[Study on preparation of salvianolic acid phospholipid compound].
To prepare salvianolic acid phospholipid compound. With the compound of salvianolic acids and soybean phospholipid as the index, mono-factor experiment and orthogonal design experiment were conducted to screen its technical parameters. According to the results, the optimal preparation conditions of salvianolic acid phospholipid compound were that THF were taken as the reaction solvent, the concentration time was 3 h, the reactant concentration was 5 g x L(-1), the mass ratio of salvianolic acids and phospholipid was 1: 1.5, and the reaction temperature was 40 degrees C. The oil/water partition coefficient of the prepared salvianolic acid phospholipid compound significant increased in water and buffers with different pH values. The results of phase analysis such as DSC, XRD and FTIR indicated that salvianolic acids existed in phospholipid in an amorphous state.


Continuous Water Filling in a Graphene Nanochannel: A Molecular Dynamics Study.
Low dimensional materials especially carbon materials hold high promise in the fields of water purification, mineral separation, energy harvesting/conversion, and so on. The fluidic devices fabricated by direct synthesis, lithography, or self-assembly of low dimensional materials provide opportunities for exploring the novel properties and applications of nanoconfined transport. Here, continuous filling of water and acetone molecules into a graphene nanochannel is investigated. A stairlike nonlinear dependence of the number of filling water molecules on interlayer distance d is found when d < 1 nm due to the existence of out-plane layered and in-plane ordered monolayer structure, while near-linear dependence is found for acetone because of the freely rotating configurations along with varying d during the filling process. The entropy, potential energy, and free energy of the confined system during the continuous filling are analyzed to understand the structural evolution of water. The energy-costs are discussed depending on the structure evolution of water during the filling, which is crucial to understanding the swelling and capillary condensation widely existing in the angstrom/nanometer-scale separation membranes.


Factors Influencing Parents' Decisions to Create a Business for Their Adult Child With Intellectual Disability.
Obtaining and maintaining work can be a challenge for many people with intellectual disability (ID) and parents can play an integral role in supporting their child to secure employment. The purpose of this qualitative research study was to understand factors that influence parents' decisions to create a business for their adult child with ID. Nine parents were identified through purposeful and snowball sampling. Parents participated in individual interviews and data were analyzed using thematic analysis. Our findings suggest that school experiences, expectations for work, presence of specialized support, and encouragement and suggestions from others influenced parents' decisions to create a business. In light of the findings, we discuss how parents' previous experiences and responsiveness influenced the creation of the business.


Cholesterol fatty liver. Morphological changes in the course of its development in rabbits.
Livers from 90 rabbits used in a factorial experiment relating cholesterol contents of various tissues to their serum cholesterol levels and duration of exposure were observed under light microscope. Livers from eight additional rabbits fed a 2% cholesterol diet for various periods up to 90 days were fixed in an aldehyde fixative containing 0.2% digitonin and observed under electron microscope. Digitonin-induced laminar and microtubular structures appeared five hours after cholesterol feeding. Fat vacuoles in both hepatocytes and Kupffer cells were first noted on the third day and increased in number and size to the 60th day but decreased on the 90th day. Adaptation of the liver to such excessive fat accumulation was evidenced by the gradual decrease of fat vacuoles and increase of binucleated cells.


The incidence of positive cultures in women suspected of having PID/Salpingitis
OBJECTIVES: To determine the incidence of GC and chlamydia in women with suspected acute pelvic inflammatory disease. A secondary objective was to investigate the clinical usefulness of physical exam findings of vaginal discharge, cervical motion, and adnexal tenderness. METHODS: This was a retrospective chart review of patients seen in the ED. Patients were entered into the study if they had PID/salpingitis as their discharge diagnosis and cultures performed for GC and chlamydia. RESULTS: A total of 133 charts were reviewed. 13 patients were excluded due to incomplete charting of history and physical exam or inability to obtain culture results. Of the remaining 120 patients, 70 cultures were negative for any growth. 10 cultures were positive for GC and 10 cultures were positive for chlamydia. In reviewing the physical exam findings in women with negative cultures, 74% had discharge, 93% had cmt, and 66% had adnexal tenderness. For women with cultures positive for GC and chlamydia, 90% had discharge, 80% had cmt, and 75% had adnexal tenderness. For vaginal discharge the sens, spec, ppv, npv were 0.90, 0.26, 0.35, 0.90. For cmt the sens, spec, ppv, npv were 0.80, 0.07, 0.20, 0.55. For adnexal tenderness the sens, spec, ppv, npv were 0. 75, 0.34, 0.25, 0.83. No combination of the three physical exam findings increased the ppv. CONCLUSIONS: The incidence of positive cultures in women suspected of having PID/salpingitis is 16%. The physical exam findings were not predictive of disease secondary to the high number of false positives. Although 16% positives may warrant empiric treatment, patients should not be told they have PID/salpingitis until the cultures are available.


Reduction of atmospheric fine particle level by restricting the idling vehicles around a sensitive area.
Atmospheric particles are a major problem that could lead to harmful effects on human health, especially in densely populated urban areas. Chiayi is a typical city with very high population and traffic density, as well as being located at the downwind side of several pollution sources. Multiple contributors for PM2.5 (particulate matter with an aerodynamic diameter ≥2.5 μm) and ultrafine particles cause complicated air quality problems. This study focused on the inhibition of local emission sources by restricting the idling vehicles around a school area and evaluating the changes in surrounding atmospheric PM conditions. Two stationary sites were monitored, including a background site on the upwind side of the school and a campus site inside the school, to monitor the exposure level, before and after the idling prohibition. In the base condition, the PM2.5 mass concentrations were found to increase 15% from the background, whereas the nitrate (NO3-) content had a significant increase at the campus site. The anthropogenic metal contents in PM2.5 were higher at the campus site than the background site. Mobile emissions were found to be the most likely contributor to the school hot spot area by chemical mass balance modeling (CMB8.2). On the other hand, the PM2.5 in the school campus fell to only 2% after idling vehicle control, when the mobile source contribution reduced from 42.8% to 36.7%. The mobile monitoring also showed significant reductions in atmospheric PM2.5, PM0.1, polycyclic aromatic hydrocarbons (PAHs), and black carbon (BC) levels by 16.5%, 33.3%, 48.0%, and 11.5%, respectively. Consequently, the restriction of local idling emission was proven to significantly reduce PM and harmful pollutants in the hot spots around the school environment. The emission of idling vehicles strongly affects the levels of particles and relative pollutants in near-ground air around a school area. The PM2.5 mass concentration at a campus site increased from the background site by 15%, whereas NO3- and anthropogenic metals also significantly increased. Meanwhile, the PM2.5 contribution from mobile source in the campus increased 6.6% from the upwind site. An idling prohibition took place and showed impressive results. Reductions of PM2.5, ionic component, and non-natural metal contents were found after the idling prohibition. The mobile monitoring also pointed out a significant improvement with the spatial analysis of PM2.5, PM0.1, PAH, and black carbon concentrations. These findings are very useful to effectively improve the local air quality of a densely city during the rush hour.


Specific fluorescent labeling of two functional domains in RNA polymerase alpha subunit.
A monomercury derivative of fluoresceine acetate (FMMA) was previously suggested as a specific reagent reacting with only one of four cysteine (Cys) residues in the alpha. subunit of Escherichia coli RNA polymerase. Here, we analyzed the reactivity against FMMA of both isolated alpha subunit and alpha subunit assembled in the holoenzyme. In both cases, the highest reactivity was identified for Cys-269 positioned in the regulatory helix of C-terminal domain (CTD) which includes the contact sites for both class-I transcription factors and DNA UP elements. Substitution of Ala for both Cys-269 and Cys-176 completely eliminates the reactivity of alpha subunit against the fluorescent dye, supporting the prediction that another reactive amino acid under native conformation is Cys-176, which is positioned within or near the region important for alpha dimerization and its binding of beta' subunit. In the isolated alpha subunit, the reactivity against FMMA is different between these two Cys residues and the order is from Cys-269 to Cys-176. Mutant alpha-subunits, bearing only one Cys residue at either 269 or 176, could be reconstituted into locally modified and active enzymes. This FMMA modification system may provide a tool suitable for studies of intra- and intermolecular interactions of this subunit.


Antioxidant activity of Carica papaya & Persea americana fruits against cadmium induced neurotoxicity, nephrotoxicity, and hepatotoxicity in rats with a computational approach.
Cadmium is widely reported to interfere with the proper functioning of cells by disrupting cellular redox balance, causing apoptosis, and leading to hepatocellular damage, neurotoxicity, pulmonary edema, cancer, and cardiac and neurodegenerative diseases. Treatment of Cd toxicity with drugs brings undesirable side effects, making it necessary to remove Cd from the body safely without harmful effects. This study aimed to determine how Cd causing malfunctioning of cells could be treated with antioxidant-rich avocado and papaya fruit juices. This work fixated on elucidating and comparing the effects of avocado and papaya fruit juice on Cd-dependent impairment in memory and spatial learning. In addition, various markers of tissue damage, such as the concentration of biomarkers in liver and kidney tissue, the expression of antioxidant enzymes and Cd-induced lipid peroxidation, were analyzed. in silico studies of the phytochemical constituents of avocado and papaya (ligands) were docked against antioxidant enzymes Catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) as macromolecules showed strong hydrogen binding with significant binding capacities. To develop the Cd in vivo model, rats were administered CdCl2 (200 ppm) in drinking water for 7 weeks. After induction of Cd toxicity, rats were post-treated with avocado and papaya (10% w/v each) in a standard diet. After post-treatment, memory and learning were assessed using the Morris water maze behavioural test. Biochemical tests for liver and kidney biomarkers were monitored. To determine the level of ROS, lipid peroxidation was determined by Malondialdehyde (MDA) assay. Gene expression of SOD, CAT and GPx were determined via qRT-PCR. This study demonstrated that Cd accumulation in the liver, kidney and hippocampal tissues was reduced after treatment with avocado and papaya. SOD, CAT and GPX gene expression were upregulated after avocado and papaya juice treatment. Moreover, a comparative analysis between avocado and papaya fruit juices clarified that papaya has more active potential for improving memory and learning, upregulating the expression of antioxidant enzymes, and reducing lipid peroxidation in the liver, kidney, and hippocampus. This study suggests that a diet containing papaya and avocado can help treat the lethal effects caused by Cd. Because their active constituents can improve health at the cellular and molecular levels.


Organogenesis of the ovary: a comparative review on vertebrate ovary formation.
The general perspective of ovary organogenesis is that the ovary is the default organ which develops in the absence of testis-promoting factors. Testis formation, on the other hand, is a male-specific event promoted by active components that override the default ovarian process. However, when comparing the sex determination mechanism among different vertebrate species, it is apparent that this default view of ovary formation can only be applied to mammals. In species such as reptiles and birds, ovary formation is an active process stimulated by estrogen. Remnants of this estrogen-dominant pathway are still present in marsupials, a close relative of eutherian mammals, like humans and mice. Although initial formation of the mammalian ovary has become strictly regulated by genetic components and is therefore independent of estrogen, the feminizing effect of estrogen regains its command in adult ovaries. When estrogen production, or its signaling, is inhibited, transdifferentiation of ovarian tissues to testis structures occur in adult females. Taken together, these observations prompt us to reconsider the process of ovary organogenesis as the default organ and question if testis development is actually the default pathway.


[Correlations between prolactin and somatotropic hormone in human breast cancer].
The authors review any possible correlation between prolactin and growth hormone in human breast cancer. They find neither a significant relationship between growth hormone and breast cancer nor between prolactin and growth hormone. In many cases however, prolactin levels may be used as a neoplastic marker. The excess of prolactin could originate either in a tumor factor stimulating its secretion by the hypophysis or in an ectopic production of the hormone by tumor tissue.


Novel peptoids for the detection and suppression of reactive oxygen and nitrogen species.
Novel peptoids useful for the detection and suppression of various components contributing to oxidative stress and for elucidation of the interplay between these species are presented. Oxidative stress involves redox-active metal ion activation/generation of RONS (reactive oxygen and nitrogen species). For detection of RONS, the peptoid probes consist of a conjugate designed to (1) complex redox-active and non-redox-active metal ions, and (2) differentiate between RONS based upon the reaction products following RONS attack on the probe. For suppression of RONS, subtle modifications in peptoid structure impart catalase and superoxide dismutase activities to the peptoids upon ferric or cupric ion complexation.


Expression of BARF1 gene encoded by Epstein-Barr virus in nasopharyngeal carcinoma biopsies.
We reported previously that the EBV BARF1 open reading frame encodes a Mr 31,000-33,000 protein (p31) with potential transforming and oncogenic properties. This gene was found capable of transforming both: (a) the rodent fibroblast lines Balbc/3T3 and NIH3T3 into cells producing aggressive tumors in newborn rats; and (b) the human EBV-negative B-cell line Louckes into cells leading to small tumors, which disappeared 3 weeks after injection. Our recent study showed that BARF1 ORF expression may confer the property of immortalization to primary kidney epithelial cells (M. X. Wei et al., Oncogene, 14: 3073-3081, 1997). Because this suggested that BARF1 could be involved in epithelial malignancy, we investigated its transcriptional and translational expressions in Algerian nasopharyngeal carcinoma (NPC) biopsies by reverse transcription-PCR and immunoblotting using rabbit polyclonal antisera prepared against two synthetic peptides corresponding to distinct, predicted epitopes of the BARF1 protein (NGGVMKEKD, amino acids 172-180, and GKNDKEE, amino acids 203-209). The BARF1 ORF was found to be transcribed and translated in >85% of our NPC biopsies, with high p31 protein level detected in several NPC patient biopsies as well as in NPC-derived xenografts. Our observation of BARF1 expression in a large proportion of NPC epithelial cells suggests that this EBV gene might play an important role in the malignant transformation of human epithelial cells in vivo.


Angiolipoma an Uncommon Breast Mass in Men: A Case Series.
Angiolipomas are uncommon benign masses of the breast which are rarely described in the male breast. They do not have a typical mammographic appearance and can present with concerning features such as microcalcifications or irregular borders. Ultrasound is helpful in evaluating these masses most commonly appearing as oval, circumscribed, and hyperechoic. Clinical, radiological, and pathological information needs to be carefully evaluated as angiolipomas can be confused with malignant pathology. Three cases of angiolipomas of the male breast are reported in this study with mammographic, sonographic, and pathologic correlation.


Reciprocal and multi-species chromosome BAC painting in crucifers (Brassicaceae).
In crucifer cytogenomics, BAC contigs of Arabidopsis thaliana have been used as probes for comparative chromosome painting among species. Here we successfully tested chromosome-specific BAC contigs of A. thaliana (n = 5) and A. halleri (n = 8) as probes for reciprocal BAC painting. Furthermore, BAC contigs of both Arabidopsis species were applied as multi-species painting probes to a third crucifer species, Noccaea caerulescens (n = 7), revealing their shared chromosome homeology. Specifically, we found homeology across portions of chromosomes At2, Ah4, and Nc4, which reflects their shared common origin with chromosome AK4 of the Ancestral Crucifer Karyotype (n = 8). We argue that multi-species and multi-directional painting will significantly expedite comparative cytogenomics in Brassicaceae and other plant families.


Visual hallucinations.
Visual hallucinations have intrigued neurologists and physicians for generations due to patients' vivid and fascinating descriptions. They are most commonly associated with Parkinson's disease and dementia with Lewy bodies, but also occur in people with visual loss, where they are known as Charles Bonnet syndrome. More rarely, they can develop in other neurological conditions, such as thalamic or midbrain lesions, when they are known as peduncular hallucinosis. This review considers the mechanisms underlying visual hallucinations across diagnoses, including visual loss, network dysfunction across the brain and changes in neurotransmitters. We propose a framework to explain why visual hallucinations occur most commonly in Parkinson's disease and dementia with Lewy bodies, and discuss treatment approaches to visual hallucinations in these conditions.


Reactions of the ionized enol tautomer of acetanilide: elimination of HNCO via a novel rearrangement.
The reactions of ionised acetanilide, C(6)H(5)NH(=O)CH(3)(.+), and its enol, C(6)H(5)NH(OH)=CH(2)(.+), have been studied by a combination of tandem mass spectrometric and computational methods. These two isomeric radical cations have distinct chemistries at low internal energies. The keto tautomer eliminates exclusively CH(2)=C=O to give ionised aniline. In contrast, the enol tautomer loses H-N=C=O, via an unusual skeletal rearrangement, to form predominantly ionised methylene cyclohexadiene. Hydrogen atom loss also occurs from the enol tautomer, with the formation of protonated oxindole. The mechanisms for H-N=C=O and hydrogen atom loss both involve cyclisation; the former proceeds via a spiro transition state formed by attachment of the methylene group to the ipso position, whereas the latter entails the formation of a five-membered ring by attachment to the ortho position. The behaviour of labelled analogues reveals that these two processes have different site selectivities. Hydrogen atom loss involves a reverse critical energy and is subject to an isotope effect. Surprisingly, attempts to promote the enolisation of ionised acetanilide by proton-transport catalysis were unsuccessful. In a reversal of the usual situation for ionised carbonyl compounds, ionised acetanilide is actually more stable than its enol tautomer. The enol tautomer was resistant to proton-transport catalysed ketonisation to ionised acetanilide, possibly because the favoured geometry of the encounter complex with the base molecule is inappropriate for facilitating tautomerisation.


Dynamics of colloidal particles in ice.
We use x-ray photon correlation spectroscopy (XPCS) to probe the dynamics of colloidal particles in polycrystalline ice. During freezing, the dendritic ice morphology and rejection of particles from the ice created regions of high particle density, where some of the colloids were forced into contact and formed disordered aggregates. The particles in these high density regions underwent ballistic motion, with a characteristic velocity that increased with temperature. This ballistic motion is coupled with both stretched and compressed exponential decays of the intensity autocorrelation function. We suggest that this behavior could result from ice grain boundary migration.


No evidence for a role of the catechol-O-methyltransferase pain sensitivity haplotypes in chronic widespread pain.
The aim of this study was to investigate the association between the catechol-O-methyltransferase (COMT) 'pain sensitivity' haplotypes and chronic widespread pain (CWP) in two distinct cohorts. Cases of CWP and controls free of pain were selected from two population-based studies: the Epidemiology of Functional Disorders study (EPIFUND) (UK) and the European Male Ageing Study (European). The number of cases and controls were 164 and 172, and 204 and 935, respectively. Identical American College of Rheumatology criteria were used in both studies to ascertain CWP status. The EPIFUND study had three time points and cases were classified as subjects with CWP at two or three time points and controls as those free of pain at all three time points. Four single nucleotide polymorphisms (SNP): rs6269, rs4633, rs4818 and rs4680 (V158M) were genotyped using Sequenom technology. Allele and genotype frequencies were compared and haplotype analysis was conducted using PLINK software. No differences in allele or genotype frequencies for any of the four SNP were observed between cases and controls for either cohort. Haplotype analysis also showed no difference in the frequency of haplotypes between cases and controls. There was no evidence of association between the COMT 'pain sensitivity' haplotypes and CWP in two population-based cohorts.


Pseudoangiomatous stromal hyperplasia (PASH) of the breast: a clinicopathological study of 79 cases.
Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign lesion that can present as a palpable nodule or as an incidental finding in breast biopsies. The study comprised 79 cases diagnosed at Loyola University Medical Center from 2002 to 2009. The pathology slides were reviewed to document the distribution, type, and association with preneoplastic or neoplastic epithelial lesions. Z-test for independent proportions is used for analysis. A total of 76 patients were female and 3 were male. In all, 59.8% of patients presented with a breast mass and in 40.2% the lesion was an incidental finding. Classical PASH morphology was seen in 97.6% and proliferative PASH in 2.4%. Associated epithelial lesions were benign proliferative changes in 60.4%, atypical ductal and atypical lobular hyperplasia in 25.6% and infiltrating carcinoma in 11% of cases. Based on these results, extensive sampling of biopsy specimen with PASH and appropriate clinical and radiologic follow-up is recommended.


Green tea polyphenol epigallocatechin-3-gallate (EGCG) differentially inhibits interleukin-1 beta-induced expression of matrix metalloproteinase-1 and -13 in human chondrocytes.
Interleukin-1beta (IL-1beta)-induced inflammatory response in arthritic joints include the enhanced expression and activity of matrix metalloproteinases (MMPs), and their matrix degrading activity contribute to the irreversible loss of cartilage and may also be associated with sustained chronic inflammation. We have earlier shown that green tea (Camellia sinensis) polyphenol epigallocatechin-3-gallate (EGCG) was non-toxic to human chondrocytes [Singh R, Ahmed S, Islam N, Goldberg VM, and Haqqi TM (2002) Arthritis Rheum 46: 2079-2086] and inhibits the expression of inflammatory mediators in arthritic joints [Haqqi TM, Anthony DD, Gupta S, Ahmed N, Lee MS, Kumar GK, and Mukhtar H (1999) Proc Natl Acad Sci USA 96: 4524-4529]. Here we show that EGCG at micromolar concentrations was highly effective in inhibiting the IL-1beta-induced glycosaminoglycan (GAG) release from human cartilage explants in vitro. EGCG also inhibited the IL-1beta-induced mRNA and protein expression of MMP-1 and MMP-13 in human chondrocytes. Importantly, EGCG showed a differential, dose-dependent inhibitory effect on the expression and activity of MMP-13 and MMP-1. A similar differential dose-dependent inhibition of transcription factors NF-kappaB and AP-1 by EGCG was also noted. These results for the first time demonstrate a differential dose-dependent effect of EGCG on the expression and activity of MMPs and on the activities of transcription factors NF-kappaB and AP-1 and provide insights into the molecular basis of the reported anti-inflammatory effects of EGCG. These results also suggest that EGCG or compounds derived from it may be therapeutically effective inhibitors of IL-1beta-induced production of matrix-degrading enzymes in arthritis.


Pre-stimulated Mice with Carbon Tetrachloride Accelerate Early Liver Regeneration After Partial Hepatectomy.
The liver has a high capacity of its regeneration. Most hepatic cells are quiescent unless otherwise stimulated such as their injury or ablation. A previous study suggest that pre-activated hepatic cells have a positive effect on their regeneration. In this study, we examined whether the pre-activated hepatic cells for regeneration accelerate the subsequent liver regeneration. We administered a single injection of carbon tetrachloride (CCl4) to mice 7 days before partial hepatectomy (PHx). Liver weight/body weight ratio and several parameters for cell proliferation such as mitotic index and the number of Ki67 positive cells in the liver were examined after PHx as indexes of liver regeneration. Compared to control mice, those pre-stimulated with CCl4 showed earlier liver regeneration 48 h after PHx. Regardless of their accelerated regeneration, pre-stimulated mice showed less cell proliferation than did control mice during liver regeneration. Hepatic fibrosis was not observed in both control and CCl4-pretreated mice after PHx. Mice pre-treated with CCl4 showed the higher matrix metalloproteinase 9 (MMP9) expression than those pre-treated with olive oil. When matrix metalloproteinase 9 (MMP9) activity was inhibited, the pre-stimulated mice did not demonstrate accelerated liver regeneration and they returned to the original state for cell proliferations after PHx. Pre-activated liver by CCl4 promoted its subsequent regeneration after PHx. This was not a cause of fibrosis and partly dependent on MMP9 pre-activity rather than cell proliferation in liver. Our findings would not only provide a novel strategy for liver regeneration without cell proliferation as much as possible and also propose a new method for liver transplantation.


Ultrasonic predator-prey interactions in water-convergent evolution with insects and bats in air?
Toothed whales and bats have independently evolved biosonar systems to navigate and locate and catch prey. Such active sensing allows them to operate in darkness, but with the potential cost of warning prey by the emission of intense ultrasonic signals. At least six orders of nocturnal insects have independently evolved ears sensitive to ultrasound and exhibit evasive maneuvers when exposed to bat calls. Among aquatic prey on the other hand, the ability to detect and avoid ultrasound emitting predators seems to be limited to only one subfamily of Clupeidae: the Alosinae (shad and menhaden). These differences are likely rooted in the different physical properties of air and water where cuticular mechanoreceptors have been adapted to serve as ultrasound sensitive ears, whereas ultrasound detection in water have called for sensory cells mechanically connected to highly specialized gas volumes that can oscillate at high frequencies. In addition, there are most likely differences in the risk of predation between insects and fish from echolocating predators. The selection pressure among insects for evolving ultrasound sensitive ears is high, because essentially all nocturnal predation on flying insects stems from echolocating bats. In the interaction between toothed whales and their prey the selection pressure seems weaker, because toothed whales are by no means the only marine predators placing a selection pressure on their prey to evolve specific means to detect and avoid them. Toothed whales can generate extremely intense sound pressure levels, and it has been suggested that they may use these to debilitate prey. Recent experiments, however, show that neither fish with swim bladders, nor squid are debilitated by such signals. This strongly suggests that the production of high amplitude ultrasonic clicks serve the function of improving the detection range of the toothed whale biosonar system rather than debilitation of prey.


Deguelin inhibits human hepatocellular carcinoma by antiangiogenesis and apoptosis.
Deguelin is a rotenoid isolated from several plant species, which has been reported to have chemopreventive effects in skin, mammary, colon and lung cancers. The effects of deguelin on the proliferation and apoptosis of hepatic cancer cells were assessed by MTT assay and flow cytometric analysis. The growth of hepatic cancer cells (HepG2, Huh7 and SK-Hep1) was inhibited by deguelin in a dose-dependent manner. HepG2 cells of all the cell lines were the most sensitive to deguelin (IC50 = 0.62 microM). The proportion of sub-G1 apoptotic cells increased from 5.19 to 41.27% by deguelin (0.01-10 microM) treatment for 3 days in the HepG2 cells. The effects of deguelin on anti-angiogenesis of the HepG2 cells were assessed by using Western blot and RT-PCR analysis. Treatment of HepG2 cells with deguelin for 16 h under hypoxia conditions reduced the expression of the hypoxia-inducible factor 1alpha protein and vascular endothelial growth factor mRNA in a dose-dependent manner. In order to investigate whether deguelin shows antiangiogenic activities, we performed in vitro and in vivo angiogenesis assays. In a tube formation assay, deguelin remarkably reduced the capillary network formation of human umbilical vein endothelial cells (HUVECs) on Matrigel beds. Furthermore, deguelin markedly decreased the migration of HUVECs compared to the control and reduced angiogenesis on the CAM of chick embryos. These results suggest that deguelin is potentially useful as a chemotherapeutic agent in hepatocellular carcinoma.


Psychological and physiological correlates of insulin resistance at fasting and in response to a meal in African Americans and Whites.
African Americans are more insulin resistant than are Whites. The purpose of this study was to characterize physiologic and psychological (stress coping style) correlates of insulin resistance in African Americans and Whites. We examined African American (n = 67) and White (n = 41) men and women aged 18-45 years with body mass index 18-35 kg/m2. We used the homeostasis model assessment (HOMA-IR) and area under the curve for insulin (AUC) after a standardized meal as measure of insulin resistance. We obtained anthropometric measures and determined maximal aerobic power (VO(2max)) by treadmill exercise. We used stress profile to assess stress and coping style. Postprandial insulin AUCs were higher in African Americans than in Whites. Anthropometric measures and VO(2max)) were related to HOMA-IR and AUC. Although self-reported stress level did not differ between Whites and African Americans, positive appraisal predicted reduced HOMA-IR and negative appraisal coping style predicted increased insulin AUC. Psychosocial factors may be determinants of health and targets of intervention for obesity-related disorders such as insulin resistance. Existing behavioral intervention programs, designed with a sole emphasis on exercise and nutrition, may fall short of optimal effectiveness.


Early Commencement of Enteral Feeds in Gastroschisis: A Systematic Review of Literature.
Introduction There are no evidence-based strategies to improve feed tolerance in gastroschisis. Early commencement of enteral feeds (CEF) is known to improve feed tolerance in preterm infants. It is possible that infants with gastroschisis may also benefit from early CEF. Objective To conduct a systematic review to evaluate the relationship between time of CEF, and time to reach full enteral feeds (FEF), duration of parenteral nutrition (PN), and duration of hospital stay (HS). Methods PubMed, EMBASE, Cochrane CENTRAL, and relevant conference abstracts were searched in December 2015. Studies of any design reporting on time to CEF and one or more of the outcomes of interest were included. Meta-regression analysis was conducted to find the association between time to CEF and the outcomes of interest. Results There were no randomized controlled trials (RCTs) comparing early (≤7 days from birth) versus delayed (>7 days) CEF. Forty-two observational studies on gastroschisis (4,835 infants) where feed-related information was available were included. Meta-regression results indicated that each day delay in CEF was associated with a delay of an additional 1.4 days (95% confidence interval [CI]: 0.95, 1.85) to FEF, 2.05 days (95% CI: 1.50, 2.59) to the duration of PN, and 1.91 days (95% CI: 1.37, 2.45) to the duration of HS. Sensitivity analysis after excluding studies that provided information exclusively on complex gastroschisis continued to show beneficial effects of early CEF. Conclusion Early CEF may be associated with early attainment of FEF in gastroschisis. RCTs comparing early versus delayed CEF are needed urgently.


A population-based study of periodontal care among those with and without diabetes.
Our objectives were to describe the prevalence of periodontal care (a marker of periodontitis) among persons with and without diabetes and to examine the association between periodontal care and diabetes. We conducted a cross-sectional analysis, using 5 years of electronic data from a population-based cohort (N = 46,132), aged 40 to 70 years, with dental and medical insurance, and ≥ 1 dental and ≥ 1 medical visit. Periodontal care (yes/no) was defined by dental claims codes for procedures used to manage periodontitis. The association between periodontal care and diabetes was determined using logistic regression adjusted for and stratified by age, sex, insurance type, smoking status, body mass index (BMI) (in kilograms per square meter), and resource utilization band (RUB) (a measure of expected health care utilization attributable to comorbidity). Overall, 11.2% (5,153 of 46,132) met diabetes criteria. The age-adjusted prevalence of periodontal care among those with and without diabetes was 39.1% and 32.5%, respectively (P <0.0001). The association between diabetes and periodontal care decreased with increasing age (interaction, P <0.0001), adjusting for BMI and RUB. The aged-stratified, adjusted odds ratio (OR) for periodontal care associated with diabetes was highest among those aged 40 to 44 years [OR, 1.6; confidence interval (CI), 1.30 to 1.97] and lowest among those aged 60 to 64 years (OR, 0.97; CI, 0.81 to 1.15) and was significant only among those aged 40 to 54 years. We found that the prevalence of periodontal care was significantly higher among those with diabetes compared to those without diabetes and that the magnitude of this association decreased with increasing age.


Duodenum-derived fibromatosis that invaded the muscular layer of intestinal wall: A rare case report.
Intraabdominal fibromatosis is a rare benign tumor that often affects the mesentery or retroperitoneum, and can infiltrate adjacent organs. However, it is rare for fibromatosis to arise from the small intestinal wall. A 27-year-old female with a tangible abdominal tumor is described. The computed tomography (CT) scan revealed a 7.5 cm, small intestine-associated tumor in the right abdomen. The patient received tumor resection and intestinal anastomosis. Further pathological examination confirmed the tumor as a duodenal fibromatosis that infiltrated the intestinal wall. To the best of our knowledge, this is the first report of a duodenum-derived fibromatosis that invaded the muscular layer of the intestine. Our study demonstrated that an unexplained abdominal mass should be noteworthy and properly treated.


Test-retest stability of the Repeatable Battery for the Assessment of Neuropsychological Status in schizophrenia.
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was designed as a cognitive screening test, providing both a total scale score and five specific cognitive ability index scores. This study examined the test-retest stability of the RBANS in individual patients with schizophrenia relative to a healthy comparison group. A total of 181 patients with schizophrenia or schizoaffective disorder were recruited from three clinical settings. Healthy comparison subjects were recruited as part of the RBANS standardization. Participants were administered one form of the RBANS on one occasion and another form at a later date, with intervals ranging from 1 to 134 days. Intraclass correlation coefficients for the RBANS total scale were 0.84 for the patients with schizophrenia and 0.77 for the healthy comparison subjects. Confidence intervals and percentile data for the total scale change scores were similar for both groups. The RBANS demonstrated reasonable intraclass correlation coefficient test-retest reliability for both schizophrenia patients and healthy comparison subjects. Confidence intervals are comparable to those previously published for the WAIS-R and Wechsler Memory Scale-Revised, suggesting that retest measurement error is not dramatically increased in the RBANS, despite the brevity of the test. These data may serve as an informative guide for using the RBANS to evaluate neuropsychological change on the level of the individual subject.


Aphidicolin-induced topological and recombinational events in simian virus 40.
Highly compacted (40S) SV40 DNA replication intermediates formed in vivo during aphidicolin exposure and immediately broke down in two stages. In the rapid initial stage, single strand DNA breaks caused loss of superhelicity in the 40S replication intermediates. This DNA breakage was accompanied by the formation of strong, permanent protein-DNA crosslinks which reached a maximum as nicking of the aberrant DNA replication intermediates was completed. These protein-associated DNA strand breaks were not repaired. In the slower second stage of breakdown, the aberrant DNA replication intermediates remained nicked and strongly associated with protein as they underwent DNA replication fork breakage and recombinational changes to produce high molecular weight forms.


Comparison of Social Media Utilization Among Vascular Surgeons, Interventional Cardiologists, and Interventional Radiologists at Academic Training Institutions.
Social media platforms, especially Twitter, are increasingly utilized across medical practice, education, and research. However, little is known about differences in social media use among physicians of varying specialties and its impact on recruitment of trainees. Our objective was to describe differences in social media use among vascular interventional proceduralists at academic training institutions. We identified institutions with training programs in vascular surgery (VS), interventional radiology (IR), and interventional cardiology (IC). Faculty providers were identified in each specialty at these institutions. A standardized search was used to identify non-anonymous social media profiles on Facebook, Instagram, and Twitter in September 2019. Influencers were defined as physicians with more than 1,000 Twitter followers. Follow ratio was defined as the number of followers divided by the number of accounts followed. Between-specialty differences were analyzed. A total of 1,330 providers (n = 454 VS, n=451 IR, n = 425 IC) were identified across 47 institutions in 27 states. Across all physicians, a minority of providers utilize social media (Facebook: 24.9%, n = 331; Instagram: 10.8%, n = 143; Twitter: 18.0%, n = 240). VS were significantly more likely to use Instagram (P = 0.001) but there was not a significant difference in utilization of Facebook and Twitter. Among Twitter users, VS had fewer followers on average (median 178, inter-quartile range [IQR] 39-555) than IR (median 272, IQR 50-793, P = 0.26) and IC (median 286, IQR 71-1257, P = 0.052). IC were most likely to be influencers (30.9%, n = 25) followed by IR (17.9%, n = 15) and VS (10.7%, n = 8, P = 0.006). On average, interventional cardiologists had the highest follow ratio (mean 4.9 ± 7.1) compared to interventional radiologists (mean 3.2 ± 5.5) and vascular surgeons (mean 2.5 ± 3.3, P < 0.001). A minority of academic vascular interventional proceduralists utilize social media in a non-anonymous manner. On Twitter, interventional cardiologists are most likely to be influencers based on number of followers and, on average, have the highest follow ratio. Vascular surgeons could potentially benefit from pursuing greater influence and visibility on social media as a means to recruit trainees.


Administration off label of recombinant factor-VIIa (rFVIIa) to patients with blunt or penetrating brain injury without coagulopathy.
Traumatic brain contusions may increase in size over time or may develop at a delay after injury. This may lead to neurological deterioration, long term morbidity or even death. Coagulation disorders after injury can contribute to progression of haemorrhage. Recombinant activated factor VII (rFVIIa) was used in 12 patients with a severe head injury who had no systemic coagulopathy but who were considered to be at risk of progression of their intracranial lesion. Twelve consecutive patients suffering from life-threatening acute head injuries from blunt (3 cases) and penetrating mechanisms were given with rFVIIa, either to prevent the expected development of brain contusion or to assist in bleeding control during surgery. In 11 patients, rFVIIa was given by the attending neurosurgeon. Two of the patients died of their severe penetrating injuries one of whom had severe vasospasm 2 days after administration of rFVIIa. The other 11 patients did not appear to suffer any treatment-related adverse effects. When the drug was given prophylactically to prevent brain resection (6 cases) or to limit the need for widening resection (5 cases), marked control was achieved in seven cases, and a lesser effect was observed in the other 4 cases. We conclude that, in a small and highly individually selected series of patients with severe head injury, the administration of rFVIIa did not lead to adverse effects. Although the majority of patients were considered to be at high risk of progression of their lesions, this occurred in only one. The early use of rFVIIa in head injured patients without systemic coagulopathy may reduce the occurrence of enlargement of contusions, the requirement of further operation, and adverse outcome. Prospective randomised controlled studies are required to investigate this.


Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma.
To evaluate the distribution and density of epidermal growth factor (EGF) receptors (EGF-Rs) on urothelium, immunohistological studies using a monoclonal antibody to the binding portion of the human EGF-R were performed on frozen specimens of normal urothelium (N = 20), urothelium from patients with nonurothelial urological malignancies (N = 15) and inflammatory diseases (N = 8), low grade superficial transitional cell carcinomas (TCC) (N = 13), high grade superficial or invasive TCC (N = 28), and endoscopically normal appearing urothelium from patients with low grade superficial (N = 5) or high grade (N = 21) TCC elsewhere in the bladder (or ipsilateral renal pelvis/ureter). EGF-Rs are found only on the basal layer of epithelial cells (with scattered representation on intermediate cells) in 95% of normal urothelial specimens and 100% of pathological specimens without urothelial malignancy. Alternatively, 92.3% of specimens of low grade superficial TCC and 100% of high grade TCCs had EGF-Rs richly expressed on the superficial as well as the deeper layers of urothelium. This "malignant" distribution of EGF-Rs was also found on all specimens of endoscopically normal appearing urothelium in patients with TCC elsewhere. The density of EGF-Rs correlated closely with tumor grade on both "premalignant" and frankly neoplastic urothelium. We conclude that the expression of EGF-Rs on urothelium favors the interaction of premalignant and malignant tissue with urinary EGF. To determine if altering the physiochemical environment of urine could interfere with this interaction, the effects of pH on the binding of and growth responses to EGF were assessed on four human TCC cell lines. Scatchard plots demonstrated that varying pH from 5.0 to 7.5 did not significantly change the total number of receptors, but EGF-R affinity was reduced approximately 20-fold as pH decreased from 7.5 to 5 in each TCC target. Similarly, significant growth stimulation by EGF at pH 7.5 was abrogated at pH less than or equal to 7.0 while growth rates in the absence of EGF remained unchanged at lower pHs. It thus appears that urinary acidification may hold promise in the management and prevention of recurrent bladder cancer.


Induction of neutrophil degranulation by S100A9 via a MAPK-dependent mechanism.
S100A9 is a proinflammatory protein, expressed abundantly in the cytosol of neutrophils and monocytes. High extracellular S100A9 concentrations have been correlated with chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease, as well as with phagocyte extravasation. This study tested the hypothesis that S100A9 induces degranulation in human neutrophils. S100A9 was found to up-regulate the surface expression of CD35 and CD66b, proteins contained in secretory vesicles and specific/gelatinase granules, respectively. In addition, gelatinase and albumin, stored, respectively, in specific/gelatinase granules and secretory vesicles, were detected in the supernatants of neutrophils stimulated with S100A9. In contrast, stimulation with S100A9 had no effect on CD63 expression or MPO secretion, two proteins contained in azurophilic granules. S100A9 induced the phosphorylation of the MAPKs, ERK1/2, p38, and JNK. Inhibition of p38 and JNK but not ERK1/2, with specific inhibitors (SB203580, JNKII, and PD98059, respectively), blocked neutrophil degranulation induced by S100A9. Taken together, these results support the hypothesis and clearly indicate that S100A9 induces the degranulation of secretory and specific/gelatinase granules but not of azurophilic granules in a process involving p38 and JNK and further support its classification as a DAMP.


Glycerated hemoglobin alpha 2 beta 2(82) (EF6) N-epsilon-glyceryllysine: a new post-translational modification occurring in erythrocyte bisphosphoglyceromutase deficiency.
A new minor Hb fraction initially designated Hbx, has been found in the hemolysate of a erythremic patient that we have previously described with a complete erythrocyte bisphosphoglyceromutase (BPGM) (E.C.22.214.171.124.) deficiency. Hbx (3.5% of the total) was detected by isoelectric focusing (IEF) and exhibited electrophoretic and chromatographic properties similar to that of several variants of the Hb central cavity. By density fractionation of red cells, it was demonstrated that Hbx was an aging hemoglobin as in the case of glycated Hb A1c. Functional studies revealed a low oxygen affinity and almost complete inhibition of the allosteric effect of the organic phosphate effectors. Structural studies demonstrated an absence of tryptic cleavage between the peptides beta T9 and beta T10 suggesting the presence of an adduct on Lys beta 82 or on a neighboring residue. FAB mass spectrometry, CID/MIKE spectra and a specific enzymatic assay with glyoxylate reductase, demonstrated that the 82 adduct was a glycerate moiety. It was concluded that Hbx was a glycerylated Hb: alpha 2 A beta 2(82) (EF6) N-epsilon-glyceryllysine, to our knowledge the first example of glycerylated protein. The mechanism of formation of glyceryl-Hb, which was found in the four studied subjects with a BPGM deficiency, remains to be determined.


Effects of heterogeneous structure and diffusion permeability of body tissues on decompression gas bubble dynamics.
To gain insight into the special nature of gas bubbles that may form in astronauts, aviators and divers, we developed a mathematical model which describes the following: 1) the dynamics of extravascular bubbles formed in intercellular cavities of a hypothetical tissue undergoing decompression; and 2) the dynamics of nitrogen tension in a thin layer of intercellular fluid and in a thick layer of cells surrounding the bubbles. This model is based on the assumption that, due to limited cellular membrane permeability for gas, a value of effective nitrogen diffusivity in the massive layer of cells in the radial direction is essentially lower compared to conventionally accepted values of nitrogen diffusivity in water and body tissues. Due to rather high nitrogen diffusivity in intercellular fluid, a bubble formed just at completion of fast one-stage reduction of ambient pressure almost instantly grows to the size determined by the initial volume of the intercellular cavity, surface tension of the fluid, the initial nitrogen tension in the tissue, and the level of final pressure. The rate of further bubble growth and maximum bubble size depend on comparatively low effective nitrogen diffusivity in the cell layer, the tissue perfusion rate, the initial nitrogen tension in the tissue, and the final ambient pressure. The tissue deformation pressure performs its conservative action on bubble dynamics only in a limited volume of tissue (at a high density of formed bubbles). Our model is completely consistent with the available data concerning the random latency times to the onset of decompression sickness (DCS) symptoms associated with hypobaric decompressions simulating extravehicular activity. We believe that this model could be used as a theoretical basis for development of more adequate methods for the DCS risk prediction.


Pulmonary thromboembolism in liver transplantation: a retrospective review of the first 25 years.
The evidence on the state of 'haemostasis' at the time of liver transplantation (LT) is conflicting, with recent publications that suggest a hypercoagulable state, in contrast to traditionally held views. These findings raise the issue of thrombo-embolic complications after LT, an area of interest which has received little attention in recent published literature. We therefore conducted a retrospective review of our experience of 3000 liver transplants over 25 years. Our prospective transplant database was reviewed to find all patients who were suspected to have had a pulmonary embolism (PE) during or following LT. Paediatric transplants were excluded. A part of this database was cross referenced against hospital records to corroborate its accuracy. Clinical records of all these patients were reviewed and relevant aspects collated and analyzed. Following exclusion of the paediatric recipients, 2 149 adults were reviewed to find 36 patients in whom a PE was suspected (median age 49), 21 of whom were within 90 days of transplant (median duration 22 days). PE was ruled out in 10, unconfirmed in two, confirmed in eight patients; and in one, air embolism was found. All PEs occurred in hospital, but aetiology of liver failure was varied. Of note, two patients died of an on-table PE and one patient of chronic rejection/disease recurrence (Primary Sclerosing Cholangitis). The remaining five are still alive (median survival of 65 months). Although thromboprophylaxis is now routine in our unit, its use in these patients could not be confirmed from records available. Fifteen PE were suspected and confirmed after 90 days from transplant (six within, and nine out with the first year). Acute PE in the setting of LT has an incidence rate in our series of 0.37% that would appear to be lower than previously reported and lower than one would expect after a 'major complex' category operation. This potentially suggests that the overall haemostatic function in these patients is still weighted towards hypocoagulation with the resultant risk of excessive bleeding. Aetiology of liver disease did not seem to confer a higher risk in our series. The prognosis after post-operative PE appears good although sudden death due to an on-table embolism is a rare but significant risk.


Predator-driven trait diversification in a dragonfly genus: covariation in behavioral and morphological antipredator defense.
Proof for predation as an agent shaping evolutionary trait diversification is accumulating, however, our understanding how multiple antipredator traits covary due to phenotypic differentiation is still scarce. Species of the dragonfly genus Leucorrhinia underwent shifts from lakes with fish as top predators to fishless lakes with large dragonfly predators. This move to fishless lakes was accompanied by a partial loss and reduction of larval spines. Here, we show that Leucorrhinia also reduced burst swimming speed and its associated energy fuelling machinery, arginine kinase activity, when invading fishless lakes. This results in patterns of positive phylogenetic trait covariation between behavioral and morphological antipredator defense (trait cospecialization) and between behavioral antipredator defense and physiological machinery (trait codependence). Across species patterns of trait covariation between spine status, burst swimming speed and arginine kinase activity also matched findings within the phenotypically plastic L. dubia. Our results highlight the importance of predation as a factor affecting patterns of multiple trait covariation during phenotypic diversification.


Predicting male fertility from the sperm methylome: application to 120 bulls with hundreds of artificial insemination records.
Conflicting results regarding alterations to sperm DNA methylation in cases of spermatogenesis defects, male infertility and poor developmental outcomes have been reported in humans. Bulls used for artificial insemination represent a relevant model in this field, as the broad dissemination of bull semen considerably alleviates confounding factors and enables the precise assessment of male fertility. This study was therefore designed to assess the potential for sperm DNA methylation to predict bull fertility. A unique collection of 100 sperm samples was constituted by pooling 2-5 ejaculates per bull from 100 Montbéliarde bulls of comparable ages, assessed as fertile (n = 57) or subfertile (n = 43) based on non-return rates 56 days after insemination. The DNA methylation profiles of these samples were obtained using reduced representation bisulfite sequencing. After excluding putative sequence polymorphisms, 490 fertility-related differentially methylated cytosines (DMCs) were identified, most of which were hypermethylated in subfertile bulls. Interestingly, 46 genes targeted by DMCs are involved in embryonic and fetal development, sperm function and maturation, or have been related to fertility in genome-wide association studies; five of these were further analyzed by pyrosequencing. In order to evaluate the prognostic value of fertility-related DMCs, the sperm samples were split between training (n = 67) and testing (n = 33) sets. Using a Random Forest approach, a predictive model was built from the methylation values obtained on the training set. The predictive accuracy of this model was 72% on the testing set and 72% on individual ejaculates collected from an independent cohort of 20 bulls. This study, conducted on the largest set of bull sperm samples so far examined in epigenetic analyses, demonstrated that the sperm methylome is a valuable source of male fertility biomarkers. The next challenge is to combine these results with other data on the same sperm samples in order to improve the quality of the model and better understand the interplay between DNA methylation and other molecular features in the regulation of fertility. This research may have potential applications in human medicine, where infertility affects the interaction between a male and a female, thus making it difficult to isolate the male factor.


Antiviral Activity of Jamaican Medicinal Plants and Isolated Bioactive Compounds.
Plants have had historical significance in medicine since the beginning of civilization. The oldest medical pharmacopeias of the African, Arabian, and Asian countries solely utilize plants and herbs to treat pain, oral diseases, skin diseases, microbial infections, multiple types of cancers, reproductive disorders among a myriad of other ailments. The World Health Organization (WHO) estimates that over 65% of the world population solely utilize botanical preparations as medicine. Due to the abundance of plants, plant-derived medicines are more readily accessible, affordable, convenient, and have safer side-effect profiles than synthetic drugs. Plant-based decoctions have been a significant part of Jamaican traditional folklore medicine. Jamaica is of particular interest because it has approximately 52% of the established medicinal plants that exist on earth. This makes the island particularly welcoming for rigorous scientific research on the medicinal value of plants and the development of phytomedicine thereof. Viral infections caused by the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), hepatitis virus B and C, influenza A virus, and the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) present a significant global burden. This is a review of some important Jamaican medicinal plants, with particular reference to their antiviral activity.


A rare form of solitary osteocartilaginous exostosis from anterior iliac spine: report of two cases.
Occurrence of exostosis from the metaphyseal regions of long bones and sometimes from the flat bones is well known. In the pelvis these lesions are almost invariably of the sessile variety. Tubular exostosis from the anterior iliac spine has not been reported in the literature. The 2 cases that attracted our attention because of pressure on neurovascular bundles are exhibited to put on record the occurrence of this rare form of exostosis.


Alpha L-integrin I domain cyclic peptide antagonist selectively inhibits T cell adhesion to pancreatic islet microvascular endothelium.
Insulitis is a hallmark feature of autoimmune diabetes that ultimately results in islet beta-cell destruction. We examined integrin requirements and specific inhibition of integrin structure in T cell and monocyte adhesion to pancreatic islet endothelium. Examination of cell surface integrin expression on WEHI 7.1 T cells revealed prominent expression of beta-, beta(1)-, alpha(L)-integrins, and low expression of alpha(M)-integrins; whereas WEHI 274.1 monocytes showed significant staining for beta(2)-, beta(1)-, alpha(M)-molecules and no expression of alpha(L)-molecules. Unstimulated islet endothelium showed constitutive levels of ICAM-1 counter-ligand expression with minimal VCAM-1 expression; however, TNF-alpha stimulation increased cell surface density of both molecules. TNF-alpha increased T cell and monocyte rolling and adhesion under hydrodynamic flow conditions. Administration of a cyclic peptide competitor for the alpha(L)-integrin I domain binding sites (cyclo1,12-PenITDGEATDSGC) blocked T cell adhesion without inhibiting monocyte adhesion. Examination of T cell rolling revealed that cLAB.L treatment increased the average rolling velocity on activated endothelium and significantly decreased the fraction of T cells rolling at < or =50 microm/s, suggesting that cLAB.L treatment interferes with signal activation events required for the conversion of T cell rolling to firm adhesion. These data demonstrate for the first time that cyclic peptide antagonists against alpha(L)-integrin I domain attenuate T cell recruitment to islet endothelium.


[Antenna form of chlorophyll of photosystem II in chloroplasts].
Low temperature fluorescence spectra and second derivatives of chlorophyll absorption spectra in leaves, chloroplasts of mesophyll and parenchyme bundle sheath cells (BSC) were studied. It has been shown that in ontogenesis of BSC chloroplasts of Zea mays leaves along with a decrease of the activity of the PS-2 and a reduction of granal regions the fluorescence maximum of chlorophyll decreases at 695 nm. The change of this fluorescence band is concerned with the disturbance of the form of chlorophyll "a" absorbing at 684 nm and performing the function of an antenna of the pigment-protein complex of PS-2. Similarities in the distribution of chlorophyll forms between three pigment-protein complexes of chloroplast membranes in green algae and higher plants are discussed.


Combined analysis of microbial metagenomic and metatranscriptomic sequencing data to assess in situ physiological conditions in the premature infant gut.
Microbes alter their transcriptomic profiles in response to the environment. The physiological conditions experienced by a microbial community can thus be inferred using meta-transcriptomic sequencing by comparing transcription levels of specifically chosen genes. However, this analysis requires accurate reference genomes to identify the specific genes from which RNA reads originate. In addition, such an analysis should avoid biases in transcript counts related to differences in organism abundance. In this study we describe an approach to address these difficulties. Sample-specific meta-genomic assembled genomes (MAGs) were used as reference genomes to accurately identify the origin of RNA reads, and transcript ratios of genes with opposite transcription responses were compared to eliminate biases related to differences in organismal abundance, an approach hereafter named the "diametric ratio" method. We used this approach to probe the environmental conditions experienced by Escherichia spp. in the gut of 4 premature infants, 2 of whom developed necrotizing enterocolitis (NEC), a severe inflammatory intestinal disease. We analyzed twenty fecal samples taken from four premature infants (4-6 time points from each infant), and found significantly higher diametric ratios of genes associated with low oxygen levels in samples of infants later diagnosed with NEC than in samples without NEC. We also show this method can be used for examining other physiological conditions, such as exposure to nitric oxide and osmotic pressure. These study results should be treated with caution, due to the presence of confounding factors that might also distinguish between NEC and control infants. Nevertheless, together with benchmarking analyses, we show here that the diametric ratio approach can be applied for evaluating the physiological conditions experienced by microbes in situ. Results from similar studies can be further applied for designing diagnostic methods to detect NEC in its early developmental stages.


Calpain-dependent cytoskeletal rearrangement exploited for anthrax toxin endocytosis.
The protective antigen component of Bacillus anthracis toxins can interact with at least three distinct proteins on the host cell surface, capillary morphogenesis gene 2 (CMG2), tumor endothelial marker 8, and β1-integrin, and, with the assistance of other host proteins, enters targeted cells by receptor-mediated endocytosis. Using an antisense-based phenotypic screen, we discovered the role of calpains in this process. We show that functions of a ubiquitous Ca(2+)-dependent cysteine protease, calpain-2, and of the calpain substrate talin-1 are exploited for association of anthrax toxin and its principal receptor, CMG2, with higher-order actin filaments and consequently for toxin entry into host cells. Down-regulated expression of calpain-2 or talin-1, or pharmacological interference with calpain action, did not affect toxin binding but reduced endocytosis and increased the survival of cells exposed to anthrax lethal toxin. Adventitious expression of wild-type talin-1 promoted toxin endocytosis and lethality, whereas expression of a talin-1 mutant (L432G) that is insensitive to calpain cleavage did not. Disruption of talin-1, which links integrin-containing focal adhesion complexes to the actin cytoskeleton, facilitated association of toxin bound to its principal cell-surface receptor, CMG2, with higher-order actin filaments undergoing dynamic disassembly and reassembly during endocytosis. Our results reveal a mechanism by which a bacterial toxin uses constitutively occurring calpain-mediated cytoskeletal rearrangement for internalization.


Screening for obesity-related complications among obese children and adolescents: 1999-2008.
Obesity is becoming an increasingly prevalent problem among American children. Screening for obesity associated comorbid conditions has been shown to be inconsistent. The current study was undertaken to explore patterns of ordering screening tests among obese pediatric patients. We analyzed electronic medical records (EMR) from 69,901 patients ages 2-18 years between June 1999 and December 2008. Obese children who had documented diagnoses of obesity were identified based on International Classification of Diseases, Ninth Revision codes. Screening rates for glucose, liver, and lipid abnormalities were assessed. Regression analysis was used to examine impact of patient characteristics and temporal trends were analyzed. Of the 9,251 obese diagnosed patients identified, 22% were screened for all three included obesity-related conditions: diabetes, liver, and lipid abnormalities; 52% were screened for glucose abnormalities; 30% for liver abnormalities; and 41% for lipid abnormalities. Increasing BMI and age were associated with increased rates of screening. Females and Hispanic patients were more likely to be screened. The majority of screening was ordered under "basic metabolic panel," "hepatic function panel," and "full lipid profile" for each respective condition. The percentages of patients screened generally increased over time, although the percentages screened for diabetes and lipid abnormalities seemed to plateau or decrease after 2004. Even after diagnosis, many obese patients are not receiving recommended laboratory screening tests. Screening increased during the study period, but remains less than ideal. Providers could improve care by more complete laboratory screening in patients diagnosed with obesity.


Biopipe: a flexible framework for protocol-based bioinformatics analysis.
We identify several challenges facing bioinformatics analysis today. Firstly, to fulfill the promise of comparative studies, bioinformatics analysis will need to accommodate different sources of data residing in a federation of databases that, in turn, come in different formats and modes of accessibility. Secondly, the tsunami of data to be handled will require robust systems that enable bioinformatics analysis to be carried out in a parallel fashion. Thirdly, the ever-evolving state of bioinformatics presents new algorithms and paradigms in conducting analysis. This means that any bioinformatics framework must be flexible and generic enough to accommodate such changes. In addition, we identify the need for introducing an explicit protocol-based approach to bioinformatics analysis that will lend rigorousness to the analysis. This makes it easier for experimentation and replication of results by external parties. Biopipe is designed in an effort to meet these goals. It aims to allow researchers to focus on protocol design. At the same time, it is designed to work over a compute farm and thus provides high-throughput performance. A common exchange format that encapsulates the entire protocol in terms of the analysis modules, parameters, and data versions has been developed to provide a powerful way in which to distribute and reproduce results. This will enable researchers to discuss and interpret the data better as the once implicit assumptions are now explicitly defined within the Biopipe framework.


Clozapine-induced agranulocytosis/granulocytopenia: mechanisms and monitoring.
Clozapine-induced agranulocytosis/granulocytopenia (CIAG) is an uncommon condition, but potentially fatal in consequences. The pathogenesis, despite multiple experiments, is not fully elucidated. The current theory suggests reactive oxygen species - nitrenium ion as the most important factor of CIAG. In this review, mechanism and monitoring of CIAG will be discussed. The mechanism of CIAG seems to have an autoimmune background, rather than toxic. Clozapine has a high potential to undergo biochemical activation to nitrenium ion. The role of the primary metabolite of clozapine - N-desmethylclozapine - is in decline. Nitrenium ion is mainly synthesized by CYP3A4, CYP2D6, and myeloperoxidase system in leukocytes. An important component of CIAG pathogenesis is genetic aberration in human leukocyte antigen genes, and also genes associated with apoptosis and ubiquitination. Clozapine monitoring regimes differ between countries. US-derived clozapine Risk Evaluation and Mitigation Strategy is the most tolerant in the aspect of blood parameter thresholds. Therefore, it provides the opportunities for physician to continue the treatment and also to rechallenge the drug after the episode of CIAG. Each patient with the episode of CIAG should be assessed individually, with special attention to risk factors and drug-drug interactions. Upon that, the decision about clozapine rechallenge or withdrawal should be made.


Understanding the effects of chronic kidney disease on cardiovascular risk: are there lessons to be learnt from healthy kidney donors?
Chronic kidney disease (CKD) is now a recognized global public health problem. It is highly prevalent and strongly associated with hypertension and cardiovascular disease (CVD); far more patients with a glomerular filtration rate below 60 ml min(-1) per 1.73 m(2) will die from cardiovascular causes than progress to end-stage renal disease. A better understanding of the complex mechanisms underlying the development of CVD among CKD patients is required if we are to begin devising therapy to prevent or reverse this process. Observational studies of CVD in CKD are difficult to interpret because renal impairment is almost always accompanied by confounding factors. These include the underlying disease process itself (for example, diabetes mellitus and systemic vasculitis) and the complications of CKD, such as hypertension, anaemia and inflammation. Kidney donors provide an ideal opportunity to study healthy subjects without manifest vascular disease who experience an acute change from having normal to modestly impaired renal function at the time of uninephrectomy. Prospectively examining the cardiovascular consequences of uninephrectomy using donors as a model of CKD may provide useful insight into the pathophysiology of CVD in CKD and, therefore, into how the CVD risk associated with renal impairment might eventually be reduced.


A new inhalation technique for improved effect of aerosolized drugs in asthma. The shrug of the shoulder method.
A new, simple technique for inhalation of aerosolized drugs is described: During the breathholding period after inhalation from a pressurized aerosol the patient lifts his right and lowers his left shoulder and vice versa to "disperse" the drug as well as possible in the lungs. Twenty outpatients suffering from reversible bronchial obstruction inhaled two puffs from a pressurized terbutaline aerosol in the morning on two consecutive days using the new inhalation technique on one day and their ordinary technique on the other in this randomised, cross-over trial. Compared with the conventional method the new inhalation technique significantly improved bronchodilation as measured by forced expiratory volume in 1st s and forced vital capacity during a period of 6 h. The new method of inhalation may improve treatment with aerosolized drugs.


The relationship between weight-adjusted-waist index and total bone mineral density in adults aged 20-59.
According to reports, obesity has a significant impact on bone health. And the weight-adjusted-waist index (WWI), superior to BMI and waist circumference (WC), is a new obesity indicator arising in recent years. This research investigated the relationship between WWI and total bone mineral density (BMD) for adults aged 20 to 59. Using data from the 2011-2018 NHANES, we looked into the independent link between WWI and total BMD as well as its nonlinearity using weighted multiple linear regression and smooth curve fitting. Two-stage linear regression models were employed to calculate the threshold effects. There were additional subgroup analyses and testing for interactions. Multiple linear regression studies on a total of 10,372 individuals showed a significant inverse link between WWI and total BMD in adults between 20 and 59 [β = -0.04, 95% CI: (-0.04, -0.03), P<0.0001]. And smoking, race, and chronic kidney disease (CKD) had no significant effect on this negative connection (P for interaction >0.05). In addition, we found a nonlinear relationship between WWI and total BMD in diabetic and CKD patients, for which the saturation point was 11.38 cm/√kg in the CKD patient group and 10.29 cm/√kg in the diabetic patient group. Our analysis demonstrated a significant inverse association between WWI and total BMD in adults aged 20-59.


Patient gender and communication with physicians: results of a community-based study.
An observational study of 648 routine medical visits with 69 physicians examined patient gender in relation to patient and physician communication, patient preference for the physician's communication style, patient satisfaction, and the physician's awareness of the patient's satisfaction. Data consisted of audiotapes as well as patient and physician questionnaires. Women appeared to be more actively engaged in the talk of medical visits--they sent and received more emotionally charged talk and were judged by independent raters as more anxious and interested both globally and in terms of voice quality than men. Consistent with the more emotional talk, women reported preferring a more "feeling-oriented" physician than male patients did. Mean levels of satisfaction with communication did not differ by gender, and communication predictors of satisfaction were similar for male and female patients, although they were stronger for male patients. Physicians were significantly less aware of some aspects of female patients' satisfaction compared to male patients' satisfaction. In light of the weaker correlations between patients' communication and their satisfaction for women, we suggest that women provided fewer obvious cues to their satisfaction. Training in communication skills may increase open discussion about feelings and emotions and may also produce greater physician sensitivity to patients' satisfaction, particularly with female patients.


Discriminating isogenic cancer cells and identifying altered unsaturated fatty acid content as associated with metastasis status, using k-means clustering and partial least squares-discriminant analysis of Raman maps.
Raman spectroscopy is a label-free, real-time diagnostic tool that shows great promise in identifying cell differences. We have evaluated the discriminatory power of Raman spectroscopy using a unique model system consisting of two isogenic cancer cell lines derived from the MDA-MB-435 cell line. The two cell lines are equally tumorigenic in mice, but while M-4A4 gives rise to metastasis, NM-2C5 only disseminates single cells that remain dormant in distant organs. Previous comparative proteomic and transcriptomic analyses of the two cell lines have shown that they differ only in the expression level of a few proteins and genes. Raman maps were recorded of single cells after fixation and drying using 785 nm laser excitation. K-means clustering reduced the amount of data from each cell and improved the signal-to-noise ratio of cluster-averaged spectra. Spectra representing the nucleus were discarded as they showed much smaller differences between the two cell lines compared to cytoplasm spectra. Partial least squares-discriminant analysis (PLS-DA) was applied to distinguish the two cell lines. A cross-validated PLS-DA resulted in 92% correctly classified samples. Spectral differences were assigned to a higher unsaturated fatty acid content in the metastatic vs nonmetastatic cell line. Our study demonstrates the unique ability of Raman spectroscopy to distinguish minute differences at the subcellular level and yield new biological information. Our study is the first to demonstrate the association between polyunsaturated fatty acid content and metastatic ability in this unique cell model system and is in agreement with previous studies on this topic.


[Limit of duration of anabiosis in microorganisms].
The extrapolation of data obtained at high temperatures which are used for sterilization shows that the energy of heat excitation must limit the extreme duration of anabiosis to 10(4)-10(5) years at conventional temperatures for the most resistant forms of microorganisms. The span of time within which these forms survive can be limited due to racemization of amino acids and low thermostability of some of them.


Shewanella vesiculosa sp. nov., a psychrotolerant bacterium isolated from an Antarctic coastal area.
Two strains of psychrotolerant bacteria, designated M7(T) and M5, isolated from Antarctic coastal marine environments were studied to determine their taxonomic position. The organisms comprised Gram-negative, rod-shaped, facultatively anaerobic cells that were motile by means of single polar flagella. Neither of the bacterial isolates had a requirement for Na(+). These two psychrotolerant strains grew at temperatures ranging from -4 to 30 degrees C. Both strains were capable of producing H(2)S from thiosulfate and were able to use sodium nitrate and trimethylamine N-oxide as terminal electron acceptors during anaerobic growth. 16S rRNA gene sequence analysis placed M7(T) and M5 within the genus Shewanella; the strains showed the highest similarity (99.9 and 99.2 % respectively) with respect to the type strains of Shewanella livingstonensis and Shewanella frigidimarina. However the levels of gyrB sequence similarity between strain M7(T) and the type strains of S. livingstonensis and S. frigidimarina were 87.6 and 87.4 %, respectively. DNA-DNA hybridization experiments performed between the Antarctic isolate M7(T) and S. livingstonensis LMG 19866(T) and S. frigidimarina LMG 19475(T) revealed levels of relatedness of 32 and 35 %, respectively. Strain M5 showed 100 % DNA relatedness with respect to strain M7(T). The DNA G+C content of these bacteria was 42 mol%. Several phenotypic characteristics, the cellular fatty acid compositions and the quinone content of strains M7(T) and M5 served to differentiate them from related shewanellae. On the basis of the data from this polyphasic taxonomic study, M7(T) and M5 constitute a single genospecies. They represent a novel species of the genus Shewanella, for which the name Shewanella vesiculosa sp. nov. is proposed. The type strain is M7(T) (=LMG 24424(T) =CECT 7339(T)).


Kinetic differences in intestinal and systemic interferon-gamma and antigen-specific antibodies in chickens experimentally infected with Eimeria maxima.
Kinetic differences between systemic vs. intestinal and humoral vs. cellular immune responses were elucidated in chickens experimentally infected with Eimeria maxima by comparing interferon-gamma (IFN-gamma) and parasite-specific antibody levels in the intestine and serum during the course of infection. The level of serum IFN-gamma correlated significantly with fecal oocyst shedding (r2 = 0.97), thereby establishing the importance of cell-mediated immunity in coccidia infection. Moreover, intestinal IFN-gamma levels increased sooner than those in sera (4 vs. 6 days postinfection) and both were observed prior to the appearance of parasite-specific antibodies (8-10 days postinfection), again indicating the importance of intestinal cellular immunity in coccidiosis. Although immunoglobulin (Ig)G, IgA, and IgM isotypes of the antigen-specific antibody response increased significantly in both the intestine and serum after E. maxima infection, intestinal IgA-specific antibodies showed the most dramatic increase. However, the relevance of this observation in the context of primary Eimeria infection is unclear because the coccidia parasites have reached the final stages of their life cycle by this time. These results thus demonstrate the importance of T-cell immune responses against coccidia, characterized by local IFN-gamma secretion in the intestine, in mediating host protective immune response to coccidia.


Effect of dietary essential amino acid limitations upon the susceptibility to Salmonella typhimurium and the effect upon humoral and cellular immune responses in mice.
We investigated the effects of dietary essential amino acid limitations on the susceptibility of mice to Salmonella typhimurium infections and on humoral and cellular immune (cell-mediated immune) responses of mice. Mice fed synthetic diets limited (significantly less than optimum concentration) in a single essential amino acid (leucine, isoleucine, valine, or lysine) for 3 weeks after they were weaned exhibited significantly enhanced susceptibility to S. typhimurium infection, as evidenced by the higher levels of mortality and spread of the bacterial cells in their livers and spleens compared with mice fed the control diet. Compared with mice fed the control diet, mice fed the diet limited in leucine had a lower ability to clear S. typhimurium cells from the peritoneal cavity 5 min after intraperitoneal injection, whereas mice fed the diet limited in lysine had a greater ability. The in vivo phagocytosis and in vitro bactericidal kinetics against S. typhimurium cells by peritoneal macrophages were not significantly different in the control group and the groups of mice fed experimental diets. Certain experimental groups exhibited significantly lower resistance and antibody response against S. typhimurium SL3770 on day 5 after immunization with heat-killed S. typhimurium SL3770. On day 8 after immunization, the levels of serum antibody against S. typhimurium in the mice fed the experimental diets were comparable to the levels in mice fed the control diet. However, the levels of serum transferrin and complement C3 were significantly lower in mice fed certain experimental diets. The cellular immune capacities of mice fed any of the experimental diets were not impaired compared with the capacities of mice fed the control diet, as measured by spleen cell responsiveness to phytohemagglutinin and the ability to clear infecting Listeria monocytogenes cells from livers and spleens.


Genomic signals of diversification along ecological gradients in a tropical lizard.
Studies of rainforest diversification that simultaneously consider the effects of genetic drift and natural selection are rare. We use Amplified Fragment Length Polymorphism genome scans of the African rainforest lizard Trachylepis affinis from Cameroon to examine the spatial patterns and environmental associations of both neutrally evolving loci and those thought to be under selection. Bayesian selection scans revealed that approximately 7% of the genome may be under divergent selection. Using non-linear environmental modelling techniques, we fit patterns of genetic differentiation recovered from the pooled neutral data and from individual loci showing a signature of natural selection. Neutral differentiation occurred along a cline from coastal lowland rainforest inland toward the gallery forests-savanna mosaic (ecotone), and was associated with both geographic distance and changing precipitation patterns. Loci under selection were differentiated predominantly along the forest-ecotone gradient-in concordance with morphological divergence in traits related to fitness. A second set of these loci was differentiated between lowland and montane habitats. A third set of loci was indicative of divergent selection between rainforest refugia. Niche models and demographic signals in mitochondrial sequence data support a population expansion out of a core rainforest area into savanna since the last glacial maximum. Our findings indicate adaptive diversification in T. affinis may be taking place along the forest-ecotone gradient during range expansions or contractions, and that refugial isolation augmented by divergent adaptation to different rainforest environments appears to play a less significant role.


Effects of Nd: YAG laser irradiation on the root canal wall dentin of human teeth: a SEM study.
The purpose of this study was to observe the morphological and histological changes on the root canal walls after Nd:YAG laser application. Twenty vital, recently extracted single-rooted human teeth were used for this study. Root canals were cleaned and shaped by a conventional step-back technique--by means of k files up to a 20 k-file type at working length--and subsequently shaped by Ni-Ti root-canal rotary instrumentation up to 30/06 and irrigated with 2.5% hypochlorite solution. Ten teeth (control group) were left unlased, while the other ten teeth were irradiated with Nd:YAG laser by means of a 320 microns fibre inserted in the root canal at 1 mm from the apex with a power of 1.5 Watt and a frequency of 15 pps for five seconds in retraction with rotating movements. The control specimen showed debris and smear layer on the root canal surface obscuring the dentin tubules. The root canal walls irradiated with Nd:YAG laser showed a clear glazed surface, some open dentinal tubules and some surface craters with cracks. Such results confirm that smear layer and debris are removable with Nd:YAG laser, however clearing all root canal walls is still difficult and, if the energy level and duration of application are inadequate, a certain degree of thermal damage and morphological changes in dentin structure are observable.


18F-fluorodeoxyglucose positron emission tomography/computed tomography in the assessment of occult primary head and neck cancers--an audit and review of published studies.
To assess the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with squamous cell and undifferentiated cancer neck nodes and no primary site on conventional assessment. Seventy-eight patients with neck nodal metastases from an unknown primary cancer were studied. PET/CT was carried out in all patients, 1h after FDG injection. Uptake suspicious of an occult primary cancer was found in 46/78 (59.0%) patients. Subsequent investigations confirmed a primary site in the base of the tongue in 14, pharyngeal palatine tonsil in 14, post cricoid in one, lung in one. PET/CT diagnosed primary cancers in 30/78 patients (38.5%); sensitivity, specificity, positive predictive value, negative predictive value: 30/30 (100.0%), 32/48 (66.7%), 30/46 (65.2%), 32/32 (100.0%), respectively. PET/CT detected additional disease in four patients: contralateral nodal disease in two, mediastinal nodal disease in one and liver metastases in one. FDG PET/CT is of value in the assessment of patients with occult head and neck primary cancers. However, false-positive results remain a limitation of the investigation.


Sport participation may protect socioeconomically disadvantaged youths with refugee backgrounds from experiencing behavioral and emotional difficulties.
Youth with refugee backgrounds experience social and socioeconomic difficulties that arise following resettlement. Research has found that sport participation generally provides youth with a protective milieu that is especially beneficial for the most disadvantaged youth. Accordingly, the current study examines whether sport participation is related to positive psychosocial outcomes for resettled adolescent refugees, and if these effects are greater for those living in socioeconomically disadvantaged communities. Data were from a large, nationally representative cohort of refugees recently resettled in Australia (Building New Life in Australia study, BNLA). Self-reported social and emotional well-being was collected from 415 youth who entered the country as refugees (Mage = 14.04, SD = 1.99) at three years post settlement were used. A moderated regression analysis indicated that refugee youth living in socioeconomically disadvantaged neighborhoods who participated in sports reported significantly better outcomes compared to those refugee youth in economically similar neighborhoods who did not participate in sport. In contrast, refugee youth residing in more socioeconomically advantaged communities had better developmental outcomes, regardless of sport participation. Sport participation is a protective factor for youth with refugee backgrounds. Community socioeconomic disadvantage moderates this relationship, whereby stronger effects were observed for adolescents in more disadvantaged communities. Protecting the most disadvantaged in our society is a human rights imperative, and the current study indicates that sport participation could contribute to these efforts among resettled refugee populations.


Pharmacokinetics of chloramphenicol base in horses and comparison to compounded formulations.
Chloramphenicol is commonly used in horses; however, there are no studies evaluating the pharmacokinetics of veterinary canine-approved tablets. Studies using different formulations and earlier analytical techniques led to concerns over low bioavailability in horses. Safety concerns about human health have led many veterinarians to prescribe compounded formulations that are already in suspension or paste form. The objective of this study was to evaluate the pharmacokinetics of approved chloramphenicol tablets in horses, along with compounded preparations. The hypothesis was that chloramphenicol has low absorption and a short half-life in horses leading to low serum concentrations and that compounded preparations have lower relative bioavailability. Seven horses were administered chloramphenicol tablets (50 mg/kg orally). In a crossover design, they were administered two compounded preparations to compare all three formulations at the same dose (50 mg/kg). Cmax was 5.25 ± 4.07 μg/ml at 4.89 hr, 4.96 ± 3.31 μg/ml at 4.14 hr, and 3.84 ± 2.96 μg/ml at 4.39 hr for the tablets, paste, and suspension, respectively. Elimination half-life was 2.65 ± 0.75, 3.47 ± 1.47, and 4.36 ± 4.54 hr for tablets, paste, and suspension, respectively. The AUC0→∞ was 17.93 ± 7.69, 16.25 ± 1.85, and 14.00 ± 5.47 hr*μg/ml for the tablets, compounded paste, and compounded suspension, respectively. Relative bioavailability of compounded suspension and paste was 78.1% and 90.6%. Cmax after administration of all formulations did not reach the recommended MIC target of 8 μg/ml set by the Clinical Laboratory Standards Institute (CLSI) for most bacteria. Multidose studies are warranted, but the low serum concentrations suggest that bacteria with MIC values lower than CLSI recommendations should be targeted in adult horses.


Effect of simvastatin on left ventricular mass in hypercholesterolemic rabbits.
Epidemiological studies showed that hypercholesterolemia is associated with higher left ventricular mass. Endothelin signaling is activated in hyperlipidemic animals and may contribute to progressive ventricular hypertrophy. Simvastatin has been shown to inhibit endothelin-1. However, the behavior of simvastatin on ventricular hypertrophy in hyperlipidemic animals is not well understood. In this study, we evaluated the hemodynamic, biochemical, and morphological responses to simvastatin in cholesterol-fed (1%) rabbits. The left ventricular weight increased 8 wk after cholesterol feeding compared with that in normocholesterolemic rabbits. Simvastatin at a clinical therapeutic dose (1.2 mg x kg(-1) x day(-1)) significantly decreased left ventricular weight by 14% and left ventricular myocyte sizes by 14% as isolated by enzymatic dissociation. Hypercholesterolemia upregulated ventricular preproendothelin-1 mRNA as assessed by real-time quantitative RT-PCR and elevated production of cardiac endothelin-1 concentration. The increased endothelin-1 responses can be inhibited after simvastatin administration. Left ventricular mass indexed by body weight positively correlated with tissue endothelin-1 levels (P = 0.0003). In Langendorff-perfused rabbit hearts, hyperlipidemia led to significant QT prolongation compared with normocholesterolemia, which can be reversed by administering simvastatin. In contrast, simvastatin-induced beneficial effects were reversed by the addition of mevalonate. The addition of bosentan, a nonspecific endothelin receptor blocker, improved the response in hypercholesterolemic rabbits and did not have additional beneficial effects in simvastatin-treated rabbits. The results of the present study suggest that the antihypertropic and electrocardiographic effects of simvastatin at a clinical therapeutic dose are mediated through inhibition of tissue endothelin-1 expression, which is linked to mevalonate metabolism, and result in an amelioration of cardiomyocyte hypertrophy development by an atherogenic diet.


Mobility and self-care trajectories for individuals with cerebral palsy (aged 1-21 years): a joint longitudinal analysis of cohort data from the Netherlands and Canada.
A good understanding of developmental trajectories is crucial for making prognoses, planning interventions, and monitoring progress in children and adolescents with cerebral palsy. Our study aimed to describe developmental trajectories of mobility and self-care capability in a large sample of children and adolescents with cerebral palsy from the Netherlands and Canada. We did longitudinal data analyses of cohorts from the Netherlands (Pediatric Rehabilitation Research in the Netherlands; PERRIN) and Ontario, Canada (Adolescent Study of Quality of Life, Mobility, and Exercise; ASQME). All participants had a confirmed diagnosis of cerebral palsy and ranged in age from 1 year to 17 years at baseline, and were recruited from rehabilitation centres and university medical centres. Individuals diagnosed with additional conditions affecting motor function other than cerebral palsy (eg, spina bifida or muscle diseases) were excluded. After baseline assessment, up to three follow-up assessments were done at 1 year intervals. The whole spectrum of severity of cerebral palsy was represented in terms of motor function, using the Gross Motor Function Classification System (GMFCS). Mobility and self-care capability were assessed with the Pediatric Evaluation of Disability Inventory (PEDI). We applied non-linear mixed-effects modelling to estimate limits, rates, and variations of development. For both projects, recruitment took place between 2002 and 2007. The combined dataset included 551 individuals with cerebral palsy (321 individuals from the PERRIN programme and 230 from ASQME), aged 1 year to 17 years at baseline, with longitudinal data available for up to 4 years. On the basis of a total of 1754 PEDI observations, we created developmental curves for ages 1-21 years. Both for mobility and self-care, limits and rates of development differed among individuals across GMFCS levels, resulting in distinct curves. For individuals classified as being in GMFCS level I, the estimated mean limit for mobility and self-care were both higher than 90 (95·6, 95% CI 94·5-96·7 for mobility and 91·8, 90·1-93·4 for self-care), indicating capability for most if not all items on the PEDI. By comparison, the estimated mean limits for children in levels II-V varied from 83·0 (80·3-85·7) to 23·6 (20·7-26·4), with increasing limitations in mobility and self-care capability for higher GMFCS levels. Individuals with lower GMFCS levels (ie, less severe cerebral palsy) showed higher developmental limits that were reached during a longer period of development. However, among individuals within the same GMFCS level, we found substantial interindividual variation in development for mobility, and even more so for self-care. Prognosis for mobility and self-care capability can largely be based on developmental trajectories for children and adolescents with cerebral palsy grouped by GMFCS level. The interindividual variation in development within GMFCS levels indicates that, in addition to GMFCS level, other contextual factors need to be considered when discussing prognosis and management. Using the curves for individuals with cerebral palsy aged 1 year to 21 years, we illustrate how this new knowledge can be applied in paediatric practice. The Netherlands Organisation for Health Research and Development and the Canadian Institutes of Health Research.