Ulva (Chlorophyta, Ulvales) Biodiversity in the North Adriatic Sea (Mediterranean, Italy): Cryptic Species and New Introductions.
Ulva Linnaeus (Ulvophyceae, Ulvales) is a genus of green algae widespread in different aquatic environments. Members of this genus show a very simple morphology and a certain degree of phenotypic plasticity, heavily influenced by environmental conditions, making difficult the delineation of species by morphological features alone. Most studies dealing with Ulva biodiversity in Mediterranean waters have been based only on morphological characters and a modern taxonomic revision of this genus in the Mediterranean is not available. We report here the results of an investigation on the diversity of Ulva in the North Adriatic Sea based on molecular analyses. Collections from three areas, two of which subject to intense shipping traffic, were examined, as well as historical collections of Ulva stored in the Herbarium Patavinum of the University of Padova, Italy. Molecular analyses based on partial sequences of the rbcL and tufA genes revealed the presence of six different species, often with overlapping morphologies: U. californica Wille, U. flexuosa Wulfen, U. rigida C. Agardh, U. compressa Linnaeus, U. pertusa Kjellman, and one probable new taxon. U. californica is a new record for the Mediterranean and U. pertusa is a new record for the Adriatic. Partial sequences obtained from historical collections show that most of the old specimens are referable to U. rigida. No specimens referable to the two alien species were found among the old herbarium specimens. The results indicate that the number of introduced seaweed species and their impact on Mediterranean communities have been underestimated, due to the difficulties in species identification of morphologically simple taxa as Ulva.


Xyloglucan glucosyltransferase in Golgi membranes from Pisum sativum (pea).
Cell membranes from etiolated Pisum sativum (pea) tissues were separated by ultracentrifugation on linear sucrose density gradients and assayed for membrane marker and glycosyltransferase activity. Membrane fractions were shown to incorporate glucose from UDP-D-[14C]glucose into polysaccharides with glycosyl linkages consistent with synthesis of xyloglucan. A combined assay using g.c., radiogas proportional counting and m.s. was employed to determine the identities of 14C-labelled glycosyl residues and the glycosyl linkages between them. In glucan synthase I assays, membrane fractions enriched for Golgi membranes showed 14C incorporation into 4- and 4,6-glucose residues, with minor incorporation into 3-glucose residues. In glucan synthase II assays, all 14C incorporation was into 3- and 3,4-glucose. There was a shift in glycosyl linkage of 14C incorporation from predominantly 4-glucose at low UDP-glucose concentration to predominantly 3- and 3,4-glucose at high UDP-glucose concentrations. Mn2+ stimulated incorporation of radioactivity into 4,6-glucose residues characteristic of xyloglucan polysaccharides. Addition of exogenous UDP-xylose to assay mixtures stimulated incorporation into 4,6-glucose, with a maximum at 15 microM UDP-xylose.


So you wanted to do surgery and they keep talking about research: a discussion for the surgical resident and intern.
Surgical residents and interns frequently misunderstand the relation between surgery and research, and the contribution of surgical research to clinical practice. The problem is that the effects of research must be viewed in the long term. Once the resident can do this, the importance of research to surgery is evident and surgical research can be seen for what it is, the growing surface of surgery. Training to do surgical research has many parallels with clinical training. A core-training period in investigation provides the resident with the right mental approaches to investigation so that training in a specific area of research may be done later. Surgical scientists must be excellent clinicians as well as scientists and so long training periods are required. Four years of clinical practice training and 3 of research training are probably ideal. Shorter periods of research training may be valuable for many surgical residents, particularly those who have had little research experience. Training should be tailored to the trainee's desired role in surgery.


Point-of-Care Testing.
This article provides an overview of the current use of point-of-care testing (POCT) and its utility for patients' self-management of chronic disease states. Pharmacists utilize POCT to provide rapid laboratory diagnostic results as a monitoring tool in the management of their patients and in order to improve medication outcomes. Considerations for the transition to use of POCT in the home to further improve disease management and improve health care cost-effectiveness are discussed. Devices available for home use include those suitable for management of diabetes mellitus, hypertension, congestive heart failure, and anticoagulation. Many of these devices include software capabilities enabling patients to share important health information with health care providers using a computer. Limitations and challenges surrounding implementation of home POCT for patients include reliability of instrumentation, ability to coordinate data collection, necessary training requirements, and cost-effectiveness. Looking forward, the successful integration of POCT into the homes of patients is contingent on a concerted effort made by all members of the health care team.


Impact of hypoalphalipoproteinemia on quality of life in Taiwanese women with central obesity.
To investigate the relationship between health-related quality of life (HRQoL) and different cutoff value of low level of high-density lipoprotein cholesterol (HDL-C) in Taiwanese women with different definition of obesity. Prospective observational study in women with central obesity was conducted in Taipei City Hospital. A total of 572 women were screened at our clinic, and 227 of them with a body mass index ≧27 kg/m2 defined by the Department of Health in Taiwan and weight circumference ≧80 cm were eligible for the study. We defined two groups as group A-low HDL (HDL-C < 40 mg/dL) and group B-high HDL (HDL-C < 50 mg/dL) according to different definition of hypoalphalipoproteinemia in obese women. Significantly reduced HRQoL score was noted in group A-low HDL compared to group A-high HDL (HDL-C ≧ 40 mg/dL), but not between group B-low HDL and group B-high HDL (HDL-C ≧ 50 mg/dL). Positively correlation was noted between HDL-C level and physical domain of HRQoL score. HDL-C contributes independently to physical domain of HRQoL score after controlling for other factors. Decreased leptin and adiponectin level were noted in hypoalphalipoproteinemia groups. Taiwanese obese women with hypoalphalipoproteinemia have adverse impact on HRQoL, especially when the HDL-C level is lower than 40 mg/dL. Both hypoalphalipoproteinemia and hypertension accounted for a great variance to lower scores of physical domain of HRQoL with positively correlation with HDL-C level observed. Decreased leptin and adiponectin were also observed in hypoalphalipoproteinemia group, which implied increased cardiovascular risk. HDL-C level may deem as another indicator for HRQoL in women with central obesity.


[Supply and demand in the meetings between mental health professionals and family members of people with mental disorders].
This paper is a development of a doctoral thesis presented at the Federal University of Espírito Santo. It seeks to analyze the elucidation of needs, development of supply and demand in the provision of care and the relationship between mental health professionals and family members of people with mental disorders. A qualitative research approach was used as the method of choice to achieve the proposed objectives. Semi-structured interviews were conducted with mental health professionals from two psychosocial care centers (CAPS) in the city of Vitória, Espírito Santo, and with family members of frequenters of these institutions. After thematic analysis of content, senses, meanings and values assigned to the needs, supplies and demands present in this relationship were revealed. It highlighted the disparity between supply and demand and the lack of awareness of the needs of family members and their demands related to the routines of mental institutions. Using ethics in the philosophy of Spinoza as a benchmark, the ramifications of this process are discussed in the meetings between mental health professionals and family members of people with mental disorders and the micropolitics of the provision of care in the context of these actors.


PNIPAAm-grafted-collagen as an injectable, in situ gelling, bioactive cell delivery scaffold.
We synthesized two thermoresponsive, bioactive cell scaffolds by decorating the backbone of type I bovine collagen with linear chains of poly(N-isopropylacrylamide) (PNIPAAm), with the ultimate aim of providing facile delivery via injection and support of retinal pigment epithelial (RPE) cells into the back of the eye for the treatment of retinal degenerative diseases. Both scaffolds displayed rapid, subphysiological phase transition temperatures and were capable of noninvasively delivering a liquid suspension of cells that gels in situ forming a cell-loaded scaffold, theoretically isolating treatment to the injection site. RPE cells demonstrated excellent viability when cultured with the scaffolds, and expulsion of cells arising from temperature-induced PNIPAAm chain collapse was overcome by incorporating a room-temperature incubation period prior to scaffold phase transition. These results indicate the potential of using PNIPAAm-grafted-collagen as a vehicle for the delivery of therapeutic cells to the subretinal space.


Genetic regulation of mouse liver metabolite levels.
We profiled and analyzed 283 metabolites representing eight major classes of molecules including Lipids, Carbohydrates, Amino Acids, Peptides, Xenobiotics, Vitamins and Cofactors, Energy Metabolism, and Nucleotides in mouse liver of 104 inbred and recombinant inbred strains. We find that metabolites exhibit a wide range of variation, as has been previously observed with metabolites in blood serum. Using genome-wide association analysis, we mapped 40% of the quantified metabolites to at least one locus in the genome and for 75% of the loci mapped we identified at least one candidate gene by local expression QTL analysis of the transcripts. Moreover, we validated 2 of 3 of the significant loci examined by adenoviral overexpression of the genes in mice. In our GWAS results, we find that at significant loci the peak markers explained on average between 20 and 40% of variation in the metabolites. Moreover, 39% of loci found to be regulating liver metabolites in mice were also found in human GWAS results for serum metabolites, providing support for similarity in genetic regulation of metabolites between mice and human. We also integrated the metabolomic data with transcriptomic and clinical phenotypic data to evaluate the extent of co-variation across various biological scales.


Low Levels of Fecal Calprotectin 3 Months After Surgery Predict Subsequent Endoscopic Postoperative Remission in Crohn's Disease.
In Crohn's disease (CD) few data are available on the usefulness of monitoring fecal calprotectin (FC) in the early postoperative setting. We assessed prospectively the accuracy of FC measured 3 months after surgery to predict the risk of endoscopic postoperative recurrence (POR) within 1 year after resection. In 55 consecutive CD patients who had undergone ileocolonic resection samples were collected 3 months after surgery for measuring serum CRP and FC. Endoscopic POR was assessed by ileocolonoscopy within 6-12 months (median 7 months). Receiver operating characteristic (ROC) curves were generated to assess accuracy of the markers, to determine the best threshold and to calculate sensitivity, specificity, positive and negative predictive values. In contrast with median CRP levels, median FC concentrations measured 3 months after surgery were significantly higher in patients who later experienced endoscopic POR (Rutgeerts ≥ i2) compared with those who stayed in endoscopic remission within the following 6-12 months (205 μg/g IQR [106-721] vs. 103 μg/g IQR [60-219], p = 0.008). Area under the ROC curve for FC was 0.71. The best cutoff value of FC to identify patients in subsequent endoscopic remission 3 months after surgery was 65 μg/g (96% sensitivity, 31% specificity, 50% positive and 91% negative predictive values). In multivariate analysis, FC < 65 µg/g at 3 months was the only factor associated with subsequent endoscopic remission. FC measured 3 months after surgery below 65 μg/g is an accurate marker to identify CD patients who will later stay in endoscopic remission within 1 year after resection.


The web-surfing bariatic patient: the role of the internet in the decision-making process.
Health-related information on the Internet is constantly increasing, but its quality and accountability are difficult to assess. Patients browse the Net to get more information, but the impact of the Internet on their decisions about surgical techniques, referral centers, or surgeon choice are still not clear. This study aimed to describe the role of the Internet in the decision-making process of obese patients seeking bariatric surgery. Two hundred and twelve candidates for bariatric surgery were asked to answer a questionnaire evaluating their access to the Internet, the usefulness and trustworthiness of Internet-retrieved information, the verification of the information, and the role of the information in the decision-making process. Two hundred and twelve patients answered the questionnaire. Of these, 95.1% had access to the Internet and 77.8% reported having researched about bariatric surgery. Their main interests were the surgical techniques (81.4%) and other patients' experiences (72.3%). The favorite Web sites were those affiliated to public hospitals or edited by other patients. The accountability of the e-information was mainly evaluated by discussion with the general practitioner (GP) (83.0%) or family members and friends (46.8%). One patient in four decided to undergo bariatric surgery mainly based on e-information, while discussion about treatment options with the GP and the hospital reputation were taken into account in 77.8 and 51.7% of cases, respectively. Most patients seeking bariatric surgery search for health information online. E-information seems to have an important role in the decision-making process of patients who are candidates for bariatric surgery.


Psychiatric examinations on handcuffed convicts in Brazil: ethical concerns.
Psychiatric examinations in official institutions of the Brazilian government include examinations of individual convicts--some of whom are highly dangerous--carried out by court decision. These individuals are taken handcuffed under police escort from penitentiaries to the examination site. In most Brazilian states, medical examiners or experts adopt the basic procedure of asking the police officers to remove the handcuffs from the convict for the examination to be carried out. This article analyzes, from the bioethical standpoint, the behavior of 49 forensic psychiatrists in eight Brazilian states in relation to procedures adopted as protection measures against any possible danger posed by their examinees. In the context of a developing country, where sophisticated protection means are not available, the practice of keeping convicts handcuffed during such examinations is compared to other measures and more advisable alternatives are discussed from the ethical standpoint. Considering the dilemma between showing minimum respect for the autonomy of examinees and ensuring the security of examiners, the need to adopt equitable procedures based on the recognition of the different needs of examiners and examinees is addressed.


Sacubitril/valsartan in cardiovascular disease: evidence to date and place in therapy.
Cardiovascular (CV) disease is a major cause of morbidity and mortality in the developing and the developed world. Mortality from CV disease had plateaued in the recent years raising concerning alarms about the sustained efficacy of available preventive and treatment options. Heart failure (HF) is among the major contributors to the CV-related health care burden, a persisting concern despite the use of clinically proven guideline-directed therapies. A requirement for more efficient medical therapies coupled with recent advances in bio-innovation led to the creation of sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), which demonstrated substantial CV benefit when compared with the standard of care, enalapril, in patients with HF and reduced ejection fraction. Further investigations of this novel combination ARNI at the tissue level shed light into the anti-remodeling and cardioprotective effects of sacubitril/valsartan, while clinical studies in the phenotypes of HF with preserved ejection fraction, hypertension and subsets, coronary outcomes, postmyocardial infarction, and renal disease suggested that this combination could be beneficial across a wide spectrum of CV disease. Sacubitril/valsartan is a much-needed therapeutic advance in the avenue of CV disease.


Differentiation of human neural stem cells into neural networks on graphene nanogrids.
Graphene nanogrids (crossed graphene nanoribbons synthesized by the oxidative unzipping of multi-walled carbon nanotubes) on a SiO2 matrix containing TiO2 nanoparticles (NPs) were applied as a photocatalytic stimulator in the accelerated differentiation of human neural stem cells (hNSCs) into two-dimensional neural networks. The hydrophilic graphene nanogrids exhibited patterned proliferations of hNSCs (consistent with patterns of the nanogrids), in contrast with the usual random growths occurring on quartz substrates. The number of cell nuclei differentiated on reduced graphene oxide nanoribbon (rGONR) grid/TiO2 NPs/SiO2 increased ∼5.9 and 26.8 fold compared to the number of cells on quartz substrates, after three weeks of differentiation, in the dark and under photo stimulation, respectively. The stimulation, originated by the injection of photoexcited electrons from the TiO2 NPs into the cells on the nanogrids, also resulted in changing the number of differentiated neurons and glial cells in the patterned neural network by factors of ∼1.8 and 0.17, respectively. A higher differentiation on the rGONR grids than rGO sheets was assigned to the physical stress induced by the surface topographic features of the nanogrids. The current-voltage properties of the neural networks differentiated on the electrically disconnected rGONR grids demonstrated effective cell-to-cell and cell-to-rGONR couplings after three weeks of the stimulated differentiation.


The skin in mastocytosis.
The most frequent site of organ involvement in patients with any form of mastocytosis is the skin. Cutaneous expressions include urticaria pigmentosa, mastocytoma, diffuse and erythrodermic cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. The cutaneous lesions tend to appear early in life. Although urticaria pigmentosa has been reported in 12 pairs of twins and one set of triplets, the majority of affected individuals have no familial association. Most patients with systemic mastocytosis have skin lesions; however, an occasional patient will have systemic disease with no other skin features than flushing. In lesional cutaneous sites and in non-lesional skin, there is an increase in the number of mast cells. Electron microscopy shows quantitative differences between lesional skin mast cells from patients with and without systemic disease. The mast cells from adult patients with systemic disease have a larger mean cytoplasmic area, nuclear size, and granule diameter. The granules contain predominantly grating/lattice structures. The cutaneous mast cells contain tryptase and chymase. They retain their functional reactivities to relevant secretory stimuli, such as C3a, morphine sulfate, and calcium ionophore A23187. Lesional skin contains histamine, leukotriene B4, prostaglandin D2, 5-hydroxyeicosatetraenoic acid, platelet-activating factor, and heparin. Treatment of the cutaneous manifestations includes the use of H1 and H2 antihistamines, oral disodium cromoglycate, psoralens plus ultraviolet A photochemotherapy, and potent topical corticosteroid preparations.


A Framework for Competencies for the Use of Mobile Technologies in Psychiatry and Medicine: Scoping Review.
To ensure quality care, clinicians need skills, knowledge, and attitudes related to technology that can be measured. This paper sought out competencies for mobile technologies and/or an approach to define them. A scoping review was conducted to answer the following research question, "What skills are needed for clinicians and trainees to provide quality care via mHealth, have they been published, and how can they be made measurable and reproducible to teach and assess them?" The review was conducted in accordance with the 6-stage scoping review process starting with a keyword search in PubMed/Medical Literature Analysis and Retrieval System Online, APA PsycNET, Cochrane, EMBASE, PsycINFO, Web of Science, and Scopus. The literature search focused on keywords in 4 concept areas: (1) competencies, (2) mobile technologies, (3) telemedicine mode, and (4) health. Moreover, 2 authors independently, in parallel, screened the search results for potentially relevant studies based on titles and abstracts. The authors reviewed the full-text articles for final inclusion based on inclusion/exclusion criteria. Inclusion criteria were keywords used from concept area 1 (competencies) and 2 (mobile technologies) and either 3 (telemedicine mode) or 4 (health). Exclusion criteria included, but were not limited to, keywords used from a concept area in isolation, discussion of skills abstractly, outline or listing of what clinicians need without detail, and listing immeasurable behaviors. From a total of 1232 results, the authors found 78 papers eligible for a full-text review and found 14 papers directly relevant to the 4 key concepts. Although few studies specifically discussed skills, the majority were clinical studies, and the literature included no lists of measurable behaviors or competency sets for mobile technology. Therefore, a framework for mobile technology competencies was built according to the review, expert consensus, and recommendations of the Institute of Medicine's Health Professions Education Summit and Accreditation Council of Graduate Medical Education framework. This framework borrows from existing competency framework domains in telepsychiatry and social media (patient care, medical knowledge, practice-based learning and improvement, systems-based practice, professionalism, and interpersonal skills and communication) and added domains of mHealth clinical decision support, device/technology assessment/selection, and information flow management across an electronic health record platform. mHealth Asynchronous components require additional traditional learning, teaching, supervisory and evaluation practices. Interactive curricula with case-, problem-, and system-based teaching may help faculty focus on decision making and shape skills and attitudes to complement clinical exposure. Research is needed on how to customize implementation and evaluation of mHealth competencies and to ensure skill development is linked to the quality of care. This will require the management of organizational change with technology and the creation of a positive electronic culture in a complex policy and regulatory environment.


Supporting Analysis of Dimensionality Reduction Results with Contrastive Learning.
Dimensionality reduction (DR) is frequently used for analyzing and visualizing high-dimensional data as it provides a good first glance of the data. However, to interpret the DR result for gaining useful insights from the data, it would take additional analysis effort such as identifying clusters and understanding their characteristics. While there are many automatic methods (e.g., density-based clustering methods) to identify clusters, effective methods for understanding a cluster's characteristics are still lacking. A cluster can be mostly characterized by its distribution of feature values. Reviewing the original feature values is not a straightforward task when the number of features is large. To address this challenge, we present a visual analytics method that effectively highlights the essential features of a cluster in a DR result. To extract the essential features, we introduce an enhanced usage of contrastive principal component analysis (cPCA). Our method, called ccPCA (contrasting clusters in PCA), can calculate each feature's relative contribution to the contrast between one cluster and other clusters. With ccPCA, we have created an interactive system including a scalable visualization of clusters' feature contributions. We demonstrate the effectiveness of our method and system with case studies using several publicly available datasets.


Responses to exercise in the heat related to measures of hypothalamic serotonergic and dopaminergic function.
We have studied 12 recreationally active men to measure their responses to exercise in the heat and relate these to measures of hypothalamic function explored with a buspirone [5-hydroxytryptamine 1A (5-HT(1A)) agonist, dopaminergic D(2) antagonist] neuroendocrine challenge, with and without pretreatment with pindolol (5-HT(1A) antagonist). Pindolol treatment allowed the serotonergic and non-serotonergic components of prolactin release to be distinguished. Subjects exercised at 73 (5)% maximal rate of oxygen uptake (VO(2max)) until volitional fatigue at 35 degrees C (relative humidity, 30%). On another two occasions they underwent a buspirone challenge [0.5 mg (kg body mass)(-1)], once with, and once without, pindolol [0.5 mg (kg body mass)(-1)] pretreatment and the circulating plasma concentrations of prolactin were measured for the next 2.5 h. Rectal temperature increased throughout exercise, whilst mean skin temperature remained constant. There was a wide inter-subject variation in prolactin response to the neuroendocrine challenges. The proportion of the prolactin response to buspirone attributable to a non-serotonergic component (most likely dopaminergic) correlated both with exercise duration (r=0.657, P=0.028), rectal temperature at fatigue (r=0.623, P=0.041) and the rate of temperature rise (r=-0.669, P=0.024). Our results suggest that high activity of the dopaminergic pathways in the hypothalamus is a predictor of exercise tolerance in the heat.


Noninvasive visualization of the left main coronary artery by cross-sectional echocardiography.
Real time cross-sectional echocardiographic studies of the left main coronary artery (LMCA) were performed in 15 normal patients, 15 patients with angiographically proven coronary artery disease but normal left main coronary segments, three patients with greater than 75% obstruction of the left main coronary artery, and one patient with a larger aneurysm of the left main coronary artery. In normal subjects the LMCA evaginates from in inferolateral wall of the aorta. The artery appears as two dominant parallel linear echoes separated by a clear space representing the lumen of the vessel. The LMCA courses beneath the right ventricular outflow tract and can generally be followed to its expected point of bifurcation. Confirmation that this structure was in fact the LMCA was obtained by injection of cardiogreen dye directly into the LMCA in two cases and by visualization of dye in this structure following aortic flush in one case. In the three cases with obstructive lesions of the LMCA, there was an area of inward bending of the parallel vessel wall echoes resulting in varying degrees of narrowing of the arterial lumen. In the case with the aneurysmal dilatation of the LMCA, an echo-free circular bulge in the distal portion of the LMCA was recorded. This study demonstrates the fesibility of recording the left main coronary artery using the cross-sectional echocardiographic technique.


Dynamic 2D and 3D mapping of hyperpolarized pyruvate to lactate conversion in vivo with efficient multi-echo balanced steady-state free precession at 3 T.
The aim of this study was to acquire the transient MRI signal of hyperpolarized tracers and their metabolites efficiently, for which specialized imaging sequences are required. In this work, a multi-echo balanced steady-state free precession (me-bSSFP) sequence with Iterative Decomposition with Echo Asymmetry and Least squares estimation (IDEAL) reconstruction was implemented on a clinical 3 T positron-emission tomography/MRI system for fast 2D and 3D metabolic imaging. Simulations were conducted to obtain signal-efficient sequence protocols for the metabolic imaging of hyperpolarized biomolecules. The sequence was applied in vitro and in vivo for probing the enzymatic exchange of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate. Chemical shift resolution was achieved using a least-square, iterative chemical species separation algorithm in the reconstruction. In vitro, metabolic conversion rate measurements from me-bSSFP were compared with NMR spectroscopy and free induction decay-chemical shift imaging (FID-CSI). In vivo, a rat MAT-B-III tumor model was imaged with me-bSSFP and FID-CSI. 2D metabolite maps of [1-13 C]pyruvate and [1-13 C]lactate acquired with me-bSSFP showed the same spatial distributions as FID-CSI. The pyruvate-lactate conversion kinetics measured with me-bSSFP and NMR corresponded well. Dynamic 2D metabolite mapping with me-bSSFP enabled the acquisition of up to 420 time frames (scan time: 180-350 ms/frame) before the hyperpolarized [1-13 C]pyruvate was relaxed below noise level. 3D metabolite mapping with a large field of view (180 × 180 × 48 mm3 ) and high spatial resolution (5.6 × 5.6 × 2 mm3 ) was conducted with me-bSSFP in a scan time of 8.2 seconds. It was concluded that Me-bSSFP improves the spatial and temporal resolution for metabolic imaging of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate compared with either of the FID-CSI or EPSI methods reported at 3 T, providing new possibilities for clinical and preclinical applications.


Radiography of posttraumatic syringomyelia.
Posttraumatic syringomyelia was studied in 15 patients. Gas myelography in 12 patients showed a definite spinal cord swelling in 10 and a probable cord enlargement in two. Plain spinal computed tomography (CT) in four patients demonstrated intramedullary radiolucent zones in three. After intrathecal injection of metrizamide in 10 patients, cysts were opacified in eight. Postoperative CT in two patients demonstrated collapse of the cyst in one. Gas myelography shows the extent and site of maximal dilatation of the cyst where a shunt can be placed. CT is less invasive and provides a definitive diagnosis.


Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model.
To characterize a long-term elevated intraocular pressure (IOP) glaucoma model in the rat with respect to electroretinographic (ERG) changes and the pattern and mechanism of retinal ganglion cell (RGC) death. METHODS; An approximate doubling of IOP was induced in one eye (G) of female Wistar rats (150-180 g) by cautery of 3 episcleral/limbal veins. At intervals over 3 to 4 months, measurements of IOP and ERG changes (contact-lens electrode) were made in both the G and contralateral normal (N) eyes. At the end of 3 to 4 months of elevated IOP, RGCs were fluorescently labeled with Fluorogold (retrogradely from the superior colliculus), or retinas were labeled by intravitreal injection of a mitochondrial potential indicator dye and stained for apoptotic nuclei with a DNA dye. Flatmounts of fixed, dye-labeled retinas were examined by epifluorescence, confocal, or interference contrast microscopy. Elevated IOP was consistently maintained for up to 4 months in G eyes, but ERG a- and b-waves showed a statistically significant decline, of 30% to 40% in amplitude, after 3 months. Loss of RGCs in G retinas was primarily focal with no statistically significant loss demonstrable outside of the focal areas when assessed by an area sampling method for counting RGCs, which totaled 2% to 3% of the entire retinal area. Mitochondrial membrane potential of cells in the RGC layer was reduced by 17.5% (P: < 0.05) in regions surrounding areas of focal loss compared with comparable locations in control N eyes. After 3.5 months' elevated IOP the G retinas showed cell nuclei at various stages of apoptosis, from initial DNA condensation to fragmentation. The three-vein episcleral/limbal vein occlusion model for inducing glaucomatous pathology in the rat eye gives a consistent long-term elevation of IOP. After 3 to 4 months of approximately 100% increased IOP, the ERG responses begin to decline, there is a variable focal loss of RGCs, and some of the remaining RGCs show characteristics of stress and apoptosis. These changes seem consistent with retinal damage in human glaucoma (focal field defects), and this rat model appears to mimic some features of primary open-angle glaucoma.


Hypoxia-induced Fos expression in neurons projecting to the pressor region in the rostral ventrolateral medulla.
Previous studies in anaesthetized animals have shown that the hypoxia-induced increase in sympathetic vasomotor activity is largely dependent on synaptic excitation of sympathoexcitatory pressor neurons in the rostral part of the ventrolateral medulla. The primary aim of this study was to determine, in conscious rabbits, the distribution of neurons within the brain that have properties characteristic of interneurons conveying excitatory inputs to the rostral ventrolateral medullary pressor region in response to systemic hypoxia. In a preliminary operation, a retrogradely-transported tracer, fluorescent-labelled microspheres, was injected into the physiologically-identified pressor region in the rostral ventrolateral medulla. After a waiting period of one to two weeks, the conscious rabbits were subjected to moderate hypoxia (induced by breathing 10% O2 in N2) for a period of 60 min. Control groups of animals were exposed to room air or to mild hypoxia (12% O2 in N2). Moderate hypoxia resulted in a modest hypertension of approximately 15 mmHg, and in the expression of Fos (a marker of neuronal activation) in many neurons in the nucleus tractus solitarius, the rostral, intermediate and caudal parts of the ventrolateral medulla, the Kölliker-Fuse nucleus, locus coeruleus, subcoeruleus and A5 area in the pons as well as in several midbrain and forebrain regions, including the periaqueductal grey in the midbrain and the paraventricular, supraoptic and arcuate nuclei in the hypothalamus. Fos expression was also observed in these regions in rabbits subjected to mild hypoxia or normoxia, but it was much reduced compared to rabbits subjected to moderate hypoxia. Approximately half of the neurons in the ventrolateral medulla, 27% of neurons in the nucleus tractus solitarius, and 49-81% of neurons in the locus coeruleus, sub-coeruleus and A5 area that expressed Fos following moderate hypoxia were also immunoreactive for tyrosine hydroxylase, and were therefore catecholamine cells. Approximately half of the neurons in the nucleus tractus solitarius and two-thirds of neurons in the Kölliker-Fuse nucleus that expressed Fos following moderate hypoxia were retrogradely labelled from the rostral ventrolateral medullary pressor region. Similarly, approximately one quarter of Fos-positive cells in the caudal and intermediate ventrolateral medulla were retrogradely labelled, but very few Fos-positive/retrogradely-labelled cells were found in other pontomedullary or suprapontine brain regions. The results indicate that systemic hypoxia results in activation of neurons in several discrete nuclei in the brainstem and forebrain, including neurons in all the major pontomedullary catecholamine cell groups. However, neurons that are activated by systemic hypoxia and that also project to the rostral ventrolateral medullary pressor region are virtually confined to the lower brainstem, primarily in the nucleus tractus solitarius and Kölliker-Fuse nucleus and to a lesser extent the caudal/intermediate ventrolateral medulla. In a previous study from our laboratory, we determined the distribution of neurons in the brainstem that are activated by hypertension and that also project to the rostral ventrolateral medullary pressor region. [Polson et al. (1995) Neuroscience 67, 107-123]. Comparison of the present results with those from this previous study indicates that the hypoxia-activated neurons in the nucleus tractus solitarius and Kölliker-Fuse nucleus that project to the rostral ventrolateral medulla are likely to be interneurons conveying excitatory chemoreceptor signals, while those in the caudal/intermediate ventrolateral medulla are likely to be mainly interneurons conveying inhibitory baroreceptor signals, activated by the rise in arterial blood pressure associated with the hypoxia-induced hypertension.


Label-free optical imaging of membrane patches for atomic force microscopy.
In atomic force microscopy (AFM), finding sparsely distributed regions of interest can be difficult and time-consuming. Typically, the tip is scanned until the desired object is located. This process can mechanically or chemically degrade the tip, as well as damage fragile biological samples. Protein assemblies can be detected using the back-scattered light from a focused laser beam. We previously used back-scattered light from a pair of laser foci to stabilize an AFM. In the present work, we integrate these techniques to optically image patches of purple membranes prior to AFM investigation. These rapidly acquired optical images were aligned to the subsequent AFM images to ~40 nm, since the tip position was aligned to the optical axis of the imaging laser. Thus, this label-free imaging efficiently locates sparsely distributed protein assemblies for subsequent AFM study while simultaneously minimizing degradation of the tip and the sample.


The nonstructural glycoprotein of rotavirus affects intracellular calcium levels.
Rotavirus infection of monkey kidney cells has been reported to result in a significant increase in the concentration of intracellular calcium. This increase in intracellular calcium was associated with viral protein synthesis and cytopathic effects in infected cells. We tested the effect of individual rotavirus proteins on intracellular calcium concentrations in insect Spodoptera frugiperda (Sf9) cells. Insect cells were infected with wild-type baculovirus or baculovirus recombinants that contained an individual rotavirus gene. The cells were harvested at different times postinfection, and the intracellular calcium concentration was measured by using fura-2 as a fluorescent calcium indicator. We found that the concentration of intracellular calcium was increased nearly fivefold in infected Sf9 cells that expressed the nonstructural glycoprotein (NSP4) of group A rotavirus, and this increase in intracellular calcium concentration coincided with NSP4 expression. A similar result was observed in insect cells expressing NSP4 from a group B rotavirus, suggesting the conservation of this function among rotavirus groups. Expression of the other 10 rotavirus proteins or of wild-type baculovirus proteins in Sf9 cells did not significantly increase intracellular calcium levels. These results suggest that the nonstructural glycoprotein NSP4 is responsible for the increase in cytosolic calcium observed in rotavirus-infected cells.


Prevalence and correlates of frailty in older hypertensive outpatients according to different tools: the HYPER-FRAIL pilot study.
To date, few studies have investigated frailty in hypertensive individuals. This study aimed at identifying the prevalence of frailty in a sample of hypertensive older outpatients using six different identification tools. Clinical correlates of frailty and agreement between different frailty definitions were also investigated. The HYPER-FRAIL pilot study recruited hypertensive patients aged at least 75 years from two geriatric outpatient clinics of Careggi Hospital, Florence, Italy. Four frailty scales [Fried Frailty Phenotype, Frailty Index, Clinical Frailty Scale (CFS), Frailty Postal Score] and two physical performance tests [Short Physical Performance Battery (SPPB) and usual gait speed] were applied. The Cohen's kappa coefficient was calculated to assess agreement between measures. Multiple logistic regression was used to identify clinical features independently associated with frailty. Among 121 participants (mean age 81, 60% women), frailty prevalence varied between 33 and 50% according to the tool used. Moderate agreement was observed between Fried Frailty Phenotype, Frailty Index and SPPB, and between Frailty Index and CFS. Agreement was minimal or weak between the remaining measures (K < 0.60). Use of walking aids and depressive symptoms were independently associated with frailty, regardless of the definition used. Frailty correlates also included dementia, disability and comorbidity burden, but not office and 24-h blood pressure values. Frailty is highly prevalent among older hypertensive outpatients, but agreement between different frailty tools was moderate-to-weak. Longitudinal studies are needed to assess the prognostic role of different frailty tools and their clinical utility in the choice of antihypertensive treatment.


A microcomputer-based system for coronary artery Doppler studies.
Intra-vascular Doppler catheters are becoming popular as research tools for studies of the coronary circulation. Velocity estimates can be obtained from Doppler signals sampled with such catheters, and used to calculate various derived parameters which can then be correlated with the haemodynamic situation under investigation. This note discusses the requirements necessary for a system to perform the acquisition of the high-frequency Doppler signals obtained from catheter-tipped transducers, and a system developed to capture, process and store Doppler, ECG and pressure signals is described. Software used to calculate parameters from the stored waveforms is discussed and examples of the system outputs presented.


The role of uncertainty in attentional and choice exploration.
The exploitation-exploration (EE) trade-off describes how, when making a decision, an organism must often choose between a safe alternative with a known pay-off, and one or more riskier alternatives with uncertain pay-offs. Recently, the concept of the EE trade-off has been extended to the examination of how organisms distribute limited attentional resources between several stimuli. This work suggests that when the rules governing the environment are certain, participants learn to "exploit" by attending preferentially to cues that provide the most information about upcoming events. However, when the rules are uncertain, people "explore" by increasing their attention to all cues that may provide information to help in predicting upcoming events. In the current study, we examine how uncertainty affects the EE trade-off in attention using a contextual two-armed bandit task, where participants explore with both their attention and their choice behavior. We find evidence for an influence of uncertainty on the EE trade-off in both choice and attention. These findings provide support for the idea of an EE trade-off in attention, and that uncertainty is a primary motivator for exploration in both choice and attentional allocation.


Protective effects of alisol B 23-acetate from edible botanical Rhizoma alismatis against carbon tetrachloride-induced hepatotoxicity in mice.
Carbon tetrachloride (CCl4)-induced hepatotoxicity is a common syndrome with simultaneous severe hepatocyte death and acute cholestasis. The purpose of the present study is to investigate the hepatoprotective effect of alisol B 23-acetate (AB23A), a natural triterpenoid from edible botanical Rhizoma alismatis, on acute hepatotoxicity induced by CCl4 in mice, and further to elucidate the involvement of farnesoid X receptor (FXR), signal transducers and activators of transcription 3 (STAT3) in the hepatoprotective effect. H&E staining, BrdU immunohistochemistry and TUNEL assay were used to identify the amelioration of histopathological changes, hepatocyte proliferation and apoptosis. Real-time PCR and western blot assay were used to elucidate the mechanisms underlying AB23A hepatoprotection. The results indicated that AB23A treatment in a dose-dependent manner resulted in protection against hepatotoxicity induced by CCl4via FXR activation. Through FXR activation, AB23A promoted hepatocyte proliferation via an induction in hepatic levels of FoxM1b, Cyclin D1 and Cyclin B1. AB23A also reduced hepatic bile acids through a decrease in hepatic uptake transporter Ntcp, bile acid synthetic enzymes Cyp7a1, Cyp8b1, and an increase in efflux transporter Bsep, Mrp2 expression. In addition, AB23A induced the expression of STAT3 phosphorylation, and STAT3 target genes Bcl-xl and SOCS3, resulting in decreased hepatocyte apoptosis. In conclusion, AB23A produces a protective effect against CCl4-induced hepatotoxicity, due to FXR and STAT3-mediated gene regulation.


Epidemiology and Phylogenetic Analysis of Viral Respiratory Infections in Vietnam.
Acute respiratory infections (ARIs) impose a major public health burden on fragile healthcare systems of developing Southeast Asian countries such as Vietnam. The epidemiology, genetic diversity and transmission patterns of respiratory viral pathogens that circulate in this region are not well characterized. We used RT-PCR to screen for 14 common respiratory viruses in nasal/throat samples from 4326 ARI patients from 5 sites in Vietnam during 2012-2016. 64% of patients tested positive for viruses; 14% tested positive multiple co-infecting viruses. The most frequently detected viruses were Respiratory syncytial virus (RSV, 23%), Human Rhinovirus (HRV, 13%), Influenza A virus (IAV, 11%) and Human Bocavirus (HBoV, 7%). RSV infections peaked in July to October, were relatively more common in children <1 year and in the northernmost hospital. IAV infections peaked in December to February and were relatively more common in patients >5 years in the central region. Coinfection with IAV or RSV was associated with increased disease severity compared with patients only infected with HBoV or HRV. Over a hundred genomes belonging to 13 families and 24 genera were obtained via metagenomic sequencing, including novel viruses and viruses less commonly associated with ARIs. Phylogenetic and phylogeographic analyses further indicated that neighboring countries were the most likely source of many virus lineages causing ARIs in Vietnam and estimated the period that specific lineages have been circulating. Our study illustrates the value of applying the state-of-the-art virus diagnostic methods (multiplex RT-PCR and metagenomic sequencing) and phylodynamic analyses at a national level to generate an integrated picture of viral ARI epidemiology.


Effect of calcium hydroxide and double and triple antibiotic pastes on the bond strength of epoxy resin-based sealer to root canal dentin.
The aim of this study was to evaluate the effects of calcium hydroxide (CH) and triple (TAP) and double (DAP) antibiotic pastes on the bond strength of an epoxy resin-based sealer (AH Plus Jet; Dentsply DeTrey, Konstanz, Germany) to the root canal dentin. Sixty-four single-rooted human mandibular premolars were decoronated and prepared using the rotary system to size 40. The specimens were randomly divided into a control group (without intracanal dressing) and 3 experimental groups that received an intracanal dressing with either CH, DAP, or TAP (n = 16). The intracanal dressing was removed by rinsing with 10 mL 17% EDTA followed by 10 mL 2.5% sodium hypochlorite. The root canals were then obturated with gutta-percha and AH Plus Jet sealer. A push-out test was used to measure the bond strength between the root canal dentin and the sealer. The data were analyzed using 2-way analysis of variance and Tukey post hoc tests to detect the effect of the independent variables (intracanal medicaments and root canal thirds) and their interactions on the push-out bond strength of the root canal filling material to the root dentin (P = .05). The push-out bond strength values were significantly affected by the intracanal medicaments (P < .001) but not by the root canal thirds (P > .05). In the middle and apical third, the bond strength of the TAP group was higher than those of the CH and DAP groups (P < .05). The DAP and CH did not affect the bond strength of the epoxy resin-based sealer. Additionally, the TAP improved the bond strength of the epoxy resin-based sealer in the middle and apical thirds.


Outbreak of tuberculosis associated with a church.
Investigation of an outbreak of tuberculosis (TB) in a West Midlands health district in 1999 revealed spread in an extended family network and to church contacts. Within the family four cases of smear positive TB, four cases of smear negative infection, and 14 cases requiring chemoprophylaxis were identified. One of the infectious cases visited a local church on two occasions, which resulted in a further 16 cases of infection including one case of tuberculous meningitis. DNA fingerprinting of isolates from five culture positive cases indicated that the same strain of Mycobacterium tuberculosis was responsible. This outbreak is a reminder that while outbreaks of TB usually arise within households or family networks, where close contact over extended periods provides more opportunity for exposure, community outbreaks of TB can occur after only causal contact.


[Effect of carbon dioxide on free radical processes as affected by artificial hypobiosis in rats].
High CO2 concentrations in the inspired air have been studied for their effect on the free-radical oxidation of lipids in the lipids in the blood, its serum and mitochondria of the rat liver under artificial hypobiosis. Kinetics of free-radical oxidation of lipids was estimated from the changes in chemiluminescence parameters as well as the content of products which react with thiobarbituric acid. It is found that in animals in the state of artificial hypobiosis the intensity of free-radical oxidation of lipids was rather less as compared with animals which did not fall into hypobiosis because of the exclusion of CO2 from the inspired air. The data obtained permit concluding that the increase of CO2 concentration in the inspired air prevents from the development of the oxidative stress. It is evident that the increase of CO2 in the inspired air occurs before the formation of the adaptational mechanisms, directed to the preventing of lesion of membrane lipids under artificial hypobiosis.


Interaction of FKBP5 gene variants and adverse life events in predicting depression onset: results from a 10-year prospective community study.
The binding protein FKBP5 is an important modulator of the function of the glucocorticoid receptor, the main receptor of the stress hormone system. This turns the FKBP5 gene into a key candidate for gene-environment interactions, which are considered critical for pathogenesis of stress-related disorders. The authors explored gene-environment interactions between FKBP5 gene variants and adverse life events in predicting the first occurrence of a major depressive episode. The analyses were based on 884 Caucasians in a 10-year prospective community study. At baseline, they were 14-24 years old and did not fulfill criteria for a major depressive episode. The DSM-IV-based Munich Composite International Diagnostic Interview was used to assess adverse life events preceding baseline and major depressive episodes during follow-up. On the basis of previous findings, five single-nucleotide polymorphisms (SNPs) within the FKBP5 gene were selected for genotyping. While the authors did not observe genetic main effects, they found interactions between the five SNPs and traumatic (but not separation) events, with the strongest effect for severe trauma. The effect of trauma on incident major depressive episodes was evident among subjects homozygous for the minor alleles but not subjects with other genotypes. The findings were replicated in the U.K. Environmental Risk Longitudinal Twin Study. These hypothesis-driven results suggest that an interaction between FKBP5 genotype and trauma is involved in the onset of depression. Subjects homozygous for the minor alleles of the investigated FKBP5 SNPs seem to be particularly sensitive to effects of trauma exposure in terms of triggering depression onset.


Using occupation to facilitate self-awareness in people who have acquired brain injury: a pilot study.
Impaired self-awareness in people who have had an acquired brain injury (ABI) is a complex phenomenon that impedes rehabilitation progress and outcome. This pilot study investigated the effect of an occupation-based intervention program on the self-awareness and emotional status of people after ABI. Four male adults with impaired self-awareness following ABI participated in this study. Each received a 10-week individualized program that focused on the performance of three occupations for 1 to 2 hours per week. A facilitative approach was taken, using techniques to improve self-awareness described in the literature. Repeated measures of participants'self-awareness and emotional status were taken pre- and post-intervention, and analyzed descriptively. Results indicated preliminary support for the effectiveness of the program in facilitating participants' self-awareness. However, consideration of baseline and follow-up data indicated a complex picture. Increased anxiety was found to accompany improvements in participants' self-awareness in all four cases. This study will assist occupational therapists with program development for clients who have had an acquired brain injury.


Complement proteins detected through iTRAQ-based proteomics analysis of serum from black carp Mylopharyngodon piceus in response to experimentally induced Aeromonas hydrophila infection.
The black carp Mylopharyngodon piceus is one of the culturally important '4 famous domestic fishes' in China. Recently, infectious diseases caused by Aeromonas hydrophila have drastically altered the operation of the black carp farming industry. In the present study, isobaric tags for relative and absolute quantitation (iTRAQ) were combined with mass spectrometry analysis to screen for differentially abundant black carp serum proteins in response to experimentally induced A. hydrophila infection. A total of 86 differentially abundant proteins were quantified at 24 h post-infection, including 78 down-regulated proteins and 8 up-regulated proteins. The down-regulated proteins included complement C1q subcomponent subunit C, complement factor B/C2A, complement factor B/C2B, complement C3-Q1, complement C3, and complement C4-2. Bioinformatic analysis indicated that the differentially abundant proteins were mainly associated with complement and coagulation cascades (27.9%). Moreover, real-time PCR (qPCR) analysis revealed changes in the gene expression of both C3 and B/C2A in blood cells, liver, kidney, gills, and intestines of the black carp infected with A. hydrophila. However, mRNA expression levels did not consistently correlate with the corresponding protein levels. A polyclonal antibody was prepared using a synthetic C3 peptide. Immunofluorescence analysis showed that the expression of C3 in the kidney was increased with A. hydrophila infection. This work provides a useful characterization of the impact of A. hydrophila infection on the complement system of the black carp.


In-office distal Symes lesser toe amputation: a safe, reliable, and cost-effective treatment of diabetes-related tip of toe ulcers complicated by osteomyelitis.
Diabetes-related tip of lesser toe ulcers have typically been associated with both underlying hammertoe contracture and peripheral neuropathy. The combination of digital deformity and neuropathy commonly results in non-healing, deep sores that frequently become complicated by osteomyelitis. We report on a well-known, but poorly reported, technique for surgical management of non-healing tip of lesser toe ulcers. After approval by the institutional review board, a review was performed of consecutive patients who had undergone office-based distal Symes toe amputation for a non-healing tip of lesser toe ulcer from January 2007 to December 2012. A variety of clinical, laboratory, and radiographic data were collected. A total of 48 consecutive patients (48 toe ulcers) were identified for inclusion in the present study. All patients had ulcers at the time of surgery, and no patient developed repeat ulceration of the involved digit postoperatively. Of the 48 patients, 44 (92%) had hammertoe deformity preoperatively. Also, 30 patients (63%) had positive probe-to-bone results, and 29 (97%) of these patients had culture or histologic findings positive for osteomyelitis. Of the 48 patients (48 ulcers), 73% had positive bone cultures, 69% had positive pathologic findings demonstrating osteomyelitis, and 100% had clean margins. Methicillin-resistant Staphylococcus epidermidis was the most common pathogen isolated (13 of 48, 27%). No patient required additional amputation related to the operative digit. The mean follow-up period was 28.79 months. Our results have shown that in-office distal Symes lesser toe amputation is a safe, reliable, and likely cost-effective treatment of non-healing tip of lesser toe ulcers complicated by osteomyelitis. This office-based procedure allows bone biopsy diagnosis, removes the non-healing ulcer, confirms clear margins regarding the osteomyelitis, and addresses the underlying toe deformity to minimize the chances of repeat ulceration.


Vertical transmission of feather lice between adult blackbirds Turdus merula and their nestlings: a lousy perspective.
There is limited information about the natural history of the transmission of feather lice (Phthiraptera) from parent birds to their young. This article therefore examines the transmission of 4 species of feather lice from parent blackbirds to their nestlings in an English population, and addresses questions formulated from the perspective of the lice. The lice that disperse onto the several young in the nest were mostly found on the larger chicks, those with higher survival prospects. The lice dispersing to chicks were overwhelmingly nymphs, which cannot be sexed morphologically, and so the prediction that the adult lice dispersing would be disproportionately female, potential founders of a new population, was only supported for the most numerous species, Brueelia merulensis. There was no evidence that louse dispersal to chicks was density dependent and more likely when the parents were more heavily infested. Finally, I predicted that lice might aggregate on female blackbirds, which undertake more brooding, to increase their chance of transmission to nestlings. For 1 louse species, B. merulensis, prevalence, but not louse intensity, was higher on female than male blackbirds. For 2 other louse species, Philopterus turdi and Menacanthus eurysternus, no differences between male and female blackbirds were detected.


Breeding and Genetics Symposium: inferring causal effects from observational data in livestock.
Data regularly recorded in commercial herds have been used extensively for estimation of disease incidence rates, for inferences regarding genetic and phenotypic associations between traits, or for developing predictive models for economically important traits. Some studies have also used field data to investigate potential causal relationships between variables. However, inferring causal effects from observational data is complex due to potential confounding effects and careful analyses using specific statistical and data mining techniques as well as different sets of assumptions are required. Nonetheless, although virtually unknown in the agricultural research community, such methods are available and have been used in many other fields. In this paper, we review and discuss the analysis of observational data using field-recorded information and its potential utility in the study of causal effects in livestock. It is our postulation that there is much to be learned from such data, which can be used either to explicitly investigate causal relationships between variables or to generate hypotheses for further investigation using controlled experiments or additional field-recorded data.


Insulin fibrillation: toward strategies for attenuating the process.
Dark days for diabetic patients were transformed into an era of hope when the therapeutic usage of insulin was discovered. However, those initial glory days changed to being somewhat gloomy, when it was discovered that insulin easily undergoes undesirable, fast, and non-reversible aggregation and fibrillation. After more than half a century of intensive attempts to limit the rate of the insulin aggregation and fibrillation, there is no clear-cut strategy for eliminating these processes once and for all. A plethora of studies focused on using various organic compounds to combat the process, whereas other researchers believe that the process can be inhibited (or altered) by well-designed nanoparticles. In an attempt to inhibit insulin aggregation, some other approaches, such as protein/peptide inhibitors, have been considered for therapeutic purposes. Beyond biological processes and interactions between biological molecules, there are also strong physicochemical laws. Therefore, the goal of this article is to provide an overview of chemical, physical, and biological studies dedicated to the analysis of approaches that attenuate and inhibit insulin aggregation and fibrillation. After a detailed characterization of the insulin fibrillation process, this review focuses on various aspects related to the inhibition and modulation of insulin fibrillation using nanoparticles, proteins/peptides, and cyclic and non-cyclic compounds. Hopefully, these findings will pave the way for scientists in various fields to increase the stability of pharmaceutical proteins and peptides.


School quality ratings are weak predictors of students' achievement and well-being.
In England, all state-funded schools are inspected by an independent government agency, the Office for Standards in Education, Children's Services and Skills (Ofsted). Inspections aim to hold schools accountable and to promote the improvement of education, with the results made available to the public. Ofsted reports intend to index school quality, but their influence on students' individual outcomes has not been previously studied. The aim of the current study was to explore the extent to which school quality, as indexed by Ofsted ratings, is associated with students' educational achievement, well-being and school engagement. We use an England population-based sample of 4,391 individuals, for whom school performance at age 11 and GCSE grades at age 16 were accessed from the National Pupil Database, and who completed measures of well-being and school engagement at age 16. We found that Ofsted ratings of secondary school quality accounted for 4% of the variance in students' educational achievement at age 16, which was further reduced to 1% of the variance after we accounted for prior school performance at age 11 and family socioeconomic status. Furthermore, Ofsted ratings were weak predictors of school engagement and student well-being, with an average correlation of .03. Our findings suggest that differences in school quality, as indexed by Ofsted ratings, have little relation to students' individual outcomes. Accordingly, our results challenge the usefulness of Ofsted ratings as guides for parents and students when choosing secondary schools.


The normal range for secondary Swain-Schaad exponents without tunneling or kinetic complexity.
An analysis is presented of the range of secondary Swain-Schaad exponents to be expected at 25 degrees C in the absence of tunneling or kinetic complexity. From 15 996 sets of exact harmonic semiclassical equilibrium isotope effects for simple C-H/D/T exchange reactions and 954 sets of exact harmonic semiclassical secondary H/D/T kinetic isotope effects for C-H positions in simple organic reactions, the distribution of Swain-Schaad exponents versus magnitude of the isotope effect is determined. This distribution defines when a secondary Swain-Schaad exponent may be considered to implicate nonsemiclassical behavior, revises the expected Swain-Schaad exponent for extrapolation of secondary isotope effects, and serves as a guide to the uncertainty in such extrapolations.


HIV Testing, Risk Behaviors, and Fear: A Comparison of Documented and Undocumented Latino Immigrants.
Latino immigrants in the United States are at elevated risk for HIV infection and delayed HIV diagnosis. Immigration documentation status and its contribution to fears are important barriers to accessing health services including HIV testing. A currently changing political climate within the United States may have increased the complexity of the intersection of documentation status and health care access. This study used an anonymous survey conducted in March and April 2017 in New York City to compare: sociodemographic characteristics, HIV testing behaviors, HIV risk behaviors, and perceptions of fear around HIV testing among documented and undocumented Latino immigrants (N = 301). We found that undocumented immigrants reported lower levels of education, income, and health insurance than did documented immigrants. However, groups did not differ in having tested for HIV in the last 12 months, in future intentions to test for HIV, or in emotional/cognitive perceptions of fear around HIV testing. Undocumented immigrants reported lower rates of having ever tested for HIV in their lifetime (68.6%) than documented immigrants (80.5%) (p = 0.027). In conclusion, we found that despite sociodemographic challenges, undocumented immigrants had similar HIV testing behaviors as their documented counterparts in our study community. Further understanding of the mitigating factors that resulted in seemingly equal access to HIV testing in this community for undocumented immigrants is warranted.


Investigations on a solar humidification dehumidification desalination system equipped with various packing materials and multi-stage bubble column dehumidifier.
This work presents the theoretical and experimental investigation of a solar-powered humidification dehumidification desalination (HDD) system with different humidifier packing materials and a two-stage bubble column dehumidifier (BCD). Naturally available coconut shells (CS) and coconut shells with drilled holes (CSH) on the surface to improve water permeability were used as packing materials in the humidifier, and their performance was compared with that of commercial-type pall ring (PR) and raschig ring (RR) packings. An in-house developed numerical model of the HDD system in conjunction with a flat plate solar water collector was used in this study. Steady-state experimental results showed that CSH packing exhibited the highest volumetric mass transfer coefficient (0.00852 kg/s), resulting in maximum humidifier efficiency (96%) and freshwater yield (2.16 kg/hr), followed by PR (0.00841 kg/s, 94%, and 2.137 kg/hr), CS (0.00831 kg/s, 90%, and 2.127 kg/hr), and RR (0.0081 kg/s, 81%, and 2.087 kg/hr) at feedwater mass flow rate of 1.5 kg/min and humidifier inlet temperature of 75 [Formula: see text]. Furthermore, transient outdoor test results showed that using a two-stage configuration in a BCD increased the daily average effectiveness to 0.93, as against 0.79 for a single-stage BCD. Employing CSH instead of PR and RR packings in the humidifier reduced freshwater costs by 6.2% and 7.6%, respectively.


Preparation of a soft and interconnected macroporous hydroxypropyl cellulose methacrylate scaffold for adipose tissue engineering.
This study describes the preparation and characterization of a biodegradable 3D hydrogel constructed from hydroxypropyl cellulose (HPC), modified with bifunctional methacrylic anhydride (MA) to form hydroxypropyl cellulose methacrylate (HPC-MA), for adipose tissue engineering applications. The hydrogels were prepared from three different concentrations (10 wt%, 15 wt% and 20 wt%) of HPC-MA with 0.35 degree of substitution. HPC-MA hydrogel scaffolds with open biphasic features were prepared by exploiting the thermal responsive phase behavior of HPC and temperature mediated phase separation of HPC-MA. The resulting scaffolds exhibited pore sizes ranging from 30 to 300 μm and an interconnected porosity of ∼90%. The swelling ratio (SR) and storage modulus of HPC-MA scaffolds were in the range of 12.94 to 35.83 and 0.75 to 4.28 kPa, respectively. The swelling ratio and storage modulus suggested that the scaffold exhibits high water retention, allowing medium exchange during cell culturing and that it is suitable for adipose tissue regeneration. The HPC-MA scaffolds were found to be biocompatible to human adipose-derived stem cells (ASCs). ASCs were successfully differentiated into the adipocytes inside the scaffolds, and therefore demonstrated the potential application of these HPC-MA scaffolds for adipose tissue engineering.


[On the role of insufficient mitochondrial energy production in primary hypertension: the neurogenic constitutive of the pathogenesis].
There are accumulated evidences on existence of an imbalance between energy production and consumption in tissues in primary hypertension resulting in insufficient compensation of energy and its deficiency in cells (human essential hypertension, spontaneous hypertension in rats, SHR). An origin of these abnormalities resides in an alteration of cell mitochondrion ATP-synthetic function which ground is calcium overload of mitochondria due to increased cytosolic calcium redundantly entering into mitochondria and development of insufficiency of mPT pore removing calcium from matrix of the organells. There is an energy production deficiency in brain tissue of individuals with primary hypertension that is not initially caused by alteration of cerebral blood circulation of ischemic type. The mentioned energy abnormality is determined by decreased ability of brain mitochondria to synthesize ATP as a result of their calcium overload due to altered cell calcium handling in hypertension (so called membrane defect). In these conditions the registered normal or insignificantly changed cerebral blood flow in primary hypertension may be a result of systemic blood pressure increase in response to energy deficiency in brain tissue. Mechanisms mediating development of systemic hypertension include as the most important activation of vasomtor centers of brain stem. Other systems influencing vascular flow and peripheral resistance also contribute. Among those redundant (under conditions of calcium overload) production of oxidative radicals by mitochondria canceling vasorelaxing effect of NO should be specifically mentioned. The structural remodeling of peripheral circulation including rarefaction of capillary network provides for irreversibility of hypertension.


Iron Overload, Oxidative Stress and Calcium Mishandling in Cardiomyocytes: Role of the Mitochondrial Permeability Transition Pore.
Iron (Fe) plays an essential role in many physiological processes. Hereditary hemochromatosis or frequent blood transfusions often cause iron overload (IO), which can lead to cardiomyopathy and arrhythmias; however, the underlying mechanism is not well defined. In the present study, we assess the hypothesis that IO promotes arrhythmias via reactive oxygen species (ROS) production, mitochondrial membrane potential (∆Ψm) depolarization, and disruption of cytosolic Ca dynamics. In ventricular myocytes isolated from wild type (WT) mice, both cytosolic and mitochondrial Fe levels were elevated following perfusion with the Fe3+/8-hydroxyquinoline (8-HQ) complex. IO promoted mitochondrial superoxide generation (measured using MitoSOX Red) and induced the depolarization of the ΔΨm (measured using tetramethylrhodamine methyl ester, TMRM) in a dose-dependent manner. IO significantly increased the rate of Ca wave (CaW) formation measured in isolated ventricular myocytes using Fluo-4. Furthermore, in ex-vivo Langendorff-perfused hearts, IO increased arrhythmia scores as evaluated by ECG recordings under programmed S1-S2 stimulation protocols. We also carried out similar experiments in cyclophilin D knockout (CypD KO) mice in which the mitochondrial permeability transition pore (mPTP) opening is impaired. While comparable cytosolic and mitochondrial Fe load, mitochondrial ROS production, and depolarization of the ∆Ψm were observed in ventricular myocytes isolated from both WT and CypD KO mice, the rate of CaW formation in isolated cells and the arrhythmia scores in ex-vivo hearts were significantly lower in CypD KO mice compared to those observed in WT mice under conditions of IO. The mPTP inhibitor cyclosporine A (CsA, 1 µM) also exhibited a protective effect. In conclusion, our results suggest that IO induces mitochondrial ROS generation and ∆Ψm depolarization, thus opening the mPTP, thereby promoting CaWs and cardiac arrhythmias. Conversely, the inhibition of mPTP ameliorates the proarrhythmic effects of IO.


Toxicity profiling of water contextual zinc oxide, silver, and titanium dioxide nanoparticles in human oral and gastrointestinal cell systems.
Engineered nanoparticles (ENPs) are increasingly detected in water supply due to environmental release of ENPs as the by-products contained within the effluent of domestic and industrial run-off. The partial recycling of water laden with ENPs, albeit at ultra-low concentrations, may pose an uncharacterized threat to human health. In this study, we investigated the toxicity of three prevalent ENPs: zinc oxide, silver, and titanium dioxide over a wide range of concentrations that encompasses drinking water-relevant concentrations, to cellular systems representing oral and gastrointestinal tissues. Based on published in silico-predicted water-relevant ENPs concentration range from 100 pg/L to 100 µg/L, we detected no cytotoxicity to all the cellular systems. Significant cytotoxicity due to the NPs set in around 100 mg/L with decreasing extent of toxicity from zinc oxide to silver to titanium dioxide NPs. We also found that noncytotoxic zinc oxide NPs level of 10 mg/L could elevate the intracellular oxidative stress. The threshold concentrations of NPs that induced cytotoxic effect are at least two to five orders of magnitude higher than the permissible concentrations of the respective metals and metal oxides in drinking water. Based on these findings, the current estimated levels of NPs in potable water pose little cytotoxic threat to the human oral and gastrointestinal systems within our experimental boundaries.


Biomechanics of human movement with applications to the study of human locomotion.
A review of the biomechanics of human movement is presented and covers the neural control of voluntary movement, as it manifests itself in the electromyogram, through to detailed kinetic analyses and simulation studies. The body of knowledge of muscle performance is covered in detail, from the individual motor unit characteristics, through recruitment patterns to the static and dynamic characteristics of the total muscle and its relationship to the electromyogram. A summary of research into the movement of the skeletal (segmental) system itself covers the kinematic data collection systems, the link-segment modeling with anthropometric measures, and the inverse dynamics solution of the joint kinetics. A critique of current simulation models reveals a diversity of simplifications and assumptions that seriously affect the interpretation of results. Similarly, a critical assessment of the literature pertaining to mechanical energy, work, power and efficiency exposes many varied and anomalous techniques and correspondingly confusing interpretations. At all phases of the review the author attempts to reconcile differences, criticize obvious errors, and identify important contributions.


Differences and changes in human papillomavirus type 16 variant status in human immunodeficiency virus-positive adults are not uncommon.
Human papillomavirus type 16 (HPV-16) genotype variants have been the subject of several investigations, but study participants have rarely been sampled more than once. In this study, among a cohort of human immunodeficiency virus (HIV)-infected adults, HPV-16 variants were investigated in samples collected concurrently from the anus and cervix, as well as in serial samples collected from the same anatomical site at 12-month intervals. HPV-16 variants in stored extracts of cervical and anal samples were determined from subjects with multiple visits and at least one sample positive for HPV-16. Seven polymorphic nucleotide positions within the E6 region were analysed by pyrosequencing to determine genotype variants. Of 364 samples examined, 176 anal and 39 cervical swabs from 84 different subjects yielded unequivocal sequences of eight major HPV-16 variants. Eight samples contained probable novel HPV-16 variants and in one sample two variants were detected. In eight out of 29 (27.6%) anal-cervical sample pairs positive for HPV-16, discordant variants were found. From 57 anal and nine cervical sample series of HPV-16-positive samples, a change in HPV-16 variant status over time was seen in nine (13.6%) instances (seven anal and two cervical) from eight different participants. Changes in HPV-16 variants in HIV-infected adults were seen most frequently when different anatomical sites were sampled, but were also observed over time.


Predicting outcome following mild traumatic brain injury: protocol for the longitudinal, prospective, observational Concussion Recovery (CREST) cohort study.
Mild traumatic brain injury (mTBI) is a complex injury with heterogeneous physical, cognitive, emotional and functional outcomes. Many who sustain mTBI recover within 2 weeks of injury; however, approximately 10%-20% of individuals experience mTBI symptoms beyond this 'typical' recovery timeframe, known as persistent post-concussion symptoms (PPCS). Despite increasing interest in PPCS, uncertainty remains regarding its prevalence in community-based populations and the extent to which poor recovery may be identified using early predictive markers. (1) Establish a research dataset of people who have experienced mTBI and document their recovery trajectories; (2) Evaluate a broad range of novel and established prognostic factors for inclusion in a predictive model for PPCS. The Concussion Recovery Study (CREST) is a prospective, longitudinal observational cohort study conducted in Perth, Western Australia. CREST is recruiting adults aged 18-65 from medical and community-based settings with acute diagnosis of mTBI. CREST will create a state-wide research dataset of mTBI cases, with data being collected in two phases. Phase I collates data on demographics, medical background, lifestyle habits, nature of injury and acute mTBI symptomatology. In Phase II, participants undergo neuropsychological evaluation, exercise tolerance and vestibular/ocular motor screening, MRI, quantitative electroencephalography and blood-based biomarker assessment. Follow-up is conducted via telephone interview at 1, 3, 6 and 12 months after injury. Primary outcome measures are presence of PPCS and quality of life, as measured by the Post-Concussion Symptom Scale and the Quality of Life after Brain Injury questionnaires, respectively. Multivariate modelling will examine the prognostic value of promising factors. Human Research Ethics Committees of Royal Perth Hospital (#RGS0000003024), Curtin University (HRE2019-0209), Ramsay Health Care (#2009) and St John of God Health Care (#1628) have approved this study protocol. Findings will be published in peer-reviewed journals and presented at scientific conferences. ACTRN12619001226190.


Functional drivers of resistance to anti-CD19 CAR-T cell therapy in diffuse large B cell lymphoma.
Chimeric antigen receptor T-cell therapy targeting CD19 (CAR-19) promotes impressive durable remissions for relapsed or refractory (rel/ref) large B-cell lymphoma (LBCL) patients with historically poor prognoses. Despite this, over half of patients still fail to respond or eventually progress. Studies to reveal mechanisms of resistance have examined host clinical parameters, CAR-19 product composition, and tumor microenvironment (TME) alterations, while a relative paucity of studies has analyzed contributions by genomic alterations in tumor cells. Factors associated with outcome include increased tumor volume, specific characteristics of infused CAR-T products, infiltration by myeloid cells in tumor microenvironments, and markers of complexity in LBCL genomes. Functional laboratory studies of resistance are largely absent in the current literature, illustrating a need for experiments in genetically accurate immunocompetent systems to confirm candidate alterations' roles in resistance and inform future improvements. In this review, we highlight key studies that have elucidated biomarkers of resistance in hosts, CAR products, TMEs, and comparatively understudied tumor-intrinsic mediators encoded by tumor genomes. We conclude with an experimental framework suitable for CAR-19 resistance biomarker identification and laboratory functional validation.


Deep anaesthesia reduces postoperative analgesic requirements after major urological procedures.
There is evidence from previous studies that deeper anaesthetic levels reduce postoperative pain along with analgesic requirements. The aim of this study was to confirm this observation during major urological procedures under sevoflurane anaesthesia. Seventy ASA I or II patients undergoing radical prostatectomy or nephrectomy were randomly allocated into two groups: the L-BIS group with BIS (bispectral index scale) values kept within a range of 20-30 and the H-BIS group with values within the range of 50-60. Sevoflurane was the main anaesthetic agent used, along with inhalation of nitrous oxide and continuous remifentanil infusion. Postoperative analgesia was achieved mainly through morphine and ketamine, which was continuously infused by pump, and intravenous parecoxib. Additional analgesics (paracetamol, parecoxib and morphine) were administered in persistent (continuous, lasting longer than predicted and requiring repeated doses of analgesics) postoperative pain. The number of patients who demanded additional analgesia during the first 24 h was recorded, as well as the number of administrations performed, along with visual analogue scale (VAS) scores at 8 and 24 h. Sixty patients completed the study, 30 in each group. VAS scores at 8 h were significantly higher in the H-BIS group, both at rest [1 (0-4) vs. 2 (0-8), P = 0.036] and on cough [1 (0-5) vs. 2 (2-9), P = 0.021], but at 24 h were similar between the two groups. Four patients in the L-BIS group and 17 patients in the H-BIS group demanded additional analgesia (P < 0.0009), although the patients in the L-BIS group needed significantly fewer additional doses of analgesics than those in the H-BIS group [0 (0-2) vs. 1 (0-5), P < 0.0008]. The results show that intraoperative deep anaesthetic levels during major urological procedures, achieved with high sevoflurane concentrations, lead to reduced postoperative analgesic requirements.


Lung Transplant Patients Show a Dissimilar Peripheral B-Cell Subset Ratio Compared With Healthy Controls.
Lung transplant is a last treatment option for patients with end-stage pulmonary disease. Chronic lung allograft dysfunction, which generally manifests as bronchiolitis obliterans syndrome, is a major long-term survival limitation. Bronchiolitis obliterans syndrome is diagnosed when forced expiratory volume in 1 second declines > 20% in the absence of known causes. B cells can either contribute or restrain the development of bronchiolitis obliterans syndrome (eg, via induction of alloimmune antibodies, regulation of cellular immunity, and induction of tolerance). Here, we explored how peripheral B-cell subsets were altered in lung transplant recipients with bronchiolitis obliterans syndrome. Fresh whole blood samples were analyzed from 42 lung transplant recipients, including 17 with bronchiolitis obliterans syndrome; samples from these groups were compared with 10 age-matched healthy control samples. B-cell subsets were analyzed using flow cytometry, and relative distributions of subsets were compared. Changes in forced expiratory volume in 1 second were also determined. Absolute B-cell count was significantly increased in transplant recipients with bronchiolitis obliterans syndrome. Transitional (CD24+CD38+) and naïve (CD27-IgD+) B cells were decreased in lung transplant patients, with transitional B cells almost absent in those with bronchiolitis obliterans syndrome. Double-negative (CD27-IgD-) memory B cells were significantly increased (P < .001). No differences were found for plasmablasts (CD38+CD24-) and switched (CD27+IgD-) and non-switched (CD27+IgD+) memory B cells. Correlation analyses showed positive correlations between lung function and naïve B cells in transplant recipients (P = .0245; r = -0.458). Peripheral B-cell count and subset distribution were altered in lung transplant recipients with and without bronchiolitis obliterans syndrome compared with healthy controls. Transitional and naïve B-cell decreases may be caused by differentiation toward double-negative B-cells, which were increased. The correlation between forced expiratory volume and naïve B cells during follow-up care may be clinically interesting to investigate.


Integration of radiologist peer review into clinical review workstation.
Professional peer review of random prior radiologist's interpretations is mandated by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). The JCAHO expects documentation of 5% rate of random peer-review cases. Countless hours are spent in departments fulfilling these requirements. The integration of the peer-review process into the radiologist's interpretation workflow was expected to increase the percentage of documented peer review, yet decrease the time and effort for this documentation. radStation clinical review workstations are deployed at every reading station. When a requisition is bar-coded, radStation retrieves the patient's clinical information and automatically displays the prior comparison report. If the radiologist agrees with the prior report, a single click on a "quality assurance' agree box documents the agreement. In the case of a discordance, an additional dialog box automatically appears and the radiologist enters the reason for disagreement and then submits the case as a discrepancy. The system holds the discordance for 3 to 5 working days, then notifies the original radiologist via E-mail that a prior interpretation has been submitted for peer review, lists the submitted discrepancy reason, and provides a link to display the discordant report. The peer-review database is separate from the existing radiology information system (RIS). At the end of every month, summary reports of all peer-review activity are generated automatically. Initial benchmarks of our deployed system anticipate documentation of long-term random peer-review rate at greater than 50% of interpreted cases. The system enhances the peer-review process by integrating it with the normal interpretation workflow. The time to complete peer review using radStation is less than 1 second per normal case and less than 60 seconds for a discordant case. The E-mail notification system is fully automated, eliminating the need for secretarial involvement in the data collection. This system has completely replaced a manual paper-based system. The integration of peer review directly into the radiologist's interpretation workstation greatly enhances the capability to easily exceed JCAHO standards. The overall increase in peer-review documentation should continue to improve the ability to document a consistent high quality of patient care.


Radioimmunoassay of growth hormone-dependent insulinlike growth factor binding protein in human plasma.
A specific radioimmunoassay has been established for a growth hormone-dependent insulinlike growth factor (IGF) binding protein (BP) from human plasma. Although the assay was directed against a 53-kD, acid-stable BP subunit, the main immunoreactive BP in the circulation had an apparent molecular mass of approximately 125 kD. Only higher primate species showed cross-reactivity, and IGF-I, IGF-II, and other peptides were without effect. Circulating BP levels in healthy subjects rose threefold from early childhood to puberty. In 65 adults aged 18 to 65, the mean level (+/- SD) was 6.12 +/- 1.43 micrograms/ml, and declined with age. Strong growth hormone-dependence of BP was also seen; there was a 2.2-fold increase in active acromegaly and a 50-80% reduction in growth hormone deficiency. Poorly controlled diabetic subjects had BP levels 40% below normal, whereas in renal failure and third-term pregnancy a mild elevation was seen. Measurement of BP may provide a useful adjunct to IGF assays in growth disorders.


Magnetocardiographic analysis of the two-dimensional distribution of intra-QRS fractionated activation.
The spatial distribution of high-frequency components in magnetic signals during the QRS complex of the human heartbeat was investigated. Cardiomagnetic signals were recorded simultaneously using 49 first-order magnetogradiometer channels of a multi-SQUID system with a low noise power density. The QRS fragmentation score S, as a measure of the fragmentation of the bandpass-filtered QRS complex, was examined for its sensitivity and specificity to discriminate 34 healthy volunteers, 42 post-myocardial infarction patients and 43 patients with coronary heart disease and with a history of malignant sustained ventricular tachycardia or ventricular fibrillation. The multichannel information was visualized by two-dimensional mapping of the score values of the single channels. By averaging the score values for the seven central channels, S7, the score values of all 49 channels, S49, and calculating the standard deviation for all 49 channels, D49, a higher sensitivity and specificity for detecting patients with ventricular tachycardia (VT) or ventricular fibrillation (VF) was reached than by analysis of a single channel. Combination of these parameters furnishes a sensitivity of 90% and a specificity of 70% for identifying patients prone to VT/VF. The results were compared with diagnostic information obtained from the QRS duration of the signal as well as with results obtained by modified QRS integral mapping.


Ozone levels in passenger cabins of commercial aircraft on North American and transoceanic routes.
Ozone levels in airplane cabins, and factors that influence them, were studied on northern hemisphere commercial passenger flights on domestic U.S., transatlantic, and transpacific routes. Real-time data from 76 flights were collected in 2006--2007 with a battery-powered UV photometric monitor. Sample mean ozone level, peak-hour ozone level, and flight-integrated ozone exposures were highly variable across domestic segments (N = 68), with ranges of < 1.5 to 146 parts per billion by volume (ppbv), 3--275 ppbv, and < 1.5 to 488 ppbv-hour, respectively. On planes equipped with ozone catalysts, the mean peak-hour ozone level (4.7 ppbv, N = 22)was substantially lower than on planes not equipped with catalysts (47 ppbv, N = 46). Peak-hour ozone levels on eight transoceanic flight segments, all on planes equipped with ozone catalysts, were in the range < 1.5 to 65 [corrected] ppbv. Seasonal variation on domestic routes without converters is reasonably modeled by a sinusoidal curve that predicts peak-hour levels to be approximately 70 ppbv higher in Feb--March than in Aug--Sept The temporal trend is broadly consistent with expectations, given the seasonal cycle in tropopause height. Episodically elevated (>100 ppbv) ozone levels on domestic flights were associated with winter-spring storms that are linked to enhanced exchange between the lower stratosphere and the upper troposphere.


Epidemiology of contralateral breast cancer.
Two to 11% of women diagnosed with breast cancer will develop contralateral breast cancer in their lifetime. Women with a first primary are at a 2-6-fold increased risk of developing contralateral breast cancer compared with the risk in the general population of women developing a first primary cancer. The incidence rate of contralateral breast cancer varies from four to eight per 1000 person-years. To assess the risk factors associated with the development of contralateral breast cancer among women with a first primary breast cancer, the epidemiological literature concerning these factors was reviewed and summarized. Studies have shown that a family history of breast cancer, an early age at initial diagnosis, and a lobular histology of the first primary breast cancer increase the risk of developing contralateral breast cancer. Although chemotherapy and tamoxifen therapy may reduce this risk, there are inconsistent results regarding the effects of radiotherapy and the effects of reproductive, environmental and other factors. Additional analytical studies addressing all potential risk factors associated with the development of contralateral breast cancer are necessary in view of the increasing incidence and survival of women with a first primary.


Prevalence and Associated Factors of Musculoskeletal Disorders among Young Dentists in Indonesia.
Introduction: Musculoskeletal problems are often work related. Dentists have been reported to have a high prevalence of musculoskeletal problems. Dentists have to perform repetitive tasks, often in awkward and nonergonomic positions in their practice. Materials and Methods: This is a cross-sectional study. Five-hundred copies of Nordic Musculoskeletal Questionnaire were distributed to dentists who participated in a congress of a regional branch of the Indonesian Dentist Association. Data such as sex, length of practice, the presence of assistance, smoking, occupational stress, body mass index, hand dominance, and exercise were collected. Dentist who had practised for more than five years were excluded. Results: Two hundred and forty-one respondents fulfilled the research criteria. Musculoskeletal symptoms occurred in 63.5% respondents. Fatigue and pain were the most common manifestations of musculoskeletal symptoms among dentists (36.5 and 24.9% respectively). Prolonged sitting was the most common aggravating factor (26.6%) while exercise successfully relieved symptoms in 35.3% of respondents. Neck, upper back and lower back were the most common sites involved with prevalence of 25.7, 22.4, and 20.7% respectively. Neck was also the most common site of the symptoms preventing normal work during the preceding 12 months (8.3%). Exercise and stress are associated with the presence of musculoskeletal symptoms (p=0.01 and p<0.01 respectively). Exercise is associated with fatigue (p<0.01) and click (p<0.01), stress is associated with pain (p=0.00), stiffness (p=0.00), fatigue (p<0.01), and discomfort (p<0.01). Conclusions: The prevalence of musculoskeletal disorders in young dentists is 63.5%. Neck is the most common affected region. Stress and exercise are the main associated factor for musculoskeletal problems in dentists.


[Cystic lymphangioma of the adrenal gland].
Cystic lymphangioma of the adrenal gland is a rare tumor, which is often sub-clinical. Preoperative diagnosis is difficult. We present a case of a 47 year-old female in whom an incidental left cystic mass of 12 cm by 10 cm with no features of malignancy was discovered by ultrasound scan. A further computed tomography scan confirmed the ultrasound findings. Biochemical screening ruled out a secreting adrenal tumor. Because of the size of the cyst, the lesion was resected and the diagnosis of benign adrenal cystic lymphangioma was histologically confirmed. Computed tomography is the reference examination for delineating the topography and extent of the lesion, especially when it is large. Although imaging can characterize the cystic nature of a lesion, it sometimes fails to establish a specific diagnosis, so surgery or fine needle aspiration should be done for a definitive diagnosis. The characteristic features of cystic adrenal lymphangioma are discussed together with a review of the recent literature.


Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer.
Psammoma bodies are often observed in papillary carcinomas of the thyroid. Recently we reported that osteopontin (OPN) appears to play an important role in the development of psammoma bodies in meningiomas. Because the morphology and components of psammoma bodies in papillary carcinoma of the thyroid are similar to those of psammoma bodies in meningioma, we examined whether OPN was related to the psammoma bodies in papillary carcinoma of the thyroid. Expression of OPN mRNA was examined by Northern blotting and in situ hybridization. Immunohistochemistry was performed to localize the deposition of OPN protein and to identify the type of OPN mRNA-expressing cells. The expression of OPN mRNA was detected in papillary thyroid carcinomas but not in normal thyroid tissue. Osteopontin mRNA-expressing cells were present around the psammoma bodies, and the localization of OPN protein was consistent with that of psammoma bodies. The OPN mRNA-expressing cells were identified as CD68-positive macrophages. Osteopontin produced by macrophages may play a significant role in the development of psammoma bodies in papillary carcinoma of the thyroid.


Bronchopulmonary dysplasia. A radiologic-pathologic correlation.
In 26 deaths from the neonatal unit with a histologic diagnosis of bronchopulmonary dysplasia (BPD), the histologic stage was compared to the radiologic stage according to the criteria described by Northway and Rosan. In 18 patients (69%), the histologic stage corresponded exactly to the radiologic stage. In the remaining eight patients (31%), there was a difference of one stage. If the 14 cases of Stages I and II were taken together there would be a discrepancy of one stage between the histologic and radiologic stages in 50%. However, with Stages III and IV the discrepancy was only 8.3%. There appears to be better correlation as the severity of BPD increases.