Maternal work conditions and child development.
How do maternal work conditions, such as psychological stress and physical hazards, affect children's development? Combining data from the Child Development Supplement of the Panel Study of Income Dynamics and the Occupational Information Network allows us to shed some light on this question. We employ various techniques including OLS with extensive controls, a value added approach and individual fixed effects in order to address potential endogeneity problems. Our results reveal that mothers' exposure to work-related hazards negatively affects children's cognitive development and to work-related stress negatively affects children's behavioral development. While maternal time investments play a small but significant role in mediating these negative associations, paternal time investments neither reinforce nor compensate these associations.


The Profile Of Severe Burn Injury Patients With Sepsis In Hasan Sadikin Bandung General HospitaL.
Burn injury remains a major global health issue. An estimated 180,000 people die annually due to burn injury, and most cases occur in low- and middle-income countries, including Indonesia. Several complications of burns may lead to mortality, and sepsis is one of the major threats, with the risk of developing multi organ dysfunction syndrome. This study applied a descriptive-retrospective method on 3-year medical records of severe burn injury patients. The data were classified according to age, etiology, outcome, antibiotic resistance, and pathogens of sepsis. There were 100 medical records of severe burn injury, and 55% of them were accompanied by sepsis. The highest number of sepsis cases was found in the age category of 40-50 years old. Nearly 80% of the cases were fire-related burns. Blood and burn wound culture of recovered patients showed 55% contamination with gram-positive bacteria, and 50% of them with Staphylococcus hominis. Contamination of blood and burn wound culture of deceased patients with gram-negative bacteria was 100%, 60% of them with Pseudomonas Aeruginosa. There is a more than 50% chance of severe burn patients falling into septic conditions. More than half of the patients were infected with gram-negative bacteria. Pseudomonas aeruginosa remains the main culprit of septic burn-related death.


Pharmacokinetic investigation of imatinib using accelerator mass spectrometry in patients with chronic myeloid leukemia.
To investigate the potential use of accelerator mass spectrometry (AMS) in the study of the clinical pharmacology of imatinib. Six patients who were receiving imatinib (400 mg/d) as part of their ongoing treatment for chronic myeloid leukemia (CML) received a dose containing a trace quantity (13.6 kBq) of (14)C-imatinib. Blood samples were collected from patients before and at various times up to 72 h after administration of the test dose and were processed to provide samples of plasma and peripheral blood lymphocytes (PBL). Samples were analyzed by AMS, with chromatographic separation of parent compound from metabolites. In addition, plasma samples were analyzed by liquid chromatography/mass spectrometry (LCMS). Analysis of the AMS data indicated that imatinib was rapidly absorbed and could be detected in plasma up to 72 h after administration. Imatinib was also detectable in PBL at 24 h after administration of the (14)C-labeled dose. Comparison of plasma concentrations determined by AMS with those derived by LCMS analysis gave similar average estimates of area under plasma concentration time curve (26 +/- 3 versus 27 +/- 11 microg/mL.h), but with some variation within each individual. Using this technique, data were obtained in a small number of patients on the pharmacokinetics of a single dose of imatinib in the context of chronic dosing, which could shed light on possible pharmacologic causes of resistance to imatinib in CML.


Survival analysis of heart failure patients: A case study.
This study was focused on survival analysis of heart failure patients who were admitted to Institute of Cardiology and Allied hospital Faisalabad-Pakistan during April-December (2015). All the patients were aged 40 years or above, having left ventricular systolic dysfunction, belonging to NYHA class III and IV. Cox regression was used to model mortality considering age, ejection fraction, serum creatinine, serum sodium, anemia, platelets, creatinine phosphokinase, blood pressure, gender, diabetes and smoking status as potentially contributing for mortality. Kaplan Meier plot was used to study the general pattern of survival which showed high intensity of mortality in the initial days and then a gradual increase up to the end of study. Martingale residuals were used to assess functional form of variables. Results were validated computing calibration slope and discrimination ability of model via bootstrapping. For graphical prediction of survival probability, a nomogram was constructed. Age, renal dysfunction, blood pressure, ejection fraction and anemia were found as significant risk factors for mortality among heart failure patients.


Effects of chemistry, manufacturing and concentration of the dye basic fuchsin regarding its use in quantitative cytophotometry.
Four separately manufactured preparations of basic fuchsin were compared to determine the effects of concentration, chemistry, and the manufacturing process for their quantitative value in the nuclear Feulgen reaction. In order to make the necessary comparisons, the two wavelength method of quantitative cytophotometry was employed to analyse each stain application regarding DNA measurements. Chicken erythrocytes, and myxamoebae and plasmodia of Didymium iridis were employed as experimental tissues. Results indicated that all four preparations of the stains yielded acceptable and valid quantitative data in relative DNA values. Differing manufacturers and dye concentrations had no appreciable effect on relative quantitative measurements. However, the maximum staining intensity was affected by differences both in the chemical structure of the individual stains and by the products from various manufacturers. The maximum dye intensity and accurate quantitative absolute values for DNA measurement were best obtained by the use of basic fuchsin having the same colour index (Cl) 42510 as that manufactured by Fisher Scientific Incorporated.


Community-acquired methicillin-resistant Staphylococcus aureus clones circulating in Belgium from 2005 to 2009: changing epidemiology.
The present study reports the evolution of the demographic characteristics and the molecular epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in Belgium from 2005 to 2009. Four hundred and ten CA-MRSA isolates were prospectively collected and screened for the presence of Panton-Valentin leucocidin (PVL) and toxic shock syndrome toxin 1 (TSST-1) encoding genes, while clinical information were recorded. PVL- and TSST-1-positive isolates were genotyped by pulsed-field gel electrophoresis (PFGE). Staphylococcal cassette chromosome mec (SCCmec) type, spa type and multilocus sequence type (MLST) were determined on representative isolates. One hundred and fifty-nine (39 %) isolates were PVL-positive. PVL-positive isolates were significantly more frequently isolated from skin or soft tissue than PVL-negative isolates, causing mainly subcutaneous abscesses and furuncles. Patients with PVL-positive CA-MRSA were significantly younger than patients with PVL-negative CA-MRSA. Eighty-seven percent of the PVL-positive isolates belonged to a limited number (n = 7) of PFGE types belonging to sequence types (ST) ST80, ST8, ST30, ST5, ST152, ST338 and a new ST, a single-locus variant of ST1. A temporal evolution of the distribution of these PFGE types was observed, characterised by (1) the dissemination of the ST8-SCCmecIV arcA-positive (USA300) genotype and (2) a genetic diversification. Forty-seven (11 %) strains were TSST-1-positive, of which 65 % clustered into four PFGE types, all belonging to ST5. The epidemiology of CA-MRSA in Belgium is changing, as the rapid diffusion of the USA300 clone seems to occur, together with a clonal diversification.


Molecular evolution and phylogeny of the atpB-rbcL spacer of chloroplast DNA in the true mosses.
The nucleotide variation of a noncoding region between the atpB and rbcL genes of the chloroplast genome was used to estimate the phylogeny of 11 species of true mosses (subclass Bryidae). The A+T rich (82.6%) spacer sequence is conserved with 48% of bases showing no variation between the ingroup and outgroup. Rooted at liverworts, Marchantia and Bazzania, the monophyly of true mosses was supported cladistically and statistically. A nonparametric Wilcoxon Signed-Ranks test Ts statistic for testing the taxonomic congruence showed no significant differences between gene trees and organism trees as well as between parsimony trees and neighbor-joining trees. The reconstructed phylogeny based on the atpB-rbcL spacer sequences indicated the validity of the division of acrocarpous and pleurocarpous mosses. The size of the chloroplast spacer in mosses fits into an evolutionary trend of increasing spacer length from liverworts through ferns to seed plants. According to the relative rate tests, the hypothesis of a molecular clock was supported in all species except for Thuidium, which evolved relatively fast. The evolutionary rate of the chloroplast DNA spacer in mosses was estimated to be (1.12 +/- 0.019) x 10(-10) nucleotides per site per year, which is close to the nonsynonymous substitution rates of the rbcL gene in the vascular plants. The constrained molecular evolution (total nucleotide substitutions, K approximately 0.0248) of the chloroplast DNA spacer is consistent with the slow evolution in morphological traits of mosses. Based on the calibrated evolutionary rate, the time of the divergence of true mosses was estimated to have been as early as 220 million years ago.


Down-regulation of acetolactate synthase compromises Ol-1- mediated resistance to powdery mildew in tomato.
In a cDNA-AFLP analysis comparing transcript levels between powdery mildew (Oidium neolycopersici)-susceptible tomato cultivar Moneymaker (MM) and near isogenic lines (NILs) carrying resistance gene Ol-1 or Ol-4, a transcript-derived fragment (TDF) M11E69-195 was found to be present in NIL-Ol-1 but absent in MM and NIL-Ol-4. This TDF shows homology to acetolactate synthase (ALS). ALS is a key enzyme in the biosynthesis of branched-chain amino acids valine, leucine and isoleucine, and it is also a target of commercial herbicides. Three ALS homologs ALS1, ALS2, ALS3 were identified in the tomato genome sequence. ALS1 and ALS2 show high similarity, whereas ALS3 is more divergent. Transient silencing of both ALS1 and ALS2 in NIL-Ol-1 by virus-induced gene silencing (VIGS) resulted in chlorotic leaf areas that showed increased susceptibility to O. neolycopersici (On). VIGS results were confirmed by stable transformation of NIL-Ol-1 using an RNAi construct targeting both ALS1 and ALS2. In contrast, silencing of the three ALS genes individually by RNAi constructs did not compromise the resistance of NIL-Ol-1. Application of the herbicide chlorsulfuron to NIL-Ol-1 mimicked the VIGS phenotype and caused loss of its resistance to On. Susceptible MM and On-resistant line NIL-Ol-4 carrying a nucleotide binding site and leucine rich repeat (NB-LRR) resistance gene were also treated with chlorsulfuron. Neither the susceptibility of MM nor the resistance of NIL-Ol-4 was affected. ALS is neither involved in basal defense, nor in resistance conferred by NB-LRR type resistance genes. Instead, it is specifically involved in Ol-1-mediated resistance to tomato powdery mildew, suggesting that ALS-induced change in amino acid homeostasis is important for resistance conferred by Ol-1.


ECG-gated 16-MDCT of the coronary arteries: assessment of image quality and accuracy in detecting stenoses.
The aim of this study was to investigate image quality and diagnostic accuracy in detecting coronary artery lesions using a 16-MDCT scanner. Thirty-seven patients (28 men, nine women) underwent unenhanced helical CT and MDCT angiography of the coronary arteries. After patients received oral beta-blocker medication, CT scans were obtained during a single breath-hold with a 16-MDCT scanner using ECG-gating (0.75-mm collimation, 2.8-mm table feed/rotation, 0.42-sec rotation time). The image quality was assessed in terms of artifacts and segment visibility by two reviewers. Stenosis severity was compared with the results of conventional invasive coronary angiography. The data evaluation of the image quality was based on a total of 488 segments, of which 380 segments were considered to have diagnostic image quality. One hundred eight segments (22.1%) could not be sufficiently evaluated because of severe calcifications (35 segments) and motion artifacts (73 segments). The mean calcium score (Agatston score equivalent [ASE]) was 524.3 +/- 807.6. Twenty-eight (75.7%) of the 37 patients had an ASE of less than 1,000 (mean ASE, 90.8 +/- 152.3 [SD]), and nine (24.3%) patients had an ASE of 1,000 or greater (mean ASE, 1,761.0 +/- 637.6). For detecting lesions 50% or greater (without any exclusion criteria), the overall sensitivity, specificity, positive predictive value, and negative predictive value were 59%, 87%, 61%, and 87%, respectively. When limiting the number of patients to those with a calcium score of less than 1,000 ASE, the threshold-corrected sensitivity for lesions 50% or greater was 93%; specificity, 94%; positive predictive value, 68%; and negative predictive value, 99%. In patients with no or moderate coronary calcification, MDCT of coronary arteries using 16-MDCT technology allows the reliable detection of coronary artery stenoses with high diagnostic accuracy. Obtaining an initial unenhanced scan was found to be mandatory to avoid performing useless examinations in patients with severe calcifications.


Bacteriotherapy using fecal flora: toying with human motions.
The intestinal flora may play a key role in the pathogenesis of certain gastrointestinal (GI) diseases. Components of bowel flora such as Lactobacillus acidophilus and Bifidobacterium bifidus have long been used empirically as therapeutic agents for GI disorders. More complex combinations of probiotics for therapeutic bacteriotherapy have also recently become available, however the most elaborate mix of human-derived probiotic bacteria is, by definition, the entire fecal flora. Fecal bacteriotherapy uses the complete normal human flora as a therapeutic probiotic mixture of living organisms. This type of bacteriotherapy has a longstanding history in animal health and has been used sporadically against chronic infections of the bowel, especially as a treatment of last resort for patients with severe Clostridium difficile syndromes including recurrent diarrhea, colitis, and pseudomembranous colitis. Encouraging results have also been observed following infusions of human fecal flora in patients with inflammatory bowel disease, irritable bowel syndrome, and chronic constipation. The therapeutic use of fecal bacteriotherapy is reviewed here and possible mechanisms of action and potential applications explored. Published reports on fecal bacteriotherapy are few in number, and detail the results of small uncontrolled open studies and case reports. Nevertheless, given the promising clinical responses, formal research into fecal bacteriotherapy is now warranted.


Visible-light-driven hydrogen evolution using a polyoxometalate-based copper molecular catalyst.
Polyoxometalate-based copper clusters as promising hydrogen evolution catalysts are rarely reported. Here, [Cu5(OH)4(H2O)2(A-α-SiW9O33)2]10- (1) was tested as an effective molecular catalyst for visible-light-driven H2 evolution. A high turnover number (TON) of 718.9 was achieved in the photocatalytic reaction. Many stability experiments showed that compound 1 could maintain its structure intact during the photocatalytic process.


Quantitative assessment of lactate and progerin production in normal human cutaneous cells during normal ageing: effect of an Alaria esculenta extract.
Anti-ageing products are of a great importance in cosmetic fields. However, even if numerous strategies have been proposed to fight against skin ageing or to minimize its aesthetic impact since the beginning of the 'scientific cosmetology' era, the products basing their efficacy on the observation of pathological situations are rare. The most obvious pathology linked to the ageing of skin (notably) consists in the Hutchinson-Gilford Progeria Syndrome (HGPS), a rare disorder characterized by accelerated ageing and early death. In this disease the lamin A, a protein participating (with others lamins) in the formation of the nuclear lamina and implicated in nuclear stability, chromatin structure and gene expression, is present in a truncated version called progerin. In this study, we have examined the lactate and the progerin production of human normal cutaneous cells issued from subjects of different ages. Using a sensitive and specific progerin ELISA assay developed in house, we so provide the first quantitative demonstration of an increased progerin expression and lactate production in skin during ageing. Moreover, we have also demonstrated that in the selected experimental conditions, it was possible to down-regulate the progerin production of aged cells by using an algae extract. As this extract, an Alaria esculenta extract, could be used in cosmetic formulations, we suggest that a better understanding of the skin pathologies could be a useful tool in developing efficient active compounds, attractive for but not limited to cosmetic purposes.


Autophagy inhibition improves the chemotherapeutic efficacy of cruciferous vegetable-derived diindolymethane in a murine prostate cancer xenograft model.
Prostate cancer is the second leading cause of cancer-related deaths in men in North America and there is an urgent need for development of more effective therapeutic treatments against this disease. We have recently shown that diindolylmethane (DIM) and several of its halogenated derivatives (ring-DIMs) induce death and protective autophagy in human prostate cancer cells. However, the in vivo efficacy of ring-DIMs and the use of autophagy inhibitors as adjuvant therapy have not yet been studied in vivo. The objective of this study was to determine these effects on tumor growth in nude CD-1 mice bearing bioluminescent androgen-independent PC-3 human prostate cancer cells. We found that chloroquine (CQ) significantly sensitized PC-3 cells to death in the presence of sub-toxic concentrations of DIM or 4,4'-Br2DIM in vitro. Moreover, a combination of DIM (10 mg/kg) and CQ (60 mg/kg), 3× per week, significantly decreased PC-3 tumor growth in vivo after 3 and 4 weeks of treatment. Furthermore, 4,4'-Br2DIM at 10 mg/kg (3× per week) significantly inhibited tumour growth after 4 weeks of treatment. Tissues microarray analysis showed that DIM alone or combined with CQ induced apoptosis marker TUNEL; the combination also significantly inhibited the cell proliferation marker Ki67. In conclusion, we have confirmed that DIM and 4,4'-Br2DIM are effective agents against prostate cancer in vivo and shown that inhibition of autophagy with CQ enhances the anticancer efficacy of DIM. Our results suggest that including selective autophagy inhibitors as adjuvants may improve the efficacy of existing and novel drug therapies against prostate cancer.


Survival of people on antiretroviral treatment in Zambia: a retrospective cohort analysis of HIV clients on ART.
Provision of free anti-retroviral therapy in Zambia started in June 2004. There were only 15,000 people on treatment as at December that year, mainly due to lack of access. This number rose to 580,000 people as at December 2013. The general objective of this study was to determine survival of people on ART and to examine associated predictors for survival. The study included ART patients enrolled between the year 2002 and 2013 (n=10,395) in 285 health facilities in Zambia. Patient files were analyzed retrospectively. The study used Kaplan Meier and Cox-proportional hazard models to describe the relationship between lost to follow up and age, sex, baseline CD4 cell count and weight. Results showed that lost to follow up accounted for 90% of the clients that had dropped out, while 10% was to deaths. Low baseline CD4 count (p-value 0.001, HR 0.9994, (95% CI 0.9993, 0.9996) at initiation was associated with lost to follow up together with weight at initiation (p-value 0.031, HR 0.9987 at 95% CI (0.9975, 0.9998)) of ART. This study has demonstrated that lost to follow up is a substantial contributing factor to drop outs among HIV patients on treatment. Strengthening of community treatment supporters especially immediate family members in emphasizing to the client the need to continue treatment is necessary. The health facility could do more in emphasizing the importance of treatment especially in the initial stages. Further, in order to reduce opportunistic infections and probable deaths during treatment, cotrimoxazole prophylaxis should be maintained so as to raise the CD4 levels. Improved nutritional assessment and counseling to boost the nutritional status of the clients throughout should be encouraged.


Specific inhibition of tissue kallikrein 1 with a human monoclonal antibody reveals a potential role in airway diseases.
KLK1 (tissue kallikrein 1) is a member of the tissue kallikrein family of serine proteases and is the primary kinin-generating enzyme in human airways. DX-2300 is a fully human antibody that inhibits KLK1 via a competitive inhibition mechanism (Ki=0.13 nM). No binding of DX-2300 to KLK1 was observed in a surface-plasmon-resonance biosensor assay when KLK1 was complexed to known active-site inhibitors, suggesting that DX-2300 recognizes the KLK1 active site. DX-2300 did not inhibit any of the 21 serine proteases that were each tested at a concentration of 1 microM. We validated the use of DX-2300 for specific KLK1 inhibition by measuring the inhibition of KLK1-like activity in human urine, saliva and bronchoalveolar lavage fluid, which are known to contain active KLK1. In human tracheobronchial epithelial cells grown at the air/liquid interface, DX-2300 blocked oxidative-stress-induced epidermal-growth-factor receptor activation and downstream mucus cell proliferation and hypersecretion, which have been previously shown to be mediated by KLK1. In an allergic sheep model of asthma, DX-2300 inhibited both allergen-induced late-phase bronchoconstriction and airway hyper-responsiveness to carbachol. These studies demonstrate that DX-2300 is a potent and specific inhibitor of KLK1 that is efficacious in in vitro and in vivo models of airway disease.


Residues of corticotropin releasing factor-binding protein (CRF-BP) that selectively abrogate binding to CRF but not to urocortin 1.
Corticotropin releasing factor-binding protein (CRF-BP) binds CRF and urocortin 1 (Ucn 1) with high affinity, thus preventing CRF receptor (CRFR) activation. Despite recent progress on the molecular details that govern interactions between CRF family neuropeptides and their cognate receptors, little is known concerning the mechanisms that allow CRF-BP to bind CRF and Ucn 1 with picomolar affinity. We conducted a comprehensive alanine scan of 76 evolutionarily conserved residues of CRF-BP and identified several residues that differentially affected the affinity for CRF over Ucn 1. We determined that both neuropeptides derive their similarly high affinity from distinct binding surfaces on CRF-BP. Alanine substitutions of arginine 56 (R56A) and aspartic acid 62 (D62A) reduce the affinity for CRF by approximately 100-fold, while only marginally affecting the affinity for Ucn 1. The selective reduction in affinity for CRF depends on glutamic acid 25 in the CRF peptide, as substitution of Glu(25) reduces the affinity for CRF-BP by approximately 2 orders of magnitude, but only in the presence of both Arg(56) and Asp(62) in human CRF-BP. We show that CRF-BP(R56A) and CRF-BP(D62A) have lost the ability to inhibit CRFR1-mediated responses to CRF that activate luciferase induction in HEK293T cells and ACTH release from cultured rat anterior pituitary cells. In contrast, both CRF-BP mutants retain the ability to inhibit Ucn 1-induced CRFR1 activation. Collectively our findings demonstrate that CRF-BP has distinct and separable binding surfaces for CRF and Ucn 1, opening new avenues for the design of ligand-specific antagonists based on CRF-BP.


Synthesis, crystal and electronic structures of Pt-rich phosphides EuPt3P and EuPt6P2.
Two new ternary Pt-rich phosphides, EuPt6P2 and EuPt3P, have been prepared via a two-step solid state reaction. Their crystal structures have been determined from powder XRD data. EuPt6P2 is isostructural to SrPt6P2 (cubic, Pa3[combining macron], a = 8.4603(1) Å); its crystal structure comprises corner-sharing Pt6P trigonal prisms hosting Eu2+ cations in the cuboctahedral voids of the framework. EuPt3P is isostructural to the SrPt3P anti-perovskite (P4/nmm, a = 5.7452(1) Å and c = 5.4212(1) Å). Magnetization measurements reveal the magnetic response caused by the Eu2+(4f7) cations. EuPt6P2 is paramagnetic exhibiting no phase transitions down to 1.8 K, whereas EuPt3P orders ferromagnetically below 19 K. Similar to SrPt6P2 and SrPt3P, the new compounds are metallic with states near the Fermi level predominantly formed by the 5d orbitals of Pt.


Convolution-based interpolation for fast, high-quality rotation of images.
This paper focuses on the design of fast algorithms for rotating images and preserving high quality. The basis for the approach is a decomposition of a rotation into a sequence of one-dimensional translations. As the accuracy of these operations is critical, we introduce a general theoretical framework that addresses their design and performance. We also investigate the issue of optimality and present an improved least-square formulation of the problem. This approach leads to a separable three-pass implementation of a rotation using one-dimensional convolutions only. We provide explicit filter formulas for several continuous signal models including spline and bandlimited representations. Finally, we present rotation experiments and compare the currently standard techniques with the various versions of our algorithm. Our results indicate that the present algorithm in its higher-order versions outperforms all standard high-accuracy methods of which we are aware, both in terms of speed and quality. Its computational complexity increases linearly with the order of accuracy. The best-quality results are obtained with the sine-based algorithm, which can be implemented using simple one-dimensional FFTs.


Grafton and local bone have comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions.
Prospective multicenter randomized clinical trail. The goal of our 2-year prospective study was to perform a randomized clinical trial comparing the outcomes of Grafton demineralized bone matrix (DBM) Matrix with local bone with that of iliac crest bone graft (ICBG) in a single-level instrumented posterior lumbar fusion. There has been extensive research and development in identifying a suitable substitute to replace autologous ICBG that is associated with known morbidities. DBMs are a class of commercially available grafting agents that are prepared from allograft bone. Many such products have been commercially available for clinical use; however, their efficacy for spine fusion has been mostly based on anecdotal evidence rather than randomized controlled clinical trials. Forty-six patients were randomly assigned (2:1) to receive Grafton DBM Matrix with local bone (30 patients) or autologous ICBG (16 patients). The mean age was 64 (females [F] = 21, males [M] = 9) in the DBM group and 65 (F = 9, M = 5) in the ICBG group. An independent radiologist evaluated plain radiographs and computed tomographic scans at 6-month, 1-year, and 2-year time points. Clinical outcomes were measured using Oswestry Disability Index (ODI) and Medical Outcomes Study 36-Item Short Form Health Survey. Forty-one patients (DBM = 28 and ICBG = 13) completed the 2-year follow-up. Final fusion rates were 86% (Grafton Matrix) versus 92% (ICBG) (P = 1.0 not significant). The Grafton group showed slightly better improvement in ODI score than the ICBG group at the final 2-year follow-up (Grafton [16.2] and ICBG [22.7]); however, the difference was not statistically significant (P = 0.2346 at 24 mo). Grafton showed consistently higher physical function scores at 24 months; however, differences were not statistically significant (P = 0.0823). Similar improvements in the physical component summary scores were seen in both the Grafton and ICBG groups. There was a statistically significant greater mean intraoperative blood loss in the ICBG group than in the Grafton group (P < 0.0031). At 2-year follow-up, subjects who were randomized to Grafton Matrix and local bone achieved an 86% overall fusion rate and improvements in clinical outcomes that were comparable with those in the ICBG group.


Three-Dimensional Triptycene-Based Covalent Organic Frameworks with ceq or acs Topology.
The growth of three-dimensional covalent organic frameworks (3D COFs) with new topologies is still considered as a great challenge due to limited availability of high-connectivity building units. Here we report the design and synthesis of 3D triptycene-based COFs, termed JUC-568 and JUC-569, following the deliberate symmetry-guided design principle. By combining a triangular prism (6-connected) node with a planar triangle (3-connected) or another triangular prism node, the targeted COFs adopt non-interpenetrated ceq or acs topology, respectively. Both materials show permanent porosity and impressive performance in the adsorption of CO2 (∼98 cm3/g at 273 K and 1 bar), CH4 (∼48 cm3/g at 273 K and 1 bar), and especially H2 (up to 274 cm3/g or 2.45 wt % at 77 K and 1 bar), which is highest among porous organic materials reported to date. This research thus provides a promising strategy for diversifying 3D COFs based on complex building blocks and promotes their potential applications in energy storage and environment-related fields.


Genetic manipulation of anaerobic cellulolytic bacteria.
Transposon Tn1545 was introduced into the chromosome of the ruminal cellulolytic bacterium Eubacterium cellulosolvens. This was achieved by conjugal transfer of the transposon from Clostridium beijerinckii at a frequency of about 1 per 10(4) recipient cells. Transconjugants of E. cellulosolvens were resistant to both tetracycline and erythromycin. E. cellulosolvens could also serve as a donor for conjugal transfer of Tn1545 back into C. beijerinckii.


Plasma interleukin responses as predictors of outcome stratification in patients after major trauma: a prospective observational two centre study.
There is a need to develop objective risk stratification tools to define efficient care pathways for trauma patients. Biomarker-based point of care testing may strengthen existing clinical tools currently available for this purpose. The dysregulation of pro- and anti-inflammatory cytokines in the pathogenesis of organ failure is well recognised. This study was carried out to evaluate whether blood concentrations of IL-6, IL-10, and IL-6:IL-10 ratios in the early stages of the illness are significantly different in patients with worsening organ function. In this prospective observational cohort study, plasma concentrations of IL-6 and IL-10 on days 1, 3 and 5 were measured in 91 major trauma patients using a multiplexed cytometric bead array approach. A composite measure of adverse outcome - defined as SOFA ≥ 2 or mortality at 7 days, was the primary outcome. IL-6 and IL-10 concentrations in early samples (days 1, 3 & 5) in patients who developed SOFA ≥ 2 on day 7 were compared against those who did not. Similar composite outcome groups at day 5 and in groups with worsening or improving SOFA scores (ΔSOFA) at days 7 and 5 were undertaken as secondary analyses. Stratification on day 7, 44 (48%) patients showed adverse outcomes. These adverse outcomes associated with significantly greater IL-6 concentrations on days 1 and 5 (Day 1: 47.65 [23.24-78.68] Vs 73.69 [39.93 - 118.07] pg/mL, P = 0.040 and Day 5: 12.85 [5.80-19.51] Vs 28.90 [8.78-74.08] pg/mL; P = 0.0019). Similarly, IL-10 levels were significantly greater in the adverse outcome group on days 3 and 5 (Day 3: 2.54 [1.76-3.19] Vs 3.16 [2.68-4.21] pg/mL; P = 0.044 and Day 5: 2.03 [1.65-2.55] Vs 2.90 [2.00-5.06] pg/mL; P <0.001). IL-6 and IL-10 concentrations were also significantly elevated in the adverse outcome groups at day 3 and day 5 when stratified on day 5 outcomes. Both IL-6 and IL-6:IL-10 were found to be significantly elevated on days 1 and 3 when stratified based on ΔSOFA at day 5. This significance was lost when stratified on day 7 scores. Early IL-6 and IL-10 concentrations are significantly greater in patients who develop worsening organ functions downstream. These differences may provide an alternate biomarker-based approach to strengthen risk stratification in trauma patients.


Adjuvant Vaginal Use of Sildenafil Citrate in a Hormone Replacement Cycle Improved Live Birth Rates Among 10,069 Women During First Frozen Embryo Transfers.
To investigate the effects of sildenafil citrate (SC) on live birth rates (LBR) during women undergoing their first frozen embryo transfers (FET) with hormone replacement therapy (HRT). This retrospective cohort study included a total of 10,069 infertile women with adequate endometrial thickness (≥7 mm when progesterone was initiated) in their first FET cycle with hormone replacement therapy. Women received either vaginal SC or no adjuvant during their first transfer cycle depending on patient or physician preference. In the sildenafil group, 1098 women underwent HRT FET with adjuvant vaginal use of SC, and 8971 women were included as controls. The primary outcome measure was LBR, defined as the likelihood of live birth per transfer cycle. Endometrial thickness (EMT), implantation, chemical pregnancy, clinical pregnancy, miscarriage, ongoing pregnancy, birth weight and preterm delivery (PTB) were also recorded. Baseline characteristics were comparable between the two groups. In the crude analysis, the unadjusted LBR was significantly higher in the vaginal SC group (scHRT-FET) than in the control group (HRT-FET) (40.3% vs 36.1%). After adjustment for 12 pregnancy-related confounding factors, logistic regression analysis showed that LBR remained significantly higher in the scHRT-FET group than in the HRT-FET group (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.14-1.49). Furthermore, after adjustment, the ongoing pregnancy rate was significantly higher (aOR 1.29, 95% CI 1.13-1.47), and the miscarriage rate was significantly lower (aOR 0.58, 95% CI 0.43-0.77), in the scHRT-FET group compared to the HRT-FET group. Adjuvant vaginal use of SC did not increase the endometrial thickness and had no significant effect on birth weight or PTB. Adjuvant vaginal use of SC in HRT FET was associated with higher LBR and improved pregnancy outcomes in an infertile population with adequate endometrial thickness. The beneficial effect of SC may be due not to an increase in EMT but instead to improve endometrial blood flow and receptivity, which might merit clinicians' attention for improving general IVF practices.


Comparison of antiestrogen and progestogen therapy for initial treatment and consequences of their combination for second-line treatment of recurrent breast cancer.
A randomized clinical trial involving postmenopausal patients with estrogen receptor positive recurrent breast cancer is reported. Of 168 patients entered, 156 were evaluable, of whom 79 received oral tamoxifen citrate 10 mg twice daily and 77 oral megestrol acetate 40 mg four times a day. Partial response (PR) plus complete response (CR) rates (both arms, 34%) and time-to-disease progression were similar in both arms. Side effects and toxicity were minimal with both regimens, although more patients who received tamoxifen complained of hot flushes (33% v 11%) and more patients who received megestrol acetate had a 10% or greater weight gain at 6 months from baseline (51% v 19%). On progression of disease, 73 patients who had achieved a CR, PR, or stable response received the alternative hormonal treatment in addition to the original hormonal therapy. Ten of 40 patients (25%) who began treatment with megestrol acetate had a further CR or PR; none of 33 patients originally receiving tamoxifen had a response when megestrol acetate was added. Similarly, patients who received tamoxifen as an addition to their original megestrol acetate treatment also had a significantly longer time to second progression than did those in the comparative arm. It was concluded that as initial hormonal therapy for relapsed patients, either tamoxifen or megestrol acetate can be used with confidence. However, it is suggested that tamoxifen and megestrol acetate should not be used in combination, except for those few occasions when tamoxifen is added as second-line therapy following a completed megestrol acetate response, and the megestrol acetate is continued for its palliative effects on appetite and weight gain. Possible mechanisms behind these results are discussed.


Neurodegeneration in newborn rats following propofol and sevoflurane anesthesia.
Propofol and sevoflurane are commonly used drugs in pediatric anesthesia. Exposure of newborn rats to a variety of anesthetics has been shown to induce apoptotic neurodegeneration in the developing brain. Newborn Wistar rats were treated with repeated intraperitoneal injections of propofol or sevoflurane inhalation and compared to controls. Brains were examined histopathologically using the De Olmos cupric silver staining. Additionally, a summation score of the density of apoptotic cells was calculated for every brain. Spatial memory learning was assessed by the Morris Water Maze (MWM) test and the hole board test, performed in 7 weeks old animals who underwent the same anesthetic procedure. Brains of propofol-treated animals showed a significant higher neurodegenerative summation score (24,345) when compared to controls (15,872) and to sevoflurane-treated animals (18,870). Treated animals also demonstrated persistent learning deficits in the hole board test, whereas the MWM test revealed no differences between both groups. Among other substances acting via GABAA agonism and/or NMDA antagonism propofol induced neurodegeneration in newborn rat brains whereas a sevoflurane based anesthesia did not. The significance of these results for clinical anesthesia has not been completely elucidated. Future studies have to focus on the detection of safe anesthetic strategies for the developing brain.


Topology recapitulates morphogenesis of neuronal dendrites.
Branching allows neurons to make synaptic contacts with large numbers of other neurons, facilitating the high connectivity of nervous systems. Neuronal arbors have geometric properties such as branch lengths and diameters that are optimal in that they maximize signaling speeds while minimizing construction costs. In this work, we asked whether neuronal arbors have topological properties that may also optimize their growth or function. We discovered that for a wide range of invertebrate and vertebrate neurons the distributions of their subtree sizes follow power laws, implying that they are scale invariant. The power-law exponent distinguishes different neuronal cell types. Postsynaptic spines and branchlets perturb scale invariance. Through simulations, we show that the subtree-size distribution depends on the symmetry of the branching rules governing arbor growth and that optimal morphologies are scale invariant. Thus, the subtree-size distribution is a topological property that recapitulates the functional morphology of dendrites.


Risk factors for breakthrough infection in children with primary vesicoureteral reflux.
Despite the widespread application of endoscopic therapy and the debate surrounding the use of prophylactic antibiotics to treat children with vesicoureteral reflux, many pediatric urologists still favor medical management. Breakthrough infection is one of the absolute indications for surgery. Data to predict breakthrough infection are warranted to manage cases of primary reflux. We reviewed medical records of 72 girls and 138 boys (mean +/- SD age at diagnosis 2.66 +/- 3.23 years) with primary vesicoureteral reflux who were followed with antibiotic prophylaxis at Aichi Children's Health and Medical Center. We examined multiple factors by univariate/multivariate analysis to elucidate risk factors for breakthrough infection. Breakthrough infection developed in 59 children (28%). On univariate analysis higher reflux grade (p <0.05) and abnormal renal scan determined by (99m)technetium dimercapto-succinic acid (p <0.0001) were significantly associated with breakthrough infection. On multivariate analysis abnormal renal scan was an independent risk factor for breakthrough infection (OR 11.08, 95% CI 0.76-1.72, p <0.0001). Abnormal renal scan is an independent risk factor for breakthrough infection. Parents and physicians should remain aware that these patients are at high risk for breakthrough infection, which potentially could lead to renal damage.


Genetic variation at the growth hormone (GH1) and growth hormone receptor (GHR) loci as a risk factor for hypertension and stroke.
An increased prevalence of both hypertension and cerebrovascular stroke is apparent in growth hormone (GH) deficiency whilst hypertension is a frequent complication in acromegaly. This has suggested a possible link between GH, stature and arterial function. Since the risk of both hypertension and stroke also appears to be inversely correlated with adult height, we have instigated an exploratory study to assess whether inter-individual variation in the genes encoding human growth hormone (GH1) and the GH receptor (GHR) might be associated with an increased risk of hypertension and stroke. GH1 promoter haplotypes were found to differ significantly not only between hypertensive patients (n = 111) and controls (n = 121) but also between stroke patients (n = 155) and controls (n = 158). Intriguingly, the association between GH1 promoter haplotype and risk of hypertension was much greater in females than in males. An inverse correlation between height and central systolic blood pressure was apparent in both hypertensive patients and normal controls but was much stronger in individuals carrying at least one GH1 promoter risk haplotype. The GH1 genotype therefore constitutes a risk factor for hypertension that interacts with stature. A strong association was found between the presence of at least one GH1 risk haplotype and a family history of stroke at an early age (odds ratio: 9.07, 95% confidence interval: 1.14-72.22). Three novel GH variants (Arg16His, Phe176Cys, Cys189Arg) were identified during the course of this study. Although two exhibited markedly reduced biological activity in vitro, their clinical significance remains unclear. No association was found between GHR genotype and either hypertension or stroke, nor was any interaction noted between GHR and GH1 genotypes in terms of a disease association. However, an association between GHRd3 genotype and hypertension was observed among stroke patients, particularly females. Elevated HDL was found to be a risk factor for hypertension in individuals lacking a copy of the GHRd3 allele. Weak associations with GHR genotype were also noted for peripheral systolic and diastolic blood pressure in hypertensive patients. Although the underlying mechanisms are still unclear, our findings are consistent with a complex relationship between height, hypertension, GH1 promoter haplotype, GHR polymorphism and the risk of stroke.


[Association between the need for optical correction prescription and other ocular conditions in school children].
To verify the relation between prescription of eyeglasses and presence of ocular infections found in the " Eye to Eye Campaign" carried out in the city of Recife in 2004. School-aged children seen in the " Eye to Eye Campaign" in Recife, in 2004. Stages recommended by the Brazilian Ophthalmologic Council (CBO) were followed, from preparation of teachers to select children to appointment with ophthalmologists. The patients were divided into two groups according to the need of eyeglasses, and related to presence or not of ocular conditions. This is a cross-section study and the results were analyzed by the statistical software Epi Info version 6.0. In a group of 1994 school-aged patients, 686 needed eyeglasses (34.4% - Group 1), 543 (27.2%) did not had any ocular diseases, while 143 (7.17%) had some ocular condition. A total of 1308 children (65.5% - Group 2) did not require eyeglasses. Among those, 256 (62.5%) did not show any ophthalmologic condition, whereas 52 (2.6%) had some type of ocular diseases. Groups 1 and 2 were compared and children in need of eyeglasses had a 5.24-fold (95% confidence interval: 3.87 to 7.10) greater relative risk of developing ocular diseases than children who did not require correction, and the difference was statistically significant (p=0.0000001). We conclude that school-aged children in need of eyeglasses are more likely to suffer ocular diseases, and a complete ophthalmologic examination should be performed in childhood by qualified ophthalmologists to detect and treat several disorders and also prescribe adequate correction.


Activation of TRPM3 by a potent synthetic ligand reveals a role in peptide release.
Transient receptor potential (TRP) cation channel subfamily M member 3 (TRPM3), a member of the TRP channel superfamily, was recently identified as a nociceptor channel in the somatosensory system, where it is involved in the detection of noxious heat; however, owing to the lack of potent and selective agonists, little is known about other potential physiological consequences of the opening of TRPM3. Here we identify and characterize a synthetic TRPM3 activator, CIM0216, whose potency and apparent affinity greatly exceeds that of the canonical TRPM3 agonist, pregnenolone sulfate (PS). In particular, a single application of CIM0216 causes opening of both the central calcium-conducting pore and the alternative cation permeation pathway in a membrane-delimited manner. CIM0216 evoked robust calcium influx in TRPM3-expressing somatosensory neurons, and intradermal injection of the compound induced a TRPM3-dependent nocifensive behavior. Moreover, CIM0216 elicited the release of the peptides calcitonin gene-related peptide (CGRP) from sensory nerve terminals and insulin from isolated pancreatic islets in a TRPM3-dependent manner. These experiments identify CIM0216 as a powerful tool for use in investigating the physiological roles of TRPM3, and indicate that TRPM3 activation in sensory nerve endings can contribute to neurogenic inflammation.


Leveraging pleiotropy to discover and interpret GWAS results for sleep-associated traits.
Genetic association studies of many heritable traits resulting from physiological testing often have modest sample sizes due to the cost and burden of the required phenotyping. This reduces statistical power and limits discovery of multiple genetic associations. We present a strategy to leverage pleiotropy between traits to both discover new loci and to provide mechanistic hypotheses of the underlying pathophysiology. Specifically, we combine a colocalization test with a locus-level test of pleiotropy. In simulations, we show that this approach is highly selective for identifying true pleiotropy driven by the same causative variant, thereby improves the chance to replicate the associations in underpowered validation cohorts and leads to higher interpretability. Here, as an exemplar, we use Obstructive Sleep Apnea (OSA), a common disorder diagnosed using overnight multi-channel physiological testing. We leverage pleiotropy with relevant cellular and cardio-metabolic phenotypes and gene expression traits to map new risk loci in an underpowered OSA GWAS. We identify several pleiotropic loci harboring suggestive associations to OSA and genome-wide significant associations to other traits, and show that their OSA association replicates in independent cohorts of diverse ancestries. By investigating pleiotropic loci, our strategy allows proposing new hypotheses about OSA pathobiology across many physiological layers. For example, we identify and replicate the pleiotropy across the plateletcrit, OSA and an eQTL of DNA primase subunit 1 (PRIM1) in immune cells. We find suggestive links between OSA, a measure of lung function (FEV1/FVC), and an eQTL of matrix metallopeptidase 15 (MMP15) in lung tissue. We also link a previously known genome-wide significant peak for OSA in the hexokinase 1 (HK1) locus to hematocrit and other red blood cell related traits. Thus, the analysis of pleiotropic associations has the potential to assemble diverse phenotypes into a chain of mechanistic hypotheses that provide insight into the pathogenesis of complex human diseases.


Optimizing cell seeding and retention in a three-dimensional bioengineered cardiac ventricle: The two-stage cellularization model.
Current cell seeding techniques focus on passively directing cells to a scaffold surface with the addition of dynamic culture to encourage cell permeation. In 3D tissue engineered constructs, cell retention efficiency is dependent on the cell delivery method, and biomaterial properties. Passive cell delivery relies on cell migration to the scaffold surface; biomaterial surface properties and porosity determine cell infiltration capacity. As a result, cell retention efficiencies remain low. The development of an effective two-stage cell seeding technique, coupled with perfusion culture, provides the potential to improve cellularization efficiency, and retention. This study, uses a chitosan bioengineered open ventricle (BEOV) scaffold to produce a two-stage perfusion cultured ventricle (TPCV). TPCV were fabricated by direct injection of 10 million primary rat neonatal cardiac cells, followed by wrapping of the outer scaffold surface with a 3D fibrin gel artificial heart muscle patch; TPCV were perfusion cultured for 3 days. The average biopotential output was 1.731 mV. TPCV cell retention following culture was approximately 5%. Cardiac cells were deposited on the scaffold surface and formed intercellular connections. Histological assessment displayed localized cell clusters, with some dissemination, and validated the observed presence of intercellular and gap-junction interactions. The study demonstrates initial effectiveness of our two-stage cell delivery concept, based on function and biological metrics. Biotechnol. Bioeng. 2016;113: 2275-2285. © 2016 Wiley Periodicals, Inc.


Methylcyclopentanoid monoterpenes mediate interactions among insect herbivores.
Beetles secrete an array of chemicals generally believed to mitigate attack by predators. Methylcyclopentanoid monoterpenes secreted by larvae of the willow leaf beetle, Plagiodera versicolora, deter feeding by conspecific adults. Furthermore, the secretion elicits a strong repugnancy response in larvae of another willow herbivore, Nymphalis antiopa. Leaves bearing beetle larvae are less likely than leaves not bearing beetles to be frequented and consumed by Nymphalis larvae. Predator defense may not be the sole function of glandular secretions produced by herbivorous insects; secretions may also mediate interactions among herbivores that use a common resource.


Guidance on validation of lethal control measures for foodborne pathogens in foods.
Food manufacturers are required to obtain scientific and technical evidence that a control measure or combination of control measures is capable of reducing a significant hazard to an acceptable level that does not pose a public health risk under normal conditions of distribution and storage. A validation study provides evidence that a control measure is capable of controlling the identified hazard under a worst-case scenario for process and product parameters tested. It also defines the critical parameters that must be controlled, monitored, and verified during processing. This review document is intended as guidance for the food industry to support appropriate validation studies, and aims to limit methodological discrepancies in validation studies that can occur among food safety professionals, consultants, and third-party laboratories. The document describes product and process factors that are essential when designing a validation study, and gives selection criteria for identifying an appropriate target pathogen or surrogate organism for a food product and process validation. Guidance is provided for approaches to evaluate available microbiological data for the target pathogen or surrogate organism in the product type of interest that can serve as part of the weight of evidence to support a validation study. The document intends to help food manufacturers, processors, and food safety professionals to better understand, plan, and perform validation studies by offering an overview of the choices and key technical elements of a validation plan, the necessary preparations including assembling the validation team and establishing prerequisite programs, and the elements of a validation report.


[Leg heaviness and stasis microangiopathy. Preventive and therapeutic approaches].
Venous insufficiency of the legs is a frequent and insidious disorder which, through its consequences' cascade, lead to some cutaneous microangiopathy with relative ischemia. Chronic leg ulcer is the late issue of the process accompanied by varied medical and socio-economic aspects. The pathogeny of the cutaneous lesions is directly related to alterations in hemorrheology and leukocyte adhesion inside capillaries. Elastic contention and some venotropic drugs exert preventive effects on the development of leg ulcers. They also bring some therapeutic improvement of the symptoms of leg heaviness.


Structural signatures of enzyme binding pockets from order-independent surface alignment: a study of metalloendopeptidase and NAD binding proteins.
Detecting similarities between local binding surfaces can facilitate identification of enzyme binding sites and prediction of enzyme functions, and aid in our understanding of enzyme mechanisms. Constructing a template of local surface characteristics for a specific enzyme function or binding activity is a challenging task, as the size and shape of the binding surfaces of a biochemical function often vary. Here we introduce the concept of signature binding pockets, which captures information on preserved and varied atomic positions at multiresolution levels. For proteins with complex enzyme binding and activity, multiple signatures arise naturally in our model, forming a signature basis set that characterizes this class of proteins. Both signatures and signature basis sets can be automatically constructed by a method called SOLAR (Signature Of Local Active Regions). This method is based on a sequence-order-independent alignment of computed binding surface pockets. SOLAR also provides a structure-based multiple sequence fragment alignment to facilitate the interpretation of computed signatures. By studying a family of evolutionarily related proteins, we show that for metzincin metalloendopeptidase, which has a broad spectrum of substrate binding, signature and basis set pockets can be used to discriminate metzincins from other enzymes, to predict the subclass of metzincins functions, and to identify specific binding surfaces. Studying unrelated proteins that have evolved to bind to the same NAD cofactor, we constructed signatures of NAD binding pockets and used them to predict NAD binding proteins and to locate NAD binding pockets. By measuring preservation ratio and location variation, our method can identify residues and atoms that are important for binding affinity and specificity. In both cases, we show that signatures and signature basis set reveal significant biological insight.


Generation of two-temporal-mode photon states by vector four-wave mixing.
Photon pair states and multiple-photon squeezed states have many applications in quantum information science. In this paper, Green functions are derived for spontaneous four-wave mixing in the low- and high-gain regimes. Nondegenerate four-wave mixing in a strongly-birefringent medium generates signal and idler photons that are associated with only one pair of temporal (Schmidt) modes, for a wide range of pump powers and arbitrary pump shapes. The Schmidt coefficients (expected photon numbers) depend sensitively on the pump powers, and the Schmidt functions (shapes of the photon wavepackets) depend sensitively on the pump powers and shapes, which can be controlled.


Protective immunity against HSV-2 in the mouse vagina.
Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that infects the genital tract. The high prevalence of HSV-2 in humans underscores the need to develop an effective vaccine. Efforts to develop vaccines to protect women against this and other sexually transmitted pathogens would be facilitated by a better understanding of the immune mechanisms that protect the female reproductive tract against infections in animal models. Such information would be invaluable in developing vaccine strategies to promote the type and magnitude of immune responses in the genital tract that would effectively protect against infection. This review focuses on recent studies using a progestin-treated adult mouse model to explore mucosal immunity to HSV-2 in the vagina. Evidence indicating a major role for both humoral and T cell immunity is presented.


An Updated Comparative Study on the Impact of COVID-19 Infection and Vaccination in Patients with Inflammatory Bowel Disease and Irritable Bowel Syndrome.
This study assessed the differences in swabbing rates, vaccine uptake, COVID-19 infection, hospitalization rates and outcomes in patients suffering from inflammatory bowel disease (IBD) on immunomodulation and patients diagnosed with irritable bowel syndrome (IBS). A population consisting of 250 IBD and 250 IBS patients was randomly selected from the local database. Apart from demographic data, the following data was collected: number of COVID-19 swabs taken, vaccination rates, type of vaccine administered, infection secondary to COVID-19, hospitalization and outcomes. IBD patients performed significantly more swabs tests for SARS-CoV-2 detection compared with IBS patients in both phases of the study. Whilst the IBS cohort recorded a larger number of COVID-19 infection and less hospitalisations whilst infected, IBD patients had a better outcome whilst infected since hospitalisation reason in the latter was not related to COVID-19 infection. IBD patients had a larger uptake of COVID-19 vaccines. This study was the first of its nature locally and internationally as it compared two unrelated cohorts of patients followed up in gastroenterology. Vaccination rates in both cohorts were higher than those reported internationally. In concordance with international studies, IBD patients are not at an increased risk of worse outcomes from COVID-19 infection compared to non-IBD cohorts.


Functional requirements of a computer-based patient record system.
The installation of a computer-based patient record system represents a substantial capital investment, but the system can help provide higher quality health care at significantly lower cost. This article examines the functional requirements of such a system, as well as the steps required for implementation.


Isolation of integrin-based adhesion complexes.
The integration of cells with their extracellular environment is facilitated by cell surface adhesion receptors, such as integrins, which play important roles in both normal development and the onset of pathologies. Engagement of integrins with their ligands in the extracellular matrix, or counter-receptors on other cells, initiates the intracellular assembly of a wide variety of proteins into adhesion complexes such as focal contacts, focal adhesions, and fibrillar adhesions. The proteins recruited to these complexes mediate bidirectional signaling across the plasma membrane, and, as such, help to coordinate and/or modulate the multitude of physical and chemical signals to which the cell is subjected. The protocols in this unit describe two approaches for the isolation or enrichment of proteins contained within integrin-associated adhesion complexes, together with their local plasma membrane/cytosolic environments, from cells in culture. In the first protocol, integrin-associated adhesion structures are affinity isolated using microbeads coated with extracellular ligands or antibodies. The second protocol describes the isolation of ventral membrane preparations that are enriched for adhesion complex structures. The protocols permit the determination of adhesion complex components via subsequent downstream analysis by western blotting or mass spectrometry.


Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids.
Mesenchymal stem cells (MSCs) secrete endogenous factors such as vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) that promote angiogenesis, modulate the inflammatory microenvironment, and stimulate wound repair, and MSC spheroids secrete more trophic factors than dissociated, individual MSCs. Compared to injection of cells alone, transplantation of MSCs in a biomaterial can enhance their wound healing potential by localizing cells at the defect site and upregulating trophic factor secretion. To capitalize on the therapeutic potential of spheroids, we engineered a fibrin gel delivery vehicle to simultaneously enhance the proangiogenic and anti-inflammatory potential of entrapped human MSC spheroids. We used multifactorial statistical analysis to determine the interaction between four input variables derived from fibrin gel synthesis on four output variables (gel stiffness, gel contraction, and secretion of VEGF and PGE2). Manipulation of the four input variables tuned fibrin gel biophysical properties to promote the simultaneous secretion of VEGF and PGE2 by entrapped MSC spheroids while maintaining overall gel integrity. MSC spheroids in stiffer gels secreted the most VEGF, while PGE2 secretion was highest in more compliant gels. Simultaneous VEGF and PGE2 secretion was greatest using hydrogels with intermediate mechanical properties, as small increases in stiffness increased VEGF secretion while maintaining PGE2 secretion by entrapped spheroids. The fibrin gel formulation predicted to simultaneously increase VEGF and PGE2 secretion stimulated endothelial cell proliferation, enhanced macrophage polarization, and promoted angiogenesis when used to treat a wounded three-dimensional human skin equivalent. These data demonstrate that a statistical approach is an effective strategy to formulate fibrin gel formulations that enhance the wound healing potential of human MSCs. Mesenchymal stem cells (MSCs) are under investigation for wound healing applications due to their secretion of bioactive factors that enhance granulation tissue formation, blood vessel ingrowth, and reduce inflammation. However, the effectiveness of cell-based therapies is reduced due to poor engraftment and high rates of cell death when transplanted into harsh environments characteristic of large wounds. Compared to dissociated cells, MSCs exhibit increased overall function when aggregated into three-dimensional spheroids, and transplantation of cells using biomaterials is one strategy for guiding cell function in the defect site. The present study demonstrates that the biophysical properties of fibrin hydrogels, designed for use as a cell carrier, can be engineered to dictate the secretion of bioactive factors by entrapped MSC spheroids. This strategy enables MSCs to contribute to wound healing by synergistically promoting neovascularization and modulating the inflammatory milieu.


Unexplored potential: Biologically active compounds produced by microorganisms from hard-to-reach environments and their applications.
Rapid development of antibiotic resistance of bacteria and fungi, as well as cancer drug resistance, has become a global medical problem. Therefore, alternative methods of treatment are considered. Studies of recent years have focused on finding new biologically active compounds that may be effective against drug-resistant cells. High biodiversity of hard-to-reach environments offers sources to search for novel molecules potentially applicable for medical purposes. In this review article, we summarize and discuss compounds produced by microorganisms from hot springs, glaciers, caves, underground lakes, marine ecosystems, and hydrothermal vents. Antibacterial, antiviral, antifungal, anticancer, anti-inflammatory, and antioxidant potential of these molecules are presented and discussed. We conclude that using compounds derived from microorganisms occurring in extreme environments might be considered in further studies on development of treatment procedures for diseases caused by drug-resistant cells.


A serological survey of Bacillus anthracis reveals widespread exposure to the pathogen in free-range and captive lions in Zimbabwe.
Numerous unknown factors influence anthrax epidemiology in multi-host systems, especially at wildlife/livestock/human interfaces. Serology tests for anti-anthrax antibodies in carnivores are useful tools in identifying the presence or absence of Bacillus anthracis in a range. These were employed to ascertain whether the disease pattern followed the recognized high- and low-risk anthrax zonation in Zimbabwe and also to establish whether anthrax was absent from Hwange National Park in which there have been no reported outbreaks. African lions (Panthera leo) (n = 114) drawn from free-range protected areas and captive game parks located in recognized high- and low-risk zones across Zimbabwe were tested for antibodies to anthrax PA antigen using the ELISA immunoassay. A random selection of 27 lion sera samples comprising 17 seropositive and 10 seronegative sera was further tested in the species-independent toxin neutralization assay (TNA) in order to validate the former as a surveillance tool for anthrax in African lions. Using the ELISA-PA immunoassay, 21.9% (25/114) of the lions tested positive for antibodies to anthrax. Seropositivity was recorded in all study areas, and there was no significant difference (p = .852) in seropositivity between lions in high- and low-risk anthrax zones. Also, there was no significant difference (McNemar's chi-square test = 0.9, p = .343) in the proportion of lions testing positive to anti-PA anthrax antibodies on ELISA-PA immunoassay compared with the TNA, with fair agreement between the two tests [kappa (K) statistic = 0.30; 0.08 < K<0.613]. Results of this study indicate that anthrax could be more widespread than 42 currently realized in Zimbabwe, and present in recognized high- and low-risk zones, including 43 where it has not been reported in over 20 years such as Hwange National Park. This is also the 44 first report documenting the presence of anthrax lethal toxin-neutralizing antibodies in naturally 45 infected carnivores, further confirming exposure to B. anthracis. The research results point to a 46 need for revisiting the currently recognized anthrax risk zones in Zimbabwe. This should be based 47 on improved surveillance of the disease in both wild and domestic animals for better understanding and control of the disease.


Opposite environmental regulation of heroin and amphetamine self-administration in the rat.
The circumstances of drug taking are thought to play a role in drug abuse but the evidence of it is anecdotal. Previous studies have shown that the intravenous self-administration of cocaine is facilitated in rats non-residing in the test chambers relative to rats that live in the test chambers at all times. We investigated here whether environmental context could exert its modulatory influence on heroin and amphetamine self-administration as well. Independent groups of rats were given the possibility to self-administer different doses of heroin or amphetamine (12.5, 25.0, or 50.0 microg/kg). Some animals were housed in the self-administration chambers (resident groups) whereas other rats were transported to the self-administration chambers only for the test sessions (non-resident groups). Amphetamine-reinforcing effects were more pronounced in non-resident rats than in resident rats, as previously reported for cocaine. Quite unexpectedly, the opposite was found for heroin. Because of this surprising dissociation, some of the rats trained to self-administer amphetamine were later given the opportunity to self-administer heroin. Also in this case, resident rats took more heroin than non-resident rats. These findings suggest an unforeseen dissociation between opioid and psychostimulant reward and demonstrate that even in the laboratory rat some contexts are associated with the propensity to self-administer more opioid than psychostimulant drugs and vice versa, thus indicating that drug taking is influenced not only by economical or cultural factors but also can be modulated at a much more basic level by the setting in which drugs are experienced.


Assessing the Economics of an Entry-Level Physician Assistant Doctoral Degree.
An entry-level doctoral degree for the physician assistant (PA) profession has been a perennial issue since the master's degree approval in 2000 and the 2009 release of the Clinical Doctorate Summit Report. Many PA counterparts have transitioned to required or optional doctoral degrees for entry into practice. Although the PA profession has not adopted an entry-level doctorate, postgraduate doctoral programs have proliferated. This study's aim was to compare the cost of post-PA doctoral degrees to the estimated cost of an entry-level PA doctorate. Cost of a post-PA doctoral degree was obtained from data on 15 postgraduate doctoral programs associated with PAEA member programs. Historical, aggregated data on PA program characteristics were collected from PAEA Annual Program Survey reports to estimate costs for an entry-level doctorate and to propose a likely model. For comparison, educational program data from health professions that have transitioned to entry-level doctorates were assessed. The average cost for postgraduate PA programs is significantly higher than the projected add-on cost for an entry-level PA doctorate, which ranges from $5,731 to $15,563. Directors of post-PA doctorate programs report that enrollments are generally near or at capacity. Implementation of an entry-level doctorate by accredited PA educational programs has the potential for significant economic and chronological advantages over postgraduate doctoral programs.


Lung Adenocarcinoma: Correlation of Quantitative CT Findings with Pathologic Findings.
Purpose To identify the ability of computer-derived three-dimensional (3D) computed tomographic (CT) segmentation techniques to help differentiate lung adenocarcinoma subtypes. Materials and Methods This study had institutional research board approval and was HIPAA compliant. Pathologically classified resected lung adenocarcinomas (n = 41) with thin-section CT data were identified. Two readers independently placed over-inclusive volumes around nodules from which automated computer measurements were generated: mass (total mass) and volume (total volume) of the nodule and of any solid portion, in addition to the solid percentage of the nodule volume (percentage solid volume) or mass (percentage solid mass). Interobserver agreement and differences in measurements among pathologic entities were evaluated by using t tests. A multinomial logistic regression model was used to differentiate the probability of three diagnoses: invasive non-lepidic-predominant adenocarcinoma (INV), lepidic-predominant adenocarcinoma (LPA), and adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA). Results Mean percentage solid volume of INV was 35.4% (95% confidence interval [CI]: 26.2%, 44.5%)-higher than the 14.5% (95% CI: 10.3%, 18.7%) for LPA (P = .002). Mean percentage solid volume of AIS/MIA was 8.2% (95% CI: 2.7%, 13.7%) and had a trend toward being lower than that for LPA (P = .051). Accuracy of the model based on total volume and percentage solid volume was 73.2%; accuracy of the model based on total mass and percentage solid mass was 75.6%. Conclusion Computer-assisted 3D measurement of nodules at CT had good reproducibility and helped differentiate among subtypes of lung adenocarcinoma. (©) RSNA, 2016.


Ligand-dependent regulation of retinoic acid receptor alpha in rat testis: in vivo response to depletion and repletion of vitamin A.
Male animals are sterile due to testicular degeneration in the absence of retinoic acid (RA) or functional retinoic acid receptor-alpha (RAR alpha). This degeneration can be reversed by injecting retinol, a precursor of RA, into vitamin A-deficient (VAD) rats. To determine the relationship between this ligand-dependent testicular degeneration and regeneration and the expression levels of RAR alpha messenger RNA and protein, testes were depleted and then replenished with retinol in vivo. Results showed that RAR alpha messenger RNA and protein levels declined to VAD amounts after 7 weeks on a VAD diet. This decline was due to decreased RAR alpha levels in early meiotic spermatocytes and the loss of advanced germ cells. Interestingly, the advanced germ cells still contained RAR alpha, but the protein was primarily cytoplasmic instead of nuclear, indicating inactivity as a transcription factor. In VAD testis, RAR alpha levels were low and then increased primarily in Sertoli cells after retinol replenishment. TUNEL analyses showed that most germ cells at the basal aspect of seminiferous tubules were undergoing apoptosis during degeneration. These results indicate that RAR alpha is either down-regulated or inactivated in RA-deficient testis and coincident with that, testes degenerate by apoptosis or selective loss of germ cells.


Screening and characterization of estrogenic activity from a hydroxystilbene library.
Compounds that either inhibit or induce an estrogen response in vivo are important as potential drugs and biochemical tools. Non-steroidal stilbene analogs such as tamoxifen are known to function as both estrogen agonists and antagonists depending upon the analog structure. This family of compounds is amenable to parallel-manifold synthesis because stilbene analogs are easily synthesized using a single-step olefination reaction. We have prepared a small 23-component hydroxystilbene library using a solid phase synthesis approach. The library was screened for estrogenic and antiestrogenic activity using a cell-based bioassay that measures estrogen receptor-mediated transcription of a reporter gene. Three of the analogs proved to have dose-dependent estrogenic activity with EC50 values between 5 microM and 15 microM. Further characterization of the hydroxystilbene-mediated estrogenic activity suggests that the agonist activity results from direct binding to the steroid site on the estrogen receptor with IC50 values of 1-10 microM. The results of this study show that classic olefination chemistry can be adapted to a solid-phase format for parallel synthesis of analog libraries. Although yields varied for the individual analogs, sufficient quantity of pure material was obtained directly from the resin for structural characterization and biological evaluation. This study further validates solid-phase organic synthesis as a useful approach for rapid parallel-manifold library synthesis to augment both lead compound discovery and optimization.


Genetic modifiers interact with Cpe(fat) to affect body weight, adiposity, and hyperglycemia.
Obesity and Type II diabetes are complex diseases in the human population. The existence of a large number of contributing loci and gene-gene as well as gene-environment interactions make it difficult to identify the disease genes underlying these complex traits. In mouse models of obesity and Type II diabetes such as the murine fat mutation, genetic crosses can be used to dissect the genetic complexity influencing the observed phenotypes. The underlying defect in the fat mutant is a Ser202Pro change in carboxypeptidase E (CPE), an enzyme responsible for the final proteolytic processing step of prohormone intermediates. On the HRS/J (HRS) inbred strain background, mice homozygous for the fat mutation exhibit early onset hyperinsulinemia followed by postpubertal moderate obesity without hyperglycemia. In contrast, on the C57BLKS/J (BKS) genetic background, fat/fat mice become severely obese, hyperinsulinemic, and hyperglycemic. Therefore, in the Cpe(fat) genetic model, the fat mutation is necessary but not sufficient for the development of obesity, Type II diabetes, and related metabolic disorders. To dissect the susceptibility loci responsible for modifying obesity- and diabetes-associated traits, we characterized, both genetically and phenotypically, fat/fat male progeny from a large intercross between BKS. HRS-fat/fat and HRS-+/+ mice. Four major loci were mapped, including a locus for body weight (body weight 1) on chromosome 14; a locus for hyperglycemia (fat-induced diabetes 1) on chromosome 19; a locus for hyperglycemia, hyperinsulinemia, and hypercholesterolemia (fat-induced diabetes 2) on chromosome 5; and a locus for adiposity and body weight (fat-induced adiposity 1) on chromosome 11. The identification of these interacting genetic determinants for obesity and Type II diabetes may allow better definition of the obesity/diabetes-related hormone signaling pathways and ultimately may provide new insights into the pathogenesis of these complex diseases.


Development and characterization of 11 microsatellite loci for the Mona Island iguana (Cyclura cornuta stejnegeri).
We isolated and characterized 11 microsatellite loci in the Mona Island iguana (Cyclura cornuta stejnegeri). Eleven loci exhibit moderate to high allelic diversity (two to 12 alleles, mean = 4.5) and polymorphism (mean observed heterozygosity, 0.56; range, 0.26 to 0.78) in 41 adults. This marker set has low probability of identity and high parentage exclusion power and will be suitable for studies of paternity, social organization and relatedness in this species.


Age-gaps in sexual partnerships: seeing beyond 'sugar daddies'.
We examine for the first time age-mixing in sexual relationships in a population with very high HIV incidence and prevalence in rural South Africa. The highest levels of age assortativity (the pairing of like with like) were casual partnerships reported by men, the lowest levels were spousal relationships reported by women. Given the age-sex distribution of HIV prevalence in this population, interventions to decrease age-gaps in spousal relationships may be effective in reducing HIV incidence.


Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease.
Glycosphingolipids (GSLs) are essential constituents of cell membranes and lipid rafts and can modulate signal transduction events. The contribution of GSLs in osteoclast (OC) activation and osteolytic bone diseases in malignancies such as the plasma cell dyscrasia multiple myeloma (MM) is not known. Here, we tested the hypothesis that pathological activation of OCs in MM requires de novo GSL synthesis and is further enhanced by myeloma cell-derived GSLs. Glucosylceramide synthase (GCS) inhibitors, including the clinically approved agent N-butyl-deoxynojirimycin (NB-DNJ), prevented OC development and activation by disrupting RANKL-induced localization of TRAF6 and c-SRC into lipid rafts and preventing nuclear accumulation of transcriptional activator NFATc1. GM3 was the prevailing GSL produced by patient-derived myeloma cells and MM cell lines, and exogenous addition of GM3 synergistically enhanced the ability of the pro-osteoclastogenic factors RANKL and insulin-like growth factor 1 (IGF-1) to induce osteoclastogenesis in precursors. In WT mice, administration of GM3 increased OC numbers and activity, an effect that was reversed by treatment with NB-DNJ. In a murine MM model, treatment with NB-DNJ markedly improved osteolytic bone disease symptoms. Together, these data demonstrate that both tumor-derived and de novo synthesized GSLs influence osteoclastogenesis and suggest that NB-DNJ may reduce pathological OC activation and bone destruction associated with MM.


[The epizootiological role of the population organization of the stock of fleas on the long-tailed suslik in a natural focus of plague in Tuva].
Spatial location of epizootic events in the Tuva plague focus is determined at a considerable degree by the population structure of the flea Citellophilus tesquorum--the main plague microbe vector. Within the enzootic territory occupied by five populations of the long-tailed ground squirrel (Citellus undulatus) there are six populations of C. tesquorum. Each population of fleas has a corresponding autonomic plague focus. Various conditions for the microbe life activity in these populations are recovered. The circulation of the microbe is closely connected with certain intrapopulation groupings of fleas--the nuclei of populations.


Differential gene expression of human stem progenitor cells derived from early stages of in utero human hematopoiesis.
Hematopoietic stem progenitor cells (HSPCs) are highly enriched in a rare subset of Lin-CD34+CD38- cells. Independent of stage of human development, HSPC function segregates to the subset of Lin-CD34+CD38- cells. However, fetal-derived HSPCs demonstrate distinct self-renewal and differentiation capacities compared with their adult counterparts. Here, to characterize the molecular nature of fetal HSPCs, suppressive subtractive hybridization was used to compare gene expression of HSPCs isolated from fetal blood (FB-HSPCs) versus adult mobilized peripheral blood (MPB-HSPCs). We identified 97 differentially expressed genes that could be annotated into distinct groups that include transcription factors, cell cycle regulators, and genes involved in signal transduction. Candidate regulators, such as Lim only domain-2 (LMO2), nuclear factor-kappa B (NF-kappaB), tripartite motif 28 (Trim28), and N-myc protooncogene (MYCN), and a novel homeobox gene product were among transcripts that were found to be differentially expressed and could be associated with specific proliferation and differentiation properties unique to FB-HSPCs. Interestingly, the majority of genes associated with signal transduction belong to Ras pathway, highlighting the significance of Ras signaling in FB-HSPCs. Genes differentially expressed in FB-HSPCs versus adult MPB-HSPCs were verified using quantitative real-time polymerase chain reaction (Q-PCR). This approach also resulted in the identification of a transcript that is highly expressed in FB-HSPCs but not detectable in more differentiated Lin-CD34+CD38+ FB progenitors. Our investigation represents the first study to compare phenotypically similar, but functionally distinct, HSPC populations and to provide a gene profile of unique human HSPCs with higher proliferative capacity derived from early in utero human blood development.


[Interaction between health personnel and young pregnant women during prenatal control: a qualitative study].
To explore the interaction between health personnel and young pregnants, beginning from the meanings of sexuality, pregnancy and prenatal control in a Lima National Hospital. A qualitative study was conducted, including observations of the interaction during the consult, in-depth interviews to young pregnants (14) and health personnel (9), and a focus group of young pregnant women. There are perceptions and socio-cultural valuations that don't favor communication between both groups. Health personnel rise as an argument the fact that having prompt sexual relations means that the youngsters assume the role of adults, and also consider that these weren't prepared bio-psychologically and socially to be mothers. In this conception, the body of the youngster is considered a means of control, intervention and power in the presence of the obstetrician. Nevertheless, for the pregnant youngsters it represents its value as future mothers. The meanings of the prenatal control for the health personnel are oriented to the biomedical aspects from the risk approach; emphasizing in the transmission of sexually transmitted diseases; on the other hand, for the teens the behavior of the health staff is important and differs, women offer a kind, warm attention, without overlooking the scientific and cognitive aspects, while males, in most of the cases, have a more operative and cognitive interaction. The interaction between health personnel and pregnant women varies according to the gender of the health staff and has different meanings for the pregnant, which is important to take into account in order to improve the attention in prenatal control of young women.


High blood pressure and associated risk factors as indicator of preclinical hypertension in rural West Africa: A focus on children and adolescents in The Gambia.
Hypertension is fast becoming a major public health problem across sub-Saharan Africa. We sought to determine the prevalence of high blood pressure (BP) and associated risk factors as indicator of preclinical hypertension in a rural Gambian population.We analyzed data on 6160 healthy Gambians cross-sectionally. Attention was given to 5 to <18-year olds (N = 3637), as data from sub-Saharan Africa on this young age group are scarce. High BP was defined as systolic blood pressure (SBP) above the 95th percentile for age-sex specific height z scores in <18-year olds employing population-specific reference values. Standard high BP categories were applied to ≥18-year olds.In <18-year olds, the multivariable analysis gave an adjusted high BP prevalence ratio of 0.95 (95% confidence interval [CI] 0.92-0.98; P = 0.002) for age and 1.13 (95% CI 1.06-1.19; P < 0.0001) for weight-for-height z score (zWT-HT); sex and hemoglobin were not shown to affect high BP. In adults age 1.05 (95% CI 1.04-1.05; P < 0.0001), body mass index z score 1.28 (95% CI 1.16-1.40; P < 0.0001), hemoglobin 0.90 (95% CI 0.85-0.96; P < 0.0001) and high fasting glucose 2.60 (95% CI 2.02-3.36; P < 0.0001, though the number was very low) were confirmed as risk factors for high BP prevalence; sex was not associated.The reported high BP prevalence and associated risk factors in adults are comparable to other studies conducted in the region. The observed high BP prevalence of 8.2% (95% CI 7.4-9.2) in our generally lean young Gambians (<18 years) is alarming, given that high BP tracks from childhood to adulthood. Hence there is an urgent need for further investigation into risk factors of pediatric high BP/hypertension even in rural African settings.


Real-Time Assembly of Coordination Patterns in Human Infants.
Flexibility and generativity are fundamental aspects of functional behavior that begin in infancy and improve with experience. How do infants learn to tailor their real-time solutions to variations in local conditions? On a nativist view, the developmental process begins with innate prescribed solutions, and experience elaborates on those solutions to suit variations in the body and the environment. On an emergentist view, infants begin by generating a variety of strategies indiscriminately, and experience teaches them to select solutions tailored to the current relations between their body and the environment. To disentangle these accounts, we observed coordination patterns in 11-month-old pre-walking infants with a range of cruising (moving sideways in an upright posture while holding onto a support) and crawling experience as they cruised over variable distances between two handrails they held for support. We identified infants' coordination patterns using a novel combination of computer-vision, machine-learning, and time-series analyses. As predicted by the emergentist view, the least experienced infants generated multiple coordination patterns inconsistently regardless of body size and handrail distance, whereas the most experienced infants tailored their coordination patterns to body-environment relations and switched solutions only when necessary. Moreover, the beneficial effects of experience were specific to cruising and not crawling, although both skills involve anti-phase coordination among the four limbs. Thus, findings support an emergentist view and suggest that everyday experience with the target skill may promote "learning to learn," where infants learn to assemble the appropriate solution for new problems on the fly.


Characterization of the alpha adrenoceptor-mediated effects and antihypertensive activity of ICI 106270: comparison with clonidine.
Clonidine and ICI 106270 are centrally acting antihypertensive agents which act through stimulation of medullary alpha-2 adrenoceptors. Both compounds are equipotent agonists at alpha-2 adrenoceptors as assessed in functional studies in isolated organs and in radioligand binding studies. In addition, clonidine and ICI 106270 possess the same degree of selectivity for alpha-2 adrenoceptors over alpha-1 adrenoceptors. Clonidine and ICI 106270 are equipotent antihypertensive agents after intracisternal administration to spontaneously hypertensive rats, consistent with the observations made in vitro that both compounds are equipotent alpha-2 adrenoceptor agonists. Both compounds were less potent in lowering blood pressure after i.v. administration than after intracisternal administration, thus confirming a central mechanism of action. Interestingly, clonidine was a more potent antihypertensive agent than ICI 106270 after i.v. administration, which, in view of the equal potencies observed after intracisternal administration, suggests that diffusion of ICI 106270 into the central nervous system is selectively retarded, relative to clonidine, by the blood-brain barrier. The differences observed in the rate of penetration of the blood-brain barrier are consistent with the higher pka and corresponding higher extent of ionization (at physiological pH) and lower lipophilicity of ICI 106270 relative to clonidine. A relatively large difference between the i.v. and p.o. antihypertensive potencies was observed for ICI 106270 which indicates poor p.o. absorption of ICI 106270 relative to clonidine, again likely resulting from the greater proportion of ICI 106270 existing in the ionized species.(ABSTRACT TRUNCATED AT 250 WORDS)


Insights from a national survey into why substance abuse treatment units add prevention and outreach services.
Previous studies have found that even limited prevention-related interventions can affect health behaviors such as substance use and risky sex. Substance abuse treatment providers are ideal candidates to provide these services, but typically have little or no financial incentive to do so. The purpose of this study was therefore to explore why some substance abuse treatment units have added new prevention and outreach services. Based on an ecological framework of organizational strategy, three categories of predictors were tested: (1) environmental, (2) unit-level, and (3) unit leadership. A lagged cross-sectional logistic model of 450 outpatient substance abuse treatment units revealed that local per capita income, mental health center affiliation, and clinical supervisors' graduate degrees were positively associated with likelihood of adding prevention-related education and outreach services. Managed care contracts and methadone treatment were negatively associated with addition of these services. No hospital-affiliated agencies added prevention and outreach services during the study period. Findings supported the study's ecological perspective on organizational strategy, with factors at environmental, unit, and unit leadership levels associated with additions of prevention and outreach services. Among the significant predictors, ties to managed care payers and unit leadership graduate education emerge as potential leverage points for public policy. In the current sample, units with managed care contracts were less likely to add prevention and outreach services. This is not surprising, given managed care's emphasis on cost control. However, the association with this payment source suggests that public managed care programs might affects prevention and outreach differently through revised incentives. Specifically, government payers could explicitly compensate substance abuse treatment units in managed care contracts for prevention and outreach. The effects of supervisor graduate education on likelihood of adding new prevention and outreach programs suggests that leaders' education can affect organizational strategy. Foundation and government officials may encourage prevention and outreach by funding curricular enhancements to graduate degree programs demonstrating the importance of public goods. Overall, these findings suggest that both money and professional education affect substance abuse treatment unit additions of prevention and outreach services, as well as other factors less amenable to policy intervention.


[Tension pneumocephalus complicated from bacterial meningitis - a report of case presenting "Mount Fuji sign" in brain CT].
A 39-year-old man was suffered from bacterial meningitis spread from sphenoid sinusitis. During the first several days of the hospitalization, his clinical and laboratory findings were improved by the antibiotics. But he developed impaired consciousness and paraparesis on the sixth hospital day. A CT scan of the brain revealed pneumocephalus with compression of frontal lobes and the widening of the interhemispheric space between the tips of the frontal lobes, which was known as "Mount Fuji sign". Tension pneumocephalus was diagnosed on the basis of the clinical symptoms and the characteristic CT findings. As the bacterial meningitis itself was improving, the surgical treatment was not performed, but the antibiotics therapy continued. He gradually recovered and discharged without any other complications. The mechanism of tension pneumocephalus could not be disclosed. However, it was speculated that tension pneumocephalus was formed due to combined conditions of following factors; the fistula formation between sphenoid sinus and subdural space, the reduced CSF pressure on lumbar puncture, and a ball-valve mechanism though the fistula. We would emphasize that "Mount Fuji sign"on CT or MRI was the important finding to diagnose tension pneumocephalus.


Assessment of intrauterine methylmercury exposure affecting child development: messages from the newborn.
In evaluating the health effects in the offspring born to the mothers exposed to methylmercury (MeHg) during pregnancy, biomarkers obtained from maternal blood and hair, and umbilical cord have been employed for the exposure assessment. However, which biomarker is employed may affect the study conclusion. In this sense, umbilical cord mercury concentration appears to be a direct exposure biomarker of the fetus. We present an overview of the studies addressing umbilical cord and mercury and scrutinize the usefulness of umbilical cord samples for intrauterine exposure assessment of MeHg. The mean total mercury concentration in cord blood ranged from 0.5 to 35.6 microg/L among the studies reviewed. In Japanese populations, MeHg concentrations in dry cord tissue did not exceed 0.4 microg/g. Also, dry cord tissue would be preferable to wet tissue because the definition of wet weight of the umbilical cord is ambiguous. The cord blood-to-maternal blood ratio of mercury concentrations differed considerably among mother-child pairs despite the significant positive correlation between the cord and maternal mercury concentrations. Moreover, the increased cord mercury concentration was associated with some neurobehavioral and neurophysiological deficits in child. Therefore, mercury concentrations in cord blood and tissue can be accepted as more useful and valid biomarkers of fetal exposure to MeHg, for assessing a dose-response relationship in children at the developmental stage, than maternal mercury concentrations at parturition. Because umbilical cord blood has been used for cord-blood stem cell transplants, dry umbilical cord tissue should be effectively utilized for the advancement of medical sciences.


Advances in interventional pulmonology.
Interventional pulmonology (IP) remains a rapidly expanding and evolving subspecialty focused on the diagnosis and treatment of complex diseases of the thorax. As the field continues to push the leading edge of medical technology, new procedures allow for novel minimally invasive approaches to old diseases including asthma, chronic obstructive pulmonary disease and metastatic or primary lung malignancy. In addition to technologic advances, IP has matured into a defined subspecialty, requiring formal training necessary to perform the advanced procedures. This need for advanced training has led to the need for standardization of training and the institution of a subspecialty board examination. In this review, we will discuss the dynamic field of IP as well as novel technologies being investigated or employed in the treatment of thoracic disease.