Differential gene expression in the EphA4 knockout spinal cord and analysis of the inflammatory response following spinal cord injury.
Mice lacking the axon guidance molecule EphA4 have been shown to exhibit extensive axonal regeneration and functional recovery following spinal cord injury. To assess mechanisms by which EphA4 may modify the response to neural injury a microarray was performed on spinal cord tissue from mice with spinal cord injury and sham injured controls. RNA was purified from spinal cords of adult EphA4 knockout and wild-type mice four days following lumbar spinal cord hemisection or laminectomy only and was hybridised to Affymetrix All-Exon Array 1.0 GeneChips™. While subsequent analyses indicated that several pathways were altered in EphA4 knockout mice, of particular interest was the attenuated expression of a number of inflammatory genes, including Arginase 1, expression of which was lower in injured EphA4 knockout compared to wild-type mice. Immunohistological analyses of different cellular components of the immune response were then performed in injured EphA4 knockout and wildtype spinal cords. While numbers of infiltrating CD3+ T cells were low in the hemisection model, a robust CD11b+ macrophage/microglial response was observed post-injury. There was no difference in the overall number or spread of macrophages/activated microglia in injured EphA4 knockout compared to wild-type spinal cords at 2, 4 or 14 days post-injury, however a lower proportion of Arginase-1 immunoreactive macrophages/activated microglia was observed in EphA4 knockout spinal cords at 4 days post-injury. Subtle alterations in the neuroinflammatory response in injured EphA4 knockout spinal cords may contribute to the regeneration and recovery observed in these mice following injury.


Neural mechanisms of persistent aggression.
While aggression is often conceptualized as a highly stereotyped, innate behavior, individuals within a species exhibit a surprising amount of variability in the frequency, intensity, and targets of their aggression. While differences in genetics are a source of some of this variation across individuals (estimates place the heritability of behavior at around 25-30%), a critical driver of variability is previous life experience. A wide variety of social experiences, including sexual, parental, and housing experiences can facilitate "persistent" aggressive states, suggesting that these experiences engage a common set of synaptic and molecular mechanisms that act on dedicated neural circuits for aggression. It has long been known that sex steroid hormones are powerful modulators of behavior, and also, that levels of these hormones are themselves modulated by experience. Several recent studies have started to unravel how experience-dependent hormonal changes during adulthood can create a cascade of molecular, synaptic, and circuit changes that enable behavioral persistence through circuit level remodeling. Here, we propose that sex steroid hormones facilitate persistent aggressive states by changing the relationship between neural activity and an aggression "threshold".


Center-Center Surgical Technique With Dynamic Syndesmosis Fixation: A Cadaveric Pilot Study.
The objective of this cadaveric biomechanical study was to evaluate if the center-center surgical technique is a reliable and repeatable method of achieving proper syndesmotic reduction when using dynamic syndesmotic fixation. Nine fresh frozen above-knee cadaveric lower extremities were used. Computerized tomography (CT) scans were first obtained for each intact specimen as the baseline for comparison. A simulated complete syndesmotic disruption was created by transection of all deltoid and syndesmotic ligaments. Instability of the ankle was confirmed with stress imaging using fluoroscopy. Each unstable specimen was repaired using the center-center surgical technique with dynamic syndesmosis fixation. A series of measurements from the axial CT images of intact and repaired specimens were used to determine the anatomic distal tibiofibular relationships for comparison of changes from intact to postfixation. All radiographic measurements were performed by 4 independent foot and ankle surgeons. The level of inter-rater reliability for all the measurements was found to be "moderate" to "excellent" agreement (ICC value: 0.865-0.983, 95% confidence interval: 0.634-0.996). There was no statistical difference found between rotational alignment of native and postfixation (a/b: p = .843; b-a: p = .125; θ: p = .062). There was a statistical difference detected for lateral alignment at the center of fibularis incisura between native and postfixation (average: -0.6 ± 0.8 mm, range: -2.3 to 1.2 mm, p < .001). There was no statistical difference found for the anteroposterior translation alignment between native and postfixation (d/e: p = .251; f: p = .377). This study demonstrated the use of the center-center surgical technique as a viable and repeatable method for achieving anatomical reduction of the tibiofibular syndesmosis when used with dynamic fixation modalities.


Detection of imminent collisions by drivers with Alzheimer's disease and Parkinson's disease: a preliminary study.
The aim of this study was to assess whether patients with neurodegenerative disease, namely Alzheimer's disease (AD) and Parkinson's disease (PD), differed from age-matched, neurologically normal comparison participants in their ability to detect impending collisions. Six AD patients and 8 PD patients, together comprising the neurodegenerative disease group, and 18 comparison participants completed a collision detection simulation task where they must judge whether approaching objects would collide with them or pass by them. The neurodegenerative disease group was less sensitive in detecting collisions than the comparison group, and sensitivity worsened with increasing number of objects in the display and increasing time to contact of those objects. Poor performance on tests of cognition and visual attention were associated with poor collision detection sensitivity. The results of this study indicate that neurodegenerative disease impairs the ability to accurately detect impending collisions and that these decrements are likely the combined result of visual and cognitive disturbances related to disease status.


N-activated β-lactams as versatile reagents for acyl carrier protein labeling.
Acyl carrier proteins are critical components of fatty acid and polyketide biosynthesis. Their primary function is to shuttle intermediates between active sites via a covalently bound phosphopantetheine arm. Small molecules capable of acylating this prosthetic group will provide a simple and reversible means of introducing novel functionality onto carrier protein domains. A series of N-activated β-lactams are prepared to examine site-specific acylation of the phosphopantetheine-thiol. In general, β-lactams are found to be significantly more reactive than our previously studied β-lactones. Selectivity for the holo over apo-form of acyl carrier proteins is demonstrated indicating that only the phosphopantetheine-thiol is modified. Incorporation of an N-propargyloxycarbonyl group provides an alkyne handle for conjugation to fluorophores and affinity labels. The utility of these groups for mechanistic interrogation of a critical step in polyketide biosynthesis is examined through comparison to traditional probes. In all, we expect the probes described in this study to serve as valuable and versatile tools for mechanistic interrogation.


Changes in phenol red absorbance in response to electrical stimulation of frog skeletal muscle fibers.
Intact single twitch fibers from frog muscle were stretched to long sarcomere length, micro-injected with the pH indicator dye phenol red, and activated by action potential stimulation. Indicator-related absorbance changes (denoted by delta A0 and delta A90) were measured with 0 degree and 90 degrees polarized light (oriented, respectively, parallel and perpendicular to the fiber axis). Two components of delta A were detected that had generally similar time courses. The "isotropic" component, calculated as the weighted average (delta A0 + 2 delta A90)/3, had the wavelength dependence expected for a change in myoplasmic pH. If calibrated in pH units, this signal's peak amplitude, which occurred 15-20 ms after stimulation, corresponded to a myoplasmic alkalization of average value 0.0025 +/- 0.0002 (+/- SEM; n = 9). The time course of this change, as judged from a comparison with that of the fibers' intrinsic birefringence signal, was delayed slightly with respect to that of the myoplasmic free [Ca2+] transient. On average, the times to half-peak and peak of the phenol red isotropic signal lagged those of the birefringence signal by 2.4 +/- 0.2 ms (+/- SEM; n = 8) and 8.4 +/- 0.5 ms (+/- SEM; n = 4), respectively. The other component of the phenol red signal was "dichroic," i.e., detected as a difference (delta A0-delta A90 greater than 0) between the two polarized absorbance changes. The wavelength dependence of this signal was similar to that of the phenol red resting dichroic signal (Baylor and Hollingworth. 1990. J. Gen. Physiol. 96:449-471). Because of the presence of the active dichroic signal, and because approximately 80% of the phenol red molecules appear to be bound in the resting state to either soluble or structural sites, the possibility exists that myoplasmic events other than a change in pH underlie the phenol red isotropic signal.


Effects of Drugs Formerly Suggested for COVID-19 Repurposing on Pannexin1 Channels.
Although many efforts have been made to elucidate the pathogenesis of COVID-19, the underlying mechanisms are yet to be fully uncovered. However, it is known that a dysfunctional immune response and the accompanying uncontrollable inflammation lead to troublesome outcomes in COVID-19 patients. Pannexin1 channels are put forward as interesting drug targets for the treatment of COVID-19 due to their key role in inflammation and their link to other viral infections. In the present study, we selected a panel of drugs previously tested in clinical trials as potential candidates for the treatment of COVID-19 early on in the pandemic, including hydroxychloroquine, chloroquine, azithromycin, dexamethasone, ribavirin, remdesivir, favipiravir, lopinavir, and ritonavir. The effect of the drugs on pannexin1 channels was assessed at a functional level by means of measurement of extracellular ATP release. Immunoblot analysis and real-time quantitative reversetranscription polymerase chain reaction analysis were used to study the potential of the drugs to alter pannexin1 protein and mRNA expression levels, respectively. Favipiravir, hydroxychloroquine, lopinavir, and the combination of lopinavir with ritonavir were found to inhibit pannexin1 channel activity without affecting pannexin1 protein or mRNA levels. Thusthree new inhibitors of pannexin1 channels were identified that, though currently not being used anymore for the treatment of COVID-19 patients, could be potential drug candidates for other pannexin1-related diseases.


Trends in Hospitalizations for Acute Kidney Injury - United States, 2000-2014.
Acute kidney injury is a sudden decrease in kidney function with or without kidney damage, occurring over a few hours or days. Diabetes, hypertension, and advanced age are primary risk factors for acute kidney injury. It is increasingly recognized as an in-hospital complication of sepsis, heart conditions, and surgery (1,2). Its most severe stage requires treatment with dialysis. Acute kidney injury is also associated with higher likelihood of long-term care, incidence of chronic kidney disease and hospital mortality, and health care costs (1,2). Although a number of U.S. studies have indicated an increasing incidence of dialysis-treated acute kidney injury since the late 1990s (3), no data are available on national trends in diabetes-related acute kidney injury. To estimate diabetes- and nondiabetes-related acute kidney injury trends, CDC analyzed 2000-2014 data from the National Inpatient Sample (NIS) (4) and the National Health Interview Survey (NHIS) (5). Age-standardized rates of acute kidney injury hospitalizations increased by 139% (from 23.1 to 55.3 per 1,000 persons) among adults with diagnosed diabetes, and by 230% (from 3.5 to 11.7 per 1,000 persons) among those without diabetes. Improving both patient and provider awareness that diabetes, hypertension, and advancing age are frequently associated with acute kidney injury might reduce its occurrence and improve management of the underlying diseases in an aging population.


Cryo-electron Microscopy of Adeno-associated Virus.
Adeno-associated virus (AAV) has a single-stranded DNA genome encapsidated in a small icosahedrally symmetric protein shell with 60 subunits. AAV is the leading delivery vector in emerging gene therapy treatments for inherited disorders, so its structure and molecular interactions with human hosts are of intense interest. A wide array of electron microscopic approaches have been used to visualize the virus and its complexes, depending on the scientific question, technology available, and amenability of the sample. Approaches range from subvolume tomographic analyses of complexes with large and flexible host proteins to detailed analysis of atomic interactions within the virus and with small ligands at resolutions as high as 1.6 Å. Analyses have led to the reclassification of glycan receptors as attachment factors, to structures with a new-found receptor protein, to identification of the epitopes of antibodies, and a new understanding of possible neutralization mechanisms. AAV is now well-enough characterized that it has also become a model system for EM methods development. Heralding a new era, cryo-EM is now also being deployed as an analytic tool in the process development and production quality control of high value pharmaceutical biologics, namely AAV vectors.


Abused by the Patriarchy: Male Victims, Masculinity, "Honor"-Based Abuse and Forced Marriages.
The causes and effects of what is often referred to as "honor"-based violence/abuse (HBV/A) and forced marriages on men and boys is an under-researched field of patriarchal violence. This lack of research has resulted in an imperfect understanding of how and why men become victims of HBV/A and an absence of an effective theoretical framework in which to analyze their experiences. Through an examination of 29 Case Files obtained through a gender-neutral domestic abuse refuge charity in the East Midlands, the United Kingdom, this original research will explore the ways that men, particularly younger males and those who do not conform to cultural norms of masculinity, are harmed by patriarchal structures. In doing so, this article brings to light new data and adds to the patriarchal framework for understanding HBV/A and why it is committed against men. The results of this study reveal that the ways in which HBV/A and forced marriages were presented in the Case Files present both analogies to and distinctions with the infliction of Violence Against Women and Girls (VAWG) in similar circumstances. This discovery is important for several reasons: (a) it demonstrates that men and boys are harmed by patriarchy and that patriarchal theories of violence must therefore evolve to better recognize groups of male victims; (b) it provides a typological framework to identify the different types of male victims, the types of abuse and the perpetrators involved, including the involvement of mothers as primary and secondary perpetrators; and (c) that male victims require appropriate intervention and must be taken seriously by state agencies if men are to come forward and disclose abuse.


The mode of action of immunological adjuvants.
Adjuvants augment immune responses to antigens and influence the balance between cell-mediated and humoral responses, as well as the isotypes of antibodies formed. New adjuvant formulations include antigen-carrying vehicles and small molecules with immunomodulating activity. Widely used two-phase vehicles comprise liposomes and microfluidized squalene or squalane emulsions. These are believed to target antigens to antigen-presenting cells, including dendritic cells (DC), follicular dendritic cells (FDC) and B-lymphocytes. Activation of complement generates C3d, which binds CR2 (CD21) on FDC and B-lymphocytes, thereby stimulating the proliferation of the latter and the generation of B-memory. Targeting of antigens to DC may favour cell-mediated immunity. Immunomodulating agents induce the production of cytokine cascades. In a primary cascade at injection sites TNF-alpha, GM-CSF and IL-1 are produced. TNF-alpha promotes migration of DC to lymphoid tissues, while GM-CSF and IL-1 accelerate the maturation of DC into efficient antigen-presenting cells for T-lymphocytes. In a secondary cytokine cascade in draining lymph nodes, DC produce IL-12, which induces Th1 responses with the production of IFN-gamma. The cytokines elicit cell-mediated immune responses and the formation of antibodies of protective isotypes, such as IgG2a in the mouse and IgG1 in humans. Antibodies of these isotypes activate complement and collaborate with antibody-dependent effector cells in protective immune responses.


Synergy effect of science and technology policies on innovation: Evidence from China.
This paper explores the synergy effect of the government subsidies, tax incentives, and government procurement on innovation based on synergy theory, and further analyzes its path and mechanism in the process of innovation. We find that government subsidies, tax incentives, and government procurement exert positive synergy effect on innovation. Furthermore, in the process of innovation, government subsidies are shown to play strongest roles in the stages of innovation input and technological development, while government procurement is the most crucial in the transformation stage of technological innovation, and tax incentives play balanced roles. We also find that innovation resource input, innovation technology spillover, and innovation cooperation all play partial mediating roles in the synergy effect of science and technology policies on innovation. This paper applies the synergy theory to the field of innovation policies, which enriches and expands relevant researches, and provides micro-evidence for in-depth understanding of the effect of science and technology policies on innovation.


[Effectiveness of a cryosurgical method in the treatment of primary localized skin cancer].
The long-term results of cryosurgical treatment of primary localized cutaneous cancer were studied in 930 patients with 1154 solitary and primary multiple synchronous and metachronous tumors. A high effectiveness of the method was established. The maximum therapeutical effect was noted in patients with I stage tumors and exophytic form of growth, the minimal one--with IIA stage tumors and endophytic form of growth irrespective of their location and histologic structure.


Interannual variability in the timing of New England shellfish toxicity and relationships to environmental forcing.
Routine monitoring along the coast of the Gulf of Maine (GoM) reveals shellfish toxicity nearly every summer, but at varying times, locations, and magnitudes. The responsible toxin is known to be produced by the dinoflagellate Alexandrium fundyense, yet there is little apparent association between Alexandrium abundance and shellfish toxicity. One possibility is that toxic cells are persistent in offshore areas and variability in shellfish toxicity is caused not by changes in overall abundance, but rather by variability in transport processes. Measurements of offshore Alexandrium biomass are scarce, so we bypass cell abundance as an explanatory variable and focus instead on the relations between shellfish toxicity and concurrent metrics of GoM meteorology, hydrology, and oceanography. While this yields over two decades (1985-2005) of data representing a variety of interannual conditions, the toxicity data are gappy in spatial and temporal coverage. We address this through a combination of parametric curve fitting and hierarchical cluster analysis to reveal eight archetypical modes of seasonal toxicity timing. Groups of locations are then formed that have similar interannual patterns in these archetypes. Finally, the interannual patterns within each group are related to available environmental metrics using classification trees. Results indicate that a weak cross-shore sea surface temperature (SST) gradient in the summer is the strongest correlate of shellfish toxicity, likely by signifying a hydrological connection between offshore Alexandrium populations and near-shore shellfish beds. High cumulative downwelling wind strength early in the season is revealed as a precursor consistent with this mechanism. Although previous studies suggest that alongshore transport is important in moving Alexandrium from the eastern to western GoM, alongshore SST gradient is not an important correlate of toxicity in our study. We conclude by discussing the implications of our results for designing efficient and effective shellfish monitoring programs along the GoM coast.


Four recombinant isoforms of Cor a I, the major allergen of hazel pollen, show different IgE-binding properties.
Previous studies showed that pollens from trees of the order Fagales (e.g. birch, alder, hazel and hornbeam) all contain one major allergen. These proteins are cross-reactive between these tree species, and approximately 95% of tree-pollen-allergic patients display IgE binding to these allergens. Using the reported N-terminal amino acid sequence of the hazel pollen allergen Cor a I, it was possible to amplify Cor-a-I cDNA by use of the polymerase chain reaction. Four clones with cDNA inserts were isolated. All four clones contained an open reading frame of 477 nucleotides (159 amino acids) but differed in length of their 3'-non-coding regions. Within the overlapping regions, the nucleotide sequence of the 3'-non-coding regions of the four clones were nearly identical. The open reading frames coded for different isoforms of the major hazel pollen allergen, Cor a I. The clones were designated Cor a I/5, 6, 11 and 16, respectively. Comparison of the deduced amino acid sequences of these Cor a I isoforms revealed identities of 96-99%. The sequence identities between the Cor a I isoforms and Bet v I, the major birch pollen allergen, were 71-73% (80.5-83% similarity). Comparing amino acid sequences of Cor a I isoforms with the published sequences of Aln g I, the major allergen from alder, and Car b I and isoforms, the major allergen from hornbeam, 75.5-76.7% identity (83.6-85% similarity) and 83.6-89.9% sequence identity (89.3-95% similarity), respectively, was found. The four Cor a I cDNAs were subcloned into plasmid pKK223-3 and expressed in Escherichia coli as non-fusion proteins; their capacity to bind serum IgE from tree-pollen-allergic patients was investigated. The four cloned isoforms showed an apparent molecular mass of 17 kDa in SDS/PAGE, identical to the natural, pollen-derived Cor a I. IgE antibodies from tree-pollen-allergic patients reacted with all four recombinant isoforms. However, we noted marked differences in the IgE-binding patterns of the distinct isoforms. Furthermore, Cor a I/11 was the only isoform recognized by the anti-(Bet v I) mAb, BIP 1. Our results demonstrate that Cor a I isoforms display different antigenic and allergenic properties, very likely due to few but significant changes in their amino acid sequences. These findings have implications for the development of reagents for diagnosis and immunotherapy of type I allergies.


Factors that affect decisions to receive (or not receive) life-sustaining treatment in advance care planning.
This study identifies factors that affect decisions people make regarding whether they want to receive life-sustaining treatment. It is an interpretive-descriptive study based on qualitative data from three focus groups (N = 23), representing a diverse population in central Pennsylvania. Study sites included a suburban senior center serving a primarily White, middle-class population; an urban senior center serving a frail, underserved, African American population; and a breast cancer support group. The most important factors affecting whether participants wished to receive life-sustaining medical treatment were prognosis, expected quality of life, burden to others, burden to oneself in terms of the medical condition and treatment, and effect on mental functioning and independence. Our findings contribute to the knowledge of the complex factors that influence how people make decisions about advance care planning and life-sustaining treatments. This understanding is critical if nurses are to translate the patient's goals, values, and preferences into an actionable medical plan.


Transcranial ultrasound as a risk marker for Parkinson's disease.
The question of early, even premotor, detection of Parkinson's disease (PD) has become a major issue because the effect of neuroprotective therapies depends on the time they are started. A number of clinical premotor markers which are helpful especially in the early diagnosis are being discussed; however, they are mostly unspecific and already signs of the progressing neurodegenerative process. An increasingly important risk marker for PD is genetic predisposition, as the number of known disease causing and modulating genes is increasing. Still, only the minority of PD cases can be attributed to monogenetic forms. Substantia nigra (SN) hyperechogenicity, assessed by transcranial sonography, has been shown to be a typical marker for PD. Because of its stability during the disease course, this echofeature is very helpful in early and differential diagnosis. Moreover, functional neuroimaging studies indicate a vulnerability of the nigrostriatal system of yet healthy subjects with SN hyperechogenicity. This vulnerability may become clinically relevant with age, under neuroleptic therapy, or under demanding motor tasks. The fact that still unaffected mutation carriers for monogenetic PD show this echofeature and that over the years some subjects with SN hyperechogenicity have already been observed to develop PD indicates that it may be regarded as a risk factor--a hypothesis which is currently being investigated in large prospective investigations.


Method of synthesized phase objects for pattern recognition: matched filtering.
To solve the pattern recognition problem, a method of synthesized phase objects is suggested. The essence of the suggested method is that synthesized phase objects are used instead of real amplitude objects. The former is object-dependent phase distributions calculated using the iterative Fourier-transform (IFT) algorithm. The method is experimentally studied with a Vander Lugt optical-digital 4F-correlator. We present the comparative analysis of recognition results using conventional and proposed methods, estimate the sensitivity of the latter to distortions of the structure of objects, and determine the applicability limits. It is demonstrated that the proposed method allows one: (а) to simplify the procedure of choice of recognition signs (criteria); (b) to obtain one-type δ-like recognition signals irrespective of the type of objects; (с) to improve signal-to-noise ratio (SNR) for correlation signals by 20 - 30 dB on average. The spatial separation of the Fourier-spectra of objects and optical noises of the correlator by means of the superposition of the phase grating on recognition objects at the recording of holographic filters and at the matched filtering has additionally improved SNR (>10 dB) for correlation signals. To introduce recognition objects in the correlator, we use a SLM LC-R 2500 device. Matched filters are recorded on a self-developing photopolymer.


[Bloodsucking mosquitoes on the irrigated lands of Kara-Kalpakia. 2. The annual cycle of Anopheles pulcherrimus].
The authors characterize the annual cycle of An. pulcherrimus population, distinguish the stages of this cycle that differ by the population composition and number and by the size of its area. The spatial structure of the population depends on the site of water bodies for wintering and the conditions at different territories. High numbers of mosquitoes were found in the southern part of the oasis at villages of rice-growing farmers. Mosquito population densities in the central parts of the oasis are much lower and are increased nearby sandy islets.


Effects of Nigella sativa oil and thymoquinone on oxidative stress and neuropathy in streptozotocin-induced diabetic rats.
We examined whether Nigella sativa (NS) oil and its active constituent thymoquinone (TQ) attenuate oxidative stress in the heart and brain in an experimental model of diabetes mellitus using streptozotocin (STZ). Oxidative stress was assessed by measuring cardiac and brain nitric oxide (NO), lipid peroxide levels, glutathione (GSH) and antioxidant enzyme activities, i.e. glutathione-S-transferase (GST) and catalase. Cardiac metabolic damage was estimated by measuring cardiac creatine kinase muscle and brain types (CK-MB). Brain monoamine levels were also evaluated. STZ diabetes induced a significant increase in heart and brain NO and malondialdehyde concentrations compared with the control group. These changes were attenuated by posttreatment of rats with NS oil and TQ. STZ diabetes induced oxidative stress via a significant decrease in GST, GSH and catalase. These lowered levels were improved by either NS oil or TQ administration. Serum CK-MB was decreased in the diabetic rats, which recovered with NS oil and TQ administration. During the course of diabetes, there was a marked increase in norepinephrine and dopamine concentrations and a marked decrease in serotonin concentration compared to the control group. These findings were partly reversed by oral administration of either NS oil or TQ. It is concluded that NS and TQ correct STZ-diabetes-induced alterations in CK-MB and brain monoamines due to their antioxidant properties.


Children subjected to cardiac surgery for congenital heart disease. Part 1 - emotional and psychological outcomes.
This study investigated the psychological and emotional functioning of children with congenital heart disease (CHD) subjected to surgery. Children aged 2-12 years with CHD who underwent cardiac surgery were enrolled. Information was collected prior to surgery and 12 months or later following surgery. Measures included assessment of the child's receptive vocabulary, adaptive behaviour skills, emotional and behavioural development, temperament and parent quality of life, as well as surgical data. Similar information was collected from a control group prior to undergoing non-cardiac surgery. Of the 69 children contacted to enrol, completed pre- and post-surgical data were obtained from 39 children, and pre-surgical data from 12 controls. Children with CHD subjected to surgery displayed psychological and emotional functioning indistinguishable from normative populations or the control group. These findings persisted at reassessment 12-50 months after surgery. Psychological functioning at follow-up was most closely related to functioning prior to surgery. Significant residual defects and the need for further surgery were associated with poorer functioning. The results suggest an optimistic psychological and emotional outcome following cardiac surgery. This study may assist in identifying children most at risk of adverse outcomes after cardiac surgery and help guide therapeutic interventional programmes.


Longitudinal teaching of obstetrics in family practice residency programs.
Family practice residency programs teach obstetrics using both hospital service block rotations and longitudinal management of family practice center pregnant patients. A national survey was conducted to identify characteristics and outcomes of residencies using family physicians and/or obstetricians as preceptors for the longitudinal teaching of obstetrics. Obstetricians were used as preceptors in both outpatient and delivery room settings in 18% of residencies. Family physicians were used in the outpatient setting and obstetricians in the delivery room in 27% of programs. The 37% of programs using family physician faculty as preceptors in both outpatient and delivery room settings differed from other programs in four significant ways: they were most likely to be medical school or military residency programs; they were most likely to be located in the north central and mountain states; they reported greater general satisfaction with their preceptors; and more of their graduates practiced obstetrics after residency.


Unfolded aplanats for high-concentration photovoltaics.
The exigencies of high-concentration photovoltaics motivate optics that (1) obviate the need for optical bonds, (2) exhibit maximal optical tolerance, (3) are not damaged at off-axis orientation, and (4) allow convenient location of the solar cell and heat sink. We show that dual-mirror unfolded aplanats can satisfy all these criteria. Lens enhancement improves compactness and, with millimeter-scale cells, concentrator depth is only a few centimeters, amenable to precise large-volume fabrication.


Prescription opioid dispensing in New South Wales, Australia: spatial and temporal variation.
Patterns of opioid dispensing often exhibit substantial temporal and geographical variability, which has implications for public health policy decisions and interventions. The study examined recent trends in prescription opioid dispensing and identified high dispensing areas and factors associated with the doses dispensed. Three years (1 January 2013-31 December 2015) of dispensing data of prescription opioids in local government areas (LGAs) for New South Wales (NSW), Australia's most populous state, were analyzed. The proportion of individuals who were dispensed opioids was computed for four age-groups. A Chi-square test was used to examine trends over time in proportions of the population who were dispensed opioids in four age-groups. The number of prescriptions over time and quantities in daily defined dose/1000 people/day (denoted DDD) were also examined. LGAs with relatively high levels of dispensing were identified and mapped. A multivariate regression model was used to identify factors associated with DDD. Overall, codeine, oxycodone and tramadol were the main opioids in terms of DDD, number of prescriptions and number of individuals who were dispensed these medications. Quantity (in DDD), and population dispensed to were consistently higher for women than men over time. Proportions of individuals who were dispensed opioids increased significantly over time in all four age-groups. In the multivariate model, age, urbanization, sex and socio-economic indexes for areas were significantly associated with doses dispensed among opioid users. All areas with very high dispensing were outside major metropolitan areas. Given that over-use of opioids is a major public health problem and that long-term use has substantial side effects including dependence, it is important to understand spatial patterns of opioid prescribing to enable targeted interventions. Nationwide implementation of real-time drug-monitoring programs and access to monitoring databases from both doctor and pharmacy point-of-care sources may potentially reduce excessive and undue use of opioid.


Background correction of personal dose distributions by a novel unfolding algorithm.
The dosimetry service Seibersdorf monitors more than 20,000 persons with typical monitoring period of one month. The use of thermoluminescence (TL)-dosemeters during the last 30 years allows measurements of even low dose values (some 10 muSv) with sufficient uncertainty. Consideration of the natural background contribution or transport dose which needs to be subtracted from the measured dose requires special protocols which differ significantly from country to country. The chosen protocol has not only a strong influence on the individual dose values (especially for low doses) but changes significantly the whole dose distribution function, as well as the corresponding statistical describing parameters (mean doses, median values, etc.) of these distributions. On the basis of the measured (uncorrected) distribution function the attempt was made to extract both the background doses as well as the remaining occupationally caused dose contribution. For this approach the uncorrected dose values of all customers from several years were analysed and a superposition of two independent log-normal distributions was assumed. By means of a new unfolding algorithm both components were isolated and the corresponding parameters were calculated. The paper gives a detailed description of the procedure and summarises the resulting dose distributions.


Cabazitaxel for the second-line treatment of metastatic hormone-refractory prostate cancer: a NICE single technology appraisal.
The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of cabazitaxel (Jevtana®, sanofi-aventis, UK) to submit evidence of its clinical and cost effectiveness for the second-line treatment of metastatic hormone-refractory prostate cancer (mHRPC). The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. Clinical evidence was derived from a multinational randomized open-label phase III trial of cabazitaxel plus prednisone or prednisolone in men with mHRPC that had progressed during or following treatment with docetaxel. The comparator was mitoxantrone plus prednisone or prednisolone. Use of cabazitaxel was associated with a statistically significant improvement in overall survival, median progression-free survival and time to tumour progression. However, it was also associated with an increased incidence of adverse events such as neutropenia. Utility data were based on interim results from the early access programme for cabazitaxel. Data were only available for a small number of patients with stable disease, resulting in great uncertainty as to the effect of cabazitaxel on quality of life. For their economic evaluation, the manufacturer estimated that the use of cabazitaxel was associated with an incremental cost of £74,908 per QALY gained. However, the ERG disagreed with the manufacturer over two key methodological points. The first concerned modelling and extrapolating survival; the second point was concerned with the choice of patient population. The ERG altered the manufacturer's evaluation to take into account these two points of disagreement. The resulting cost per QALY gained was £82,950. The NICE Appraisal Committee believed the analysis presented by the ERG to be more plausible, and likely to be an underestimate of the cost per QALY. They concluded that whilst the clinical effectiveness of cabazitaxel had been proven, it was not likely to represent a cost-effective use of NHS resources and so its use could not be recommended.


Preservation of the value of rice paddy fields: Investigating how to prevent farmers from abandoning the fields by means of evolutionary game theory.
The evolution of group cooperation is still an evolutionary puzzle and has been studied from the perspective of not only evolutionary ecology but also social sciences. Some socio-ecological problems are caused by collapse of group cooperation. By applying theoretical studies about the evolution of cooperation, we can elucidate what causes the problems and find solutions. One of the appropriate examples is maintaining rice paddy field landscapes, which are a grand spectacle in Asia, and some are UNESCO world heritage sites. These magnificent landscapes and the associated biodiversity are at risk of abandonment for social and financial reasons. Rice paddy fields can be preserved not only by regular cultivation, which requires farmers to invest effort in cultivation, but also by the maintenance of common facilities such as irrigation canals. To investigate how this landscape might be preserved, we developed an agent-based model in which each farmer makes two types of efforts: an effort for land cultivation and an effort for collective action such as common facility maintenance. Additionally, we consider the side effects of rice production such as field deterioration from abandonment and water use competition. These factors determine the utility of each player who imitates the level of efforts necessary to invest in land cultivation and common facility maintenance of one with higher utility. This decision-making of each player can be described by the evolutionary game theory. We find that maintenance effort promotes cultivation effort, but not vice versa, even though we usually consider that each farmer's cultivation effort makes rice field landscape sustainable. We also find that if players and their near neighbors are responsible for maintaining their common facilities together, they continue to maintain them and cultivate, but if all players are responsible for maintaining all facilities in the whole farmland, players are likely to quit facility maintenance and stop cultivation. Competition for water use among all players, however, promotes cultivation more than competition among neighbors only. Therefore, rice paddy field landscapes can be sustainable if neighbors, but not the whole players, are responsible for maintaining their common facilities and cooperate together, and if the water usage of all players, but not neighbors, influences the productivity of each rice field.


An integrated map of Arabidopsis thaliana for functional analysis of its genome sequence.
The genome of the model plant species Arabidopsis thaliana has recently been sequenced. To accelerate its current genome research, we developed a whole-genome, BAC/BIBAC-based, integrated physical, genetic, and sequence map of the A. thaliana ecotype Columbia. This new map was constructed from the clones of a new plant-transformation-competent BIBAC library and is integrated with the existing sequence map. The clones were restriction fingerprinted by DNA sequencing gel-based electrophoresis, assembled into contigs, and anchored to an existing genetic map. The map consists of 194 BAC/BIBAC contigs, spanning 126 Mb of the 130-Mb Arabidopsis genome. A total of 120 contigs, spanning 114 Mb, were anchored to the chromosomes of Arabidopsis. Accuracy of the integrated map was verified using the existing physical and sequence maps and numerous DNA markers. Integration of the new map with the sequence map has enabled gap closure of the sequence map and will facilitate functional analysis of the genome sequence. The method used here has been demonstrated to be sufficient for whole-genome physical mapping from large-insert random bacterial clones and thus is applicable to rapid development of whole-genome physical maps for other species.


Copy Number Variation Analysis of IL22 and LCE3C in Different Subtypes of Psoriasis in a Chinese Han Population.
BACKGROUND Psoriasis is a chronic, immune-mediated and hyperproliferative skin disease with both genetic and environmental components. Copy number variations (CNV) of IL22 and LCE3C-LCE3B deletion have been confirmed to be predisposed to psoriasis vulgaris (PsV) in several ethnic groups. However, it remains to be clarified whether CNVs of IL22 and LCE3C are associated with different subtypes of psoriasis (psoriatic arthritis, PsA; erythrodermic psoriasis, EP; and generalized pustular psoriasis, GPP). MATERIAL AND METHODS We enrolled 897 Han Chinese individuals, including 478 patients and 419 healthy controls, and detected CNVs of IL22 and LCE3C using the comparative CT method by real-time PCR, and Pearson's χ² test was used to evaluated the copy number difference among subtypes. RESULTS CNVs of IL22 were significantly higher in PsV than in healthy controls (P<0.001). CNV of LCE3C in PsV, PsA, and GPP groups were significantly lower compared to healthy controls. When linked with clinical parameters, mild psoriasis carried less IL22 copy numbers than that in severe psoriasis (P=0.043). Neither IL22 or LCE3C CNVs were associated with age of onset. CONCLUSIONS CNVs of LCE3C and IL22 might differentially contribute to subtypes of psoriasis. These findings suggest complex and diverse genetic variations in and among different clinical subtypes of psoriasis.


IgG Avidity: an Important Serologic Marker for the Diagnosis of Tick-Borne Encephalitis Virus Infection.
A total of 52 serum samples from patients with symptoms suggestive of tick-borne encephalitis virus (TBEV) infection and positive IgM and/or IgG antibodies were tested for IgG avidity. Acute/recent TBEV infection was confirmed by low/borderline avidity index (AI) in 94.8% IgM positive/IgG positive samples, while in 5.2% high AI was found indicating persisting IgM antibodies. Majority of IgM negative/IgG positive samples (78.6%) showed high AI consistent with past TBEV infection. However, in 21.3% patients without measurable IgM antibodies current/recent infection was confirmed by AI. IgG avidity represents an additional serologic marker that improves diagnosis of TBEV, especially in cases of atypical antibody response.


[NADH- and NADPH-dependent formation of superoxide radicals in liver nuclei].
A method for the quantitation of the superoxide radical generation rate (V) in murine liver nuclei by the oxidation of 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine O2-. radicals with the formation of a stable nitroxyl radical recorded by the EPR method, has been developed. It was shown that NADP- and NADPH-dependent superoxide radical generation is suppressed by superoxide dismutase (approximately by 90%). The Km values for NADH and NADPH are 1.5 x 10(-6) and 4.4 x 10(-7) M, respectively; the maximal rate (0.2 nmol.min-1.mg protein-1) is equal for both substrates. Cyanide (greater than 2 mM) causes a practically complete inhibition of the O2-. generation by both substrates. It is suggested that there exists a single readily autooxidized site of O2-. generation by both substrates for NADH- and NADPH-dependent site of the electron transport chain in nuclear membranes.


Death among primates: a critical review of non-human primate interactions towards their dead and dying.
For the past two centuries, non-human primates have been reported to inspect, protect, retrieve, carry or drag the dead bodies of their conspecifics and, for nearly the same amount of time, sparse scientific attention has been paid to such behaviours. Given that there exists a considerable gap in the fossil and archaeological record concerning how early hominins might have interacted with their dead, extant primates may provide valuable insight into how and in which contexts thanatological behaviours would have occurred. First, we outline a comprehensive history of comparative thanatology in non-human primates, from the earliest accounts to the present, uncovering the interpretations of previous researchers and their contributions to the field of primate thanatology. Many of the typical behavioural patterns towards the dead seen in the past are consistent with those observed today. Second, we review recent evidence of thanatological responses and organise it into distinct terminologies: direct interactions (physical contact with the corpse) and secondary interactions (guarding the corpse, vigils and visitations). Third, we provide a critical evaluation regarding the form and function of the behavioural and emotional aspects of these responses towards infants and adults, also comparing them with non-conspecifics. We suggest that thanatological interactions: promote a faster re-categorisation from living to dead, decrease costly vigilant/caregiving behaviours, are crucial to the management of grieving responses, update position in the group's hierarchy, and accelerate the formation of new social bonds. Fourth, we propose an integrated model of Life-Death Awareness, whereupon neural circuitry dedicated towards detecting life, i.e. the agency system (animate agency, intentional agency, mentalistic agency) works with a corresponding system that interacts with it on a decision-making level (animate/inanimate distinction, living/dead discrimination, death awareness). Theoretically, both systems are governed by specific cognitive mechanisms (perceptual categories, associative concepts and high-order reasoning, respectively). Fifth, we present an evolutionary timeline from rudimentary thanatological responses likely occurring in earlier non-human primates during the Eocene to the more elaborate mortuary practices attributed to genus Homo throughout the Pleistocene. Finally, we discuss the importance of detailed reports on primate thanatology and propose several empirical avenues to shed further light on this topic. This review expands and builds upon previous attempts to evaluate the body of knowledge on this subject, providing an integrative perspective and bringing together different fields of research to detail the evolutionary, sensory/cognitive, developmental and historical/archaeological aspects of primate thanatology. Considering all these findings and given their cognitive abilities, we argue that non-human primates are capable of an implicit awareness of death.


Molecular entanglement and electrospinnability of biopolymers.
Electrospinning is a fascinating technique to fabricate micro- to nano-scale fibers from a wide variety of materials. For biopolymers, molecular entanglement of the constituent polymers in the spinning dope was found to be an essential prerequisite for successful electrospinning. Rheology is a powerful tool to probe the molecular conformation and interaction of biopolymers. In this report, we demonstrate the protocol for utilizing rheology to evaluate the electrospinnability of two biopolymers, starch and pullulan, from their dimethyl sulfoxide (DMSO)/water dispersions. Well-formed starch and pullulan fibers with average diameters in the submicron to micron range were obtained. Electrospinnability was evaluated by visual and microscopic observation of the fibers formed. By correlating the rheological properties of the dispersions to their electrospinnability, we demonstrate that molecular conformation, molecular entanglement, and shear viscosity all affect electrospinning. Rheology is not only useful in solvent system selection and process optimization, but also in understanding the mechanism of fiber formation on a molecular level.


Native-language N400 and P600 predict dissociable language-learning abilities in adults.
Language learning aptitude during adulthood varies markedly across individuals. An individual's native-language ability has been associated with success in learning a new language as an adult. However, little is known about how native-language processing affects learning success and what neural markers of native-language processing, if any, are related to success in learning. We therefore related variation in electrophysiology during native-language processing to success in learning a novel artificial language. Event-related potentials (ERPs) were recorded while native English speakers judged the acceptability of English sentences prior to learning an artificial language. There was a trend towards a double dissociation between native-language ERPs and their relationships to novel syntax and vocabulary learning. Individuals who exhibited a greater N400 effect when processing English semantics showed better future learning of the artificial language overall. The N400 effect was related to syntax learning via its specific relationship to vocabulary learning. In contrast, the P600 effect size when processing English syntax predicted future syntax learning but not vocabulary learning. These findings show that distinct neural signatures of native-language processing relate to dissociable abilities for learning novel semantic and syntactic information.


Cardiopulmonary bypass in the successful resuscitation of a 28-year-old woman with cardiac arrest.
This patient remained hospitalized for several weeks, and her stay was relatively uneventful. She extubated herself 2 days after admission, after an operative procedure to remove the cannulas and repair the right femoral cutdown site. A fasciotomy of her right calf was done for compartment syndrome. The patient had minor neurologic deficits of short-term memory loss and spatial depth perception loss. These deficits, attributed to postresuscitative hypoxia, eventually resolved. Extensive cardiac testing performed to pinpoint the underlying cause of her cardiac dysfunction were inconclusive. Because no cause was found, an automatic implantable cardiodefribrillator was recommended to prevent future cardiac events. The patient agreed and the device was implanted before her discharge. With expert occupational therapy, physical rehabilitation, nursing care, and medical treatment the patient regained her previous level of functioning. Her October wedding was postponed to December, but she was able to return to work in November 1990.


Development of a risk stratification model for pharmaceutical care in HIV patients.
The increasing number of HIV-patients and their complexity makes it necessary to develop risk classification tools to improve the optimization of resources. To design a risk-stratified model for pharmaceutical care (PC) in HIV-patients. A cross-sectional, multicenter study. An expert panel was created by Hospital Pharmacist experienced in PC for HIV-patients. The study was designed in 4 phases. The first phase included a review of literature and the development of a summary of the scientific evidence available. According to their score, patients were stratified into three levels of PC. In the second and third phases, a sample of patients was assessed and data information was recorded. The overall analysis also allowed pharmacists to define the actions to be applied at each level of priority.Finally, each stratification model was applied to a new sample of patients to verify their applicability and usefulness. Results: All variables included in the model were weighted in terms of their relative relevance compared to the rest. A sample of 215 patients was evaluated to obtain their score and distribution: Priority-1: score ≥ 32 and 10% of the sample; Priority-2: 18-31.9 and 30%; Priority-3: ≤ 17 and 60%. The PC interventions corresponding to each level of priority were classified into "pharmacotherapeutic monitoring", "training, education and patient tracking" and "coordination of all the healthcare team members". This study supported the design and adaptation of a selection and stratification model for PC in HIV-patients as a tool to identify those who may benefit from priority intervention.


Specific affinity-labeling of the nociceptin ORL1 receptor using a thiol-activated Cys(Npys)-containing peptide ligand.
We previously showed that an antagonist-based peptide ligand, H-Cys(Npys)-Arg-Tyr-Tyr-Arg- Ile-Lys-NH2 , captures the free thiol groups in the ligand-binding site of the nociceptin receptor ORL1. However, the exact receptor sites of this thiol-disulfide exchange reaction have not been uncovered, although such identification would help to clarify the ligand recognition site. Since the Cys→Ala substitution prevents the reaction, we performed the so-called Ala scanning for all the Cys residues in the transmembrane (TM) domains of the ORL1 receptor. Seven different mutant receptors were soundly expressed in the COS-7 cells and examined for their specific affinity labeling by a competitive binding assay using nociceptin and [(3) H]nociceptin. The results of in vitro Ala scanning analyses revealed that the labeled residues were Cys59 in TM1, Cys215 and Cys231 in TM5, and Cys310 in TM7. The present study has provided a novel method of Cys(Npys)-affinity labeling for identification of the ligand-binding sites in the ORL1 receptor. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 460-469, 2016.


Cytogenetic heterogeneity negatively impacts outcomes in patients with acute myeloid leukemia.
Clonal heterogeneity is a hallmark of malignant transformation. In acute myeloid leukemia, acquired cytogenetic abnormalities are important independent predictors of initial response to therapy, remission duration, and overall survival. However, whether the presence of multiple cytogenetically characterized clones affects outcomes in acute myeloid leukemia is still not well defined. The aim of this study was to assess the prognostic impact of cytogenetic clonal heterogeneity in acute myeloid leukemia. This analysis included 1403 newly diagnosed acute myeloid leukemia patients fit for intensive chemotherapy, aged between 15 and 88 years, enrolled on Southwest Oncology Group protocols. The presence of multiple cytogenetic clones was found in 164 (24%) patients with abnormal karyotype. The proportion of patients with clonal heterogeneity increased with age, being present in 20% of patients under 40 years of age, but in 30% of those aged over 70 years (P=0.03). Clonal heterogeneity was significantly more common in association with unfavorable karyotype. Clonal heterogeneity was associated with decreased response rates and inferior event-free, relapse-free and overall survival, and was confirmed as an independent predictor of poor prognosis in multivariable analysis. Subgroup analysis showed that clonal heterogeneity adds prognostic information particularly in the unfavorable karyotype group. Our results confirm the negative prognostic impact of clonal heterogeneity in acute myeloid leukemia patients with abnormal karyotype. (clinicaltrials.gov identifiers: 014343329; 01338974; 00899171; 1059734; 01059734; 00899743; 0143329; 00023777; 00085709; 01360125; 00004217).


[Public perceptions of the risk of Asian dust storms in Seoul and its metropolitan area].
In spite of the recent increased concern for Asian dust storms, there are few studies concerning how dangerous the general public recognizes these dust storms to be. This study examined the public's perceptions of the risk of the Asian dust storms and also the source of the information concerning the risk. A telephone interview survey using a standardized questionnaire was done for the adults living in Seoul and its metropolitan area from May 15th, 2003 to May 16th, 2003. The contents of the questionnaire were the sociodemographic characteristics, the perceptions of risk to the Asian dust storms, and the coping strategy of the study participants. The study participants get their information on Asian dust storms mainly from TV newscasts and they have a good knowledge of them. They regard it as one of the most dangerous health risks, along with dioxin. They think that it is associated with allergic rhinitis, conjunctivitis and bronchial asthma, etc. Of the 500 study participants, 201(40.2%) persons suffered bodily discomforts during the Asian dust storm period. Although there are uncertainties about the health risks of Asian dust storms, the public thinks these dust storms are very dangerous to health in many ways. This negative perception will not disappear easily. To fill the gap of the public's perceptions of the risk and the objective evidence of its health effects, more studies about its health effects and the methods to reduce exposure are required.


Quality of life on long-term parenteral nutrition: can it be an indication for intestinal transplantation?
Long-term outcomes in patients with intestinal failure and following intestine transplantation have improved significantly over the last decade. With these improvements, listing criteria for intestine transplantation are reevaluated and the role of quality of life (QoL) in patients' outcome is increasingly studied and emphasized. Here, we review the recent literature on QoL before and after intestine transplantation and discuss whether QoL should be considered as a listing criterion for intestine transplantation. Patients on home parenteral nutrition, experience lower QoL compared with healthy population and equal or lower QoL than patients with other chronic diseases. After transplantation, QoL improves and is comparable in some QoL domains to that of the general population. These findings are limited by heterogeneous study designs and sample size. Although QoL improves after intestine transplantation, long-term survival of patients receiving HPN surpass postintestine transplantation survival. Poor QoL is not associated with an increased mortality in patients receiving HPN. Current survival outcomes of intestine transplantation do not justify poor QoL as a single listing criterion for intestine transplantation. However, intestine transplantation should be considered in patients with unique circumstances of extremely poor QoL. This approach may change once postintestine transplantation patient survival will further improve.


The mitochondrial genome of Angiostrongylus mackerrasae is distinct from A. cantonensis and A. malaysiensis.
The native rat lungworm (Angiostrongylus mackerrasae) and the invasive rat lungworm (Angiostrongylus cantonensis) occur in eastern Australia. The species identity of A. mackerrasae remained unquestioned until relatively recently, when compilation of mtDNA data indicated that A. mackerrasae sensu Aghazadeh et al. (2015b) clusters within A. cantonensis based on their mitochondrial genomes (mtDNA). To re-evaluate the species identity of A. mackerrasae, we sought material that would be morphologically conspecific with A. mackerrasae. We combined morphological and molecular approaches to confirm or refute the specific status of A. mackerrasae. Nematodes conspecific with A. mackerrasae from Rattus fuscipes and Rattus rattus were collected in Queensland, Australia. Morphologically identified A. mackerrasae voucher specimens were characterized using amplification of cox1 followed by the generation of reference complete mtDNA. The morphologically distinct A. cantonensis, A. mackerrasae and A. malaysiensis are genetically distinguishable forming a monophyletic mtDNA lineage. We conclude that A. mackerrasae sensu Aghazadeh et al. (2015b) is a misidentified specimen of A. cantonensis. The availability of the mtDNA genome of A. mackerrasae enables its unequivocal genetic identification and differentiation from other Angiostrongylus species.


Comparative anti-caries effects of tablet and liquid fluorides in cleft children.
Children with cleft lip and/or palate are at a higher risk for developing caries of the primary incisors compared with non-cleft children. To determine whether fluoride in tablet or liquid form would be more efficacious with children with cleft lip and/or palate, a two-year clinical investigation was conducted to test the anti-caries effects. One-hundred and fifteen cleft children (59 boys and 56 girls) between 22 and 26 months old were randomly selected into control, tablet and liquid fluoride groups. The amount of administered fluoride was 0.25 mg F daily in non-fluoridated Taiwan. Dental examinations were conducted using mirrors and #23 explorers. Caries were assessed using the DMF index in the baseline, first year and second year. The results showed that children in the tablet and liquid groups had a significantly lower DMFT increment than in the control group (p < 0.05). In the DMFS index, children in the liquid group showed a significantly lower caries increment than in the control group (p < 0.01), and children in the tablet group presented a borderline, but non-significant statistical difference when compared with the control group (p = 0.065). No significant statistical difference was found in either DMFT or DMFS between tablet and liquid fluoride administrations (p = 0.521 and p = 0.383, respectively). It is concluded that dietary fluoride supplements in liquid form show efficacy in reducing early childhood caries in the cleft children. Liquid fluoride showed slightly better numerical anti-caries effect than tablet fluoride, which is possibly due to its ease of administration with small children.


Inducible displacement of a trabecular metal tibial monoblock component.
Radiostereometric analysis is a highly accurate technique that can be used for measuring micromotion at the bone-implant interface. The purpose of this study was to compare the inducible displacement of the uncemented Trabecular Metal (TM; Zimmer, Warsaw, Ind) tibial monoblock component with that of a cemented implant. Inducible displacement of 14 uncemented TM components and 11 cemented components was measured 24 to 48 months postoperatively. Longitudinal migration of the implants was also measured with radiostereometric analysis at 6, 12, and 24 months postoperatively. The uncemented TM group had significantly lower inducible displacement than the cemented components. Significant correlations were found between longitudinal migration and the inducible displacement tests. The low values of inducible displacement in the TM group indicated good fixation and a promising long-term prognosis.


Modeling enzootic raccoon rabies from land use patterns - Georgia (USA) 2006-2010.
We analyzed how land-use patterns and changes in urbanization influence reported rabid raccoons in Georgia from 2006 - 2010. Using Geographical Information Systems and rabies surveillance data, multivariate analysis was conducted on 15 land-use variables that included natural topography, agricultural development, and urbanization to model positive raccoon rabies cases while controlling for potential raccoon submission bias associated with higher human population densities. Low intensity residential development was positively associated with reported rabid raccoons while a negative association was found with evergreen forest. Evergreen forests may offer a barrier effect where resources are low and raccoon populations are not supported. Areas with pure stands of upland evergreen forest might be utilized in baiting strategies for oral rabies vaccination programs where fewer or no baits may be needed. Their use as a barrier should be considered carefully in a cost-effective strategy for oral rabies vaccination (ORV) programs to contain the western spread of this important zoonotic disease.


A genome-wide association study of host genetic determinants of the antibody response to Anthrax Vaccine Adsorbed.
Several lines of evidence have supported a host genetic contribution to vaccine response, but genome-wide assessments for specific determinants have been sparse. Here we describe a genome-wide association study (GWAS) of protective antigen-specific antibody (AbPA) responses among 726 European-Americans who received Anthrax Vaccine Adsorbed (AVA) as part of a clinical trial. After quality control, 736,996 SNPs were tested for association with the AbPA response to 3 or 4 AVA vaccinations given over a 6-month period. No SNP achieved the threshold of genome-wide significance (p=5 × 10(-8)), but suggestive associations (p<1 × 10(-5)) were observed for SNPs in or near the class II region of the major histocompatibility complex (MHC), in the promoter region of SPSB1, and adjacent to MEX3C. Multivariable regression modeling suggested that much of the association signal within the MHC corresponded to previously identified HLA DR-DQ haplotypes involving component HLA-DRB1 alleles of *15:01, *01:01, or *01:02. We estimated the proportion of additive genetic variance explained by common SNP variation for the AbPA response after the 6 month vaccination. This analysis indicated a significant, albeit imprecisely estimated, contribution of variation tagged by common polymorphisms (p=0.032). Future studies will be required to replicate these findings in European Americans and to further elucidate the host genetic factors underlying variable immune response to AVA.


[Importance of the post-prandial glycemia in the management of type 2 diabetes].
Cardiovascular disease is the main cause of mortality in diabetic patients. The risk of cardiovascular disease occurs at a lower glycemic level compared to microvascular complications. Post-prandial hyperglycemia seems to play a major role in the development of atherosclerotic lesions. In this article we review the evidence regarding the prognostic value of post-challenge hyperglycaemia relative to the risk of cardiovascular disease, explore the physio-pathologic mechanisms responsible for the negative effects of post-prandial hyperglycaemia and detail the benefits of treatment aimed at controlling post-prandial glycaemia.


Does acetylsalicylic acid or warfarin affect the accuracy of fecal occult blood tests?
Current guidelines for screening of colorectal cancer do not offer specific recommendations for cessation of antithrombotic agents prior to fecal occult blood test (FOBT). To asess the accuracy of FOBT in patients taking acetylsalicylic acid (ASA) or warfarin. A literature search was conducted for studies that investigated the accuracy of FOBT in patients taking ASA and warfarin. The primary outcome was the pooled relative risk (RR) for true positive FOBT for detecting significant colonic neoplasia in patients taking ASA or warfarin compared with controls. The secondary outcome was a pooled RR for true positive in guaiac FOBT (g-FOBT) compared with immunochemical FOBT (i-FOBT). Five observational studies included 759 patients taking ASA and 1652 control subjects. In patients taking ASA, pooled RR for true positive FOBT was 0.82 (95% confidence interval [CI] 0.73-0.93, P=0.0009), pooled RR for true positive g-FOBT was 0.69 (95% CI 0.60-0.79, P<0.0001), whereas pooled RR for true positive i-FOBT was 1.013 (95% CI 0.81-1.30, P=0.8182). Five observational studies included 806 patients taking warfarin and 10 338 control subjects. In patients taking warfarin, pooled RR for true positive FOBT was 1.559 (95% CI 1.349-1.801, P<0.0001). The results of our meta-analysis demonstrate that in patients taking ASA, there is a decrease in the positive predictive value (PPV) of g-FOBT but no significant difference in the PPV of i-FOBT compared with control subjects for detecting significant neoplasia. In patients taking warfarin, the PPV of FOBT was increased for detection of colorectal cancer compared with control subjects.


Simultaneous Stress and Field Control of Sustainable Switching of Ferroelectric Phases.
In ferroelectrics, manifestation of a strong electromechanical coupling is attributed to both engineered domain morphology and phase transformations. However, realization of large sustainable and reversible strains and polarization rotation has been limited by fatigue, nonlinearity and hysteresis losses. Here, we demonstrate that large strain and polarization rotation can be generated for over 40 × 10(6) cycles with little fatigue by realization of a reversible ferroelectric-ferroelectric phase transition in [011] cut Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 (PIN-PMN-PT) relaxor ferroelectric single crystal. Direct tuning of this effect through combination of stress and applied electric field, confirmed both macroscopically and microscopically with x-ray and Raman scattering, reveals the local symmetry while sweeping through the transition with a low applied electric field (<0.2 MV/m) under mechanical stress. The observed change in local symmetry as determined by x-ray scattering confirms a proposed polarization rotation mechanism corresponding to a transition between rhombohedral and orthorhombic phases. These results shed more light onto the nature of this reversible transformation between two ferroelectric phases and advance towards the development of a wide range of ferroic and multiferroic devices.


Savant Genome Browser 2: visualization and analysis for population-scale genomics.
High-throughput sequencing (HTS) technologies are providing an unprecedented capacity for data generation, and there is a corresponding need for efficient data exploration and analysis capabilities. Although most existing tools for HTS data analysis are developed for either automated (e.g. genotyping) or visualization (e.g. genome browsing) purposes, such tools are most powerful when combined. For example, integration of visualization and computation allows users to iteratively refine their analyses by updating computational parameters within the visual framework in real-time. Here we introduce the second version of the Savant Genome Browser, a standalone program for visual and computational analysis of HTS data. Savant substantially improves upon its predecessor and existing tools by introducing innovative visualization modes and navigation interfaces for several genomic datatypes, and synergizing visual and automated analyses in a way that is powerful yet easy even for non-expert users. We also present a number of plugins that were developed by the Savant Community, which demonstrate the power of integrating visual and automated analyses using Savant. The Savant Genome Browser is freely available (open source) at www.savantbrowser.com.


The Prevalence of Substance Misuse and its Effects among Omani College Students: A Cross-sectional Study.
Many studies have confirmed that the use of alcohol, tobacco, and cannabis is prevalent among university students. This study aimed to assess the prevalence of substance misuse among college students in Oman, identifying the most commonly used substances, and reviewing the effect of substance misuse on the students' performance. This cross-sectional study was conducted in a higher learning institution in an urban setting in Oman from April 2018 to December 2018. A descriptive, self-administered online questionnaire, the Alcohol, Smoking, and Substance Involvement Screening Test, version 3.0 (Arabic version), adapted from the World Health Organization was sent to 12 000 students at the college. The sample size was calculated using online software (Raosoft), with a margin of error of 5% and a confidence level of 95%. A total of 375 students responded (response rate = 3.1%). The overall lifetime prevalence for any substance misuse (including tobacco and alcohol) among the participants was 41.3%, with the overall prevalence without tobacco or alcohol at 29.9%. Tobacco was the most common substance used, with a prevalence of around 23.5%, followed by alcohol at 10.7%. Male students had a significantly higher rate of substance abuse, for any substance, compared to female students (p < 0.001). There was a significant correlation between tobacco use, alcohol misuse, and misuse of other substances. Most of the adverse effects attributed to substance misuse reported by the respondents in this study were social (27.7%) and health-related (25.8%) problems. The impact of substance abuse on their performance was also high (23.8%). Furthermore, 15.4% of the respondents had financial problems, and 4.7%% were struggling with legal issues. Notably, only 49.1% of the respondents perceived that substance misuse was a serious problem. Although college students are expected to be more aware of the negative impacts of substance misuse, this study found a high prevalence of smoking, alcohol, and other substance misuses among the group of Omani college students. Further research in this field is essential, and the results of this study have shed light on a critical problem among Omani college students. It is hoped that the findings of this study will be used and built on in future research to recognize students at risk of substance misuse from early school life, leading to early intervention, and potentially preventing the possible negative consequences.


The use of research evidence in public health decision making processes: systematic review.
The use of research evidence to underpin public health policy is strongly promoted. However, its implementation has not been straightforward. The objectives of this systematic review were to synthesise empirical evidence on the use of research evidence by public health decision makers in settings with universal health care systems. To locate eligible studies, 13 bibliographic databases were screened, organisational websites were scanned, key informants were contacted and bibliographies of included studies were scrutinised. Two reviewers independently assessed studies for inclusion, extracted data and assessed methodological quality. Data were synthesised as a narrative review. 18 studies were included: 15 qualitative studies, and three surveys. Their methodological quality was mixed. They were set in a range of country and decision making settings. Study participants included 1063 public health decision makers, 72 researchers, and 174 with overlapping roles. Decision making processes varied widely between settings, and were viewed differently by key players. A range of research evidence was accessed. However, there was no reliable evidence on the extent of its use. Its impact was often indirect, competing with other influences. Barriers to the use of research evidence included: decision makers' perceptions of research evidence; the gulf between researchers and decision makers; the culture of decision making; competing influences on decision making; and practical constraints. Suggested (but largely untested) ways of overcoming these barriers included: research targeted at the needs of decision makers; research clearly highlighting key messages; and capacity building. There was little evidence on the role of research evidence in decision making to reduce inequalities. To more effectively implement research informed public health policy, action is required by decision makers and researchers to address the barriers identified in this systematic review. There is an urgent need for evidence to support the use of research evidence to inform public health decision making to reduce inequalities.


Vascular components of cerebrospinal fluid compensation.
The aim of the study was to assess how cerebrospinal fluid (CSF) pressure-volume compensation depends on cerebrovascular tone. In 26 New Zealand White rabbits, intracranial pressure (ICP), arterial blood pressure, and basilar artery blood flow velocity were measured continuously. Saline was infused into the cranial subarachnoid space to assess CSF compensatory parameters: the resistance to CSF outflow, the elastance coefficient, and the amplitude of the ICP pulsatile waveform. Infusions were repeated on two different levels of CO2 concentration in the arterial blood (PaCO2), at normotension and hypotension, and after the death of the animal. An increase in PaCO2 from a mean of 27 to 48 mm Hg was accompanied by an 18% increase in the resistance to CSF outflow (p<0.005) and a 64% increase (p<0.05) in the elastance coefficient. A decrease in arterial blood pressure from a mean of 100 to 51 mm Hg caused a 25% decrease in CSF outflow resistance (p<0.01) but did not affect the elastance coefficient. Postmortem, a 23% decrease in the CSF outflow resistance was associated with a 102% decrease in the elastance coefficient. Cerebrovascular parameters have a limited but significant impact on CSF infusion studies. The vascular component of ICP may be identified as a significant factor contributing to this phenomenon. During infusion studies, physiological parameters influencing vascular conditions should be maintained as stable as possible.


Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self-renewal and early development.
Chromatin-associated proteins are essential for the specification and maintenance of cell identity. They exert these functions through modulating and maintaining transcriptional patterns. To elucidate the functions of the Jmjd2 family of H3K9/H3K36 histone demethylases, we generated conditional Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c/Gasc1 single, double and triple knockout mouse embryonic stem cells (ESCs). We report that while individual Jmjd2 family members are dispensable for ESC maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired ESC self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions. We further show that Jmjd2a and Jmjd2c both localize to H3K4me3-positive promoters, where they have widespread and redundant roles in preventing accumulation of H3K9me3 and H3K36me3. Jmjd2 catalytic activity is required for ESC maintenance, and increased H3K9me3 levels in knockout ESCs compromise the expression of several Jmjd2a/c targets, including genes that are important for ESC self-renewal. Thus, continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity.


Prospective Study of Serum Uric Acid Levels and First Stroke Events in Chinese Adults With Hypertension.
Objectives: We investigated the association between serum uric acid (SUA) levels and the risk of the first stroke in Chinese adults with hypertension. Methods: A total of 11, 841 hypertensive patients were selected from the Chinese Hypertension Registry for analysis. The relationship between SUA levels and first stroke was determined using multivariable Cox proportional hazards regression, smoothing curve fitting, and Kaplan-Meier survival curve analysis. Results: During a median follow-up of 614 days, 99 cases of the first stroke were occurred. Cox proportional hazards models indicated that SUA levels were not significantly associated with the first stroke event [adjusted-hazard ratio (HR) per SD increase: 0.98, 95% CI 0.76-1.26, P = 0.889]. In comparison to the group without hyperuricemia (HUA), there were no significantly higher risks of first stroke events (adjusted-HR: 1.22, 95% CI 0.79-1.90, P = 0.373) in the population with HUA. However, in the population less than 60 years old, subjects with HUA had a significantly higher risk of the first stroke than the population without HUA (adjusted-HR: 4.89, 95% CI 1.36-17.63, P = 0.015). In subjects older than 60 years, we did not find a significant relationship between HUA and first stroke (adjusted-HR: 0.97, 95% CI 0.60-1.56, P = 0.886). Survival analysis further confirmed this discrepancy (log-rank P = 0.013 or 0.899 for non-aging or aging group). Conclusion: No significant evidence in the present study indicated that increased SUA levels were associated with the risk of first stroke in the Chinese adults with hypertension. Age played an interactive role in the relationship between HUA and the first stroke event.


Genus Coltivirus (family Reoviridae): genomic and morphologic characterization of Old World and New World viruses.
We report a genomic and morphologic study of the European Eyach (EYA) virus (genus Coltivirus, family Reoviridae) and a comparative analysis with the American Colorado tick fever (CTF) virus (the type species of the genus). The previously established, but distant, antigenic relationship between these viruses was strengthened by genetic findings (presence of cognate genes, amino acid identity between 55 and 88%, similar conserved terminal motifs, suspected read-through phenomenon in segment 9 of both viruses) and by indistinguishable ultramicroscopic morphologies. Moreover, putative constitutive modifying enzyme activities were suspected to be carried out by homologous viral proteins (RNA-dependent RNA polymerase, methyl/guanylyl transferase, NTPase). These findings, together with the comparative analysis to genomes of southeast Asian isolates, support the recent classification of arboviruses with 12 segments of dsRNA within two distinct genera (genus Coltivirus and genus Seadornavirus) and raise interesting questions about the evolutionary origins of coltiviruses. The previously proposed hypothesis that EYA virus was derived from an ancestral virus introduced in Europe with the migration of lagomorphs from North-America, would imply a divergence date between American and European isolates of over 50 million years ago (MYA). This analysis allows for the first time to propose an evolutionary rate for virus dsRNA genomes which was found to be in the order of 10(-8) to 10(-9) mutations/nt/year, a rate similar to that of dsDNA genomes.


Exercise intervention designed to improve strength and dynamic balance among community-dwelling older adults.
Loss of balance and falling are critical concerns for older adults. Physical activity can improve balance and decrease the risk of falling. The purpose of this study was to evaluate a simple, low-cost exercise program for community-dwelling older adults. Sixteen senior adults were evaluated using the Senior Fitness Test for measures of functional strength, aerobic endurance, dynamic balance and agility, and flexibility. In addition, measures of height, weight, resting blood pressure, blood lipids, and cognitive function were obtained. Participants then attended a 10-week exercise class including stretching, strengthening, and balance-training exercises. At the completion of the program, significant improvements were observed in tests measuring dynamic balance and agility, lower and upper extremity strength, and upper extremity flexibility. The results indicate that exercise programs such as this are an effective, low-cost solution to improving health and factors that affect falling risk among older adults.


Anaphylaxis: an unusual complication of hemodialysis.
Anaphylaxis is a rare complication of hemodialysis. Unless there is a high index of suspicion, symptoms may not be immediately recognized as a manifestation of hypersensitivity and prompt attention may be delayed. To improve physician awareness of this problem we report a patient who developed a severe anaphylactic reaction within minutes of beginning dialysis. Review of the literature indicates that hypersensitivity reactions are most commonly associated with Cuprophan dialyzers. Although the etiology has not been established, recurrence can be prevented by selection of a different type of dialysis membrane.


Immunologic studies of membrane mutants of a highly metastatic murine tumor.
MDAY-D2 is a highly tumorigenic and anaplastic DBA/2 strain murine transplantable tumor capable of rapid and widespread spontaneous metastatic growth. It was therefore chosen as an ideal murine tumor model for the study of factors affecting metastatic growth. Two approaches were taken in an effort to obtain stable qualitative and quantitative low-metastatic variants of MDAY-D2, namely, cloning of multiple sublines and derivation of lectin-resistant (LecR) mutants. In the first method, 20 clones were isolated, and of these, three initially showed a marked reducstion in ability to metastasize from a subcutaneous site. However, these clones proved to be unstable both in vivo and in vitro. In the LecR selection experiments, 18 independent variants were obtained using chemical mutagenesis followed by treatment with wheat germ agglutinin (WGA), phytohemagglutinin (PHA), or concanavalin A (Con A). All of the variants proved to be highly metastatic except two WGAR variants, designated MDWI and MDW3. They proved to be nontumorigenic in normal DBA/2 hosts even when as many as 5 X 10(6) cells were injected, and this was found to be a stable change. Despite this fact, the nontumorigens an unchanged expression of H-2d and Ly-6.2 alloantigens and Fc receptors. The variants were, however, tumorigenic and metastatic in severely immunosuppressed (nude) mice, but not in moderately immunosuppressed 250-R-irradiated DBA/2 hosts. The results demonstrate that 1) stable membrane mutant sublines possessing radically altered growth properties in vivo can occasionally be obtained by selection of LecR variants, and 2) their growth and metastatic properties can be greatly affected by the immunologic status of the host. The possibility that the chemical mutagen treatment itself induced, or was responsible for, MDW1 and MDW3 variant formation is also discussed.


Type A dissection of the ascending thoracic aorta during percutaneous coronary intervention.
Retrograde dissection of the aorta is extremely rare during percutaneous coronary intervention (PCI), but is a recognized and potentially life-threatening complication. We describe a case in which retrograde dissection of the aorta, necessitating urgent surgical repair, occurred during an attempt to open a chronically occluded right coronary artery. Initially localized, the dissection extended during an attempt to seal the right coronary ostium. Our experience suggests that if localized aortic retrograde dissection occurs, the management will depend on the stability of the distal coronary vessel. If stable, a conservative approach may be preferable to an attempt to seal the dissection.


Use of a Toxin Neutralization Assay To Characterize the Serologic Response to Adenylate Cyclase Toxin after Infection with Bordetella pertussis.
Adenylate cyclase toxin (ACT) is an essential virulence factor of Bordetella pertussis, and antibodies to ACT protect against B. pertussis infection in mice. The toxin is therefore a strong candidate antigen for addition to future acellular pertussis vaccines. In order to characterize the functionality of the immunologic response to ACT after infection, we developed an assay for testing the ability of serum samples from subjects infected with B. pertussis to neutralize ACT-induced cytotoxicity in J774 macrophage cells. Baboons develop neutralizing anti-ACT antibodies following infection with B. pertussis, and all sera from baboons with positive anti-ACT IgG enzyme-linked immunosorbent assay (ELISA) results neutralized ACT cytotoxicity. The toxin neutralization assay (TNA) was positive in some baboon sera in which ELISA remained negative. Of serum samples obtained from humans diagnosed with pertussis by PCR, anti-ACT IgG ELISA was positive in 72%, and TNA was positive in 83%. All samples positive for anti-ACT IgG ELISA were positive by TNA, and none of the samples from humans without pertussis neutralized toxin activity. These findings indicate that antibodies to ACT generated following infection with B. pertussis consistently neutralize toxin-induced cytotoxicity and that TNA can be used to improve understanding of the immunologic response to ACT after infection or vaccination.


Multivariate partial linear varying coefficients model for gene-environment interactions with multiple longitudinal traits.
Correlated phenotypes often share common genetic determinants. Thus, a multi-trait analysis can potentially increase association power and help in understanding pleiotropic effect. When multiple traits are jointly measured over time, the correlation information between multivariate longitudinal responses can help to gain power in association analysis, and the longitudinal traits can provide insights on the dynamic gene effect over time. In this work, we propose a multivariate partially linear varying coefficients model to identify genetic variants with their effects potentially modified by environmental factors. We derive a testing framework to jointly test the association of genetic factors and illustrated with a bivariate phenotypic trait, while taking the time varying genetic effects into account. We extend the quadratic inference functions to deal with the longitudinal correlations and used penalized splines for the approximation of nonparametric coefficient functions. Theoretical results such as consistency and asymptotic normality of the estimates are established. The performance of the testing procedure is evaluated through Monte Carlo simulation studies. The utility of the method is demonstrated with a real data set from the Twin Study of Hormones and Behavior across the menstrual cycle project, in which single nucleotide polymorphisms associated with emotional eating behavior are identified.


Existing and Emerging Technologies for Point-of-Care Testing.
The volume of point-of-care testing (PoCT) has steadily increased over the 40 or so years since its widespread introduction. That growth is likely to continue, driven by changes in healthcare delivery which are aimed at delivering less costly care closer to the patient's home. In the developing world there is the challenge of more effective care for infectious diseases and PoCT may play a much greater role here in the future. PoCT technologies can be split into two categories, but in both, testing is generally performed by technologies first devised more than two decades ago. These technologies have undoubtedly been refined and improved to deliver easier-to-use devices with incremental improvements in analytical performance. Of the two major categories the first is small handheld devices, providing qualitative or quantitative determination of an increasing range of analytes. The dominant technologies here are glucose biosensor strips and lateral flow strips using immobilised antibodies to determine a range of parameters including cardiac markers and infectious pathogens. The second category of devices are larger, often bench-top devices which are essentially laboratory instruments which have been reduced in both size and complexity. These include critical care analysers and, more recently, small haematology and immunology analysers. New emerging devices include those that are utilising molecular techniques such as PCR to provide infectious disease testing in a sufficiently small device to be used at the point of care. This area is likely to grow with many devices being developed and likely to reach the commercial market in the next few years.


Higher vitamin D levels in HIV-infected out-patients on treatment with boosted protease inhibitor monotherapy.
We investigated the vitamin D status of patients receiving frequently used types of combination antiretroviral therapy (cART), including boosted protease inhibitor (PI) monotherapy. For this cross-sectional study, out of 450 HIV-infected patients followed in the Hospital Severo Ochoa (Madrid, Spain), we selected 352 patients for whom vitamin D levels had been measured (January 2009 to December 2010). We collected the following data: demographics, cART duration, main cART regimen, viral load (VL), CD4 cell count, and concentrations of 25(OH)-vitamin D [25(OH)-D], parathyroid hormone (PTH), albumin and calcium. Vitamin D status cut-off points were: (1) deficiency (vitDd): 25(OH)-D < 20 ng/mL; (2) insufficiency (vitDi): 25(OH)-D from 20 to 29.99 ng/mL; and (3) optimal (vitDo): 25(OH)-D ≥ 30 ng/mL. The percentages of patients with vitDd, vitDi and vitDo were 44, 27.6 and 28.5%, respectively. Twenty-nine out of 30 (96.7%) Black patients had vitDd or vitDi, vs. 71.6% in the global sample (P < 0.001). Former injecting drug users (IDUs) had a higher prevalence of vitDo (P < 0.001) than patients in other transmission categories. Among patients with vitDd, vitDi and vitDo, the proportions of patients with a VL ≤ 50 HIV-1 RNA copies/mL were 77.4, 68 and 91%, respectively (P < 0.0001). Of the cART regimens, only boosted PI monotherapy was associated with significant differences in vitamin D levels (P = 0.039). Multivariate logistic regression analysis showed an increased risk of vitDi or vitDd associated with the following variables: Black vs. Caucasian ethnicity [odds ratio (OR) 10.6; 95% confidence interval (CI) 1.2-94; P = 0.033]; heterosexual (OR 2.37; 95% CI 1.13-4.93; P = 0.022) or men who have sex with men (MSM) (OR 3.25; 95% CI 1.25-8.50; P = 0.016) transmission category vs. former IDU; and VL > 50 copies/mL (OR 2.56; 95% CI 1.10-7.25; P = 0.040). A lower risk of vitamin D insufficiency or deficiency was found in patients on boosted PI monotherapy vs. no treatment (OR 0.08; 95% CI 0.01-0.6; P = 0.018). Our data show an increased risk of vitamin D deficiency or insufficiency in patients with detectable VL and a Black ethnic background. Among cART regimens, boosted PI monotherapy was associated with a lower risk of vitamin D deficiency or insufficiency. The more favourable vitamin D status in former IDUs was probably attributable to a higher frequency of outdoor jobs in this group of patients.


Continuous phrophylcatic anticonvulsants in selected childrens with febrile convulsions.
The recurrence rate of febrile convulsions is assessed in 108 children who had had either prolonged or repeated initial fits or had both a positive family history and persisting neurological disorder. Only 7 of 40 (17%) who received continuous prophylactic phenobarbitone or primidone for at minimum of 18 months had another fit compared with 40 of 68 (59%) children who were untreated (p less than 0.0005). Indications for continuous therapy are discussed.


Senescence-Associated miRNAs and Their Role in Pancreatic Cancer.
Replicative senescence is irreversible cell proliferation arrest for somatic cells which can be circumvented in cancers. Cellular senescence is a process, which may play two opposite roles. On the one hand, this is a natural protection of somatic cells against unlimited proliferation and malignant transformation. On the other hand, cellular secretion caused by senescence can stimulate inflammation and proliferation of adjacent cells that may promote malignancy. The main genes controlling the senescence pathways are also well known as tumor suppressors. Almost 140 genes regulate both cellular senescence and cancer pathways. About two thirds of these genes (64%) are regulated by microRNAs. Senescence-associated miRNAs can stimulate cancer progression or act as tumor suppressors. Here we review the role playing by senescence-associated miRNAs in development, diagnostics and treatment of pancreatic cancer.


Pulp blood flow and sensibility in patients with a history of dental trauma undergoing maxillary expansion.
To assess changes in pulp blood flow (PBF) and pulp sensibility (PS) in teeth of patients with a history of dental trauma undergoing maxillary expansion. Twenty-five patients requiring rapid maxillary expansion (RME) had the pulp status of their maxillary anterior teeth assessed using laser Doppler flowmetry, electric pulp testing, and thermal testing (CO2 snow). Each patient was tested at T1 (prior to expansion), T2 (2 weeks after rapid expansion), and T3 (3 months after expansion). Relationships between PBF, time interval, and history of trauma were evaluated using linear mixed modelling. Within the Trauma group, PBF was significantly lower (P ≤ .05) at T2 and T3 in comparison to T1 and significantly lower (P ≤ .05) at T2 in comparison to T3. In the Non-trauma group, PBF at T2 was significantly lower (P ≤ .05) than PBF at T1 and T3; however, no significant difference (P > .05) in PBF was observed when comparing PBF at T1 and T3. In both groups, PS was maintained in almost all teeth (>90%). RME in healthy teeth causes reduction of PBF before reestablishment of pretreatment values. RME in traumatized teeth causes reduction of PBF without PBF being reestablished to pretreatment levels. Teeth with a history of compromise may have reduced adaptive capacity under insults such as RME, which should be appreciated during the informed consent process.