Towards a genotyping system for Streptococcus agalactiae (group B streptococcus): use of mobile genetic elements in Australasian invasive isolates.
This study forms part of the development of an integrated genotyping system for Streptococcus agalactiae (group B streptococcus, GBS) that can be used to study the population genetics of the organism and the pathogenesis and epidemiology of GBS disease. In recent previous studies, two sets of markers, the capsular polysaccharide synthesis (cps) gene cluster and surface protein antigen genes, have been used to assign molecular serotypes (MS) and protein-gene profiles (PGP) to more than 200 isolates. In the present study, five mobile genetic elements (MGE) have been used as a third set of markers, to characterize further 194 invasive isolates, recovered from blood or cerebrospinal fluid (CSF). Of these, 97 % contained one or more of the five MGE, the distribution of which was related to MS and PGP, as illustrated by MS III, which is divisible into four serosubtypes with different combinations of the MGE (or none). Fifty-six different genotypes and eight genetic clusters were identified, each with different combinations of the three sets of molecular markers. Five predominant genotypes (Ia-1, Ib-1, III-1, III-2 and V-1) contained 62 % of the isolates and five of the eight genetic clusters contained 92 % of the isolates. The 17 CSF isolates were relatively widely distributed between 10 genotypes and across seven of the eight clusters. Further study is needed to determine whether these genotypes or clusters share common markers of increased virulence. In future, comparison of invasive with colonizing strains of GBS may elucidate the significance of these findings.


Impact of urban atmospheric environment on hospital admissions in the elderly.
To analyze the impact of intra-urban atmospheric conditions on circulatory and respiratory diseases in elder adults. Cross-sectional study based on data from 33,212 hospital admissions in adults over 60 years in the city of São Paulo, southeastern Brazil, from 2003 to 2007. The association between atmospheric variables from Congonhas airport and bioclimatic index, Physiological Equivalent Temperature, was analyzed according to the district's socioenvironmental profile. Descriptive statistical analysis and regression models were used. There was an increase in hospital admissions due to circulatory diseases as average and lowest temperatures decreased. The likelihood of being admitted to the hospital increased by 12% with 1ºC decrease in the bioclimatic index and with 1ºC increase in the highest temperatures in the group with lower socioenvironmental conditions. The risk of admission due to respiratory diseases increased with inadequate air quality in districts with higher socioenvironmental conditions. The associations between morbidity and climate variables and the comfort index varied in different groups and diseases. Lower and higher temperatures increased the risk of hospital admission in the elderly. Districts with lower socioenvironmental conditions showed greater adverse health impacts.


Psychometric properties of the state-trait inventory for cognitive and somatic anxiety (STICSA) in friendship dyads.
Recently, Gros, Antony, Simms, and McCabe (2007) demonstrated support for the psychometric properties of a new measure of state and trait anxiety, the State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA). In the present study, we further investigated the STICSA-Trait Version in 127 friendship dyads with a self-report from one participant (target) and an other-report of the target from a friend (informant). Consistent with previous research, confirmatory factor analyses supported the 2-factor structure of the STICSA-Trait in the target and informant reports. Moreover, the STICSA-Trait Cognitive and Somatic Anxiety subscales showed acceptable convergent and discriminant validity with related measures of anxiety. In addition, the STICSA-Trait subscales demonstrated adequate internal consistency and self-other agreement across the target and informant reports. Together, these findings provide additional support for the STICSA-Trait subscales as reliable and valid measures of cognitive and somatic anxiety.


Functional characteristics of children diagnosed with Childhood Apraxia of Speech.
The purpose of this study was to describe the complex array of functional problems in children diagnosed by their treating speech/language pathologist with Childhood Apraxia of Speech (CAS), a poorly understood, severe speech sound disorder. We asked parents (n = 201) attending the first national parent conference on CAS to voluntarily complete a survey, which evaluated 43 functional domains from the International Classification of Functioning, Disability, and Health-Children and Youth version (ICF-CY). The survey also included questions about co-existing medical, developmental, and mental health conditions and about service utilization. Data were analyzed using descriptive statistics and exploratory factor analysis. The most prevalent functional problems in addition to communication were attention (focus), vestibular function, temperament, fine hand use, maintaining attention, and learning to write. Four orthogonal factors accounted for 23% of the variance in functional problems: Cognitive and Learning Problems, Social Communication Difficulties, Behavioral Dysregulation, and Other Oral Motor Problems. Over half the sample had health, mental health, and developmental conditions. Almost all of the children used early intervention and speech/language therapy services. The ICF-CY provided a systematic approach for describing and categorizing functional problems in children with CAS. The identified factors should guide the multidisciplinary team in conducting comprehensive evaluations, rehabilitation, and long-term follow-up of children with CAS.


Monoclonal antibodies.
Monoclonal antibodies are essential tools for many molecular immunology investigations. In particular, when used in combination with techniques such as epitope mapping and molecular modelling, monoclonal antibodies enable the antigenic profiling and visualisation of macromolecular surfaces. In addition, monoclonal antibodies have become key components in a vast array of clinical laboratory diagnostic tests. Their wide application in detecting and identifying serum analytes, cell markers, and pathogenic agents has largely arisen through the exquisite specificity of these unique reagents. Furthermore, the continuous culture of hybridoma cells that produce these antibodies offers the potential of an unlimited supply of reagent. In essence, when compared with the rather limited supply of polyclonal antibody reagents, the feature of a continuous supply enables the standardisation of both the reagent and the assay technique. Clearly, polyclonal and monoclonal antibodies have their advantages and disadvantages in terms of generation, cost, and overall applications. Ultimately, monoclonal antibodies are only produced when necessary because their production is time consuming and frustrating, although greatly rewarding (at least most of the time!). This is especially apparent when a monoclonal antibody can be applied successfully in a routine pathology laboratory or can aid in the clinical diagnosis and treatment of patients. In this article, the generation and application of monoclonal antibodies are demystified to enable greater understanding and hopefully formulate novel ideas for clinicians and scientists alike.


REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial.
The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients. To outline the statistical analysis plan for the REVISE trial. REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated. The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment. This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide. www. gov NCT03374800. November 21, 2017.


Water Holding as Determinant for the Elastically Stored Energy in Protein-Based Gels.
To evaluate the importance of the water holding capacity for the elastically stored energy of protein gels, a range of gels were created from proteins from different origin (plant: pea and soy proteins, and animal: whey, blood plasma, egg white proteins, and ovalbumin) varying in network morphology set by the protein concentration, pH, ionic strength, or the presence of specific ions. The results showed that the observed positive and linear relation between water holding (WH) and elastically stored energy (RE) is generic for globular protein gels studied. The slopes of this relation are comparable for all globular protein gels (except for soy protein gels) whereas the intercept is close to 0 for most of the systems except for ovalbumin and egg white gels. The slope and intercept obtained allows one to predict the impact of tuning WH, by gel morphology or network stiffness, on the mechanical deformation of the protein-based gel. Addition of charged polysaccharides to a protein system leads to a deviation from the linear relation between WH and RE and this deviation coincides with a change in phase behavior.


Resection enterostomy versus Hartmann's procedure for emergency colonic resections.
If a primary anastomosis is considered too risky after emergency colon resection either a resection enterostomy or an end stoma with closure of the distal bowel (Hartmann's procedure) is possible. This study analyzes the rate of restoration of intestinal continuity and other surgical outcomes after resection enterostomy placement versus Hartmann's procedure for emergency colon resections. All patients who underwent emergency colorectal resections between August 2009 and June 2014 at the University Medical Center Mannheim were reviewed in regard to therapeutic approach, rate of restoration of bowel continuity, and surgical morbidity after the primary operation and after reversal surgery. Fifty-five patients in whom both studied interventions would have been technically feasible were further analyzed. The rate of revisional surgery was significantly higher in the resection enterostomy cohort after the primary operation. There were no significant differences regarding morbidity, mortality, and the rate of restoration of intestinal continuity. Overall, bowel continuity could be restored in 63% (29/46) of the surviving patients. The median time of surgery of the initial as well as of the reversal surgery was significantly longer in the Hartmann's group. Five of 13 patients underwent protective ileostomy placement in the Hartmann's group at the time of the reversal (vs. none in the resection enterostomy group). The bowel continuity can be restored in the majority of patients after emergency colonic resection. Conclusive evidence which surgical option should be preferred when a primary anastomosis is considered too risky-Hartmann's procedure or resection enterostomy-is still lacking.


A Medipix quantum area detector allows rotation electron diffraction data collection from submicrometre three-dimensional protein crystals.
When protein crystals are submicrometre-sized, X-ray radiation damage precludes conventional diffraction data collection. For crystals that are of the order of 100 nm in size, at best only single-shot diffraction patterns can be collected and rotation data collection has not been possible, irrespective of the diffraction technique used. Here, it is shown that at a very low electron dose (at most 0.1 e(-) Å(-2)), a Medipix2 quantum area detector is sufficiently sensitive to allow the collection of a 30-frame rotation series of 200 keV electron-diffraction data from a single ∼100 nm thick protein crystal. A highly parallel 200 keV electron beam (λ = 0.025 Å) allowed observation of the curvature of the Ewald sphere at low resolution, indicating a combined mosaic spread/beam divergence of at most 0.4°. This result shows that volumes of crystal with low mosaicity can be pinpointed in electron diffraction. It is also shown that strategies and data-analysis software (MOSFLM and SCALA) from X-ray protein crystallography can be used in principle for analysing electron-diffraction data from three-dimensional nanocrystals of proteins.


Influence of bioassay volume, water column height, and octanol-water partition coefficient on the toxicity of pesticides to rainbow trout.
Effects of water volume and water column height on toxicity of cypermethrin, carbaryl, dichlorvos, tetradifon, maneb, captan, carbosulfan endosulfan and HgCl₂ to juvenile rainbow trout (Oncorhynchus mykiss, 3.2 ± 0.7 g) were evaluated in different glass aquaria under static conditions. When fish were exposed to the chemical compounds in 23 cm water column height (25 L), their mortality ranged between 0% and 58%. At the same water volume, but lower water column height (9 cm), mortality of fish increased significantly and was in a range from 60% to 95%. At the same water column height, toxic effects of chemicals were significantly higher in 25 L water volume than that of 8.5 L, water except maneb which has lowest (-0.45) octanol-water partition coefficient value. Mortality rates ratio of 9 and 23 cm water column height ranged between 1.12 and 90 while mortality rates ratio of 9 and 25 L water volume ranged between 1.20 and 4.0. Because actual exposure concentrations were not affected by either water volume or water column height, we propose that increased pesticides' toxicity was related to an increase in bioassay volume, since more pesticide molecules were able to interact with or accumulate the fish. However, there seem to be no relationship between the effects of water volume, water column height and Kow value of chemicals with regard to toxicity in juvenile rainbow trout.


Trends in group inequalities and interindividual inequalities in BMI in the United States, 1993-2012.
Marked increases in mean body mass index (BMI) and prevalence of obesity and overweight in the United States are well known. However, whether these average increases were accompanied by changing dispersion (or SD) remains understudied. We investigated population-level changes in the BMI distribution over time to understand how changes in dispersion reflect between-group compared with within-group inequalities in weight gain in the United States. Using data from the Behavioral Risk Factor Surveillance System survey (1993-2012), we analyzed associations between mean, SD, and median BMI and BMI at the 5th and 95th percentiles for 3,050,992 non-Hispanic white, non-Hispanic black, and Hispanic men and women aged 25-64 y. Overall, an increase of 1.0 in mean BMI (in kg/m²) was associated with an increase of 0.70 (95% CI: 0.67, 0.73) in the SD of BMI. A change of 1.0 in median BMI was associated with a change of 0.18 (95% CI: 0.14, 0.21) in the BMI value at the 5th percentile compared with a change of 2.94 (95% CI: 2.81, 3.07) at the 95th percentile. Quantile-quantile plots showed unequal changes in the BMI distribution, with pronounced changes at higher percentiles. Similar patterns were observed in subgroups stratified by sex, race-ethnicity, and education with non-Hispanic black women and women with less than a high school education having highest mean BMI, SD of BMI, and BMI values at the 5th and 95th percentiles. Mean BMI and the percentage of overweight and obese individuals do not fully describe population changes in BMI. Increases in within-group inequality in BMI represent an underrecognized characteristic of population-level weight gain. Crucially, similar increases in dispersion within groups suggest that growing inequalities in BMI at the population level are not driven by these socioeconomic and demographic factors. Future research should focus on understanding factors driving inequalities in weight gain between individuals.


Probe alignment and design issues of microelectromechanical system based optical coherence tomography endoscopic imaging.
Endoscopic optical coherence tomography (OCT) imaging has been demonstrated using microelectromechanical system (MEMS) technology by several research groups. The focus of this work is to study how the OCT imaging performance is affected by the radius of curvature of MEMS mirrors as well as the optical alignment accuracy inside small imaging probes. The goal of this study is to provide guidance for assembly tolerance and design optimization of OCT endoscopic probes. Gaussian beam propagation is used for theoretical analysis which is confirmed by optical simulation and verified experimentally with a time-domain OCT system as well. It has been found that the OCT imaging is very sensitive to the distance from the fiber end to the gradient-index (GRIN) lens, which needs to be controlled within 0.1 mm to achieve working distance (WD) longer than 3.5 mm and lateral resolution around 25 μm. The impact on image quality of the MEMS mirror is negligible if the radius of curvature of the mirror surface is greater than 200 mm. In addition, we studied the astigmatism introduced by cylindrical plastic tubing; the maximum astigmatism ratio is 1.1 when the WD is around 2.5 mm.


Protein phosphatase 2A regulatory subunit B55α functions in mouse oocyte maturation and early embryonic development.
Protein phosphatase 2A regulatory subunit B55α (PP2A-B55α) has been studied in mitosis. However, its functions in mammalian meiosis and early embryonic development remain unknown. Here, we report that PP2A-B55α is critical for mouse oocyte meiosis and preimplantation embryo development. Knockdown of PP2A-B55α in oocytes led to abnormal asymmetric division, disordered spindle dynamics, defects in chromosome congression, an increase in aneuploidy, and induction of the DNA damage response. Moreover, knockdown of PP2A-B55α in fertilized mouse zygotes impaired development to the blastocyst stage. The impairment of embryonic development might have been due to induction of sustained DNA damage in embryos, which caused apoptosis and inhibited cell proliferation and outgrowth potential at the blastocyst stage. Overall, these results provide a novel insight into the role of PP2A-B55α as a novel meiotic and embryonic competence factor at the onset of life.


Visualizing and Quantifying Wettability Alteration by Silica Nanofluids.
An aqueous suspension of silica nanoparticles or nanofluid can alter the wettability of surfaces, specifically by making them hydrophilic and oil-repellent under water. Wettability alteration by nanofluids has important technological applications, including for enhanced oil recovery and heat transfer processes. A common way to characterize the wettability alteration is by measuring the contact angles of an oil droplet with and without nanoparticles. While easy to perform, contact angle measurements do not fully capture the wettability changes to the surface. Here, we employed several complementary techniques, such as cryo-scanning electron microscopy, confocal fluorescence and reflection interference contrast microscopy, and droplet probe atomic force microscopy (AFM), to visualize and quantify the wettability alterations by fumed silica nanoparticles. We found that nanoparticles adsorbed onto glass surfaces to form a porous layer with hierarchical micro- and nanostructures. The porous layer can trap a thin water film, which reduces contact between the oil droplet and the solid substrate. As a result, even a small addition of nanoparticles (0.1 wt %) lowers the adhesion force for a 20 μm sized oil droplet by more than 400 times from 210 ± 10 to 0.5 ± 0.3 nN as measured by using droplet probe AFM. Finally, we show that silica nanofluids can improve oil recovery rates by 8% in a micromodel with glass channels that resemble a physical rock network.


A review on antidiabetic activity of Citrullus colocynthis Schrad.
Current studies have elaborated diabetes mellitus as one of the most prevalent endocrine disorder throughout the world. Citrullus colocynthis (C. colocynthis) is one of the most common traditional plants used as remedy against diabetes mellitus. It is well recognized by its hypoglycemic effect, which is substantiated in current phytotherapy. Its undesired effects include the disturbance of gastrointestinal and urinary tracts. This review article encompasses various blood glucose lowering studies that have been carried out till date. Various parts of plants used in extract preparation were roots, fruits, seeds, rinds and leaves. The nature of these extracts was ethnolic, methanolic, or aqueous and their doses varied from 10 to 500 mg/kg body weight/day. All these published articles elaborate C. colocynthis as a potential antiglycemic medicinal plant.


Light transport in tissue.
The propagation of light in tissue may be calculated by exact transport theory, or the approximate diffusion theory, provided the optical properties are known at the source wavelength. Optical properties for the exact methods are the absorption coefficient, scattering coefficient, and angular distribution of scattering. Appropriate properties for diffusion theory are the diffusion length and diffusion coefficient (corrected for anisotropic scattering). Computer programs and analytical solutions (for some simple geometries) exist, but the optical properties have to be determined experimentally and are not well defined as yet. The radiant energy fluence rate and the diffuse transmittance and reflectance have been measured in several tissues and in a few geometries, but there are gaps in the data as a function of wavelength. Calculations and measurements reveal that very large errors can result if the optical properties (for example, the diffusion length) are inaccurate, if anisotropic scattering is neglected, or if the finite size of the irradiating light beam is not taken into account. Furthermore, the radiant energy fluence and transmittance are perturbed by local regions of lesser or greater absorption, although recovery of the fluence and transmittance occurs beyond some three diffusion lengths.


Training intervention for health care staff in the provision of existential support to patients with cancer: a randomized, controlled study.
When a patient receives a cancer diagnosis, existential issues become more compelling. Throughout the illness trajectory, patients with cancer are cared for in oncology wards, by home care teams or in hospices. Nurses working with these patients are sometimes aware of the patients' existential needs but do not feel confident when discussing these issues. To determine the effects of a training intervention, where the focus is on existential issues and nurses' perceived confidence in communication and their attitude toward caring for dying patients. This was a randomized, controlled trial with a training intervention comprising theoretical training in existential issues combined with individual and group reflection. In total, 102 nurses in oncology and hospice wards and in palliative home care teams were randomized to a training or non-training group. Primary outcomes, confidence in communication, and attitude toward the care of dying patients were measured at baseline, immediately after the training, and five to six months later. Confidence in communication improved significantly in the training group from baseline (before the training) to both the first and second follow-up, that is, immediately after the training and five months later. The attitude toward caring for the dying did not improve in the training group. This study shows that short-term training with reflection improves the confidence of health care staff when communicating, which is important for health care managers with limited resources. Further studies are needed to explore how patients experience the communication skills of health care staff after such training.


The role of collective efficacy in exercise adherence: a qualitative study of spousal support and type 2 diabetes management.
Adhering to increased exercise is often reported as one of the greatest challenges facing adults living with diabetes, a perception shared by the married middle-aged and older adults living with diabetes who participated in this study. Understanding how that challenge can best be met is both research and program relevant. Drawing on the social cognitive theory and social support literature, this qualitative study explored the powerful couple relationship in Type 2 diabetes management. The overarching goal of this paper was to illuminate the potentially key role of collective efficacy in exercise adherence in order to develop and test interventions that provide more effective supports for adults living with diabetes. Analyses revealed three core themes used by the couples to describe their perceived beliefs: 'Collective support', 'Collective motivation' and 'Collective responsibility'. Our findings provide insights regarding how collective beliefs of spousal support may influence the adoption and maintenance of an exercise program. As health educators look for approaches to improve exercise adherence in diabetes management, it is important to understand how couples can be empowered to assume responsibility for their management.


Time to ACT: launching an Addiction Care Team (ACT) in an urban safety-net health system.
Across the USA, morbidity and mortality from substance use are rising as reflected by increases in acute care hospitalisations for substance use complications and substance-related deaths. Patients with substance use disorders (SUD) have long and costly hospitalisations and higher readmission rates compared to those without SUD. Hospitalisation presents an opportunity to diagnose and treat individuals with SUD and connect them to ongoing care. However, SUD care often remains unaddressed by hospital providers due to lack of a systems approach and addiction medicine knowledge, and is compounded by stigma. We present a blueprint to launching an interprofessional inpatient addiction care team embedded in the hospital medicine division of an urban, safety-net integrated health system. We describe key factors for successful implementation including: (1) demonstrating the scope and impact of SUD in our health system via a needs assessment; (2) aligning improvement areas with health system leadership priorities; (3) involving executive leadership to create goal and initiative alignment; and (4) obtaining seed funding for a pilot programme from our Medicaid health plan partner. We also present challenges and lessons learnt.


Multiobjective Design Optimization of a Biconcave Mobile-Bearing Lumbar Total Artificial Disk Considering Spinal Kinematics, Facet Joint Loading, and Metal-on-Polyethylene Contact Mechanics.
Total disk arthroplasty (TDA) using an artificial disk (AD) is an attractive surgical technique for the treatment of spinal disorders, since it can maintain or restore spinal motion (unlike interbody fusion). However, adverse surgical outcomes of contemporary lumbar TDAs have been reported. We previously proposed a new mobile-bearing AD design concept featuring a biconcave ultrahigh-molecular-weight polyethylene (UHMWPE) mobile core. The objective of this study was to develop an artificial neural network (NN) based multiobjective optimization framework to refine the biconcave-core AD design considering multiple TDA performance metrics, simultaneously. We hypothesized that there is a tradeoff relationship between the performance metrics in terms of range of motion (ROM), facet joint force (FJF), and polyethylene contact pressure (PCP). By searching the resulting three-dimensional (3D) Pareto frontier after multiobjective optimization, it was found that there was a "best-tradeoff" AD design, which could balance all the three metrics, without excessively sacrificing each metric. However, for each single-objective optimum AD design, only one metric was optimal, and distinct sacrifices were observed in the other two metrics. For a commercially available biconvex-core AD design, the metrics were even worse than the poorest outcomes of the single-objective optimum AD designs. Therefore, multiobjective design optimization could be useful for achieving native lumbar segment biomechanics and minimal PCPs, as well as for improving the existing lumbar motion-preserving surgical treatments.


Ammonium transport and pH regulation by K(+)-Cl(-) cotransporters.
The Na(+)-K(+)-Cl(-) cotransporters (NKCCs), which belong to the cation-Cl(-) cotransporter (CCC) family, are able to translocate NH4(+) across cell membranes. In this study, we have used the oocyte expression system to determine whether the K(+)-Cl(-) cotransporters (KCCs) can also transport NH4(+) and whether they play a role in pH regulation. Our results demonstrate that all of the CCCs examined (NKCC1, NKCC2, KCC1, KCC3, and KCC4) can promote NH4(+) translocation, presumably through binding of the ion at the K(+) site. Moreover, kinetic studies for both NKCCs and KCCs suggest that NH4(+) is an excellent surrogate of Rb(+) or K(+) and that NH4(+) transport and cellular acidification resulting from CCC activity are relevant physiologically. In this study, we have also found that CCCs are strongly and differentially affected by changes in intracellular pH (independently of intracellular [NH4(+)]). Indeed, NKCC2, KCC1, KCC2, and KCC3 are inhibited at intracellular pH <7.5, whereas KCC4 is activated. These results indicate that certain CCC isoforms may be specialized to operate in acidic environments. CCC-mediated NH4(+) transport could bear great physiological implication given the ubiquitous distribution of these carriers.


Predictors of vaginal bleeding during the first two trimesters of pregnancy.
This study evaluates maternal age, race, cigarette smoking, prior spontaneous abortion, prior induced abortion, and prior preterm birth in relation to vaginal bleeding during the first two trimesters of pregnancy. Information on vaginal bleeding and predictors came from the Pregnancy, Infection, and Nutrition Study, which enrolled 2806 pregnant women at 24-29 weeks' gestation during 1995-2000 in central North Carolina, USA. Generalised estimating equations were applied to take into account repeated episodes of vaginal bleeding during pregnancy. Women with advanced maternal age and passive smoking exposure were more likely to experience more intense vaginal bleeding during pregnancy, as were women with prior preterm birth. More intense bleeding was also more likely to be reported among women with multiple prior spontaneous abortions or multiple prior induced abortions, but not among women with a single prior spontaneous or induced abortion. The combination of prior spontaneous and induced abortion showed a dose-response association with the occurrence of vaginal bleeding during pregnancy.


Trends in consultant clinical activity and the effect of the 2003 contract change: retrospective analysis of secondary data.
To explore trends in the clinical activity of hospital specialists in English National Health Service (NHS) hospitals, and test the effect of contract reform. Retrospective secondary analysis of hospital episode statistics, describing trends and testing for a contract effect using multilevel interrupted time series analysis. Ten surgical and medical specialties in English NHS hospitals from 1999 to 2009. Participants Hospital consultants on full time or maximum part-time English NHS hospitals. A new contract offered to NHS consultants in October 2003, with higher pay alongside job planning and appraisal. Inpatient finished consultant episodes (FCEs) per consultant per month, with and without accounting for case-mix differences. In most specialties there was a statistically significant downward trend in FCEs per consultant per month. On average in the surgical specialties, FCEs reduced by 0.14 per month (95% CI -0.16 to -0.11) and in medicine there was a smaller reduction of 0.08 FCEs per month (95% CI -0.1 to -0.06). NHS patients symptoms have increased in severity over time, and the downward trend is reduced after case-mix-adjustment, and reversed in general and geriatric medicine. The effect of the contract on clinical activity was minimal. In five specialties there was no statistically significant effect, but in five specialties there was a statistically significant negative effect. Consultant clinical activity, as measured by FCEs per month, has shown a general downward trend from 1999 to 2009. The consultant contract was not associated with an increase in consultant clinical activity rates.


Prednisolone for repeated implantation failure associated with high natural killer cell levels.
Women with unexplained repeated IVF failure present a considerable challenge. Some cases are believed to be due to immunological dysfunction preventing effective embryo implantation. As data are still being collected, doctors are faced with the dilemma of treating patients (or not) in the absence of randomised control trial evidence. This review explores a pragmatic approach in using natural killer cell analysis as a means of targeting suitable patients who might attempt treatment with additional immunosuppressive therapy.


Reverse shoulder arthroplasty: State-of-the-art.
The reverse shoulder arthroplasty conceived by Paul Grammont in 1985 has gradually gained popularity as a treatment for multiple shoulder diseases. Unlike previous reverse shoulder prosthesis characterized by unsatisfactory results and a high glenoid implant failure rate, the Grammont design has immediately shown good clinical outcomes. This semi constrained prosthesis solved the issues of the very first designs by medializing and distalizing the center of rotation with an increased stability of the replacement of the component. The indication was initially limited to cuff tear arthropathy (CTA). It has then been expanded to irreparable massive cuff tears and displaced humeral head fractures. The most frequent problems of this design are a limited postoperative external rotation and scapular notching. Different modifications to the original Grammont design have been proposed with the aim of decreasing the risk of failure and complications and improving the clinical outcomes. Both the position and version/inclination of the glenosphere and the humeral configuration (e.g. neck shaft angle) influence the RSA outcomes. A lateralized glenoid (whether with bone or metal) and a 135° Inlay system configuration leads to a moment arm which is the closest to the native shoulder. Clinical research will focus on implant designs reducing bone adaptations and revision rate, strategies to prevent more effectively infections. Furthermore, there is still room for improvement in terms of better postoperative internal and external rotations and clinical outcomes after RSA implanted for humeral fracture and revision shoulder arthroplasty.


Fish oil supplementation in early infancy modulates developing infant immune responses.
Maternal fish oil supplementation during pregnancy has been associated with altered infant immune responses and a reduced risk of infant sensitization and eczema. To examine the effect of early postnatal fish oil supplementation on infant cellular immune function at 6 months of age in the context of allergic disease. In a double-blind randomized controlled trial (ACTRN12606000281594), 420 infants of high atopic risk received fish oil [containing 280 mg docosahexaenoic acid (DHA) and 110 mg eicosapentanoic acid (EPA)] or control oil daily from birth to 6 months. One hundred and twenty infants had blood collected at 6 months of age. Fatty acid levels, induced cytokine responses, T cell subsets and monocyte HLA-DR expression were assessed at 6 months of age. Infant allergies were assessed at 6 and 12 months of age. DHA and EPA levels were significantly higher in the fish oil group and erythrocyte arachidonic acid (AA) levels were lower (all P < 0.05). Infants in the fish oil group had significantly lower IL-13 responses (P = 0.036) to house dust mite (HDM) and higher IFNγ (P = 0.035) and TNF (P = 0.017) responses to phytohaemaglutinin (PHA). Infants with relatively high DHA levels had lower Th2 responses to allergens including lower IL-13 to β-lactoglobulin (BLG) (P = 0.020), and lower IL-5 to BLG (P = 0.045). Postnatal fish oil supplementation increased infant n-3 polyunsaturated fatty acid (PUFA) levels and associated with lowered allergen-specific Th2 responses and elevated polyclonal Th1 responses. Our results add to existing evidence of n-3 PUFA having immunomodulatory properties that are potentially allergy-protective.


Hazard analysis and critical control points of weaning foods.
Hazards and critical control points were identified during the preparation, feeding and storage of weaning foods fed to the children (6-24 months) belonging to low income group (LIG) families using survey methods, spot and indepth observations and microbial analysis. High microbial counts were obtained for the weaning food samples procured from the families that were rated as poor for both personal hygiene and environmental sanitation. Food samples that were held at ambient temperature (25-35 degrees C) showed high counts of coliforms, AMCC, yeast and mold, Staphylococcus aureus and Bacillus cereus. Spice mixtures and mop samples also revealed high counts for all these organisms. Coliforms were not isolated from the water samples of all the 10 households. However, a high count of Bacillus cereus (10(3-5)/ml) was observed in water samples of two selected households. The hazards and critical control points identified were high initial contamination of raw foods, poor environmental sanitation and personal hygiene, feeding of overnight moist foods stored at ambient temperature and insufficient steaming of these foods.


Canine spontaneous glioma: a translational model system for convection-enhanced delivery.
Canine spontaneous intracranial tumors bear striking similarities to their human tumor counterparts and have the potential to provide a large animal model system for more realistic validation of novel therapies typically developed in small rodent models. We used spontaneously occurring canine gliomas to investigate the use of convection-enhanced delivery (CED) of liposomal nanoparticles, containing topoisomerase inhibitor CPT-11. To facilitate visualization of intratumoral infusions by real-time magnetic resonance imaging (MRI), we included identically formulated liposomes loaded with Gadoteridol. Real-time MRI defined distribution of infusate within both tumor and normal brain tissues. The most important limiting factor for volume of distribution within tumor tissue was the leakage of infusate into ventricular or subarachnoid spaces. Decreased tumor volume, tumor necrosis, and modulation of tumor phenotype correlated with volume of distribution of infusate (Vd), infusion location, and leakage as determined by real-time MRI and histopathology. This study demonstrates the potential for canine spontaneous gliomas as a model system for the validation and development of novel therapeutic strategies for human brain tumors. Data obtained from infusions monitored in real time in a large, spontaneous tumor may provide information, allowing more accurate prediction and optimization of infusion parameters. Variability in Vd between tumors strongly suggests that real-time imaging should be an essential component of CED therapeutic trials to allow minimization of inappropriate infusions and accurate assessment of clinical outcomes.


Sensitivity and versatility of an adaptive system for controlling cyclic movements using functional neuromuscular stimulation.
This study evaluated an adaptive control system (the PG/PS control system [2]) that had been designed for generating cyclic movements using functional neuromuscular stimulation (FNS). Extensive simulations using computer-based models indicated that a broad range of control system parameter values performed well across a diverse population of model systems. The fact that manual tuning is not required for each individual makes this control system particularly attractive for implementation in FNS systems outside of research laboratories.


Dolutegravir-induced growth and lifespan effects in Caenorhabditis elegans.
Integrase strand transfer inhibitor (INSTIs)-based combination antiretroviral treatment in people living with HIV (PLWH) has been reportedly correlated with several adverse effects, such as weight gain, fetal defects or psychiatric disorders. To comprehensively understand the adverse effect of INSTIs, our study utilized Caenorhabditis Elegans (C. elegans) as a model to investigate how dolutegravir (DTG) affected its life cycle, growth, reproduction and lifespan. Our results indicated that DTG enhanced body growth at the early stage of treatment, but no change was detected for long-term treatment. The treatment also influenced the reproductive system, decreased egg-hatching but had no effect on egg-laying. Besides, DTG resulted in lifespan reduction, which is dependent on increased levels of reactive oxidative species (ROS) accumulation. Treatment with N-acetyl-cysteine (NAC) in worms restrained intracellular ROS accumulation and improved DTG-induced lifespan reduction. Our study demonstrates for the first time the effect of DTG treatment on life cycle. DTG-induced adverse effects are potentially associated with intracellular ROS accumulation. Quenching ROS accumulation might provide a novel strategy for dealing with the adverse effects of INSTIs.


Canceling Crosstalk Sound in Bone Conduction Hearing: An Accelerometer-Based Approach.
Bone conduction hearing aids offer a unique solution for people with conductive hearing loss, providing a direct transmission of sound to the cochlea. However, a common issue called "crosstalk" can occur, where sound intended for one ear is received by the opposite ear via bone conduction, affecting the ability to localize sound sources and understand speech in noise. To address this issue, we investigated whether canceling "crosstalk" at an accelerometer located on the mastoid would create a "quiet zone" that reaches the cochlea in the inner ear. Our evaluation with individuals having normal hearing abilities showed that their hearing thresholds were improved with crosstalk cancellation than without. These results indicate that although designed to cancel "crosstalk" at the mastoid, the cancellation still reached the cochlea, making it perceptible and potentially beneficial for those with conductive hearing loss.


Regulation of longevity and stress resistance by Sch9 in yeast.
The protein kinase Akt/protein kinase B (PKB) is implicated in insulin signaling in mammals and functions in a pathway that regulates longevity and stress resistance in Caenorhabditis elegans. We screened for long-lived mutants in nondividing yeast Saccharomyces cerevisiae and identified mutations in adenylate cyclase and SCH9, which is homologous to Akt/PKB, that increase resistance to oxidants and extend life-span by up to threefold. Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 were required for this life-span extension. These results indicate that longevity is associated with increased investment in maintenance and show that highly conserved genes play similar roles in life-span regulation in S. cerevisiae and higher eukaryotes.


Characteristics of sports participation and psychosocial health in children: Results of a cross-sectional study.
Several studies suggest that sports participation is beneficial for psychosocial health. There is, however, only a limited number of studies about the relationship of specific characteristics of sports participation with psychosocial health. The present study investigated associations between characteristics of sports participation and three aspects of psychosocial health, i.e. internalising problems, externalising problems and prosocial behaviour. The examined characteristics of sports participation pertained to individual versus team sports, indoor versus outdoor sports, involvement in competition or not, and contact sports versus non-contact sports. Cross-sectional data were collected from 1768 Dutch children aged 10-12 years who were member of a sports club. These children completed the Movement and Sports Monitor Questionnaire Youth aged 8-12 years (MSMQ) and the Strength and Difficulties Questionnaire (SDQ). Linear multilevel analyses and logistic generalised estimating equation were conducted. Children participating in team sports, outdoor sports, or competition showed fewer internalising problems than children engaged in individual sports, indoor sports, or only training. The associations with internalising problems were stronger for boys than for girls. Children participating in non-contact sports showed fewer externalising problems than children performing non-contact sports as well as contact sports. Children practising indoor sports or non-contact sports showed better prosocial behaviour than children doing outdoor or contact sports. In conclusion, the form of sports participation seemed to matter highly with respect to internalising problems, especially for boys, and, to a lesser extent, with respect to externalising problems and prosocial behaviour. This offers starting points for developing tailor-made sports programmes for children.


Rate of infant carrying impacts infant spontaneous motor tempo.
Rhythm production is a critical component of human interaction, not least forming the basis of our musicality. Infants demonstrate a spontaneous motor tempo (SMT), or natural rate of rhythmic movement. Here, we ask whether infant SMT is influenced by the rate of locomotion infants experience when being carried. Ten-month-old, non-walking infants were tested using a free drumming procedure before and after 10 min of being carried by an experimenter walking at a slower (98 BPM) or faster (138 BPM) than average tempo. We find that infant SMT is differentially impacted by carrying experience dependent on the tempo at which they were carried: infants in the slow-walked group exhibited a slower SMT from pre-test to post-test, while infants in the fast-walked group showed a faster SMT from pre-test to post-test. Heart rate data suggest that this effect is not due to a general change in the state of arousal. We argue that being carried during caregiver locomotion is a predominant experience for infants throughout the first years of life, and as a source of regular, vestibular, information, may at least partially form the basis of their sense of rhythm.


Reducing workers' compensation costs.
Employers can reduce their workers' compensation costs by encouraging internal communication and education before and after injuries occur. Comprehensive workers' compensation programs can be developed by integrating the management of employee benefits and workers' compensation claims.


Meta-analysis of randomised trials comparing thiopurines in childhood acute lymphoblastic leukaemia.
Mercaptopurine has been used in continuing treatment of childhood acute lymphoblastic leukaemia since the mid 1950s. Recent advances in the understanding of thiopurine pharmacology indicated that thioguanine (TG) might be more effective than mercaptopurine (MP). The US and UK cooperative groups began randomised thiopurine trials and agreed prospectively to a meta-analysis. All randomised trials of TG versus MP were sought, and data on individual patients were analysed by standard methods. Combining three trials (from US, UK and Germany), the overall event-free survival (EFS) was not significantly improved with TG (odds ratio (OR)=0.89; 95% confidence interval 0.78-1.03). Apparent differences in results between trials may be partly explained by the different types of patients studied. The larger treatment effect reported in males in the US trial was confirmed in the other trials. There was heterogeneity between sex/age subgroups (P=0.001), with significant EFS benefit of TG only observed for males aged <10 years old (OR=0.70; 0.58-0.84), although this did not result in a significant difference in overall survival (OR=0.83; 0.62-1.10). Additional toxicity occurs with TG. Mercaptopurine remains the standard thiopurine of choice, but further study of TG may be warranted to determine whether it could benefit particular subgroups.


Transepithelial exit of leucocytes: inflicting, reflecting or resolving airway inflammation?
The passage of infiltrated tissue granulocytes across airway epithelium into airway lumen is generally considered to be a pathogenic process in asthma and chronic obstructive pulmonary disease (COPD). An alternative hypothesis is proposed here-namely that the transepithelial egression of infiltrated leucocytes acts to rid diseased airway tissues of proinflammatory cells efficiently and non-injuriously. Several clinical observations previously discussed as 'unexpected' and 'puzzling' support this hypothesis. In acutely resolving allergen challenge-induced inflammation, in patients with mild asthma, airway wall eosinophils disappear without evidence of apoptosis but with evidence of a developing airway lumen eosinophilia. In the same postchallenge resolution phase, lymphocytes, neutrophils and mast cells exhibit peak numbers in airway lumen of individuals with asthma. In severe asthma requiring intubation, clinical improvement is similarly parallelled by a marked increase over several days in airway lumen neutrophils. Increased numbers of sputum neutrophils and lymphocytes also occur as symptoms improve in COPD over several months after smoking cessation. Conversely, when the transepithelial exit of leucocytes has been inhibited in inflamed animal airways the inflammation in the airway wall has been much aggravated. Finally, transepithelial egression of numerous granulocytes and lymphocytes clearly can occur without any harm to airway epithelial barriers. The present hypothesis of 'resolution through egression' provides a novel interpretation of common airway lumen data, cautions against administration of agents that impede leucocyte egression in inflammatory airway diseases and infers new approaches in disease resolution research.


Acute hypertriglyceridemia promotes intestinal lymphatic lipid and drug transport: a positive feedback mechanism in lipid and drug absorption.
Elevated systemic levels of triglyceride-rich lipoproteins (TRL) are a risk factor for the development of atherosclerosis. In patients with metabolic syndrome (MetS), intestinal TRL overproduction contributes to high systemic TRL levels, and recent studies suggest that systemic changes in MetS such as increases in plasma fatty acids and insulin resistance stimulate intestinal TRL production. The current study has examined whether increases in systemic TRL influence intestinal lipid transport and lipoprotein assembly pathways and evaluates the impact of these changes on the absorption and lymphatic transport of lipids and a model lipophilic drug (halofantrine). Mesenteric lymph-duct or bile-duct cannulated rats were administered IV saline or (14)C-labeled chylomicron (CM) (to increase systemic TRL) and intraduodenal (3)H lipids and drug. Changes to biliary lipid output and lymphatic lipid and drug transport were subsequently examined. Increasing systemic TRL concentrations stimulated a significant increase in lymphatic lipid and drug transport. The increased lipids in lymph were not derived from bile or the intestinal blood supply (fatty acid or IV infused (14)C-CM). Rather, an increase in lymphatic transport of duodenally sourced lipids was evident. Increasing plasma levels of TRL therefore stimulated lipid absorption and lymphatic transport via a positive feedback process. The data also suggest that the changes to intestinal TRL formation that result from raised systemic TRL levels may impact on the absorption of highly lipophilic drugs and therefore the reproducibility of drug treatments.


The metabolism of high intakes of tryptophan, nicotinamide and nicotinic acid in the rat.
1. The metabolic fate of high dietary intakes of nicotinamide, nicotinic acid and tryptophan, and of acute doses of nicotinamide and nicotinic acid, has been studied in the rat. A new high-pressure liquid chromatography method for measurement of the principal urinary metabolites of niacin is described. 2. Administration to rats of a single oral dose of nicotinamide or nicotinic acid (up to 100 mg/kg body-weight), or maintenance for 3 weeks on diets providing 150 mg nicotinamide or nicotinic acid/kg diet, resulted in only a small increase in the liver content of nicotinamide nucleotide coenzymes (NAD and NADP). The quantitative metabolism of nicotinamide and nicotinic acid differed, suggesting that intestinal bacterial deamidation is not the major fate of nicotinamide. 3. A high dietary intake of tryptophan (5.9 g/kg diet) led to a considerable increase in liver NAD(P) and also in urinary excretion of niacin metabolites. The results suggest that, as indicated by enzyme kinetic studies (Bender et al. 1982), the utilization of nicotinamide and nicotinic acid for nucleotide synthesis is limited, while there is little or no limitation of NAD(P) synthesis from the tryptophan metabolite quinolinic acid.


Androgens regulate SMAD ubiquitination regulatory factor-1 expression and prostate cancer cell invasion.
Prostate cancer (PCa) is the most commonly diagnosed male cancer in the United States and is a hormone-driven disease. Androgens have been recognized as a major promoter of PCa development and progression. However, the mechanism of androgen action in PCa, especially in PCa cell invasion and metastasis remains largely unclear. SMAD ubiquitination regulatory factor-1 (SMURF1) is a C2-WW-HECT-domain E3 ubiquitin ligase that plays important roles in cancer cell metastasis. Whether there is a relationship between androgens and SMURF1 expression is not known. The effect of androgens on the expression of SMURF1 in PCa cell lines was examined by Western blot analyses and reverse transcription-polymerase chain reaction (RT-PCR). Gene transfection was performed by electroporation to manipulate the expression levels of proteins studied. The binding of AR to the SMURF1 gene enhancer was determined by chromatin immunoprecipitation (ChIP) assay. Cell migration and invasion was measured by wound healing and Matrigel invasion assays, respectively. We found that expression of SMURF1 is upregulated by androgens in PCa cell lines and that this effect of androgens is mediated through the androgen receptor (AR). We further showed that androgens regulate SMURF1 expression at transcriptional level and provided evidence that AR transcriptionally activates SMURF1 by binding to its enhancer that contains a canonical half androgen responsive element (ARE). Finally, we demonstrated that SMURF1 is important for androgen-induced invasion of PCa cells. We demonstrate for the first time that SMURF1 is a bona fide target gene of the AR. Our findings also suggest a potential role of SMURF1 in PCa metastasis.


The transcription factor CREMtau and cAMP regulate promoter activity of the Na,K-ATPase alpha4 isoform.
The Na,K-ATPase is an essential enzyme of the plasma membrane that plays a key role in numerous cell processes that depend on the transcellular gradients of Na(+) and K(+). Among the various isoforms of the catalytic subunit of the Na,K-ATPase, alpha4 exhibits the most limited pattern of expression, being restricted to male germ cells. Activity of alpha4 is essential for sperm function, and alpha4 is upregulated during spermatogenesis. The present study addressed the transcriptional control of the human Na,K-ATPase alpha4 gene, ATP1A4. We describe that a 5' untranslated region of the ATP1A4 gene (designated -339/+480 based on the ATP1A4 transcription initiation site) has promoter activity in luciferase reporter assays. Computer analysis of this promoter region revealed consensus sites (CRE) for the cyclic AMP (cAMP) response element modulator (CREM). Accordingly, dibutyryl cAMP (db-cAMP) and ectopic expression of CREMtau, a testis specific splice variant of CREM were able to activate the ATP1A4 promoter driven expression of luciferase in HEK 293 T, JEG-3 and GC-1 cells. Further characterization of the effect of db-cAMP and CREMtau on deleted constructs of the ATP1A4 promoter (-339/+80, and +25/+480), and on the -339/+480 region carrying mutations in the CRE sites showed that db-cAMP and CREMtau effect required the CRE motif located 263 bp upstream the transcription initiation site. EMSA experiments confirmed the CRE sequence as a bonafide CREMtau binding site. These results constitute the first demonstration of the transcriptional control of ATP1A4 gene expression by cAMP and by CREMtau, a transcription factor essential for male germ cell gene expression.


Mapping the pinhole formation pathway of S21.
Phage holins are small, lethal membrane proteins of two general types: canonical holins, like λ S105, which oligomerizes and forms large membrane holes of unprecedented size; and pinholins, like S(21) 68 of lambdoid phage 21, which forms homo-heptameric channels, or pinholes, with a lumen of <2 nm. Pinholes depolarize the membrane, leading to activation of secreted endolysins and murein degradation. S(21) 68 has two transmembrane domains, TMD1 and TMD2. TMD2 alone lines the pinhole, making heterotypic interactions involving two surfaces, A and B. Mutational analysis on S(21) 68 suggested that S(21) 68 initially forms inactive dimer, with TMD1 inhibiting TMD2 both in cis and trans. When TMD1 exits the membrane to the periplasm, it liberates TMD2 to participate in the pathway to pinhole formation. In this study, further mutational analysis suggests a refined pinhole formation pathway, with the existence of at least two intermediate states. We propose that the pathway begins in the activated dimer state, with a homotypic TMD2 interface involving the A surface. Evidence is presented for a further oligomeric state involving a heterotypic A:B interaction. Moreover, the data suggest that a glycine-zipper motif present in the A interface of TMD2 is involved in every stage downstream of the inactive dimer.


Helicobacter pylori Infection and Predictors Among Dyspeptic Adult Patients in Southwest Ethiopia: Cross-Sectional Study.
Globally, H. pylori infection affects approximately 4.4 billion people. The burden of the infection varies within and between countries, with a higher prevalence reported from developing countries including Ethiopia. Thus, this study aimed to determine the magnitude and predictors of H. pylori infection among dyspeptic patients who visited Wachemo University Nigist Eleni Mohammed Memorial Referral Hospital, Southwest Ethiopia. Consecutive willing dyspeptic adult patients (n=405) were enrolled in a cross-sectional study done from September to December 18, 2019. Socio-demographic and behavioral characteristics of the study participants were gathered by a pretested structured questionnaire. Stool samples were examined for H. pylori antigens using Wondfo one step H. pylori feces test kit. SPSS version 20 was utilized to compute descriptive statistics, binary and multivariate logistic regression. A p-value of <0.05 was considered statistically significant. Mean age of patients was 30 (± 7.4 SD) years, and 56.8% of participants were females. About 51.4% (208/405) of adult dyspeptic patients were infected with H. pylori. Being female gender (AOR꞊ 2.56, CI 95% ꞊1.61-4.07, p꞊0.001), consumption of alcohol (AOR꞊1.95, CI 95% ꞊1.02-3.73, p꞊ 0.019) and being undernourished (underweighted) (AOR꞊ 4.59, CI 95%꞊ 1.28-16.45, p꞊0.019) were independent predictors of H. pylori infection. In the study area, high (51.4%) magnitude of H. pylori infection was observed in dyspeptic patients and significantly associated with female gender, alcohol consumption, and undernourishment.


[Spatial orientation of sinuses of the popliteal lymph node in the rabbit].
Two structural and functional portions were identified in popliteal lymph node of the mature rabbit. The one of them that occupies the lymph node anterior margin is an entry site of lymph predominantly from deep tissues of leg and foot, while the other one collects lymph mostly from surface structures of leg and foot and occupies superior and inferior poles and posterior margin of lymph node. It was established that spatial orientation of sinuses was determined by structural and functional portion they belong to. Medullar intermediate sinuses of the lymph node part I were demonstrated to be more strictly oriented as compared to that of portion II.


Cardiac glycoside poisoning involved in deaths from traditional medicines.
Autopsy cases (from all areas of South Africa except the Cape Province) are referred for chemical investigation to the Johannesburg Forensic Chemistry Laboratory of the State Health Department. Over a 1-year period in 41 autopsies where death was presumed to have been caused by a herbal medicine, the presence of cardiac glycosides was sought and was found in 44%. Most of the cases were from the Transvaal, followed by Natal. Clinical histories of the patients revealed that gastrointestinal irritation was the most common syndrome experienced after traditional medicine administration (54%). It is concluded that in patients presenting with gastro-intestinal symptoms, presumably due to poisoning by traditional medicines, cardiac glycoside poisoning should be suspected.


Leg ulcers: a common problem with sometimes uncommon etiologies.
In the U.S., leg ulcers present a significant clinical problem, occurring at a rate of approximately 600,000 new cases per year. In most cases, the cause of ulceration is venous or arterial in nature. One uncommon but significant cause of leg ulcers is sqaumous cell carcinoma (SCC). Although the incidence of SCC is higher in white than black populations, blacks with SCC typically exhibit involvement of areas of the skin that are not chronically sun-exposed, especially the lower extremeties. Predisposing factors include burn scars, chronic infection or ulceration, and chronic discoid lupus erythematosus. Leg ulcers of atypical presentation or those that fail to heal should alert the clinician to consider uncommon etiologies.


Tyrosinase Electrochemical Biosensors Monitoring Medicinally Significant Substances.
Nowadays in biosensing, development of analytical techniques is focused on improvement for monitoring biologically active species in living organisms, especially in real-time analysis. This article provides an overview of applications of electrochemical tyrosinase biosensors in the analysis of medicinally significant substances, also known as biomarkers. At the beginning, special attention is paid to characterisation of the tyrosinase enzyme, explanation of reaction mechanisms of tyrosinase with various types of electrochemical transducers and techniques needed for stable immobilization of this biocatalyst on the transducer surface used. In this case, amperometric transducers represent the most frequently used type of electrochemical sensing because they usually provide sensitive current response to the presence of analyte in the sample. Many scientific works suggest that these very selective bioanalytical devices could find application in the clinical diagnosis of various serious diseases because they represent the effective analytical tools for diagnosis of neurodegenerative disorders, detection of microbial pathogens responsible for foodborne illness and diagnosis of cytopathology, especially melanoma cancer. Additionally, various kinds of electrochemical tyrosinase biosensors are presented which were developed to determine the catalytic activity of other enzymes significant for human metabolism, medicaments and their metabolic products, several hormones, amino acids and proteins. Despite all of their advantages, it is necessary to state that tyrosinase biosensors are still not used in the routine laboratory practice due to their relatively short service life which is not longer than one month unfortunately. Never-ending development of catalytic polymers imitating the tyrosinase active site could be one of ways to solve this serious drawback.


Reducing physical restraints in pediatrics: A quality improvement mixed-methods analysis of implementing a clinical debriefing process after behavioural health emergencies in a Children's Hospital.
An increasing number of pediatric patients with mental and behavioral health (MBH) conditions present to Emergency Department (ED) and inpatient settings with behavioral events that require physical restraint (PR). PR usage is associated with adverse outcomes. Clinical debriefing (CD) programs have been associated with improved performance but have not been studied in this population. After implementing an MBH-CD program in our Children's Hospital, we aimed to decrease the baseline (7/2018-3/2021) rate of a second PR episode (2PR) by 50 % in the ED and inpatient settings over two years. A multidisciplinary team implemented an MBH-CD process in April 2021 for hospital teams to use immediately after behavioral events. We included patients ≤18 years old, with an ED or inpatient discharge MBH diagnosis, between July 2018 and June 2023. Pre- and post-implementation secondary outcomes included the ED median duration of PR and the ED PR time per 1000 h of ED care. ED and inpatient mean length of stay (LOS) and mean monthly visits (MMV) in pre- and post-implementation were also compared. Qualitative analysis identified major themes. Post-implementation, the ED significantly decreased 2PR rate by 67 %; in inpatients, no significant change was demonstrated. Median duration of ED PR decreased from 112 to 71 min (p = 0.006) and ED PR time significantly decreased by 82 % (14.8 to 2.7 h per 1000 h). In the post-implementation period, mean LOS (ED and inpatient) and MMV (ED only) were significantly higher. Fifty-one percent of 494 behavioral alerts were debriefed. Median debriefing duration was 6 min (IQR 4,10). Common themes included cooperation and coordination (23 %) and clinical standards (14 %). Clinical debriefing implementation was associated with significant improvement in ED patient outcomes. Inpatient outcomes were unchanged, but debriefings in both settings should enable frontline teams to continuously identify opportunities to improve future outcomes.


Mechanistic insights of 2,4-D sorption onto biochar: Influence of feedstock materials and biochar properties.
Objective of this study was to investigate the mechanisms of 2,4-Dichlorophynoxy acetic acid (2,4-D) sorption on biochar in aqueous solutions. Sorption isotherm, kinetics, and desorption experiments were performed to identify the role of biochars' feedstock and production conditions on 2,4-D sorption. Biochars were prepared from various green wastes (tea, burcucumber, and hardwood) at two pyrolytic temperatures (400 and 700°C). The tea waste biochar produced at 700°C was further activated with steam under a controlled flow. The sorption of 2,4-D was strongly dependent on the biochar properties such as specific surface area, surface functional groups, and microporosity. The steam activated biochar produced from tea waste showed the highest (58.8mgg-1) 2,4-D sorption capacity, which was attributed to the high specific surface area (576m2g-1). The mechanism of 2,4-D removal from aqueous solution by biochar is mainly attributed to the formation of heterogeneous sorption sites due to the steam activation.


Randomized Trial of Academic Training and Medication Decision-Making for Adolescents with ADHD in Usual Care.
Objective: This study tested two family-based interventions designed for delivery in usual care: Changing Academic Support in the Home for Adolescents with ADHD (CASH-AA), containing motivational interventions, homework management and schoolwork organization training, and family-school partnership building; and Medication Integration Protocol (MIP), containing ADHD psychoeducation, medication decision-making, and integrated medication management.Method: This study used a cluster randomized design to test CASH-AA + MIP versus CASH-AA Only for adolescents with ADHD in five sites. Therapists (N = 49) were site clinicians randomized to condition. Clients (N = 145) included 72% males; 42% White Non-Hispanic, 37% Hispanic American, 15% African American, and 6% more than one race; average age was 14.8 years. Fidelity data confirmed protocol adherence and between-condition differentiation.Results: One-year improvements were observed across conditions in several outcomes. Overall, CASH-AA + MIP produced greater declines in adolescent-report inattentive symptoms and delinquent acts. Similarly, among non-substance users, CASH-AA + MIP clients attended more treatment sessions. In contrast, among substance users, CASH-AA Only clients showed greater declines in caregiver-report hyperactive symptoms and externalizing.Conclusions: This study provides initial experimental support for family-based ADHD medication decision-making when coupled with academic training in usual care. The treatment protocols, CASH-AA and MIP, showed positive effects in addressing not only ADHD symptoms but also common co-occurring problems, and youth with substance use problems benefitted along with non-using peers.


Identification of an allatotropin from adult manduca sexta.
A peptide that strongly stimulates the secretion of juvenile hormone from corpora allata in vitro (allatotropin) has been purified from extracts of heads of pharate adult Manduca sexta. The primary structure of this 13-residue peptide has been determined: H-Gly-Phe-Lys-Asn-Val-Glu-Met-Met-Thr-Ala-Arg-Gly-Phe-NH(2). This neurohormone has no sequence similarity with any known neuropeptide from other organisms. Synthetic allatotropin, as well as truncation fragments, including one with the five amino terminal residues deleted, showed in vitro activity indistinguishable from that of native allatotropin.


Peroxidasin protein expression and enzymatic activity in metastatic melanoma cell lines are associated with invasive potential.
Peroxidasin, a heme peroxidase, has been shown to play a role in cancer progression. mRNA expression has been reported to be upregulated in metastatic melanoma cell lines and connected to the invasive phenotype, but little is known about how peroxidasin acts in cancer cells. We have analyzed peroxidasin protein expression and activity in eight metastatic melanoma cell lines using an ELISA developed with an in-house peroxidasin binding protein. RNAseq data analysis confirmed high peroxidasin mRNA expression in the five cell lines classified as invasive and low expression in the three non-invasive cell lines. Protein levels of peroxidasin were higher in the cell lines with an invasive phenotype. Active peroxidasin was secreted to the cell culture medium, where it accumulated over time, and peroxidasin protein levels in the medium were also much higher in invasive than non-invasive cell lines. The only well-established physiological role of peroxidasin is in the formation of a sulfilimine bond, which cross-links collagen IV in basement membranes via catalyzed oxidation of bromide to hypobromous acid. We found that peroxidasin secreted from melanoma cells formed sulfilimine bonds in uncross-linked collagen IV, confirming peroxidasin activity and hypobromous acid formation. Moreover, 3-bromotyrosine, a stable product of hypobromous acid reacting with tyrosine residues, was detected in invasive melanoma cells, substantiating that their expression of peroxidasin generates hypobromous acid, and showing that it does not exclusively react with collagen IV, but also with other biomolecules.


Cell factory-derived bioactive molecules with polymeric cryogel scaffold enhance the repair of subchondral cartilage defect in rabbits.
We have explored the potential of cell factory-derived bioactive molecules, isolated from conditioned media of primary goat chondrocytes, for the repair of subchondral cartilage defects. Enzyme-linked immunosorbent assay (ELISA) confirms the presence of transforming growth factor-β1 in an isolated protein fraction (12.56 ± 1.15 ng/mg protein fraction). These bioactive molecules were used alone or with chitosan-agarose-gelatin cryogel scaffolds, with and without chondrocytes, to check whether combined approaches further enhance cartilage repair. To evaluate this, an in vivo study was conducted on New Zealand rabbits in which a subchondral defect (4.5 mm wide × 4.5 mm deep) was surgically created. Starting after the operation, bioactive molecules were injected at the defect site at regular intervals of 14 days. Histopathological analysis showed that rabbits treated with bioactive molecules alone had cartilage regeneration after 4 weeks. However, rabbits treated with bioactive molecules along with scaffolds, with or without cells, showed cartilage formation after 3 weeks; 6 weeks after surgery, the cartilage regenerated in rabbits treated with either bioactive molecules alone or in combinations showed morphological similarities to native cartilage. No systemic cytotoxicity or inflammatory response was induced by any of the treatments. Further, ELISA was done to determine systemic toxicity, which showed no difference in concentration of tumour necrosis factor-α in blood serum, before or after surgery. In conclusion, intra-articular injection with bioactive molecules alone may be used for the repair of subchondral cartilage defects, and bioactive molecules along with chondrocyte-seeded scaffolds further enhance the repair. Copyright © 2015 John Wiley & Sons, Ltd.


A model of contact-induced language change: Testing the role of second language speakers in the evolution of Mozambican Portuguese.
Language change is accelerated by language contact, especially by contact that occurs when a group of speakers shifts from one language to another. This has commonly been explained by linguistic innovation occurring during second language acquisition. This hypothesis is based on historical reconstructions of instances of contact and has not been formally tested on empirical data. In this paper, we construct an agent-based model to formalize the hypothesis that second language speakers are responsible for accelerated language change during language shift. We compare model predictions to a unique combination of diachronic linguistic and demographic data from Maputu, Mozambique. The model correctly predicts an increased proportional use of the novel linguistic variants during the period we study. We find that a modified version of the model is a better fit to one of our two datasets and discuss plausible reasons for this. As a general conclusion concerning typological differences between contact-induced and non-contact-induced language change, we suggest that multiple introductions of a new linguistic variant by different individuals may be the mechanism by which language contact accelerates language change.


[Diagnostics and comprehensive treatment of patients with odontogenic lymphadenitis complicated by phlegmons].
The duthor detected special changes in oral liquid of macro and trace substances concentrations and their ratio in dynamics of convalescence for 24 patients with odontogenic lymphadenitis complicated by phlegmon. It was established that termination of inflammatory process on earlier terms at addition in complex treatment of this pathology of polyvitaminic complex considerably lowering strontium concentration in oral liquid (Patent RU 2210378 from 20.08.2003).


SARS-CoV-2 N Gene G29195T Point Mutation May Affect Diagnostic Reverse Transcription-PCR Detection.
Rapid onsite whole-genome sequencing of two suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) N gene diagnostic escape samples revealed a previously unreported N gene point mutation at genome position 29195. Because the G29195T mutation occurs within a region probed by a commonly referenced U.S. CDC N gene reverse transcription (RT)-PCR assay, we hypothesize that the G29195T mutation rendered the N gene target of a proprietary commercial assay undetectable. The putative diagnostic escape G29195T mutation demonstrates the need for nearly real-time surveillance, as emergence of a novel SARS-CoV-2 variant with the potential to escape diagnostic tests continues to be a threat. IMPORTANCE Accurate diagnostic detection of SARS-CoV-2 currently depends on the large-scale deployment of RT-PCR assays. SARS-CoV-2 RT-PCR assays target predetermined regions in the viral genomes by complementary binding of primers and probes to nucleic acid sequences in the clinical samples. Potential diagnostic escapes, such as those of clinical samples harboring the G29195T mutation, may result in false-negative SARS-CoV-2 RT-PCR results. The rapid detection and sharing of potential diagnostic escapes are essential for diagnostic laboratories and manufacturers around the world, to optimize their assays as SARS-CoV-2 continues to evolve.


Burden of disease, treatment utilization, and the impact on education and employment in patients with sickle cell disease: A comparative analysis of high- and low- to middle-income countries for the international Sickle Cell World Assessment Survey.
The international Sickle Cell World Assessment Survey (SWAY) reported a high impact of sickle cell disease (SCD) on patients' daily lives globally. In this study, we analyzed whether the reported burden differed between patients from the USA (n = 384) and other high-income (HI; n = 820) or low- to middle-income (LMI; n = 941) countries. We assessed symptoms and complications, incidence/management of vaso-occlusive crises (VOCs), treatment utilization/satisfaction, and the impact of SCD on education/employment. Certain symptoms (bone aches, insomnia, and joint stiffness) and complications (swollen/painful fingers/toes, gallstones, vision problems, blood clots, and asthma) were reported proportionally more by patients in the USA than in the HI/LMI countries. Self-reported VOCs were more common (mean [SD]: 7.1 [5.7] vs. 5.5 [8.9] and 4.4 [4.6] in the previous 12 months) and were managed more often by hospitalization (52% vs. 24% and 32%) in the USA than the HI and LMI countries. A higher proportion of patients from the USA than the HI/LMI countries reported a negative impact of SCD on their employment/schooling. Although high overall satisfaction with current treatments was reported globally, most patients indicated a strong desire for alternative pain medications. There are likely several reasons for the relatively high patient-reported burden in the USA group compared with the HI/LMI countries, including an older population and differences in newborn screening programs and pediatric/adult transition of care. It is clear that there is an urgent need for improved understanding and management of SCD globally, not just in the USA.


The independent effects of personality and situations on real-time expressions of behavior and emotion.
The joint influence of persons and situations on behavior has long been posited by personality and social psychological theory (Funder, 2006; Lewin, 1951). However, a lack of tools for real-time behavioral and situation assessment has left direct investigations of this sort immobilized. This study combines recent advances in situation assessment and experience sampling methodology to examine the simultaneous effects of personality traits and situation characteristics on real-time expressions of behavior and emotion in N = 210 participants. The results support an additive model such that both personality traits and situation characteristics independently predict real-time expressions of behavior and emotion. These results have implications for several prominent theoretical perspectives in personality, including both trait and cognitive theories.


Cost-effectiveness of Confirmatory Testing Before Treatment of Onychomycosis.
Onychomycosis is the most common disease of the nail in adults. International guidelines urge health care professionals to perform confirmatory diagnostic testing before initiating systemic therapy. This approach was determined to be cost-effective in studies from the late 1990s but has not been evaluated more recently. The effect of testing on the costs of efinaconazole, 10%, topical solution treatment is unknown. To evaluate the cost and potential harm associated with 3 approaches to onychomycosis evaluation before treatment with oral terbinafine or efinaconazole, 10%. A decision analysis that compared the costs of 3 onychomycosis management algorithms based on recently published data of test statistics, disease prevalence, and relevant costs: (1) empirical therapy without confirmatory testing, (2) pretreatment confirmatory testing with potassium hydroxide (KOH) stain followed by periodic acid-Schiff (PAS) evaluation if KOH testing is negative, and (3) pretreatment testing with PAS. There was no direct patient evaluation. Selection of included studies was based on outcome variables and the quality of study design. The study was conducted from April 1, 2014, to September 1, 2015. Primary outcomes included direct cost of onychomycosis testing and therapy and cost to avoid harm when treating patients with oral terbinafine. At a disease prevalence of 75%, per-patient cost savings of empirical terbinafine therapy without confirmatory testing was $47 compared with the KOH screening model and $135 compared with PAS testing. The cost of testing necessary to prevent a single case of clinically relevant liver toxic effects related to terbinafine at a prevalence of 75% was between $18.2 million and $43.7 million for KOH screening and between $37.6 million and $90.2 million for PAS testing. At a prevalence of 75%, KOH screening and PAS testing before treatment with efinaconazole, 10%, saved $272 and $406 per patient per nail, respectively. These results show that empirical treatment with terbinafine for patients with suspected onychomycosis is more cost-effective than confirmatory testing across all prevalence of disease, with minimal effect on patient safety. In contrast, confirmatory testing before treatment with efinaconazole, 10%, is associated with reduced costs. Blanket recommendations for confirmatory testing before systemic therapy should be reconsidered and replaced with recommendations tailored to specific therapies.


Treatment dilemmas in asymptomatic children with primary hemophagocytic lymphohistiocytosis.
Asymptomatic carriers (ACs) of pathogenic biallelic mutations in causative genes for primary hemophagocytic lymphohistiocytosis (HLH) are at high risk of developing life-threatening HLH, which requires allogeneic hematopoietic stem cell transplantation (HSCT) to be cured. There are no guidelines on the management of these asymptomatic patients. We analyzed the outcomes of pairs of index cases (ICs) and subsequently diagnosed asymptomatic family members carrying the same genetic defect. We collected data from 22 HSCT centers worldwide. Sixty-four children were evaluable. ICs presented with HLH at a median age of 16 months. Seven of 32 ICs died during first-line therapy, and 2 are alive after chemotherapy only. In all, 23/32 underwent HSCT, and 16 of them are alive. At a median follow-up of 36 months from diagnosis, 18/32 ICs are alive. Median age of ACs at diagnosis was 5 months. Ten of 32 ACs activated HLH while being observed, and all underwent HSCT: 6/10 are alive and in complete remission (CR). 22/32 ACs remained asymptomatic, and 6/22 have received no treatment and are in CR at a median follow-up of 39 months. Sixteen of 22 underwent preemptive HSCT: 15/16 are alive and in CR. Eight-year probability of overall survival (pOS) in ACs who did not have activated HLH was significantly higher than that in ICs (95% vs 45%; P = .02), and pOS in ACs receiving HSCT before disease activation was significantly higher than in ACs receiving HSCT after HLH activation (93% vs 64%; P = .03). Preemptive HSCT in ACs proved to be safe and should be considered.


IBD5 polymorphisms in inflammatory bowel disease: association with response to infliximab.
Inflammatory bowel diseases (IBD) are multifactorial pathologies of unknown etiology. One susceptibility locus, IBD5, has been mapped to chromosome 5q31. We analyzed our Spanish cohorts of Crohn's disease (CD) and ulcerative colitis (UC) patients to determine whether this locus is associated with IBD, and to ascertain the main clinical phenotype influenced by this risk factor. The kind of interaction, either genetic heterogeneity or epistasis, between this IBD5 susceptibility region and the NOD2/CARD15 gene mutations was studied as well. Finally, we assessed whether this locus can predict response to infliximab therapy. A case control study was performed with 274 CD and 211 UC patients recruited from a single center and 511 healthy ethnically matched controls. Two polymorphisms were genotyped in the IBD5 locus and three in the CARD15/NOD2 gene. Our results evidence association only with CD especially with the fistulizing phenotype and in the absence of NOD2/CARD15 variants (mutant allele frequency in patients vs controls: OR = 2.03, 95% CI = 1.35-3.06, P<0.01). The frequency of the IBD5 homozygous mutant genotype significantly increased in CD patients lacking response to infliximab (RR = 3.88, 95% CI = 1.18-12.0, P<0.05). UC patients overall do not show association with 5q31 polymorphisms, although a similar trend to the one observed in CD is found within the worse prognosis group. The IBD5 variants may enhance an individual carrier's risk for CD, mainly in the absence of the NOD2/CARD15 mutations and in fistulizing patients. The data presented suggest the potential role of the 5q31 polymorphisms as markers of response to infliximab.


Maintaining Sexual Desire in Long-Term Relationships: A Systematic Review and Conceptual Model.
The most universally experienced sexual response is sexual desire. Though research on this topic has increased in recent years, low and high desire are still problematized in clinical settings and the broader culture. However, despite knowledge that sexual desire ebbs and flows both within and between individuals, and that problems with sexual desire are strongly linked to problems with relationships, there is a critical gap in understanding the factors that contribute to maintaining sexual desire in the context of relationships. This article offers a systematic review of the literature to provide researchers, educators, clinicians, and the broader public with an overview and a conceptual model of nonclinical sexual desire in long-term relationships. First, we systematically identified peer-reviewed, English-language articles that focused on the maintenance of sexual desire in the context of nonclinical romantic relationships. Second, we reviewed a total of 64 articles that met inclusion criteria and synthesized them into factors using a socioecological framework categorized as individual, interpersonal, and societal in nature. These findings are used to build a conceptual model of maintaining sexual desire in long-term relationships. Finally, we discuss the limitations of the existing research and suggest clear directions for future research.


Voices from the past: comparing the rapid prompting method and facilitated communication.
This article briefly reviews the history and damage caused by facilitated communication (FC) and highlights the parallels between FC and the Rapid Prompting Method (RPM). FC involves a therapist (or facilitator) supporting the hand of a person with autism while a message is typed on a letter board. FC is widely acknowledged to be a pseudoscientific, unsafe, and unethical treatment for people with autism. RPM is a more recent intervention for people with autism that involves the facilitator holding and moving the letter board while the individual with autism moves their own hand. Those who espouse the perceived benefits of FC and RPM make strikingly similar claims of hidden intelligence and extraordinary communication abilities in people with autism following treatment. Clients, proponents, and practitioners of RPM should demand scientific validation of RPM in order to ensure the safety of people with disabilities that are involved with RPM.


Interleukin-10-819 promoter polymorphism in association with gastric cancer risk.
Potential functional allele T/C single nucleotide polymorphism (SNP) of Interleukin 10 (IL-10) promoter -819 (rs1800871) has been implicated in gastric cancer risk. We aimed to explore the role of T/C SNP of IL-10 -819 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. 11 studies were ultimately eligible for the meta-analysis of IL-10 -819 T/C SNP. We adopted the most probably appropriate genetic model (recessive model). Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication biases were estimated. IL-10 -819 TT genotype is associated with the overall reduced gastric cancer risk among Asians and even apparently observed among high quality subgroup Asians. IL-10-819 TT genotype is not statistically associated with the overall reduced gastric cancer susceptibility in persons with H. pylori infection compared with controls without H. pylori infection. IL-10 -819 TT genotype is reversely associated with diffuse-subtype risk but not in intestinal-subtype risk. IL-10 -819 TT genotype is not reversely associated with non-cardia or cardia subtype gastric cancer susceptibility. IL-10 -819 TT genotype seems to be more protective from gastric cancer in Asians. Whether IL-10 -819 TT genotype may be protective from gastric cancer susceptibility in persons infected with H. pylori or in diffuse-subtype cancer needs further exploring in the future well-designed high quality studies among different ethnicity populations. Direct sequencing should be more used in the future.


Random study of hexamethylmelamine, 5-fluorouracil, and melphalan in treatment of advanced carcinoma of the ovary.
The effectiveness of melphalan, hexamethylmelamine, and 5-fluorouracil was compared in the treatment of patients with advanced ovarian cancer. Patients responded the best to hexamethylmelamine, which, however, was associated with considerable neurotoxicity. Patients responded the worst to 5-fluorouracil, which occasionally induced severe gastrointestinal toxicity. Patients treated with melphalan continued to demonstrate the response rate reported for several years in the literature. Melphalan seemed the best choice as a second-line drug. It induced not only the longest survival rate among patients, but also the only two complete responses as a second-line drug. Hexamethylmelamine has shown no activity as a third-line drug to date.


Perceived influence of psychological consultation on psychological well-being, body image, and intimacy following bilateral prophylactic mastectomy: A qualitative analysis.
This study explored whether psychological consultation offered to women prior to bilateral prophylactic mastectomy (BPM) appeared to provide psychosocial benefit to younger women (<35 years) at high risk of developing breast cancer due to a mutation or family history. Qualitative interviews guided by interpretative phenomenological analysis were conducted retrospectively with 26 women who had undergone BPM. Participants were recruited from New Zealand and Australia, via a genetics clinic, registry, research cohort, and online. Three themes were identified: psychological well-being and adjustment, satisfaction with intimacy, and body image. Participants that had seen a psychologist reported being more prepared for BPM and appeared to adjust positively post-surgery. They appeared to have improved psychological well-being, reported satisfaction with intimacy, and a more positive body image, compared with those who had no support. Women who undergo psychological consultation prior to BPM appear to adjust positively after surgery. Implications for practice include standard psychological consultation for younger women (>35 years) considering BPM.


The role of tissue-fixed macrophages in apoptosis in the developing kidney.
Programmed cell death (PCD) and cell type involving dying cells in the developing mouse and human fetal kidneys were investigated using the modified TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method in combination with immunohistochemistry. We identified many TUNEL-positive apoptotic cells mainly in the nephrogenic region in the developing mouse and human fetal kidneys. Tissue-fixed macrophages were widely distributed throughout the developing mouse and human fetal kidneys, including the nephrogenic zone. Most of the apoptotic cells in the nephrogenic zone were phagocytosed by tissue-fixed macrophages, suggesting that tissue-fixed macrophages play an important role in the process of PCD in the developing mouse kidney and human fetal kidney.


An analysis of patients' psychosocial adjustment and values before and after coronary artery surgery.
This study describes the impact of coronary artery bypass graft (CABG) surgery on patients' personal values. The relationship between the difference in value ranks and psychosocial adjustment to CABG surgery was also investigated. A one-group pretest-posttest design was employed to identify the differences between pre- and postsurgery value ranks. A consecutive sample of 67 participants ranked two sets of 18 values using the Rokeach Value Survey 1 day before and 6 months after surgery. At 6 months after surgery, psychosocial adjustment was also measured, using the Psychosocial Adjustment to Illness Scale (PAIS). A Pearson product-moment correlation was calculated to test the hypothesis that a direct relationship exists between the difference in value ranks and positive psychosocial adjustment to CABG surgery. Fifty-six participants completed the 6-month follow-up survey. The median value ranks for the three most and least important values of each set were essentially the same for the ranks obtained before and after surgery. The PAIS results obtained 6 months after surgery indicated that all but 4 of the 56 participants had a positive psychosocial adjustment to surgery. There was no significant relationship between PAIS and value difference scores.


A Unified Framework for Investigating Aperiodic and Periodic Components in the Hearbeat Dynamics Spectrum: a Feasibility Study.
Heart Rate Variability (HRV) series is a widely used, non-invasive, and easy-to-acquire time-resolved signal for evaluating autonomic control on cardiovascular activity. Despite the recognition that heartbeat dynamics contains both periodic and aperiodic components, the majority of HRV modeling studies concentrate on only one component. On the one hand, there are models based on self-similarity and 1/f behavior that focus on the aperiodic component; on the other hand, there is the conventional division of the spectral domain into narrow-band oscillations, which considers HRV as a combination of periodic components. Taking inspiration from a recent parametrization of EEG power spectra, here we evaluate the applicability of a unified modeling framework to quantitatively assess heartbeat dynamics spectra as a mixture of aperiodic and periodic components. The proposed model is applied on publicly-available, real HRV series collected during postural changes from 10 healthy subjects. Results show that the proposed modeling effectively characterizes different experimental conditions and may complement HRV standard analysis defined in the frequency domain.


Correlations of oil and protein with isoflavone concentration in soybean [Glycine max (L.) Merr.].
Twelve isoflavones were detected by high-performance liquid chromatography in seeds of 17 soybean [Glycine max (L.) Merrill] cultivars grown at three locations. 6' '-O-Malonyldaidzin and 6' '-O-malonylgenistin together constituted 71-81% of total isoflavones, which ranged in concentration from 2038 to 9514 microg/g and averaged 5644 microg/g across locations and cultivars. The total as well as several individual isoflavones had a moderate negative correlation with oil across locations and cultivars. Six cultivars had a moderate or strong negative correlation of total isoflavones with oil. Five cultivars had a moderate or strong positive correlation of total isoflavones with protein. These results suggest that judicious selection of germplasm for soybean breeding may facilitate development of soybean lines with desirable isoflavone concentrations.


Interpretive subgroup analysis extends modified grounded theory research findings in oncologic music therapy.
Following an investigation into oncologic patients' experiences of the helpfulness of music therapy (O'Callaghan & McDermott, 2004), it was considered that examining relationships between specific patient characteristics and their responses could yield further interesting understandings. "Interpretative subgroup analysis" is introduced, which adapts principles of subgroup analysis in quantitative research to textual data analysis. Anonymous written responses from 128 oncologic patients were analyzed to compare responses from (a) those that had one music therapy session with those who had more than one session, (b) males and females, and (c) middle and older aged respondents. The number of music therapy sessions had scant effect on reported music therapy experiences, and males were much more likely to return questionnaires but much less likely to participate. Unlike some females, males always described positive affective responses when experiencing both sad and positive memories. Variations in the middle and older aged subgroups were evident in type of affective response, and emphases in descriptions of memories and music therapy's effect. Implications of these findings for music therapy practice are considered. Interpretive subgroup analysis is recommended for extending understanding of subjective within group experiences in music therapy research incorporating a grounded theory approach and large enough samples.