Spatial interaction among nontoxic phytoplankton, toxic phytoplankton, and zooplankton: emergence in space and time.
In homogeneous environments, by overturning the possibility of competitive exclusion among phytoplankton species, and by regulating the dynamics of overall plankton population, toxin-producing phytoplankton (TPP) potentially help in maintaining plankton diversity-a result shown recently. Here, I explore the competitive effects of TPP on phytoplankton and zooplankton species undergoing spatial movements in the subsurface water. The spatial interactions among the species are represented in the form of reaction-diffusion equations. Suitable parametric conditions under which Turing patterns may or may not evolve are investigated. Spatiotemporal distributions of species biomass are simulated using the diffusivity assumptions realistic for natural planktonic systems. The study demonstrates that spatial movements of planktonic systems in the presence of TPP generate and maintain inhomogeneous biomass distribution of competing phytoplankton, as well as grazer zooplankton, thereby ensuring the persistence of multiple species in space and time. The overall results may potentially explain the sustainability of biodiversity and the spatiotemporal emergence of phytoplankton and zooplankton species under the influence of TPP combined with their physical movement in the subsurface water.


Radiation therapy and breast cancer risk.
Exposure to ionizing radiation has clearly been established as one of the risk factors for the development of breast cancer. Much data on the relationship between radiation exposures and subsequent breast cancer are derived from atomic bomb survivors and women who received medical exposures either for diagnostic or therapeutic purposes. Although these populations differ in background breast cancer risks and the dose, quality, and timing of radiation, consistent findings include an increased risk with younger age at exposure, long latency to breast cancer development, and increasing risk with increasing radiation dose. Although therapeutic radiation is rarely used to treat benign conditions, it remains an important and effective treatment modality for a wide range of cancers. Increased knowledge of radiation-related breast cancer and modifying influences plays an important role in guiding the initial treatment approach for young women and optimizing long-term follow-up care.


Aorto-internal iliac artery endovascular reconstruction for critical limb ischaemia: a case report.
The internal iliac artery and cruciate anastomosis are important collateral vessels in severe aortoiliac occlusive disease. This report describes a patient with left leg rest pain due to occlusion of the left common and external iliac arteries. In addition, there was a high-grade stenosis of the right common iliac artery. Direct catheter canulation of the left internal iliac artery revealed that it was patent. Endovascular stent placement was successful in re-establishing blood flow into the left internal iliac artery. Ischaemic rest pain was relieved and the ankle brachial index was maintained at 0.85 at 6 months follow-up.


The Physical and Athletic Performance Characteristics of Division I Collegiate Female Soccer Players by Position.
Lockie, RG, Moreno, MR, Lazar, A, Orjalo, AJ, Giuliano, DV, Risso, FG, Davis, DL, Crelling, JB, Lockwood, JR, and Jalilvand, F. The physical and athletic performance characteristics of Division I collegiate female soccer players by position. J Strength Cond Res 32(2): 334-343, 2018-Playing positions in soccer can exhibit different movement demands during a match, contributing to variations in physical and performance characteristics. National Collegiate Athletic Association (NCAA) soccer features different substitution rules when compared to FIFA-sanctioned matches, which could influence each players' characteristics. Therefore, this study determined the athletic performance characteristics of Division I female soccer players. Twenty-six players (3 goalkeepers; 8 defenders; 10 midfielders; 5 forwards) from the same squad completed assessments of: lower-body power (vertical and standing broad jump); linear (0-5, 0-10, 0-30 meter [m] sprint intervals) and change-of-direction (pro-agility shuttle; arrowhead change-of-direction speed test) speed; and soccer-specific fitness (Yo-Yo Intermittent Recovery Test [YYIRT] levels 1 and 2). Players were split into position groups, and a Kruskal-Wallis H test with post hoc pairwise analyses (p ≤ 0.05) calculated significant between-group differences. There were no differences in age, height, or body mass between the positions. Midfielders had a faster 0-5 m time compared with the defenders (p = 0.017) and the goalkeepers (p = 0.030). The defenders (p = 0.011) and midfielders (p = 0.013) covered a greater YYIRT2 distance compared with the goalkeepers. There were no other significant between-position differences. Overall, Division I collegiate female players from the same squad demonstrated similar characteristics as measured by soccer-specific performance tests, which could allow for flexibility in position assignments. However, a relatively homogenous squad could also indicate commonality in training prescription, particularly regarding acceleration and high-intensity running. Strength and conditioning coaches may have to consider the specific movement demands of individual positions when training these capacities.


Recurrent lymphoma of the lung: computed tomography appearance.
To describe the computed tomography findings of recurrent lymphoma involving the lung. Computed tomography scans of 15 patients with biopsy-proven recurrent lymphoma involving the lung were reviewed. Group mean age of enrolled patients was 38 years (range: 14-68 years). Pathologic specimens were obtained by thoracoscopic or open wedge biopsy (n = 8), transbronchial biopsy (n = 5), and fine needle aspiration (n = 2). Nodules, the most common manifestation, were present in all patients; nodules were greater than 10 in number in 12 (80%) of 15 cases and predominantly 6-10 mm in size in 8 cases (53%). Nodular distribution was bilateral and multilobar except in 2 patients, in whom a solitary pulmonary nodule was found. Lymphadenopathy was the second most common finding; it was seen in 13 (87%) of 15 cases and involved an average of 5 nodal stations. Recurrent lymphoma in the lung most commonly manifests as multiple pulmonary nodules that are typically bilateral and multilobar in distribution.


Plitidepsin has a safe cardiac profile: a comprehensive analysis.
Plitidepsin is a cyclic depsipeptide of marine origin in clinical development in cancer patients. Previously, some depsipeptides have been linked to increased cardiac toxicity. Clinical databases were searched for cardiac adverse events (CAEs) that occurred in clinical trials with the single-agent plitidepsin. Demographic, clinical and pharmacological variables were explored by univariate and multivariate logistic regression analysis. Forty-six of 578 treated patients (8.0%) had at least one CAE (11 patients (1.9%) with plitidepsin-related CAEs), none with fatal outcome as a direct consequence. The more frequent CAEs were rhythm abnormalities (n = 31; 5.4%), mostly atrial fibrillation/flutter (n = 15; 2.6%). Of note, life-threatening ventricular arrhythmias did not occur. Myocardial injury events (n = 17; 3.0%) included possible ischemic-related and non-ischemic events. Other events (miscellaneous, n = 6; 1.0%) were not related to plitidepsin. Significant associations were found with prostate or pancreas cancer primary diagnosis (p = 0.0017), known baseline cardiac risk factors (p = 0.0072), myalgia present at baseline (p = 0.0140), hemoglobin levels lower than 10 g/dL (p = 0.0208) and grade ≥2 hypokalemia (p = 0.0095). Treatment-related variables (plitidepsin dose, number of cycles, schedule and/or total cumulative dose) were not associated. Electrocardiograms performed before and after plitidepsin administration (n = 136) detected no relevant effect on QTc interval. None of the pharmacokinetic parameters analyzed had a significant impact on the probability of developing a CAE. In conclusion, the most frequent CAE type was atrial fibrillation/atrial flutter, although its frequency was not different to that reported in the age-matched healthy population, while other CAEs types were rare. No dose-cumulative pattern was observed, and no treatment-related variables were associated with CAEs. Relevant risk factors identified were related to the patient's condition and/or to disease-related characteristics rather than to drug exposure. Therefore, the current analysis supports a safe cardiac risk profile for single-agent plitidepsin in cancer patients.


Recognition of multiple drugs by a single protein: a trivial solution of an old paradox.
Multidrug-efflux transporters recognize scores of structurally dissimilar toxic compounds and expel them from cells. The broad chemical specificity of these transporters challenges some of the basic dogmas of biochemistry and remains unexplained. To understand, at least in principle, how a protein can recognize multiple compounds, we analysed the transcriptional regulator of the Bacillus subtilis multidrug transporter Bmr. This regulator, BmrR, binds multiple dissimilar hydrophobic cations and, by activating the expression of the Bmr transporter, causes their expulsion from the cell. Crystallographic analysis of the complexes of the inducer-binding domain of BmrR with some of its inducers revealed that ligands cause disordering of the surface alpha-helix and penetrate the hydrophobic core of the protein, where they form multiple van der Waals and stacking interactions with hydrophobic amino acids and an electrostatic bond with the buried glutamic residue. Mutational analysis of the binding site suggests that each ligand forms a unique set of atomic contacts with the protein: each tested mutation exerted disparate effects on the binding of different ligands. The example of BmrR demonstrates that a protein can bind multiple compounds with micromolar affinities by using only electrostatic and hydrophobic interactions. Its ligand specificity can be broadened by the flexibility of the binding site. It therefore seems that the commonly expressed fascination with the broad specificity of multidrug transporters is misdirected and originates from an almost exclusive familiarity with the more sophisticated processes of specific molecular recognition that predominate among existing proteins.


Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex.
Prolonged hypokalemia causes vasopressin-resistant polyuria. We have recently shown that another cause of severe polyuria, chronic lithium therapy, is associated with decreased aquaporin-2 (AQP2) water channel expression (Marples, D., S. Christensen, E.I. Christensen, P.D. Ottosen, and S. Nielsen, 1995. J. Clin. Invest., 95: 1838-1845). Consequently, we studied the effect in rats of 11 days' potassium deprivation on urine production and AQP2 expression and distribution. Membrane fractions were prepared from one kidney, while the contralateral kidney was perfusion-fixed for immunocytochemistry. Immunoblotting and densitometry revealed a decrease in AQP2 levels to 27+/-3.4% of control levels (n=11, P<0.001) in inner medulla, and 34+/-15% of controls (n=5, P<0.05) in cortex. Urine production increased in parallel, from 11+/-1.4 to 30+/-4.4 ml/day (n=11, P<0.01). After return to a potassium-containing diet both urine output and AQP2 labels normalized within 7 d. Immunocytochemistry confirmed decreased AQP2 labeling in principal cells of both inner medullary and cortical collecting ducts. AQP2 labeling was predominantly associated with the apical plasma membrane and intracellular vesicles. Lithium treatment for 24 d caused a more extensive reduction of AQP2 levels, to 4+/-1% of control levels in the inner medulla and 4+/-2% in cortex, in association with severe polyuria. The similar degree of downregulation in medulla and cortex suggests that interstitial tonicity is not the major factor in the regulation of AQP2 expression. Consistent with this furosemide treatment did not alter AQP2 levels. In summary,hypokalemia, like lithium treatment, results in a decrease in AQP2 expression in rat collecting ducts, in parallel with the development of polyuria, and the degree of downregulation is consistent with the level of polyuria induced, supporting the view that there is a causative link.


Adaptation and validation of the Physical Activity Questionnaire for Older Children (PAQ-C) among Czech children.
The study aimed to adapt the standardized Physical Activity Questionnaire for Older Children (PAQ-C) into the Czech language and assess its psychometric properties. A forwards-and-backwards translation method was carried out to prepare the Czech PAQ-C version (PAQ-C/CZ), followed by adjustments based on socio-cultural aspects. In the next phase, participants (n = 169) wore accelerometers for seven days. On the 8th day, participants completed the PAQ-C/CZ in school so that it was possible to determine the concurrent validity (correlation between the accelerometer and PAQ-C/CZ data, Spearman's r), internal consistency (Cronbach's alpha), item/scale properties (corrected item-total correlations, CITCs), and factor structure (exploratory factor analysis, EFA) for PAQ-C/CZ. In the last phase, participants (n = 63) completed the PAQ-C/CZ twice on two consecutive school days in the morning to determine the test-retest reliability (intraclass correlation coefficient, ICC; independent sample T-test). The PAQ-C/CZ indicated moderate internal consistency (alpha = 0.77), acceptable item/scale properties (CITCs = 0.29-0.61), and good test-retest reliability (ICC = 0.73-0.94). The EFA findings suggested a single factor model (factor load = 0.32-0.73) for PAQ-C/CZ, with items 2, 3, and 4 contributing low to the total score. Results on concurrent validity showed low but significant association (r = 0.28, p < 0.05) between accelerometer and PAQ-C/CZ data. Considering the study results, the PAQ-C/CZ can be recommended as a tool for moderate-to-vigorous physical activity assessment in large-sample research studies only, but with an emphasis on the interpretation of the correct results.


The effects of buspirone on perceived exertion and time to fatigue in man.
Male subjects exercised at 80% maximal rate of O2 uptake (VO2,max) following oral administration of either placebo or the partial 5-HT1A agonist buspirone (45 mg), using a paired design. Ratings of perceived exertion were higher following buspirone and time to volitional fatigue (median and inter-quartile range) fell significantly by approximately a third from 26 min (24-30 min) on placebo to 16 min (11-19 min) following buspirone. Serum prolactin was significantly elevated following buspirone administration, indicating increased hypothalamic 5-HT1A receptor stimulation. There were no significant differences in blood lactate or serum glucose between the trials. This study supports the possible central modulation of exercise tolerance by serotonergic pathways, although a role for dopamine cannot be excluded.


Human papilloma and other DNA virus infections of the cervix: A population based comparative study among tribal and general population in India.
Despite being preventable, cervical cancer remains a major health concern among women. Persistent Human Papillomavirus (HPV) and other viral co-infections may influence cervical dysplasia. We determined and compared the prevalence and risk factors of cervical viral infections among the tribal and general population of southern coastal Karnataka, India. A population-based cross-sectional survey was conducted among 1140 and 1100 women from tribal and general population, respectively. Cervical infections with HPV, Epstein-Barr Virus (EBV), Cytomegalovirus (CMV) and Herpes-Simplex Virus (HSV) were examined using polymerase chain reactions (PCR) and DNA sequencing. HPV prevalence was higher among tribal women (40.6%) than general population (14.3%) while the prevalence of EBV (55.1%) and CMV (49.4%) were lower among tribal women than general population (74.3% and 77.5%, respectively). HSV infection was observed in tribal women only (1.8%). Among HR-HPV strains, HPV-18 was predominant among tribal population (28.3%) while, HPV-16 was predominant among the general population (9.1%). Infections were associated with age, educational status, unemployment and personal hygiene of tribal women. Phylogenetic analysis revealed that HPV-16 variants of tribal participants were closely related to non-European sublineages indicating greater risk of HPV persistence and carcinogenesis. The study provides a comparative estimate for DNA virus infections of the cervix among women from general as well as tribal population in this region and also reveals a different type-specific pattern of viral infection. Further research is required to delineate the role of specific interactions between multiple virus infections and their role in carcinogenesis.


Massage therapy for essential tremor: quieting the mind.
Essential tremor (ET) is a neurological disorder causing rhythmical shaking of part of the body. The condition is known to have an inheritable tendency and can present in more than one family member, known as familial tremor. Treatment of the disorder is commonly by way of prescription medication. ET is progressive and in its mildest form can be sensed and/or observed when performing simple motor skills or activities of daily living (ADL). To examine the influence of massage therapy on the severity of ET using an activity-based rating scale pre- and post-treatment. The study period included five consecutive weekly sessions. The subject, a 63-year-old female, indicated her hands and head as the primary areas affected by ET. The treatment aim was to reduce sympathetic nervous system firing; therefore, the massage techniques implemented were relaxation-based. Methods included Swedish massage, hydrotherapy, myofascial release, diaphragmatic breathing, remedial exercise education and affirmative symptom management recommendations. Drawings of an Archimedes spiral for comparison pre- and post-treatment provided an objective, visual representation of tremor intensity affecting fine motor control. Goniometric measurements were taken to mark changes in cervical range of motion. Tremor intensity decreased after each session; demonstrated by improved fine motor skills. The client also reported an increased functionality in cervical range, which was documented during the first and last visits. The results suggest that tremors, symptomatic to ET, can be eased through initiatives that encourage a parasympathetic response. Massage therapy has shown to be a valuable method of treatment for ET. Tremor severity can present in an irregular pattern due to subjective individual triggers; therefore, further controlled research is required to lessen the variability between subjects and to validate these findings.


Structural insights into substrate traffic and inhibition in acetylcholinesterase.
Acetylcholinesterase (AChE) terminates nerve-impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter, acetylcholine. Substrate traffic in AChE involves at least two binding sites, the catalytic and peripheral anionic sites, which have been suggested to be allosterically related and involved in substrate inhibition. Here, we present the crystal structures of Torpedo californica AChE complexed with the substrate acetylthiocholine, the product thiocholine and a nonhydrolysable substrate analogue. These structures provide a series of static snapshots of the substrate en route to the active site and identify, for the first time, binding of substrate and product at both the peripheral and active sites. Furthermore, they provide structural insight into substrate inhibition in AChE at two different substrate concentrations. Our structural data indicate that substrate inhibition at moderate substrate concentration is due to choline exit being hindered by a substrate molecule bound at the peripheral site. At the higher concentration, substrate inhibition arises from prevention of exit of acetate due to binding of two substrate molecules within the active-site gorge.


Everolimus in advanced pancreatic neuroendocrine tumors: the clinical experience.
The incidence of neuroendocrine tumors (NET) has increased dramatically in the past 30 years. This information has revitalized basic and clinical research into the molecular biology of NET and has resulted in the recent approval of new therapies for pancreatic NET (pNET), including the oral inhibitor of the mTOR everolimus. Everolimus significantly improved progression-free survival among patients with pNET in the phase III RADIANT-3 study. Here, we review the clinical studies showing the efficacy of everolimus in pNET and summarize the translational science from these studies. To understand the mechanisms of resistance and cause of treatment failure, we compared the type of progression events observed in the everolimus and placebo arms of the RADIANT-3 study. Comparison of the everolimus arm to the placebo arm indicated the fractions of progression events due to new metastasis only (21% vs. 22%), growth of preexisting lesions only (54% vs. 49%), and new metastasis along with growth of preexisting lesions (24% vs. 27%) were similar. These results suggest that although everolimus delays disease progression in patients with pNET, patients who experience disease progression while on everolimus do not appear to have a more aggressive metastatic phenotype than those whose disease progresses while on placebo.


Adverse effects of red blood cell transfusions in neonates: a systematic review and meta-analysis.
Controversy exists regarding the contribution of blood transfusions to a range of adverse clinical outcomes in neonates. The aim of our systematic review was to identify the broader literature on harmful effects and associations potentially attributable to red blood cell (RBC) transfusions. A comprehensive search of MEDLINE (PubMed) and EMBASE was undertaken. Eligible studies included both randomized controlled trials (RCTs) and nonrandomized studies examining the effects of small volume (10-20 mL/kg) RBC transfusions on neonates. Primary outcomes of interest were mortality, chronic lung disease, retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. Two independent authors conducted a review of abstracts and then of full-text article reviews as well as data extraction and quality assessments. Sixty-one studies were eligible for inclusion, including 16 (26%) randomized studies. The majority of studies were nonrandomized (n = 45; 74%), which included 32 observational studies with and 13 studies without a comparator group. There was no evidence that rates of mortality differed between restrictive and liberal strategies for transfusion (eight RCTs: risk ratio, 1.24; 95% confidence interval, 0.89-1.672, heterogeneity = 0%) or for necrotizing enterocolitis (five RCTs: risk ratio, 1.45; 95% confidence interval, 0.91-2.33; heterogeneity = 0%). A liberal strategy also was not superior to restrictive transfusion practice in the pooled randomized studies for rates of retinopathy of prematurity, chronic lung disease, or intraventricular hemorrhage. Statistically significant differences in a range of harmful outcomes between neonates exposed to restrictive and liberal RBC transfusion practice were not found. However, the risks of bias identified in many studies and the lack of consistent reporting and definitions of events limits our conclusions.


Leaders, leadership and future primary care clinical research.
A strong and self confident primary care workforce can deliver the highest quality care and outcomes equitably and cost effectively. To meet the increasing demands being made of it, primary care needs its own thriving research culture and knowledge base. Review of recent developments supporting primary care clinical research. Primary care research has benefited from a small group of passionate leaders and significant investment in recent decades in some countries. Emerging from this has been innovation in research design and focus, although less is known of the effect on research output. Primary care research is now well placed to lead a broad re-vitalisation of academic medicine, answering questions of relevance to practitioners, patients, communities and Government. Key areas for future primary care research leaders to focus on include exposing undergraduates early to primary care research, integrating this early exposure with doctoral and postdoctoral research career support, further expanding cross disciplinary approaches, and developing useful measures of output for future primary care research investment.


Diastolic viscous properties of the intact canine left ventricle.
The viscoelastic model of the ventricle predicts that the rate of change of volume (strain rate) is a determinant of the instantaneous pressure in the ventricle during diastole. Because relaxation is not complete before the onset of filling, one cannot distinguish the individual effects of relaxation and viscosity unless the passive and active components that determine the ventricular pressure are separated. To overcome this problem, we used the method of ventricular volume clamping to compare the pressures in the fully relaxed ventricle at a given volume at zero strain rate (static pressure) and high strain rate (dynamic pressure). Six open-chest, fentanyl-anesthetized dogs were instrumented with micromanometers and an electronically controlled mitral valve occluder in series with the electromagnetic flow probe. We reasoned as follows: If there were significant viscosity, then the dynamic pressure would be higher than the static pressure. The static pressure was measured when the ventricle was completely relaxed following a mitral valve occlusion after an arbitrary filling volume had been achieved. The dynamic pressure was determined by delaying the onset of filling until relaxation was complete and then measuring the pressure at the same volume that was achieved when the static pressure was measured. In 19 different hemodynamic situations, the dynamic and static pressures were identical (mean difference, 0.1 +/- 0.8 mm Hg), indicating that in the passive ventricle viscoelastic effects are insignificant and do not contribute to the left ventricular diastolic pressure under normal filling rates.


Human cytomegalovirus chemokine receptor US28 induces migration of cells on a CX3CL1-presenting surface.
Human cytomegalovirus (HCMV)-encoded G protein-coupled-receptor US28 is believed to participate in virus dissemination through modulation of cell migration and immune evasion. US28 binds different CC chemokines and the CX3C chemokine CX3CL1. Membrane-anchored CX3CL1 is expressed by immune-activated endothelial cells, causing redirection of CX3CR1-expressing leukocytes in the blood to sites of infection. Here, we used stable transfected cell lines to examine how US28 expression affects cell migration on immobilized full-length CX3CL1, to model how HCMV-infected leukocytes interact with inflamed endothelium. We observed that US28-expressing cells migrated more than CX3CR1-expressing cells when adhering to immobilized CX3CL1. US28-induced migration was G protein-signalling dependent and was blocked by the phospholipase Cβ inhibitor U73122 and the intracellular calcium chelator BAPTA-AM. In addition, migration was inhibited in a dose-dependent manner by competition from CCL2 and CCL5, whereas CCL3 had little effect. Instead of migrating, CX3CR1-expressing cells performed 'dancing-on-the-spot' movements, demonstrating that anchored CX3CL1 acts as a strong tether for these cells. At low receptor expression levels, however, no significant difference in migration potential was observed when comparing the migration of CX3CR1- and US28-expressing cells. Thus, these data showed that, in contrast to CX3CR1, which promotes efficient cell capture upon binding to anchored CX3CL1, US28 acts to increase the migration of cells upon binding to the same ligand. Overall, this indicates that infected cells probably move more than uninfected cells in inflamed tissues with high CX3CL1 expression, with soluble chemokines affecting the final migration.


Escherichia coli O157:H7 infection in humans.
To review the clinical relevance of Escherichia coli O157:H7 infection, including the epidemiology of the infection and its clinical presentations, pathogenesis, microbiology, diagnosis, treatment, and prevention. Articles on E. coli O157:H7 were identified through MEDLINE and the bibliographies of relevant articles. All articles and case reports describing E. coli O157:H7 and its infection were selected. The data were abstracted without judgments about study design. Data quality and validity were assessed by independent author reviews. Infection with E. coli O157:H7 presents with a wide spectrum of clinical manifestations, including asymptomatic carriage, nonbloody diarrhea, hemorrhagic colitis, the hemolytic-uremic syndrome, and thrombotic thrombocytopenic purpura. Not only is E. coli O157:H7 an important agent for hemorrhagic colitis, it is also one of the leading causes of bacterial diarrhea. Patients at extremes of age have an increased risk for infection and associated complications. Transmission of E. coli O157:H7 is primarily food-borne. Undercooked meat is the most common culprit, and secondary person-to-person spread is also important. The organism produces at least two Shiga-like toxins that differ antigenically, physicochemically, immunologically, and in their biological effects. These toxins are thought to have direct pathogenic significance in E. coli O157:H7 infection. This infection is usually diagnosed from a positive stool culture, from the presence of Shiga-like toxins, or both. Timely collection (within 7 days of illness onset) of a stool sample for culture is imperative for a high recovery rate. Treatment is primarily supportive and includes the management of complications as necessary. Antibiotic therapy has not been proved beneficial. Important public health measures include educating the public on the danger of eating undercooked meat, increasing physician awareness of E. coli O157:H7 infection, and mandating case reporting. Infection with E. coli O157:H7 presents with many clinical manifestations and should be included in the differential diagnosis for any patient with new-onset bloody diarrhea. Development of the hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura should raise strong suspicion of E. coli O157:H7 infection and should lead to prompt evaluation. If infection is confirmed, it should be reported to public health officials.


Permethrin pesticide induces NURR1 up-regulation in dopaminergic cell line: Is the pro-oxidant effect involved in toxicant-neuronal damage?
The mechanisms associated to the development of neurodegeneration due to pesticide exposure are not clear yet. In this study we evaluated how permethrin pesticide (PERM) can influence the Nurr1 gene and protein expression, and if a pro-oxidant activity of the pesticide contributes to up-regulation of Nurr1 in a dopaminergic cell line. Incubation of PC12 cells with 1μM PERM for 72h, leads to over expression of Nurr1 gene. This effect occurs with both corn oil and extra virgin olive oil (EVO) used to solubilize the toxicant. In order to investigate if the Nurr1 up-regulation induced by PERM, was associated to the pro-oxidant activity of the pesticide, anti-oxidants as glutathione (GSH), tocotrienols (TOC) and Electrolyzed Reduced Water (ERW) were tested. RT-PCR of Nurr1 showed that its up-regulation was significantly reduced in the presence of antioxidants, especially by addition of ERW. Western-blot analysis reveals that ERW was able to counterbalance the up-regulation of Nurr1 protein induced by permethrin exposure.


A tsunami about 1000 years ago in puget sound, washington.
Water surged from Puget Sound sometime between 1000 and 1100 years ago, overrunning tidal marshes and mantling them with centimeters of sand. One overrun site is 10 kilometers northwest of downtown Seattle; another is on Whidbey Island, some 30 kilometers farther north. Neither site has been widely mantled with sand at any other time in the past 2000 years. Deposition of the sand coincided-to the year or less-with abrupt, probably tectonic subsidence at the Seattle site and with landsliding into nearby Lake Washington. These findings show that a tsunami was generated in Puget Sound, and they tend to confirm that a large shallow earthquake occurred in the Seattle area about 1000 years ago.


Target therapy: new drugs or new combinations of drugs in malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is a disease with a poor prognosis due to its aggressive nature. The management of patients with MPM is controversial. Considering that the contribution of surgery and radiation therapy in the management of this disease is not yet established, systemic treatments are predominantly considered during the course of MPM. Unfortunately, the currently therapeutic armamentarium is scarce and its outcomes still appear modest. New treatment strategies are needed. In preclinical setting, cell cycle regulation, apoptosis, growth factor pathways, and angiogenesis pathways involved in the development of MPM have been identified. However, in clinical setting, several drugs targeting these pathways resulted without a significant activity. A deeper knowledge of the biology and pathogenesis of this disease is required to develop more effective tools for diagnosis, therapy and prevention. This paper reviews therapeutic advances in MPM, with a particular focus on new drugs and new association of drugs of target therapy.


The Chloroplast Tubulin Homologs FtsZA and FtsZB from the Red Alga Galdieria sulphuraria Co-assemble into Dynamic Filaments.
FtsZ is a homolog of eukaryotic tubulin and is present in almost all bacteria and many archaea, where it is the major cytoskeletal protein in the Z ring, required for cell division. Unlike some other cell organelles of prokaryotic origin, chloroplasts have retained FtsZ as an essential component of the division machinery. However, chloroplast FtsZs have been challenging to study because they are difficult to express and purify. To this end, we have used a FATT tag expression system to produce as soluble proteins the two chloroplast FtsZs from Galdieria sulphuraria, a thermophilic red alga. GsFtsZA and GsFtsZB assembled individually in the presence of GTP, forming large bundles of protofilaments. GsFtsZA also assembled in the presence of GDP, the first member of the FtsZ/tubulin superfamily to do so. Mixtures of GsFtsZA and GsFtsZB assembled protofilament bundles and hydrolyzed GTP at a rate approximately equal to the sum of their individual rates, suggesting a random co-assembly. GsFtsZA assembly by itself in limiting GTP gave polymers that remained stable for a prolonged time. However, when GsFtsZB was added, the co-polymers disassembled with enhanced kinetics, suggesting that the GsFtsZB regulates and enhances disassembly dynamics. GsFtsZA-mts (where mts is a membrane-targeting amphipathic helix) formed Z ring-like helices when expressed in Escherichia coli Co-expression of GsFtsZB (without an mts) gave co-assembly of both into similar helices. In summary, we provide biochemical evidence that GsFtsZA assembles as the primary scaffold of the chloroplast Z ring and that GsFtsZB co-assembly enhances polymer disassembly and dynamics.


Bioethics for clinicians: 17. Conflict of interest in research, education and patient care.
A conflict of interest occurs in a situation in which professional judgement regarding a primary interest, such as research, education or patient care, may be unduly influenced by a secondary interest, such as financial gain or personal prestige. Conflicts of interest exist in every walk of life, including medicine and science. There is nothing inherently unethical in finding oneself in a conflict of interest. Rather, the key questions are whether one recognizes the conflict and how one deals with it. Strategies include disclosing the conflict, establishing a system of review and authorization, and prohibiting the activities that lead to the conflict.


NCCN Task Force Report: Oral chemotherapy.
Oral chemotherapy is emerging as a new option for well-selected patients who can manage potentially complex oral regimens and self-monitor for potential complications. If a choice between oral and parenteral therapy is available, patients may opt for oral chemotherapy because it is more convenient to administer, allows them to avoid multiple office visits, and gives them a sense of control over their own cancer care. Whether these potential advantages are maintained in regimens that combine oral and parenteral drugs is less clear. The use of oral chemotherapeutic agents profoundly affects all aspects of oncology, including creating significant safety and adherence issues, shifting some traditional roles and responsibilities of oncologists, nurses, and pharmacists to patients and caregivers. The financing of chemotherapy is also affected. To address these issues, the NCCN convened a multidisciplinary task force consisting of oncologists, nurses, pharmacists, and payor representatives to discuss the impact of the increasing use of oral chemotherapy.


Bridging experiments and theory: isolating the effects of metal-ligand interactions on viscoelasticity of reversible polymer networks.
Polymer networks cross-linked by reversible metal-ligand interactions possess versatile mechanical properties achieved simply by varying the metal species and quantity. Although prior experiments have revealed the dependence of the network's viscoelastic behavior on the dynamics of metal-ligand interaction, a theoretical framework with quantitative relations that would enable efficient material design, is still lacking. One major challenge is isolating the effect of metal-ligand interaction from other factors in the polymer matrix. To address this challenge, we designed a linear precursor free from solvents, chain entanglements and polymer-metal phase separation to ensure that relaxation of the network is mainly governed by the dissociation and association of the metal-ligand cross-links. The rheological behavior of the networks was thoroughly characterized regarding the changes in cross-link density, binding stoichiometry and coordination stability, allowing quantitative comparison between experimental results and the sticky Rouse model. Through this process, we noticed that the presence of reversible cross-links increases the network modulus at high frequency compared to the linear polymer, and that the effective metal-ligand dissociation time increases dramatically with increasing the cross-link density. Informed by these findings, we modified the expression of the sticky Rouse model. For the polymer in which the metal center and ligands bond in a paired association, the relaxation follows our enhanced sticky Rouse model. For the polymer in which each reversible cross-link consists of multiple metal centers and ligands, the relaxation timescale is significantly extended due to greater restriction on the polymer chains. This systematic study bridges experiments and theory, providing deeper understanding of the mechanical properties of metallopolymers and facilitating material design.


Diet, physical activity and energy balance and their impact on breast and prostate cancers.
Obesity, physical activity status and circulating levels of sex steroid hormones and growth factor proteins are intrinsically linked to energy balance. Epidemiological studies have previously reported associations between these factors and the risk of hormone-related cancers such as prostate and breast cancer in men and postmenopausal women. An increasing number of intervention studies in 'at-risk' populations and cancer survivors are now investigating the effects of lifestyle interventions that promote negative energy balance on circulating levels of sex hormones and growth factor proteins as surrogate markers of cancer risk. Evidence from these studies suggests that lifestyle interventions can improve insulin sensitivity, alter the balance of circulating sex steroid hormones and insulin-like growth factor (IGF) axis proteins (including IGF-1 and the IGF binding proteins 1 and 3) and change the functioning of immune cells in peripheral blood. Such changes could influence the risk of developing hormone-related cancers, as well as having the potential to improve disease-free survival in patients recovering from cancer treatment. However, despite promising results, the methodological quality of most intervention studies has been limited due to small subject numbers, lack of adequate control groups or non-randomised designs and the absence of long-term follow-up measures. More intervention studies with randomised controlled designs, higher numbers of subjects and longer-term follow-up measures are needed to establish which combination of specific dietary and physical activity interventions work best for reducing risk in 'at-risk' populations and survivors, optimal dose-response relationships and the magnitude of change in surrogate markers of cancer risk that is required to induce a protective effect.


Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts.
Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.


A Proposed Set of Metrics to Reduce Patient Safety Risk From Within the Anatomic Pathology Laboratory.
Anatomic pathology laboratory workflow consists of 3 major specimen handling processes. Among the workflow are preanalytic, analytic, and postanalytic phases that contain multistep subprocesses with great impact on patient care. A worldwide representation of experts came together to create a system of metrics, as a basis for laboratories worldwide, to help them evaluate and improve specimen handling to reduce patient safety risk. Members of the Initiative for Anatomic Pathology Laboratory Patient Safety (IAPLPS) pooled their extensive expertise to generate a list of metrics highlighting processes with high and low risk for adverse patient outcomes. : Our group developed a universal, comprehensive list of 47 metrics for patient specimen handling in the anatomic pathology laboratory. Steps within the specimen workflow sequence are categorized as high or low risk. In general, steps associated with the potential for specimen misidentification correspond to the high-risk grouping and merit greater focus within quality management systems. Primarily workflow measures related to operational efficiency can be considered low risk. Our group intends to advance the widespread use of these metrics in anatomic pathology laboratories to reduce patient safety risk and improve patient care with development of best practices and interlaboratory error reporting programs.


Radionuclide thyroid studies: analysis of use and correlation with physical findings.
We assessed all thyroid radionuclide studies done at a single institution during one year and evaluated the indication for ordering each study as well as the concordance of study results with those of physical examination. We found that thyroid radionuclide imaging was overused, with at most 66% of scans being indicated (using the most generous classification of a proposed rating for indications). Radioactive iodine uptake measurement done without scanning was probably underused. Concordance between the results of physical examination and scanning was reflected by an overall agreement rate of 51%; agreement between results of scanning and physical examination beyond what might be expected by chance alone was reflected by a kappa value of .34. Concordance was strongest for diffuse goiters and weakest for normal findings.


Efficacy of pulsed dye laser in cosmetically distressing facial dermatoses in skin types IV and V.
Pulsed dye laser (PDL) has revolutionized treatment of vascular dermatoses. It has been successfully employed to treat several non-vascular conditions in fair skinned individuals without producing significant pigmentary and textural complications. A preliminary study was undertaken to assess its efficacy in cosmetically distressing facial, vascular and non-vascular dermatoses in Indian patients with skin types IV and V. Nine patients of ages 7 to 55 years, with facial verruca plana (VP- 4 cases), angiofibromas (AF- 4 cases) and multiple pyogenic granulomas (PG- one case) were recruited. They had no systemic complaints. Laser parameters used were (spot size/fluence/wavelength/pulse duration):VP- 5mm/5.5-7.5J/585nm/0.45ms; AF-5mm/6-8.5J/585nm/0.45ms;PG- 5mm/7J/585 and 595nm alternately/1.5ms. Response was assessed clinically and photographically. All VP lesions completely resolved after 2-4 sessions (mean 3.25 sessions), AF showed 50% regression in all cases after 2-3 sessions (mean 2.5 sessions) and > or =75% subsidence after 3-7 sessions (mean 5.5 sessions) and in PG, after 3 sessions, there was complete subsidence of small satellite lesions with moderate shrinkage of larger papules and complete resolution after 5 sessions. Complications included transient hyperpigmentation/hypopigmentation only. There was no recurrence during next 6 months. PDL offers significant cosmetic improvement in facial dermatoses in Indian patients.


High-field (9.4 T) MRI of brain dysmyelination by quantitative mapping of magnetic susceptibility.
The multilayered myelin sheath wrapping around nerve axons is essential for proper functioning of the central nervous system. Abnormal myelination leads to a wide range of neurological diseases and developmental disorders. Non-invasive imaging of myelin content is of great clinical importance. The present work demonstrated that loss of myelin in the central nervous system of the shiverer mouse results in a dramatic reduction of magnetic susceptibility in white matter axons. The reduction resulted in a near extinction of susceptibility contrast between gray and white matter. Quantitative magnetic susceptibility imaging and diffusion tensor imaging were conducted on a group of control and shiverer mice at 9.4 T. We measured the resonance frequency distribution of the whole brain for each mouse. Magnetic susceptibility maps were computed and compared between the two groups. It was shown that the susceptibility contrast between gray and white matter was reduced by 96% in the shiverer compared to the controls. Diffusion measurements further confirmed intact fiber pathways in the shiverer mice, ruling out the possibility of axonal injury and its potential contribution to the altered susceptibility. As an autosomal recessive mutation, shiverer is characterized by an almost total lack of central nervous system myelin. Our data provide new evidences indicating that myelin is the predominant source of susceptibility differences between deep gray and white matter observed in magnetic resonance imaging. More importantly, the present study suggests that quantitative magnetic susceptibility is a potential endogenous biomarker for myelination.


Chlamydia (Chlamydophila) pneumoniae-induced cell death in human coronary artery endothelial cells is caspase-independent and accompanied by subcellular translocations of Bax and apoptosis-inducing factor.
Atherosclerosis and coronary heart disease are causing high morbidity and mortality worldwide. Different risk factors have been demonstrated, but the exact mechanisms behind these diseases are still not fully understood. Recent studies have suggested Chlamydia pneumoniae to be involved in the pathogenesis, and increased apoptotic indexes in atherosclerotic plaques have been documented. In this study, we show that C. pneumoniae induces apoptosis and necrosis in populations of human coronary artery endothelial cells. Apoptosis was determined by TUNEL and flow cytometry after staining of cells with annexin V and propidium iodide, and defined as TUNEL-reactive or annexin V-positive, propidium iodide-negative cells. The apoptosis was induced within 2 h postinfection and increased with inoculation dose. The general caspase inhibitor z-VAD-fmk did not affect apoptotic frequencies. By immunochemistry and immunoblot, we demonstrated activation and subcellular translocation of the proapoptotic protein Bax, and translocation of apoptosis-inducing factor from the cytosol to the nucleus. These results indicate that C. pneumoniae-induced apoptosis in human coronary artery endothelial cells is caspase-independent and regulated by Bax and apoptosis-inducing factor.


Core beliefs and underlying assumptions in bulimia nervosa and depression.
In a pilot study, core beliefs and underlying assumptions were investigated in patients with bulimia nervosa, patients with depression and female controls, using a new self-report measure. The patients with bulimia nervosa did not differ from the patients with depression in negative self beliefs but they did differ in assumptions concerned with weight, shape and eating. Both groups of patients also differed from the female controls, with the exception of one comparison including the depressed patients. The findings support recent developments in cognitive theories of eating disorders. Treatment implications are briefly discussed.


Single tap identification for fast BCI control.
One of the major aims of BCI research is devoted to achieving faster and more efficient control of external devices. The identification of individual tap events in a motor imagery BCI is therefore a desirable goal. EEG is recorded from subjects performing and imagining finger taps with their left and right hands. A Differential Evolution based feature selection wrapper is used in order to identify optimal features in the spatial and frequency domains for tap identification. Channel-frequency band combinations are found which allow differentiation of tap vs. no-tap control conditions for executed and imagined taps. Left vs. right hand taps may also be differentiated with features found in this manner. A sliding time window is then used to accurately identify individual taps in the executed tap and imagined tap conditions. Highly statistically significant classification accuracies are achieved with time windows of 0.5 s and more allowing taps to be identified on a single trial basis.


Identification of a Paralog-Specific Notch1 Intracellular Domain Degron.
Upon Notch pathway activation, the receptor is cleaved to release the Notch intracellular domain (NICD), which translocates to the nucleus to activate gene transcription. Using Xenopus egg extracts, we have identified a Notch1-specific destruction signal (N1-Box). We show that mutations in the N1-Box inhibit NICD1 degradation and that the N1-Box is transferable for the promotion of degradation of heterologous proteins in Xenopus egg extracts and in cultured human cells. Mutation of the N1-Box enhances Notch1 activity in cultured human cells and zebrafish embryos. Human cancer mutations within the N1-Box enhance Notch1 signaling in transgenic zebrafish, highlighting the physiological relevance of this destruction signal. We find that binding of the Notch nuclear factor, CSL, to the N1-Box blocks NICD1 turnover. Our studies reveal a mechanism by which degradation of NICD1 is regulated by the N1-Box to minimize stochastic flux and to establish a threshold for Notch1 pathway activation.


Jaw in a Day: State of the Art in Maxillary Reconstruction.
Reconstruction of maxillary defects following tumor extirpation is challenging because of combined aesthetic and functional roles of the maxilla. One-stage reconstruction combining osseous free flaps with immediate osseointegrated implants are becoming the standard for mandibular defects, and have similar potential for maxillary reconstruction. A woman with maxillary Ewing sarcoma successfully treated at age 9 with neoadjuvant chemotherapy, right hemimaxillectomy, and obturator prosthetic reconstruction presented for definitive reconstruction, complaining of poor obturator fit, and hypernasality. Her reconstruction was computer-simulated by a multidisciplinary team, consisting of left hemi-Lefort I advancement and right maxillary reconstruction with a free fibula flap with immediate osseointegrated implants and dental prosthesis. Full dental restoration, midface projection, and oral fistula corrections were achieved in 1 operative stage using this approach. This patient demonstrates a successful approach for maxillary reconstruction using computer-planned orthognathic surgery with free fibula reconstruction and immediate osseointegrated implants with dental prosthesis.


Present status of laboratory diagnosis of human taeniosis/cysticercosis in Europe.
Human cysticercosis (CC) is a parasitic zoonosis caused by the larval stage (cyst) of the Taenia solium. Cysts can establish in the human central nervous system (neurocysticercosis, NCC) and other organs and tissues; they also develop in pigs, the natural intermediate host. Human taeniosis may be caused by T. solium, Taenia saginata and Taenia asiatica tapeworms; these infections are usually asymptomatic, but show a significant relevance as they perpetuate the parasites' life cycle, and, in the case of T. solium, they are the origin of (N)CC. In European Union (EU) member states and associated countries, the occurrence of autochthonous T. solium cases is debated, and imported cases have significantly increased lately; the status of T. asiatica has been never reported, whereas T. saginata is prevalent and causes an economic impact due to condemned carcasses. Based on their effects on the EU society, the specific diagnosis of these pathologies is relevant for their prevention and control. The aims of this study were to know the diagnostic tests used in European laboratories for human taeniosis/cysticercosis by means of a questionnaire, to determine potential gaps in their detection, and to obtain preliminary data on the number of diagnosed taeniosis/CC cases.


Dysplastic Ichthyosis uteri-like changes of the entire endometrium associated with a squamous cell carcinoma of the uterine cervix.
Ichthyosis uteri is an exceedingly rare condition in which the entire surface of the endometrium is replaced by stratified squamous epithelium. Originally described as an endometrial response to iatrogenically-introduced caustic substances, similar changes have since been described in association with a variety of inflammatory conditions of the endometrium. We describe herein a heretofore undescribed example of a moderately differentiated squamous cell carcinoma of the uterine cervix associated with extensive ichthyosis uteri-like changes of the entire adjacent endometrium. Additionally, the squamous epithelium of the latter also showed multifocal changes diagnostic of a low-grade squamous intraepithelial lesion. The potential genesis of this composite of findings is discussed, as is the neoplastic potential of ichthyosis uteri. It is concluded that a squamous cell carcinoma of the cervix extended proximally into the endometrium, and that there was a colonization of a pre-existing ichthyosis uteri by associated human papillomavirus. The possibility of significant cervical pathology should be considered when plaques of squamous epithelium with low grade dysplastic changes are identified in an endometrial biopsy or curettage.


Heritable somatic excision of a Drosophila transposon.
A mutation in the white gene of Drosophila mauritiana that results from insertion of the transposable element mariner is genetically unstable in both germ cells and somatic cells. Somatic instability is indicated by the occurrence of animals having mosaic eyes with patches of pigmented cells on a peach-colored background. Normally uncommon, the frequency of mosaicism is so greatly enhanced in a particular mutant strain that virtually every animal in the strain is an eye-color mosaic. The molecular basis of the mosaicism is the excision of the mariner element from its location in the DNA of the white gene in somatic cells. The phenomenon results from a single dominant genetic factor located in chromosome 3. Genetic control over the excision of transposable elements may play a role in determining the persistence of transposable elements in the genome.


Community-level plant-soil feedbacks explain landscape distribution of native and non-native plants.
Plant-soil feedbacks (PSFs) have gained attention for their potential role in explaining plant growth and invasion. While promising, most PSF research has measured plant monoculture growth on different soils in short-term, greenhouse experiments. Here, five soil types were conditioned by growing one native species, three non-native species, or a mixed plant community in different plots in a common-garden experiment. After 4 years, plants were removed and one native and one non-native plant community were planted into replicate plots of each soil type. After three additional years, the percentage cover of each of the three target species in each community was measured. These data were used to parameterize a plant community growth model. Model predictions were compared to native and non-native abundance on the landscape. Native community cover was lowest on soil conditioned by the dominant non-native, Centaurea diffusa, and non-native community cover was lowest on soil cultivated by the dominant native, Pseudoroegneria spicata. Consistent with plant growth on the landscape, the plant growth model predicted that the positive PSFs observed in the common-garden experiment would result in two distinct communities on the landscape: a native plant community on native soils and a non-native plant community on non-native soils. In contrast, when PSF effects were removed, the model predicted that non-native plants would dominate all soils, which was not consistent with plant growth on the landscape. Results provide an example where PSF effects were large enough to change the rank-order abundance of native and non-native plant communities and to explain plant distributions on the landscape. The positive PSFs that contributed to this effect reflected the ability of the two dominant plant species to suppress each other's growth. Results suggest that plant dominance, at least in this system, reflects the ability of a species to suppress the growth of dominant competitors through soil-mediated effects.


Plasmodium infection, anaemia and mosquito net use among school children across different settings in Kenya.
To investigate risk factors, including reported net use, for Plasmodium infection and anaemia among school children and to explore variations in effects across different malaria ecologies occurring in Kenya. This study analysed data for 49 975 school children in 480 schools surveyed during a national school malaria survey, 2008-2010. Mixed effects logistic regression was used to investigate factors associated with Plasmodium infection and anaemia within different malaria transmission zones. Insecticide-treated net (ITN) use was associated with reduction in the odds of Plasmodium infection in coastal and western highlands epidemic zones and among boys in the lakeside high transmission zone. Other risk factors for Plasmodium infection and for anaemia also varied by zone. Plasmodium infection was negatively associated with increasing socio-economic status in all transmission settings, except in the semi-arid north-east zone. Plasmodium infection was a risk factor for anaemia in lakeside high transmission, western highlands epidemic and central low-risk zones, whereas ITN use was only associated with lower levels of anaemia in coastal and central zones and among boys in the lakeside high transmission zone. The risk factors for Plasmodium infection and anaemia, including the protective associations with ITN use, vary according to malaria transmission settings in Kenya, and future efforts to control malaria and anaemia should take into account such heterogeneities among school children.


A Dyadic Action Control Trial in Overweight and Obese Couples (DYACTIC).
Enhancing physical activity in overweight and obese individuals is an important means to promote health in this target population. The Health Action Process Approach (HAPA), which was the theoretical framework of this study, focuses on individual self-regulation variables for successful health behavior change. One key self-regulation variable of this model is action control with its three subfacets awareness of intentions, self-monitoring and regulatory effort. The social context of individuals, however, is usually neglected in common health behavior change theories. In order to integrate social influences into the HAPA, this randomized controlled trial investigated the effectiveness of a dyadic conceptualization of action control for promoting physical activity. This protocol describes the design of a single-blind randomized controlled trial, which comprises four experimental groups: a dyadic action control group, an individual action control group and two control groups. Participants of this study are overweight or obese, heterosexual adult couples who intend to increase their physical activity. Blocking as means of a gender-balanced randomization is used to allocate couples to conditions and partners to either being the target person of the intervention or to the partner condition. The ecological momentary intervention takes place in the first 14 days after baseline assessment and is followed by another 14 days diary phase without intervention. Follow-ups are one month and six months later. Subsequent to the six-months follow-up another 14 days diary phase takes place.The main outcome measures are self-reported and accelerometer-assessed physical activity. Secondary outcome measures are Body Mass Index (BMI), aerobic fitness and habitual physical activity. This is the first study examining a dyadic action control intervention in comparison to an individual action control condition and two control groups applying a single-blind randomized control trial. Challenges with running couples studies as well as advantages and disadvantages of certain design-related decisions are discussed. This RCT was funded by the Swiss National Science Foundation (PP00P1_133632/1) and was registered on 27/04/2012 at http://www.isrctn.com/ISRCTN15705531.


Structural basis for alternating access of a eukaryotic calcium/proton exchanger.
Eukaryotic Ca(2+) regulation involves sequestration into intracellular organelles, and expeditious Ca(2+) release into the cytosol is a hallmark of key signalling transduction pathways. Bulk removal of Ca(2+) after such signalling events is accomplished by members of the Ca(2+):cation (CaCA) superfamily. The CaCA superfamily includes the Na(+)/Ca(2+) (NCX) and Ca(2+)/H(+) (CAX) antiporters, and in mammals the NCX and related proteins constitute families SLC8 and SLC24, and are responsible for the re-establishment of Ca(2+) resting potential in muscle cells, neuronal signalling and Ca(2+) reabsorption in the kidney. The CAX family members maintain cytosolic Ca(2+) homeostasis in plants and fungi during steep rises in intracellular Ca(2+) due to environmental changes, or following signal transduction caused by events such as hyperosmotic shock, hormone response and response to mating pheromones. The cytosol-facing conformations within the CaCA superfamily are unknown, and the transport mechanism remains speculative. Here we determine a crystal structure of the Saccharomyces cerevisiae vacuolar Ca(2+)/H(+) exchanger (Vcx1) at 2.3 Å resolution in a cytosol-facing, substrate-bound conformation. Vcx1 is the first structure, to our knowledge, within the CAX family, and it describes the key cytosol-facing conformation of the CaCA superfamily, providing the structural basis for a novel alternating access mechanism by which the CaCA superfamily performs high-throughput Ca(2+) transport across membranes.


Emerging investigator series: towards a framework for establishing the impacts of pharmaceuticals in wastewater irrigation systems on agro-ecosystems and human health.
Use of reclaimed wastewater for agricultural irrigation is seen as an attractive option to meet agricultural water demands of a growing number of countries suffering from water scarcity. However, reclaimed wastewater contains pollutants which are introduced to the agro-environment during the irrigation process. While water reuse guidelines do consider selected classes of pollutants, they do not account for the presence of pollutants of emerging concern such as pharmaceuticals and the potential risks these may pose. Here we use source-pathway-receptor analysis (S-P-R) to develop a holistic framework for evaluating the impacts of pharmaceuticals, present in wastewater used for agricultural irrigation, on human and ecosystem health and evaluate the data availability for the framework components. The developed framework comprised of 34 processes and compartments but a good level of knowledge was available for only five of these suggesting that currently it is not possible to fully establish the impacts of pharmaceuticals in wastewater irrigation systems. To address this, work is urgently needed to understand the fate and transport of pharmaceuticals in arable soil systems and the effects of chronic low-level exposure to these substances on microbes, invertebrates, plants, wildlife and humans. In addition, research pertaining to the fate, uptake and effects of pharmaceutical mixtures and metabolites is lacking as well as data on bio-accessibility of pharmaceuticals after ingestion. Scientific advancements in the five areas prioritised in terms of future research are needed before we are able to fully quantify the agricultural and human health risks associated with reclaimed wastewater use.


Transfusion-transmitted hepatitis C: A cluster of cases in transfusion-dependent thalassaemia patients in Sri Lanka.
To report the clinical and virologic epidemiology of a recent epidemic of hepatitis C in thalassaemia patients in Sri Lanka. Transfusion-dependent thalassaemia patients remain at risk for hepatitis C virus (HCV). Here, we report a cluster of recent HCV infections in Sri Lankan thalassaemia patients and examine the phylogenetic relationship of viral sequences. We conducted two prospective cross-sectional surveys of 513 patients in four Sri Lankan thalassaemia centres in 2014/2015 and re-surveyed one centre in 2016. We screened for anti-HCV antibodies using the CTK Biotech enzyme-linked immunosorbent assay (ELISA) kits and confirmed active infection by reverse transcription-polymerase chain reaction (RT-PCR) for HCV-RNA. HCV genomes were sequenced by unbiased target enrichment. Anti-HCV antibodies were found in 116/513 (22.6%) of patients initially tested. Active hepatitis C infection was found in 26 patients with no cases of active hepatitis B infection. Of 26 patients with HCV, two were infected with genotype 1(a), and the rest had 3(a). In a single centre (Ragama), 122 patients (120 new cases and two previously tested, but negative) were retested for anti-HCV antibodies. 32/122 (26.2%) patients were seropositive. Twenty-three (23/122; 18.8%) of these new cases were confirmed by HCV PCR (all genotype 3[a]). There is a significant cluster of recent HCV cases in multiply transfused thalassaemia patients in several centres in Sri Lanka. Most of the viruses shared a close phylogenetic relationship. The results are consistent with recent continuing transfusion-transmitted HCV infection. Routine surveillance for HCV of chronically transfused patients is required irrespective of screening of blood products.


Talking to Cows: Reactions to Different Auditory Stimuli During Gentle Human-Animal Interactions.
The quality of the animal-human relationship and, consequently, the welfare of animals can be improved by gentle interactions such as stroking and talking. The perception of different stimuli during these interactions likely plays a key role in their emotional experience, but studies are scarce. During experiments, the standardization of verbal stimuli could be increased by using a recording. However, the use of a playback might influence the perception differently than "live" talking, which is closer to on-farm practice. Thus, we compared heifers' (n = 28) reactions to stroking while an experimenter was talking soothingly ("live") or while a recording of the experimenter talking soothingly was played ("playback"). Each animal was tested three times per condition and each trial comprised three phases: pre-stimulus, stimulus (stroking and talking) and post-stimulus. In both conditions, similar phrases with positive content were spoken calmly, using long low-pitched vowels. All tests were video recorded and analyzed for behaviors associated with different affective states. Effects on the heifers' cardiac parameters were assessed using analysis of heart rate variability. Independently of the auditory stimuli, longer durations of neck stretching occurred during stroking, supporting our hypothesis of a positive perception of stroking. Observation of ear positions revealed longer durations of the "back up" position and less ear flicking and changes of ear positions during stroking. The predicted decrease in HR during stroking was not confirmed; instead we found a slightly increased mean HR during stroking with a subsequent decrease in HR, which was stronger after stroking with live talking. In combination with differences in HRV parameters, our findings suggest that live talking might have been more pleasurable to the animals and had a stronger relaxing effect than "playback." The results regarding the effects of the degree of standardization of the stimulus on the variability of the data were inconclusive. We thus conclude that the use of recorded auditory stimuli to promote positive affective states during human-animal interactions in experimental settings is possible, but not necessarily preferable.


Perceptions of Response Burden Associated with Completion of Patient-Reported Outcome Assessments in Oncology.
Patient response burden is often raised as a human subject concern in consideration of the length or complexity of patient-reported outcome (PRO) instruments used in oncology. To quantify patient response burden and identify its predictive factors. Data were collected presurgically during a prospective trial that used a comprehensive symptom and health-related quality-of-life (HRQOL) PRO assessment. A subset of patients also completed HRQOL interviews. Response burden was captured using an internally developed six-item instrument. Demographic and clinical characteristics as well as HRQOL scores were examined as potential predictors using hierarchical regression. Response burden was used to predict participant dropout at the first follow-up interval. A total of 275 patients (mean age 67.5 years; 23.6% female) completed surveys (n = 126) or surveys in addition to interviews (n = 149). Patients experienced low response burden (mean 12.19 ± 11.65). Repetitive questions were identified by 60 patients (21.8%), whereas 31.6% indicated that additional information should be gathered; 35 patients (12.7%) identified repetitive questions and expressed a desire for additional items. Low self-reported cognitive function was a significant predictor of higher response burden (β = -0.20; t(270) = -3.38; P = 0.01; model-adjusted R2 = 0.04). Response burden was not a significant predictor of study dropout. Despite completing a large battery of PRO measures and interviews, patients reported minimal response burden, with nearly one-third expressing that more questions should have been asked. Patients with lower cognitive function are more likely to report higher response burden when completing PRO measures. Further examination of patient characteristics related to response burden may reveal useful pathways for tailoring patient-centered interventions.


Body conformal antennas for superficial hyperthermia: the impact of bending contact flexible microstrip applicators on their electromagnetic behavior.
Hyperthermia is a powerful radiosensitizer for treatment of superficial tumors. This requires body conformal antennas with a power distribution as homogeneous as possible over the skin area. The contact flexible microstrip applicators (CFMA) operating at 434 MHz exist in several sizes, including the large size 3H and 5H. This paper investigates the behavior of the electromagnetic fields for the 3H and 5H CFMA in both flat and curved configurations, and the impact on performance parameters like the penetration depth (PD) and the effective heating depth (EHD). The underlying theory behind the electromagnetic behavior in curved situations is presented as well as numerical simulations of both flat and curved configurations. The results are compared to measurements of the electromagnetic field distributions in a cylindrical patient model. Due to their large size multimode solutions may exist, and our results confirm their existence. These multimode solutions affect both the power distribution and PD/EHD, with a dependence on applicator curvature. Therefore, the performance parameters like PD and EHD need to be carefully assessed when bending large size CFMA applicators to conform to the patient body. This conclusion also holds for other types of large size surface current applicators.


[Frequency of loss of heterozygosity on chromosome 17 in intrahepatic cholangiocarcinoma].
BACKGROUNDS/AIM: Intrahepatic cholangiocarcinoma is the second most common intrahepatic neoplasm. Carcinogenesis is believed to be a multistage process that occurs as a result of mutations in oncogenes and tumor suppressor genes. Loss of heterozygosity (LOH) is the phenotype of genetic instability which has been used as a tool for detecting genetic phenotype alterations. Large number of the molecular alterations have been described in human cancer. Among them, that of p53 is quite common. The aim of this study was to determine the frequency of LOH at chromosome 17p related with p53. Twenty cases who underwent hepatic resection due to intrahepatic cholangiocarcinoma, were included. LOH was analysed with four microsatellite markers by PCR. For the clinicopathologic parameters, tumor size, differentiation, and metastasis were evaluated. Fifteen patients (75%) showed LOH at one of the loci at the least. Five patients were LOH-high and 10 were LOH-low. The highest frequency of LOH was observed at D17S5 by 38.9%. Those of TP53, D17S796 and D17S513 were 29.4%, 21.4% and 35.3%, respectively. In addition, LOH tended to be more frequent when the tumor is mass forming type, poorly differentiated, or has tumor emboli or vascular invasion. This study showed that LOH was positive in 75% on chromosome 17p in intrahepatic cholangiocarcinoma which was relatively frequent at D17S5.


Computer-assisted design of butterfly bileaflet valves for the mitral position.
This paper describes the application of computer testing to a design study of butterfly bileaflet mitral prostheses having flat or curved leaflets. The curvature is in the plane normal to the pivot axes and is such that the convex sides of the leaflets face each other when the valve is open. The design parameters considered are the curvature of the leaflets and the location of the pivot points. In this study, stagnation is assessed by computing the smallest value (over the three openings of the valve) of the peak velocity, and hemodynamic performance is judged by a benefit/cost ratio: the net stroke volume divided by the mean transvalvular pressure difference. Unlike the case of a pivoting single-disc valve, the inclusion of a constraint on the maximum angle of opening of the leaflets is found to be essential for adequate, competent performance. Results are presented with both 85 degrees and 90 degrees constraints, since best performance is achieved with the opening-angle constraint in this range. Asymmetry of leaflet motion which is observed with flat leaflets in the mitral position is reduced with modest leaflet curvature. Leaflet curvature also ameliorates central orifice stagnation, which is observed with flat leaflets. Curvature of the valve produces the following improvements in comparison with the best flat valve when the opening-angle constraint is 85 degrees: a 38% increase in the minimum peak velocity and a 16% increase in the hemodynamic benefit/cost ratio. With a 90 degrees constraint the corresponding improvements are 34% and 20%, respectively.


Quality control by DNA repair.
Faithful maintenance of the genome is crucial to the individual and to species. DNA damage arises from both endogenous sources such as water and oxygen and exogenous sources such as sunlight and tobacco smoke. In human cells, base alterations are generally removed by excision repair pathways that counteract the mutagenic effects of DNA lesions. This serves to maintain the integrity of the genetic information, although not all of the pathways are absolutely error-free. In some cases, DNA damage is not repaired but is instead bypassed by specialized DNA polymerases.


In vitro expression and analysis of secreted fowlpox virus CC chemokine-like proteins Fpv060, Fpv061, Fpv116 and Fpv121.
The four CC chemokine-like proteins (Fpv060, Fpv061, Fpv116 and Fpv121) of fowlpox virus (FWPV) were over-expressed as His-tagged versions from a T7 promoter/EMCV IRES construct in vitro, by coupled transcription/translation, or in cell culture, by co-infection with two recombinant FWPVs (one expressing the chemokine-like protein and one expressing T7 RNA polymerase). All, except Fpv116, appeared to be glycosylated in the presence of microsomal membranes in vitro. In culture, all were secreted (even though secretion of Fpv061 was not predicted). Secreted forms of Fpv060 and Fpv121 were the most abundant forms of those two proteins. Glycosidase analysis of cellular and secreted forms confirmed that Fpv060, Fpv061 and Fpv121 were N-glycosylated and that the most abundant, cellular form of Fpv061 had been glycosylated but remained Endo H-sensitive (retained in the endoplasmic reticulum or Golgi). N-terminal sequence analysis of His-tagged Fpv060 and Fpv121 showed that they were processed at the predicted signal cleavage sites. Fpv060- and Fpv061-specific antipeptide sera allowed confirmation that the expression, processing and secretion of the native proteins were as determined for the His-tagged proteins. Isolation of knock-out mutants showed that all four proteins were non-essential for replication in tissue culture.


Diabody-Ig: a novel platform for the generation of multivalent and multispecific antibody molecules.
Multivalent mono- or bispecific antibodies are of increasing interest for therapeutic applications, such as efficient receptor clustering and activation, or dual targeting approaches. Here, we present a novel platform for the generation of Ig-like molecules, designated diabody-Ig (Db-Ig). The antigen-binding site of Db-Ig is composed of a diabody in the VH-VL orientation stabilized by fusion to antibody-derived homo- or heterodimerization domains, e.g., CH1/CL or the heavy chain domain 2 of IgE (EHD2) or IgM (MHD2), further fused to an Fc region. In this study, we applied the Db-Ig format for the generation of tetravalent bispecific antibodies (2 + 2) directed against EGFR and HER3 and utilizing different dimerization domains. These Db-Ig antibodies retained the binding properties of the parental antibodies and demonstrated unhindered simultaneous binding of both antigens. The Db-Ig antibodies could be purified by a single affinity chromatography resulting in a homogenous preparation. Furthermore, the Db-Igs were highly stable in human plasma. Importantly, only one short peptide linker (5 aa) per chain is required to generate a Db-Ig molecule, reducing the potential risk of immunogenicity. The presence of a fully functional Fc resulted in IgG-like pharmacokinetic profiles of the Db-Ig molecules. Besides tetravalent bispecific molecules, this modular platform technology further allows for the generation of other multivalent molecules of varying specificity and valency, including mono-, bi-, tri- and tetra-specific molecules, and thus should be suitable for numerous applications.


Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions.
Voltage-gated Kv1.3 and Ca2+-dependent KCa3.1 are the most prevalent K+ channels expressed by human and rat T cells. Despite the preferential upregulation of Kv1.3 over KCa3.1 on autoantigen-experienced effector memory T cells, whether Kv1.3 is required for their induction and function is unclear. Here we show, using Kv1.3-deficient rats, that Kv1.3 is involved in the development of chronically activated antigen-specific T cells. Several immune responses are normal in Kv1.3 knockout (KO) rats, suggesting that KCa3.1 can compensate for the absence of Kv1.3 under these specific settings. However, experiments with Kv1.3 KO rats and Kv1.3 siRNA knockdown or channel-specific inhibition of human T cells show that maximal T-cell responses against autoantigen or repeated tetanus toxoid stimulations require both Kv1.3 and KCa3.1. Finally, our data also suggest that T-cell dependency on Kv1.3 or KCa3.1 might be irreversibly modulated by antigen exposure.


Caring for Caregivers (C4C): study protocol for a pilot feasibility randomised control trial of Positive Written Disclosure for older adult caregivers of people with psychosis.
The caregivers of people who experience psychosis are themselves at risk of developing physical and mental health problems. This risk is increased for older adult caregivers who also have to manage the lifestyle and health changes associated with ageing. As a consequence, older adult caregivers are in particular need of support; we propose a Written Emotional Disclosure (WED) intervention, called Positive Written Disclosure (PWD). This is a pilot randomised controlled trial of PWD compared to a neutral writing control and a no writing condition. We aim to recruit 60 participants, 20 in each arm. This study will utilise a mixed-methods approach and collect quantitative (questionnaires) and qualitative (interviews) data. Quantitative data will be collected at baseline and 1, 3, and 6 months post baseline. Participants who complete a writing task (PWD or neutral writing control) will be invited to complete an exit interview to discuss their experiences of the intervention and study. The study is supported by a patient and public involvement group. The results of this trial will determine whether a definitive trial is justified. If so, the quantitative and qualitative findings will be used to refine the intervention and study protocols. ISRCTN, ISRCTN79116352. Registered on 23 January 2017.


Effects of a combined physical and psychosocial training for children with cancer: a randomized controlled trial.
Physical fitness and psychosocial function is often reduced in children during or shortly after cancer treatment. This study evaluates the effect of a combined physical exercise and psychosocial intervention on cardiorespiratory fitness, muscle strength, body composition, psychosocial function and health-related quality of life (HrQoL). In addition, intervention mediators, applicability and adherence were examined. This multicenter randomized controlled trial included 68 children with cancer [mean age 13.2 (SD: 3.1) years; 54% male] during treatment or within 12-months post-treatment. The 12-week intervention consisted of 24 individual physical exercise sessions supervised by a physiotherapist, and 6 psychosocial training sessions for children and 2 for parents. Physical fitness and psychosocial function were assessed at baseline, directly post-intervention and at 12 months' post-baseline. Generalized estimating equations were used to simultaneously assess intervention effects at short and long-term. Additionally, we evaluated within-group differences over time. Potential physical and psychosocial mediators in the intervention effect on HrQoL were examined using the product-of-coefficient test. Applicability and adherence were assessed by trainer-report. This study was able to compare 26 children who received the study intervention, with 33 children who received usual care. No significant differences in the effects of the intervention were found on physical fitness and psychosocial function at short-term. At 12-months follow-up, significantly larger improvements in lower body muscle strength (β = 56.5 Newton; 95% CI: 8.5; 104.5) were found in the intervention group when compared to the control group. Within-group changes showed significant improvements over time in HrQoL and bone density in both groups. Intervention effects on HrQoL were not significantly mediated by physical fitness and psychological function. Intervention applicability was satisfactory with an average session attendance of 67% and 22% dropout (mainly due to disease recurrence). This 12-week physical exercise and psychosocial training intervention for children with cancer was applicable and showed satisfactory adherence. We found no significant between-group differences in effect, except for a significant improvement in lower body muscle strength at long-term in the intervention group compared to the control group. Yet, both the intervention and the control group showed improvements in bone mineral density and HrQoL over time. The trial was registered at the Dutch Trial Registry ( NTR1531 ). Registered 12 November 2008.


Enhanced delayed matching performance in younger and older macaques administered the 5-HT4 receptor agonist, RS 17017.
Recent evidence indicates that the 5-HT4 subtype of serotonin receptor may modulate central cholinergic activity in regions of the mammalian CNS important to memory such as the frontal cortex, hippocampus and amygdala. These receptors could represent targets for drugs designed for the symptomatic therapy of Alzheimer's disease (AD) and other disorders of memory. In the present study, the binding activity of RS 17017 (previously described as a selective 5-HT4 agonist) was assessed across a number of neurotransmitter receptors and binding sites, pharmacokinetic data were obtained, and the compound was evaluated in macaques for mnemonic effects via a computer-assisted delayed matching-to-sample task (DMTS). Binding data confirmed the 5-HT4 selectivity of the compound, while pharmacokinetic results revealed low oral bioavailability, but a large volume of distribution of the compound. Significant and reproducible improvements in DMTS accuracy were observed after oral administration of the compound across a dose-effect series in both younger and older monkeys. The results suggest that RS 17017 offers a potential for memory enhancement in disorders involving cognitive decline, and are consistent with a role for central 5-HT4 receptors in memory. Improvements in DMTS performance in aged monkeys may have particular implications for neurodegenerative conditions such as AD, whereas positive results in the younger monkeys indicate that RS 17017 (or similar compounds) may have additional potential in the therapeutics of memory disorders not necessarily associated with advanced age.


Similar properties of transient, persistent, and resurgent Na currents in GABAergic and non-GABAergic vestibular nucleus neurons.
Sodium currents in fast firing neurons are tuned to support sustained firing rates >50-60 Hz. This is typically accomplished with fast channel kinetics and the ability to minimize the accumulation of Na channels into inactivated states. Neurons in the medial vestibular nuclei (MVN) can fire at exceptionally high rates, but their Na currents have never been characterized. In this study, Na current kinetics and voltage-dependent properties were compared in two classes of MVN neurons with distinct firing properties. Non-GABAergic neurons (fluorescently labeled in YFP-16 transgenic mice) have action potentials with faster rise and fall kinetics and sustain higher firing rates than GABAergic neurons (fluorescently labeled in GIN transgenic mice). A previous study showed that these neurons express a differential balance of K currents. To determine whether the Na currents in these two populations were different, their kinetics and voltage-dependent properties were measured in acutely dissociated neurons from 24- to 40-day-old mice. All neurons expressed persistent Na currents and large transient Na currents with resurgent kinetics tuned for fast firing. No differences were found between the Na currents expressed in GABAergic and non-GABAergic MVN neurons, suggesting that differences in properties of these neurons are tuned by their K currents.


The role of T cells in mouse cytomegalovirus myocarditis.
BALB/c mice infected with murine cytomegalovirus (MCMV) developed myocarditis. Athymic nu/nu mice infected with the virus did not develop myocarditis, in contrast to heterozygous T-cell competent nu/+mice. MCMV-infected BALB/c mice given cyclosporin A(CsA) a drug which inhibits the activation of T cells, showed a delay in the development of myocarditis relative to CsA-untreated mice infected with MCMV. However, BALB/c mice infected with MCMV, regardless of CsA treatment, developed both anti-MCMV antibodies and autoantibodies. Nu/nu mice infected with MCMV did not produce the anti-MCMV antibody response or the multiple autoantibody response which was observed in nu/+ MCMV-infected mice. Both nu/nu and CsA-treated animals displayed greater organ distribution of viral antigen than control MCMV-infected animals. These results suggest that the presence of a thymus is required for both the development of myocarditis and the multiple autoantibody response, which includes autoantibodies to cardiac muscle, and that CsA immunosuppression does not abrogate either myocarditis or the antibody response in mice following MCMV infection.


BNC nanoshells: a novel structure for atomic storage.
Quantum molecular dynamics (QMD) and density functional theory are employed in this work in order to study the structural and electronic properties of carbon, boron nitride or hybrid BNC nanoshells. The studied nanoshells can be formed by stacking two zigzag graphene nanoribbons, two zigzag boron nitride nanoribbons or one zigzag graphene nanoribbon on a boron nitride nanoribbon. In all cases only one of the edges of the ribbon is passivated, while the other one is left unpassivated. Our QMD results show that these nanoribbons collapse just a few femtoseconds after the beginning of the simulation, forming a coalesced structure in the shape of a shell. Our band structure calculations revealed that this structures may be metallic or semiconductor, depending on its stoichiometry. Furthermore, a spin splitting for energies near the Fermi level is predicted for both the pure carbon and the hybrid BNC-nanoshell systems. We further show that when a transverse electric field is applied to these systems, the nanoshell structure tends to open up. This effect can lead to the application of these nanoshells for molecular storage. As a proof of concept, We investigate this storage effect for the H2 molecule.


Field dependence and the factor structure of the General Health Questionnaire in normal subjects.
The factor structure of the General Health Questionnaire (GHQ) was investigated in a non-clinical sample in relation to the role of field dependence (assessed by the Hidden Figures Test) in influencing the extent to which different aspects of psychoneurotic disturbance are differentiated. Greater differentiation was achieved by the field independent (FI) group than by the field dependent (FD) group, as shown by: (i) the proportion of variance accounted for by the general factor in the principal components analysis of the 60-item GHQ data was lower (17 per cent) in the FI group than in the FD group (33 per cent); (ii) the factor loadings in the FI group, but not the FD group, corresponded closely with the four subscales of the 28-item scaled GHQ; (iii) the interscale correlations were significantly lower in the FI group than in the FD group. The implications of these findings are discussed, particularly their relevance to 'unitary' and 'distinct-syndrome' models of minor anxiety and depressive disorders, and the greater probability of occurrence of mixed states in field dependent subjects.


Laparoscopic revision of bariatric procedures: is it feasible?
Reoperative bariatric surgery is required in 10 per cent to 20 per cent of patients secondary to weight regain or complications of the previous procedure. This study evaluates the feasibility of performing the revision procedure laparoscopically. A retrospective review of all patients undergoing revision of a previous weight loss procedure between October 1998 and November 2003 was conducted. Demographics, indications for surgery, operative findings, and complications were reviewed. Thirty-nine revisions were performed in 37 patients. Indications for revision were failure to lose weight (22), gastric outlet stricture (10), refractory gastroesophageal reflux (GERD) (6), and blind loop syndrome (1). All 39 procedures were revised to Roux-en-Y gastric bypass (RYGBP), with 18 open revisions (OR) and 21 laparoscopic revisions (LR). Ten of the 21 LR (48%) were converted to an open procedure due to adhesions or unclear anatomy. Early complications requiring operation were noted in five procedures (two OR, three LR). Nine patients (seven OR, two LR) required surgery at least 3 months following their revision. One patient died (LR). The difference in body mass index (kg/m2) (BMI) pre- and post-op was 43.3+/-9.9 versus 37.4+/-9.2, P = 0.01 (follow-up 5 months), but no significant BMI differences between LR and OR patients were seen. Revisional bariatric surgery is associated with more complications requiring surgery early in the laparoscopic population versus more late complications in those approached open. Revisional bariatric surgery can be approached laparoscopically and with acceptable morbidity comparable to patients whose revision is approached open.


AiRCare: A naturalistic evaluation of the effectiveness of a protracted telephone-based recovery assistance program on continuing care outcomes.
Substance use disorder treatments are increasingly being contextualized within a disease management framework. Within this context, there is an identified need to maintain patients in treatment for longer periods of time in order to help them learn how to manage their disease. One way to meet this need is through telephone-based interventions that engage patients, and include more active outreach attempts and involvement of the patient's family. This study sought to evaluate the effectiveness of three formats of an intensive 12-month post-discharge telephone-based case management approach (AiRCare) on adherence to continuing care plans and substance use outcomes. Data were abstracted from electronic medical records for 379 patients (59.9% male) discharged from a residential treatment program located in the southwestern U.S. from 2013 to 2015. Patients were categorized into one of three groups and received telephone contacts based on their self-selection upon admission to residential treatment (i.e., patient only, family only, and both patient and family). Outcome variables included re-engagement and re-admission rates, quality of life, abstinence rates at 6 and 12 months, and compliance with continuing care plans. Favorable short- and long-term outcomes were found for the majority of patients, irrespective of case management group. There appeared to be some value in the addition of family contacts to patient contacts with respect to reducing risk for 12-month re-admission to residential care. These positive but preliminary indications of the effectiveness of AiRCare require replication in a well-powered, randomized controlled trial.