Blood pressure and associated cardiovascular risk factors in adolescents of Mexico City.
To determine the prevalence of high blood pressure and associated cardiovascular risk factors in Mexican adolescents. A cross-sectional study was conducted in 770 male and 1076 female students (12 to 16 years old) from eight randomly selected high schools in Mexico City. Anthropometry, blood pressure and fasting lipids and lipoproteins were measured. Blood pressure levels were adjusted for age, gender, and height. The prevalence rates of hypertension (systolic blood pressure (SBP) and/or diastolic (DBP) > or =95th percentile), and pre-hypertension (SBP or DBP > or =90th but <95th percentile) were 10.6 and 10%, respectively. Compared to normotensive subjects, those with high blood pressure showed a significantly higher prevalence of obesity, overweight, and dyslipidemia. A stepwise multiple regression analysis showed that waist (18.3%), Tanner stage (4.7%), age (2.1%), gender (0.6%), and body mass index (BMI, 0.3%) accounted for 26% of the variance in SBP; whereas BMI (8.7%), age (4.8%), Tanner stage (1.7%), waist (0.4%), and gender (0.4%) accounted for 15.9% of the variance in DBP. These results reveal a high prevalence of high blood pressure in adolescents living in Mexico City. Prehypertensive and hypertensive subjects showed a higher prevalence of cardiovascular risk factors, suggesting that, as adults, these adolescents will be at a higher risk of developing cardiovascular disease.


Model of the home food environment pertaining to childhood obesity.
The home food environment can be conceptualized as overlapping interactive domains composed of built and natural, sociocultural, political and economic, micro-level and macro-level environments. Each type and level of environment uniquely contributes influence through a mosaic of determinants depicting the home food environment as a major setting for shaping child dietary behavior and the development of obesity. Obesity is a multifactorial problem, and the home food environmental aspects described here represent a substantial part of the full environmental context in which a child grows, develops, eats, and behaves. The present review includes selected literature relevant to the home food environment's influence on obesity with the aim of presenting an ecologically informed model for future research and intervention in the home food environment.


Differential regulation of cell-cell contact, invasion and anoikis by hScrib and hDlg in keratinocytes.
The components of the Scrib/Dlg tumour suppressor complex have complementary roles in Drosophila and loss of both proteins is a common event in many different human tumours. However no studies have directly addressed the respective contributions of loss of hScrib and hDlg in the same human cell background to cellular phenotypes associated with cell transformation. In human HaCaT keratinocytes we show that removal of hScrib greatly reduces cell-cell contact and cell-matrix interactions, and promotes an invasive phenotype. Conversely, in cells lacking hDlg1 cell-cell contacts are maintained and there are decreases in both cell growth and invasion. However, hDlg-depleted cells show increased resistance to a specialized form of apoptosis known as anoikis, to which cells lacking hScrib are highly susceptible. Thus whilst it has been widely assumed that hScrib and hDlg have complementary roles, these studies in fact demonstrate that hScrib and hDlg1 have distinct and opposing functions in human keratinocytes.


Accuracy and reproducibility of aortic annulus sizing using a dedicated three-dimensional computed tomography reconstruction tool in patients evaluated for transcatheter aortic valve replacement.
To evaluate the accuracy and reproducibility of aortic annulus sizing using a multislice computed tomography (MSCT) based aortic root reconstruction tool compared with conventional imaging among patients evaluated for transcatheter aortic valve replacement (TAVR). Patients referred for TAVR underwent standard preprocedural assessment of aortic annulus parameters using MSCT, angiography and transoesophageal echocardiography (TEE). Three-dimensional (3D) reconstruction of MSCT images of the aortic root was performed using 3mensio (3mensio Medical Imaging BV, Bilthoven, The Netherlands), allowing for semi-automated delineation of the annular plane and assessment of annulus perimeter, area, maximum, minimum and virtual diameters derived from area and perimeter (aVD and pVD). A total of 177 patients were enrolled. We observed a good inter-observer variability of 3D reconstruction assessments with concordance coefficients for agreement of 0.91 (95% CI: 0.87-0.93) and 0.91 (0.88-0.94) for annulus perimeter and area assessments, respectively. 3D derived pVD and aVD correlated very closely with a concordance coefficient of 0.97 (0.96-0.98) with a mean difference of 0.5±0.3 mm (pVD-aVD). 3D derived pVD showed the best, but moderate concordance with diameters obtained from coronal MSCT (0.67, 0.56-0.75; 0.3±1.8 mm), and the lowest concordance with diameters obtained from TEE (0.42, 0.31-0.52; 1.9±1.9 mm). MSCT-based 3D reconstruction of the aortic annulus using the 3mensio software enables accurate and reproducible assessment of aortic annulus dimensions.


[Eye toxicity of antimalarial agents].
We relate the evolution of a patient with Systemic Lupus Erythematosus with mucocutaneous, hematological, joint and renal expression. The skin lesions were treated with Chloroquine and Hydroxychloroquine and severe ocular toxicity related with antimalarials agent was developed. We revised the antimalarials use in Rheumatology, their utility, doses, adverse events and risk factors as cumulate doses, ideal daily doses, renal function and ophthalmological reviews recommendations.


Phagocytosis of concanavalin A in normal and enucleated cultures of mammalian cells.
The fate of concanavalin A (Con A) bound to normal and enucleated L cells was followed at the ultrastructural level over a 20-h period. In both enucleates and normal cells the Con A is seen to be distributed in a uniform manner over the entire cell surface following a 30-min pulse with a low concentration of Con A. In the subsequent chase period the cells then aggregate the Con A and Con A sites into large clusters on the cell membrane. The cells then phagocytoze the Con A and large phagocytic vacuoles containing it are observed. Thus, enucleated cells are capable of phagocytozing Con A and its sites in the same manner as normal cells.


Immunizing efficacy of a Kenyan strain of Schistosoma mansoni in rhesus monkeys (Macaca mulatta).
The efficacy as an immunizing agent of the Kenyan strain of Schistosoma mansoni against challenge infection in rhesus monkeys was demonstrated. An initial exposure of 200 cercariae immunized monkeys against a challenge dose of 2,000 cercariae administered 16 weeks later. The penetration rate in rhesus monkeys was 99%, the same as in baboons. The prolongation of the time for immunity to develop in baboons, compared to rhesus monkeys, shown with this strain of S. mansoni is therefore not due to a reduced potential for immunization by this strain in the rhesus monkey.


UK-based, multisite, prospective cohort study of small bowel obstruction in acute surgical services: National Audit of Small Bowel Obstruction (NASBO) protocol.
Small bowel obstruction (SBO) is a common indication for emergency laparotomy in the UK, which is associated with a 90-day mortality rate of 13%. There are currently no UK clinical guidelines for the management of this condition. The aim of this multicentre prospective cohort study is to describe the burden, variation in management and associated outcomes of SBO in the UK adult population. UK hospitals providing emergency general surgery are eligible to participate. This study has three components: (1) a clinical preference questionnaire to be completed by consultants providing emergency general surgical care to assesses preferences in diagnostics and therapeutic approaches, including laparoscopy and nutritional interventions; (2) site resource profile questionnaire to indicate ease of access to diagnostic services, operating theatres, nutritional support teams and postoperative support including intensive care; (3) prospective cohort study of all cases of SBO admitted during an 8-week period at participating trusts. Data on diagnostics, operative and nutritional interventions, and in-hospital mortality and morbidity will be captured, followed by data validation. This will be conducted as a national audit of practice in conjunction with trainee research collaboratives, with support from patient representatives, surgeons, anaesthetists, gastroenterologists and a clinical trials unit. Site-specific reports will be provided to each participant site as well as an overall report to be disseminated through specialist societies. Results will be published in a formal project report endorsed by stakeholders, and in peer-reviewed scientific reports. Key findings will be debated at a focused national meeting with a view to quality improvement initiatives.


Isoniazid resistance and death in patients with tuberculous meningitis: retrospective cohort study.
To determine whether initial isoniazid resistance is associated with death during the treatment of tuberculous meningitis. Retrospective cohort study. National Tuberculosis Surveillance System at the Centers for Disease Control in the United States. Patients with a clinical diagnosis of tuberculous meningitis, reported to the National Tuberculosis Surveillance System between 1 January 1993 and 31 December 2005. All cause mortality during antituberculous treatment. Between 1993 and 2005, 1896 patients had a clinical diagnosis of tuberculous meningitis and positive cultures from any site. In 123 (6%) of these patients, isoniazid resistance was present on initial susceptibility testing. The unadjusted association between initial isoniazid resistance and subsequent death among these 1896 patients did not reach statistical significance (odds ratio 1.38, 95% confidence interval 0.94 to 2.02). However, among 1614 patients with positive cerebrospinal fluid cultures, a significant unadjusted association was found between initial isoniazid resistance and subsequent death (odds ratio 1.61, 1.08 to 2.40). This association increased after adjustment for age, race, sex, and HIV status (odds ratio 2.07, 1.30 to 3.29). Isoniazid resistance on initial susceptibility testing was associated with subsequent death among cases of tuberculous meningitis with positive cerebrospinal fluid cultures. Randomised controlled trials are needed to evaluate the optimal empirical regimen for treating patients with tuberculous meningitis who are at high risk for both initial isoniazid resistance and poor clinical outcomes.


[Some considerations about the use of carbon sources in jasmonic acid production.].
The effect of different carbon sources as sucrose, fructose, glucose and molasses were studied in relation to jasmonic acid production. The best results were obtained with a simple medium made up by final molasses, potassium nitrate and acid potassium phosphate, without the addition of other salts like Fe, Zn, Cu, Mo, etc. This alternative guaranteed a 100% increase in jasmonic acid production, compared to pattern medium, since a concentration of 2.08 g/l was obtained.


The hindlimb myology of Milvago chimango (Polyborinae, Falconidae).
We describe the hindlimb myology of Milvago chimango. This member of the Falconidae: Polyborinae is a generalist and opportunist that can jump and run down prey on the ground, unlike Falconinae that hunt birds in flight and kill them by striking with its talons. Due to differences in the locomotion habits between the subfamilies, we hypothesized differences in their hindlimb myology. Gross dissections showed that the myology of M. chimango is concordant with that described of other falconids, except for the following differences: the m. flexor cruris medialis has one belly with a longitudinal division; the m. iliotibialis lateralis does not have a connection with the m. iliofibularis; the m. fibularis longus is strongly aponeurotic; the m. tibialis cranialis lacks an accessory tendons and the m. flexor hallucis longus has one place of origin, instead of two. The presence of the m. flexor cruris lateralis can be distinguished as it has been described absent for the Falconidae. We associated its presence with the predominant terrestrial habit of the M. chimango. Each muscle dissected was weighed and the relationship between flexors and extensors at each joint was assessed. The extensor muscles predominated in all joints in M. chimango. Among the flexors, the m. flexor hallucis longus was the heaviest, which could be related to the importance of the use of its talons to obtain food.


Damage to bulbospinal serotonin-, tyrosine hydroxylase-, and TRH-containing axons occurs early in the development of experimental allergic encephalomyelitis in rats.
Spinal cord monoaminergic and peptidergic axonal damage occurring during the development of experimental allergic encephalomyelitis (EAE) was assessed using immunohistochemistry. Spinal cord axons immunoreactive for serotonin, catecholamines, or a thyrotropin-releasing hormone marker peptide were found to be markedly swollen and distorted by the earliest stage of detectable paralysis during EAE development (the flaccid tail stage). As clinical signs progressed to complete hindlimb paralysis, axonal damage became increasingly extensive. Axonal damage was equally pronounced whether EAE was induced by inoculation with purified myelin basic protein or with whole spinal cord homogenate, suggesting that the damage did not result from an immune attack directed against specific monoaminergic and/or peptidergic antigens present in the inoculant. However, two observations suggested that mechanical or chemical factors associated with the inflammatory foci contribute to the axonal damage: first, distorted axons were nearly always located adjacent to blood vessels or the pial surface, sites at which inflammation occurs during EAE. Second, the severity of axonal damage correlated with the severity of the inflammation. The early onset of axonal damage during development of EAE and the close correlation that was found between the severity of axonal damage and the severity of clinical signs suggested that the axonal damage may contribute to the clinical signs of the disease.


Epilepsy in children with trisomy 18.
Although the reported incidence of epilepsy associated with trisomy 18 is 25-50%, there have been no detailed descriptions of the characteristics of trisomy 18-related epilepsy. We investigated the characteristics of epilepsy in children with trisomy 18 who remained alive for over 1 year by sending questionnaires to pediatric neurologists belonging to the Kyoto Multi-institutional Study Group of Pediatric Neurology. Eleven patients with trisomy 18 were enrolled (age at the study, from 15 to 134 months; median, 43 months), of whom seven (64%) had epilepsy. The age at seizure onset ranged from 1 to 42 months (median: 11 months). Among the seven patients with epilepsy, two had focal epilepsy, four had generalized epilepsy including infantile spasms in three, and the remaining one had an unclassified type. Seizure seminology included complex partial seizures in both the patients with focal epilepsy. At the time of the investigation, three children with generalized epilepsy still had daily seizures, while the remaining four were seizure-free. In conclusion, the characteristics of epilepsy in patients with trisomy 18 were as follows: over half of the children developed epilepsy during infancy or early childhood; infantile spasms might be one of the common epileptic syndromes; the epilepsy was intractable in half of the children, especially in those with generalized epilepsy.


Effects of chromophore dissociation on the optical properties of rare-Earth-doped polymers.
The observed dissociation of tetrakis rare-earth chromophores in rare-earth-doped organic polymers is reported, and a time-resolved spectroscopic technique is presented to determine quantitatively the fractional concentrations of different chromophore species in various solvents. Based on this technique, the equilibrium constants of tetrakis rare-earth chromophores in rare-earth-doped polymers are determined. Thus, the equilibrium constants for tetrakis rare-earth compounds of benzoyltrifluoroacetonate (BTF), for example, Sm(BTF)(4)P and Eu(BTF)(4)P in methyl methacrylate monomer, are K = 4.7 ? 0.5 x 10(-4) M and K = 1.2 ? 0.5 x 10(-4) M, respectively. In contrast, the tetrakis rare-earth compounds of hexafluoroacetylacetonate (HFA), for example, Sm(HFA)(4)Net(4) and Eu(HFA)(4)Net(4), are quite stable and show no evidence of dissociation. We further characterize the dissociation of several chromophore systems and discuss the influence such dissociation has on overall optical performance. The results enable determination of optimal doping concentrations as well as preferred rare-earth chromophore preparation and doped polymer fabrication procedures.


A two-stage evolutionary process for designing TSK fuzzy rule-based systems.
Nowadays, fuzzy rule-based systems are successfully applied to many different real-world problems. Unfortunately, relatively few well-structured methodologies exist for designing and, in many cases, human experts are not able to express the knowledge needed to solve the problem in the form of fuzzy rules. Takagi-Sugeno-Kang (TSK) fuzzy rule-based systems were enunciated in order to solve this design problem because they are usually identified using numerical data. In this paper we present a two-stage evolutionary process for designing TSK fuzzy rule-based systems from examples combining a generation stage based on a (mu, lambda)-evolution strategy, in which the fuzzy rules with different consequents compete among themselves to form part of a preliminary knowledge base, and a refinement stage in which both the antecedent and consequent parts of the fuzzy rules in this previous knowledge base are adapted by a hybrid evolutionary process composed of a genetic algorithm and an evolution strategy to obtain the final Knowledge base whose rules cooperate in the best possible way. Some aspects make this process different from others proposed until now: the design problem is addressed in two different stages, the use of an angular coding of the consequent parameters that allows us to search across the whole space of possible solutions, and the use of the available knowledge about the system under identification to generate the initial populations of the Evolutionary Algorithms that causes the search process to obtain good solutions more quickly. The performance of the method proposed is shown by solving two different problems: the fuzzy modeling of some three-dimensional surfaces and the computing of the maintenance costs of electrical medium line in Spanish towns. Results obtained are compared with other kind of techniques, evolutionary learning processes to design TSK and Mamdani-type fuzzy rule-based systems in the first case, and classical regression and neural modeling in the second.


Tau Positron Emission Tomographic Imaging in the Lewy Body Diseases.
The causes of cognitive impairment in dementia with Lewy bodies (DLB) and Parkinson disease (PD) are multifactorial. Tau pathologic changes are commonly observed at autopsy in individuals with DLB and PD dementia, but their contribution to these diseases during life is unknown. To contrast tau aggregation in DLB, cognitively impaired persons with PD (PD-impaired), cognitively normal individuals with PD (PD-normal), and healthy persons serving as control participants, and to evaluate the association between tau aggregation, amyloid deposition, and cognitive function. This cross-sectional study was conducted from January 1, 2014, to April 28, 2016, in a tertiary care center's memory and movement disorders units. Twenty-four patients with Lewy body disease (7 DLB, 8 PD-impaired, and 9 PD-normal) underwent multimodal brain imaging, cognitive testing, and neurologic evaluation, and imaging measures were compared with those of an independently acquired group of 29 controls with minimal brain amyloid burden as measured with carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET). Imaging with fluorine 18-labeled AV-1451 ([18F]AV-1451) (formerly known as [18F]T807), [11C]PiB PET, magnetic resonance imaging (MRI), neurologic examination, and detailed cognitive testing using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale. Main outcomes were differentiation of diagnostic groups on the basis of [18F]AV-1451 binding, the association of [18F]AV-1451 binding with [11C]PiB binding, and the association of [18F]AV-1451 binding with cognitive impairment. All but 3 individuals underwent amyloid imaging with [11C]PiB PET. The hypotheses being tested were formulated before data collection. Mini-Mental State Examination (range, 0-30, with 30 being best) and Clinical Dementia Rating scale sum-of-boxes scale (range, 0-18, with 0 being best) were used for assessment of cognitive function. In patients with DLB, cortical [18F]AV-1451 uptake was highly variable and greater than in the controls, particularly in the inferior temporal gyrus and precuneus. Foci of increased [18F]AV-1451 binding in the inferior temporal gyrus and precuneus were also evident in PD-impaired patients. Elevated cortical [18F]AV-1451 binding was observed in 4 of 17 patients with Lewy body disease with low cortical [11C]PiB retention. For DLB and PD-impaired patients, greater [18F]AV-1451 uptake in the inferior temporal gyrus and precuneus was associated with increased cognitive impairment as measured with the MMSE and the Clinical Dementia Rating scale sum-of-boxes score. Patients with Lewy body disease manifest a spectrum of tau pathology. Cortical aggregates of tau are common in patients with DLB and in PD-impaired patients, even in those without elevated amyloid levels. When present, tau deposition is associated with cognitive impairment. These findings support a role for tau copathology in the Lewy body diseases.


Differential induction of tumor necrosis factor by bacteria expressing rough and smooth lipopolysaccharide phenotypes.
The lipid A portion of the lipopolysaccharide (LPS) molecule of gram-negative bacteria has the ability to turn on the production of tumor necrosis factor (TNF) in macrophage cells. The question addressed in this paper was whether the presence of the polysaccharide moiety on the LPS molecule had any bearing on this ability. The question was asked (i) by using isolated LPS from a series of Salmonella mutants having progressively less polysaccharide attached to the lipid A portion of the molecule and (ii) by using whole bacteria expressing alternatively the smooth or rough LPS phenotype. Isolated LPS and bacteria were examined for their abilities to induce bioactive TNF in the mouse macrophage cell line RAW 264.7. The results indicated that the presence of long- or short-chain polysaccharide moieties had no bearing on the ability of the isolated LPS molecule to induce TNF. However, the presence of long-chain polysaccharides attached to the lipid moiety on the intact smooth bacterium was associated with a decreased ability to induce TNF. To test whether the bacteria were inducing TNF by a cell (bacterium)-to-cell (macrophage) contact mechanism or through a releasable product, the bacteria were removed from direct contact with the macrophage cells by using a Transwell filter insert. Under these conditions the rough bacteria continued to induce TNF, while the smooth bacteria were no longer capable of doing so. When filtrates from the bacteria were examined in the Limulus amebocyte lysate assay, the results showed that the rough bacteria were releasing approximately a log order more Limulus amebocyte lysate activity than the smooth bacteria. The results of this study suggest that rough bacteria may be superior inducers of TNF compared with their smooth counterparts because of a greater propensity to shed their LPS.


Transport Phenomena of Water in Molecular Fluidic Channels.
In molecular-level fluidic transport, where the discrete characteristics of a molecular system are not negligible (in contrast to a continuum description), the response of the molecular water system might still be similar to the continuum description if the time and ensemble averages satisfy the ergodic hypothesis and the scale of the average is enough to recover the classical thermodynamic properties. However, even in such cases, the continuum description breaks down on the material interfaces. In short, molecular-level liquid flows exhibit substantially different physics from classical fluid transport theories because of (i) the interface/surface force field, (ii) thermal/velocity slip, (iii) the discreteness of fluid molecules at the interface and (iv) local viscosity. Therefore, in this study, we present the result of our investigations using molecular dynamics (MD) simulations with continuum-based energy equations and check the validity and limitations of the continuum hypothesis. Our study shows that when the continuum description is subjected to the proper treatment of the interface effects via modified boundary conditions, the so-called continuum-based modified-analytical solutions, they can adequately predict nanoscale fluid transport phenomena. The findings in this work have broad effects in overcoming current limitations in modeling/predicting the fluid behaviors of molecular fluidic devices.


Biorobotic simulations might offer some advantages over purely computational ones.
A slight modification of Webb's diagrammatic representation of the dimensions for describing models is proposed which extends it to cover a range of theoretical models as well as material models. It is also argued that beyond a certain level robotic simulations could offer a number of real advantages over computer simulations of organisms interacting with their environment.


A penny saved is ten dollars earned: fifteen ways to lower overhead and boost the bottom line.
As expenses rise and reimbursements remain flat or decline, it's more important than ever to scrutinize practice expenditures on a regular basis. This article provides tips for evaluating individual line items on the profit and loss statement and identifying expenses that can be reduced without sacrificing quality of care or patient satisfaction. When aggregated, even seemingly small reductions add up to big annual savings.


The experimental evaluation and molecular dynamics simulation of a heat-enhanced transdermal delivery system.
Transdermal delivery systems are useful in cases where preferred routes such as the oral route are not available. However, low overall extent of delivery is seen due to the permeation barrier posed by the skin. Chemical penetration enhancers and invasive methods that disturb the structural barrier function of the skin can be used to improve transdermal drug delivery. However, for suitable drugs, a fast-releasing transdermal delivery system can be produced by incorporating a heating source into a transdermal patch. In this study, a molecular dynamics simulation showed that heat increased the diffusivity of the drug molecules, resulting in faster release from gels containing ketoprofen, diclofenac sodium, and lidocaine HCl. Simulations were confirmed by in vitro drug release studies through lipophilic membranes. These correlations could expand the application of heated transdermal delivery systems for use as fast-release-dosage forms.


Functional characterization of the duck and turkey fatty acyl elongase enzymes ELOVL5 and ELOVL2.
In most Western countries, the consumption of fish is low and insufficient to provide the recommended daily intake of the n-3 (ω-3) long-chain polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). Poultry has the potential to be a sustainable source of EPA and DHA if poultry species are capable of synthesizing these n-3 PUFAs from dietary plant-derived α-linolenic acid (ALA; 18:3n-3). In most animals, the elongation of very long-chain fatty acids (ELOVL) enzyme ELOVL2 is essential for conversion of dietary ALA to DHA because only ELOVL2 and not ELOVL5 can elongate docosapentaenoic acid (DPA; 22:5n-3) to 24:5n-3, the precursor of DHA. The chicken is the only poultry species in which elongase enzymes have been functionally characterized, and chicken ELOVL5 had unique DPA-to-24:5n-3 activity, which may enable chickens to synthesize more DHA than other animals. By using a yeast expression system, we examined the duck and turkey elongases, ELOVL2 and ELOVL5, to understand if all poultry species have similar potential to synthesize EPA and DHA. The duck and turkey ELOVL5 enzymes were active with C18-20 PUFAs only. The duck ELOVL2 had a broad substrate specificity with C18-22 PUFAs, whereas the turkey ELOVL2 was active only with EPA and C22 PUFAs. Both duck and turkey ELOVL2 enzymes catalyzed 2 rounds of EPA elongation, with the products being DPA and its elongation product, 24:5n-3. With exogenous DPA, both duck and turkey ELOVL2 synthesized 24:5n-3, with the duck ELOVL2 being more active than the turkey ELOVL2. The reason for the lack of DPA elongation activity by the duck and turkey ELOVL5 enzymes compared with the chicken ELOVL5 could not be elucidated by protein sequence comparisons. By using the elongase enzyme activities only as a predictor of DHA synthesis, ducks may have a similar ability to chickens to convert increasing dietary ALA to DHA.


[Cathepsin D in primary breast cancer in correlation with various prognostic factors].
The concentration of total cathepsin D, which is regarded as an additional prognostic factor, was measured in 87 patients with primary breast cancer by a radioimmunoassay in tumour cytosol. The distribution of values was approximately log normal with a median value of 49 pmol/mg protein. Relating the level of cathepsin D to other prognostic factors, no significant association to the patients' age, menopausal status, tumour size, axillary lymph node involvement, distant metastases, type of tumour, histological grading or hormone receptor status could be established. Therefore, cathepsin D seems to be independent from other established prognostic criteria, which is a prerequisite for this protease to be useful as an additional prognostic marker.


Sleep, mental health status, and medical errors among hospital nurses in Japan.
Medical error involving nurses is a critical issue since nurses' actions will have a direct and often significant effect on the prognosis of their patients. To investigate the significance of nurse health in Japan and its potential impact on patient services, a questionnaire-based survey amongst nurses working in hospitals was conducted, with the specific purpose of examining the relationship between shift work, mental health and self-reported medical errors. Multivariate analysis revealed significant associations between the shift work system, General Health Questionnaire (GHQ) scores and nurse errors: the odds ratios for shift system and GHQ were 2.1 and 1.1, respectively. It was confirmed that both sleep and mental health status among hospital nurses were relatively poor, and that shift work and poor mental health were significant factors contributing to medical errors.


Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist.
Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix - 150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group) - as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P=0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects. (Funded by AbbVie; Elaris EM-I and EM-II ClinicalTrials.gov numbers, NCT01620528 and NCT01931670 .).


Effect of Helicobacter pylori eradication therapy on risk of hospitalization for a major ulcer event.
To compare Helicobacter pylori eradication therapy with antisecretory therapy alone on the risk of hospitalization for a major ulcer event. Retrospective, population-based cohort study. The 2000-2006 National Health Insurance database in Taiwan. A total of 838,176 patients diagnosed with a gastrointestinal ulcer and who filled at least one prescription for antiulcer therapy, either H. pylori eradication therapy (331,364 patients [39.53%]) or antisecretory therapy alone (506,812 patients [60.47%]), between January 1, 2001, and December 31, 2006. The primary outcome was hospitalization for a major ulcer event, defined as a gastrointestinal ulcer with hemorrhage and/or perforation. Cox proportional hazards models, adjusted for demographic and clinical characteristics, were used to compare the risk of hospitalization for a major ulcer event between the group receiving H. pylori eradication therapy (triple or quadruple combination therapy that includes an antisecretory agent) and the group receiving antisecretory therapy alone (histamine₂-receptor blocker or proton pump inhibitor). The H. pylori eradication therapy group was divided into initial users (combination therapy received immediately after gastrointestinal ulcer diagnosis) and late users (combination therapy received after antisecretory therapy with time lag ≤ 180 days, 181-365 days, or > 365 days from ulcer diagnosis). A secondary analysis was conducted in the three late H. pylori eradication therapy subgroups to determine if risk of hospitalization for major ulcer events differed by timing of receipt of therapy. Compared with the antisecretory therapy alone group, the H. pylori therapy group (initial users) had a significantly decreased risk of hospitalization for major ulcer events (adjusted hazard ratio [AHR] 0.57, 95% confidence interval [CI] 0.54-0.59, p<0.001). However, later use of H. pylori therapy was associated with a higher risk of hospitalization for major ulcer events (time lag 181-365 days, AHR 1.68, 95% CI 1.51-1.86, p<0.001; > 365 days, AHR 1.74, 95% CI 1.67-1.80, p<0.001) compared with those who received H. pylori therapy within 6 months (≤ 180 days) after gastrointestinal ulcers were diagnosed. Helicobacter pylori therapy given within 6 months of a diagnosis of gastrointestinal ulcer was associated with a reduced risk of hospitalization for major ulcer events. Our findings extend the evidence from clinical trials that report the value of H. pylori eradication therapy in reducing ulcer recurrence by documenting the real-world benefit of reducing the risk of hospitalization for major gastrointestinal ulcer events.


Detection of ciprofloxacin through surface plasmon resonance nanosensor with specific recognition sites.
The novel nanosensor based on Surface Plasmon Resonance (SPR) was developed for sensitive and selective detection of ciprofloxacin via molecularly imprinted nanoparticles (MIP/NPs). NPs were synthesized through miniemulsion polymerization technique with methacrylic acid as a functional monomer. FTIR, SEM, zetasizer and contact angle measurements were used for the characterization of MIP/NPs. After modification the SPR chip surface, the nanosensor was used for detection of ciprofloxacin in aqueous solution. According to selected concentration range, the correlation coefficient and limit of detections were obtained as 0.993 (R2) and 3.21 and 7.1 ppb in ultrapure water and SWW, respectively. Association kinetic analysis, Scatchard, Freundlich, Langmuir and Freundlich-Langmuir isotherms were also performed on the data to investigate adsorption behaviour of ciprofloxacin on the surface of nanosensor. Tetracycline and enrofloxacin were used as competitor agents to examine the selectivity of nanosensor. Performance of the SPR nanosensor was also investigated by using synthetic wastewater (SWW) for detection of CPX. The reusability of nanosensor was investigated and good repeatability was obtained with 5.81% RSD. As a result, selective, simple and low-cost method to detect ciprofloxacin in aqueous solution was developed by combining MIP/NPs and SPR.


Factors facilitating or hampering nurses identification of stroke in emergency calls.
To explore the factors that facilitate or hamper identification of stroke in emergency calls concerning patients with stroke who have fallen or been in a lying position. Early identification of stroke in emergency calls is vital but can be complicated as the patients may be unable to express themselves and the callers generally are bystanders. In a previous study, we found presentation of fall or the patient being in a lying position to be the major problem in 66% of emergency calls concerning, but not dispatched as acute stroke. A qualitative study using interpretive phenomenology. Analysis of transcribed emergency calls concerning 29 patients with stroke diagnoses at hospital discharge, in 2011 and presented with fall/lying position. Patients' ability to express themselves, callers' knowledge of the patient and of stroke, first call-takers' and nurses' authority, nurses' coaching and nurses' expertise skills facilitated or hindered the identification of stroke. Certain aspects are adjustable, but some are determined by the situation or on callers' and patients' abilities and thus difficult to change. Nurses' expertise skills were the only theme found to have a decisive effect of the identification of stroke on its own. To increase identification of stroke in emergency calls concerning stroke, the first call-takers' and nurses' action, competence and awareness of obstacles are crucial and if strengthened would likely increase the identification of stroke in emergency calls. In complicated cases, nurses' expertise skills seem essential for identification of stroke.


Three centered hydrogen bonds of the type C=O···H(N)···X-C in diphenyloxamide derivatives involving halogens and a rotating CF3 group: NMR, QTAIM, NCI and NBO studies.
The existence of three centered C=O···H(N)···X-C hydrogen bonds (H-bonds) involving organic fluorine and other halogens in diphenyloxamide derivatives has been explored by NMR spectroscopy and quantum theoretical studies. The three centered H-bond with the participation of a rotating CF3 group and the F···H-N intramolecular hydrogen bonds, a rare observation of its kind in organofluorine compounds, has been detected. It is also unambiguously established by a number of one and two dimensional NMR experiments, such as temperature perturbation, solvent titration, (15)N-(1)H HSQC, and (19)F-(1)H HOESY, and is also confirmed by theoretical calculations, such as quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO) and non-covalent interaction (NCI).


Reporting and interpretation of randomized controlled trials with statistically nonsignificant results for primary outcomes.
Previous studies indicate that the interpretation of trial results can be distorted by authors of published reports. To identify the nature and frequency of distorted presentation or "spin" (ie, specific reporting strategies, whatever their motive, to highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or to distract the reader from statistically nonsignificant results) in published reports of randomized controlled trials (RCTs) with statistically nonsignificant results for primary outcomes. March 2007 search of MEDLINE via PubMed using the Cochrane Highly Sensitive Search Strategy to identify reports of RCTs published in December 2006. Articles were included if they were parallel-group RCTs with a clearly identified primary outcome showing statistically nonsignificant results (ie, P > or = .05). Two readers appraised each selected article using a pretested, standardized data abstraction form developed in a pilot test. From the 616 published reports of RCTs examined, 72 were eligible and appraised. The title was reported with spin in 13 articles (18.0%; 95% confidence interval [CI], 10.0%-28.9%). Spin was identified in the Results and Conclusions sections of the abstracts of 27 (37.5%; 95% CI, 26.4%-49.7%) and 42 (58.3%; 95% CI, 46.1%-69.8%) reports, respectively, with the conclusions of 17 (23.6%; 95% CI, 14.4%-35.1%) focusing only on treatment effectiveness. Spin was identified in the main-text Results, Discussion, and Conclusions sections of 21 (29.2%; 95% CI, 19.0%-41.1%), 31 (43.1%; 95% CI, 31.4%-55.3%), and 36 (50.0%; 95% CI, 38.0%-62.0%) reports, respectively. More than 40% of the reports had spin in at least 2 of these sections in the main text. In this representative sample of RCTs published in 2006 with statistically nonsignificant primary outcomes, the reporting and interpretation of findings was frequently inconsistent with the results.


"It's what we're here for:" nurses caring for military personnel during the Persian Gulf Wars.
Military nursing service during wartime represents significant contributions to a unique type of health care. The purposes of this study were to: (1) generate themes that elucidate combat nursing experiences, (2) honor nurses who served by sharing their stories, and (3) permanently archive accounts of nursing personnel who served during the Persian Gulf Wars during the late 20th and early 21st centuries. Eleven military nurses who provided health care to American troops in the Persian Gulf participated in a historical study as part of the ongoing Nurses at War oral history project documenting the experiences of nurses during times of armed conflict. The overriding theme, "It's what we're here for," demonstrates the commitment of nurses: a commitment to care and to sacrifice. Other themes drawn from the study included lessons learned from their wartime nursing experiences, sacrifices made, and chronicles of caring. During armed conflict in the Persian Gulf Wars, military nurses' personal stories demonstrated the importance of being engaged in making meaningful professional and historical contributions. These nurses displayed professional commitment and hardiness in the face of difficult life circumstances, saying, "We did what we had to do."


Clinical impact of gait training enhanced with visual kinematic biofeedback: Patients with Parkinson's disease and patients stable post stroke.
As the world's population ages, falls, physical inactivity, decreased attention and impairments in balance and gait arise as a consequence of decreased sensation, weakness, trauma and degenerative disease. Progressive balance and gait training can facilitate postural righting, safe ambulation and community participation. This small randomized clinical trial evaluated if visual and kinematic feedback provided during supervised gait training would interfere or enhance mobility, endurance, balance, strength and flexibility in older individuals greater than one year post stroke (Gobbi et al., 2009) or Parkinson's disease (PD) (Gobbi et al., 2009). Twenty-four individuals consented to participate. The participants were stratified by diagnosis and randomly assigned to a control (usual gait training (Gobbi et al., 2009)) or an experimental group (usual gait training plus kinematic feedback (Gobbi et al., 2009)). At baseline and 6 weeks post training (18 h), subjects completed standardized tests (mobility, balance, strength, range of motion). Gains were described across all subjects, by treatment group and by diagnosis. Then they were compared for significance using nonparametric statistics. Twenty-three subjects completed the study with no adverse events. Across all subjects, by diagnosis (stroke and PD) and by training group (control and experimental), there were significant gains in mobility (gait speed, step length, endurance, and quality), balance (Berg Balance), range of motion and strength. There were no significant differences in the gain scores between the control and experimental groups. Subjects chronic post stroke made greater strength gains on the affected side than subjects with PD but otherwise there were no significant differences. In summary, during supervised gait training, dynamic visual kinematic feedback from wireless pressure and motion sensors had similar, positive effects as verbal, therapist feedback. A wireless kinematic feedback system could be used at home, to provide feedback and motivation for self correction of gait while simultaneously providing data to the therapist (at a distance).


Neonatal intensive care provision in the United Kingdom 1992-3. British Association of Perinatal Medicine.
Medical neonatal units in the United Kingdom were surveyed in 1994 to determine for 1992-3 the number of cots, medical and nursing staff, workload, the ability of units to retrieve data and to assess any changes that might have occurred since the NHS reforms. There was an 84% response rate. Many units were unable to provide workload and birthweight specific information. Cot occupancy, and there-fore the exposure of individual neonatal nurses to babies requiring intensive care, increased in direct proportion to unit workload. In spite of this a third of all neonatal intensive care, even for babies of < 100 g, is provided by units with ventilator workloads of 50 or fewer babies a year. There was a 25% increase in intensive care level 1 (ICL1) cot provision between 1989 and 1993, but no change in the total number of cots. Consistent maintenance of a common dataset by all units undertaking neonatal intensive care would do much to assist future planning.


Cumulative Roles for Epstein-Barr Virus, Human Endogenous Retroviruses, and Human Herpes Virus-6 in Driving an Inflammatory Cascade Underlying MS Pathogenesis.
Roles for viral infections and aberrant immune responses in driving localized neuroinflammation and neurodegeneration in multiple sclerosis (MS) are the focus of intense research. Epstein-Barr virus (EBV), as a persistent and frequently reactivating virus with major immunogenic influences and a near 100% epidemiological association with MS, is considered to play a leading role in MS pathogenesis, triggering localized inflammation near or within the central nervous system (CNS). This triggering may occur directly via viral products (RNA and protein) and/or indirectly via antigenic mimicry involving B-cells, T-cells and cytokine-activated astrocytes and microglia cells damaging the myelin sheath of neurons. The genetic MS-risk factor HLA-DR2b (DRB1*1501β, DRA1*0101α) may contribute to aberrant EBV antigen-presentation and anti-EBV reactivity but also to mimicry-induced autoimmune responses characteristic of MS. A central role is proposed for inflammatory EBER1, EBV-miRNA and LMP1 containing exosomes secreted by viable reactivating EBV+ B-cells and repetitive release of EBNA1-DNA complexes from apoptotic EBV+ B-cells, forming reactive immune complexes with EBNA1-IgG and complement. This may be accompanied by cytokine- or EBV-induced expression of human endogenous retrovirus-W/-K (HERV-W/-K) elements and possibly by activation of human herpesvirus-6A (HHV-6A) in early-stage CNS lesions, each contributing to an inflammatory cascade causing the relapsing-remitting neuro-inflammatory and/or progressive features characteristic of MS. Elimination of EBV-carrying B-cells by antibody- and EBV-specific T-cell therapy may hold the promise of reducing EBV activity in the CNS, thereby limiting CNS inflammation, MS symptoms and possibly reversing disease. Other approaches targeting HHV-6 and HERV-W and limiting inflammatory kinase-signaling to treat MS are also being tested with promising results. This article presents an overview of the evidence that EBV, HHV-6, and HERV-W may have a pathogenic role in initiating and promoting MS and possible approaches to mitigate development of the disease.


Calculated reactivities of potentially carcinogenic intermediates of the cyclopenta-fused isomers of benz[a]anthracene.
Delocalization energies have been calculated for carbocations formed from several epoxide intermediates of the cyclopenta-fused isomers of benz[a]anthracene. Except for the epoxides of benz[l]aceanthrylene, the largest calculated delocalization energies associated with the other benzaceanthrylenes result from ring-opening of the epoxide on the cyclopenta-ring yielding an alpha' type carbocation. Benz[l]aceanthrylene exhibits special behavior resulting from steric crowding in the bay-region of the molecule. For this molecule the calculated ease of epoxide ring opening is essentially the same for the bay-region epoxide and for the epoxide on the five-membered ring. Relative values of delocalization energy should provide an important index for ranking the reactivity of metabolites of the benzaceanthrylenes and benzacephenanthrylene that are potentially involved in the initiation of mutagenesis/carcinogenesis.


Diverse physiological properties of hypoglossal motoneurons innervating intrinsic and extrinsic tongue muscles.
The mammalian tongue contains eight muscles that collaborate to ensure that suckling, swallowing, and other critical functions are robust and reliable. Seven of the eight tongue muscles are innervated by hypoglossal motoneurons (XIIMNs). A somatotopic organization of the XII motor nucleus, defined in part by the mechanical action of a neuron's target muscle, has been described, but whether or not XIIMNs within a compartment are functionally specialized is unsettled. We hypothesize that developing XIIMNs are assigned unique functional properties that reflect the challenges that their target muscle faces upon the transition from in utero to terrestrial life. To address this, we studied XIIMNs that innervate intrinsic and extrinsic tongue muscles, because intrinsic muscles play a more prominent role in suckling than the extrinsic muscles. We injected dextran-rhodamine into the intrinsic longitudinal muscles (IL) and the extrinsic genioglossus, and physiologically characterized the labeled XIIMNs. Consistent with earlier work, IL XIIMNs (n = 150) were located more dorsally within the nucleus, and GG XIIMNs (n = 55) more ventrally. Whole cell recordings showed that resting membrane potential was, on average, 9 mV more depolarized in IL than in GG XIIMNs (P = 0.0019), and the firing threshold in response to current injection was lower in IL (-31 ± 23 pA) than in GG XIIMNs (225 ± 39 pA; P < 0.0001). We also found that the appearance of net outward currents in GG XIIMNs occurred at more hyperpolarized membrane potentials than IL XIIMNs, consistent with lower excitability in GG XIIMNs. These observations document muscle-specific functional specializations among XIIMNs.NEW & NOTEWORTHY The hypoglossal motor nucleus contains motoneurons responsible for innervating one of seven different muscles with notably different biomechanics and patterns of use. Whether or not motoneurons innervating the different muscles also have unique functional properties (e.g., spiking behavior, synaptic physiology) is poorly understood. In this work we show that neonatal hypoglossal motoneurons innervating muscles that shape the tongue (intrinsic longitudinal muscles) have different electrical properties than those innervating the genioglossus, which controls tongue position.


Role of poly(ADP-ribosyl)ation in DNA-PKcs- independent V(D)J recombination.
V(D)J recombination is critical to the generation of a functional immune system. Intrinsic to the assembly of antigen receptor genes is the formation of endogenous DNA double-strand breaks, which normally are excluded from the cellular surveillance machinery because of their sequestration in a synaptic complex and/or rapid resolution. In cells deficient in double-strand break repair, such recombination-induced breaks fail to be joined promptly and therefore are at risk of being recognized as DNA damage. Poly(ADP-ribose) polymerase-1 is an important factor in the maintenance of genomic integrity and is believed to play a central role in DNA repair. Here we provide visual evidence that in a recombination inducible severe combined immunodeficient cell line poly(ADP-ribose) formation occurs during the resolution stage of V(D)J recombination where nascent opened coding ends are generated. Poly(ADP-ribose) formation appears to facilitate coding end resolution. Furthermore, formation of Mre11 foci coincide with these areas of poly(ADP-ribosyl)ation. In contrast, such a response is not observed in wild-type cells possessing a functional catalytic subunit of DNA-dependent protein kinase (DNA-PK(cs)). Thus, V(D)J recombination invokes a DNA damage response in cells lacking DNA-PK(cs) activity, which in turn promotes DNA-PK(cs)-independent resolution of recombination intermediates.


Molecular methods to distinguish reactive and neoplastic lymphocyte expansions and their importance in transitional neoplastic states.
Although lymphoma and leukemia usually can be diagnosed by routine cytology and histology, some cases present a diagnostic challenge for pathologists and clinicians. Often the dilemma lies in determining whether a population of lymphocytes is reactive or neoplastic. We review currently available methods for analyzing lymphocyte populations by immunophenotyping and by identifying clonally rearranged immunoglobulin and T-cell receptor genes and discuss how these tests can be used to clarify such diagnostic dilemmas. We also describe the detection of chromosomal abnormalities and methods on the horizon, such as gene expression profiling, to identify diagnostically useful oncogenes. Finally, we review the emerging concept of transitional neoplastic states, in which reactive lymphocytes transform to neoplastic lymphocytes in the presence of continued antigenic stimulation, such as that caused by infection with Helicobacter pylori. The existence of transitional neoplastic states underscores the need for an array of molecular diagnostic tools that would improve our ability to characterize lymphocyte populations in human and animal patients and enhance early detection of neoplastic lymphocytes such that eradication of the infectious or inflammatory stimulus could lead to cure.


Computer generated polarization holograms: phase recording by polarization effect in photodichroic materials.
A new algorism of computer holography utilizing the anisotropic interaction of light with photodichroic materials is proposed. The most unique feature of this technique lies in the realization of phase information recording without the use of detour phase or optical path difference effect. Basic principles of information recording and reconstruction scheme using M centers in alkali halide crystals such as sodium fluoride are described in detail, and several technical merits and problems associated with the proposed algorism are discussed. This new method will provide a real-time holographic system where accurate recordability and high storage capacity are attainable due to its possibility of recording a calculated complex amplitude of wavefront only by means of controlling the polarization direction of illuminating beam.


Electronic coherence and nonlinear susceptibilities of conjugated polyenes.
A dynamic theory that connects electronic motions and the nonlinear optical response of conjugated polyenes is developed by introducing the concept of electronic normal modes. A useful picture for the mechanism of optical nonlinearities is obtained by identifying the few dominant modes. This quasi-particle electron-hole representation establishes a close analogy with small semiconductor particles (quantum dots) and is very different from the traditional approach based on electronic eigenstates. The effective conjugation length (coherence size), which controls the scaling and saturation of the static third-order susceptibility X((3)) with the number of double bonds, is related to the coherence of the relative motion of electron-hole pairs created upon optical excitation.


On the use of lonafarnib in myelodysplastic syndrome and chronic myelomonocytic leukemia.
Lonafarnib is an orally bio-available farnesyltransferase inhibitor that prevents farnesylation of specific target proteins including Ras. In a multicenter study, 67 patients with advanced myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) were treated with a continuous oral dose of 200-300 mg of lonafarnib and were evaluated for hematologic, pathologic and pharmacodynamic response. The median age of patients was 70 years (range 44-86). There were 32 patients with MDS (RAEB-20 and RAEB-t-12) and 35 with CMML. Overall 16 (24%) of the patients responded with two patients achieving a complete remission and one a partial response. Responses were seen in 6/32 and 10/35 patients with MDS and CMML, respectively. Of the 19 patients who were platelet transfusion-dependent prior to treatment, 5 (26%) became transfusion-free for a median duration of 185 days. A decrease in the farnesylation of the HDJ-2 protein measured in patient-derived cells was observed in the majority of patients during treatment with lonafarnib, but no clear correlation between changes in farnesylation and clinical effect could be made. Gastrointestinal toxicity was significant with 19% of patients discontinuing therapy due to diarrhea, nausea and/or anorexia. Lonafarnib has demonstrable activity in patients with advanced MDS and CMML.


Survival of Vibrio cholerae O1 in ceviche and its reduction by heat pretreatment of raw ingredients.
The survival of Vibrio cholerae O1 serotypes Inaba and Ogawa was determined in ceviche prepared from inoculated ground fish. Ground mackerel purchased from a seafood distribution center was inoculated with V. cholerae and stored at 8 or 20 degrees C. Counts of V. cholerae decreased in 2.6 to 2.7 log10 CFU/g during 96 h of storage at 8 degrees C or 2.5 to 2.6 log10 CFU/g during 24 h at 20 degrees C. Survival studies indicated that serotype Inaba decreased its number following a linear or retarded trend, whereas serotype Ogawa followed an accelerated death trend. No effect of the initial level of inoculum was observed. Odor scores of ceviche indicated that this food became marginally acceptable within as little as 48 h of storage at 8 degrees C or 3 h at 20 degrees C and were related to total volatile nitrogen values but not to aerobic plate counts, pH, or coliform counts. A heat pretreatment that consisted of stirring 100 g of inoculated ground fish into 40 ml of boiling water produced an 8-log reduction of V. cholerae within 3 min without affecting the color, odor, or flavor of ceviche prepared with such pretreated fish. According to this study, V. cholerae present in contaminated ceviche will likely survive longer than the shelf life of this food. Preheating the ground raw fish used for preparing ceviche for 3 min should effectively eliminate V. cholerae O1, providing science-based conditions for implementing a critical control point if a hazard analysis critical control point plan were to be developed for preparation of ceviche.


PD-1 blockade inhibits osteoclast formation and murine bone cancer pain.
Emerging immune therapy, such as with the anti-programmed cell death-1 (anti-PD-1) monoclonal antibody nivolumab, has shown efficacy in tumor suppression. Patients with terminal cancer suffer from cancer pain as a result of bone metastasis and bone destruction, but how PD-1 blockade affects bone cancer pain remains unknown. Here, we report that mice lacking Pdcd1 (Pd1-/-) demonstrated remarkable protection against bone destruction induced by femoral inoculation of Lewis lung cancer cells. Compared with WT mice, Pd1-/- mice exhibited increased baseline pain sensitivity, but the development of bone cancer pain was compromised in Pd1-/- mice. Consistently, these beneficial effects in Pd1-/- mice were recapitulated by repeated i.v. applications of nivolumab in WT mice, even though nivolumab initially increased mechanical and thermal pain. Notably, PD-1 deficiency or nivolumab treatment inhibited osteoclastogenesis without altering tumor burden. PD-L1 and CCL2 are upregulated within the local tumor microenvironment, and PD-L1 promoted RANKL-induced osteoclastogenesis through JNK activation and CCL2 secretion. Bone cancer upregulated CCR2 in primary sensory neurons, and CCR2 antagonism effectively reduced bone cancer pain. Our findings suggest that, despite a transient increase in pain sensitivity following each treatment, anti-PD-1 immunotherapy could produce long-term benefits in preventing bone destruction and alleviating bone cancer pain by suppressing osteoclastogenesis.


The Use of Clinical Registries in the United States: A Landscape Survey.
The use of information from clinical registries for improvement and value-based payment is increasing, yet information about registry use is not widely available. We conducted a landscape survey to understand registry uses, focus areas and challenges. The survey addressed the structure and organization of registry programs, as well as their purpose and scope. The survey was conducted by the National Quality Registry Network (NQRN), a community of organizations interested in registries. NQRN is a program of the PCPI, a national convener of medical specialty and professional societies and associations, which constitute a majority of registry stewards in the United States. We surveyed 152 societies and associations, asking about registry programs, governance, number of registries, purpose and data uses, data collection, expenses, funding and interoperability. The response rate was 52 percent. Many registries were self-funded, with 39 percent spending less than $1 million per year, and 32 percent spending $1-9.9 million. The typical registry had three full-time equivalent staff. Registries were frequently used for quality improvement, benchmarking and clinical decision support. 85 percent captured outpatient data. Most registries collected demographics, treatments, practitioner information and comorbidities; 53 percent captured patient-reported outcomes. 88 percent used manual data entry and 18 percent linked to external secondary data sources. Cost, interoperability and vendor management were barriers to continued registry development. Registries captured data across a broad scope, audited data quality using multiple techniques, and used a mix of automated and manual data capture methods. Registry interoperability was still a challenge, even among registries using nationally accepted data standards.


Intoxication due to alkylmercury-treated seed--1971-72 outbreak in Iraq: clinical aspects.
Sixty-six hospitalized patients suffering from chronic methylmercury poisoning were examined in Baghdad during 1972. The poisoning was attributed to consumption of home-made bread prepared from seed wheat treated with mercurial fungicide. The age incidence ranged between 4 and 70 years.Of the various clinical features encountered, neurological symptoms and signs were predominant and included muscular weakness, numbness, unsteady gait, paraesthesia, dysarthria, mental disturbances and, in severe cases, blindness, partial deafness, stupor, coma, and death. Involvement of the cardiovascular, urinary, gastrointestinal and haemopoietic systems, which was commonly encountered in ethylmercury poisoning in the 1960 outbreak in Iraq, was unusual.The severity of symptoms and signs was, broadly speaking, dose-dependent; high exposure led to severe clinical manifestations, but variations existed. Criteria, based on the clinical manifestations, were set for grading the severity of cases. The series included 2 asymptomatic cases, 20 mild, 20 moderate, 14 severe, and 10 very severe. In the latter group 5 patients died from failure of the central nervous system.The severely poisoned patients died irrespective of the medical treatment received. After 2 years of observation, most patients graded as mild or moderate cases lost their symptoms completely. Severe cases improved slowly, although ataxia, diminution of visual field and acuity and paraesthesia were still present. Thus, the previously accepted view that neurological signs were irreversible has been disproved.


Antitumor peptides from marine organisms.
The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.


Cellular adaptation to drug exposure: evolution of the drug-resistant phenotype.
The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. For etoposide (VP-16), increased expression of MDR-1 or MRP and alterations in topoisomerase IIalpha have been shown to confer tolerance. To further understand resistance to VP-16, three sublines, designated MCF-7-VP17, ZR-75B-VP13, and MDA-MB-231-VP7, were initially isolated as single clones from parental cells by exposure to VP-16. Subsequently, a population of cells from each subline was exposed to 3-fold higher drug concentrations, allowing stable sublines to be established at higher extracellular drug concentrations. Characterization of the resistant sublines demonstrates the adaptation that occurs with advancing drug concentrations during in vitro selections. Reduced topoisomerase II mRNA and protein levels were observed in the initial isolates. This reduction was accompanied by a decrease in topoisomerase II activity and cellular growth rate and was associated with 6-314-fold resistance to topoisomerase II poisons. With advancing resistance, MRP expression increased and VP-16 accumulation decreased. This adaptation allowed for partial restoration of topoisomerase II activity as a result of increased expression (MCF-7-VP17 and ZR-75B-VP13) or hyperphosphorylation (MDA-MB-231-VP7), with a resultant increase in growth rate. In MDA-MB-231-VP7 cells, hyperphosphorylation coincided with increased casein kinase II mRNA and protein levels, suggesting a role for this kinase in the acquired hyperphosphorylation. In this cell line, hyperphosphorylation mediated the increased activity despite a fall in topoisomerase IIalpha protein levels secondary to an acquired 600-bp deletion in one topoisomerase IIalpha allele, which resulted in reduced protein levels. In all three sublines, high levels of resistance were attained as a result of synergism between the reduced topoisomerase IIalpha levels and MRP overexpression. These studies demonstrate how cellular adaptation to increasing drug pressure occurs and how more than one mechanism can contribute to the resistant phenotype when increasing selecting pressure is applied. Reduced expression of topoisomerase II is sufficient to confer substantial resistance early in the selection process, with synergy from MRP overexpression helping to confer high levels of resistance.


The essence of Native American nursing.
This article emerged at the "Gathering of Wisdom: American Indian Nursing Summit III," which took place in October 1997 on the Flathead Indian Reservations in Polson, Montana. This gathering described and clarified the distinctiveness of Native American nursing. Nursing literature has explored the essence of nursing from a variety of perspectives. This article describes a process of discovery in which seven themes emerged on the essence of Native American nursing. These themes, in ascending order of significance, are caring, traditions, respect, connection, holism, trust, and spirituality. These themes are connected and interwoven throughout the center of Native American culture and can provide a creative outlook for transcultural nursing and nursing in general. Furthermore, these themes provide a vehicle for care delivery innovation.


In vitro mesenchymal trilineage differentiation and extracellular matrix production by adipose and bone marrow derived adult equine multipotent stromal cells on a collagen scaffold.
Directed differentiation of adult multipotent stromal cells (MSC) is critical for effective treatment strategies. This study was designed to evaluate the capability of equine MSC from bone marrow (BMSC) and adipose tissue (ASC) on a type I collagen (COLI) scaffold to undergo chondrogenic, osteogenic and adipogenic differentiation and form extracellular matrix (ECM) in vitro. Following determination of surface antigen expression, MSC were loaded into scaffolds in a perfusion bioreactor and loading efficiency was quantified. Cell-scaffold constructs were assessed after loading and 7, 14 and 21 days of culture in stromal or induction medium. Cell number was determined with DNA content, cell viability and spatial uniformity with confocal laser microscopy and cell phenotype and matrix production with light and scanning electron microscopy and mRNA levels. The MSC were positive for CD29 (>90 %), CD44 (>99 %), and CD105 (>60 %). Loading efficiencies were >70 %. The ASC and BMSC cell numbers on scaffolds were affected by culture in induction medium differently. Viable cells remained uniformly distributed in scaffolds for up to 21 days and could be directed to differentiate or to maintain an MSC phenotype. Micro- and ultrastructure showed lineage-specific cell and ECM changes. Lineage-specific mRNA levels differed between ASC and BMSC with induction and changed with time. Based on these results, equine ASC and BMSC differentiate into chondrogenic, osteogenic and adipogenic lineages and form ECM similarly on COLI scaffolds. The collected data supports the potential for equine MSC-COLI constructs to support diverse equine tissue formation for controlled biological studies.


Parents' views of cancer-directed therapy for children with no realistic chance for cure.
Previous literature suggests that parents often wish to continue cancer-directed therapy for their children with incurable cancer. We assessed parents' experiences with treatment for their children with cancer and no realistic chance of cure. We administered questionnaires to 141 parents of children with cancer who died after receiving care at one of two cancer centers. Parents were asked whether the child benefited and suffered from treatment administered after the parent recognized that cure was not a realistic expectation, and whether they would recommend cancer-directed therapy to other families of children with advanced cancer. Fifty-three (38%) of 141 children received cancer-directed therapy after the parent recognized that the child had no realistic chance for cure. Most of these parents felt that their child had experienced at least some suffering resulting from the therapy (61%, 31 of 51) and little to no benefit (57%, 29 of 51). Fifty-one (38%) of 135 parents overall would recommend standard chemotherapy and 46 (33%) of 140 would recommend experimental chemotherapy to families of children with advanced cancer. Even parents who would not recommend standard chemotherapy generally felt the physician should offer it (91%, 88 of 97). Parents who reported that their children experienced suffering resulting from cancer-directed therapy (odds ratio = 0.46; P = .02) were less likely to recommend standard chemotherapy to other families. Although many parents choose treatment for their children with incurable cancer, bereaved parents often would not recommend such therapy. Parents who felt their children suffered as a result of cancer treatment were particularly unlikely to recommend it.


TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer.
Squamous cell carcinoma of the head and neck (SCCHN) is a common, aggressive, treatment-resistant cancer with a high recurrence rate and mortality, but the mechanism of treatment resistance remains unclear. Here we describe a mechanism where the AAA-ATPase TRIP13 promotes treatment resistance. Overexpression of TRIP13 in non-malignant cells results in malignant transformation. High expression of TRIP13 in SCCHN leads to aggressive, treatment-resistant tumors and enhanced repair of DNA damage. Using mass spectrometry, we identify DNA-PKcs complex proteins that mediate nonhomologous end joining (NHEJ), as TRIP13-binding partners. Using repair-deficient reporter systems, we show that TRIP13 promotes NHEJ, even when homologous recombination is intact. Importantly, overexpression of TRIP13 sensitizes SCCHN to an inhibitor of DNA-PKcs. Thus, this study defines a new mechanism of treatment resistance in SCCHN and underscores the importance of targeting NHEJ to overcome treatment failure in SCCHN and potentially in other cancers that overexpress TRIP13.


Postweaning diarrhea in swine: effects of oxytetracycline on enterotoxigenic Escherichia coli infection.
Investigators have found that oxytetracycline decreases the adhesion of K88+ Escherichia coli to intestinal epithelial cells in vitro. This occurs with oxytetracycline-sensitive E coli at drug concentrations less than those required to prevent growth and with E coli that are resistant to the drug. We conducted experiments to determine whether oxytetracycline alters the disease caused by an oxytetracycline-resistant K88+ enterotoxigenic strain of E coli. Oxytetracycline-treated pigs (inoculated with K88+ E coli) did not differ from nontreated pigs in the incidence or severity of diarrhea, nor in the shedding of K88+ E coli. However, during recovery, weight gain by treated pigs was slower than that of nontreated pigs. The control pigs were not inoculated with E coli, and they remained clinically normal. Oxytetracycline-treated controls gained weight faster than nontreated controls. Some controls were genetically resistant to K88+ E coli, others were susceptible. The K88-resistant oxytetracycline-treated controls gained weight faster than the K88-susceptible oxytetracycline-treated and non-treated controls.


The presence of an iron-sulfur cluster in adenosine 5'-phosphosulfate reductase separates organisms utilizing adenosine 5'-phosphosulfate and phosphoadenosine 5'-phosphosulfate for sulfate assimilation.
It was generally accepted that plants, algae, and phototrophic bacteria use adenosine 5'-phosphosulfate (APS) for assimilatory sulfate reduction, whereas bacteria and fungi use phosphoadenosine 5'-phosphosulfate (PAPS). The corresponding enzymes, APS and PAPS reductase, share 25-30% identical amino acids. Phylogenetic analysis of APS and PAPS reductase amino acid sequences from different organisms, which were retrieved from the GenBank(TM), revealed two clusters. The first cluster comprised known PAPS reductases from enteric bacteria, cyanobacteria, and yeast. On the other hand, plant APS reductase sequences were clustered together with many bacterial ones, including those from Pseudomonas and Rhizobium. The gene for APS reductase cloned from the APS-reducing cyanobacterium Plectonema also clustered together with the plant sequences, confirming that the two classes of sequences represent PAPS and APS reductases, respectively. Compared with the PAPS reductase, all sequences of the APS reductase cluster contained two additional cysteine pairs homologous to the cysteine residues involved in binding an iron-sulfur cluster in plants. Mössbauer analysis revealed that the recombinant APS reductase from Pseudomonas aeruginosa contains a [4Fe-4S] cluster with the same characteristics as the plant enzyme. We conclude, therefore, that the presence of an iron-sulfur cluster determines the APS specificity of the sulfate-reducing enzymes and thus separates the APS- and PAPS-dependent assimilatory sulfate reduction pathways.


Large-scale energy budget of impulsive magnetic reconnection: Theory and simulation.
We evaluate the large-scale energy budget of magnetic reconnection utilizing an analytical time-dependent impulsive reconnection model and a numerical 2-D MHD simulation. With the generalization to compressible plasma, we can investigate changes in the thermal, kinetic, and magnetic energies. We study these changes in three different regions: (a) the region defined by the outflowing plasma (outflow region, OR), (b) the region of compressed magnetic fields above/below the OR (traveling compression region, TCR), and (c) the region trailing the OR and TCR (wake). For incompressible plasma, we find that the decrease inside the OR is compensated by the increase in kinetic energy. However, for the general compressible case, the decrease in magnetic energy inside the OR is not sufficient to explain the increase in thermal and kinetic energy. Hence, energy from other regions needs to be considered. We find that the decrease in thermal and magnetic energy in the wake, together with the decrease in magnetic energy inside the OR, is sufficient to feed the increase in kinetic and thermal energies in the OR and the increase in magnetic and thermal energies inside the TCR. That way, the energy budget is balanced, but consequently, not all magnetic energy is converted into kinetic and thermal energies of the OR. Instead, a certain fraction gets transfered into the TCR. As an upper limit of the efficiency of reconnection (magnetic energy → kinetic energy) we find ηeff=1/2. A numerical simulation is used to include a finite thickness of the current sheet, which shows the importance of the pressure gradient inside the OR for the conversion of kinetic energy into thermal energy.


Development of a highly sensitive assay for enzyme-mediated reductive degradation of polychlorinated dibenzo-p-dioxin.
The degradation of 2-chloro-4,5-O-(4'-methyl-7', 8'-diphenyl)ether (CMDPE), an analog of 2,7-dichlorodibenzo-p-dioxin (2,7-DCDD), mediated by Geobacillus sp. UZO 3 cell-free extract was monitored. Ethyl acetate extracts of a complete reaction mixture incubated at 65°C for 18 h were analyzed either by thin layer chromatography (TLC) fractionation coupled with spectrometric detection or by gas chromatography-mass spectrometry (GC-MS). The reaction product 4-methylumbelliferone (4MU) was successfully isolated by TLC and visualized by a transilluminator at 450 nm. The 4MU, 4-chlorophenol, and reaction intermediate 6-chlorophenoxy-4-methylumbelliferone were all successfully detected by GC-MS. The presence of these compounds suggest that Geobacillus sp. UZO 3 cell-free extract also catalyzes the reductive cleavage of the diaryl ether bonds of CMDPE in a similar mechanism previously reported in 2,7-DCDD. In the present study, the authors describe a simple and highly sensitive fluorescent assay for a new dioxin degrading enzyme(s).


Efficacy and Safety of Brodalumab in Patients with Moderate-to-Severe Plaque Psoriasis and Skin of Color: Results from the Pooled AMAGINE-2/-3 Randomized Trials.
Data on treatment outcomes in patients with psoriasis who have skin of color are limited. Brodalumab has shown efficacy in patients with moderate-to-severe plaque psoriasis. Our objective was to evaluate the efficacy, safety, and health-related quality of life associated with brodalumab in patients with skin of color participating in two phase III, multicenter, randomized, double-blind, placebo- and active comparator-controlled studies (AMAGINE-2/-3). Patients were self-categorized into racial subgroups (black, Asian, or white) or the non-mutually exclusive ethnic subgroup Hispanic/Latino. Patients were randomized to receive brodalumab 210 mg every 2 weeks (Q2W) or ustekinumab (45 mg in patients weighing ≤ 100 kg and 90 mg in patients weighing > 100 kg) for 52 weeks. Skin clearance was monitored using the Psoriasis Area and Severity Index (PASI) and Static Physician's Global Assessment (sPGA). Treatment-emergent adverse events (TEAEs) were summarized by treatment and racial and ethnic subgroup. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI). During the 12-week induction phase, 613 patients received ustekinumab (black, n = 20; Asian, n = 24; white, n = 551; Hispanic/Latino, n = 68) and 1236 patients received brodalumab 210 mg Q2W (black, n = 36; Asian, n = 39; white, n = 1116; Hispanic/Latino, n = 132). At week 52, a total of 590 patients received continuous ustekinumab (black, n = 19; Asian, n = 23; white, n = 532; Hispanic/Latino, n = 64) and 339 patients were re-randomized to continue receiving brodalumab 210 mg Q2W (black, n = 10; Asian, n = 7; white, n = 308; Hispanic/Latino, n = 40). Among patients who received brodalumab 210 mg Q2W, skin clearance response rates were similar across racial and ethnic subgroups at week 12 and week 52; rates of 75%, 90%, and 100% improvement in PASI from baseline were also higher, as was sPGA score ≤ 1, than in patients who received ustekinumab across all racial and ethnic subgroups. Rates of TEAEs and ≥ 5-point improvement in DLQI score were similar across racial and ethnic subgroups. Brodalumab 210 mg Q2W is well tolerated and efficacious across diverse racial and ethnic subgroups in patients with psoriasis, including black, Asian, white, and Hispanic/Latino patients. ClinicalTrials.gov identifier NCT01708603 (AMAGINE-2); NCT01708629 (AMAGINE-3).


Product line management. Formalizing clinical product lines as part of patient focused restructuring.
Patient Focused Care is entirely consistent with clinical Product Line Management. In fact, as with Patient Focused Care and CQI/TQM, these two initiatives are better together than apart. To take advantage of this opportunity, you may have to modify your existing mechanism for Product Line Management. But the added benefits of more successful Product Line Management will make any modifications a temporary distraction. Down goes the perceived hurdle.


Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.
To determine whether adult survivors (>or= 18 years of age) of childhood acute lymphoblastic leukemia (ALL) are at increased risk for obesity and to assess patient and treatment variables that influence risk. A retrospective cohort of participants of the Childhood Cancer Survivor Study was used to compare 1,765 adult survivors of childhood ALL to 2,565 adult siblings of childhood cancer survivors. Body-mass index (BMI; kilograms per square meter), calculated from self-reported heights and weights, was used to determine the prevalence of being overweight (BMI, 25-29.9) or obese (BMI >or= 30.0). Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for being overweight or obese among ALL survivors relative to the sibling control group. The age- and race-adjusted OR for being obese in survivors treated with cranial radiation doses >or= 20 Gy in comparison with siblings was 2.59 for females (95% CI, 1.88 to 3.55; P <.001) and 1.86 for males (95% CI, 1.33 to 2.57; P <.001). The OR for obesity was greatest among females diagnosed at 0 to 4 years of age and treated with radiation doses >or= 20 Gy (OR, 3.81; 95% CI, 2.34 to 5.99; P <.001). Obesity was not associated with treatment consisting of chemotherapy only or with cranial radiation doses of 10 to 19 Gy. Cranial radiotherapy >or= 20 Gy is associated with an increased prevalence of obesity, especially in females treated at a young age. It is imperative that healthcare professionals recognize this risk and develop strategies to enhance weight control and encourage longitudinal follow-up.


Stylar glycoproteins bind to S-RNase in vitro.
S-RNases determine the specificity of S-specific pollen rejection in self-incompatible plants of the Solanaceae, Rosaceae, and Scrophulariaceae. They are also implicated in at least two distinct types of unilateral interspecific incompatibility in Nicotiana. However, S-RNase itself is not sufficient for most types of pollen rejection, and evidence for its direct interaction with pollen tubes is limited. Thus, non-S-RNase factors also are required for pollen rejection. As one approach to identifying such factors, we tested whether SC10-RNase from Nicotiana alata would bind to other stylar proteins in vitro. SC10-RNase was immobilized on Affi-gel, and binding proteins were analyzed by SDS-PAGE and immunoblotting. In addition to SC10-RNase and a small protein similar to lily chemocyanin, the most prominent binding proteins include NaTTS, 120K, and NaPELPIII, these latter three being arabinogalactan proteins previously shown to interact directly with pollen tubes. We also show that SC10-RNase and these glycoproteins migrate as a complex in a native PAGE system. Our hypothesis is that S-RNase forms a complex with these glycoproteins in the stylar ECM, that the glycoproteins interact directly with the pollen tubes and thus that the initial interaction between the pollen tube and S-RNase is indirect.


Application of MLP neural network to predict X-ray spectrum from tube voltage, filter material, and filter thickness used in medical imaging systems.
The X-ray energy spectrum is crucial for image quality and dosage assessment in mammography, radiography, fluoroscopy, and CT which are frequently used for the diagnosis of many diseases including but not limited to patients with cardiovascular and cerebrovascular diseases. X-ray tubes have an electron filament (cathode), a tungsten/rubidium target (anode) oriented at an angle, and a metal filter (aluminum, beryllium, etc.) that may be placed in front of an exit window. When cathode electrons meet the anode, they generate X-rays with varied energies, creating a spectrum from zero to the electrons' greatest energy. In general, the energy spectrum of X-rays depends on the electron beam's energy (tube voltage), target angle, material, filter thickness, etc. Thus, each imaging system's X-ray energy spectrum is unique to its tubes. The primary goal of the current study is to develop a clever method for quickly estimating the X-ray energy spectrum for a variety of tube voltages, filter materials, and filter thickness using a small number of unique spectra. In this investigation, two distinct filters made of beryllium and aluminum with thicknesses of 0.4, 0.8, 1.2, 1.6, and 2 mm were employed to obtain certain limited X-ray spectra for tube voltages of 20, 30, 40, 50, 60, 80, 100, 130, and 150 kV. The three inputs of 150 Multilayer Perceptron (MLP) neural networks were tube voltage, filter type, and filter thickness to forecast the X-ray spectra point by point. After training, the MLP neural networks could predict the X-ray spectra for tubes with voltages between 20 and 150 kV and two distinct filters made of aluminum and beryllium with thicknesses between 0 and 2 mm. The presented methodology can be used as a suitable, fast, accurate and reliable alternative method for predicting X-ray spectrum in medical applications. Although a technique was put out in this work for a particular system that was the subject of Monte Carlo simulations, it may be applied to any genuine system.


Response to the meningococcal meningitis epidemic (MME) at Aminu Kano Teaching Hospital, Kano (2008-2009).
In December 2008 an outbreak of Meningococcal Meningitis swept across sub Saharan Africa with Nigeria, especially its northern states worst affected. The management of Aminu Kano Teaching Hospital constituted an Emergency Preparedness & Response (EPR) committee. Over the course of 18 weeks from 5 January 2009 to 15 May 2009, AKTH managed 222 cases of suspected meningitis with 14 deaths (case fatality rate [CFR] of 6.3%). Twenty three per cent (23%) were microbiologically proven as meningococcal meningitis while 9% were confirmed to be pneumococcal meningitis. Male to female ratio was 1:1 with most patients (81%) aged below 14 years. The epidemic peaked in weeks 10 and 13 with 38 admissions in the respective weeks. Meningococcemia with purpura fulminans, post meningitic immune complex cutaneous vasculitis and polyarthritis were observed. Control measures instituted included provision of free ceftriaxone, chemoprophylaxis to contacts, vaccines to staff/families, and creation of dedicated isolation wards. Clinical management guidelines were developed and hospital staffs were also enlightened. Lessons learnt included the difficulty of discriminating between nosocomial transmission and community clusters; relative increase in pneumococcal meningitis during the epidemic; unreliability of penicillin/chloramphenicol; the utility of internet for communication; and the inadequacy of vaccines to meet staff & public demand.


Intraoperative Needle Tip Tracking with an Integrated Fibre-Optic Ultrasound Sensor.
Ultrasound is an essential tool for guidance of many minimally-invasive surgical and interventional procedures, where accurate placement of the interventional device is critical to avoid adverse events. Needle insertion procedures for anaesthesia, fetal medicine and tumour biopsy are commonly ultrasound-guided, and misplacement of the needle may lead to complications such as nerve damage, organ injury or pregnancy loss. Clear visibility of the needle tip is therefore critical, but visibility is often precluded by tissue heterogeneities or specular reflections from the needle shaft. This paper presents the in vitro and ex vivo accuracy of a new, real-time, ultrasound needle tip tracking system for guidance of fetal interventions. A fibre-optic, Fabry-Pérot interferometer hydrophone is integrated into an intraoperative needle and used to localise the needle tip within a handheld ultrasound field. While previous, related work has been based on research ultrasound systems with bespoke transmission sequences, the new system-developed under the ISO 13485 Medical Devices quality standard-operates as an adjunct to a commercial ultrasound imaging system and therefore provides the image quality expected in the clinic, superimposing a cross-hair onto the ultrasound image at the needle tip position. Tracking accuracy was determined by translating the needle tip to 356 known positions in the ultrasound field of view in a tank of water, and by comparison to manual labelling of the the position of the needle in B-mode US images during an insertion into an ex vivo phantom. In water, the mean distance between tracked and true positions was 0.7 ± 0.4 mm with a mean repeatability of 0.3 ± 0.2 mm. In the tissue phantom, the mean distance between tracked and labelled positions was 1.1 ± 0.7 mm. Tracking performance was found to be independent of needle angle. The study demonstrates the performance and clinical compatibility of ultrasound needle tracking, an essential step towards a first-in-human study.


The relationship between cesarean section and labor induction.
Numerous study results vary when analyzing the relationship between labor induction and the likelihood of cesarean delivery; and few have accounted for the multiple influences of maternal sociodemographic characteristics combined with the provider and hospital in subsequent birth outcomes such as cesarean section. This study evaluated the likelihood of cesarean birth following labor induction while accounting for maternal, hospital, and provider characteristics. A cross-sectional retrospective descriptive design using secondary data was employed to determine what variation in cesarean births was due to differences of hospitals, providers, and patients using the Quality Health Outcomes Model (QHOM). Data were partitioned by primiparous and multiparous women. The individual demographic, system, and provider outcomes in all hospitals and single birth center for Maricopa County in 2005 (N=62,816) were analyzed, using both random effects and fixed effects models. For primiparous women, an increased likelihood of cesarean births was associated with medical inductions, maternal age, being Black, and the number of prenatal visits; and less likely in teaching hospitals and women with higher educational attainment. In multiparous women, cesarean births were associated with increased maternal age and medical inductions; and less likely in for-profit hospitals and following elective induction. Labor inductions were associated with an increased likelihood of cesarean sections based on parity, age, race, number of prenatal visits, education, and hospital teaching status and ownership. Because the QHOM emphasizes multiple contextual variables that influence the delivery and outcomes of care, it can prove ideal for the study of birth outcomes following interventions such as the induction of labor. Nurses should be well educated about the risks of elective labor induction prior to term gestation and "elective" cesarean birth.


Volumetric in vivo imaging of intracochlear microstructures in mice by high-speed spectral domain optical coherence tomography.
There is considerable interest in developing new methods for in vivo imaging of the complex anatomy of the mammalian cochlea for clinical as well as fundamental studies. In this study, we explored, the feasibility of spectral domain optical coherence tomography (SD-OCT) for 3-D in vivo imaging of the cochlea in mice. The SD-OCT system employed in this study used a broadband light source centered at 1300 nm, and the imaging speed of the system was 47,000 A-scans per second using the InGaAs camera. The system was capable of providing fully processed, high-resolution B-scan images [512 (axial) x 128 (lateral) pixels] at 280 frames per sec. The 3-D imaging acquisition time for a whole cochlea was approximately 0.45 sec. The traditional SD-OCT structural imaging algorithm was used to reconstruct 3-D cochlear morphology. We demonstrated that SD-OCT can be successfully used for in vivo imaging of important morphological features within the mouse cochlea, such as the otic capsule and structures within, including Reissner's membrane, the basilar membrane, tectorial membrane, organ of Corti, and modiolus of the apical and middle turns.


"We Won't Retire Without Skeletons in the Closet": Healthcare-Related Regrets Among Physicians and Nurses in German-Speaking Swiss Hospitals.
Physicians and nurses are expected to systematically provide high-quality healthcare in a context marked by complexity, time pressure, heavy workload, and the influence of nonclinical factors on clinical decisions. Therefore, healthcare professionals must eventually deal with unfortunate events to which regret is a typical emotional reaction. Using semistructured interviews, 11 physicians and 13 nurses working in two different hospitals in the German-speaking part of Switzerland reported a total of 48 healthcare-related regret experiences. Intense feelings of healthcare-related regrets had far-reaching repercussions on participants' health, work-life balance, and medical practice. Besides active compensation strategies, social capital was the most important coping resource. Receiving superiors' support was crucial for reaffirming professional identity and helped prevent healthcare professionals from quitting their job. Findings suggest that training targeting emotional coping could be beneficial for quality of life and may ultimately lead to lower job turnover among healthcare professionals.


Functional overlap between the mec-8 gene and five sym genes in Caenorhabditis elegans.
Earlier work showed that the Caenorhabditis elegans gene mec-8 encodes a regulator of alternative RNA splicing and that mec-8 null mutants have defects in sensory neurons and body muscle attachment but are generally viable and fertile. We have used a genetic screen to identify five mutations in four genes, sym-1-sym-4, that are synthetically lethal with mec-8 loss-of-function mutations. The phenotypes of sym single mutants are essentially wild type. mec-8; sym-1 embryos arrest during embryonic elongation and exhibit defects in the attachment of body muscle to extracellular cuticle. sym-1 can encode a protein containing a signal sequence and 15 contiguous leucine-rich repeats. A fusion of sym-1 and the gene for green fluorescent protein rescued the synthetic lethality of mec-8; sym-1 mutants; the fusion protein was secreted from the apical hypodermal surface of the embryo. We propose that SYM-1 helps to attach body muscle to the extracellular cuticle and that another gene that is dependent upon mec-8 for pre-mRNA processing overlaps functionally with sym-1. RNA-mediated interference experiments indicated that a close relative of sym-1 functionally overlaps both sym-1 and mec-8 in affecting muscle attachment. sym-2, sym-3, and sym-4 appear to provide additional functions that are essential in the absence of mec-8(+).