The observation of vibrating pear-shapes in radon nuclei.
There is a large body of evidence that atomic nuclei can undergo octupole distortion and assume the shape of a pear. This phenomenon is important for measurements of electric-dipole moments of atoms, which would indicate CP violation and hence probe physics beyond the Standard Model of particle physics. Isotopes of both radon and radium have been identified as candidates for such measurements. Here, we observed the low-lying quantum states in 224Rn and 226Rn by accelerating beams of these radioactive nuclei. We show that radon isotopes undergo octupole vibrations but do not possess static pear-shapes in their ground states. We conclude that radon atoms provide less favourable conditions for the enhancement of a measurable atomic electric-dipole moment.


Branching pattern formation that reflects the history of signal propagation.
In living organisms, branching structures are often observed in open systems. During the process of structure formation/deformation, signal propagation can be observed. Branching paths often deform depending on the history of signal propagation. To gain a better understanding of the process of pattern formation that results in characteristic geometrical paths, we adopt a system in which the dynamics of path formation are correlated with signal propagation. This model involves both branch-generation dynamics and signal-propagation dynamics, and we introduced positive feedback between these two dynamic processes. We studied the geometrical properties of path deformation and the pattern of signal propagation using a discretized reaction-diffusion model. The proposed model can qualitatively reproduce different branching patterns and means of signal propagation. One remarkable result is that the mutual interaction of these two dynamic processes leads to autonomous wave generation, similar to a pacemaker or the generation of spiral waves. Because the autonomous wave generation in the signal is spontaneous, the shapes of the branching paths become distorted. We discuss the correlation between path deformation and signal propagation as a first step in understanding signal processing for such complex deformable paths.


Localization transition of stiff directed lines in random media.
We investigate the localization of stiff directed lines with bending energy by a short-range random potential. Using perturbative arguments, Flory arguments, and a replica calculation, we show that a stiff directed line in 1+d dimensions undergoes a localization transition with increasing disorder for d>2/3. We demonstrate that this transition is accessible by numerical transfer matrix calculations in 1+1 dimensions and analyze the properties of the disorder-dominated phase. On the basis of the two-replica problem, we propose a relation between the localization of stiff directed lines in 1+d dimensions and of directed lines under tension in 1+3d dimensions, which is strongly supported by identical free energy distributions. This shows that pair interactions in the replicated Hamiltonian determine the nature of directed line localization transitions with consequences for the critical behavior of the Kardar-Parisi-Zhang (KPZ) equation. Furthermore, we quantify how the persistence length of the stiff directed line is reduced by disorder.


Luteinizing hormone-releasing hormone is a primary signaling molecule in the neuroimmune network.
The brain-pituitary-reproductive axis and the brain thymus-lymphoid axis are linked by an array of internal mechanisms of communication that use similar signals (neurotransmitters, peptides, growth factors, hormones) acting on similar recognition targets. Moreover, such communication networks form the basis and control each step and every level of reproductive physiology. This presentation highlights the extent to which endocrine, neural, glial, or immunologically competent cells may achieve their specific functions using common mechanisms, but employing them to different degrees. In particular, this work will focus on LHRH, the chief hormone orchestrating reproductive events. Within the thymus LHRH plays a unique role of immunomodulator, contributing to the sex-dependent changes in immune responsiveness during the estrous-menstrual cycle as well as pregnancy. From the recent cloning and sequencing of lymphocyte LHRH, the expression of LHRH receptor mRNA in lymphocyte, the transduction mechanisms involved, and the steroidogenic sensitivity of the intralymphocyte LHRH system. It would appear that this peptide may act as an immunological response modifier in the brain-pituitary-lymphoid-gonadal axis. The interplay between neuronal, endocrine, and immune compartments is further emphasized in the study of LHRH-astroglial interactions. Astrocytes are able to manufacture a wide variety of signaling agents and can secrete immunoregulatory molecules that influence immune cells, as well as the glial cells themselves. Astroglia and the immortalized hypothalamic LHRH (GT1-1) neurons communicate with an array of mechanisms, via soluble mediators as well as cell-to-cell contacts. Manipulation of astroglial-derived cytokines and nitric oxide (NO) in GT1-1 neuron-astroglia cocultures, underscores a potential cross-talk between different intra/inter-cellular mediators in the dynamic control of LHRH release. Further studies aimed to disclose at a biochemical and a molecular level such bidirectional, informative network will give us new insights into more general issues concerned with the malfunction of the neuroendocrine-immune axis.


Dissecting the effect of targeting the epidermal growth factor receptor on TGF-β-induced-apoptosis in human hepatocellular carcinoma cells.
Transforming growth factor-beta (TGF-β) induces apoptosis in hepatocytes, a process that is inhibited by the epidermal growth factor receptor (EGFR) pathway. The aim of this work was to ablate EGFR in hepatocellular carcinoma (HCC) cells to understand its role in impairing TGF-β-induced cell death. Response to TGF-β in terms of apoptosis was analyzed in different HCC cell lines and the effect of canceling EGFR expression was evaluated. TGF-β induces apoptosis in some HCC cells (such as Hep3B, PLC/PRF/5, Huh7, or SNU449), but it also mediates survival signals, coincident with the up-regulation of EGFR ligands. Inhibition of the EGFR, either by targeted knock-down with specific siRNA or by pharmacological inhibition, significantly enhances apoptotic response. TGF-β treatment in EGFR targeted knock-down cells correlates with higher levels of the NADPH oxidase NOX4 and changes in the expression profile of BCL-2 and IAP families. However, other HCC cells, such as HepG2, which show over activation of the Ras/ERKs pathway, SK-Hep1, with an endothelial phenotype, or SNU398, where the TGF-β-Smad signaling is altered, show apoptosis resistance that is not restored through EGFR blockade. The inhibition of EGFR in HCC may enhance TGF-β-induced pro-apoptotic signaling. However, this effect may only concern those tumors with an epithelial phenotype which do not bear alterations in TGF-β signaling nor exhibit an over-activation of the survival pathways downstream of the EGFR.


The dominant hemimelia mutation uncouples epithelial-mesenchymal interactions and disrupts anterior mesenchyme formation in mouse hindlimbs.
Epithelial-mesenchymal interactions are essential for both limb outgrowth and pattern formation in the limb. Molecules capable of communication between these two tissues are known and include the signaling molecules SHH and FGF4, FGF8 and FGF10. Evidence suggests that the pattern and maintenance of expression of these genes are dependent on a number of factors including regulatory loops between genes expressed in the AER and those in the underlying mesenchyme. We show here that the mouse mutation dominant hemimelia (Dh) alters the pattern of gene expression in the AER such that Fgf4, which is normally expressed in a posterior domain, and Fgf8, which is expressed throughout are expressed in anterior patterns. We show that maintenance of Shh expression in the posterior mesenchyme is not dependent on either expression of Fgf4 or normal levels of Fgf8 in the overlying AER. Conversely, AER expression of Fgf4 is not directly dependent on Shh expression. Also the reciprocal regulatory loop proposed for Fgf8 in the AER and Fgf10 in the underlying mesenchyme is also uncoupled by this mutation. Early during the process of limb initiation, Dh is involved in regulating the width of the limb bud, the mutation resulting in selective loss of anterior mesenchyme. The Dh gene functions in the initial stages of limb development and we suggest that these initial roles are linked to mechanisms that pattern gene expression in the AER.


Feasibility and Reproducibility of Left Atrium Measurements Using Different Three-Dimensional Echocardiographic Modalities.
Left atrium (LA) volume is a biomarker of cardiovascular outcomes. Three-dimensional echocardiography (3DE) provides an accurate LA evaluation, but data regarding the optimal 3DE method is scarce. We assessed the feasibility and reproducibility of LA measurements using different 3DE methods. One hundred and ninety-four patients were prospectively analyzed. Conventional 3DE and two semi-automatic 3DE algorithms (Tomtec™ and Dynamic Heart Model (DHM)) were used in 110 patients. Intra- and interobserver reproducibility and intervendor comparison were performed in additional patients' subsets. Forty patients underwent cardiac magnetic resonance (CMR). Feasibility was 100% for Tomtec, 98.2% for DHM, and 72.8% for conventional 3DE. Tomtec volumes were higher than 3DE and DHM (p < 0.001). Reproducibility was better for DHM (intraobserver LA maximum volume (LAmax) ICC 0.99 (95% CI 1.0-0.99), LA minimum volume (LAmin) 0.98 (95% CI 0.95-0.99), LApreA 0.96 (95% CI 0.91-0.98); interobserver LAmax ICC 0.98 (95% CI 0.96-0.99), LAmin 0.99 (95% CI 0.99-1.00), and LApreA 0.97 (95% CI 0.94-0.99)). Intervendor comparison showed differences between left ventricle (LV) software adapted for LA (p < 0.001). Tomtec underestimated the least LA volumes compared to CMR. These findings emphasize that dedicated software should be used for LA assessment, for consistent clinical longitudinal follow-up and research.


Radical Alkynylations with EthynylBenziodoXolones: from Photocatalysis to Direct Excitation.
Ethynylbenziodoxolones (EBXs) have recently emerged as potent reagents for the alkynylation of radicals. Their combination with photocatalysis allows the synthesis of valuable alkynes at room temperature. Herein, we discuss two photomediated strategies for the synthesis of internal alkynes. The first transformation is a 1,2-oxyalkynylation of N- and O-alkenes using 4ClCzIPN as a photocatalyst. The second strategy makes use of EBXs as strong photooxidants allowing the oxidation of a variety of substrates with no need for a photocatalyst.


Correlation of genetic markers of rejection with biopsy findings following human pancreas transplant.
Acute rejection after pancreas transplantation remains a significant problem and contributes to immunologic graft loss. No clinical markers of pancreas rejection have been universally accepted. Recent studies have identified several cytotoxic genes as possible markers of acute rejection in renal and islet cell transplant recipients. However, these markers of rejection have not been evaluated in pancreas transplant recipients. This study evaluated the differential expression of granzyme B, perforin, and human leukocyte antigen (HLA)-DRA in peripheral blood between patients with and without biopsy-proven pancreas rejection (n = 7 per group). Gene expression levels were analyzed using real time reverse transcriptase polymerase chain reaction assays. Expression of these genes in controls (n = 17) with and without type 1 diabetes was also analyzed. Patients with biopsy-proven pancreas rejection had higher levels of granzyme B, perforin, and HLA-DRA than patients who did not have rejection, although the difference was not statistically significant. Moreover, patients with biopsy-proven pancreas rejection had a significantly higher level of granzyme B than control subjects with type 1 diabetes (p <or= 0.03). Our findings suggest that, with additional evaluation of a larger number of patients as well as a longitudinal approach, analyses of granzyme B expression levels in peripheral blood may be shown to be a non-invasive method of monitoring pancreas allograft rejection.


Tobacco, Sunflower and High Biomass SRC Clones Show Potential for Trace Metal Phytoextraction on a Moderately Contaminated Field Site in Belgium.
Phytoextraction could be a potential management option for diffusely Cd-Zn-Pb-polluted agricultural land in Northeast Belgium. The use of high yielding crops with a sufficiently high metal accumulation is preferred as these are expected to both gradually decontaminate the soil while generating an income through biomass valorization. To find out which high biomass crop possessed the highest and most constant (in time) phytoextraction potential on these soils, different plant species and different mutants or clones of each species, were evaluated during consecutive years. Biomass production and metal accumulation of pre-selected tobacco somaclonal variants (Nicotiana tabacum L.) and pre-selected sunflower mutants (Helianthus annuus L.) were investigated for two productivity years, while the phytoextraction potential of experimental poplar (Populus) and willow (Salix) in short rotation coppice (SRC) was assessed at the end of the second cutting cycle (after two times four growing seasons). The tobacco clones and the sunflower mutants showed efficient extraction of, respectively, Cd and Zn, while the highest simultaneous extractions of Cd and Zn were gained with some SRC clones. Variation in biomass production and metal accumulation were high for all crops over the years. The highest biomass production was observed for the experimental poplar clone of the crossing type Populus deltoides (P. maximowiczii x P. trichocarpa) with 9.9 ton DW per ha per year. The remediation period to reach legal threshold values for the pseudo-total content of Cd in this specific soil was estimated to be at least 60 years. Combining estimated phytoextraction potential and economic and environmental aspects, the SRC option is proposed as the most suitable crop for implementing metal phytoextraction in the investigated area.


Morphogenesis of human bronchial diverticulum. A scanning electron microscopic study.
Diverticulosis of the bronchial wall was found in patients not only with, but also without, chronic obstructive lung disease; it appeared to start as submicroscopic depressions and dilatations of the ducts of the bronchial gland on the mucosal surface. Multiple depressions and dilatations fused to form a diverticulum which herniated between and through the smooth-muscle cellular bundles. Rupture of the latter resulted in large diverticula. Cough and a weakened bronchial wall, from whatever causes, likely lead to bronchial diverticulosis. Exaggerated but unequal formations of bronchial diverticula at the sites of dichotomy suggest either that the effect of cough could be different between segments or subsegments, or that there are local differences in connective-tissue atrophy, inflammation, and structural defects. Mucous plugs, macrophages, red blood cells, inhaled particles, and probably carcinogens are accumulated at the bronchial diverticula, which apparently interfere with airway cleansing and also cause continuous local irritation. The relationship between bronchial diverticulosis and small-airway disease or lung cancer needs further clarification.


A Perspective on the Potential of Opsins as an Integral Mechanism of Photobiomodulation: It's Not Just the Eyes.
Objective: To investigate the potential relationship between opsins and photobiomodulation. Background: Opsins and other photoreceptors occur in all phyla and are important in light-activated signaling and organism homeostasis. In addition to the visual opsin systems of the retina (OPN1 and OPN2), there are several non-visual opsins found throughout the body tissues, including encephalopsin/panopsin (OPN3), melanopsin (OPN4), and neuropsin (OPN5), as well as other structures that have light-sensitive properties, such as enzymes, ion channels, particularly those located in cell membranes, lysosomes, and neuronal structures such as the nodes of Ranvier. The influence of these structures on exposure to light, including self-generated light within the body (autofluorescence), on circadian oscillators, and circadian and ultradian rhythms have become increasingly reported. The visual and non-visual phototransduction cascade originating from opsins and other structures has potential significant mechanistic effects on tissues and health. Methods: A PubMed and Google Scholar search was made using the search terms "photobiomodulation", "light", "neuron", "opsins", "neuropsin", "melanopsin", "encephalopsin", "rhodopsin", and "chromophore". Results: This review was examined the influence of neuropsin (also known as kallikrein 8), encephalopsin, and melanopsin specifically on ion channel function, and more broadly on the central and peripheral nervous systems. The relationship between opsins 3, 4, and 5 and photobiomodulation mechanisms was evaluated, along with a proposed role of photobiomodulation through opsins and light-sensitive organelles as potential alleviators of symptoms and accelerators of beneficial regenerative processes. The potential clinical implications of this in musculoskeletal conditions, wounds, and in the symptomatic management of neurodegenerative disease was also examined. Conclusions: Systematic research into the pleotropic therapeutic role of photobiomodulation, mediated through its action on opsins and other light-sensitive organelles may assist in the future execution of safe, low-risk precision medicine for a variety of chronic and complex disease conditions, and for health maintenance in aging.


Socioemotional self-perceptions, family climate, and hopeful thinking among students with learning disabilities and typically achieving students from the same classes.
This study aimed at examining the adjustment of students with learning disabilities (LD) and at exploring the mediating role of hope. By means of a multidimensional approach, the interactions between risk and protective factors emerging from internal and external resources among 856 high school students (10th to 12th grades) were analyzed. A total of 529 typically achieving students and 327 students with LD attending general education classes in seven high schools completed seven instruments measuring sense of coherence, basic psychological needs, loneliness, family climate, hope, academic self-efficacy, and effort. The students' achievements in English, history, and mathematics were collected. The analysis used structural equation modeling, and the results emphasized the significant role of hope as a mediator between risk and protective factors and academic self-efficacy and its significance for students with and without LD in explaining achievements and effort investment.


Signal-averaged electrocardiography for detection of ventricular tachycardia using fast Fourier transform filtering on a standard ECG cart.
Signal-averaged electrocardiography has been advocated as a technique to predict the occurrence of ventricular tachycardia, especially in patients with ischemic heart disease. We studied a heterogeneous population of 77 patients referred for electrophysiologic testing using a recently developed fast Fourier transform filtering system available as part of a standard electrocardiography cart. The sensitivity, specificity, and positive predictive accuracy of this system were consistent with those previously determined using bidirectional Butterworth filters or finite impulse response filtering techniques. This new filtering approach in generation of signal-averaged ECG data for detection of ventricular tachycardia has promise but will require use in larger groups to establish its true clinical value.


Examining the Prevalence Rates of Preexisting Maternal Medical Conditions and Pregnancy Complications by Source: Evidence to Inform Maternal and Child Research.
Objectives We sought to examine whether there are systematic differences in ascertainment of preexisting maternal medical conditions and pregnancy complications from three common data sources used in epidemiologic research. Methods Diabetes mellitus, chronic hypertension, gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHD), placental abruption and premature rupture of membranes (PROM) among 4821 pregnancies were identified via birth certificates, maternal self-report at approximately 4 months postpartum and by discharge codes from the Statewide Planning and Research Cooperative System (SPARCS), a mandatory New York State hospital reporting system. The kappa statistic (k) was estimated to ascertain beyond chance agreement of outcomes between birth certificates with either maternal self-report or SPARCS. Results GHD was under-ascertained on birth certificates (5.7 %) and more frequently indicated by maternal report (11 %) and discharge data (8.2 %). PROM was indicated more on birth certificates (7.4 %) than maternal report (4.5 %) or discharge data (5.7 %). Confirmation across data sources for some outcomes varied by maternal age, race/ethnicity, prenatal care utilization, preterm delivery, parity, mode of delivery, infant sex, use of infertility treatment and for multiple births. Agreement between maternal report and discharge data with birth certificates was generally poor (kappa < 0.4) to moderate (0.4 ≤ kappa < 0.75) but was excellent between discharge data and birth certificates for GDM among women who underwent infertility treatment (kappa = 0.79, 95 % CI 0.74, 0.85). Conclusions for Practice Prevalence and agreement of conditions varied across sources. Condition-specific variations in reporting should be considered when designing studies that investigate associations between preexisting maternal medical and pregnancy-related conditions with health outcomes over the life-course.


Improved in situ hybridization efficiency with locked-nucleic-acid-incorporated DNA probes.
Low signal intensity due to poor probe hybridization efficiency is one of the major drawbacks of rRNA-targeted in situ hybridization. There are two major factors affecting the hybridization efficiency: probe accessibility and affinity to the targeted rRNA molecules. In this study, we demonstrate remarkable improvement in in situ hybridization efficiency by applying locked-nucleic-acid (LNA)-incorporated oligodeoxynucleotide probes (LNA/DNA probes) without compromising specificity. Fluorescently labeled LNA/DNA probes with two to four LNA substitutions exhibited strong fluorescence intensities equal to or greater than that of probe Eub338, although these probes did not show bright signals when they were synthesized as DNA probes; for example, the fluorescence intensity of probe Eco468 increased by 22-fold after three LNA bases were substituted for DNA bases. Dissociation profiles of the probes revealed that the dissociation temperature was directly related to the number of LNA substitutions and the fluorescence intensity. These results suggest that the introduction of LNA residues in DNA probes will be a useful approach for effectively enhancing probe hybridization efficiency.


Business process reengineering: a pathway for performance improvement.
Health care materiel management executives are coping with a revolutionary environment. Demands and constraints are being placed on hospitals that necessitate both long-term solutions and rapid responses. Materiel management executives can play a vital role in transforming their areas from a passive service center to an active command center. It is essential that the materiel management executive play an active role in the change process.


The effect of stimulus rate upon common peroneal, posterior tibial, and sural nerve somatosensory evoked potentials.
We examined the effect of stimulus rate on somatosensory evoked potentials (SEPs) following stimulation of the common peroneal nerve (CPN) at the knee, and the posterior tibial nerve (PTN) and sural nerve (SN) at the ankle. We measured the amplitude of P40-N50 and N50-P60 in the PTN-SEP and corresponding amplitude of CPN-SEP and SN-SEP at the rate of 2.3, 3.4, 4.1, and 5.1 Hz. When the stimulation rate was increased from 2.3 to 5.1 Hz, the P40-N50 amplitude decreased by 50% for the CPN-SEP and 20% for the PTN-SEP. Also, the N50-P60 amplitude was reduced by 30% in the CPN-SEP and 20% in the PTN-SEP. In contrast, this change in stimulus rate produced no significant amplitude decline in the SN-SEP. Blocking the peroneal nerve with lidocaine just distal to the stimulating electrodes eliminated the descending peroneal nerve volley and abolished the amplitude attenuation observed with the faster stimulus rate. The findings suggest that at higher rates of stimulation, the afferent volleys induced by the movements that follow mixed nerve stimulation interfere with the SEP produced by electrical activation of the sensory afferents. The interference is greater when the more proximal site of the mixed nerve is stimulated.


A novel conduit-based coaptation device for primary nerve repair.
Conduit-based nerve repairs are commonly used for small nerve gaps, whereas primary repair may be performed if there is no tension on nerve endings. We hypothesize that a conduit-based nerve coaptation device will improve nerve repair outcomes by avoiding sutures at the nerve repair site and utilizing the advantages of a conduit-based repair. The left sciatic nerves of female Sprague-Dawley rats were transected and repaired using a novel conduit-based device. The conduit-based device group was compared to a control group of rats that underwent a standard end-to-end microsurgical repair of the sciatic nerve. Animals underwent behavioral assessments at weekly intervals post-operatively using the sciatic functional index (SFI) test. Animals were sacrificed at four weeks to obtain motor axon counts from immunohistochemistry. A sub-group of animals were sacrificed immediately post repair to obtain MRI images. SFI scores were superior in rats which received conduit-based repairs compared to the control group. Motor axon counts distal to the injury in the device group at four weeks were statistically superior to the control group. MRI tractography was used to demonstrate repair of two nerves using the novel conduit device. A conduit-based nerve coaptation device avoids sutures at the nerve repair site and leads to improved outcomes in a rat model. Conduit-based nerve repair devices have the potential to standardize nerve repairs while improving outcomes.


Evaluation and management of infection stones.
In summary, all patients with infection stones should undergo a preoperative diagnostic evaluation in order to identify any underlying metabolic abnormalities. All organisms infecting the urinary tract should be identified and appropriate antibacterial therapy instituted 48 to 72 hours preoperatively. Surgery should be undertaken not only to remove all stones but to correct any anatomic abnormalities within the kidney in order to improve urinary drainage and to diminish urinary stasis and infection. Postoperatively, all recurrent urinary tract infections should be treated vigorously. Continual efforts should be made to maintain a sterile urinary tract. All identified metabolic abnormalities will require appropriate treatment.


Localization and targeting of isocitrate lyases in Saccharomyces cerevisiae.
Native isocitrate lyase from castor bean and a C-terminally truncated variant were expressed in Saccharomyces cerevisiae under the control of a galactose-inducible promoter. Both forms of isocitrate lyase were targeted to the yeast peroxisomes. They co-fractionated with catalase on sucrose-density-gradient centrifugation of a post-nuclear supernatant prepared from cells grown on oleic acid plus galactose, but were found in the cytosolic fractions when the cells were grown under conditions that repress peroxisome formation. The endogenous S. cerevisiae isocitrate lyase was found solely in the cytoplasmic fractions, even under growth conditions that induce peroxisome proliferation. This result shows that the presence of isocitrate lyase in peroxisomes is not essential for a functional glyoxylate cycle. Although the heterologous enzyme was transported to peroxisomes it was not enzymically active. Immunocytochemical studies provide independent evidence that the plant enzyme is imported into the matrix of yeast peroxisomes.


Sperm in hot water: direct and indirect thermal challenges interact to impact on brown trout sperm quality.
Climate change alters the thermal habitat of aquatic species on a global scale, generating novel environmental challenges during all life stages, including reproduction. Changes in water temperature profoundly influence the performance of ectothermic aquatic organisms. This is an especially crucial issue for migratory fish, because they traverse multiple environments in order to reproduce. In externally fertilizing migratory fish, gametes are affected by water temperature indirectly, within the reproductive organ in which they are produced during migration, as well as directly, upon release into the surrounding medium at the spawning grounds. Both direct (after release) and indirect (during production) thermal impacts on gamete quality have been investigated, but never in conjunction. Here, we assessed the cumulative influence of temperature on brown trout, Salmo trutta, sperm quality during sperm production (male acclimation temperature) as well as upon release (sperm activation water temperature) on two consecutive dates during the brown trout spawning season. Early in the season, warm acclimation of males reduced their fertilization probability (lower sperm velocity) when compared with cold-acclimated males, especially when the activation water temperature was also increased beyond the thermal optimum (resulting in a lower proportion of motile sperm with lower velocity). Later in the season, sperm quality was unaffected by acclimation temperature and thermal sensitivity of sperm was reduced. These results give novel insights into the complex impacts of climate change on fish sperm, with implications for the reproduction and management of hatchery and wild trout populations in future climate scenarios.


Physical and psychosocial ergonomic risk factors for low back pain in automobile manufacturing workers.
To examine the association between ergonomic physical and psychosocial exposures and the risk of prevalent and incident low back pain (LBP) in a longitudinal cohort of automobile manufacturing workers. Ergonomic exposure intensity and LBP presence were determined through questionnaires at baseline (n=1181) and to workers in the same job 1 year later (n=505). Models were constructed using log-binomial regression with special attention to interactions between ergonomic exposures. Awkward back posture (prevalence ratio (PR) 1.12, 95% CI 1.07 to 1.17), hand force (PR 1.06, 95% CI 1.02 to 1.10), physical effort (PR 1.10, 95% CI 1.04 to 1.16) and whole body vibration (PR 1.04, 95% CI 1.01 to 1.08) were each associated cross-sectionally with LBP. Awkward back posture (RR 1.13, 95% CI 0.98 to 1.31) and hand force (RR 1.07, 95% CI 0.93 to 1.22) also predicted incident LBP, although estimates were statistically less precise. Neither job control, psychological demands, nor job strain was independently related to risk of incident LBP. Among participants reporting high physical ergonomic exposures and moderate to high job control, increasing job demands was associated with a reduced LBP risk (RR 0.72, 95% CI 0.52 to 1.00). Among participants reporting high physical exposures and low job control, psychological demands was associated with an increased LBP risk (RR 1.30, 95% CI 1.02 to 1.66). Psychosocial workplace interventions for LBP should prioritise jobs in which there are high physical ergonomic exposures. Future studies of LBP should examine the interactions between physical ergonomic risk factors.


Milk composition during lactation suggests a mechanism for male biased allocation of maternal resources in the tammar wallaby (Macropus eugenii).
Recent research has found empirical evidence in support of the Trivers-Willard Hypothesis that offspring sex allocation is correlated with maternal investment. Tammar wallabies birthing sons have higher investment ability; however a mechanism for sex specific differential allocation of maternal resources in wallabies remains elusive. In metatherians the majority of maternal investment is during lactation. To examine if differential allocation occurs during lactation, we measured total milk protein, lipid and carbohydrates, from mothers with male and female pouch young, during phase 2B (100-215 days post partum) and phase 3 (215-360 days post partum) of lactation. Mothers of sons allocated significantly higher levels of protein than mothers of daughters during phase 2B of lactation, however no sex specific difference in maternal allocation was found for lipids, carbohydrates, or any milk component during phase 3 of lactation. We were unable to measure milk production to establish any differences in the amount of milk allocated. However, with the production of more milk comes a dilution effect on milk components. Given that we find no apparent dilution of milk components may suggest equality in milk production. Offspring body weight at 14 months of age was related to protein allocation during phase 2B of lactation, providing a maternal mechanism for differential allocation with fitness consequences. We believe collection of earlier phase 2A (0-100 days post partum) milk may yield important results given that differential investment in metatherians may be most apparent early in lactation, prior to any significant maternal investment, when a decision on termination of investment can be made with very little energetic loss to the mother. Interestingly, small mothers did not birth sons and better maternal condition was associated with raising sons. These data are in support of TWH and demonstrate a potential mechanism through which condition dependent and sex specific maternal investment may occur.


Implications of the Emergency Medical Treatment and Labor Act (EMTALA) during public health emergencies and on alternate sites of care.
Hospitals throughout the country are using innovative strategies to accommodate the surge of patients brought on by the novel H1N1 virus. One strategy has been to help decompress the amount of patients seeking care within emergency departments by using alternate sites of care, such as tents, parking lots, and community centers as triage, staging, and screening areas. As at any other time an individual presents on hospital property, hospitals and providers must be mindful of the requirements of the Emergency Medical Treatment and Labor Act. In this article we review the act and its implications during public health emergencies, with a particular focus on its implications on alternative sites of care.


The history of external ventricular drainage.
External ventricular drainage (EVD) is one of the most commonly performed neurosurgical procedures. It was first performed as early as 1744 by Claude-Nicholas Le Cat. Since then, there have been numerous changes in technique, materials used, indications for the procedure, and safety. The history of EVD is best appreciated in 4 eras of progress: development of the technique (1850-1908), technological advancements (1927-1950), expansion of indications (1960-1995), and accuracy, training, and infection control (1995-present). While EVD was first attempted in the 18th century, it was not until 1890 that the first thorough report of EVD technique and outcomes was published by William Williams Keen. He was followed by H. Tillmanns, who described the technique that would be used for many years. Following this, many improvements were made to the EVD apparatus itself, including the addition of manometry by Adson and Lillie in 1927, and continued experimentation in cannulation/drainage materials. Technological advancements allowed a great expansion of indications for EVD, sparked by Nils Lundberg, who published a thorough analysis of the use of intracranial pressure (ICP) monitoring in patients with brain tumors in 1960. This led to the application of EVD and ICP monitoring in subarachnoid hemorrhage, Reye syndrome, and traumatic brain injury. Recent research in EVD has focused on improving the overall safety of the procedure, which has included the development of guidance-based systems, virtual reality simulators for trainees, and antibiotic-impregnated catheters.


siRNAs: their potential as therapeutic agents--Part I. Designing of siRNAs.
RNA interference (RNAi) is a novel and essential biological process, as well as a powerful experimental tool with the potential to be used in therapeutic development. RNAi-based strategies have the capability of being able to be driven from bench to bedside. It is very important to develop the precise tools for designing the siRNAs to get the most efficient knockdown of the target genes and to reduce any off-target effects. In this review we have discussed the strategies and parameters required for effective siRNA designing and synthesis, based on already published literature.


A joint model for dynamic prediction in uveitis.
Uveitis is characterised as a recurrent inflammation of the eye and an ongoing inflammation can have severe impact on the visual acuity of the patient. The Rotterdam Eye Hospital has been collecting data on every uveitis patient visiting the hospital since 2000. We propose a joint model for the inflammation and visual acuity with the purpose of making dynamic predictions. Dynamic prediction models allow predictions to be updated during the follow-up of the patient based on the patient's disease history. The joint model consists of a submodel for the inflammation, the event history outcome, and one for the visual acuity, the longitudinal outcome. The inflammation process is described with a two-state reversible multistate model, where transition times are interval censored. Correlated log-normal frailties are included in the multistate model to account for the within eye and within patient correlation. A linear mixed model is used for the visual acuity. The joint model is fitted in a two-stage procedure and we illustrate how the model can be used to make dynamic predictions. The performance of the method was investigated in a simulation study. The novelty of the proposed model includes the extension to a multistate outcome, whereas, previously, the standard has been to consider survival or competing risk outcomes. Furthermore, it is usually the case that the longitudinal outcome affects the event history outcome, but in this model, the relation is reversed.


Transfer of orbital angular momentum from a super-continuum, white-light beam.
Beams with helical phasefronts described by exp(ilphi) carry an orbital angular momentum equivalent to lh per photon. Using diffractive optics this helical phase structure can be applied to every spectral component of the beam such that a spatially coherent white-light beam can carry orbital angular momentum without any chromatic distortion. This achromatic property can be hard to achieve in spin angular momentum where pure circular polarization is difficult to maintain across a finite spectral bandwidth. We illustrate the achromatic, helical phase structure of a white-light beam by observing the transfer of its orbital angular momentum to particles held in optical tweezers.


The benefits to communities and individuals of screening for active tuberculosis disease: a systematic review.
Screening for tuberculosis (TB) disease aims to improve early TB case detection. The ultimate goal is to improve outcomes for people with TB and to reduce Mycobacterium tuberculosis transmission in the community through improved case detection, reduction in diagnostic delays and early treatment. Before screening programmes are recommended, evidence is needed of individual and/or community-level benefits. We conducted a systematic review of the literature to assess the evidence that screening for TB disease 1) initially increases the number of TB cases initiated on anti-tuberculosis treatment, 2) identifies cases earlier in the course of disease, 3) reduces mortality and morbidity, and 4) impacts on TB epidemiology. A total of 28 798 publications were identified by the search strategy: 27 087 were excluded on initial screening and 1749 on full text review, leaving 62 publications that addressed at least one of the study questions. Screening increases the number of cases found in the short term. In many settings, more than half of the prevalent TB cases in the community remain undiagnosed. Screening tends to find cases earlier and with less severe disease, but this may be attributed to case-finding studies using more sensitive diagnostic methods than routine programmes. Treatment outcomes among people identified through screening are similar to outcomes among those identified through passive case finding. Current studies provide insufficient evidence to show that active screening for TB disease impacts on TB epidemiology. Individual and community-level benefits from active screening for TB disease remain uncertain. So far, the benefits of earlier diagnosis on patient outcomes and transmission have not been established.


AE2 Cl-/HCO3- exchanger is required for normal cAMP-stimulated anion secretion in murine proximal colon.
Anion secretion by colonic epithelium is dependent on apical CFTR-mediated anion conductance and basolateral ion transport. In many tissues, the NKCC1 Na(+)-K(+)-2Cl(-) cotransporter mediates basolateral Cl(-) uptake. However, additional evidence suggests that the AE2 Cl(-)/HCO(3)(-) exchanger, when coupled with the NHE1 Na(+)/H(+) exchanger or a Na(+)-HCO(3)(-) cotransporter (NBC), contributes to HCO(3)(-) and/or Cl(-) uptake. To analyze the secretory functions of AE2 in proximal colon, short-circuit current (I(sc)) responses to cAMP and inhibitors of basolateral anion transporters were measured in muscle-stripped wild-type (WT) and AE2-null (AE2(-/-)) proximal colon. In physiological Ringer, the magnitude of cAMP-stimulated I(sc) was the same in WT and AE2(-/-) colon. However, the I(sc) response in AE2(-/-) colon exhibited increased sensitivity to the NKCC1 inhibitor bumetanide and decreased sensitivity to the distilbene derivative SITS (which inhibits AE2 and some NBCs), indicating that loss of AE2 results in a switch to increased NKCC1-supported anion secretion. Removal of HCO(3)(-) resulted in robust cAMP-stimulated I(sc) in both AE2(-/-) and WT colon that was largely mediated by NKCC1, whereas removal of Cl(-) resulted in sharply decreased cAMP-stimulated I(sc) in AE2(-/-) colon relative to WT controls. Inhibition of NHE1 had no effect on cAMP-stimulated I(sc) in AE2(-/-) colon but caused a switch to NKCC1-supported secretion in WT colon. Thus, in AE2(-/-) colon, Cl(-) secretion supported by basolateral NKCC1 is enhanced, whereas HCO(3)(-) secretion is diminished. These results show that AE2 is a component of the basolateral ion transport mechanisms that support anion secretion in the proximal colon.


Anticipation of delayed action-effects: learning when an effect occurs, without knowing what this effect will be.
According to the ideomotor principle, behavior is controlled via a retrieval of the sensory consequences that will follow from the respective movement ("action-effects"). These consequences include not only what will happen, but also when something will happen. In fact, recollecting the temporal duration between response and effect takes time and prolongs the initiation of the response. We investigated the associative structure of action-effect learning with delayed effects and asked whether participants acquire integrated action-time-effect episodes that comprise a compound of all three elements or whether they acquire separate traces that connect actions to the time until an effect occurs and actions to the effects that follow them. In three experiments, results showed that participants retrieve temporal intervals that follow from their actions even when the identity of the effect could not be learned. Furthermore, retrieval of temporal intervals in isolation was not inferior to retrieval of temporal intervals that were consistently followed by predictable action-effects. More specifically, when tested under extinction, retrieval of action-time and action-identity associations seems to compete against each other, similar to overshadowing effects reported for stimulus-response conditioning. Together, these results suggest that people anticipate when the consequences of their action will occur, independently from what the consequences will be.


Age and risk of pulmonary arterial hypertension in scleroderma.
To investigate whether age at disease onset is a risk factor for pulmonary arterial hypertension (PAH) in scleroderma. Scleroderma center. Seven hundred nine consecutive scleroderma patients who underwent echocardiography. The risk of PAH associated with age at disease onset was modeled as both a continuous and categorical variable. Risk estimates were adjusted for sex, race, scleroderma subtype, disease duration, smoking status, FVC, anticentromere and antitopoisomerase I antibody status. Overall, 274 patients (38.6%), 272 patients by Doppler echocardiography and 2 patients by M-mode echocardiography, had PAH at baseline or during follow-up. There were 114 patients with mild PAH (right ventricular systolic pressure [RVSP], 36 to 45 mm Hg), 66 patients with moderate PAH (RVSP, 46 to 55 mm Hg), and 92 patients with severe PAH (RVSP > or =56 mm Hg). A 52% increase in risk of PAH was demonstrated for every 10 years of age at disease onset (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.31 to 1.76). In addition, there was a twofold greater risk of PAH (OR, 2.30; 95% CI, 1.32 to 3.99) for late-onset (age > or =60 years) vs earlier-onset (< 60 years) disease. These associations remained evident and were somewhat strengthened when the analyses were restricted to patients with moderate and severe PAH. We identified increasing age at scleroderma onset as a risk factor for PAH. Vigilance among these high-risk patients may provide an opportunity to intervene prior to development of irreversible pulmonary vascular disease.


Assessment of absorption of transdermal ondansetron in normal research cats.
Objectives The objective of this study was to assess the absorption of transdermal ondansetron in healthy cats. Methods Five research cats with unremarkable complete blood count, biochemistry and urinalysis were used for both single- and multiple-dose application studies. For single-dose application, 4 mg ondansetron in 0.1 ml Lipoderm gel was applied once to the internal ear pinna. Blood samples were collected via jugular catheter over a 48 h period following administration (0, 15 mins, 30 mins, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h and 48 h). For multiple-dose application, 4 mg ondansetron in 0.1 ml Lipoderm gel was applied for five consecutive days before blood samples were obtained in the same manner. Serum was separated and frozen prior to analysis. Ondansetron was measured via liquid chromatography coupled to tandem mass spectrometry. Results Analysis revealed no clinically relevant drug levels in serum after either single- or multiple-dose administration of 4 mg transdermal ondansetron. Conclusions and relevance Transdermal application of 4 mg ondansetron does not result in clinically relevant serum concentrations of drug. Despite characteristics of the drug that imply suitability for transdermal application, this does not appear to be an acceptable method of drug delivery for this medication at this dose. This study highlights the importance of assessing the suitability of each medication for transdermal administration.


Web-based Fully Automated Cephalometric Analysis: Comparisons between App-aided, Computerized, and Manual Tracings.
To compare the accuracy of cephalometric analyses made with fully automated tracings, computerized tracing, and app-aided tracings with equivalent hand-traced measurements, and to evaluate the tracing time for each cephalometric analysis method. Pre-treatment lateral cephalometric radiographs of 40 patients were randomly selected. Eight angular and 4 linear parameters were measured by 1 operator using 3 methods: computerized tracing with software Dolphin Imaging 13.01(Dolphin Imaging and Management Solutions, Chatsworth, Calif, USA), app-aided tracing using the CephNinja 3.51 app (Cyncronus LLC, WA, USA), and web-based fully automated tracing with CephX (ORCA Dental AI, Las Vegas, NV). Correction of CephX landmarks was also made. Manual tracings were performed by 3 operators. Remeasurement of 15 radiographs was carried out to determine the intra-examiner and inter-examiner (manual tracings) correlation coefficient (ICC). Inter-group comparisons were made with one-way analysis of variance. The Tukey test was used for post hoc testing. Overall, greater variability was found with CephX compared with the other methods. Differences in GoGn-SN (°), I-NA (°), I-NB (°), I-NA (mm), and I-NB (mm) were statistically (p<0.05) and clinically significant using CephX, whereas CephNinja and Dolphin were comparable to manual tracings. Correction of CephX landmarks gave similar results to CephNinja and Dolphin. All the ICCs exceeded 0.85, except for I-NA (°), I-NB (°), and I-NB (mm), which were traced with CephX. The shortest analyzing time was obtained with CephX. Fully automatic analysis with CephX needs to be more reliable. However, CephX analysis with manual correction is promising for use in clinical practice because it is comparable to CephNinja and Dolphin, and the analyzing time is significantly shorter.


Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking.
The underlying genetic and epigenetic mechanisms driving functional adaptations in neuronal excitability and excessive alcohol intake are poorly understood. Small-conductance Ca2+-activated K+ (KCa2 or SK) channels encoded by the KCNN family of genes have emerged from preclinical studies as a key contributor to alcohol-induced functional neuroadaptations in alcohol-drinking monkeys and alcohol-dependent mice. Here, this cross-species analysis focused on KCNN3 DNA methylation, gene expression, and single nucleotide polymorphisms, including alternative promoters in KCNN3, that could influence surface trafficking and function of KCa2 channels. Bisulfite sequencing analysis of the nucleus accumbens tissue from alcohol-drinking monkeys and alcohol-dependent mice revealed a differentially methylated region in exon 1A of KCNN3 that overlaps with a predicted promoter sequence. The hypermethylation of KCNN3 in the accumbens paralleled an increase in the expression of alternative transcripts that encode apamin-insensitive and dominant-negative KCa2 channel isoforms. A polymorphic repeat in macaque KCNN3 encoded by exon 1 did not correlate with alcohol drinking. At the protein level, KCa2.3 channel expression in the accumbens was significantly reduced in very heavy-drinking monkeys. Together, our cross-species findings on epigenetic dysregulation of KCNN3 represent a complex mechanism that utilizes alternative promoters to potentially impact the firing of accumbens neurons. Thus, these results provide support for hypermethylation of KCNN3 as a possible key molecular mechanism underlying harmful alcohol intake and alcohol use disorder.


Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat.
A major clinical concern with the use of cannabinoid receptor 1 (CB1) direct agonists is that these compounds increase alcohol drinking and drug abuse-related behaviours. As an alternative approach, CB1-receptor-mediated activity can be facilitated by increasing anandamide levels with the use of hydrolase fatty acid amide hydrolase (FAAH) inhibitors. Using the selective FAAH inhibitor URB597, we investigated whether activation of the endogenous cannabinoid tone increases alcohol abuse liability, as what happens with the CB1 receptor direct agonists. URB597 was tested on alcohol self-administration in Wistar rats and on homecage alcohol drinking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. In Wistar rats, URB597 effects on alcohol-induced anxiety and on stress-, yohimbine- and cue-induced reinstatement of alcohol seeking were also evaluated. For comparison, the effect of the CB1 receptor antagonist rimonabant on ethanol self-administration was also tested. Under our experimental condition, intraperitoneal (IP) administration of URB597 (0.0, 0.3 and 1.0 mg/kg) neither increased voluntary homecage alcohol drinking in msP rats nor facilitated fixed ratio 1 and progressive ratio alcohol self-administration in nonselected Wistars. In the reinstatement tests, the compound did not have effects on cue-, footshock stress- and yohimbine-induced relapse. Conversely, URB597 completely abolished the anxiogenic response measured during withdrawal after an acute IP administration of alcohol (3.0 g/kg). Rimonabant (0.0, 0.3, 1.0 and 3.0 mg/kg) significantly reduced ethanol self-administration. Results demonstrate that activation of the endocannabinoid anandamide system by selective inhibition of FAAH does not increase alcohol abuse risks but does reduce anxiety associated to alcohol withdrawal. We thus can speculate that medication based on the use of endocannabinoid system modulators such as URB597 may offer important advantages compared to treatment with direct CB1 receptor activators.


Survival trends in patients with gastric and esophageal adenocarcinomas: a population-based study.
To use a population-based approach to describe survival trends in patients diagnosed as having gastric or esophageal adenocarcinoma. A population-based complete chart review of all inpatient and outpatient records, using the resources of the Rochester Epidemiology Project, was conducted in Olmsted County, Minnesota (population 124,277), a primarily rural county with one large urban area. All residents of Olmsted County who were diagnosed as having gastric or esophageal adenocarcinoma from January 1, 1971, through December 31, 2000, were included in the study. The main outcomes were median survival and 2-year and 5-year survival rates, by decade of diagnosis. From 1971 through 2000, median survival for patients with gastric adenocarcinoma (n=121) decreased from 5.5 months to 3.2 months, whereas median survival for patients with esophageal adenocarcinoma (n=65) increased from 8.5 months to 11.7 months. Decade of diagnosis was not significantly associated with patient survival for either gastric or esophageal adenocarcinoma (P>.05). There was no significant shift in stage of disease at diagnosis during the 30-year period for either gastric or esophageal adenocarcinoma (P>.05). No significant change has occurred in the survival rates of this patient population with gastric or esophageal adenocarcinoma, which is representative of the US white population.


[Surgical correction of vertical reflux of blood in musculo-venous pump of the lower limbs and pelvis in patients with varicose veins].
The authors have made an analysis of results of treatment of 469 patients with the varicose disease. During operations on them surgical correction of vertical reflux of blood was performed by means of extravasal correction of incompetent valves of the femoral, popliteal and tibial veins, resection or obturation of the posterior tibial veins. Traditional methods (frame spiral and fascioplication) and original ones (three ligatures and tension of the valve cusps through the frame spiral coil) were used. Elimination of the vertical reflux of blood in each of the four pumps (abdomino-caval and femoral ones, those of the leg and foot) forming the musculo-venous pump, results in getting 7% greater amount of excellent and good results, bad results were obtained in 3.4% less number of cases. The period of temporary loss of working ability becomes shorter.


Human papovavirus infection of an SV40-transformed human embryonic kidney cell line.
Human embryonic kidney cells were transformed at their third passage with an origin-defective mutant of SV40, 1-11. One clone of these cells, SV1, demonstrated several phenotypes of transformation including high-density growth and anchorage independence. The SV1 cells also were 100% T antigen-positive when tested by immunofluorescence and immunoprecipitation assays. These cells with the SV40 T protein were able to support the persistent replication of BK viral DNA but did not support virus multiplication. The SV1 cells would also support the replication of the Sau 3A A fragment of the BK genome cloned into pBR 322. However, SV1 cells would not support multiplication of JC virus or replication of JC DNA.


Paradigm Shift in Antimicrobial Resistance Pattern of Bacterial Isolates during the COVID-19 Pandemic.
Antimicrobial resistance (AMR) is an emerging public health problem in modern times and the current COVID-19 pandemic has further exaggerated this problem. Due to bacterial co-infection in COVID-19 cases, an irrational consumption of antibiotics has occurred during the pandemic. This study aimed to observe the COVID-19 patients hospitalized from 1 March 2019 to 31 December 2020 and to evaluate the AMR pattern of bacterial agents isolated. This was a single-center study comprising 494 bacterial isolates (blood and urine) that were obtained from patients with SARS-CoV-2 admitted to the ICU and investigated in the Department of Microbiology of a tertiary care hospital in Delhi, India. Out of the total bacterial isolates, 55.46% were gram negative and 44.53% were gram positive pathogens. Of the blood samples processed, the most common isolates were CoNS (Coagulase Negative Staphylococcus) and Staphylococcus aureus. Amongst the urinary isolates, most common pathogens were Escherichia coli and Staphylococcus aureus. A total of 60% MRSA was observed in urine and blood isolates. Up to 40% increase in AMR was observed amongst these isolates obtained during COVID-19 period compared to pre-COVID-19 times. The overuse of antibiotics gave abundant opportunity for the bacterial pathogens to gradually develop mechanisms and to acquire resistance. Since the dynamics of SARS-COV-2 are unpredictable, a compromise on hospital antibiotic policy may ultimately escalate the burden of drug resistant pathogens in hospitals. A shortage of trained staff during COVID-19 pandemic renders it impossible to maintain these records in places where the entire hospital staff is struggling to save lives. This study highlights the extensive rise in the use of antibiotics for respiratory illness due to COVID-19 compared to antibiotic use prior to COVID-19 in ICUs. The regular prescription audit followed by a constant surveillance of hospital infection control practices by the dedicated teams and training of clinicians can improve the quality of medications in the long run and help to fight the menace of AMR.


Improved preparation and physical studies of polybutylcyanoacrylate nanocapsules.
An improved method for the preparation of alkylcyanoacrylate nanocapsules is proposed that involves the intermediate synthesis of a well defined adduct of a single monomer unit to an ethanol molecule. It leads to thinner capsule walls and, generally, to a more reproducible capsule structure. The chemical composition of the intermediate organic phase has been studied by nuclear magnetic resonance spectroscopy. The morphology and size of resulting structures is analysed, applying analytical ultracentrifugation and light microscopic particle tracking. The sizes of capsules prepared in the described manner depend on the concentrations of the oil and the monomer components, as is shown by the results of a set of experiments following a simple factorial design.


Walking Children Through a Minefield: How Professionals Experience Exploring Adverse Childhood Experiences.
Understanding the challenges of professionals in addressing child adversity is key to improving the detection, protection, and care of exposed children. We aimed to synthesize findings from qualitative studies of professionals' lived experience of addressing child adversity. Through a systematic search, we identified eight qualitative studies and synthesized them using metaethnography. We generated three themes, "feeling inadequate," "fear of making it worse," and "facing evil," and one overarching metaphor, "walking children through a minefield." The professionals felt that they lacked the means necessary to explore child adversity, that they were apprehensive of worsening the child's situation, and that their work with child adversity induced emotional discomfort. This metasynthesis indicated that the professionals' efficiency in exploring abuse relied upon their ability to manage emotional and moral distress and complexity. To support children at risk, we propose developing professionals' ability to build relationships, skills in emotion regulation, and proficiency in reflective practice.


Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits.
Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet-induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression.


Dual AAV-based PCDH15 gene therapy achieves sustained rescue of visual function in a mouse model of Usher syndrome 1F.
Mutations in the PCDH15 gene, encoding protocadherin-15, are among the leading causes of Usher syndrome type 1 (USH1F), and account for up to 12% USH1 cases worldwide. A founder truncating variant of PCDH15 has a ∼2% carrier frequency in Ashkenazi Jews accounting for nearly 60% of their USH1 cases. Although cochlear implants can restore hearing perception in USH1 patients, presently there are no effective treatments for the vision loss due to retinitis pigmentosa. We established a founder allele-specific Pcdh15 knockin mouse model as a platform to ascertain therapeutic strategies. Using a dual-vector approach to circumvent the size limitation of adeno-associated virus, we observed robust expression of exogenous PCDH15 in the retinae of Pcdh15KI mice, sustained recovery of electroretinogram amplitudes and key retinoid oxime, substantially improved light-dependent translocation of phototransduction proteins, and enhanced levels of retinal pigment epithelium-derived enzymes. Thus, our data raise hope and pave the way for future gene therapy trials in USH1F subjects.


Expression of cytochromes P450 in human breast tissue and tumors.
In an effort to determine which members of the cytochrome P450 (CYP) superfamily are expressed in human breast tissue and tumors, RNA-polymerase chain reaction studies have been undertaken. Detection of expressed CYP mRNAs identifies those forms of the enzyme that are capable of expression in breast tissue, and provides insight into the potential for in situ xenobiotic and therapeutic drug metabolism. CYP1A1 mRNA was present in (5/11) breast tissues and (6/13) tumors. When normal and tumor tissues were from the same individuals, higher amplification occurred in normal tissues. CYP1B1 mRNA was present in all but one tissue, and CYP2C mRNA forms were present in all of the tissues. CYP3A4 mRNA was present in (8/11) normal breast tissues and (2/13) tumor tissues, and CYP3A5 mRNA was present in (9/11) normal tissues and (2/13) tumor tissues. The expression of the CYP3A mRNA forms was not coincident, suggesting differential regulation. CYP2D6 mRNA was present in (10/11) normal breast tissue and (10/13) tumors. Two splice variants of CYP2D6 mRNA were also detected; one with a 207 bp intron spliced in was detected in all of the normal tissue samples and (11/13) tumors, whereas another (which lacks a 3'-portion of exon 6) was detected in (9/11) normal breast tissues and (7/13) tumors. Thus, examples of each of the xenobiotic-metabolizing CYP1, CYP2, and CYP3 subfamilies were detected in low levels in human normal breast tissue and tumors. The machinery for possible in situ bioactivation of xenobiotics and modification of therapeutic drugs is thus present in human breast tissue.


Gamma scintigraphy of a 123I-labelled N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugate containing galactosamine following intravenous administration to nude mice bearing hepatic human colon carcinoma.
Polymer drug conjugates composed of N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer covalently bound doxorubicin, and containing additionally galactosamine to facilitate hepatocyte-specific targeting (HPMA copolymer-dox-gal), were synthesised to contain a small amount (approximately 1 mol%) of the monomer methacryloyltyrosinamide to permit radioiodination with [123I]iodide. After intravenous administration to both normal mice and nude mice bearing hepatic human colon carcinoma, the biodistribution of the conjugate was monitored using the gamma camera, and also by dissection analysis. Efficient liver accumulation of HPMA copolymer-dox-gal was seen in the gamma camera images within 20 min, both in normal and tumour-bearing animals. Quantitatively liver uptake was approximately 40% dose administered/g liver. Images of the tumour-bearing animals showed clearly a much lower accumulation of HPMA copolymer-dox-gal in the colon carcinoma deposits within the liver (3-9% dose/g tumour), and this lack of uptake was verified by ex vivo imaging of the tumour-containing liver and also by dissection analysis. It can be concluded that 123I-labelled HPMA copolymer conjugates offer great potential as effective imaging agents and can be used for future non-invasive clinical studies. This nuclear imaging method will enable optimisation of the dosing schedule by identification of doses of HPMA copolymer-dox-gal that display receptor saturation (and hence diminished targeting efficiency). In addition this conjugate can provide negative images of liver-associated tumour deposits that do not express the asialoglycoprotein receptor.


High prevalence of Helicobacter pylori infection in duodenal ulcer perforations not caused by non-steroidal anti-inflammatory drugs.
There has been controversy regarding the relationship between Helicobacter pylori and perforated peptic ulcer, which is known to have a high recurrence rate if only simple patch repair is performed. The aim of this study was to evaluate the association between H. pylori infection and intake of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with perforated duodenal ulcers. Of the 73 patients recruited over a 16-month period, 51 (70 per cent) had evidence of H. pylori infection by intraoperative gastroscopy and antral biopsies. The infection rate rose to 80 per cent if NSAID users were excluded. The H. pylori-infected group was significantly younger (mean 47.6 versus 62.5 years), with a male preponderance (49 of 51 versus 14 of 22 patients), and had significantly less NSAID consumption (three of 51 versus ten of 22) and more prolonged dyspepsia (40 of 51 versus ten of 22), compared with H. pylori-negative patients. H. pylori infection probably plays an important role in the causation of non-NSAID-induced duodenal ulcer perforation. Whether eradication of the bacteria can alleviate the strong ulcer diathesis in this subgroup of patients is unknown.


A syndrome resembling feline dysautonomia (Key-Gaskell syndrome) in a dog.
Dysautonomia, or autonomic nervous system dysfunction, was diagnosed in a 1-year-old dog. Clinical signs of disease included diarrhea, vomiting, prolapse of nictitating membranes, and urinary incontinence. Bilateral keratoconjunctivitis sicca, xerostomia, and decreased anal sphincter tone were also observed. On the basis of response to atropine, results of intradermal histamine testing and gastric motility studies, and ocular response to parasympathomimetics and sympathomimetics (direct and indirect acting), autonomic nervous system function was determined to be abnormal. Treatment with metoclopramide hydrochloride and bethanechol chloride resulted in improved attitude, appetite, Schirmer tear test response, and decrease in frequency of vomiting within 24 hours. Bladder function and anal tone improved within 3 weeks.


Parenteral nutrition.
Although there have been no fundamental changes in the nature and practice of parenteral nutrition during the review period, there have been important observations with respect to adjunctive hormonal manipulation and the recognition of new hazards that warrant review. Papers summarized include those demonstrating benefit from addition of growth hormone, and of medium-chain triglycerides, and those indicating that there is no apparent aggravation to osteoporosis, even with long-term intravenous nutrition. General advice is given on the place for new interventions and avoidance of complications. The relative safety of long-term parenteral nutrition is reconfirmed. Interesting new manipulations of the hormonal and lipid milieu may prove to be important developments.


Rolling adhesion through an extended conformation of integrin alphaLbeta2 and relation to alpha I and beta I-like domain interaction.
In vivo, beta(2) integrins and particularly alpha(L)beta(2) (LFA-1) robustly support firm adhesion of leukocytes, but can also cooperate with other molecules in supporting rolling adhesion. Strikingly, a small molecule alpha/beta I-like allosteric antagonist, XVA143, inhibits LFA-1-dependent firm adhesion, while at the same time it enhances adhesion in shear flow and rolling both in vitro and in vivo. XVA143 appears to induce the extended conformation of integrins as shown by increased activation epitope exposure. Fab to the beta(2) I-like domain converts firm adhesion to rolling adhesion, but does not enhance adhesion. Residue alpha(L)-Glu-310 in the linker following the I domain is critical for communication to the beta(2) I-like domain, rolling, integrin extension, and activation by Mn(2+) of firm adhesion. The results demonstrate the importance of integrin extension in rolling, and suggest that rolling and firm adhesion are mediated by extended conformations of alpha(L)beta(2) that differ in the affinity of the alpha(L) I domain for ICAM-1.


Prevalence of gallstones in 1,229 patients submitted to surgical laparoscopic treatment of GERD and esophageal achalasia: associated cholecystectomy was a safe procedure.
Association between esophageal achalasia/ gastroesophageal reflux disease (GERD) and cholelithiasis is not clear. Epidemiological data are controversial due to different methodologies applied, the regional differences and the number of patients involved. Results of concomitant cholecistectomy associated to surgical treatment of both diseases regarding safety is poorly understood. To analyze the prevalence of cholelithiasis in patients with esophageal achalasia and gastroesophageal reflux submitted to cardiomyotomy or fundoplication. Also, to evaluate the safety of concomitant cholecistectomy. Retrospective analysis of 1410 patients operated from 2000 to 2013. They were divided into two groups: patients with GERD submitted to laparocopic hiatoplasty plus Nissen fundoplication and patients with esophageal achalasia to laparoscopic cardiomyotomy plus partial fundoplication. It was collected epidemiological data, specific diagnosis and subgroups, the presence or absence of gallstones, surgical procedure, operative and clinical complications and mortality. All groups/subgroups were compared. From 1,229 patients with GERD or esophageal achalasia, submitted to laparoscopic cardiomyotomy or fundoplication, 138 (11.43%) had cholelitiasis, occurring more in females (2.38:1) with mean age of 50,27 years old. In 604 patients with GERD, 79 (13,08%) had cholelitiasis. Lower prevalence occurred in Barrett's esophagus patients 7/105 (6.67%) (p=0.037). In 625 with esophageal achalasia, 59 (9.44%) had cholelitiasis, with no difference between chagasic and idiopathic forms (p=0.677). Complications of patients with or without cholecystectomy were similar in fundoplication and cardiomyotomy (p=0.78 and p=1.00).There was no mortality or complications related to cholecystectomy in this series. Prevalence of cholelithiasis was higher in patients submitted to fundoplication (GERD). Patients with chagasic or idiopatic forms of achalasia had the same prevalence of cholelithiasis. Gallstones occurred more in GERD patients without Barrett's esophagus. Simultaneous laparoscopic cholecystectomy was proved safe.


The diversity and abundance of bacteria inhabiting seafloor lavas positively correlate with rock alteration.
Young, basaltic ocean crust exposed near mid-ocean ridge spreading centers present a spatially extensive environment that may be exploited by epi- and endolithic microbes in the deep sea. Geochemical energy released during basalt alteration reactions can theoretically support chemosynthesis, contributing to a trophic base for the ocean crust biome. To examine associations between endolithic microorganisms and basalt alteration processes, we compare the phylogenetic diversity, abundance and community structure of bacteria existing in several young, seafloor lavas from the East Pacific Rise at approximately 9 degrees N that are variably affected by oxidative seawater alteration. The results of 16S rRNA gene analyses and real-time, quantitative polymerase chain reaction measurements show that the abundance of prokaryotic communities, dominated by the bacterial domain, positively correlates with the extent of rock alteration--the oldest, most altered basalt harbours the greatest microbial biomass. The bacterial community overlap, structure and species richness relative to alteration state is less explicit, but broadly corresponds to sample characteristics (type of alteration products and general alteration state). Phylogenetic analyses suggest that the basalt biome may contribute to the geochemical cycling of Fe, S, Mn, C and N in the deep sea.


Squamate metabolic rates decrease in winter beyond the effect of temperature.
The reptilian form of hibernation (brumation) is much less studied than its mammalian and insect equivalents. Hibernation and brumation share some basic features but may differ in others. Evidence for hypometabolism in brumating reptiles beyond the effect of temperature is sporadic and often ignored. We calculated the standard metabolic rates (SMR, oxygen uptake during inactivity), in winter and/or summer, of 156 individuals representing 59 species of Israeli squamates across all 17 local families. For 32 species, we measured the same individuals during both seasons. We measured gas exchange continuously in a dark metabolic chamber, under the average January high and low temperatures (20°C and 12°C), during daytime and nighttime. We examined how SMR changes with season, biome, body size, temperature and time of day, using phylogenetic mixed models. Metabolic rates increased at sunrise in the diurnal species, despite no light or other external cues, while in nocturnal species the metabolic rates did not increase. Cathemeral species shifted from a diurnal-like diel pattern in winter to a nocturnal-like pattern in summer. Regardless of season, Mediterranean species SMRs were 30% higher than similar-sized desert species. Summer SMR of all species together scaled with body size with an exponent of 0.84 but dropped to 0.71 during brumation. Individuals measured during both seasons decreased their SMR between summer and winter by a 47%, on average, at 20°C and by 70% at 12°C. Q10 was 1.75 times higher in winter than in summer, possibly indicating an active suppression of metabolic processes under cold temperatures. Our results challenge the commonly held perception that squamate physiology is mainly shaped by temperature, with little role for intrinsic metabolic regulation. The patterns we describe indicate that seasonal, diel and geographic factors can trigger remarkable shifts in metabolism across squamate species.


Efficient access to 2-isobetulinic acid, 2-isooleanolic acid, and 2-isoursolic acid.
An efficient access to 2-isobetulin, 2-isobetulinic acid, 2-isooleanolic acid, and 2-isoursolic acid has been developed. The key step is a novel one-pot conversion of 2,3-dihydroxy triterpenes to 3-deoxy-2-oxo triterpenes. This method provides a new access to 3-deoxy-2-substituted pentacyclic triterpenes as potential therapeutic agents against metabolic diseases, tumors, and HIV infection.


Morphometric study of suprascapular notch in Indian dry scapulae with specific reference to the incidence of completely ossified superior transverse scapular ligament.
The suprascapular notch, a depression on the lateral part of the superior border of the scapula, medial to the coracoid process, is bridged by the superior transverse scapular ligament, which is sometimes ossified and the foramen which is thus completed, transmits the suprascapular nerve to the supraspinatus fossa. Variations in the morphology of suprascapular notch have been identified as one of the causes of suprascapular nerve entrapment. Rengachary et al. classified this notch into six types, based on its shape. To study morphological variations of suprascapular notch in Indian dry scapulae and to analyze the incidence of completely ossified superior transverse scapular ligament with other ethnic populations which have been cited earlier. A total of 400 human dry scapulae which were obtained from the Department of Anatomy of selected eight medical colleges were analyzed. The type of suprascapular notch was noted and it was recorded as per the description given by Rengachary et al. The results of the present study were compared with the results of previous authors in different populations. In our study, out of 400 scapulae, 40 (10%), were identified to have completely ossified superior transverse scapular ligaments. The frequencies of various types of suprascapular notches were: Type I -20%, Type II -10%, Type III -52%, Type IV -4%, Type V -4%, Type VI -10%. Since the suprascapular nerve entrapment syndrome might be caused by complete ossification of superior transverse scapular ligament with formation of suprascapular foramen and other morphometric variations of suprascapular notch, the knowledge on such variations is essential for clinicians, for making a proper diagnosis and for planning the most suitable surgical intervention.


Targeting Biomechanical Endurance of Dental-Implant Abutments Using a Diamond-Like Carbon Coating.
Abutment components (i.e., fixtures associated with oral implants) are essentially made of titanium (Ti), which is continuously exposed to the hash oral environment, resulting in scratching. Thus, such components need to be protected, and surface treatments are viable methods for overcoming long-term damage. Diamond-like carbon (DLC), an excellent protective material, is an alternative surface-treatment material for Ti abutments. Here, we demonstrate that a silicon interlayer for DLC film growth and the pulsed-direct current plasma-enhanced chemical vapor deposition (DC-PECVD) method enables the deposition of an enhanced protective DLC film. As a result, the DLC film demonstrated a smooth topography with a compact surface. Furthermore, the DLC film enhanced the mechanical (load-displacement, hardness, and elastic modulus) and tribological properties of Ti as well as increased its corrosion resistance (16-fold), which surpassed that of a bare Ti substrate. The biofilm formed (Streptococcus sanguinis) after 24 h exhibited an equal bacterial load (∼7 Log colony-forming units) for both the groups (Ti and DLC). In addition, the DLC film exhibited good cytocompatibility, owing to its noncytotoxicity toward human gingival fibroblast cells. Therefore, DLC deposition via DC-PECVD can be considered to be a promising protective and cytocompatible alternative for developing implant abutments with enhanced mechanical, tribological, and electrochemical properties.


Exploring fNIRS-Based Brain State Recognition and Visualization through the use of Explainable Convolutional Neural Networks.
Functional near infrared spectroscopy (fNIRS) is a neuroimaging technique that has grown vigorously in recent years. With noticeable attention, machine learning methods have also been applied to fNIRS. However, the current approach lacks interpretability of the results. In recent years, the utilization and investigation of fNIRS have experienced significant growth and are now being utilized in clinical research. However, the collection of clinical fNIRS data is limited in sample size. Therefore, our aim is to utilize the collected fNIRS data from all channels and achieve interpretable analysis results with minimal human manipulation, channel selection or feature extraction. We developed an fNIRS-based interpretable model and used class-specific gradient information to visualize the biomarkers captured by the model via locating the important region. The accuracy of our model's classification was 6% higher than that of the conventional SVM method under within-subject classification. The model focuses on signals from the left brain in the classification of right-hand finger tapping task, while in the task of classifying left-handed movements, the model relies on signals from the right brain. These results were consistent with current understanding of physiology.Clinical Relevance- The machine learning-based fNIRS model has the potential to be used for the diagnosis and prediction of therapeutic efficacy in clinical settings.


Development of the World Health Organization Measles Programmatic Risk Assessment Tool Using Experience from the 2009 Measles Outbreak in Namibia.
In the World Health Organization (WHO) African region, reported measles cases decreased by 80% and measles mortality declined by 88% during 2000-2012. Based on current performance trends, however, focused efforts will be needed to achieve the regional measles elimination goal. To prioritize efforts to strengthen implementation of elimination strategies, the Centers for Disease Control and Prevention and WHO developed a measles programmatic risk assessment tool to identify high-risk districts and guide and strengthen program activities at the subnational level. This article provides a description of pilot testing of the tool in Namibia using comparisons of high-risk districts identified using 2006-2008 data with reported measles cases and incidence during the 2009 outbreak. Of the 34 health districts in Namibia, 11 (32%) were classified as high risk or very high risk, including the district of Engela where the outbreak began in 2009. The district of Windhoek, including the capital city of Windhoek, had the highest overall risk score-driven primarily by poor population immunity and immunization program performance-and one of the highest incidences during the outbreak. Other high-risk districts were either around the capital district or in the northern part of the country near the border with Angola. Districts categorized as high or very high risk based on the 2006-2008 data generally experienced high measles incidence during the large outbreak in 2009, as did several medium- or low-risk districts. The tool can be used to guide measles elimination strategies and to identify programmatic areas that require strengthening.


Differential survival rates among low-birth-weight black and white infants in a tertiary care hospital.
Birth-weight-specific mortality is lower for black prematures than white prematures of similar low birth weight. The reason for this well-recognized phenomenon is unknown. We investigated the extent to which black and white infants differ in their gestational maturity and incidence of potentially lethal risk factors, and the effect these factors might have on differential mortality risk. The population studied comprised babies born alive in a tertiary care hospital with birth weights from 700 to 1800 g over a 4 1/2-year period. Univariate analysis showed no important difference between races for the incidence of lung disease, Apgar scores, birth weight, or gestational age. Infants with a birth weight below the 10th percentile (small for gestational age) were more likely to be black, and infants with a birth weight above the 90th percentile (large for gestational age) who had a survival disadvantage were usually white. The crude odds ratio for the white race was 1.79 (1.18-2.73). When the demographic, morbidity, and growth variables were put into a logistic model, the odds ratio changed only slightly, to 1.52 (1.14-2.03). We conclude that the majority of the black-white difference in birth-weight-specific survival is not due to a higher incidence of black small-for-gestational-age infants, nor is it due to differences in major morbidities associated with death.


[The use of antibiotic prophylaxis prior to dental procedures for the prevention of prosthetic joint infection].
Prosthetic joint infection (PJI) is a severe illness which may cause pain and discomfort, may damage the quality of life and may even be life-threatening. A variety of studies have demonstrated the presence of bacteria in a small but potentially dangerous number of prosthetic joint infections that may have originated in the oral cavity. Some dental treatments such as calculus removal, extractions, dental implants placements etc. and daily oral hygiene routines such as tooth brushing may cause bacteremia. Recently the American Academy of Orthopaedic Surgeons (AAOS) published updated guidelines for antibiotic prophylaxis to prevent prosthetic joint infections. These guidelines suggest a direct and established connection between dental treatments and prosthetic joint infections, and expand the criteria to prescribe antibiotic prophylaxis prior to dental procedures associated with bacteremia. The purpose of this review is to introduce these new guidelines, and to review the literature regarding the relationship between dental care and prosthetic joint infections.


Development of a continuously perfused ex vivo kidney training model for laparoscopic partial nephrectomy: validity and efficiency.
Suture hemostasis is essential for laparoscopic partial nephrectomy (LPN). This study aimed to develop, validate, and test the efficacy of a continuously-perfused training model (CPTM) in LPN with high-level simulated bleeding. The CPTM was constructed using fresh porcine kidneys with renal arteries continuously perfused with red-dyed liquid gelatin. Twenty-nine participants with expert, intermediate, or novice laparoscopic experience levels were recruited. The expert and intermediate participants evaluated the CPTM, and the novice participants were randomly assigned to one of two groups to complete training on a CPTM or dry box training model (DBTM). Messick's framework criteria were utilized to assess the validity and training efficacy of the model. The data were analyzed using the Mann-Whitney U, Kruskal-Wallis, and Friedman tests. A value of P<0.05 was considered statistically significant. Positive comments were provided by all experts and intermediates for the Content. The Relationships with other variables demonstrated significant differences among novices, intermediates, and experts in all metrics (P<0.05). The Consequences showed that the CPTM helped novices acquire LPN skills. The training efficacy was significantly better than that of the DBTM (P<0.05). There were no significant differences between the final performances of the novices and initial performances of the experts (P>0.05). Synthesizing all metrics, the LPN skills learned using CPTMs were significantly improved in the 12th round of training. The CPTM offered high-level simulation of bleeding with realistic tissue texture for acquiring LPN skills. Training of no fewer than 12 rounds is recommended for a novice's LPN training on the CPTM.


Startle neural activity is additive with normal cortical initiation-related activation.
The current study examined the process of response initiation in a simple reaction time (RT) task using a startling acoustic stimulus (SAS), which has been shown to trigger a prepared movement through an involuntary initiation pathway. The SAS was presented within the RT interval (concurrent with, and 25, 50, 75, 100, and 125 ms following the "go" signal), with the observed response latency used to examine the relative contributions of voluntary and involuntary activation to response initiation. Our results clearly indicate that both voluntary and startle-related initiation activation jointly contribute to the observed RT. The data support a model in which startle-related neural activity is additive with voluntary cortical initiation-related activation. This result also provides indirect support for the hypothesis that both voluntary and SAS-related involuntary activation involve a similar process of response output.


Do environmental differences between lakes in northwestern Argentinean Patagonia affect the infection of Philureter trigoniopsis (monogenea) in Galaxias maculatus (osmeriformes)?
Philureter trigoniopsis is the only parasite found in the ureters and urinary bladder of Galaxias maculatus in Patagonian Andean lakes. The dynamics of this endoparasitic monogenean were studied in Lake Gutiérrez, a body of water with scarce shoreline vegetation, where the host has an annual cycle of migration to the deep pelagic zone of the lake. To compare variations of the infection related to differences between lakes, G. maculatus specimens were sampled monthly with baited traps from September 1998 to November 1999 in Lake Moreno, which is an oligotrophic body of water with emergent shoreline vegetation and where the fish do not migrate to the deep pelagic areas of the lake. In addition, data for summer infections of P. trigoniopsis from 10 Andean Patagonian lakes that differ in aquatic vegetation, depth, and area were compared. In Lake Moreno prevalence of P. trigoniopsis showed a seasonal pattern, with 1-yr-old fish exhibiting the highest values of prevalence and mean intensity. Negative correlations between water temperature and prevalence and between age of fish and abundance were found. Our results suggest that age of fish may be the main factor structuring the distribution of P. trigoniosis in populations of G. maculatus. At the regional level the relationship between the infection and the characteristics of the lakes was also observed, with prevalence and mean intensity of P. trigoniopsis in G. maculatus higher in large deep lakes without macrophytes.


Dysregulated Maturation of the Functional Connectome in Antipsychotic-Naïve, First-Episode Patients With Adolescent-Onset Schizophrenia.
Schizophrenia has been conceptualized as a brain network disorder rooted in dysregulated neurodevelopmental processes. Recent neuroimaging studies revealed disrupted brain connectomic organization in adult schizophrenia patients. However, altered developmental trajectories of the functional connectome during the adolescent maturational stage have not been examined. The present study combined functional MRI with a graph theoretical approach to examine functional network topology and its age-related development in 39 medication naïve, first-episode patients with adolescent-onset schizophrenia and 31 matched controls (age range: 12-18 years). Patients demonstrated impaired large-scale integration as reflected by reduced global efficiency as well as decreased regional nodal efficiency in highly integrative network hubs, most consistently the hippocampal formation and the precuneus. Furthermore, the left hippocampus showed opposite age-efficiency associations in healthy controls and patients, indicating dysregulated maturational trajectories in adolescent schizophrenia and a particular vulnerability of this region during early pathological attack. The findings allow an integrative perspective on network and neurodevelopmental perspectives on schizophrenia, suggesting that dysregulated maturation of the functional connectome during adolescence might reflect an early marker for the disorder.


Population pharmacokinetic model of valproate and prediction of valproate serum concentrations in children with epilepsy.
Using sparse data of valproate (VPA) serum concentrations to build a population pharmacokinetic (PPK) model of VPA in Chinese children with epilepsy and to predict serum concentrations for new patients using a Bayesian approach. Two hundred epileptic children, whose VPA serum concentrations were collected, were divided randomly into two groups (A and B, n=100 each). The PPK parameter values of group A were calculated to establish a PPK Model by using the NPEM Program of USC*PACK software. Based on it, VPA serum concentrations of group B were predicted with the Bayesian Fitting Program of the USC*PACK software. To assess the accuracy and precision of prediction, a paired-comparisons t-test was run between predicted and observed concentrations, and then the mean prediction error (MPE), mean square prediction error (MSPE), root mean square prediction error (RMSPE), and coincidence rates for different percentages of prediction error were all calculated. Optimum PPK parameters were: Ka, 2.522+/-2.743 h(-1); Vs, 0.329+/-0.496 L/kg; and Kel, 0.0438+/-0.0384 h(-1). For group B, there was no significant difference between predicted and observed concentrations. MPE was -0.43 mg/L, MSPE was 115.40 (mg/L)2, and RMSPE was 5.47 mg/L. The coincidence rates for percentages of prediction error, which were less than 5 %, 10 %, 15 %, 20 %, 25 %, and 30 %, were 62 %, 74 %, 82 %, 85 %, 89 %, and 93 %, respectively. A PPK model of VPA in epileptic children was successfully established. Based on it, VPA serum concentrations can be predicted accurately with a Bayesian approach.


Teratological studies of hydroxypropylmethylcellulose acetate succinate in rats.
A teratogenicity study was carried out in S1c: SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1,250 and 2,500 mg/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on Day 21 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the offsprings was observed. The incidences of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. HPMCAS caused no effects on parturition, lactation, postnatal growth and reproductive ability of the male and female offspring.


Mismatch repair protein immunohistochemistry: a useful population screening strategy for Lynch syndrome.
Lynch syndrome (LS), the most frequent form of hereditary colorectal cancer, shows a highly penetrant, autosomal dominant pattern of inheritance. Distinction of LS colorectal carcinoma instances from the much more common sporadic colorectal carcinoma cases is of paramount importance. Revised Bethesda Guidelines were developed to diagnose LS by evaluating a combination of clinical and pathologic data. The aim of the present study was to evaluate the usefulness of the pathology items included in the Revised Bethesda Guidelines. We have prospectively studied a series of 1624 consecutive colorectal carcinomas with an algorithm including immunohistochemical analysis of mismatch repair proteins and molecular study of microsatellite instability and BRAF c.1799 T > A (p.V600E) gene mutations. Patients with tumors showing LS features were referred for germline mutation analysis. By applying our algorithmic approach, we were able to identify LS features in 89 colorectal cancer patients, of whom only 27 met Revised Bethesda Guidelines pathology criteria. Of the 89 patients, 47 were then studied at the Genetic Counseling Unit, and LS was confirmed in 18, of whom 7 had not been identified by the Revised Bethesda Guidelines. Our study shows that the Revised Bethesda Guidelines failed to detect 70% of patients at risk of LS. Our algorithmic approach is a realistic and effective tool for LS identification. We strongly recommend the implementation of universal population screening for LS among all patients with newly diagnosed colorectal carcinoma.


Simple densitometer for microbiology laboratories.
A densitometer composed of a microscope and a colorimeter is described. Results obtained with the microscope densitometer and with a standard densitometer compare favorably.