Veno-venous bridges: the forerunners of the sinus venosus defect.
Differentiation of the so-called sinus venosus defect from other defects permitting shunting between the atrial chambers remains problematic. The lesion is not a true septal defect, and current theories to explain the existence of the sinus venosus defect fall short. The presence of persistent systemic to pulmonary venous connections has been proposed to explain the existence of the sinus venosus defect. Clinical histories and radiological findings of six patients are reviewed. Three patients have veno-venous bridges, two have partial anomalous pulmonary venous connections, and one patient has a sinus venosus defect. The clinical information is reviewed, along with current developmental and morphological considerations. We provide radiographic, developmental, and morphological evidence to support the theory that a so-called sinus venosus defect is the consequence of persistence of foetal systemic to pulmonary veno-venous bridges, rather than of deficiencies in atrial septation.


Heat and Drought Stress Impact on Phenology, Grain Yield, and Nutritional Quality of Lentil (Lens culinaris Medikus).
Lentil (Lens culinaris Medikus) is a protein-rich cool-season food legume with an excellent source of protein, prebiotic carbohydrates, minerals, and vitamins. With climate change, heat, and drought stresses have become more frequent and intense in lentil growing areas with a strong influence on phenology, grain yield, and nutritional quality. This study aimed to assess the impact of heat and drought stresses on phenology, grain yield, and nutritional quality of lentil. For this purpose, 100 lentil genotypes from the global collection were evaluated under normal, heat, and combined heat-drought conditions. Analysis of variance revealed significant differences (p < 0.001) among lentil genotypes for phenological traits, yield components, and grain quality traits. Under no stress conditions, mineral concentrations among lentil genotypes varied from 48 to 109 mg kg-1 for iron (Fe) and from 31 to 65 mg kg-1 for zinc (Zn), while crude protein content ranged from 22.5 to 32.0%. Iron, zinc, and crude protein content were significantly reduced under stress conditions, and the effect of combined heat-drought stress was more severe than heat stress alone. A significant positive correlation was observed between iron and zinc concentrations under both no stress and stress conditions. Based on grain yield, crude protein, and iron and zinc concentrations, lentil genotypes were grouped into three clusters following the hierarchical cluster analysis. Promising lentil genotypes with high micronutrient contents, crude protein, and grain yield with the least effect of heat and drought stress were identified as the potential donors for biofortification in the lentil breeding program.


Healthcare access and burden of care for patients with Lyme disease: a large United States survey.
To evaluate the challenges faced by Lyme disease patients in obtaining adequate healthcare. A web-based survey conducted over nine months was analyzed for the study. The survey focused on medical status, access to healthcare, and burden of illness. For inclusion in the study, survey respondents had to reside in the United States, be more than 10 years old, and have clinically diagnosed Lyme disease with chronic symptoms and positive laboratory testing. Responses from 2424 patients were included in the study. Half of the respondents reported seeing at least seven physicians before the diagnosis of Lyme disease was made. Nearly half had Lyme disease for more than 10 years and traveled over 50 miles to obtain treatment. Most respondents experienced symptoms lasting six months or more despite receiving at least 21 days of antibiotic treatment. A quarter of respondents had been on public support or received disability benefits due to Lyme disease symptoms, and over half had visited an emergency room at least once as a result of these symptoms. Lyme disease patients frequently endure extensive delays in obtaining an initial diagnosis, have poor access to healthcare and suffer a severe burden of illness.


Pharmacist-based Donepezil Outpatient Consultation Service to improve medication persistence.
Donepezil is widely used to delay the progression of cognitive dysfunction in patients with Alzheimer's disease (AD), but the efficacy of pharmacotherapy is often reduced by poor adherence to medication. In order to improve adherence by providing information about AD and the significance of pharmacotherapy, the Donepezil Outpatient Consultation Service (DOCS) was set up. The influence of this service on medication persistence was assessed in the present study. Among outpatients starting donepezil therapy, we enrolled 59 patients between April 2008 and September 2010 before establishment of the DOCS (non-DOCS group) and 52 patients between October 2010 and March 2012 who attended the DOCS (DOCS group). Each patient's and their caregiver's understanding about the clinical features of AD and pharmacotherapy with donepezil were also assessed. Their understanding was compared before and after the DOCS, and the 1-year medication persistence rate and the reasons for discontinuation were also investigated. The 1-year medication persistence rate was significantly higher in the DOCS group than in the non-DOCS group (73.1% vs 49.2%, P = 0.008). We examined the association of medication persistence with age, sex, clinical dementia rating, living alone, and attending the DOCS. As a result, medication persistence was significantly higher in patients attending the DOCS. The main reasons for discontinuation of donepezil were transfer elsewhere (11) and gastrointestinal side effects (5) in the non-DOCS group, and transfer (9) and gastrointestinal side effects (3) in the DOCS group. The overall score for understanding was 2.5 ± 1.7 before attending the DOCS and it increased significantly to 5.7 ± 0.7 afterward (P < 0.001). The DOCS consultation provided by hospital pharmacists for AD patients and their caregivers improved understanding about the clinical features of dementia and provided pharmacological knowledge about antidementia drugs, leading to better adherence to pharmacotherapy that could maximize its effect.


New insights into the epidemiology of ANCA-associated vasculitides in Germany: results from a claims data study.
ANCA-associated vasculitides (AAV) are rare, potentially life-threatening autoimmune diseases characterized by systemic inflammation and organ damage. AAV prevalence rates reported in Europe vary considerably and robust data sources are often lacking. This study aimed to examine the feasibility of claims data analysis as a complementary method to registry-based studies to assess the epidemiology of AAV. In this retrospective observational study, anonymized longitudinal claims data from years 2013-2016 from German statutory health insurance companies (data source: InGef, Institute for Applied Health Research) have been analysed on an age- and gender-stratified cohort of ∼3 million persons representative of the German population. In this cohort, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients were identified. The study cohort revealed a prevalence for GPA and MPA of 210 and 46 cases per million people, respectively. The annual incidence comprised 34 GPA cases and 13 MPA cases per million people per year. Hence, 17 500 AAV patients (GPA and MPA) are estimated to live in Germany, with an annual increase of 3200 patients. According to their demographic and disease-specific characteristics, AAV patients identified in this claims data approach are representative. This is the first study using claims data to assess the epidemiology of AAV. In Germany, AAV was diagnosed more frequently than it was estimated by previous self-reporting registry-based studies. The findings indicate that epidemiological data of AAV may have been underestimated but may also reflect improved diagnostic methods and disease recognition.


Psychiatric Status across Body Mass Index in a Mediterranean Spanish Population.
Mental and body weight disorders are among the major global health challenges, and their comorbidity may play an important role in treatment and prevention of both pathologies. A growing number of studies have examined the relationship between psychiatric status and body weight, but our knowledge is still limited. The present study aims to investigate the cross-sectional relationships of psychiatric status and body mass index (BMI) in Málaga, a Mediterranean city in the South of Spain. A total of 563 participants were recruited from those who came to his primary care physician, using a systematic random sampling, non-proportional stratified by BMI categories. Structured clinical interviews were used to assess current Axes-I and II mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). BMI was calculated as weight (Kg) divided by square of height in meters (m2). Logistic regression was used to investigate the association between BMI and the presence of any mental disorder. BMI was introduced in the models using restricted cubic splines. We found that high BMI values were directly associated with mood and adjustment disorders, and low BMI values were directly associated with avoidant and dependent personality disorders (PDs). We observed an inverse relationship between low BMI values and cluster A PDs. There were not significant relationships between anxiety or substance-related disorders and BMI. Psychiatric status and BMI are related in a Mediterranean Spanish population. A multidisciplinary approach to both pathologies becomes increasingly more necessary.


Summary of the 8th Annual Bladder Cancer Think Tank: Collaborating to move research forward.
The 8th Annual Bladder Cancer Think Tank (BCAN-TT) brought together a multidisciplinary group of clinicians, researchers, and patient advocates in an effort to advance bladder cancer research. With the theme of "Collaborating to Move Research Forward," the meeting included three panel presentations and seven small working groups. The panel presentations and interactive discussions focused on three main areas: gender disparities, sexual dysfunction, and targeting novel pathways in bladder cancer. Small working groups also met to identify projects for the upcoming year, including: (1) improving enrollment and quality of clinical trials; (2) collecting data from multiple institutions for future research; (3) evaluating patterns of care for non-muscle-invasive bladder cancer; (4) improving delivery of care for muscle-invasive disease; (5) improving quality of life for survivors; (6) addressing upper tract disease; and (7) examining the impact of health policy changes on research and treatment of bladder cancer. The goal of the BCAN-TT is to advance the care of patients with bladder cancer and to promote collaborative research throughout the year. The meeting provided ample opportunities for collaboration among clinicians from multiple disciplines, patients and patient advocates, and industry representatives.


The Hubble hypothesis and the developmentalist's dilemma.
Developmental psychopathology stands poised at the close of the 20th century on the horns of a major scientific dilemma. The essence of this dilemma lies in the contrast between its heuristically rich open system concepts on the one hand, and the closed system paradigm it adopted from mainstream psychology for investigating those models on the other. Many of the research methods, assessment strategies, and data analytic models of psychology's paradigm are predicated on closed system assumptions and explanatory models. Thus, they are fundamentally inadequate for studying humans, who are unparalleled among open systems in their wide ranging capacities for equifinal and multifinal functioning. Developmental psychopathology faces two challenges in successfully negotiating the developmentalist's dilemma. The first lies in recognizing how the current paradigm encourages research practices that are antithetical to developmental principles, yet continue to flourish. I argue that the developmentalist's dilemma is sustained by long standing, mutually enabling weaknesses in the paradigm's discovery methods and scientific standards. These interdependent weaknesses function like a distorted lens on the research process by variously sustaining the illusion of theoretical progress, obscuring the need for fundamental reforms, and both constraining and misguiding reform efforts. An understanding of how these influences arise and take their toll provides a foundation and rationale for engaging the second challenge. The essence of this challenge will be finding ways to resolve the developmentalist's dilemma outside the constraints of the existing paradigm by developing indigenous research strategies, methods, and standards with fidelity to the complexity of developmental phenomena.


The Antibody Response Following a Booster With Either a 10- or 13-valent Pneumococcal Conjugate Vaccine in Toddlers Primed With a 13-valent Pneumococcal Conjugate Vaccine in Early Infancy.
Both the 13- and 10-valent pneumococcal conjugate vaccines (PCV-13; PCV-10) are immunogenic and effective against vaccine-type pneumococcal disease when given to young children. However, limited data are available regarding the interchangeability of these 2 vaccines. UK children (n = 178) who had previously been vaccinated with PCV-13 at 2 and 4 months were randomized to receive either a PCV-13 or a PCV-10 booster at 12 months of age. PCV-13 vaccine-type antipolysaccharide serum immunoglobulin G (IgG) concentrations and opsonophagocytic assay titers were measured before and at 1 and 12 months following vaccination. The primary objective was to assess noninferiority of PCV-10 compared with PCV-13. For 8 of the PCV-10 serotypes at least 97% of participants in both groups had IgG concentrations ≥0.35 µg/mL at 1 month after vaccination; inferior responses were seen for serotypes 5 and 9V following the PCV-10 compared with the PCV-13 booster. Post booster geometric mean IgG concentrations and opsonophagocytic assay titers were significantly superior for most serotypes in PCV-13 compared with PCV-10 recipients, whereas similar or inferior responses were seen for serotypes 4, 18C, and 19F. Although some increase in antibody was seen in PCV-10 recipients against the serotypes 6A and 19A (serotypes that cross-react with 6B and 19F in PCV-10, respectively) at 1-month post booster, these responses were significantly lower than in the PCV-13 group. In PCV-13 primed infants, a PCV-10 booster is generally less immunogenic than a PCV-13 booster. For the 3 serotypes in PCV-10 with higher antigen content and/or conjugation to diphtheria or tetanus toxoid carrier proteins, higher or similar booster responses were seen in PCV-10 recipients. Although these findings suggest that responses are generally better with a PCV-13 booster among PCV-13 primed children, the clinical significance of these differences in immunogenicity is unclear.


Inhomogeneous Response of Articular Cartilage: A Three-Dimensional Multiphasic Heterogeneous Study.
Articular cartilage exhibits complex mechano-electrochemical behaviour due to its anisotropy, inhomogeneity and material non-linearity. In this work, the thickness and radial dependence of cartilage properties are incorporated into a 3D mechano-electrochemical model to explore the relevance of heterogeneity in the behaviour of the tissue. The model considers four essential phenomena: (i) osmotic pressure, (ii) convective and diffusive processes, (iii) chemical expansion and (iv) three-dimensional through-the-thickness heterogeneity of the tissue. The need to consider heterogeneity in computational simulations of cartilage behaviour and in manufacturing biomaterials mimicking this tissue is discussed. To this end, healthy tibial plateaus from pigs were mechanically and biochemically tested in-vitro. Heterogeneous properties were included in the mechano-electrochemical computational model to simulate tissue swelling. The simulation results demonstrated that swelling of the heterogeneous samples was significantly lower than swelling under homogeneous and isotropic conditions. Furthermore, there was a significant reduction in the flux of water and ions in the former samples. In conclusion, the computational model presented here can be considered as a valuable tool for predicting how the variation of cartilage properties affects its behaviour, opening up possibilities for exploring the requirements of cartilage-mimicking biomaterials for tissue engineering. Besides, the model also allows the establishment of behavioural patterns of swelling and of water and ion fluxes in articular cartilage.


Nicotinic receptors at the amino acid level.
nAChRs are pentameric transmembrane proteins into the superfamily of ligand-gated ion channels that includes the 5HT3, glycine, GABAA, and GABAC receptors. Electron microscopy, affinity labeling, and mutagenesis experiments, together with secondary structure predictions and measurements, suggest an all-beta folding of the N-terminal extracellular domain, with the connecting loops contributing to the ACh binding pocket and to the subunit interfaces that mediate the allosteric transitions between conformational states. The ion channel consists of two distinct elements symmetrically organized along the fivefold axis of the molecule: a barrel of five M2 helices, and on the cytoplasmic side five loops contributing to the selectivity filter. The allosteric transitions of the protein underlying the physiological ACh-evoked activation and desensitization possibly involve rigid body motion of the extracellular domain of each subunit, linked to a global reorganization of the transmembrane domain responsible for channel gating.


Physiological effects of transcendental meditation.
Oxygen consumption, heart rate, skin resistance, and electroenceph-alograph measurements were recorded before, during, and after subjects practiced a technique called transcendental meditation. There were significant changes between the control period and the meditation period in all measurements. During meditation, oxygen consumption and heart rate decreased, skin resistance increased, and the electroencephalogram showed specific changes in certain frequencies. These results seem to distinguish the state produced by transcendental meditation from commonly encountered states of consciousness and suggest that it may have practical applications.


A Quantitative System for Studying Metastasis Using Transparent Zebrafish.
Metastasis is the defining feature of advanced malignancy, yet remains challenging to study in laboratory environments. Here, we describe a high-throughput zebrafish system for comprehensive, in vivo assessment of metastatic biology. First, we generated several stable cell lines from melanomas of transgenic mitfa-BRAF(V600E);p53(-/-) fish. We then transplanted the melanoma cells into the transparent casper strain to enable highly quantitative measurement of the metastatic process at single-cell resolution. Using computational image analysis of the resulting metastases, we generated a metastasis score, μ, that can be applied to quantitative comparison of metastatic capacity between experimental conditions. Furthermore, image analysis also provided estimates of the frequency of metastasis-initiating cells (∼1/120,000 cells). Finally, we determined that the degree of pigmentation is a key feature defining cells with metastatic capability. The small size and rapid generation of progeny combined with superior imaging tools make zebrafish ideal for unbiased high-throughput investigations of cell-intrinsic or microenvironmental modifiers of metastasis. The approaches described here are readily applicable to other tumor types and thus serve to complement studies also employing murine and human cell culture systems.


[Organization of psychological activities in Italian cardiac rehabilitation and prevention. Survey on the implementation of guidelines for psychological activities in cardiac rehabilitation and prevention].
The present study was developed as part of a comprehensive evaluation of the state of the art of knowledge and implementation of the Italian Guidelines for psychological activities in Cardiac Rehabilitation, published in 2003 by the Working Group of Psychology of the Italian Society of Cardiac Rehabilitation (GICR). A questionnaire was designed to collect detailed information on facilities, organization, staffing level, professional background and activities carried out by psychologists working in Italian Cardiac Rehabilitation Units (CRU). Out of 144 Italian CRU (inventory 2004), 107 reported structured psychological programmes. The questionnaires were sent by conventional mail to the referring psychologist of these 107 CRU; they were invited to participate in the survey on a purely voluntary basis. Responses were received from 70 (65.4%) of 107 CRU. 55 CRU (79.8%) report a good knowledge of the published GL; 10.1% declare that the psychologists did not know the current GL. 84.5% consider the GL to be fully applicable, while 15.5% believe that they are only partly applicable. Psychological assessment is performed through clinical interview (94.3%) and psychometric tests (81.4%). 92.8% of the CRU use screening instruments in order to evaluate psychosocial risk factors, in particular anxiety and depression (64.3%). Quality of life (22.8%) and cognitive impairment (17.1%) are not routinely assessed. Educational interventions are planned in 87.1% of the CR programme and are extended to the family members (51%) as well as counselling (57%). Psychological programme includes smoking (56%) and eating behaviour (55%) group interventions. Stress management is routinely planned in 69% of the CRU. Psychological intervention tailored to individual needs of the patients is performed in 62.9% CRU. Written final reports are available in 88.6% cases. The follow-up is carried out by 48.6% of the CRU, 15.7% in a structured way. CONCLUSIONS. The survey shows wide discrepancies in the provision of psychological activities in Italian CRU. Nevertheless psychological assessment and interventions seem acceptably coherent with current national GL on CR.


An experimental investigation on intra-fractional organ motion effects in lung IMRT treatments.
Respiration-induced tumour motion can potentially compromise the use of intensity-modulated radiotherapy (IMRT) as a dose escalation tool for lung tumour treatment. We have experimentally investigated the intra-fractional organ motion effects in lung IMRT treatments delivered by multi-leaf collimator (MLC). An in-house made motor-driven platform, which moves sinusoidally with an amplitude of 1 cm and a period of 4 s, was used to mimic tumour motion. Tumour motion was simulated along cranial-caudal direction while MLC leaves moved across the patient from left to right, as in most clinical cases. The dose to a point near the centre of the tumour mass was measured according to geometric and dosimetric parameters from two five-field lung IMRT plans. For each field, measurement was done for two dose rates (300 and 500 MU min(-1)), three MLC delivery modes (sliding window, step-and-shoot with 10 and 20 intensity levels) and eight equally spaced starting phases of tumour motion. The dose to the measurement point delivered from all five fields was derived for both a single fraction and 30 fractions by randomly sampling from measured dose values of each field at different initial phases. It was found that the mean dose to a moving tumour differs slightly (<2-3%) from that to a static tumour. The variation in breathing phase at the start of dose delivery results in a maximum variation around the mean dose of greater than 30% for one field. The full width at half maximum for the probability distribution of the point dose is up to 8% for all five fields in a single fraction, but less than 1-2% after 30 fractions. In general, lower dose rate can reduce the motion-caused dose variation and therefore might be preferable for lung IMRT when no motion mitigation techniques are used. From the two IMRT cases we studied where tumour motion is perpendicular to MLC leaf motion, the dose variation was found to be insensitive to the MLC delivery mode.


Pattern composed of two-dimensional diffusion dots for showing dynamic images.
A new type of diffusion pattern is proposed. The proposed patterns are composed of 2D diffusion dots. The diffusion dots are created on a photoresist plate by recording the image of a local area of a piece of ground glass dot by dot. An imaging lens covered by a mask with a slit aperture is used to form the image. By changing the orientation of the slit aperture on the mask plane, the diffusion dots can have different microintensity distributions for the same incident light beam. Therefore the diffusion dots created by the same slit aperture orientation show the same brightness, and the diffusion dots created by different slit orientations show different brightness for the same illuminating and viewing conditions. Thus a proposed diffusion pattern can show dynamic images by changing its illuminating or viewing directions. By applying the double-exposure technique to the diffusion dots of a pattern, the pattern not only can show dynamic effects but also can possess several hidden features for identifying the pattern. Therefore the proposed patterns are dynamic and anticounterfeiting.


IL6 Mediates Immune and Colorectal Cancer Cell Cross-talk via miR-21 and miR-29b.
Tumors are surrounded and infiltrated by a variety of stromal cell types, including fibroblasts, immune cells, and vascular endothelial cells, which interact with malignant cells to generate the tumor microenvironment (TME). This complex environment is thought to be regulated by the tumor in order to promote its survival and progression and thus constitutes a potential target for cancer therapy. However, intercellular communication within the microenvironment is not yet well understood. The current study investigates the mechanism by which cancer and immune cells communicate using an in vitro coculture model. It is demonstrated that IL6, a proinflammatory cytokine, secreted by immune cells promotes colorectal cancer cell invasiveness. In addition, in the presence of IL6, the cancer cells were able to secrete circulating miRNAs miR-21 and miR-29b to further induce immune cell IL6 production. Activated immune cells were also found to release miR-21 into the TME. Taken together, these mechanistic findings provide a better understanding of intercellular communication between immune and cancer cells in the TME and offer insight into some of the key players that mediate this cross-talk. This study demonstrates that cocultured cancer and immune cells communicate via IL6 and circulating miRNAs to sustain chronic inflammation and promote prometastatic cancer cell behavior. In addition, critical players are identified that mediate intercellular communication in the TME and suggest possible therapeutic approaches that target the microenvironment.


Potential regenerative treatment strategies for intervertebral disc degeneration in dogs.
Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3-7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lumbosacral spine at about 6-8 years of age. IVD degeneration is characterized by changes in the biochemical composition and mechanical integrity of the IVD. In the degenerated IVD, the content of glycosaminoglycan (GAG, a proteoglycan side chain) decreases and that of denatured collagen increases. Dehydration leads to tearing of the annulus fibrosus (AF) and/or disc herniation, which is clinically characterized by pain and/or neurological signs. Current treatments (physiotherapy, anti-inflammatory/analgesic medication, surgery) for IVD disease may resolve neurological deficits and reduce pain (although in many cases insufficient), but do not lead to repair of the degenerated disc. For this reason, there is interest in new regenerative therapies that can repair the degenerated disc matrix, resulting in restoration of the biomechanical function of the IVD. CD dogs are considered a suitable animal model for human IVD degeneration because of their spontaneous IVD degeneration, and therefore studies investigating cell-, growth factor-, and/or gene therapy-based regenerative therapies with this model provide information relevant to both human and canine patients. The aim of this article is to review potential regenerative treatment strategies for canine IVD degeneration, with specific emphasis on cell-based strategies.


Small-subunit rRNA sequences and whole DNA relatedness concur for the reassignment of Pasteurella piscicida (Snieszko et al.) Janssen and Surgalla to the genus Photobacterium as Photobacterium damsela subsp. piscicida comb. nov.
The taxonomic status of Pasteurella piscicida (strain NCIMB 2058T [T = type strain] and a strain isolated from the environment) was investigated by performing phylogenetic analyses of small-subunit rRNA sequences, DNA-DNA hybridization analyses, and biochemical characterization analyses. The results of the phylogenetic analyses and the levels of DNA-DNA complementarity demonstrated conclusively that Pasteurella piscicida is extremely closely related to Photobacterium damsela ATCC 33539T. Since the two taxa exhibited a level of DNA-DNA relatedness of 80%, they are members of the same species. The high level of DNA relatedness and the presence of specific morphological and biochemical characteristics support the hypothesis that two subspecies should be recognized. On the basis of its phylogenetic position, we concluded that Pasteurella piscicida should be renamed Photobacterium damsela subsp. piscicida comb. nov.


Assessment of the EuroQol 5-Dimension Questionnaire for Detection of Clinically Significant Global Health-Related Quality-of-Life Improvement Following Functional Septorhinoplasty.
Nasal airway obstruction is a common presenting complaint among patients in otolaryngology practices, and its treatment necessitates critical outcomes evaluation and cost-utility analysis. To evaluate the utility and applicability of the EuroQol 5-Dimension (EQ5D) global health-related quality-of-life (HRQoL) questionnaire for the assessment of clinical outcomes in functional septorhinoplasty. Prospective cohort study at a university-based tertiary medical center of patients undergoing functional septorhinoplasty for treatment of nasal obstruction. Patient demographic characteristics, operative intervention, and preoperative and postoperative Nasal Obstruction Symptom Evaluation (NOSE) and EQ5D scores were collected and analyzed between November 2013 and June 2016. Comparison of preoperative and postoperative EQ5D and NOSE scores at 2 and 6 or more months following surgery (long-term follow-up). A total of 135 patients (56.3% male; mean [SD] age, 36.8 [14.8] years) completed EQ5D and NOSE surveys preoperatively and postoperatively, with mean (SD) follow-up of 5.82 (4.1) months. Of these, 117 completed the 2-month survey and 64 completed their last survey at 6 or more months. Baseline NOSE and EQ5D visual analog scale (VAS) scores were moderately correlated (r = -0.37, P < .001) as were changes in NOSE and EQ5D VAS scores at long-term follow-up (r = -0.33, P = .007). Mean baseline NOSE score of 64.3 (95% CI, 60.5-68.2) decreased to 24.8 (95% CI, 18.8-30.9) at long-term follow-up (P < .001). The frequency of patients reporting problems in the EQ5D domains of pain/discomfort and usual activity decreased by more than half in the long-term follow-up group (30 [47%] vs 14 [22%] and 11 [17%] vs 4 [6%]; P = .002 and .02, respectively). The minimal clinically important difference of the EQ5D VAS score was calculated at 9.5. The EQ5D VAS scores had statistically and clinically significant improvement at long-term follow-up in patients with NOSE score improvements of 30 to 60 points (EQ5D VAS increased from mean [SD] of 72.3 [20] to 85.9 [10]; P < .001) and 65 to 100 points (EQ5D VAS increased from mean [SD] of 66.2 [25] to 82.0 [13]; P = .01). The EQ5D, a global HRQoL instrument, was able to detect clinically significant improvement following functional septorhinoplasty for nasal obstruction. Nasal valve correction improved not only disease-specific quality of life but also global HRQoL. The ability to calculate health utility values from the EQ5D and its low response burden make it an attractive tool for septorhinoplasty outcomes research. 4.


The role of endoscopic retrograde pancreatography in the treatment of traumatic pancreatic duct injury.
The status of the main pancreatic duct (MPD) is the most important determinant of the morbidity and mortality associated with pancreatic trauma. Early diagnosis and optimal treatment are critical, especially when there is MPD injury. Twenty-three patients with pancreatic trauma were studied prospectively with respect to clinical and laboratory findings, CT, and endoscopic retrograde pancreatography (ERP). Treatment modalities and clinical outcome were assessed in relation to ERP findings. The pancreatic duct was injured in 14 of 23 patients (11 MPD, 3 branch duct). Contrast leakage from the MPD into peritoneal cavity at ERP confirmed MPD injury in 8 patients, who underwent surgical exploration. Three patients with leakage from a branch duct into the pancreatic parenchyma recovered with conservative treatment. Three patients in whom ERP demonstrated contrast leakage from the MPD confined to the parenchyma underwent successful transpapillary stent insertion with complete resolution of the leak at 3-month follow-up. Patients who underwent ERP more than 72 hours after trauma had a significantly higher rate of pancreas-associated complications and a tendency to remain hospitalized longer than patients who underwent ERP earlier. Early ERP is one of the most useful methods for demonstrating MPD injury. ERP assists with treatment planning based on the degree of pancreatic duct injury.


Association of heterozygous hemochromatosis C282Y gene mutation with hand osteoarthritis.
To determine if there is an association between radiographic osteoarthritis (OA) of the hand and the presence of hemochromatosis HFE gene mutations. One hundred seventy-six patients with radiographic OA of the hand were randomly selected from an academic rheumatology practice. We measured serum transferrin saturation (TS) and ferritin levels, and genotyped for the presence of the 2 common HFE mutations, C282Y and H63D. The prevalences of HFE mutations in these patients were compared to those in a hemochromatosis screening study from the same primary care patient base. There was a significantly increased prevalence of the C282Y mutation in the OA population compared to the unselected controls (12.5 vs 7.8%; p = 0.029). The prevalence of C282Y in OA was higher among older patients: 15.75% in the group older than 65 years versus 4.08% in the younger group. The mean TS level was higher among OA patients who were heterozygous for C282Y compared to those who lacked both HFE mutations (35.75 vs 25.93%; p < 0.0001). This difference was also found in the general population. This is the first report to show an increased risk of OA among individuals who are heterozygous for the C282Y HFE mutation. The increase in this mutation in patients older than 65 suggests that this is associated with a late onset subset of OA. If this association is substantiated by larger randomized controlled studies, it could have major therapeutic implications in the development of specific therapy directed at individuals heterozygous for C282Y HFE mutation.


The mPEG-PCL Copolymer for Selective Fermentation of Staphylococcus lugdunensis Against Candida parapsilosis in the Human Microbiome.
Many human skin diseases, such as seborrheic dermatitis, potentially occur due to the over-growth of fungi. It remains a challenge to develop fungicides with a lower risk of generating resistant fungi and non-specifically killing commensal microbes. Our probiotic approaches using a selective fermentation initiator of skin commensal bacteria, fermentation metabolites or their derivatives provide novel therapeutics to rein in the over-growth of fungi. Staphylococcus lugdunensis (S. lugdunensis) bacteria and Candida parapsilosis (C. parapsilosis) fungi coexist in the scalp microbiome. S. lugdunensis interfered with the growth of C. parapsilosis via fermentation. A methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymer functioned as a selective fermentation initiator of S. lugdunensis, selectively triggering the S. lugdunensis fermentation to produce acetic and isovaleric acids. The acetic acid and its pro-drug diethyleneglycol diacetate (Ac-DEG-Ac) effectively suppressed the growth of C. parapsilosis in vitro and impeded the fungal expansion in the human dandruff. We demonstrate for the first time that S. lugdunensis is a skin probiotic bacterium that can exploit mPEG-PCL to yield fungicidal short-chain fatty acids (SCFAs). The concept of bacterial fermentation as a part of skin immunity to re-balance the dysbiotic microbiome warrants a novel avenue for studying the probiotic function of the skin microbiome in promoting health.


Competition between different variegating rearrangements for limited heterochromatic factors in Drosophila melanogaster.
Position effect variegation (PEV) results from the juxtaposition of a euchromatic gene to heterochromatin. In its new position the gene is inactivated in some cells and not in others. This mosaic expression is consistent with variability in the spread of heterochromatin from cell to cell. As many components of heterochromatin are likely to be produced in limited amounts, the spread of heterochromatin into a normally euchromatic region should be accompanied by a concomitant loss or redistribution of the protein components from other heterochromatic regions. We have shown that this is the case by simultaneously monitoring variegation of a euchromatic and a heterochromatic gene associated with a single chromosome rearrangement. Secondly, if several heterochromatic regions of the genome share limited components of heterochromatin, then some variegating rearrangements should compete for these components. We have examined this hypothesis by testing files with combinations of two or more different variegating rearrangements. Of the nine combinations of pairs of variegating rearrangements we studied, seven showed nonreciprocal interactions. These results imply that many components of heterochromatin are both shared and present in limited amounts and that they can transfer between chromosomal sites. Consequently, even nonvariegation portions of the genome will be disrupted by re-allocation of heterochromatic proteins associated with PEV. These results have implications for models of PEV.


SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells.
SAMHD1 is a cellular triphosphohydrolase (dNTPase) proposed to inhibit HIV-1 reverse transcription in non-cycling immune cells by limiting the supply of the dNTP substrates. Yet, phosphorylation of T592 downregulates SAMHD1 antiviral activity, but not its dNTPase function, implying that additional mechanisms contribute to viral restriction. Here, we show that SAMHD1 is SUMOylated on residue K595, a modification that relies on the presence of a proximal SUMO-interacting motif (SIM). Loss of K595 SUMOylation suppresses the restriction activity of SAMHD1, even in the context of the constitutively active phospho-ablative T592A mutant but has no impact on dNTP depletion. Conversely, the artificial fusion of SUMO2 to a non-SUMOylatable inactive SAMHD1 variant restores its antiviral function, a phenotype that is reversed by the phosphomimetic T592E mutation. Collectively, our observations clearly establish that lack of T592 phosphorylation cannot fully account for the restriction activity of SAMHD1. We find that SUMOylation of K595 is required to stimulate a dNTPase-independent antiviral activity in non-cycling immune cells, an effect that is antagonized by cyclin/CDK-dependent phosphorylation of T592 in cycling cells.


High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTRs). To assess SSTR expression and the efficacy of SSAs in mMCC, a high-grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA. Thirty-three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response-evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152-358). Twelve of 19 patients did not have a response-evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143-1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. In contrast to other high-grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side-effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.


Solidarity: a (new) ethic for global health policy.
This article explores solidarity as an ethical concept underpinning rules in the global health context. First, it considers the theoretical conceptualisation of the value and some specific duties it supports (ie: its expression in the broadest sense and its derivative action-guiding duties). Second, it considers the manifestation of solidarity in two international regulatory instruments. It concludes that, although solidarity is represented in these instruments, it is often incidental. This fact, their emphasis on other values and their internal weaknesses diminishes the action-guiding impact of the solidarity rules. The global health and human subject research scene needs a completely new instrument specifically directed at means by which solidarity can be achieved, and a reformed infrastructure dedicated to realising that value.


COMPUTER AIDED IMAGE SEGMENTATION AND CLASSIFICATION FOR VIABLE AND NON-VIABLE TUMOR IDENTIFICATION IN OSTEOSARCOMA.
Osteosarcoma is one of the most common types of bone cancer in children. To gauge the extent of cancer treatment response in the patient after surgical resection, the H&E stained image slides are manually evaluated by pathologists to estimate the percentage of necrosis, a time consuming process prone to observer bias and inaccuracy. Digital image analysis is a potential method to automate this process, thus saving time and providing a more accurate evaluation. The slides are scanned in Aperio Scanscope, converted to digital Whole Slide Images (WSIs) and stored in SVS format. These are high resolution images, of the order of 109 pixels, allowing up to 40X magnification factor. This paper proposes an image segmentation and analysis technique for segmenting tumor and non-tumor regions in histopathological WSIs of osteosarcoma datasets. Our approach is a combination of pixel-based and object-based methods which utilize tumor properties such as nuclei cluster, density, and circularity to classify tumor regions as viable and non-viable. A K-Means clustering technique is used for tumor isolation using color normalization, followed by multi-threshold Otsu segmentation technique to further classify tumor region as viable and non-viable. Then a Flood-fill algorithm is applied to cluster similar pixels into cellular objects and compute cluster data for further analysis of regions under study. To the best of our knowledge this is the first comprehensive solution that is able to produce such a classification for Osteosarcoma cancer. The results are very conclusive in identifying viable and non-viable tumor regions. In our experiments, the accuracy of the discussed approach is 100% in viable tumor and coagulative necrosis identification while it is around 90% for fibrosis and acellular/hypocellular tumor osteoid, for all the sampled datasets used. We expect the developed software to lead to a significant increase in accuracy and decrease in inter-observer variability in assessment of necrosis by the pathologists and a reduction in the time spent by the pathologists in such assessments.


[Changes in the dehydrogenase and GABA transaminase activity in the cerebral cortex during corazol kindling].
The experiments on (CBA X C57BL/6)F1 mice have shown that regular corazol injections in subliminal doses stimulated seizure susceptibility (pharmacological kindling). Cytophotometric assay of the activity of oxidative metabolism enzymes (glutamate dehydrogenase, malate dehydrogenase, succinate dehydrogenase, alpha-oxoglutarate dehydrogenase, lactate dehydrogenase) and GABA-transaminase in the sensorimotor cortex of kindled mice in post-convulsive period, and 24 hours or 30 days after corazol injections were discontinued, has revealed some specific alterations of the enzymes under study, that suggest the existence of two phases of energy metabolism disturbances. The first phase (24 hours after corazol injections were discontinued) is characterized by intensified succinic acid oxidation, while the second phase (30 days after the last injection) is characterized by anaerobic glycolysis in neuronal and glial cells. Inhibition of GABA-transaminase activity was particularly marked in postconvulsive period. From a molecular point of view these data may be considered as enzyme disturbances during stimulation of seizure susceptability or seizure activity and as a compensation component ensuring anticonvulsive mechanisms and reparative processes (antagonistic principle of molecular mechanism regulation) during activation of antiepileptic system.


The seasoned executive's decision-making style.
Leaders make decisions every day of their lives, but how they do it changes dramatically over the course of their careers. At lower levels, the job is to get widgets out the door; action is at a premium. At higher levels, the job involves decisions about which widgets to offer and how to develop them. To climb the corporate ladder and be effective in new roles, managers need to change the way they use information and evaluate options. Based on a study of the decision-making profiles of more than 120,000 executives, the authors found that people make decisions very differently in public than they do in private and that the decision styles of successful managers evolve in highly predictable patterns. The most successful managers and executives become increasingly open and interactive in their leadership (or public) styles, and more analytic in their thinking (or private) styles, as they progress in their careers. The research shows that decision-making profiles do a complete flip over the course of a career; that is, the decision profile of a successful CEO is the opposite of a successful first-line supervisor's. When does the major change in focus occur? Somewhere between the manager level and the director level, executives find that formerly effective decision styles no longer work so well. At this point, decision styles fall into a "convergence zone", where managers use all styles more or less equally. From then on, the executives continue to evolve their styles. The most successful managers come to the convergence zone quickly and continue to adjust their styles as their careers progress. Low performers seem to stagnate once they hit the convergence zone; their styles do not evolve in new directions. Clearly, relying on past successes and habits is no guarantee of success-indeed, it may be the road to failure.


Undertaking cause-specific mortality measurement in an unregistered population: an example from Tigray Region, Ethiopia.
The lack of adequate documentation of deaths, and particularly their cause, is often noted in African and Asian settings, but practical solutions for addressing the problem are not always clear. Verbal autopsy methods (interviewing witnesses after a death) have developed rapidly, but there remains a lack of clarity as to how these methods can be effectively applied to large unregistered populations. This paper sets out practical details for undertaking a representative survey of cause-specific mortality in a population of several million, taking Tigray Region in Ethiopia as a prototype. Sampling was designed around an expected level of maternal mortality ratio of 400 per 100,000 live births, which needed measuring within a 95% confidence interval of approximately ±100. Taking a stratified cluster sample within the region at the district level for logistic reasons, and allowing for a design effect of 2, this required a population of around 900,000 people, equating to six typical districts. Since the region is administered in six geographic zones, one district per zone was randomly selected. The survey was implemented as a two-stage process: first, to trace deaths that occurred in the sampled districts within the preceding year, and second to follow them up with verbal autopsy interviews. The field work for both stages was undertaken by health extension workers, working in their normally assigned areas. Most of the work was associated with tracing the deaths, rather than undertaking the verbal autopsy interviews. This approach to measuring cause-specific mortality in an unregistered Ethiopian population proved to be feasible and effective. Although it falls short of the ideal situation of continuous civil registration and vital statistics, a survey-based strategy of this kind may prove to be a useful intermediate step on the road towards full civil registration and vital statistics implementation.


The molecular evolution of neuropeptides: prospects for the '90s.
Three distinct opioid precursors have been identified in the central nervous system of mammals: proopiomelanocortin (POMC), proenkephalin, and prodynorphin. These precursors are derived from separate genes, synthesized in distinct neurons, and yield unique sets of opioid end products. This review will discuss the general mechanisms involved in the biosynthesis of neuropeptide precursors and consider the roles of posttranscriptional and posttranslational processing mechanisms in the generation of multiple sets of end products from a single gene. In addition, techniques that can be used for isolating and characterizing neuropeptide genes, mRNAs, and end products will be reviewed. These introductory comments will serve as the framework for a discussion of the phylogeny of the opioid precursors in the major groups of non-mammalian vertebrates.


Nut Consumption for Cognitive Performance: A Systematic Review.
Diet is considered an important modifiable lifestyle factor capable of attenuating early cognitive changes in healthy older people. The inclusion of nuts in the diet has been investigated as a dietary strategy for maintenance of brain health across the lifespan. This review aimed to present up-to-date evidence regarding the association between nut intake and cognitive performance. Four databases (Ovid MEDLINE, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, and Embase) were systematically searched from inception to April 2020. Eligible articles were interventional or observational studies in humans aged ≥18 y that measured the effects (or association) of nuts (almond, hazelnut, macadamia, pistachio, walnut, pecan, pine nut, Brazil nut, cashew, peanut) on cognitive outcomes. Out of the 2374 articles identified in the searches, 22 involving 43,793 participants met the criteria and were ultimately included in this review. Memory (immediate and delayed), attention, processing speed, executive function, and visual-spatial ability, as well as risk of mild cognitive impairment, were the outcomes investigated. Lack of consistency across the studies regarding study design, types of nut used, and cognitive outcomes measured resulted in inconsistent evidence that the regular consumption of mixed nuts has a protective effect on cognition in adults of different ages. Nonetheless, we observed that studies targeting populations with a higher risk of cognitive decline tended to find a more favorable outcome. Furthermore, homogeneous findings were observed in the studies that specifically addressed the association between walnut consumption and cognitive performance: out of the 6 studies, including 2 randomized controlled trials, only 1 did not find a positive association.


Interplay between hepatitis B virus and the innate immune responses: implications for new therapeutic strategies.
Hepatitis B virus (HBV) infection is still a worldwide health problem; however, the current antiviral therapies for chronic hepatitis B are limited in efficacy. The outcome of HBV infection is thought to be the result of complex interactions between the HBV and the host immune system. While the role of the adaptive immune responses in the resolution of HBV infection has been well characterized, the contribution of innate immune mechanisms remains elusive until recent evidence implicates that HBV appears to activate the innate immune response and this response is important for controlling HBV infection. Here, we review our current understanding of innate immune responses to HBV infection and the multifaceted evasion by the virus and discuss the potential strategies to combat chronic HBV infection via induction and restoration of host innate antiviral responses.


Variability in recording and scoring of respiratory events during sleep in Europe: a need for uniform standards.
Uniform standards for the recording and scoring of respiratory events during sleep are lacking in Europe, although many centres follow the published recommendations of the American Academy of Sleep Medicine. The aim of this study was to assess the practice for the diagnosis of sleep-disordered breathing throughout Europe. A specially developed questionnaire was sent to representatives of the 31 national sleep societies in the Assembly of National Sleep Societies of the European Sleep Research Society, and a total of 29 countries completed the questionnaire. Polysomnography was considered the primary diagnostic method for sleep apnea diagnosis in 10 (34.5%), whereas polygraphy was used primarily in six (20.7%) European countries. In the remaining 13 countries (44.8%), no preferred methodology was used. Fifteen countries (51.7%) had developed some type of national uniform standards, but these standards varied significantly in terms of scoring criteria, device specifications and quality assurance procedures between countries. Only five countries (17.2%) had published these standards. Most respondents supported the development of uniform recording and scoring criteria for Europe, which might be based partly on the existing American Academy of Sleep Medicine rules, but also take into account differences in European practice when compared to North America. This survey highlights the current varying approaches to the assessment of patients with sleep-disordered breathing throughout Europe and supports the need for the development of practice parameters in the assessment of such patients that would be suited to European clinical practice.


Impact cratering on a granular bed by hydrogel spheres having intermediate property between solid and liquid.
We investigated the low speed impact on a granular bed by a hydrogel sphere and especially focused on the resultant crater diameter. Though the crater diameter depends only on the impact kinetic energy for the solid sphere impact cratering, it also depends on the elastic energy for the hydrogel sphere. The hydrogel sphere impact cratering is classified into two dynamics: small and large indentation of the sphere. For the small indentation, the crater diameter is proportional to the 1/4 power of the energy for ejecting granular materials, which is calculated by substituting the elastic energy stored in the sphere from the impact kinetic energy. Considering the force balance between the inertial force and the indentation, we derived the relation between the impact kinetic energy, Young's modulus, and the crater diameter. In the large limit of Young's modulus, the relation leads to the 1/4 power law observed in solid sphere impact. The dependency of Young's modulus on the crater diameter for the large indentation of the sphere is larger than the impact with small indentation.


Adhesive Sponge Based on Supramolecular Dimer Interactions as Scaffolds for Neural Stem Cells.
Improving cell-material interactions of nonadhesive scaffolds is crucial for the success of biomaterials in tissue engineering. Due to their high surface area and open pore structure, sponges are widely reported as absorbent materials for biomedical engineering. The biocompatibility and biodegradability of polysaccharide sponges, coupled with the chemical functionalities of supramolecular dimers, make them promising combinations for the development of adhesive scaffolds. Here, a supramolecular tactic based on (UPy)-modified polysaccharide associated with three-dimensional structure of sponges was developed to reach enhanced cellular adhesion. For this purpose, three approaches were examined individually in order to accomplish this goal. In the first approach, the backbone polysaccharides with noncell adhesive properties were modified via a modular tactic using UPy-dimers. Hereupon, the physical-chemical characterizations of the supramolecular sponges were performed, showing that the presence of supramolecular dimers improved their mechanical properties and induced different architectures. In addition, small-angle neutron scattering (SANS) measurements and rheology experiments revealed that the UPy-dimers into agarose backbone are able to reorganize in thinning aggregates. It is also demonstrated that the resulted UPy-agarose (AGA-UPy) motifs in surfaces can promote cell adhesion. Finally, the last approach showed the great potential for use of this novel material in bioadhesive scaffolds indicating that neural stem cells show a spreading bias in soft materials and that cell adhesion was enhanced for all UPy-modified sponges compared to the reference, i.e. unmodified sponges. Therefore, by functionalizing sponge surfaces with UPy-dimers, an adhesive supramolecular scaffold is built which opens the opportunity its use neural tissues regeneration.


Association of F18-fluoro-ethyl-tyrosin uptake and 5-aminolevulinic acid-induced fluorescence in gliomas.
Malignant gliomas are highly infiltrative tumours with a fatal prognosis. F18-fluoroethyl-tyrosine (FET)-positron emission tomography (PET) often reveals a broader extension of these tumours compared with contrast-enhanced magnetic resonance imaging (MRI). Complete resection of the contrast-enhancing lesion is aspired. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) improved the extent of resection. In this study, we investigated whether the FET uptake correlates with the extent of resection using 5-ALA-induced fluorescence. Thirteen patients who underwent preoperative and postoperative MRI, FET-PET and fluorescence-guided neuronavigated resection were included in this study. The areas in which intraoperative fluorescence terminated the resection were marked. After fusion of PET and MRI, the standardized uptake value (SUV) of FET related to normal brain (SUV(R)) was measured in regions of interest corresponding to resected and remaining tissue, respectively. Receiver-operating characteristic (ROC) curve analysis determined the optimal threshold of the relative SUV anticipating 5-ALA-induced fluorescence. During resection a vivid fluorescence was present in all patients. Histology revealed glioblastomas in 11 cases, an anaplastic astrocytoma in one case and a low-grade astrocytoma in one case. The median FET SUV(R) was higher in areas corresponding to the fluorescent tumour compared with the non-fluorescent normal brain (2.321 vs 1.142, p < 0.0001, t-test). A SUV(R) greater than 1.374 predicted the fluorescence with a sensitivity of 0.87 [95% confidence interval (CI): 0.74-0.94] and a specificity of 0.94 (CI: 0.84-0.99). The area under the ROC curve was 0.9656 (CI: 0.9364-0.9948). FET uptake predicts the 5-ALA-induced fluorescence in glioma patients. Thus, FET-PET provides useful information for planning glioma resection.


Cross-Mapping of Nursing Care Terms Recorded in Italian Hospitals into the Standardized NNN Terminology.
To evaluate if nursing diagnoses, interventions, and outcomes, as recorded by nurses in Italian hospitals, were semantically equivalent to the NANDA-I, NIC, and NOC (NNN) terminology. A cross-mapping study using a multicenter design. Terms indicating nursing diagnoses, interventions, and outcomes were collected using the D-Catch instrument. Cross-mapping of these terms with NNN terminology was performed. A sample of 137 nursing documentations was included. Over 80% of nursing diagnostic terms, interventions, and outcomes were cross-mapped into NNN terminology. The study showed that most of the natural terms used by nurses were semantically equivalent to the standardized terms of NNN terminology. In Italy, the use of NNN terminology is recommended; however, further development of this terminology is needed.


Inflammation Following Traumatic Brain Injury in Humans: Insights from Data-Driven and Mechanistic Models into Survival and Death.
Inflammation induced by traumatic brain injury (TBI) is a complex mediator of morbidity and mortality. We have previously demonstrated the utility of both data-driven and mechanistic models in settings of traumatic injury. We hypothesized that differential dynamic inflammation programs characterize TBI survivors vs. non-survivors, and sought to leverage computational modeling to derive novel insights into this life/death bifurcation. Thirteen inflammatory cytokines and chemokines were determined using Luminex™ in serial cerebrospinal fluid (CSF) samples from 31 TBI patients over 5 days. In this cohort, 5 were non-survivors (Glasgow Outcome Scale [GOS] score = 1) and 26 were survivors (GOS > 1). A Pearson correlation analysis of initial injury (Glasgow Coma Scale [GCS]) vs. GOS suggested that survivors and non-survivors had distinct clinical response trajectories to injury. Statistically significant differences in interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, and tumor necrosis factor-α (TNF-α) were observed between TBI survivors vs. non-survivors over 5 days. Principal Component Analysis and Dynamic Bayesian Network inference suggested differential roles of chemokines, TNF-α, IL-6, and IL-10, based upon which an ordinary differential equation model of TBI was generated. This model was calibrated separately to the time course data of TBI survivors vs. non-survivors as a function of initial GCS. Analysis of parameter values in ensembles of simulations from these models suggested differences in microglial and damage responses in TBI survivors vs. non-survivors. These studies suggest the utility of combined data-driven and mechanistic models in the context of human TBI.


Cellular regulation in Friend virus induced erythroleukemia. Studies with anemic mice of genotype Sl/Sld.
Genetically anemic SI/SI(d) mice have been shown previously to have a defective hematopoietic environment which prevents extensive erythroid differentiation of normal hematopoietic stem cells and also confers resistance to the erythroleukemia-inducing virus, Friend spleen focus-forming virus (SFFV). In this study, we show that the relative resistance of SI/SI(d) mice to transformation by SFFV is not due to the inability of SFFV to replicate, nor is it because SFFV cannot transform erythroid cells, in the spleens of these mice. Injection of syngeneic +/+ mouse spleen cells, previously infected in vivo with SFFV, into secondary SI/SI(d) recipients resulted in marked splenic enlargement, and the appearance of large numbers of erythropoietin (Epo)-independent erythroid colonies in plasma clot culture. The cellular proliferation observed in these SI/SI(d) secondary recipients appeared to be due to infection and transformation of host SI/SI(d) cells rather than the growth of possible tumor colony-forming units (TCFU) present in the infected +/+ spleens, because preirradiation of the SI/SI(d) recipients abolished the splenomegaly and appearance of Epo- independent erythroid colonies. Furthermore, prior irradiation (1,200 rads) of donor spleen cells from SFFV-infected +/+ mice only slightly reduced spleen focus formation in unirradiated SI/SI(d) recipients. The conclusion that SI/SI(d) target cells could be infected and transformed by SFFV was confirmed directly by injecting a high titered preparation of SFFV into SI/SI(d) mice. SI/SI(d) mice were not absolutely resistant to infection or transformation by SFFV. Nevertheless, cells from the spleens of SFFV-infected mice were unable to form tumor colonies (TCFU) in irradiated SI/SI(d) recipients, suggesting that TCFU are either present at an undetectably low frequency in these spleens, or that they are still subject to the regulatory influences of the Steel locus.


Shared genetic susceptibility between trigger finger and carpal tunnel syndrome: a genome-wide association study.
Trigger finger and carpal tunnel syndrome are the two most common non-traumatic connective tissue disorders of the hand. Both of these conditions frequently co-occur, often in patients with rheumatoid arthritis. However, this phenotypic association is poorly understood. Hypothesising that the co-occurrence of trigger finger and carpal tunnel syndrome might be explained by shared germline predisposition, we aimed to identify a specific genetic locus associated with both diseases. In this genome-wide association study (GWAS), we identified 2908 patients with trigger finger and 436579 controls from the UK Biobank prospective cohort. We conducted a case-control GWAS for trigger finger, followed by co-localisation analyses with carpal tunnel syndrome summary statistics. To identify putative causal variants and establish their biological relevance, we did fine-mapping analyses and expression quantitative trait loci (eQTL) analyses, using fibroblasts from healthy donors (n=79) and tenosynovium samples from patients with carpal tunnel syndrome (n=77). We conducted a Cox regression for time to trigger finger and carpal tunnel syndrome diagnosis against plasma IGF-1 concentrations in the UK Biobank cohort. Phenome-wide analyses confirmed a marked association between carpal tunnel syndrome and trigger finger in the participants from UK Biobank (odds ratio [OR] 11·97, 95% CI 11·1-13·0; p<1 × 10-300). GWAS for trigger finger identified five independent loci, including one locus, DIRC3, that was co-localised with carpal tunnel syndrome and could be fine-mapped to rs62175241 (0·76, 0·68-0·84; p=5·03 × 10-13). eQTL analyses found a fibroblast-specific association between the protective T allele of rs62175241 and increased DIRC3 and IGFBP5 expression. Increased plasma IGF-1 concentrations were associated with both carpal tunnel syndrome and trigger finger in participants from UK Biobank (hazard ratio >1·04, p<0·02). In this GWAS, the DIRC3 locus on chromosome 2 was significantly associated with both carpal tunnel syndrome and trigger finger, possibly explaining their co-occurrence. The disease-protective allele of rs62175241 was associated with increased expression of long non-coding RNA DIRC3 and its transcriptional target, IGBP5, an antagonist of IGF-1 signalling. These findings suggest a model in which IGF-1 is a driver of both carpal tunnel syndrome and trigger finger, and in which the DIRC3-IGFBP5 axis directly antagonises fibroblastic IGF-1 signalling. Wellcome Trust, National Institute for Health Research, Medical Research Council.


Shielding effect of radiation dose reduction fiber during the use of C-arm fluoroscopy: a phantom study.
This study evaluated the shielding effect of a newly developed dose-reduction fiber (DRF) made from barium sulfate, in terms of radiation doses delivered to patients' radiosensitive organs and operator during C-arm fluoroscopy and its impact on the quality of images. A C-arm fluoroscopy unit was placed beside a whole-body phantom. Radiophotoluminescent glass dosimeters were attached to the back and front of the whole-body phantom at 20 cm intervals. Radiation doses were measured without DRF and with it applied to the back (position 1), front (position 2) or both sides (position 3) of the phantom. To investigate the impact of DRF on the quality of fluoroscopic images, step-wedge and modulation transfer function phantoms were used. The absorbed radiation doses to the back of the phantom significantly decreased by 25.3-88.8% after applying DRF to positions 1 and 3. The absorbed radiation doses to the front of the phantom significantly decreased by 55.3-93.6% after applying DRF to positions 2 and 3. The contrast resolution values for each adjacent step area fell in the range 0.0119-0.0209, 0.0128-0.0271, 0.0135-0.0339 and 0.0152-0.0339 without and with DRF applied to positions 1, 2 and 3, respectively. The investigated DRF effectively reduces absorbed radiation doses to patients and operators without decreasing the quality of C-arm fluoroscopic images. Therefore, routine clinical use of the DRF is recommended during the use of C-arm fluoroscopy.


Long-term blood cholesterol-lowering effects of a dietary fiber supplement.
The study evaluated the blood cholesterol-lowering effects of a dietary supplement of water-soluble fibers (guar gum, pectin) and mostly non-water-soluble fibers (soy fiber, pea fiber, corn bran) in subjects with mild to moderate hypercholesterolemia (LDL cholesterol, 3.37-4.92 mmol/L). After stabilization for 9 weeks on a National Cholesterol Education Program Step 1 Diet, subjects were randomly assigned to receive 20 g/d of the fiber supplement (n = 87) or matching placebo (n = 82) for 15 weeks and then receive the fiber supplement for 36 weeks. The efficacy analyses included the 125 subjects (58 fiber; 67 placebo) who were treatment and diet compliant. One hundred two (52 fiber; 50 placebo) completed the 15-week comparative phase. Of these subjects 85 (45 fiber; 40 placebo) elected to continue in the 36-week noncomparative extension phase. The mean decreases during the 15-week period for LDL cholesterol (LDL-C), total cholesterol (TC), and LDL-C/HDL-C ratio were greater (P < 0.001) in the fiber group. The mean changes from pre-treatment values in LDL-C, TC, and LDL-C/HDL-C ratio for subjects in the fiber group were -0.51 mmol/L (-12.1%), -0.53 mmol/L (-8.5%), and -0.30 (-9.4%), respectively. The corresponding changes in the placebo group were -0.05 mmol/L (-1.3%), -0.05 mmol/L (-0.8%), and 0.05 (1.5%), respectively. The fiber supplement had no significant effects (P > 0.05) on HDL cholesterol (HDL-C), triglyceride, iron, ferritin, or vitamin A or E levels. Similar effects were seen over the subsequent 36-week noncomparative part of the study. The fiber supplement provided significant and sustained reductions in LDL-C without reducing HDL-C or increasing triglycerides over the 51-week treatment period.


Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial.
RTS,S/AS01E is the lead candidate malaria vaccine. We recently showed efficacy against clinical falciparum malaria in 5-17 month old children, during an average of 8 months follow-up. We aimed to assess the efficacy of RTS,S/AS01E during 15 months of follow-up. Between March, 2007, and October, 2008, we enrolled healthy children aged 5-17 months in Kilifi, Kenya, and Korogwe, Tanzania. Computer-generated block randomisation was used to randomly assign participants (1:1) to receive three doses (at month 0, 1, and 2) of either RTS,S/AS01E or human diploid-cell rabies vaccine. The primary endpoint was time to first clinical malaria episode, defined as the presence of fever (temperature ≥37·5°C) and a Plasmodium falciparum density of 2500/μL or more. Follow-up was 12 months for children from Korogwe and 15 months for children from Kilifi. Primary analysis was per protocol. In a post-hoc modelling analysis we characterised the associations between anti-circumsporozoite antibodies and protection against clinical malaria episodes. This study is registered with ClinicalTrials.gov, number NCT00380393. 894 children were assigned, 447 in each treatment group. In the per-protocol analysis, 82 of 415 children in the RTS,S/AS01E group and 125 of 420 in the rabies vaccine group had first or only clinical malaria episode by 12 months, vaccine efficacy 39·2% (95% CI 19·5-54·1, p=0·0005). At 15 months follow-up, 58 of 209 children in the RTS,S/AS01E group and 85 of 206 in the rabies vaccine group had first or only clinical malaria episode, vaccine efficacy 45·8% (24·1-61·3, p=0·0004). At 12 months after the third dose, anti-circumsporozoite antibody titre data were available for 390 children in the RTS,S/AS01E group and 391 in the rabies group. A mean of 15 months (range 12-18 months) data were available for 172 children in the RTS,S/AS01E group and 155 in the rabies group. These titres at 1 month after the third dose were not associated with protection, but titres at 6·5 months were. The level of protection increased abruptly over a narrow range of antibody concentrations. The most common adverse events were pneumonia, febrile convulsion, gastroenteritis, and P falciparum malaria. RTS,S/AS01E confers sustained efficacy for at least 15 months and shows promise as a potential public health intervention against childhood malaria in malaria endemic countries. PATH Malaria Vaccine Initiative (MVI), GlaxoSmithKline.


Sox1 marks an activated neural stem/progenitor cell in the hippocampus.
The dentate gyrus of the hippocampus continues generating new neurons throughout life. These neurons originate from radial astrocytes within the subgranular zone (SGZ). Here, we find that Sox1, a member of the SoxB1 family of transcription factors, is expressed in a subset of radial astrocytes. Lineage tracing using Sox1-tTA;tetO-Cre;Rosa26 reporter mice shows that the Sox1-expressing cells represent an activated neural stem/progenitor population that gives rise to most if not all newly born granular neurons, as well as a small number of mature hilar astrocytes. Furthermore, a subpopulation of Sox1-marked cells have long-term neurogenic potential, producing new neurons 3 months after inactivation of tetracycline transactivator. Remarkably, after 8 weeks of labeling and a 12-week chase, as much as 44% of all granular neurons in the dentate gyrus were derived from Sox1 lineage-traced adult neural stem/progenitor cells. The fraction of Sox1-positive cells within the radial astrocyte population decreases with age, correlating with a decrease in neurogenesis. However, expression profiling shows that these cells are transcriptionally stable throughout the lifespan of the mouse. These results demonstrate that Sox1 is expressed in an activated stem/progenitor population whose numbers decrease with age while maintaining a stable molecular program.


Impact of vaccinating HCWs on the ward and possible influence of avian flu threat.
The aim of the study was to evaluate the impact of a 2-year vaccination program on the compliance of healthcare workers (HCWs) employed in an acute care university hospital to influenza vaccination. The study was carried out in October/November from 2004 to 2006 in a 286-bed acute care university hospital located in northern Italy employing 523 HCWs. The study cohort consisted of 473 HCWs continuously present in the hospital from 2004 to 2006. In 2005 and 2006, a vaccination campaign was made available in the wards that supplemented a pre-existing (2004) employee health service program. A personalized informative letter was sent to all HCWs explaining the risks and benefits of influenza vaccination for both patients and HCWs and indicating the scheduling of the additional vaccination service. The additional 2005 and 2006 campaigns produced significantly higher vaccination rates among HCWs than those achieved in previous years, from 10.4% in 2004 to 36.6% in 2005 and 23.2% in 2006. The year 2005 was characterized by an avian flu threat, which likely accounted for the highest vaccination rate of the 3-year study period. Physicians had the highest vaccination rates in the 3-year period (20.8%), while nurses in 2005 had the highest single vaccination rate (42.5%). Providing easy access to vaccination in the wards is a useful approach for improving vaccination rates among HCWs, but further tailored interventions are needed because overall vaccination rates remain too low. Subgroups, such as nurses and ancillary staff, should be considered as specific targets of such vaccination programs.


Impact of exercise training on ventricular properties in a canine model of congestive heart failure.
Exercise training improves functional class in patients with chronic heart failure (CHF) via effects on the periphery with no previously documented effect on intrinsic left ventricular (LV) properties. However, because methods used to evaluate in vivo LV function are limited, it is possible that some effects of exercise training on the failing heart have thus far eluded detection. Twelve dogs were instrumented for cardiac pacing and hemodynamic recordings. Hearts were paced rapidly for 4 wk. Six of the dogs received daily treadmill exercise (CHF(EX), 4.4 km/h, 2 h/day) concurrent with rapid pacing, while the other dogs remained sedentary (CHFs). Hemodynamic measurements taken in vivo at the end of 4 wk revealed relative preservation of maximum rate of pressure rise (2,540 +/- 440 vs. 1,720 +/- 300 mmHg/s, P < 0.05) and LV end-diastolic pressure (9 +/- 5 vs. 19 +/- 4 mmHg, P < 0.05) in CHF(EX) compared with CHFs. The hearts were then isolated and cross perfused for in vitro measurement of isovolumic pressure-volume relations; these results were compared with those of six normal dogs (N). Systolic function was similarly depressed in both groups of pacing animals [end-systolic elastance (Ees) values of 1.66 +/- 0.47 in CHFs, 1.77 +/- 0.38 in CHF(EX), and 3.05 +/- 0.81 mmHg/ml in N, with no changes in volume axis interceptors of the end-systolic pressure-volume relationship]. The diastolic myocardial stiffness constant, k, was elevated in CHFs and was normalized by exercise training (32 +/- 3 in CHFs, 21 +/- 3 in CHF(EX), 20 +/- 4 in N). Thus daily exercise training preserved in vivo hemodynamics during 4 wk of rapid cardiac pacing and was accompanied by a significant change in diastolic myocardial stiffness in vitro. These findings suggest that changes in heart function may contribute to the overall beneficial hemodynamic effects of exercise training in CHF by a significant effect on diastolic properties.


Exciton formation, relaxation, and decay in PCDTBT.
The nature and time evolution of the primary excitations in the pristine conjugated polymer, PCDTBT, are investigated by femtosecond-resolved fluorescence up-conversion spectroscopy. The extensive study includes data from PCDTBT thin film and from PCDTBT in chlorobenzene solution, compares the fluorescence dynamics for several excitation and emission wavelengths, and is complemented by polarization-sensitive measurements. The results are consistent with the photogeneration of mobile electrons and holes by interband π-π* transitions, which then self-localize within about 100 fs and evolve to a bound singlet exciton state in less than 1 ps. The excitons subsequently undergo successive migrations to lower energy localized states, which exist as a result of disorder. In parallel, there is also slow conformational relaxation of the polymer backbone. While the initial self-localization occurs faster than the time resolution of our experiment, the exciton formation, exciton migration, and conformational changes lead to a progressive relaxation of the inhomogeneously broadened emission spectrum with time constants ranging from about 500 fs to tens of picoseconds. The time scales found here for the relaxation processes in pristine PCDTBT are compared to the time scale (<0.2 ps) previously reported for photoinduced charge transfer in phase-separated PCDTBT:fullerene blends (Phys. Rev. B 2010, 81, 125210). We point out that exciton formation and migration in PCDTBT occur at times much longer than the ultrafast photoinduced electron transfer time in PCDTBT:fullerene blends. This disparity in time scales is not consistent with the commonly proposed idea that photoinduced charge separation occurs after diffusion of the polymer exciton to a fullerene interface. We therefore discuss alternative mechanisms that are consistent with ultrafast charge separation before localization of the primary excitation to form a bound exciton.


Antithrombotic therapy for non-ST-segment elevation acute coronary syndromes: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
This chapter about antithrombotic therapy for coronary artery disease is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicans Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggestions are weaker as there is uncertainty regarding the benefits, risks and costs such that individual patients' values may lead to different choices (for a full understanding of the grading see the "Grades of Recommendation for Antithrombotic Agents" chapter by Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations are the following: for all patients presenting with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS), without a clear allergy to aspirin, we recommend immediate aspirin (162 to 325 mg po) and then daily oral aspirin (75 to 100 mg) [Grade 1A]. For NSTE ACS patients who are at at least moderate risk for an ischemic event and who will undergo an early invasive management strategy, we recommend "upstream" treatment either with clopidogrel (300 mg po bolus, followed by 75 mg/d) or a small-molecule IV glycoprotein (GP) IIb/IIIa inhibitor (eptifibatide or tirofiban) [Grade 1A]. For NSTE ACS patients who are at least moderate risk for an ischemic event and for whom an early conservative or a delayed invasive strategy of management is to be used, we recommend "upstream" treatment with clopidogrel (300 mg oral bolus, followed by 75 mg/d) [Grade 1A]. For NSTE ACS patients who undergo PCI, we recommend treatment with both clopidogrel and an IV GP IIb/IIIa inhibitor (Grade 1A). We recommend a loading dose of 600 mg of clopidogrel given at least 2 h prior to planned PCI followed by 75 mg/d (Grade 1B). For all patients presenting with NSTE ACS, we recommend anticoagulation with UFH or LMWH or bivalirudin or fondaparinux over no anticoagulation (Grade 1A). For NSTE ACS patients who will undergo an early invasive strategy of management, we recommend UFH (with a GP IIb/IIIa inhibitor) over either LMWH or fondaparinux (Grade 1B). For NSTE ACS patients in whom an early conservative or a delayed invasive strategy of management is to be used, we recommend fondaparinux over enoxaparin (Grade 1A) and LMWH over UFH (Grade 1B). We recommend continuing LMWH during PCI treatment of patients with NSTE ACS when it has been started as the "upstream" anticoagulant (Grade 1B). In low- to moderate-risk patients with NSTE ACS undergoing PCI, we recommend either bivalirudin with provisional ("bail-out") GP IIb/IIIa inhibitors or UFH plus a GP IIb/IIIa inhibitor over alternative antithrombotic regimens (Grade 1B).


Thrombin-induced inositol trisphosphate production by rabbit platelets is inhibited by ethanol.
Ethanol has an inhibitory effect on some platelet functions, but the mechanisms by which it exerts this effect are not known. Using suspensions of washed platelets, we observed that ethanol (1-9 mg/ml) did not affect the aggregation of rabbit platelets stimulated with ADP (0.5-10 microM). When platelets were prelabelled with 5-hydroxy[14C]tryptamine, aggregation and secretion of granule contents in response to thrombin (0.01-0.10 unit/ml) were not inhibited by ethanol, but these responses to thrombin at lower concentrations (less than 0.01 unit/ml) were inhibited by ethanol (2-4 mg/ml). Platelets were prelabelled with [3H]inositol so that increases in inositol phosphates upon stimulation could be assessed by measuring the amount of label in these compounds. ADP-induced increases in IP (inositol phosphate) and IP2 (inositol bisphosphate) were not affected by ethanol. IP3 (inositol trisphosphate) was not changed by ADP or ethanol. Although ethanol did not affect the increases in IP, IP2 and IP3 caused by stimulation of platelets with thrombin at concentrations greater than 0.01 unit/ml, ethanol did inhibit the increases observed at 2 and 3 min in these inositol phosphates caused by lower concentrations of thrombin (less than 0.01 unit/ml). Since ADP did not cause formation of IP3 in rabbit platelets, and since no thromboxane B2 was detected in platelets stimulated with the lower concentrations of thrombin, it is unlikely that the inhibitory effect of ethanol in IP3 formation was due to effects on further stimulation of platelets by released ADP or by thromboxane A2. Ethanol may inhibit platelet responses to thrombin by inhibiting the production of the second messenger, IP3.


Study profile: the Durban Diabetes Study (DDS): a platform for chronic disease research.
The Durban Diabetes Study (DDS) is a population-based cross-sectional survey of an urban black population in the eThekwini Municipality (city of Durban) in South Africa. The survey combines health, lifestyle and socioeconomic questionnaire data with standardised biophysical measurements, biomarkers for non-communicable and infectious diseases, and genetic data. Data collection for the study is currently underway and the target sample size is 10 000 participants. The DDS has an established infrastructure for survey fieldwork, data collection and management, sample processing and storage, managed data sharing and consent for re-approaching participants, which can be utilised for further research studies. As such, the DDS represents a rich platform for investigating the distribution, interrelation and aetiology of chronic diseases and their risk factors, which is critical for developing health care policies for disease management and prevention. For data access enquiries please contact the African Partnership for Chronic Disease Research (APCDR) at firstname.lastname@example.com or the corresponding author.


Differential uranyl(v) oxo-group bonding between the uranium and metal cations from groups 1, 2, 4, and 12; a high energy resolution X-ray absorption, computational, and synthetic study.
The uranyl(vi) 'Pacman' complex [(UO2)(py)(H2L)] A (L = polypyrrolic Schiff-base macrocycle) is reduced by Cp2Ti(η2-Me3SiC[triple bond, length as m-dash]CSiMe3) and [Cp2TiCl]2 to oxo-titanated uranyl(v) complexes [(py)(Cp2TiIIIOUO)(py)(H2L)] 1 and [(ClCp2TiIVOUO)(py)(H2L)] 2. Combination of ZrII and ZrIV synthons with A yields the first ZrIV-uranyl(v) complex, [(ClCp2ZrOUO)(py)(H2L)] 3. Similarly, combinations of Ae0 and AeII synthons (Ae = alkaline earth) afford the mono-oxo metalated uranyl(v) complexes [(py)2(ClMgOUO)(py)(H2L)] 4, [(py)2(thf)2(ICaOUO)(py) (H2L)] 5; the zinc complexes [(py)2(XZnOUO)(py)(H2L)] (X = Cl 6, I 7) are formed in a similar manner. In contrast, the direct reactions of Rb or Cs metal with A generate the first mono-rubidiated and mono-caesiated uranyl(v) complexes; monomeric [(py)3(RbOUO)(py)(H2L)] 8 and hexameric [(MOUO)(py)(H2L)]6 (M = Rb 8b or Cs 9). In these uranyl(v) complexes, the pyrrole N-H atoms show strengthened hydrogen-bonding interactions with the endo-oxos, classified computationally as moderate-strength hydrogen bonds. Computational DFT MO (density functional theory molecular orbital) and EDA (energy decomposition analysis), uranium M4 edge HR-XANES (High Energy Resolution X-ray Absorption Near Edge Structure) and 3d4f RIXS (Resonant Inelastic X-ray Scattering) have been used (the latter two for the first time for uranyl(v) in 7 (ZnI)) to compare the covalent character in the UV-O and O-M bonds and show the 5f orbitals in uranyl(vi) complex A are unexpectedly more delocalised than in the uranyl(v) 7 (ZnI) complex. The Oexo-Zn bonds have a larger covalent contribution compared to the Mg-Oexo/Ca-Oexo bonds, and more covalency is found in the U-Oexo bond in 7 (ZnI), in agreement with the calculations.


The emerging role for repetitive transcranial magnetic stimulation in optimizing the treatment of adolescent depression.
Major depressive disorder (MDD) in adolescents is a common illness and significant public health problem. Treatment is challenging because of recurrences and limited modalities. Selective serotonin reuptake inhibitors and cognitive behavioral therapy are considered the standard of care in severe or treatment-resistant MDD in this age group. However, responses to these interventions are often suboptimal. A growing body of research supports the efficacy of repetitive transcranial magnetic stimulation (rTMS) for the treatment of MDD in adults. Induced seizures are a primary safety concern, although this is rare with appropriate precautions. There is, however, limited experience with rTMS as a therapeutic intervention for adolescent psychiatric disturbances. This review will summarize the rTMS efficacy and safety data in adults and describe all published experience with adolescent MDD. Applications in other adolescent psychiatric illnesses such as schizophrenia and attention-deficit/hyperactivity disorder are reviewed. Safety and ethical issues are paramount with investigational treatments in adolescent psychiatric illnesses. However, further research with rTMS in adolescent MDD is imperative to establish standards for optimal stimulation site, treatment parameters, and its role in treatment algorithms. These may diverge from adult data. Early intervention with neuromodulation could also hold the promise of addressing the developmental course of dysfunctional neurocircuitry.


'Diarrhetic' type shellfish poisoning in Nigeria.
The safety of shellfish found and consumed in Nigeria is doubtful because no investigations have been carried out on their toxicity. The occurrence and toxicity of toxins in the commonly consumed Nigerian shellfish from Lagos, Warri, Oron, and Port Harcourt (PH) were investigated. Albino Wistar mice treated with chloroform extract of hepatopancreas (HP) from PH shellfish died 7-8 min post treatment. They convulsed for 30-60 s prior to death. The aqueous phase obtained from the diethyl ether extraction of the same HP resulted in the death of one out of two mice injected with it, 39 min post treatment.


Morphometry of the basal cell layer of oral leukoplakia and oral squamous cell carcinoma using computer-aided image analysis.
To study and compare the changes in nuclear and cellular size, shape and nuclear-cytoplasmic ratio of the cells in the basal layer of oral leukoplakia and well-differentiated oral squamous cell carcinoma (SCC) with normal buccal mucosa, using computer-aided image analysis in tissue sections. This was a retrospective study conducted on tissue sections on a total number of 70 cases to determine the various morphometric parameters. The data collected in this study were analyzed statistically by computing descriptive statistics, viz., percentage, mean, standard deviation, standard error of mean, 95% confidence interval for mean. The difference in the control and study groups for various diagnostic variables was compared by means of analysis of variance (ANOVA), Student's t-test for independent samples, wherever applicable. Mann-Whitney U-test and Kruskal-Wallis test were used where the data were found to be asymmetrical and the standard deviations were also different. The results were considered statistically significant whenever P ≤ 0.05. Our results were significant for the morphometric parameter, size. The values of nuclear perimeter and area, cellular perimeter and area increased gradually from the normal buccal mucosa to leukoplakia, reaching the highest value in SCC. There was statistically significant difference in the nuclear and cellular areas to differentiate between leukoplakia and squamous cell carcinoma. Two variables which were used to study the shape, "form perimeter (PE)" and "contour index (CI)", showed significant difference between normal buccal mucosa and leukoplakia and between normal buccal mucosa and SCC. The morphometric parameter, nuclear-cytoplasmic ratio, in our results showed an increase in leukoplakia and SCC compared to normal buccal mucosa, but the difference was not significant between leukoplakia and SCC. The morphometric parameter, size, was useful to differentiate between normal, potentially malignant leukoplakia and SCC.


DUF1220 domains, cognitive disease, and human brain evolution.
We have established that human genome sequences encoding a novel protein domain, DUF1220, show a dramatically elevated copy number in the human lineage (>200 copies in humans vs. 1 in mouse/rat) and may be important to human evolutionary adaptation. Copy-number variations (CNVs) in the 1q21.1 region, where most DUF1220 sequences map, have now been implicated in numerous diseases associated with cognitive dysfunction, including autism, autism spectrum disorder, mental retardation, schizophrenia, microcephaly, and macrocephaly. We report here that these disease-related 1q21.1 CNVs either encompass or are directly flanked by DUF1220 sequences and exhibit a dosage-related correlation with human brain size. Microcephaly-producing 1q21.1 CNVs are deletions, whereas macrocephaly-producing 1q21.1 CNVs are duplications. Similarly, 1q21.1 deletions and smaller brain size are linked with schizophrenia, whereas 1q21.1 duplications and larger brain size are associated with autism. Interestingly, these two diseases are thought to be phenotypic opposites. These data suggest a model which proposes that (1) DUF1220 domain copy number may be involved in influencing human brain size and (2) the evolutionary advantage of rapidly increasing DUF1220 copy number in the human lineage has resulted in favoring retention of the high genomic instability of the 1q21.1 region, which, in turn, has precipitated a spectrum of recurrent human brain and developmental disorders.


Differences in physical activity prevalence and trends from 3 U.S. surveillance systems: NHIS, NHANES, and BRFSS.
Three U.S. surveillance systems-National Health Interview Survey (NHIS), National Health and Nutrition Examination Survey (NHANES), and Behavioral Risk Factor Surveillance System (BRFSS)--estimate physical activity prevalence. Survey differences were examined qualitatively. Prevalence estimates by sex, age, and race/ethnicity were assessed for comparable survey periods. Trends were examined from NHIS 1998 to 2007, NHANES 1999 to 2006, and BRFSS 2001 to 2007. Age-adjusted prevalence estimates appeared most similar for NHIS 2005 (physically active: 30.2%, inactive: 40.7%) and NHANES 2005 to 2006 (physically active: 33.5%, inactive: 32.4%). In BRFSS 2005, prevalence of being physically active was 48.3% and inactive was 13.9%. Across all systems, men were more likely to be active than women; non-Hispanic whites were most likely to be active; as age increased, overall prevalence of being active decreased. Prevalence of being active exhibited a significant increasing trend only in BRFSS 2001 to 2007 (P < .001), while prevalence of being inactive decreased significantly in NHANES 1999 to 2006 (P < .001) and BRFSS 2001 to 2007 (P < .001). Different ways of assessing physical activity in surveillance systems result in different prevalence estimates. Before comparing estimates from different systems, all aspects of data collection and data analysis should be examined to determine if comparisons are appropriate.