Metabolic predictors of pain, fatigue, depression and quality of life in people with long-term type 1 diabetes-the Dialong study.
To examine associations of metabolic parameters (mean 30 years' time-weighted HbA1c and low-density lipoprotein-cholesterol [LDL-c], current methionine sulfoxide [MetSO], advanced glycation end products [AGEs], inflammatory markers and hypoglycaemia) with pain, fatigue, depression and quality of life (QoL) in people with long-term type 1 diabetes. A total of 104 persons with type 1 diabetes ≥45 years duration were included. Participants completed questionnaires measuring bodily pain (RAND-36 bodily pain domain with lower scores indicate higher levels of bodily pain), fatigue (Fatigue Questionnaire), depression (Patient Health Questionnaire), overall QoL (World Health Organization Quality of Life-BREF) and diabetes-related QoL (Audit of Diabetes-Dependent Quality of Life). In this observational study, mean time-weighted HbA1c and LDL-c were calculated based on longitudinal measures obtained from medical records of up to 34 years, while current HbA1c , LDL-c and inflammatory markers were analysed in blood samples and collagen MetSO and AGEs in skin biopsies. History of hypoglycaemia was self reported. Associations between metabolic parameters and questionnaire scores were analysed using linear regression analyses and are reported as standardized regression coefficients (beta). Of the metabolic variables, higher mean time-weighted HbA1c was associated with higher levels of bodily pain and total fatigue (beta [p-value]) -0.3 (<0.001) and 0.2 (0.001). Long-term chronic hyperglycaemia may have a negative influence on pain and fatigue in people with type 1 diabetes. These results may assist health care workers in emphasizing the importance of strict glycaemic control in people with diabetes and identifying and treating type 1 diabetes-related pain and fatigue.


Compiling and using input-output frameworks through collaborative virtual laboratories.
Compiling, deploying and utilising large-scale databases that integrate environmental and economic data have traditionally been labour- and cost-intensive processes, hindered by the large amount of disparate and misaligned data that must be collected and harmonised. The Australian Industrial Ecology Virtual Laboratory (IELab) is a novel, collaborative approach to compiling large-scale environmentally extended multi-region input-output (MRIO) models. The utility of the IELab product is greatly enhanced by avoiding the need to lock in an MRIO structure at the time the MRIO system is developed. The IELab advances the idea of the "mother-daughter" construction principle, whereby a regionally and sectorally very detailed "mother" table is set up, from which "daughter" tables are derived to suit specific research questions. By introducing a third tier - the "root classification" - IELab users are able to define their own mother-MRIO configuration, at no additional cost in terms of data handling. Customised mother-MRIOs can then be built, which maximise disaggregation in aspects that are useful to a family of research questions. The second innovation in the IELab system is to provide a highly automated collaborative research platform in a cloud-computing environment, greatly expediting workflows and making these computational benefits accessible to all users. Combining these two aspects realises many benefits. The collaborative nature of the IELab development project allows significant savings in resources. Timely deployment is possible by coupling automation procedures with the comprehensive input from multiple teams. User-defined MRIO tables, coupled with high performance computing, mean that MRIO analysis will be useful and accessible for a great many more research applications than would otherwise be possible. By ensuring that a common set of analytical tools such as for hybrid life-cycle assessment is adopted, the IELab will facilitate the harmonisation of fragmented, dispersed and misaligned raw data for the benefit of all interested parties.


Factors affecti̇ng health-promoting behavi̇ors i̇n nursi̇ng students: A structural equation modeling approach.
The purpose of this study is to evaluate the effectiveness of the Mindfulness-based Stress Reduction program applied to a sample of Turkish nursing students. The study was designed as a randomized controlled trial. Program sessions of 90-95 minutes were given twice a week for 12 weeks. The data were collected using the Nursing Education Stress Scale, the Mindfulness Scale, and the Stress Management Styles Scale. A statistically significant difference was found in the mean post-test and mean follow-up scores obtained by the control group and the experimental group on the Nursing Education Stress Scale and its sub-dimensions. On the Mindfulness Scale, a statistically significant difference was found between the mean pre-test and post-test scores obtained by the experiment and control groups. The results derived from this study suggest that the mindfulness-based stress reduction program is effective in reducing the stress experienced by students during nursing education, increasing their mindfulness, strengthening their coping mechanisms for stress, increasing their use of self-confident and optimistic approaches, and decreasing their use of the helpless approach.


Dynamics of protein and fluid secretion from the major salivary glands of rat: relevance of research findings to clinically observed defective secretion in cystic fibrosis.
Although there are indications of a defect in secretion of protein from exocrine cells in cystic fibrosis (CF), this remains an aspect of CF research that has not been adequately addressed. Using salivary glands of rat as model systems, and following the effects of parasympathetic and sympathetic autonomic nerve stimulation on these glands, we demonstrate the existence of three separate pathways through which secretion of protein can be evoked from serous and mucous exocrine cells. These pathways allow the secretion of proteins from the intracellular compartments in a constitutive, intermediate or regulated manner. The primary aspects of secretory profile including concentration and the degree of hydration of secreted material differ greatly between the pathways, are cell type specific, and presumably are a direct consequence of controlled changes in the levels of second messengers induced upon stimulation of these cells. As previously published reports suggest that only the beta-adrenergic regulated pathway is affected by CF, differences between the pathways in their secretory profiles may influence the development of lung disease, through disparate disturbances in the secretion of protein and fluid from serous and mucous cells of the submucosal glands that line the bronchiolar tree in humans. We gratefully acknowledge support from The Wellcome Trust and from The European Union Biomed II Programme.


Prophylactic treatment for preeclampsia in high-risk teenage primigravidae with nitric oxide donors: a pilot study.
Preeclampsia is associated with significant morbidity and mortality especially in high-risk groups. Impairment of endogenous nitric oxide has been shown to be associated with the disease and prophylactic therapy may ameliorate this condition and improve pregnancy outcome. This study valuated nitric oxide donors prophylactic treatment for preeclampsia in high-risk teenage primigravidae. The study included three hundred primigravidae aged ≤ 20 years with singleton pregnancy. Abdominal pulsed color Doppler ultrasound was done at 24 weeks gestation and pregnancies with uterine artery diastolic notch were randomly allocated to a control group received placebo vaginal tablets and a study group received isosorbid mononitrate 20 mg tablet once daily applied vaginally until delivery. Incidence of preeclampsia and maternal, fetal, and neonatal outcome in both groups. The study group had significant lower incidence of preeclampsia, preterm birth, intrauterine growth restriction and of neonatal admission to the intensive care (p < 0.05). Nitric oxide donors prophylactic treatment for preeclampsia in high-risk teenage pregnancies decrease the incidence of preeclampsia and improve maternal, fetal, and neonatal outcomes. Further studies on larger sample size are required to confirm these results.


The association between TNF-α, IL-10 gene polymorphisms and primary Sjögren's syndrome: a meta-analysis and systemic review.
Previous studies have evaluated the associations of TNF-α, IL-10 gene polymorphisms and susceptibility to pSS, but the results remained controversial. To assess the associations between TNF-α-308, IL-10-1082, -819, -592 polymorphisms and pSS risk, a meta-analysis was conducted. The available articles were searched in PubMed, EMBASE and MEDLINE. ORs with 95% CIs were calculated to determine the strength of associations by fixed-effects or random-effects models. The data about IL-10-1082, -819, -592 polymorphisms were analyzed in the additive, dominant and recessive modes. The associations between haplotypes of IL-10 gene and susceptibility to pSS were also assessed. A total of 9 relevant studies were identified in the meta-analyses. TNF-α-308 A allele was significantly associated with pSS (OR = 1.8, 95% CI: 1.53-2.13). The IL-10 -1082 G allele and the genotype "GCC/ATA" were identified as a candidate genetic risk factor for pSS. Under the dominant model for -819 and -582, the overall ORs suggested that individuals with genotype (CC+TC) or (CC+AC) may have a 59% increased risk of pSS in Caucasians population (OR = 1.59, 95% CI:1.09-1.23). Besides, the genotype "ATA/ATA" may be a protective factor against the development of pSS in Caucasians (OR = 0.40, 95% CI:0.19-0.84). The meta-analysis demonstrated TNF-α-308 A, IL-10-1082 G allele were significantly associated with pSS susceptibility, supporting these alleles were predisposing factors for pSS. In Caucasian population, the genotype "ATA/ATA" may be a protective factors.


A versatile waveform generator for testing neuroelectric signal processors.
A multi-channel waveform generator was designed for testing neuroelectric signal processors. Smooth transient signals that resemble action potentials or evoked potentials are generated by a second order switched capacitor filter excited by brief rectangular pulses. The choice of an integrated circuit switched capacitor filter simplified the design by circumventing some of the disadvantages of conventional active filters. The waveform generator is versatile, with several signal parameters being independently adjustable from front panel controls: duration, waveshape, latency, amplitude and signal-to-noise ratio. The generator has been used for testing evoked potential acquisition and processing systems, for evaluating the effects of analog filters on evoked potentials and for testing systems designed to detect and classify trains of multi-unit action potentials.


N-Acetyl-D-Glucosamine Acts as Adjuvant that Re-Sensitizes Starvation-Induced Antibiotic-Tolerant Population of E. Coli to β-Lactam.
Bacterial tolerance to antibiotics causes reduction in efficacy in antimicrobial treatment of chronic and recurrent infections. Nutrient availability is one major factor that determines the degree of phenotypic antibiotic tolerance. In an attempt to test if specific nutrients can reverse phenotypic tolerance, we identified N-acetyl-D-glucosamine (GlcNAc) as a potent tolerance-suppressing agent and showed that it could strongly re-sensitize a tolerant population of E. coli to ampicillin. Such re-sensitization effect was attributable to two physiology-modulating effects of GlcNAc. First, uptake of GlcNAc by the tolerant population triggers formation of the peptidoglycan precursor UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) and subsequently re-activates the peptidoglycan biosynthesis process, rendering the organism susceptible to β-lactam antibiotics. Second, activation of glycolysis by-products of GlcNAc catabolism drives the re-sensitization process. Our findings imply that GlcNAc may serve as a non-toxic β-lactam adjuvant that enhances the efficacy of treatment of otherwise hard-to-treat bacterial infections due to phenotypic antibiotic tolerance.


Bacterial response to eukaryotic cells. Analysis of differentially expressed proteins using nano liquid chromatography-electrospray ionization tandem mass spectrometry.
Host-bacteria interactions have mostly been investigated with regard to the host response or to activities of pathogenic bacteria. In contrast, we aim to identify reactions of non-pathogenic bacteria that result from their contact with host cells of the gastrointestinal tract. In a proteomic approach, the response of non-pathogenic human Escherichia coli bacteria on gut epithelial cells (rat IEC-6) was investigated in an in vitro co-culture model. For this purpose, a sensitive analytical procedure was developed based on the identification of two-dimensional polyacrylamide gel electrophoresis separated proteins by online nanoLC-electrospray ionization MS/MS using a quadrupole time-of-flight tandem mass spectrometer for accurate mass determination. We demonstrate here the efficiency of this technique by the identification of a total of 43 differentially expressed proteins, out of which 25 were up-regulated and 18 were down-regulated. They represent a wide range of molecular weight and different metabolic and physiological functions.


Primary laryngeal peripheral T-cell lymphoma--An autopsy report with review of literature.
Primary laryngeal non-Hodgkin's lymphomas are very rare constituting 1% of all laryngeal tumors. Of these, the peripheral T-cell lymphomas are extremely rare with <10 case reports in English literature. Laryngeal lymphomas are clinically confused with the more common laryngeal malignancies like squamous cell carcinoma, thus, histopathological examination is mandatory for diagnosing, sub-typing and guiding therapy for these lymphomas. We report a case of rare primary laryngeal peripheral T-cell lymphoma with autopsy findings.


Does research participation make a difference in residency training?
The American Board of Orthopaedic Surgery requirements state that an orthopaedic residency must offer at least 5 years of clinical education and some exposure to research. To expose residents to basic research, some programs, including ours, have a research track that allows for 1 year of basic science research. The degree to which research productivity during residency-which may be something that can perhaps be influenced by interventions like research tracks during residency-affects residency graduates' future research contributions is unknown. Our research goals were to determine whether (1) residents who published in a peer-reviewed journal during residency were more likely to publish in their careers after graduation; (2) residents who participated in an elective research year were more likely to publish at least one paper in a peer-reviewed journal during residency; and (3) residents who participated in the research year were more likely to choose academic careers. Using questionnaires, online PubMed searches, and office contact, the career paths (academic versus private practice) and publications in peer-reviewed journals of all 122 Case Western Reserve University orthopaedics residents who completed training from 1987 to 2006 were analyzed. Seventy-five percent of residents who published peer-reviewed research during residency continued with peer-reviewed publications in their careers versus 55% of residents who did not publish during residency (p = 0.02). No difference in career paths was observed between the Case Western Reserve University research and traditional track-trained surgeons. During residency, however, research track-trained surgeons were more likely to publish in peer-reviewed journals (71% versus 41% of traditional track-trained surgeons, p < 0.01). Residents who publish in a peer-reviewed journal during residency are more likely to continue publishing in their future careers as orthopaedic surgeons. Future studies are needed to elucidate the causative factors in the association between publishing in a peer-reviewed journal during training and further contributions later in an orthopaedic surgeon's career.


[Endemic air-borne contact dermatitis? Frequent occurrence of a rare contact allergy in a waste collection facility].
Numerous cases of work-related air-borne contact dermatitis of the face were encountered in a waste collection facility. Potential allergens contained in the dust at the facility could be identified. In 5 of 7 symptomatic workers a type-IV sensitization to p-aminodiphenylamine could be documented. Since there is no commercial patch test preparation for p-aminodiphenylamine available, it had to be prepared for each patient individually. After identifying the allergen, a change in the work routine led to a reduction of dust emissions and afterwards no cases of air-borne contact dermatitis of the face recurred.


The role of computed tomography in the staging of bladder cancer.
Computed tomography of the pelvis has been performed in 60 patients with epithelial bladder tumours. The CT findings have been compared with the clinical staging (T-stage), lymphography (N-stage) and wherever possible the surgical staging (P-stage). Although the intraluminal tumour was visualised in a high proportion of examinations, the greatest value of CT is in the accurate delineation of the extravesical extension of the growth. This is likely to be the primary role of CT in the staging of bladder cancer. Difficulties in detecting invasion of contiguous organs, particularly the prostate, and the failure to demonstrate nodal involvement within the pelvis were noted. The technique has clear advantages over more invasive investigations and the additional information provided over and above clinical staging is seen as a major advance in the assessment of these tumours.


Optical Coherence Microscopy.
The present chapter aims at demonstrating the capabilities of optical coherence microscopy (OCM) for applications in biomedical imaging. We furthermore review the functional imaging capabilities of OCM focusing on lable-free optical angiography. We conclude with a section on digital wavefront control and a short outlook on future developments, in particular for contrast enhancement techniques.


The Effects of Air Pollution on the Development of Atopic Disease.
Air pollution is defined as the presence of noxious substances in the air at levels that impose a health hazard. Thus, there has been long-standing interest in the possible role of indoor and outdoor air pollutants on the development of respiratory disease. In this regard, asthma has been of particular interest but many studies have also been conducted to explore the relationship between air pollution, allergic rhinitis, and atopic dermatitis. Traffic-related air pollutants or TRAP refers to a broad group of pollutants including elemental carbon, black soot, nitrogen dioxide (NO2), nitric oxide (NO), sulfur dioxide (SO2), particulate matter (PM2.5 and PM10), carbon monoxide (CO), and carbon dioxide (CO2). In this review, we aim to examine the current literature regarding the impact of early childhood exposure to TRAP on the development of asthma, allergic rhinitis, and atopic dermatitis. Although there is growing evidence suggesting significant associations, definitive conclusions cannot be made with regard to the effect of TRAP on these diseases. This conundrum may be due to a variety of factors, including different definitions used to define TRAP, case definitions under consideration, a limited number of studies, variation in study designs, and disparities between studies in consideration of confounding factors. Regardless, this review highlights the need for future studies to be conducted, particularly with birth cohorts that explore this relationship further. Such studies may assist in understanding more clearly the pathogenesis of these diseases, as well as other methods by which these diseases could be treated.


Alteration of Skin Mechanical Properties in Patients Undergoing Botulinum Toxin Type A Injections of Forehead Rhytides.
Although application of botulinum toxin type A (BTX-A) for the treatment of forehead rhytides has become very popular, the effects of its intramuscular injections on the skin mechanical properties remain unclear. We prospectively investigated the alterations in the mechanical properties of the skin of patients who received intramuscular injections of botulinum toxin A (BTX-A) for forehead rhytides and compared two injection doses. Of the 42 enrolled patients, one randomly assigned half received intramuscular injections of two units (group I), and the other half received four units (group II) of BTX-A in each injection point. The baseline and post-treatment skin mechanical parameters, including gross elasticity (R2), net elasticity (R5), viscoelastic ratio (R6) and biological elasticity (R7), were measured using the Cutometer(®) and compared. Treatment with BTX-A resulted in significant overall alterations in the mechanical properties of skin at the injection sites of both treatment groups during the 16-week period, and no significant differences were observed between groups. Significant decreases in biological elasticity, net elasticity and viscoelasticity properties were observed at 2 weeks follow-up and began to recover at that time. All of the skin mechanical properties recovered to baseline levels by 16 weeks of follow-up in both dosage groups, which indicates that the higher dosage (4 units) did not delay relapse compared to the two-unit dosage. We concluded that intramuscular injections of BTX-A significantly regulated the gross elasticity, net elasticity, functional elasticity and viscoelastic elasticity at the injection point over a radius of 1.5 cm at 2, 4 and 8 weeks follow-up. The alteration in the skin measurements had completely diminished by the 16-week follow-up. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Comparative evaluation of BD Phoenix and vitek 2 systems for species identification of common and uncommon pathogenic yeasts.
The BD Phoenix system was evaluated for species-level identification of yeasts (250 clinical isolates) and compared with the Vitek 2 system, using ribosomal internal transcribed spacer (ITS) sequence analysis as the gold standard. Considering only the species included in each system's database, 96.3% (236/245) and 91.4% (224/245) of the isolates were correctly identified by BD Phoenix and Vitek 2, respectively.


Reclassification of clinically-detected sequence variants: Framework for genetic clinicians and clinical scientists by CanVIG-UK (Cancer Variant Interpretation Group UK).
Variant classifications may change over time, driven by emergence of fresh or contradictory evidence or evolution in weighing or combination of evidence items. For variant classifications above the actionability threshold, which is classification of likely pathogenic or pathogenic, clinical actions may be irreversible, such as risk-reducing surgery or prenatal interventions. Variant reclassification up or down across the actionability threshold can therefore have significant clinical consequences. Laboratory approaches to variant reinterpretation and reclassification vary widely. Cancer Variant Interpretation Group UK is a multidisciplinary network of clinical scientists and genetic clinicians from across the 24 Molecular Diagnostic Laboratories and Clinical Genetics Services of the United Kingdom (NHS) and Republic of Ireland. We undertook surveys, polls, and national meetings of Cancer Variant Interpretation Group UK to evaluate opinions about clinical and laboratory management regarding variant reclassification. We generated a consensus framework on variant reclassification applicable to cancer susceptibility genes and other clinical areas, which provides explicit recommendations for clinical and laboratory management of variant reclassification scenarios on the basis of the nature of the new evidence, the magnitude of evidence shift, and the final classification score. In this framework, clinical and laboratory resources are targeted for maximal clinical effect and minimal patient harm, as appropriate to all resource-constrained health care settings.


Preconditioning adipose-derived mesenchymal stem cells with dimethyl fumarate promotes their therapeutic efficacy in the brain tissues of rats with Alzheimer's disease.
Transplantation of mesenchymal stem cell (MSC) has been suggested to be a promising method for treating neurodegenerative conditions, including Alzheimer's disease (AD). However, the poor survival rate of transplanted MSCs has limited their therapeutic application. This study aimed to evaluate whether preconditioning MSCs with dimethyl fumarate (DMF), a Nrf2 inducer, could enhance MSC therapeutic efficacy in an amyloid-β (Aβ1-42)-induced AD rat model. The survival and antioxidant capacity of MSCs treated with DMF were assessed in vitro. Aβ1-42 intrahippocampal injection was used to create a rat model of AD. Following the transplantation of MSCs preconditioned with DMF and using the Morris blue maze test, spatial learning and memory were assessed. Using RT-qPCR, we evaluated the gene expression related to apoptosis and neurotrophins in the hippocampus region. Treatment with DMF enhanced cell survival and Nrf2 protein expression in MSCs in vitro. Preconditioning with DMF also enhanced the efficacy of transplanted MSCs in rescuing learning and spatial memory deficits in Aβ-AD rats. Besides, DMF preconditioning enhanced the neuroprotective effect of transplanted MSCs in the hippocampus of rats treated with Aβ1-42 by decreasing the expression of apoptotic markers (Bax, caspase 3, and cytochrome c), and elevating the expression of the anti-apoptotic marker Bcl2 and neurotrophins, including BDNF and NGF. Preconditioning MSCs with DMF boosted the therapeutic efficacy of these cells; therefore, it could serve as a targeted strategy for increasing the therapeutic efficacy of MSCs in treating neurodegenerative disorders, including AD.


Quorum quenching affects biofilm development in an anaerobic membrane bioreactor (AnMBR): from macro to micro perspective.
The first experimental study on the influence of acyl homoserine lactones (AHLs) degrading quorum quenching (QQ) consortium on the dynamics of biofilm bio-communities (i.e., from suspended biomass to initial biofilm and mature biofilm) in an anaerobic membrane bioreactor (AnMBR) at a microscopic scale (denoted as QQAnMBR) was reported. QQ did not change the overall bacterial community of the suspended biomass, inclusive of the key functional bacteria. Moreover, the retarded initial biofilm formation was attributed to not only the lower extracellular polymeric substance content of suspended biomass, but also the decelerated colonization of the AHL-regulated low-abundance in suspended biomass but pioneering keystone taxa Rhodocyclaceae;g- on membrane surface. However, pioneering fouling-related taxa such as Sulfurovum and Rhodocyclaceae;g- still played paramount roles in the delayed initial biofilm formation in the QQAnMBR. Furthermore, the microbial assemblies of the mature biofilm were changed in the QQAnMBR, probably attributable to the abiotic microbial floc attachment.


Lung function in preschool children with a history of wheezing measured by forced oscillation and plethysmographic specific airway resistance.
Wheezing is common in preschool children, but objective evidence for airway obstruction and its reversibility are rarely available in clinical practice. We assessed whether abnormalities of lung function and bronchodilator response can be detected in preschool children using the forced oscillation technique and measurements of specific airway resistance. Fifty-nine children with a history of wheeze and 24 healthy controls aged 3-6 years were recruited. Resistance and reactance at 6 and 8 Hz (Rrs6, Rrs8, Xrs6 and Xrs8, respectively) were measured using the forced oscillation technique and specific airway resistance was measured in a plethysmograph. z-Scores were calculated from published reference data. Tests were repeated 15 min after 400 mcg salbutamol. Bronchodilator response was expressed as the log-transformed ratio of postbronchodilator/prebronchodilator values. Technically acceptable measurements using the forced oscillation technique were obtained in n = 77 (93%) of children and in n = 56 (68%) using plethysmography. There was no significant difference in baseline lung function or bronchodilator response, assessed by either technique, between those with a history of wheeze and healthy controls. Measurement of lung function is feasible in preschool children, but neither of these techniques was able to identify diminished lung function or reversibility to bronchodilator in children with a history of wheeze.


The sequences of MinE responsible for its subcellular localization analyzed by competitive binding method in Escherichia coli.
The subcellular localization of a protein is important for its proper function. Escherichia coli MinE is a small protein with clear subcellular localization, which provides a good model to study protein localization mechanism. In the present study, a series of recombinant minEs truncated in one end or in the middle regions, fused with egfp, was constructed, and these recombinant proteins could compete to function with the chromosomal MinE. Our results showed that the sequences related to the subcellular localization of MinE span several functional domains, demonstrating that MinE positioning in cells depends on multiple factors. The eGFP fusions with some truncated MinE from N-terminal resulted in different cell phenotypes and localization features, implying that these fusions can interfere chromosomal MinE's function, similar to MinE36-88 phenotype in the previous report. The amino acid in the region (32-48) is sensitive to change MinE conformation and influence its dimerization. Some truncated protein structure could be unstable. Thus, the MinE localization is prerequisite for its proper anti-MinCD function and some new features of MinE were demonstrated. This approach can be extended for subcellular localization research for other essential proteins.


Nutrient ratios influence variability in Pseudo-nitzschia species diversity and particulate domoic acid production in the Bay of Seine (France).
The population dynamics of different Pseudo-nitzschia species, along with particulate domoic acid (pDA) concentrations, were studied from May 2012 to December 2013 in the Bay of Seine (English Channel, Normandy). While Pseudo-nitzschia spp. blooms occurred during the two years of study, Pseudo-nitzschia species diversity and particulate domoic acid concentrations varied greatly. In 2012, three different species were identified during the spring bloom (P. australis, P. pungens and P. fraudulenta) with high pDA concentrations (∼1400ngl-1) resulting in shellfish harvesting closures. In contrast, the 2013 spring was characterised by a P. delicatissima bloom without any toxic event. Above all, the results show that high pDA concentrations coincided with the presence of P. australis and with potential silicate limitation (Si:N<1), while nitrate concentrations were still replete. The contrasting environmental conditions between 2012 and 2013 highlight different environmental controls that might favour the development of either P. delicatissima or P. australis. This study points to the key role of Pseudo-nitzschia diversity and cellular toxicity in the control of particulate domoic acid variations and highlights the fact that diversity and toxicity are influenced by nutrients, especially nutrient ratios.


Mueller maneuver and LV function in coronary artery disease.
Decreasing pleural pressure impedes the ejection of blood from the left ventricle (LV), may lead to decreased LV compliance because of interdependence effects and leads to increased transmural LV systolic and diastolic pressure. Previous work from this laboratory has shown that patients with coronary artery disease (CAD) often develop akinetic segments of the LV wall during the Mueller maneuver. In the presence of increased LV transmural pressure regional akinesis could be caused either by the development of regional ischemia or by mechanical inhibition of motion of an area of nonfunctional myocardium as would be caused by previous myocardial infarction (MI). The present study was designed to distinguish between these two mechanisms by determining if the presence of CAD alone is sufficient to lead to regional akinesis or if prior MI is necessary. We used first pass radionuclide ventriculography (RVG) in the 30 degrees LAD supine position to measure LV ejection fraction (EF), end-diastolic (EDV) and end-systolic (ESV) volumes, heart rate and to assess regional wall motion during the Mueller maneuver. This was done in four groups of subjects: 13 normal subjects, 25 patients with CAD but no prior MI, 13 patients with prior nontransmural MI and 36 patients with prior transmural MI. All subjects had angina pectoris and underwent contrast coronary arteriography. Most also underwent routine contrast left ventriculography as well. There were no significant differences among the three patient groups as regards medications, extent and severity of CAD, and response to routine exercise tolerance testing. EF decreased significantly in the three patient groups (4%-9%, p less than 0.01) but not in the normals during the Mueller maneuver. Heart rate increased (5-10 bpm, p less than 0.05) in the normals and in patient groups 2 and 4. EDV decrease in all four subject groups (8%-10%, p less than 0.01), while ESV remained unchanged. Akinesis of the LV wall developed during the Mueller maneuver only in one group-2 patient, but did so in 17/36 patients with prior transmural MI (group 4, p less than 0.001). One-half of the akinetic LV wall segments seen during the Mueller maneuver on RVG were not seen on routine contrast ventriculography. We tested the effects of posture (supine versus upright) on the response to the Mueller maneuver in six normal subjects and found no changes in the response of EDV and ESV to the Mueller maneuver.(ABSTRACT TRUNCATED AT 400 WORDS)


Improved Survival After Pelvic Fracture: 13-Year Experience at a Single Trauma Center Using a Multidisciplinary Institutional Protocol.
To analyze pelvic fracture mortality rates before and after initiation of a multidisciplinary pelvic fracture protocol. Retrospective database analysis. Prospective data from our Level-I National Trauma Registry of The American College of Surgeons (NTRACS) database. A total of 1682 trauma patients with pelvic fractures from 2000 to 2013 were compared with a control group of 42,629 without pelvic fractures. Initiation of a multidisciplinary institutional protocol to guide the initial management of trauma patients with pelvic fractures. Patients were grouped into 3 periods (group 1: 2000-2003, group 2: 2004-2007, group 3: 2008-2013). Multivariate logistic regression analysis was conducted to assess associations between mortality and age, shock (systolic blood pressure less than or equal to 90 mm Hg), head injury (Glasgow Coma Scale less than or equal to 8), Injury Severity Score (ISS), and time period. Unadjusted mortality rates decreased [12.5%-11.0% (P = 0.72)]; however, ISS increased [19.1-22.7 (P < 0.01)]. Age, shock, head injury, increasing ISS, and earlier period were significantly associated with mortality. Adjusted mortality decreased over time [odds ratio for 2000-2003 vs. 2008-2013: 2.05, 95% confidence interval = (1.26, 3.33) and odds ratio for 2004-2007 vs. 2008-2013: 1.71, 95% confidence interval = (1.09, 2.67)]. From 2000 to 2003, an unstable fracture pattern in the healthiest cohort significantly increased mortality compared with the stable fracture pattern cohort (8.6% and 0.0%, P < 0.01). In subsequent intervals, there was no statistically significant association between stable versus unstable fracture patterns and mortality. Adjusted pelvic fracture mortality rates have significantly decreased over time. In the healthiest patients with unstable pelvic fractures, the mortality rate is now similar to that of patients with stable fracture patterns. With sustained institutional effort to address pelvic fractures, mortality rates can be diminished. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Synergistic inhibition of cell migration by tetraspanin CD82 and gangliosides occurs via the EGFR or cMet-activated Pl3K/Akt signalling pathway.
The metastasis suppressor CD82/KAI-1, which is a member of the tetraspanin superfamily, has been proposed to exert its activity together with glycosphingolipids. However, the mechanism of CD82 inhibition has not been fully elucidated. The present study aimed to investigate the synergistic inhibition of cell migration by the tetraspanin CD82 and gangliosides and to correlate this inhibition with activation of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR/cMet) in Hepa1-6 cell lines, whose motility and migration is stimulated by epidermal growth factor (EGF) and hepatocyte growth factor (HGF) in vitro. We found that Hepa1-6 cells transfected with the CD82 gene exhibited decreased migration in response to EGF and HGF. EGF-stimulated phosphorylation of EGFR at Tyr1173 was inhibited in these cells, which contributed to the attenuation of EGFR. Ectopic expression of CD82 in Hepa1-6 cells inhibited HGF-stimulated tyrosine phosphorylation of cMet at Tyr1313 and Tyr1365 without affecting the expression of cMet. These inhibitory effects were enhanced when CD82 was introduced with Ganglioside GM3 alone or GM2/GM3. Reduction of CD82 expression by RNA interference together with depletion of glycosphingolipids with P4 significantly enhanced cell motility and increased the expression of EGFR and its phosphorylation at Tyr1173 in response to EGF. Increased cell motility and HGF-dependent activation of cMet at Tyr1313 and Tyr1365 resulted from decreased CD82 levels and increased GM3. Furthermore, CD82 expression selectively attenuated EGFR and cMet signalling via phosphatidylinositol 3-kinase/Akt but had no affect on the activity of the MAPK signalling pathway. These results suggest that the synergistic effects of CD82 and GM3 or GM2/GM3 on EGFR expression and phosphorylation and cMet activation are responsible for CD82 inhibition of EGF- and HGF-dependent cell motility and migration of Hepa1-6 cells.


To Be Cautious or Not: Tension Pneumothorax After First Tracheostomy Tube Exchange.
Tracheostomy tube change is a relatively common procedure once a tracheo-cutaneous tract matures. Regular tracheostomy tube changes prevent the formation of granulation tissue and reduce bacterial colonization (Yaremchuk and Yaremchuk in Laryngoscope 113(1):1-10, 2003). However, serious complications such as subcutaneous emphysema, loss of airway and mediastinitis, can occur if the tube exchange is performed inappropriately. We present a rare association of tension pneumothorax following a tracheostomy tube exchange in a 50-year-old patient who underwent tracheotomy 3 days back. The patient was successfully managed conservatively with chest tube and supportive care.


Phase angle as a key marker of muscular and bone quality in community-dwelling independent older adults: A cross-sectional exploratory pilot study.
The aim of the present cross-sectional exploratory pilot study was to analyze the ability of the Phase Angle (PhA) to predict physical function, muscle strength and bone indicators, upon adjusting for potential confounders [age, sex, lean mass, and body mass index (BMI)]. This study included 56 physically independent older adults (age, 68.29 ± 3.01 years; BMI, 28.09 ± 4.37 kg/m2). A multi-frequency segmental bioelectrical impedance analysis was used to measure PhA at 50 KHz. Additionally, physical function was assessed through four functional capacity tests [30-sec chair-stand; seated medicine ball throw (SMBT); timed up & go; and 6-min walking test (6 MWT)], muscle strength through the handgrip test (dominant side) and maximal isokinetic strength of the dominant knee flexor and extensor. Moreover, bone indicators and body composition were assessed through the dual energy X-ray absorptiometry. PhA was significantly associated with SMBT (r = 0.375, effect size (ES) = moderate); 6 MWT (r = 0.396, ES = moderate); 30-sec chair-stand (rho = 0.314, ES = moderate); knee extension (rho = 0.566, ES = large) and flexion (r = 0.459, ES = moderate); handgrip (rho = 0.432, ES = moderate); whole-body bone mineral content (BMC) (r = 0.316, ES = moderate); femoral neck BMC (r = 0.469, ES = moderate); and femoral neck bone mineral density (BMD) (rho = 0.433, ES = moderate). Additionally, the results of multiple regression analysis demonstrated that PhA is significantly associated with SMBT (p < 0.001; R2 = 0.629), 6 MWT (p = 0.004; R2 = 0.214), knee extension (p < 0.001; R2 = 0.697), knee flexion (p < 0.001; R2 = 0.355), handgrip test (p < 0.001; R2 = 0.774), whole-body BMC (p < 0.001; R2 = 0.524), femoral neck BMC (p = 0.001; R2 = 0.249), and femoral neck BMD (p = 0.020; R2 = 0.153). The results of the preliminary analysis suggested that PhA is linked to muscle strength and some factors related to physical function and bone quality in community-dwelling older adults.


Effect of chronic hypoxia and high sucrose diet on body weights and glycolytic enzyme activities in liver, heart, and gastrocnemius of Sprague-Dawley and Wistar rats.
Pyruvate kinase and glucosephosphate isomerase activities were measured in liver, heart, and gastrocnemius of Sprague-Dawley and Wistar rats subjected to chronic hypoxia. Animals were fed Purina chow or a high sucrose diet. In terms of changes in body weight, Sprague-Dawleys acclimated better on Purina chow whereas Wistars adjusted better on the high sucrose diet. These two groups had the lowest heart weight:body weight ratios. Only heart enzyme activities were above levels of pair-fed controls in both strains with hypoxia. Diet affected enzyme activities in hypoxic animals: for rats on high sucrose diet, pyruvate kinase activity was greater in all tissues of both strains except gastrocnemius of Sprague-Dawleys; glucosephosphate isomerase was higher in liver of both strains and only gastrocnemius of Wistars.


The influence of pedicle screw placement on thoracic trabecular strain.
Experimental study. Although pedicle screw loosening and fracture are not uncommon, there is little understanding of the loading relationship between the pedicle screw and surrounding bone. There is even less understanding of the trabecular bone mechanics one a pedicle screw has been removed. To investigate and understand the influence of the presence of pedicle screw placement and subsequent removal on vertebral trabecular strain under axial loading. Orthopaedic Research Laboratories, University of California, Davis, USA. Six cadaver spines were biomechanically loaded and the minimum principal and maximum shear strains were measured using texture correlation. The treatments were divided into three conditions as follows: (1) before screw placement, (2) during screw placement, and (3) after screw removal. The obtained data were statistically analyzed. Trabecular strain adjacent to the pedicle screw was increased following pedicle screw placement and remained high following pedicle screw removal. The current study demonstrates that pedicle screw placement greatly influences the trabecular bone and introduces weakness in the area following screw removal.


Evolution of occlusion and temporomandibular disorder in orthodontics: Past, present, and future.
Occlusion has been an important consideration in orthodontics since the beginning of the discipline. Early emphasis was placed on the alignment of the teeth, the stability of the intercuspal position, and the esthetic value of proper tooth positioning. These factors remain important to orthodontists, but orthopedic principles associated with masticatory functions must also be considered. Orthopedic stability in the masticatory structures should be a routine treatment goal to help reduce risk factors associated with developing temporomandibular disorders.


Transaneurysmal aortic balloon tamponade.
A method consisting of direct transaneurysmal insertion of a double lumen balloon catheter designed to gain control of the inflow into ruptured or difficult to dissect aneurysms is presented.


Induction of genotoxicity and mutagenic potential of heavy metals in Thai occupational workers.
Heavy metals are widely used in many industries in Thailand and found in the environment. Occupational exposure to heavy metals is often chronic and caused by environmental contaminations, potentially leading to mutations and cancer. Although the genotoxic effects of occupational exposure to multiple heavy metals have been extensively studied, the findings regarding their genotoxicity are conflicting. In this study, we focused on investigating the genotoxic effects of certain heavy metals mixtures, including lead (Pb), copper (Cu), zinc (Zn), and tin (Sn), to which workers are exposed in the manufacturing industry. The cytokinesis-blocked micronucleus (CBMN) assay in peripheral blood lymphocytes was performed, and DNA damage was assessed by measuring tumour-associated protein levels and 8-hydroxy-2'-deoxyguanosine (8-OHdG) generated by oxidative stress that causes cytotoxicity. The occupational exposure group included 110 workers exposed to heavy metal mixtures and 105 matched control subjects. We found statistically significant differences in the blood Pb, Sn, and Cu levels between the exposed workers and the control subjects (p < 0.001). Analysis of micronuclei (MN) in peripheral blood lymphocytes revealed a significantly increased frequency of MN in exposed workers compared with that in control subjects (p<0.05). Non-smoking exposed workers were selected for 8-OHdG formation and mutant p53 tests, and significant differences in the mean plasma 8-OHdG concentration (p < 0.001) were found between the occupational exposure and the control group, but no differences were found in the levels of mutant p53. Thus, chronic exposure to different heavy metals causes genotoxic effects in humans. Furthermore, the CBMN assay and 8-OHdG formation can be used as surrogate biomarkers to identify and monitor groups with higher carcinogenic risk in the early stages of toxicity. In summary, our results indicate that mixtures of heavy metals (Pb, Sn, and Cu) in manufacturing industries pose an elevated health risk due to DNA damage.


Expression and regulation of interleukin-1 receptors in the brain. Role in cytokines-induced sickness behavior.
Sickness behavior refers to the coordinated set of behavior changes that develop in sick individuals during the course of an infection. At the molecular level, these changes are due to the effects of proinflammatory cytokines as interleukin-1 on the brain. The purpose of this article is not to review the entire field of cytokines and behavior, but rather to address the role of interleukin-1 receptors (IL-1Rs) in sickness behavior. We briefly describe the notion of sickness behavior and present the distribution of IL-1Rs in the central nervous system of the human, mouse and rat. We then bring arguments in favor of the functionality of the various subtypes of receptors and evaluate the nature of the signaling pathways activated by brain IL-1Rs to initiate central modifications leading to symptoms of sickness. Finally, modulation of IL-1 action on its receptor by various opposing factors including glucocorticoids and anti-inflammatory cytokines is discussed.


Persistent T cell proliferation and MDSCs expansion precede incomplete CD4+ T cell recovery in people with acute HIV-1 infection with early ART.
HIV-1 infection causes T cell dysfunction that cannot be fully restored by anti-retroviral therapy (ART). Myeloid-derived suppressor cells (MDSCs) expand and suppress T cell function during viral infection. In this study, we evaluated the dynamics of phenotypes and function of T cells and MDSCs and the effects of their interaction on CD4+ T cell reconstitution in people with acute HIV-1 infection (PWAH) with early ART. Flow cytometry was used to detect the phenotypic dynamics and function of T cells and MDSCs at pre-ART, 4, 24, 48, and 96 weeks of ART. We observed that T cells were hyper-activated and hyper-proliferative in PWAH at pre-ART. Early ART normalized T cell activation but not their proliferation. T cell proliferation, enriched in PD-1+ T cells, was persisted and negatively associated with CD4+ T-cell counts after ART. Moreover, M-MDSCs frequency was increased and positively correlated with T cell proliferation after 96 weeks of ART. M-MDSCs persisted and inhibited T cell proliferation ex vivo, which could be partially reversed by PD-L1 blockade. Further, we found higher frequencies of proliferative CD4+ T cells and M-MDSCs in PWAH with lower CD4+ T cell numbers (<500 cells/μL) compared to PWAH with higher CD4+ T cell numbers (>600 cells/μL) after 96 weeks of ART. Our findings indicate that persistent T cell proliferation, MDSCs expansion, and their interaction may affect CD4+ T-cell recovery in PWAH with early ART.


Remote ischemic preconditioning on neovascularization and follicle viability on ovary autotransplantation in rats.
Verify the optimum remote vascular occlusion time to reduce ovarian injury in autologous transplants in rats. Twenty-four adult female rats were assigned to four groups: GC (control group): bilateral oophorectomy followed by ovary transplant; GIPC (ischemic preconditioning group): remote ischemic preconditioning at the iliac artery for 5, 10, and 15 minutes (GIPC-5, GIPC-20, and GIPC-15) previous to bilateral oophorectomy and ovarian transplantation. The right ovary was fixed in the retroperitoneum. Euthanasia was performed 4 days after the surgical procedure. The follicles were counted and classified as developing versus atretic. The immunohistochemical assay identified vascular factor of endothelial growth (VEGF) in the ovarian stroma and assessed the proliferation capacity by means of the Ki-67 in the ovarian follicles. Every group showed an inflammatory infiltrate, luteous body, and ovarian follicles in several phases of development. The ischemic preconditioning groups displayed greater amounts of viable ovarian follicles and increased vascularization and vasodilatation than the control group. GIPC-15 showed the highest amount of viable follicles compared to the others (P < .05 GIPC-15 vs GC; GIPC-15 vs GIPC-5). More VEGF-labeled cells were observed in GIPC-10 than the control group (P < .05, GIPC-10 vs GC). The proliferation index assessed by Ki-67 marking showed GC: 80%; GIPC-5: 76%; GIPC-10: 67%; and GIPC-15: 64% (P > .05). The PCI-15 cohort seem to be the most adequate timing to achieve functional support and preservation of a greater number of viable ovarian follicles.


Cytogenetics and molecular genetics of Wilms' tumor of childhood.
We describe the way in which application of cytogenetic and molecular genetic techniques to the study of Wilms' tumor (WT) of the kidney and the associated congenital disorders, such as sporadic aniridia and the Beckwith-Wiedemann syndrome, has led to identification of two regions on the short arm of chromosome 11 (11p13 and 11p15) involved in tumor development. In addition, evidence shows that genomic imprinting may be an important factor in transformation. Such investigations have led to cloning of a candidate WT gene (WT1) from 11p13. Linkage studies in familial studies suggest that an additional locus is involved. Analysis of the cytogenetic data available on this tumor suggests that this may be situated on 1p, 16q, or 17p.


Drinking motives, personality traits and life stressors-identifying pathways to harmful alcohol use in adolescence using a panel network approach.
Models of alcohol use risk suggest that drinking motives represent the most proximal risk factors on which more distal factors converge. However, little is known about how distinct risk factors influence each other and alcohol use on different temporal scales (within a given moment versus over time). We aimed to estimate the dynamic associations of distal (personality and life stressors) and proximal (drinking motives) risk factors, and their relationship to alcohol use in adolescence and early adulthood using a novel graphical vector autoregressive (GVAR) panel network approach. We estimated panel networks on data from the IMAGEN study, a longitudinal European cohort study following adolescents across three waves (aged 16, 19 and 22 years). Our sample consisted of 1829 adolescents (51% females) who reported alcohol use on at least one assessment wave. Risk factors included personality traits (NEO-FFI: neuroticism, extraversion, openness, agreeableness and conscientiousness; SURPS: impulsivity and sensation-seeking), stressful life events (LEQ: sum scores of stressful life events), and drinking motives [drinking motives questionnaire (DMQ): social, enhancement, conformity, coping anxiety and coping depression]. We assessed alcohol use [alcohol use disorders identification test (AUDIT): quantity and frequency] and alcohol-related problems (AUDIT: related problems). Within a given moment, social [partial correlation (pcor) = 0.17] and enhancement motives (pcor = 0.15) co-occurred most strongly with drinking quantity and frequency, while coping depression motives (pcor = 0.13), openness (pcor = 0.05) and impulsivity (pcor = 0.09) were related to alcohol-related problems. The temporal network showed no predictive associations between distal risk factors and drinking motives. Social motives (beta = 0.21), previous alcohol use (beta = 0.11) and openness (beta = 0.10) predicted alcohol-related problems over time (all P < 0.01). Heavy and frequent alcohol use, along with social drinking motives, appear to be key targets for preventing the development of alcohol-related problems throughout late adolescence. We found no evidence for personality traits and life stressors predisposing towards distinct drinking motives over time.


Experimental and modeling approaches in characterizing coating uniformity in a pan coater: a literature review.
This review provides a comprehensive record of experimental and modeling approaches that can be used to study the effect of critical process parameters affecting the coating uniformity in pharmaceutical coating operation. Explicit reference is given to the development of the approach and its previous usage with particular emphasis on the advantages, limitations and model assumptions.


Correlation Analysis Between Expression Levels of Hepatic Growth Hormone Receptor, Janus Kinase 2, Insulin-Like Growth Factor-I Genes and Dwarfism Phenotype in Bama Minipig.
Animal growth and development are complex and sophisticated biological metabolic processes, in which genes plays an important role. In this paper, we employed real-time quantitative PCR (RT-qPCR) to analyze the expression levels of hepatic GHR, JAK2 and IGF-I genes in 1, 30, 180 day of Bama minipig and Landrace with attempt to verify the correlation between the expression of these growth-associated genes and the dwarfism phenotype of Bama minipig. The results showed that the expression levels of these 3 genes in Bama minipigs were down-regulated expressed from 1 day to 30 day, and which was up-regulated expressed in Landrace. The expression levels of the 3 genes on 1, 30, 180 day were prominently higher in Landrace than in Bama minipigs. The significant differences of the 3 genes expression levels on 1 day between this two breeds indicate that different expressions of these genes might occur before birth. It is speculated that the down-regulated expression of the 3 genes may have a close correlation with the dwarfism phenotype of Bama minipig. More investigations in depth of this study is under progress with the help of biochip nanotechnology.


Dorsal raphe nucleus projecting retinal ganglion cells: Why Y cells?
Retinal ganglion Y (alpha) cells are found in retinas ranging from frogs to mice to primates. The highly conserved nature of the large, fast conducting retinal Y cell is a testament to its fundamental task, although precisely what this task is remained ill-defined. The recent discovery that Y-alpha retinal ganglion cells send axon collaterals to the serotonergic dorsal raphe nucleus (DRN) in addition to the lateral geniculate nucleus (LGN), medial interlaminar nucleus (MIN), pretectum and the superior colliculus (SC) has offered new insights into the important survival tasks performed by these cells with highly branched axons. We propose that in addition to its role in visual perception, the Y-alpha retinal ganglion cell provides concurrent signals via axon collaterals to the DRN, the major source of serotonergic afferents to the forebrain, to dramatically inhibit 5-HT activity during orientation or alerting/escape responses, which dis-facilitates ongoing tonic motor activity while dis-inhibiting sensory information processing throughout the visual system. The new data provide a fresh view of these evolutionarily old retinal ganglion cells.


Investigating Nursing Leadership in Intensive Care Units of Hospitals of Northern Greece and Its Relationship to the Working Environment.
The relationship between leadership and the work environment has been studied by many authors at the organization level, but not specifically in intensive care units (ICUs). The aim of this study was to investigate the possible relationship between the work environment and nursing leadership in intensive care units. This is a correlation study. The study population consisted of nurses and nursing assistants with at least 6 months of experience in ICUs of Northern Greece hospitals. Data were collected using the Greek version of the Practice Environment Scale of the Nursing Work Index (PES-NWI) and the Multifactor Leadership Questionnaire (MLQ). Statistical analysis of data was done with IBM SPSS v. 22.0. A total of 64 nurses aged 43.6 ± 6.4 years were included. In the work environment, the dimensions of nursing staff competence (2.4 ± 0.6) and relationships between nursing staff and physicians (2.4 ± 0.6) were higher, and the dimensions of nursing staff involvement in decision-making in hospital (2.3 ± 0.6), nursing authorities on the quality of healthcare (2.2 ± 0.6), and supervisor abilities and support to nursing staff (2.2 ± 0.6) had the lowest score. The highest scores on the leadership questionnaire were personalized interest (2.6 ± 0.8), and exceptional management (passive) (2.6 ± 0.9). The work environment was not related to nursing leadership. Nurses need individual development plans that include the type of knowledge, skills, attitudes, and values required for leadership. In this context, continuing training centers play an important role because they are responsible for training and developing leaders who are fit for work in intensive care.


Barrett's esophagus prevalence and epidemiology.
These epidemiologic studies suggest that gastroesophageal reflux and incompetence of the LES are the most important factors in development of this condition. An unexplained genetic factor must be present, however, to explain the predominance of BE in white middle-aged men.


[Induction of interferon production with dextran sulfate].
Interferon-inducing activity of polyanions (dextran Sulfate, native DNA, polyphosphate, polypentose, polyanetole sulfate, heparin) was studied. Dextran sulfate applied parenterally and enterally was found to be capable of inducing endogenous interferon production in white mice. The maximal titers of interferon (160 units/ml) were seen in the blood serum of mice upon administering the preparation in a dose of 20 mg/kg body mass. No substantial differences were discovered in the time course of interferon production whatever the route of administration.


Minicircle classes heterogeneity within the TcIII and TcIV discrete typing units of Trypanosoma cruzi.
The taxon Trypanosoma cruzi, causative agent of Chagas disease, is composed of several discrete typing units (DTUs) named TcI-TcVI, and Tcbat. The history of the taxon T. cruzi is known, even though several controversial aspects remain as the relationships between TcIII and TcIV. We analyzed cloned T. cruzi stocks pertaining to the seven DTUs by filter hybridization tests of PCR amplicons from minicircle variable regions and kinetoplast DNA probes. Minicircle DNA blots from the cloned stocks and filter hybridization with one TcI, one TcII, one TcV, one TcVI, three TcIII, one TcIV from North America and one TcIV kinetoplast DNA probes from South America revealed minicircle variable region cross-reaction in some T. cruzi DTUs probed. TcIII was heterogeneous in minicircle class composition, even though two TcIII probes revealed that a small fraction of minicircles cross-hybridized with the minicircles from the TcIII, TcV and TcVI DTUs. The minicircles of TcIV from North America cross-reacted only with TcIV from North America but not with TcIV stocks from Brazil and Bolivia. The results on minicircle cross-hybridizations are discussed in the context of RNA editing, mitochondrial function in T. cruzi DTUs.


Deliberate self-harm among Chinese medical students: A population-based study.
The phenomenon of deliberate self-harm (DSH) among college students has received increased attention in recent decades. Adopting a psychosocial perspective, this study aims to describe self-reported DSH among Chinese medical college students, assess respective associations between uncertainty stress and social capital with DSH, and explore the mechanism linking these three phenomena. A cross-sectional survey employing multi-stage, sampling was conducted. 4446 undergraduate students were recruited from 22 participating Chinese medical universities. Perceived stress from uncertainty and social capital were assessed among the students. The Chi-square test and multiple logistic regression models assessed correlates of DSH. Relationship among social capital, uncertainty stress, and DSH were examined by means of Structural Equation Modeling. The prevalence of DSH in the past 12 months among Chinese students was 9.6%. The most common types of physical DSH reported were scratching, cutting, and pinching. Age (χ(2)=26.63, p<0.01), gender (χ(2)=30.24, p<0.01), major field (χ(2)=28.13, p<0.01), and annual household income (χ(2)=11.10, p<0.05) were statistically associated with DSH. Uncertainty stress is a unique correlate of DSH, and shows a stronger association than do three certainty stressors. Social capital is also a strong correlate of DSH, especially cognitive social capital. Moreover, social capital may be indirectly associated with DSH through impacting uncertainty stress. This study was a cross-sectional and thus could not evaluate causal relationships. We recommend that a DSH intervention study should target uncertainty stress management and social capital accumulation. This study provides scientific evidence and theoretical foundation for future DSH interventions, with a view to enhancing the mental health of medical college students.


Transforming growth factor β3 for the prevention of vocal fold scarring.
Vocal fold scarring poses a therapeutic challenge. It causes hoarseness and decreases the quality of life. Transforming growth factor β3 (TGFβ3) is highly expressed in fetal wounds that heal without scarring, and administration of TGFβ3 has been reported to prevent scarring of the skin and the buccal mucosa. Thus TGFβ3 is considered to be a key molecule in scar-free healing. This study aimed to examine the ability of TGFβ3 to prevent vocal fold scarring, with particular attention paid to the distribution of extracellular matrices and functional outcomes. Prospective study using an animal model. Ten beagles were used in this study; 500 μL of TGFβ3 (0.5 μg/mL: 5 beagles) or saline (5 beagles) was injected into the vocal fold lamina propria. Fifteen minutes after injection, vocal folds were injured by stripping off the entire layer of the lamina propria. Six months after surgery, animals were euthanized and the larynges were harvested. Vibratory and histologic examinations were performed. The administration of TGFβ3 suppressed granulation-tissue formation and scarring. TGFβ3-treated vocal folds showed significantly better vibratory properties, resembling normal vocal folds. Histologic analysis revealed favorable restoration of elastin and hyaluronic acid in the lamina propria. The distribution of collagen was well organized, and collagen deposition was less dense in TGFβ3-treated vocal folds compared to sham-treated vocal folds. Administration of TGFβ3 before injury significantly suppressed scar formation and induced favorable restoration of extracellular matrices in the vocal fold lamina propria, resulting in much improved phonatory function.


Semi-automated segmentation methods of SSTR PET for dosimetry prediction in refractory meningioma patients treated by SSTR-targeted peptide receptor radionuclide therapy.
Tumor dosimetry with somatostatin receptor-targeted peptide receptor radionuclide therapy (SSTR-targeted PRRT) by 177Lu-DOTATATE may contribute to improved treatment monitoring of refractory meningioma. Accurate dosimetry requires reliable and reproducible pretherapeutic PET tumor segmentation which is not currently available. This study aims to propose semi-automated segmentation methods to determine metabolic tumor volume with pretherapeutic 68Ga-DOTATOC PET and evaluate SUVmean-derived values as predictive factors for tumor-absorbed dose. Thirty-nine meningioma lesions from twenty patients were analyzed. The ground truth PET and SPECT volumes (VolGT-PET and VolGT-SPECT) were computed from manual segmentations by five experienced nuclear physicians. SUV-related indexes were extracted from VolGT-PET and the semi-automated PET volumes providing the best Dice index with VolGT-PET (Volopt) across several methods: SUV absolute-value (2.3)-threshold, adaptative methods (Jentzen, Otsu, Contrast-based method), advanced gradient-based technique, and multiple relative thresholds (% of tumor SUVmax, hypophysis SUVmean, and meninges SUVpeak) with optimal threshold optimized. Tumor-absorbed doses were obtained from the VolGT-SPECT, corrected for partial volume effect, performed on a 360° whole-body CZT-camera at 24, 96, and 168 h after administration of 177Lu-DOTATATE. Volopt was obtained from 1.7-fold meninges SUVpeak (Dice index 0.85 ± 0.07). SUVmean and total lesion uptake (SUVmeanxlesion volume) showed better correlations with tumor-absorbed doses than SUVmax when determined with the VolGT (respective Pearson correlation coefficients of 0.78, 0.67, and 0.56) or Volopt (0.64, 0.66, and 0.56). Accurate definition of pretherapeutic PET volumes is justified since SUVmean-derived values provide the best tumor-absorbed dose predictions in refractory meningioma patients treated by 177Lu-DOTATATE. This study provides a semi-automated segmentation method of pretherapeutic 68Ga-DOTATOC PET volumes to achieve good reproducibility between physicians. SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET are predictive of tumor-absorbed doses in refractory meningiomas treated by 177Lu-DOTATATE, justifying to accurately define pretherapeutic PET volumes. This study provides a semi-automated segmentation of 68Ga-DOTATOC PET images easily applicable in routine. • SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET images provide the best predictive factors of tumor-absorbed doses related to 177Lu-DOTATATE PRRT in refractory meningioma. • A 1.7-fold meninges SUVpeak segmentation method used to determine metabolic tumor volume on pretherapeutic 68Ga-DOTATOC PET images of refractory meningioma treated by 177Lu-DOTATATE is as efficient as the currently routine manual segmentation method and limits inter- and intra-observer variabilities. • This semi-automated method for segmentation of refractory meningioma is easily applicable to routine practice and transferrable across PET centers.


Micronuclei in peripheral blood and bone marrow cells of mice exposed to 42 GHz electromagnetic millimeter waves.
The genotoxic potential of 42.2 +/- 0.2 GHz electromagnetic millimeter-wave radiation was investigated in adult male BALB/c mice. The radiation was applied to the nasal region of the mice for 30 min/day for 3 consecutive days. The incident power density used was 31.5 +/- 5.0 mW/cm2. The peak specific absorption rate was calculated as 622 +/- 100 W/kg. Groups of mice that were injected with cyclophosphamide (15 mg/kg body weight), a drug used in the treatment of human malignancies, were also included to determine if millimeter-wave radiation exposure had any influence on drug-induced genotoxicity. Concurrent sham-exposed and untreated mice were used as controls. The extent of genotoxicity was assessed from the incidence of micronuclei in polychromatic erythrocytes of peripheral blood and bone marrow cells collected 24 h after treatment. The results indicated that the incidence of micronuclei in 2000 polychromatic erythrocytes was not significantly different among untreated, millimeter wave-exposed, and sham-exposed mice. The group mean incidences were 6.0 +/- 1.6, 5.1 +/- 1.5 and 5.1 +/- 1.3 in peripheral blood and 9.1 +/- 1.1, 9.3 +/- 1.6 and 9.1 +/- 1.6 in bone marrow cells, respectively. Mice that were injected with cyclophosphamide exhibited significantly increased numbers of micronuclei, 14.6 +/- 2.7 in peripheral blood and 21.3 +/- 3.9 in bone marrow cells (P< 0.0001). The drug-induced micronuclei were not significantly different in millimeter wave-exposed and sham-exposed mice; the mean incidences were 14.3 +/- 2.8 and 15.4 +/- 3.0 in peripheral blood and 23.5 +/- 2.3 and 22.1 +/- 2.5 in bone marrow cells, respectively. Thus there was no evidence for the induction of genotoxicity in the peripheral blood and bone marrow cells of mice exposed to electromagnetic millimeter-wave radiation. Also, millimeter-wave radiation exposure did not influence cyclophosphamide-induced micronuclei in either type of cells.


Efficacy of Allisartan Isoproxil in the Treatment of Mild-to-Moderate Essential Hypertension.
Allisartan isoproxil is a selective nonpeptide angiotensin II (AT1) receptor blocker developed by China, this study aimed to assess its clinical efficacy for essential hypertension (EH). Patients with mild-to-moderate EH, selected at 44 sites in China from September 9, 2016, to December 7, 2018, were administered 240 mg allisartan isoproxil daily for 4 weeks. Patients with controlled blood pressure (BP) continued monotherapy for 8 weeks, others were randomly assigned (1:1) to A + D group (allisartan isoproxil 240 mg + indapamide 1.5 mg) or A + C group (allisartan isoproxil + amlodipine besylate 5 mg) for 8 weeks. BP were measured at week 4, 8 and 12. 2,126 patients were included in the analysis. After 12 weeks of treatment, systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased by 19.24 ± 12.02 and 10.63 ± 8.89 mm Hg, respectively, and the overall BP control rate was 78.56%. The sitting blood pressures (SBP/DBP) decreased by 19.12 ± 11.71/10.84 ± 8.73 mm Hg in patients with 12 weeks allisartan isoproxil monotherapy (both P < 0.0001). The BP reductions and control rates were comparable between A + D and A + C groups. 48 patients with monotherapy-controlled BP underwent ambulatory BP monitoring, with a mean decrease in ambulatory BP of 10.04 ± 10.87/5.50 ± 8.07 mm Hg after 12 weeks of treatment, and consistent reductions between day and night. SBP and DBP had trough-to-peak ratios of 64.64% and 62.63% and smoothness indices of 3.82 and 2.92, respectively. An allisartan isoproxil-based antihypertensive regimen can effectively control BP in patients with mild-to-moderate EH. CTR20160138 (Registration and Information Disclosure Platform for China Drug Clinical Studies, http://www.chinadrugtrials.org.cn/index.html).


Picropodophyllin inhibits tumor growth of human nasopharyngeal carcinoma in a mouse model.
Insulin-like growth factor-1 receptor (IGF-1R) is a cell membrane receptor with tyrosine kinase activity and plays important roles in cell transformation, tumor growth, tumor invasion, and metastasis. Picropodophyllin (PPP) is a selective IGF-1R inhibitor and shows promising antitumor effects for several human cancers. However, its antitumor effects in nasopharyngeal carcinoma (NPC) remain unclear. The purpose of this study is to investigate the antitumor activity of PPP in NPC using in vitro cell culture and in vivo animal model. We found that PPP dose-dependently decreased the IGF-induced phosphorylation and activity of IGF-1R and consequently reduced the phosphorylation of Akt, one downstream target of IGF-1R. In addition, PPP inhibited NPC cell proliferation in vitro. The half maximal inhibitory concentration (IC50) of PPP for NPC cell line CNE-2 was ≤1 μM at 24h after treatment and ≤0.5 μM at 48 h after treatment, respectively. Moreover, administration of PPP by intraperitoneal injection significantly suppressed the tumor growth of xenografted NPC in nude mice. Taken together, these results suggest targeting IGF-1R by PPP may represent a new strategy for treatment of NPCs with positive IGF-1R expression.


Workplace empowerment and magnet hospital characteristics: making the link.
To test a theoretical model linking nurses' perceptions of workplace empowerment, magnet hospital characteristics, and job satisfaction in 3 independent studies of nurses in different work settings. Strategies proposed in Kanter's structural empowerment theory have the potential to result in work environments that are described in terms of magnet hospital characteristics. Identifying factors that contribute to work conditions that attract and retain highly qualified committed nurses, such as those found in magnet hospitals, that can be put in place by nursing administrators is extremely important for work redesign to promote professional nursing practice. Secondary analyses of data from 3 studies were conducted--2 of staff nurses and 1 with acute care nurse practitioners working in Ontario, Canada. The Conditions of Work Effectiveness Questionnaire-II, the NWI-R, and measures of job satisfaction were used to measure the major study variables.RESULTS The results of all 3 studies support the hypothesized relationships between structural empowerment and the magnet hospital characteristics of autonomy, control over practice environment, and positive nurse-physician relationships. The combination of access to empowering work conditions and magnet hospital characteristics was significantly predictive of nurses' satisfaction with their jobs. These findings suggest that nursing leaders' efforts to create empowering work environments can influence nurses' ability to practice in a professional manner, ensuring excellent patient care quality and positive organizational outcomes.


Determinants of birthplace among middle-to lower-class women in Indonesia: A study using the Indonesian Demographic and Health Survey.
One of the factors contributing to a high maternal mortality rate is the utilization of non-healthcare facilities as a birthplace for women. This study analyzed determinants affecting birthplace in middle-to lower-class women in Indonesia. This study analyzed the 2017 Indonesian Demographic and Health Survey (IDHS) data. The total national sample size was 49,627 eligible women. Our sample included 11,104 women, aged 15-49, who had delivered babies and were of low-to-middle economic status. The type of survey dataset was individual record dataset. Data were analyzed with chi-square and multivariate logistic regression tests using Stata 16 software. About 64.99% middle to lower class women in Indonesia delivered in healthcare facilities. Women aged 45-49 (OR = 2.103; 95% CI = 1.13-3.93), who graduated from higher schools (OR = 2.885; 95% CI = 1.76-4.73), whose husbands had higher education (OR = 2.826; 95% CI = 1.69-4.74) and were employed (OR = 2.523; 95% CI = 1.23-5.17), who considered access to healthcare facilities was not a problem (OR = 1.528; 95% CI = 1.28-1.82), who had a single child (OR = 2.349; 95% CI = 1.97-2.80), and who lived in urban areas (OR = 2.930; 95% CI = 2.40-3.57) were determinants that significantly correlated with women giving birth in healthcare facilities. This study provides insights for policymakers and healthcare centers in the community to strengthen access to healthcare services and devise health promotion strategies for pregnant mothers. Policy interventions designed for middle- to lower-class women should be implemented to support vulnerable groups.


Restrictive dermopathy: a rare laminopathy.
Restrictive dermopathy (RD) belongs to the laminopathies and mostly shows an autosomal recessive heredity pattern. This rare genetic disorder is lethal for the newborn in the neonatal period. Clinical and pathological findings are distinctive and allow for a specific diagnosis in most cases. Furthermore, polyhydramnios, decreased foetal movement, facial dysmorphisms and arthrogryposis are characteristic of RD. Respiratory insufficiency leads to an early neonatal death. We present the case of an affected infant and a review of the previously reported cases in the literature. The infant showed thin, shiny skin with exfoliating desquamation, a small, round and open mouth, low-set ears, a small pinched nose, joint contractures at all four extremities and distinctive pulmonic atelectasis. It died 3 h and 20 min post-partum. Histologically, the skin showed the typical pattern of an RD with the epidermis covered by an exfoliated, hyperkeratotic horn layer, clearly hypoplastic hair follicles and a considerably reduced dermis thickness, although it had a massive subcutaneous adipose tissue. Electron microscopically, the diagnosis was confirmed. It is important to know about this disease and to distinguish it from others like keratinization malfunctions such as ichtyosis, congenital, developmental and akinesia disturbance, etc., to know the prognosis for the affected newborn and to provide sufficient (genetic) counselling to the families. This disorder is caused by dominant mutations of the LMNA (primary laminopathy) or recessive mutations of the ZMPSTE24 (FACE1) (secondary laminopathy) genes.


Effect of food restriction on the insulin signalling pathway in rat skeletal muscle and adipose tissue.
We tried to elucidate the effects of a brief and severe model of food restriction on insulin sensitivity in female rats, focusing on key proteins involved in the insulin signalling pathway in skeletal muscle and adipose tissue after 5, 10 and 15 days of food restriction. Using euglycemic clamp, we detected that food-restricted rats are significantly less sensitive to insulin action than control rats. However, the time of restriction promotes a progressive increase on insulin sensitivity. The analysis of the insulin signalling pathway showed a tissue-specific regulation of several proteins involved in insulin signalling. In skeletal muscle, insulin receptor substrate 1 and Glut4 are up-regulated at the end of the food restriction period, just the opposite of what we found in adipose tissue. In conclusion, a 50% reduction of food intake modulates insulin sensitivity through a tissue-specific regulation of the insulin signalling pathway in the main target tissues for this hormone.


Improving starch for food and industrial applications.
Progress in understanding starch biosynthesis, and the isolation of many of the genes involved in this process, has enabled the genetic modification of crops in a rational manner to produce novel starches with improved functionality. For example, potato starches have been created that contain unprecedented levels of amylose and phosphate. Amylose-free short-chain amylopectin starches have also been developed; these starches have excellent freeze-thaw stability without the need for chemical modification. These developments highlight the potential to create even more modified starches in the future.


Venular valves and retrograde perfusion.
Forced retrograde perfusion through the venous system with arterial blood can provide adequate oxygen to peripheral tissues at rest through veno-capillary networks which is the basis for surgical restoration of blood flow by distal vein arterialization (DVA). To be successful such surgery requires disruption of valve leaflets in the veins, which can be accomplished easily in the larger vessels. However, the smallest veins (venules) of less than 100 μm in diameter, also possess valves, are distributed widely throughout all tissues and are too fine for any effective surgical interference. Thus venular valves cannot be disrupted or dissected with presently available technology. Nevertheless, clinical observations suggest that retrograde peripheral blood flow is rapidly established after DVA surgery. There is as yet no rational explanation for this phenomenon. In the present study, using Laplace's law, we attempt to elucidate the mechanical properties of venules and their valves. We speculate that the remarkably thin venular walls (and especially those of the smaller vessels which have the thinnest walls), are capable of considerable, rapid distension when subjected to increased hemostatic pressure. The increase in diameter of venules in response to the increased blood pressure renders their valve leaflets incompetent, so that the valves themselves cannot close the vessel lumen. In addition, the thin bicuspid leaflets may also be forced open retrogradely by the increased blood pressure.


An unusual presentation of paediatric Listeria meningitis with selective spinal grey matter involvement and acute demyelinating polyneuropathy.
Paediatric Listeria meningitis is rare, especially in immuno-competent children, but associated with significant mortality and morbidity and frequent complications. We report an unusual case of Listeria meningitis in a previously healthy 35 month-old girl with selective spinal grey matter involvement and demyelination in neurophysiological studies. Despite adequate antibiotic treatment, the case was initially complicated by ventriculitis, hydrocephalus and tonsillar herniation through the foramen magnum, requiring external ventricular drainage and subsequent ventriculoperitoneal shunt insertion. Paucity of movements, hypotonia, areflexia and bladder dysfunction then became evident. Electromyogram and nerve conduction studies showed acute inflammatory demyelinating polyneuropathy and the patient received intravenous immunoglobulin followed by corticosteroids. MRI scans with contrast revealed extensive whole cord selective grey matter signal changes. She required extensive neurorehabilitation, making gradual (but incomplete) recovery. Spinal cord involvement is rare in neuro-listeriosis and there no previous paediatric reports of Listeria-related myelitis or demyelinating polyneuropathy. The mechanism behind these presentations is unclear but an auto-immune response to the infection might be considered.


Photolabeled sites with a tetrodotoxin derivative in the domain III and IV of the electroplax sodium channel.
Forty three percent of the labeled sites, at least, in the electroplax sodium channel with a photoactivable tetrodotoxin derivative were identified by probing protease-digested labeled fragments with several sequence-directed antibodies. They are located in the loop between segments S5 and S6 of domain IV, as well as the region containing transmembrane segment S6 and adjacent extracellular and cytoplasmic sequences in domain III. No photolabeled fragments were detected in the corresponding region of domain I. These results suggest that C-11 of tetrodotoxin where the photoreactive moiety is attached orients to the region between S5 and S6 in domain III and IV. Probable orientation of the tetrodotoxin molecule in sodium channels is considered by taking together with the recent report of the site-directed mutagenesis.


High sensitivity C-reactive protein (CRP) reference intervals in the elderly.
High sensitivity C-reactive protein is a useful marker in clinical practice; however, reference intervals are not available for all age groups. Therefore, the aim of this study was to determine reference intervals for elderly people. The non-parametric reference limits were calculated for the two genders, subdivided into two age classes (50-64 and 65-91 years). In our selected sample population, we did not observe significant gender differences.


Laparoscopic Resection of Residual Retroperitoneal Tumor Mass in Advanced Nonseminomatous Testicular Germ Cell Tumors; a Feasible and Safe Oncological Procedure.
Ten-year oncological experience of the University Medical Center Groningen with conventional laparotomy (C-RRRTM) and laparoscopy (L-RRRTM) is described concerning resection of residual retroperitoneal tumor masses (RRTM) in a large series of patients with advanced nonseminomatous testicular germ cell tumors (NSTGCT). 150 consecutive patients with disseminated NSTGCT required adjunctive surgery after combination chemotherapy. L-RRRTM was scheduled in 89 and C-RRRTM in 61 patients. Median residual tumor diameter was 20 mm in the L-RRRTM versus 42 mm in the C-RRRTM group (p < 0.001). Conversion rate was 15% in the L-RRRTM group. Perioperative complications occurred in 5 patients (6%) in the L-RRRTM and 7 (12%, NS) in the C-RRRTM group. Median duration of L-RRRTM was 156 minutes vs. 221 minutes for C-RRRTM (p < 0.001). 17/89 patients in the L-RRRTM group had postoperative complications versus 18/61 patients in the C-RRRTM group (NS). Median postoperative stay in the L-RRRTM group was 2 vs. 6 days in the C-RRRTM group (p < 0.001). During a median follow-up of 79 months, 27 patients had recurrences: 8 (9%) in the L-RRRTM group and 19 (31%) in the C-RRRTM group (p < 0.001). Laparoscopic resection of RRTM for advanced NSTGCT is feasible and an oncologically safe option in appropriately selected patients.


Efficacy and Tolerance of Intensity Modulated Radiation Therapy for Skull Base Meningioma.
The purpose of this study was to evaluate the efficacy and tolerance of normofractionated stereotactic radiation therapy (RT) and intensity modulated RT with helical tomotherapy for skull base meningioma. Between January 2009 and 2014, 46 patients with skull base meningioma were treated with normofractionated intensity modulated RT in stereotactic conditions (50%) or with helical tomotherapy (50%). Most of the lesions were localized in the cavernous sinus (59%). The mean planning target volume was 47.2 mL (range, 1.1-223 mL). After treatment, 5 lesions exhibited a partial response radiologically and 39 lesions were stable. At the time of treatment, 35 patients were symptomatic with a mean of 2 symptoms per patient. The most frequent symptoms were visual impairment (41%), cranial nerve dysfunction (20%), and headache (16%). The median follow-up time was 42 months (range, 10-76 months). After RT, 71% of patients exhibited an improvement of at least 1 symptom with a median interval of 15.6 months (range, 5.3-30.5 months). The most frequent improved symptoms were cranial nerve deficits (47%), visual impairment (45%), and headache (42%).The clinical response was correlated with the clinical target volume (CTV) margin (P = .06), extended clinical follow-up time (P = .004), and larger planning target volume (P = .05) by univariate analysis. Taking in account correlation factors, in the multivariate analysis, only CTV was a favorable significant factor of clinical improvement (P = .049; hazard ratio: 5 95%; confidence interval, 1.1-28). We observed 3 cases of trigeminal nerve dysfunction at 4.2, 5.7, and 24.6 months; 2 cases of visual disturbance at 10.1 and 24 months; 2 cases of neurocognitive disorders at 12.9 and 35.2 months; and 1 case of stroke at 20.3 months. RT for skull base meningiomas is an effective and safe treatment, leading in most cases to clinical improvement. The addition of a CTV margin to meningioma volume improved the symptoms of patients.


Mass gathering events: a retrospective analysis of the triage categories, type of injury or medical complaint and medical usage rates.
Adequate on-site first aid delivery at mass gatherings (MGs) is one of the cornerstones to ensure safe and healthy MGs. We investigated medical usage rates, frequency of triage categories and type of injury or medical complaint, among attendees at MGs in Belgium. We analysed the Medical Triage and Registration Informatics System database, which includes prospectively collected person-level data regarding individuals visiting on-site posts at MGs in Belgium. MGs attended by >10 000 people and organised ≥5 times between 2009 and 2018 were included. We determined the proportion of patients in each triage category ('first aid' vs 'medical condition' vs 'medical emergency' vs 'no treatment') and each type of injury or medical complaint, and we calculated patient presentation rate (PPR) and transfer to hospital rate (TTHR). Twenty-eight MGs, totalling 194 events, were included involving 148 265 patient visits. 'First aid' was the most common triage category (80%, n=118 514). The need for a nurse/physician ('medical condition'), and for the treatment of life-threatening conditions ('medical emergency') was rare (8.9%, n=13 052, and 0.6%, n=860, of all patient presentations, respectively), but remarkably higher during indoor electronic dance music (EDM) events (17.8% (n=26 391) and 4.0% (n=5930), of all patient presentations, respectively). 'Skin wounds' were the most common injury category (42.4%, n=62 275). 'Respiratory problems', 'neurological problems', 'intoxication', 'heart complaints' and 'gastrointestinal complaints' were more frequent during indoor (electronic) dance, whereas 'burns', 'fracture/contusion' and 'skin wounds' were higher during outdoor music, sports events and city festivals, respectively. PPR (per 10 000 attendees) was highest for outdoor EDM and outdoor music (median 130 (IQR 79) and 129 (IQR 104), respectively). TTHR (per 10 000 attendees) was highest for indoor EDM (median 4.4 (IQR 8.5)). Medical usage rates, proportion of patients in triage and injury or medical complaint categories varied across different MG categories, suggesting opportunities for planning medical coverage at these events.


Eliciting Help Without Pity: The Effect of Changing Media Images on Perceptions of Disability.
This study investigated whether newer, more positive disability charity images can elicit helping behavior without producing pity. One hundred sixty-one university undergraduate students were presented with 35 older (1960-1990) and newer (1991-2010) disability charity images and completed a questionnaire about each image. Results indicate that overall, identification with depicted individuals was low; positive attitudes and perceptions of capabilities were moderate to high. Newer images led to more positive responses, but no significant difference in willingness to help. Eliciting pity through negative depictions of disability appears not to be a necessary precondition for eliciting helping behavior toward people with disabilities.


The Effect of Maternal Vitamin D Supplementation on Vitamin D Status of Exclusively Breastfeeding Mothers and Their Nursing Infants: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
The optimal vitamin D supplementation plan during lactation is unclear. We investigated the effect of maternal vitamin D supplementation on mother-infant dyads' vitamin D status during lactation. All controlled trials that compared vitamin D supplements to placebo or low doses of vitamin D in breastfeeding mothers were included. Pooled effect size and the associated 95% CI for each outcome were estimated using random-effects models. A 1-stage random-effect dose-response model was used to estimate the dose-response relation across different vitamin D dosages and serum 25-hydroxy vitamin D [25(OH)D] concentrations. We identified 19 clinical trials with 27 separate comparison groups (n = 3337 breastfeeding mothers). Maternal vitamin D supplement dosages were associated with circulating 25(OH)D concentrations in breastfeeding women in a nonlinear fashion. Supplementation with 1000 IU of vitamin D/d increased serum 25(OH)D concentrations by 7.8 ng/mL, whereas there was a lower increase in concentrations at vitamin D doses of >2000 IU/d (3.07 and 2.05 ng/mL increases between 2000-3000 and 3000-4000 IU/d, respectively). A linear relation was observed between maternal vitamin D supplementation dosage and the infants' circulating 25(OH)D concentrations. Each additional 1000 IU of maternal vitamin D intake was accompanied by a 2.7 ng/mL increase in serum 25(OH)D concentration in their nursing infants. The subgroup analysis showed that maternal vitamin D supplementation was accompanied by a statistically significant increase in infants' 25(OH)D concentration in the trials with a duration of >20 wk, vitamin D supplementation >1000 IU/d, East Indian participants, maternal BMI <25 kg/m2, and studies with an overall low risk of bias. Long-term maternal supplementation with vitamin D at a high dose (>6000 IU/d) effectively corrected vitamin D deficiency in both mothers and infants. Nevertheless, infants with 25(OH)D concentrations over 20 ng/mL may require a relatively low maternal dose to maintain vitamin D sufficiency.


Serum HER2 extracellular domain levels and HER2 circulating tumor cell status in patients with metastatic breast cancer.
To shed light on the clinical role of HER2 status in serum as extracellular domain (ECD) and corresponding circulating tumor cells (CTCs) in metastatic breast cancer patients. 68 patients were analyzed. Serum HER2 was determined by ADVIA Centaur(®) Serum HER2 test. CellSearch System was performed for CTC quantification. HER2 was overexpressed in 21 primary tumors. In total, 19 patients had ECD >15 ng/ml (the cut-off used), 48 patients had at least one CTC. ECD positivity was associated with CTC number (p = 0.01), HER2-positive CTC (p = 0.01) and the ratio HER2-positive CTC/total CTC (p = 0.02). ECD was not associated with survival. ECD in combination with HER2 CTC status would deserve further investigation in larger series for addressing its putative prognostic relevance.


Multipolar cells in the ventral cochlear nucleus project to the dorsal cochlear nucleus and the inferior colliculus.
When retrograde markers are placed in the dorsal cochlear nucleus two classes of labeled cells are found in the ventral cochlear nucleus. These are multipolar cells and granule cells. The structure and distribution of labeled multipolar cells greatly resemble those seen following injection of retrograde markers into the contralateral inferior colliculus. When one retrograde marker is placed in the dorsal cochlear nucleus and another simultaneously placed into the contralateral inferior colliculus, large numbers of multipolar cells containing both markers are found in the ventral cochlear nucleus. These findings show that all or most cells in the ventral cochlear nucleus that project to the inferior colliculus also send collaterals to the ipsilateral dorsal cochlear nucleus.


Triflavonoids of Ochna calodendron.
Phytochemical investigation of the dichloromethane extract of Ochna calodendron leaves resulted in the isolation and identification of three known isoflavones, irilone, 3'-methoxyirilone and prunetin, one cyanoglucoside, menisdaurin, in addition to two new triflavonoid constituents, namely caloflavans A and B. The structures of the new compounds were established by spectroscopic methods (EI-MS, FAB-MS, 1H NMR, 13C NMR, HMBC and HMQC).


Nonparasitic Splenic Cysts in Children: Outcomes after Sclerotherapy or Surgical Resection as Initial Management.
Management of splenic cysts in children remains undefined. Sclerotherapy is an innovative, less invasive treatment. This study examined the safety and preliminary effectiveness of sclerotherapy for splenic cysts in children compared with those of surgical treatment. A retrospective review of pediatric patients treated for nonparasitic splenic cysts from 2007 to 2021 was performed at a single institution. Posttreatment outcomes for patients who underwent either expectant management, sclerotherapy, or surgery were reviewed. Thirty patients aged between 0 and 18 years met the inclusion criteria. Cysts in 3 of 8 patients who underwent sclerotherapy were either unresolved or recurred. Patients who underwent sclerotherapy and required surgery for residual symptomatic cyst had an initial cyst diameter of >8 cm. Symptoms resolved in 5 of 8 patients who underwent sclerotherapy, with a significantly reduced cyst size compared with that in patients with continued symptoms who underwent sclerotherapy (61.4% vs 7.0%, P = .01). Sclerotherapy is an effective treatment for splenic cysts, particularly those measuring <8 cm. However, surgical excision may be preferable for large cysts.


Ultrastructural aspects of cartilage formation, mineralization, and degeneration during primary antler growth in fallow deer (Dama dama).
Due to their rapid growth, regular replacement and easy accessibility, deer antlers are considered a useful model for the study of cartilage and bone differentiation and mineralization in mammals. The present study describes, for the first time, the cellular and extracellular matrix changes associated with cartilage formation, mineralization and degeneration in primary antlers on the ultrastructural level. Growing primary antlers of 3 to 4 cm length were obtained from six fallow bucks, aged about 10 months. It was shown that the chondroblasts were derived from progenitor cells of the antler perichondrium and differentiated into mature chondrocytes that subsequently underwent hypertrophic changes. Concomitant with cell hypertrophy, formation of a lacunar and a perilacunar extracellular matrix was observed, the latter containing numerous collagenous fibers. Mineralization of the extracellular matrix occurred via matrix vesicles and the formation of apatite crystals at distinct sites of the collagenous fibers. The hypertrophic chondrocytes of the mineralized cartilage then degenerated, a process that was also occasionally observed in more distally located cells surrounded by still unmineralized matrix. No morphological indications of a transdifferentiation of hypertrophic chondrocytes into bone forming cells, i.e., co-occurrence of a degenerating chondrocyte and a viable osteogenic cell in intact lacunae, were found. The cellular and extracellular matrix changes seen in primary antlers resemble those described for secondary antlers. Our results further indicate that the hypertrophic chondrocytes of primary antlers eventually undergo apoptosis, thereby providing further evidence that metaplastic conversion of cartilage into bone does not play a role in antler growth.