Air pollutants and hospital admissions due to cardiovascular diseases in São José do Rio Preto, Brazil.
This study aimed to estimate the effects of environmental pollutants on the increase of hospitalizations due to cardiovascular diseases. This was an ecological study conducted in the city of São José do Rio Preto, São Paulo, Brazil, with data from hospital admissions with diagnoses in the categories of I-00 to I-99, from October, 1, 2011, to September 30, 2012. Fineparticulate matter (PM2,5), ozone, carbon monoxide, nitrogen oxide and nitrogen dioxide were the pollutants studied; they were estimated by CATT-BRAMs model. The use of an additive Poisson regression model showed association between exposure to PM2,5 and hospital admission due to cardiovascular diseases. In the fifth day after exposure to this pollutant (lag 5), the relative risk for hospitalization due to cardiovascular diseases increased 15 percent in according to 10 µg/m3 increase on PM2,5 concentrations. There were 650 avoidable hospital admissions and an excess of R$ 1.9 million in hospital expenses. Thus, it was possible to identify the association between exposure to PM2,5 and hospital admission due cardiovascular diseases in medium-sized cities, like São José do Rio Preto.


The clinical potential of etrolizumab in ulcerative colitis: hypes and hopes.
Antiadhesion molecules are effective and safe in patients with ulcerative colitis (UC). Etrolizumab, a monoclonal antibody targeting both α4β7 and αEβ7, represents a promising therapy for patients with UC, since this novel mechanism of action may be effective in blocking leukocyte recruitment both at the vascular and at the mucosal level. Preliminary studies show that etrolizumab is effective in inducing clinical response and remission, and mucosal healing. Moreover, new predictors of response have recently been identified, opening the way to a tailored therapeutic approach. This review of the literature aims to present and discuss the most recent evidence on etrolizumab in UC, focusing on the clinical implications of the use of etrolizumab in UC.


The evolution of the language faculty: clarifications and implications.
In this response to Pinker and Jackendoff's critique, we extend our previous framework for discussion of language evolution, clarifying certain distinctions and elaborating on a number of points. In the first half of the paper, we reiterate that profitable research into the biology and evolution of language requires fractionation of "language" into component mechanisms and interfaces, a non-trivial endeavor whose results are unlikely to map onto traditional disciplinary boundaries. Our terminological distinction between FLN and FLB is intended to help clarify misunderstandings and aid interdisciplinary rapprochement. By blurring this distinction, Pinker and Jackendoff mischaracterize our hypothesis 3 which concerns only FLN, not "language" as a whole. Many of their arguments and examples are thus irrelevant to this hypothesis. Their critique of the minimalist program is for the most part equally irrelevant, because very few of the arguments in our original paper were tied to this program; in an online appendix we detail the deep inaccuracies in their characterization of this program. Concerning evolution, we believe that Pinker and Jackendoff's emphasis on the past adaptive history of the language faculty is misplaced. Such questions are unlikely to be resolved empirically due to a lack of relevant data, and invite speculation rather than research. Preoccupation with the issue has retarded progress in the field by diverting research away from empirical questions, many of which can be addressed with comparative data. Moreover, offering an adaptive hypothesis as an alternative to our hypothesis concerning mechanisms is a logical error, as questions of function are independent of those concerning mechanism. The second half of our paper consists of a detailed response to the specific data discussed by Pinker and Jackendoff. Although many of their examples are irrelevant to our original paper and arguments, we find several areas of substantive disagreement that could be resolved by future empirical research. We conclude that progress in understanding the evolution of language will require much more empirical research, grounded in modern comparative biology, more interdisciplinary collaboration, and much less of the adaptive storytelling and phylogenetic speculation that has traditionally characterized the field.


Re-insurance in the Swiss health insurance market: Fit, power, and balance.
Risk equalization mechanisms mitigate insurers' incentives to practice risk selection. On the other hand, incentives to limit healthcare spending can be distorted by risk equalization, particularly when risk equalization payments depend on realized costs instead of expected costs. In addition, cost based risk equalization mechanisms may incentivize health insurers to distort the allocation of resources among different services. The incentives to practice risk selection, to limit healthcare spending, and to distort the allocation of resources can be measured by fit, power, and balance, respectively. We apply these three measures to evaluate the risk adjustment mechanism in Switzerland. Our results suggest that it performs very well in terms of power but rather poorly in terms of fit. The latter indicates that risk selection might be a severe problem. We show that re-insurance can reduce this problem while power remains on a high level. In addition, we provide evidence that the Swiss risk equalization mechanism does not lead to imbalances across different services.


Cycads: fossil evidence of late paleozoic origin.
Plant fossils from Lower Permian strata of the southwestern United States have been interpreted as cycadalean megasporophylls. They are evidently descended from spermopterid elements of the Pennsylvanian Taeniopteris complex; thus the known fossil history of the cycads is extended from the Late Triassic into the late Paleozoic. Possible implications of the Permian fossils toward evolution of the angiosperm carpel are considered.


SU-E-T-482: A More Accurate Bare 12 5I Spectrum.
To compare measured energy spectra of 125 I brachytherapy seeds with Monte Carlo calculated energy spectra when using the bare 125 I energy spectrum recommended by TG43 and the one presented in NCRP Report 58 and to determine the impact of these different spectra on the calculation of the dose rate constant. The energy spectrum, absorbed dose at 1 cm on the bisector and air kerma strength of 10 different 125 I seeds were calculated using the EGSnrc BrachyDose Monte Carlo code. Energy bin width was 0.2 keV. The simulations were done with the bare 125 I energy spectrum recommended by TG43 or NCRP Report 58. Statistical uncertainties for the energy spectra were 0.02% and 0.1% or less for the other clinical parameters. Results are compared with published measuredvalues. There is close agreement between the measured and calculated branching ratio generated by 125 I seeds when simulated using the spectrum presented in NCRP58. However, for all seeds a 7% lower value is observed in the 31 keV peak when using data suggested by TG43. On the other hand, differences in the average energy, air kerma, absorbed dose and dose rate constant are undetectable (less than statistical uncertainty, <0.1%) when performed with either spectrum. For dosimetric parameter calculations, the bare 125 I energy spectra presented in TG43 and NCRP58 produce indistinguishable results. However, for branching ratio investigation purposes, there is a clear difference in the 31 keV peak between values obtained using the different 125 I bare energy spectra. Measured 125 I branching ratios are in close agreement with those calculated using the bare 125 I energy spectrum presented in NCRP58. Reassessment of the bare 125 I energy spectrum recommended in TG43 is suggested.


High concentration solar collector of the stepped spherical type: optical design characteristics.
An analysis of the optical design characteristics of a new high concentration solar collector is presented. This type of collector consists of spherical segments that are sections of a spherical cap by planes perpendicular to its axis. These ring-shaped spherical segments are so arranged along their common axis that the planes of their circles of least confusion are superposed. The optical characteristics and simulation of this system are developed to provide information for the engineering design of this type of solar energy collector system. The calculations are checked by a laser scanning onto a breadboard mock-up.


Identification of IncA/C Plasmid Replication and Maintenance Genes and Development of a Plasmid Multilocus Sequence Typing Scheme.
Plasmids of incompatibility group A/C (IncA/C) are becoming increasingly prevalent within pathogenic Enterobacteriaceae They are associated with the dissemination of multiple clinically relevant resistance genes, including blaCMY and blaNDM Current typing methods for IncA/C plasmids offer limited resolution. In this study, we present the complete sequence of a blaNDM-1-positive IncA/C plasmid, pMS6198A, isolated from a multidrug-resistant uropathogenic Escherichia coli strain. Hypersaturated transposon mutagenesis, coupled with transposon-directed insertion site sequencing (TraDIS), was employed to identify conserved genetic elements required for replication and maintenance of pMS6198A. Our analysis of TraDIS data identified roles for the replicon, including repA, a toxin-antitoxin system; two putative partitioning genes, parAB; and a putative gene, 053 Construction of mini-IncA/C plasmids and examination of their stability within E. coli confirmed that the region encompassing 053 contributes to the stable maintenance of IncA/C plasmids. Subsequently, the four major maintenance genes (repA, parAB, and 053) were used to construct a new plasmid multilocus sequence typing (PMLST) scheme for IncA/C plasmids. Application of this scheme to a database of 82 IncA/C plasmids identified 11 unique sequence types (STs), with two dominant STs. The majority of blaNDM-positive plasmids examined (15/17; 88%) fall into ST1, suggesting acquisition and subsequent expansion of this blaNDM-containing plasmid lineage. The IncA/C PMLST scheme represents a standardized tool to identify, track, and analyze the dissemination of important IncA/C plasmid lineages, particularly in the context of epidemiological studies.


Insulin resistance as a predictor of age-related diseases.
The current study was initiated to evaluate the ability of insulin resistance to predict a variety of age-related diseases. Baseline measurements of insulin resistance and related variables were made between 1988-1995 in 208 apparently healthy, nonobese (body mass index < 30 kg/m2) individuals, who were then evaluated 4-11 yr later (mean +/- SEM = 6.3 +/- 0.2 yr) for the appearance of the following age-related diseases: hypertension, coronary heart disease, stroke, cancer, and type 2 diabetes. The effect of insulin resistance on the development of clinical events was evaluated by dividing the study group into tertiles of insulin resistance at baseline and comparing the events in these 3 groups. Clinical endpoints (n = 40) were identified in 37 individuals (18%) of those evaluated, including 12 with hypertension, 3 with hypertension + type 2 diabetes, 9 with cancer, 7 with coronary heart disease, 4 with stroke, and 2 with type 2 diabetes. Twenty-eight out of the total 40 clinical events were seen in 25 individuals (36%) in the most insulin-resistant tertile, with the other 12 occurring in the group with an intermediate degree of insulin resistance. Furthermore, insulin resistance was an independent predictor of all clinical events, using both multiple logistic regression and Cox's proportional hazards analysis. The fact that an age-related clinical event developed in approximately 1 out of 3 healthy individuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 yr, whereas no clinical events were observed in the most insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-related diseases.


Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon-inducible cytochrome(s) P-450 in human liver microsomes.
The microsomal metabolism of caffeine and its primary dimethylxanthine metabolites, paraxanthine, theophylline, and theobromine, was investigated in 15 different human livers, including those from two known nonsmokers and one known smoker. At least two distinct enzymes with differing substrate affinities have the potential to catalyze most methylxanthine N-demethylations and C8-hydroxylations in vitro; however, at the low methylxanthine concentrations routinely encountered in vivo, participation by the high affinity site is expected to predominate. It appears that the high affinity enzyme is a polycyclic aromatic hydrocarbon-inducible isozyme of cytochrome P-450, based on competitive inhibition by 7-ethoxyresorufin and benzo[a]pyrene, and based on a significant (p less than 0.001) correlation between 7-ethoxyresorufin-O-deethylation and methylxanthine demethylation rates. alpha-Naphthoflavone inhibited all methylxanthine demethylations in excess of 80% in two high activity livers, whereas 8-hydroxylations were generally inhibited less. Kinetic analysis of paraxanthine 7-demethylation in four different liver preparations resulted in similar Km values of 1.2 +/- 0.5 mM (mean +/- SD), whereas Vmax values varied 8-fold, compatible with participation by the same high affinity isozyme. Notable was the high degree of inter-liver variation in metabolic rates, with the known smoker showing the second highest activity among a 20-fold range in paraxanthine demethylation rates, consistent with polycyclic aromatic hydrocarbon-related enzyme induction. Maximal inhibition of paraxanthine 8-hydroxylation by alpha-naphthoflavone left similar residual activities in the 15 liver preparations, indicating the presence of an enzyme activity that was not inducible. Furthermore, in low activity livers, more than 80% of paraxanthine 8-hydroxylation was mediated by an isozyme of cytochrome P-450 insensitive to inhibition by alpha-naphthoflavone. Our in vitro data show that the proportion of demethylation relative to hydroxylation products of paraxanthine correlate with 7-ethoxyresorufin O-deethylation rates. Taken together, the data provide a rationale for a potential in vivo marker of polycyclic aromatic hydrocarbon-inducible cytochrome P-450 activity based on a urinary metabolite ratio of paraxanthine 7-demethylation to 8-hydroxylation products after caffeine intake.


Decreased expression of DNA topoisomerase I in camptothecin-resistant tumor cell lines as determined by a monoclonal antibody.
DNA topoisomerase I (topo I) has been identified as a principal target of a plant alkaloid camptothecin (CPT) and its derivative (CPT-11). The latter compound is expected to be a clinically useful antitumor agent. Three human tumor cell lines resistant to CPT (A549/CPT, HT-29/CPT, St-4/CPT) were isolated in vitro, and a murine tumor cell line resistant to CPT-11 (P388/CPT) was isolated in vivo by continuous exposure of the drugs. A549/CPT, HT-29/CPT, and St-4/CPT showed 1.8-, 6.9-, and 8.8-fold more resistance to CPT, and P388/CPT showed 45-fold more resistance to CPT than did the parental line. To examine the possible involvement of topo I in drug-resistant mechanisms, a monoclonal antibody was developed by using purified human topo I as antigen. The antibody T14C (immunoglobulin G1) recognized both human and murine topo I, as shown by Western blot analysis. By using this monoclonal antibody, cellular contents of topo I were examined in CPT-resistant tumor lines. Respective contents of topo I in HT-29/CPT, St-4/CPT, and P388/CPT were approximately 8-, 4-, and 3-fold less than those in their parental cell lines. A549/CPT, a weak CPT-resistant line, possessed amounts of topo I similar to those of the parental line. HT-29/CPT showed lower topo I activity than did the parental HT-29 in the nuclear extracts and in the hydroxylapatite column-eluted fractions. Purified topo I from HT-29 and HT-29/CPT showed similar catalytic activity when the same amounts of protein were used. These results indicate that the quantitative reduction of topo I content seems to be the most frequently occurring event in the development of resistance to camptothecin.


Mass spectrometry-driven proteomics: an introduction.
Proteins are reckoned to be the key actors in a living organism. By studying proteins, one engages into deciphering a complex series of events occurring during a protein's life span. This starts at the creation of a protein, which is tightly controlled on both a transcriptional (Williams and Tyler, 2007, Curr Opin Genet Dev 17, 88-93) and a translational level (Van Der Kelen et al., 2009, Crit Rev Biochem Mol Biol 44, 143-168). During translation, a primary strand of amino acids undergoes a complex folding process in order to obtain a native three-dimensional protein structure (Gross et al., 2003, Cell 115, 739-750). Proteins take on a plethora of functions, such as complex formation, receptor activity, and signal transduction, which ultimately adds up to a cellular phenotype. Consequently, protein analysis is of major interest in molecular biology and involves annotating their presence and localization, as well as their modification state and biochemical context. To accomplish this, many methods have been developed over the last decades, and their general principles and important recent advances in large-scale protein analysis or proteomics are discussed in this review.


Chromosomal differentiation of Anopheles funestus from Luanda and Huambo Provinces, western and central Angola.
The chromosomal polymorphism of Anopheles funestus sensu stricto from Angola was analyzed from indoor-resting samples collected in 11 peri-urban and rural sites of the Luanda and Huambo Provinces, which are > 450 km apart and have distinct eco-climatic conditions. Five polymorphic paracentric inversions were observed (scored chromatids range = 202 to 248): 2Ra, 2Rh, 3Ra, 3Rb, and 3La. Inversions 3Rb and 3La were highly polymorphic; the 2Ra and 3Ra arrangements were absent in Luanda. No significant departures from Hardy-Weinberg and linkage equilibria were found at the locality, commune, or province level (sites <or= 50 km from each other), indicating panmixia in each locale. Pooling the Luanda and Huambo samples produced a Wahlund effect, with significant levels of genetic differentiation suggestive of restrictions to gene flow due to geographic distance. The observation that differentiation was limited to inversions 2Ra and 3Ra can also be interpreted as divergent selection acting on these chromosomal regions between populations from the two provinces.


Angiotensinogen gene-inducible enhancer-binding protein 1, a member of a new family of large nuclear proteins that recognize nuclear factor kappa B-binding sites through a zinc finger motif.
Transcriptional activation of the rat angiotensinogen gene during the acute-phase response is dependent on a previously characterized acute-phase response element (APRE) that binds at least two types of nuclear proteins: a cytokine-inducible activity indistinguishable from nuclear factor kappa-B (NF kappa B) and a family of C/EBP-like proteins. We screened a rat liver cDNA expression library with a labeled APRE DNA probe and isolated a single clone that encodes a sequence-specific APRE-binding protein. This new protein, the angiotensinogen gene-inducible enhancer-binding protein 1 (AGIE-BP1), is encoded by a large continuous open reading frame and contains a zinc finger motif virtually identical to the DNA-binding domain of a recently described human protein, MBP-1/PRDII-BF1, and a homologous mouse protein, alpha A-CRYBP1. Outside the binding domain, the sequences diverged considerably. Southern blot analysis indicated that AGIE-BP1 and alpha A-CRYBP1 are encoded by separate genes, thus defining a new family of DNA-binding proteins. Electrophoretic mobility shift assays, methylation interference, and DNase I footprint protection assays with the bacterially expressed DNA-binding domain of AGIE-BP1 demonstrated a binding specificity indistinguishable from that of purified NF kappa B. Antiserum raised against the bacterially expressed DNA-binding domain of AGIE-BP1 detected on immunoblots of cellular proteins a large (greater than 250-kDa) nuclear protein. Northern (RNA) blot analysis of RNAs from different rat tissues and cell lines indicated different levels of expression of the large (greater than 10-kb) AGIE-BP1 transcript in different tissues. The potential role of AGIE-BP1 in the regulation of gene expression is discussed.


Immune Mediator Pharmacogenomics: TCL1A SNPs and Estrogen-Dependent Regulation of Inflammation.
This review describes the important functional implications of TCL1A single nucleotide polymorphisms (SNPs) discovered during pharmacogenomic studies of aromatase inhibitor-induced musculoskeletal adverse events that were subsequently shown to influence the expression of cytokines, chemokines, toll-like receptors (TLR), and NF-κB in a SNP and estrogen-dependent fashion. Functional genomic studies of these SNPs led to the discovery of novel mechanisms that may contribute to disease pathophysiology and which may also increase our understanding of pharmacogenomic aspects of regulation of the expression of inflammatory mediators. Specifically, TCL1A expression was induced by estrogens in a SNP-dependent fashion, resulting in downstream effects on the expression of immune mediators that included IL17RA, IL17A, CCR6, CCL20 TLR2, TLR7, TLR9, TLR10 and NF-κB. These observations have potential implications for inflammatory diseases such as rheumatoid arthritis-a disease for which two thirds of patients are women. Strikingly, this genomic phenomenon could be "reversed" by estrogen receptor antagonist treatment-once again in a SNP-dependent, i.e., in a pharmacogenomic fashion. Specifically, differential SNP-dependent effects on estrogen receptor binding to estrogen response elements before and after estrogen receptor blockade might be associated with mechanisms underlying the SNP genotype and estrogen-dependent regulation of TCL1A and the expression of downstream immune mediators. Furthermore, this SNP and estrogen-dependent phenotypic response could be "reversed" by SERM treatment. These observations could potentially open the way to understand, predict and even pharmacologically manipulate the expression of selected immune mediators in a SNP-dependent fashion.


The challenges of undergraduate mental health nursing education from the perspectives of heads of schools of nursing in Queensland, Australia.
The shortage of a skilled mental health nursing workforce is persistent and worsening. Research consistently demonstrates the inability of the comprehensive model of nursing education to meet nursing workforce needs in mental health. Introducing specialisation in mental health at undergraduate level has been suggested as a strategy to address this problem. Exploration of barriers to this educational approach is essential. The aim of this research is to examine with Queensland Heads of Schools of Nursing, the perceived barriers to a specialist mental health nursing stream within an undergraduate nursing programme. Qualitative exploratory methods, involving in-depth telephone interviews with Heads of Schools of Nursing in Queensland, Australia. Data were analysed thematically. Participants encountered a number of barriers revealed in five main themes: academic staffing; staff attitudes; funding and resource implications; industry support; entry points and articulation pathways. Barriers to the implementation of mental health nursing specialisation in undergraduate programmes are evident. While these barriers pose real threats, potential solutions are also evident. Most notably is the need for Schools of Nursing to become more co-operative in mounting mental health nursing specialisations in a smaller number of universities, where specialist expertise is identified. Quality mental health services rely on a sufficiently skilled and knowledgeable nursing workforce. To achieve this it is important to identify and implement the educational approach best suited to prepare nurses for practice in this field.


Global food insecurity. treatment of major food crops with elevated carbon dioxide or ozone under large-scale fully open-air conditions suggests recent models may have overestimated future yields.
Predictions of yield for the globe's major grain and legume arable crops suggest that, with a moderate temperature increase, production may increase in the temperate zone, but decline in the tropics. In total, global food supply may show little change. This security comes from inclusion of the direct effect of rising carbon dioxide (CO2) concentration, [CO2], which significantly stimulates yield by decreasing photorespiration in C3 crops and transpiration in all crops. Evidence for a large response to [CO2] is largely based on studies made within chambers at small scales, which would be considered unacceptable for standard agronomic trials of new cultivars or agrochemicals. Yet, predictions of the globe's future food security are based on such inadequate information. Free-Air Concentration Enrichment (FACE) technology now allows investigation of the effects of rising [CO2] and ozone on field crops under fully open-air conditions at an agronomic scale. Experiments with rice, wheat, maize and soybean show smaller increases in yield than anticipated from studies in chambers. Experiments with increased ozone show large yield losses (20%), which are not accounted for in projections of global food security. These findings suggest that current projections of global food security are overoptimistic. The fertilization effect of CO2 is less than that used in many models, while rising ozone will cause large yield losses in the Northern Hemisphere. Unfortunately, FACE studies have been limited in geographical extent and interactive effects of CO2, ozone and temperature have yet to be studied. Without more extensive study of the effects of these changes at an agronomic scale in the open air, our ever-more sophisticated models will continue to have feet of clay.


Divergent responses of viral and bacterial communities in the gut microbiome to dietary disturbances in mice.
To improve our understanding of the stability of mammalian intestinal communities, we characterized the responses of both bacterial and viral communities in murine fecal samples to dietary changes between high- and low-fat (LF) diets. Targeted DNA extraction methods for bacteria, virus-like particles and induced prophages were used to generate bacterial and viral metagenomes as well as 16S ribosomal RNA amplicons. Gut microbiome communities from two cohorts of C57BL/6 mice were characterized in a 6-week diet perturbation study in response to high fiber, LF and high-refined sugar, milkfat (MF) diets. The resulting metagenomes from induced bacterial prophages and extracellular viruses showed significant overlap, supporting a largely temperate viral lifestyle within these gut microbiomes. The resistance of baseline communities to dietary disturbances was evaluated, and we observed contrasting responses of baseline LF and MF bacterial and viral communities. In contrast to baseline LF viral communities and bacterial communities in both diet treatments, baseline MF viral communities were sensitive to dietary disturbances as reflected in their non-recovery during the washout period. The contrasting responses of bacterial and viral communities suggest that these communities can respond to perturbations independently of each other and highlight the potentially unique role of viruses in gut health.


Eye banking and screening for Creutzfeldt-Jakob disease.
To quantify the risk of Creutzfeldt-Jakob disease (CJD) among cornea donors, evaluate supplemental screening strategies, and address concerns about the adequacy of current methods of screening tissue donors in the United States. Reported data on deaths due to CJD and from all causes were used to estimate the rate of CJD among cornea donors. The impact of increased screening on risk of CJD and donor supply was evaluated. Only 1.3 of the approximately 45 000 cornea donors in the United States each year might be expected to have CJD. Most of the estimated risk (91%) is due to preclinical (asymptomatic) disease and therefore could not be eliminated by screening for signs or symptoms. If only the highest-risk age group (60 to 69 years) were screened and specificity were 90%, more than 21 000 otherwise acceptable donors would incorrectly be excluded over a period of 17.5 years to correctly exclude a single donor with symptomatic CJD. Currently, the risk of CJD transmission following cornea transplantation is remarkably low. Screening for symptoms of CJD would have minimal impact on safety, but would reduce donor supply and likely result in many patients not receiving needed treatment.


Bacterial glycosyltransferase toxins.
Mono-glycosylation of host proteins is a common mechanism by which bacterial protein toxins manipulate cellular functions of eukaryotic target host cells. Prototypic for this group of glycosyltransferase toxins are Clostridium difficile toxins A and B, which modify guanine nucleotide-binding proteins of the Rho family. However, toxin-induced glycosylation is not restricted to the Clostridia. Various types of bacterial pathogens including Escherichia coli, Yersinia, Photorhabdus and Legionella species produce glycosyltransferase toxins. Recent studies discovered novel unexpected variations in host protein targets and amino acid acceptors of toxin-catalysed glycosylation. These findings open new perspectives in toxin as well as in carbohydrate research.


Prophylactic Platelet Transfusions for Critically Ill Patients With Thrombocytopenia: A Single-Institution Propensity-Matched Cohort Study.
Thrombocytopenia is frequently encountered in critically ill patients, often resulting in prophylactic transfusion of platelets for the prevention of bleeding complications. However, the efficacy of this practice remains unclear. The objective of this study was to determine the relationship between prophylactic platelet transfusion and bleeding complications in critically ill patients. This is a retrospective cohort study of adults admitted to surgical, medical, or combined medical-surgical intensive care units (ICUs) at a single academic institution between January 1, 2009, and December 31, 2013. Inclusion criteria included age ≥18 years and a platelet count measured during ICU admission. Propensity-matched analyses were used to evaluate associations between prophylactic platelet transfusions and the outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of ICU and hospital-free days and changes in sequential organ failure assessment scores. A total of 40,693 patients were included in the investigation with 3227 (7.9%) receiving a platelet transfusion and 1065 (33.0%) for which platelet transfusion was prophylactic in nature. In propensity-matched analyses, 994 patients with prophylactic platelet transfusion were matched to those without a transfusion. Patients receiving prophylactic platelets had significantly higher red blood cell transfusion rates (odds ratio 7.5 [5.9-9.5]; P < .001), fewer ICU-free days (mean [standard deviation] 20.8 [9.1] vs 22.7 [8.3] days; P = .004), fewer hospital-free days (13.0 [9.7] vs 15.8 [9.4] days; P < .001), and less improvement in sequential organ failure assessment scores (mean decrease of 0.2 [3.6] vs 1.8 [3.3]; P < .001) in the subsequent 24 hours. These findings appeared robust, persisting in multiple predefined sensitivity analyses. Prophylactic administration of platelets in the critically ill was not associated with improved clinical outcomes, though residual confounding may exist. Further investigation of platelet transfusion strategies in this population is warranted.


The Essential Oil of Cymbopogon citratus Stapt and Carvacrol: An Approach of the Antitumor Effect on 7,12-Dimethylbenz-[α]-anthracene (DMBA)-Induced Breast Cancer in Female Rats.
C. citratus essential oil and carvacrol have shown an antitumor effect on breast tumor cell lines; the main objective of this research was to evaluate the antitumor effect of the essential oil of Cymbopogon citratus (EOCc) and carvacrol on 7,12-dimethylbenz [a] anthracene (DMBA)-induced breast cancer in female rats. Cancer was induced by a single administration of DMBA at dose of 80 mg/kg body weight (BW). A total of 54 female Holtzman rats were randomly assigned into 9 groups (n = 6). Group I: PS (Physiological saline); Group II: DMBA; Groups III, IV, and V: DMBA + EOCc at doses of 50, 100 and 200 mg/kg/day BW, respectively; Groups VI, VII, and VIII: DMBA + carvacrol at doses of 50, 100 and 200 mg/kg/day BW, respectively; and group IX: DMBA + EOCc + carvacrol at doses of 100 mg/kg/day BW. The treatment lasted 14 weeks. As results, EOCc showed a reduction in tumors as well as necrosis and mitosis. Animals treated with carvacrol did not show necrosis, mitosis, or infiltration. Carvacrol at dose of 100 mg/kg/day BW revealed a significant decrease in the cumulative tumor volume down to 0.11 ± 0.05 cm3 compared to 0.38 ± 0.04 cm3 of the DMBA group (p < 0.01). It is concluded that EOCc and carvacrol had an antitumor effect on DMBA-induced breast cancer in female rats.


Somatic symptom disorder in dermatology.
Somatic symptom disorder (SSD) is defined by the prominence of somatic symptoms associated with abnormal thoughts, feelings, and behaviors related to the symptoms, resulting in significant distress and impairment. Individuals with these disorders are more commonly encountered in primary care and other medical settings, including dermatology practice, than in psychiatric and other mental health settings. What defines the thoughts, feelings, and behaviors as abnormal is that they are excessive, that is, out of proportion to other patients with similar somatic symptoms, and that they result in significant distress and impairment. SSD may occur with or without the presence of a diagnosable dermatologic disorder. When a dermatologic disorder is present, SSD should be considered when the patient is worrying too much about his or her skin, spending too much time and energy on it, and especially if the patient complains of many nondermatologic symptoms in addition. The differential diagnosis includes other psychiatric disorders, including depression, anxiety disorders, delusions of parasitosis, and body dysmorphic disorder. This paper describes SSD and its applicability in dermatologic practice, with illustrative cases.


Telerehabilitation and emerging virtual reality approaches to stroke rehabilitation.
Stroke is the leading cause of permanent motor disability in the United States, and the rapidly aging population makes finding large-scale treatment solutions to this problem a national priority. Telerehabilitation is an emerging approach that is being used for the effective treatment of multiple diseases, and is beginning to show promise for stroke. The purpose of this review is to identify and highlight the areas of telerehabilitation that require the most research attention. Although there are many different forms of telerehabilitation approaches being attempted for stroke, the only approach that is currently showing moderate-strong evidence for efficacy is videogame-driven telerehabilitation (VGDT). However, targeted research is still required to determine the feasibility of VGDT: metrics regarding system usability, cost-effectiveness, and data privacy concerns still require major attention. VGDT is an emerging approach that shows enormous promise for stroke rehabilitation. Future studies should focus less on developing custom task controllers and therapy games and more on developing innovative, online data acquisition and analytics pipelines, as well as understanding the patient population so that the rehabilitation experience can be better customized.


Genetic diversity and relationships among Venezuelan equine encephalitis virus field isolates from Colombia and Venezuela.
During field studies of enzootic Venezuelan equine encephalitis (VEE) viruses associated with epizootic emergence, a large number of virus isolates were made in sylvatic foci of Venezuela and Colombia. To rapidly characterize these isolates, antigenic subtypes were determined by means of immunofluorescence and by single-strand conformational polymorphism (SSCP) analysis by use of an 856-bp fragment from the P62 gene, which we used to distinguish genetic variants. Representative isolates were sequenced to assess the sensitivity of SSCP to detect genetic differences. The SSCP analysis distinguished isolates differing by as little as 1 nucleotide; overall, differences of > or = 1 nucleotide were recognized 89% of the time, and the sensitivity to distinguish strains that differed by only 1 or 4 nucleotides was 17 and 57%, respectively. Phylogenetic analyses of representative sequences showed that all recent isolates from the Catatumbo region of western Venezuela and the middle Magdalena Valley of Colombia were closely related to epizootic subtype IAB and IC strains; strains from Yaracuy and Miranda States were more distantly related. Cocirculation of the same virus genotype in both Colombian and Venezuelan foci indicated that these viruses are readily transported between enzootic regions separated by > 300 km. The SSCP analysis appears to be a simple, fast, and relatively efficient method of screening VEE virus isolates to identify meaningful genetic variants.


Association of objective visual impairment with suicidal ideation and suicide attempts among adults aged ≥50 years in low/middle-income countries.
There is currently limited literature on the association between visual impairment and suicidal thoughts and behaviours, especially among older adults from low/middle-income countries (LMICs). Thus, we aimed to investigate the associations of objectively measured distance visual impairment with suicidal ideation and suicide attempts among adults aged ≥50 years from six LMICs and to identify potential mediators. Cross-sectional, community-based, nationally representative data from the WHO Study on global AGEing and adult health were analysed. Objective distance visual acuity was measured using the tumbling E logMAR chart, and vision impairment was categorised as none, mild, moderate and severe. Self-reported information on past 12-month suicidal ideation and suicide attempts was also collected. Multivariable logistic regression and mediation analysis were conducted. Data on 34 129 individuals aged ≥50 years (mean (SD) age, 62.4 (16.0) years; 47.9% men) were analysed. After adjustment for potential confounders, compared with no visual impairment, severe visual impairment was significantly associated with suicidal ideation (OR=9.50; 95% CI=2.47 to 36.52). Moderate and severe visual impairment were significantly associated with a 2.22 (95% CI=1.14 to 4.35) and 11.50 (95% CI=1.44 to 91.88) times higher odds of suicide attempts, respectively. Disability, poor self-rated health, mobility and loneliness explained 14.0%, 9.3%, 7.2% and 6.3% of the association between moderate/severe visual impairment and suicide attempts, respectively. Interventions to reduce suicidal ideation and suicide attempts among older adults with visual impairment in LMICs are required, targeting identified mediators, while using tested strategies for suicide prevention per se in LMICs may yield beneficial outcomes.


Histology of microscopic colitis-review with a practical approach for pathologists.
Microscopic colitis has emerged as a major cause of chronic watery non-bloody diarrhoea, particularly in elderly females. The term is used as an umbrella term to categorize a subgroup of colitides with distinct clinicopathological phenotypes and no significant endoscopic abnormalities. Lymphocytic colitis is defined by an increased number of surface intraepithelial lymphocytes, and collagenous colitis by a thickened collagen band underneath the surface epithelium. There is increased inflammation in the lamina propria, but only little or no crypt architectural distortion. Incomplete and variant forms showing less characteristic features have been reported under different names. The differential diagnosis mainly includes resolving infectious colitis and changes related to the intake of drugs such as non-steroidal anti-inflammatory drugs. Substantial clinical and histological overlap between lymphocytic and collagenous colitis has been described, raising the suspicion that the conditions are two histological manifestations of the same entity, possibly representing different manifestations during the disease course or different stages of disease development. In this review, we provide a practical approach for pathologists, with a focus on diagnostic criteria and differential diagnosis, and discuss recent insights into the pathogenesis of disease and the relationship with classic chronic inflammatory bowel disease, i.e. Crohn's disease and ulcerative colitis.


The origin of cultivated mangosteen (Garcinia mangostana L. var. mangostana): Critical assessments and an evolutionary-ecological perspective.
Mangosteen (Garcinia mangostana var. mangostana) is a popular tropical fruit, yet many aspects of its biology and evolutionary history are little known. Its origin remains contentious, although recent findings suggest G. mangostana L. var. malaccensis (Hook. f.) Nazre (synonym: G. malaccensis Hook. f.) as the sole progenitor. We review hypotheses on the origin of mangosteen and clarify points that have been affected by errors of fact and interpretation. The narrow focus and lack of detail in published results make their interpretation difficult. When possible, we support our interpretations with field observations and examination of herbarium specimens. We outline the main biological traits (e.g., dioecy, facultative apomixis, and polyploidy) of mangosteen and its wild relatives to infer traits that might have evolved during domestication of mangosteen. We find no clear indication that apomixis and polyploidy evolved during domestication. Polyploidy is known in the wild relatives, but apomixis has not yet been demonstrated. Also, we propose a testable new evolutionary-ecological framework that we call "Forest-Dusun Interface" to infer processes in the origin of mangosteen. Dusun (Malay) refers to subsistence orchards in this context. Lastly, we propose future studies to address identified knowledge gaps.


An attenuation-partition based iterative phase retrieval algorithm for in-line phase-contrast imaging.
For medical applications of the in-line phase-contrast x-ray imaging, phase retrieval is a crucial step for quantitative imaging such as reconstructing the 3-D distribution of tissue linear attenuation coefficients and refraction indices. The conventional phase retrieval algorithms, such as the transport of intensity equation (TIE) based algorithms, are not robust against the quantum noise that appears in acquired images due to the radiation dose constraints in medical imaging. In this work a new attenuation-partition based iterative phase retrieval algorithm is proposed. This new algorithm takes advantage of the correlation between the attenuation and phase-shift, and is much robust against noise in acquired images. Phase retrieval results from experimental images show that this new iterative algorithm is fast and robust, and it has good potential for medical x-ray imaging applications.


Extracellular cation sensing by the enterocyte: prediction of a novel divalent cation "receptor".
We report that the divalent cation Ni2+ elicits elevations in the cytosolic free Ca2+ concentration ([Ca2+]) in cultured enterocytes. These elevations were monophasic, each response consisting of a rapid initial transient rise of cytosolic [Ca2+] to a peak value followed by an exponential decline. The magnitude of the cytosolic [Ca2+] elevation varied with the concentration of applied Ni2+. In some cells, a single application of Ni2+ induced oscillatory changes in cytosolic [Ca2+]. There was also evidence for use-dependent inactivation: a conditioning application of Ni2+ substantially attenuated the response resulting from its subsequent application. Our findings thus demonstrate the existence of a divalent cation-sensing "receptor" on the enterocyte. This putative receptor may play a role in regulating mineral absorption across the enterocyte membrane.


Signaling lymphocyte activation molecule regulates development of colitis in mice.
Signaling lymphocyte activation molecule (Slamf)1 is a co-stimulatory receptor on T cells and regulates cytokine production by macrophages and dendritic cells. Slamf1 regulates microbicidal mechanisms in macrophages, therefore we investigated whether the receptor affects development of colitis in mice. We transferred CD45RB(hi) CD4(+) T cells into Rag(-/-) or Slamf1(-/-)Rag(-/-) mice to induce colitis. We also induced colitis by injecting mice with an antibody that activates CD40. We determined the severity of enterocolitis based on disease activity index, histology scores, and levels of cytokine production, and assessed the effects of antibodies against Slamf1 on colitis induction. We quantified migration of monocytes and macrophage to inflamed tissues upon induction of colitis or thioglycollate-induced peritonitis and in response to tumor necrosis factor-α in an air-pouch model of leukocyte migration. Colitis was reduced in Slamf1(-/-)Rag(-/-) mice, compared with Rag(-/-) mice, after transfer of CD45RB(hi) CD4(+) T cells or administration of the CD40 agonist. The numbers of monocytes and macrophages were reduced in inflamed tissues of Slamf1(-/-)Rag(-/-) mice, compared with Rag(-/-) mice, after induction of colitis and other inflammatory disorders. An antibody that inhibited Slamf1 reduced the level of enterocolitis in Rag(-/-) mice. Slamf1 contributes to the development of colitis in mice. It appears to indirectly regulate the appearance of monocytes and macrophages in inflamed intestinal tissues. Antibodies that inhibit Slamf1 reduce colitis in mice, so human SLAMF1 might be a therapeutic target for inflammatory bowel disease.


Molecular-Level Interactions between Engineered Materials and Cells.
Various recent experimental observations indicate that growing cells on engineered materials can alter their physiology, function, and fate. This finding suggests that better molecular-level understanding of the interactions between cells and materials may guide the design and construction of sophisticated artificial substrates, potentially enabling control of cells for use in various biomedical applications. In this review, we introduce recent research results that shed light on molecular events and mechanisms involved in the interactions between cells and materials. We discuss the development of materials with distinct physical, chemical, and biological features, cellular sensing of the engineered materials, transfer of the sensing information to the cell nucleus, subsequent changes in physical and chemical states of genomic DNA, and finally the resulting cellular behavior changes. Ongoing efforts to advance materials engineering and the cell-material interface will eventually expand the cell-based applications in therapies and tissue regenerations.


Di-n-butyl phthalate modifies PMA-induced macrophage differentiation of THP-1 monocytes via PPARγ.
The present study examined the effects of di-n-butyl phthalate (DBP) on phorbol myristate acetate (PMA)-induced macrophage differentiation of THP-1 monocytes, determined by morphological classification and flow cytometry. Focusing on the expression of the surface marker CD36, the potential role of peroxisome proliferator-activated receptor gamma (PPARγ) was examined using various PPARγ agonists and antagonists. As the PPARγ ligand-binding domain contains multiple ligand-binding sites (LBS), agonist and antagonists targeting the different sites were used. DBP accelerated PMA-induced morphological changes and increased expression of CD36, although to a lesser degree than the PPARγ agonists rosiglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). A proteomics screening revealed that DBP enhanced the expression of PPARγ-regulated proteins. During combined exposures, DBP partly attenuated the effect of rosiglitazone, an agonist binding reversibly to PPARγ's canonical LBS. In contrast, DBP increased expression of CD36 in combination with 15d-PGJ2 which binds irreversibly to the canonical LBS. Thus, DBP appears to interact with both the canonical and alternative LBS. Accordingly, the antagonist GW9662, which binds to the canonical LBS, only partly reduced the DBP-induced CD36 expression, while the dual-site antagonist SR16832 completely blocked the effects of DBP. Overall, the results show that DBP modifies PMA-induced differentiation of THP-1 cells through interaction with PPARγ.


RNA-binding proteins control gene expression and cell fate in the immune system.
RNA-binding proteins (RBPs) are essential for the development and function of the immune system. They interact dynamically with RNA to control its biogenesis and turnover by transcription-dependent and transcription-independent mechanisms. In this Review, we discuss the molecular mechanisms by which RBPs allow gene expression changes to occur at different speeds and to varying degrees, and which RBPs regulate the diversity of the transcriptome and proteome. These proteins are nodes for integration of transcriptional and signaling networks and are intimately linked to intermediary metabolism. They are essential components of regulatory feedback mechanisms that maintain immune tolerance and limit inflammation. The role of RBPs in malignancy and autoimmunity has led to their emergence as targets for the development of new therapeutic modalities.


Shape completion time depends on the size of the occluded region.
Observers made speeded discriminations of whole, occluded, and mosaic shapes. Shape matching times increased with the amount of occluded shape (Experiment 1), as did the time to merely discriminate 2 shapes (Experiments 2-4). By contrast, the time to judge the shape of the visible portion decreased with larger occluded regions (Experiments 5-7). Experiments 3 and 6 used motion parallax to show that different perceptual operations are involved in discriminating occluded versus mosaic shapes. Experiments 4 and 7 showed that shape completion was unaffected by spatial attention. Results suggest that shape completion is a rapid and obligatory aspect of perception. However, they also show that the time course of completion varies with the size of the hidden region.


Structure and reactivity of the first-row d-block metal-superoxo complexes.
In the first-row of d-block metals, ten elements are included, such as scandium (Sc, 3d1), titanium (Ti, 3d2), vanadium (V, 3d3), chromium (Cr, 3d54s1), manganese (Mn, 3d5), iron (Fe, 3d6), cobalt (Co, 3d7), nickel (Ni, 3d8), copper (Cu, 3d104s1) and zinc (Zn, 3d10). The synthesis, characterization, and reactivity of first-row d-block metal-superoxo complexes are discussed together with the structures of the end-on (η1) and side-on (η2) metal-superoxo complexes in this review article. Electron transfer from electron donors to O2 is enhanced by binding of Sc3+ to produce an end-on type Sc(iii)-superoxo complex. Metal-superoxo complexes such as Ti(iv)-superoxo, oxovanadium(v)-superoxo, Cr(iii)-superoxo, Fe(iii)-superoxo, Co(iii)-superoxo, Ni(iii)-superoxo and Cu(ii)-superoxo species generally undergo hydrogen atom transfer reactions. A Cr(iii)-superoxo complex undergoes not only hydrogen atom transfer but also oxygen atom transfer reactions. In the presence of protons (e.g., trifluoromethanesulfonic acid, HOTf), much enhanced acid catalysis was observed in oxygen atom transfer reactions from a nonheme Cr(iii)-superoxo complex, [(Cl)(TMC)CrIII(O2)]+, to thioanisole. The enhanced reactivity of [(Cl)(TMC)CrIII(O2)]+ by HOTf results from proton-coupled electron transfer (PCET) from electron donors, including thioanisole, to [(Cl)(TMC)CrIII(O2)]+. A manganese(iv)-superoxo complex plays a very important role in thermal and photoinduced dioxygen activation by a Mn(iii) corrolazine complex. A metal-superoxide complex using the last element in the first-row of transition metals, that is a Zn(ii)-superoxide complex, is produced to accelerate the reduction of O2˙- in a SOD (superoxide dismutase) model.


Main-chain polyacetal conjugates with HIF-1 inhibitors: temperature-responsive, pH-degradable drug delivery vehicles.
Main-chain polymer-drug conjugates are prepared from polyacetals (PA) and three hydrophobic diol-based HIF-1 inhibitors. The new conjugates are temperature-responsive with lower critical solution temperature (LCST) behavior and are intrinsically pH-degradable. While soluble in plasma at room temperature, they lose solubility above a target temperature that can be adjusted to virtually any temperature of physicological interest, providing mechanisms for site-specific delivery by active thermal targeting or temperature-induced gelation. The reverse phase transition temperature can be precisely tuned by proper choice of four structural variables that characterize the amphiphilic diol and divinyl ether monomers used in the synthesis, or by adjusting the content of drug incorporated within the polymer. These main-chain PA-drug conjugates also allow for site-specific controlled release as they degrade in acidic microenvironments such as tumors. The degradation rates increase with decreasing pH, degradation products are neutral, and pristine drug is released, without any remnants of the conjugation chemistry.


Reduced posterior hippocampal volume in posttraumatic stress disorder.
Hippocampal volume is reduced in posttraumatic stress disorder (PTSD). In the present study, we sought to determine whether volume loss is homogenously distributed or confined to a certain part of the structure. Twenty-two adult outpatients with PTSD (11 after prolonged prepubertal trauma and 11 after single adult trauma) and 22 matched healthy subjects were scanned at the National Institute of Mental Health using high-resolution 3T magnetic resonance imaging between September 2003 and August 2004. PTSD diagnosis was conferred using the Structured Clinical Interview for DSM-IV. Volumes of whole, anterior, and posterior hippocampus and subiculum were compared between groups. Total hippocampal volume was lower in patients with PTSD (p = .02), with a significant diagnosis by hippocampal-subregion interaction (p = .02). Post hoc analysis revealed significantly smaller posterior hippocampi in PTSD (p = .006), with no difference in the volumes of anterior hippocampus or subiculum. No volume differences were found between PTSD participants with prolonged childhood abuse compared to single adult trauma exposure. The posterior hippocampus has been associated with storage, processing, and retrieval of spatiotemporal memories, central to the protective function of fear conditioning. Volume deficit in the posterior hippocampus may indicate malfunction in this faculty, leading to the exaggerated conditioned fear response observed in PTSD.


A prospective cohort study investigating associations between hyperemesis gravidarum and cognitive, behavioural and emotional well-being in pregnancy.
To investigate the association between hyperemesis gravidarum and altered cognitive, behavioural and emotional well-being in pregnancy. The study cohort consisted of 3423 nulliparous women recruited in the Screening for Pregnancy Endpoints (SCOPE) study performed in Auckland, New Zealand; Adelaide, Australia; Cork, Ireland; Manchester and London, United Kingdom between November 2004 and August 2008. Women were interviewed at 15±1 weeks' gestation and at 20±1weeks' gestation. Women with a diagnosis of hyperemesis gravidarum (HG) were compared with women who did not have a diagnosis of HG. Main outcome measures included the Short form State- Trait Anxiety Inventory (STAI) score (range 6-24), Perceived Stress Scale score (PSS, range 0-30), Edinburgh Postnatal Depression Scale (EPDS) score (range 0-30 or categories a-c) and behavioural responses to pregnancy score (limiting/resting [range 0-20] and all-or-nothing [range 0-28]). During the study period 164 women suffered from HG prior to their 15 week interview. Women with HG had significantly higher mean STAI, PSS, EPDS and limiting response to pregnancy scores compared to women without HG. These differences were observed at both 15±1 and 20±1 weeks' of gestation. The magnitude of these differences was greater in women with severe HG compared to all women with HG. Women with severe HG had an increased risk of having a spontaneous preterm birth compared with women without HG (adjusted OR 2.6 [95% C.I. 1.2, 5.7]). This is the first large prospective study on women with HG. Women with HG, particularly severe HG, are at increased risk of cognitive, behavioural and emotional dysfunction in pregnancy. Women with severe HG had a higher rate of spontaneous preterm birth compared to women without HG. Further research is required to determine whether the provision of emotional support for women with HG is beneficial.


Magnetic tweezers-based 3D microchannel electroporation for high-throughput gene transfection in living cells.
A novel high-throughput magnetic tweezers-based 3D microchannel electroporation system capable of transfecting 40 000 cells/cm(2) on a single chip for gene therapy, regenerative medicine, and intracellular detection of target mRNA for screening cellular heterogeneity is reported. A single cell or an ordered array of individual cells are remotely guided by programmable magnetic fields to poration sites with high (>90%) cell alignment efficiency to enable various transfection reagents to be delivered simultaneously into the cells. The present technique, in contrast to the conventional vacuum-based approach, is significantly gentler on the cellular membrane yielding >90% cell viability and, moreover, allows transfected cells to be transported for further analysis. Illustrating the versatility of the system, the GATA2 molecular beacon is delivered into leukemia cells to detect the regulation level of the GATA2 gene that is associated with the initiation of leukemia. The uniform delivery and a sharp contrast of fluorescence intensity between GATA2 positive and negative cells demonstrate key aspects of the platform for gene transfer, screening and detection of targeted intracellular markers in living cells.


Simple sari cloth filtration of water is sustainable and continues to protect villagers from cholera in Matlab, Bangladesh.
A simple method for filtering water to reduce the incidence of cholera was tested in a field trial in Matlab, Bangladesh, and proved effective. A follow-up study was conducted 5 years later to determine whether the filtration method continued to be employed by villagers and its impact on the incidence of cholera. A total of 7,233 village women collecting water daily for their households in Bangladesh were selected from the same study population of the original field trial for interviewing. Analysis of the data showed that 31% of the women used a filter of which 60% used sari filters for household water. Results showed that sari filtration not only was accepted and sustained by the villagers and benefited them, including their neighbors not filtering water, in reducing the incidence of cholera, the latter being an unexpected benefit.


Applications of peptide and protein-based materials in bionanotechnology.
In this critical review we highlight recent advances in the use of peptide- and protein-related materials as smart building blocks in nanotechnology. Peptides and proteins can be very practical for new material synthesis and device fabrications. For example, peptides and proteins have superior specificity for target binding as seen in the antibody recognition and this biological recognition function can be used to assemble them into specific structures and shapes in large scale, as observed in the S-layer protein assembly. Collagens are assembled from triple helix peptides in micron-size with precise recognition between peptides and these biological assemblies can undergo smart structural change with pH, ionic strength, temperature, electric/magnetic fields. In addition, assemblies of peptides can template complex 3D crystallization processes with catalytic function, thus enabling to grow various materials in physiological conditions at low temperature in aqueous solution. The biomimetic growth of nanomaterials in aqueous solution is extremely useful when they are applied to therapeutics and medical imaging in vivo since these nanomaterials will be well dispersed in bodies. Peptides also play significant roles in signal transduction pathways in cells. For example, neuropeptides are used as neurotransmitters between synapses and these peptides bind receptors on the surface of cells to cascade the signal transduction. These versatile functions of peptides are extremely practical and here we discuss them with examples of relevant applications such as nanoreactors, sensors, electronics, and stimulus-responsive materials. It should be noted that peptide/protein assemblies can be applied to build up micron-scale materials that still feature excellent nano-scale ensembles, which essentially bridges the nano-world and the micro-world (86 references).


Exercise training increases sarcolemmal and mitochondrial fatty acid transport proteins in human skeletal muscle.
Fatty acid oxidation is highly regulated in skeletal muscle and involves several sites of regulation, including the transport of fatty acids across both the plasma and mitochondrial membranes. Transport across these membranes is recognized to be primarily protein mediated, limited by the abundance of fatty acid transport proteins on the respective membranes. In recent years, evidence has shown that fatty acid transport proteins move in response to acute and chronic perturbations; however, in human skeletal muscle the localization of fatty acid transport proteins in response to training has not been examined. Therefore, we determined whether high-intensity interval training (HIIT) increased total skeletal muscle, sarcolemmal, and mitochondrial membrane fatty acid transport protein contents. Ten untrained females (22 +/- 1 yr, 65 +/- 2 kg; .VO(2peak): 2.8 +/- 0.1 l/min) completed 6 wk of HIIT, and biopsies from the vastus lateralis muscle were taken before training, and following 2 and 6 wk of HIIT. Training significantly increased maximal oxygen uptake at 2 and 6 wk (3.1 +/- 0.1, 3.3 +/- 0.1 l/min). Training for 6 wk increased FAT/CD36 at the whole muscle (10%) and mitochondrial levels (51%) without alterations in sarcolemmal content. Whole muscle plasma membrane fatty acid binding protein (FABPpm) also increased (48%) after 6 wk of training, but in contrast to FAT/CD36, sarcolemmal FABPpm increased (23%), whereas mitochondrial FABPpm was unaltered. The changes on sarcolemmal and mitochondrial membranes occurred rapidly, since differences (< or =2 wk) were not observed between 2 and 6 wk. This is the first study to demonstrate that exercise training increases fatty acid transport protein content in whole muscle (FAT/CD36 and FABPpm) and sarcolemmal (FABPpm) and mitochondrial (FAT/CD36) membranes in human skeletal muscle of females. These results suggest that increases in skeletal muscle fatty acid oxidation following training are related in part to changes in fatty acid transport protein content and localization.


Estimating the cost of diabetes mellitus-related events from inpatient admissions in Sweden using administrative hospitalization data.
To estimate short- and long-term costs of inpatient hospitalization in Sweden for major diabetes mellitus-related events. Costs were estimated using administrative hospital data from the Swedish National Board of Health and Welfare, which is linked to the Swedish National Diabetes Register. Data were available for 179 749 patients with diabetes in Sweden from 1998 to 2003 (mean and median duration of 6 years' follow-up). Costing of inpatient admissions was based on Nordic diagnosis-related groups (NordDRG). Multiple regression analysis (linear and generalizing estimating equation models) was used to estimate inpatient care costs controlling for age, sex and co-morbidities. The data on hospitalizations were converted to costs (euro) using 2003 exchange rates. The average annual costs (linear model) associated with inpatient admissions for a 60-year-old male in the year the first event first occurred were as follows: euro6488 (95% CI 5034, 8354) for diabetic coma; euro6850 (95% CI 6514, 7204) for heart failure; euro7853 (95% CI 7559, 8144) for non-fatal stroke; euro8121 (95% CI 7104, 9128) for peripheral circulatory complications; euro8736 (95% CI 8474, 9001) for non-fatal myocardial infarction (MI); euro10 360 (95% CI 10 085, 10 643) for ischaemic heart disease; euro11 411 (95% CI 10 298, 12 654) for renal failure; and euro14 949 (95% CI 13 849, 16 551) for amputation. On average, the costs were higher when co-morbidity was accounted for (e.g. MI with co-morbidity was twice as costly as MI alone). Average hospital inpatient costs associated with common diabetes-related events can be estimated using panel data regression methods. These could assist in modelling of long-term costs of diabetes and in evaluating the cost effectiveness of improving care.


Investigation of the limitations of the highly pixilated CdZnTe detector for PET applications.
We are investigating the feasibility of a high resolution positron emission tomography (PET) insert device based on the CdZnTe detector with 350 µm anode pixel pitch to be integrated into a conventional animal PET scanner to improve its image resolution. In this paper, we have used a simplified version of the multi pixel CdZnTe planar detector, 5 mm thick with 9 anode pixels only. This simplified 9 anode pixel structure makes it possible to carry out experiments without a complete application-specific integrated circuits readout system that is still under development. Special attention was paid to the double pixel (or charge sharing) detections. The following characteristics were obtained in experiment: energy resolution full-width-at-half-maximum (FWHM) is 7% for single pixel and 9% for double pixel photoelectric detections of 511 keV gammas; timing resolution (FWHM) from the anode signals is 30 ns for single pixel and 35 ns for double pixel detections (for photoelectric interactions only the corresponding values are 20 and 25 ns); position resolution is 350 µm in x,y-plane and ∼0.4 mm in depth-of-interaction. The experimental measurements were accompanied by Monte Carlo (MC) simulations to find a limitation imposed by spatial charge distribution. Results from MC simulations suggest the limitation of the intrinsic spatial resolution of the CdZnTe detector for 511 keV photoelectric interactions is 170 µm. The interpixel interpolation cannot recover the resolution beyond the limit mentioned above for photoelectric interactions. However, it is possible to achieve higher spatial resolution using interpolation for Compton scattered events. Energy and timing resolution of the proposed 350 µm anode pixel pitch detector is no better than 0.6% FWHM at 511 keV, and 2 ns FWHM, respectively. These MC results should be used as a guide to understand the performance limits of the pixelated CdZnTe detector due to the underlying detection processes, with the understanding of the inherent limitations of MC methods.


Timing of laparoscopic surgery in gallstone pancreatitis.
To study the effect of the timing of laparoscopic cholecystectomy following acute gallstone pancreatitis. University-based county teaching hospital. Retrospective case series. One hundred forty-two patients with gallstone pancreatitis treated by laparoscopic cholecystectomy between April 1991 and September 1993. There were 16 men and 126 women, with a mean age of 39.5 years. The mean serum amylase level at admission was 1616 U/L. All patients were operated on more than 48 hours after admission, after clinical and biochemical resolution of pancreatitis. Preoperative endoscopic retrograde cholangiopancreatography was performed in 25 patients (more than 48 hours after admission), with common bile duct stones being identified and removed in 10. Twenty patients had three or more Ranson's criteria. Of these, nine had laparoscopic cholecystectomy attempted within the first week of admission. Six (67%) of these patients required conversion to open procedures (two for common bile duct exploration, one for repair of a common hepatic duct injury, and three for anatomic distortion due to inflammation). The mean postoperative stay of the nine patients was 5.4 days. The other 11 patients with three or more Ranson's criteria were operated on after 1 week, and only two required conversion to open cholecystectomy (18%). The mean postoperative stay in these 11 patients was 2.3 days. The difference in conversion rate approached but did not reach statistical significance (P = .08). The postoperative stay, however, was significantly shorter in the group of patients who underwent late operations (P = .03). There were 122 patients with fewer than three Ranson's criteria. In this group, there was no difference in length of postoperative stay between patients operated on earlier and those operated on later (2.4 vs 3.9 days; P = .49; n = 74 and n = 48, respectively). Of these 122 procedures, eight were converted to open procedures (6.6%). There was no significant difference in conversion rates in these patients regardless of whether they were operated on earlier or later. Based on these data, we believe, first, that laparoscopic cholecystectomy is safe in patients recovering from gallstone pancreatitis (mortality rate, 0%; bile duct injury, 0.7%). Furthermore, early operation can safely be recommended in patients with mild pancreatitis. However, in patients with three or more Ranson's criteria, operation during the first week following admission is associated with an increase in operative complications, an increased rate of conversion, and longer postoperative stays.


Cofilin Loss in Drosophila Muscles Contributes to Muscle Weakness through Defective Sarcomerogenesis during Muscle Growth.
Sarcomeres, the fundamental contractile units of muscles, are conserved structures composed of actin thin filaments and myosin thick filaments. How sarcomeres are formed and maintained is not well understood. Here, we show that knockdown of Drosophila cofilin (DmCFL), an actin depolymerizing factor, disrupts both sarcomere structure and muscle function. The loss of DmCFL also results in the formation of sarcomeric protein aggregates and impairs sarcomere addition during growth. The activation of the proteasome delays muscle deterioration in our model. Furthermore, we investigate how a point mutation in CFL2 that causes nemaline myopathy (NM) in humans affects CFL function and leads to the muscle phenotypes observed in vivo. Our data provide significant insights to the role of CFLs during sarcomere formation, as well as mechanistic implications for disease progression in NM patients.


[Sleep disorders in dementia patients].
Dementia is characterized by cognitive and also behavioral and psychological symptoms of dementia (BPSD). The most prominent BPSD are depression and apathy but sleep disorders also complicate the clinical course of dementia. These symptoms are a severe burden for patients and caregivers and are difficult to treat partly due to comorbidities. Common sleep disorders in dementia are insomnia, hypersomnia, circadian rhythm alterations and aberrant nocturnal motor behavior. Sleep duration and rapid eye movement (REM) sleep are reduced. The diagnostic assessment of sleep disorders should include an evaluation of the underlying risk factors and a detailed sleep history for which several assessment instruments are available. The therapy of sleep disorders of dementia is primarily nonpharmacological: sleep counseling, sleep hygiene regulation, relaxation and psychotherapy techniques are given priority. Pharmacological treatment often has severe side effects in this elderly, vulnerable population and can only be considered if other nonpharmacological options have been unsuccessful. The application of medication should be limited in time and dosage. The pharmacological therapeutic options are critically discussed in detail.


Influence of slope steepness, foot position and turn phase on plantar pressure distribution during giant slalom alpine ski racing.
The purpose of this study was to investigate the evolution of ground reaction force during alpine skiing turns. Specifically, this study investigated how turn phases and slope steepness affected the whole foot normal GRF pattern while performing giant slalom turns in a race-like setting. Moreover, the outside foot was divided into different plantar regions to see whether those parameters affected the plantar pressure distribution. Eleven skiers performed one giant slalom course at race intensity. Runs were recorded synchronously using a video camera in the frontal plane and pressure insoles under both feet's plantar surface. Turns were divided according to kinematic criteria into four consecutive phases: initiation, steering1, steering2 and completion; both steering phases being separated by the gate passage. Component of the averaged Ground Reaction Force normal to the ski's surface([Formula: see text], /BW), and Pressure Time Integral relative to the entire foot surface (relPTI, %) parameters were calculated for each turn phases based on plantar pressure data. Results indicated that [Formula: see text] under the total foot surface differed significantly depending on the slope (higher in steep sections vs. flat sections), and the turn phase (higher during steering2 vs. three other phases), although such modifications were observable only on the outside foot. Moreover, [Formula: see text] under the outside foot was significantly greater than under the inside foot.RelPTI under different foot regions of the outside foot revealed a global shift from forefoot loading during initiation phase, toward heel loading during steering2 phase, but this was dependent on the slope studied. These results suggest a differentiated role played by each foot in alpine skiing turns: the outside foot has an active role in the turning process, while the inside foot may only play a role in stability.


Pathway analysis of smoking quantity in multiple GWAS identifies cholinergic and sensory pathways.
Cigarette smoking is a common addiction that increases the risk for many diseases, including lung cancer and chronic obstructive pulmonary disease. Genome-wide association studies (GWAS) have successfully identified and validated several susceptibility loci for nicotine consumption and dependence. However, the trait variance explained by these genes is only a small fraction of the estimated genetic risk. Pathway analysis complements single marker methods by including biological knowledge into the evaluation of GWAS, under the assumption that causal variants lie in functionally related genes, enabling the evaluation of a broad range of signals. Our approach to the identification of pathways enriched for multiple genes associated with smoking quantity includes the analysis of two studies and the replication of common findings in a third dataset. This study identified pathways for the cholinergic receptors, which included SNPs known to be genome-wide significant; as well as novel pathways, such as genes involved in the sensory perception of smell, that do not contain any single SNP that achieves that stringent threshold.


Crystal chemistry of Mg substitution in NaMnPO4 olivine: concentration limit and cation distribution.
Metal ion substitution in phospho-olivines is an effective way to improve their performance as electrode materials in lithium ion and alternative sodium ion batteries. In this contribution, we examine in detail the crystal structure of Mg-substituted NaMnPO4. The preferential occupancy of the alkaline M1 position by Mg2+ ions has been found for the first time - a phenomenon which appears to be opposite to the case of Mg-substituted LiMnPO4, where Mg2+ and Mn2+ reside in the M2 position. Mg solubility in NaMnPO4 is limited in the range of 0.10 < Mg/(Mg + Mn) < 0.15 mole part. Mg-substituted NaMnPO4 is prepared at 200 °C by ionic exchange reactions involving the participation of mixed dittmarite salts, KMn1-xMgxPO4·H2O. The structural aspects of Mg substitution in NaMnPO4 are studied by combination of powder X-ray diffraction using the Rietveld analysis with IR and electron paramagnetic resonance spectroscopy. The morphologies of precursors and target olivines are examined by means of SEM and EDS. In order to understand the crystal chemistry of Mg-substituted NaMnPO4, we use solid solutions between LiMnPO4 and LiMgPO4 as references. The reference compositions of LiMn1-xMgxPO4 are prepared using the same KMn1-xMgxPO4·H2O precursors as in the case of Mg-substituted NaMnPO4.


Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation.
This review focused on the treatment-emergent mania/hypomania (TEM) associated with repetitive transcranial magnetic stimulation (rTMS) treatment of depression. English-language literature published from 1966-2006 and indexed in Medline was searched. Ten of 53 randomized controlled trials on rTMS treatment of depression specifically addressed TEM. The pooled TEM rate is 0.84% for the active treatment group and 0.73% for the sham group. The difference is not statistically significant. Along with case reports, a total of 13 cases of TEM associated with rTMS treatment of depression have been published. Most of these patients were diagnosed with bipolar disorder and the majority of patients experiencing TEM took medication concurrent with rTMS. The parameters of rTMS used in these cases were scattered over the spectrum of major parameters explored in previous studies. Most train durations and intervals were within the published safety guidelines of the field. Reducing the frequency of sessions from two per day to one per day might be associated with a lower likelihood of TEM recurrence. The severity of manic symptoms varied significantly, but all cases responded to treatment that included a decrease or discontinuation of antidepressant and/or rTMS treatment and/or use of anti-manic medication. Current data suggests that rTMS treatment carries a slight risk of TEM that is not statistically higher than that associated with sham treatment. More systematic studies are needed to better understand TEM associated with rTMS. Special precautions and measures should be adopted to prevent, monitor, and manage TEM in research and practice.


The influence of different osteosynthesis configurations with locking compression plates (LCP) on stability and fracture healing after an oblique 45° angle osteotomy.
Locking compression plates are used in various configurations with lack of detailed information on consequent bone healing. In this in vivo study in sheep 5 different applications of locking compression plate (LCP) were tested using a 45° oblique osteotomy simulating simple fracture pattern. 60 Swiss Alpine sheep where assigned to 5 different groups with 12 sheep each (Group 1: interfragmentary lag screw and an LCP fixed with standard cortex screws as neutralisation plate; Group 2: interfragmentary lag screw and LCP with locking head screws; Group 3: compression plate technique (hybrid construct); Group 4: internal fixator without fracture gap; Group 5: internal fixator with 3mm gap at the osteotomy site). One half of each group (6 sheep) was monitored for 6 weeks, and the other half (6 sheep) where followed for 12 weeks. X-rays at 3, 6, 9 and 12 weeks were performed to monitor the healing process. After sacrifice operated tibiae were tested biomechanically for nondestructive torsion and compared to the tibia of the healthy opposite side. After testing specimens were processed for microradiography, histology, histomorphometry and assessment of calcium deposition by fluorescence microscopy. In all groups bone healing occurred without complications. Stiffness in biomechanical testing showed a tendency for higher values in G2 but results were not statistically significant. Values for G5 were significantly lower after 6 weeks, but after 12 weeks values had improved to comparable results. For all groups, except G3, stiffness values improved between 6 and 12 weeks. Histomorphometrical data demonstrate endosteal callus to be more marked in G2 at 6 weeks. All five configurations resulted in undisturbed bone healing and are considered safe for clinical application.


Williams syndrome and memory: a neuroanatomic and cognitive approach.
Williams Syndrome (WS) is described as displaying a dissociation within memory systems. As the integrity of hippocampal formation (HF) is determinant for memory performance, we examined HF volumes and its association with memory measures in a group of WS and in a typically development group. A significantly reduced intracranial content was found in WS, despite no differences were observed for HF absolute volumes between groups. When volumes were normalized, left HF was increased in WS. Moreover, a lack of the normal right > left HF asymmetry was observed in WS. No positive correlations were found between volumetric and neurocognitive data in WS. In sum, a relative enlargement of HF and atypical patterns of asymmetry suggest abnormal brain development in WS.


Site-directed mutagenesis at aspartate and glutamate residues of xylanase from Bacillus pumilus.
To elucidate the reaction mechanism of xylanase, the identification of amino acids essential for its catalysis is of importance. Studies have indicated the possibility that the reaction mechanism of xylanase is similar to that of hen's egg lysozyme, which involves acidic amino acid residues. On the basis of this assumption, together with the three-dimensional structure of Bacillus pumilus xylanase and its amino acid sequence similarity to other xylanases of different origins, three acidic amino acids, namely Asp-21, Glu-93 and Glu-182, were selected for site-directed mutagenesis. The Asp residue was altered to either Ser or Glu, and the Glu residues to Ser or Asp. The purified mutant xylanases D21E, D21S, E93D, E93S, E182D and E182S showed single protein bands of about 26 kDa on SDS/PAGE. C.d. spectra of these mutant enzymes show no effect on the secondary structure of xylanase, except that of D21E, which shows a little variation. Furthermore, mutations of Glu-93 and Glu-182 resulted in a drastic decrease in the specific activity of xylanase as compared with mutation of Asp-21. On the basis of these results we propose that Glu-93 and Glu-182 are the best candidates for the essential catalytic residues of xylanase.


Effect of meteorological factors and air pollutants on out-of-hospital cardiac arrests: a time series analysis.
We aimed to investigate the effects of meteorological factors and air pollutants on out-of-hospital cardiac arrest (OHCA) according to seasonal variations because the roles of these factors remain controversial to date. A total of 38 928 OHCAs of cardiac origin that occurred within eight metropolitan areas between 2012 and 2016 were identified from the Korean nationwide emergency medical service database. A time series multilevel approach based on Poisson analysis following a Granger causality test was used to analyse the influence of air pollution and 13 meteorological variables on OHCA occurrence. Particulate matter (PM) ≤2.5 µm (PM2.5), average temperature, daily temperature range and humidity were significantly associated with a higher daily OHCA risk (PM2.5: 1.59%; 95% CI: 1.51% to 1.66% per 10µg/m3, average temperature 0.73%, 95% CI: 0.63% to 0.84% per 1°C, daily temperature range: 1.05%, 95% CI: 0.63% to 1.48% per 1°C, humidity -0.48, 95% CI: -0.40 to -0.56 per 1%) on lag day 1. In terms of the impact of these four risk factors in different seasons, average temperature and daily temperature range were highly associated with OHCA in the summer and winter, respectively. However, only PM2.5 elevation (to varying extents) was an independent and consistent OHCA risk factor irrespective of the season. PM2.5, average temperature, daily temperature range and humidity were independently associated with OHCA occurrence in a season-dependent manner. Importantly, PM2.5 was the only independent risk factor for OHCA occurrence irrespective of seasonal changes.


Profile of gynecologic malignancies reported at a tertiary care center in India over the past decade: comparative evaluation with international data.
Comprehensive statistics on gynecologic malignancies reported from India are deficient. This study was performed to ascertain the profile of gynecologic cancers reported at our center regarding incidence, histologic subtypes, frequency of involvement at various sites and stage at presentation. We endeavored to compare our data with gynecologic cancers reported at other national and international centers. Retrospective review of records of gynecologic cancers obtained from Departments of Pathology and Gynecology, at a tertiary care center, Delhi from January 2000 to December 2009 was performed. Comparison with international data was performed using Fishcher's exact test and chi square tests. A total of 1315 gynecologic cancers were reported. Cervical malignancies were the commonest at our center as compared to uterine malignancies in data from Surveillance, Epidemiology, and End Results (SEER) Program of United States and European Union. All malignancies except cervical cancers affected a younger age group at our center than in the US population. Cervical cancer presented at a relatively more advanced stage, ovarian cancers at more localized stages, whereas uterine cancers presented at similar stages as compared to Western data. Our registry presents composite data from North India. Higher age and advanced stage at presentation of cervical cancers suggests lacunae in screening programs available. Ovarian malignancies were more localized at presentation than in the Western population for which environmental or genetic factors may be causative.


Generating dialogical practices in mental health: experiences from southern norway, 1998-2008.
In Norway and many other countries, political guidelines prescribe the development of mental health strategies with both a service user's perspective and a treatment system established by the local authority. The development of new strategies frequently involves challenges regarding procedures and treatment as well as a view of knowledge and humanity. Dialogical practices might provide a solution for these challenges not only because of its procedures but also due to its attitudes toward service users. The aim is to explore the implementation of three dialogical practice programs in Southern Norway from 1998 to 2008 and to critically analyze and discuss the authors' experiences during the implementation process. Three different programs of dialogical practices were initiated, established, and evaluated within the framework of participatory action research. Sustainable changes succeed individually and organizationally when all participants engage as partners during the implementation of new mental health practices. Generating dialogic practice requires shared understanding of the Open Dialogue Approach (ODA) and collaboration between professional networks and among the leaders. Developing a collaboration area that includes service users in all stages of the projects was one of the essential implementation factors. Other factors involved a common vision of ODA by the leaders and the actors, similar experiences, and a culture of collaboration. However, ODA challenged traditional medical therapy and encountered obstacles to collaboration. Perhaps the best way of surmounting those obstacles is to practice ODA itself during the implementation process.


Vaccinating Italian infants with a new multicomponent vaccine (Bexsero®) against meningococcal B disease: A cost-effectiveness analysis.
The European Medicines Agency has approved a multicomponent serogroup B meningococcal vaccine (Bexsero®) for use in individuals of 2 months of age and older. A cost-effectiveness analysis (CEA) from the societal and Italian National Health Service perspectives was performed in order to evaluate the impact of vaccinating Italian infants less than 1 y of age with Bexsero®, as opposed to non-vaccination. The analysis was carried out by means of Excel Version 2011 and the TreeAge Pro® software Version 2012. Two basal scenarios that differed in terms of disease incidence (official and estimated data to correct for underreporting) were considered. In the basal scenarios, we considered a primary vaccination cycle with 4 doses (at 2, 4, 6 and 12 months of age) and 1 booster dose at the age of 11 y, the societal perspective and no cost for death. Sensitivity analyses were carried out in which crucial variables were changed over probable ranges. In Italy, on the basis of official data on disease incidence, vaccination with Bexsero® could prevent 82.97 cases and 5.61 deaths in each birth cohort, while these figures proved to be three times higher on considering the estimated incidence. The results of the CEA showed that the Incremental Cost Effectiveness Ratio (ICER) per QALY was €109,762 in the basal scenario if official data on disease incidence are considered and €26,599 if estimated data are considered. The tornado diagram indicated that the most influential factor on ICER was the incidence of disease. The probability of sequelae, the cost of the vaccine and vaccine effectiveness also had an impact. Our results suggest that vaccinating infants in Italy with Bexsero® has the ability to significantly reduce meningococcal disease and, if the probable underestimation of disease incidence is considered, routine vaccination is advisable.


Intermittent flushing improves cannula patency compared to continuous infusion for peripherally inserted venous catheters in newborns: results from a prospective observational study.
Peripheral cannulas in newborns are commonly used for intravenous treatment. However sustained maintenance of cannula patency is often difficult to achieve in this age group. This study compares the duration for which cannula patency can be maintained in newborns under continuous infusion, or an intermittent flushing regimen, with normal saline. A prospective observational study was conducted during a 12-month period. All newborns admitted to the 16-bed intermediate care unit, who required intravenous treatment, received either continuous peripheral infusion with 0.9% saline at an infusion rate of 2 mL/h or an intravenous cannula, which was flushed with 1 mL of 0.9% saline at least once every 24 h. A total of 53 patients with 86 cannulas were included. Twenty-five (47%) patients received 41 continuous infusions. The intermittent flushing group consisted of 28 (53%) patients with 45 cannulas administered. The cannula patency was significantly longer in the intermittent flushing group (mean 62.1 vs. 92.8 h, P=0.01). The patient's underlying disease and the cannula insertion site were not related with the duration of the cannula patency. Our study shows that intermittent cannula flushing is associated with improved cannula patency for peripherally inserted venous catheters in newborns.


Overview of patient dosimetry in diagnostic radiology in the USA for the past 50 years.
This review covers the role of medical physics in addressing issues directly related to patient dosimetry in radiography, fluoroscopy, mammography, and CT. The sections on radiography and fluoroscopy radiation doses review the changes that have occurred during the last 50 to 60 years. A number of technological improvements have contributed to both a significant reduction in patient and staff radiation doses and improvements to the image quality during this period of time. There has been a transition from film-screen radiography with hand dip film processing to electronic digital imaging utilizing CR and DR. Similarly, fluoroscopy has progressed by directly viewing image intensifiers in darkened rooms to modern flat panel image receptor systems utilizing pulsed radiation, automated variable filtration, and digitally processed images. Mammography is one of the most highly optimized imaging procedures performed, because it is a repetitive screening procedure that results in annual radiation exposure. Mammography is also the only imaging procedure in the United States in which the radiation dose is regulated by the federal government. Consequently, many medical physicists have studied the dosimetry associated with screen-film and digital mammography. In this review, a brief history of mammography dose assessment by medical physicists is discussed. CT was introduced into clinical practice in the early 1970s, and has grown into one of the most important modalities available for diagnostic imaging. CT dose quantities and measurement techniques are described, and values of radiation dose for different types of scanner are presented. Organ and effective doses to adult patients are surveyed from the earliest single slice scanners, to the latest versions that include up to two x-ray tubes and can incorporate as many as 256 detector channels. An overview is provided of doses received by pediatric patients undergoing CT examinations, as well as methods, and results, of studies performed to assess the radiation absorbed by the conceptus of pregnant patients.


Slide preparation and staining procedures for reliable results using computerized morphology.
The purpose of this study was to standardize slide preparation and staining procedures to improve the efficiency and effectivity of the IVOS system on normal sperm morphology readings with regard to the strict criteria. Semen samples from patients attending the Reproductive Biology Unit, Tygerberg Hospital, were used. In experiment 1, five different Diff-Quik staining procedures, including the standard procedure, were evaluated on each of 22 patients and the effect of slide preparation within 1 h or more than 5 h after collection and the effect of immediate fixation versus fixation after 24 h were observed. In experiment 2, the manual evaluation time per slide (n = 20) by two technicians was compared with the time taken by computer. In experiment 1 the median % normal for the 5 different staining procedures was 6, 6.5, 9.5, 8.5, and 5.5%. No significant difference was found between the different staining procedures (p = .60, nonparametric Friedman test). In experiment 2 the mean time for manual assessment by two technicians was 3 min:6 s and 3 min:53 s per slide as compared to 4 min:39 s by computer. For experiment 1, slides can be prepared immediately or after 5 h. Fixation time also does not interfere with the computer's ability to identify normal forms. For experiment 2, the IVOS system is competitive regarding assessment time. Standardization of optimum staining procedures is important to ensure repeatability and comparability. Therefore, slides should be prepared immediately after liquefaction and fixed immediately after air drying.


Development of a model of the coronary arterial tree for the 4D XCAT phantom.
A detailed three-dimensional (3D) model of the coronary artery tree with cardiac motion has great potential for applications in a wide variety of medical imaging research areas. In this work, we first developed a computer-generated 3D model of the coronary arterial tree for the heart in the extended cardiac-torso (XCAT) phantom, thereby creating a realistic computer model of the human anatomy. The coronary arterial tree model was based on two datasets: (1) a gated cardiac dual-source computed tomography (CT) angiographic dataset obtained from a normal human subject and (2) statistical morphometric data of porcine hearts. The initial proximal segments of the vasculature and the anatomical details of the boundaries of the ventricles were defined by segmenting the CT data. An iterative rule-based generation method was developed and applied to extend the coronary arterial tree beyond the initial proximal segments. The algorithm was governed by three factors: (1) statistical morphometric measurements of the connectivity, lengths and diameters of the arterial segments; (2) avoidance forces from other vessel segments and the boundaries of the myocardium, and (3) optimality principles which minimize the drag force at the bifurcations of the generated tree. Using this algorithm, the 3D computational model of the largest six orders of the coronary arterial tree was generated, which spread across the myocardium of the left and right ventricles. The 3D coronary arterial tree model was then extended to 4D to simulate different cardiac phases by deforming the original 3D model according to the motion vector map of the 4D cardiac model of the XCAT phantom at the corresponding phases. As a result, a detailed and realistic 4D model of the coronary arterial tree was developed for the XCAT phantom by imposing constraints of anatomical and physiological characteristics of the coronary vasculature. This new 4D coronary artery tree model provides a unique simulation tool that can be used in the development and evaluation of instrumentation and methods for imaging normal and pathological hearts with myocardial perfusion defects.