Joint association of physical activity and overweight with subsequent psychotropic medication: a register-linked follow-up study among employees.
Physical activity level and overweight have shown associations with mental health problems but it is not known whether the risk of mental health problems due to overweight varies by physical activity. We examined joint association of physical activity and overweight with subsequent psychotropic medication among 40-60-year-old employees. The questionnaire survey data were derived from Helsinki Health Study baseline postal questionnaires in 2000-02 among employees of the City of Helsinki aged 40-60 years (n = 8960, response rate 67%). Baseline survey data were linked with prospective register data on prescribed psychotropic medication (ATC-codes N05 and N06, except N06D) among those with written consent (74%) for such linkage. The analyses included 6169 responders (78% women, corresponding to the target population). We divided participants into six groups according to their baseline self-reported body mass index and leisure-time physical activity using physically highly active normal-weight participants as a reference group. We used Cox regression analysis adjusted for age, gender, psychotropic medication prior to baseline, and socioeconomic position, marital status, working conditions, limiting long-standing illness, alcohol use, and smoking. At baseline, 49% were overweight and 23% were physically inactive. After adjusting for age and gender, inactive normal-weight (hazard ratio (HR) 1.3, 95% CI 1.1-1.5), moderately active overweight (HR 1.3, 95% CI 1.1-1.5) and inactive overweight (HR 1.4, 95% CI 1.2-1.6) had higher risk for any psychotropic medication compared with group of highly active normal-weight. After adjusting for prior medication, only the inactive overweight group had higher risk (HR 1.4, 95% CI 1.2-1.6). Other covariates made but a minor contribution to the examined associations. For antidepressants the associations were somewhat stronger than for sedatives. Both normal-weight and physical activity help prevent psychotropic medication but physical activity dominates the association over normal-weight.


Dermoscopic yellow structures in basal cell carcinoma.
Yellowish structures in dermoscopy comprise milia-like cysts (MLCs) and yellow lobular-like structures. This study aimed at establishing the frequency of these features in BCC and at describing their dermoscopic details. A retrospective analysis of digital dermoscopic images referring to 400 BCCs was performed. Images were evaluated for the presence of starry and cloudy MLCs and yellow lobular-like structures. Among the 400 BCCs constituting our database, 40 presented yellowish structures (10%). "Yellow" BCCs were located more frequently on the head and were mainly of the nodular type. MLCs were observed in 7.75% of the cases (with a mean number of 4.9 MLCs per lesion), whereas yellow globules were noticed in 4.2% /ucodep of the lesions. In the presence of BCC specific dermoscopic criteria, the observation of MLCs and yellow lobular-like structures should not prompt the dermatologist to exclude the diagnosis of BCC.


Anti‑tumor effects of anti‑epileptic drugs in malignant glioma cells.
Patients with glioblastoma frequently suffer epileptic seizures and often require anticonvulsant therapy during the treatment course. The present study investigated four common antiepileptic drugs, perampanel, carbamazepine (CBZ), sodium valproate (VPA) and levetiracetam (LEV), which are expected to have antitumor effects, and determined the most beneficial drug for the treatment of malignant glioma by comparing antitumor effects such as inhibition of cell proliferation and suppression of migration and invasion (using Transwell assays). The inhibition of cell growth was investigated using six malignant glioma cell lines (A‑172, AM‑38, T98G, U‑138MG, U‑251MG and YH‑13). Significant inhibition of cell proliferation was observed in all six cell lines treated with perampanel, three cell lines treated with CBZ, four cell lines treated with VPA and two cell lines treated with LEV at the therapeutic blood concentration levels for the drugs to be used as antiepileptics. Further antitumor effects in combination with temozolomide were investigated using T98G and U‑251MG cell lines, and were confirmed in both cell lines with perampanel and in T98G cells with LEV, but not observed with CBZ and VPA. Cell migration was significantly suppressed in both T98G and U‑251MG cell lines with perampanel, but not with CBZ, VPA or LEV. To investigate the mechanisms by which perampanel suppresses the migration of malignant glioma cells, the expression of mRNA related to epithelial‑mesenchymal transition following perampanel treatment was analyzed using reverse transcription‑quantitative PCR in the T98G and U‑251MG cell lines. The expression of Rac1 and RhoA, which constitute the cytoskeleton that enhances cell motility, were reduced in both cell lines. Furthermore, the expression of the mesenchymal marker N‑cadherin, which promotes cell migration and infiltration, was decreased, but the expression of the epithelial marker E‑cadherin, which strengthens cell‑cell adhesion and reduces cell motility, was increased. Furthermore, the expression of matrix metalloproteinase‑2, a proteolytic enzyme, was reduced. These effects may reduce cell motility and increase adhesion between cells, suggesting that perampanel treatment suppressed cell migration. In conclusion, the present study suggests that perampanel may be more beneficial in terms of antitumor efficacy than other antiepileptic drugs for the treatment of malignant glioma.


Sleep and Mental Health in Undergraduate Students with Generally Healthy Sleep Habits.
Whereas previous research has indicated that sleep problems tend to co-occur with increased mental health issues in university students, relatively little is known about relations between sleep quality and mental health in university students with generally healthy sleep habits. Understanding relations between sleep and mental health in individuals with generally healthy sleep habits is important because (a) student sleep habits tend to worsen over time and (b) even time-limited experience of sleep problems may have significant implications for the onset of mental health problems. In the present research, 69 university students with generally healthy sleep habits completed questionnaires about sleep quality and mental health. Although participants did not report clinically concerning mental health issues as a group, global sleep quality was associated with mental health. Regression analyses revealed that nighttime sleep duration and the frequency of nighttime sleep disruptions were differentially related to total problems and clinically-relevant symptoms of psychological distress. These results indicate that understanding relations between sleep and mental health in university students with generally healthy sleep habits is important not only due to the large number of undergraduates who experience sleep problems and mental health issues over time but also due to the potential to intervene and improve mental health outcomes before they become clinically concerning.


Viscoelasticity of the trachea and its effects on flow limitation.
To test the hypothesis that peak expiratory flow is determined by the wave-speed-limiting mechanism, we studied the time dependency of the trachea and its effects on flow limitation. For this purpose, we assessed the relationship between transmural pressure and cross-sectional area [the tube law (TL)] of six excised human tracheae under controlled conditions of static (no flow) and forced expiratory flow. We found that TLs of isolated human tracheae followed quite well the mathematical representation proposed by Shapiro (Shapiro AH. J Biomech Eng 99: 126-147, 1977) for elastic tubes. Furthermore, we found that the TL measured at the onset of forced expiratory flow was significantly stiffer than the static TL. As a result, the stiffer TL measured at the onset of forced expiratory flow predicted theoretical maximal expiratory flows far greater than those predicted by the more compliant static TL, which in all cases studied failed to explain peak expiratory flows measured at the onset of forced expiration. We conclude that the observed viscoelasticity of the tracheal walls can account for the measured differences between maximal and "supramaximal" expiratory flows seen at the onset of forced expiration.


Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals.
The aim of the study was to explore the relationships between lymphocyte and monocyte activation, inflammation, and subclinical vascular disease among HIV-1-infected patients on antiretroviral therapy (ART). Baseline mean common carotid artery (CCA) intima-media thickness (IMT) and carotid plaque (IMT > 1.5 cm) were evaluated in the first 60 subjects enrolled in the Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV (SATURN-HIV) trial. All subjects were adults on stable ART with evidence of heightened T-cell activation (CD8(+)CD38(+)HLA-DR(+) ≥ 19%) or increased inflammation (high-sensitivity C-reactive protein ≥ 2 mg/L). All had fasting low-density lipoprotein (LDL) cholesterol ≤ 130 mg/dL. Seventy-eight per cent of patients were men and 65% were African-American. Median (interquartile range) age and CD4 count were 47 (43, 52) years and 648 (511, 857) cells/μL, respectively. All had HIV-1 RNA < 400 HIV-1 RNA copies/mL. Mean CCA-IMT was correlated with log-transformed CD8(+)CD38(+)HLA-DR(+) percentage (r = 0.326; P = 0.043), and concentrations of interleukin-6 (r = 0.283; P = 0.028), soluble vascular cell adhesion molecule (sVCAM; r = 0.434; P = 0.004), tumour necrosis factor-α receptor-I (TNFR-I; r = 0.591; P < 0.0001) and fibrinogen (r = 0.257; P = 0.047). After adjustment for traditional cardiovascular disease (CVD) risk factors, the association with TNFR-I (P = 0.007) and fibrinogen (P = 0.033) remained significant. Subjects with plaque (n = 22; 37%) were older [mean (standard deviation) 51 (7.7) vs. 43 (9.4) years, respectively; P = 0.002], and had a higher CD8(+)CD38(+)HLA-DR(+) percentage [median (interquartile range) 31% (24, 41%) vs. 23% (20, 29%), respectively; P = 0.046] and a higher sVCAM concentration [mean (standard deviation) 737 (159) vs. 592 (160) ng/mL, respectively; P = 0.008] compared with those without plaque. Pro-inflammatory monocyte subsets and serum markers of monocyte activation (soluble CD163 and soluble CD14) were not associated with CCA-IMT or plaque. Participants in SATURN-HIV have a high level of inflammation and immune activation that is associated with subclinical vascular disease despite low serum LDL cholesterol.


A multiparametric approach to studies of self-organization of globular proteins
This review analyzes the problem of using a multiparametric approach to studies of the process of globular protein folding. The principles of the most widespread contemporary physicochemical methods for studying the structural properties of globular protein molecules are considered. The specific information that can be obtained by using these structural methods is discussed.


Digestive Disease Week 2019.
We review selected sessions on the questionable benefits of fecal microbiota transplant; intrahepatic cholestasis of pregnancy; weight-loss drugs in combination with intragastric balloon endoscopy; and beta blockers in pancreatic cancer.


Indium mediated allylation in peptide and protein functionalization.
Indium-mediated allylation has been used in the site-selective functionalization of N-terminal aldehydes of peptides and proteins. This is the first demonstration of indium-mediated C-C bond formation in protein labelling studies under mild and environmentally friendly conditions.


Mandatory changes of specific names to agree in gender with Talitriator Methuen, 1913, which is masculine (Crustacea: Amphipoda: Talitridae).
The genus Talitriator Methuen, 1913 was originally erected for T. eastwoodae Methuen, 1913, a talitrid amphipod or "land-hopper" from South Africa that was fixed as the type species of this genus by monotypy. Talitriator now includes seven species of land-hopper inhabiting South Africa as well as Saint Helena and Ascension islands in the Southern Atlantic (Stock Biernbaum 1994; Griffiths 1999; Horton et al. 2018). Although Methuen (1913) did not explicitly explain the etymology of the generic name, it obviously combines the name of the talitrid type genus Talitrus Bosc, 1802 (stem: Talitr-; from Latin talitrum, a rapping or flick of a finger: Jaeger 1962), with the connecting vowel "i" and the Latin masculine agentive suffix "-ator". On account of the final suffix, the gender of the name Talitriator is masculine. Under Articles 31.2 and 34.2 of the International Code of Zoological Nomenclature [hereafter "the Code"] (International Commission on Zoological Nomenclature 1999), a Latin adjective that is used as a species-group name must agree in gender with the generic name it is combined with. Article 34.2 further specifies that an incorrect gender ending must be changed (a "mandatory change", as opposed to either an "emendation" or an "incorrect subsequent spelling": cf. Article 33.1 of the Code). This gender-agreement rule has largely been ignored in publications concerning species of Talitriator, with adjectival names most often being spelled with the feminine suffix "-a" regardless of generic assignment.


[Fertility after ectopic pregnancy: the population-based register of the urban area around Lille, Northern France].
The aims of this work were the evaluation of the reproductive outcome after ectopic pregnancy, and the assessment of the role of infertility risk factors and treatment's strategy. All patients in the population-based register of the urban area around Lille, Northern France, were followed-up. 345 women treated between April 1994 and March 1997, who were trying to become pregnant were interviewed by telephone every 6 months and then every year. The cumulative pregnancy rates were calculated by the Kaplan-Meier estimation. Associations between infertility risk factors and intrauterine pregnancy were tested by the logrank test, and by a Cox model for multivariate analysis. The mean duration of follow-up was 22 months, and 228 (66%) women had obtained a new pregnancy at the time of the analysis. 23 (10%) of the first pregnancies were recurrences. For women for whom EP occurred with an IUCD (17 patients), the 1 year intrauterine pregnancy (IUP) reached 67%. For the others, the 1 year IUP rate was 56%, and reached 67% after 2 years. After adjusting factors associated with fertility with a Cox regression, 3 factors seemed to lower reproductive performances: age > 35 years, previous history of infertility, and anterior tubal damage. More than half the women treated for EP obtained spontaneously a normally progressive pregnancy after 1 year. Reproductive performances are associated with characteristics of the patients, but do not depend on radical or conservative treatment.


EEG Resting-State Networks in Dementia with Lewy Bodies Associated with Clinical Symptoms.
Dementia with Lewy bodies (DLB) is characterized by progressive cognitive decline, fluctuating cognition, visual hallucinations, rapid eye movement sleep behavior disorder, and parkinsonism. DLB is the second most common type of degenerative dementia of all dementia cases. However, DLB, particularly in the early stage, is underdiagnosed and sometimes misdiagnosed with other types of dementia. Thus, it is of great interest investigating neurophysiological markers of DLB. We introduced exact low-resolution brain electromagnetic tomography (eLORETA)-independent component analysis (ICA) to assess activities of 5 electroencephalography (EEG) resting-state networks (RSNs) in 41 drug-free DLB patients. Compared to 80 healthy controls, DLB patients had significantly decreased activities in occipital visual and sensorimotor networks, where DLB patients and healthy controls showed no age dependences in all EEG-RSN activities. Also, we found correlations between all EEG-RSN activities and DLB symptoms. Specifically, decreased occipital α activity showed correlations with worse brain functions related to attention/concentration, visuospatial discrimination, and global cognition. Enhanced visual perception network activity correlated with milder levels of depression and anxiety. Enhanced self-referential network activity correlated with milder levels of depression. Enhanced memory perception network activity correlated with better semantic memory, visuospatial discrimination function, and global cognitive function as well as with severer visual hallucination. In addition, decreased sensorimotor network activity correlated with a better semantic memory. These results indicate that eLORETA-ICA can detect EEG-RSN activity alterations in DLB related to symptoms. Therefore, eLORETA-ICA with EEG data can be a useful noninvasive tool for sensitive detection of EEG-RSN activity changes characteristic of DLB and for understanding the neurophysiological mechanisms underlying this disease.


Sperm storage in caecilian amphibians.
Female sperm storage has evolved independently multiple times among vertebrates to control reproduction in response to the environment. In internally fertilising amphibians, female salamanders store sperm in cloacal spermathecae, whereas among anurans sperm storage in oviducts is known only in tailed frogs. Facilitated through extensive field sampling following historical observations we tested for sperm storing structures in the female urogenital tract of fossorial, tropical caecilian amphibians. In the oviparous Ichthyophis cf. kohtaoensis, aggregated sperm were present in a distinct region of the posterior oviduct but not in the cloaca in six out of seven vitellogenic females prior to oviposition. Spermatozoa were found most abundantly between the mucosal folds. In relation to the reproductive status decreased amounts of sperm were present in gravid females compared to pre-ovulatory females. Sperm were absent in females past oviposition. Our findings indicate short-term oviductal sperm storage in the oviparous Ichthyophis cf. kohtaoensis. We assume that in female caecilians exhibiting high levels of parental investment sperm storage has evolved in order to optimally coordinate reproductive events and to increase fitness.


Progress in Clinical Encapsulated Islet Xenotransplantation.
At the 2015 combined congress of the Cell Transplant Society, International Pancreas and Islet Transplant Association, and International Xenotransplantation Association, a symposium was held to discuss recent progress in pig islet xenotransplantation. The presentations focused on 5 major topics - (1) the results of 2 recent clinical trials of encapsulated pig islet transplantation, (2) the inflammatory response to encapsulated pig islets, (3) methods to improve the secretion of insulin by pig islets, (4) genetic modifications to the islet-source pigs aimed to protect the islets from the primate immune and/or inflammatory responses, and (5) regulatory aspects of clinical pig islet xenotransplantation. Trials of microencapsulated porcine islet transplantation to treat unstable type 1 diabetic patients have been associated with encouraging preliminary results. Further advances to improve efficacy may include (1) transplantation into a site other than the peritoneal cavity, which might result in better access to blood, oxygen, and nutrients; (2) the development of a more biocompatible capsule and/or the minimization of a foreign body reaction; (3) pig genetic modification to induce a greater secretion of insulin by the islets, and/or to reduce the immune response to islets released from damaged capsules; and (4) reduction of the inflammatory response to the capsules/islets by improvements in the structure of the capsules and/or in genetic engineering of the pigs and/or in some form of drug therapy. Ethical and regulatory frameworks for islet xenotransplantation are already available in several countries, and there is now a wider international perception of the importance of developing an internationally harmonized ethical and regulatory framework.


Orbital Vascular Anomalies: A Nomenclatorial, Etiological, and Nosologic Conundrum.
Vascular anomalies are a heterogeneous group of disorders that frequently present in the periorbital region. They encompass 2 broad entities: vascular tumors, which possess a proliferative endothelium, and vascular malformations, which are basically localized defects of vascular morphogenesis. The primary goal of this review was to address inaccurate or controversial terminology in the oculoplastic literature concerning orbital and periorbital vascular anomalies and to categorize these lesions in an abridged and simplified hierarchical list that adheres as much as possible to the most recent (2018) iteration for the classification of vascular lesions proposed by the International Society for the Study of Vascular Anomalies (ISSVA). The secondary goal of this review was to review and update information regarding the genetic underpinnings of vascular anomalies and the downstream signaling pathways that are subsequently affected as a result of these genetic errors. A literature review was conducted in PubMed, MEDLINE, PubMed Central, National Center for Biotechnology Information Bookshelf, and Embase for several related keywords including "vascular anomalies, vascular malformations, vascular tumors, and cavernous venous malformation," both with and without adding the keywords "eyelid," "orbital," and "periorbital." In addition, a detailed search was conducted for controversial or obsolete keywords like "cavernous hemangioma," "lymphangioma," and "varices," again in their systemic and orbital/periorbital context. Crucial issues in the 2018 ISSVA classification regarding the proper categorization of orbital vascular anomalies, particularly venous lesions, were critically evaluated and revised, and a regional, simplified, and abridged modification of the ISSVA 2018 classification was proposed. Interdisciplinary and intradisciplinary dialogue concerning orbital vascular anomalies is seriously compromised due to the lack of a unanimous agreement on terminology and the absence of a unified classification concept system. The authors recommend that oculoplastic surgeons adopt ISSVA terminology whenever technically possible and scientifically sound. However, they also propose modifying the ISSVA 2018 classification specifically to adapt to the peculiarities of vascular anomalies in the periorbital region. At present, the simplified classification proposed here is a preliminary first step towards managing patients with orbital vascular anomalies with greater diagnostic and therapeutic precision, until such time in the future when the entire genetic makeup of orbital vascular anomalies is more completely elucidated. Optimistically, this could pave the way for a more robust classification and the ultimate therapeutic cure.


Dental caries and fluorosis in children from high and low fluoride areas of Morocco.
The purpose of this study was to estimate the prevalence and the severity of dental caries and dental fluorosis in primary and permanent teeth of 582 subjects, aged 7 to 16 years, from the fluorosis area of Khouribga and the non-fluorosis area of Beni Mellal, Morocco. At age-group 7-10, where 67.8 percent of primary teeth were present, about 35 percent of the children were affected in the high-fluoride area and the community fluorosis index was 0.86. The percentage and average number of erupted permanent teeth were higher in Beni Mellal than in Khouribga for 11-12 and 13-14-year-old age-groups. Significant differences in caries prevalence were observed between the high- and low-fluoride areas. In both regions, high and low prevalence of dental caries was observed in the primary and permanent teeth, respectively.


A protein chip designed to differentiate visually antibodies in chickens which were infected by four different viruses.
This study aimed to develop a visual protein chip that can differentiate the antibodies induced by avian influenza virus, Newcastle disease virus, infectious bronchitis virus and infectious bursal disease virus, simultaneously. Proteins from the four viruses were purified and spotted onto an aldehyde group-modified glass slide at 2mg/ml. After that, the protein chip was reacted with the corresponding positive serum against these viruses, hybridized with a colloidal gold-labeled secondary antibody and visualized by silver staining. A diagnostic protein chip was constructed to differentiate antibodies of four poultry diseases This protein chip showed good sensitivity compared with traditional methods, and it was more than 400 times as sensitive as the agar gel precipitin methods used to detect avian influenza and infectious bursal disease. The protein chip was used to test known serum samples of the four poultry diseases and field serum samples. The results showed that this method could hybridize specifically with the corresponding antibodies with strong signals and without cross-hybridization. In conclusion, this protein chip can be used to differentiate the antibodies induced by the four avian viruses.


Per-Arylation of Pillar[n]arenes: An Effective Tool to Modify the Properties of Macrocycles.
Installation of various substituents is a reliable and versatile way to alter the properties of macrocyclic molecules, but high-yield and controlled methods are not always available especially for multifold reactions. Herein, we report 10- and 12-fold introduction of aryl substituents onto both rims of cylinder-shaped pillar[n]arenes, which usually have alkoxy substituents slanting to the cylinder axes. Although alkoxy pillar[5]arenes exist as D5-symmetric enantiomeric pairs, arylated pillar[5]arenes provide crushed single-crystal structures and stereoisomerism including C2-symmetric conformations depending on the aryl groups. Pillar[n]arenes with 2-benzofuranyl groups display bright fluorescence with quantum yields of 88-90% and no host-guest complexation with electron-deficient molecules in solution due to large deviation from alkoxy compounds. A benzofuran-appended pillar[6]arene instead captures small gaseous molecules in the solid state, probably owing to outside spaces surrounded by aromatic rings.


A systematic literature search on psychological first aid: lack of evidence to develop guidelines.
Providing psychological first aid (PFA) is generally considered to be an important element in preliminary care of disaster victims. Using the best available scientific basis for courses and educational materials, the Belgian Red Cross-Flanders wants to ensure that its volunteers are trained in the best way possible. To identify effective PFA practices, by systematically reviewing the evidence in existing guidelines, systematic reviews and individual studies. Systematic literature searches in five bibliographic databases (MEDLINE, PsycINFO, The Cochrane Library, PILOTS and G-I-N) were conducted from inception to July 2013. Five practice guidelines were included which were found to vary in the development process (AGREE II score 20-53%) and evidence base used. None of them provides solid evidence concerning the effectiveness of PFA practices. Additionally, two systematic reviews of PFA were found, both noting a lack of studies on PFA. A complementary search for individual studies, using a more sensitive search strategy, identified 11 237 references of which 102 were included for further full-text examination, none of which ultimately provides solid evidence concerning the effectiveness of PFA practices. The scientific literature on psychological first aid available to date, does not provide any evidence about the effectiveness of PFA interventions. Currently it is impossible to make evidence-based guidelines about which practices in psychosocial support are most effective to help disaster and trauma victims.


Benefits of powered standing wheelchair devices for adolescents with Duchenne muscular dystrophy in the first year of use.
Poorer physical and mental health often accompany loss of walking in Duchenne muscular dystrophy. This study assessed the impacts of powered wheelchair standing device (PWSD) use on muscle and joint pain, joint angles when standing and mental health in adolescents with Duchenne muscular dystrophy. Fourteen adolescents and parents participated in a stepped wedge design study over 12 months. During a baseline and intervention period, adolescents described pain and mental health, and parents reported their child's mental health. Video data were collected to measure hip, knee and ankle joint angles in the preferred standing position. Compared with baseline and adjusting for covariates, standing wheelchair use was associated with no change in muscle or joint pain or videoed joint angles in standing. Child-reported Strengths and Difficulties total scores decreased (coefficient -3.1, 95% confidence interval -4.6, -1.5); and parent-reported Personal Adjustment and Role Skills Scale total scores increased (coefficient 7.9, 95% confidence interval 3.3-12.5). PWSD use was associated with maintenance of musculoskeletal status and advantages to mental health. Long-term observations are necessary to improve understanding of how to support wellbeing in adolescents with Duchenne muscular dystrophy.


Complex clonal and plasmid epidemiology in the first outbreak of Enterobacteriaceae infection involving VIM-1 metallo-beta-lactamase in Spain: toward endemicity?
We report the emergence and spread of metallo-beta-lactamases (MBLs) among enterobacterial isolates at Ramón y Cajal University Hospital (Madrid, Spain). During the period from March 2005 through September 2006, 25 patients (52% of whom were in the intensive care unit) were infected and/or colonized with single or different MBL-producing Enterobacteriaceae isolates (Klebsiella pneumoniae, 14 patients; Enterobacter cloacae, 12 patients; Escherichia coli, 1 patient; and/or Klebsiella oxytoca, 1 patient). Clonal analysis (XbaI pulsed-field gel electrophoresis) revealed that all K. pneumoniae isolates belonged to the same clone, but 6 patterns were found among the E. cloacae isolates. Carbapenems were affected to different degrees (minimum inhibitory concentration, < or = 1 to > 8 microg/mL), as were aminoglycosides and ciprofloxacin. The bla(VIM-1) MBL gene was present in all isolates; in addition, the bla(SHV-12) extended-spectrum beta-lactamase gene was detected in K. pneumoniae and E. coli isolates. The bla(VIM-1) gene was detected within a 4.0-kb class 1 integron (bla(VIM-1)-aacA4-dfrII-aadA1-catB2) in K. pneumoniae and E. coli and in a 2.5-kb class 1 integron (bla(VIM-1)-aacA4-aadA1) in E. cloacae and K. oxytoca isolates. The bla(VIM-1) gene was transferable (filter-mating) in 14 of 14 K. pneumoniae isolates, 4 of 11 E. cloacae isolates, and 1 of 1 E. coli isolate. A 60-kb plasmid belonging to the IncI1 group was detected in the epidemic VIM-1-K. pneumoniae clone. Plasmids of 300- or 435-kb belonging to IncH12 group were found among E. cloacae isolates. K. pneumoniae-MBL monoclonal epidemics coexisted with E. cloacae-MBL multiclonal epidemics in our hospital. The spread of the bla(VIM-1) gene among Enterobacteriaceae was driven by clonal spread associated with intergeneric plasmid transfer with different class I integron platforms. Such complex epidemiology might anticipate endemicity and should be considered for the design of containment epidemiology strategies.


What survivors want: Understanding the needs of sexual assault survivors.
Sexual assault is a pervasive crime on our college campuses and many survivors do not seek post-assault resources. This study will explore components of alternative interventions to consider in the development of campus-based interventions for sexual assault survivors. Three stakeholder groups including survivors (n = 8), healthcare providers (n = 6), and advocates (n = 19) were recruited from May 2014 to December 2014 from two university campus communities using flyers and purposive sampling. A qualitative study design utilized semi-structured interviews and semi-structured focus groups with survivors, healthcare providers, and advocates. Five themes emerged to consider for future campus-based sexual assault interventions: (a) culture of caring, (b) one-stop shop, (c) validation, (d) survivor control and agency, and (e) confidentiality. Although accessible and effective options for post-assault care do currently exist, participants described alternative future interventions that were either (a) print materials or (b) technology-based.


SpindleU-Net: An Adaptive U-Net Framework for Sleep Spindle Detection in Single-Channel EEG.
The sleep spindles in EEG have become one type of biomarker used to assess cognitive abilities and related disorders, and thus their detection is crucial for clinical research. This task, traditionally performed by sleep experts, is time-consuming. Many methods have been proposed to automate this process, yet an increase in performance is still expected. Inspired by the application in image segmentation, we propose a point-wise spindle detection method based on the U-Net framework with an attention module (SpindleU-Net). It maps the sequences of arbitrary-length EEG inputs to those of dense labels of spindle or non-spindle on freely chosen intervals. The attention module that focuses on the salient spindle region allows better performance, and a task-specific loss function is defined to alleviate the problem of imbalanced classification. As a deep learning method, SpindleU-Net outperforms state-of-the-art methods on the widely used benchmark dataset of MASS as well as the DREAMS dataset with a small number of samples. On MASS dataset it achieves average F1 scores of 0.854 and 0.803 according to its consistency with the annotations by two sleep experts respectively. On DREAMS dataset, it shows the average F1 score of 0.739. Its cross-dataset performance is also better compared to other methods, showing the good generalization ability for cross-dataset applications.


[A prospective cohort study on effects of levonorgestrel-releasing intrauterine system for adenomyosis with severe dysmenorrhea].
To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with severe dysmenorrhea in a prospective cohort study. From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients' parameters were recorded prospectively, including symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, carrying status of LNG-IUS, menstruation patterns and adverse effects. Changes of scores and patterns of pain during follow-up were analyzed. Totally 1 100 women meets inclusion criteria, among which 640 cases (58.18%, 640/1 100) had severe dysmeorrhea, with median follow-up period of 35 months (range 1-60 months), and accumulative carrying rate of 65% at 60 months follow-up. After placement of LNG-IUS, scores of pain and ratio of severe dysmenorrhea had decreased significantly compared with baselines (all P<0.01), the scroes of visual analog scale (VAS) were 8.1±0.9, 5.5±2.4, 4.6±2.4, 3.3±2.2, 2.2±2.1, 2.2±1.8, 1.4±1.6 and 1.3±1.3 at 0, 3, 6, 12, 24, 36, 48 and 60 months respectively. During 36 months after placement of LNG-IUS, scores of pain had improved significantly compared with preceding period (all P<0.01). We found no universal dependent factors predicting improvement of pain, which was neither relevant with simultaneous changes of menstruation patterns nor adverse effects (all P>0.05). LNG-IUS is effective for adenomyosis of severe dysmenorrhea. Improvement of pain is independent on patients characters, menstruation patterns or adverse effects.


Oral microbiome and systemic antineoplastics in cancer treatment: A systematic review.
Oral mucositis is one of the most common side effects in cancer patients receiving systemic antineoplastics. However, the underlying biological mechanisms leading to this condition are still unclear. For this reason, it has been hypothesised that systemic antineoplastics may cause an imbalance on the oral microbiota that subsequently triggers oral mucosa damage. A systematic review was performed following the PRISMA protocol and the PICO question established was: patients diagnosed with cancer, who are candidates for receiving systemic antineoplastics (P=Patients), that undergo oral microbiome determinations (I=Intervention), before and after systemic antineoplastics administration (C=Comparison), to analyse changes in the oral microbiome composition (O=Outcome). The bibliographic search was carried out in PubMed and other scientific repositories. Out of 166 obtained articles, only 5 met eligibility criteria. Acute myeloid leukaemia (AML) was the most frequent type of cancer (40 %) among the participants. Only one of the studies included a control group of healthy subjects. Heterogeneity in the protocols and approaches of the included studies hindered a detailed comparison of the outcomes. However, it was stated that a decrease in bacteria α diversity is often associated with oral mucositis. On the other hand, fungal diversity was not associated with oral mucositis although α diversity was lower at baseline on patients developing oral candidiasis. There is insufficient scientific evidence of oral microbiological changes in patients undergoing systemic antineoplastics. Further investigations ought to be carried out to identify microorganisms that might play a key role in the pathogenesis of oral mucosa damage in patients undergoing systemic antineoplastics.


Multiscale Modulation of Nanocrystalline Cellulose Hydrogel via Nanocarbon Hybridization for 3D Neuronal Bilayer Formation.
Bacterial biopolymers have drawn much attention owing to their unconventional three-dimensional structures and interesting functions, which are closely integrated with bacterial physiology. The nongenetic modulation of bacterial (Acetobacter xylinum) cellulose synthesis via nanocarbon hybridization, and its application to the emulation of layered neuronal tissue, is reported. The controlled dispersion of graphene oxide (GO) nanoflakes into bacterial cellulose (BC) culture media not only induces structural changes within a crystalline cellulose nanofibril, but also modulates their 3D collective association, leading to substantial reduction in Young's modulus (≈50%) and clear definition of water-hydrogel interfaces. Furthermore, real-time investigation of 3D neuronal networks constructed in this GO-incorporated BC hydrogel with broken chiral nematic ordering revealed the vertical locomotion of growth cones, the accelerated neurite outgrowth (≈100 µm per day) with reduced backward travel length, and the efficient formation of synaptic connectivity with distinct axonal bifurcation abundancy at the ≈750 µm outgrowth from a cell body. In comparison with the pristine BC, GO-BC supports the formation of well-defined neuronal bilayer networks with flattened interfacial profiles and vertical axonal outgrowth, apparently emulating the neuronal development in vivo. We envisioned that our findings may contribute to various applications of engineered BC hydrogel to fundamental neurobiology studies and neural engineering.


Molecular mechanisms of the phospho-dependent prolyl cis/trans isomerase Pin1.
Since its discovery 10 years ago, Pin1, a prolyl cis/trans isomerase essential for cell cycle progression, has been implicated in a large number of molecular processes related to human diseases, including cancer and Alzheimer's disease. Pin1 is made up of a WW interaction domain and a C-terminal catalytic subunit, and several high-resolution structures are available that have helped define its function. The enzymatic activity of Pin1 towards short peptides containing the pSer/Thr-Pro motif has been well documented, and we discuss the available evidence for the molecular mechanisms of its isomerase activity. We further focus on those studies that examine its cis/trans isomerase function using full-length protein substrates. The interpretation of this research has been further complicated by the observation that many of its pSer/Thr-Pro substrate motifs are located in natively unstructured regions of polypeptides, and are characterized by minor populations of the cis conformer. Finally, we review the data on the possibility of alternative modes of substrate binding and the complex role that Pin1 plays in the degradation of its substrates. After considering the available work, it seems that further analysis is required to determine whether binding or catalysis is the primary mechanism through which Pin1 affects cell cycle progression.


Human proangiogenic circulating hematopoietic stem and progenitor cells promote tumor growth in an orthotopic melanoma xenograft model.
We previously identified a distinct population of human circulating hematopoietic stem and progenitor cells (CHSPCs; CD14(-)glyA(-)CD34(+)AC133(+/-)CD45(dim)CD31(+) cells) in the peripheral blood (PB) and bone marrow, and their frequency in the PB can correlate with disease state. The proangiogenic subset (pCHSPC) play a role in regulating tumor progression, for we previously demonstrated a statistically significant increase in C32 melanoma growth in NOD.Cg-Prkdc (scid) (NOD/SCID) injected with human pCHSPCs (p < 0.001). We now provide further evidence that pCHSPCs possess proangiogenic properties. In vitro bio-plex cytokine analyses and tube forming assays indicate that pCHSPCs secrete a proangiogenic profile and promote vessel formation respectively. We also developed a humanized bone marrow-melanoma orthotopic model to explore in vivo the biological significance of the pCHSPC population. Growth of melanoma xenografts increased more rapidly at 3-4 weeks post-tumor implantation in mice previously transplanted with human CD34(+) cells compared to control mice. Increases in pCHSPCs in PB correlated with increases in tumor growth. Additionally, to determine if we could prevent the appearance of pCHSPCs in the PB, mice with humanized bone marrow-melanoma xenografts were administered Interferon α-2b, which is used clinically for treatment of melanoma. The mobilization of the pCHSPCs was decreased in the mice with the humanized bone marrow-melanoma xenografts. Taken together, these data indicate that pCHSPCs play a functional role in tumor growth. The novel in vivo model described here can be utilized to further validate pCHSPCs as a biomarker of tumor progression. The model can also be used to screen and optimize anticancer/anti-angiogenic therapies in a humanized system.


New records of six deep-sea caridean shrimps (Crustacea: Decapoda) from the Ryukyu Islands and its adjacent waters, southwestern Japan.
Six species of caridean shrimps from four families are recorded from Japanese waters for the first time on the basis of material from the Ryukyu Islands and its adjacent waters, collected during research cruises of the T/RV "Toyoshio-maru" of Faculty of Applied Biological Science, Hiroshima University: two species of Crangonidae, Lissosabinea unispinosa Komai, 2006 and Pseudopontophilus serratus Komai, 2004; one species of Oplophoridae, Systellaspis pellucida (Filhol, 1885); one species of Pandalidae, Calipandalus elachys Komai Chan, 2003; and two species of Pasiphaeidae, Pasiphaea debitusae Hayashi, 1999 and P. gracilis Hayashi, 1999. Of them, L. unispinosa, Pseudopontophilus serratus, Pasiphaea debitusae and P. gracilis are heretofore known from the South-West Pacific localities, and then the geographical ranges of these four species are greatly extended to the north and west. Illustrations and/or colour images are provided for each species to supplement previous descriptions and to give evidence for identification.


Possible involvement of cationic-drug sensitive transport systems in the blood-to-brain influx and brain-to-blood efflux of amantadine across the blood-brain barrier.
The purpose of this study was to characterize the brain-to-blood efflux transport of amantadine across the blood-brain barrier (BBB). The apparent in vivo efflux rate constant for [(3) H]amantadine from the rat brain (keff ) was found to be 1.53 × 10(-2) min(-1) after intracerebral microinjection using the brain efflux index method. The efflux of [(3) H]amantadine was inhibited by 1-methyl-4-phenylpyridinium (MPP(+) ), a cationic neurotoxin, suggesting that amantadine transport from the brain to the blood across the BBB potentially involves the rat plasma membrane monoamine transporter (rPMAT). On the other hand, other selected substrates for organic cation transporters (OCTs) and organic anion transporters (OATs), as well as inhibitors of P-glycoprotein (P-gp), did not affect the efflux transport of [(3) H]amantadine. In addition, in vitro studies using an immortalized rat brain endothelial cell line (GPNT) showed that the uptake and retention of [(3) H]amantadine by the cells was not changed by the addition of cyclosporin, which is an inhibitor of P-gp. However, cyclosporin affected the uptake and retention of rhodamine123. Finally, the initial brain uptake of [(3) H]amantadine was determined using an in situ mouse brain perfusion technique. Notably, the brain uptake clearance for [(3) H]amantadine was significantly decreased with the co-perfusion of quinidine or verapamil, which are cationic P-gp inhibitors, while MPP(+) did not have a significant effect. It is thus concluded that while P-gp is not involved, it is possible that rPMAT and the cationic drug-sensitive transport system participate in the brain-to-blood efflux and the blood-to-brain influx of amantadine across the BBB, respectively.


Carbofuran affects cellular autophagy and developmental senescence through the impairment of Nrf2 signalling.
Carbofuran is a broad-spectrum synthetic pesticide. Its exposure to non-target mammals affects the biological system through the induction of oxidative stress. Since oxidative stress is a major contributing factor to cellular autophagy and senescence, our present investigation determined the impacts of carbofuran-induced oxidative stress on cellular autophagy and senescence. A transmembrane protein, Spinster homolog 1 (Spns1), is involved in autophagic lysosomal metabolism. Its mutation accelerates the cellular senescence and shortens the lifespan. Using a transgenic zebrafish line, expressing fluorescent microtubules-associated protein 1 light chain 3 (EGFP-LC3) at the membrane of the autophagosome, we found that carbofuran affects autophagic lysosomal biogenesis in wild-type zebrafish and exacerbates autophagic defect in spns1-mutant zebrafish. In real-time mortality study, carbofuran has shortened the lifespan of wild-type fish. Nrf2 is a stress-responsive transcription factor that regulates the expression of antioxidant genes (such as gstp1) in the prevention of oxidative stress-mediated cellular damage. To assess the effect of carbofuran on Nrf2 signalling, we established a dual-monitoring transgenic zebrafish line, expressing gstp1 promoter-driven EGFP and mCherry-tagged Neh2 domain of Nrf2. Our results suggested that the exposure of carbofuran has down-regulated both Nrf2 and Gstp1 expressions. Overall, carbofuran affects cellular autophagy and accelerates senescence by enervating the Nrf2 signalling.


Principles and philosophies for speech and language therapists working with people with primary progressive aphasia: an international expert consensus.
Primary progressive aphasia (PPA) is a language-led dementia associated with Alzheimer's pathology and fronto-temporal lobar degeneration. Multiple tailored speech and language interventions have been developed for people with PPA. Speech and language therapists/speech-language pathologists (SLT/Ps) report lacking confidence in identifying the most pertinent interventions options relevant to their clients living with PPA during their illness trajectory. The aim of this study was to establish a consensus amongst 15 clinical-academic SLT/Ps on best practice in selection and delivery of speech and language therapy interventions for people with PPA. An online nominal group technique (NGT) and consequent focus group session were held. NGT rankings were aggregated and focus groups video recorded, transcribed, and reflexive thematic analysis undertaken. The results of the NGT identified 17 items. Two main themes and seven further subthemes were identified in the focus groups. The main themes comprised (1) philosophy of person-centredness and (2) complexity. The seven subthemes were knowing people deeply, preventing disasters, practical issues, professional development, connectedness, barriers and limitations, and peer support and mentoring towards a shared understanding. This study describes the philosophy of expert practice and outlines a set of best practice principles when working with people with PPA.Implications for rehabilitationPrimary progressive aphasia (PPA) describes a group of language led dementias which deteriorate inexorably over time.Providing speech and language therapy for people with PPA is complex and must be person centred and bespoke.This study describes the philosophy of expert practice and outlines a set of best practice principles for speech and language therapists/pathologists working with people with people with PPA.


Chemotactic activity of elastin-derived peptides.
Elastin-derived peptides, produced by digesting human aortic elastin and bovine ligament elastin with human neutrophil elastase, were tested for chemotactic activity. At 100 micrograms protein/ml, elastin digests were nearly as active for monocytes as saturating amounts of complement-derived chemotactic activity. Neutrophils and alveolar macrophages showed less response to elastin peptidces than did monocytes. Fractionation of the digests by gel filtration chromatography disclosed that maximal chemotactic activity eluted in fractions corresponding to 14,000-20,000 mol wt containing most of the desmosine cross-links in the digests. Whole human serum and rabbit anti-elastin immunoglobulin inhibited the chemotactic activity. Purified desmosine also showed chemotactic activity for monocytes, maximal at 10 nM. These findings suggest that elastin-degradation products enriched in cross-linking regions recruit inflammatory cells in vivo and that elastin proteolysis, characteristic of emphysema, may be a signal for recruitment of mononuclear phagocytes into the lungs.


Fatty acid synthase inhibition induces differential expression of genes involved in apoptosis and cell proliferation in ocular cancer cells.
Fatty acid synthase (FASN), a lipogenic multienzyme complex, is overexpressed in the ocular cancer, retinoblastoma, and is strongly correlated with tumor invasion. Dietary nutrients are reported to exert anticancer effects through inhibition of lipid metabolism. Differential gene expression in cultured retinoblastoma cells induced by cerulenin, a chemical inhibitor of FASN, was evaluated by cDNA microarray analysis. Cerulenin treatment resulted in significant upregulation of cytochrome c (CYCS) by 1.2-fold, whereas S-phase kinase-associated protein-2 (SKP2), a negative regulator of cell cycle, and the lipid metabolic genes (PPARA, RXRA, and ACACB) were significantly downregulated by -1.59-, -1.8-, -1.83-, and -1.5-fold, respectively, in comparison with untreated cancer cells. The expressions of key differentially expressed genes were confirmed by quantitative real-time PCR. The altered expression of genes involved in cell proliferation, cell signaling, apoptosis, and cell cycle, correlated with the anticancer effects of cerulenin. FASN inhibition may thus be a potential strategy in retinoblastoma management.


[Correlation between neck pressure pain threshold and forward head posture in patients with temporomandibular joint disorders].
Objective: To investigate the association between neck muscles pressure pain thresholds (PPT) and forward head posture (FHP) in patients with temporomandibular disorders (TMD). Methods: A total of 145 TMD patients, including 23 males and 122 females with a median age of 28 years, were enrolled in the Department of Rehabilitation Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from December 2019 to April 2020. Informations of FHP and neck muscles PPT were collected for all participants. FHP was characterized by the craniocervical angle (CVA) between C7, the tragus of the ear and the horizontal line. Each of the participants completed a questionaire of the neck disability index (NDI). The patients with CVA≤51 ° were asigned into FHP group, otherwise the patients with CVA>51° were asigned into non-FHP group. PPT were measured at the midpoint of the upper trapezius and 1 cm aside from C5-C6 articular pillars. Nonparametric test and Spearman correlation analysis were conducted for the data analysis. Results: There were 70 patients in the FHP group and 75 patients in the non-FHP group. The trapezius PPT of the FHP group [2.82(0.86) kg] was significantly higher than that of the non-FHP group [2.46(0.80) kg] (P<0.01). No significant differences in PPT and NDI were observed between the two groups (P>0.05). Low correlation was found between trapezius PPT and FHP negatively (r=-0.273, P<0.01) and no correlation was found between C5-C6 PPT and FHP (r=-0.124, P>0.05). PPT in trapezius and C5-C6 was negatively correlated with NDI in moderate (r=-0.301, P<0.01) and low (r=-0.206, P<0.05) levels. Conclusions: The trapezius PPT was correlated with FHP negatively. The more FHP, the more pain tolerant of trapezius muscles. There was no correlation between neck function and FHP directly. The higher threshold was followed by better neck function.


Role of methionine in the regulation of serine hydroxymethyltransferase in Eschericia coli.
Significant derepression of serine hydroxymethyltransferase is observed when metE or metF mutants of Escherichia coli K-12 are grown on D-methionine sulfoxide instead of L-methionine. The derepression is not prevented by addition of glycine, adenosine, guanosine, guanosine, and thymidine to the growth medium of methionine-limited metF cells showing that the effect is not due to a secondary deficiency of these nutrients. On the other hand, methionine-limited growth of a metA mutant leads to derepression of met regulon enzymes, but only a marginal increase in serine hydroxymethyltransferase activity. A prototrophic metJ strain grown on minimal medium has about the same serine hydroxymethyltransferase as the wild type. The enzyme activity of the metJ strain is not influenced by methionine, but it is partially repressed by glycine, adenosine, and thymidine. metK strains have about twice as much serine hydroxymethyltransferase activity as wild-type cells when grown on minimal medium; but when both types of cells are grown on medium supplemented with glycine, adenosine, guanosine, and thymidine, their enzyme activities are about the same. The results show that methionine limitation can lead to depression of serine hydroxymethyltransferase, but that the regulatory system is different from the one which controls the methionine regulon.


Evaluation of Steaming and Drying of Black Sesame Seeds for Nine Cycles Using Grey-Correlation Analysis Based on Variation-Coefficient Weight.
This study aimed to improve the steaming process of black sesame seeds. A comprehensive evaluation was conducted using the grey-correlation method based on the variation-coefficient weight to observe the treatments of normal-pressure (NPS) and high-pressure (HPS) steaming (with/without soaking in water) for nine cycles. Their effects on the contents of water, protein, fat, ash, melanin, sesamin, and sesamolin of black sesame seeds, as well as the sensory score of the black sesame pill, were determined. We found that with varied steaming methods and increased steaming cycles, the contents of the nutritional and functional components of black sesame seeds and the sensory score of the black sesame pill differed. The results of the variation-coefficient method showed that water, protein, fat, ash, melanin, sesamin, sesamolin, and sensory score had different effects on the quality of black sesame seeds with weighting factors of 34.4%, 5.3%, 12.5%, 11.3%, 13.9%, 11.3%, 7.8%, and 3.5%, respectively. The results of two-factor analysis of variance without repeated observations indicated that the grey-correlation degree of HPS was the largest among the different steaming treatments, and the following sequence was HPS after soaking in water (SNPS), NPS, and SNPS. There was no significant difference between NPS and SNPS (p < 0.05). Moreover, with increased cycles, the value of the grey-correlation degree increased. The comprehensive score of the procedure repeated nine times was significantly higher than other cycles (p < 0.05). The results of the grey-correlation degree and grade analysis showed that the best steaming process of black sesame seeds was HPS for nine cycles, followed by HPS for eight cycles and NPS after soaking in water (SNPS) for nine cycles. These findings could provide a scientific basis for replacing SNPS with HPS to simplify steaming and realize the parametric steaming of black sesame seeds, and thus, ensure the quality of black-sesame products.


Anti-inflammatory components of Chrysanthemum indicum flowers.
One new octulosonic acid derivative, chrysannol A (1), along with 17 known compounds (2-18), were isolated from Chrysanthemum indicum flowers. Their structures were determined from 1D NMR, 2D NMR, HR-ESI-MS spectral data, and comparisons with previous reports. The effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compound 8 showed the highest inhibition of NO production of 46.09% at a concentration of 10.0μM. Compounds 7, 10, 11, and 16 inhibited TNF-α secretion at all concentration tested (0.4, 2.0, and 10.0μM), with inhibition values ranging from 22.27% to 33.13%. In addition, compound 8 and 9 decrease COX-2 and iNOS protein on Western blot analysis in dose dependent manner.


Selection and evaluation of micro-organisms for biocontrol of Verticillium dahliae in olive.
To identify potential biological control agents against Verticillium wilt in olive through a mass screening approach. A total of 47 strains and nine mixtures of micro-organisms were evaluated against Verticillium dahliae in a three stage screening: (i) in vitro, by the effect on the mycelial growth and spore germination of the pathogen; (ii) in natural infested soil, by the effect on the reduction of microsclerotia of the pathogen; (iii) in planta, by the effect on the infection of olive plants under controlled conditions. Various fungal and bacterial strains and mixtures inhibited the pathogen and showed consistent biocontrol activity against Verticillium wilt of olive. The screening has resulted in promising fungi and bacteria strains with antagonistic activity against Verticillium, such as two non-pathogenic Fusarium oxysporum, one Phoma sp., one Pseudomonas fluorescens and two mixtures of micro-organisms that may possess multiple modes of action. This study provides a practical basis for the potential use of selected strains as biocontrol agents for the protection of olive plants against V. dahliae infection. In addition, our study presented an effective method to evaluate antagonistic micro-organisms of V. dahliae in olive.


The potential role of fowlpox virus in rational vaccine design.
The design of optimal vaccines requires detailed knowledge of how protective immune responses are generated in vivo under normal circumstances. This approach to vaccine development, where the immune correlates of protection are defined and vaccines are designed to elicit the same response, is called rational vaccine design. Poxviruses are attractive candidates for inclusion in such design strategies owing to their large genome, which allows for the inclusion of multiple heterologous genes, including those encoding antigens, co-stimulatory molecules and cytokines. Fowlpox virus, the prototypical member of the Avipoxvirus genus, is particularly suitable, as it is also incapable of replicating in mammalian cells. The potential of recombinant fowlpox virus as a safe vaccine vector is being evaluated currently in a number of clinical trials for diseases, including HIV, malaria and various types of cancer. Despite their promise, intricate details regarding how fowlpox virus interacts with the host immune system have not been resolved. In this review, the issues surrounding the use of fowlpox virus as a vaccine vector and possible strategies for enhancing its efficacy are discussed.


High hepatitis E virus antibody positive rates in dogs and humans exposed to dogs in the south-west of China.
Hepatitis E (HE) is a zoonotic viral disease caused by hepatitis E virus (HEV). The objective of this study was to investigate the prevalence of HEV infection among dogs and humans exposed to dogs in the south-west region of China. A total of 4,490 dog serum samples and 2,206 relative practitioner serum samples were collected from 18 pet hospitals and dog farms in Yunnan, Sichuan and Guizhou province, and the anti-HEV IgG antibodies were detected by ELISA. The results showed that the total positive rate of anti-HEV antibodies was 36.55% with the highest rate in city stray dogs, and the differences in distinct species and growth phases were significant. The positive rate of anti-HEV antibody in veterinarian and farm staff-related practitioners was significantly higher than the general population. The finding of the present survey suggested that high HEV seroprevalence in dogs and humans exposed to dogs in the south-west area of China poses a significant public health concern. It is urgent to improve integrated strategies to detect, prevent and control HEV infection in dogs and humans exposed to dogs in this area.


Calculation of portal contribution to hepatic blood flow with 99mTc-microcolloids. A noninvasive method to diagnose liver graft rejection.
The portal contribution (PC) to hepatic blood flow was calculated in 13 liver graft patients and 13 normal volunteers. The method is based on the quantification and normalization of the liver and spleen activity after the administration of 7 mCi (259 MBq) of 99mTc microcolloid. Forty examinations were performed in liver grafts and 13 in normal subjects. The PC was significantly higher in normal native liver (64.0 +/- 3.0%) than in functioning grafts (58.8 +/- 3.1%). In acutely rejecting patients, PC was significantly lower (52.4 +/- 2.0%) than in functioning grafts and similar to that observed in cholangitis (53.5 +/- 0.7%). The PC increases again once rejection has resolved (57.3 +/- 2.6%). During hepatitis post-transplant PC values (59.7 +/- 3.4%) were similar to those observed in functioning grafts. Overall, PC values over 55% are very unlikely to be due to rejection.


Aggressive periodontitis: laser Nd:YAG treatment versus conventional surgical therapy.
The aim of the study was to compare two methods of treatment for aggressive periodontitis: traditional surgical and Nd:YAG laser, evaluating their possible objective clinical advantages. A total of 36 hemiarches of 18 patients were analysed, 10 males and 8 females of average age of 14, selected according to predefined criteria. Overall we examined 70 radicular surfaces (sites) of 50 teeth. Each hemiarch to treat was randomly assigned to one of two treatment groups. The results, analysed using the Friedman's test, showed a clinically appreciable validity both for the surgical and the laser treatment, while the Wilcoxon signed-rank test didn't highlight any statistically significant difference between the two types of treatment. The laser itself appears as a valid alternative to conventional therapy, in relation to the young age of the patients and for individuals at increased anaesthesiological risk and/or with coagulation and platelet function disorders.


Thrombotic storm in a teenager with previously undiagnosed ulcerative colitis.
Venous thrombosis can complicate inflammatory bowel diseases, both in adult and pediatric patients, and a few adult cases of thrombotic storm, ie, thrombosis at multiple sites occurring over a period of a few days to a few weeks, have been described. However, venous thrombosis as the first manifestation of an inflammatory bowel disease is extremely rare. We report the case of a 14-year-old girl presenting with ascites and marked hypertransaminasemia resulting from hepatic vein occlusion (Budd-Chiari syndrome). Despite anticoagulant therapy, in the following days she developed criteria suggestive of thrombotic storm to include cerebral vein, right atrial thrombosis, and bilateral pulmonary embolism. Thrombolytic treatment with recombinant-tissue plasminogen activator was started, with resolution of all venous thromboses and without bleeding complications. Additional examinations revealed a severely active ulcerative pancolitis, which did not respond to medical treatment and required surgery. No thrombophilia abnormality nor other risk factors for thrombosis were detected. We conclude that an underlying inflammatory state, such as ulcerative colitis, should be suspected in pediatric patients with venous thrombosis storm.


Successful treatment by double filtrate plasmapheresis in a pregnant woman with the rare P blood group and a history of multiple early miscarriages.
Individuals of P type, a rare blood group, have anti-PP(1)P(k) antibody in their serum, which causes spontaneous abortion in the early stages. We report a patient of p type suffering from multiple spontaneous abortions. We also review previously reported cases from published work. A 36-year-old woman (gravida 2, para 0) was referred to our hospital because of habitual abortion. At the third pregnancy, we started double filtration plasmapheresis (DFPP) from 7 weeks 3 days to remove the antibody. We attained rapid decline in the titer and normal fetal growth. Gradual tapering of the DFPP frequency caused neither a rebound of the titer nor growth retardation. During the course, she experienced only one episode of catheter infection as an adverse effect. At 37 weeks 3 days, after 57 DFPP repetitions, a 2496 g girl was delivered by cesarean section. The infant suffered neither from anemia nor from severe jaundice. A review of previous reports indicates that the titer of the pathogenic antibody should be kept as low as possible from the early gestational stage in P-incompatible habitual abortion cases, otherwise the case typically comes to an unfavorable outcome. Plasma exchanges with fresh plasma potentially induce contamination by either known or unknown pathogens. Such risks are reduced using DFPP because the volume of albumin solution that replaces fresh plasma is less than that by plasma exchange. The present case, along with previous reports, shows that DFPP is an effective therapy for treating P-incompatible pregnancy.


Effect of neuropeptides (SP and CGRP) on antigen presentation by macrophages.
There is increasing evidence that neuropeptides regulate various functions of immune cells, including macrophages, which have functional receptors for neuropeptides. We have studied the effects of substance P (SP) and calcitonin gene-related peptide (CGRP) on the presentation of herpes simplex virus type-one (HSV-1) antigens by mouse peritoneal macrophages. Macrophages were treated with live or heat-killed virus in the presence or absence of one or both neuropeptides, then fixed. In vitro proliferation of lymphocytes, derived from intranasally immunized mice, was used to assess antigen presentation by the macrophages. Lymphocytes derived from cervical lymph nodes exhibited a greater proliferative response to heat-killed viral antigens than did lymphocytes derived from spleen. Macrophages treated with live virus did not induce lymphocyte proliferation in the immunized mice, but those treated with heat-killed viral particles did. When macrophages were treated with heat-killed virus in the presence of CGRP, the lymphocyte proliferative response was decreased; however, the effects of SP and SP + CGRP were not statistically significant. The results of interleukin-2 production were in accordance with proliferation assays. These findings suggest that neuropeptides regulate immune responses partly through their effects on macrophage function, including antigen presentation.


Biologicals for pediatric patients with atopic dermatitis: practical challenges and knowledge gaps.
Biologicals are becoming increasingly important in the therapeutic landscape of pediatric patients with moderate-to-severe atopic dermatitis (AD). Currently, dupilumab and tralokinumab are registered for the treatment of moderate-to-severe AD, and novel biologicals are expected to follow. Dupilumab was the first biological registered for AD in pediatric patients and was recently approved for patients aged six months to five years. Current and emerging biologicals may address the unmet need for effective and safe treatment options for pediatric AD patients, however, little is known about the practical implementation of biologicals in infants and preschoolers (aged <6 years), including the timing of treatment initiation, discontinuation, and long-term administration of the subcutaneous injections. Currently, only a small number of biologicals are approved for the treatment of infants and preschoolers for other inflammatory diseases. Consequently, data on the practical implementation of biological treatment remain scarce. In addition, long-term effects, impact on co-morbidities, and impact on live-accentuated vaccination are still unknown. With the introduction of biologicals for AD from the age of six months, potential challenges within the implementation of biologicals may arise. Therefore, we aim to discuss current practical challenges and knowledge gaps of the treatment with biologicals in infants and preschoolers with AD.


Pink- and orange-pigmented Planctomycetes produce saproxanthin-type carotenoids including a rare C45 carotenoid.
Planctomycetes are ubiquitous and environmentally important Gram-negative aquatic bacteria with key roles in global carbon and nitrogen cycles. Many planctomycetal species have a pink or orange colour and have been suggested to produce carotenoids. Potential applications as food colorants or anti-oxidants have been proposed. Hitherto, the planctomycetal metabolism is largely unexplored and the strain pigmentation has not been explored. For a holistic view of the complex planctomycetal physiology, we analysed carotenoid profiles of the pink-pigmented strain Rhodopirellula rubra LF2T and of the orange strain Rubinisphaera brasiliensis Gr7. During LC-MS/MS analysis of culture extracts, we could identify three saproxanthin-type carotenoids including a rare C45 carotenoid. These compounds, saproxanthin, dehydroflexixanthin and 2'-isopentenyldehydrosaproxanthin, derive from the common carotenoid precursor lycopene and are characterized by related end groups, namely a 3-hydroxylated β-carotene-like cyclohexene ring as one end group and simple hydration on the other end of the molecule. Based on the observed molecule structure we present putative pathways for their biosynthesis. Results support Planctomycetes as a promising, yet mostly untapped source of carotenoids.


Suppressive immunoregulatory effects of three antidepressants via inhibition of the nuclear factor-κB activation assessed using primary macrophages of carp (Cyprinus carpio).
Antidepressants, having been applied for the treatment of major depressive disorder and other conditions for decades, are among the most commonly detected human pharmaceuticals in the aquatic environment. This study evaluated the immunotoxicity of acute exposure to environmentally relevant concentrations of amitriptyline, fluoxetine and mianserin using an in vitro primary macrophage model isolated from red common carp (Cyprinus carpio), and also explored their potential mechanisms of action. A potential suppressive immunoregulatory effect of antidepressant exposure was suggested based on the observed suppressive effects on oxidative stress parameters, bactericidal activity, NO production, and NO synthase activity, as well as pro-inflammatory cytokine gene expression, and a significant stimulatory effect on anti-inflammatory interleukin-10 and interferon cytokine gene expression and ATPase activities in macrophages after 6h-exposure to three individual antidepressants and a combination thereof. Notably, we also found these effects were significantly associated with a corresponding decrease in nuclear factor-κB (NF-κB) activity after antidepressants exposure, and the NF-κB antagonist significantly restrained the effects of antidepressants on gene expression of cytokines, indicating that antidepressants could alter the response of various immune-associated components via the inhibition of NF-κB. Moreover, time-dependent lethal concentrations of three antidepressants on primary macrophages were firstly determined at mg/L levels, and the synergetic effects of antidepressant mixtures were suggested and in particular, for some parameters including total antioxidant capacity and cytokine genes expression, they could be significantly affected by antidepressants exposure at concentrations as low as 10ng/L, which together thereby revealed the potential risk of antidepressants to aquatic life.


Membrane prestin expression correlates with the magnitude of prestin-associated charge movement.
Full expression of electromotility, generation of non-linear capacitance (NLC), and high-acuity mammalian hearing require prestin function in the lateral wall of cochlear outer hair cells (OHCs). Estimates of the number of prestin molecules in the OHC membrane vary, and a consensus has not emerged about the correlation between prestin expression and prestin-associated charge movement in the OHC. Using an inducible prestin-expressing cell line, we demonstrate that the charge density, but not the voltage at peak capacitance, directly correlates with the amount of prestin in the plasma membrane. This correlation is evident in studies involving a controlled increase of prestin expression with time after induction and inducer dose-response. Conversely, membrane prestin levels and charge density gradually decline together following the reduction of prestin levels from a steady state by removal of the inducer. Thus, charge density directly correlates with the level of membrane prestin expression, whereas changing membrane levels of prestin have no effect on the voltage at peak capacitance in this inducible prestin-expressing cell line.


Monitoring of Mycoplasma genitalium growth and evaluation of antibacterial activity of antibiotics tetracycline and levofloxacin using a wireless magnetoelastic sensor.
Mycoplasma genitalium (Mg) is the smallest and simplest self-replicating bacteria lacking of cell wall and is a human pathogen causing various diseases. This paper describes the real-time, long-term and in situ monitoring of the growth of Mg and evaluation of the effect of the antibiotics tetracycline and levofloxacin on the growth using a wireless magnetoelastic sensor. The sensor is fabricated by coating a magnetoelastic strip with a polyurethane protecting film. In response to a time-varying magnetic field, the sensor longitudinally vibrates at a resonance frequency, emitting magnetic flux that can be remotely detected by a pick-up coil. No physical connections between the sensor and the detection system are required. The wireless property facilitates aseptic operation. The adhesion of Mg on the sensor surface results in a decrease in the resonance frequency, which is proportional to the concentration of Mg. The shift of the resonance frequency-time curves shows that under routine culture condition the growth curve of Mg is composed of three phases those are lag, logarithmic and stationary phase, respectively. In the presence of the antibiotics, the lag phase in the growth inhibition curves is prolonged obviously and the stationary phase is substituted by a decline phase. The growth inhibition of Mg is related to the concentration of the antibiotics. The MIC50 (minimal inhibitory concentration) of Mg incubated in the presence of the antibiotics for 120h is calculated to be 1.5 and 0.5 microg/mL for tetracycline and levofloxacin, respectively.


Assessing impulsivity changes in Alzheimer disease.
Impulsive behaviors are common in brain-damaged patients including those with neurodegenerative diseases such as Alzheimer disease (AD). The objective of this study was to develop and validate a short version of the UPPS Impulsive Behavior Scale assessing changes on 4 different dimensions of impulsivity, namely urgency, (lack of) premeditation, (lack of) perseverance, and sensation seeking, arising in the course of a neurodegenerative disease. To this end, caregivers of 83 probable AD patients completed a short questionnaire adapted from the UPPS Impulsive Behavior Scale. Exploratory and confirmatory factor analyses of the data were performed and revealed that a model with 4 distinct but related latent variables corresponding to 4 different dimensions of impulsivity fit the data best. Furthermore, the results showed that lack of perseverance, followed by lack of premeditation and urgency, increased after the onset of the disease, whereas sensation seeking decreased. Overall, the multifaceted nature of impulsivity was confirmed in a sample of AD patients, whose caregivers reported significant changes regarding each facet of impulsivity. Consequently, the short version of the UPPS Impulsive Behavior Scale opens up interesting prospects for a better comprehension of behavioral symptoms of dementia.


Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps.
A tricyclic lactam is reported in a four step synthesis sequence via Beckmann rearrangement and ring-rearrangement metathesis as key steps. Here, we used a simple starting material such as dicyclopentadiene.


Multifrequency rhythms of immunological functions.
Chrono-immunological functions are reviewed starting from the first studies on circadian variations in the count of circulating blood eosinophils to the most recent studies on lymphocyte subpopulation periodicities. Serum Ig levels, complement components, plaque forming cells, phagocytosis, autologous mixed lymphocyte reactions, have also been demonstrated to be circadian periodic. Transplant immunology is also known to show circadian and circa septan periodicities in the rejection of transplanted organs. Rhythms of susceptibility to a series of allergens and bronchial asthma symptoms characterize chronobiology in allergy. A periodic pattern is a common finding in the recurrence of the symptoms in rheumatoid arthritis. Finally, the beginnings of chrono-immunotherapy of experimental and human tumors are briefly reviewed. The conclusion that can be drawn from this short overview is that the demonstration of the periodicity in such a big number of variables in health and the modifications of the relevant parameters in disease, emphasize the importance of the predictable, since periodic, part of the variations that can be shown by the immunological findings.


Human study and experimental behavior of Schistosoma mansoni isolates from patients with different clinical forms of schistosomiasis.
Twenty Schistosoma mansoni strains were isolated from three groups of patients (intestinal, hepatointestinal and hepatosplenic clinical forms) born and living in the town of Capitão Andrade, Minas Gerais, Brazil. Schistosomal isolate from each group was inoculated into three sets of mice with 25, 50 and 100 cercariae. The animals were killed 90 and 180 days after infection and submitted to extensive histopathological study of the liver, lung, intestine and spleen to determine qualitative and quantitative morphological characteristics, mainly of the granulomas. The histopathological changes caused the same patterns of infection in mice and were proportional to the inoculum and the time of infection, confirming the relevance of quantitative aspects in the determination of the disease. These data indicate three possibilities: (1) mouse model is not adequate to predict possible differences in the S. mansoni isolates obtained from patients; (2) field isolates are probably genetic polymorphic and undifferentiated; (3) schistosomiasis in human does not depend on parasite intrinsic factors, but on multivariable factors, such as intensity and duration of infection, time of infection, age and gender and other characteristics such as host response.


[Use of microalgae for nutritional purposes].
Mass cultures of planktonic microalgae can render large quantities of proteinaceous matter. The good nutritional quality of microalgal protein has been proven both for animals and for human. The toxicologic safety of microalgal biomasses is, however, not yet sufficiently established. This requires further toxicologic studies, before cultivated mocralgae can commercially be utilized as ingredients of animal feed, or as food additives. Both types of nutritional application may become economically feasible.


Topical immunotherapy with diphenylcyclopropenone in the treatment of chronic extensive alopecia areata.
Highly variable results have been described for the use of topical diphenylcyclopropenone (DPCP) in the treatment of alopecia areata (AA). We enrolled 41 patients in a prospective open clinical trial. Of these, 17 patients had either AA totalis (AAT) or AA universalis (AAU), and 24 had severe alopecia (> 50% scalp involvement). After sensitization with DPCP 2% in acetone, progressively higher concentrations were applied once a week for a period of 6-12 months. Of the 41 patients, 38 (16 with AAT or AAU and 22 with extensive AA) completed therapy. Significant hair regrowth was observed in 15 of the 38 patients (39.5%) at 6 months: 5 with AAT or AAU (31.25%) and 10 with extensive alopecia (45.4%). The above results were sustained in 66.6% of patients for a 12-month-follow up- period. In our study, topical immunotherapy with DPCP proved to be an effective treatment, with prolonged therapeutic results.


Caesarean section on request: are there loco-regional factors influencing maternal choice? An Italian experience.
We aimed to evaluate regional differences in women's motivations and in obstetricians' attitudes re 'caesarean section on request' between obstetricians practicing in Southern and Northern Italy. An anonymous questionnaire was sent to 70 randomly selected specialists practicing in the Veneto region and Sicily. Demographic characteristics, percentage of caesarean section, increase of caesarean section on demand, maternal motivations and the role played by anxiety, relatives and instrumental examinations were analysed. Moreover, obstetricians' opinion and their behaviour in fulfilling, or not, the maternal request were evaluated. Among the emotional reasons, fear of pain was more frequently reported in Sicily (p = 0.045), and previous negative experiences and gestational anxiety in the Veneto region (p = 0.009; p = 0.001). As regards instrumental examinations influencing maternal request, a significant difference was found for ultrasonography (28% in Sicily vs 60% in Veneto, p = 0.002). The husband's role was more frequently reported in the Veneto region (p = 0.006). Obstetricians of both regions noticed a rising rate of caesarean section on maternal request. The reasons for this upward trend are complex, vary from one region to another and are influenced by local socio-cultural and healthcare background.


C-phycocyanin attenuates cisplatin-induced nephrotoxicity in mice.
Although cisplatin is a highly effective antineoplastic agent, nephrotoxicity is its major clinical problem. Recently, it was reported that Spirulina, a blue-green algae, has potent antioxidant properties. The aim of this study was to establish the possible protective role of C-phycocyanin (PC), one of the active ingredients of Spirulina, against cisplatin-induced nephrotoxicity. This study was carried out using human kidney-2 (HK-2) cells and male C57BL6 mice. Cells and mice were divided into four groups; untreated control group, PC-treated control group, cisplatin-treated group, and PC plus cisplatin-treated group. The molecular, functional, and structural parameters were measured. PC significantly attenuated blood urea nitrogen, serum creatinine, renal histological damages, and apoptotic cell death in cisplatin-treated mice. The cisplatin-induced cell death was significantly attenuated in cells pretreated with PC. PC also significantly attenuated the elevation of p-ERK, p-JNK, and p-p38 induced by cisplatin treatment. The expression of Bax, caspase-9, and caspase-3 in cisplatin-treated cells were also decreased by PC treatment. In conclusion, PC ameliorates cisplatin-induced nephrotoxicity and, at least in part, suppression of p-ERK, p-JNK, p-p38, Bax, caspase-9, and caspase-3 may be involved in this mechanism.


Evaluating the lower-body electromyogram signal acquired from the feet as a noise reference for standing ballistocardiogram measurements.
The ballistocardiogram (BCG) is a measure of the reaction force of the body to cardiac ejection of blood. A variety of systems can be used for BCG detection, including beds, tables, chairs, and weighing scales. Weighing scales, in particular, have several practical advantages over the alternatives: low cost, small size, unobtrusiveness, and familiarity to the user; one disadvantage is that the subject must stand during the recording, rather than sit or lay supine, resulting in a higher susceptibility to motion artifacts in the measured signal. This paper evaluates the electromyogram (EMG) signal acquired from the feet of the subject during BCG recording as a noise reference for standing BCG measurements. As a subject moves while standing on the scale, muscle contractions in the feet are detected by the EMG signal, and used to flag segments of the BCG signal that are corrupted by elevated noise. For the purposes of evaluating this method, estimates of the BCG noise-to-signal ratio (NSR) were independently calculated with an ensemble average method, using the R-wave of a simultaneously-acquired chest ECG as a timing reference. The linear correlation between EMG power alone and BCG NSR from 14 subjects was found to be moderate ( r = 0.58, F-statistic p -value 0.05); combined with body-mass index (BMI), multiple linear regression yielded a stronger correlation ( r = 0.73, F -statistic p-value = 0.01). Additionally, an example usage of the lower-leg EMG for improving BCG measurement robustness is provided.


Advanced Hysteroscopic Surgery: Quality Assurance in Teaching Hospitals.
Advanced hysteroscopic surgery (AHS) is a vitally important technique in the armamentarium for the management of many day-to-day clinical problems, such as menorrhagia, surgical excision of uterine myomata and septa in the management of female infertility, hysteroscopic excision of chronically retained products of conception (placenta accreta), and surgical removal of intramural ectopic pregnancy. In today's climate of accountability, it is necessary that gynecologists take a more active role in assuring the quality of their work. In this article, we discuss the quality assurance system from the point of view of the surgical audit meetings in some of the major teaching hospitals affiliated with the University of Queensland (Brisbane, Queensland, Australia).


Failure Mechanism of Tensile CFRP Composite Plates with Variable Hole Diameter.
Real thin-walled composite structures such as aircraft or automotive structures are exposed to the development of various types of damage during operation. The effect of circular hole size on the strength of a thin-walled plate made of carbon fibre-reinforced polymer (CFRP) was investigated in this study. The test object was subjected to tensile testing to investigate the strength and cracking mechanism of the composite structure with variable diameter of the central hole. The study was performed using two independent test methods: experimental and numerical. With increasing diameter of the central hole, significant weakening of the composite plate was observed. The study showed qualitative and quantitative agreement between the experimental and numerical results. The results confirmed the agreement of the proposed FEM model with the experimental test. The novelty of this study is the use of the popular XFEM technique to describe the influence of the hole size on the cracking and failure of the composite structure. In addition, the study proposes a new method for determining the experimental and numerical damage and failure loads of a composite plate under tension.


Changes in pituitary responsiveness during the ovulatory cycle of the Japanese quail, in vitro.
Anterior pituitary glands from ovulating Japanese quail (Coturnix coturnix) were used to investigate variation in sensitivity to chicken luteinizing hormone-releasing hormone (cLHRH I; Gln8-LHRH). Grouping the pituitaries by ovulatory stage provided preliminary evidence of changes in sensitivity to LHRH during the ovulatory cycle. Pituitaries taken from quail before the preovulatory LH surge were responsive to cLHRH I, while pituitaries from the other times of the cycle showed minimal response to cLHRH I. Female pituitary glands release less LH than those of males. These data indicate a change in sensitivity to LHRH in the female quail that may be due to changes in gonadal steroids or the pool of releaseable LH from the pituitary.


A comparative study of the RuiBreath and NIOX VERO analyzers for detecting fractional exhaled nitric oxide.
Fractional exhaled nitric oxide (FeNO) measurement is a reliable, noninvasive marker of airway inflammation. Portable FeNO analyzers facilitate the assessment of airway inflammation in primary care. Differences between analyzers from different manufacturers are not comparable. Here, we aimed to compare the FeNO values obtained by a new portable device (RuiBreath, Guangzhou Ruipu Medical Technology Co., Ltd, Guangzhou, China) to those obtained by the widely used NIOX VERO portable analyzer (Aerocrine AB, Solna, Sweden) in patients with asthma. This prospective validation study enrolled patients (≥14 years old) with asthma over a 2-month period (July and August 2019) at the Beijing Chao-Yang Hospital. At least one valid FeNO measurement was obtained using each analyzer for all the participants. There were 197 participants in this study. The FeNONIOX and FeNORuiBreath values significantly differed (P=0.016). After log-transformation, a difference was found only when the FeNONIOX was <25 ppb (P<0.001). The FeNONIOX and FeNORuiBreath values had a significant correlation (r=0.938, P<0.001), which was confirmed by the Altman-Bland plot. Using a receiver-operating characteristic curve analysis, when using 49 ppb as the cut-off point for the two devices in identifying patients with symptomatic asthma symptoms, the sensitivity and specificity were 0.42 and 0.88, respectively, by NIOX, and 0.40 and 0.89, respectively, by RuiBreath. This is the first report of FeNO values obtained by the new portable RuiBreath FeNO analyzer. The FeNORuiBreath values are reliable and directly comparable with the FeNONIOX values.


Urothelial bladder carcinoma metastasizing to the eye: A systematic review and case report.
The eye is a rare site for disseminated malignancies; nevertheless, several tumors may metastasize to ocular structures. Few cases of urothelial and bladder cancer with eye involvement have been described in the literature thus far. The rarity of metastatic ocular localization implies an accurate differential diagnosis among the possible primary tumor sites. However, a specific diagnostic algorithm is not currently available, nor a defined therapeutic approach. Eye metastases are associated with advanced disease and poor prognosis. Physicians should be made aware of the possibility of eye involvement in patients with a past medical history of urothelial bladder cancer associated with ocular symptoms. The present case reports discusses the first documented case, to the best of our knowledge, of an urothelial bladder cancer metastasizing to the retro bulbar region that infiltrates the lacrimal gland. Furthermore, the report provides a systematic qualitative review of the current literature on eye metastases from urothelial bladder cancer using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.


Sodium pump regulation of locomotor control circuits.
Sodium pumps are ubiquitously expressed membrane proteins that extrude three Na+ ions in exchange for two K+ ions, using ATP as an energy source. Recent studies have illuminated additional, dynamic roles for sodium pumps in regulating the excitability of neuronal networks in an activity-dependent fashion. We review their role in a novel form of short-term memory within rhythmic locomotor networks. The data we review derives mainly from recent studies on Xenopus tadpoles and neonatal mice. The role and underlying mechanisms of pump action broadly match previously published data from an invertebrate, the Drosophila larva. We therefore propose a highly conserved mechanism by which sodium pump activity increases following a bout of locomotion. This results in an ultraslow afterhyperpolarization (usAHP) of the membrane potential that lasts around 1 min, but which only occurs in around half the network neurons. This usAHP in turn alters network excitability so that network output is reduced in a locomotor interval-dependent manner. The pumps therefore confer on spinal locomotor networks a temporary memory trace of recent network performance.


Influence of ultraviolet irradiation treatment on porcelain bond strength of titanium surfaces.
To determine the effect of titanium (Ti) surface modification by ultraviolet irradiation (UVI) on the bond strength between Ti and porcelain. Grade 2 Ti plates were allotted to five groups: sandblasted (SA), 15 min UVI (UV), SA+5 min UVI (SA+UV5), SA+10 min UVI (SA+UV10), and SA+15 min UVI (SA+UV15). After surface treatment, porcelain was added. A precious metal (MC) was used for comparison with Ti. The effects of 24-h storage at room temperature versus thermal cycling only at 5 and 55°C in water were evaluated. Subsequently, the tensile strength of each sample was tested. Data were analyzed using one-way analysis of variance and the Tukey test. In both the room temperature and thermal cycling groups, the MC and SA+15 min UVI samples showed significantly greater bond strengths than the other samples (p<0.05). UVI processing efficiently increases the bond strength between porcelain and the Ti surface.


Functional Independence Score in Haemophilia: a new performance-based instrument to measure disability.
Morbidity in haemophilia has been described predominantly in terms of musculoskeletal dysfunction and assessed by the clinical and radiological joint scores. These scores document changes in a particular joint, but do not reflect the impact of these changes on the individual in terms of his overall musculoskeletal function. Several self-assessment instruments have been used to measure musculoskeletal function but none have been specifically validated for use in haemophilia. In order to objectively assess musculoskeletal function of patients with haemophilia, we developed Functional Independence Score in Hemophilia (FISH), a performance-based instrument. FISH measures the patient's independence in performing seven activities under three categories: self-care (grooming and eating, bathing and dressing), transfers (chair and floor) and mobility (walking and step climbing). Each function is graded from 1 to 4 depending on the amount of assistance needed in performing the function. We evaluated 35 patients who were over 10 years old and had had at least three major bleeds per year. All subjects were scored for clinical (World Federation of Hemophilia, WFH score) and radiological changes (Pettersson's score). Functional independence of the patient was assessed using the Stanford Health Assessment Questionnaire (HAQ) and the FISH. Correlation of the FISH score was modest with both the WFH clinical score (r = -0.68) and the radiological score (r = -0.44). While there was good correlation between FISH and HAQ (r = -0.90), FISH had better internal consistency than HAQ (Cronbach's alpha 0.83 vs. 0.66). FISH appears to be a promising disease-specific instrument for assessing overall musculoskeletal function in haemophilia. It requires evaluation in different patient populations.


Smokeless tobacco product prices and taxation in Bangladesh: findings from the International Tobacco Control Survey.
Smokeless tobacco use occupies a significant portion of overall tobacco consumption in Bangladesh. Yet very little is known about the effectiveness of tax and price policy in controlling the use of smokeless tobacco use in the country. The paper examines the price distribution of various smoked (cigarette, bidi) and smokeless tobacco products (zarda, gul) using the univariate Epanechnikov kernel density function. It estimates the own and cross price elasticity of demand for the most widely used smokeless tobacco product zarda using two-step regression analysis. The analysis is based on data from the ITC Bangladesh Wave 3 Survey which is a nationally representative cohort survey of tobacco users and nonusers conducted in in Bangladesh during 2011-12. The price elasticity of lower price brands of zarda is estimated at -0.64 and of higher priced brands at -0.39, and the cross price elasticity of zarda with respect to cigarette price at 0.35. The tax increase on smokeless tobacco needs to be greater than the tax increase on smoked tobacco to bridge the wide price differential between the two types of products that currently encourages downward substitution from smoked to smokeless tobacco and discourages quitting behavior. This paper argues that increasing tax on smokeless tobacco simultaneously with the tax increase on smoked tobacco can have significant negative impact on the prevalence of smokeless tobacco use in Bangladesh. Finally, a specific excise system replacing the existing ad valorem excise tax can substantially contribute to the revenue collection performance from smokeless tobacco products.