Serial VCG/ECG analysis using neural networks.
Serial ECG analysis is an important diagnostic tool in which two or more successive ECG recordings from the same patient are compared in order to find changes due to, e.g. myocardial infarction. The present study investigates a new approach to serial analysis which is based on artificial neural networks. Interrecording changes are sometimes falsely detected due to electrode misplacement or positional changes of the heart. In order to compensate for such problems, a new technique for VCG loop alignment was employed. A study population of 1000 patients with two recordings was used and manually scrutinized by three experienced ECG interpreters. Pathological changes indicating newly developed infarcts were found in 256 patients. Different combinations of VCG/ECG measurements served as input data to the neural network. The best performance of the neural network was obtained when ECG and VCG measurements were combined and the resulting sensitivity was 69% at a specificity of 90%. The use of only ECG or VCG measurements reduced the sensitivity to 63% and 60%, respectively. The results indicated that serial analysis based on neural networks did not improve significantly when VCG loop alignment was included.


Renal function after preeclampsia: a longitudinal pilot study.
Women with a history of preeclampsia are at increased risk to develop end-stage renal disease. In this longitudinal study, we evaluated renal function in women with a history of severe preeclampsia and parous controls over a period of 14 years. Renal function was measured 1 and then 14 years postpartum by para-aminohippurate and inulin clearances in 20 women with a history of severe preeclampsia and 8 parous controls. The difference in glomerular filtration rate 1 year postpartum between women with a history of preeclampsia and parous controls (112 ± 10 and 125 ± 8 ml/min/1.73 m(2), p < 0.01) had disappeared 14 years postpartum (104 ± 10 and 109 ± 13 ml/min/1.73 m(2), p = 0.37). There was a consistent trend for a lower effective renal plasma flow both 1 and 14 years postpartum (477 ± 90 and 543 ± 92, p = 0.09 and 473 ± 85 and 543 ± 98 ml/min/1.73 m(2), p = 0.07). This explorative study suggests no accelerated renal function loss in the first decade after preeclampsia.


Medical and psychological management of recurrent abortion, history of postneonatal death, ectopic pregnancy and infertility: successful implementation of IVF for multifactorial reproductive dysfunction. A case report.
The medical and psychological treatment for a 37-year-old Caucasian G6 P1051 woman who presented for evaluation of secondary infertility and recurrent pregnancy loss is described. Although one living child had been conceived without medical assistance, that delivery preceded the present evaluation by ten years and involved a different partner. With the current husband, the patient had two miscarriages and a left ectopic pregnancy. The couple had attempted controlled ovarian hyperstimulation and in vitro fertilization (IVF) elsewhere, but the cycle was cancelled due to poor follicular response. About one year before consultation at our institution, the couple established a pregnancy although the infant was born at 24 weeks with a cardiac anomaly, living only 40 days. Additionally, a persistent cervical lesion required cone biopsy before any fertility treatment could resume. Andrology evaluation found the husband's sperm DNA fragmentation index to be 48.6%. This constellation of stressors represented substantial emotional issues and psychological therapy/counseling was recommended. After obtaining psychological clearance, the couple underwent IVF and 16 oocytes were retrieved. Four embryos were transferred, and a healthy male infant was delivered at term. Although multifactorial infertility can be associated with very poor reproductive outcomes, the advanced reproductive technologies merit consideration during management of complex clinical challenges. Standard IVF strategies can be optimized by inclusion of thorough psychological assessment and counseling.


Malocclusions in a juvenile medieval skull material.
From a mostly medieval skull material--the "Schreiner collections" in Oslo--juvenile crania were selected as follows: Group A: Crania with complete and intact primary dentition. n = 20. Group B: Crania with early mixed dentition. Incisors only erupted or under eruption. n = 47. Group C: Crania with late mixed dentition. n = 14. The author recorded visually: Sagittal and transversal dental relation, frontal dental contact, anterior cross-bite, rotation and crowding. There was good basal stability. Sagittally 1 moderately postnormal dentition was recorded, transversally there were no anomalies. Slight anterior cross-bite was recorded in 1 case, anterior cross-bite of one and two lateral incisors respectively in 2 others, and tête-à-tête contact in 3 cases. Crowding was recorded in 6 cases, in one of them being general, in the others located solely in the mandibular incisor segment. Broken contact and more or less pronounced rotation occurred in these dentitions. Rotation was also recorded in 2 other cases. The prevalence of malocclusions of the type that can be related to continuing finger-sucking or sucking of dummylike objects was very low in this material. This observation prompted the author to discuss a hypothesis concerning the aetiology of dummy- and finger-sucking habits.


Self-assembly and calcium-binding sites in laminin. A three-arm interaction model.
Laminin, a four-arm glycoprotein, polymerizes in vitro into networks similar to those found in basement membranes. We have dissected this calcium-dependent assembly by analyzing proteolytic fragment binding using equilibrium gel filtration, ultracentrifugation, and electron microscopy. The cathepsin G fragment C1-4 (three short arms) was found to aggregate with a critical concentration similar to that for laminin. Like laminin polymerization, this assembly was inhibited by the smaller elastase short arm fragments E4 (B1 domains VI and V) and E1' (A-B2 short arm complex). Fragment E4 bound directly to E1' in a calcium-dependent manner (KD = 1.4 microM). In contrast, homologous self-interactions of short arm fragments and all interactions of long arm fragments were considerably weaker or nonexistent. While electron micrographs of E1' or E4 alone contained mostly monomers, those of E1'/E4 mixtures contained dimers and oligomers with E1' dimers connected to each other through their A and B2 arms, often with visible E4 molecules at their junctions. 45Ca2+ bound principally to fragment E1' with localization to the end of the B2 chain. These data support a model in which polymerization requires the interaction of all three ligands, one from each short arm, with calcium activating assembly by binding to the B2 short arm.


Effects of Transition Metal Substituents on Interfacial and Electronic Structure of CH3NH3PbI3/TiO2 Interface: A First-Principles Comparative Study.
To evaluate the influence of transition metal substituents on the characteristics of CH3NH3PbI3/TiO2, we investigated the geometrical and electronic properties of transition metal-substituted CH3NH3PbI3/TiO2 by first-principles calculations. The results suggested that the substitution of Ti4+ at the five-fold coordinated (Ti5c) sites by transition metals is energetically favored. The substituted interface has enhanced visible light sensitivity and photoelectrocatalytic activity by reducing the transition energies. The transition metal substitution can effectively tune the band gap of the interface, which significantly improves the photo-reactivity. The substituted systems are expected to be more efficient in separating the photo-generated electrons-holes and active in the visible spectrum.


The mechanism of activity-dependent sodium channel inhibition by the antidepressants fluoxetine and desipramine.
The effect of monoamine uptake inhibitor-type antidepressants on sodium channels of hippocampal neurons was investigated. Members of the tricyclic group of antidepressants are known to modify multiple targets, including sodium channels, whereas selective serotonin-reuptake inhibitors (SSRIs) are regarded as highly selective compounds, and their effect on sodium channels was not investigated in detail. In this study, a representative member of each group was chosen: the tricyclic antidepressant desipramine and the SSRI fluoxetine. The drugs were roughly equipotent use-dependent inhibitors of sodium channels, with IC(50) values approximately 100 microM at -150 mV holding potential, and approximately 1 microM at -60 mV. We suggest that therapeutic concentrations of antidepressants affect neuronal information processing partly by direct, activity-dependent inhibition of sodium channels. As for the mechanism of inhibition, use-dependent inhibition by antidepressants was believed to be due to a preferential affinity to the fast-inactivated state. Using a voltage and perfusion protocol by which relative affinities to fast-versus slow-inactivated states could be assessed, we challenged this view and found that the affinity of both drugs to slowinactivated state(s) was higher. We propose a different mechanism of action for these antidepressants, in which slow rather than fast inactivation plays the dominant role. This mechanism is similar but not equivalent with the novel mechanism of usedependent sodium channel inhibition previously described by our group (Neuroscience 125:1019-1028, 2004; Neuroreport 14:1945-1949, 2003). Our results suggest that different drugs can produce use-dependent sodium channel inhibition by different mechanisms.


Aspirin and proton pump inhibitor combination therapy for prevention of cardiovascular disease and Barrett's esophagus.
Aspirin, used at low doses (75-325 mg daily), prevents aggregation of platelets and is prescribed for patients as pharmacologic prevention of cardiovascular disease. Despite the well-documented beneficial effects of aspirin, prolonged use is associated with damage to the gastrointestinal (GI) mucosa in the upper and lower GI tract. Patient risk of hemorrhage and peptic ulcer formation is increased with older age, previous ulcer history, Helicobacter pylori infection, and concomitant use of nonsteroidal anti-inflammatory drugs, corticosteroids, or antithrombotic agents. As termination of aspirin therapy can precipitate a cardiovascular event, patients at risk need co-therapy with gastroprotective agents, such as proton pump inhibitors (PPIs), to reduce the GI side effects of aspirin treatment. Fixed-dose combinations of low-dose aspirin and gastroprotective agents have been designed to increase medication compliance, improve clinical outcomes, and reduce the overall cost of therapy. Prolonged use of PPIs may, however, lead to serious adverse effects or, in some cases, reduce the cardioprotective effects of aspirin. Hence, physicians need to carefully consider the benefits and risks associated with the condition of each patient to optimize clinical outcomes of combination therapy. A growing body of clinical evidence indicates that aspirin may decrease the risk of colorectal and other GI cancers, as well as reduce progression from Barrett's esophagus (BE) to esophageal adenocarcinoma. Furthermore, PPIs have recently been shown to reduce neoplastic transformation in patients with BE. Thus, the use of a fixed-dose aspirin/PPI combination could potentially provide chemopreventive benefit to patients with BE, and, at the same time, treat the underlying gastroesophageal reflux responsible for the condition.


Computer program for analyzing donor photobleaching FRET image series.
The photobleaching fluorescence resonance energy transfer (pbFRET) technique is a spectroscopic method to measure proximity relations between fluorescently labeled macromolecules using digital imaging microscopy. To calculate the energy transfer values one has to determine the bleaching time constants in pixel-by-pixel fashion from the image series recorded on the donor-only and donor and acceptor double-labeled samples. Because of the large number of pixels and the time-consuming calculations, this procedure should be assisted by powerful image data processing software. There is no commercially available software that is able to fulfill these requirements. New evaluation software was developed to analyze pbFRET data for Windows platform in National Instrument LabVIEW 6.1. This development environment contains a mathematical virtual instrument package, in which the Levenberg-Marquardt routine is also included. As a reference experiment, FRET efficiency between the two chains (beta2-microglobulin and heavy chain) of major histocompatibility complex (MHC) class I glycoproteins and FRET between MHC I and MHC II molecules were determined in the plasma membrane of JY, human B lymphoma cells. The bleaching time constants calculated on pixel-by-pixel basis can be displayed as a color-coded map or as a histogram from raw image format. In this report we introduce a new version of pbFRET analysis and data processing software that is able to generate a full analysis pattern of donor photobleaching image series under various conditions. .


Depiction of facial nerve paresis in the gallery of portraits carved in stone by George Matthew the Dalmatian on the Sibenik Cathedral dating from the 15th century.
The introductory segment of this paper briefly describes George Matthew the Dalmatian, the architect who, between 1441 and 1473, oversaw the construction of the Cathedral of St. James in Sibenik, a city on the Croatian side of the Adriatic coast. Of the most impressive details included in this monumental construction and sculptural flamboyant gothic production infused with distinctive Dalmatian spirit is a frieze of 71 stone and three lion portraits encircling the outer apse wall. From the intriguing amalgamation of portraits of anonymous people this master came across in his surrounding, the fiftieth head in the row has been selected for this occasion. On the face of a younger man the authors have recognized and described pathognomonic right-sided facial nerve paresis. The question posed here is whether this is coincidental or it represents the master's courage, given that instead of famous people in the cathedral he situated not only ordinary people but also those "labelled" and traditionally marginalized, thus, in the most beautiful manner, foreshadowing the forthcoming spirit of Humanism and Renaissance in Croatian and European art.


The unrecognized paradigm shift in nursing: implications, problems, and possibilities.
An important paradigm (or worldview) shift is occurring in science that affects the nature of nursing education, practice, and research. The shift from positivism to postmodernism and now to neomodernism has received little attention in US nursing and as such may forestall many opportunities related to such change. The nature of this paradigm shift and its effects on selected aspects of nursing education, practice, and research are described, and related implications, problems, and possibilities are explored. Neomodernism is discussed as one future for nursing that encompasses aspects of both positivism and postmodernism but yet goes beyond these to include important metanarratives as traditional values and beliefs of nursing. The work of Laudan and Lakatos are explored as supportive of this neomodernist approach.


Buccal dental microwear texture and catarrhine diets.
Two-dimensional dental microwear analyses on occlusal and nonocclusal enamel surfaces have been widely applied to reconstruct the feeding behaviors of extant primates and to infer ecological adaptations in fossil hominins. To date, analyses of dental microwear texture, using three-dimensional, Scale-Sensitive Fractal Analysis approaches has only been applied to occlusal surfaces. Here, for the first time, we apply this 3D proxy to buccal enamel surfaces of catarrhine primates of known feeding ecologies to assess the utility of nonocclusal microwear texture variables as indicators of dietary habits. Buccal microwear texture attributes were collected from high-resolution second molar casts in a sample of seven extant African catarrhine taxa with differing dietary behaviors. A white-light confocal microscope with a 100× objective lens was used to record six microwear texture variables that assess complexity, anisotropy, heterogeneity, and textural fill volume. The physical properties and variation in hardness of ingested foods is reflected by significant differences in the microwear variables on buccal enamel surfaces between species, which is in agreement with early reports using 2D microwear signatures of the same samples. Species that consume hard brittle items showed high buccal enamel complexity and low anisotropy values, while folivorous species that consume tough foods revealed high anisotropy and low complexity enamel patterns. Buccal microwear texture analysis on enamel surfaces clearly reflects diet-related variation in nonhuman primates. Our findings indicate that microwear texture attributes on nonworking enamel surfaces provide an alternative procedure for reconstructing dietary behavior when wear facets on occlusal surfaces are lacking.


Measuring Critical Care Providers' Attitudes About Controlled Donation After Circulatory Death.
Unfavorable attitudes and insufficient knowledge about donation after cardiac death among critical care providers can have important consequences for the appropriate identification of potential donors, consistent implementation of donation after cardiac death policies, and relative strength of support for this type of donation. The lack of reliable and valid assessment measures has hampered research to capture providers' attitudes. Design and Research Aims: Using stakeholder engagement and an iterative process, we developed a questionnaire to measure attitudes of donation after cardiac death in critical care providers (n = 112) and examined its psychometric properties. Exploratory factor analysis, internal consistency, and validity analyses were conducted to examine the measure. A 34-item questionnaire consisting of 4 factors (Personal Comfort, Process Satisfaction, Family Comfort, and System Trust) provided the most parsimonious fit. Internal consistency was acceptable for each of the subscales and the total questionnaire (Cronbach α > .70). A strong association between more favorable attitudes overall and knowledge ( r = .43, P < .001) provides evidence of convergent validity. Multivariable regression analyses showed that white race ( P = .002) and more experience with donation after cardiac death ( P < .001) were significant predictors of more favorable attitudes. Study findings support the utility, reliability, and validity of a questionnaire for measuring attitudes in critical care providers and for isolating targets for additional education on donation after cardiac death.


Prognostic factors in patients with carcinoma of the vulva--our own experience and literature review.
The objective was the analysis of prognostic factors and treatment outcomes of 104 patients with vulvar cancer, treated between 1990 and 2003 in the Center of Oncology, Maria Sklodowska-Curie Memorial Institute, Cracow, Poland. The median age of patients was 67. Advanced disease (TNM III and IVA) was found in 54 (51.9%) patients and grade 2 and 2 in 50 (48.1%). Inguinal lymph nodes were clinically uni- or bilaterally involved in 40.4% of patients. Fifty-seven (54.8%) patients underwent radical vulvectomy with bilateral inguinal lymphadenectomy and 47 (45.2%) radical vulvectomy only. Cancer differentiation was well in 38 (36.2%) of patients, moderate in 38 (36.2%) and poor in 28 (36.6%). Adjuvant radiotherapy was applied in 30 (28.8%) cases. Five-year overall survival rate was observed in 44.4% of patients. Depending on TNM grade, 5-year OS rates were 61.4% for grade 1, 54.9% for grade 2, 40.1% for grade 3 and 13.3% for IVA. In patients aged < 70, 5-year OS rate was 54.7% compared to 30.5% for those > or = 70. Among patients with G1 cancer differentiation 64.4% survived five years, with G2 39.1% and with G3 24.9%, respectively. Univariate analysis revealed a statistically significant, unfavorable impact of age > or = 70, with G3 cancer differentiation, clinically confirmed inguinal lymph node involvement and TNM classification stage on 5-year overall survival. Cox multivariate analysis demonstrated that independent prognostic factors for 5-year survival were the age of the patient, clinical status of inguinal lymph nodes and TNM classification grade.


[Anal intraepithelial neoplasia].
Human papillomavirus (HPV) is responsible for anal condylomata, anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma. AIN is a premalignant condition that can progress to invasive carcinoma through different grades of severity of the disease called AIN I, AIN II and AIN III. This paper looks at the current definition, diagnostic methods and management of AIN. The incidence of AIN has increased significantly in the last decades. The groups at risk are mainly patients with infection with human immunodeficiency virus, immunossuppressed patients and patients affected by HPV related diseases (e.g., cervical cancer or anal condyloma). Accurate diagnosis of AIN lesions consists of accurate grading and disease extension. Low grade AIN (AIN I) or in extensive lesions, follow-up is advised to determine the possible evolution to anal squamous cell carcinoma. In cases of more severe and localized lesions (AIN II and AIN III), surgical resection should be considered if the predictive postoperative morbidity is low. Screening programs for AIN are not currently in place and there might be much effort to study the management of HPV in these patients.


[Effect of electro-acupuncture on metabolites in the cerebral cortex of ulcerative colitis rats based on Pi/Wei-brain related theory].
To study the effect of electro-acupuncture (EA) at points along Foot Yangming Channel on metabolite of ulcerative colitis (UC) rats' cerebral cortex and to identify key metabolites by referring to Pi/Wei-brain related theory in Chinese medicine (CM). The UC rat model was set up by dextran sulfate sodium (DSS) method. Male SD rats were randomly divided into the model group and the EA group, 13 in each group. Another 13 rats were recruited as the blank control group. Rats in the blank control group and the model group received no EA. EA was performed at Zusanli (ST36), Shangjuxu (ST37), and Tianshu (ST25) for 5 days by using disperse-dense wave. Then all rats were sacrificed. Their recto-colon and the ileocecal junction were pathomorphologically observed by light microscope and transmission electron microscope (TEM). Cerebral cortexes were extracted. Water-soluble and lipid-soluble brain tissue metabolites were respectively extracted for metabolic research using 1H nuclear magnetic resonance (1H-NMR). EA could obviously improve the general condition of UC model rats, decrease the value of DAI, reduce the infiltration of inflammatory cells in the intestinal tract, stabilize structures such as mitochondria, endoplasmic reticulum and so on (P <0.05). 1HNMR analysis showed that in the model group, contents of glutamic acid, cholesterol, very low density lipoproein (VLDL) in the pallium obviously decreased, while alanine and low density lipoprotein (LDL) significantly increased. After EA, levels of lactic acid, glutamic acid, total cholesterol (TC), and VLDL all increased, and levels of alanine and LDL decreased. All indices were approximate to those of the blank control group. EA at Foot Yangming channel was found to have some effect on metabolites in the brain tissue of UC model rats, which had specific metabonomic material basis and mechanism based on the Pi/Wei-brain related theory.


Neutrophilic Inflammation in the Immune Responses of Chronic Obstructive Pulmonary Disease: Lessons from Animal Models.
Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide, which is characterized by chronic bronchitis, destruction of small airways, and enlargement/disorganization of alveoli. It is generally accepted that the neutrophilic airway inflammation observed in the lungs of COPD patients is intrinsically linked to the tissue destruction and alveolar airspace enlargement, leading to disease progression. Animal models play an important role in studying the underlying mechanisms of COPD as they address questions involving integrated whole body responses. This review aims to summarize the current animal models of COPD, focusing on their advantages and disadvantages on immune responses and neutrophilic inflammation. Also, we propose a potential new animal model of COPD, which may mimic the most characteristics of human COPD pathogenesis, including persistent moderate-to-high levels of neutrophilic inflammation.


Colloids exposed to random potential energy landscapes: From particle number density to particle-potential and particle-particle interactions.
Colloidal particles were exposed to a random potential energy landscape that has been created optically via a speckle pattern. The mean particle density as well as the potential roughness, i.e., the disorder strength, were varied. The local probability density of the particles as well as its main characteristics were determined. For the first time, the disorder-averaged pair density correlation function g((1))(r) and an analogue of the Edwards-Anderson order parameter g((2))(r), which quantifies the correlation of the mean local density among disorder realisations, were measured experimentally and shown to be consistent with replica liquid state theory results.


Spatial heterogeneity of neighborhood-level water and sanitation access in informal urban settlements: A cross-sectional case study in Beira, Mozambique.
Rapid urbanization, resulting in population growth within informal settlements, has worsened exclusion and inequality in access to water and sanitation (WASH) services in the poorest and most marginalized communities. In this study, we describe the heterogeneity in water service satisfaction and WASH access in low-income, peri-urban neighborhoods of Beira, Mozambique, and examine whether this heterogeneity can be explained by distance to water distribution mains. Using spatial statistics and regression analyses, we identify spatial heterogeneity in household WASH access, as well as consumer-reported satisfaction with water services (services, pressure, quality, and sufficient quantity). We find that as distance from the water main increased, both access to an improved water source at the household and satisfaction with water pressure decreases, and water supply intermittency increases, controlling for household density and socioeconomic status. The odds of a household having access to a water source at the household or on the compound decreases with every 100-meter increase in distance from a water main pipe (odds ratio [OR] 0.87, 95% confidence interval [CI]: 0.82, 0.92). Satisfaction with water services also decreases with every 100-meter increase in distance from a water main pipe (OR: 0.80; 95% CI: 0.69, 0.94). Days of availability in the past week decreases by a factor of 0.22 for every 100-meter increase in distance from the water main (95% CI: -0.29, -0.15). Findings from this study highlight the unequal household access to water and sanitation in urban informal settlements, even within low-income neighborhoods. Describing this heterogeneity of access to water services, sanitation, and satisfaction-and the factors influencing them-can inform stakeholders and guide the development of infrastructural solutions to reduce water access inequities within urban settings.


Recent advances in the clinical pharmacology of Parkinson's disease.
The introduction of levodopa in the treatment of Parkinson's disease had modified both the prognosis and the current concepts of the disease, Although levodopa remains the most potent drug for the treatment of Parkinson's disease, its long-term use is associated with fluctuations in motor performance, abnormal movements and psychotic hallucinations. These late side-effects remain difficult to treat and thus raise questions as to the benefits and risks of first-time treatment with levodopa. Levodopa mainly alleviates akinesia and rigidity and to a lesser extent, tremor. Levodopa increases life expectancy. This paper reviews some recent developments in the pharmacology of Parkinson's disease. Recent findings indicate that not only central dopamine but also several other central neurotransmitter and receptor changes are involved in the pathophysiology of Parkinson's disease. New data on autonomic dysfunction in Parkinson's disease are presented. New methods of investigation (clinical rating scales, pharmacological tests, imaging techniques, etc.) are reviewed. Finally, future strategies, e.g. the development of potent new symptomatic drugs (selective D2 and D1 agonists, new formulations of apomorphine, COMT inhibitors, new routes of administration, etc.) and etiopathogenic agents (antioxidative and anti-free radical drugs, etc.) are discussed.


[Hodgkin's disease and HIV: relations between CD4/CD8 rate, histology and stage].
Hodgkin's disease (HD) is not currently accepted as an AIDS diagnostic criterion by the Centers for Disease Control (Atlanta), although there are reports on a higher incidence of the disease in HIV infected patients, with the special feature of a marked clinical and histological aggressiveness. A review of the literature was made and a total of 54 cases of HD compiled of patients with HIV infection. The relationships between the absolute counts of CD4 and the CD4/CD8 ratio with histopathology and with the stage at diagnosis was investigated. No significant differences were found between the absolute counts of CD4 and CD4/CD8 ratio with the clinical stage of disease, histopathologic subgroup or presence of B symptoms in HD. Nevertheless, lower CD4 counts were observed in more advanced clinical stages and in patients with B symptoms; the highest CD4/CD8 ratios were observed in patients with more advanced disease. It is hypothesized that immunological disturbances caused by HIV would lead to more aggressive histological lesions and more advanced stages of HD in HIV-positive patients. Thus, the inclusion of HD as a diagnostic criterion of AIDS would be warranted.


Legionnaire's disease and acute renal failure: a case report and literature review.
A case report is presented of a young man admitted to a general hospital with leukocytosis, elevated temperature, right lower lobe infiltrate, and confusion. A diagnosis of rhabdomyolysis, acute renal failure, and Legionnaire's disease was made. The patient subsequently had a respiratory arrest and died on the 29th hospital day. This triad is currently an enigma in the field of internal medicine. The diagnosis of each entity is elusive, and in many cases must be made by the astute clinician. Diagnostic features along with early intervention measures and their expected outcomes are discussed. Recognition of the interrelationship of these diseases, risk factors, and vague clinical presentations might allow further prospective intervention methods and diagnostic procedures to be undertaken to avoid the fatal consequences seen in this disease triad.


The role of nonlinear factor-to-indicator relationships in tests of measurement equivalence.
Measurement invariance is a necessary condition for the evaluation of factor mean differences over groups or time. This article considers the potential problems that can arise for tests of measurement invariance when the true factor-to-indicator relationship is nonlinear (quadratic) and invariant but the linear factor model is nevertheless applied. The factor loadings and indicator intercepts of the linear model will diverge across groups as the factor mean difference increases. Power analyses show that even apparently small quadratic effects can result in rejection of measurement invariance at moderate sample sizes when the factor mean difference is medium to large. Recommendations include the identification of nonlinear relationships using diagnostic plots and consideration of newly developed methods for fitting nonlinear factor models.


Multifaceted TGF-β signaling, a master regulator: From bench-to-bedside, intricacies, and complexities.
Physiological embryogenesis and adult tissue homeostasis are regulated by transforming growth factor-β (TGF-β), an evolutionarily conserved family of secreted polypeptide factors, acting in an autocrine and paracrine manner. The role of TGF-β in inflammation, fibrosis, and cancer is complex and sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage of the disease. Under pathological conditions, especially fibrosis and cancer, overexpressed TGF-β causes extracellular matrix deposition, epithelial-mesenchymal transition, cancer-associated fibroblast formation, and/or angiogenesis. In this review article, we have tried to dive deep into the mechanism of action of TGF-β in inflammation, fibrosis, and carcinogenesis. As TGF-β and its downstream signaling mechanism are implicated in fibrosis and carcinogenesis blocking this signaling mechanism appears to be a promising avenue. However, targeting TGF-β carries substantial risk as this pathway is implicated in multiple homeostatic processes and is also known to have tumor-suppressor functions. There is a need for careful dosing of TGF-β drugs for therapeutic use and patient selection.


Doped nanostructured zinc oxide films grown by electrodeposition.
ZnO thin films doped with either In or Al are n-type oxide materials of interest for application in electronic devices and thin-film solar cells. In this work, the doped ZnO films were electrodeposited at 80 degrees C from an aqueous solution on polycrystalline conductive Indium Tin Oxide covered glass substrates. The incorporation of the dopants into the ZnO film has been verified by energy dispersive X-ray spectrum, X-Ray diffraction and optical transmission analysis. The optical and surface structure properties of the ZnO doped films are strongly affected by the In and Al concentrations in the electrodeposition solution as evidenced by optical transmission and reflection measurements, and scanning electron microscopy.


[Evaluation of the diagnostic usefulness for ultrasonographic and echocardiographic lethal markers in fetal pulmonary hypoplasia. Analysis of 11 cases].
Results of ultrasonographic and echocardiographic studies of 11 fetuses were analysed retrospectively in relation to their pulmonary hypoplasia. Congenital malformations, quality of hydramnios and echocardiographical measurements of fetal chest were estimated. The best symptoms of pulmonary hypoplasia were: oligo/ahydramnios, absence of fetal breathing movements and malformations in fetal chest cavity (diaphragmatic hernia, cardiomegaly, hydrothorax). Systemic malformations were present in each case. The measurements such as CC, CA, HA, (CA-HA) x 100/CA were not accurate enough and we did not find any statistical differences between the control and the studied group. Finding several factors predisposing to lung hypoplasia means that its lethal form may be present in fetus.


[A case of dural sinus thrombosis during the medication of medroxyprogesterone acetate].
It is reported that medroxyprogesterone acetate (MPA) causes venous thrombosis as one of the side effects. A 49-year-old woman suffering from metastatic lung carcinoma from breast carcinoma was administered MPA 1200 mg/day for about four months. Thereafter she complained of dizziness about two weeks but the general practitioners could detect no abnormality on physical examinations and on brain CT X-ray findings. Six days later, she died suddenly at her home. Forensic autopsy findings revealed the marked superior sagital sinus thrombosis and the malignant lymphadenomatosis caused by metastatic lung carcinoma. As the patient had not disease or trauma causing dural sinus thrombosis except for the administration of MPA, we concluded that superior sagital sinus thrombosis was due to the medication of MPA. This case illustrates that forensic pathologist should consider the major side effect of some drugs like our case.


Glomerular filtration rate as a kidney outcome of diabetic kidney disease: a focus on new antidiabetic drugs.
Diabetes has reached epidemic proportions, both in Korea and worldwide and is associated with an increased risk of chronic kidney disease and kidney failure (KF). The natural course of kidney function among people with diabetes (especially type 2 diabetes) may be complex in real-world situations. Strong evidence from observational data and clinical trials has demonstrated a consistent association between decreased estimated glomerular filtration rate (eGFR) and subsequent development of hard renal endpoints (such as KF or renal death). The disadvantage of hard renal endpoints is that they require a long follow-up duration. In addition, there are many patients with diabetes whose renal function declines without the appearance of albuminuria, measurement of the eGFR is emphasized. Many studies have used GFR-related parameters, such as its change, decline, or slope, as clinical endpoints for kidney disease progression. In this respect, understanding the trends in GFR changes could be crucial for developing clinical management strategies for the prevention of diabetic complications. This review focuses on the clinical implication of the eGFR-related parameters that have been used so far in diabetic kidney disease. We also discuss the use of recently developed new antidiabetic drugs for kidney protection, with a focus on the GFR as clinical endpoints.


Mercury: major issues in environmental health.
In the past, methylmercury compounds were manufactured as fungicides or appeared as unwanted byproducts of the chemical industry, but today the methylation of inorganic mercury in aquatic sediments and soils is the predominant if not the sole source of methylmercury. This form of mercury is bioaccumulated to a high degree in aquatic food chains to attain its highest concentrations in edible tissues in long-lived predatory fish living in both fresh and ocean waters. It is well absorbed from the diet and distributes within a few days to all tissues in the body. It crosses without hindrance the blood-brain and placental barriers to reach its principal target tissue, the brain. It is eliminated chiefly in the feces after conversion to inorganic mercury. The biological half-time of methylmercury in human tissues is about 50 days, but there is wide individual variation. Adult poisoning is characterized by focal damage to discrete anatomical areas of the brain such as the visual cortex and granule layer of the cerebellum. A latent period of weeks or months may ensue before the appearance of signs and symptoms of poisoning. The latter manifest themselves as paresthesia, ataxia, constriction of the visual fields, and hearing loss. The prenatal period is the most sensitive stage of the life cycle to methylmercury. Prenatally poisoned infants exhibit a range of effects from severe cerebral palsy to subtle developmental delays. Methylmercury is believed to inhibit those processes in the brain specially involved in development and growth such as neuronal cell division and migration.


The first reported case of rabbit hemorrhagic disease in Canada.
In March 2011, rabbit hemorrhagic disease (RHD) was suspected in a 1-year-old male neutered lop-eared rabbit that had acute onset liver failure. Gross pathology, histopathology, immunohistochemistry, partial nucleic acid sequencing and phylogenetic analysis of the major capsid protein (VP60) and animal inoculation studies all supported this diagnosis making it the first confirmed case of RHD in Canada. In March 2011, rabbit hemorrhagic disease (RHD) was suspected in a 1-year-old male neutered lop-eared rabbit that had acute onset liver failure. Gross pathology, histopathology, immunohistochemistry, partial nucleic acid sequencing and phylogenetic analysis of the major capsid protein (VP60) and animal inoculation studies all supported this diagnosis making it the first confirmed case of RHD in Canada.


Speculation on the evolution of stem cells.
Profoundly different patterns of potency and division are exhibited by mammalian embryonic and adult stem cells. Additional confusion surrounds stem-cell surrogates, cache and reserve cells having some characteristics of stem cells and not others. Mystification may have been introduced historically with the concepts of determinate and regulative development, but, hopefully, the muddle can be resolved by tracing the evolution of stem cells in Metazoa. Blastomeres in marine sponges, cnidarians, lophotrochozoans, small ecdysozoans (e.g., Caenorhabditis elegans), and some deuterostomes (e.g., echinoderms and ascidians) exhibit determinative development. Their larval and adult cells have narrow potencies, sometimes coupled to virtually unlimited proliferation, and function in the growth, maintenance and regulation of body size. The embryos of larger arthropods and deuterostomes with well-provisioned eggs or viviparity, on the other hand, exhibit regulative development, while their larval "set-aside" or adult stem cells function in the growth, maintenance, and regulation of organ size coupled to constrained proliferation and cell turnover. Mammalian embryonic stem cells would seem adapted to rapid proliferation, functioning in part to enclose yolk or to acquire access to maternal resources. The cellular products of embryonic stem cells routinely come under global influences and give rise to the cells of germ layers and organ rudiments. Mammalian adult stem cells resemble the blastomeres of planktonic and benthic organisms with small eggs and may have evolved in mature organisms as an adaptation to the growth and maintenance of tissues via proliferation and the regulation of organ size via cell loss (e.g., terminal differentiation). Cancer stem cells, instrumental in metastasis, would seem to ignore mechanisms normally functioning in the removal of excess cells. Strategies for regenerative therapies in adult mammals, therefore, might be based on stimulating growth of adult stem cells or their surrogates in specific tissues rather than on introducing embryonic stem cells into adults. Likewise, strategies for the containment of cancer might be based on promoting normal pathways of cell loss, the basal mode for handling excess cells.


Bicruciate Ligament Reconstruction in a Professional Rugby Player: Clinical Presentation and Literature Review.
The association of an anterior cruciate ligament (ACL) tear and a posterior cruciate ligament (PCL) injury is rare in athletes, and to our knowledge it has never been described in a professional rugby player. We report the case of a 27-year-old international professional rugby player who presented with an ACL tear associated with chronic posterior laxity on a former PCL tear. The procedure associated arthroscopic ACL and PCL reconstruction in a one-stage operation with two autografts, bone-patellar tendon-bone and hamstring tendon, respectively. At 7 months postoperatively, the patient had returned to playing rugby at the same level of play. The therapeutic strategy successfully met the established goals of returning to sports at the same level of play with excellent functional results after 2 years of follow-up. A literature review was performed via PubMed. The inclusion criteria were the studies in English language, assessing the return-to-sport after bicruciate ligament reconstruction in athletes. Eight studies were included in analysis. Only one study has focused on the return-to-sport in 24 competitive athletes and two other studies have included 1 professional athlete each. The overall rate of the return-to-sport after bicruciate reconstruction varied between 100% and 50%.


The temporoparietal junction modulates self-other motor representations during online and offline social motor conflict: an rTMS study.
The aim of this study was to investigate the role of the temporoparietal junction (TPJ) during tasks of imitation and counter-imitation of observed actions. Twenty individuals participated in two experiments. One experiment was an imitation/counter-imitation task, requiring the participant to imitate or counter-imitate an observed movement. The second experiment required the participant to plan a movement, then to imitate an observed movement that could be either the same or different from that planned. In both experiments, participants executed the task in a baseline session and in a session following inhibitory trains of repetitive transcranial magnetic stimulation on the right TPJ and on the right ventral premotor cortex. In both experiments, repetitive transcranial magnetic stimulation of the right TPJ decreased reaction times of incongruent responses--that is, it facilitated the execution of movements different from those previously observed or planned. These findings provide an example of modulation of self-other interactions using noninvasive neuromodulation of the right TPJ.


Scanning electron microscope imaging of onychomycosis.
Although scanning electron microscope technology has been used for more than 60 years in many fields of medical research, no studies have focused on obtaining high-resolution microscopic images of onychomycosis of the toenail caused by Trichophyton rubrum in a geriatric population. To provide new insight into the intricate structure and behavior of chronic toenail onychomycosis, we produced three-dimensional images of onychomycosis obtained from two geriatric patients with confirmed growth of T rubrum. The photomicrographs illustrate the pervasive integration and penetration of the fungus hyphal elements, underscoring the clinical difficulty of obtaining rapid treatment of fungal infections in the distal and lateral subungual space of the human toenail. Although the scanning electron microscope may not be a practical diagnostic tool for most physicians, it remains invaluable for the researcher to obtain insight into the spatial orientation, behavior, and appearance of onychomycosis.


LPA in neural cell development.
Lysophosphatidic acid (LPA) elicits diverse cellular responses through cell surface LPA receptors in nervous system-derived cells and cell lines. The developing nervous system is one of the major loci for LPA receptor expression. Recent studies have also revealed that metabolic pathways of LPA are present in the nervous system. A growing body of literature suggests a crucial role for LPA in neuronal development processes, including neurogenesis, neuronal migration, neuritogenesis, and myelination.


Additive Intraocular Pressure-Lowering Effects of Ripasudil with Glaucoma Therapeutic Agents in Rabbits and Monkeys.
Ripasudil hydrochloride hydrate (K-115), a specific Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor, is developed for the treatment of glaucoma and ocular hypertension. Topical administration of ripasudil decreases intraocular pressure (IOP) by increasing conventional outflow through the trabeculae to Schlemm's canal, which is different from existing agents that suppress aqueous humor production or promote uveoscleral outflow. In this study, we demonstrated that ripasudil significantly lowered IOP in combined regimens with other glaucoma therapeutic agents in rabbits and monkeys. Ripasudil showed additional effects on maximum IOP lowering or prolonged the duration of IOP-lowering effects with combined administration of timolol, nipradilol, brimonidine, brinzolamide, latanoprost, latanoprost/timolol fixed combination, and dorzolamide/timolol fixed combination. These results indicate that facilitation of conventional outflow by ripasudil provides additive IOP-lowering effect with other classes of antiglaucoma agents. Ripasudil is expected to have substantial utility in combined regimens with existing agents for glaucoma treatment.


The nocturnal acoustical intensity of the intensive care environment: an observational study.
The intensive care unit (ICU) environment exposes patients to noise levels that may result in substantial sleep disruption. There is a need to accurately describe the intensity pattern and source of noise in the ICU in order to develop effective sound abatement strategies. The objectives of this study were to determine nocturnal noise levels and their variability and the related sources of noise within an Australian tertiary ICU. An observational cross-sectional study was conducted in a 24-bed open-plan ICU. Sound levels were recorded overnight during three nights at 5-s epochs using Extech (SDL 600) sound monitors. Noise sources were concurrently logged by two research assistants. The mean recorded ambient noise level in the ICU was 52.85 decibels (dB) (standard deviation (SD) 5.89), with a maximum noise recording at 98.3 dB (A). All recorded measurements exceeded the WHO recommendations. Noise variability per minute ranged from 9.9 to 44 dB (A), with peak noise levels >70 dB (A) occurring 10 times/hour (SD 11.4). Staff were identified as the most common source accounting for 35% of all noise. Mean noise levels in single-patient rooms compared with open-bed areas were 53.5 vs 53 dB (p = 0.37), respectively. Mean noise levels exceeded those recommended by the WHO resulting in an acoustical intensity of 193 times greater than the recommended and demonstrated a high degree of unpredictable variability, with the primary noise sources coming from staff conversations. The lack of protective effects of single rooms and the contributing effects that staffs have on noise levels are important factors when considering sound abatement strategies.


Prevention of lower respiratory herpes simplex virus infection with acyclovir in patients with the adult respiratory distress syndrome.
Herpes simplex virus (HSV) type I commonly occurs in the lower respiratory tract (LRT) of seriously ill patients, particularly those with the adult respiratory distress syndrome (ARDS), but it is not known whether HSV is a benign mucosal colonizer or a pathogen. The aims of this study were to determine whether the antiviral agent acyclovir could prevent this occurrence, and if so, whether prevention improved the outcome. Forty-five patients with ARDS underwent double-blind randomization into a treatment group (22 subjects) who received prophylactic acyclovir intravenously, 5 mg/kg every 8 h, and a control group (23 subjects). Upper and lower respiratory secretions were examined for the presence of HSV before randomization and twice weekly thereafter. Seven patients were excluded because of HSV detection prior to treatment. There were no significant differences between the remaining 17 acyclovir and 21 control patients in age, sex, distribution of primary diagnostic categories, and severity of primary illness. Only 1 patient (6%) in the acyclovir group developed HSV after treatment compared with 15 (71%) in the control group (p less than 0.001), but there was no improvement in the acyclovir group in the severity of respiratory failure, the duration of ventilator support (acyclovir, 20 +/- 19 days; control, 14 +/- 11 days), or mortality (acyclovir, 8 of 17, 47%; control, 9 of 21, 43%). We conclude that acyclovir is effective in preventing the high incidence of HSV in patients with ARDS, but that this prevention does not improve outcome. Routine prophylaxis of HSV is not recommended.


Analyzing engagement in a web-based intervention platform through visualizing log-data.
Engagement has emerged as a significant cross-cutting concern within the development of Web-based interventions. There have been calls to institute a more rigorous approach to the design of Web-based interventions, to increase both the quantity and quality of engagement. One approach would be to use log-data to better understand the process of engagement and patterns of use. However, an important challenge lies in organizing log-data for productive analysis. Our aim was to conduct an initial exploration of the use of visualizations of log-data to enhance understanding of engagement with Web-based interventions. We applied exploratory sequential data analysis to highlight sequential aspects of the log data, such as time or module number, to provide insights into engagement. After applying a number of processing steps, a range of visualizations were generated from the log-data. We then examined the usefulness of these visualizations for understanding the engagement of individual users and the engagement of cohorts of users. The visualizations created are illustrated with two datasets drawn from studies using the SilverCloud Platform: (1) a small, detailed dataset with interviews (n=19) and (2) a large dataset (n=326) with 44,838 logged events. We present four exploratory visualizations of user engagement with a Web-based intervention, including Navigation Graph, Stripe Graph, Start-Finish Graph, and Next Action Heat Map. The first represents individual usage and the last three, specific aspects of cohort usage. We provide examples of each with a discussion of salient features. Log-data analysis through data visualization is an alternative way of exploring user engagement with Web-based interventions, which can yield different insights than more commonly used summative measures. We describe how understanding the process of engagement through visualizations can support the development and evaluation of Web-based interventions. Specifically, we show how visualizations can (1) allow inspection of content or feature usage in a temporal relationship to the overall program at different levels of granularity, (2) detect different patterns of use to consider personalization in the design process, (3) detect usability issues, (4) enable exploratory analysis to support the design of statistical queries to summarize the data, (5) provide new opportunities for real-time evaluation, and (6) examine assumptions about interactivity that underlie many summative measures in this field.


Unravelling the genetics of prostate cancer.
This review describes what is currently known about the genetics of prostate cancer. Traditionally, the genetics of a suspected inherited cancer predisposition have generally been thought of in terms of a single, high-risk gene with a dominant mode of inheritance. Such a gene might be observed in families, as has been documented in familial breast cancer (BRCA1/2), familial colorectal cancer (HNPCC), retinoblastoma (RB1), and Wilms tumor (WT1). This review investigates the evidence for the existence, first of familial prostate cancer, and second, for the presence of such a high-risk gene in those families by epidemiological and experimental approaches. Another current area of interest in prostate cancer is the investigation of the contribution of common lower penetrance genes to the disease. This alternative approach has become popular, as it raises the issue of frequently seen genetic variations such as single nucleotide polymorphisms (SNPs) having relevance to the risk of developing the disease. Finally, this article will explore the way forward, with emphasis on worldwide collaboration from teams attempting to find the genes responsible for the disease and investment in new technologies that will aid in their discovery.


Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation.
Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer.


Disease activity and treatment efficacy using patient-level Psoriasis Area and Severity Index scores from tildrakizumab phase 3 clinical trials.
It is unclear whether primary efficacy outcomes in plaque psoriasis clinical trials represent residual disease during treatment. To evaluate supplementing dichotomous efficacy with residual disease activity. This post hoc analysis used pooled, patient-level data after tildrakizumab 100 mg (N = 616) or placebo (N = 309) treatment from reSURFACE 1/2 (NCT01722331/NCT01729754) phase 3 clinical trials of patients with moderate to severe plaque psoriasis. Median baseline Psoriasis Area and Severity Index (PASI) was 17.9 for patients receiving tildrakizumab 100 mg. At Week 12, median PASI was 2.9, whereas dichotomous PASI 90 response rate was 36.9%, and absolute PASI <5.0, <3.0, and <1.0 were 64.0%, 50.8%, and 23.3%, respectively. At Week 28, median PASI was 1.7, whereas PASI 90 response rate was 51.9%, and absolute PASI <5.0, <3.0, and <1.0 were 75.3%, 62.8%, and 38.0%, respectively. Dermatology Life Quality Index and PASI scores were correlated through Week 28 (r = 0.51, p ≤ .0001). Disease activity was more reliably estimated by PASI scores than percentage PASI improvement; this may partially explain efficacy disparities between clinical trials and practice. These results suggest supplementing dichotomous PASI improvement with PASI scores and consideration of patient treatment goals could facilitate clinical decisions.


Target discovery of cytotoxic withanolides from Physalis angulata var. villosa via reactivity-based screening.
The reactivity-based screening (RBS) was developed for directed discovery of cytotoxic withanolides. In this study, a thiol probe, 4-chlorobenzenethiol, was used to selectively attack cytotoxic withanolides containing potential pharmacophore, 2(3)-en-1-one in ring A (AEO) and 5β,6β-epoxy in ring B (BE), from the plant extract of Physalis angulata var. villosa. The screening was performed based on the potential mechanism of 4-chlorobenzenethiol nucleophilic addition to AEO, followed by detection of adducts using liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS). Guided by RBS, eleven target withanolides, including five new compounds, physagulides R-V (10-14) and six known ones (2, 7-9, 15, 16) were discovered. All of them exhibited cytotoxicity against the both tested cell lines, especially, compounds 2, 7, 8 and 14 showed potent activities with IC50 values of 1.57-6.29 μM. The results suggested that RBS was efficient and accurate for rapid identification of cytotoxic withanolides and could guide isolation of target components from the complex medicinal plant extract.


Modulation of macrophage structure and function by low level He-Ne laser irradiation.
Studies have shown that He-Ne laser irradiation can affect the biological functions of macrophages. The aim of the present study was to investigate the effect of He-Ne laser irradiation on the various functional parameters of macrophages and look for possible correlations in the effects to understand the mechanisms involved. Mice peritoneal macrophages were irradiated with a He-Ne laser (632.8 nm, approximately 10 W m(-2)) at energy densities ranging from 100 to 600 J m(-2) and the activities of lysozyme and cathepsin, phagocytosis, and cell spreading (markers of cell activation), as well as changes in NAD(P)H autofluorescence, were monitored. He-Ne laser irradiation was observed to lead to significant changes in all the parameters investigated. While lysozyme activity and spreading of the peripheral membrane were found to increase with the irradiation dose over the dose range investigated, the phagocytotic activity of macrophages, the activity of cathepsin, the observed decease in cell membrane fluidity and the observed increase in NAD(P)H level showed a peak at 200 J m(-2). Possible reasons for and the significance of the observed correlations are discussed.


Mitral valve endocarditis due to Abiotrophia defectiva in a 14th week pregnant woman.
Infective endocarditis during pregnancy carries a high mortality risk, both for the mother and for the foetus and requires a multidisciplinary team in the management of complicated cases. We report our experience with a 39-year old patient, affected by an acute active mitral endocarditis due to Abiotrophia defectiva at the 14th gestational week, strongly motivated to continue the pregnancy. Our patient successfully underwent mitral valve replacement with a normothermic high-flow cardiopulmonary bypass under continuous intraoperative foetal monitoring. Caesarean section occurred at the 38th gestational week. The delivery was uneventful and both the mother and child are doing well at the 16-month follow-up.


Gender-specific early postnatal catch-up growth after intrauterine growth retardation by food restriction in swine with obesity/leptin resistance.
The effects of undernutrition during pregnancy on prenatal and postnatal development of the offspring were evaluated in sows with obesity/leptin resistance. Females were fed, from day 35 of pregnancy onwards, a diet fulfilling either 100% (group control, n=10) or 50% of the nutritional requirements (group underfed, n=10). In the control group, maternal body weight increased during pregnancy (P<0.05) while it decreased or remained steady in the underfed group. At days 75 and 100 of gestation, plasma triglycerides were lower but urea levels were higher in restricted than in control sows (P<0.05 for both). Assessment of the offspring indicated that the trunk diameter was always smaller in the restricted group (P<0.01 at day 50, P<0.005 at days 75 and 100 and P<0.0001 at birth) while head measurements were similar through pregnancy, although smaller in the restricted than in the control group at birth (P<0.05). Newborns from restricted sows were also lighter than offspring from control females (P<0.01) and had higher incidence of growth retardation (P<0.01). Afterwards, during lactation, early postnatal growth in restricted piglets was modulated by gender. At weaning, males from restricted sows were still lighter than their control counterparts (P<0.05), while females from control and underfed sows were similar. Thus, the current study indicates a gender-related differential effect in the growth patterns of the piglets, with females from restricted sows evidencing catch-up growth to neutralise prenatal retardation and reaching similar development than control counterparts.


Autologous hematopoietic stem cell transplantation for mediastinal extramedullary plasmocytoma.
Extramedullary plasmocytoma (EMP) is a rare cell neoplasm most frequently localised in the upper respiratory tract. We report the case of a 43 year-old-man, with an unusual presentation of EMP developing in the mediastinum, two years after a diagnosis of solitary plasmocytoma of the bone which was successfully treated by local irradiation. In this aggressive presentation, we decided to perform an autologous hematopoietic stem cell transplantation. Two months after transplantation, CT scan showed disappearance of the mediastinal mass and immunofixation of the serum was normal. Selected cases of diffuse EMP, could benefit from intensive treatment followed by autologous hematopoietic stem cell transplantation.


Regulation of synaptic connections in the rabbit ciliary ganglion.
One of the intriguing questions about the establishment of synaptic connections is how appropriate numbers of different axons come to innervate each target neuron. A reorganization of connections in early postnatal life appears to be an important aspect of this process, since many of the axons terminals that initially innervate target cells are subsequently lost. The rabbit ciliary ganglion is a remarkably simple neural ensemble in which to examine this rearrangement of developing synaptic connections. Using this system we have found that a reduction in the number of axons innervating each cell occurs without any change in the number of ciliary ganglion cells or preganglionic neurons; therefore the rearrangement is not based on cell death. The number of different axons that ultimately innervate each cell is, however, influenced in some way by the geometry of individual target neurons. Thus, mature ganglion cells that lack dendrites are generally innervated by a single axon, while neurons with increasingly complex dendritic arbors receive innervation from a commensurate number of different axons. At birth, on the other hand, neurons with or without dendritic processes receive about the same number of preganglionic inputs. These results suggest that the geometry of the target cell influences the competitive interaction between different axons innervating the same neuron. Indeed, an important function of dendrites may be to regulate the number of axons that innervate each nerve cell.


Rural anaesthesia practice: attitudes and recruitment following a period of anaesthetic training in rural and regional hospitals. A survey of new consultants.
The provision of specialist anaesthetic services to rural and remote locations in Australia poses an ongoing challenge. Initiatives to improve delivery of specialist anaesthetic services include the provision of anaesthesia training opportunities at rural hospitals. Previous surveys of trainees demonstrated the positive effect of rural training on attitudes toward subsequent practice in rural areas. We aimed first to survey attitudes of specialist anaesthetists towards anaesthetic training at rural and regional hospitals. We then compared the current workplace of those who had experienced a period of training at rural/regional hospitals versus those who did not. A web-based survey was distributed to fellows of the Australian and New Zealand College of Anaesthetists who had commenced consultant practice in the preceeding five years. Six hundred and fifteen surveys were distributed with a response rate of 53%. Respondents held their rural training experience in high regard. Anaesthetic specialists with a period of training in rural/regional areas were more likely to subsequently practise in rural areas compared to those who did not.


Impact of Radiation Therapy on Biological Parameters in Cancer Patients: Sub-analysis from the RIT Prospective Epidemiological Study.
Scarce data investigate the impact of radiotherapy (RT) on biology markers. An analysis of ancillary study of RIT (Radiation Impact on Thromboembolic events) prospective trial was carried out. All patients with non-metastatic solid tumors and treated with radiotherapy and/or brachytherapy in curative and consenting to have blood samples were included. A significant decrease in white blood count, (i.e. lymphocytes, monocytes, neutrophils and basophils) and platelet counts was observed after RT and maintained at 6 months. Whereas, eosinophils, D-dimers and hemoglobin levels were affected respectively 3 months and 6 months after RT initiation. Conversely, red cells count and CRP level were not affected by RT. This study is an advocacy to develop an understanding of basic immune system in relation with RT.


Cardiometabolic health, diet and the gut microbiome: a meta-omics perspective.
Cardiometabolic diseases have become a leading cause of morbidity and mortality globally. They have been tightly linked to microbiome taxonomic and functional composition, with diet possibly mediating some of the associations described. Both the microbiome and diet are modifiable, which opens the way for novel therapeutic strategies. High-throughput omics techniques applied on microbiome samples (meta-omics) hold the unprecedented potential to shed light on the intricate links between diet, the microbiome, the metabolome and cardiometabolic health, with a top-down approach. However, effective integration of complementary meta-omic techniques is an open challenge and their application on large cohorts is still limited. Here we review meta-omics techniques and discuss their potential in this context, highlighting recent large-scale efforts and the novel insights they provided. Finally, we look to the next decade of meta-omics research and discuss various translational and clinical pathways to improving cardiometabolic health.


Rapid mass movement of chloroplasts during segment formation of the calcifying siphonalean green alga, Halimeda macroloba.
The calcifying siphonalean green alga, Halimeda macroloba is abundant on coral reefs and is important in the production of calcium carbonate sediments. The process by which new green segments are formed over-night is revealed here for the first time. Growth of new segments was visualised by epifluorescence and confocal microscopy and by pulse amplitude modulation (PAM) fluorimetry. Apical colourless proto-segments were initiated on day 1, and formed a loose network of non-calcified, non-septate filaments, containing no chloroplasts. Rapid greening was initiated at dusk by i) the mass movement of chloroplasts into these filaments from the parent segment and ii) the growth of new filaments containing chloroplasts. Greening was usually complete in 3-5 h and certainly before dawn on day 2 when the first signs of calcification were apparent. Mass chloroplast movement took place at a rate of ∼0.65 µm/s. Photosynthetic yield and rate remained low for a period of 1 to several hours, indicating that the chloroplasts were made de novo. Use of the inhibitors colchicine and cytochalasin d indicated that the movement process is dependent on both microtubules and microfilaments. This unusual process involves the mass movement of chloroplasts at a high rate into new segments during the night and rapid calcification on the following day and may be an adaptation to minimise the impact of herbivorous activity.


Atomically Dispersed Aluminum Sites in Hexagonal Boron Nitride Nanofibers for Boosting Adsorptive Desulfurization Performance.
The exploitation of highly efficient and cost-effective selective adsorbents for adsorptive desulfurization (ADS) remains a challenge. Fortunately, single-atom adsorbents (SAAs) characterized by maximized atom utilization and atomically dispersed adsorption sites have great potential to solve this problem as an emerging class of adsorption materials. Herein, aiming at improving the efficiency of ADS performance via the economical and feasible strategy, the desirable SAAs have been fabricated by uniformly anchoring aluminum (Al) atoms on hexagonal boron nitride nanofibers (BNNF) via an in situ pyrolysis method. Remarkably, Al-BN-1.0 exhibited a superior adsorption capacity of 46.1 mg S/g adsorbent for dibenzothiophene, with a 45% increase in adsorption capacity compared to the pristine BNNF. Additionally, it demonstrated excellent adsorption of other thiophene sulfides. Moreover, the ADS mechanisms have been investigated through special adsorption experiments combined with density functional theory (DFT) calculations. It was demonstrated that the superior ADS performance and selectivity of Al-BN-1.0 originate from the sulfur-aluminum (S-Al) and π-π interactions cooperating synergistically. This work would cast light on a novel fabrication strategy for the SAAs based on the two-dimensional material with a tunable metal site configurations and densities for varied selective adsorption and separation.


[Breast cancer during pregnancy].
As women in western countries delay childbearing, it has been hypothesized that the incidence of breast cancer diagnosed during pregnancy will increase. Breast carcinoma during pregnancy(BCP) put the health of the mother in conflict with that of the fetus. The aim is to give optimal treatment to the mother to maximise the chances of survival, whilst minimising the risk of harm of the fetus. Few breast surgeons or oncologist develop expertise in this area owing the rarity of the association. We report the epidemiology, pathology, clinical picture, therapeutic management and fetal outcome of pregnant women with breast cancer treated in our institution.


Formulation, optimization, in vivo pharmacokinetic, behavioral and biochemical estimations of minocycline loaded chitosan nanoparticles for enhanced brain uptake.
The minocycline hydrochloride (MH), at higher doses, is useful in the treatment of neurodegenerative disorders and owing to its antioxidant potential, it may have nootropic effects. MH loaded nanoparticles (MHNP) were coated with tween 80 (cMHNP) to improve its brain uptake followed by their optimization employing two factor-three level (3(2)) central composite design (CCD) in order to minimize particle size and maximize drug entrapment efficiency (DEE) and validated. The optimized formulations were further subjected to in vitro drug release study; in vivo biodistribution studies in male wistar rats. The pharmacodynamic study was carried out using elevated plus maze (EPM) and Morris water maze (MWM) behavioral models for nootropic activity in swiss albino mice; and biochemical estimations (acetylcholine esterase, reduced glutathione, malondialdehyde and brain nitrite level). After intravenous (i.v.) administration, the concentration of MH in brain of cMHNP (6.21±0.64 µg/mL) treated rats was significantly higher with MH solution treated (0.70±0.06 µg/mL) as well as MHNP (1.03±0.12 µg/mL) treated animals. Pharmacodynamic studies revealed a significant improvement in memory of MH, MHNP and cMHNP treated swiss albino mice than saline treated control group. However, cMHNP revealed maximum decrease in transfer latency (TL) in EPM and maximum increase in time spent in target quadrant (TSTQ) in MWM. Although cMHNP did not produce significant change in brain acetylcholinesterase, but, significantly increased reduced glutathione, malondialdehyde and reduced brain nitrite level as compared to saline, MH solution and MHNP treated groups. The results suggest that cMHNP is a promising candidate for improved brain uptake of MH with better nootropic effect.


The importance of determining the mode of inheritance for the estimation of recurrence risks.
Recurrence risks for the generalised single locus model and for the multifactorial model have been derived and compared. First the areas of overlap for the two models were determined and sets of parameters chosen to represent these overlap areas. Certain sets of parameters for the single locus model give recurrence risks in sibships similar to these for multifactorial inheritance. Other sets (representing very low penetrant dominant genes) give markedly lower risks. Similar results hold for more complex family histories. Empiric risks for families with two or more affected individuals are needed so as to indicate the trend of the increase in risk which could then be extrapolated to other families and be used in genetic counseling.


Dexamethasone rapidly induces Kv1.5 K+ channel gene transcription and expression in clonal pituitary cells.
Glucocorticoids specifically increase Kv1.5 K+ channel mRNA in normal and clonal (GH3) rat pituitary cells. Here, we demonstrate that dexamethasone, a glucocorticoid agonist, rapidly induces Kv1.5 gene transcription, but does not affect Kv1.5 mRNA turnover (t1/2 approximately 0.5 hr) in GH3 cells. Immunoblots indicate that the steroid also increases the expression of the 76 kd Kv1.5 protein approximately 3-fold within 12 hr without altering its half-life (t1/2 approximately 4 hr). In contrast, Kv1.4 protein expression is unaffected. Finally, we find that the induction of Kv1.5 protein is associated with an increase in a noninactivating component of the voltage-gated K+ current. Our results indicate that hormones and neurotransmitters may act within hours to regulate excitability by controlling K+ channel gene expression.


Deuterohemin-Peptide Enzyme Mimic-Embedded Metal-Organic Frameworks through Biomimetic Mineralization with Efficient ATRP Catalytic Activity.
An enzyme mimic harboring iron porphyrin (DhHP-6) embedded in zeolite imidazolate framework-8 (ZIF-8) was constructed through a biomimetic mineralization approach to obtain composite DhHP-6@ZIF-8. The composite was then used as a catalyst in the atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMA500) in which poly(PEGMA500) could be synthesized with monomer conversion of 76.1% and Mn of 45 900 g/mol, stronger than that obtained when using free DhHP-6 as a catalyst. More importantly, it could efficiently overcome the drawbacks of free DhHP-6 and achieve the easy separation of DhHP-6 from the catalytic system and the elimination of iron residues in the synthesized polymer. In addition, it exhibited an enhanced recyclability with monomer conversion of 75.7% after five cycles and favorable stability during the ATRP reaction with <3.0% of DhHP-6 release within 100 h. Thus, the enzyme mimic-ZIF-8 composite developed through biomimetic mineralization can be potentially used as an effective catalyst for preparing well-defined polymers with biomedical applications.


Ethical decisions in the care of a patient terminally ill with metastatic cancer.
A case of a patient with metastatic cancer raises the issues of patient refusal of treatment, euthanasia, and unintended side effects of therapy. For each management dilemma, there are relevant ethical and legal considerations, justifications, and conclusions. In addition, psychological and social influences on the decision process tend to limit deliberation.


Studies on intracellular structures of COS cells by X-ray microscopy.
COS-7 cells, fixed with glutaraldehyde, were studied using the transmission X-ray microscope at the electron storage ring BESSY, Berlin. The border of the cell, the nucleus, nucleoli and mitochondria of the cells were clearly visualized with the X-ray microscope. In addition, we found many X-ray dense granules preferentially located around the nucleus. Electron microscopy showed that numerous multivesicular bodies, whose structures belong to the endosome-lysosomal system, were present around the nucleus. The size and localization patterns of the X-ray dense granules were quite similar to those of multivesicular bodies. These results strongly suggest that the X-ray dense granules are multivesicular bodies.


The effect of biofeedback treatment on voiding and urodynamic parameters in children with voiding dysfunction.
We studied the effects of biofeedback treatment on voiding and urodynamic parameters in children with voiding dysfunction. We prospectively studied 188 children between June 1998 and November 2003. Biofeedback was performed with a urodynamics processor that enables simultaneous recording of urine flow and electromyography, and visual display of flow/electromyography activity. At the beginning of the study this treatment was performed once weekly. After patients understood the concept and performed homework regularly sessions were scheduled at 3 to 4-week intervals and continued for 6 months. All children were evaluated at 6 months and again at 2 years after completing biofeedback training. The number of the children completing biofeedback was 168 (89.4%). Improvement was obtained in all parameters, ranging from 59.2% to 87.8% at 6 months. Maximum improvement was acquired with flattened voiding in 65 of 74 children (87.8%), whereas the least improvement was acquired with daytime wetting in 58 of 98 children (59.2%). These improvements continued at 2-year followup, and ranged from 53.1% to 87.3%. While the rate of improvement for nocturnal enuresis, staccato voiding, detrusor-sphincter dyssynergia, vesicoureteral reflux and urinary tract infection had increased, the remaining parameters had decreased at 2-year followup. Biofeedback training is a simple, effective and well tolerated treatment modality in children for various parameters resulting from bladder dysfunction. Motivation and willingness to participate in biofeedback treatment are important selection criteria.


Measurement of UV Emission from a Diffusing Optical Fiber Using Radiochromic Film.
Analysis of the emission pattern from optical diffuser tips is vital to their usage in biomedical applications, especially as they find growing functionality beyond established phototherapy techniques. The use of ultraviolet radiation with diffuser tips increases the need to accurately characterize these devices, both for effective application and to avoid potentially dangerous exposure conditions. This study presents a new method to capture the diffusion pattern at a high resolution through the use of radiochromic film. The film is positioned in a cylinder around the diffuser, light is emitted from the diffuser onto the film and the film expresses a color change relative to the exposure amount. The resulting emission map shows the distribution of power from the diffuser in all direction. This method, which is both quick and inexpensive, generates high-resolution data much simpler than previously published works which required precise goniometric positioning.


Diastereomeric Crowding Effects in the Competitive DNA Intercalation of Ru(phenanthroline)2dipyridophenazine2+ Enantiomers.
The biexponential excited-state emission decay characteristic of DNA intercalated tris-bidentate dppz-based ruthenium complexes of the general form Ru(L)2dppz2+ has previously been explained by a binding model with two distinct geometry orientations of the bound ligands, with a distinct lifetime associated with each orientation. However, it has been found that upon DNA binding of Ru(phen)2dppz2+ the fractions of short and long lifetimes are strongly dependent on environmental factors such as salt concentration and, in particular, temperature. Analyzing isothermal titration calorimetry for competitive binding of Ru(phen)2dppz2+ enantiomers to poly(dAdT)2, we find that a consistent binding model must assume that the short and long lifetimes states of intercalated complexes are in equilibrium and that this equilibrium is altered when neighboring bound ligands affect each other. The degree of intercomplex binding is found to be a subtle manifestation of several attractive and repulsive factors that are highly likely to directly reflect the strong diastereomeric difference in the binding enthalpy and entropy values. In addition, as the titration progresses and the binding sites on the DNA lattice become increasingly occupied, a general resistance for the saturation of the binding sites is observed, suggesting diastereomeric crowding of the neighboring bound ligands.


Protection of suckling mice from the heat-stable enterotoxin of Escherichia coli by human milk.
Human milk contained a factor or factors that protected suckling mice from lethal fluid loss due to Escherichia coli heat-stable toxin. This protective effect was present throughout lactation. The factor was heat stable, acid and alkali stable (pH 2 and 12), and of low molecular weight. Ion-exchange chromatography indicated that it was uncharged at neutral pH. The factor was insensitive to proteinase K digestion and partitioned in the aqueous phase in 2:1 (vol/vol) chloroform-methanol. Acid hydrolysis (2 N HCl at 100 C for 3 hr) destroyed the protective effect. Neither an amino acid mix simulating human milk nor lactose in phosphate-buffered saline was protective. These data indicate that the protective factor in human milk is neither a lipid nor a protein but appears to be a carbohydrate.


Aortic valve surgery in patients with left ventricular dysfunction.
Patient with advanced left ventricular dysfunction and heart failure symptoms, either secondary to severe aortic stenosis and a low transvalvular gradient, or chronic aortic insufficiency are sometimes referred for cardiac transplantation. Now, with improvements in both myocardial protection and better valve prostheses, aortic valve surgery for patients with even the most advanced ventricular dysfunction can be performed with low risk.


Extension of the T-bridge method for measuring the thermal conductivity of two-dimensional materials.
In this paper, the T-bridge method is extended to measure the thermal properties of two-dimensional nanomaterials. We present an analysis of the measureable positions, width, and thermal resistance of two-dimensional materials. For verification purposes, the thermal conductivity of a SiO2 nanoribbon was measured. To enhance the thermal contact between the nanoribbon and the heater in the setup, the nanoribbon was dipped into either isopropanol or water in order to promote a sticking force. Also, focused ion beam deposition was used to deposit the nanoribbon onto the contact. The thermal conductivities of all three cases were identical, showing that water dipping could be used to enhance the thermal contact. Due to the simple structure of this method and the analysis provided herein, the T-bridge method can be widely used for measuring the thermal conductivity of two-dimensional materials.


Factors Associated With Care Workers' Intention to Leave Employment in Nursing Homes: A Secondary Data Analysis of the Swiss Nursing Homes Human Resources Project.
The emerging care personnel shortage in Swiss nursing homes is aggravated by high turnover rates. As intention to leave is a predictor of turnover, awareness of its associated factors is essential. This study applied a secondary data analysis to evaluate the prevalence and variability of 3,984 nursing home care workers' intention to leave. Work environment factors and care worker outcomes were tested via multiple regression analysis. Although 56% of care workers reported intention to leave, prevalences varied widely between facilities. Overall, intention to leave showed strong inverse relationships with supportive leadership and affective organizational commitment and weaker positive relationships with stress due to workload, emotional exhaustion, and care worker health problems. The strong direct relationship of nursing home care workers' intention to leave with affective organizational commitment and perceptions of leadership quality suggest that multilevel interventions to improve these factors might reduce intention to leave.


Editorial Perspective: Speaking up for developmental language disorder - the top 10 priorities for research.
Developmental language disorder (DLD) is one of the most common neurodevelopmental conditions, yet is chronically underserved, with far fewer children receiving clinical services than expected from prevalence estimates, and very little research attention relative to other neurodevelopmental conditions of similar prevalence and severity. This editorial describes a research priority-setting exercise undertaken by the Royal College of Speech and Language Therapists, which aims to redress this imbalance. From consultations with researchers, practitioners and individuals with lived experience, 10 research priorities emerge. Our goal is to share these priorities with the wider research community, to raise awareness and encourage research collaboration to improve outcomes for young people with DLD.


Photoinduced and Palladium-Catalyzed Remote Desaturation of Amide Derivatives.
A photoinduced and palladium-catalyzed remote desaturation of O-acyl hydroxamides to unsaturated amides under mild conditions has been achieved. The formation of the alkyl Pd(II) intermediate by the recombination of alkyl radical and Pd(I) species is critical to achieve this efficient and selective desaturation of alkanes. This reaction features good site-selectivity, is terminal oxidant-free, and produces moderate to excellent yields for a variety of unsaturated amides. Remarkably, this approach enables late-stage desaturation of complex and biologically important molecules.


An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation.
Simulation games are becoming increasingly popular in education, but more insight in their critical design features is needed. This study investigated the effects of fidelity of open patient cases in adjunct to an instructional e-module on students' cognitive skills and motivation. We set up a three-group randomized post-test-only design: a control group working on an e-module; a cases group, combining the e-module with low-fidelity text-based patient cases, and a game group, combining the e-module with a high-fidelity simulation game with the same cases. Participants completed questionnaires on cognitive load and motivation. After a 4-week study period, blinded assessors rated students' cognitive emergency care skills in two mannequin-based scenarios. In total 61 students participated and were assessed; 16 control group students, 20 cases students and 25 game students. Learning time was 2 h longer for the cases and game groups than for the control group. Acquired cognitive skills did not differ between groups. The game group experienced higher intrinsic and germane cognitive load than the cases group (p = 0.03 and 0.01) and felt more engaged (p < 0.001). Students did not profit from working on open cases (in adjunct to an e-module), which nonetheless challenged them to study longer. The e-module appeared to be very effective, while the high-fidelity game, although engaging, probably distracted students and impeded learning. Medical educators designing motivating and effective skills training for novices should align case complexity and fidelity with students' proficiency level. The relation between case-fidelity, motivation and skills development is an important field for further study.


The trapezoidal cylinder phase: a new mode of self-assembly in liquid-crystalline soft matter.
A new rectangular columnar liquid crystalline phase with p2gg lattice is reported, which represents a polygonal cylinder array composed of cylinders with trapezoidal cross section. In these polygonal cylinders, one of the sides has a different length and is composed of a different material than the others. This tiling pattern was obtained in two series of T-shaped facial amphiphilic triblock molecules in which a rigid rod-like p-terphenyl core is substituted laterally by a polar and flexible oligoethylene glycol chain, terminated either by a hydrogen-bonding COOH group or by a Li carboxylate group, and having identical or different alkyl groups in the terminal positions. The trapezoidal cylinder phase provides an improved packing for relatively long and rigid alkyl chains at lower temperature and more space inside the polygonal cylinders than triangular cylinders. This combination of conformational and space-filling effects leads to different phase sequences. The trapezoidal cylinder phases pave the way to a new level of complexity in LC engineering and show the huge potential of the general concept of polyphilic tectons for the design of new complex soft matter structures.


Ask-Advise-Connect: a new approach to smoking treatment delivery in health care settings.
Several national health care-based smoking cessation initiatives have been recommended to facilitate the delivery of evidence-based treatments, such as quitline (telephone-based tobacco cessation services) assistance. The most notable examples are the 5 As (Ask, Advise, Assess, Assist, Arrange) and Ask. Advise. Refer. (AAR) programs. Unfortunately, rates of primary care referrals to quitlines are low, and most referred smokers fail to call for assistance. To evaluate a new approach--Ask-Advise-Connect (AAC)--designed to address barriers to linking smokers with treatment. A pair-matched, 2-treatment-arm, group-randomized design in 10 family practice clinics in a single metropolitan area. Five clinics were randomized to the AAC (intervention) and 5 to the AAR (control) conditions. In both conditions, clinic staff were trained to assess and record the smoking status of all patients at all visits in the electronic health record, and smokers were given brief advice to quit. In the AAC clinics, the names and telephone numbers of smokers who agreed to be connected were sent electronically to the quitline daily, and patients were called proactively by the quitline within 48 hours. In the AAR clinics, smokers were offered a quitline referral card and encouraged to call on their own. All data were collected from February 8 through December 27, 2011. Ten clinics in Houston, Texas. Smoking status assessments were completed for 42,277 patients; 2052 unique smokers were identified at AAC clinics, and 1611 smokers were identified at AAR clinics. Linking smokers with quitline-delivered treatment. Impact was based on the RE-AIM (Reach, Efficacy, Adoption, Implementation, and Maintenance) conceptual framework and defined as the proportion of all identified smokers who enrolled in treatment. In the AAC clinics, 7.8% of all identified smokers enrolled in treatment vs 0.6% in the AAR clinics (t4 = 9.19 [P < .001]; odds ratio, 11.60 [95% CI, 5.53-24.32]), a 13-fold increase in the proportion of smokers enrolling in treatment. The system changes implemented in the AAC approach could be adopted broadly by other health care systems and have tremendous potential to reduce tobacco-related morbidity and mortality.


Implication of laparoscopy and peritoneal cytology in the staging of early pancreatic cancer.
Staging of pancreatic cancer still represents a challenge for surgeons involved in this field. Diagnostic methods of radiological imaging used routinely (CT, NMR, angiography) may understage this neoplasm. In fact, the presence of peritoneal or subglissonian hepatic micrometastases (< 2 cm) is a frequent surprise at laparotomy and forces the surgeon to use a palliative procedure. Actually this policy has not to be followed because the possibility to perform non-surgical palliation of jaundice or pain respectively by percutaneous radiological stent insertion and celiac alcoholization. In this viewpoint, preoperative staging has acquired an important role for a correct treatment, be it surgical or medical. Laparoscopy allows it to overcome the understaging produced by the more common diagnostic means, with the possibility to view directly the celomatic space and the surface of the abdominal viscera; moreover, during this procedure it is possible to perform a peritoneal washing to obtain other information about the cancer stage. In our experience, 56 patients were judged as resectable by radiologic methods; 31 were excluded from surgery by laparoscopy; 10 of the remaining 25 cases were submitted to radical resection. The operative resectability rate resulted in 40%, against 18% in cases where we submitted to surgery all the patients. Seven patients underwent peritoneal washing, always with a negative result; all were submitted to surgery and radically resected. In our opinion, laparoscopy and peritoneal washing represent useful tools in the staging of patients affected by pancreatic cancer.


Next Steps Toward Eradication of Hepatitis C in the Era of Direct Acting Antivirals.
After the introduction of safe and highly effective hepatitis C virus (HCV) treatments, eradication of HCV in the next 20 years is the ultimate goal. Since 2011, the advent of first generation direct acting antivirals (DAAs) were started and followed by the introduction of a new wave of DAAs in 2013 which exhibit outstanding efficacy. It is obvious that the eradication of hepatitis C is not restricted to development of DAAs. An electronic search of available literature published was conducted in all peer-reviewed journal indexed in PubMed, Scopus and Google scholar. The literature search was done among articles related treatment of hepatitis C with DAAs in different patient groups with mass screening of the patients and cost benefit of new treatments as main key words. There are major steps that should be taken to eradicate HCV, including (1) the development of screening strategies, particularly for groups such as intravenous drug users and recipients of blood or blood products before the introduction of HCV screening in donors; (2) the development of strategies to overcome issues with the high cost of recently introduced treatments; (3) special attention to special patient groups, such as HIV/HCV co-infection, hemophilia, thalassemia, hemodialysis, and liver-transplant patients; and (4) development of preventive strategies, such as the development of an efficient HCV vaccine, special attention to harm reduction in high-risk groups, and promotion of mass awareness of HCV. The eradication of HCV will require significant governmental financial investment for screening, prevention, and treatment of infected patients. Although, we have a long way to eradication of HCV, the next steps could be including proper planning to patient finding, availability of new treatments to all patients and development of HCV prevention strategies such as vaccines.


Clinical social work in a medical setting.
This paper, using case vignette and discussion, will elaborate on two specific functions of the clinical social worker practicing in a medical setting. The first, helping patient, family and staff to acknowledge the psychological impact of physical illness; the second is helping a family to accept that there may be no organic etiology for a symptom, and that the symptom may be psychogenic in origin. Barriers to performing these functions are discussed as well as reasons why the social worker is in an ideal position to integrate medical and psychological information into a coherent and practical treatment plan.


Visual elements in direct-to-consumer advertising: Messages communicated to patients with arthritis.
Direct-to-consumer (DTC) advertising saturates popular health magazines, communicating persuasive messages to readers that may influence attitudes and behaviors. This research used a two-prong approach to investigate the visual elements used in DTC advertising and their influence on consumers' understanding of a disease and its treatment options. An analysis was conducted of DTC advertisements (N = 62) from a population sample of Arthritis Today magazine, 2000-2010. Three panels of people with arthritis were used to validate the findings and discuss implications for health literacy. Pharmaceutical companies have an opportunity to communicate tailored messages to readers of niche publications and improve disease management.