Astragalus membranaceus ameliorates reproductive toxicity induced by cyclophosphamide in male mice.
The root of Astragalus membranaceus B(UNGE) (AM) is a medicinal herb that has been capable of reducing the adverse effects of conventional chemotherapy. To investigate the effects of AM on cyclophosphamide (CP)-induced reproductive toxicity in mouse testes, 5-week-old male imprinting control region mice were divided into five groups; CP was treated on the first day of each week for 5 weeks (100 mg/kg, i.p.), and AM was treated for 5 days a week for 5 weeks. At the end of the treatment period, the testes were taken out, cleared of the adhering tissues, and weighed. Epididymis was taken out and used for sperm analysis. Testis samples were frozen for real-time quantitative PCR and Western blot analysis. AM treatment increased diminished relative testes weight, and sperm count and motility in mice treated with CP. CP treatment has detrimental effects on the expression of cAMP-responsive element modulator (CREM), a transcription factor that is highly expressed in male germ cells and is crucial to post-meiotic germ cell differentiation. AM restored CREM at both the mRNA and protein levels. AM has beneficial influences and appears able to ameliorate relative testes weight, sperm parameters, and CREM expression against CP-induced reproductive toxicity.


Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy.
The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean ± standard deviation parameter estimates were 25.2 ± 17.3 liters for the central volume, 0.89 ± 1.17 h(-1) for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 ± 6.60 h(-1) for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 ± 2.35 liters/h for hemodiafiltration clearance, and 4.69 ± 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (≥25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (Cmax)/MIC ratio of ≥8 and a minimal concentration of ≤2.5 mg/liter at the end of the dosing interval. The mean clearance of amikacin was 1.8 ± 1.3 liters/h by CVVHDF and 1.3 ± 1 liters/h by CVVH. On the basis of simulations, a strategy of an extended-interval high loading dose of amikacin (25 mg/kg every 48 h) associated with therapeutic drug monitoring (TDM) should be the preferred approach for aminoglycoside treatment in critically ill patients receiving continuous renal replacement therapy (CRRT). (This study is a substudy of a trial registered at ClinicalTrials.gov under number NCT01403220.).


[Temporal lobe epilepsy and active neurocysticercosis: two representative case reports].
There are limited evidences reported of temporal lobe epilepsy associated with active cysticercosis in cystic stage. The objective is to present the correlation between active cysticercosis in topographical zones associated with temporal lobe epilepsy, with neuropsychiatric manifestations and pattern of secondarily generalized partial seizures. Two cases of adult patients with neuropsychiatric manifestations of one year evolution, refractory to antipsychotic drug treatment, and who subsequently appear late onset partial-secondarily generalized seizures. Cysticercosis active presence in the temporal lobe in one patient, and the insula in the other, is identified. A better clinical control after albendazol treatment and subsequently anticonvulsant therapy only remained to evaluate pertinence of pharmacological withdrawal criteria. Active neurocysticercosis, may be the cause of acquired neuropsychiatric disorders and temporal lobe epilepsy of late onset when the topography is in the mesolimbic circuit. Early etiologic diagnosis and appropriate treatment allows adequate control of their symptoms and potentially final cure.


[Sepsis in surgery: pathogenesis, new therapeutic approaches].
Sepsis and septic shock are phenomena with a characteristic clinical picture and etiologically related to injury. Chains of events from injury (e.g., infection) through activation of immunological system to multiple organ failure are responsible for sepsis. Neutralization of endotoxins, TNF, interleukins and so on, can improve the treatment of sepsis in the future.


Effectiveness of an online continuing education course in infant hearing health for primary care professionals.
To evaluate the effectiveness of an online continuing education course on infant hearing health for primary care professionals. A prospective longitudinal study with interrupted time series pre-test/post-test design. The effectiveness of the online course was assessed by comparing pre- vs. post-training performance and analysing responses to evaluations of the quality of the course. The sample comprised individuals enrolled between September 2018 and August 2019 in a Ministry of Health course, "Actions in primary care for the early identification of hearing impairment" offered on the AVASUS platform. Of the 2908 individuals registered, 1842 (63.3%) completed the course. Their ages ranged from 18 to 77 years, and 67.4% of them were females. Students and doctors were overrepresented among the enrollees. All Brazilian states were included in the sample. Comparisons of pre- and post-training performances showed a significant improvement in knowledge, and 99.3% of the participants provided positive comments regarding the quality of the course. The course is an effective distance learning tool on infant hearing health for primary care professionals. The online course circumvents the limitations posed by geographical barriers and also facilitates decentralisation.


Olanzapine abuse.
Olanzapine is a thienobenzodiazepine that blocks especially the serontonin (5-hydroxytryptamine [5-HT]) 5-HT2A and the dopamine D2 receptors as well as muscarinic (M1), histamine (H1), 5-HT2C, 5-HT3 to 5-HT6, adrenergic (α(l)), and D4 receptors. This case report presents an olanzapine abuse. A 48-year-old, primary school graduate, married woman applied to psychiatry clinic with tachycardia, insomnia, and anxiety complaints. In psychiatric evaluations, it was determined that these complaints have been continuing for 15 years at intervals and that she has been using citalopram 40 mg/day and olanzapine 50 mg/day for the last 3 years. As diabetes mellitus was diagnosed in follow-ups, interruption of olanzapine treatment was planned. The patient stated that she started taking the medicine again upon discomfort, increase in anxiety, dysphoria, insomnia, and nervousness, which started just after olanzapine was interrupted. She said that she was feeling dense stress when she did not take the medicine, and she thought that this situation would recover only by taking that medicine and hence she could not discontinue the medicine. In addition to medications with obvious abuse potential such as benzodiazepines and methylphenidate, and other stimulants, abuse of a number of commonly prescribed psychiatric medications has been reported. There are only 2 cases of olanzapine abuse in literature.


Synthesis of Highly Functionalized Pyridines: A Metal-Free Cascade Process.
Herein, we report a new process for the synthesis of highly functionalized pyridines based on a tandem Pummerer-type rearrangement, aza-Prins cyclization, and elimination-induced aromatization. This formal [5+1] cyclization provides pyridines in good yields with easily accessible starting materials. The synthetic potential of our new method is further demonstrated in the modification of the frameworks of BINOL and some natural products.


[Atherogenic changes of blood lipids and their components in patients after ischemic stroke].
The aim of the study is to analyze frequency and character of blood lipids abnormalities in patients after ischemic stroke (IS). Blood lipids were studied in 54 patients who survived ischemic stroke at 38-70 years. Atherogenic dyslipidemia was found in 49 (90.7%) patients, 37% had a selective low level of HDL cholesterol (< 37 mg/dl). Patients with dyslipidemia, IV type, (27.8%) showed a high level of triglycerides (413 +/- 72mg/dl) and patients with IIa or IIb types--LDLP cholesterol (223 +/- 12.5 mg/dl). A complete analysis of blood lipids allows detecting atherogenic dislipedimia in the majority of patients who survived ischemic stroke (90.7%), which can be treated with statins or fibrates. An adequate therapy of such patients may significantly improve prognosis for those who survived ischemic stroke and, in some cases, prevent its development.


Effect of acute exercise and prolonged training on insulin response to intravenous glucose in vivo in rat.
Physical training causes hypoinsulinemia and enhanced insulin sensitivity. Insulin sensitivity is also enhanced by a single bout of exercise. However, changes in beta-cell responsiveness with acute exercise are ill defined. To clarify these relationships intravenous glucose tolerance tests were performed in 1) physically trained rats (3 different levels), 48 h after the last bout of exercise; 2) untrained rats, 0.5, 4, and 24 h after a single bout of exercise; or 3) sedentary control rats. The total area under the glucose-stimulated insulin response curve (GSIR) was negatively correlated with total distance run during training (r = -0.45, P less than 0.05), whereas glucose tolerance was improved (P less than 0.005 vs. controls) with intensive training. GSIR was suppressed by 38% (P less than 0.01 vs. controls) 0.5 h after a single bout of exercise. This effect persisted for 4 h but was not present after 24 h. These results indicate that a single bout of exercise induces suppression of GSIR which lasts less than 24 h. In contrast, physical training induces prolonged suppression (for at least 48 h) of GSIR, proportional to the intensity of training, and improved glucose tolerance.


A New Concept to Achieve Optimal Weight Gain in Malnourished Infants on Total Parenteral Nutrition.
Infants with intestinal failure (IF) are at increased risk of malnutrition and require adapted nutrition support. Optimal weight gain during nutrition rehabilitation should occur at the velocity of statural age (adjusted to the 50th percentile of height) and not chronological age. The aim of this study was to assess the relationship between weight gain during catch-up growth, nonprotein energy intake (NPEI) provided by total parenteral nutrition (TPN), and resting energy expenditure (REE) in children with severe malnutrition due to IF. This retrospective study included all infants with severe malnutrition treated with TPN for IF between January 1, 2010, and December 31, 2013. They all had no or minimal oral intake (<10% REE). The REE was calculated using the Schofield equations. Seventeen children were included (11 boys) with a mean age at TPN onset of 5 mo. They were followed for a mean duration of 39 days. On admission, body weight and height were -3.1 ± 0.9 and -3.3 ± 1.3 SD, respectively. The indications for TPN were short bowel syndrome (n = 10), congenital enteropathy (microvillous inclusion disease, n = 6) and chronic intestinal pseudo-obstruction syndrome (n = 1). After 28 days of nutrition rehabilitation with full NPEI from TPN, the observed weight gain was 110 ± 5% of optimal weight gain for statural age. The mean NPEI from TPN was 104.3 ± 8.0 kcal/kg/d. The mean ratio of NPEI over REE was 2.1 ± 0.2. Optimal weight gain was achieved with NPEI from TPN twice the REE in severely malnourished infants with IF. NPEI values were adequate and not excessive for age.


Oral Metal-Organic Gel Protected Whole-Cell Biosensor for in Situ Monitoring Nitrosamines in the Gastrointestinal Tract.
Nitrite, a type of food additive, has been proved convertible to genotoxic nitrosamines in the gastrointestinal tract by intestinal flora. There is no appropriate method for in situ detection of nitrosamines. Herein, plasmid-introduced Saccharomyces cerevisiae, which can respond to nitrosamine-induced DNA damage and activate pMAG1-based DNA damage repair (DDR), was designed as whole-cell biosensors (WCBs) for monitoring the in situ generated nitrosamines by a reporter gene expressing enhanced green fluorescent protein (EGFP). In order to protect the validity of WCBs (pMAG1 yeast) from the gastric acid environment, a type of metal-organic gel (MOG), coordinated by Fe3+ and 2,2'-thiodiacetic acid (TDA), was prepared to embed the WCBs. The MOG(Fe-TDA) is gastric acid resistant and can deliver the pMAG1 yeast to the gut without compromising the performance of pMAG1 yeast to detect in situ generated nitrosamines. The genotoxicity of nitrosamines converted from nitrite was successfully detected in the gastrointestinal tract of mice.


Regulation by Nrf2 of IL-1β-induced inflammatory and oxidative response in VSMC and its relationship with TLR4.
Introduction: Vascular oxidative stress and inflammation play an important role in the pathogenesis of cardiovascular diseases (CVDs). The proinflammatory cytokine Interleukin-1β (IL-1β) participates in the vascular inflammatory and oxidative responses and influences vascular smooth muscle cells (VSMC) phenotype and function, as well as vascular remodelling in cardiovascular diseases. The Toll-like receptor 4 (TLR4) is also involved in the inflammatory response in cardiovascular diseases. A relationship between Interleukin-1β and Toll-like receptor 4 pathway has been described, although the exact mechanism of this interaction remains still unknown. Moreover, the oxidative stress sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) promotes the transcription of several antioxidant and anti-inflammatory genes. Nuclear factor-erythroid 2-related factor 2 activators have shown to possess beneficial effects in cardiovascular diseases in which oxidative stress and inflammation are involved, such as hypertension and atherosclerosis; however, the molecular mechanisms are not fully understood. Here, we analysed the role of Toll-like receptor 4 in the oxidative and inflammatory effects of Interleukin-1β as well as whether nuclear factor-erythroid 2-related factor 2 activation contributes to vascular alterations by modulating these effects. Materials: For this purpose, vascular smooth muscle cells and mice aortic segments stimulated with Interleukin-1β were used. Results: Interleukin-1β induces MyD88 expression while the Toll-like receptor 4 inhibitor CLI-095 reduces the Interleukin-1β-elicited COX-2 protein expression, reactive oxygen species (ROS) production, vascular smooth muscle cells migration and endothelial dysfunction. Additionally, Interleukin-1β increases nuclear factor-erythroid 2-related factor 2 nuclear translocation and expression of its downstream proteins heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and superoxide dismutase-2, by an oxidative stress-dependent mechanism; moreover, Interleukin-1β reduces the expression of the nuclear factor-erythroid 2-related factor 2 inhibitor Keap1. The nuclear factor-erythroid 2-related factor 2 activator tert-butylhydroquinone (tBHQ) reduces the effects of Interleukin-1β on the increased reactive oxygen species production and the expression of the proinflammatory markers (p-p38, p-JNK, p-c-Jun, COX-2), the increased cell proliferation and migration and prevents the Interleukin-1β-induced endothelial dysfunction in mice aortas. Additionally, tert-butylhydroquinone also reduces the increased MyD88 expression, NADPHoxidase activity and cell migration induced by lipopolysaccharide. Conclusions: In summary, this study reveals that Toll-like receptor 4 pathway contributes to the prooxidant and proinflammatory Interleukin-1β-induced effects. Moreover, activation of nuclear factor-erythroid 2-related factor 2 prevents the deleterious effects of Interleukin-1β, likely by reducing Toll-like receptor 4-dependent pathway. Although further research is needed, the results are promising as they suggest that nuclear factor-erythroid 2-related factor 2 activators might protect against the oxidative stress and inflammation characteristic of cardiovascular diseases.


Effect of Zn2+ on halohydrin dehalogenase expression and accumulation through multi-parameter correlation research with Escherichia coli P84A/MC1061.
Using 5 Zn2+ supplementation strategies in a 50 L batch bioreactor named FUS-50L(A), possible correlations among Zn2+ content and addition timing, physiologic activity (PA), halohydrin dehalogenase (HheC) accumulation of Escherichia coli P84A/MC1061 were systematically investigated. First, Zn2+ was confirmed as the significant factor, and its optimal concentration for HheC expression was 3.87 mg/L through fermentation experiments in shaking flasks. Second, based on experimental results from the different strategies, it was found that PA, nutrient consumption rate (NCR) and specific growth rate (μ) for E. coli P84A/MC1061 were promoted in the log phase (4-8 h) under appropriate Zn2+ concentrations in the lag phase and late log phase. Furthermore cell biomass was also increased to a higher level and the maximum HheC activity (i.e. HheCmax) was increased by 9.80%, and the time to reach HheCmax was reduced from 16 to 12 hours. Furthermore, appropriate supplementation of Zn2+ caused higher μ for E. coli P84A/MC1061, which resulted in more rapid accumulation of increased acetic acid concentrations, leading to higher acetic acid consumption avoiding any negative effects on producing HheC because of carbon source being exhausted prematurely and acetic acid being consumed rapidly.


Individual DNA identification from ancient human remains.
Individual identification of ancient human remains is one of the most fundamental requisites for studies of paleo-population genetics, including kinship among ancient people, intra- and interpopulation structures in ancient times, and the origin of human populations. However, knowledge of these subjects has been based mainly on circumstantial archaeological evidence for kinship and intrapopulation structure and on genetic studies of modern human populations. Here we describe individual identification of ancient humans by using short-nucleotide tandem repeats and mtDNAs as genetic markers. The application of this approach to kinship analysis shows clearly the presence or absence of kinship among the ancient remains examined.


Developing a Genetically Encoded, Cross-Species Biosensor for Detecting Ammonium and Regulating Biosynthesis of Cyanophycin.
Responding to nitrogen status is essential for all living organisms. Bacteria have evolved various complex and exquisite regulatory systems to control nitrogen metabolism. However, natural nitrogen regulatory systems, owing to their complexity, often function only in their original hosts and do not respond properly when transferred to another species. By harnessing the Lactococcus GlnRA system, we developed a genetically encoded, cross-species ammonium biosensor that displays a dynamic range up to 9-fold upon detection of ammonium ion. We demonstrated applications of this ammonium biosensor in three different species (Escherichia coli, Pseudomonas putida, and Synechocystis sp.) to detect different nitrogen sources. This ammonium sensor was further used to regulate the biosynthesis of a nitrogen-rich polymer, cyanophycin, based on ammonium concentration. Given the importance of nitrogen responses, the developed biosensor should be broadly applicable to synthetic biology and bioengineering.


The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.
DNA replication is a tightly controlled process that ensures the faithful duplication of the genome. However, DNA damage arising from both endogenous and exogenous assaults gives rise to DNA replication stress associated with replication fork slowing or stalling. Therefore, protecting the stressed fork while prompting its recovery to complete DNA replication is critical for safeguarding genomic integrity and cell survival. Specifically, the plasticity of the replication fork in engaging distinct DNA damage tolerance mechanisms, including fork reversal, repriming, and translesion DNA synthesis, enables cells to overcome a variety of replication obstacles. Furthermore, stretches of single-stranded DNA generated upon fork stalling trigger the activation of the ATR kinase, which coordinates the cellular responses to replication stress by stabilizing the replication fork, promoting DNA repair, and controlling cell cycle and replication origin firing. Deregulation of the ATR checkpoint and aberrant levels of chronic replication stress is a common characteristic of cancer and a point of vulnerability being exploited in cancer therapy. Here, we discuss the various adaptive responses of a replication fork to replication stress and the roles of ATR signaling that bring fork stabilization mechanisms together. We also review how this knowledge is being harnessed for the development of checkpoint inhibitors to trigger the replication catastrophe of cancer cells.


Microarray gene expression analysis of chemosensitivity for docetaxel, cisplatin and 5-fluorouracil (TPF) combined chemotherapeutic regimen in hypopharyngeal squamous cell carcinoma.
To screen out a set of candidate genes which could help to determine whether patients with hypopharyngeal squamous cell carcinoma (HSCC) could benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy. Gene-expression profiles in 12 TPF-sensitive patients were compared to 9 resistant controls by microarray analysis. Subsequently, expression levels of potential biomarkers in chemosensitive cell line FaDu after TPF treatment were observed by quantitative real-time polymerase chain reaction (qRT-PCR). Through microarray analysis, 1,579 differentially expressed genes were identified, of which 815 were up-regulated in TPF chemotherapy-responsive tissues whereas 764 were down-regulated. Gene ontology (GO) analysis suggested these genes participating in physiological processes including transcription and its regulation, cellular signal transduction and metabolic process. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed that MAPK and Jat/STAT signaling pathways occupied important roles in TPF chemotherapeutic sensitivity. Moreover, in vitro cell culture experiments revealed the expression alternations of IL-6, MAPK14, JUN, CDK5 and CAMK2A exposed to TPF treatment by qRT-PCR, whilst providing an insight into the mechanism underlying TPF chemotherapeutic response in HSCC. These results provided a battery of genes related to TPF chemotherapeutic sensitivity and might act as molecular targets in HSCC treatment. Moreover, these candidate biomarkers could contribute to HSCC individualized treatment.


Complete eventration of right hemidiaphragm: A rare presentation.
Eventration of the diaphragm is a term used to describe an abnormal elevation of part or whole of the hemidiaphragm, where the whole or part of the diaphragm is made up of a thin fibro membranous sheet replacing normal diaphragmatic musculature. Complete and partial eventration both can occur, however, complete eventration of the right hemidiaphragm in an adult female, as presented in this patient, is rarely seen.


Trait Emotional Intelligence and School Burnout: The Mediating Role of Resilience and Academic Anxiety in High School.
The main aim of the current study was to investigate the role of trait emotional intelligence (TEI) in preventing students' school burnout directly and indirectly via anxiety and academic resilience. The data were derived from a sample of 1235 high school students (962 females and 273 males), ranging in age between 13 and 17 years (mean = 15.46; stand deviation = 1.22). Structural equation modelling revealed a strong indirect effect of TEI on school burnout, mediated via anxiety and resilience. Overall, students with high TEI were less likely to experience school anxiety and more likely to exhibit resilience which, in turn, reduced school burnout risk. Findings are discussed with reference to the wider role of TEI in educational contexts and highlight the need and potential for scientifically driven interventions to enhance emotional adjustment at school and in life, more generally.


Ruxolitinib combined with doxorubicin, etoposide, and dexamethasone for the treatment of the lymphoma-associated hemophagocytic syndrome.
Case reports suggest that ruxolitinib-containing treatment could increase the clinical response rate of patients with hemophagocytic syndrome (HPS). This study aimed to explore the effect of ruxolitinib-containing treatment for patients with lymphoma-associated hemophagocytic syndrome (LAHS). This was a retrospective study of patients with LAHS hospitalized at the First Affiliated Hospital of Guangdong Pharmaceutical University between October 2017 and September 2019. Patients were treated with HLH-94 (etoposide and dexamethasone) or R-DED regimen (ruxolitinib, doxorubicin, etoposide, and dexamethasone). The clinical characteristics, treatment responses, and overall survival (OS) were compared. The patients were divided into the HLH-94 group (n = 34) and the R-DED group (n = 36). Compared with HLH-94, R-DED might effectively improve the clinical manifestations, including fever and splenomegaly in patients with LAHS, and control the systemic cytokine storm. The response rate at 2 weeks was 54.8% in the HLH-94 group, which was lower than in the R-DED group (83.3%) (p = 0.011). The OS was significantly prolonged in the R-DED group compared with the HLH-94 group (median, 5 vs. 1.5 months, p = 0.003). The multivariable analysis showed that lower IL-10 levels [hazard ratio (HR)] = 1.000, [95% confidence interval (CI)] 1.000-1.000, p = 0.012), R-DED regimen (HR = 0.196, 95% CI 0.084-0.457, p < 0.001), and non-NK/T-cell lymphoma (HR = 0.254, 95% CI 0.102-0.628, p = 0.003) were associated with better OS. The prognosis of patients with LAHS was generally poor. Ruxolitinib can be combined with chemotherapy in HPS. It is feasible, with no early signals of increased toxicity.


A large-scale screening and functional sorting of tumour microenvironment prognostic genes for breast cancer patients.
The aim of this study was to systematically establish a comprehensive tumour microenvironment (TME)-relevant prognostic gene and target miRNA network for breast cancer patients. Based on a large-scale screening of TME-relevant prognostic genes (760 genes) for breast cancer patients, the prognostic model was established. The primary TME prognostic genes were selected from the constructing database and verified in the testing database. The internal relationships between the potential TME prognostic genes and the prognosis of breast cancer patients were explored in depth. The associated miRNAs for the TME prognostic genes were generated, and the functions of each primary TME member were investigated in the breast cancer cell line. Compared with sibling controls, breast cancer patients showed 55 differentially expressed TME prognostic genes, of which 31 were considered as protective genes, while the remaining 24 genes were considered as risk genes. According to the lambda values of the LASSO Cox analysis, the 15 potential TME prognostic genes were as follows: ENPEP, CCDC102B, FEZ1, NOS2, SCG2, RPLP2, RELB, RGS3, EMP1, PDLIM4, EPHA3, PCDH9, VIM, GFI1, and IRF1. Among these, there was a remarkable linear internal relationship for CCDC102B but non-linear relationships for others with breast cancer patient prognosis. Using the siRNA technique, we silenced the expression of each TME prognostic gene. Seven of the 15 TME prognostic genes (NOS2, SCG2, RGS3, EMP1, PDLIM4, PCDH9, and GFI1) were involved in enhancing cell proliferation, destroying cell apoptosis, promoting cell invasion, or migration in breast cancer. Six of them (CCDC102B, RPLP2, RELB, EPHA3, VIM, and IRF1) were favourable for maintaining cell invasion or migration. Only two of them (ENPEP and FEZ1) were favourable for the processes of cell proliferation and apoptosis. This integrated study hypothesised an innovative TME-associated genetic functional network for breast cancer patients. The external relationships between these TME prognostic genes and the disease were measured. Meanwhile, the internal molecular mechanisms were also investigated.


How to promote the healthy development of continuous participation in smart medical and elderly care systems: The dual perspective of perceived value and risk.
In an environment with an ageing population, elderly care has become a focus of social attention. The combination of smart medical care with elderly care and how to encourage the elderly to participate in the systems and enjoy a higher quality of life have become social priorities. We aimed to analyse the perceived risk and value associations of self-health management-conscious older adults regarding smart medical and elderly care systems (SMECS) and to explore the mechanisms of SMECS affecting them. Using a Likert scale, we conducted a questionnaire-based survey and collected 387 valid responses. This was a cross-sectional study, and various key data were collected relating to the continued participation of older users in SMECS. Partial least squares structural equation modelling was used to explore the data. According to the data analysis, price, operability and personalisation all have significant correlations with perceived value and perceived risk. Perceptions of value and risk influence the continuous participation of the elderly, and this has a potentially positive effect on their mental and physical health. Under the home-based care model, economic factors and technological accessibility were important factors affecting the elderly's continuous participation in SMECS. A personalised programme for the elderly warrants attention. In addition, the effect of perceived risk from the health-related systems was stronger than their perceived value. This research can help elderly users bridge the digital divide and enjoy smart health and medical care.


Lung assist device technology with physiologic blood flow developed on a tissue engineered scaffold platform.
There is no technology available to support failing lung function for patients outside the hospital. An implantable lung assist device would augment lung function as a bridge to transplant or possible destination therapy. Utilizing biomimetic design principles, a microfluidic vascular network was developed for blood inflow from the pulmonary artery and blood return to the left atrium. Computational fluid dynamics analysis was used to optimize blood flow within the vascular network. A micro milled variable depth mold with 3D features was created to achieve both physiologic blood flow and shear stress. Gas exchange occurs across a thin silicone membrane between the vascular network and adjacent alveolar chamber with flowing oxygen. The device had a surface area of 23.1 cm(2) and respiratory membrane thickness of 8.7 ± 1.2 μm. Carbon dioxide transfer within the device was 156 ml min(-1) m(-2) and the oxygen transfer was 34 ml min(-1) m(-2). A lung assist device based on tissue engineering architecture achieves gas exchange comparable to hollow fiber oxygenators yet does so while maintaining physiologic blood flow. This device may be scaled up to create an implantable ambulatory lung assist device.


Development of an affirming and customizable electronic survey of sexual and reproductive health experiences for transgender and gender nonbinary people.
To address pervasive measurement biases in sexual and reproductive health (SRH) research, our interdisciplinary team created an affirming, customizable electronic survey to measure experiences with contraceptive use, pregnancy, and abortion for transgender and gender nonbinary people assigned female or intersex at birth and cisgender sexual minority women. Between May 2018 and April 2019, we developed a questionnaire with 328 items across 10 domains including gender identity; language used for sexual and reproductive anatomy and events; gender affirmation process history; sexual orientation and sexual activity; contraceptive use and preferences; pregnancy history and desires; abortion history and preferences; priorities for sexual and reproductive health care; family building experiences; and sociodemographic characteristics. Recognizing that the words people use for their sexual and reproductive anatomy can vary, we programmed the survey to allow participants to input the words they use to describe their bodies, and then used those customized words to replace traditional medical terms throughout the survey. This process-oriented paper aims to describe the rationale for and collaborative development of an affirming, customizable survey of the SRH needs and experiences of sexual and gender minorities, and to present summary demographic characteristics of 3,110 people who completed the survey. We also present data on usage of customizable words, and offer the full text of the survey, as well as code for programming the survey and cleaning the data, for others to use directly or as guidelines for how to measure SRH outcomes with greater sensitivity to gender diversity and a range of sexual orientations.


Human herpesvirus type 6 DNAemia and infection following allogeneic stem cell transplantation with a focus on long-term outcome.
Cases of human herpesvirus type 6 (HHV-6) infection and disease were retrospectively analysed in a cohort of 97 allogeneic haematopoietic stem cell transplantation (allo-SCT) patients in Gothenburg, Sweden (1997-2001). Altogether 54 of 97 (56%) patients were tested for HHV-6. HHV-6 DNAemia was detected in 15 of the tested patients at a median of 76 (range 24-387) days after SCT. Nine of these patients were treated against HHV-6 infection and disease for a total of 11 treatment episodes. The morbidity associated with HHV-6 DNAemia following allo-SCT was in most cases moderate. The overall 1-y survival among the patients with HHV-6 DNAemia was 11/15 (73%) and the 5-y survival was 10/15 (67%), which was not significantly different from the whole cohort.


Evaluation of a neutron boost in head and neck cancer. Results of the randomized RTOG trial 78-08.
Patients with untreated squamous cell cancer of the head and neck region were randomized to receive either a boost of 25-30 Gy using photon-beam irradiation (photons) or an equivalent boost using neutron-beam irradiation (neutrons). All patients received an initial 45-50 Gy of wide-field photon irradiation. A total of 57 patients was evaluable on the neutron arm and 58 were evaluable on the photon arm. The proportion of patients with complete responses was 60 and 64% on the neutron and photon arms, respectively. The locally disease-free proportion at 2 years was estimated to be 20 and 31%, and the 2-year survival was estimated to be 32 and 41%, respectively. These differences are not statistically significant. There was a higher rate of severe complications on the neutron arm, 16 versus 7%. Thus, there was no evidence that a neutron boost produces better initial tumor clearance, local tumor control, or survival than a photon boost, and it may produce more complications.


Nitrocompound activation by cell-free extracts of nitroreductase-proficient Salmonella typhimurium strains.
A characterization of nitrocompounds activation by cell-free extracts (CFE) of wild-type (AB(+)), SnrA deficient (B(+)), Cnr deficient (A(+)) and SnrA/Cnr deficient (AB(-)) Salmonella typhimurium strains has been done. The Ames mutagenicity test (S. typhimurium his(+) reversion assay) was used, as well as nitroreductase (NR) activity determinations where the decrease in absorbance generated by nitrofurantoin (NFN) reduction and NADP(H) oxidation in the presence of NFN, nitrofurazone (NFZ), metronidazole (MTZ) and 4-nitroquinoline-1-oxide (4NQO) were followed. Different aromatic and heterocyclic compounds were tested for mutagenic activation: 2-nitrofluorene (2-NF); 2,7-dinitrofluorene (2,7-DNF); 1-nitropyrene (1-NP), 1,3-dinitropyrene (1,3-DNP); 1,6-dinitropyrene (1,6-DNP); and 1,8-dinitropyrene (1,8-DNP). Differential mutagenicity was found with individual cell free extracts, being higher when the wild type or Cnr containing extract was used; nevertheless, depending on the nitrocompound, activation was found when either NR, SnrA or Cnr, were present. In addition, all nitrocompounds were more mutagenic after metabolic activation by CFE of NR proficient strains, although AB(-) extract still showed activation capacity. On the other hand, NR activity was predominantly catalyzed by wild type CFE followed by A(+), B(+) and AB(-) extracts in that order. We can conclude that results from the Ames test indicate that Cnr is the major NR, while NFN and NFZ reductions were predominantly catalyzed by SnrA. The characterization of the residual NR activity detected by the mutagenicity assay and the biochemical determinations in the AB(-) CFE needs further investigation.


Leveraging delay discounting for health: Can time delays influence food choice?
Delay discounting, the tendency to choose smaller immediate rewards over larger delayed rewards, is theorized to promote consumption of immediately rewarding but unhealthy foods at the expense of long-term weight maintenance and nutritional health. An untested implication of delay discounting models of decision-making is that selectively delaying access to less healthy foods may promote selection of healthier (immediately available) alternatives, even if they may be less desirable. The current study tested this hypothesis by measuring healthy versus regular vending machine snack purchasing before and during the implementation of a 25-s time delay on the delivery of regular snacks. Purchasing was also examined under a $0.25 discount on healthy snacks, a $0.25 tax on regular snacks, and the combination of both pricing interventions with the 25-s time delay. Across 32,019 vending sales from three separate vending locations, the 25-s time delay increased healthy snack purchasing from 40.1% to 42.5%, which was comparable to the impact of a $0.25 discount (43.0%). Combining the delay and the discount had a roughly additive effect (46.0%). However, the strongest effects were seen under the $0.25 tax on regular snacks (53.7%) and the combination of the delay and the tax (50.2%). Intervention effects varied substantially between vending locations. Importantly, time delays did not harm overall vending sales or revenue, which is relevant to the real-world feasibility of this intervention. More investigation is needed to better understand how the impact of time delays on food choice varies across populations, evaluate the effects of time delays on beverage vending choices, and extend this approach to food choices in contexts other than vending machines. ClinicalTrials.gov, NCT02359916.


Uterine Rupture with Massive Late Postpartum Hemorrhage due to Placenta Percreta Left Partially In Situ.
Placental adhesive disorders involve the growth of placental tissue into or through the uterine wall. Among these disorders, placenta percreta is the rarest one. However, it may cause significant complications. This report aimed to report a neglected patient with placenta percreta who developed uterine rupture with life-threatening late postpartum intra-abdominal hemorrhage. On admission, the patient had acute abdomen with moderate abdominal distention and was subjected to emergency laparotomy. A full-thickness defect of the anterior uterine wall involving the hysterotomy site was seen. Placental tissues occupied both sides of the incision and posterior bladder wall was also invaded by placenta. Total abdominal hysterectomy with partial resection of the posterior bladder wall was performed.


Mouse preimplantation embryos exhibit receptor-mediated binding and transcytosis of maternal insulin-like growth factor I.
High-resolution microscopy in conjunction with colloidal gold-labeled insulin-like growth factor I (IGF-I) has been used to provide evidence that the IGF-I receptor is first detected in 8-cell-stage mouse embryos, confirming the results of previous reverse transcriptase polymerase chain reaction (RT-PCR) studies. Specificity for the IGF-I receptor was demonstrated by displacement with unlabeled IGF-I and dual-labeling experiments with colloidal gold-labeled or unlabeled insulin. Labeled IGF-I ligand is internalized by means of receptor-mediated endocytosis following its concentration in coated pits, and it can be visualized within cytoplasmic organelles. Immunocytochemical analyses at the blastocyst stage, using gold-labeled antibodies to the receptor, confirmed the expression of IGF-I receptors on all cells of the embryo. Similar studies with antibodies directed against the ligand demonstrated that IGF-I internalized by the embryo in vivo is maternally derived. Approximately 40% of blastocysts showed apical plasma membrane binding of gold-labeled ligand ("responders"), while approximately 60% did not demonstrate binding ("nonresponders"); however, both classes of embryo expressed receptors on basolateral membranes of trophectoderm cells and on the surface of inner masses. Functional studies show that incubating embryos in physiological levels of IGF-I (40 ng/ml) results in increased numbers of cells in the inner cell mass (p < 0.05), but not the trophectoderm, as compared to controls.


High Glucose Variability Increases Mortality Risk in Hospitalized Patients.
Glucose variability (GV) is common among hospitalized patients, but the prognostic implications are not understood. Investigate the association between GV, hospital length of stay (LOS), and mortality. GV was assessed by coefficient of variance (CV) and standard deviation (SD) of glucose values during hospitalization. Historical prospectively collected data of patients hospitalized between January 2011 and December 2013. Patients ≥18 years old. LOS, and in-hospital and mortality at end of follow-up. The cohort included 20,303 patients (mean age ± SD, 70 ± 17 years; 51% men; median follow-up, 1022 days), of whom 8565 patients (42%) had diabetes mellitus (DM). Mean LOS was longer with higher CV or SD tertiles in patients without and with DM. In-hospital mortality was 8.2%, associated with higher tertiles of CV (4%, 10%, 19%) and SD (4%, 11%, 21%) in patients without DM and with DM (3%, 5%, 10%; and 2%, 4%, 9%, respectively). Mortality at the end of follow-up was increased in patients without DM with higher CV (28%, 42%, 55%) and SD (28%, 44%, 57%) tertiles and in patients with DM (26%, 35%, 45%; and 25%, 34%, 44%, respectively). Multivariate analysis indicated increased risk for in-hospital and end of follow-up mortality, in both groups. Adjustment for glucocorticoid treatment or hypoglycemia did not affect the results. Glucose levels during hospitalization and GV were two independent factors affecting LOS and in-hospital mortality. In each CV tertile, mortality was higher with median glucose ≥180 mg/dL, compared with <180 mg/dL. In hospitalized patients with and without DM, increased GV is associated with longer hospitalization and increased short- and long-term mortality.


Increasing heat storage by wearing extra clothing during upper body exercise up-regulates heat shock protein 70 but does not modify the cytokine response.
Plasma heat shock protein 70 (HSP70) concentrations rise during heat stress, which can independently induce cytokine production. Upper body exercise normally results in modest body temperature elevations. The aim of this study was to investigate the impacts of additional clothing on the body temperature, cytokine and HSP70 responses during this exercise modality. Thirteen males performed 45-min constant-load arm cranking at 63% maximum aerobic power (62 ± 7%V̇O2peak) in either a non-permeable whole-body suit (intervention, INT) or shorts and T-shirt (control, CON). Exercise resulted in a significant increase of IL-6 and IL-1ra plasma concentrations (P < 0.001), with no difference between conditions (P > 0.19). The increase in HSP70 from pre to post was only significant for INT (0.12 ± 0.11ng∙mL-1, P < 0.01 vs. 0.04 ± 0.18 ng∙mL-1, P = 0.77). Immediately following exercise, Tcore was elevated by 0.46 ± 0.29 (INT) and 0.37 ± 0.23ºC (CON), respectively (P < 0.01), with no difference between conditions (P = 0.16). The rise in mean Tskin (2.88 ± 0.50 and 0.30 ± 0.89ºC, respectively) and maximum heat storage (3.24 ± 1.08 and 1.20 ± 1.04 J∙g-1, respectively) was higher during INT (P < 0.01). Despite large differences in heat storage between conditions, the HSP70 elevations during INT, even though significant, were very modest. Possibly, the Tcore elevations were too low to induce a more pronounced HSP70 response to ultimately affect cytokine production.


[Cardiac tamponade after laparoscopic operation for a traumatic].
Cardiac tamponade is a rare complication of diaphragmatic hernia repair. We report a case of a 79-year-old female, who underwent a laparoscopic procedure with mesh implantation. Tackers were used to secure the mesh to the diaphragm. Nine hours after surgery the patient died from circulatory collapse. Autopsy showed perforation of the pericardium and the right coronary artery by a tacker. A review of the literature reveals nine earlier reported cases. In three of these cases the complication resulted in death. Rapid diagnosis and intervention can decrease mortality. To avoid further incidents it is necessary to consider alternatives to tacks.


Diastolic dysfunction measured by tissue Doppler imaging in children with end-stage renal disease: a report of the RICH-Q study.
Early detection of cardiovascular disease in children with end-stage renal disease is essential in order to prevent cardiovascular morbidity and mortality in early adulthood. Tissue Doppler imaging has shown to be a promising method to detect and quantify subtle abnormalities in diastolic function. We therefore compared assessment of diastolic function by conventional echocardiography and tissue Doppler imaging. We performed conventional echocardiography and tissue Doppler imaging in 38 children with end-stage renal disease and 76 healthy controls. We compared outcomes on parameters related to diastolic function (E/a ratio for conventional echocardiography and E/E' ratio for tissue Doppler imaging) for both groups using multiple linear regression analysis. Diastolic dysfunction was defined as E/a ratio <1 or E/E' ratio > 95th percentile for age. To assess the intra-observer reproducibility, the coefficient of variation was calculated. Children with end-stage renal disease had on average a lower E/a ratio (p = 0.004) and a higher mitral and septal E/E' ratio (both p < 0.001) compared with controls. In all, two children with end-stage renal disease (5%) had diastolic dysfunction according to the E/a ratio, 11 according to the mitral E/E' ratio (29%), and 16 according to the septal E/E' ratio (42%) compared with none of the controls (p = 0.109, p < 0.001, and p < 0.001, respectively). The coefficients of variation of the mitral (7%) and septal E/E' ratio (4%) were smaller than the coefficient of variation of the E/a ratio (11%). Tissue Doppler imaging is a more sensitive and reliable method to detect diastolic dysfunction than conventional E/a ratio in children with end-stage renal disease.


HOW STRONG IS THE RELATIONSHIP BETWEEN RAINFALL VARIABILITY AND CAATINGA PRODUCTIVITY? A CASE STUDY UNDER A CHANGING CLIMATE.
Despite the knowledge of the influence of rainfall on vegetation dynamics in semiarid tropical Brazil, few studies address and explore quantitatively the various aspects of this relationship. Moreover, Northeast Brazil is expected to have its rainfall reduced by as much as 60% until the end of the 21st Century, under scenario AII of the IPCC Report 2010. We sampled and analyzed satellite-derived monthly rainfall and a vegetation index data for 40 sites with natural vegetation cover in Paraíba State, Brazil from 2001 to 2012. In addition, the anomalies for both variables were calculated. Rainfall variation explained as much as 50% of plant productivity, using the vegetation index as a proxy, and rainfall anomaly explained 80% of the vegetation productivity anomaly. In an extreme dry year (2012), with 65% less rainfall than average for the period 2001-2012, the vegetation index decreased by 25%. If such decrease persists in a long term trend in rainfall reduction, this could lead to a disruption in this ecosystem functioning and the dominant vegetation could become even more xeric or desert-like, bringing serious environmental, social and economical impacts.


Reconstruction of a large post-traumatic cranial defect with a customized titanium plaque.
The treatment of serious cranial defects has always been a fascinating and controversial issue for craniofacial surgeons and in the last years many solutions have been proposed. One of the most effective method is a personalized titanium plaque prepared by processing anatomical data obtained with a CAT of the patient. A case of wide cranial defect on the left fronto-parietal region in a 56-year-old man treated with a personalized titanium plaque obtained by processing the data of a spiral CAT of the skull is described. No complications were observed in the postoperative course and follow-up after 6 moths showed that the patient was in good general condition.


Occult double RV physiology complicating VSD repair.
Double-chamber right ventricle (DCRV) is an uncommon congenital abnormality usually described in children. It occurs due to partitioning of the right ventricle by prominent muscle bundles. In this case report, we describe an adult in cardiogenic shock postoperatively from repair of a ventricular septal defect in whom a previously undiagnosed DCRV was found to be clinically significant.


Complications associated with Boston keratoprosthesis type 1 and glaucoma drainage devices.
To compare the complications leading to best-corrected visual acuity (BCVA) loss in patients with Boston keratoprosthesis type 1 (KPro) and glaucoma drainage device (GDD) and those with KPro alone. Retrospective case series of all patients who underwent KPro surgery at the Centre Hospitalier de l'Université de Montréal between 2008 and 2011. Preoperative diagnoses, BCVA and complications were tabulated and analysed. KPro surgery was performed in 96 eyes: 18 eyes (19%) had KPro and GDD while 78 eyes (81%) had KPro only. Median BCVA at postoperative 6 months was 20/150 in both groups. Seven eyes (39%) with KPro and GDD experienced vision loss due to complications such as glaucoma progression (three eyes, 22%), tube occlusion (four eyes, 22%) and choroidal haemorrhage (three eyes, 17%). Vitreous incarceration was the most common cause of tube occlusion. Vitreoretinal, glaucoma and infectious complications caused BCVA loss in 16 eyes (21%) with KPro alone (p=0.13). Glaucoma progression is a major cause of visual decline post-KPro. However, GDD implantation should only be performed in carefully selected patients. Because of a high risk of vitreous incarceration within the tube, a complete pars plana vitrectomy should be performed prior to GDD implantation.


Developing trauma care systems: the trauma nurse coordinator.
Emergency medical services/trauma care systems offer unique opportunities for nurse administrators in community hospitals and medical centers to encourage a professional practice model for trauma care in the department of nursing. The first article in this series (May 1988) provided an overview of trauma care and the planning and operational functions of nursing departments in trauma care facilities. In this article, the authors acknowledge trauma nursing as a specialty and discuss the role and functions of the trauma nurse coordinator in organizing and providing trauma care.


Late HIV diagnosis among immigrants in Spain vs. native-born Spaniards, 2010-15.
In 2012, the central government of Spain enacted Royal Decree-Law (RDL) 16/2012 and Royal Decree (RD) 1192/2012, which abolished universal healthcare coverage, thus limiting access to care for undocumented immigrants. Free health care was also no longer granted to anyone who has never been employed. In this context, this study investigated the prevalence of late HIV diagnoses (LHDs) among immigrants living in Spain vs. native-born Spaniards. Data (n = 5943) from the 2010 to 2015 Cohort of the Spanish AIDs Research Network were used, including HIV-positive and antiretroviral therapy (ART)-naïve patients throughout Spain. Multivariate logistic models were fitted to compare the prevalence of LHD among the groups, adjusting for covariates. The prevalence of LHD in the total sample was 39.5%. Compared with native-born Spaniards (n = 4445), immigrants (n = 1488) were more likely to have LHD (37.4% vs. 45.7%, respectively; P < 0.001). Multivariate analysis showed that the prevalence ratio of LHD among immigrants vs. native-born Spaniards was 1.15 [95% confidence interval (CI), 1.02-1.28], after adjusting for covariates. This disparity widened from 2010 to 2011 (APR = 1.14, 95% CI, 1.02-1.29) to 2012-15 (APR = 1.28, 95% CI, 1.17-1.39), although the change was not statistically significant. Immigrants in Spain had a higher risk of LHD compared with native-born counterparts. LHD is an important healthcare marker due to the positive benefits of early HIV diagnosis, including prevention, improvements in health outcomes and decreases in overall cost of treatment. More research is needed on the causes of the disparity and potential social and policy interventions to reduce the prevalence of LHD among immigrants.


Peripheral venous malformations with a dominant outflow vein: results of ethanol embolization.
Venous malformations are the most common form of symptomatic vascular malformations. VM s could classify into low-flow lesions (VMs) and high-flow lesions (AVMs). For low-flow venous lesions, direct percutaneous puncture with injection of sclerosing agents (sclerotherapy) has been described as a successful therapy. In this article, we want to introduce a patient who treated with ethanol sclerotherapy for VM located in the right flank. The patients were a 35-year-old man with right flank mass, skin discoloration and hemorrhagic foci. Color Doppler ultrasonography showed low flow vascular malformation while Magnetic Resonance Imaging (MRI) showed that the mass contained fat tissue with branching tubular signal void structures inside. The draining vein was first coiled via tortuous venous malformation vessels access and then VM was embolized.Under ultrasonographic guide, direct puncture of one branches of venous malformation was performed, and contrast media were injected. The patient underwent the sclerotherapy every month for four consecutive months. The patient was followed up for a year, and clinical examination revealed 40-50% size reduction of the lesion while no bleeding was detected from the lesion during the follow-up period. Sclerotherapy with ethanol is a useful method for embolizing VMs.


[The application and research advances of Brucella vaccines].
Brucellosis is a crucial zoonosis caused by Brucella, which has some traits of wide hosts, great infectivity and difficulty in cure. Brucellosis caused great losses to farming and people's health. Vaccination is the main measure used to control Brucellosis, and some attenuated Brucella strains were often used as vaccines. To find more effective vaccines, Scientists are now constructing recombinant strains, DNA vaccines and subunit vaccines, as well as inducing new attenuated strains from isolations. The present applications of B. abortus strain 19 (S19) , B. melitensis Rev. 1 (Rev. 1), B. suis strain 2 (S2), B. abortus strain 45/20 (45/20) and rough strain B. abortus 51 (RB51) were discussed. And some recent research work on Brucella vaccines, such as Brucella recombinant vaccines, DNA vaccines and so on, were reviewed in this paper.


[Role transition and working adaption in new nursing graduates: a qualitative study].
The role transition process is full of stresses and challenges for nurses. Between 35-61% nurses leave their job within the first year. Past cross-sectional quantitative studies have not provided deep descriptions of either the dynamic role transition or work adaption processes of new nurses. The purpose of this study was to understand the role transition experience of new nurses as they transitioned into clinical practice during their first three months on the job. A qualitative approach was used. Data were collected through a semi-structured interview from 50 new nurses. Data were analyzed using category-content analysis. Three stages were identified in the new nurse work adaption process over the first three-month period. These included (1) Understanding: New nurse knowledge and skills are insufficient to handle routine work, adapting to the role transition is difficult, feelings of anxiety emerge related to fears of incompetence, communication difficulties must be faced in the handover process, new nurses adopt feelings of attachment to their preceptors, they must work to adopt appropriate attitudes and approaches to nursing practice, and support is sought from family, teachers and friends; (2) Acclimation: Learning to care for patients independently, seeking role models, learning to adapt to night shifts, trying to identify with co-workers, and seeking support from colleagues, preceptors and head nurses; (3) Acceptance: Managing nursing work better in terms of time and organization, feeling gradual acceptance from co-workers, restoring personal enthusiasm for work, starting to consider other, non-work related matters, experiencing and appreciating the support of co-workers and head nurses. CONCLUSIONS/IMPLICATION: New nurses face a critical role transition process through their first three months on the job. Guidance and leadership from experienced nurses and multiple support systems can assist new nurses to acclimate to their role. Research results provide information for educators and administrators to better understand the adaption process of new nurses, and offer a reference for developing future strategies to improve nurse competency in handling their work.


[The ultrastructure of the paratympanic organ (Vitali) in Gallus domesticus: preliminary studies].
The sensory epithelium of the paratypanic organ (Vitali) was studied by means of the electron microscope. Two kinds of cells are present. One type extends from the basement membrane to the surface of the epithelium; their nuclei are arranged close to the connective tissue and are surrounded by a pale cytoplasm. The distal part of these cells, which are denser and richer in organelles, possess microvilli. The cells of the second type are located above the basement membrane and are found between the upper parts of the cells of the first type. Their cytoplasm is rich in small round vesicles, free ribosomes and cisternae of rough endoplasmic reticulum are present especially in the infranuclear zone. The apical part contains a Golgi apparatus lysosomes and multive sicular bodies. At the apex each cell possesses a cuticular plate numerous stereocilia and one kinocilium. The stereocilia become increasingly longer from one side of the cell surface to the other and the kinocilium is situated on the side where the stereocilia are longest. Nervous fibers are present in the epithelium and are in close contact with the cells of the second type. The cells we have described are remarkably similar to the supporting and hair cells of the vestibular sensory epithelium.


Identification of adipose tissue primordia in perirenal tissues of pig fetuses: utility of phosphatase histochemistry.
Perirenal adipose tissue samples were obtained from fetuses removed from pregnant (crossbred) sows at 3 stages of gestation (70, 90 and 110 days). Phosphatase histochemistry, succinate dehydrogenase (SDH) histochemistry and factor VIII antigen immunocytochemistry were conducted on fresh-frozen cryostat sections. Age-associated changes in nucleosidediphosphatase (NDPase) reactions in the arteriolar system were correlated with the morphological development of the medial layer of arterioles and arteries. For instance, a strong NDPase reaction in small arterioles was associated temporally with the assumption of a normal smooth-muscle cell morphology and arrangement in the medial layer. Age-associated changes in blood vessel reactions for factor VIII antigen and alkaline phosphatase activity were not correlated with morphological development. In the youngest fetuses, alkaline phosphatase activity was evident in large and small arterioles, but in the oldest fetuses, alkaline phosphatase activity was restricted to the smallest arterioles and vessels associated with them. Arteriolar differentiation was demonstrable with either adenosine triphosphatase (ATPase) or inosine diphosphatase (IDPase) reactions. Primordial stromal cells around differentiated arterioles were reactive for ATPase but not for IDPase activities. In older fetuses, there were large areas that contained ATPase-reactive stromal cells, no adipocytes, differentiated (ATPase and IDPase) arterioles and few capillaries. Positive reactions for SDH were evident in the ATPase-reactive stromal areas that contained no adipocytes. Differentiated adipocytes were SDH- and ATPase-reactive. These data illustrate the utility of differential phosphatase histochemistry to identify adipose tissue primordia.


Functional Nanoclay Suspension for Printing-Then-Solidification of Liquid Materials.
Additive manufacturing (AM) enables the freeform fabrication of complex structures from various build materials. The objective of this study is to develop a novel Laponite nanoclay-enabled "printing-then-solidification" additive manufacturing approach to extrude complex three-dimensional (3D) structures made of various liquid build materials. Laponite, a member of the smectite mineral family, is investigated to serve as a yield-stress support bath material for the extrusion printing of liquid build materials. Using the printing-then-solidification approach, the printed structure remains liquid and retains its shape with the help of the Laponite support bath. Then the completed liquid structures are solidified in situ by applying suitable cross-linking mechanisms. Finally, the solidified structures are harvested from the Laponite nanoclay support bath for any further processing as needed. Due to its chemical and physical stability, liquid build materials with different solidification/curing/gelation mechanisms can be fabricated in the Laponite bath using the printing-then-solidification approach. The feasibility of the proposed Laponite-enabled printing-then-solidification approach is demonstrated by fabricating several complicated structures made of various liquid build materials, including alginate with ionic cross-linking, gelatin with thermal cross-linking, and SU-8 with photo-cross-linking. During gelatin structure printing, living cells are included and the postfabrication cell viability is above 90%.


Lysosomal enzyme trafficking between phagosomes, endosomes, and lysosomes in J774 macrophages. Enrichment of cathepsin H in early endosomes.
In this study we take advantage of recently developed methods using J774 macrophages to prepare enriched fractions of early endosomes, late endosomes, dense lysosomes, as well as phagosomes of different ages enclosing 1-micron latex beads to investigate the steady state distribution and trafficking of lysosomal enzyme activity between these organelles. At steady state these cells appear to possess four different cellular structures, in addition to phagolysosomes, where acid hydrolases were concentrated. The first site of hydrolase concentration was the early endosomes, which contained the bulk of the cellular cathepsin H. This enzyme was acquired by phagosomes significantly faster than the other hydrolases tested. The second distinct site of lysosomal enzyme concentration was the late endosomes which contain the bulk of cathepsin S. The third and fourth large pools of hydrolases were found in two functionally distinct types of dense lysosomes, only one of which was found to be secreted in the presence of chloroquine or bafilomycin. Among this secreted pool was soluble furin, generally considered only as a membrane-bound trans-Golgi network resident protein. Thus, the organelles usually referred to as "lysosomes" in fact encompass a growing family of highly dynamic but functionally distinct endocytic organelles.


PP2A:B56epsilon is required for Wnt/beta-catenin signaling during embryonic development.
The Wnt/beta-catenin pathway plays important roles during embryonic development and growth control. The B56 regulatory subunit of protein phosphatase 2A (PP2A) has been implicated as a regulator of this pathway. However, this has not been investigated by loss-of-function analyses. Here we report loss-of-function analysis of PP2A:B56epsilon during early Xenopus embryogenesis. We provide direct evidence that PP2A:B56epsilon is required for Wnt/beta-catenin signaling upstream of Dishevelled and downstream of the Wnt ligand. We show that maternal PP2A:B56epsilon function is required for dorsal development, and PP2A:B56epsilon function is required later for the expression of the Wnt target gene engrailed, for subsequent midbrain-hindbrain boundary formation, and for closure of the neural tube. These data demonstrate a positive role for PP2A:B56epsilon in the Wnt pathway.


[Preparation of three functional monoclonal antibodies against human FL molecule and analysis of their bioactivity].
To Prepare three functional monoclonal antibodies(mAbs) against human FL molecule and analyze their bioactivity. The cell line L929-FL transfected with human FL gene was used as immunogen. The hybridomas secreting the antibodies against human FL were obtained by fusing splenoecytes from the immunized mice with murine myeloma cells(Sp2/0). Their subclasses were analyzed using fast-strip method. The monoclonal antibodies were produced in mouse peritoneal cavity and purified by Protein G affinity chromatography. The inhibitory effect of mAbs against FL on leukemia cell lines U937 and HL-60 was detected by MTT. The apoptosis of U937 and HL-60 cells stained by annexin-V/PI was determined by FCM. Three hybridomas named 3C2, 3C6 and 8D10 were successfully obtained, which secreted monoclonal antibodies against human FL molecule stably. Their subclasses were the mouse IgG2a with kappa light chains. The three monoclonal antibodies recognized the FL molecule on U937 and HL-60 cells that also coexpressed Flt3 molecule. When U937 and HL-60 cells were cultured in presence of 3C2, 3C6 and 8D10, their proliferation was reduced as compared to that in control in MTT assay(P < 0.05). The analysis of annexin-V/PI binding to U937 and HL-60 cells by FCM showed the mAbs had the apoptotogenic activity of the monoclonal antibodies against human FL molecule. 3C2, 3C6 and 8D10 are three funtional monoclonal antibodies against human FL molecule. They may be of some value in the study of the roles of FL/Flt3 interaction in leukemia pathogenesis.


Acceptability and efficacy of an emollient containing ceramide-precursor lipids and moisturizing factors for atopic dermatitis in pediatric patients.
Atopic eczema or dermatitis (AD) is associated with atopy and is characterized by reduced skin hydration and an impaired skin barrier in the epidermis. We investigated the patient acceptability and efficacy of an emollient containing ceramide-precursor lipids and moisturizing factors (LMF) in AD. Consecutive AD patients were recruited. Swabs and cultures were obtained from the right antecubital fossa and the worst-affected eczematous area, and disease severity [according to the SCORing Atopic Dermatitis (SCORAD) Index], skin hydration, and transepidermal water loss (TEWL) were measured prior to and after 2 weeks' use of the LMF moisturizer. The general acceptability of treatment was documented as being 'very good', 'good', 'fair', or 'poor'. Twenty-four AD patients [mean age 13.8 (standard deviation 5.7) years] were recruited. Two thirds of the patients reported very good or good acceptability of the LMF moisturizer, whereas one third reported fair or poor acceptability. There were no inter-group differences in the pre-use clinical parameters of age, objective SCORAD score, pruritus score, sleep disturbance score, skin hydration, TEWL, topical corticosteroid use, oral antihistamine use, or acceptability of previously used proprietary emollients. However, patients in the fair/poor acceptability group were more likely to have Staphylococcus aureus colonization and to be female (odds ratio 13, 95 % confidence interval 1.7-99.4; p = 0.021). Following use of the LMF moisturizer, the objective SCORAD score, pruritus score, and sleep disturbance score were lower in the very good/good acceptability group than in the fair/poor acceptability group. The mean objective SCORAD score improved (from 31.5 to 25.7; p = 0.039) and skin hydration improved [from 30.7 arbitrary units (a.u.) to 36.0 a.u.; p = 0.021] in the very good/good acceptability group. When the data were analyzed for the strength of the agreement of the rating of acceptability, the κ values were 0.338 (fair) for use of body wash and 0.118 (poor) for use of emollients before and after the trial. The LMF moisturizer was considered acceptable by two thirds of the patients with AD. It seems that patients who found the moisturizer acceptable were less likely to be female or to be colonized by S. aureus before switching to the product, and they had less severe eczema, less pruritus, and less sleep disturbance after its use than patients who did not find the product acceptable. Gender and S. aureus colonization may have influenced the patient acceptability and clinical efficacy of the LMF moisturizer. The lack of agreement with regard to the acceptability of the moisturizer implies that there is room for parent/patient education to improve compliance.


Monitoring therapeutic interventions in critically ill septic patients.
Sepsis is the leading cause of admission to intensive care units in the United States. Although the treatment of sepsis is complex and multimodal, nutrition support plays an important role in the management of these patients. The diagnosis of sepsis, disease category, and severity of illness and the change in sepsis severity and organ function over time affect the delivery of nutrition support. This paper reviews the diagnostic criteria of sepsis, the use of "sepsis biomarkers," and regional and global markers of organ function in sepsis and quantitative measures of illness severity and organ dysfunction.


No conclusive evidence that histologically found granulomas and acute local reactions following hylan G-F 20 injections are related or have clinical significance.
Osteoarthritic (OA) knee pain can be successfully treated with hylan G-F 20 (Synvisc, Sanofi Biosurgery, Cambridge, MA) with few local adverse events. However, a few studies have identified hyaluronate positive (HA+) granulomas in the synovial tissue of patients treated with hylan G-F 20 raising the question of their relationship and clinical significance. To understand the potential relationship of HA+ granulomas with the occurrence of acute local reactions (ALRs), we evaluated the synovial tissue of OA patients undergoing total knee replacement that had previously been treated with hylan G-F 20 (n = 101) or had not been treated (n = 20). Granulomas were observed in nine patients, of which eight were in the hylan G-F 20 group (7.9%); HA+ granulomas were identified in six of these eight patients (5.9%). Three of the six patients with HA+ granulomas experienced an ALR within 30 days of administering an injection. Overall, we found no consistent relationship between histologically found HA+ granulomas and the occurrence of an ALR following hylan G-F 20 treatment. These microscopic granulomas were not associated with any symptoms and likely have little clinical significance. The low occurrence of granulomas and/or ALRs should not preclude use of hylan G-F 20 for the treatment of knee pain associated with OA.


Prenatal co-exposure to manganese and depression and 24-months neurodevelopment.
Normal prenatal neurodevelopment follows stages that are potentially influenced by both chemical and psychosocial environments. Exposure to elevated manganese during this critically vulnerable period has been found to be neurotoxic. Independently, maternal prenatal depression has been associated with subsequent neurodevelopmental decrements in children. The association between child neurodevelopment and prenatal co-exposure to manganese and maternal depression has not been sufficiently studied. During pregnancy and at birth, we measured maternal blood and cord blood manganese levels respectively. Maternal depression was assessed in the 3rd trimester of pregnancy using the Edinburgh Depression Scale. Neurodevelopment was evaluated at 24 months of age with the Bayley Scales of Infant Development. A multivariate multiple regression model was used to analyze cognitive, language and motor scores simultaneously for 473 children from the PROGRESS birth cohort in Mexico City. Over 25% of our study participants reported having depressive symptoms. 3rd trimester blood manganese as well as depressive symptoms were independently negatively associated with all neurodevelopment scores in adjusted models. In stratified analyses, the negative association between manganese (maternal as well as cord blood) and 24-month language scores was stronger among women with depressive symptoms. Receptive language was mostly affected. Inverted U-shaped curves were seen for the association between with cord blood manganese and neurodevelopment scores. Our findings are in line with previous studies of manganese and depression neurotoxicity. The prenatal period may be particularly sensitive to manganese and depression co-exposures and should be of interest for public health interventions to promote healthy emotional and nutritional pregnancies.


Population Structure, Genetic Diversity, and Evolutionary History of Kleinia neriifolia (Asteraceae) on the Canary Islands.
Kleinia neriifolia Haw. is an endemic species on the Canarian archipelago, this species is widespread in the coastal thicket of all the Canarian islands. In the present study, genetic diversity and population structure of K. neriifolia were investigated using chloroplast gene sequences and nuclear SSR (simple sequence repeat). The differentiation among island populations, the historical demography, and the underlying evolutionary scenarios of this species are further tested based on the genetic data. Chloroplast diversity reveals a strong genetic divergence between eastern islands (Gran Canaria, Fuerteventura, and Lanzarote) and western islands (EI Hierro, La Palma, La Gomera, Tenerife), this west-east genetic divergence may reflect a very beginning of speciation. The evolutionary scenario with highest posterior probabilities suggests Gran Canaria as oldest population with a westward colonization path to Tenerife, La Gomera, La Palma, and EI Hierro, and eastward dispersal path to Lanzarote through Fuerteventura. In the western islands, there is a slight decrease in the effective population size toward areas of recent colonization. However, in the eastern islands, the effective population size increase in Lanzarote relative to Gran Canaria and Fuerteventura. These results further our understanding of the evolution of widespread endemic plants within Canarian archipelago.


One-carbon metabolism and global DNA methylation in mothers of individuals with Down syndrome.
Down syndrome (DS) is the most common chromosomal disorder, resulting from the failure of normal chromosome 21 segregation. Studies have suggested that impairments within the one-carbon metabolic pathway can be of relevance for the global genome instability observed in mothers of individuals with DS. Based on the association between global DNA hypomethylation, genome instability, and impairments within the one-carbon metabolic pathway, the present study aimed to identify possible predictors, within the one-carbon metabolism, of global DNA methylation, measured by methylation patterns of LINE-1 and Alu repetitive sequences, in mothers of individuals with DS and mothers of individuals without the syndrome. In addition, we investigated one-carbon genetic polymorphisms and metabolites as maternal predisposing factors for the occurrence of trisomy 21 in children. Eighty-three samples of mothers of children with DS with karyotypically confirmed free trisomy 21 (case group) and 84 of mothers who had at least one child without DS or any other aneuploidy were included in the study. Pyrosequencing assays were performed to access global methylation. The results showed that group affiliation (case or control), betaine-homocysteine methyltransferase (BHMT) G742A and transcobalamin 2 (TCN2) C776G polymorphisms, and folate concentration were identified as predictors of global Alu DNA methylation values. In addition, thymidylate synthase (TYMS) 28-bp repeats 2R/3R or 3R/3R genotypes are independent maternal predisposing factors for having a child with DS. This study adds evidence that supports the association of impairments in the one-carbon metabolism, global DNA methylation, and the possibility of having a child with DS.


Autoradiographic evidence of visual cortical projections to the frontal cortex in the cat.
In II adult cats, areas 17, 18, 19 as well as the lateral suprasylvian area were separately injected with L-[5-3H] proline and their efferent projections to the frontal cortex were autoradiographically searched. Only area 19 and lateral suprasylvian area showed such projections; terminal sites were localized in the ventral and dorsal banks of the cruciate sulcus and in the adjacent mesial surface of the brain. The possibility that these labeled regions may correspond to the monkey's frontal eye field is discussed.


Eat all that and you'll be sick.
Up to 500,00 people could have undiagnosed diabetes in England. As many as one in two people who have diabetes may not be coded properly under payment by results. Children born to women who have diabetes have five times the average still birth rate.


Stability of a practical measure of recovery from resistance training.
McLester et al. (2003) proposed a practical protocol to determine optimal recovery times between resistance training workouts. For this protocol to be useful, it must be stable. The purpose of this study was to investigate the stability of that protocol. College-aged resistance trained men (n = 10) performed 3 sets to volitional failure using a 10-repetition maximum load for 6 exercises. Recovery was evaluated on 4 occasions by the number of repetitions performed for each individual exercise after recovery periods of 48, 72, 96, and 120 hours in counterbalanced order. To evaluate stability, this procedure was performed twice. The number of repetitions after each recovery interval were compared with initial baseline performances. A priori, adequate stability was defined as 70% of the participants achieving similar recovery duration on both trials. Pooled repetitions over all 6 exercises indicated that 80% of participants returned to baseline strength levels after the same recovery duration for both trials. However, when individual muscle group repetition performance was evaluated, stability varied from 20 to 70%. Variability in rest, nutrition, prior activity, and other factors probably induced instability in individual strength measures, but not sufficiently to influence the aggregate results. Some muscle groups may have greater sensitivity to variations in ecological factors such as these. We believe that the tested protocol may be useful in establishing recovery times for multimuscle group workouts, but not stable enough to be useful in establishing recovery times for individual muscle groups.


Altered directional connectivity between emotion network and motor network in Parkinson's disease with depression.
Depression is common in patients with Parkinson's disease (PD), which can make all the other symptoms of PD much worse. It is thus urgent to differentiate depressed PD (DPD) patients from non-depressed PD (NDPD).The purpose of the present study was to characterize alterations in directional brain connectivity unique to Parkinson's disease with depression, using resting state functional magnetic resonance imaging (rs-fMRI).Sixteen DPD patients, 20 NDPD patients, 17 patients with major depressive disorder (MDD) and 21 healthy control subjects (normal controls [NC]) underwent structural MRI and rs-fMRI scanning. Voxel-based morphometry and directional brain connectivity during resting-state were analyzed. Analysis of variance (ANOVA) and 2-sample t tests were used to compare each pair of groups, using sex, age, education level, structural atrophy, and/or HAMD, unified PD rating scale (UPDRS) as covariates.In contrast to NC, DPD showed significant gray matter (GM) volume abnormalities in some mid-line limbic regions including dorsomedial prefrontal cortex and precuneus, and sub-cortical regions including caudate and cerebellum. Relative to NC and MDD, both DPD and NDPD showed significantly increased directional connectivity from bilateral anterior insula and posterior orbitofrontal cortices to left inferior temporal cortex. As compared with NC, MDD and NDPD, alterations of directional connectivity in DPD were specifically observed in the pathway from bilateral anterior insula and posterior orbitofrontal cortices to right basal ganglia.Resting state directional connectivity alterations were observed between emotion network and motor network in DPD patients after controlling for age, sex, structural atrophy. Given that these alterations are unique to DPD, it may provide a potential differential biomarker for distinguishing DPD from NC, NDPD, and MDD.


The California Psychological Inventory and the Semantic Differential dimensions.
The feasibility of describing first order factors and scales of the California Psychological Inventory (CPI) by using the factors of the semantic differential and rated adjustment and introversion-extraversion was investigated in samples of 150 male and 80 female college students. Results indicated that both the semantic differential and the ratings significantly overlapped with the CPI, but that the degree of the relationship was not large enough to support the contention that the semantic differential factors are sufficient to describe completely what is being measured by the CPI. The relationships did prove useful, however, in further clarifying the nature of the CPI.


Use of colour and spectral Doppler ultrasonography in stallion andrology.
Doppler ultrasonography is an important tool in the andrological evaluation in humans; however, this method is not so extensively used by equine andrologists. Spectral or pulse Doppler is a useful non-invasive method for the early diagnosis of subfertility problems in the male, especially those triggered by vascular disturbance. The identification of any disturbance in the blood flow of the testis is crucial for a correct diagnosis of various testicular and scrotal disorders but also to monitor the therapeutic outcome following treatment. The aim of this review is to provide an update on the current use of colour and spectral Doppler ultrasound in stallion andrology, and to promote the use of this technique during the soundness reproductive examination of the stallion, as this particular branch of reproductive medicine is receiving increasing interest.


Interest and applicability of acute care surgery among surgeons in Quebec: a provincial survey.
Acute care surgery (ACS) comprises trauma and emergency surgery. The purpose of this new specialty is to involve trauma and nontrauma surgeons in the care of acutely ill patients with a surgical pathology. In Quebec, few acute care surgery services (ACSS) exist, and the concept is still poorly understood by most general surgeons. This survey was meant to determine the opinions and interest of Quebec general surgeons in this new model. We created a bilingual electronic survey using a Web interface and sent it by email to all surgeons registered with the Association québécoise de chirurgie. A reminder was sent 2 weeks later to boost response rates. The response rate was 36.9%. Most respondents had academic practices, and 16% worked in level 1 trauma centres. Most respondents had a high operative case load, and 66% performed at least 10 urgent general surgical cases per month. Although most (88%) thought that ACS was an interesting field, only 45% were interested in participating in an ACSS. Respondents who deemed this concept least applicable to their practices were more likely to be working in nonacademic centres. Despite a strong interest in emergency general surgery, few surgeons were interested in participating in an ACSS. This finding may be explained by lack of comprehension of this new model and by comfort with traditional practice. We aim to change this paradigm by demonstrating the feasibility and benefits of the new ACSS at our centre in a follow-up study.


Frequency of Occurrence and Population-Dynamic Consequences of Different Forms of Density-Dependent Emigration.
Emigration is a fundamental process affecting species' local, regional, and large-scale dynamics. The paradigmatic view in ecology is that emigration is density independent (DIE) or positive density dependent (+DDE). However, alternative forms are biologically plausible, including negative (-DDE), U-shaped (uDDE), and hump-shaped (hDDE) forms. We reviewed the empirical literature to assess the frequency of different forms of density-dependent emigration and whether the form depended on methodology. We also developed a reaction-diffusion model to illustrate how different forms of DDE can affect patch-level population persistence. We found 145 studies, the majority representing DIE (30%) and +DDE (36%). However, we also regularly found -DDE (25%) and evidence for nonlinear DDE (9%), including one case of uDDE and two cases of hDDE. Nonlinear DDE detection is likely hindered by the use of few density levels and small density ranges. Based on our models, DIE and +DDE promoted stable and persistent populations. uDDE and -DDE generated an Allee effect that decreases minimum patch size. Last, -DDE and hDDE models yielded bistability that allows the establishment of populations at lower densities. We conclude that the emigration process can be a diverse function of density in nature and that alternative DDE forms can have important consequences for population dynamics.


Acute Multifocal Nonhematogenous Methicillin-Sensitive Staphylococcus aureus Osteomyelitis in a Healthy Adolescent: An Atypical Presentation.
Osteomyelitis represents inflammation and infection of bone tissue by a pathogen. Acute osteomyelitis is more likely to be unifocal compared to a chronic process which tends to be multifocal and recurrent. Early diagnosis, aggressive appropriate antibiotic therapy and a multidisciplinary approach are essential for a satisfactory prognosis and improved outcome. We report an atypical case of acute multifocal methicillin-sensitive Staphylococcus aureus (MSSA) osteomyelitis.


Effect of spatial distribution of dissipated power on modeling of SMR BAW resonators at high power levels.
The modeling of bulk acoustic wave resonators at elevated power levels has been improved by taking the spatial distribution of the dominating loss mechanisms into account. The spatial distribution of the dissipated power enables more accurate modeling of the temperature increase caused by the applied power. Thus, it is also possible to more accurately model the frequency shifts of the resonators' impedance curves resulting from the temperature increase caused by the applied power. Simulation and measurement results for the temperatures and impedances of the resonators with different layerstacks at high power loads are presented. The simulation and measurement results are in good agreement, confirming the presented modeling approach. Furthermore, the de-embedding procedure used to obtain vectorial scattering parameters of the resonators during high power loads, the according measurement setup, and the procedure for measuring absolute temperatures by infrared thermography are discussed.


Retroviruses as carcinogens and pathogens: expectations and reality.
Retroviruses (without transforming genes) are thought to cause leukemias and other cancers in animals and humans because they were originally isolated from those diseases and because experimental infections of newborns may induce leukemias with probabilities of 0 to 90%. According to this hypothesis viral cancers should be contagious, polyclonal, and preventable by immunization. However, retroviruses are rather widespread in healthy animals and humans where they typically cause latent infections and antiviral immunity. The leukemia risk of such infections is less than 0.1% and thus about as low as that of virus-free controls. Indeed retroviruses are not sufficient to initiate transformation because of the low percentage of symptomatic virus carriers and the complete lack of transforming function in vitro; because of the striking discrepancies between the long latent periods of 0.5 to 10 years for carcinogenesis and the short eclipse of days to weeks for virus replication and direct pathogenic and immunogenic effects; because there is no gene with a late transforming function, since all genes are essential for replication; because host genes, which do not inhibit virus, inhibit tumorigenesis up to 100% if intact and determine the nature of the tumor if defective; and above all because of the monoclonal origin of viral leukemias, defined by viral integration sites that are different in each tumor. On these bases the probability that a virus-infected cell will become transformed is estimated to be about 10(-11). The viruses are also not necessary to maintain transformation, since many animal and all bovine and human tumors do not express viral antigens or RNA or contain only incomplete proviruses. Thus as carcinogens retroviruses do not necessarily fulfill Koch's first postulate and do not or only very rarely (10(-11)) fulfill the third. Therefore it has been proposed that retroviruses transform inefficiently by activating latent cellular oncogenes by for example provirus integration. This predicts diploid tumors with great diversity, because integration sites are different in each tumor. However, the uniformity of different viral and even nonviral tumors of the same lineage, their common susceptibility to the same tumor resistance genes, and transformation-specific chromosome abnormalities shared with non-viral tumors each argue for cellular transforming genes. Indeed clonal chromosome abnormalities are the only known transformation-specific determinants of viral tumors. Since tumors originate with these abnormalities, these or associated events, rather than preexisting viruses, must initiate transformation.(ABSTRACT TRUNCATED AT 250 WORDS)


Multidisciplinary management for the treatment of proximal posterior inferior cerebellar artery aneurysms.
Aneurysms of the proximal posterior inferior cerebellar artery (PICA) are rare. The management of proximal PICA aneurysms is challenging with either surgical or endovascular treatment. We report our successful experience of treating PICA aneurysms with a multimodal approach. Of 2382 treated aneurysms, 22 aneurysms in 21 patients (male:female 8:13, mean age 48.9 years) were enrolled from March 1998 to December 2015. We treated the aneurysms with a multimodal approach and performed angiography to examine aneurysm regrowth at the 12 months follow-up. Clinical outcomes were evaluated based on the modified Rankin Score (mRS) at the time of discharge and 12 months postoperatively. The treatment modality was mainly dependent on the character of the aneurysms and the clinical presentation of the patients. Microsurgery was performed in seven patients, which entailed proximal occlusion with distal revascularization in two and microsurgical clipping in five. Endovascular treatment was performed in 10 patients because of a serious medical condition, or vertebral artery (VA)/ or PICA tortuosity. Four were treated with coil embolization and six with stent or balloon-assisted coil embolization. Combined surgical and endovascular treatment was applied in four patients. They were treated with distal revascularization followed by occlusion with coils of the aneurysm-incorporated PICA. All patients achieved complete cure of the PICA aneurysms without complications except for one case of cerebrospinal fluid (CSF) leakage. Endovascular and microvascular neurosurgeons should work closely in managing these challenging problems. Neurosurgeons should consider multimodal treatment in these cases including trapping after occipital artery (OA)-PICA bypass.


[RADIOSURGERY FOR PITUITARY ADENOMAS].
Pituitary adenomas represent one of the most common types of intracranial tumors, accounting for 10-20% of intracranial tumors. While their macroscopic appearance and anatomical location are relatively homogeneous, pituitary tumors differ widely, generating a variety of neurological and endocrine clinical sequelae. Treatment options include hormone suppressive medical therapy, microscopic or endoscopic neurosurgical resection, radiosurgery, radiation therapy, or observation depending on the biochemical profile and the clinical status of the patient. Some pituitary adenomas spread locally to invade surrounding meninges (Dura) and cavernous sinus, hampering a complete surgical resection. Radiosurgery is most commonly utilized as adjunctive treatment following incomplete surgical resection leaving residual tumor, tumor recurrence, or failure of medical therapy. We present a comprehensive literature review of the radiosurgery series for treatment of different pituitary adenomas including nonfunctioning adenomas, ACTH- and GH-secreting adenomas, as well as prolactinomas. While post-radiosurgery radiographic tumor control for nonfunctioning adenomas is excellent, typically at 90%, the rates of endocrine biochemical remission for functioning adenomas are lower than the tumor control rates. A higher dose is needed to attain endocrine remission as compared to attaining only tumor control. The highest endocrine remission rates are achieved by patients with Cushing's disease and the lowest in those with prolactinomas. The most common complication of radiosurgery is delayed hypopituitarism followed by cranial neuropathies. The effect of suppressive medications on radiosurgery outcomes remains controversial. Due to the rare but well-documented occurrence of late recurrence following endocrine remission, long-term and rigorous clinical and radiographic follow-up is necessary for all pituitary adenoma patients.


Memory cost of absorbing conditions for the finite-difference time-domain method.
Three absorbing layers are investigated using standard rectilinear finite-difference schemes. The perfectly matched layer (PML) is compared with basic lossy layers terminated by two types of absorbing boundary conditions, all simulated using equivalent memory consumption. Lossy layers present the advantage of being scalar schemes, whereas the PML relies on a staggered scheme where both velocity and pressure are split. Although the PML gives the lowest reflection magnitudes over all frequencies and incidence angles, the most efficient lossy layer gives reflection magnitudes of the same order as the PML from mid- to high-frequency and for restricted incidence angles.


Red cell organic phosphates during administration of salicylates.
The effect of salicylates on erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) was studied in vivo in 3 groups of healthy subjects receiving acetylsalicyclic acid (18 persons), sodium salicylate (5 persons) and salicylamide (7 persons) in therapeutic dosage. No effect was found on 2,3-DPG in any of the 3 groups. ATP was significantly decreased (p less than 0.05) when acetylsalicylic acid or sodium salicylate was given.


Two new rhabdoviruses (Rhabdoviridae) isolated from birds during surveillance for arboviral encephalitis, northeastern United States.
Two novel rhabdoviruses were isolated from birds during surveillance for arboviral encephalitis in the northeastern United States. The first, designated Farmington virus, is a tentative new member of the Vesiculovirus genus. The second, designated Rhode Island virus, is unclassified antigenically, but its ultrastructure and size are more similar to those of some of the plant rhabdoviruses. Both viruses infect birds and mice, as well as monkey kidney cells in culture, but their importance for human health is unknown.