate is a midline fibro-cartilaginous meniscus attached proximally to the well-identifiable checkrein ligaments and distally to the base of the phalanges. Knowledge of these details and variations allows for better understanding of the finger and hand ultrasound.


Bacterial effector activates jasmonate signaling by directly targeting JAZ transcriptional repressors.
Gram-negative bacterial pathogens deliver a variety of virulence proteins through the type III secretion system (T3SS) directly into the host cytoplasm. These type III secreted effectors (T3SEs) play an essential role in bacterial infection, mainly by targeting host immunity. However, the molecular basis of their functionalities remains largely enigmatic. Here, we show that the Pseudomonas syringae T3SE HopZ1a, a member of the widely distributed YopJ effector family, directly interacts with jasmonate ZIM-domain (JAZ) proteins through the conserved Jas domain in plant hosts. JAZs are transcription repressors of jasmonate (JA)-responsive genes and major components of the jasmonate receptor complex. Upon interaction, JAZs can be acetylated by HopZ1a through a putative acetyltransferase activity. Importantly, P. syringae producing the wild-type, but not a catalytic mutant of HopZ1a, promotes the degradation of HopZ1-interacting JAZs and activates JA signaling during bacterial infection. Furthermore, HopZ1a could partially rescue the virulence defect of a P. syringae mutant that lacks the production of coronatine, a JA-mimicking phytotoxin produced by a few P. syringae strains. These results highlight a novel example by which a bacterial effector directly manipulates the core regulators of phytohormone signaling to facilitate infection. The targeting of JAZ repressors by both coronatine toxin and HopZ1 effector suggests that the JA receptor complex is potentially a major hub of host targets for bacterial pathogens.


Abecarnil and alprazolam in humans: behavioral, subjective and reinforcing effects.
Abecarnil, a novel beta-carboline, is under development for the treatment of Generalized Anxiety Disorder. This study compared the behavioral, subjective and reinforcing effects of abecarnil to those of the benzodiazepine alprazolam in 14 healthy males with histories of sedative drug abuse. Placebo, abecarnil (10, 20, 40 mg) and alprazolam (1.0, 2.0, 4.0 mg) were administered p.o. in a double-blind, cross-over design. Abecarnil and alprazolam produced comparable dose-dependent decreases in behavioral performance on balance, circular lights, digit-recall and digit-symbol-substitution tasks that peaked 2-4 hr after drug administration. Both drugs produced a profile of sedative effects and were categorized by subjects as predominantly barbiturate- or benzodiazepine-like. However, the high dose of alprazolam increased subject-ratings of sleepy, fatigued and tired; these ratings were significantly different from both placebo and all doses of abecarnil. Abecarnil and alprazolam produced comparable dose-dependent increases in ratings of drug strength. The highest dose of alprazolam produced increases in Next Day ratings of drug liking, good effects, monetary value of the drug, and desire to take the drug again that were significantly greater than placebo and the highest dose of abecarnil. Abecarnil, but not alprazolam, produced increases in Next Day ratings of "bad effects" that were significantly greater than placebo. The highest dose of alprazolam produced increases in a direct measure of drug reinforcement (drug vs. money Multiple-Choice Procedure) that were significantly greater than placebo and all doses of abecarnil. Collectively, these data suggest that abecarnil may have less potential for abuse than alprazolam in a sedative-abusing population.


Outcomes of a prospective trial of student-athlete drug testing: the Student Athlete Testing Using Random Notification (SATURN) study.
To assess the effects of random drug and alcohol testing (DAT) among high school athletes. This was a 2-year prospective randomized controlled study of a single cohort among five intervention high schools with a DAT policy and six schools with a deferred policy, serially assessed by voluntary, confidential questionnaires. DAT school athletes were at risk for random testing during the full academic year. Positive test results were reported to parents or guardians, with mandatory counseling. Indices of illicit drug use, with and without alcohol use, were assessed at the beginning and end of each school year for the past month and prior year. Potential mediating variables were evaluated. Student-athletes from intervention and control schools did not differ in past 1-month use of illicit drug or a combination of drug and alcohol use at any of the four follow-up periods. At the end of the initial school year and after 2 full school years, student-athletes at DAT schools reported less drug use during the past year (p < .01) compared to athletes at the deferred policy schools. Combining past year drug and alcohol use together, student-athletes at DAT schools reported less use at the second and third follow-up assessments (p < .05). Paradoxically, DAT athletes across all assessments reported less athletic competence (p < .001), less belief authorities were opposed to drug use (p < .01), and indicated greater risk-taking (p < .05). At the final assessment, DAT athletes believed less in testing benefits (p < .05) and less that testing was a reason not to use drugs (p < .01). No DAT deterrent effects were evident for past month use during any of four follow-up periods. Prior-year drug use was reduced in two of four follow-up self-reports, and a combination of drug and alcohol use was reduced at two assessments as well. Overall, drug testing was accompanied by an increase in some risk factors for future substance use. More research is needed before DAT is considered an effective deterrent for school-based athletes.


Optical lattice on an atom chip.
Optical dipole traps and atom chips are two very powerful tools for the quantum manipulation of neutral atoms. We demonstrate that both methods can be combined by creating an optical lattice potential on an atom chip. A red-detuned laser beam is retroreflected using the atom chip surface as a high-quality mirror, generating a vertical array of purely optical oblate traps. We transfer thermal atoms from the chip into the lattice and observe cooling into the two-dimensional regime. Using a chip-generated Bose-Einstein condensate, we demonstrate coherent Bloch oscillations in the lattice.


Evolutionary branching in a finite population: deterministic branching vs. stochastic branching.
Adaptive dynamics formalism demonstrates that, in a constant environment, a continuous trait may first converge to a singular point followed by spontaneous transition from a unimodal trait distribution into a bimodal one, which is called "evolutionary branching." Most previous analyses of evolutionary branching have been conducted in an infinitely large population. Here, we study the effect of stochasticity caused by the finiteness of the population size on evolutionary branching. By analyzing the dynamics of trait variance, we obtain the condition for evolutionary branching as the one under which trait variance explodes. Genetic drift reduces the trait variance and causes stochastic fluctuation. In a very small population, evolutionary branching does not occur. In larger populations, evolutionary branching may occur, but it occurs in two different manners: in deterministic branching, branching occurs quickly when the population reaches the singular point, while in stochastic branching, the population stays at singularity for a period before branching out. The conditions for these cases and the mean branching-out times are calculated in terms of population size, mutational effects, and selection intensity and are confirmed by direct computer simulations of the individual-based model.


The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels.
The omega-conotoxins from fish-hunting cone snails are potent inhibitors of voltage-gated calcium channels. The omega-conotoxins MVIIA and CVID are selective N-type calcium channel inhibitors with potential in the treatment of chronic pain. The beta and alpha(2)delta-1 auxiliary subunits influence the expression and characteristics of the alpha(1B) subunit of N-type channels and are differentially regulated in disease states, including pain. In this study, we examined the influence of these auxiliary subunits on the ability of the omega-conotoxins GVIA, MVIIA, CVID and analogues to inhibit peripheral and central forms of the rat N-type channels. Although the beta3 subunit had little influence on the on- and off-rates of omega-conotoxins, coexpression of alpha(2)delta with alpha(1B) significantly reduced on-rates and equilibrium inhibition at both the central and peripheral isoforms of the N-type channels. The alpha(2)delta also enhanced the selectivity of MVIIA, but not CVID, for the central isoform. Similar but less pronounced trends were also observed for N-type channels expressed in human embryonic kidney cells. The influence of alpha(2)delta was not affected by oocyte deglycosylation. The extent of recovery from the omega-conotoxin block was least for GVIA, intermediate for MVIIA, and almost complete for CVID. Application of a hyperpolarizing holding potential (-120 mV) did not significantly enhance the extent of CVID recovery. Interestingly, [R10K]MVIIA and [O10K]GVIA had greater recovery from the block, whereas [K10R]CVID had reduced recovery from the block, indicating that position 10 had an important influence on the extent of omega-conotoxin reversibility. Recovery from CVID block was reduced in the presence of alpha(2)delta in human embryonic kidney cells and in oocytes expressing alpha(1B-b). These results may have implications for the antinociceptive properties of omega-conotoxins, given that the alpha(2)delta subunit is up-regulated in certain pain states.


A randomized controlled trial of an internal family systems-based psychotherapeutic intervention on outcomes in rheumatoid arthritis: a proof-of-concept study.
To conduct a proof-of-concept randomized trial of an Internal Family Systems (IFS) psychotherapeutic intervention on rheumatoid arthritis (RA) disease activity and psychological status. Patients with RA were randomized to either an IFS group for 9 months (n = 39) or an education (control) group (n = 40) that received mailed materials on RA symptoms and management. The groups were evaluated every 3 months until intervention end and 1 year later. Self-assessed joint pain (RA Disease Activity Index joint score), Short Form-12 physical function score, visual analog scale for overall pain and mental health status (Beck Depression Inventory, and State Trait Anxiety Inventory) were assessed. The 28-joint Disease Activity Score-C-reactive Protein 4 was determined by rheumatologists blinded to group assignment. Treatment effects were estimated by between-group differences, and mixed model repeated measures compared trends between study arms at 9 months and 1 year after intervention end. Of 79 participants randomized, 68 completed the study assessments and 82% of the IFS group completed the protocol. Posttreatment improvements favoring the IFS group occurred in overall pain [mean treatment effects -14.9 (29.1 SD); p = 0.04], and physical function [14.6 (25.3); p = 0.04]. Posttreatment improvements were sustained 1 year later in self-assessed joint pain [-0.6 (1.1); p = 0.04], self-compassion [1.8 (2.8); p = 0.01], and depressive symptoms [-3.2 (5.0); p =0.01]. There were no sustained improvements in anxiety, self-efficacy, or disease activity. An IFS-based intervention is feasible and acceptable to patients with RA and may complement medical management of the disease. Future efficacy trials are warranted. ClinicalTrials.gov identifier: NCT00869349.


Stability and effect on the soft tissue profile of mandibular advancement with sagittal split osteotomy and rigid internal fixation.
The stability and the effect on the soft tissue profile of mandibular advancement with sagittal split osteotomy and rigid internal fixation was studied prospectively in 30 consecutive patients, 17 to 32 years old, who had a distal occlusion. Profile roentgen cephalometric recordings were made immediately before and shortly after surgery as well as 13 months postsurgically. The mean advancement of the mandible 3 to 8 days after surgery was 5 mm. On average, there was only a small increase in the anterior facial height. At the follow-up after 13 months, the advancement of the mandible had, in most cases, partially relapsed so that the median net effect was 70%. In six subjects, however, the mandible had advanced slightly further. The skeletal relapse was partially masked by compensatory movements of the maxillary incisors so that the mean net effect on the overjet was 83%. The amount of relapse was positively correlated to the magnitude of advancement during surgery. Likewise, a postsurgical relapse of the anterior facial height was positively correlated to the magnitude of advancement during surgery. Likewise, a postsurgical relapse of the anterior facial height was positively correlated to the magnitude of the vertical surgical displacement anteriorly and posteriorly. The soft tissue chin closely followed the underlying hard tissue. The mean net effect on the labial fold, however, was smaller, 88% of the mandibular advancement. The net effect on the lower lip was 66% of the advancement of the mandibular incisor.


Reduced cerebral cortical but elevated striatal concentration of somatostatin-like immunoreactivity in dominantly inherited olivopontocerebellar atrophy.
Somatostatin-like immunoreactivity (SLI) was measured in the brains of nine patients with dominantly inherited olivopontocerebellar atrophy (OPCA), who all had a marked deficit of the cholinergic marker choline-acetyltransferase (ChAT) in the cerebral cortex and striatum. Mean concentrations of SLI in OPCA were significantly reduced by 42-58% in parietal and occipital cortices and frontal cortical eye fields, but were normal in other cortical areas, including two subdivisions of the temporal cortex which show marked depletions of both SLI and ChAT in Alzheimer's disease. This dissociation of SLI and ChAT indicates that a cortical cholinergic deficit does not invariably lead to reduction of somatostatin. In the caudate nucleus, the region of OPCA brain having the most severe ChAT deficit (-81%), SLI levels were significantly elevated by 46% and were negatively and significantly correlated with ChAT activities (r = -0.66). The SLI alterations could be due to abnormal somatostatin metabolism or release, or an increased number of somatostatin-containing neurons and could contribute to the brain dysfunction of OPCA.


A poroelastic continuum model of the cupula partition and the response dynamics of the vestibular semicircular canal.
Using mixture theory, an axisymmetric continuum model is presented describing the response dynamics of the vestibular semicircular canals to canal-centered head rotation in which the cupula partition is modeled as a poroelastic mixture of interpenetrating solid and fluid constituents. The solid matrix of the cupula is assumed to behave as a linear elastic material, whereas the fluid constituent is assumed to be Newtonian. A regular perturbation analysis of the fluid dynamics in the canal provides a dynamic boundary condition, which acts across the cupula partition. Numerical solution of the coupled system of momentum equations provides the spatio-temporal displacement fields for both the fluid and solid constituents of the cupula. Results indicate that at frequencies above 1 Hz, the fluid constituent is dynamically entrained by the solid matrix such that their motions are bound as if to exist as a single component. The resulting high-frequency response is consistent with the macromechanical response predicted by single-component viscoelastic models of the cupula. Below 1 Hz, the dynamic coupling between the fluid and solid constituents weakens and the transcupular differential pressure is sufficient to force fluid through the mixture with little deformation of the solid matrix. Results are sensitive to the precise value of the cupular permeability. One of the most important distinctions between the present analysis and previous impermeable models of the cupula arises at the micromechanical level in terms of the local fluid flow that is predicted to occur within the cupula and around the ciliary bundles and sensory hair cells. Another important result reveals that the permeation dynamics predicted below 1 Hz gives rise to the same low-frequency macromechanical response as would occur with an impermeable viscoelastic structure having a much greater stiffness. Current estimates of the mechanical stiffness of the cupula, based solely on afferent nerve data, may therefore overestimate the true value intrinsic to the solid matrix by as much as an order of magnitude.


80Gb/s clock recovery with phase locked loop based on LiNbO3 modulators.
In this paper, we present a scheme for extracting a 10GHz clock from the 80Gb/s optical time division multiplexed (OTDM) return to zero (RZ) data stream. The proposed clock recovery is based on the offset locking technique. By using the input data composed of a repeating "10100000" pattern, residue jitter free operation for clock recovery is demonstrated. The method utilizes a LiNbO3 Mach-Zehnder (MZ) intensity modulator for cross-correlation detections.


Monoclonal antibody-based therapies for bacterial infections.
This review highlights recent developments in the development of monoclonal antibodies to treat bacterial disease, including preclinical advances and the status of current clinical trials. Monoclonal antibody (mAb) therapy is becoming increasingly promising in the infectious disease field. Though bacterial exotoxins continue to be a mainstay of mAb targets, searches for protein targets on the surface of bacteria have uncovered new mechanisms of antibody-mediated action against bacteria. Additionally, surveys of the polysaccharide serotype prevalence among antibiotic-resistant bacterial populations have yielded opportunities to leverage human selective pressures to our clinical advantage. Several mAb candidates are progressing through clinical development with great promise, especially those with structures altered to provide maximum benefit. Although other clinical trials have recently proved unsuccessful, these failures and lessons from immune profiling provide opportunities to understand how vulnerabilities of certain targets may change in different disease states. Despite the hurdles of identifying effective targets and understanding how mAbs provide protection within different infections, we show that the progress made in these fields is a positive indication of mAbs becoming more widely accepted as the future for treating bacterial infections.


Mercury concentrations in Bicknell's thrush and other insectivorous passerines in Montane forests of northeastern North America.
Anthropogenic input of mercury (Hg) into the environment has elevated risk to fish and wildlife, particularly in northeastern North America. Investigations into the transfer and fate of Hg have focused on inhabitants of freshwater aquatic ecosystems, as these are the habitats at greatest risk for methylmercury (MeHg) biomagnification. Deviating from such an approach, we documented MeHg availability in a terrestrial montane ecosystem using a suite of insectivorous passerines. Intensive and extensive sampling of Bicknell's thrush (Catharus bicknelli) indicated significant heterogeneity in MeHg availability across 21 mountaintops in northeastern North America. Southern parts of the breeding range tended to be at greater risk than northern parts. Mean blood Hg concentrations for Bicknell's thrush at 21 distinct breeding sites ranged from 0.08 to 0.38 ug/g (ww) and at seven Greater Antillean wintering sites ranged from 0.03 to 0.42 ug/g (ww). Overall concentrations were significantly greater in wintering than in breeding areas. Mercury exposure profiles for four passerine species on Mt. Mansfield, Vermont indicated greatest MeHg uptake in Bicknell's thrush and yellow-rumped warbler (Dendroica coronata) and lowest in blackpoll warbler (Dendroica striata) and white-throated sparrow (Zonotrichia albicollis). The MeHg and total Hg ratio in blood in these four species was nearly 1:1. There was no correlation between blood and feather Hg concentrations in breeding Bicknell's thrush, in part because of apparent retention of winter Hg body burdens, within-season variation of MeHg availability, and confounding factors such as influences from age. Adult thrushes had significantly higher concentrations of feather Hg than did young-of-the-year. Although individual patterns of inter-year feather Hg concentrations were disordered, some individuals exhibited bioaccumulation of MeHg. Female blood Hg concentrations were significantly lower than males', in part because females have additional depurating mechanisms through eggs. Older male Bicknell's thrushes that breed in New England are therefore likely at greatest risk. Mechanisms for Hg methylation in montane areas without standing water are not yet fully understood. However, recent studies indicate that MeHg is present in forest tree leaves and leaf detritus; saturated soils and other moist microhabitats may also contribute to MeHg availability. Our finding of a correlation between regional litterfall Hg flux patterns and Bicknell's thrush blood Hg concentrations demonstrates on-site availability of MeHg. Further investigations into MeHg availability in montane environments are recommended to assess risk to insectivorous passerines, particularly the Bicknell's thrush.


Person-centred ward climate as experienced by mentally lucid residents in long-term care facilities.
To assess the content validity and reliability of the Person-centred Climate Questionnaire-Patient version in long-term care facilities, to describe residents' perceptions of the extent to which their ward climate was person-centred and to explore whether person-centredness was associated with facility and resident characteristics, such as facility and ward size, having a sensory garden and having a primary caregiver. The importance of the physical environment to persons with dementia has been investigated. However, research is lacking regarding the extent to which mentally lucid residents experience their physical and psycho-social ward climate as person-centred and the factors influencing their experience. Cross-sectional survey design. The Person-centred Climate Questionnaire-Patient version was translated into Norwegian with forward and backward translation. The content validity index for scales was assessed. The Person-centred Climate Questionnaire -Patient version was completed by 145 mentally lucid residents in 17 Norwegian long-term care facilities. Reliability was assessed by Cronbach's α and item-total correlations. Test-retest reliability was assessed by paired samples t-test and Spearman's correlation. To explore differences based on facility and resident characteristics, independent-samples t-test and one-way anova were used. The content validity index for scales was satisfactory. The Person-centred Climate Questionnaire-Patient version was internally consistent and had satisfactory test-retest reliability. The climate was experienced as highly person-centred. No significant differences were found, except that residents in larger facilities experienced the climate as more person-centred in relation to everyday activities (subscale 2) than residents in smaller facilities. The Norwegian version of the Person-centred Climate Questionnaire-Patient version can be regarded as reliable in a long-term care facility context. Perceived degree of person-centredness was not associated with facility or resident characteristics, such as the number of residents, having a sensory garden or knowing that one has a primary caregiver. A person-centred climate can be attained in different kinds of long-term care facilities.


Different ways of understanding the construct of successful aging: Iranian immigrants speak about what aging well means to them.
This article presents the variations in themes and notions of successful aging that were found in a project that aimed to shed light on the value orientations that people prefer and the understandings of successful aging that they uphold. The project, which aimed also to study the way in which the process of migration challenges the notions in question, shed light on the various types of logic that Iranian immigrants to Sweden use when trying to make sense of the construct of successful aging. This article departs from these variations and discusses, among other things, the inevitable decay with which the aging process seems to be associated; the different purpose-related ideologies that people use when trying to explain how the decay in question ought to be handled; the way in which time-related ideas influence the manner in which notions of aging well are framed; the manner in which divergent views regarding activity shape the understandings of successful aging that people uphold; and the way in which ideas regarding autonomy and dependence shape the way in which one defines a good old age. The complexity of logic types utilized by the informants suggests that, if researchers are to further their understanding of the meaning of the construct of successful aging, they need to dismantle people's ideas as well as the way in which they use culture when trying to make sense of what aging well entails. The article finishes with a brief discussion regarding the importance of intracultural variation and suggests that researchers need a better understanding of culture's impact on the manner in which the construct in question is understood if they are to develop the successful aging paradigm in a culturally informed manner.


Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury.
Chronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity. 298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or ⩾1year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition. Out of 298 patients enrolled 273 (92%) resolved ⩽1year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p=0.011], dyslipidemia [OR: 4.26, p=0.04] and severe DILI [OR: 14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001). Main drug classes involved in chronicity were statins (24%) and anti-infectives (24%). Histological examination in chronic patients demonstrated two cases with ductal lesion and seven with cirrhosis. One year is the best cut-off point to define chronic DILI or prolonged recovery, with risk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery. Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.


Binge drinking, cognitive performance and mood in a population of young social drinkers.
Binge drinking may lead to brain damage and have implications for the development of alcohol dependence. The aims of the present study were to determine individual characteristics as well as to compare mood states and cognitive function between binge and nonbinge drinkers and thus further validate the new tool used to identify these populations among social drinkers. The lowest and the highest 33.3% from a database of 245 social drinkers' binge scores derived from the Alcohol Use Questionnaire (AUQ) were used as cutoff points to identify nonbinge drinkers and binge drinkers in a further population of 100 young healthy volunteers. Personality characteristics, expectations of the effects of alcohol and current mood were evaluated. Cognitive performance was tested with a Matching to Sample Visual Search task (MTS) and a Spatial Working Memory task (SWM) both from the CANTAB battery, and a Vigilance task from the Gordon Diagnostic System. The binge drinkers had less positive mood than the nonbinge drinkers. In the MTS choice time on an 8-pattern condition and movement time on an 8- and 4-pattern condition was found to be faster in the binge drinkers compared to nonbinge drinkers. A gender by binge drinking interaction in the SWM and the Gordon Diagnostic System task revealed that female binge drinkers were worse on both these tasks than the female nonbinge drinkers. These results confirm previous findings in binge drinkers and suggest that in a nondependent alcohol-drinking group, differences can be seen in mood and cognitive performance between those that binge drink and those that do not.


Sugar Selectivity and Other Characteristics of Phloem Loading in Beta vulgaris L.
The rate of phloem loading, its selectivity, and the disposition of labeled carbon were studied following application of (14)C-labeled sugars to the free space of source leaves of sugar beet (Beta vulgaris L.). Buffered 10 mm solutions of (14)C-labeled sucrose, fructose, stachyose, mannitol, 3-0-methyl glucose or l-glucose were applied to the abraded epidermis of source leaves held in the dark. Distribution of the labeled carbon from sugar taken up from the free space was studied by micro-densitometry of autoradiographs. Uptake of labeled sugar from the free space, partition between mesophyll and minor veins, metabolic conversions, export and respiration were followed during the 3-hr time course studies. Rates of sugar uptake into the minor veins, flux rates through the sieve element-companion cell complex membrane and concentration ratios between free space and the interior of the minor vein phloem cells were compared for the six sugars studied for evidence of active uptake. The composition of the free space solution in leaves photosynthesizing in (14)CO(2) was studied by vacuum infiltration of the source leaf air spaces and removal of the solution by centrifugation. Labeled compounds in this solution were compared to those in an aqueous ethanol extract of the same leaf pieces.The results in sugar beet source leaves support the concept of direct, active uptake of sucrose from free space into minor veins. This is not the case for fructose, 3-0-methyl glucose, mannitol, or stachyose. The latter two sugars, which are translocated in some plants, are not loaded into the minor veins at a rate sufficient to make them a significant component of the material translocated. The rate of phloem loading is controlled in part by mesophyll metabolism, especially as it affects the availability of sucrose to the free space. Both the rate and selectivity of export are controlled by uptake from the free space into the sieve element-companion cell complex of the minor veins.


Tinbergen on mirror neurons.
Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology-the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible 'best explanation' for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of 'survival value', should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding-or another social cognitive function-by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories.


The evolution of amniote gastrulation: the blastopore-primitive streak transition.
In the animal kingdom, gastrulation, the process by which the primary germ layers are formed involves a dramatic transformation in the topology of the cells that give rise to all of the tissues of the adult. Initially formed as a mono-layer, this tissue, the epiblast, becomes subdivided through the internalization of cells, thereby forming a two (bi-laminar) or three (tri-laminar) layered embryo. This morphogenetic process coordinates the development of the fundamental body plan and the three-body axes (antero-posterior, dorso-ventral, and left-right) and begins a fundamental segregation of cells toward divergent developmental fates. In humans and other mammals, as well as in avians, gastrulating cells internalize along a structure, called the primitive streak, which builds from the periphery toward the center of the embryo. How these morphogenetic movements are orchestrated and evolved has been a question for developmental biologists for many years. Is the primitive streak a feature shared by the whole amniote clade? Insights from reptiles suggest that the primitive streak arose independently in mammals and avians, while the reptilian internalization site is a structure half-way between an amphibian blastopore and a primitive streak. The molecular machinery driving primitive streak formation has been partially dissected using mainly the avian embryo, revealing a paramount role of the planar cell polarity (PCP) pathway in streak formation. How did the employment of this machinery evolve? The reptilian branch of the amniote clade might provide us with useful tools to investigate the evolution of the amniote internalization site up to the formation of the primitive streak. WIREs Dev Biol 2017, 6:e262. doi: 10.1002/wdev.262 For further resources related to this article, please visit the WIREs website.


Study protocol of a mixed-methods evaluation of a cluster randomized trial to improve the safety of NSAID and antiplatelet prescribing: data-driven quality improvement in primary care.
Trials of complex interventions are criticized for being 'black box', so the UK Medical Research Council recommends carrying out a process evaluation to explain the trial findings. We believe it is good practice to pre-specify and publish process evaluation protocols to set standards and minimize bias. Unlike protocols for trials, little guidance or standards exist for the reporting of process evaluations. This paper presents the mixed-method process evaluation protocol of a cluster randomized trial, drawing on a framework designed by the authors. This mixed-method evaluation is based on four research questions and maps data collection to a logic model of how the data-driven quality improvement in primary care (DQIP) intervention is expected to work. Data collection will be predominately by qualitative case studies in eight to ten of the trial practices, focus groups with patients affected by the intervention and quantitative analysis of routine practice data, trial outcome and questionnaire data and data from the DQIP intervention. We believe that pre-specifying the intentions of a process evaluation can help to minimize bias arising from potentially misleading post-hoc analysis. We recognize it is also important to retain flexibility to examine the unexpected and the unintended. From that perspective, a mixed-methods evaluation allows the combination of exploratory and flexible qualitative work, and more pre-specified quantitative analysis, with each method contributing to the design, implementation and interpretation of the other.As well as strengthening the study the authors hope to stimulate discussion among their academic colleagues about publishing protocols for evaluations of randomized trials of complex interventions. DATA-DRIVEN QUALITY IMPROVEMENT IN PRIMARY CARE TRIAL REGISTRATION: ClinicalTrials.gov: NCT01425502.


How the ideology of low fat conquered america.
This article examines how faith in science led physicians and patients to embrace the low-fat diet for heart disease prevention and weight loss. Scientific studies dating from the late 1940s showed a correlation between high-fat diets and high-cholesterol levels, suggesting that a low-fat diet might prevent heart disease in high-risk patients. By the 1960s, the low-fat diet began to be touted not just for high-risk heart patients, but as good for the whole nation. After 1980, the low-fat approach became an overarching ideology, promoted by physicians, the federal government, the food industry, and the popular health media. Many Americans subscribed to the ideology of low fat, even though there was no clear evidence that it prevented heart disease or promoted weight loss. Ironically, in the same decades that the low-fat approach assumed ideological status, Americans in the aggregate were getting fatter, leading to what many called an obesity epidemic. Nevertheless, the low-fat ideology had such a hold on Americans that skeptics were dismissed. Only recently has evidence of a paradigm shift begun to surface, first with the challenge of the low-carbohydrate diet and then, with a more moderate approach, reflecting recent scientific knowledge about fats.


Bangladesh policy on prevention and control of non-communicable diseases: a policy analysis.
This paper is aimed at critically assessing the extent to which Non-Communicable Disease NCD-related policies introduced in Bangladesh align with the World Health Organization's (WHO) 2013-2020 Action Plan for the Global Strategy for the Prevention and Control of NCDs. The authors reviewed all relevant policy documents introduced by the Government of Bangladesh since its independence in 1971. The literature review targeted scientific and grey literature documents involving internet-based search, and expert consultation and snowballing to identify relevant policy documents. Information was extracted from the documents using a specific matrix, mapping each document against the six objectives of the WHO 2013-2020 Action Plan for the Global Strategy for the Prevention and Control of NCDs. A total of 51 documents were identified. Seven (14%) were research and/or surveys, nine were on established policies (17%), while seventeen (33%) were on action programmes. Five (10%) were related to guidelines and thirteen (25%) were strategic planning documents from government and non-government agencies/institutes. The study covered documents produced by the Government of Bangladesh as well as those by quasi-government and non-government organizations irrespective of the extent to which the intended policies were implemented. The policy analysis findings suggest that although the government has initiated many NCD-related policies or programs, they lacked proper planning, implementation and monitoring. Consequently, Bangladesh over the years had little success in effectively addressing the growing burden of non-communicable diseases. It is imperative that future research critically assess the effectiveness of national NCD policies by monitoring their implementation and level of population coverage.


Patterns of spinal cord malformation in cloacal exstrophy.
The objective of this study was to assess the prevalence and spectrum of spinal dysraphism in a cohort of children with cloacal exstrophy (CEX) using MRI. Children with CEX presenting between 1999 and 2019 with baseline spinal MRI were included. The images were reviewed in consensus to assess the type of dysraphism. The dysraphisms were initially reviewed and described based on their descriptive anatomy, and then classified according to anomalies of gastrulation, primary neurulation, or secondary neurulation. Thirty-four children were included. Thirty-three of these children had closed spinal dysraphism, and 1 had a normal spine. Of the 33 cases of closed spinal dysraphism, the conus and/or filum terminale were involved in all cases. The most common malformations were spinal lipoma (n = 20) and terminal myelocystocele (n = 11). The lipomas were heterogeneous: 4 dorsal, 9 transitional, 4 chaotic, and 3 terminal. A large subgroup (10/20, 50%) within the lipomas had an unusual morphology of noncontiguous double lipomas, the proximal fat related to the conus and the distal fat within the filum. These were difficult to characterize using existing classifications. In 2 cases, only a thickened filum was noted. The majority of these malformations were compatible with a disorder of secondary neurulation. Complex spinal dysraphisms are consistently associated with CEX. The unusual dysraphism patterns found in this group of patients highlight the limitations of current embryological classifications. Given the propensity for neurological deterioration in this group of patients, spinal MRI should be routinely performed. The type and distribution of malformations seen have implications for the wider understanding of the pathogenesis and classification of lumbosacral lipomas.


Post-traumatic pseudoaneurysm of internal carotid artery: a cause of intractable epistaxis.
In this case report, the authors are presenting a case of a 35-year-old lady who presented to our clinic with recurrent episodes of massive epistaxis and loss of right eye vision for last 6 months following road traffic accident. There was no other significant medical and surgical history. Bleeding episodes were sometimes very severe with loss up to 400-500 cc and would stop spontaneously. She was given multiple blood transfusions after these episodes. A complete otorhinolaryngological examination including rigid endoscopy and coagulation investigation did not reveal any abnormality. CT with contrast of paranasal region showed blood within the right sphenoid sinus with linear fracture of the lateral wall with post-traumatic cavernous pseudoaneurysm of internal carotid artery localised to right sphenoid sinus. That was managed successfully by embolisation using a detachable balloon and a coil. She was followed up in the clinic at 6 weeks and 6 months interval with no symptoms.


Detection of neuroendocrine tumours in the small intestines using contrast-enhanced multiphase Ga-68 DOTATOC PET/CT: the potential role of arterial hyperperfusion.
Interpretation of small intestinal neuroendocrine tumours (NETs) by Ga-68 DOTATOC PET/CT can be difficult. The potential benefit of arterial hyperperfusion for the detection of NETs was evaluated. Between 2006 and 2009, 320 consecutive Ga-68 DOTATOC PET/CT examinations, performed for NETs, revealed 40 lesions suggesting intestinal NETs in 25 patients. Two groups of lesions were distinguished: epigastric lesions evaluable in the arterial and venous CT scan (Group 1) and hypogastrial lesions evaluable in the venous CT scan only (Group 2). Lesions were jointly rated by two radiologists and a nuclear medicine physician. Maximum standard uptake values (SUVmax) of lesions and background were assessed. The reference standard was histology (available for 28 lesions) or follow-up (for a mean of 22.9 months). PET detected all suspicious lesions but was false positive in 3 lesions. In Group 1 the arterial scan performed significantly better than the venous scan (p = 0.008). Diagnostic performance was better in Group 1 than in Group 2 (p < 0.001). SUVmax of true positive lesions were significantly higher than background SUVmax (p < 0.001) and SUVmax of false positive lesions (p = 0.005). The arterial phase of multiphase Ga-68 DOTATOC PET/CT might improve the localization of intestinal NETs and, thereby, improve the overall diagnostic accuracy of this modality in the assessment of intestinal NETs by adding information about lesion perfusion not available when only venous CT is performed.


Brucellosis in Omani children: a multicenter experience over 15 years.
Brucellosis, a common zoonotic disease worldwide, can lead to serious complications in humans. In Oman, the disease occurs most often in the south, but is increasing in the north. Describe brucellosis in children in the Northern Governorate in Oman. Retrospective, observational. Hospitals in the Northern Governorate in Oman. We collected data on the demographics, distribution, common clinical presentations, risk factors, laboratory findings, therapy, and complications of confirmed cases of brucellosis. We included all brucellosis cases up to the age of 13 years at the Child Health Department in Royal, Suhar, Al Rustaq and Nizwa Hospitals over a 15-year period. Descriptive findings of brucellosis. 57 confirmed cases. The 57 confirmed cases of Brucella had a mean age of 6 years. Most of the cases were from Dhakhiliya 21 (36.8%) and Batinah 18 (31.6%). Consumption of raw milk was documented in 75% and 41% had animal contact. From 2010, there was a marked rise of the cases with a maximum rise was noticed in 2019 with a total of 10 cases. The main clinical manifestations were fever (92%, n=52), arthritis (44%, n=25), which involved mainly knees and hips. Forty-two had bacteremia, 41% anemia, 10% osteomyelitis/septic arthritis, one case with congenital brucellosis and one case neurobrucellosis (1.8%). Forty cases had positive serology results of which 19 had positive cultures. Most cases had received cotrimoxazole and rifampin as the primary treatment regimen 22 (40%). Four patients relapsed (7%) after treatment completion. This study showed the distribution and clinical characteristics of brucellosis in different regions in the Northern Governorate in Oman. Although the numbers of cases remained low, the gradual increase is concerning for public health and preventive strategies. Further studies are needed to compare this data with the Southern region. Retrospective study with small sample size.


Inhibition by dietary menhaden oil of cyclooxygenase-1 and -2 in N-nitrosomethylurea-induced rat mammary tumors.
Studies in laboratory animals and epidemiological surveys suggest a relationship between the type and amount of dietary fat and mammary cancer. One mechanism proposed to explain this relationship is modulation by dietary fat, of mammary tumor eicosanoid levels through action at the rate limiting enzyme in eicosanoid synthesis, cyclooxygenase (COX). Until recently there have been no studies which have examined COX gene expression in human breast or rodent mammary tissues. In this study we have demonstrated the presence of two immunoreactive isoforms of cyclooxygenase (COX-1 and -2), and the modulating effects of n-3 fatty acids on their expression, in N-nitrosomethylurea (NMU)-induced rat mammary tumors. Three different high fat diets were compared namely, corn oil (CO) 23%; CO 18% menhaden oil (MO) 5%; CO, 5%/MO 18%; low fat corn oil (5%) served as a control. It was found that immunoreactive COX-2 protein levels were approximately 3x higher than COX-1 levels in NMU-induced mammary tumors. Moreover, the high menhaden oil diet (rich in n-3 fatty acids) significantly suppressed both COX-1 (-28%) and COX-2 (-36%) protein levels when compared to the high corn oil diet. No differences were found among the other treatment groups when compared pair-wise or with low-fat control. The mechanism(s) by which n-3 fatty acids suppress COX-1 and COX-2 remain to be determined.


Socioeconomic Status and Racial or Ethnic Differences in Participation: Web-Based Survey.
Web-based survey data collection has been widely used because of its advantages, although attaining and retaining participants can be challenging. There are several factors associated with successful Web-based survey participation; yet little is known regarding racial or ethnic and socioeconomic differences in the progress of a Web-based survey. This study aimed to examine racial or ethnic and socioeconomic status (SES) differences in participation in a Web-based survey. We conducted a secondary data analysis of a study dataset containing information on parents of preschool children. We used 2 phases of Web-based surveys: (1) screening questions including race or ethnicity information and (2) full survey with a consent form. Once potential participants submitted the screening questions, including their racial or ethnic information, the team sent the full survey link to potential participants who met study eligibility criteria. We calculated the proportion of racial or ethnic groups in each of the following areas: consent, partial survey completion, and total survey completion. A total of 487 participants (236 non-Hispanic white, 44 Hispanic, 137 black, and 70 Asian) completed initial screening questions, and a total of 458 participants met study eligibility criteria. Compared with black participants, non-Hispanic white and Asian participants were more likely to consent to participate in the study (odds ratio [OR] 1.73, 95% CI 1.08-2.78, P=.02; OR 2.07, 95% CI 1.04-4.13, P=.04, respectively). There was no racial or ethnic difference with respect to the completion of demographic questions or completion of a partial survey. Finally, compared with black participants, non-Hispanic white participants were more likely to complete the entire survey (OR 3.36, 95% CI 1.51-7.06, P<.001). With respect to SES, less educated non-Hispanic white participants were less likely to complete the survey compared with their counterparts with more education (OR 0.15, 95% CI 0.50-1.48, P<.001). We found a significant difference among racial or ethnic groups as well as different education levels in Web-based survey participation. Survey researchers need to consider the SES and racial or ethnic differences in Web-based survey participation and develop strategies to address this bias in participation and completion in their research.


A review on brain structures segmentation in magnetic resonance imaging.
Automatic brain structures segmentation in magnetic resonance images has been widely investigated in recent years with the goal of helping diagnosis and patient follow-up in different brain diseases. Here, we present a review of the state-of-the-art of automatic methods available in the literature ranging from structure specific segmentation methods to whole brain parcellation approaches. We divide first the algorithms according to their target structures and then we propose a general classification based on their segmentation strategy, which includes atlas-based, learning-based, deformable, region-based and hybrid methods. We further discuss each category's strengths and weaknesses and analyze its performance in segmenting different brain structures providing a qualitative and quantitative comparison. We compare the results of the analyzed works for the following brain structures: hippocampus, thalamus, caudate nucleus, putamen, pallidum, amygdala, accumbens, lateral ventricles, and brainstem. The structures on which more works have focused on are the hippocampus and the caudate nucleus. In general, the accumbens (0.69 mean DSC) is the most difficult structure to segment whereas the structures that seem to get the best results are the brainstem, closely followed by the thalamus and the putamen with 0.88, 0.87 and 0.86 mean DSC, respectively. Atlas-based approaches achieve good results when segmenting the hippocampus (DSC between 0.75 and 0.90), thalamus (0.88-0.92) and lateral ventricles (0.83-0.93), while deformable methods perform good for caudate nucleus (0.84-0.91) and putamen segmentation (0.86-0.89). There is not yet a single automatic segmentation approach that can emerge as a standard for the clinical practice, providing accurate brain structures segmentation. Future trends need to focus on combining multi-atlas methods with learning-based or deformable approaches. Employing atlases to provide spatial robustness and modeling the structures appearance with supervised classifiers or Active Appearance Models could lead to improved segmentation results.


From single-site tantalum complexes to nanoparticles of Ta x N y and TaO x N y supported on silica: elucidation of synthesis chemistry by dynamic nuclear polarization surface enhanced NMR spectroscopy and X-ray absorption spectroscopy.
Air-stable catalysts consisting of tantalum nitride nanoparticles represented as a mixture of Ta x N y and TaO x N y with diameters in the range of 0.5 to 3 nm supported on highly dehydroxylated silica were synthesized from TaMe5 (Me = methyl) and dimeric Ta2(OMe)10 with guidance by the principles of surface organometallic chemistry (SOMC). Characterization of the supported precursors and the supported nanoparticles formed from them was carried out by IR, NMR, UV-Vis, extended X-ray absorption fine structure, and X-ray photoelectron spectroscopies complemented with XRD and high-resolution TEM, with dynamic nuclear polarization surface enhanced NMR spectroscopy being especially helpful by providing enhanced intensities of the signals of 1H, 13C, 29Si, and 15N at their natural abundances. The characterization data provide details of the synthesis chemistry, including evidence of (a) O2 insertion into Ta-CH3 species on the support and (b) a binuclear to mononuclear transformation of species formed from Ta2(OMe)10 on the support. A catalytic test reaction, cyclooctene epoxidation, was used to probe the supported nanoparticles, with 30% H2O2 serving as the oxidant. The catalysts gave selectivities up to 98% for the epoxide at conversions as high as 99% with a 3.4 wt% loading of Ta present as Ta x N y /TaO x N y .


Single Cell Protein-State-of-the-Art, Industrial Landscape and Patents 2001-2016.
By 2050, the world would need to produce 1,250 million tonnes of meat and dairy per year to meet global demand for animal-derived protein at current consumption levels. However, growing demand for protein will not be met sustainably by increasing meat and dairy production because of the low efficiency of converting feed to meat and dairy products. New solutions are needed. Single cell protein (SCP), i.e., protein produced in microbial and algal cells, is an option with potential. Much of the recent interest in SCP has focused on the valorisation of side streams by using microorganisms to improve their protein content, which can then be used in animal feed. There is also increased use of mixed populations, rather than pure strains in the production of SCP. In addition, the use of methane as a carbon source for SCP is reaching commercial scales and more protein-rich products are being derived from algae for both food and feed. The following review addresses the latest developments in SCP production from various organisms, giving an overview of commercial exploitation, a review of recent advances in the patent landscape (2001-2016) and a list of industrial players in the SCP field.


Endothelin mediates superoxide production and vasoconstriction through activation of NADPH oxidase and uncoupled nitric-oxide synthase in the rat aorta.
Experiments were designed to test the hypothesis that elevated levels of endothelin 1 (ET-1) in the vasculature activate NADPH oxidase and/or uncoupled nitric-oxide synthase (NOS), resulting in O2-* production, and mediate increased constriction. Rat aortic rings were incubated with ET-1 or vehicle in the presence and absence of superoxide dismutase (SOD), ebselen (glutathione peroxidase mimetic), apocynin (NADPH oxidase inhibitor), L-NAME (Nomega-nitro-L-arginine methyl ester) (NOS inhibitor), tetrahydrobiopterin (BH4) (NOS cofactor), or selective ETA and ETB receptor antagonists (BQ-123 [cyclo(D-Asp-Pro-D-Val-Leu-D-Trp)] and A-192621 [[2R-(4-propoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N-(2,6-diethylphenyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid]], respectively). O2-* production was monitored by oxidized dihydroethidine staining and/or lucigenin chemiluminescence. ET-1 significantly increased O2-* production compared with vehicle. SOD, ebselen, and apocynin inhibited the ET-1-induced increase in O2-* in intact and endothelium-denuded aorta. L-NAME and BH4 inhibited the ET-1-induced increase in O2-* in intact tissue, whereas these two compounds had no effect on ET-1-induced O2-* in endothelium-denuded aorta. Preincubation with BQ-123 or A-192621, individually, had no effect on ET-1-induced O2-*; however combining both antagonists inhibited the ET-1-stimulated increase in O2-*. Rat aortic rings were incubated with ET-1 or vehicle in the presence or absence of sepiapterin (BH4 synthesis substrate) or apocynin and mounted on wire myographs to determine isometric force generation in response to increasing KCl concentrations. ET-1 increased the contractile response to KCl compared with vehicle. Treatment with either sepiapterin or apocynin attenuated the ET-1-mediated increase with no effect of sepiapterin or apocynin alone. These data support the hypothesis that ET-1 increases vascular tone, in part, through ETA/ETB receptor activation of O2-* production from NADPH oxidase and NOS uncoupling.