Effects of iso-nutrient fertilization on plankton production in earthen ponds of Bangladesh.
The experiment was conducted to evaluate the effects of iso-nutrients fertilization on fertilizer combinations, containing a similar amount of nitrogen (N) and phosphorus (P) were the production of plankton in earthen ponds for a period of eight weeks. Two different were tested in triplicate using six earthen ponds of 100 m2 each. The fertilizer combinations of cow manure, urea and Triple Super Phosphate (TSP) at the rate 5000, 125 and 100 kg ha(-1), respectively, containing approximately 102 kg N and 65 kg P was used for treatment-1 (T-l). Another combination of poultry-manure, urea and TSP at the rate of 2000, 125 and 100 kg ha(-1), respectively, was considered as the treatment-2 (T-2). The application rate of poultry manure was adjusted to make the nutrient (N and P) content of fertilizer combination in T-2 similar to that in T-1. Four groups of phytoplankton namely, Bacillariophyceae, Chlorophyceae, Cyanophyceae and Euglenophyceae and two groups of zooplankton namely, Crustacea and Rotifera were identified. The mean abundance of both phytoplankton (78.25 +/- 6.33 x 10(4) cells L(-1)) and zooplankton (57.63 +/- 4.59 x 10(4) cells L(-1)), were significantly higher (p < 0.05) in earthen ponds which treated with poultry manure. The result showed that despite iso-nutrients content, the nutrient status of poultry manure proved to be superior to cow manure.


Music Therapy When Death Is Imminent: A Phenomenological Inquiry.
Music therapists have described powerful case examples and personal experiences of providing music therapy for clients who are actively dying that suggest a complex experience that merits further exploration. This phenomenological study was conducted to gain a better understanding of the lived experience of music therapists working with clients who are actively dying. Four music therapists (2 female, 2 male), with an average of 10 years' hospice care experience, participated in semi-structured interviews. Data were analyzed using a phenomenological approach (Moustakas, 1994). Ten themes were distilled from the interviews and grouped into four categories: ongoing assessment, intuitive processes, countertransference, and the role of aesthetics and transformation. Participants described a flexible, dynamic clinical and personal process informed by ongoing assessment. These findings point to the importance of further discussion surrounding the clinical implications of the music therapist's internal experience and the role of assessment, intuition, and aesthetics in hospice music therapy.


Understanding Trust Drivers of S-commerce.
Trust has emerged as a pillar in the acceptance and use of new technologies in the ever-changing digital landscape, notably in the booming field of social commerce. The importance of this study lies in the fact that it explores in-depth the aspects of customer trust in Instashopping using new constructs that have yet to be explored in s-commerce literature. Focusing on Instashopping, the research proposed a multi-dimensional model of trust to examine the dynamics of user trust in social commerce platforms and analyses the effects of various factors, including institution-based trust, disposition to trust, personal inventiveness, perceived page quality, and overall web experience. Structural equation modelling and confirmatory factor analysis were used to examine data from 267 responses in a survey of university students in the United Arab Emirates who have used Instagram for shopping. The analysis showed that user trust and trusting beliefs were significantly influenced by the disposition to trust, institution-based trust, and general web experience. Still, no significant association was found between perceived site quality and trusting beliefs. These findings highlight the crucial part that user trust plays in social commerce platform success and how important it is for online platforms to build and maintain user trust. The work also contributes theoretically to the knowledge body by comprehensively analysing trust dynamics in social commerce. In practice, the knowledge gained can help organisations plan their strategy for gaining and keeping client trust, which is essential for long-term success in the digital arena. To ensure long-term success, organisations must emphasise building and maintaining customer trust.


Metal concentration and health risk assessment of fifteen wild mushrooms collected from the Ankara University Campus (Turkey).
The aim of this study is to analyze Fe, Mn, Cu, Zn, Co, Cd, Pb, and Ni contents of Cyclocybe cylindracea, Armillaria mellea, Bjerkandera adusta, Rheubarbariboletus armeniacus, Coprinellus disseminatus, C. micaceus, C. comatus, Inonotus hispidus, Lepista nuda, Leucoagaricus leucothites, Pleurotus ostreatus, Cerioporus squamosus, Schizophyllum commune, Scleroderma verrucosum, and Trametes trogii collected from the Ankara University Besevler 10th Year Campus (Turkey), an area where human settlement and traffic are intense. In addition to the elemental analysis, the daily intake of metal (DIM) and health risk index (HRI) values of the edible ones were also calculated. Fe, Mn, Cu, Zn, Co, Cd, Pb, and Ni concentrations of the samples were found to be 112.0-5079.0, 3.0-124.0, 4.0-77.0, 2.0-196.0, 0.18-2.98, 0.18-5.3, 0.04-10.98, and 0.22-8.23 mg/kg dry weight, respectively. As a result of DIM and HRI analysis, C. cylindracea, L. nuda, and C. squamosus were found to be within the reference dose limits determined by competent authorities and can be safely consumed in terms of all metals studied. However, the Cd, Co, and Fe contents of C. micaceus were found to be above 1.0 (1.06, 4.25, and 7.06, respectively). In addition, it has been found that A. mellea, R. armeniacus, C. comatus, L. leucothites, and P. ostreatus are toxic in terms of Cd/Co, Fe/Pb, Co/Fe, Cd, and Fe contents, respectively. As the area in question is a traffic intensive area, it has been concluded that the emissions of the vehicles should be controlled in terms of legal limits and that the consumption of some mushrooms in this region should not be preferred until necessary measures are taken.


Occupational biomechanics of athletes and dancers: a comparative approach.
Muscle strains represent more than a third of all injuries in both dancers and athletes. Although often overlooked, anatomic variations play an important role in the etiology of these injuries, as does strength imbalance between agonists and antagonists. The incidence of spondylolysis is unusually high in ballet dancers and certain athletic groups, such as gymnasts, javelin throwers, and weight-lifters. Mechanical factors play a major role and can be exacerbated by congenital abnormalities. Various permanent adaptive musculoskeletal changes have been described both in dancers and athletes, especially those that start at a very young age. Task-related adaptive changes can also be seen in isokinetic strength measurements of various muscle groups, such as the spine muscles of Flamenco dancers. Shoes and floor surfaces can be directly responsible in part or in whole for many sports and dance injuries. "Vibration-pressure" diagrams are suggested as an objective way to document their effect on biomechanical behavior.


Computer-aided design of modular protein devices: Boolean AND gene activation.
Many potentially useful synthetic gene networks require the expression of an engineered gene if and only if two different DNA-binding proteins exist in sufficient concentration. While some natural and engineered systems activate gene expression according to a logical AND-like behavior, they often utilize allosteric or cooperative protein-protein interactions, rendering their components unsuitable for a toolbox of modular parts for use in multiple applications. Here, we develop a quantitative model to demonstrate that a small system of interacting fusion proteins, called a protein device, can activate an engineered gene according to the Boolean AND behavior while using only modular protein domains and DNA sites. The fusion proteins are created from transactivating, DNA-binding, non-DNA binding, and protein-protein interaction domains along with the corresponding peptide ligands. Using a combined kinetic and thermodynamic model, we identify the characteristics of the molecular components and their rates of constitutive production that maximize the fidelity of AND behavior. These AND protein devices facilitate the creation of complex genetic programs and may be used to create gene therapies, biosensors and other biomedical and biotechnological applications that turn on gene expression only when multiple DNA-binding proteins are simultaneously present.


Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates.
Vaccination against SARS-CoV-2 provides an effective tool to combat the COIVD-19 pandemic. Here, we combined antigen optimization and nanoparticle display to develop vaccine candidates for SARS-CoV-2. We first displayed the receptor-binding domain (RBD) on three self-assembling protein nanoparticle (SApNP) platforms using the SpyTag/SpyCatcher system. We then identified heptad repeat 2 (HR2) in S2 as the cause of spike metastability, designed an HR2-deleted glycine-capped spike (S2GΔHR2), and displayed S2GΔHR2 on SApNPs. An antibody column specific for the RBD enabled tag-free vaccine purification. In mice, the 24-meric RBD-ferritin SApNP elicited a more potent neutralizing antibody (NAb) response than the RBD alone and the spike with two stabilizing proline mutations in S2 (S2P). S2GΔHR2 elicited two-fold-higher NAb titers than S2P, while S2GΔHR2 SApNPs derived from multilayered E2p and I3-01v9 60-mers elicited up to 10-fold higher NAb titers. The S2GΔHR2-presenting I3-01v9 SApNP also induced critically needed T-cell immunity, thereby providing a promising vaccine candidate.


Anthropogenic changes to the nighttime environment.
How the relative impacts of anthropogenic pressures on the natural environment vary between different taxonomic groups, habitats, and geographic regions is increasingly well established. By contrast, the times of day at which those pressures are most forcefully exerted or have greatest influence are not well understood. The impact on the nighttime environment bears particular scrutiny, given that for practical reasons (e.g., researchers themselves belong to a diurnal species), most studies on the impacts of anthropogenic pressures are conducted during the daytime on organisms that are predominantly day active or in ways that do not differentiate between daytime and nighttime. In the present article, we synthesize the current state of knowledge of impacts of anthropogenic pressures on the nighttime environment, highlighting key findings and examples. The evidence available suggests that the nighttime environment is under intense stress across increasing areas of the world, especially from nighttime pollution, climate change, and overexploitation of resources.


Inhibins and activins regulate mammary epithelial cell differentiation through mesenchymal-epithelial interactions.
Inhibins and activins are members of the transforming growth factor beta (TGFbeta) family. Female mice in which both alleles encoding the inhibin betaB subunit have been deleted are unable to nurse their pups. We have now identified a cause of lactation failure in these mice. Ductal elongation and alveolar morphogenesis are retarded. During puberty and pregnancy, ductal outgrowth and alveolar development are limited and morphologically abnormal endbuds persist in the glands of postpartum females. The alveolar lumina fail to expand at parturition due to the absence of secreted milk. Transplantation experiments have been performed to determine whether the absence of systemic- or mammary-derived betaB subunits are the cause for the incomplete and aberrant development. While transplanted intact glands from wild-type mice grew normally in betaB-deficient hosts, betaB-deficient glands remained underdeveloped in wild-type hosts. However, betaB-deficient epithelium developed normally when transplanted into the fat pad of wild-type hosts. This demonstrates that ductal elongation and epithelial cell differentiation during puberty and pregnancy require activin/inhibin signalling from the stroma. The results further show that distinct, though related, activins and inhibins perform unique functions and are not able to compensate for the absence of activin B and AB and inhibin B in the process of mammogenesis. The betaB-deficient mice provide the first genetic evidence for stromal signalling in the adult mammary gland in vivo.


Comparison and Optimization of Different Methods for the In Vitro Production of Plasmodium falciparum Gametocytes.
The generation of sexually committed parasites (gametocytogenesis) is poorly understood in malaria. If the mechanisms regulating this process were elucidated, new opportunities for blocking malaria transmission could be revealed. Here we compare several methods described previously for the in vitro production of Plasmodium falciparum gametocytes. Our approach relies on the combination of several factors that we demonstrated as impacting on or being critical to gametocytogenesis. An improved method has been developed for the in vitro production of P. falciparum gametocytes as the first step toward obtaining adequate numbers of pure gametocytes for in vitro studies, such as, for example, the identification of transmission blocking drugs.


Cutaneous melanoma of the head and neck. A review of 399 cases.
A retrospective search of the Duke University Melanoma Clinic patients identified 399 cases with primary malignant melanoma located in the head and neck region. Ninety-five percent of the deaths in this series were from metastatic melanoma. Various clinical and pathological data were examined and their effects on survivability and disease-free intervals were evaluated. The characteristics noted included sex, age, depth of the invasion, thickness, site of the lesion, histologic type, and nodal status. A multivariate regression analysis identified the following factors as having a negative effect on survival: nodular histologic type, scalp primary, increasing Clark level, and male sex. In comparing head and neck, extremity, and truncal primary sites, the median survival for patients with head and neck malignant melanomas was notably less. These differences correlated with a higher incidence for male patients, for patients with thicker lesions, and for patients with an increased frequency of nodular histologic type.


ABA-hypersensitive germination3 encodes a protein phosphatase 2C (AtPP2CA) that strongly regulates abscisic acid signaling during germination among Arabidopsis protein phosphatase 2Cs.
The phytohormone abscisic acid (ABA) regulates physiologically important developmental processes and stress responses. Previously, we reported on Arabidopsis (Arabidopsis thaliana) L. Heynh. ahg mutants, which are hypersensitive to ABA during germination and early growth. Among them, ABA-hypersensitive germination3 (ahg3) showed the strongest ABA hypersensitivity. In this study, we found that the AHG3 gene is identical to AtPP2CA, which encodes a protein phosphatase 2C (PP2C). Although AtPP2CA has been reported to be involved in the ABA response on the basis of results obtained by reverse-genetics approaches, its physiological relevance in the ABA response has not been clarified yet. We demonstrate in vitro and in vivo that the ahg3-1 missense mutation causes the loss of PP2C activity, providing concrete confirmation that this PP2C functions as a negative regulator in ABA signaling. Furthermore, we compared the effects of disruption mutations of eight structurally related PP2C genes of Arabidopsis, including ABI1, ABI2, HAB1, and HAB2, and found that the disruptant mutant of AHG3/AtPP2CA had the strongest ABA hypersensitivity during germination, but it did not display any significant phenotypes in adult plants. Northern-blot analysis clearly showed that AHG3/AtPP2CA is the most active among those PP2C genes in seeds. These results suggest that AHG3/AtPP2CA plays a major role among PP2Cs in the ABA response in seeds and that the functions of those PP2Cs overlap, but their unique tissue- or development-specific expression confers distinct and indispensable physiological functions in the ABA response.


Outcomes of octogenarians receiving aortic repair.
Abdominal aortic aneurysm (AAA) repair is recommended for aneurysms greater than 5.5 cm in men and 5 cm in women. Because AAA is more common among the elderly, we sought to evaluate contemporary practices of elective AAA repair and 2-year postoperative outcomes in octogenarians. We identified octogenarians undergoing elective AAA repair in the Vascular Quality Initiative from 2012 to 2019. We included patients undergoing endovascular (EVAR) and open (OAR) aortic repair. Demographics and comorbid conditions were compared between patient groups. Frailty was calculated using previously published methods. Patients with frailty scores above the 75th percentile of the operative cohort were considered high frailty. The primary outcome was 1- and 2-year mortality. Secondary outcomes included postoperative complications. Standard statistical methods were utilized. Cox proportional hazard models were used to identify factors that affect mortality. The frequency of AAA repair in octogenarians has remained stable. Of all aortic operations, 21.4% were performed on octogenarians; 9735 (23.3% of 41,712) EVAR and 755 (10.3% of 7325) OARs. Among octogenarian patients, 42.0% of EVARs were under size thresholds: 48.3% males ≤5.5 cm diameter and 21.5% females ≤5.0 cm diameter compared with 18.8% OARs: 23.4% males and 10.7% females. Additionally, 25.6% had high frailty scores. Among octogenarians, 1- and 2-year mortality was 9.3% ± 0.3% and 14.8% ± 0.4% for EVAR and 15.2% ± 1.3% and 18.9% ± 1.5% for OAR patients, respectively (P < .01). In-hospital mortality rate was higher after OAR (0.87% EVAR vs 7.55% OAR; P < .01) and differed with frailty (EVAR, low frailty 0.2% vs high frailty 1.7%; OAR, low frailty 2.3% vs high frailty 15.6%). For EVAR, patient factors associated with mortality included heart failure (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.06-1.25; P = .001) and dialysis (HR, 1.71; 95% CI, 1.13-2.59; P = .012). For OAR, coronary artery disease (HR, 1.55; 95% CI, 0.98-2.44; P = .062) was associated with mortality. Statin use was protective of mortality for all patients (EVAR: HR, 0.68; 95% CI, 0.60-0.78; P < .01): OAR: HR, 0.58; 95% CI, 0.37-0.92; P = .020). Among octogenarians, high frailty was independently associated with 2-year mortality (EVAR: HR, 3.36; 95% CI, 2.62-4.31; P < .01 and OAR: HR, 2.35; 95% CI, 1.09-5.10; P = .030). Nationally, a large portion of elective AAA repair in octogenarians is performed below recommended size thresholds, one-quarter of whom are frail with poor long-term 2-year mortality rates. High 2-year mortality following AAA repair in this age group exceeds the published risk of rupture for 5- to 5.5-cm AAA, suggesting that increase in the size threshold of elective repair among octogenarians should be explored.


How to assess eating disorder severity in males?The DSM-5 severity index versus severity based on drive for thinness.
Using a male eating disorder (ED) sample, this study assessed the clinical utility of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) severity indices for males with anorexia nervosa (AN) and bulimia nervosa (BN) and compared it to an alternative transdiagnostic severity categorisation based on drive for thinness (DT). The participants included 143 males with an ED (60 [42.0%] AN and 83 [58.0%] BN) diagnosis, who were classified using these two severity classifications. The different severity categories were then compared based on ED symptoms, general psychopathology, and personality traits. Our results revealed that the DSM-5 "mild" and DT "low" severity categories were most prevalent in the AN and BN male patients. Clinically significant findings were strongest for the DT categorisation for both AN and BN. The current findings provide initial support for an alternative transdiagnostic DT severity classification for males that may be more clinically meaningful than the DSM-5 severity indices.


Concomitant infections, parasites and immune responses.
Concomitant infections are common in nature and often involve parasites. A number of examples of the interactions between protozoa and viruses, protozoa and bacteria, protozoa and other protozoa, protozoa and helminths, helminths and viruses, helminths and bacteria, and helminths and other helminths are described. In mixed infections the burden of one or both the infectious agents may be increased, one or both may be suppressed or one may be increased and the other suppressed. It is now possible to explain many of these interactions in terms of the effects parasites have on the immune system, particularly parasite-induced immunodepression, and the effects of cytokines controlling polarization to the Th1 or Th2 arms of the immune response. In addition, parasites may be affected, directly or indirectly, by cytokines and other immune effector molecules and parasites may themselves produce factors that affect the cells of the immune system. Parasites are, therefore, affected when they themselves, or other organisms, interact with the immune response and, in particular, the cytokine network. The importance of such interactions is discussed in relation to clinical disease and the development and use of vaccines.


Striking paucity of HLA-A, B, C and beta 2-microglobulin on human neuroblastoma cell lines.
Monoclonal antibodies to beta 2-microglobulin (beta 2m), and to the native two-chain molecule, were used to assess the expression of the HLA-A, B, C molecules on human neuroblastoma-derived cell lines. In radioimmuno-, cytotoxic, and microscopic assays, employing fresh and fixed cells, neuroblastoma cells show at best weak activity as compared to glial or lymphoid cells. In binding inhibition assays, neuroblastoma extracts were 200- to 1800-fold less efficient in inhibiting the antibodies than were glial or lymphoid extracts. Immunoprecipitation and SDS-PAGE analysis confirmed that a beta m-like chain is synthesized by the neuroblastoma cells, but the HLA chain could not be visualized by this technique. HLA-A, B, C and beta 2m levels are known to vary among tissues and cell lines. Yet the magnitude of the differences between the neuroblastoma and lymphoid lines is much greater than the reported differences in expression between some of these same lymphoid lines and many other nonlymphoid malignant or nonmalignant cell types. Metastatic neuroblastoma tumor in bone marrow also showed weak HLA-A, B, C activity, with the cells appearing negative in microscopic assays. Possible clinical implications are discussed.


[Trophoblastic beta-globulin in immunoglobulin preparations].
The content of trophoblastic beta-globulin in 142 lots of commercial immunoglobulin preparations from 20 manufacturers, produced from placental, abortion and donor blood sera, has been studied. 83% of lots from abortion blood serum and 94% of lots from placental blood serum have been found to contain the admixture of this beta-globulin, its concentration in the lots from placental blood serum being significantly higher. The method for the detection of trophoblastic beta-globulin may be used for evaluating the quality of immunoglobulin preparations as it indicates the degree of their purification from placental proteins.


Visuoperceptual Analysis of the Videofluoroscopic Study of Swallowing: An International Delphi Study.
The Videofluoroscopic Swallow Study (VFSS) is a commonly used dysphagia assessment that is routinely analysed visuoperceptually. However, no consensus exists regarding which visuoperceptual measures should be used to analyse VFSSs. Current visuoperceptual measures for VFSSs are limited by poor quality and incomplete or indeterminate psychometric properties. This study aimed to establish the content validity for a new visuoperceptual VFSS measure for oropharyngeal dysphagia in adults, by identifying relevant domains of the construct and generating items and corresponding response scales. Consensus among experts in dysphagia and VFSS from over 20 countries was achieved across three rounds of anonymous online surveys, using the Delphi technique. Participants judged relevance and comprehensiveness of definitions of visuoperceptual domains of VFSS and the relevance of various domains to the overall construct. After reaching consensus on definitions of relevant domains, consensus on items were established using the same process. Participants achieved consensus on definitions of 32 domains recommended for analysis, and at least one item per domain (range 1-4). Domains selected by participants included both those which occur in existing measures and domains which have not been included in any measures to date. This study will form the basis for content validity of a new measure for VFSS. This first phase of developing a visuoperceptual measure of VFSS resulted in the identification of 32 domains and 60 items for oropharyngeal dysphagia. Developers can now advance to the next phase of measure construction; prototype development and psychometric testing.


The neuro-immune interaction in airway inflammation through TRPA1 expression in CD4+ T cells of asthmatic mice.
Asthma is an inflammatory disorder of the airways dominated by a Th2-type pattern. Recently, an emerging interest arises whether transient receptor potential ankyrin 1 (TRPA1) plays a potential role in the adaptive immune response. In this study, the role of TRPA1 in the development and exacerbation of asthma was explored. The classic OVA-induced asthma and OVA plus PM2.5-induced exacerbated asthma model were used. The CD4+ T cells were sorted from spleen in asthmatic and exacerbated asthmatic mice. In the BALB/c mice treated with OVA, the increased phenotype of asthma was obtained, accompanied by the high expression of TRPA1 in lung tissue and levels of IL-4, IL-13, NGF, PGD2 in BAL. In contrast, genetic deletion or pharmacological inhibition of TRPA1 alleviated the phenotype of asthma. Similarly, in wild type (WT) C57BL/6 mice treated with OVA, the high expression of TRPA1 in lung tissues was obtained, and the levels of IL-4, IL-13, NGF, PGD2 in BAL remarkably increased when compared with those in the TRPA1 deleted mice. Furthermore, high expression of TRPA1 was detected in CD4+ T cells of OVA-treated WT C57BL/6 mice. Additional detection in the asthmatic mice exacerbated by OVA plus PM2.5 also showed high TRPA1 expression in lung tissue and CD4+ T cells. All evidence confirmed that TRPA1 is essential for the development and exacerbation of asthma. More importantly, the expression of TRPA1 in CD4+ T cells of different asthmatic mice suggested that it might be involved in neuro-immune interactions in airway inflammation of asthmatic mice.


Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta.
Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher's exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47-74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50-84) mg/L, in comparison to those who remained NAb-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a one-standard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.


Ionogran in revision arthroplasty.
Glass ionomer cement (Ionocem) was developed for use in bone surgery and is reported to be notably biocompatible. Between 1991 and 1994 we performed revision operations for aseptic loosening of arthroplasties of the hip on 45 patients using this material in its granulate form (Ionogran) mixed with homologous bone as a bone substitute. Of these 45 patients, 42 were followed up for a mean of 42 months. Early reloosening of the acetabular component has occurred in ten after a mean of 30 months. Histological examination showed large deposits of aluminium in the adjacent connective tissue and bone. Osteoblastic function and bone mineralisation were clearly inhibited. The serum levels of aluminium were also increased. The toxic damage at the bone interface caused by high local levels of aluminium must be seen as an important factor in the high rate of early reloosening. Our findings cast doubt on the biocompatibility of this material and we do not recommend continuation of its further use in orthopaedic surgery.


Reduction of peristalsis-related gastrointestinal streak artifacts with dual-energy CT: a patient and phantom study.
The purpose of the study was to assess the ability of rapid-kV switching (rs) dual-energy computed tomography (DECT) to reduce peristalsis-related streak artifact. rsDECT images of 100 consecutive patients (48 male, 52 female, mean age 57 years) were retrospectively evaluated in this institutional review board-approved study. Image reconstructions included virtual monochromatic 70 and 120 keV images, as well as iodine(-water) and water(-iodine) material decomposition images. We recorded the presence and severity of artifacts qualitatively (4-point scale) and quantitatively [iodine/water concentrations, Hounsfield units, gray scale values (GY)] and compared to corresponding unaffected reference tissue. Similar measures were obtained in DECT images of a peristalsis phantom. Wilcoxon signed-rank and paired t tests were used to compare results between different image reconstructions. Peristalsis-related streak artifacts were found in 49 (49%) of the DECT examinations. Artifacts were significantly more severe in 70, 120, and water(-iodine) images than in iodine(-water) images (qualitative readout P < 0.001, each). Quantitative measurements were significantly different between the artifact and the reference tissue in 70, 120 keV, and water(-iodine) images (P < 0.001 for both HU and GY for each image reconstruction), but not significantly different in iodine(-water) images (iodine concentrations P = 0.088 and GY P = 0.111). Similar results were seen in the peristalsis DECT phantom study. Peristalsis-related streak artifacts seen in 70, 120 keV, and water(-iodine) images are substantially reduced in iodine(-water) images at rsDECT.


[Reparative regeneration of microvascular anastomosis].
Dynamics of reparative regeneration of the sutural anastomosis of the abdominal aorta has been studied in 90 white mice during the time from 1 day up to 1 year. The operation has been performed by means of microsurgical technique. Histological, histochemical, electron microscopic and radioautographic (3H-thymidine and 3H-uridine labelling) methods have been used. By the 7th day fibrin is organized on the adventitia, the scar along the resection line is formed, endothelial lining and middle layer of the vascular wall are restored. As sources of regeneration in the anastomosis serve cellular elements preserved in the lesion margins. Further maturation of the formed structures and formation of the initial thickening by migrating smooth muscle cells of the middle layer take place. Completeness and typicity depend on preservation of the elastic carcass in the middle layer and adventitia.


Optimal Utility of H-Reflex RDD as a Biomarker of Spinal Disinhibition in Painful and Painless Diabetic Neuropathy.
Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2-4 and 2-5 at 1 Hz, AUC = 0.84 (95%CI 0.76-0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.


Controlled Flexible Coordination in Tripodal Iron(II) Phosphane Complexes: Effects on Reactivity.
The possibility to alter properties of metal complexes without significant steric changes is a useful tool to tailor the reactivity of the complexes. Herein we present the synthesis of iron complexes with the tripodal phosphane ligands Triphos and Triphos(Si) and report on their different coordination properties. Whereas reaction of Triphos(Si) and FeX2 (X = Cl, Br) exclusively afforded (Triphos(Si))FeX2 with a κ(2)-coordinated ligand, the homologous C-derived Fe complexes show rapid conversion in solution to afford [(Triphos)Fe(CH3CN)3][Fe2Cl6] or [(Triphos)Fe(CH3CN)3][FeBr4], respectively. The structural conversion was found to be temperature- and solvent-dependent and was accompanied by a linear change of the overall magnetization. The different ligand influence was shown to have a significant effect on the ability of (Triphos(Si))FeCl2 and (Triphos)FeCl2 to perform the Sonogashira cross-coupling reaction of 4-iodotoluene and phenyl acetylene as well as the hydrosilylation of acetophenone. The results presented herein show the different coordination properties of two structurally homologous tripodal ligands and demonstrate the importance of geometrically controlled ligand field splitting on the stability and reactivity of metal complexes. The C/Si exchange therefore provides a simple and straightforward tool to manipulate properties and reactivity of metal complexes.


Wilson disease and idiopathic copper toxicosis.
The pathogenic agent of both Wilson disease (WD) and non-Indian childhood cirrhosis (which we term idiopathic copper toxicosis, or ICT) is copper accumulating to excess in the liver. Inheritance of a pair of alleles of an autosomal recessive gene on chromosome 13 is necessary and sufficient to cause such copper accumulation in WD; reducing the dietary intake of copper cannot prevent the development of WD. In contrast, the lethal accumulations of copper in children with ICT have been attributed primarily to an increased dietary intake of copper. However, 64 124 child-year exposures of children under the age of 6 y to drinking water containing a copper concentration of approximately 125.9 micromol/L (8 mg/L) produced no deaths from any form of liver disease. Moreover, the ICT of seven infants was attributed primarily to drinking water containing < 110.2 micromol Cu/L (7 mg/L) despite evidence of the presence of a genetic defect in three of the patients, one of whom was exclusively breast-fed. These data suggest that ICT cannot be caused solely by increased dietary intake of copper and occurs only in children with an identified genetic defect.


Immunohistochemical and ultrastructural characterization of the ovarian surface epithelium of Japanese quail (Coturnix japonica).
Contrary to humans, most ovarian tumors in other species do not arise from the ovarian surface epithelium but are of follicular-, stromal- or germ-cell origin. One of the few species where ovarian cancer arises from the ovarian surface epithelium (OSE) is chicken (Gallus domesticus). Little is known about the morphology of the OSE in other avian species. In our study we analyzed the OSE morphology of Japanese quail (Coturnix japonica) using ultrastructural and histochemical techniques. Carbohydrate residues have been studied by using a panel of fluorescein isothiocyanate labeled lectins. Japanese quails are commonly used animal models in biomedical research as their housing is comparatively inexpensive and they show a short generation interval. Our ultrastructural and histochemical results demonstrate that the quail ovarian surface epithelium shows characteristic features which resemble the epithelia of both chicken and human. Additionally, the ovarian surface epithelium of the Japanese quail contains cytokeratin as well as vimentin intermediate filaments in their cytoplasm. Therewith and among other parts the quail OSE shows many characteristic features also seen in those of humans, which may qualify quail's ovary as a potential animal model for human ovarian carcinomas.


Phenotypic Switching Can Speed up Microbial Evolution.
Stochastic phenotype switching has been suggested to play a beneficial role in microbial populations by leading to the division of labour among cells, or ensuring that at least some of the population survives an unexpected change in environmental conditions. Here we use a computational model to investigate an alternative possible function of stochastic phenotype switching: as a way to adapt more quickly even in a static environment. We show that when a genetic mutation causes a population to become less fit, switching to an alternative phenotype with higher fitness (growth rate) may give the population enough time to develop compensatory mutations that increase the fitness again. The possibility of switching phenotypes can reduce the time to adaptation by orders of magnitude if the "fitness valley" caused by the deleterious mutation is deep enough. Our work has important implications for the emergence of antibiotic-resistant bacteria. In line with recent experimental findings, we hypothesise that switching to a slower growing - but less sensitive - phenotype helps bacteria to develop resistance by providing alternative, faster evolutionary routes to resistance.


Learning the Mental Health Impact of COVID-19 in the United States With Explainable Artificial Intelligence: Observational Study.
The COVID-19 pandemic has affected the health, economic, and social fabric of many nations worldwide. Identification of individual-level susceptibility factors may help people in identifying and managing their emotional, psychological, and social well-being. This study is focused on learning a ranked list of factors that could indicate a predisposition to a mental disorder during the COVID-19 pandemic. In this study, we have used a survey of 17,764 adults in the United States from different age groups, genders, and socioeconomic statuses. Through initial statistical analysis and Bayesian network inference, we have identified key factors affecting mental health during the COVID-19 pandemic. Integrating Bayesian networks with classical machine learning approaches led to effective modeling of the level of mental health prevalence. Overall, females were more stressed than males, and people in the age group 18-29 years were more vulnerable to anxiety than other age groups. Using the Bayesian network model, we found that people with a chronic mental illness were more prone to mental disorders during the COVID-19 pandemic. The new realities of working from home; homeschooling; and lack of communication with family, friends, and neighbors induces mental pressure. Financial assistance from social security helps in reducing mental stress during the COVID-19-generated economic crises. Finally, using supervised machine learning models, we predicted the most mentally vulnerable people with ~80% accuracy. Multiple factors such as social isolation, digital communication, and working and schooling from home were identified as factors of mental illness during the COVID-19 pandemic. Regular in-person communication with friends and family, a healthy social life, and social security were key factors, and taking care of people with a history of mental disease appears to be even more important during this time.


Nocturia in patients with overactive bladder.
Nocturia is a frequent urinary symptom in overactive bladder (OAB) patients, which usually exerts a negative impact upon their quality of life. This study describes the profile of the OAB patient with nocturia, in order to contribute to the adequate identification and medical management of these subjects. Multicenter, national observational study of 1454 patients over 18 years of age,previously diagnosed with OAB. The relationship between nocturia and different personal and clinical variables was studied, and logistic regression models were used to identify variables independently associated with nocturia in both women and men. 84.6% of the patients presented nocturia, considering the restrictive criterion of two or more micturition episodes per night (96.8% according to the ICS definition). Urinary symptoms of frequency, urgency and urge incontinence were associated in a bivariate analysis with nocturia for both genders, while the voiding difficulty variable "pain" was only associated in women, and the voiding difficulty variable "straining" only in men. Older age and presence of comorbidities were associated both in bivariate analysis and independently in logistic regression models to the presence of nocturia in OAB patients of both genders. This study revealed that the profile of subjects with previously diagnosed OAB and nocturia corresponded to older age and the presence of comorbidities of a certain impact for both men and women. The profile for OAB patients with nocturia differs from those previously reported for patients suffering from nocturia and other urinary pathologies.


High-Throughput Screening of Microbial Isolates with Impact on Caenorhabditis elegans Health.
With its small size, short lifespan, and easy genetics, Caenorhabditis elegans offers a convenient platform to study the impact of microbial isolates on host physiology. It also fluoresces in blue when dying, providing a convenient means of pinpointing death. This property has been exploited to develop high-throughput label-free C. elegans survival assays (LFASS). These involve time-lapse fluorescence recording of worm populations set in multiwell plates, from which population median time of death can be derived. The present study adopts the LFASS approach to screen multiple microbial isolates at once for the effects on C. elegans susceptibility to severe heat and oxidative stresses. Such microbial screening pipeline, which can notably be used to prescreen probiotics, using severe stress resistance as a proxy for host health is reported here. The protocol describes how to grow both C. elegans gut microbiota isolate collections and synchronous worm populations in multiwell arrays before combining them for the assays. The example provided covers the testing of 47 bacterial isolates and one control strain on two worm strains, in two stress assays in parallel. However, the approach pipeline is readily scalable and applicable to the screening of many other modalities. Thus, it provides a versatile setup to rapidly survey a multiparametric landscape of biological and biochemical conditions that impact C. elegans health.


Electronic Nicotine Delivery Systems: An Updated Policy Statement from the American Association for Cancer Research and the American Society of Clinical Oncology.
Combustible tobacco use has reached historic lows, demonstrating the importance of proven strategies to reduce smoking since publication of the 1964 Surgeon General's report. In contrast, the use of electronic nicotine delivery systems (ENDS), specifically e-cigarettes, has grown to alarming rates and threatens to hinder progress against tobacco use. A major concern is ENDS use by youth and adults who never previously used tobacco. While ENDS emit fewer carcinogens than combustible tobacco, preliminary evidence links ENDS use to DNA damage and inflammation, key steps in cancer development. Furthermore, high levels of nicotine can also increase addiction, raise blood pressure, interfere with brain development, and suppress the immune system. The magnitude of long-term health risks will remain unknown until longitudinal studies are completed. ENDS have been billed as a promising tool for combustible tobacco cessation, but further evidence is needed to assess their potential efficacy for adults who smoke. Of concern, epidemiological studies estimate that approximately 15% to 42% of adults who use ENDS have never used another tobacco product, and another 36% to 54% "dual use" both ENDS and combustible tobacco. This policy statement details advances in science related to ENDS and calls for urgent action to end predatory practices of the tobacco industry and protect public health. Importantly, we call for an immediate ban on all non-tobacco-flavored ENDS products that contain natural or synthetic nicotine to reduce ENDS use by youth and adults who never previously used tobacco. Concurrently, evidence-based treatments to promote smoking cessation and prevent smoking relapse to reduce cancer incidence and improve public health remain top priorities for our organizations. We also recognize there is an urgent need for research to understand the relationship between ENDS and tobacco-related disparities.


Characterization of a phylogenetically distinct extradiol dioxygenase involved in the bacterial catabolism of lignin-derived aromatic compounds.
The actinobacterium Rhodococcus jostii RHA1 grows on a remarkable variety of aromatic compounds and has been studied for applications ranging from the degradation of polychlorinated biphenyls to the valorization of lignin, an underutilized component of biomass. In RHA1, the catabolism of two classes of lignin-derived compounds, alkylphenols and alkylguaiacols, involves a phylogenetically distinct extradiol dioxygenase, AphC, previously misannotated as BphC, an enzyme involved in biphenyl catabolism. To better understand the role of AphC in RHA1 catabolism, we first showed that purified AphC had highest apparent specificity for 4-propylcatechol (kcat/KM ∼106 M-1 s-1), and its apparent specificity for 4-alkylated substrates followed the trend for alkylguaiacols: propyl > ethyl > methyl > phenyl > unsubstituted. We also show AphC only poorly cleaved 3-phenylcatechol, the preferred substrate of BphC. Moreover, AphC and BphC cleaved 3-phenylcatechol and 4-phenylcatechol with different regiospecificities, likely due to the substrates' binding mode. A crystallographic structure of the AphC·4-ethylcatechol binary complex to 1.59 Å resolution revealed that the catechol is bound to the active site iron in a bidentate manner and that the substrate's alkyl side chain is accommodated by a hydrophobic pocket. Finally, we show RHA1 grows on a mixture of 4-ethylguaiacol and guaiacol, simultaneously catabolizing these substrates through meta-cleavage and ortho-cleavage pathways, respectively, suggesting that the specificity of AphC helps to prevent the routing of catechol through the Aph pathway. Overall, this study contributes to our understanding of the bacterial catabolism of aromatic compounds derived from lignin, and the determinants of specificity in extradiol dioxygenases.


Ontogenetic variation in the ecological stoichiometry of 10 fish species during early development.
The chemical composition and stoichiometry of vertebrate bodies changes greatly during ontogeny as phosphorus-rich bones form, but we know little about the variation among species during early development. Such variation is important because element ratios in animal bodies influence which element limits growth and how animals contribute to nutrient cycling. We quantified ontogenetic variation from embryos through 2-3 months of age in 10 species of fish in six different families, ranging in adult size from 73 to 720 mm in length. We measured whole-body concentrations (percentage of dry mass) and ratios of carbon (C), nitrogen (N), and phosphorus (P) as fish developed. We also quantified whole-body concentrations of calcium (Ca), because Ca should reflect bone development, and RNA, which can be a major pool of body P. To account for interspecific differences in adult size, we also examined how trends changed with relative size, defined as body length divided by adult length. Ontogenetic changes in body composition and ratios were relatively similar among species and were more similar when expressed as a function of relative size compared to age. Body P increased rapidly in all species (likely because of bone development) from embryos until individuals were ~5%-8% of adult size. Body N also increased, while body C, C:N, C:P, and N:P all decreased over this period. Body Ca increased with development but was more variable among species. Body RNA was low in embryos, increased rapidly in young larvae, then decreased as fish reached 5%-8% of adult size. After fish were about 5%-8% of adult size, changes in body composition were relatively slight for all elements and ratios. These results reveal a consistency in the dynamics of body stoichiometry during early ontogeny, presumably because of similar constraints on the allocation of elements to bones and other body pools. Because most changes occur when individuals are <1 month old (<10% of adult size for that species), early ontogenetic variation in body stoichiometry may be especially important for growth limitation of individuals and ecosystem-level nutrient cycling.


Bartonella henselae in Ixodes ricinus ticks (Acari: Ixodida) removed from humans, Belluno province, Italy.
The potential role of ticks as vectors of Bartonella species has recently been suggested. In this study, we investigated the presence of Bartonella species in 271 ticks removed from humans in Belluno Province, Italy. By using primers derived from the 60-kDa heat shock protein gene sequences, Bartonella DNA was amplified and sequenced from four Ixodes ricinus ticks (1.48%). To confirm this finding, we performed amplification and partial sequencing of the pap31 protein and the cell division protein ftsZ encoding genes. This process allowed us to definitively identify B. henselae (genotype Houston-1) DNA in the four ticks. Detection of B. henselae in these ticks might represent a highly sensitive form of xenodiagnosis. B. henselae is the first human-infecting Bartonella identified from Ixodes ricinus, a common European tick and the vector of various tickborne pathogens. The role of ticks in the transmission of bartonellosis should be further investigated.


Validity and reliability of three commercially available breath-by-breath respiratory systems.
Information concerning the validity and reliability of commercial on-line gas analysis systems is limited. The aim of this study was to provide a comparison of the validity and reliability of three on-line systems (Oxycon Alpha, Oxycon Pro and Pulmolab EX670) with that of Douglas bags. Two separate studies were conducted. In study 1, the three gas analysis systems were compared with Douglas bags using a metabolic simulator over four increases in ventilation. In study 2, ten subjects were split into equal groups exercising at 100 W or 150 W for 85 min on three separate occasions. Each system was used twice per visit. Study 1 demonstrated that the Oxycon Alpha and Douglas bags produced similar respiratory values over all levels of ventilation. The Oxycon Pro tended to slightly overestimate mean expiratory flow (V(E) ), oxygen uptake ( VO2), carbon dioxide production (VCO2) and respiratory exchange ratio (RER) at the higher ventilations. The Pulmolab produced large overestimations at all ventilations for and RER (up to 26.3% away from expectations), whilst values for, and were slightly underestimated at higher ventilations (up to 7.5% from expectations). The results of study 2 support the findings of study 1, with the Oxycon Pro and Oxycon Alpha producing similar results compared to Douglas bags for, and RER. The coefficients of variation for and measured using Douglas bags, Oxycon Pro and Oxycon Alpha were 3.3-5.1%, 4.7-7.0% and 4.5-6.3%, respectively, whilst that for the Pulmolab was highly variable (26.8-45.8%). The exercise study showed the Oxycon Pro and Oxycon Alpha to be both valid and reliable on-line systems for the measurement of parameters of respiration, at least at workloads up to 150 W.


Environmental temperatures of tertiary penguins.
Marine paleotemperatures, determined by oxygen isotope measurement, show that Australasian Tertiary penguins, including giant forms, lived in warm to tropical environments. Evolution from smaller species also occurred in warm environments. Mid-Tertiary fluctuations of sea temperature were controlled by alternating uplift and erosion of "Tasmantis," an unstable meridional landmass occupying and extending beyond the present position of New Zealand.


Structure and expression of MdFBCP1, encoding an F-box-containing protein 1, during Fuji apple (Malus domestica Borkh.) fruit ripening.
From database comparisons of 1,117 expressed sequence tags (ESTs) generated from ripened Fuji apple fruits, we identified ten ubiquitin (Ub)-related genes. RNA gel-blot analysis suggests that these Ub-related genes are induced by at least four distinct signaling pathways in fruits. In this study, we analyzed structure and expression of MdFBCP1, encoding an F-box-containing protein 1, in Fuji apples. MdFBCP1 transcript was predominantly expressed in the fully ripened climacteric fruits, in which serge of ethylene production occurred. The MdFBCP1 gene was also activated effectively in response to exogenous ethylene treatment, with the induction pattern being comparable to those of ACC oxidase and beta-cyanoalanine synthase. Thus, it seems likely that the expression of MdFBCP1 is closely associated with a climacteric ethylene production and ACC oxidase activity and, hence, MdFBCP1 may play a role in the ripening process of Fuji apple fruits. Yeast two hybrid and in vitro pull-down assays revealed that MdFBCP1 physically interacted with MdSkp1 and N-terminal F-box motif was essential for this interaction. These results suggest that MdFBCP1 indeed functions as an F-box-containing protein and participates in the formation of SCF complex, which acts as E3 Ub ligase. Genomic Southern blot analysis showed that MdFBCP1 exhibited different pattern of restriction enzyme digestion in three cultivars (Tsugaru, Golden Delicious and Fuji) that produce different amount of ethylene, suggesting that the MdFBCP1 gene is organized in a cultivar specific manner. Collectively, our data suggest that Ub degradation pathway may play an important role in the ripening of Fuji apple fruits.


The Effects of Abutment Finish Lines on the Penetration Characteristics of Elastomers into the Simulated Gingival Sulcus.
The aim of this study was to determine the effect of finish lines on the penetration ability of polyether and polyvinyl siloxane impression material into the simulated gingival sulcus. Three types of finish line (chamfer, deep chamfer, and radial shoulder) were impressed with two types of elastomeric impression material (polyether and polyvinyl siloxane) using a two-step impression technique. Ten samples of each finish line were prepared and then separated into two groups of impression material: polyether and polyvinyl siloxane. The model of the simulated gingival sulcus had a width of 0.1 mm and a depth of 3.5 mm with a subgingival finish line of 0.5 mm. The effect of the finish lines on the penetration ability of these impression materials was analyzed using a two-way analysis of variance (ANOVA) and Tukey's multiple comparison tests at a statistically significant level of 0.05. A two-way ANOVA revealed a significant difference among finish lines, impression materials, and their interaction. The deep chamfer and radial shoulder finish lines displayed significantly higher penetration ability than the chamfer finish line. Moreover, polyether revealed significantly higher penetration ability than polyvinyl siloxane. The finish lines affected the penetration ability of the impression materials. Therefore, the simulated gingival sulcus model demonstrates that it is an effective way of examining impression materials' penetration abilities.


Emergent Lévy behavior in single-cell stochastic gene expression.
Single-cell gene expression is inherently stochastic; its emergent behavior can be defined in terms of the chemical master equation describing the evolution of the mRNA and protein copy numbers as the latter tends to infinity. We establish two types of "macroscopic limits": the Kurtz limit is consistent with the classical chemical kinetics, while the Lévy limit provides a theoretical foundation for an empirical equation proposed in N. Friedman et al., Phys. Rev. Lett. 97, 168302 (2006)PRLTAO0031-900710.1103/PhysRevLett.97.168302. Furthermore, we clarify the biochemical implications and ranges of applicability for various macroscopic limits and calculate a comprehensive analytic expression for the protein concentration distribution in autoregulatory gene networks. The relationship between our work and modern population genetics is discussed.


Iterative multi-atlas-based multi-image segmentation with tree-based registration.
In this paper, we present a multi-atlas-based framework for accurate, consistent and simultaneous segmentation of a group of target images. Multi-atlas-based segmentation algorithms consider concurrently complementary information from multiple atlases to produce optimal segmentation outcomes. However, the accuracy of these algorithms relies heavily on the precise alignment of the atlases with the target image. In particular, the commonly used pairwise registration may result in inaccurate alignment especially between images with large shape differences. Additionally, when segmenting a group of target images, most current methods consider these images independently with disregard of their correlation, thus resulting in inconsistent segmentations of the same structures across different target images. We propose two novel strategies to address these limitations: 1) a novel tree-based groupwise registration method for concurrent alignment of both the atlases and the target images, and 2) an iterative groupwise segmentation method for simultaneous consideration of segmentation information propagated from all available images, including the atlases and other newly segmented target images. Evaluation based on various datasets indicates that the proposed multi-atlas-based multi-image segmentation (MABMIS) framework yields substantial improvements in terms of consistency and accuracy over methods that do not consider the group of target images holistically.


The impact of a combined TB/HIV intervention on the incidence of TB infection among adolescents and young adults in the HPTN 071 (PopART) trial communities in Zambia and South Africa.
HPTN071 (PopART) was a cluster randomized trial conducted in Zambian and South African (SA) communities, between 2013-2018. The PopART intervention (universal HIV-testing and treatment (UTT) combined with population-level TB symptom screening) was implemented in 14 communities. The TREATS study (2017-2021) was conducted to evaluate the impact of the PopART intervention on TB outcomes. We report on the impact of the combined TB/HIV intervention on the incidence of TB infection in a cohort of adolescents and young adults (AYA) aged 15-24 years. A random sample of AYA was enrolled between July 2018 and July 2019 in 7 intervention vs 7 standard-of-care communities. We collected questionnaire data on risk factors for TB, and blood for measuring TB infection using QuantiFERON (QFT) Plus. AYA were seen at months 12 and 24 with all procedures repeated. Primary outcome was incidence of TB infection comparing intervention and standard-of-care communities. An incident case was defined as a participant with QFT interferon-gamma response of < 0.2 IU/ml plasma ('negative') at baseline and a QFT interferon-gamma response of > = 0.7 IU/ml ('positive') at follow up. We enrolled 4,648 AYA, 2,223 (47.8%) had a negative QFT-plus result at baseline, 1,902 (85.6%) had a follow up blood sample taken at 12 months or 24 months. Among the 1,902 AYA, followed for 2,987 person-years, 213 had incident TB infection giving (7.1 per 100 person-years). TB infection incidence rates were 8.7 per 100 person-years in intervention communities compared to 6.0 per 100 person-years in standard-of-care communities. There was no evidence the intervention reduced the transmission of TB (incidence-rate-ratio of 1.45, 95%CI 0.97-2.15, p = 0.063). In our trial setting, we found no evidence that UTT combined with TB active case finding reduced the incidence of TB infection at population level. Our data will inform future modelling work to better understand the population level dynamics of HIV and TB.


Sterile and economic instrumentation in laparoscopic surgery. Experiences with 6,000 surgical laparoscopies, 1990-1996.
Because so many common surgical problems can now be addressed by the laparoscopic approach, the issue of sterile processing has to be reconsidered. Selected laparoscopic instrumentation was analyzed regarding wear and tear and decontamination after sterile processing following 6,000 surgical laparoscopies carried out between 1990 and 1996 at the Academic Hospital Moabit, Berlin. Fewer than 7.9 (parts of) instruments failed per 100 laparoscopies. Most of the repairs involved scissors. The main problems were blunting, burnt or disconnected electromechanical components, defective insulation, and damaged or lost parts of dismantable instruments. Residues of human blood proteins were detected on a few instruments. The effect of intraluminal rinsing was documented by measuring the iron content (as an indicator for blood contamination). A comparison of costs showed that it was >10 times cheaper to use instrumentation with reusable components. The sterile processing of economic reusable instrumentation for laparoscopies needs staff well trained in sterile supply. Instrument design should allow easy dismantling and rinsing of internal parts. Insulating compounds present a problem for decontamination. Disinfection with aldehydes before cleaning the lumina of instruments must be avoided because protein coagulation will occur. A tube-in-tube concept for tubular instruments offering compatibility should be favored.


PVT1: a rising star among oncogenic long noncoding RNAs.
It is becoming increasingly clear that short and long noncoding RNAs critically participate in the regulation of cell growth, differentiation, and (mis)function. However, while the functional characterization of short non-coding RNAs has been reaching maturity, there is still a paucity of well characterized long noncoding RNAs, even though large studies in recent years are rapidly increasing the number of annotated ones. The long noncoding RNA PVT1 is encoded by a gene that has been long known since it resides in the well-known cancer risk region 8q24. However, a couple of accidental concurrent conditions have slowed down the study of this gene, that is, a preconception on the primacy of the protein-coding over noncoding RNAs and the prevalent interest in its neighbor MYC oncogene. Recent studies have brought PVT1 under the spotlight suggesting interesting models of functioning, such as competing endogenous RNA activity and regulation of protein stability of important oncogenes, primarily of the MYC oncogene. Despite some advancements in modelling the PVT1 role in cancer, there are many questions that remain unanswered concerning the precise molecular mechanisms underlying its functioning.


Sparse tensor based nuclear gradients for periodic Hartree-Fock and low-scaling correlated wave function methods in the CP2K software package: A massively parallel and GPU accelerated implementation.
The development of novel double-hybrid density functionals offers new levels of accuracy and is leading to fresh insights into the fundamental properties of matter. Hartree-Fock exact exchange and correlated wave function methods, such as second-order Møller-Plesset (MP2) and direct random phase approximation (dRPA), are usually required to build such functionals. Their high computational cost is a concern, and their application to large and periodic systems is, therefore, limited. In this work, low-scaling methods for Hartree-Fock exchange (HFX), SOS-MP2, and direct RPA energy gradients are developed and implemented in the CP2K software package. The use of the resolution-of-the-identity approximation with a short range metric and atom-centered basis functions leads to sparsity, allowing for sparse tensor contractions to take place. These operations are efficiently performed with the newly developed Distributed Block-sparse Tensors (DBT) and Distributed Block-sparse Matrices (DBM) libraries, which scale to hundreds of graphics processing unit (GPU) nodes. The resulting methods, resolution-of-the-identity (RI)-HFX, SOS-MP2, and dRPA, were benchmarked on large supercomputers. They exhibit favorable sub-cubic scaling with system size, good strong scaling performance, and GPU acceleration up to a factor of 3. These developments will allow for double-hybrid level calculations of large and periodic condensed phase systems to take place on a more regular basis.


Fatigue during stretch-shortening cycle exercises: changes in mechanical performance of human skeletal muscle.
Stretch-shortening cycle (SSC), which is a normal contraction behavior of muscle, was used as a model to investigate muscular fatigue. Nine male volunteers were subjected to 100 repeated and exhaustive SSC contractions of the forearm extensors using a special sledge apparatus incorporating a force plate system. The fatigue contractions were performed on submaximal levels but the before-after comparison also included maximal drop-jump condition on the sledge as well as falls on to the floor. The results indicated that in the 100 submaximal SSCs the fatigue was characterized by increases in the contact times for both the eccentric and concentric phases of SSC, but the influence was more pronounced on the concentric part. The force-time curves during contact on the platform were influenced by fatigue so that the initial force peak became higher and the subsequent initial drop of force more pronounced. During submaximal and maximal drops, the angular velocities changed in the two phases of SSC. With progressing fatigue, the eccentric maximal angular velocity increased and the corresponding concentric velocities decreased. These changes were accompanied by slight changes in the elbow joint mechanism with respect to the contact, release, and maximal flexion angles. The results suggest that repeated SSC induces fatigue and the fatigue effects on the mechanical behavior of the muscle are very much similar to those induced by either isometric or concentric fatigue contractions. However, the transfer of the energy between eccentric and concentric phases was drastically reduced and this implies that SSCs can be used effectively to examine the fatiguability of the system regulating muscle stiffness during exercise.


The Diamond STING server.
Diamond STING is a new version of the STING suite of programs for a comprehensive analysis of a relationship between protein sequence, structure, function and stability. We have added a number of new functionalities by both providing more structure parameters to the STING Database and by improving/expanding the interface for enhanced data handling. The integration among the STING components has also been improved. A new key feature is the ability of the STING server to handle local files containing protein structures (either modeled or not yet deposited to the Protein Data Bank) so that they can be used by the principal STING components: (Java)Protein Dossier ((J)PD) and STING Report. The current capabilities of the new STING version and a couple of biologically relevant applications are described here. We have provided an example where Diamond STING identifies the active site amino acids and folding essential amino acids (both previously determined by experiments) by filtering out all but those residues by selecting the numerical values/ranges for a set of corresponding parameters. This is the fundamental step toward a more interesting endeavor-the prediction of such residues. Diamond STING is freely accessible at http://sms.cbi.cnptia.embrapa.br and http://trantor.bioc.columbia.edu/SMS.


Simultaneous determination of acidic pesticides in vegetables and fruits by liquid chromatography--tandem mass spectrometry.
A sensitive and efficient method has been developed for the simultaneous determination of 73 multi-class acidic pesticides, such as phenoxy acid and sulfonylurea herbicides, in vegetables and fruits. The sample preparation procedure was carefully optimized for the efficient removal of co-extracted matrix components. The method involves extraction of acidic pesticides with acetonitrile containing hydrochloric acid, removal of water from crude extract by salting out, and sequential cleanup by octadecylsilyl silica gel and silica gel columns. For samples containing high amounts of pigments, such as spinach, additional cleanup using a graphitized carbon column was performed prior to liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Recovery tests were performed for five times for each sample of cabbage, spinach, potato, eggplant, orange, and apple fortified at 0.01 mg kg-1. Out of the 73 tested pesticides, 70 for cabbage, 67 for spinach, 69 for potato, 67 for eggplant, 64 for orange, and 70 for apple were within the range of 70-120%, with relative standard deviations below 25%. Nitenpyram and pyrasulfotole showed low recoveries for all the samples tested, probably due to low recoveries from silica gel column. The developed method effectively removed co-extracted matrix components and was highly selective, with no interfering peaks found in the chromatograms of blank samples. The overall results indicate that the developed method is suitable for the quantitative analysis of acidic pesticide residues in vegetables and fruits.


Conventional Anti-glioblastoma Chemotherapy Affects Proteoglycan Composition of Brain Extracellular Matrix in Rat Experimental Model in vivo.
Temozolomide (TMZ) is a conventional chemotherapy drug for adjuvant treatment of glioblastoma multiforme (GBM), often accompanied by dexamethasone (DXM) to prevent brain oedema and alleviate clinical side effects. Here, we aimed to investigate an ability of the drugs to affect normal brain tissue in terms of proteoglycan (PG) composition/content in experimental rat model in vivo. Age- and brain zone-specific transcriptional patterns of PGs were demonstrated for 8, 60, and 120 days old rats, and syndecan-1, glypican-1, decorin, biglycan, and lumican were identified as the most expressed PGs. DXM treatment affected both PG core proteins expression (mainly syndecan-1, glypican-1, decorin, biglycan, lumican, versican, brevican, and NG2) and heparan sulphate (HS)/chondroitin sulphate (CS) content in organotypic brain slice culture ex vivo and experimental animals in vivo in a dose-dependent manner. TMZ treatment did not result in the significant changes in PG core proteins expression both in normal rat brain hippocampus and cortex in vivo (although generics did), but demonstrated significant effects onto polysaccharide HS/CS content in the brain tissue. The effects were age- and brain zone-specific and similar with the age-related PGs expression changes in rat brain. Combination of TMZ with DXM resulted in the most profound deterioration in PGs composition and content in the brain tissue both at core protein and glycosaminoglycan levels. Taken together, the obtained results demonstrate that conventional anti-glioblastoma therapy affects proteoglycan structure and composition in normal brain tissue, potentially resulting in deterioration of brain extracellular matrix and formation of the favourable tumorigenic niche for the expansion of the residual glioma cells. During the TMZ chemotherapy, dose and regimen of DXM treatment matter, and repetitive low DXM doses seem to be more sparing treatment compared with high DXM dose(s), which should be avoided where possible, especially in combination with TMZ.


Idiopathic intracranial hypertension and orthostatic edema may share a common pathogenesis.
Our aim was to determine the frequency of orthostatic edema (OE) in patients with idiopathic intracranial hypertension (IIH). We evaluated 30 women with IIH for evidence of OE by comparing sodium and water excretion in the recumbent and standing postures and morning and evening body weights. Data were compared with findings in 30 women with OE, 22 weight-matched obese normal subjects, and 20 lean normal subjects. The effect of treatment with diuretics or diuretics plus sympathomimetic agents was compared. Seventy-seven percent of IIH patients had evidence of peripheral edema and 80% had significant orthostatic retention of sodium or water. Excretion of a standard saline load and of a tap water load was significantly impaired in the upright posture in the IIH and OE patients compared with the lean and obese normal subjects. Diuretic therapy induced weight loss (up to 9 kg) and decreased mean weight gain from morning to evening in 5 of 12 patients treated. In seven patients also treated with diuretics plus sympathomimetic drugs, the diuretic-induced morning weight loss and morning to evening weight gain were both significantly improved with the addition of sympathomimetic agents. Therapy reduced the frequency or severity of headaches in seven patients and reduced papilledema in four patients who received no other concurrent treatment for IIH. The orthostatic retention of sodium and water and the consequent edema is very similar in IIH and OE patients, suggesting a common pathogenesis for both disorders. Diuretic therapy, dietary salt and water restriction, and planned periods of recumbency merit study as a treatment for these patients.


Fibroblasts spread on immobilized fibrin monomer by mobilizing a beta1-class integrin, together with a vitronectin receptor alphavbeta3 on their surface.
Human and murine fibroblasts were found to spread far more avidly on fibrin monomer monolayers than on immobilized fibrinogen, indicating that removal of fibrinopeptides by thrombin is a prerequisite for the fibrin-mediated augmentation of cell spreading. In fact, cell spreading was not efficiently augmented on monolayers of a thrombin-treated dysfibrinogen lacking the release of fibrinopeptide A due to an Aalpha Arg-16 --> Cys substitution. Since a synthetic Arg-Gly-Asp (RGD)-containing peptide inhibited the fibrin-mediated cell spreading, subsequent dissociation of the carboxyl-terminal globular domain of the Aalpha-chains appears to render the RGD segments accessible to the cell-surface integrins. In support of this, fibrin-augmented cell spreading was inhibited by an antibody recognizing a 12-kDa peptide segment with gamma Met-89 at its amino terminus, which is located in close association with the RGD segment at Aalpha 95-97 in the helical coiled-coil interdomainal connector. The fibrin-mediated augmentation of cell spreading was inhibited not only by an antibody against human vitronectin receptor (LM 609) but also by an antibody against the beta1 subunit of integrin (mAb13), suggesting that the beta1-class integrin together with a vitronectin receptor, alphavbeta3, is mobilized onto the surface of fibroblasts upon contact with the fibrin monomer monolayer.


Body mass index and asthma incidence among USA adults.
The aim of this study was to examine the association between body mass index (BMI) and asthma incidence. Data from the baseline examination conducted during 1971-1975, and the first follow-up conducted during 1982-1984, of the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (a cohort study) was used. Asthma was self-reported or reported by proxies. BMI was calculated from measured height and weight obtained during the baseline examination. Among 9,456 participants aged 25-74 yrs who were free of asthma at baseline, 317 participants reported a diagnosis of asthma during the follow-up interview. Compared with participants with a BMI of 18.5-<25.0 kg.m(-2), the odds ratio (OR) for those with a BMI of > or =35 kg x m(-2) was 1.87 (95% confidence interval (CI) 1.12-3.13). ORs were similar for males and females. However, only 125 of the 298 participants who recalled a date of onset reported a diagnosis that occurred after their baseline examination. Among this group of participants, BMI was not significantly associated with asthma incidence (OR 1.52, 95% CI 0.62-3.77). In conclusion, although obese people reported more "incident" asthma during follow-up, it remains unclear whether this represents reactivation of previously diagnosed asthma or the onset of new cases, and whether these new cases actually represent true asthma or respiratory symptoms misdiagnosed as asthma.


Protection Against Discolouration by Two Over-the Counter Desensitising Products.
To determine in vitro the protection potential against discolouration of two OTC (over-the-counter) desensitising products on enamel and dentin in comparison to a standard toothpaste and water by means of a spectrophotometer. A total of 96 samples of bovine enamel-dentin complex and 48 of bovine dentin were alternatively immersed in red wine, tea, coffee or water after having been treated by a sodium monofluorophosphate- and calcium phosphate-based product (Curodont Protect), an amine fluoride-based toothpaste (Elmex Red), a stannous chloride-based toothpaste (Elmex Protection Erosion) or distilled water (negative control). Initial (T0) and final colour (T1, after 4 weeks of immersion in staining solutions) of each specimen were assessed by a spectrophotometer. Statistical analysis was done by means of repeated measures ANOVA followed by Fisher's LSD post-hoc test. Differences between T0 and T1 were considered stastistically significant at p ≤ 0.05. When enamel samples were measured over a black background, ΔE00 values (T0-T1) varied from 2.2 (SD 0.7) for amine fluoride-based product/water to 53.9 (SD 7.6) for amine fluoride-based-product/red wine. When dentin samples were measured over a black background, ΔE00 values (T0-T1) varied from 5.4 (SD 0.9) stannous chloride based product/water to 61.6 (SD 3.7) amine fluoride-based product/red wine. Specifically, the application of the sodium monofluorophosphate was able to statistically significantly (p ≤ 0.05) reduce discolouration induced by the staining solutions tested only on the enamel-dentin complex, while distilled water and the stannous fluoride-based product were able to statistically significantly (p ≤ 0.05) reduce discolouration induced by the staining solutions tested in pure dentin samples.


High prevalence of smoking in patients with adrenal incidentalomas: causality or case selection?
Autonomous cortisol secretion and possible autonomous cortisol secretion (ACS/pACS) are associated to an increase of cardiovascular risk factors such as hypertension, diabetes mellitus and dyslipidaemia. To our knowledge, the prevalence of smoking, another well-established risk factor for cardiovascular disease, has not been studied in detail in people with ACS/pACS or adrenal incidentalomas. Patients with adrenal incidentalomas were examined with the 1-mg overnight dexamethasone suppression test (cortisolONDST). Information about current smoking was collected from the patient's records. We studied 1044 patients, of whom 370 (35%) were current smokers. Of these, 22% had bilateral AI compared to 12% of the non-smokers (P < 0.001). Among patients with unilateral adrenal incidentalomas, smokers had larger adrenal incidentalomas than non-smokers (22 mm vs 19 mm, P < 0.001). Smokers also more often had cortisolONDST ≥50 nmol/L than non-smokers, 54% vs 40% (P < 0.001), a finding independent of the size of the adrenal incidentaloma in patients with unilateral adrenal incidentalomas. In the present study of patients with adrenal incidentalomas, the prevalence of current smoking was higher than in the general population. Furthermore, smokers had larger unilateral adrenal incidentalomas, more often bilateral adrenal incidentalomas, and more frequently ACS/pACS. Whether smoking is a risk factor for adrenal incidentalomas and ACS/pACS or our findings are due to case selection needs to be further studied.


Circadian rhythm of protein synthesis activity in the exocrine pancreas of fed and starved rats.
Rats, either fed a solid standard chow ad libitum or starved for 24 h prior to the beginning of the experiments, were kept in a normal light-dark cycle of 12 h. At certain times over a total period of 24 h, three animals of each group were killed, their pancreata were excised and the protein synthetic capacity was determined, measuring both the amount of cellular RNA and the percentage of ribosomes active in protein synthesis. A clear-cut circadian rhythm in the synthetic activity was found, well expressed in the fed animals but less evident and shifted in time in the starved ones. The RNA/DNA ratios in the two sets of animals remained fairly constant throughout the day, but were somewhat lower in the fasted rats.


Mortality in a cohort of remote-living Aboriginal Australians and associated factors.
We aimed to describe mortality in a cohort of remote-living Aboriginal Australians using electronic record linkage. Between 2004 and 2006, 363 Aboriginal people living in remote Western Australia (WA) completed a questionnaire assessing medical history and behavioural risk factors. We obtained mortality records for the cohort from the WA Data Linkage System and compared them to data for the general population. We used Cox proportional hazards regression to identify predictors of mortality over a 9-year follow-up period. The leading causes of mortality were diabetes, renal failure, and ischaemic heart disease. Diabetes and renal failure accounted for 28% of all deaths. This differed from both the Australian population as a whole, and the general Indigenous Australian population. The presence of chronic disease did not predict mortality, nor did behaviours such as smoking. Only age, male sex, poor mobility, and cognitive impairment were risk factors. To reduce premature mortality, public health practitioners should prioritise the prevention and treatment of diabetes and renal disease in Aboriginal people in remote WA. This will require a sustained and holistic approach.


Oxygen-Generating Photo-Cross-Linkable Hydrogels Support Cardiac Progenitor Cell Survival by Reducing Hypoxia-Induced Necrosis.
Oxygen is essential to cell survival and tissue function. Not surprisingly, ischemia resulting from myocardial infarction induces cell death and tissue necrosis. Attempts to regenerate myocardial tissue with cell based therapies exacerbate the hypoxic stress by further increasing the metabolic burden. In consequence, implanted tissue engineered cardiac tissues suffer from hypoxia-induced cell death. Here, we report on the generation of oxygen-generating hydrogels composed of calcium peroxide (CPO) laden gelatin methacryloyl (GelMA). CPO-GelMA hydrogels released significant amounts of oxygen for over a period of 5 days under hypoxic conditions (1% O2). The released oxygen proved sufficient to relieve the metabolic stress of cardiac side population cells that were encapsulated within CPO-GelMA hydrogels. In particular, incorporation of CPO in GelMA hydrogels strongly enhanced cell viability as compared to GelMA-only hydrogels. Importantly, CPO-based oxygen generation reduced cell death by limiting hypoxia-induced necrosis. The current study demonstrates that CPO based oxygen-generating hydrogels could be used to transiently provide oxygen to cardiac cells under ischemic conditions. Therefore, oxygen generating materials such as CPO-GelMA can improve cell-based therapies aimed at treatment or regeneration of infarcted myocardial tissue.


Factors Influencing Engagement and Behavioral Determinants of Infant Feeding in an mHealth Program: Qualitative Evaluation of the Growing Healthy Program.
Infant feeding practices, including breastfeeding and optimal formula feeding practices, can play a role in the prevention of childhood obesity. The ubiquity of smartphone ownership among women of childbearing age provides important opportunities for the delivery of low-cost, broad reach parenting interventions delivered by mobile phone (mHealth or mobile health interventions). Little is known about how parents engage with mHealth programs targeting infant feeding and how such programs might influence infant feeding practices. The objectives of this study were to explore participant views on (1) factors influencing engagement with the Growing healthy program, an mHealth program targeting healthy infant feeding practices from birth to 9 months of age, and (2) the ways in which the program influenced behavioral determinants of capability, opportunity, and motivation for breastfeeding and optimal formula feeding behaviors. Semistructured, telephone interviews were conducted with a purposeful sample (n=24) of mothers participating in the Growing healthy program. Interviews explored participants' views about engagement with the program and its features, and the ways the program influenced determinants of infant feeding behaviors related to breastfeeding and optimal formula feeding. The interview schedule was informed by the Capability, Opportunity, Motivation, and Behavior (COM-B) model. Participants reported that engagement fluctuated depending on need and the degree to which the program was perceived to fit with existing parenting beliefs and values. Participants identified that the credibility of the program source, the user friendly interface, and tailoring of content and push notifications to baby's age and key transition points promoted engagement, whereas technical glitches were reported to reduce engagement. Participants discussed that the program increased confidence in feeding decisions. For breastfeeding mothers, this was achieved by helping them to overcome doubts about breast milk supply, whereas mothers using formula reported feeling more confident to feed to hunger and satiety cues rather than encouraging infants to finish the bottle. Participants discussed that the program provided around-the-clock, readily accessible, nonjudgmental information and support on infant feeding and helped to reinforce information received by health professionals or encouraged them to seek additional help if needed. Participants reflected that their plans for feeding were typically made before joining the program, limiting the potential for the program to influence this aspect of motivation. Rather, the program provided emotional reassurance to continue with current feeding plans. Our findings suggest that engagement with the program was influenced by an interplay between the program features and needs of the user. Participants reported that the program enhanced confidence in feeding decisions by providing a 24/7 accessible, expert, nonjudgmental support for infant feeding that complemented health professional advice. It is likely that interventions need to commence during pregnancy to maximize the impact on breastfeeding intentions and plans.


Global brain network dynamics predict therapeutic responsiveness to cannabidiol treatment for refractory epilepsy.
Refractory epilepsy is a chronic brain network disorder characterized by unresponsiveness to multiple (>2) anti-epileptic drugs. Cannabidiol, a non-psychotropic neuroactive substance, is an emerging anti-epileptic treatment that was recently approved by the US Food and Drug Administration for the treatment of refractory epilepsy, especially Lennox Gastaut syndrome and Dravet syndrome. Here, we evaluated associations between global brain network dynamics and related changes and responsiveness to cannabidiol therapy using a combination of electroencephalography phase coherence and graph theoretical analyses. Refractory epilepsy patients with Lennox Gastaut syndrome or Dravet syndrome underwent serial electroencephalography testing prior to and during cannabidiol treatment. Patients showing greater than 70% seizure frequency reduction were classified as treatment responders for the purposes of this study. We calculated inter-electrode electroencephalography phase coherence in delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz) and beta (13-30 Hz) frequency bands. Graph theoretical analysis of brain network dynamics was extracted from phase coherence to evaluate measures of network integration (i.e. characteristic path length, global efficiency and degree) and segregation (i.e. modularity and transitivity). We found that responders, relative to non-responders, showed increased network integration-as indexed by relatively higher global efficiency and lower degree-and increased network segregation-as indexed by relatively higher modularity-exclusively in the beta-frequency band. We also found that larger cannabidiol dosages were associated with increased network integration-as indexed by higher global efficiency with increasing dose-and increased network segregation-as indexed by lower transitivity with increasing dose-in the delta, theta and alpha frequency bands. In summary, we demonstrate novel effects of cannabidiol on brain network dynamics with important implications for the treatment of refractory epilepsy and, possibly, across broader research applications in the future.


[The role of the self-consciousness of schizophrenic patients in the socio-vocational readaptation].
Using clinical and special medico-psychological methods, the authors studied 154 patients with schizophrenia with different rates of the disease progression and at different stages of the disease. The authors studied the condition of the patients' self-consciousness in relation to the possibilities of their social and occupational readaptation. It has been established that the working ability of patients depends on a number of factors, including their profession and working conditions, the influence of the family, the degree of progression of the schizophrenic process and the severity of negative symptoms. At the same time the level of patients' self-consciousness exerts a considerable influence on their social and occupational readaptation which should be taken into account in developing rehabilitative measures and in the course of expert medical examination of working capacity in such patients.


First Report of Cucumber green mottle mosaic virus Infecting Greenhouse Cucumber in Canada.
In early 2013, greenhouse cucumber growers in Alberta, Canada, observed virus-like disease symptoms on mini-cucumber (Cucumis sativus) crops (e.g., 'Picowell'). Two types of symptoms were commonly observed, green mottle mosaic and necrotic spots. In the early infection, young leaves of infected cucumber plants displayed light green mottle and blisters. The infected plants were stunted in growth, with darker green blisters and green mottle mosaic symptoms on mature leaves. Disease incidence varied from one greenhouse to another. In some severe cases, diseased plants were widely distributed inside the greenhouse, resulting in 10 to 15% yield losses based on grower's estimation. Nine symptomatic samples were collected and subjected to total RNA isolation using the TRIzol reagent (Invitrogen, Carlsbad, CA). Laboratory analyses were conducted using real-time RT-PCR systems for Cucumber green mottle mosaic virus (CGMMV) (1), Melon necrotic spot virus (MNSV, Ling, unpublished), and Squash mosaic virus (SqMV) (3). All nine samples were positive for CGMMV and seven of them were in mixed infections with MNSV. Two samples were selected for validation for the presence of CGMMV using conventional RT-PCR (2) with a new primer set (CGMMVMP F1: 5'-ATGTCTCTAAGTAAGGTGTC-3' and CGMMV3'UTR R1: 5'-TGGGCCCCTACCCGGGG-3') and two previous online published primer sets, one for CGMMV MP (5' TAAGTTTGCTAGGTGTGATC-3', GenBank Accession No. AJ250104 and 5' ACATAGATGTCTCTAAGTAAG-3', AJ250105), and another for CGMMV CP (5' ACCCTCGAAACTAAGCTTTC-3', AJ243351 and 5' GAAGAGTCCAGTTCTGTTTC-3', AJ243352). The expected sizes of RT-PCR products were obtained and sequenced directly. Sequences from these three products overlapped and generated a 1,282-bp contig (KF683202). BLASTn analysis to the NCBI database showed 99% sequence identity to CGMMV isolates identified in Asia, including China (GQ277655, KC852074), India (DQ767631), Korea (AF417243), Myanmar (AB510355), and Taiwan (HQ692886), but only 92% sequence identity to other CGMMV isolates identified in Europe, including Spain (GQ411361) and Russia (GQ495274), and 95% to CGMMV isolate from Israel (KF155231). The strong sequence identity to the CGMMV Asian isolates suggests that the Canadian CGMMV isolate identified in Alberta was likely of Asian origin. In two bioassay experiments using one sample prepared in 0.01 M phosphate buffer, the similar green mottle mosaic symptoms were observed on systemic leaves in the mechanically inoculated plants and the presence of CGMMV, but not MNSV, was confirmed through real-time RT-PCR on four different cucurbits, including three Cucumis sativus cultivars (six plants in 'Marketer,' five plants in 'Poinsett 76,' six plants in 'Straight 8'), seven plants of C. melo 'Athena,' six plants of C. metulifer (PI201681), and two plants of Citrullus lanatus 'Charleston Gray.' To our knowledge, CGMMV has only been reported in Asia, Europe, and the Middle East, and this is the first report of CGMMV in the American continents. CGMMV is highly contagious and is seed borne on cucurbits. With the increasing trend in growing grafted watermelon and other cucurbits in the United States and elsewhere, it is even more important now that a vigilant seed health test program for CGMMV should be implemented. References: (1) H. Chen et al. J. Virol. Methods 149:326, 2008. (2) K.-S. Ling et al. Plant Dis. 92:1683, 2008. (3) K.-S. Ling et al. J. Phytopathol. 159:649, 2011.


Emerging insights on the pathogenesis and treatment of extranodal NK/T cell lymphomas (ENKTL).
Extranodal NK/T-cell lymphoma (ENKTL) is a rare aggressive extranodal non-Hodgkin lymphoma (NHL) universally associated with Epstein-Barr virus (EBV). ENKTL most commonly occurs in non-elderly immune competent males in Asia and South America. A number of antecedent lymphoproliferative disorders (LPDs) have been described in Asian and South American patients, but the majority of Caucasian ENKTL patients have no known preceding LPD or underlying immunodeficiency. Other than EBV, no environmental or extrinsic factor has been implicated in oncogenesis. The precise mechanisms by which EBV infects NK or T cells and the virus' role in the pathogenesis of ENKTL have not been fully deciphered. However, a number of recent discoveries including disturbances in cell signaling and mutations in tumor suppressor genes have been identified, which are providing insights into the pathogenesis of ENKTL. In this review, we highlight the molecular, viral, and genetic underpinnings of ENKTL and discuss potential therapeutic implications.


Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C).
Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1), and mucosal immune dysregulation (IL-17A, CCL20, and CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK and T lymphocytes, suggesting extravasation to affected tissues. Finally, profiling the autoantigen reactivity of MIS-C plasma revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal, and immune-cell antigens. All patients were treated with anti-IL-6R antibody and/or IVIG, which led to rapid disease resolution.


Population Structure and Dynamics of Helminthic Infection: Schistosomiasis.
While disease and outbreaks are mainly clonal for bacteria and other asexually reproducing organisms, sexual reproduction in schistosomes and other helminths usually results in unique individuals. For sexually reproducing organisms, the traits conserved in clones will instead be conserved in the group of organisms that tends to breed together, the population. While the same tools are applied to characterize DNA, how results are interpreted can be quite different at times (see another article in this collection, http://www.asmscience.org/content/journal/microbiolspec/10.1128/microbiolspec.AME-0002-2018). It is difficult to know what the real effect any control program has on the parasite population without assessing the health of this population, how they respond to the control measure, and how they recover, if they do. This review, part of the Microbiology Spectrum Curated Collection: Advances in Molecular Epidemiology of Infectious Diseases, concentrates on one approach using pooled samples to study schistosome populations and shows how this and other approaches have contributed to our understanding of this parasite family's biology and epidemiology. *This article is part of a curated collection.