History of the development of surgical treatments for moyamoya disease.
Many surgical treatments for moyamoya disease have been developed over the past 40 years. The optimum treatment for ischemic-type moyamoya disease is almost established. The first surgical treatment for the disease was the superficial temporal artery to middle carotid artery (STA-MCA) anastomosis. The discovery of spontaneous collateral formation following the STA-MCA anastomosis surgery led to the development of various indirect bypass procedures. Collateral formation and clinical outcomes from direct and indirect procedures have been compared to assess the merits and limitations of each technique. Experience and a greater understanding of the surgical effects of moyamoya disease have led to the development of surgical procedures combining various direct and indirect bypass techniques for optimal restoration of perfusion. This review of the historical development and efficacy of each procedure will aid surgeons in selecting the most appropriate surgical procedure for patients of different ages with different symptoms and disease severities.


River dolphins can act as population trend indicators in degraded freshwater systems.
Conservation attention on charismatic large vertebrates such as dolphins is often supported by the suggestion that these species represent surrogates for wider biodiversity, or act as indicators of ecosystem health. However, their capacity to act as indicators of patterns or trends in regional biodiversity has rarely been tested. An extensive new dataset of >300 last-sighting records for the Yangtze River dolphin or baiji and two formerly economically important fishes, the Yangtze paddlefish and Reeves' shad, all of which are probably now extinct in the Yangtze, was collected during an interview survey of fishing communities across the middle-lower Yangtze drainage. Untransformed last-sighting date frequency distributions for these species show similar decline curves over time, and the linear gradients of transformed last-sighting date series are not significantly different from each other, demonstrating that these species experienced correlated population declines in both timing and rate of decline. Whereas species may be expected to respond differently at the population level even in highly degraded ecosystems, highly vulnerable (e.g. migratory) species can therefore display very similar responses to extrinsic threats, even if they represent otherwise very different taxonomic, biological and ecological groupings. Monitoring the status of river dolphins or other megafauna therefore has the potential to provide wider information on the status of other threatened components of sympatric freshwater biotas, and so represents a potentially important monitoring tool for conservation management. We also show that interview surveys can provide robust quantitative data on relative population dynamics of different species.


The assessment of ice pack effect in pain reduction during digital nerve block: A randomized clinical study.
Digital nerve block is a painful procedure. Several methods have been proposed to decrease the injection pain. Applying an ice pack is a pertinent choice due to its effectiveness on pain reduction, convenience, and low costs. In this study, the degree of injection pain reduction was assessed after applying an ice pack to the site of anesthetic injection. One hundred participants with traumatic finger injury were assessed. Digital nerve block was performed in fifty patients in the intervention group after 6 min of ice application. In the control group, this procedure was done without ice. The primary outcome was the difference between the needle stick and infiltration pain scores with and without ice pack. The secondary outcome the patient satisfaction score. The protocol of this study was approved by the Institutional Review Board, and it is registered in the Iranian Registry of Clinical Trials. The pain score was assessed using a Numeric Rating Scale. Both the needle skin and infiltration pain scores were statistically significantly lower in the intervention group (P < 0.001). The mean and median needle stick pain scores were 1.5 and 1.0 in the intervention group and 6.8 and 7.0 in the control group, respectively. Moreover, the mean and median infiltration pain scores were 2.7 and 2.0 in the intervention group and 8.5 and 9.0 in the control group, respectively. Patient satisfaction score was significantly higher in the intervention group. Ice pack is inexpensive, readily available, and is easy to apply. We recommend this method to reduce the injection pain before digital nerve block in the emergency department.


Derivation of insertin.
Insertin is an actin-binding protein that has been isolated from chicken gizzard smooth muscle that has been shown to be highly homologous to amino acids 962-1292 of tensin [Weigt et al., 1992]. Because of the high homology, we investigated the question whether the mRNAs of insertin and of tensin are derived from the same gene by alternative splicing, whether insertin and tensin are encoded by two different genes, or whether insertin is a proteolytic fragment of tensin. In a Northern blot analysis, mRNA from chicken gizzard was hybridized with oligonucleotides specific for tensin and for the insertin domain of tensin. The tensin-specific oligonucleotide hybridized only with the previously reported 8- and 10-kbp RNAs. However, the insertin domain-specific oligonucleotide hybridized with a 1.2 and a 1.6 kbp RNA in addition to the 8 and 10 kbp RNA. The 1.2- and 1.6-kbp RNA occurred in small amounts, as compared with the 8- and 10-kbp RNA. Southern blot analysis of DNA cleaved by the restriction endonucleases BamH1 and HindIII demonstrated that only one gene for the insertin and tensin exists. Insertin isolated from chicken gizzard smooth muscle was investigated by mass spectrometry. The N-termini of three isolated peptides were found to begin at adjacent amino acids and were likely to be formed from tensin by proteolysis. The results suggest that, for insertin, an mRNA exists that is derived from one gene common for insertin and tensin. However, the insertin-specific mRNA contributes relatively little to expression of insertin domains in cells. Insertin preparations from chicken gizzard contain mainly insertin domains formed from tensin by proteolysis.


Comparison of Rhinovirus A-, B-, and C-Associated Respiratory Tract Illness Severity Based on the 5'-Untranslated Region Among Children Younger Than 5 Years.
Rhinoviruses (RVs) are among the most frequently detected viruses from hospitalized children with severe acute respiratory infections, being classified into RV-A, RV-B, and RV-C (4 clades: C, GAC1, GAC2, and A2). This study aimed to compare the clinical characteristics and respiratory tract illness severity between the RV species and RV-C clades in children in primary care and hospital settings in rural communities in the Philippines. Clinical samples and information of children <5 years old in the Philippines were collected from 2014 to 2016. The samples were tested by reverse-transcription polymerase chain reaction (RT-PCR) targeting the 5'-untranslated region. PCR-positive samples were sequenced, and RV species were identified by phylogenetic analysis. Overall, 3680 respiratory tract illness episodes in 1688 cohort children were documented; 713 of those were RV positive and identified as RV-A (n = 271), RV-B (n = 47), and RV-C (n = 395: C [n = 76], GAG1 [n = 172], GAG2 [n = 8], A2 [n = 138], and unidentified [n = 1]). Severe illnesses, low oxygen saturation, cough, and wheezing were more common in patients with RV-C, especially with GAC1, than in those with RV-A or RV-B. Furthermore, severe illness was significantly more common in RV-C (GAC1)-positive cases than in RV-A-positive cases (odds ratio, 2.61 [95% CI, 1.17-4.13]). Children infected with RV-C had more severe illnesses than children infected with RV-A and RV-B. Moreover, emerging clades of RV-C were associated with increased severity.


Neuroelectric blocking factors in multiple sclerosis and normal human sera.
Serum samples from 13 multiple sclerosis (MS) patients and ten normal human serum samples were applied to cerebral neocortex cultures and evaluated for their ability to block evoked electric activity. A high proportion of sera positive for neuroelectric blocking factors was found in both groups, and there was no substantial difference between serum samples from MS patients and those from normal human volunteers. Some of the neuroelectric blocking factors were thermolabile, others were thermostable, and still others may have been complement-dependent. It is concluded that the ability to block evoked electric responses in tissue cultures is a nonspecific serum property, and that it is not specifically related to the pathogenesis of demyelinating disease.


Urate crystals induce NLRP3 inflammasome-dependent IL-1β secretion and proliferation in isolated primary human T-cells.
Urate through NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-dependent caspase-1 activation stimulates macrophages to secrete inteleukin-1β (IL-1β). Urate also enhances adaptive immunity indirectly through its effect on antigen presenting cells. In this study, the direct effect of urate on isolated primary human T-cells was evaluated. Isolated T-cells were cultured with or without monosodium urate crystals in the presence or not of the NLRP3 inflammasome inhibitor glyburide. Activated cleaved caspase-1 was assessed by means of western blotting, whereas caspase-1 activity was measured colorimetrically in the cell lysates. IL-1β was measured in the supernatants by means of enzyme-linked immunosorbent assay. T-cell proliferation was assessed by means of bromodeoxyuridine labelling and immunoenzymatic detection. Urate induced caspase-1 activation and IL-1β release by T-cells. It also induced proliferation of T-cells. Glyburide inhibited urate-induced caspase-1 activation, IL-1β secretion and proliferation. Urate, a well defined danger signal, stimulates directly human T-cells in a NLRP3 infmmasomela-dependent way. The subsequent IL-1β secretion could enhance inflammation, whereas expansion of T-cell clones could facilitate a subsequent adaptive immune response. Hippokratia 2015, 19 (1): 41-46.


Quantum path-integral study of the phase diagram and isotope effects of neon.
The phase diagram of natural neon has been calculated for temperatures in the range of 17-50 K and pressures between 10(-2) and 2 x 10(3) bar. The phase coexistence between solid, liquid, and gas phases has been determined by the calculation of the separate free energy of each phase as a function of temperature. Thus, for a given pressure, the coexistence temperature was obtained by the condition of equal free energy of coexisting phases. The free energy was calculated by using nonequilibrium techniques such as adiabatic switching and reversible scaling. The phase diagram obtained by classical Monte Carlo simulations has been compared to that obtained by quantum path-integral simulations. Quantum effects related to the finite mass of neon cause that coexistence lines are shifted toward lower temperatures when compared to the classical limit. The shift found in the triple point amounts to 1.5 K, i.e., about 6% of the triple-point temperature. The triple-point isotope effect has been determined for (20)Ne, (21)Ne, (22)Ne, and natural neon. The simulation data show satisfactory agreement to previous experimental results, which report a shift of about 0.15 K between triple-point temperatures of (20)Ne and (22)Ne. The vapor pressure isotope effect has been calculated for both solid and liquid phases at triple-point conditions. The quantum simulations predict that this isotope effect is larger in the solid than in the liquid phase, and the calculated values show nearly quantitative agreement to available experimental data.


Benthic nepheloid layers in the Gulf of Maine and Alexandrium cyst inventories.
Cysts residing in benthic nepheloid layers (BNLs) documented in the Gulf of Maine have been proposed as a possible source of inoculum for annual blooms of a toxic dinoflagellate in the region. Herein we present a spatially extensive data set of the distribution and thickness of benthic nepheloid layers in the Gulf of Maine and the abundance and inventories of suspended Alexandrium fundyense cysts within these near-bottom layers. BNLs are pervasive throughout the gulf and adjacent Bay of Fundy with maximum layer thicknesses of 50-60 m observed. Mean BNL thickness is 30 m in the eastern gulf and Bay of Fundy, and 20 m in the western gulf. Cyst densities in the near-bottom particle resuspension layers varied by three orders of magnitude across the gulf with maxima of 105 cysts m-3. An important interconnection of elevated BNL cyst densities is observed between the Bay of Fundy, the Maine Coastal Current and the south-central region of the gulf. BNL cyst inventories estimated for the eastern and western gulf are each on the order of 1015 cysts, whereas the BNL inventory in the Bay of Fundy is on the order of 1016 . Although BNL cyst inventories in the eastern and western gulf are 1-2 orders of magnitude smaller than the abundance of cysts in the upper 1 cm of sediment in those regions, BNL and sediment-bound cyst inventories are comparable in the Bay of Fundy. The existence of widespread BNLs containing substantial cyst inventories indicates that these near-bottom layers represent an important source of germinating A. fundyense cysts in the region.


Simultaneous Inference of Treatment Effect Modification by Intermediate Response Endpoint Principal Strata with Application to Vaccine Trials.
In randomized clinical trials, researchers are often interested in identifying an inexpensive intermediate study endpoint (typically a biomarker) that is a strong effect modifier of the treatment effect on a longer-term clinical endpoint of interest. Motivated by randomized placebo-controlled preventive vaccine efficacy trials, within the principal stratification framework a pseudo-score type estimator has been proposed to estimate disease risks conditional on the counter-factual biomarker of interest under each treatment assignment to vaccine or placebo, yielding an estimator of biomarker conditional vaccine efficacy. This method can be used for trial designs that use baseline predictors of the biomarker and/or designs that vaccinate disease-free placebo recipients at the end of the trial. In this article, we utilize the pseudo-score estimator to estimate the biomarker conditional vaccine efficacy adjusting for baseline covariates. We also propose a perturbation resampling method for making simultaneous inference on conditional vaccine efficacy over the values of the biomarker. We illustrate our method with datasets from two phase 3 dengue vaccine efficacy trials.


Perceived norms, personal agency, and postpartum family planning intentions among first-time mothers age 15-24 years in Kinshasa: A cross-sectional analysis.
Unintended pregnancy is an important global health problem and frequently occurs during the immediate postpartum period. However, few studies have examined postpartum family planning (PPFP) intentions among adolescent girls and young women. This study assessed whether perceived norms and personal agency predicted PPFP intentions among first-time mothers age 15-24 in Kinshasa, the Democratic Republic of Congo. Data were derived from the 2018 Momentum Project baseline survey. Analysis was based on 2,418 nulliparous pregnant women age 15-24 who were approximately six months pregnant with their first child in six health zones of Kinshasa. Overall PPFP intentions were low and ten to thirteen percent of women stated they were very likely to discuss PPFP next month with (a) their husband/male partner and (b) a health worker, and to (c) obtain and (d) use a contraceptive method during the first six weeks following childbirth. The results of multivariable linear regression models indicated that the PPFP intention index was predicted by description norms, perceptions of the larger community's approval of PPFP, normative expectations, perceived behavioral control, self-efficacy, and autonomy. Rejection of family planning myths and misconceptions was also a significant predictor. Interaction terms suggested that the association of normative expectations with PPFP intentions varied across ethnic groups and that the positive association of injunctive norms with PPFP intentions was significantly increased when the larger community was perceived to disapprove of PPFP use. Normative expectations and PPFP-related self-efficacy accounted for two-thirds of the variance in PPFP intentions. The results suggested that understanding different normative influences may be important to motivate women to use contraception in the immediate postpartum period. In addition to addressing institutional, individual, and social determinants of PPFP, programs should consider integrating norm-based and empowerment strategies.


Understanding Cancer Cachexia and Its Implications in Upper Gastrointestinal Cancers.
Considerable advances in the investigation and management of oesophagogastric cancer have occurred over the last few decades. While the historically dismal prognosis associated with these diseases has improved, outcomes remain very poor. Cancer cachexia is an often neglected, yet critical, factor for this patient group. There is a persuasive argument that a lack of assessment and treatment of cachexia has limited progress in oesophagogastric cancer care. In the curative setting, the stage of the host (based on factors such as body composition, function, and inflammatory status), alongside tumour stage, has the potential to influence treatment efficacy. Phenotypical features of cachexia may decrease the survival benefit of (peri-operative) chemoradiotherapy, immunotherapy, or surgical resection in patients with potentially curative malignancy. Most patients with oesophagogastric cancer unfortunately present with disease which is not amenable, or is unlikely to respond, to these treatments. In the palliative setting, host factors can similarly impair results from systemic anti-cancer therapies, cause adverse symptoms, and reduce quality of life. To optimise treatment pathways and enhance patient outcomes, we must utilise this information during clinical decision-making. As our understanding of the genesis of cancer cachexia improves and more therapeutic options, ranging from basic (e.g. exercise and nutrition) to targeted (e.g. anti-IL1 α and anti-GDF-15), become available, there can be grounds for optimism. Cachexia can change from a hitherto neglected condition to an integral part of the oesophagogastric cancer treatment pathway.


Two populations of beta-spectrin in rat skeletal muscle.
We use immunoblotting, immunoprecipitation, and centrifugation in sucrose density gradients to show that the product of the erythrocyte beta-spectrin gene in rat skeletal muscle (muscle beta-spectrin) is present in two states, one associated with fodrin, and another that is not associated with any identifiable spectrin or fodrin subunit. Immunofluorescence studies indicate that a significant amount of beta-spectrin without alpha-fodrin is present in the myoplasm of some muscle fibers, and, more strikingly, at distinct regions of the sarcolemma. These results suggest that alpha-fodrin and muscle beta-spectrin associate in muscle in situ, but that some muscle beta-spectrin without a paired alpha-subunit forms distinct domains at the sarcolemma.


Pattern-reversal visual evoked potentials in infants: gender differences during early visual maturation.
This paper investigates gender differences in the peak latency and amplitude of the P1 component of the pattern-reversal visual evoked potential (pattern-reversal VEP) recorded in healthy term infants. Pattern-reversal VEPs in response to a series of high contrast black and white checks (check widths 120', 60', 30', 24', 12', 6') were recorded in 50 infants (20 males, 30 females) at 50 weeks post-conceptional age (PCA) and in 49 infants (22 males, 27 females) at 66 weeks PCA. Peak latency of the major component, P1, was considerably shorter in female compared with male infants. Differences in head circumference do not entirely account for the gender differences in peak latency reported here. A gender difference in P1 amplitude was not detected. These findings stress the importance of considering gender norms as well as age-matched norms when utilizing the pattern-reversal VEP in clinical investigations. Studies including a wider range of ages are clearly necessary in order to establish whether the earlier peak latencies in female infants represents a difference in the onset or rate of visual maturation.


The influential child: How children affect their environment and influence their own risk and resilience.
Views regarding children's influence on their environment and their own development have undergone considerable changes over the years. Following Bell's (1968) seminal paper, the notion of children's influence and the view of socialization as a bidirectional process have gradually gained wide acceptance. However, empirical research implementing this theoretical advancement has lagged behind. This Special Section compiles a collection of new empirical works addressing multiple forms of influential child processes, with special attention to their consequences for children's and others' positive functioning, risk and resilience. By addressing a wide variety of child influences, this Special Section seeks to advance integration of influential child processes into myriad future studies on development and psychopathology and to promote the translation of such work into preventive interventions.


Cyanobacteria Scytonema javanicum and Scytonema ocellatum Lipopolysaccharides Elicit Release of Superoxide Anion, Matrix-Metalloproteinase-9, Cytokines and Chemokines by Rat Microglia In Vitro.
Cosmopolitan Gram-negative cyanobacteria may affect human and animal health by contaminating terrestrial, marine and freshwater environments with toxins, such as lipopolysaccharide (LPS). The cyanobacterial genus Scytonema (S) produces several toxins, but to our knowledge the bioactivity of genus Scytonema LPS has not been investigated. We recently reported that cyanobacterium Oscillatoria sp. LPS elicited classical and alternative activation of rat microglia in vitro. Thus, we hypothesized that treatment of brain microglia in vitro with either cyanobacteria S. javanicum or S. ocellatum LPS might stimulate classical and alternative activation with concomitant release of superoxide anion (O₂-), matrix metalloproteinase-9 (MMP-9), cytokines and chemokines. Microglia were isolated from neonatal rats and treated in vitro with either S. javanicum LPS, S. ocellatum LPS, or E. coli LPS (positive control), in a concentration-dependent manner, for 18 h at 35.9 °C. We observed that treatment of microglia with either E. coli LPS, S. javanicum or S. ocellatum LPS generated statistically significant and concentration-dependent O₂-, MMP-9 and pro-inflammatory cytokines IL-6 and TNF-α, pro-inflammatory chemokines MIP-2/CXCL-2, CINC-1/CXCL-1 and MIP-1α/CCL3, and the anti-inflammatory cytokine IL-10. Thus, our results provide experimental support for our working hypothesis because both S. javanicum and S. ocellatum LPS elicited classical and alternative activation of microglia and concomitant release of O₂-, MMP-9, cytokines and chemokines in a concentration-dependent manner in vitro. To our knowledge this is the first report on the toxicity of cyanobacteria S. javanicum and S. ocellatum LPS to microglia, an immune cell type involved in neuroinflammation and neurotoxicity in the central nervous system.


Under the knife: a national survey of six sigma programs in US healthcare organizations.
Medical and policy literature reports many six sigma applications at specific healthcare organizations. However, there is a lack of studies that investigate the broader status of six sigma in US healthcare systems. The purpose of this paper is to present the results from a national survey of six sigma programs in US healthcare organizations. Through the design, distribution, and analysis of a nationwide survey, this paper assesses the implementation of six sigma in healthcare facilities. Two sets of surveys were designed based on whether an organization has adopted six sigma or not. Findings from this paper indicate the common six sigma projects implemented in healthcare organizations, typical implementation durations, cost benefits, and major barriers in implementation, and so on. This paper is limited by the low-response rate owing to time and budget constraints. Through the dissemination of this paper, it is hoped that more organizations will become interested in this subject and participate in future studies. This work is the first study to investigate the implementation status of six sigma in US healthcare systems. It will share experiences amongst six sigma institutions and promote its application in many institutions. The findings will provide instructive information to six sigma practitioners and researchers, and particularly to health care management.


Synthesis and properties of 4-substituted-1-piperazinyl-propyl derivatives of 1-phenyl-7-methylpyrimido-[4,5-d]pyrimidin-4-one.
In reactions of 1-phenyl-7-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimido[ 4,5-d]pyrimidin e (1) with 1-(3-chloropropyl)-4-methyl(phenyl, 3-chlorophenyl, 2-pyrimidynyl, 2-thiazolyl)piperazines (5), mixtures of isomeric N- and S-substituted derivatives of compound 1 (3 and 4) were obtained. Isomers were separated by fractional crystallization. The structure of novel compounds 3 and 4 was confirmed by elemental and spectral analyses. In pharmacological screening compounds 3b and 4b displayed rather strong analgesic action, inhibited amphetamine hyperactivity and abolished apomorphine stereotypy. Compounds 3e,3d and 4e attenuated m-chlorophenylpiperazine-induced hypothermia.


Comparison of DNA content in primary and lymph node metastases in prostate adenocarcinoma.
There is increasing evidence that nuclear DNA content has significant prognostic value for adenocarcinoma of the prostate. There also appear to be considerable differences in cellular DNA content between patient cohorts when primary tumor or pelvic lymph node metastases are measured. In addition, prostate adenocarcinoma is heterogeneous in DNA measurements; that adds confusion to studies incorporating fine needle aspiration biopsy samples. We compared cellular DNA content in 34 patients with available needle biopsies and pelvic lymph node metastases. Four groups of patients were identified: diploid-range primaries and metastases (8 patients), diploid-range primaries and aneuploid metastases (13), aneuploid primaries and metastases (10), and aneuploid primaries and diploid-range metastases (2). Patients with diploid-range primary tumors had a longer interval to progression and death than did patients with aneuploid primary tumors, although neither was significant in this small series. Patients with diploid-range lymph node metastasis had a longer interval to progression (P = .04) and survival (P = .09) than did individuals with aneuploid metastases. We conclude that the cellular DNA content of prostate cancer metastases in this series of stage D1 patients was more powerful in predicting time to progression and ultimate survival than evaluation of needle biopsy specimens of the primary cancer.


Anthelmintic drugs and nematicides: studies in Caenorhabditis elegans.
Parasitic nematodes infect many species of animals throughout the phyla, including humans. Moreover, nematodes that parasitise plants are a global problem for agriculture. As such, these nematodes place a major burden on human health, on livestock production, on the welfare of companion animals and on crop production. In the 21st century there are two major challenges posed by the wide-spread prevalence of parasitic nematodes. First, many anthelmintic drugs are losing their effectiveness because nematode strains with resistance are emerging. Second, serious concerns regarding the environmental impact of the nematicides used for crop protection have prompted legislation to remove them from use, leaving agriculture at increased risk from nematode pests. There is clearly a need for a concerted effort to address these challenges. Over the last few decades the free-living nematode Caenorhabditis elegans has provided the opportunity to use molecular genetic techniques for mode of action studies for anthelmintics and nematicides. These approaches continue to be of considerable value. Less fruitful so far, but nonetheless potentially very useful, has been the direct use of C. elegans for anthelmintic and nematicide discovery programmes. Here we provide an introduction to the use of C. elegans as a 'model' parasitic nematode, briefly review the study of nematode control using C. elegans and highlight approaches that have been of particular value with a view to facilitating wider-use of C. elegans as a platform for anthelmintic and nematicide discovery and development.


Psychiatric disorders in a cohort of individuals with Prader-Willi syndrome.
Psychiatric manifestations in Prader-Willi Syndrome (PWS) are common and often are the most debilitating problem in these individuals. We present an epidemiological nation-wide survey of psychiatric diagnoses in the PWS population, based on full-range psychiatric interviews. We studied the distribution of psychiatric diagnoses (as opposed to a symptom-based approach) in the Israel national cohort of adolescents and adults with PWS. There was a total of 53 (32 males) ages 12 years and older. All individuals and their caretakers were interviewed using standardized psychiatric questionnaires. Demographic and clinical variables, Clinical Global Impression (CGI) score, IQ, severity of hyperphagia and quality of life (QOL) were also assessed and correlations with NPD (number of psychiatric diagnoses) calculated. An overwhelming majority (89%) of the study participants had at least one psychiatric diagnosis. The most common were disruptive behavior disorders (DBD) (68%), obsessive compulsive disorder (OCD) (45%) and skin picking (35%). Individuals with DBD were at increased risk for OCD and skin picking. Psychotic disorders were found in 11%. NPD had a significant negative influence on QOL. There was no correlation between NPD and BMI, IQ, hyperphagia severity, hormonal profile or genetic subtypes. Psychiatric diagnoses are very frequent in PWS and strongly influence QOL. Furthermore, characterizing the profile of psychiatric comorbidity in PWS is crucial for planning effective interventions. Precise behavioral phenotyping in PWS in combination with a well-defined genetic etiology may aid biological research linking biological correlates to behavior.


Fishing strategies among prehistoric populations at Saquarema Lagoonal Complex, Rio de Janeiro, Brazil.
Two distinct fishing technologies were identified among the shellmound builders of the Saquarema Lagoonal Complex, in the Brazilian state of Rio de Janeiro: bone point technology and worked fish spines. These technologies were related to the acquisition of specific fish resources; Worked fish spines were used in the capture of Micropogonias furnieri (Desmarest), and bone points used for fishing specimens of the Ariidae family. Worked spines technology was predominant between 6,726 cal. years BP and 3,699 cal. years BP, while the bone point technology was dominant after 3,699 cal. years BP. It is believed these different strategies for obtaining fishing resources before 3,699 years cal. BP was related to environmental. Notably the gradual regression of relative sea level occurred during the mid- and late Holocene.


Clamp ablation of the testes compared to bilateral orchiectomy as androgen deprivation therapy for advanced prostate cancer.
Burdizzo clamp ablation of the testes (CAT) may provide an incisionless, cost-effective form of androgen deprivation therapy (ADT) in men with adenocarcinoma of the prostate (ACP) who find bilateral orchiectomy (BO) unacceptable or can not afford medical ADT. The aim of this study was to compare CAT with BO as primary ADT in men with ACP. Written, informed consent was obtained from men with locally advanced or metastatic ACP. Patients were prospectively randomized to BO (n = 9) or CAT (n = 10) under local anaesthesia, and were evaluated 3 and 7 days, 6 weeks and 3 months post-procedure. The protocol was approved by the local institutional ethics committee. Statistical analysis was performed using Student's, Mann-Whitney's and Fisher's tests. Mean duration of the procedure was significantly longer for BO than CAT (16.9 vs. 10.9 minutes). Mean pain scores during and after the procedure did not differ significantly. Serum testosterone decreased significantly on days 3 and 7 after CAT, but increased at 6 weeks, and was significantly higher than after BO. Serum luteinizing hormone increased significantly from day 3 after BO and from day 7 after CAT. Serum prostate specific antigen decreased significantly after BO, but not after CAT. Minor complications were more common after BO (89%) than CAT (40%). In the 9 men who did not achieve castrate levels of testosterone after CAT, BO was performed. CAT was quicker to perform and had a lower complication rate, but was not as effective as BO in achieving castrate serum testosterone levels.


Comparison of malignant potential between serrated adenomas and traditional adenomas.
Serrated adenoma is a discrete colorectal epithelial neoplastic lesion that can evolve into colorectal cancer. However, the degree of malignant potential has not been firmly established as yet. The purpose of the present paper was to compare the malignant potential and clinicopathological features between serrated and traditional adenomas. A total of 124 serrated adenomas from 116 patients were assessed, and 419 traditional adenomas from 200 were randomly selected. The combination of nuclear dysplasia and serration of > or =20% of crypts was regarded as serrated adenoma. The clinicopathological features of serrated and traditional adenomas were compared, and multivariate analysis performed to confirm whether the malignant potential of serrated adenoma was similar to that of traditional adenoma. The differences in age, sex, total number of adenomas, and synchronous lesions including adenoma with high-grade dysplasia and carcinoma between subjects with and without serrated adenoma were not significant. Serrated adenomas were more frequently located in the rectum and sigmoid colon (P < 0.001), and the average size of serrated adenomas was greater than that of traditional adenomas (P < 0.05). The incidence of malignant lesions including high-grade dysplasia and carcinoma in serrated adenomas was found to be lower than in traditional adenomas (3.2% vs 9.3%, P < 0.05). In the multivariate analysis, adenoma type and polyp size constituted the risk factors for the incidence of high-grade dysplasia and carcinoma. Serrated adenoma is a premalignant lesion, but it has a lower potential for the development of malignancy than traditional adenomas.


Leg morbidity and function following fibular free flap harvest.
Over a period of 3 years, 50 consecutive free fibular flaps for mandibular reconstruction were performed on 47 patients. In 38 patients (81%) a skin paddle was included with the flap to provide either mucosal lining or skin cover; in 9 patients (19%) bone alone was used. Thirty-one patients (66%) required a skin graft to close the donor defect in the leg. Donor leg morbidity and function were determined by patient questionnaire and by physical examination. Forty-one donor sites in 40 patients were available for long-term follow-up. The follow-up ranged from 4 to 39 months with an average of 17 months. Immediate postoperative infection occurred in the donor site of 1 patient (2%) and required additional surgery. There was no other immediate donor site complications when closure required skin grafting. Eleven patients (27%) had late donor site morbidity, consisting of motor weakness of the great toe in 5 patients, ankle instability and/or stiffness in 3 patients, donor site pain in 1 patient, and edema in 2 patients. All complications were graded as mild in severity by the patient and by the examiner. In this series, although most donor site defects required skin grafting, short- and long-term morbidity was minimal. After a short rehabilitation period, all patients were fully able to engage in all daily and recreational activities.


Bronchoscopic bullectomy with a one-way endobronchial valve to treat a giant bulla in an emphysematic lung: a case report.
The conventional treatment for giant bullae in patients with chronic obstructive pulmonary disease is surgical bullectomy, but it is not possible in some patients with poor lung function. Bronchoscopic bullectomy involving implantation of an endobronchial valve (EBV) has emerged as a potential alternative. Here we describe how EBV implantation in a bullous emphysema with a giant bulla in the right middle lobe led to elimination of the bulla and improvements in pulmonary function, 6-min walking distance during the 1-year follow-up. Our case suggests that bronchoscopic bullectomy with an EBV can be a safe and effective alternative to surgical bullectomy.


UPLC-based assay to assess the hydrophobicity of Antibody-Drug Conjugate (ADC) payloads.
Antibody-Drug Conjugates (ADCs) consist of antibodies attached to cytotoxic small molecules or biological agents (i.e., payloads) through chemical linkers which may be cleavable or non-cleavable. The development of new ADCs is challenging, particularly the process of attaching the linker-payload construct to the antibody (i.e., the conjugation process). One of the major problems associated with conjugation is high hydrophobicity of the payload which can lead to low yields of the ADC through aggregation and/or lower than desired Drug-Antibody Ratios (DARs). We report here a UPLC-based assay that can be used to study the physicochemical properties of ADC payloads at an early stage of development, and to provide information on whether the hydrophilic-hydrophobic balance is suitable for conjugation or further physicochemical optimization is required. The assay is relatively simple to establish and should be of use to those working in the ADC area.


Patterns of lateral neck metastasis in papillary thyroid carcinoma.
Although lymphatic metastasis does not affect overall survival for patients with differentiated thyroid carcinoma, locoregional control can be improved with cervical lymphadenectomy. The major morbidity of neck dissection (ND) for the management of regional metastases is spinal accessory (cranial nerve XI) dysfunction. To avoid this complication, some surgeons have advocated a limited ND. To establish the patterns of lateral cervical metastases in differentiated thyroid carcinoma and the role of comprehensive ND, we performed a review of our experience with comprehensive ND. Retrospective chart review. Between 1997 and 2002, a total of 39 consecutive patients (31 women and 8 men) underwent 44 NDs for the management of lateral cervical metastases. Preoperative cytologic analysis revealed papillary carcinoma in all 39 patients (100%). All specimens were labeled and mapped by the operating surgeon to identify each level. The incidence of positive disease was determined in relation to the extent of lymphadenectomy for all dissected levels. All patients underwent ND at levels II through V; 7 (17%) of the 44 ND specimens included level I nodes. The incidence of metastatic disease in level II nodes was 52% (23/44 specimens). Similarly, 25 specimens (57%) contained histologic metastases at level III. Metastatic disease was noted in 18 level IV nodes (41%) and 9 level V nodes (21%). One (14%) of the 7 specimens with level I nodes contained tumor. Cervical metastases from papillary thyroid carcinoma occur in predictable patterns, with disease commonly present at levels II through V. We believe that a comprehensive ND, including removal of transverse cervical and spinal accessory nodes, is necessary for the complete clearance of lateral metastases.


Human ribosomal protein S13 regulates expression of its own gene at the splicing step by a feedback mechanism.
The expression of ribosomal protein (rp) genes is regulated at multiple levels. In yeast, two genes are autoregulated by feedback effects of the protein on pre-mRNA splicing. Here, we have investigated whether similar mechanisms occur in eukaryotes with more complicated and highly regulated splicing patterns. Comparisons of the sequences of ribosomal protein S13 gene (RPS13) among mammals and birds revealed that intron 1 is more conserved than the other introns. Transfection of HEK 293 cells with a minigene-expressing ribosomal protein S13 showed that the presence of intron 1 reduced expression by a factor of four. Ribosomal protein S13 was found to inhibit excision of intron 1 from rpS13 pre-mRNA fragment in vitro. This protein was shown to be able to specifically bind the fragment and to confer protection against ribonuclease cleavage at sequences near the 5' and 3' splice sites. The results suggest that overproduction of rpS13 in mammalian cells interferes with splicing of its own pre-mRNA by a feedback mechanism.


Automatic Detection and Segmentation of Colorectal Cancer with Deep Residual Convolutional Neural Network.
Early and automatic detection of colorectal tumors is essential for cancer analysis, and the same is implemented using computer-aided diagnosis (CAD). A computerized tomography (CT) image of the colon is being used to identify colorectal carcinoma. Digital imaging and communication in medicine (DICOM) is a standard medical imaging format to process and analyze images digitally. Accurate detection of tumor cells in the complex digestive tract is necessary for optimal treatment. The proposed work is divided into two phases. The first phase involves the segmentation, and the second phase is the extraction of the colon lesions with the observed segmentation parameters. A deep convolutional neural network (DCNN) based residual network approach for the colon and polyps' segmentation from the CT images is applied over the 2D CT images. The residual stack block is being added to the hidden layers with short skip nuance, which helps to retain spatial information. ResNet-enabled CNN is employed in the current work to achieve complete boundary segmentation of the colon cancer region. The results obtained through segmentation serve as features for further extraction and classification of benign as well as malignant colon cancer. Performance evaluation metrics indicate that the proposed network model has effectively segmented and classified colorectal tumors with dice scores of 91.57% (on average), sensitivity = 98.28, specificity = 98.68, and accuracy = 98.82.


Do cone-beam computed tomography low-dose protocols affect the evaluation of the temporomandibular joint?
There is no established acquisition protocol based on scientific evidence for the acquisition of cone-beam computed tomography (CBCT) exams to evaluate the temporomandibular joint (TMJ). To evaluate the influence of acquisition protocols and jaw positioning on the diagnostic accuracy of TMJ condylar morphological alterations (CMA), dimension, position and excursion. Thirty-six TMJs on 18 dry skulls were imaged using a CBCT unit (OP300 Maxio, Instrumentarium, Tuusula, Finland) at two exposure settings (4.5 and 6.3 mA), three voxel resolutions (0.085, 0.125 and 0.280 mm), three jaw positions (concentric, anteriorised and posteriorised) and three jaw excursions (normoexcursion, hyperexcursion and hypoexcursion). The macroscopic anatomy examination and high-resolution CBCT images were used as ground truth for CMA. Twenty-five TMJs had at least one CMA with 11 healthy TMJs serving as controls. Three experienced oral and maxillofacial radiologists evaluated the parasagittal images for the presence of CMA, position and excursion and measured dimensions. The area under the ROC curve, sensitivity and specificity were calculated. Weighted Kappa (α = 0.05) was used to determine intra- and interexaminer reliability and comparisons between dependent variables analysed by Analysis of Variance at an a prior level of significance of 0.05. The agreement of the evaluation of the position and excursion with the reference standard was high, independent of the protocol (range, 0.75-0.91). Various combinations of acquisition protocols and jaw position did not influence the CMA evaluation. Erosion was overdiagnosed in protocols with larger voxel sizes and the detection of osteophytes greater in images with smaller voxel sizes. The anteroposterior dimension was greater in the open jaw position (p < .05). CBCT protocols using reduced radiation exposure from the CBCT machine evaluated in this study can be used to assess condylar morphology, dimension, position and excursion, without compromising diagnostic performances for these parameters.


What can morphology tell us about ecology of four invasive goby species?
This study presents a detailed comparative analysis of external morphology of four of the most invasive goby species in Europe (round goby Neogobius melanostomus, bighead goby Ponticola kessleri, monkey goby Neogobius fluviatilis and racer goby Ponticola gymnotrachelus) and interprets some ecological requirements of these species based on their morphological attributes. The results are evaluated within an ontogenetic context, and the morphological differences between the species are discussed in terms of the question: can special external shape adaptations help to assess the invasive potential of each species? The morphometric analyses demonstrate important differences between the four invasive gobies. Neogobius melanostomus appears to have the least specialized external morphology that may favour its invasive success: little specialization to habitat or diet means reduced restraints on overall ecological requirements. The other three species were found to possess some morphological specializations (P. kessleri to large prey, N. fluviatilis to sandy habitats and P. gymnotrachelus to macrophytes), but none of these gobies have managed to colonize such large areas or to reach such overall abundances as N. melanostomus.


An ATR-FTIR Sensor Unraveling the Drug Intervention of Methylene Blue, Congo Red, and Berberine on Human Tau and Aβ.
Alzheimer's disease affects millions of human beings worldwide. The disease progression is characterized by the formation of plaques and neurofibrillary tangles in the brain, which are based on aggregation processes of the Aβ peptide and tau protein. Today there is no cure and even no in vitro assay available for the identification of drug candidates, which provides direct information concerning the protein secondary structure label-free. Therefore, we developed an attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) sensor, which uses surface bound antibodies to immobilize a desired target protein. The secondary structure of the protein can be evaluated based on the secondary structure sensitive frequency of the amide I band. Direct information about the effect of a drug candidate on the secondary structure distribution of the total target protein fraction within the respective body fluid can be detected by a frequency shift of the amide I band. Thereby, the extent of the amide I shift is indicative for the compound efficiency. The functionality of this approach was demonstrated by the quantification of the effect of the drug candidate methylene blue on the pathogenic misfolded tau protein as extracted from cerebrospinal fluid (CSF). Methylene blue induces a shift from pathogenic folded β-sheet dominated to the healthy monomeric state. A similar effect was observed for congo red on pathogenic Aβ isoforms from CSF. In addition, the effect of berberine on synthetic Aβ1-42 is studied. Berberine seems to decelerate the aggregation process of synthetic Aβ1-42 peptides.


Temporal variations in blood glutathione peroxidase (GSHPx) activity in sheep at pasture in a Mediterranean area.
The present study evaluates blood GSHPx activity in 18 sheep flocks at range, to identify those seasons with the highest risk of selenium deficiency. Samples were taken from 1108 15-day-old lambs during the two usual lambing periods in this geographical area (autumn-winter and spring-summer). The overall mean values in the first period (146.69 +/- 3.41 i.u./g Hb) was higher than in the second one (107.50 +/- 3.53 i.u./g Hb). This may be explained by the special features of the climate in the Mediterranean area, which allow an optimum growth of grass from October to May. Therefore, the lambs born in spring-summer are from pregnancies in months when feeding is based only upon grazing. However, lambs born in autumn-winter comes from ewes gestating during the summer, when supplementation with cereal grains is given. As a conclusion, lambs born in spring-summer in this area are at higher risk to selenium-deficiency related disorders.


8-isoprostane increases scavenger receptor A and matrix metalloproteinase activity in THP-1 macrophages, resulting in long-lived foam cells.
Oxidative stress is a key factor in atherogenesis, in which it is closely associated with the inflammation and formation of bioactive lipids. Although 8-isoprostane is regarded as a reliable marker of oxidative stress in vivo, the pathogenic role of this F(2)-isoprostane in atherogenesis is far from clear. Based on the important role of foam cells in the initiation and progression of atherosclerosis we hereby examined the ability of 8-isoprostane to modulate oxidized (ox)LDL-induced foam cell formation and the function of these cells, particularly focusing on the effect on matrix degradation. 8-isoprostane (10 micro M) augmented the oxLDL-induced (20 micro g mL(-1)) lipid accumulation of THP-1 macrophages evaluated by Oil-Red-O staining and lipid mass quantification (colourimetric assay). Additionally, 8-isoprostane induced the expression of the scavenger receptor A type 1 (MSR-1) [mRNA and protein level], assessed by RT-PCR and Western blotting, respectively. Moreover, 8-isoprostane counteracted the oxLDL-induced apoptosis of these cells, involving both mitochondrial-protective and caspase-suppressive mechanisms. Along with these changes, 8-isoprostane increased the oxLDL-induced gene expression of matrix metalloproteinase (MMP)-9 and its endogenous inhibitor [i.e. tissue inhibitor of MMP (TIMP)-1] accompanied by enhanced total MMP activity. We show that 8-isoprostane increases foam cell formation at least partly by enhancing MSR-1 expression and by inhibiting apoptosis of these cells, inducing long-lived foam cells with enhanced matrix degrading capacity. Our findings further support a role for 8-isoprostane not only as a marker of oxidative stress in patients with atherosclerotic disorders, but also as a mediator in atherogenesis and plaque destabilization.


The Population Impact of Childhood Health Conditions on Dropout from Upper-Secondary Education.
To quantify how large a part of educational dropout is due to adverse childhood health conditions and to estimate the risk of dropout across various physical and mental health conditions. A registry-based cohort study was conducted on a 20% random sample of Finns born in 1988-1995 (n = 101 284) followed for school dropout at ages 17 and 21. Four broad groups of health conditions (any, somatic, mental, and injury) and 25 specific health conditions were assessed from inpatient and outpatient care records at ages 10-16 years. We estimated the immediate and more persistent risks of dropout due to health conditions and calculated population-attributable fractions to quantify the population impact of childhood health on educational dropout, while accounting for a wide array of sociodemographic confounders and comorbidity. Children with any health condition requiring inpatient or outpatient care at ages 10-16 years were more likely to be dropouts at ages 17 years (risk ratio 1.71, 95% CI 1.61-1.81) and 21 years (1.46, 1.37-1.54) following adjustment for individual and family sociodemographic factors. A total of 30% of school dropout was attributable to health conditions at age 17 years and 21% at age 21 years. Mental disorders alone had an attributable fraction of 11% at age 21 years, compared with 5% for both somatic conditions and injuries. Adjusting for the presence of mental disorders reduced the effects of somatic conditions. More than one fifth of educational dropout is attributable to childhood health conditions. Early-onset mental disorders emerge as key targets in reducing dropout.


Global gene expression analysis identifies PDEF transcriptional networks regulating cell migration during cancer progression.
Prostate derived ETS factor (PDEF) is an ETS (epithelial-specific E26 transforming sequence) family member that has been identified as a potential tumor suppressor. In multiple invasive breast cancer cells, PDEF expression inhibits cell migration by preventing the acquisition of directional morphological polarity conferred by changes in cytoskeleton organization. In this study, microarray analysis was used to identify >200 human genes that displayed a common differential expression pattern in three invasive breast cancer cell lines after expression of exogenous PDEF protein. Gene ontology associations and data mining analysis identified focal adhesion, adherens junctions, cell adhesion, and actin cytoskeleton regulation as cell migration-associated interaction pathways significantly impacted by PDEF expression. Validation experiments confirmed the differential expression of four cytoskeleton-associated genes with known functional associations with these pathways: uPA, uPAR, LASP1, and VASP. Significantly, chromatin immunoprecipitation studies identified PDEF as a direct negative regulator of the metastasis-associated gene uPA and phenotypic rescue experiments demonstrate that exogenous urokinase plasminogen activator (uPA) expression can restore the migratory ability of invasive breast cancer cells expressing PDEF. Furthermore, immunofluorescence studies identify the subcellular relocalization of urokinase plasminogen activator receptor (uPAR), LIM and SH3 protein (LASP1), and vasodilator-stimulated protein (VASP) as a possible mechanism accounting for the loss of morphological polarity observed upon PDEF expression.


Aerobic Degradation of Sulfadiazine by Arthrobacter spp.: Kinetics, Pathways, and Genomic Characterization.
Two aerobic sulfadiazine (SDZ) degrading bacterial strains, D2 and D4, affiliated with the genus Arthrobacter, were isolated from SDZ-enriched activated sludge. The degradation of SDZ by the two isolates followed first-order decay kinetics. The half-life time of complete SDZ degradation was 11.3 h for strain D2 and 46.4 h for strain D4. Degradation kinetic changed from nongrowth to growth-linked when glucose was introduced as the cosubstrate, and accelerated biodegradation rate was observed after the adaption period. Both isolates could degrade SDZ into 12 biodegradation products via 3 parallel pathways, of which 2-amino-4-hydroxypyrimidine was detected as the principal intermediate product toward the pyrimidine ring cleavage. Compared with five Arthrobacter strains reported previously, D2 and D4 were the only Arthrobacter strains which could degrade SDZ as the sole carbon source. The draft genomes of D2 and D4, with the same completeness of 99.7%, were compared to other genomes of related species. Overall, these two isolates shared high genomic similarities with the s-triazine-degrading Arthrobacter sp. AK-YN10 and the sulfonamide-degrading bacteria Microbacterium sp. C448. In addition, the two genomes contained a few significant regions of difference which may carry the functional genes involved in sulfonamide degradation.


Serum calcium level is related to both intima-media thickness and carotid atherosclerosis: a neglect risk factor in obese/overweight subjects.
Experimental studies suggested that high serum calcium may be important in the pathogenesis of vascular diseases. Since calcium seems to affect specifically the cerebrovascular district, aim of this study was to determine the relation between serum calcium levels, within normal range, and subclinical atherosclerosis in the carotid arteries, in a population of obese/overweight subjects. In our retrospective study we included 472 subjects (59% female) with body mass index equal to or more than 25 kg/m2. They underwent a physical examination, a biochemical assessment (including calcium evaluation) and a B-mode ultrasonography of the extracranial carotid arteries to detect carotid atherosclerosis presence and to measure intima-media thickness. Mean age of the population was 50 ±12 years. Prevalence of the Carotid atherosclerosis was 40%. Mean carotid intima-media thickness was 0,66 ± 0,18 mm. The univariate and multivariate analysis showed an association between calcium and carotid intima-media thickness (p = 0,035). We divided the population in serum calcium tertiles. We found an higher carotid atherosclerosis prevalence in the III tertile in comparison to that of the I tertile (p = 0,039). In this study we found a positive relation between serum calcium levels, within normal range, and subclinical atherosclerosis in the carotid arteries, in a population of obese/overweight subjects. It is important to consider the impact of the serum calcium levels in the overall risk assessment of patients, at least in obese subjects.


beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension.
Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.


Pathways of 4-hydroxybenzoate degradation among species of Bacillus.
The pathways used by three bacterial strains of the genus Bacillus to degrade 4-hydroxybenzoate are delineated. When B. brevis strain PHB-2 is grown on 4-hydroxybenzoate, enzymes of the protocatechuate branch of the beta-ketoadipate pathway are induced. In contrast, B. circulans strain 3 contains high levels of the enzymes of the protocatechuate 2,3-dioxygenase pathway after growth on 4-hydroxybenzoate. B. laterosporus strain PHB-7a degrades 4-hydroxybenzoate by a novel reaction sequence. After growth on 4-hydroxybenzoate, strain PHB-7a contains high levels of gentisate oxygenase (EC 188.8.131.52) and maleylpyruvate hydrolase. Whole cells of strain PHB-7a (grown on 4-hydroxylbenzoate) accumulate 2,5-dihydroxybenzoate (gentisate) from 4-hydroxybenzoate when incubated in the presence of 1mM alpha,alpha'-dipyridyl. Thus, strain PHB-7a appears to convert 4-hydroxybenzoate to gentisate, which is further degraded by the glutathione-independent gentisic acid pathway. These pathway delineations provide evidence that Bacillus species are derived from a diverse evolutionary background.


Pharmacokinetics and pharmacodynamics of clevidipine in healthy volunteers after intravenous infusion.
To determine the pharmacokinetics and pharmacodynamics of clevidipine, a new ultrashort-acting calcium antagonist, in healthy male volunteers following a constant rate infusion. Eight healthy male volunteers received 1030 nmol x min(-1) of clevidipine together with a tracer dose of 3[H]-clevidipine for 1 h as an i.v. infusion. Frequent venous blood samples and effect recordings were obtained during ongoing infusion and up to 32 h following termination of the infusion. The excretion of radioactivity in urine and faeces was followed for 7 days. A two-compartment model gave the best fit to the individual clevidipine blood levels, resulting in a mean blood clearance of 0.14 (0.03) l x min(-1) x kg(-1) and a mean volume of distribution at steady state of 0.6 (0.1) l x kg(-1). The initial half-life was 1.6 (0.3) min, and the terminal half-life was 15 (5) min. The maximum concentration of the metabolite H 152/81 was reached 2.2 (1.3) min following termination of the infusion. The mean terminal half-life of the inactive primary metabolite was 9.5 (0.8) h and the mean recovery of the radioactive dose reached 83 (3)%. Following termination of the 1 h infusion, the effect on blood pressure (BP) and heart rate was back to pre-dose values within 15 min. Clevidipine is a high clearance drug, which is rapidly metabolized to the corresponding inactive acid. The tmax value of the primary metabolite, and a virtually identical value of the initial half-life and the half-life for elimination from the central compartment, indicate that the initial rapid decline of the post-infusion blood levels is mainly due to elimination rather than distribution. The duration of action of clevidipine is short.


Immune mechanisms in the pathogenesis of chronic active hepatitis.
The present paper is a review of investigations concerning the pathogenesis of chronic active hepatitis (CAH). After a brief reexamination of the classification and etiology of CAH, details are given regarding the immunologic aspects of postviral CAH and of CAH considered as autoimmune. The work is a critical analysis of the mechanisms of both cellular immunity and humoral immunity, as well as of possible genetic disorders of the immune response.


Towards the enantioselective synthesis of (-)-euonyminol--preparation of a fully functionalised lower-rim model.
The development of a stereoselective total synthesis of β-dihydroagarofuran 4 is described. This compound contains the same oxygenation pattern on its 'lower-rim' as found in the natural sesquiterpene (-)-euonyminol (1) and it is expected that the route described should be applicable to the synthesis of that complex natural product. (-)-Euonyminol is found as the core scaffold of a series of complex macrodilactone sesquiterpenoids isolated from the Celastraceae which possess interesting biological activities (e.g. anti-HIV activity). The synthetic route builds upon an epoxidative asymmetric desymmetrisation of meso-diallylic alcohol 10 that we have reported previously. It features a lactate Ireland-Claisen rearrangement to establish the quaternary stereocentre at C11 (27→28a) and an unusual dealkylative intramolecular epoxide-opening by the C11 methyl ether to establish the tetrahydrofuranyl C-ring of the β-dihydroagarofuran skeleton (35→36).


A Retrospective Analysis of the Need for the Root Canal Therapy for the Full Crown Restorations: An Original Study.
There are numerous chances for pulpal irritation during the placement of a crown on a tooth. This study's goal was to find and examine the variables that influence the prevalence of routine root canal therapy after the teeth were restored with full coverage crowns. The hospital records were retrospectively evaluated from 2000 to 2010 for a decade. The demographics as well as the various variables that caused for the intervention with the root canal therapy for the teeth with the full crowns were evaluated. The values were compared for the significance. The total number of the teeth that were finalized in the study was 4308. Of the total teeth that were treated with full coverage crowns, 50% were metal ceramic, 42% were full ceramic, and 9% were full metal crowns. After 10 years, possibility that every tooth with a crown would survive was 91%. The most frequent adverse incident was the intervention with the RCT. Metal ceramic crowns had poor survival rates and needed the maximum intervention. Younger age-group had least survival rate than the older age-groups. Endodontic therapy is unlikely to be necessary after crown installation. As the patient's age declines and all-ceramic or PFM crowns are used, this risk rises.


[A consensus recommendation for the interpretation and reporting of copy number variation and regions of homozygosity in prenatal genetic diagnosis].
Chromosomal microdeletions and microduplications have been proven to be a significant proportion of genetic factors underlying birth defects. Chromosomal microarray analysis (CMA) and next generation sequencing-based copy number variation (CNV-seq) assay have been recommended as first-tier tests for prenatal evaluation of disease-causing CNV across the genome. With the broad application of such technologies in prenatal genetic diagnosis, there is a needed to enhance the consistency in interpretation and reporting of CNV results in clinical laboratories across China. In addition, a standard guideline for prenatal analysis and reporting of regions of homozygosity (ROH) is also required. To assist the classification, interpretation and reporting of CNV/ROH, the following recommendations have been developed, which may enhance a standard application of CMA/CNV-seq techniques in prenatal genetic diagnosis.


[Recent findings on the physiopathology of hypertension].
The numerous pathophysiological theories in the field of essential hypertension are often conflicting, and till now a comprehensive model is not available. The aetiology of human hypertension is probably multifactorial, the control mechanisms of hypertension are strictly interdependent, and the alteration of one induces readjustment of the others, so that it is very difficult to discriminate the "primum movens" from its consequences. In this review the recent acquisitions in the aetiology and the pathophysiology of arterial hypertension are analysed, with particular regard to the role of inheritance, of renal mechanisms of sodium retention, ions transport, humoral factors, central nervous system and of enhanced vascular reactivity. The activation of some of these pathophysiological factors induces the rise in peripheral vascular resistance, which is the final common pathway in the development of essential hypertension.


Surface Acoustic Wave (SAW) biosensors: coupling of sensing layers and measurement.
Surface acoustic wave (SAW) devices based on horizontally polarized surface shear waves enable direct and label-free detection of proteins in real time. Signal response changes result mainly from mass increase and viscoelasticity changes on the device surface. With an appropriate sensor configuration all types of binding reactions can be detected by determining resonant frequency changes of an oscillator. To create a biosensor, SAW devices have to be coated with a sensing layer binding specifically to the analyte. Intermediate hydrogel layers used within the coating have been proven to be very suitable to easily immobilize capture molecules or ligands corresponding to the analyte. However, aside from mass increase due to analyte binding, the SAW signal response in a subsequent binding experiment strongly depends on the morphology of the sensing layer, as this may lead to different relative changes of viscoelasticity. Bearing these points in mind, we present two basic biosensor coating procedures, one with immobilized capture molecule and a second with immobilized ligand, allowing reliable SAW biosensor signal responses in subsequent binding assays.


Different concentrations of I-123 MIBG and In-111 pentetreotide in the two main liver lobes in children: persisting regional functional differences after birth?
At examinations in children with I-123 metaiodobenzylguanidine or with In-111 pentetreotide using SPECT, we have observed a different distribution of the radiopharmaceuticals between the left and right main liver lobes. This phenomenon was studied in retrospect from clinical examinations. Seventeen children (mean age, 51 months; range, 11-150 months) with neuroblastoma or ganglioneuroma examined with both radiopharmaceuticals within 1 week using SPECT were assessed. There was no history of liver disease and all liver lobes showed uniform activity distribution. Simultaneous radiologic examinations were all normal with regard to the liver. No child with a pathologic liver chemistry test was included. The activity ratios between the left and right main liver lobes were calculated from transverse tomographic sections. The mean left:right lobar activity ratio for I-123 metaiodobenzylguanidine was 1.26+/-0.12 (null hypothesis=1.00; P<0.001) and for In-111 pentetreotide 0.88+/-0.06 (null hypothesis=1.00; P<0.001). There was no age-dependent distribution of the tracers. The correlation between the tracer uptake of the different liver lobes was very weak. A functional difference between the 2 main liver lobes in utero is believed to reflect differences of the vascular supply. The current findings indicate a persisting functional heterogeneity of the liver after birth not caused by perfusion differences. A relatively higher uptake of I-123 MIBG and a lower uptake of In-111 pentetreotide of the left liver lobe are normal findings.


Trinucleotide repeat length and rate of progression of Huntington's disease.
The Huntington's disease gene contains an expanded unstable (CAG)n repeat, and the repeat lengths have been shown to correlate with the age of onset. Using detailed clinical scales, we evaluated the rate of progression of Huntington's disease and its relationship to the number of triplet repeats. We found significant positive correlation between the rate of progression of clinical symptoms (both neurological and psychiatric) and CAG repeat length. These data suggest an important role of expanded trinucleotide repeat length in affecting the pathological process during the entire course of Huntington's disease.


Influence of injection rates of calibrating standard solution on monitoring pulse indicator continuous cardiac output.
This study aimed to investigate the influence of injection rates of calibrating standard solution on monitoring pulse indicator continuous cardiac output (PICCO, made in Germany), and thereby to provide significant references for clinical practice. A total of 108 critical patients in stroke intensive care unit were identified. All these participants received transesophageal cardiac color Doppler ultrasound, and within 15 min PICCO equipment was utilized to monitor the relevant parameters, by means of 0 °C calibrating standard solution, and the injection speeds were 2-4, 5-7, and 8-10 s. Besides, the monitoring indicators were as follows, cardiac index, global ejection fraction, global end diastolic volume index. The potential correlations were evaluated between PICCO and transesophageal cardiac color Doppler ultrasound. All the data was available, and the monitored parameters of PICOO at 2-4, 5-7, and 8-10 s were positively correlated with the parameters obtained from transesophageal cardiac color Doppler ultrasound (P < 0.05). Specially, it is worth emphasizing that the best correlation between them could be provided when the injection rate was 2-4 s. When the injection rate at 2-4 s, the parameters obtained by PICOO were much closer to that of transesophageal cardiac color Doppler ultrasound. Furthermore, the parameters of PICOO obtained at 2-4 s could better reflect cardiac function of patients.


Food Quality in Lusaka National Park: Tracking Mortality in Black Lechwe Antelopes.
Translocation is one of the fundamental tools in wildlife management but only if appropriately undertaken. In 2009, 30 black lechwe antelopes were suddenly translocated from the State House Habitat (STH) into the newly established Lusaka National Park (LNP). However, within 4 months of being translocated to LNP, 28 black lechwes (93%) died. A pathological report produced by veterinarians following a postmortem examination suggested no disease incidence affected the antelopes. The food quality of LNP was tested and compared to that in the STH and the antelopes' native habitat of the Bangweulu wetlands (BGW) to establish if variations in food quality were responsible for the antelopes' mortality. The findings suggest that the food quality in LNP was greatly inferior to that in STH, which could explain the observed high mortality of the antelopes in LNP. Further, the quality of food in LNP did not widely differ from that in the BGW, suggesting that the antelopes might not have survived had they been translocated to their native habitat, as they had already adapted to feeding on highly nutritious supplementary feed at the STH.


Novel therapies focused on the high-density lipoprotein particle.
Cardiovascular disease (CVD) remains a major burden for morbidity and mortality in the general population, despite current efficacious low-density lipoprotein-cholesterol-lowering therapies. Consequently, novel therapies are required to reduce this residual risk. Prospective epidemiological studies have shown that high-density lipoprotein-cholesterol (HDL-C) levels are inversely correlated with cardiovascular disease risk, and this initiated the quest for HDL-C-increasing therapies. Consequently, several different targets in HDL metabolism have been identified. Initial studies addressing the effect of cholesteryl ester transfer protein inhibition on cardiovascular disease outcome have been discontinued for reasons of futility or increased mortality. As of yet, 2 cholesteryl ester transfer protein inhibitors are still in phase III studies. Other HDL-based interventions, such as apolipoprotein A1-based compounds, ABC-transporter upregulators, selective peroxisome proliferator-activated receptor modulators and lecithin-cholesterol acyltransferase-based therapy, hold great promise for the future. The aim of this review is to provide a comprehensive overview of HDL-targeted pharmaceutical strategies in humans, both in early development as well as in late stage clinical trials.


Rejuvenating rice proteomics: facts, challenges, and visions.
Proteomics is progressing at an unprecedented pace, as can be exemplified by the progress in model organisms such as yeast, bacteria, and mammals. Proteomics research in plants, however, has not progressed at the same pace. Unscrambling of the genome sequences of the dicotyledoneous Arabidopsis thaliana (L.) and monocotyledoneous rice (Oryza sativa L.) plant species, respectively, has made them accessible reference organisms to study plant proteomics. Study of these two reference plants is expected to unravel the mystery of plant biology. Rice, a critically important food crop on the earth, has been termed a "cornerstone" and the "Rosetta stone" for functional genomics of cereal crops. Here, we look at the progress in unraveling rice proteomes and present the facts, challenges, and vision. The text is divided into two major parts: the first part presents the facts and the second part discusses the challenges and vision. The facts include the technology and its use in developing proteomes, which have been critically and constructively reviewed. The challenges and vision deal with the establishment of technologies to exhaustively investigate the protein components of a proteome, to generate high-resolution gel-based reference maps, and to give rice proteomics a functional dimension by studying PTMs and isolation of multiprotein complexes. Finally, we direct a vision on rice proteomics. This is our third review in series on rice proteomics, which aims to stimulate an objective discussion among rice researchers and to understand the necessity and impact of unraveling rice proteomes to their full potential.


Accurate localization of ruptured sinus of Valsalva aneurysm by real-time two-dimensional Doppler flow imaging.
The surgical approach to the repair of a ruptured sinus of Valsalva aneurysm can depend on the cardiac chamber into which rupture occurs. This report details the color flow Doppler images in two patients who developed a right sinus of Valsalva aneurysm to right atrial fistula owing to bacterial endocarditis. In both cases, the color flow Doppler image was superior to contrast aortography in identifying the chamber into which rupture had occurred. The early experience with real-time two-dimensional Doppler flow imaging suggests that this noninvasive technique is valuable in the management of ruptured sinus of Valsalva aneurysms.


[Fever and lung abscesses in anorexia nervosa after infusion therapy].
A 26 year old female patient was admitted to our hospital because of septic temperatures and chills. In the patient's history renal insufficiency has been known for several years due to agenesia of the right and pyelonephritic renal congestion of the left kidney. Long lasting anorexia nervosa had been treated by psychotherapeutical interventions for years and when failing it necessitated repeated intravenous nutrition by central venous lines. The prominent symptom of the intravenously treated young woman was fever up to 39.7 degrees C and pneumonia, which was considered by the first treating clinic to be caused directly by diminished immunoreactivity in malnutrition and preuremia. The chest X-ray confirmed pneumonia and revealed multiple abscesses in both lungs (Figure 1). After being transferred to our intensive care unit the pathophysiological context became obvious. From inspection (positive jugular pulsation), from auscultation (holosystolic murmur at the left parasternal border) tricuspid incompetence due to infective endocarditis was suspected. This was confirmed immediately by TM and two-dimensional transthoracic echocardiography, which showed a large vegetation on the anterior tricuspid valve leaflet (Figures 2a and 2b). Tricuspid regurgitation was also ascertained by color flow echocardiography (Figure 2c). Several blood cultures were positive for staphylococcus aureus. Clinical and laboratory recovery was achieved by antibiotic therapy with vancomycin and cephtazidim for 3 months.(ABSTRACT TRUNCATED AT 250 WORDS)


Relation between clinical mature and immature lymphocyte cells in human peripheral blood and their spatial label free scattering patterns.
A single living cell's light scattering pattern (LSP) in the horizontal plane, which has been denoted as the cell's "2D fingerprint," may provide a powerful label-free detection tool in clinical applications. We have recently studied the LSP in spatial scattering planes, denoted as the cell's "3D fingerprint," for mature and immature lymphocyte cells in human peripheral blood. The effects of membrane size, morphology, and the existence of the nucleus on the spatial LSP are discussed. In order to distinguish clinical label-free mature and immature lymphocytes, the special features of the spatial LSP are studied by statistical method in both the spatial and frequency domains. Spatial LSP provides rich information on the cell's morphology and contents, which can distinguish mature from immature lymphocyte cells and hence ultimately it may be a useful label-free technique for clinical leukemia diagnosis.


Anxiety And Depression In Medical Students Of A Private Medical College.
Depression and anxiety are the common mental disorders with a prevalence of 10-44% in developing countries and is the fourth leading cause of morbidity. Undergraduate medical studies are generally perceived to be more stressful for the students as compared to other undergraduate programs as students have to undergo strenuous curriculum and evaluation which may lead to many emotional stresses that may end with psychiatric disorders like depression and anxiety. This study aimed to determine the frequency of anxiety and depression in medical students of Foundation University Medical College (FUMC), Islamabad. In this cross-sectional study, Beck Depressive Inventory and Beck Anxiety Scales were used to assess anxiety and depression at three different times of the Academic year. All five-year students were included in the study. Out of a sample of 150 students, mild depression was seen in 37.46% and moderate to severe depression was observed in 14% students. About 19% of the students had moderate to severe anxiety. In Second year students time of assessment was significantly related to depression and anxiety (p-0.000). Females had higher association with depression in final year (p-0.037). High Psychiatric morbidity found needs to be identified and treated at the earliest; otherwise it can lead to serious consequences such as suicidal ideation and burnout.


Air pollution and inflammatory response in myocardial infarction survivors: gene-environment interactions in a high-risk group.
Ambient air pollution has been associated with an increased risk of hospital admission and mortality in potentially susceptible subpopulations, including myocardial infarction (MI) survivors. The multicenter epidemiological study described in this report was set up to study the role of air pollution in eliciting inflammation in MI survivors in six European cities, Helsinki, Stockholm, Augsburg, Rome, Barcelona, and Athens. Outcomes of interest are plasma concentrations of the proinflammatory cytokine interleukin 6 (IL-6) and the acute-phase proteins C-reactive protein (CRP) and fibrinogen. In addition, the study was designed to assess the role of candidate gene polymorphisms hypothesized to lead to a modification of the short-term effects of ambient air pollution. In total, 1003 MI survivors were recruited and assessed with at least 2 repeated clinic visits without any signs of infections. In total, 5813 blood samples were collected, equivalent to an average of 5.8 repeated clinic visits per subject (97% of the scheduled 6 repeated visits). Subjects across the six cities varied with respect to risk factor profiles. Most of the subjects were nonsmokers, but light smokers were included in Rome, Barcelona, and Athens. Substantial inter- and intraindividual variability was observed for IL-6 and CRP. The study will permit assessing the role of cardiovascular disease risk factors, including ambient air pollution and genetic polymorphisms in candidate genes, in determining the inter- and the intraindividual variability in plasma IL-6, CRP, and fibrinogen concentrations in MI survivors.


Coconut power: a sustainable approach for the removal of Cr6+ ions using a new coconut-based polyurethane foam/activated carbon composite in a fixed-bed column.
To attain efficient removal of hexavalent chromium (Cr6+) from aqueous solutions, a novel polyurethane foam-activated carbon (PUAC) adsorbent composite was developed. The composite material was synthesized by the binding of coconut shell-based activated carbon (AC) onto a coconut oil-based polyurethane matrix. To thoroughly characterize the physicochemical properties of the newly developed material, various analytical techniques including FTIR spectroscopy, SEM, XRD, BET, and TGA analyses were conducted. The removal efficiency of the PUAC composite in removing Cr6+ ions from aqueous solutions was evaluated through column experiments with the highest adsorption capacity of 28.41 mg g-1 while taking into account variables such as bed height, flow rate, initial Cr6+ ion concentration, and pH. Experimental data were fitted using Thomas, Yoon-Nelson, and Adams-Bohart models to predict the column profiles and the results demonstrate high breakthrough and exhaustion time dependence on these variables. Among the obtained R2 values of the models, a better fit was observed using the Thomas and Yoon-Nelson models, indicating their ability to effectively predict the adsorption of Cr6+ ions in a fixed bed column. Significantly, the exhausted adsorbent can be conveniently regenerated without any noteworthy loss of adsorption capability. Based on these findings, it can be concluded that this new PUAC composite material holds significant promise as a potent sorbent for wastewater treatment backed by its excellent performance, cost-effectiveness, biodegradability, and outstanding reusability.


Not Having Been Breastfed May Protect Chinese Women From Developing Deep Infiltrating Endometriosis: Results From Subgroup Analyses of the FEELING Study.
This study aimed to investigate potential factors, especially early-life exposures, associated with endometrioma (OMA) and/or deep infiltrating endometriosis (DIE) in Chinese women. This is a subgroup analyses of the FEELING study, which was a case-control study that investigated the clinical, lifestyle, and environmental factors associated with OMA and/or DIE in China, Russia, and France. In this subgroup analysis, the data for the Chinese participants were further analyzed using logistic regression model. All women (N = 546) had fully completed the questionnaire. The mean age of the participants was 31.8 (range: 18-41) years. Univariable analysis showed that noncyclic chronic pelvic pain, dysmenorrhea intensity class, and whether breastfed during infancy were distributed differently between patients with OMA or DIE and those with no endometriosis (non-EM) or superficial peritoneal endometriosis (SUP; P < .05). Multivariable analysis revealed that not having been breastfed was a protective factor against OMA and DIE (odds ratio [OR] = 0.33, 95% confidence interval [CI]: 0.16-0.69). Further analysis indicated not having been breastfed was a protective factor for DIE compared with non-EM (OR = 0.13, 95% CI: 0.02-0.88) and with OMA + SUP (OR = 0.19, 95% CI: 0.04-0.85) but was not a protective factor for OMA compared with non-EM (OR = 0.66, 95% CI: 0.32-1.36) and with SUP (OR = 0.63, 95% CI: 0.31-1.30). This is the first study suggesting that not having been breastfed might protect against DIE in Chinese women.


Primary meningococcal arthritis as a presentation of nodal marginal zone lymphoma.
A 68-year-old man presented with a 4-day history of worsening knee and arm pain. On examination, there was erythema and swelling of the left knee and both wrists. Joint aspiration grew Neisseria meningitidis Blood tests showed an unusually high total protein level (100 g/L) and an IgM kappa paraprotein band of 45 g/L on protein electrophoresis. CT showed widespread lymphadenopathy, hepatosplenomegaly and multilevel thoracic vertebral collapse. A bone marrow biopsy revealed a lymphoplasmacytic infiltrate and a lymph node biopsy showed features of nodal marginal zone lymphoma with plasmacytic differentiation.


Maximum likelihood estimation of structural wave components from noisy data.
In this paper, a general framework is developed for determining the underlying parameters of general signal models through the application of maximum likelihood estimation theory for functions whose variables separate. This method extends previous work in sinusoidal and exponential estimation to include models with other functional bases, such as exponential functions with nonconstant amplitudes and Bessel functions. Nonuniform spatial sampling is also possible with this technique. The maximum likelihood method is applied to the identification of wave components along one-dimensional structural elements. Results are given which demonstrate the viability and accuracy of the technique estimating exponential and Bessel function model parameters from noisy simulation data.


Therapeutic Use of Anti-Sclerostin Antibody in the Treatment of Multiple Myeloma: A Systematic Review.
Multiple myeloma is a malignant cancerous condition that is characterized by abnormal plasma cell production and can lead to bone destruction due to increased osteoclastic activity and decreased osteoblastic activity. Many therapeutic therapies are used to treat diseases, such as chemotherapy and radiotherapy. In recent years, anti-sclerostin antibody treatment has been under investigation for its effect on the multiple myeloma. The present study was conducted to assess the effective therapeutic use of anti-sclerostin antibody in the treatment of multiple myeloma. The literature search was conducted using PubMed, Google Scholar, ScienceDirect, and PubMed Central using the following MeSH terms: "multiple myeloma", "anti-sclerostin antibody", "ubiquitin-proteasome pathway", "proteasome inhibitor", "Wnt pathway". A total of 348 articles were screened. Twenty-five out of 348 were full-text articles assessed for eligibility, and four articles were used in this systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the reporting of this systematic review. A total of four randomized control trials (RCT) were included and used in this systematic review. The anti-sclerostin antibodies were various other drugs, and it was found that the anti-sclerostin antibody was effective in preventing autoantibody formation, decreasing bone destruction, and increasing trabecular bone. Anti-sclerostin antibody was found to be effective in decreasing bone destruction by reducing osteoclastic activity and increasing osteoblastic activity associated with multiple myeloma.


Changes in cardiac function after pedicle subtraction osteotomy in patients with a kyphosis due to ankylosing spondylitis.
Cardiac disease in patients with ankylosing spondylitis (AS) has previously been studied but not in patients with a kyphosis or in those who have undergone an operation to correct it. The aim of this study was to measure the post-operative changes in cardiac function of patients with an AS kyphosis after pedicle subtraction osteotomy (PSO). The original cohort consisted of 39 patients (33 men, six women). Of these, four patients (two men, two women) were lost to follow-up leaving 35 patients (31 men, four women) to study. The mean age of the remaining patients was 37.4 years (22.3 to 47.8) and their mean duration of AS was 17.0 years (4.6 to 26.4). Echocardiographic measurements, resting heart rate (RHR), physical function score (PFS), and full-length standing spinal radiographs were obtained before surgery and at the two-year follow-up. The mean pre-operative RHR was 80.2 bpm (60.6 to 112.3) which dropped to a mean of 73.7 bpm (60.7 to 90.6) at the two-year follow-up (p = 0.0000). Of 15 patients with normal ventricular function pre-operatively, two developed mild left ventricular diastolic dysfunction (LVDD) at the two-year follow-up. Of 20 patients with mild LVDD pre-operatively only five had this post-operatively. Overall, 15 patients had normal LV diastolic function before their operation and 28 patients had normal LV function at the two-year follow-up. The clinical improvement was 15 out of 20 (75.0%): cardiac function in patients with AS whose kyphosis was treated by PSO was significantly improved.


Treating pancreatitis in the acute care setting.
Acute pancreatitis is associated with significant complications and mortality. This article describes the pathophysiology and complications of, and treatments for acute pancreatitis, and the nurse's role in caring for a patient in the acute care setting.


Comparison of N-terminal pro B-natriuretic Peptide and echocardiographic indices in patients with mitral regurgitation.
Echocardiographic indices can form the basis of the diagnosis of systolic and diastolic left ventricular (LV) dysfunction in patients with Mitral regurgitation (MR). However, using echocardiography alone may bring us to a diagnostic dead-end. The aim of this study was to compare N-Terminal pro B-natriuretic peptide (BNP) and echocardiographic indices in patients with mitral regurgitation. 2D and Doppler echocardiography and BNP serum level were obtained from 54 patients with organic mild, moderate and severe MR. BNP LEVELS WERE INCREASED WITH SYMPTOMS IN PATIENTS WITH MITRAL REGURGITATION (NYHAI: 5.7 ± 1.1, NYHAII: 6.9 ± 1.5, NYHAIII: 8.3 ± 2 pg/ml, P < 0.001). BNP plasma level were significantly correlated with MPI (myocardial performance index) (r = 0.399, P = 0.004), and following echocardiographic indices: LVEDV (r = 0.45, P < 0.001), LVESV (r = 0.54, P < 0.001), LVEDD (r = 0.48, P < 0.001), LVESD (r = 0.54, P < 0.001), dp/dt (r = -0.32, P = 0.019) and SPAP (r = 0.4, P = 0.006). The present study showed that BNP may be useful in patients with MR and may confirm echocardiographic indices.


LAPAROSCOPIC MANAGEMENT OF DISTAL URETERIC STONE IN BILHARZIAL URETER: RESULTS OF A SINGLE CENTER PROSPECTIVE STUDY.
No doubt, Bilharzial ureters are complicated by distal stricture due to precipitation of Bilharzial ova in distal ureter. These cases are associated with poorly functioning and grossly hydronephroic kidneys that hinder endoscopic manipulation of the coexistent distal, high burden, long standing impacted stones. Thus, laparoscopic uretrolithotomy was performed in 51 bilharzial patients with distal ureteric stones 4 trocars were used. The ureter was opened directly over the stone and the stone was extracted. A double-J stent was inserted into the ureter which was closed by 4-0 polyglactin running suture. The results showed that among 51 cases 33 males and 18 females; the mean age was 40.13 years. the mean stone size was 2.73 cm. Conversion to open surgery was in only one case; the mean operative time 92.05 (range 75-120 minutes); postoperative pain score ranged from 20 to 60, the mean number of PO analgesic request was 1.72 (range 1-3); it was once in 21, twice in 23 and thrice in 7 cases. Hospital stay ranged from 2 to 5 with a mean of 2.74 days; total duration of follow up ranged from 7 to 12 with a mean of 9.68. Stone recurrence reported in 4 cases; ureteric stricture reported in 2 cases. Stone free rate was reported to be 100%.


Adolescent Personality as Risk and Resiliency in the Testosterone-Externalizing Association.
Previous investigations of testosterone and externalizing behavior have provided mixed findings. We tested the hypothesis that self-regulatory personality moderates the testosterone-externalizing behavior association in adolescence. Parents reported on their 13- to 18-year-old (N = 106, Mage = 16.01, SD = 1.29) children's personalities and psychopathology. Testosterone was measured via drool samples. As hypothesized, personality moderated the testosterone-externalizing behavior association. High testosterone predicted higher levels of externalizing behaviors, but only for adolescents low in Agreeableness and Conscientiousness. Also, personality acted as a resiliency factor: high levels of Conscientiousness, in the presence of high testosterone, predicted lower levels of rule breaking. Results highlight how endogenous factors, such as personality, may interact with testosterone, and emphasize the relevance of including personality moderators in future research.


Contribution of common PCSK1 genetic variants to obesity in 8,359 subjects from multi-ethnic American population.
Common PCSK1 variants (notably rs6232 and rs6235) have been shown to be associated with obesity in European, Asian and Mexican populations. To determine whether common PCSK1 variants contribute to obesity in American population, we conducted association analyses in 8,359 subjects using two multi-ethnic American studies: the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA). By evaluating the contribution of rs6232 and rs6235 in each ethnic group, we found that in European-American subjects from CARDIA, only rs6232 was associated with BMI (P = 0.006) and obesity (P = 0.018) but also increased the obesity incidence during the 20 years of follow-up (HR = 1.53 [1.07-2.19], P = 0.019). Alternatively, in African-American subjects from CARDIA, rs6235 was associated with BMI (P = 0.028) and obesity (P = 0.018). Further, by combining the two case-control ethnic groups from the CARDIA study in a meta-analysis, association between rs6235 and obesity risk remained significant (OR = 1.23 [1.05-1.45], P = 9.5×10(-3)). However, neither rs6232 nor rs6235 was associated with BMI or obesity in the MESA study. Interestingly, rs6232 was associated with BMI (P = 4.2×10(-3)) and obesity (P = 3.4×10(-3)) in the younger European-American group combining samples from the both studies [less than median age (53 years)], but not among the older age group (P = 0.756 and P = 0.935 for BMI and obesity, respectively). By combining all the case-control ethnic groups from CARDIA and MESA in a meta-analysis, we found no significant association for the both variants and obesity risk. Finally, by exploring the full PCSK1 locus, we observed that no variant remained significant after correction for multiple testing. These results indicate that common PCSK1 variants (notably rs6232 and rs6235) contribute modestly to obesity in multi-ethnic American population. Further, these results suggest that the association of rs6232 with obesity may be age-dependent in European-Americans. However, multiple replication studies in multi-ethnic American population are needed to confirm our findings.


Pharmacodynamic comparison of pitavastatin versus atorvastatin on platelet reactivity in patients with coronary artery disease treated with dual antiplatelet therapy.
Levels of platelet reactivity in patients on dual antiplatelet therapy (DAPT) can be influenced by concomitant treatment with statins. We verified if the pharmacodynamic effects of CYP3A4-metabolized statins (atorvastatin) and non-CYP3A4-metabolized statins (pitavastatin) differ in patients with coronary artery disease (CAD) treated with DAPT. A total of 155 CAD patients receiving DAPT (clopidogrel 75mg plus aspirin 100mg) entered the PORTO trial. Patients were randomly assigned to atorvastatin (20mg day) or pitavastatin (4mg day) for 30 days, and then switched to the other drug for 30 days. Platelet reactivity was expressed as VerifyNow P2Y12 platelet response units (PRU) before and after each 30-day treatment period. High platelet reactivity was defined as PRU >208. As compared with pretreatment (192±49), PRU was significantly higher after 30-day atorvastatin (210±56; P=0.003), but was unchanged after 30-day pitavastatin (199±47 PRU, NS). In the 48 patients with PRU >208 at baseline (232±44), PRU increased significantly after 30-day atorvastatin (258±41, P=0.004), but not after 30-day pitavastatin (237±43, NS). In the 107 patients with PRU <208 at baseline (174±52), PRU did not change significantly with respect to baseline either after 30-day atorvastatin (188±61, NS) or after 30-day pitavastatin (181±59, NS). Pitavastatin, a non-CYP3A4-metabolized statin, does not affect clopidogrel's response as compared with atorvastatin in patients who are borderline or poor responders to DAPT.