High Staphylococcus epidermidis Colonization and Impaired Permeability Barrier in Facial Seborrheic Dermatitis.
Seborrheic dermatitis (SD) is a common inflammatory skin condition. The etiology is unclear, although overgrowth of Malassezia on the skin has been suggested to cause SD. This study investigated whether colonization with Staphylococcus plays a role in facial SD, which was not well addressed previously. The study was conducted from September 1, 2011 to February 20, 2012 in the First Hospital of China Medical University. In the first phase, the study evaluated the level of transepidermal water loss (TEWL) and the number of colony-forming units (CFU) of Staphylococcus in defined skin areas of SD patients who were human immunodeficiency virus (HIV) seropositive (HIV [+] SD [+] group, n = 13), classical SD (HIV [-] SD [+] group, n = 24) patients, HIV seropositive-non-SD (HIV [+] SD [-] group, n = 16) patients, and healthy volunteers (HIV [-] SD [-] group, n = 16). In the second phase, we enrolled another cohort of HIV (-) SD (+) patients who applied topical fusidic acid (n = 15), tacrolimus (n = 16), or moisturizer (n = 12). Changes in the Seborrheic Dermatitis Area Severity Index (SDASI), TEWL, and Staphylococcus density were evaluated 2 weeks later. Comparisons of each index were performed using analysis of variance (ANOVA) and least significant difference method. The level of TEWL was greater through lesional sites in the HIV (+) SD (+) group than that in HIV (+) SD (-) and HIV (-) SD (-) groups (95% confidence interval [CI]: 18.873-47.071, P < 0.001 and 95% CI: 28.755-55.936, P < 0.001, respectively). The number of CFU of Staphylococcus was greater in the HIV (+) SD (+) group than that in HIV (+) SD (-) and HIV (-) SD (-) groups (95% CI: 37.487-142.744, P = 0.001 and 95% CI: 54.936-156.400, P < 0.001, respectively). TEWL was significantly more improved in patients treated with tacrolimus and fusidic acid than that in those treated with moisturizers (95% CI: 7.560-38.987, P = 0.004 and 95% CI: 4.659-37.619, P = 0.011, respectively). Topical tacrolimus and fusidic acid were significantly associated with decreased SDASI as compared with moisturizer (95% CI: 0.03-0.432, P = 0.025 and 95% CI: 0.033-0.44, P = 0.024, respectively). High colonization with Staphylococcus epidermidis, along with impaired skin permeability barrier function, contributes to the occurrence of SD.


Weak-microcavity organic light-emitting diodes with improved light out-coupling.
We propose and demonstrate weak-microcavity organic light-emitting diode (OLED) displays with improved light-extraction and viewing-angle characteristics. A single pair of low- and high-index layers is inserted between indium tin oxide (ITO) and a glass substrate. The electroluminescent (EL) efficiencies of discrete red, green, and blue weak-microcavity OLEDs are enhanced by 56%, 107%, and 26%, respectively, with improved color purity. Moreover, full-color passive-matrix bottom-emitting OLED displays are fabricated by employing low-index layers of two thicknesses. As a display, the EL efficiency of white color was 27% higher than that of a conventional OLED display.


Monochromatic aberrations in resonant optical elements applied to a focusing multilevel reflectarray.
The monochromatic aberrations produced by the phase distribution reflected by resonant sub-wavelength metallic structures are studied both analytically and numerically. Even for normal incidence, the angular dependence of the re-radiated wavefront disturbs the overall performance of the reflectarray. This effect is modelled as combination of a linear and a cubic dependence. A complete numerical simulation of a multilevel focusing reflectarray is performed using computational-electromagnetic and physical-optics-propagation methods. A modified Strehl ratio is defined to show the dependence of the focused spot behavior on aperture. The irradiance distribution is dependent on the polarization state. A small-aperture focusing reflectarray has been designed, fabricated, and tested. The irradiance distribution at the focusing plane is compared with the simulated one, showing a good agreement when residual wavefront aberrations are included.


Calcium current and activation of contraction in ventricular myocardial fibers.
In thin bundles of dog ventricular myocardium, a slow inward current (distinct from the sodium inward current) could be recorded under voltageclamp conditions. This inward current was influenced by changes in external calcium concentration, but it was not dependent on external sodium concentration. Therefore, this current which contributes an appreciable amount of charge transfer during the plateau of the action potential, is carried by calcium ions. In sodium-free solution, the flow of calcium ions into the fiber is directly related to activation of contraction. In sodium-containing solution, however, calcium inward current serves primarily to fill up some intracellular stores from which calcium can be released by moderate depolarization.


The mitogen-activated protein kinase (MAPK)-activated protein kinases MK2 and MK3 cooperate in stimulation of tumor necrosis factor biosynthesis and stabilization of p38 MAPK.
MK2 and MK3 represent protein kinases downstream of p38 mitogen-activated protein kinase (MAPK). Deletion of the MK2 gene in mice resulted in an impaired inflammatory response although MK3, which displays extensive structural similarities and identical functional properties in vitro, is still present. Here, we analyze tumor necrosis factor (TNF) production and expression of p38 MAPK and tristetraprolin (TTP) in MK3-deficient mice and demonstrate that there are no significant differences with wild-type animals. We show that in vivo MK2 and MK3 are expressed and activated in parallel. However, the level of activity of MK2 is always significantly higher than that of MK3. Accordingly, we hypothesized that MK3 could have significant effects only in an MK2-free background and generated MK2/MK3 double-knockout mice. Unexpectedly, these mice are viable and show no obvious defects due to loss of compensation between MK2 and MK3. However, there is a further reduction of TNF production and expression of p38 and TTP in double-knockout mice compared to MK2-deficient mice. This finding, together with the observation that ectopically expressed MK3 can rescue MK2 deficiency similarly to MK2, indicates that both kinases share the same physiological function in vivo but are expressed to different levels.


LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a γ-herpesvirus associated with KS and two lymphoproliferative diseases. Recent studies characterized epigenetic modification of KSHV episomes during latency and determined that latency-associated genes are associated with H3K4me3 while most lytic genes are associated with the silencing mark H3K27me3. Since the latency-associated nuclear antigen (LANA) (i) is expressed very early after de novo infection, (ii) interacts with transcriptional regulators and chromatin remodelers, and (iii) regulates the LANA and RTA promoters, we hypothesized that LANA may contribute to the establishment of latency through epigenetic control. We performed a detailed ChIP-seq analysis in cells of lymphoid and endothelial origin and compared H3K4me3, H3K27me3, polII, and LANA occupancy. On viral episomes LANA binding was detected at numerous lytic and latent promoters, which were transactivated by LANA using reporter assays. LANA binding was highly enriched at H3K4me3 peaks and this co-occupancy was also detected on many host gene promoters. Bioinformatic analysis of enriched LANA binding sites in combination with biochemical binding studies revealed three distinct binding patterns. A small subset of LANA binding sites showed sequence homology to the characterized LBS1/2 sequence in the viral terminal repeat. A large number of sites contained a novel LANA binding motif (TCCAT)3 which was confirmed by gel shift analysis. Third, some viral and cellular promoters did not contain LANA binding sites and are likely enriched through protein/protein interaction. LANA was associated with H3K4me3 marks and in PEL cells 86% of all LANA bound promoters were transcriptionally active, leading to the hypothesis that LANA interacts with the machinery that methylates H3K4. Co-immunoprecipitation demonstrated LANA association with endogenous hSET1 complexes in both lymphoid and endothelial cells suggesting that LANA may contribute to the epigenetic profile of KSHV episomes.


Assessing the effect of marine reserves on household food security in Kenyan coral reef fishing communities.
Measuring the success or failure of natural resource management is a key challenge to evaluate the impact of conservation for ecological, economic and social outcomes. Marine reserves are a popular tool for managing coastal ecosystems and resources yet surprisingly few studies have quantified the social-economic impacts of marine reserves on food security despite the critical importance of this outcome for fisheries management in developing countries. Here, I conducted semi-structured household surveys with 113 women heads-of-households to investigate the influence of two old, well-enforced, no-take marine reserves on food security in four coastal fishing communities in Kenya, East Africa. Multi-model information-theoretic inference and matching methods found that marine reserves did not influence household food security, as measured by protein consumption, diet diversity and food coping strategies. Instead, food security was strongly influenced by fishing livelihoods and household wealth: fishing families and wealthier households were more food secure than non-fishing and poorer households. These findings highlight the importance of complex social and economic landscapes of livelihoods, urbanization, power and gender dynamics that can drive the outcomes of marine conservation and management.


Clinical performance of the LCx HCV RNA quantitative assay.
This study was conducted to assess the performance of the Abbott laboratories LCx HCV RNA Quantitative Assay (LCx assay) in the clinical setting. Four clinical laboratories measured LCx assay precision, specificity, and linearity. In addition, a method comparison was conducted between the LCx assay and the Roche HCV Amplicor Monitor, version 2.0 (Roche Monitor 2.0) and the Bayer VERSANT HCV RNA 3.0 Assay (Bayer bDNA 3.0) quantitative assays. For precision, the observed LCx assay intra-assay standard deviation (S.D.) was 0.060-0.117 log IU/ml, the inter-assay S.D. was 0.083-0.133 log IU/ml, the inter-lot S.D. was 0.105-0.177 log IU/ml, the inter-site S.D. was 0.099-0.190 log IU/ml, and the total S.D. was 0.113-0.190 log IU/ml. The specificity of the LCx assay was 99.4% (542/545; 95% CI, 98.4-99.9%). For linearity, the mean pooled LCx assay results were linear (r=0.994) over the range of the panel (2.54-5.15 log IU/ml). A method comparison demonstrated a correlation coefficient of 0.881 between the LCx assay and Roche Monitor 2.0, 0.872 between the LCx assay and Bayer bDNA 3.0, and 0.870 between Roche Monitor 2.0 and Bayer bDNA 3.0. The mean LCx assay result was 0.04 log IU/ml (95% CI, -0.08, 0.01) lower than the mean Roche Monitor 2.0 result, but 0.57 log IU/ml (95% CI, 0.53, 0.61) higher than the mean Bayer bDNA 3.0 result. The mean Roche Monitor 2.0 result was 0.60 log IU/ml (95% CI, 0.56, 0.65) higher than the mean Bayer bDNA 3.0 result. The LCx assay quantitated genotypes 1-4 with statistical equivalency. The vast majority (98.9%, 278/281) of paired LCx assay-Roche Monitor 2.0 specimen results were within 1 log IU/ml. Similarly, 86.6% (240/277) of paired LCx assay and Bayer bDNA 3.0 specimen results were within 1 log, as were 85.6% (237/277) of paired Roche Monitor 2.0 and Bayer specimen results. These data demonstrate that the LCx assay may be used for quantitation of HCV RNA in HCV-infected individuals.


The sense of the body in individuals with spinal cord injury.
Increasing evidence suggests that the basic foundations of the self lie in the brain systems that represent the body. Specific sensorimotor stimulation has been shown to alter the bodily self. However, little is known about how disconnection of the brain from the body affects the phenomenological sense of the body and the self. Spinal cord injury (SCI) patients who exhibit massively reduced somatomotor processes below the lesion in the absence of brain damage are suitable for testing the influence of body signals on two important components of the self-the sense of disembodiment and body ownership. We recruited 30 SCI patients and 16 healthy participants, and evaluated the following parameters: (i) depersonalization symptoms, using the Cambridge Depersonalization Scale (CDS), and (ii) measures of body ownership, as quantified by the rubber hand illusion (RHI) paradigm. We found higher CDS scores in SCI patients, which show increased detachment from their body and internal bodily sensations and decreasing global body ownership with higher lesion level. The RHI paradigm reveals no alterations in the illusory ownership of the hand between SCI patients and controls. Yet, there was no typical proprioceptive drift in SCI patients with intact tactile sensation on the hand, which might be related to cortical reorganization in these patients. These results suggest that disconnection of somatomotor inputs to the brain due to spinal cord lesions resulted in a disturbed sense of an embodied self. Furthermore, plasticity-related cortical changes might influence the dynamics of the bodily self.


PPAR(gamma) and glucose homeostasis.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor involved in the control of metabolism. Research on PPARgamma is oriented towards understanding its role in insulin sensitization, which was inspired by the discovery that antidiabetic agents, the thiazolidinediones, were agonists for PPARgamma. PPARgamma stimulation improves glucose tolerance and insulin sensitivity in type 2 diabetic patients and in animal models of insulin resistance through mechanisms that are incompletely understood. Upon activation, PPARgamma heterodimerizes with retinoid X receptor, recruits specific cofactors, and binds to responsive DNA elements, thereby stimulating the transcription of target genes. Because PPARgamma is highly enriched in adipose tissue and because of its major role in adipocyte differentiation, it is thought that the effects of PPARgamma in adipose tissue are crucial to explain its role in insulin sensitization, but recent studies have highlighted the contribution of other tissues as well. Although relatively potent for their insulin-sensitizing action, currently marketed PPARgamma activators have some important undesirable side effects. These concerns led to the discovery of new ligands with potent antidiabetic properties but devoid of certain of these side effects. Data from human genetic studies and from PPARgamma heterozygous knockout mice indicate that a reduction in PPARgamma activity could paradoxically improve insulin sensitivity. These findings suggest that modulation of PPARgamma activity by partial agonists or compounds that affect cofactor recruitment might hold promise for the treatment of insulin resistance.


Examining outcome measures in a clinical study of stroke.
We investigated the relation between outcome and sample size for six selected stroke outcome measures to assist investigators in selecting end points for stroke studies. Data from a clinical trial of 167 stroke patients assessed shortly after admission to the hospital and 5 weeks later provided information on clinical, motor, and functional outcomes measured using a neurologic status scale, a stroke severity scale, the Fugl-Meyer Scale, the Barthel Index, and the activities of daily living and cognition subscales of the Level of Rehabilitation Scale. Data were examined using Pearson correlation coefficients and power analyses. All measures were significantly correlated. There was also substantial congruency between the subscales of a measure and its total score. The measures had variable efficiencies; the Barthel Index was the most efficient and therefore required the fewest subjects to identify a significant effect. These data suggest that careful consideration must be given to the choice of stroke outcome measures in terms of their numbers, interrelationships, and statistical properties, as these factors have important implications for the design, analysis, and conduct of clinical stroke studies.


A plant host, Nicotiana benthamiana, enables the production and study of fungal lignin-degrading enzymes.
Lignin has significant potential as an abundant and renewable source for commodity chemicals yet remains vastly underutilized. Efforts towards engineering a biochemical route to the valorization of lignin are currently limited by the lack of a suitable heterologous host for the production of lignin-degrading enzymes. Here, we show that expression of fungal genes in Nicotiana benthamiana enables production of members from seven major classes of enzymes associated with lignin degradation (23 of 35 tested) in soluble form for direct use in lignin activity assays. We combinatorially characterized a subset of these enzymes in the context of model lignin dimer oxidation, revealing that fine-tuned coupling of peroxide-generators to peroxidases results in more extensive C-C bond cleavage compared to direct addition of peroxide. Comparison of peroxidase isoform activity revealed that the extent of C-C bond cleavage depends on peroxidase identity, suggesting that peroxidases are individually specialized in the context of lignin oxidation. We anticipate the use of N. benthamiana as a platform to rapidly produce a diverse array of fungal lignin-degrading enzymes will facilitate a better understanding of their concerted role in nature and unlock their potential for lignin valorization, including within the plant host itself.


Dietary patterns associated with HbA1c and LDL cholesterol among individuals with type 1 diabetes in China.
To identify dietary patterns that influence cardiometabolic risk among individuals with type 1 diabetes (T1D) in China. Data are from a cross-sectional study of T1D in China (n=99). Dietary intake was assessed using three 24-hour recalls. Reduced rank regression was used to identify dietary patterns from a set of 20 food groups that maximized the explained variation in glycated hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) cholesterol. Dietary pattern 1 was characterized by low intakes of wheat products and high-fat cakes, and high intakes of beans and pickled vegetables. Dietary pattern 2 was characterized by low intakes of high-fat cakes, nuts/seeds, fish/shellfish, and teas/coffee, and high intakes of rice and eggs. Participants in the highest tertile of dietary pattern 1 had significantly (p<0.05) higher HbA1c and LDL cholesterol compared to participants in the lowest tertile: mean difference in HbA1c was 1.0 percentage point (11 mmol/mol) and in LDL cholesterol was 0.36 mmol/L after adjustment for age and household income. Dietary pattern 2 was not associated with HbA1c or LDL cholesterol. We identified a dietary pattern that is significantly related to HbA1c and LDL cholesterol. These findings provide support for behavioral strategies to prevent complications in individuals with T1D in China.


Image fidelity for single-layer and multi-layer silver superlenses.
In response to increasing interest in the area of subdiffraction-limited near-field imaging, the performance of several different realizable and theoretical superresolving silver-based lenses is simulated for a variety of different input object profiles. A computationally-efficient T-matrix technique is used to model the lenses, which consist of layers of silver with total width of 40 nm sandwiched between layers of polymethyl methacrylate and silicon dioxide. The lenses are exposed to nonperiodic bright- and dark-slit input patterns, with feature size varied between 1 nm and 2.5 microm. The performance of the lenses is characterized in terms of transfer function, contrast profile, error profile, and input-to-output correlation. It is shown that increasing the number of layers in a lens increases the lens' transmission coefficients at high spatial frequencies; however, this does not always lead to better imaging performance. The main reasons for this are lens-specific resonances that distort features at certain spatial frequencies, and the increased attenuation of the DC component of transmitted images, which reduces image fidelity, particularly for dark-line features. This suggests that, to achieve optimum results, the design of the superresolving lens system should take into account the characteristics of the images that it is expected to transmit.


What should be disclosed to research participants?
Debate surrounding the SUPPORT study highlights the absence of consensus regarding what information should be disclosed to potential research participants. Some commentators endorse the view that clinical research should be subject to high disclosure standards, even when it is testing standard-of-care interventions. Others argue that trials assessing standard-of-care interventions need to disclose only the information that is disclosed in the clinical care setting. To resolve this debate, it is important to identify the ethical concerns raised by clinical research and determine what consent process is needed to address them.


Prospective study of leukocyte count as a predictor of incident breast, colorectal, endometrial, and lung cancer and mortality in postmenopausal women.
The immune system and inflammation are implicated in the pathogenesis of cancer. Prospective studies linking biomarkers of inflammation with cancer incidence and mortality have been inconclusive. To determine whether there is an independent association of white blood cell (WBC) count with incident cancer in postmenopausal women, a prospective cohort study was performed at 40 US clinical centers involving 143,748 postmenopausal women aged 50 to 79 years who were free of cancer at baseline and were enrolled in the Women's Health Initiative. The main outcome measures were incident invasive breast, colorectal, endometrial, and lung cancer. In multivariate models, there was a graded association of WBC count with incidence of all 4 types of cancer. Compared with the lowest quartile of WBC count (2.50-4.79x10(9) cells/L), women with a WBC count in the upper quartile (6.80-15.00x10(9) cells/L) had a statistically significantly higher risk of invasive breast cancer (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.04-1.26), colorectal cancer (HR, 1.19; 95% CI, 1.00-1.41), endometrial cancer (HR, 1.42; 95% CI, 1.12-1.79), and lung cancer (HR, 1.63; 95% CI, 1.35-1.97). The findings were similar when cancers that occurred during the first 2 years of follow-up were excluded. Statistically significant associations remained for invasive breast cancer and endometrial cancer when the analyses were limited to nonsmokers. The WBC count was also statistically significantly associated with breast cancer, lung cancer, and overall cancer mortality. Postmenopausal women with higher WBC counts have a higher risk of incident invasive breast, colorectal, endometrial, and lung cancer, as well as a higher risk of breast, lung, and overall cancer mortality.


Thyroxine (T4) may promote re-epithelialisation and angiogenesis in wounded human skin ex vivo.
There is a pressing need for improved preclinical model systems in which to study human skin wound healing. Here, we report the development and application of a serum-free full thickness human skin wound healing model. Not only can re-epithelialization (epidermal repair) and angiogenesis be studied in this simple and instructive model, but the model can also be used to identify clinically relevant wound-healing promoting agents, and to dissect underlying candidate mechanisms of action in the target tissue. We present preliminary ex vivo data to suggest that Thyroxine (T4), which reportedly promotes skin wound healing in rodents in vivo, may promote key features of human skin wound healing. Namely, T4 stimulates re-epithelialisation and angiogenesis, and modulates both wound healing-associated epidermal keratin expression and energy metabolism in experimentally wound human skin. Functionally, the wound healing-promoting effects of T4 are at least partially mediated via fibroblast growth factor/fibroblast growth factor receptor-mediated signalling, since they could be significantly antagonized by bFGF-neutralizing antibody. Thus, this pragmatic, easy-to-use full-thickness human skin wound healing model provides a useful preclinical research tool in the search for clinically relevant candidate wound healing-promoting agents. These ex vivo data encourage further pre-clinical testing of topical T4 as a cost-efficient, novel agent in the management of chronic human skin wounds.


Modeling the UMLS using an OODB.
The Unified Medical Language System combines many well established authoritative medical informatics terminologies in one system. Such a resource is very valuable to the healthcare industry. However, the UMLS is very large and complex and poses serious comprehension problems for users and maintenance personnel. Furthermore, the sets of concepts of semantic types are not semantically uniform and thus are difficult to study. We describe a method to represent two components of the UMLS, the Metathesaurus (META) and the Semantic Network, as an OODB. The resulting UMLS OODB schema is deeper and more refined than the Semantic Network. It offers semantically uniform classes, which improves support for comprehension and navigation of META. The UMLS OODB also exposes problems in the semantic type classifications.


A nationwide study of social-emotional problems in young children in Turkey.
We aimed to assess the prevalence of social-emotional problems of Turkish children in early childhood and to understand their association with various bio-psycho-social risk factors, in order to establish guidelines in planning training programs for parents and professionals. Data from a representative sample of 1507 boys (54.3%) and 1268 girls (45.7%) aged 10-48 months were collected. The primary caregivers (mothers=91.4%) completed the Brief Infant-Toddler Social and Emotional Assessment (BITSEA), the Brief Symptom Inventory (BSI) and a form designed to gather information about various bio-psycho-social risk factors. Based on the caregiver terms, a total of 1626 children (60.1%) were reported to experience social-emotional problems. However, based on the BITSEA-problem clinical (1.5 SD) cut-off scores, 9.3% (9.1% of boys; 9.5% of girls) of all children were found to experience social-emotional problems. The variables, that showed a significant association with BITSEA-problem scores in pairwise comparisons, were entered in logistic regression analysis to determine the variables that predict the group with scores of above clinical cut-point. Higher total score of BSI of the primary caregiver, being separated from the mother for more than a month, and lower income of the family were found to be significant predictors of social-emotional problems. Caregiver reports highlight that maternal variables of mothers' psychological well-being, education and access to sources of support are closely related to the social-emotional wellbeing of their off-spring. The findings obtained from this study may be used for detection of prioritized domains in terms of management of preventive mental health services.


Case report of the patient source of the Babesia microti R1 reference strain and implications for travelers.
In 2002, a previously healthy 69-year-old man travelled to France from the United States and presented to our hospital with a febrile illness that subsequently was determined to be babesiosis. The blood isolated from this patient served as a source for propagation of the Babesia microti R1 strain with subsequent sequencing and annotation of the parasite genome. Upon admission, we obtained a medical history, performed a physical examination, and examined his blood for the presence of a blood borne pathogen by microscopy, PCR and indirect immunofluorescence antibody testing. Once the diagnosis of babesiosis was made, we reviewed the literature to assess the distribution of B. microti-associated babesiosis cases in immunocompetent patients from outside the USA. The patient recalled a tick bite during the previous month on Cape Cod, Massachusetts. The diagnosis was confirmed by identification of Babesia-infected red blood cells on blood smears, amplification of B. microti DNA in blood by PCR and the presence of B. microti antibody in the serum. This strain was the first isolate of B. microti to be fully sequenced and its annotated genome serves as a reference for molecular and cell biology studies aimed at understanding B. microti pathophysiology and developing diagnostic tests and therapies. A review of babesiosis cases demonstrates a worldwide distribution of B. microti and identifies potential emerging endemic areas where travelers may be at risk of contracting B. microti infection. This case provides clinical information about the patient infected with the R1 isolate and a review of travel risk, diagnosis and treatment of babesiosis in endemic and non-endemic areas.


Protective effect of eugenol against restraint stress-induced gastrointestinal dysfunction: Potential use in irritable bowel syndrome.
Eugenol, an essential constituent found in plants such as Eugenia caryophyllata Thunb. (Myrtaceae) is reported to possess neuroprotective and anti-stress activities. These activities can potentially be useful in the treatment of stress-induced irritable bowel syndrome (IBS). The protective effect of eugenol was assessed against restraint stress (RS)-induced IBS-like gastrointestinal dysfunction in rats. Further, its centrally mediated effect was evaluated in this model. Eugenol (12.5, 25, and 50 mg/kg), ondansetron (4.0 mg/kg, p.o.), and vehicle were administered to rats for 7 consecutive days before exposure to 1 h RS. One control group was not exposed to RS-induction. The effect of eugenol (50 mg/kg) with and without RS exposure was evaluated for mechanism of action and per se effect, respectively. The hypothalamic-pituitary-adrenal cortex (HPA)-axis function was evaluated by estimating the plasma corticosterone level. The levels of brain monoamines, namely serotonin, norepinephrine, dopamine, and their metabolites were estimated in stress-responsive regions such as hippocampus, hypothalamus, pre-frontal cortex (PFC), and amygdala. Oxidative damage and antioxidant defenses were also assessed in brain regions. Eugenol (50 mg/kg) reduced 80% of RS-induced increase in fecal pellets similar to that of ondansetron. Eugenol attenuated 80% of stress-induced increase in plasma corticosterone and modulated the serotonergic system in the PFC and amygdala. Eugenol attenuated stress-induced changes in norepinephrine and potentiated the antioxidant defense system in all brain regions. Eugenol protected against RS-induced development of IBS-like gastrointestinal dysfunction through modulation of HPA-axis and brain monoaminergic pathways apart from its antioxidant effect.


Congenital Cardiovascular Anomalies among Cases of Down Syndrome: A Hospital Based Review of Cases in TikurAnbessa Specialized Hospital, Ethiopia.
In developing countries, infants with Down syndrome and cardiac defect are at increased risk of dying. Congenital heart diseases occur in 40-50% of affected infants. Endocardial cushion defect accounts for the most. Pattern of cardiac defects in Down syndrome vary with ethnicity. The current study aims to determine pattern of cardiac defects and survival of patients in our institution. Hospital based review of cases, between April 2010 and may 2015 were made. Data were analyzed using SPSS version 20 software quantitatively with plotted Kaplan Meier survival curve done. Down syndrome cases, 53 male and 63 females with cardiac anomalies, were described. Patent ductus arteriosus occurs in 57(36.5%), Ventricular septal defect in 31(19.9%), Atrial septal defect in 30(19%), Atrio-ventricular septal defect in 29(18.6%),Tetralogy of Fallot in 4(2.6%) and others in 5(3.2%) cases. Cases were alive, lost to follow-up and died in 59, 35 and 22 cases, respectively. The overall death rate was 19% and two-third of them died during infancy with females dying at an earlier age than males. Pulmonary hypertension, hypothyroidism and gastrointestinal disorders were diagnosed in 46, 21 and 4 of the cases, respectively. Reasons for lost to follow-up were discussed. The pattern of cardiac anomalies in our study among Down syndrome cases is dominated by Patent ductus arteriosus while, the overall survival of cases is guarded as majority of deaths occurred during infancy.


Are grammatical representations useful for learning from biological sequence data?--a case study.
This paper investigates whether Chomsky-like grammar representations are useful for learning cost-effective, comprehensible predictors of members of biological sequence families. The Inductive Logic Programming (ILP) Bayesian approach to learning from positive examples is used to generate a grammar for recognising a class of proteins known as human neuropeptide precursors (NPPs). Collectively, five of the co-authors of this paper, have extensive expertise on NPPs and general bioinformatics methods. Their motivation for generating a NPP grammar was that none of the existing bioinformatics methods could provide sufficient cost-savings during the search for new NPPs. Prior to this project experienced specialists at SmithKline Beecham had tried for many months to hand-code such a grammar but without success. Our best predictor makes the search for novel NPPs more than 100 times more efficient than randomly selecting proteins for synthesis and testing them for biological activity. As far as these authors are aware, this is both the first biological grammar learnt using ILP and the first real-world scientific application of the ILP Bayesian approach to learning from positive examples. A group of features is derived from this grammar. Other groups of features of NPPs are derived using other learning strategies. Amalgams of these groups are formed. A recognition model is generated for each amalgam using C4.5 and C4.5rules and its performance is measured using both predictive accuracy and a new cost function, Relative Advantage (RA). The highest RA was achieved by a model which includes grammar-derived features. This RA is significantly higher than the best RA achieved without the use of the grammar-derived features. Predictive accuracy is not a good measure of performance for this domain because it does not discriminate well between NPP recognition models: despite covering varying numbers of (the rare) positives, all the models are awarded a similar (high) score by predictive accuracy because they all exclude most of the abundant negatives.


Attenuation of doxorubicin-induced cardiotoxicity in a human in vitro cardiac model by the induction of the NRF-2 pathway.
Dose-dependent cardiotoxicity is the leading adverse reaction seen in cancer patients treated with doxorubicin. Currently, dexrazoxane is the only approved drug that can partially protect against this toxicity in patients, however, its administration is restricted to those patients receiving a high cumulative dose of anthracyclines. Investigations into the mechanisms of cardiotoxicity and efforts to improve cardioprotective strategies have been hindered by the limited availability of a phenotypically relevant in vitro adult human cardiac model system. Here, we adapted a readily reproducible, functional 3D human multi-cell type cardiac system to emulate patient responses seen with doxorubicin and dexrazoxane. We show that administration of two NRF2 gene inducers namely the semi-synthetic triterpenoid Bardoxolone methyl, and the isothiocyanate sulfurophane, result in cardioprotection against doxorubicin toxicity comparable to dexrazoxane as evidenced by an increase in cell viability and a decrease in the production of reactive oxygen species. We further show a synergistic attenuation of cardiotoxicity when the NRF2 inducers and dexrazoxane are used in tandem. Taken together, our data indicate that the 3D spheroid is a suitable model to investigate drug induced cardiotoxicity and we reveal an essential role of the NRF2 pathway in cardioprotection providing a novel pharmacological mechanism and intervention route towards the alleviation of doxorubicin-induced toxicity.


Altered mesenchymal niche cells impede generation of normal hematopoietic progenitor cells in leukemic bone marrow.
Degeneration of normal hematopoietic cells is a shared feature of malignant diseases in the hematopoietic system. Previous studies have shown the exhaustion of hematopoietic progenitor cells (HPCs) in leukemic marrow, whereas hematopoietic stem cells (HSCs) remain functional upon relocation to non-leukemic marrow. However, the underlying cellular mechanisms, especially the specific niche components that are responsible for the degeneration of HPCs, are unknown. In this study, we focused on murine bone mesenchymal stem cells (MSCs) and their supporting function for normal hematopoietic cells in Notch1-induced acute T-cell lymphocytic leukemia (T-ALL) mice. We demonstrate that the proliferative capability and differentiation potential of T-ALL MSCs were impaired due to accelerated cellular senescence. RNA-seq analysis revealed significant transcriptional alterations in leukemic MSCs. After co-cultured with the MSCs from T-ALL mice, a specific inhibitory effect on HPCs was defined, whereas in vivo repopulating potential of normal HSCs was not compromised. Furthermore, osteoprotegerin was identified as a cytokine to improve the function of T-ALL MSCs and to enhance normal HPC output via the p38/ERK pathway. Therefore, this study reveals a novel cellular mechanism underlying the inhibition of HPC generation in T-ALL. Leukemic MSCs may serve as a cellular target for improving normal hematopoietic regeneration therapeutically.


Recombinant neutral endopeptidase-24.11 expressed in mouse neuroblastoma cells is associated with neurite membranes.
Neutral endopeptidase-24.11 (EC 22.214.171.124) (NEP) is a transmembrane metallo-endopeptidase that has been shown to be involved in the degradation of several mammalian neuropeptides, including enkephalins. The enzyme has recently been found to be specifically associated with the axonal and synaptic membranes of neurons in the globus pallidus of the pig brain. This result suggests that neurons must possess mechanisms for targeting NEP to particular membrane domains. Study of these mechanisms would greatly benefit from the existence of an established neuron-like cell line capable of expressing and targeting NEP to specific membrane domains. For this reason we have used a retroviral vector containing the cDNA for rabbit kidney NEP to express this enzyme in a mouse neuroblastoma cell line (Neuro2A). Labelling of the cell surface with an antibody coupled to colloidal gold particles and examination of the cells by electron microscopy revealed a non-uniform distribution of NEP at the surface of the cells, the protein being preferentially associated with the membrane of neurites compared with the cell body. This observation suggests that Neuro2A cells possess a mechanism for targeting NEP to specific domains of the plasma membrane. This cell line could thus constitute a good model for studying the mechanisms responsible for targeting this enzyme to specialized regions of the plasma membrane.


Analysis of purity profiles of generic lisinopril tablets marketed in Croatia.
In view of an increasing number of generic drugs emerging, a comparative study was performed including the approved lisinopril preparations in the form of tablets marketed in Croatia, to compare purity profiles of generic drugs versus the original medicinal product. Several batches of each individual medicinal product at different stages of their shelf life were analyzed. Impurities were determined by means of high performance liquid chromatography (HPLC). Impurity profiles were demonstrated to be specific for each individual drug. Original drug, as compared to its generic copies, had the lowest values and also the lowest variability of all the tested parameters--type, total number and content of impurities--suggesting that its manufacturing process is to certain degree better controlled compared to other manufacturers. A characteristic impurity C appearing in all the assessed preparations has the lowest levels in the original drug, whereas the amount of the highest unknown impurity does not exceed 0.10% in any of the analyzed preparations. Although the original drug stands out from all the generic preparations with its purity, it can be generally concluded that, as regarding impurities levels, all the analyzed medicinal products are within the ranges of specification limits; accordingly, it is therefore not expected that, in case of lisinopril tablets, administration of the original drug as compared to any of its generic drugs, will be safer for the patient.


A fluorescence light-up Ag nanocluster probe that discriminates single-nucleotide variants by emission color.
Rapid and precise screening of small genetic variations, such as single-nucleotide polymorphisms (SNPs), among an individual's genome is still an unmet challenge at point-of-care settings. One crucial step toward this goal is the development of discrimination probes that require no enzymatic reaction and are easy to use. Here we report a new type of fluorescent molecular probe, termed a chameleon NanoCluster Beacon (cNCB), that lights up into different colors upon binding SNP targets. NanoCluster Beacons (NCBs) are collections of a small number of Ag atoms templated on single-stranded DNA that fluoresce strongly when placed in proximity to particular DNA sequences, termed enhancers. Here we show the fluorescence emission color of a NCB can change substantially (a shift of 60-70 nm in the emission maximum) depending upon the alignment between the silver nanocluster and the DNA enhancer sequence. Chameleon NCBs exploit this color shift to directly detect SNPs, based on the fact that different SNPs produce a different alignment between the Ag nanocluster and the enhancer. This SNP detection method has been validated on all single-nucleotide substitution scenarios in three synthetic DNA targets, in six disease-related SNP targets, and in two clinical samples taken from patients with ovarian serous borderline tumors. Samples with single-nucleotide variations can be easily identified by the naked eye under UV excitation, making this method a reliable and low-cost assay with a simple readout format.


Health status and psychological distress among in-hospital cardiac arrest survivors in relation to gender.
To describe health status and psychological distress among in-hospital cardiac arrest (IHCA) survivors in relation to gender. This national register study consists of data from follow-up registration of IHCA survivors 3-6 months post cardiac arrest (CA) in Sweden. A questionnaire was sent to the survivors, including measurements of health status (EQ-5D-5L) and psychological distress (HADS). Between 2013 and 2015, 594 IHCA survivors were included in the study. The median values for EQ-5D-5L index and EQ VAS among survivors were 0.78 (q1-q3=0.67-0.86) and 70 (q1-q3=50-80) respectively. The values were significantly lower (p<0.001) in women compared to men. In addition, women reported more problems than men in all dimensions of EQ-5D-5L, except self-care. A majority of the respondents reported no problems with anxiety (85.4%) and/or symptoms of depression (87.0%). Women reported significantly more problems with anxiety (p<0.001) and symptoms of depression (p<0.001) compared to men. Gender was significantly associated with poorer health status and more psychological distress. No interaction effects for gender and age were found. Although the majority of survivors reported acceptable health status and no psychological distress, a substantial proportion reported severe problems. Women reported worse health status and more psychological distress compared to men. Therefore, a higher proportion of women may be in need of support. Health care professionals should make efforts to identify health problems among survivors and offer individualised support when needed.


Antioxidant activities and contents of flavonoids and phenolic acids of Talinum triangulare extracts and their immunomodulatory effects.
In this study, leaves and stems of Talinum triangulare were sequentially extracted with phosphate buffer solution to obtain PTL and PTS (phosphate buffered extracts of T. triangulare leaves and stems), with 75% ethanol to obtained ETL and ETS (ethanol extracts of T. triangulare leaves and stems), or with 90°C boiling water to obtain WTL and WTS (water extracts of T. triangulare leaves and stems). We investigated the antioxidant activities of various T. triangulare extracts, analyzed the extracts' stimulations on human mononuclear cell (MNC) growth and secretion of cytokines (interleukin-1 beta, interferon-γ, and tumor necrosis factor-α) and nitric oxide, and then assayed their subsequent inhibitions on human leukemic U937 cell growth. Results indicated that extracts of T. triangulare showed significant antioxidant activities. Among these extracts, WTS showed the highest stimulatory effect on human MNC growth. The secretion levels of interleukin-1 beta, interferon-γ, and tumor necrosis factor-α in the conditioned medium, wherein human MNC was treated with 500 μg/mL WTS for 72 hours, were 1275, 859, and 2222 pg/mL, respectively. All conditioned media obtained from human MNCs cultured with various T. triangulare extracts showed significant inhibition against U937 cell growth of over 40%. These results suggest that T. triangulare extracts may be used in health foods for their immunomodulatory potential.


Colonic motor and myoelectrical activity: a comparative study of normal subjects, psychoneurotic patients, and patients with irritable bowel syndrome.
Colonic electrical control activity and colonic motor activity in patients with IBS were compared to that found in patients who were equally psychologically disturbed but without bowel symptoms and to the colonic activity of normal subjects. A psychologic assessment was followed by measurement of activity in the rectosigmoid colon during baseline, a neutral interview, a stressful interview, and after a meal or neostigmine. Myoelectrical activity was recorded from two intraluminal bipolar suction electrodes; motor activity was recorded from two intraluminal strain gauges at the same sites. The number and duration of contractions per minute were determined by inspection of the motor activity record; the frequency content of both the motor and myoelectrical records was determined using the Fast Fourier Transform method. Patient selection was successful in producing two groups psychologically similar to each other and more disturbed than the normals. The IBS group had a greater number and duration of contractions than the normals at one recording site during baseline; there were no differences in electrical control (slow wave) activity between these same two groups. The IBS group did not differ significantly from the neurotic group on measures of either electrical control activity or motor activity. Possible reasons for the discrepancies between this and some previous studies are discussed.


Chronic venous ulcers: a review on treatment with fibrin sealant and prognostic advances using proteomic strategies.
Venous ulcers are the main causes of chronic lower-limb ulcers. The healing difficulties encourage the research and development of new products in order to achieve better therapeutic results. Fibrin sealant is one of these alternatives. Besides being a validated scaffold and drug delivery system, it possesses excellent healing properties. This review covered the last 25 years of the literature and showed that the fibrin sealant is used in various clinical situations to promote the healing of different types of ulcers, especially chronic ones. These are mostly venous in origin and usually does not respond to conventional treatment. Commercially, only the homologous fibrin sealants obtained from human blood are available, which are highly efficient but very expensive. The heterologous fibrin sealant is a non-commercial experimental low-cost product and easily produced due to the abundance of raw material. The phase I/II clinical trial is already completed and showed that the product is safe and promisingly efficacious for the treatment of chronic venous ulcers. In addition, clinical proteomic strategies to assess disease prognosis have been increasingly used. By analyzing liquid samples from the wounds through proteomic strategies, it is possible to predict before treatment which ulcers will evolve favorably and which ones will be difficult to heal. This prognosis is only possible by evaluating the expression of isolated proteins in exudates and analysis using label-free strategies for shotgun. Multicentric clinical trials will be required to evaluate the efficacy of fibrin sealant to treat chronic ulcers, as well as to validate the proteomic strategies to assess prognosis.


Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes.
Nicotine C-oxidation by recombinant human cytochrome P450 (P450 or CYP) enzymes and by human liver microsomes was investigated using a convenient high-performance liquid chromatographic method. Experiments with recombinant human P450 enzymes in baculovirus systems, which co-express human nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH)-P450 reductase, revealed that CYP2A6 had the highest nicotine C-oxidation activities followed by CYP2B6 and CYP2D6; the Km values by these three P450 enzymes were determined to be 11.0, 105, and 132 microM, respectively, and the Vmax values to be 11.0, 8.2, and 8.6 nmol/min per nmol P450, respectively. CYP2E1, 2C19, 1A2, 2C8, 3A4, 2C9, and 1A1 catalysed nicotine C-oxidation only at high (500 microM) substrate concentration. CYP1B1, 2C18, 3A5, and 4A11 had no measurable activities even at 500 microM nicotine. In liver microsomes of 16 human samples, nicotine C-oxidation activities were correlated with CYP2A6 contents at 10 microM substrate concentration, whereas such correlation coefficients were decreased when the substrate concentration was increased to 500 microM. Contribution of CYP2B6 (as well as CYP2A6) was demonstrated by experiments with the effects of orphenadrine (and also coumarin and anti-CYP2A6) on the nicotine C-oxidation activities by human liver microsomes at 500 microM nicotine. CYP2D6 was found to have minor roles since quinidine did not inhibit microsomal nicotine C-oxidation at both 10 and 500 microM substrate concentrations. These results support the view that CYP2A6 has major roles for nicotine C-oxidation at lower substrate concentration and both CYP2A6 and 2B6 play roles at higher substrate concentrations in human liver microsomes.


Therapeutic impact of dietary vitamin D supplementation for preventing right ventricular remodeling and improving survival in pulmonary hypertension.
Pulmonary hypertension (PH), caused by elevated pulmonary vascular resistance, leads to right heart failure and ultimately death. Vitamin D deficiency can predispose individuals to hypertension and left ventricular dysfunction; however, it remains unknown how serum vitamin D level is related to PH and right ventricular (RV) dysfunction. Serum 25-hydroxyvitamin D [25(OH)D] levels were assessed in PH patients for an association with disease severity. To examine whether vitamin D supplementation could prevent the development of pulmonary vascular remodeling and RV dysfunction in PH, a rat model of PH was fed either normal chow or a high vitamin D diet. The majority (95.1%) of PH patients had 25(OH)D levels in the insufficiency range, which is associated with increased mean pulmonary artery pressure, increased pulmonary vascular resistance, and decreased cardiac output in PH patients. Vitamin D supplementation significantly increased serum 25(OH)D levels and improved survival in PH rats. Interestingly, while the supplemented rats retained the typical increases in medial thickness of the muscular pulmonary arteries and RV systolic pressure, RV cardiomyocyte hypertrophy and B-type natriuretic peptide expression was significantly attenuated. Vitamin D deficiency is frequently seen in patients diagnosed with PH and low serum levels of 25(OH)D are associated with severity of PH and RV dysfunction. Vitamin D supplementation in PH rats improved survival via ameliorating pathological RV hypertrophy. These findings suggest an insufficient intake of vitamin D might potentially accelerate RV dysfunction, leading to a crucial clinical impact of vitamin D supplementation in PH.


Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions.
Randomized trials have yielded mixed results on the effects of treatment for Helicobacter pylori and little information on the effects of vitamins or garlic supplements on precancerous gastric lesions. We conducted a randomized trial to test the effects of one-time H. pylori treatment and long-term vitamin or garlic supplements in reducing the prevalence of advanced precancerous gastric lesions. Most of the adults aged 35-64 years in 13 randomly selected villages in Linqu County, Shandong Province, China, were identified and given baseline endoscopies in 1994. In 1995, 3365 eligible subjects were randomly assigned in a factorial design to three interventions or placebos: amoxicillin and omeprazole for 2 weeks in 1995 (H. pylori treatment); vitamin C, vitamin E, and selenium for 7.3 years (vitamin supplement); and aged garlic extract and steam-distilled garlic oil for 7.3 years (garlic supplement). Subjects underwent endoscopies with biopsies in 1999 and 2003, and the prevalence of precancerous gastric lesions was determined by histopathologic examination of seven standard biopsy sites. The 3365 eligible randomized subjects represented 93.5% of those with baseline endoscopy and included all baseline histologic categories except gastric cancer. Only 0.18% had normal gastric mucosa. Logistic regression was used to estimate the intervention effects on the odds of advanced precancerous gastric lesions, and t-tests were used to assess effects on histologic severity. All statistical tests were two-sided. H. pylori treatment resulted in statistically significant decreases in the combined prevalence of severe chronic atrophic gastritis, intestinal metaplasia, dysplasia, or gastric cancer in 1999 (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.62 to 0.95) and in 2003 (OR = 0.60; 95% CI = 0.47 to 0.75), and had favorable effects on the average histopathologic severity and on progression and regression of precancerous gastric lesions in 2003. H. pylori treatment did not reduce the combined prevalence of dysplasia or gastric cancer. However, fewer subjects receiving H. pylori treatment (19/1130; 1.7%) than receiving placebo (27/1128; 2.4%) developed gastric cancer (adjusted P = .14). No statistically significant favorable effects were seen for garlic or vitamin supplements. H. pylori treatment reduces the prevalence of precancerous gastric lesions and may reduce gastric cancer incidence, but further data are needed to prove the latter point. Long-term vitamin or garlic supplementation had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence.


Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells.
Tumor vasculature is derived from sprouting of local vessels (angiogenesis) and bone marrow (BM)-derived circulating cells (vasculogenesis). By using a model system of transplanting tumors into an irradiated normal tissue to prevent angiogenesis, we found that tumors were unable to grow in matrix metalloproteinase-9 (MMP-9) knockout mice, but tumor growth could be restored by transplantation of wild-type BM. Endothelial progenitor cells did not contribute significantly to this process. Rather, CD11b-positive myelomonocytic cells from the transplanted BM were responsible for tumor growth and the development of immature blood vessels in MMP-9 knockout mice receiving wild-type BM. Our results suggest that MMP-9 could be an important target for adjunct therapy to enhance the response of tumors to radiotherapy.


Transport of sodium from blood to brain in ischemic brain edema.
Brain water and sodium increase during ischemia, suggesting that the blood-brain barrier permeability to sodium is increased. To test this hypothesis we measured the permeability-surface area products of 22Na and [3H]sucrose in gerbils following 3 hours of unilateral ischemia. In animals with neurologic symptoms, unilateral carotid occlusion reduced the cerebral blood flow in the ipsilateral cerebral hemisphere to 13 +/- 4 ml/100 g/min (n = 6). The water content of the ischemic hemisphere increased from 79.0 +/- 0.6 to 80.8 +/- 0.2% (n = 7, p less than 0.001) and tissue sodium content increased from 231 +/- 17 to 359 +/- 23 mEq/kg (p less than 0.0001). However, there was a 40% reduction in the sodium permeability-surface area product of the ischemic hemisphere compared with the control side (1.65 +/- 0.44 vs 2.79 +/- 0.29 microliter/g/min, n = 6, p less than 0.001). The sucrose permeability-surface area product, a measure of blood-brain barrier integrity, was unchanged. Although ischemia was less severe in the diencephalon, the tissue water and sodium contents increased significantly on the ischemic side. In contrast to the cerebral hemisphere, however, the permeability-surface area products for both sodium and sucrose were unchanged in the ischemic diencephalon. These results suggest that the increase in tissue sodium seen in ischemic edema is not due to enhanced sodium uptake; we speculate that it results, in part, from a reduction in sodium and water clearance from the tissue.


Cooperative Object Transport in Multi-Robot Systems: A Review of the State-of-the-Art.
In recent years, there has been a growing interest in designing multi-robot systems (hereafter MRSs) to provide cost effective, fault-tolerant and reliable solutions to a variety of automated applications. Here, we review recent advancements in MRSs specifically designed for cooperative object transport, which requires the members of MRSs to coordinate their actions to transport objects from a starting position to a final destination. To achieve cooperative object transport, a wide range of transport, coordination and control strategies have been proposed. Our goal is to provide a comprehensive summary for this relatively heterogeneous and fast-growing body of scientific literature. While distilling the information, we purposefully avoid using hierarchical dichotomies, which have been traditionally used in the field of MRSs. Instead, we employ a coarse-grain approach by classifying each study based on the transport strategy used; pushing-only, grasping and caging. We identify key design constraints that may be shared among these studies despite considerable differences in their design methods. In the end, we discuss several open challenges and possible directions for future work to improve the performance of the current MRSs. Overall, we hope to increasethe visibility and accessibility of the excellent studies in the field and provide a framework that helps the reader to navigate through them more effectively.


A point-process matched filter for event detection and decoding from population spike trains.
Information encoding in neurons can be described through their response fields. The spatial response field of a neuron is the region of space in which a sensory stimulus or a behavioral event causes that neuron to fire. Neurons can also exhibit temporal response fields (TRFs), which characterize a transient response to stimulus or behavioral event onsets. These neurons can thus be described by a spatio-temporal response field (STRF). The activity of neurons with STRFs can be well-described with point process models that characterize binary spike trains with an instantaneous firing rate that is a function of both time and space. However, developing decoders for point process models of neurons that exhibit TRFs is challenging because it requires prior knowledge of event onset times, which are unknown. Indeed, point process filters (PPF) to date have largely focused on decoding neuronal activity without considering TRFs. Also, neural classifiers have required data to be behavior- or stimulus-aligned, i.e. event times to be known, which is often not possible in real-world applications. Our objective in this work is to develop a viable decoder for neurons with STRFs when event times are unknown. To enable decoding of neurons with STRFs, we develop a novel point-process matched filter (PPMF) that can detect events and estimate their onset times from population spike trains. We also devise a PPF for neurons with transient responses as characterized by STRFs. When neurons exhibit STRFs and event times are unknown, the PPMF can be combined with the PPF or with discrete classifiers for continuous and discrete brain state decoding, respectively. We validate our algorithm on two datasets: simulated spikes from neurons that encode visual saliency in response to stimuli, and prefrontal spikes recorded in a monkey performing a delayed-saccade task. We show that the PPMF can estimate the stimulus times and saccade times accurately. Further, the PPMF combined with the PPF can decode visual saliency maps without knowing the stimulus times. Similarly, the PPMF combined with a point process classifier can decode the saccade direction without knowing the saccade times. These event detection and decoding algorithms can help develop neurotechnologies to decode cognitive states from neural responses that exhibit STRFs.


Dendritic cell maturation is induced by mycoplasma infection but not by necrotic cells.
To identify environmental stimuli that induce dendritic cell (DC) maturation, we exposed human monocyte-derived immature DC to apoptotic or necrotic cells and measured the levels of expression of costimulatory molecules and cytokine production. While most necrotic or apoptotic cells did not have any effect, some induced DC maturation as detected by up-regulation of CD83 and B7.2 and production of IL-12 and IL-6. The capacity of these cell lines to induce DC maturation was due to their contamination by mycoplasma, since the maturation-inducing effect disappeared when the cells were treated with cyproxin. Furthermore, cell lines deliberately infected with mycoplasma containing supernatant acquired the capacity to induce DC maturation. Our results reveal that DC are able to sense mycoplasma infection and mature as they do in response to most viruses and bacteria. In contrast, apoptotic or necrotic cells fail to induce DC maturation.


Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1).
ICAM-1 is a cell surface glycoprotein originally defined by a monoclonal antibody (MAb) that inhibits phorbol ester-stimulated leukocyte aggregation. Staining of frozen sections and immunofluorescence flow cytometry showed intercellular adhesion molecule-1 (ICAM-1) is expressed on non-hematopoietic cells such as vascular endothelial cells, thymic epithelial cells, certain other epithelial cells, and fibroblasts, and on hematopoietic cells such as tissue macrophages, mitogen-stimulated T lymphocyte blasts, and germinal center dendritic cells in tonsils, lymph nodes, and Peyer's patches. ICAM-1 staining on vascular endothelial cells is most intense in T cell areas in lymph nodes and tonsils showing reactive hyperplasia. ICAM-1 is expressed in low amounts on peripheral blood leukocytes. Phorbol ester-stimulated differentiation of myelomonocytic cell lines greatly increases ICAM-1 expression. ICAM-1 expression on dermal fibroblasts is increased threefold to fivefold by either interleukin 1 (IL 1) or interferon-gamma at 10 U/ml over a period of 4 or 10 hr, respectively. The induction is dependent on protein and mRNA synthesis and is reversible. ICAM-1 displays Mr heterogeneity in different cell types with a Mr of 97,000 on fibroblasts, 114,000 on the myelomonocytic cell line U937, and 90,000 on the B lymphoblastoid cell JY. ICAM-1 biosynthesis involves a Mr approximately 73,000 intracellular precursor. The non-N-glycosylated form resulting from tunicamycin treatment has a Mr of 55,000. ICAM-1 isolated from phorbol myristic acetate (PMA) stimulated U937 and from fibroblasts yields an identical major product of Mr = 60,000 after chemical deglycosylation. ICAM-1 MAb interferes with the adhesion of phytohemagglutinin blasts, and the adhesion of the cell line SKW3 to human dermal fibroblast cell layers. Pretreatment of fibroblasts but not lymphocytes with ICAM-1 MAb, and of lymphocytes but not fibroblasts with lymphocyte function-associated antigen 1 MAb inhibits adhesion. Intercellular adhesion is increased by prior exposure of fibroblasts to IL 1, and correlates with induction of ICAM-1.


Monitoring of Waterborne Parasites in Two Drinking Water Treatment Plants: A Study in Sarawak, Malaysia.
The occurrence of waterborne parasites coupled with water parameters at various processing sites of two drinking water treatment plants (A and B) and seven distribution system (DS) sites in Sarawak, Malaysia were studied. Ten liters of water underwent immunomagnetic separation (IMS) technique to detect the presence of Giardia and Cryptosporidium (oo)cysts. The remaining supernatant was used to detect other parasites whilst 50 mL of water sample was each used in the detection of free-living amoebae and fecal coliforms. Sampled water was positive for Giardia (32.9%; 28/85), Cryptosporidium (18.8%; 16/85) followed by Spirometra ova-like (25.9%; 22/85), Blastocystis-like (25.9%; 22/85), nematode larvae-like (8.2%; 7/85) and Taenia ova-like (1.2%; 1/85). Meanwhile, 90.2% (55/61) samples were positive for Acanthamoeba and Naegleria via cultivation and of these, 11 isolates were confirmed as Acanthamoeba genotype T3 (5/7) and T4 (2/7) followed by Naegleria sp. (4/11), Naegleria italica (2/11), Naegleria australiensis (1/11), Naegleria angularis (1/11) and Vahlkampfia sp. (3/11). Cryptosporidium, Acanthamoeba and Naegleria were also detected in one of the seven tested DS sites. Only Giardia and Cryptosporidium showed significant correlations with fluoride and fecal coliforms. These results describe the occurrence of waterborne parasites that will assist key stakeholders in mitigating contamination at the specific sites.


Hippocampal Expression of Connexin36 and Connexin43 during Epileptogenesis in Pilocarpine Model of Epilepsy.
Gap junctions (GJs) provide direct intercellular communications that are formed by hexameric protein subunits, called connexin (Cx). The role of Cxs in epileptogenesis has not received sufficient attention. Hippocampus with critical function in epileptogenesis has a wide network of GJs. We examined the protein expression levels of hippocampal Cx36 (the prominent Cx present between GABAergic interneurons) and Cx43 (the main Cx expressed by astrocytes) during epileptogenesis in the pilocarpine model of epilepsy. Male Wistar rats received scopolamine (1 mg/kg, s.c.). Pilocarpine (380 mg/kg, i.p.) was administered 30 min thereafter to induce status epilepticus (SE). SE was stopped 2 h later by diazepam (10 mg/kg, i.p.). Cx36 and Cx43 protein expression was assessed by Western blot analysis in the hippocampus of SE-experienced rats, after injection of diazepam (F0 subgroup), after acquisition of focal seizures (F3 subgroup), and after development of generalized seizures (F5 subgroup). The control subgroups, C0, C3, and C5, were aged-matched rats, which received saline (1 ml/kg, i.p.) instead of pilocarpine. Injection of scopolamine and diazepam, and dissection of hippocampi were carried out at the same time interval as the test subgroups. SE emerged in 67.1% of pilocarpine-treated animals. Focal and generalized seizures developed 3.8±0.4 and 7.0±0.5 days after SE, respectively. Cx36 protein abundance was not significantly different between test and control groups in the three time points. However, Cx43 protein level showed 40% increase in F3 subgroup (P<0.05 compared to C3, P<0.01 compared to F0 and F5). Hippocampal Cx43 is overexpressed in pilocarpine model of epileptogenesis after acquisition of focal seizures.


What defines a view?
At a given instant we see only visible surfaces, not an object's complete 3D appearance. Thus, objects may be represented as discrete 'views' showing only those features visible from a limited range of viewpoints. We address how to define a view using Koenderink's (Koenderink & Van Doorn, Biol. Cybernet. 32 (1979) 211.) geometric method for enumerating complete sets of stable views as aspect graphs. Using objects with known aspect graphs, five experiments examined whether the perception of orientation is sensitive to the qualitative features that define aspect graphs. Highest sensitivity to viewpoint changes was observed at locations where the theory predicts qualitative transitions, although some transitions did not affect performance. Hypotheses about why humans ignore some transitions offer insights into mechanisms for object representation.


The CD59 family member Leaky/Coiled is required for the establishment of the blood-brain barrier in Drosophila.
The blood-brain barrier of Drosophila is established by the subperineurial glial cells that encase the CNS and PNS. The subperineurial glial cells are thin, highly interdigitated cells with epithelial character. The establishment of extensive septate junctions between these cells is crucial for the prevention of uncontrolled paracellular leakage of ions and solutes from the hemolymph into the nervous system. In the absence of septate junctions, macromolecules such as fluorescently labeled dextran can easily cross the blood-brain barrier. To identify additional components of the blood-brain barrier, we followed a genetic approach and injected Texas-Red-conjugated dextran into the hemolymph of embryos homozygous for chromosomal deficiencies. In this way, we identified the 153-aa-large protein Coiled, a new member of the Ly6 (leukocyte antigen 6) family, as being crucially required for septate junction formation and blood-brain barrier integrity. In coiled mutants, the normal distribution of septate junction markers such as NeurexinIV, Coracle, or Discs large is disturbed. EM analyses demonstrated that Coiled is required for the formation of septate junctions. We further show that Coiled is expressed by the subsperineurial glial cells in which it is anchored to the cell membrane via a glycosylphosphatidylinositol anchor and mediates adhesive properties. Clonal rescue studies indicate that the presence of Coiled is required symmetrically on both cells engaged in septate junction formation.


Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.
Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."


Recurrence of diffuse panbronchiolitis after lung transplantation.
Diffuse panbronchiolitis (DBP) is characterized by chronic inflammation of the upper and lower respiratory tract. DPB has been found almost exclusively in oriental populations. We describe the occurrence of a case of DPB in an African American patient who underwent bilateral sequential lung transplantation. Ten weeks after transplantation, DPB recurred in the lung allograft, with rapid and significant deterioration in graft function. Allograft function improved within a few weeks after beginning treatment with erythromycin. This early recurrence is suggestive of a systemic etiology of DPB. Although recurrence of other systemic diseases has been reported after lung transplantation, no previous patients have been reported with early functional deterioration based solely on disease recurrence.


Knockdown of ADAM10 inhibits migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a systemic autoimmune disease with high rates of morbidity and mortality. Previous studies proposed that the A disintegrin and metalloprotease (ADAM) family is involved in the regulation of inflammation and arthritis. Thus, the present study investigated whether ADAM10 is involved in the progression of RA. The effects of ADAM10 small interfering (si)RNA on the expression levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑8 and chemokine (C-X-C motif) ligand 16 (CXCL16) were determined in fibroblast‑like synoviocytes (FLS). In addition, the effects of ADAM10 siRNA on cell proliferation, invasion and migration in human RA‑FLS were assessed in vitro. The therapeutic efficacy and side‑effects of ADAM10 siRNA were examined in a mouse model of collagen‑induced arthritis (CIA). In vitro, ADAM10 silencing suppressed the expression of TNF‑α, IL‑6, IL‑8 and CXCL16 in lipopolysaccharide (LPS)‑stimulated human RA‑FLS. LPS‑induced RA‑FLS proliferation, migration and invasion were significantly attenuated by ADAM10 knockdown. ADAM10 silencing inhibited the secretion of vascular endothelial growth factor A (VEGF‑A) and matrix metalloproteinase (MMP)‑3 and ‑9 from LPS‑stimulated human RA‑FLS, in addition to inhibiting the phosphoinositide 3‑kinase/AKT activation in LPS‑stimulated human RA‑FLS. In vivo, treatment with siRNA against ADAM10 for three weeks reduced the arthritis score. Serum levels of VEGF‑A, MMP‑3 and MMP‑9 were also reduced in CIA mice. These observations indicate that the inhibition of ADAM10 may be a viable therapeutic target in the amelioration of disease progression in RA by attenuating FLS proliferation, migration and invasion.


Frequency of Streptococcus pneumoniae infection in patients with suspected meningitis in Imam Reza Hospital of Kermanshah in the west of Iran.
Streptococcus pneumoniae is the main causative agent of acute bacterial meningitis in the world. This study aimed to detect pneumoniae infection in cerebrospinal fluid (CSF) samples of patients with suspected meningitis. In this study, 200 CSF samples in patients with suspected meningitis and with negative bacterial cultures were tested. Demographic data of patients and the laboratory analysis of CSF samples were also collected in a questionnaire. Pneumococcal capsular gene spn9802 was examined by real-time PCR technique. Of 200 CSF samples from patients with the average age of 32.1±25.3 year old, 20 were positive for S. pneumoniae in patients with the average age of 35.05±24.6. The biochemical and cytological analysis of positive samples showed significant changes, including, 39.7 mg/DL protein, 46.2 mg/DL glucose and 1173 white blood cells per microliter of CSF on average. The results of this study showed the significant pneumococcal infection in culture negative CSF samples. The majority of this infection occurred in middle-aged patients and with a higher incidence rate in the winter. It seems that the traditional methods of cultivation are not sensitive enough to detect this bacterium in CSF. Alternatively, the molecular techniques such a real-time seem to be accurate, sensitive and rapid for the detection of this agent in CSF. The cytological and biochemical findings of CSF can provide valuable clues in the diagnosis of bacterial meningitis.


High levels of glucose-6-phosphatase gene and protein expression reflect an adaptive response in proliferating liver and diabetes.
The regenerating liver after partial hepatectomy is one of the few physiologic models of cellular proliferation in the adult animal. During hepatic regeneration, the animal is able to maintain metabolic homeostasis despite the acute loss of two thirds of hepatic tissue. In examining the molecular mechanisms regulating hepatic regeneration, we isolated novel immediate-early genes that are rapidly induced as the remnant liver undergoes the transition from its normal quiescent state into the G1 phase of the cell cycle. One of the most rapidly and highly induced genes which we initially termed RL-1, encodes rat glucose-6-phosphatase (rG6Pase). G6Pase mRNA peaks at 30 min and 36-48 h after hepatectomy correlating with the first and second rounds of cell division. This finding is compatible with studies that showed that G6Pase enzyme activity increases during liver regeneration. However, the increase in G6Pase mRNA is much more dramatic, indicating that it is a more sensitive indicator of this regulation. G6Pase gene expression peaks in the perinatal time period in the liver and remains elevated during the first month of life. The expression of the G6Pase gene is also dramatically elevated in BB diabetic rats, again higher than the enzyme elevation, and its relative induction after partial hepatectomy is blunted in these animals. Insulin treatment of partially hepatectomized diabetic animals downregulates the expression of G6Pase mRNA. Using specific antibodies against G6Pase, we detect a 36-kD G6Pase protein, and its level is elevated in regenerating and diabetic livers. The pattern of G6Pase mRNA expression appears to reflect similar changes in insulin and glucagon levels which accompany diabetes and hepatic proliferation. The elevation of G6Pase expression in these conditions is indicative of its importance as a regulator of glucose homeostasis in normal and abnormal physiologic states.


Effects of High-Fat Diet on eHSP72 and Extra-to-Intracellular HSP70 Levels in Mice Submitted to Exercise under Exposure to Fine Particulate Matter.
Obesity, air pollution, and exercise induce alterations in the heat shock response (HSR), in both intracellular 70 kDa heat shock proteins (iHSP70) and the plasmatic extracellular form (eHSP72). Extra-to-intracellular HSP70 ratio (H-index = eHSP70/iHSP70 ratio) represents a candidate biomarker of subclinical health status. This study investigated the effects of moderate- and high-intensity exercise in the HSR and oxidative stress parameters, in obese mice exposed to fine particulate matter (PM2.5). Thirty-day-old male isogenic B6129F2/J mice were maintained for 16 weeks on standard chow or high-fat diet (HFD). Then, mice were exposed to either saline or 50 μg of PM2.5 by intranasal instillation and subsequently maintained at rest or subjected to moderate- or high-intensity swimming exercise. HFD mice exhibited high adiposity and glucose intolerance at week 16th. HFD mice submitted to moderate- or high-intensity exercise were not able to complete the exercise session and showed lower levels of eHSP70 and H-index, when compared to controls. PM2.5 exposure modified the glycaemic response to exercise and modified hematological responses in HFD mice. Our study suggests that obesity is a critical health condition for exercise prescription under PM2.5 exposure.


Simulation of Drug Uptake in a Two Compartmental Fractional Model for a Biological System.
This paper presents a very effective numerical method for the solution of the two-compartmental pharmacokinetic model for oral drug administration. This model consists of a set of two fractional order differential equations which connect the two compartments. The first compartment represents the gut while the second compartment corresponds to the drug concentration in the target tissue. For ease of computation, the numerical solution is also created as a Matlab function.


East Ireland 1980-1994: epidemiology of neural tube defects.
The objective of the study was to describe the epidemiology of neural tube defects (NTD) in the eastern region of Ireland using the EUROCAT register of congenital malformations. EUROCAT registries monitor the prevalence of congenital anomalies in defined populations using multiple sources for case ascertainment. All cases of NTD on the Dublin EUROCAT register born between 1980 and 1994 were extracted and analysed. The crude birth prevalence rate for all NTD, spina bifida, anencephaly and encephalocoele were calculated for each year. Parameters measured were: sex ratio, stillbirth rate, proportion of low birth-weight babies (< 2500 g) and the proportion who were premature (< 37 weeks gestation). Of 821 NTD cases, 419 (51.0%) had spina bifida, 322 (39.2%) had anencephaly, 69 (8.4%) had encephalocoele and 11 (1.3%) were iniencephalic. The crude birth prevalence of NTD decreased fourfold from 46.9/10,000 births in 1980 to 11.6/10,000 in 1994. The downward trend ceased during the early 1990's. Younger mothers had significantly higher rates of NTD affected births. Twenty two per cent of NTD cases had additional non-central nervous system anomalies. In 40 cases, there was a previous family history of NTD in siblings. Seasonal effects in birth prevalence were observed. Birth notification was the most frequent mechanism of ascertainment. There was a marked fall in the birth prevalence of NTD during the 15 year period. This change was real and not accounted for by pre-natal screening and diagnostic practises with termination of pregnancy, which is not legally permissible in Ireland. Dietary factors may have had an influence. Rates of NTD in this region are still higher than many other parts of Europe. Primary prevention strategies through increased folic acid intake are necessary to further reduce NTD affected births.


Cardiogenic oscillations of nitrogen and argon concentration in expired gas in man.
1. The cardiogenic oscillations in the concentration of nitrogen and argon in expired gas, which are seen after the inspiration from residual volume of pure oxygen or a bolus of argon, have been studied in normal subjects and in patients with atrial fibrillation. 2. In the upright position of the subject, the peaks of nitrogen and argon concentration coincide with ventricular systole, although there is a transit delay along the tracheobronchial tree before any change of concentration occurs at the mouth. 3. Studies in different postures demonstrated that the effect of the heart is predominantly due to a reduction in cardiac volume during systole with a decrease in airflow from regions adjacent to the heart. These areas contain a different concentration of nitrogen and argon in the alveolar air from the more apical regions. 4. It has been shown that the results are consistent with the present concepts of the influence of gravity on the distribution of inspired air.


Patient-Reported Outcome Measures Used for Neck Disorders: An Overview of Systematic Reviews.
The evaluation of patient-reported outcome measures for the neck from multiple systematic reviews will provide a broader view of, and may identify potential conflicting or consistent results for, their psychometric properties. The purpose of this study was to conduct an overview of systematic reviews and synthesize evidence to establish the current state of knowledge on psychometric properties of patient-reported outcome measures for patients with neck disorders. In this overview of systematic reviews, an electronic search of 6 databases (MEDLINE, Embase, CINAHL, ILC, the Cochrane Central Register of Controlled Trials, and LILACS) was conducted to identify reviews that addressed at least one measurement property of outcome measures for people with neck pain. Only systematic reviews with patient-reported outcome measures were included in the analysis. Risk of bias was assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR). Data on measurement properties were extracted from each systematic review. From 13 systematic reviews, 8 patient-reported outcome measures were evaluated in 2 or more reviews. Risk-of-bias scores ranged from moderate (5-7) to high (4 and lower). Findings on internal consistency, test-retest reliability, construct validity, responsiveness to change, and content and structural validity were synthesized for the Neck Disability Index (NDI) in 11 systematic reviews; the Northwick Park Neck Pain Questionnaire and Neck Pain and Disability scale (NPDS) in 6 systematic reviews; the Copenhagen Neck Functional Disability Scale in 5 systematic reviews; the Neck Bournemouth Questionnaire in 4 systematic reviews; the Core Neck Pain Questionnaire and Patient-Specific Functional Scale in 3 systematic reviews, and the Whiplash Disability Questionnaire in 2 systematic reviews. High-quality evidence was found of good to excellent internal consistency and moderate to excellent test-retest reliability for the NDI. Moderate-quality evidence was found of good to excellent internal consistency and good test-retest reliability for the Northwick Park Neck Pain Questionnaire. High-quality evidence was found of excellent test-retest reliability and good to strong construct validity with pain scales for the Copenhagen Neck Functional Disability Scale. Moderate-quality evidence was found of unclear to excellent internal consistency and moderate to strong concurrent associations with the NDI and global assessment of change for the Neck Pain and Disability scale. Moderate-quality evidence was found of excellent internal consistency for the Whiplash Disability Questionnaire and of high test-retest reliability for the Patient-Specific Functional Scale. J Orthop Sports Phys Ther 2018;48(10):775-788. Epub 22 Jun 2018. doi:10.2519/jospt.2018.8131.


Palynological analysis of Sphaeropteris gardneri (Cyatheaceae, Pteridophyta).
The spore morphology and wall ultrastructure of Sphaeropteris gardneri (Hook.) R.M. Tryon from Brazil were analyzed with LM, SEM and TEM. The spores are trilete with an ornamentation formed of short low ridges with spines in their margins. The exospore is 2.5microm thick, two- layered in section and single or branched channels are present. The perispore is 1.2microm thick and two-layered. The inner layer has three strata: the inner stratum is formed of a network of branched and fused threads, the middle stratum has threads with a radial orientation and in the outer stratum thin, dark fibres are immersed in a less dense contrasted matrix. The outer layer of the perispore is the one that forms the echinate-ridges and is constituted of threads arranged in a compact way. Globules of different sizes are observed on the surface. The differences found in the perispore ornamentation and ultrastructure in Alsophila, which was previously studied, and those of Sphaeropteris, show a tendency to wall complexity.


Precise experimental investigation of eigenmodes in a planar ion crystal.
The accurate characterization of eigenmodes and eigenfrequencies of two-dimensional ion crystals provides the foundation for the use of such structures for quantum simulation purposes. We present a combined experimental and theoretical study of two-dimensional ion crystals. We demonstrate that standard pseudopotential theory accurately predicts the positions of the ions and the location of structural transitions between different crystal configurations. However, pseudopotential theory is insufficient to determine eigenfrequencies of the two-dimensional ion crystals accurately but shows significant deviations from the experimental data obtained from resolved sideband spectroscopy. Agreement at the level of 2.5×10(-3) is found with the full time-dependent Coulomb theory using the Floquet-Lyapunov approach and the effect is understood from the dynamics of two-dimensional ion crystals in the Paul trap. The results represent initial steps towards an exploitation of these structures for quantum simulation schemes.


Barriers to obtaining family consent for potential organ donors.
Our country suffers from a chronic shortage of organ donors, and the list of individuals in desperate need of life-saving organ transplants is growing every year. Family consent represents an important limiting factor for successful donation. We hypothesize that specific barriers to obtaining family consent can be identified and improved upon to increase organ donation consent rates. The purpose of this study was to compare families who declined organ donation to those who granted consent, specifically to identify barriers to family consent for successful organ donation. We performed a 4-year (2004-2007) retrospective study of potential organ donors covered by our regional organ procurement organization (OPO). Variables collected included age, gender, race, cause of brain death (trauma vs. medical) of the potential organ donor, and elapsed time from declaration of brain death to family approach by OPO. Potential organ donors whose family declined organ donation (DECLINE group) were compared with potential organ donors whose family consented to organ donation (CONSENT group). Groups were compared using univariate and multivariate analysis. There were a total of 827 potential organ donors during the 4-year period within our OPO region. Overall, 471 families (57%) consented to organ donation, whereas 356 families (43%) declined. Although there was no difference in male gender between the DECLINE and CONSENT groups (59% vs. 53%, p = 0.12), the DECLINE group had more medical brain deaths (73% vs. 58%, p < 0.001), more potential donors aged 50 years or older (43% vs. 34%, p < 0.001), as well as more potential organ donors of Hispanic (67% vs. 43%, p < 0.001) and African American (10% vs. 4%, p < 0.001) descent. In addition, time from declaration of brain death to family approach by OPO was longer for the DECLINE group (350 minutes vs. 112 minutes, p = 0.001). Logistic regression identified race, older age, and death from a medical cause as independent risk factors for failure of obtaining consent. Several barriers exist to family consent for successful organ donation. Family members of minority populations, medical brain deaths, and older potential donors more often decline consent for organ donation. Family education and resource utilization toward these specific populations of potential organ donors may help to improve organ donation consent rates. In addition, delayed family approach by OPO seems to be associated with decreased consent rates. System improvements to expedite family approach by OPO may likewise lead to improved consent rates.


Experiences with abortion counselling in Mexico City and Colombia: addressing women's fears and concerns.
Despite liberalised abortion laws in Colombia and Mexico City, ongoing abortion-related stigma and lack of knowledge of abortion laws can impede access to care. Organisations offering abortion services may support women seeking services by providing counselling and information. We conducted 30 in-depth interviews with women in Colombia and Mexico City after their abortion to understand their feelings of stigma, fears and concerns before accessing services, and how abortion counselling addressed those concerns. Women in both regions cited concerns about abortion safety, fears of judgement from community members and some reported self-judgement or guilt. Before arriving to care, women in Colombia were unsure if they qualified for legal abortion under the current law, and many reported fearing legal or social repercussions for seeking an abortion, whereas women in Mexico knew they could access a legal abortion in Mexico City. Women in all clinics reported satisfaction with the counselling services and felt most of their concerns were addressed. However, most women said they continued to fear judgement from members of the community after their procedure. Service-delivery organisations can provide supportive services and decrease women's fears and concerns, although interventions in communities are also needed to reduce stigma and improve information.