The effect of contact lens wear on the central and peripheral corneal endothelium.
To compare central and peripheral corneal endothelial cell morphometry in normal subjects and long-term contact lens wearers. Endothelial cell density (ECD), coefficient of variation of cell area (CV), and percentage of six-sided cells were measured by contact specular microscopy in the corneal center and temporal periphery of both eyes of 43 long-term contact lens wearers and in 84 normal subjects who had never worn contact lenses. The latter group included 43 age- and sex-matched controls for the contact lens wearers. ECDs were corrected for magnification changes due to corneal thickness. Central ECD (2,723+/-366 cells/mm2, mean +/- SD) was significantly higher than peripheral ECD (2,646+/-394 cells/mm2) for the normal group (p = 0.01) but not for the contact lens wear group (2,855+/-428 cells/mm2 central, 2,844+/-494 cells/mm2 peripheral, p = 0.84). Peripheral CV was significantly higher than central for normal subjects and contact lens wearers and was significantly higher in both center and periphery in contact lens wearers than in controls. Central percentage of six-sided cells was significantly higher than peripheral for normal subjects and contact lens wearers and was lower in both center and periphery in contact lens wearers than in controls. Central ECD was significantly higher by 3% than peripheral ECD in normal subjects, but not in contact lens wearers. The results suggest that contact lens wear causes a mild redistribution of endothelial cells from the central to the peripheral cornea. A reversal of this redistribution after contact lens wear is discontinued for refractive surgery could mask mild central endothelial damage from the refractive procedure.


Carving the cognitive niche: optimal learning strategies in homogeneous and heterogeneous environments.
A model learning system is constructed, in which an organism samples behaviors from a behavioral repertoire in response to a stimulus and selects the behavior with the highest payoff. The stimulus and most rewarding behavior may be kept in the organism's long-term memory and reused if the stimulus is encountered again. The value of the memory depends on the reliability of the stimulus, that is, how the corresponding payoffs of behaviors change over time. We describe how the inclusion of memory can increase the optimal sampling size in environments with some stimulus reliability. In addition to using memory to guide behavior, our organism may use information in its memory to choose the stimulus to which it reacts. This choice is influenced by both the organism's memory state and how many stimuli the organism can observe (its sensory capability). The number of sampled behaviors, memory length, and sensory capability are the variables that define the learning strategy. When all stimuli have the same reliability, there appears to be only a single optimal learning strategy. However, when there is heterogeneity in stimulus reliability, multiple locally optimal strategies may exist.


Expression and Role of TRIM2 in Human Diseases.
Tripartite motif (TRIM) protein family proteins contain more than 80 members in humans, and most of these proteins exhibit E3 ubiquitin ligase activity mediated through a RING finger domain. Their biological functions are very complex, and they perform diverse functions in cell evolution processes, such as intracellular signaling, development, apoptosis, protein quality control, innate immunity, autophagy, and carcinogenesis. Tripartite motif-containing protein 2 (TRIM2), a member of the TRIM superfamily, is an 81 kDa multidomain protein, also known as CMT2R or RNF86, located at 4q31.3. TRIM2 functions as an E3 ubiquitin ligase. Current studies have shown that TRIM2 can play roles in neuroprotection, neuronal rapid ischemic tolerance, antiviral responses, neurological diseases, etc. Moreover, based on some studies in tumors, TRIM2 regulates tumor proliferation, migration, invasion, apoptosis, and drug resistance through different mechanisms and plays a critical role in tumor occurrence and development. This review is aimed at providing a systematic and comprehensive summary of research on TRIM2 and at exploring the potential role of TRIM2 as a biomarker and therapeutic target in many kinds of human diseases.


The Nurse Manager Academy: an innovative approach to managerial competency development.
The quality of nursing leadership has a powerful impact on nurse retention. Hospitals that employ effective nursing leaders report increased nursing satisfaction, increased group cohesiveness, decreased job stress, and decreased turnover (Wells, Roberts, & Medlin, 2002). The Institute for Johns Hopkins Nursing has developed a unique training program for nurse managers that employs a learner-centered approach and is designed to teach the leadership skills essential to successful nursing management. The Nurse Manager Academy prepares nurse managers to assume management roles with confidence and competence, making them more likely to succeed in one of the most challenging jobs in health care today.


Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation.
Oxidative stress plays an important role in the pathogenesis of asthma via the upregulation of local inflammatory mediators and/or promoting Th2-skewing during Ag sensitization. Thioredoxin (TRX), a 12 kDa redox-active protein with antioxidative property, has been recently shown to play a protective role in various inflammatory diseases. Using a mouse model of asthma, we show here that IL-13 and eotaxin production are decreased in TRX-Tg mice leading to reduced eosinophils recruitment and mucus metaplasia. The reduction in airway inflammation occurs without the attenuation of systemic Th2 immunity in that comparable levels of Th2-type cytokines and Ig were detected in LN and serum, respectively, from TRX-Tg and WT mice. Likewise, CD4(+) T cells from both strains of mice developed similar Th1 and Th2 responses in vitro. Asthmatic lungs of TRX-Tg and WT mice contained similar amounts of GATA-3(+) and Foxp3(+) T cells. Finally, production of MIF, an upstream modulator of airway inflammation, was significantly reduced in the lungs of TRX-Tg mice. Our data suggest that TRX suppresses airway inflammation by inhibiting MIF production thereby limiting the downstream recruitment of eosinophils to the lung independently of modulating systemic Th1/Th2 immunity.


[General pharmacological study of iodixanol, a new non-ionic isotonic contrast medium].
The general pharmacological study of iodixanol, a non-ionic isotonic contrast medium, was conducted. 1) Iodixanol administered intravenously over a dose range of 320 to 3,200 mgI/kg had little or no effect on the general behavior, spontaneous locomotor activity, hexobarbital sleeping time, pain response, electroshock- or pentylenetetrazol-induced convulsion (mouse), EEG or body temperature (rabbit), gastrointestinal propulsion (mouse) or skeletal muscle contraction (rabbit). Iodixanol had no specific interaction with acetylcholine, histamine, serotonin, nicotin, BaCl2 (ileum), methacholine (trachea), isoprenaline (atrium) or oxytocin (pregnant uterus), nor had any effect on spontaneous contractility (atrium and uterus), or transmural electrostimulation-induced contractility (vas deferens) at concentrations of < or = 3.2 x 10(-3) gI/ml in vitro. Iodixanol had no effect on the cardiovascular system of dog, except that it increased femoral blood flow and respiratory rate at doses of > or = 1,000 mgI/kg. Iodixanol at 3,200 mgI/kg i.v. reduced urine output with a decrease in Na+ and Cl- excretion, whereas at 320 mgI/kg i.v., it slightly increased urine output (rat). 2) Injections of iodixanol into the cerebroventricular (0.96, 9.6 mgI/mouse and 3.2, 32 mgI/rat), left ventricular (1,920, 6,400 mgI/dog) or coronary artery (640, 1,920 mgI/dog) had no conspicuous effect on the central nervous system or the cardiovascular system, respectively. There was no marked difference among iodixanol, iohexol and iopamidol in this respect. Vascular pain during injection into the femoral artery (300-320 mgI/guinea pig) appeared to be less intense with iodixanol, compared with the other contrast media iohexol and iopamidol. These results suggest that intravenous injection of iodixanol is relatively free from pharmacological activity, and effects of iodixanol on the central nervous system (intracerebroventricular injection) and cardiovascular system (intra-left ventricular and -coronary injections) are comparable to those of iohexol and iopamidol. Furthermore, intra-femoral injection of iodixanol has less of a tendency to produce vascular pain than those of iohexol and iopamidol.


Accuracy of pediatric triage at Siriraj Hospital, Bangkok, Thailand.
Siriraj Hospital is a busy 2500-bed hospital located in Bangkok, Thailand It has over 1.7 million outpatients, including 120,000 emergency room visits a year, 20,000 of which are pediatric patients. The Pediatric Triage (Pedtriage) system has been in used since the year 2001, but the factors that affect the performance of triage nurse have not been evaluated. To compare the performance non-pediatric nurses who are responsible for pediatric patients in the emergency room before and after pediatric triage training at Siriraj Hospital. Pediatric Triage Training was set up for emergency room and outpatient department nurses between June and October 2006 The training consisted of 5 hours of didactic sessions on the concepts of pediatric triage and 4-5 hour sessions where the nurses were allowed to triage actual pediatric patients under the supervision ofa triage-training nurse. A pre-test and post-test examination was administered. The outcome of triage performance was categorized into under-triage if the patient had an urgent or emergent condition and was triaged as non-urgent, over-triage if a patient had a non-urgent condition and was triaged as urgent or emergent. Statistical description included percent, averages, and standard deviation where appropriate. A standard 4x4 contingency table was used to calculate the sensitivity and specificity. For comparison of performance, a post-hoc analysis was done where the nurses were divided into two groups, those with work experience ofless than or equal to 5 years (group 1) and more than 5 years (group 2). An independent samples t-test was used to determine the difference in performance between the two groups. Overall, performance on pre-test-post-test differedsignificantly before and after training. The nurses in Group 1 had higher pre-test scores (Group 1 mean = 62.35%, Group 2 mean = 52.41%, p-value = 0.001), were less likely to overtriage (Group 1 mean = 4.11%, Group 2 mean = 6.46%, p-value = 0.021) and had higher specificity oftriage than Group 2 (Group 1 mean = 95.61, Group 2 = 92.39, p-value = 0.019). However, the nurses in Group 2 had more improvement in their post-test scores (percent of improvement from pre-test: Group I mean = 8.56%, Group 2 = 34.69%, p-value = 0.005). Work experience is an important consideration in the triage knowledge and performance of non-pediatric nurses during triage training.


Dracunculiasis (guinea worm disease) in the Bume (Nyangaton) people of South Omo, Ethiopia.
A village-to-village search for active dracunculiasis cases was carried out in an endemic area of the Bume (Nyangaton) tribe of South Omo Region, Ethiopia. A total of 21 cases, of which 6, 5, and 10 had pre-emergent, emergent and complicated Guinea worm disease, respectively, were identified. Twenty-two worms, ranging from 1-3 per patient, were removed mainly from the lower limbs; worm appearance seems to be associated more with the right limb. Adults between the ages of 20-30 years are highly affected and infection appears to be sex-related as 14/21 (66.7%) of the cases are females. Water procured from water-holes drug in dry river beds provides an ideal situation for the transmission of dracunculiasis amongst the tribesmen. The knowledge, attitudes and perceptions of the Bume people towards the disease and the public health significance of dracunculiasis are discussed in relation to the current goal of the national and global Guinea worm eradication programme.


Hypoalbuminemia, Low Base Excess Values, and Tachypnea Predict 28-Day Mortality in Severe Sepsis and Septic Shock Patients in the Emergency Department.
The objective of this study was to develop a new nomogram that can predict 28-day mortality in severe sepsis and/or septic shock patients using a combination of several biomarkers that are inexpensive and readily available in most emergency departments, with and without scoring systems. We enrolled 561 patients who were admitted to an emergency department (ED) and received early goal-directed therapy for severe sepsis or septic shock. We collected demographic data, initial vital signs, and laboratory data sampled at the time of ED admission. Patients were randomly assigned to a training set or validation set. For the training set, we generated models using independent variables associated with 28-day mortality by multivariate analysis, and developed a new nomogram for the prediction of 28-day mortality. Thereafter, the diagnostic accuracy of the nomogram was tested using the validation set. The prediction model that included albumin, base excess, and respiratory rate demonstrated the largest area under the receiver operating characteristic curve (AUC) value of 0.8173 [95% confidence interval (CI), 0.7605-0.8741]. The logistic analysis revealed that a conventional scoring system was not associated with 28-day mortality. In the validation set, the discrimination of a newly developed nomogram was also good, with an AUC value of 0.7537 (95% CI, 0.6563-0.8512). Our new nomogram is valuable in predicting the 28-day mortality of patients with severe sepsis and/or septic shock in the emergency department. Moreover, our readily available nomogram is superior to conventional scoring systems in predicting mortality.


Development, dependence, and gender inequality in the Third World.
While there has been much recent empirical investigation of the relationship between economic development, dependence, and income inequality, the issue of gender inequality has received less systematic attention. This exploratory study is a cross-sectional investigation of the effects of industrialization and investment, debt, and export dependency on levels of female education, and on rates of female economic participation, both absolutely and relative to male rates in 60 less developed countries. Although some of the macroeconomic indicators emerge as significant predictors of gender inequality in several of the regression equations, the most important explanatory variable is cultural region. These findings fail to lend strong empirical support to either the modernization or the dependency/world system theoretical perspective. The concluding discussion speculates on the interpretation of the research findings, offers some observations on the conceptual distinctions between class and gender stratification, and suggestions some directions for future research.


Constructing health and sickness in the context of motherhood and paid work.
Changes in the labour market, especially the rise in the employment of women (lone or partnered) with children, alongside an increased policy emphasis on work as a component of active citizenship for men and women, have stimulated the development of research examining the balance between work and home. Although sociologists have long been interested in the interface between the spheres of paid work and domestic life, understandings of the subjective experience of health and illness have tended to keep the domains of family and work separate. This paper addresses the construction of health and illness as operating at the interface between the worlds of work and home. Interviews were conducted with 30 mothers in paid work and having primary school aged children; the study was located in Edinburgh, Scotland. Through an analysis of the interview accounts, this paper examines respondents' experiences and constructions of health, sickness and wellbeing in themselves and in their children. Four areas are discussed: respondents' accounts of the effects of caring and providing on their own health; respondents' accounts of the influence of workplace relationships in the construction of sickness; respondents' accounts of negotiating absence for their children's sickness and how they made sense of and defined child sickness. We argue that managing sickness, itself an anticipated but unpredictable event, gives analytical purchase to understanding the values and practices that characterise the interrelationship between work and family life. The intersections of home and work operate powerfully in respondents' constructions of health and sickness, and the analysis demonstrates how these are played out in everyday life, at home and at work.


Adolescent biological maturity and physical activity: biology meets behavior.
The decline in physical activity (PA) across adolescence is well established but influence of biological maturity on the process has been largely overlooked. This paper reviews the limited number of studies which examine the relationship between timing of biological maturity and PA. Results are generally inconsistent among studies. Other health-related behaviors are also considered in an effort to highlight the complexity of relationships between biological maturation and behavior and to provide future research directions.


Newborn nasal obstruction due to congenital nasal pyriform aperture stenosis.
Nasal obstruction is an important condition that can lead to severe respiratory distress in newborns. There are several differential diagnoses, and one of them is congenital nasal pyriform aperture stenosis (CNPAS). CNPAS is a rare case of respiratory distress caused by excessive growth of the nasal process of the maxilla and leads to narrowing of the anterior third of the nasal cavity. Diagnosis, associated anomalies, and treatment strategies are reviewed by the following presentation of two cases. We report two cases of infants diagnosed with CNPAS. The patients in the first case had no concomitant comorbidities, and the outcome was successful after surgical correction of stenosis. The patient in the second case had an associated holoprosencephaly, and although surgical correction and nasal cavity patency, the patient remains dependent on tracheostomy due to dysphagia and neurologic impairment. Airway obstruction affects 1 in 5000 children, and CNPAS is a diagnosis frequently forgotten and even unknown to neonatal and pediatric intensivists. Newborns are obligate nasal breathers, and, nasal obstruction, therefore, can lead to severe respiratory distress. CNPAS is not only rare but, many times, is not easily recognized. It is important to bear in mind the diagnostic criteria when evaluating infants with nasal obstruction. Conservative treatment should be prioritized, but surgical treatment is required in severe cases with failure to thrive and persistent respiratory distress. Respiratory distress and dysphagia may persist to some degree despite correction of the stenotic pyriform aperture due to associated narrowing of the entire nasal cavity and association with other anomalies. Final Comments: CNPAS is a rare condition and may be lethal in newborns. Differential diagnosis of nasal obstruction must be remembered to recognize this anomaly, and the otolaryngologist must be familiarized with this condition and its diagnosis. Precise surgical treatment in severe cases have high rates of success in children without other comorbidities.


[Autoaggressive characteristics of married couples, where husbands suffer from alcohol dependence].
To study autoaggressive characteristics of spouses in families of men with alcohol dependence. One hundred and twenty-five families, where a husband suffers from alcohol dependence, have been investigated. Suicidal and non-suicidal patterns of autoaggressive behavior as well as their predictors have been studied. The control group consisted of 62 families, where husbands were not alcohol dependent. It has been found that men with alcohol dependence tend to realize anivital programs through suicidal behavior and risky-victim behavioral modes. A history of a suicidal attempt was revealed in 32% of alcohol dependent men, a suicide attempt over the last two years in 12% that was considerably higher compared to the control group. The percentage in their wives was 16% and 7.2%, respectively. The suicide attempts in wives were due to 'prosuicidal' complex of emotions with the sense of shame, guilt and hopelessness. Gender differences in the ways of realization of suicidal attempts have been found. This finding can be used in addiction treatment.


Adult Conditional Knockout of PGC-1α Leads to Loss of Dopamine Neurons.
Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder. Recent studies have implicated a role for peroxisome proliferator-activated receptor γ coactivator protein-1α (PGC-1α) in PD and in animal or cellular models of PD. The role of PGC-1α in the function and survival of substantia nigra pars compacta (SNpc) dopamine neurons is not clear. Here we find that there are four different PGC-1α isoforms expressed in SH-SY5Y cells, and these four isoforms are expressed across subregions of mouse brain. Adult conditional PGC-1α knock-out mice show a significant loss of dopaminergic neurons that is accompanied by a reduction of dopamine in the striatum. In human PD postmortem tissue from the SNpc, there is a reduction of PGC-1α isoforms and mitochondria markers. Our findings suggest that all four isoforms of PGC-1α are required for the proper expression of mitochondrial proteins in SNpc DA neurons and that PGC-1α is essential for SNpc DA neuronal survival, possibly through the maintenance of mitochondrial function.


[Conversion ratio between different botulinum neuroprotein product in neurological practice].
Despite nearly 30 years of experience in the application of botulinum toxin type A (BTA) in clinical practice, many fundamental questions of therapy remain valid. There are 5 botulinum toxin type A used for neurological indications in the Russian Federation in 2017. They contain different number of active neuroprotein (150 kDa) in a therapeutic dose of the drug that may have a potential impact on the efficacy and duration of action. The current SmPC of each BTA stated that the unit of activity is unique and can not be compared with any other BTA. In scientific publications one can find many details concerning the equivalence doses of onabotulinumtoxin A (botox) and abobotulinumtoxin A (dysport) and the ratio of units varies from 1:1 to 1:11. However, according to clinical guidelines, systematic reviews and high quality research evidence of recent years, the ratio of units of abobotulinumtoxin A (dysport) and onabotulinumtoxin A (botox) is 3(2,5):1. Use of a fixed ratio of units is possible only when switching from one drug to another or in case of limiting access to specific drug. Botulinum toxin type A is the first line of therapy in the treatment of several neurological diseases. The most commonly used drugs of botulinum toxin type A (botox, dysport, xeomin) have a significant evidence base that confirms their efficacy and optimal safety profile. The main difference between botulinum toxin type A is their potential activity of action, i.e., activity units and total therapeutic dose.


Imaging cells on polymer spherulites.
Polymers are commonly used to construct tissue-engineered medical products and the conditions used to process these polymeric materials can affect their biological performance. For semi-crystalline polymers, thermal processing conditions can induce crystallization of the polymer chains into spherulites, which cause the polymer surface to become roughened. This change in surface topology can influence cell behaviours such as adhesion, morphology and proliferation. Herein, a simple microscope technique is presented, which combines fluorescence microscopy with transmitted white light microscopy using crossed polarizers. This technique allows simultaneous imaging of cells and polymer spherulites, which enables the biomaterials researcher to observe the effects of spherulites on cell alignment and morphology.


Pro-gastrin-releasing peptide (31-98) as a tumour marker of small-cell lung cancer: comparative evaluation with neuron-specific enolase.
We attempted to clarify whether serum levels of a carboxy-terminal fragment of ProGRP, ProGRP(31-98), could serve as a more accurate tumour marker in patients with SCLC than neuron-specific enolase (NSE). ProGRP(31-98) and NSE were measured retrospectively in 101 newly diagnosed untreated patients with SCLC, 111 with non-small-cell lung cancer (NSCLC) and 114 patients with non-malignant lung diseases. ProGRP(31-98) and NSE levels were determined using a sandwich enzyme-linked immunosorbent assay. Sensitivity in SCLC patients was 72.3% for ProGRP(31-98) and 62.4% for NSE. Comparing the area under curve (AUC) of 'receiver operator characteristics' of ProGRP(31-98) with that of NSE, ProGRP(31-98) was the more powerful marker in the diagnosis of SCLC (P = 0.0001). Serum levels of ProGRP(31-98) were higher in the 40 patients with extensive disease than in the 61 patients with limited disease (P = 0.0082). ProGRP(31-98) was significantly higher in patients with pure small-cell carcinoma than in patients with mixed small-cell/large-cell carcinoma (P = 0.02). In serial measurement in 16 patients responding to treatment, a high degree of correlation was noted between the decrease in serum ProGRP(31-98) levels and clinical response during the second week after treatment (P = 0.0045). These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.


Predicting biodegradation products and pathways: a hybrid knowledge- and machine learning-based approach.
Current methods for the prediction of biodegradation products and pathways of organic environmental pollutants either do not take into account domain knowledge or do not provide probability estimates. In this article, we propose a hybrid knowledge- and machine learning-based approach to overcome these limitations in the context of the University of Minnesota Pathway Prediction System (UM-PPS). The proposed solution performs relative reasoning in a machine learning framework, and obtains one probability estimate for each biotransformation rule of the system. As the application of a rule then depends on a threshold for the probability estimate, the trade-off between recall (sensitivity) and precision (selectivity) can be addressed and leveraged in practice. Results from leave-one-out cross-validation show that a recall and precision of approximately 0.8 can be achieved for a subset of 13 transformation rules. Therefore, it is possible to optimize precision without compromising recall. We are currently integrating the results into an experimental version of the UM-PPS server. The program is freely available on the web at http://wwwkramer.in.tum.de/research/applications/biodegradation/data. email@example.com.


Male contraception: where are we going and where have we been?
Progress in developing new reversible male contraception has been slow. While the hormonal approach has been clearly shown to be capable of providing effective and reversible contraception, there remains no product available. Currently, trials of a self-administered gel combination of testosterone and the progestogen Nestorone® are under way, complementing the largely injectable methods previously investigated. Novel long-acting steroids with both androgenic and progestogenic activity are also in early clinical trials. The non-hormonal approach offers potential advantages, with potential sites of action on spermatogenesis, and sperm maturation in the epididymis or at the vas, but remains in preclinical testing. Surveys indicate the willingness of men, and their partners, to use a new male method, but they continue to lack that opportunity.


Anterolateral Meniscofemoral Ligament of the Lateral Meniscus.
Anatomical variations of the meniscus are a common anomaly that knee surgeons frequently encounter. However, anomalies of the anterior horn of the lateral meniscus (AHLM) are extremely rare. In this report, we present a newly discovered anomaly of the AHML: an anterolateral meniscofemoral ligament is described with clinical features and radiographic and arthroscopic findings.


Suvorexant for the treatment of insomnia.
Suvorexant (Belsorma(®)) is the first orexin receptor antagonist approved by the US FDA (August 2014) for insomnia treatment. Following comprehensive Phase II/III studies, with up to 12 months of treatment in adult and elderly patients, there is little doubt that suvorexant induces and maintains sleep. However, the FDA and sponsor disagreed about effective versus safe doses (November 2012). The FDA considered that 5-15 mg were efficient and probably safe, whereas the sponsors had proposed 15-40 mg. The final approved doses are 5, 10, 15 and 20 mg. The major issues are next-morning somnolence and safety as seen in driving tests, with possible signs of muscle weakness, weird dreams, sleep walking, other nighttime behaviors and suicidal ideation. Despite its limitations, suvorexant's market entry offers a truly novel treatment for insomnia, paving the way for follow-up compounds and opening therapeutic avenues in other disorders for orexin receptor modulating compounds.


Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group.
Ki67 is an important biomarker with prognostic and potential predictive value in breast cancer. However, the lack of standardization hinders its clinical applicability. In this study, we aimed to investigate the reproducibility among pathologists following the guidelines of the International Ki67 in Breast Cancer Working Group (IKWG) for Ki67 scoring and to evaluate the prognostic potential of this platform in an independent cohort. Four algorithms were independently built by four pathologists based on our study cohort using an open-source digital image analysis (DIA) platform (QuPath) following the detailed guideline of the IKWG. The algorithms were applied on an ER+ breast cancer study cohort of 157 patients with 15 years of follow-up. The reference Ki67 score was obtained by a DIA algorithm trained on a subset of the study cohort. Intraclass correlation coefficient (ICC) was used to measure reproducibility. High interobserver reliability was reached with an ICC of 0.938 (CI: 0.920-0.952) among the algorithms and the reference standard. Comparing each machine-read score against relapse-free survival, the hazard ratios were similar (2.593-4.165) and showed independent prognostic potential (p ≤ 0.018, for all comparisons). In conclusion, we demonstrate high reproducibility and independent prognostic potential using the IKWG DIA instructions to score Ki67 in breast cancer. A prospective study is needed to assess the clinical utility of the IKWG DIA Ki67 instructions.


Interaction study of a lysozyme-binding aptamer with mono- and divalent cations by ACE.
Binding between an aptamer and its target is highly dependent on the conformation of the aptamer molecule, this latter seeming to be affected by a variety of cations. As only a few studies have reported on the interactions of monovalent or divalent cations with aptamers, we describe herein the use of ACE in its mobility shift format for investigating interactions between various monovalent (Na+, K+, Cs+ or divalent (Mg2+, Ca2+, Ba2+) cations and a 30-mer lysozyme-binding aptamer. This study was performed in BGEs of different natures (phosphate and MOPS buffers) and ionic strengths. First, the effective charges of the aptamer in 30 mM ionic strength phosphate and MOPS (pH 7.0) were estimated to be 7.4 and 3.6, respectively. Then, corrections for ionic strength and counterion condensation effects were performed for all studies. The effective mobility shift was attributed not only to these effects, but also to a possible interaction with the buffer components (binary or ternary complexes) as well as possible conformational changes of the aptamer. Finally, apparent binding constants were calculated for divalent cations with mathematical linearization methods, and the influence of the nature of the BGE was evidenced.


[Pyothorax due to ruptured lung abscess successfully treaed by video-assisted thoracic surgery; report of a case].
A 30-year-old female was admitted to our hospital for chest pain and dyspnea We diagnosed lung abscess of the left lung. On day 2, the patient required mechanical ventilation for pneumopyothorax due to ruptured lung abscess with acute respiratory distress syndrome. We managed this patient antibiotics, sivelestat sodium hydrate and steroid pulse therapy. Curettage and decortication for empyema cavity and closure of bronchopleural fistula was done under video-assisted thoracic surgery with minithoracotomy on day 17. Postoperative course was uneventful.


MicroRNA-214-3p inhibits the stem-like properties of lung squamous cell cancer by targeting YAP1.
Emerging evidence reveals that microRNAs (miRNAs) play a crucial role in tumor progression, but the underlying mechanism of microRNAs in lung squamous cell cancer (LSCC) remains unclear. Western-blotting and quantitative real-time PCR (q-PCR) were carried out to detect mRNA and protein expression. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8), colony-forming assay or sphere-forming assay, respectively. MiR-214-3p was markedly de-regulated in LSCC tissues and was inversely related to the level of Yes-associated protein1 (YAP1), which is the core transcription regulator of the Hippo signaling pathway. Kaplan-Meier survival curves illustrated that patients with high miR-214-3p expression demonstrated more favorable clinical outcomes. MiR-214-3p overexpression (OE) repressed proliferation and cancer stem-like cells (CSCs) properties in vitro and in vivo xenograft mouse model. Mechanistically, luciferase activity assay revealed that miR-214-3p directly targets YAP1 by specifically binding on the 3' UTR of YAP1. MiR-214-3p plays a pivotal role in CSCs properties by targeting YAP1, which provides a potential treatment strategy for LSCC patients.


Architectural and catalytic aspects of designer materials built using metalloligands of pyridine-2,6-dicarboxamide based ligands.
This perspective presents the design, synthesis and crystal structures of a large number of architectures constructed using assorted metalloligands of pyridine-2,6-dicarboxamide based ligands. The metalloligands offered various appended functional groups, whereas design strategies included varying both their position and number. A combination of these parameters resulted in the development of assorted architectures including discrete trinuclear and tetranuclear complexes as well as 1D/2D/3D coordination polymers. The metalloligand strategy not only assisted in the construction of ordered crystalline materials with varied dimensionalities but also judiciously allowed the incorporation of Lewis acidic and redox-active secondary metals in the resultant architectures. As a result, such designer architectures illustrated their noteworthy role both as homogenous and heterogeneous catalysts in different organic transformation reactions.


An evaluation of beta-hydroxybutyrate in milk and blood for prediction of subclinical ketosis in dairy cows.
The first objective of this study was to investigate the relationship between concentrations of beta-hydroxybutyrate (BHBA) in milk and blood to assess the reliability of the BHBA concentrations in milk measured by a semi quantitative keto-test paper to detect subclinical ketosis (SCK) in 50 fresh high-producing Iranian Holstein cows in Golestan Province, Iran. The second objective was the effects of SCK on milk yield and components. Concentrations of nonesterified fatty acids (NEFA) and BHBA were analyzed quantitatively in blood plasma and commercial keto-test paper was used for semi quantitative determination of BHBA concentration in milk. Milk yield was measured until 60 d after calving but milk compositions were measured until 30 d after calving. The mean plasma BHBA, milk BHBA, plasma NEFA, milk yield, milk fat percentage and milk fat: protein ratio were 1,234 micromol/L, 145 micromol/L, 0.482 mEq/L, 29.5 kg, 3.9% and 1.4, respectively. Fifty eight percent of the cows had SCK during the first month of lactation. High correlation coefficients were observed between blood BHBA and blood NEFA, and between blood and milk BHBA. The milk yield of cattle with SCK decreased (P < 0.01) but the fat percentage and milk fat: protein ratio increased (P < 0.01). The commercial keto-test paper used had a low false positive result at a cut-off point of 200 fmol of BHBA/L of milk. The results showed that the best time to assess SCK using the commercial keto-test paper was d 10, 14 and 17 after calving.


Minor gait impairment despite white matter damage in pure small vessel disease.
Gait impairment is common in patients with cerebral small vessel disease (SVD). However, gait studies in elderly SVD patients might be confounded by age-related comorbidities, such as polyneuropathy or sarcopenia. We therefore studied young patients with the genetically defined SVD CADASIL. Our aim was to examine the effects of pure SVD on single and dual task gait, and to investigate associations of gait performance with cognitive deficits and white matter alterations. We investigated single task walking and calculatory, semantic, or motoric dual task costs in 39 CADASIL patients (mean age 50 ± 8) using a computerized walkway. We obtained 3.0T MRI and neuropsychological data on processing speed, the main cognitive deficit in CADASIL. Spatiotemporal gait parameters were standardized based on data from 192 healthy controls. Associations between white matter integrity, assessed by diffusion tensor imaging, and gait were analyzed using both a global marker and voxel-wise analysis. Compared to controls, CADASIL patients showed only mild single task gait impairment, and only in the rhythm domain. The semantic dual task additionally uncovered mild deficits in the pace domain. Processing speed was not associated with gait. White matter alterations were related to single task stride length but not to dual task performance. Despite severe disease burden, gait performance in patients with pure small vessel disease was relatively preserved in single and dual tasks. Results suggest that age-related pathologies other than small vessel disease might play a role for gait impairment in elderly SVD patients.


Impaired proteostasis in obese skeletal muscle relates to altered immunoproteasome activity.
Obesity-associated inflammation and/or oxidative stress can damage intramuscular proteins and jeopardize muscle integrity. The immunoproteasome (iProt) is vital to remove oxidatively modified proteins, but this function may be compromised with obesity. We sought to elucidate whether diet-induced obesity alters intramuscular iProt content and activity in mice to identify a possible mechanism for impaired muscle proteostasis in the obese state. Total proteasome content and activity and estimates of muscle oxidative damage, inflammation, muscle mass and strength were also assessed. Twenty-three male, 5-week-old C57BL/6J mice were fed a high-fat, high-sucrose (HFS; 45% kcal fat, 17% sucrose, n = 12) or low-fat, low-sucrose (LFS; 10% kcal fat, 0% sucrose, n = 11) diet for 12 weeks. Strength was assessed via a weightlifting test. Despite no change in pro-inflammatory cytokines (P > 0.05), oxidative protein damage was elevated within the gastrocnemius (P = 0.036) and tibialis anterior (P = 0.033) muscles of HFS-fed mice. Intramuscular protein damage coincided with reduced iProt and total proteasome activity (P < 0.05), and reductions in relative muscle mass (P < 0.001). Therefore, proteasome dysregulation occurs in obese muscle and may be a critical link in muscle oxidative stress. Novelty: Our results show for the first time that immunoproteasome and total proteasome function is significantly reduced within obese muscle. Visceral fat mass is a significant predictor of diminished proteasome activity in skeletal muscle. Proteasome function is inversely correlated with an intramuscular accumulation of oxidatively damaged proteins.


Casein kinase II is a major protein phosphorylating activity in the nuclei of Xenopus laevis oocytes.
The nuclei of Xenopus laevis oocytes contain kinases capable of phosphorylating endogenous and exogenous proteins using either ATP or GTP as phosphoryl donors. These enzymes are much more active with casein and phosvitin as substrates than with histones or protamines. The protein phosphorylating activity of oocyte nuclear extracts is not regulated by cyclic nucleotides, phorbol esters, calmodulin and calcium, or phospholipids. However, the casein phosphorylating activity can be greatly enhanced by the polyamines spermine or spermidine and drastically inhibited by heparin. Fractionation of the nuclear casein kinase activities by DEAE-Sephadex chromatography and glycerol gradient centrifugation indicate that the nuclei contain enzymes with the properties of casein kinases I and II as characterized in other species. Oocyte casein kinase I (Mr 37,000) is specific for ATP as phosphoryl donor, is only slightly inhibited by 10 micrograms/ml heparin, and is not significantly stimulated by polyamines. Casein kinase II (Mr 135,000) can use both ATP and GTP as substrates, and is very sensitive to heparin inhibition and polyamine stimulation. The fact that low concentrations of heparin (10 micrograms/ml) can inhibit a large percentage of the endogenous phosphorylation of nuclear extracts or of whole nuclei indicates that casein kinase II is probably the major protein phosphorylating activity of these oocyte organelles.


Aplastic anemia in Down's syndrome.
A child with Down's syndrome was seen with pancytopenia and was found to have an aplastic bone marrow. None of the known contributing etiologies of aplastic anemia could be identified in this patient. This is the first reported case of the simultaneous appearance of these two disorders.


Nutrition education in medical school: the case of international medical students in China.
To assess the knowledge on country-specific nutrition situation, perceptions of the nutrition curricula and factors influencing capacity to offer nutrition guidance among medical students studying internationally in China compared with their home-country counterparts. Cross-sectional study. China, Ghana, India and Montenegro. International medical students in China and medical students studying in their home countries of Ghana, India and Montenegro. An online semistructured questionnaire was administered using WeChat for international students and Microsoft Forms for home-country medical students to assess students' perceived knowledge and significance of nutrition, knowledge of country-specific nutrition situation, perceptions of the nutrition curricula and perceived capacity to offer nutrition counselling. In all, 190 medical students responded to the survey: 110 international students studying in China and 80 home-country students from Ghana (40), India (20) and Montenegro (20). Home-country students rated the importance of nutrition in health and disease development higher than international students (p<0.05). International students reported not having any specific nutrition courses while home-country students had nutrition courses as part of their curriculum. Only 8.2% of international students and 13.8% of home-country students were able to correctly mention any specific national nutrition guidelines of their home countries. Home-country students were more likely to provide correct nutrition recommendations for infants (χ²(3)=26.349; p=0.001), pregnancy (χ²(3)=9.793; p=0.007), lactating mothers (χ²(3)=9.112; p=0.011), diabetes (χ²(3)=13.619; p=0.001), hypertension (χ²(3)=12.022; p=0.002), overweight/obesity (χ²(3)=8.896; p=0.012) and undernutrition (χ²(3)=7.670; p=0.022) compared with international students. Practical nutrition courses, hours of nutrition education and how often students were asked nutrition-related questions tended to affect and predict the adequacy of nutrition education received and the perceived confidence for nutrition counselling. International medical students in China are less familiar with the nutrition context in their respective home countries compared with their home-country counterparts. Medical schools in China that train significant numbers of international students need to support these students to become familiar with their respective countries' nutrition contexts.


[Choroidal hemangioma with extensive retinal detachment treated with posterior vitrectomy: case report].
To describe a case of circumscribed choroidal hemangioma with extensive retinal detachment treated with vitrectomy and endolaser photocoagulation. Interventional case report. A 41-year-old female patient was examined with a 7-day history of blurred vision and progression of visual loss in the right eye in the last 2 days. Ophthalmologic examination showed 20/400 visual acuity in the right eye and an extensive retinal detachment with an elevated red lesion on the posterior pole. Ocular ultrasound showed high a reflective membranes in the vitreous cavity (retinal detachment) and an homogeneous hiperecogenic solid lesion suggestive of choroidal hemangioma. Systemic investigation showed no abnormalities. Posterior pars plana vitrectomy with endophotocoagulation and injection of C3F8 gas was performed. After 15 days, an inferior retinal detachment was observed and the patient was submitted to a second vitrectomy with endophotocoagulation and silicon oil implant. After six months, the retina remains attached and the hemangioma shows no signs of exudation. Visual acuity remains 20/400. Posterior vitrectomy appears as an option for the treatment of circumscribed choroidal hemangiomas with extensive retinal detachment.


Review of ecotoxicological studies of widely used polystyrene nanoparticles.
With polystyrene nanoparticles being widely used in various applications, there is a great need for deeper knowledge on the safety, fate and biological effects of these particles on both individual living organisms and the whole ecosystems. Due to this, there is a growing interest in performing ecotoxicological studies using model plastic nanoparticles, and consequently it generates an increasing number of published papers describing the negative impact on wildlife caused by such nanoparticles. Polystyrene is the most studied nanosized plastic, therefore this review focuses on research conducted with manufactured polystyrene nanoparticles. The aim of the present article is to provide a critical methodological outline of the existing ecotoxicological studies on the effects of polystyrene nanoparticles on aquatic organisms. Going through the published articles, we noted that particle characterization especially in the test medium, can be improved. The analysis also highlights the importance of purifying the polystyrene nanoparticles before studying its toxicity. Furthermore, the size characterization of such nanoparticles is underemphasized, and in future studies, authors should consider including more techniques to achieve this goal. Finally, short-term or direct exposure scenarios do not add the most environmentally relevant knowledge in terms of the toxicity caused by polystyrene nanoparticles.


Increase in Penicillin and multidrug resistance in Streptococcus pneumoniae (1993-2016): Report from a tertiary care hospital laboratory, Pakistan.
To determine the trend of resistance to antimicrobials in Streptococcus pneumoniae infections, and the impact of new Clinical and Laboratory Standards Institute guidelines on 1211 among meningeal isolates. The descriptive observational retrospective study was conducted at the Aga Khan University Hospital laboratory in Karachi, and comprised Streptococcus pneumoniae isolation and antimicrobial susceptibility data over a period of 24 years, from 1993 to 2016, which was compared in terms of pre-2008 and post-2008 data, which was analysed using SPSS 19. Of the 7415 non-duplicate isolates identified, 4700(63.4%) were from male patients and 2,715(36.6%) were from female patients. The overall mean age of the patients was 38±27 years. Penicillin resistance in non-meningeal isolates during the two periods was not significantly different (p>0.05), but a significant rise in penicillin resistance in meningeal isolates was observed in the second period (p<0.05). High resistance rates were observed for co-trimoxazole, tetracycline and erythromycin, and an increased trend of multi-drug resistant strains was also noted from 1999 {n=35/317(11%)} to 2016 {n=110/314 (36%)}. The emergence of multi-drug resistant strains was evident. The spike in penicillin-resistant Streptococcus pneumoniae in meningeal isolates may have been due to the revised guidelines by the Clinical and Laboratory Standards Institute.


Type II Achalasia Is Increasing in Prevalence.
Three manometric subtypes of achalasia were defined in the Chicago Classification approximately 10 years ago: type I (aperistalsis), type II (pan-pressurization), and type III (spastic). Since the widespread use of this classification scheme, the evolving prevalence of these subtypes has not been elucidated. We aim to determine the prevalence of each subtype a decade after the adoption of the Chicago Classification. This is a retrospective cohort analysis of patients diagnosed with achalasia on high-resolution manometry (HRM) at two major academic medical centers between 2015 and 2018. Patients were excluded if they had a diagnosis of another esophageal motility disorder, previously treated achalasia, or foregut surgery. Demographic data, manometric subtype, and esophageal dilatation grade on endoscopy were obtained. Prevalence of achalasia subtypes was compared with a published historical control population (2004-2007). Fischer's exact and t tests were used for analysis. Of 147 patients in the contemporary cohort and 99 in the historical control cohort, the prevalence of type I achalasia was 8% versus 21%, type II 63% versus 50%, and type III 29% versus 29%, respectively (p = 0.01). The mean age in our population was 58 years compared to 57 years in the historical control, and the proportion of men 48% versus 47%, respectively (p = 0.78). Mean endoscopic dilatation grade in the contemporary cohort was 1.5 for type I patients, 0.9 for type II, and 0.4 for type III, compared with 1.5, 0.6, and 0.4, respectively. Overall mean dilatation grade was 0.8 in our cohort versus 0.7 in the historical control (p = 0.58). The prevalence of type II achalasia was significantly greater and prevalence of type I significantly less in our patient population compared to our predefined historical control. Other characteristics such as age and sex did not appear to contribute to these differences. Histopathological evidence has suggested that type II achalasia may be an earlier form of type I; thus, the increased prevalence of type II achalasia may be related to earlier detection of the disease. The adoption of HRM, widespread use of the Chicago Classification, and increased disease awareness in the past decade may be contributing to these changes in epidemiology.


Applying a WASH Risk Assessment Tool in a Rural South African Setting to Identify Risks and Opportunities for Climate Resilient Communities.
Climate change threatens the health and well-being of populations. We conducted a risk assessment of two climate-related variables (i.e., temperature and rainfall) and associated water, sanitation and hygiene (WASH)-related exposures and vulnerabilities for people living in Mopani District, Limpopo province, South Africa. Primary and secondary data were applied in a qualitative and quantitative assessment to generate classifications of risk (i.e., low, medium, or high) for components of hazard/threat, human exposure, and human vulnerability. Climate-related threats were likely to impact human health due to the relatively high risk of waterborne diseases and WASH-associated pathogens. Vulnerabilities that increased the susceptibility of the population to these adverse outcomes included environmental, human, physical infrastructure, and political and institutional elements. People of low socio-economic status were found to be least likely to cope with changes in these hazards. By identifying and assessing the risk to sanitation services and water supply, evidence exists to inform actions of government and WASH sector partners. This evidence should also be used to guide disaster risk reduction, and climate change and human health adaptation planning.


One-dimensional western blotting coupled to LC-MS/MS analysis to identify chemical-adducted proteins in rat urine.
The environmental toxicant hydroquinone (HQ) and its glutathione conjugates (GSHQs) cause renal cell necrosis via a combination of redox cycling and the covalent adduction of proteins within the S₃ segment of the renal proximal tubules in the outer stripe of the outer medulla (OSOM). Following administration of 2-(glutathion-S-yl)HQ (MGHQ) (400 μmol/kg, i.v., 2 h) to Long Evans (wild-type Eker) rats, Western analysis utilizing an antibody specific for quinol-thioether metabolites of HQ revealed the presence of large amounts of chemical-protein adducts in both the OSOM and urine. By aligning the Western blot film with a parallel gel stained for protein, we can isolate the adducted proteins for LC-MS/MS analysis. Subsequent database searching can identify the specific site(s) of chemical adduction within these proteins. Finally, a combination of software programs can validate the identity of the adducted peptides. The site-specific identification of covalently adducted and oxidized proteins is a prerequisite for understanding the biological significance of chemical-induced posttranslational modifications (PTMs) and their toxicological significance.


Within- and between-person effects of naltrexone on the subjective response to alcohol and craving: A daily diary investigation.
Naltrexone is an effective treatment for heavy drinking among young adults. Laboratory-based studies have shown that naltrexone dampens the subjective response to alcohol and craving. However, few studies have tested naltrexone's dynamic, within-person effects on subjective response and craving among young adults in natural drinking environments. Using daily diary data from a randomized, placebo-controlled study of naltrexone's efficacy in young adults, we examined the between-person effects of treatment condition (i.e., naltrexone vs. placebo) and medication dosage (i.e., daily, targeted, and daily + targeted) on the subjective response to alcohol and craving on drinking days. Multilevel mediation models predicted subjective response and craving from treatment condition (between-person) and medication dosage (within-person), accounting for drinking levels. All effects were disaggregated within and between persons. At the between-person level, naltrexone directly blunted intense subjective effects (i.e., "impaired", "drunk") and indirectly blunted subjective effects through reduced drinking. Naltrexone was not associated with craving. Between-person effects were not significant after alpha correction, but their effect sizes (bs = 0.14 to 0.17) exceeded the smallest effect size of interest. At the within-person level, taking two (vs. 1) pills was associated with heavier drinking, and taking one (vs. 0) pill was associated with lighter drinking, and lighter drinking was associated with a lower subjective response and craving. Treatment condition did not moderate the within-person effects of dosing on outcomes. Our findings suggest that the direct between-person effect of naltrexone was largest on intense subjective responses, blunting feelings of being "drunk" and "impaired". Future research using momentary (rather than daily) assessments could confirm and extend these findings.


Closure of the soft palate for persistent otorrhea after placement of pressure equalization tubes in cleft palate infants.
Four case reports of infants with cleft palate and intractable otorrhea following the placement of pressure equalization tubes are presented. In one patient, liquids taken orally were noted to reflux through her ears. Otorrhea was refractory to medical management in all cases and was controlled only after closure of the soft palate. Persistent otorrhea may be an indication for early closure of the soft palate in these infants.


Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3.
The role of cerebrospinal fluid (CSF) in the pathogenesis of meningiomas is unknown. Cell cultures from three human leptomeninges, five WHO grade I and seven grade II meningiomas were treated with remnant CSF from 22 patients with no central nervous system disease and normal cell indices. Cells were evaluated by CyQUANT for DNA synthesis/cell proliferation and by western blots for phosphorylation/activation of growth regulatory pathways activated in meningiomas including JAK1-STAT3, MEK1-p44/42MAPK, Akt-mTOR and Rb. Analysis of Caspase 3 activation and survivin was also performed. Finally, the effects of PDGF neutralizing antibody and cucurbitacin, a STAT3 inhibitor on CSF stimulation were tested. Compared to controls and the mitogen PDGF-BB, various CSF samples significantly stimulated DNA synthesis/cell proliferation in 20 and 22 week leptomeningeal cultures and all of the grade I and II meningioma cells tested. Collectively CSF samples, from multiple different patients, stimulated DNA synthesis in tests of 23 of 32 grade I and 18 of 28 grade II meningioma cells. CSF stimulated phosphorylation/activation of STAT3 and reduced p44/42 MAPK in the leptomeningeal, all three grade I and 1 of three grade II meningioma cells. CSF did not affect Caspase 3 activity or survivin levels. PDGF neutralizing antibody had no effect on CSF stimulation but cucurbitacin blocked PDGF and CSF stimulation. While there are limitations to the CSF available since they were not from "normal" volunteers, the studies suggest that, in some settings, CSF is potentially mitogenic to leptomeningeal and meningioma cells and may act, in part, via activation of STAT3.


Association Between the Simplest Clinical Factors and Emergency Department Dispositions: A Retrospective Observational Study.
The emergency department (ED) is a complex and busy environment that requires rapid decision making. We assessed the relationship between disposition from the ED and information that can be obtained at a glance in the ED. The presentation of the implications of commonplace information could assist healthcare providers in ensuring smooth and safe ED care. Thus, we aimed to quantitatively assess how readily obtainable findings, such as age, sex, and vital signs, are involved in the disposition of adult patients transferred to the ED. This retrospective observational study was conducted in the ED of a regional university hospital containing approximately 600 beds. Of the 685 patients included in the analysis, 351 patients were admitted to the hospital (including 12 deaths in the ED) and 334 patients were discharged from the ED. A multiple logistic regression model that included age, sex, systolic blood pressure, heart rate, respiration rate, temperature, and SpO2 as variables identified independent associations between age (p=0.003), sex (p<0.001), systolic blood pressure (p=0.023), heart rate (p<0.001), and respiratory rate (p=0.028) and admission from the ED. The receiver operating characteristic curves drawn from the multiple logistic regression model comprising these five variables had an area under the curve (AUC) of 0.701 (95% confidence interval: 0.657-0.744, p<0.001). Examination of sensitivity, specificity, and likelihood ratios (LRs) for these five variables for clinical utility showed a slightly higher sensitivity for age ≥50 years (0.849) and respiratory rate ≥18 bpm (0.769); higher specificity for systolic blood pressure ≤100 mmHg (0.938), pulse rate ≥100 bpm (0.834), and respiratory rate ≥26 bpm (0.887); higher positive LR for systolic blood pressure ≤100 mmHg (2.039) and pulse rate ≥110 bpm (2.729); and slightly lower negative LR for age ≥50 years (0.656), male sex (0.647), respiratory rate ≥20 bpm (0.669). These results are meaningful as they quantify the intuition of a skilled clinician, which can help in clinical decision making, reduce errors, and promote clinical education. Our study provides a basis for explaining to novice healthcare providers that the careful observation of ED patients, even in the absence of special laboratory tests, can help them to make judgments regarding the disposition of the patients from the ED. In conclusion, age, sex, systolic blood pressure, heart rate, and respiratory rate were independently associated with a disposition from the ED. A multivariate model including these five variables showed the moderate-quality potential to predict admission from the ED. The sensitivity, specificity, and LR of systolic blood pressure, heart rate, and respiratory rate showed the characteristics of each vital sign. These provide healthcare providers in the ED an immediate clue regarding the patient's illness.


A social-ecological assessment and feedback-intervention of an adolescent treatment agency.
This research project examined the utility of one of Moos's Social Ecology Scales as applied to a community-based, adolescent treatment facility. Real and Ideal forms of the Community Oriented Program Environment Scale (COPES) were administered to the staff and clients at two separate facilities of the same adolescent service agency. Comparisons of the social ecological profiles of the two facilities revealed anticipated differences in the perceived levels of administrative order and control. Perceptions of the environment, however, were not found to correlate with independent measures of satisfaction or with individual-difference variables. Feedback of the survey findings to the staff members provided them with useful insights in changing program activities. These findings are discussed in light of the extant literature on the use of survey-feedback designs within organizational settings. Suggestions for future research in adolescent treatment environments are offered.


[Carinal Resection with Lung Resection and Perioperative Management].
Carinal resection with lung resection is a rare surgical procedure with high risk. In-hospital mortality rates for carinal reconstruction and sleeve pneumonectomy were 6.5% and 16.7%, respectively. Thus, thoracic surgeons need to learn the procedure for patients who need the surgery. This time, we will account for preoperative evaluation, intraoperative advice, and postoperative management in carinal resection with right upper lobectomy presenting 2 cases in our hospital. Case 1 had a high caliber mismatch of bronchial stumps because of partial carinal resection, which was corrected by simple sutures of the anterior cartilage. That allowed us to perform sleeve right upper lobectomy avoiding carinal reconstruction. Case 2 was a case in which lung and bronchial tissue sticking to mediastinum due to obstructive pneumonia prevented us from anastomosing intermediate bronchus to the trachea or left main bronchus. We had to choose sleeve right pneumonectomy, and a fistula on the anastomotic site occurred later resulting in a bad course. We hope our experiences aid future patients who need the carinal resection.


A Cross-Sectional Study of the Associations between Chronotype, Social Jetlag and Subjective Sleep Quality in Healthy Adults.
Social jetlag, a mismatch between internal biological time and social schedules, and a later timing of the midpoint of sleep on work-free days as an indicator of the circadian phase of entrainment (late chronotype), may be factors associated with poor quality sleep. This study examined the association of social jetlag and chronotype with subjective sleep quality ratings in a healthy young adult cohort and interrogated the moderating effects of sex and age on these associations. A total of 1322 participants aged 18 to 40 completed the Pittsburg Sleep Quality Index (PSQI) and the Munich Chronotype Questionnaire. Later timing of midsleep on "free" days (an indicator of chronotype) had a small-to-medium association with poorer subjective sleep quality, independently of sex and age (rho = 0.212, P < 0.001). Greater social jetlag had a small association with poorer subjective sleep quality ratings (rho = 0.077), and this effect was moderated by sex with there being a relationship between social jetlag and sleep quality only in males. Social jetlag did not mediate the relationship between chronotype and sleep quality. These results indicate differential relationships of the chronotype and social jetlag with subjective sleep quality and indicate that sex is a moderating factor for sleep quality's relationship with social jetlag, but not for the association between sleep quality and chronotype.


Is the PASAT past it? Testing attention and concentration without numbers.
The Paced Auditory Serial Addition Task (PASAT) is a test of attention and concentration in which participants add each number from a taped list to the one preceding it (Gronwall & Wrightson, 1974). As it requires mental addition at an externally determined pace the task often causes anxiety (Roman, Edwall, Buchanan, & Patton 1991). We devised the Paced Auditory Serial Opposites Task (PASOT) as a nonnumerical replacement (Deary, 2001). PASOT AND PASAT were administered to 40 participants, and the correlation between them was .71. The correlations of the PASOT and other cognitive measures did not differ significantly from those of the PASAT (with the exception of the Digit Span Backward). Performing the PASOT was significantly less aversive; teh PASAT induced more negative feelings of Tense Arousal (t38 = -4.52, p < .001).


Involving seldom-heard groups in a PPI process to inform the design of a proposed trial on the use of probiotics to prevent preterm birth: a case study.
When designing clinical trials it is important to involve members of the public, who can provide a view on what may encourage or prevent people participating and on what matters to them. This is known as Public and Patient Involvement (PPI). People from minority ethnic groups are often less likely to take part in clinical trials, but it is important to ensure they are able to participate fully so that health research and its findings are relevant to a wide population. We are preparing to conduct a randomised controlled trial (RCT) to test whether taking probiotic capsules can play a role in preventing preterm birth. Women from some minority ethnic groups, for example women from West Africa, and those who are from low-income groups are more likely to suffer preterm births. Preterm birth can lead to extra costs to health services and psychosocial costs for families. In this article we describe how we engaged women in discussion about the design of the planned trial, and how we aim to use our findings to ensure the trial is workable and beneficial to women, as well as to further engage service users in the future development of the trial. Four socially and ethnically diverse groups of women in East London took part in discussions about the trial and contributed their ideas and concerns. These discussions have helped to inform and improve the design of a small practice or 'pilot' trial to test the recruitment in a 'real life' setting, as well as encourage further PPI involvement for the future full-scale trial. Background Patient and public involvement (PPI) is an important tool in approaching research challenges. However, involvement of socially and ethnically diverse populations remains limited and practitioners need effective methods of involving a broad section of the population in planning and designing research. Methods In preparation for the development of a pilot randomised controlled trial (RCT) on the use of probiotics to prevent preterm birth, we conducted a public consultation exercise in a socially disadvantaged and ethnically diverse community. The consultation aimed to meet and engage local service users in considering the acceptability of the proposed protocol, and to encourage their participation in future and ongoing patient and public involvement activities. Four discussion groups were held in the community with mothers of young children within the proposed trial region, using an inclusive approach that incorporated a modified version of the Nominal Group Technique (NGT). Bringing the consultation to the community supported the involvement of often seldom-heard participants, such as those from minority ethnic groups. Results The women involved expressed a number of concerns about the proposed protocol, including adherence to the probiotic supplement regimen and randomisation. The proposal for the RCT in itself was perceived as confirmation that probiotic supplements had potentially beneficial effects, but also that they had potentially harmful side-effects. The complexity of the women's responses provided greater insights into the challenges of even quite simple trial designs and enabled the research team to take these concerns into account while planning the pilot trial. Conclusions The use of the NGT method allowed for a consultation of a population traditionally less likely to participate in medical research. A carefully facilitated PPI exercise can allow members to express unanticipated concerns that may not have been elicited by a survey method. Findings from such exercises can be utilised to improve clinical trial design, provide insight into the feasibility of trials, and enable engagement of often excluded population groups.


Impact of ventilator-associated pneumonia on mortality and epidemiological features of patients with secondary peritonitis.
Despite the significant impact of nosocomial infections on the morbidity and mortality of patients staying in the intensive care unit (ICU), no study over the past 20 years has focused specifically on VAP following secondary peritonitis. The objective of the present study was to determine in-hospital mortality and epidemiological features attributed to ventilator-associated pneumonia (VAP) following secondary peritonitis. Prospective observational study involved 418 consecutive patients admitted in the ICU. Univariate and multivariate analyses were performed to identify risk factors associated with mortality and development of VAP. The incidence of VAP following secondary peritonitis was 9.6 %. Risk factors associated with the development of VAP were hospital-acquired peritonitis, requiring >48 h of mechanical ventilation, and SOFA score. The onset of VAP was late in majority of patients. VAP was developed about 16.8 days after the initiation of the peritonitis. Etiological microorganisms responsible for the peritonitis were different than for VAP. The 90-day in-hospital mortality rate was 47.5 % of VAP patients. Independent factors associated with 30- to 90-day in-hospital mortality were VAP and SOFA. In light of the impact on morbidity and mortality in the ICU, more attention should be given to the concurrent features among VAP and secondary peritonitis.


Resistance to Aflatoxin Accumulation in Maize Mediated by Host-Induced Silencing of the Aspergillus flavus Alkaline Protease (alk) Gene.
Aspergillus flavus is a fungal pathogen that infects maize and produces aflatoxins. Host-Induced Gene Silencing (HIGS) has been shown to reduce host infection by various fungal pathogens. Here, the A. flavus alkaline protease (alk) gene was targeted for silencing through HIGS. An RNAi vector carrying a portion of the alk gene was incorporated into the B104 maize genome. Four out of eight transformation events containing the alk gene, Alk-3, Alk-4, Alk-7 and Alk-9, were self-pollinated to T4/T6 generations. At T3, the Alk-transgenic lines showed up to 87% reduction in aflatoxin accumulation under laboratory conditions. T4 transgenic Alk-3 and Alk-7 lines, and T5 and T6 Alk-4 and Alk-9 showed an average of 84% reduction in aflatoxin accumulation compared to their null controls under field inoculations (p < 0.05). F1 hybrids of three elite maize inbred lines and the transgenic lines also showed significant improvement in aflatoxin resistance (p < 0.006 to p < 0.045). Reduced A. flavus growth and levels of fungal ß-tubulin DNA were observed in transgenic kernels during in vitro inoculation. Alk-4 transgenic leaf and immature kernel tissues also contained about 1000-fold higher levels of alk-specific small RNAs compared to null controls, indicating that the enhanced aflatoxin resistance in the transgenic maize kernels is due to suppression of A. flavus infection through HIGS of alk gene.


A new mosaic integrative and conjugative element from Streptococcus agalactiae carrying resistance genes for chloramphenicol (catQ) and macrolides [mef(I) and erm(TR)].
To investigate the genetic basis of catQ-mediated chloramphenicol resistance in Streptococcus agalactiae. Two clinical strains of catQ-positive chloramphenicol-resistant S. agalactiae (Sag236 and Sag403) were recently isolated, typed (MLST, PFGE pulsotypes, capsular types) and their antibiotic resistances investigated by phenotypic and genotypic approaches. Several molecular methods (PCR mapping, restriction assays, Southern blotting, sequencing and sequence analysis, conjugal transfer assays) were used to determine the genetic context of catQ and characterize a genetic element detected in the isolates. Sag236 and Sag403 shared the same ST (ST19), but exhibited a different capsular type (III and V, respectively) and pulsotype. Both harboured the macrolide resistance genes mef(I) and erm(TR) and the tetracycline resistance gene tet(M). Accordingly, they were resistant to chloramphenicol, erythromycin and tetracycline. catQ and mef(I) were associated in an IQ module that was indistinguishable in Sag236 and Sag403. In mating assays, chloramphenicol and erythromycin resistance proved transferable, at low frequency, only from Sag236. Transconjugants carried not only catQ and mef(I), but also erm(TR), suggesting a linkage of the three resistance genes in a mobile element, which, though seemingly non-mobile, was also detected in Sag403. The new element (designated ICESag236, ∼110 kb) results from recombination of two integrative and conjugative elements (ICEs) originally described in different streptococcal species: S. agalactiae ICESagTR7, carrying erm(TR); and Streptococcus pneumoniae ICESpn529IQ, carrying the prototype IQ module. These findings strengthen the notion that widespread streptococcal ICEs may form mosaics that enhance their diversity and spread, broaden their host range and carry new cargo genes.


Expression of GFP using Pichia pastoris vectors with zeocin or G-418 sulphate as the primary selectable marker.
Pichia pastoris is a popular host organism for expressing heterologous proteins, and various expression vectors for this yeast are currently available. Recently, vectors containing novel dominant antibiotic resistance markers have become a strong and developing field of research for this methylotropic yeast strain. We have developed new P. pastoris expression vectors, the pPICKanMX6 and pPICKanMX6alpha series. These vectors were constructed by replacing the zeocin resistance gene of the pPICZA, B, C and pPICZalphaA, B and C vectors with the Tn903 kan(R) marker from pFA6a KanMX6, which confers G-418 sulphate resistance in P. pastoris. The limits of antibiotic resistance in two transformant yeast strains were investigated, and the selection marker was shown to be stably retained. To demonstrate their usefulness, a gene encoding hexa-histidine-tagged green fluorescent protein (GFPH6) was cloned into one of the new vectors and GFP expression examined in P. pastoris cells. The protein expression levels using the pPICKanMX6B vector were comparable with that using the original plasmid, based on zeocin resistance as seen by yeast cell fluorescence. Moreover, GFPH6 was able to be isolated by immobilized metal ion affinity chromatography (IMAC) from lysates of both yeast strains. A model reporter construct has been used to demonstrate successful recombinant protein expression and its subsequent purification using these new vectors. Corresponding vectors can now also be engineered with foreign gene expression under the control of various different promoters, to increase the flexibility of P. pastoris as a cellular factory for heterologous protein production.


Single-incision versus conventional three-incision laparoscopic appendectomy: a single centre experience.
To compare the short-term outcomes of single-incision and conventional three-incision laparoscopic appendectomy (LA) at a single surgical unit. We conducted a retrospective study comparing the operative outcomes of two LA techniques between January 2009 and November 2010. LA was performed successfully in 44 patients: through a single incision in 27 patients and through three incisions in 17 patients. The time taken to resume oral intake was slightly less in the single-incision group than in the three-incision group, at 1.1 versus 1.5 days, respectively (P = 0.0419). However, blood loss and hospital stay were not significantly different, at 7.2 versus 6.4 ml (P = 0.6244) and 3.7 versus 3.8 days (P = 0.8565), respectively. The cosmetic result was better in the single-incision group, because of the well-concealed scar. Both single-incision and conventional LA are effective and minimally invasive, and should be performed according to the experience of the surgeon. Single-incision LA results in faster recovery, but larger studies are required to confirm this and to determine if these techniques can be used safely for all indications of appendectomy.


A copper-catalyzed tandem reaction for the construction of coumarin fused 9H-pyrrolo[1,2-a]indoles.
An efficient copper-catalyzed Friedel-Crafts alkylation/cyclization/isomerization sequence of 3-arylcarbonyl coumarins and 3-methyl indole was developed to afford a wide range of functionalized coumarin fused 9H-pyrrolo[1,2-a]indoles, which feature a 6-6-5-5-6 pentacyclic core, in 34-99% yields. Moreover, gram-scale experiment and chemical transformations were conducted to demonstrate the synthetic value of this protocol.


Prediction of Late-Onset Small for Gestational Age and Fetal Growth Restriction by Fetal Biometry at 35 Weeks and Impact of Ultrasound-Delivery Interval: Comparison of Six Fetal Growth Standards.
Small-for-gestational-age (SGA) infants have been associated with increased risk of adverse perinatal outcomes (APOs). In this work, we assess the predictive ability of the ultrasound-estimated percentile weight (EPW) at 35 weeks of gestational age to predict late-onset SGA and APOs, according to six growth standards, and whether the ultrasound-delivery interval influences the detection rate. To this purpose, we analyze a retrospective cohort study of 9585 singleton pregnancies. EPWs at 35 weeks were calculated to the customized Miguel Servet University Hospital (MSUH) and Figueras standards and the non-customized MSUH, Fetal Medicine Foundation (FMF), INTERGROWTH-21st, and WHO standards. As results of our analysis, for a 10% false positive rate, the detection rates for SGA ranged between 48.9% with the customized Figueras standard (AUC 0.82) and 60.8% with the non-customized FMF standard (AUC 0.87). Detection rates to predict SGA by ultrasound-delivery interval (1-6 weeks) show higher detection rates as intervals decrease. APOs detection rates ranged from 27.0% with FMF to 7.9% with the Figueras standard. In conclusion, the ability of EPW to predict SGA at 35 weeks is good for all standards, and slightly better for non-customized standards. The APO detection rate is significantly greater for non-customized standards.


CXCL12 secreted by pancreatic stellate cells accelerates gemcitabine resistance of pancreatic cancer by enhancing glycolytic reprogramming.
Pancreatic stellate cells (PSCs) are the primary cell components of pancreatic cancer (PC) and are involved in tumor growth, metastasis and resistance. However, the role and the mechanism of PSCs in gemcitabine (GEM) resistance to PC still need more investigation. We found that CXCL12 mRNA and secreted CXCL12 protein were higher in PSCs after GEM treatment. The conditioned medium (CM) from GEM-treated PSCs reduced the GEM sensitivity of PC cells. Blocking of CXCL12 in CM by anti-CXCL12 antibody partly restored the GEM sensitivity of PC cells. Blocking of CXCL12 decreased glucose consumption, lactate production, ECAR, and glycolysis-related gene expression in PC cells. The PI3K/AKT/mTOR pathway was activated by the binding of CXCL12 and CXCR4. Moreover, CXCR4 mRNA and protein expressions in PC cells were increased after GEM treatment. Our results indicated the cross-talk between PSCs and PC cells during GEM chemotherapy. CXCL12 secreted by PSCs reduces GEM sensitivity of PC cells by binding to CXCR4 and activating PI3K/AKT/mTOR-glycolysis pathway in PC. Our findings would lay the foundation for solving GEM resistance in PC.


Respiratory syncytial virus infection enhances the response to laryngeal chemostimulation and inhibits arousal from sleep in young lambs.
To evaluate the effect of respiratory syncytial virus (RSV) infection on the response to laryngeal chemostimulation (LCS) with water, five lambs were inoculated with human RSV and three lambs were given control media at an age of 3-5 days. During RSV infection, LCS resulted in increased inhibition of minute ventilation and delayed recovery of regular breathing. Sleep further increased the response, and arousal was less likely to occur in active sleep. Two of the five infected lambs needed resuscitation after LCS when arousal was absent. Histological studies showed bronchiolitis and pneumonitis. Laryngeal tastebud morphology was unchanged at 8 days after inoculation. However, infected lambs had disrupted tastebuds 4-6 weeks after infection. Failure to arouse and to terminate reflex apnea may play a role in the pathogenesis of the sudden infant death syndrome associated with respiratory tract infection.


Effects of nanotoxicity on female reproductivity and fetal development in animal models.
The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein.


HbXL99 alpha: a hemoglobin derivative that is cross-linked between the alpha subunits is useful as a blood substitute.
Under deoxygenated conditions, bis(3,5-dibromosalicyl) fumarate reacts with hemoglobin selectively to cross-link the alpha subunits between Lys-alpha 1 99 and Lys-alpha 2 99. We have characterized further the properties of this recently described hemoglobin and have demonstrated its utility as a blood substitute. The oxygen transport characteristics of the cross-linked derivative are very similar to those of whole blood. Under physiological conditions, the partial pressure of oxygen at half-saturation of hemoglobin is increased to 29 mm Hg (1 mm Hg = 133.3 kPa), compared to 12 mm Hg for hemoglobin A, fully compensating for the absence of 2,3-bisphosphoglycerate outside of the erythrocyte. The Hill coefficient is 2.9. The dependence of the oxygen affinity of HbXL99 alpha on CO2 is also identical to that of hemoglobin A. The cross-link between the alpha subunits blocks dissociation of oxyhemoglobin into alpha beta dimers and thereby prevents renal excretion of the modified hemoglobin. In the rat, the half-life of HbXL99 alpha in plasma, at a 15% volume exchange, is increased to 3.3 hr, compared to 90 min for hemoglobin A. Cross-linking HbXL99 alpha intermolecularly with bis(sulfosuccinimidyl) suberate to form predominantly a mixture of dimers and trimers further increased the half-life of the hemoglobin within the circulation by about 2-fold. The rate of autooxidation of the transfused hemoglobin was found to be markedly reduced because of the presence of an endogenous reducing system in plasma.


Sexual and Reproductive Health Content in the 3 Ps in Nurse Practitioner Education.
Nurse practitioners (NPs) in primary care provide sexual and reproductive health care, an integral component of health and well-being. This study explored the degree of inclusion of sexual and reproductive health content in the foundational courses in NP preparation including advanced health assessment, advanced physiology and pathophysiology, and advanced pharmacology, known as the 3 Ps. Qualitative interviews were conducted with 30 NPs in their first 2 years of practice. Sexual and reproductive health content was well integrated into advanced assessment courses, although participants wanted more comfort and skill with discussing sensitive sexual health issues. Advanced pharmacology and advanced pathophysiology courses were not likely to include the content. Interactive learning opportunities, such as simulation with feedback, promote communication skills with sensitive health issues. Foundational courses would benefit from a deeper understanding of the menstrual cycle, sexual functioning, and medications specific to sexual and reproductive health. [J Nurs Educ. 2022;61(3):131-136.].


Post-laser in situ keratomileusis interface Arthrographis kalrae keratitis.
We describe a case of keratomycosis caused by Arthographis kalrae after excimer laser keratomileusis. A 38-year-old female developed stromal keratitis eight weeks after refractive surgery. She developed severe corneal stromal infiltration and mild anterior segment inflammation, which could not be treated with topical voriconazole 1%, but topical natamycin 5% ameliorated her condition. A reactivation of keratomycosis symptoms was observed; therefore, longer treatment was administered to the patient. It has been reported that A. kalrae keratomycosis is associated with exposure to soil and contact lens usage. However, the patient, who lived in a rural location, was neither involved in gardening activities nor had a history of wearing contact lenses. This is the first case of post-refractive A. kalrae keratomycosis.


An enzymatic cycling method using pyruvate orthophosphate dikinase and firefly luciferase for the simultaneous determination of ATP and AMP (RNA).
A novel bioluminescent enzymatic cycling assay for ATP and AMP with concomitant use of firefly luciferase and pyruvate orthophosphate dikinase (PPDK) was developed. In this system, AMP and pyrophosphate produced from ATP by firefly luciferase were converted back into ATP by PPDK. This resulted in constant luminescence once the stable phase had been reached. Background luminescence of the reagent was reduced with adenosine phosphate deaminase by degrading ATP and AMP in the reagent. The maximum recycling ratio calculated from the integrated luminescence value was 2.64 cycles/min. The measurable ranges for ATP and AMP were equal and were between 4 x 10(-13) and 4 x 10(-17) mol/assay. The amount of yeast RNA could be estimated in the range of 1 x 10(-8) to 1 x 10(-12) g/assay by estimating the amount of AMP resulting from the degradation of RNA with nuclease P1. Various food samples were subjected to measurement of the amount of ATP + AMP + RNA to provide an index for hygiene monitoring. For beef extract, sensitivity was improved by more than 20 million compared to the previous methods relying only on the amount of ATP as an index.


EGG and acoustic analyses of different voice samples: comparison between perceptual evaluation and voice activity and participation profile.
This study investigated whether different electroglottographic (EGG) parameters may be used to estimate voice quality and loading related to it, and whether voice quality is related to self-estimation of voice problems and laryngeal status. The effect of sample type was also considered. EGG and acoustic signals of a sustained vowel [a:] (90 dB6 cm) and text reading during noise exposure were recorded from 93 female kindergarten teachers. Analyses were made from the sustained vowel and vowel [a:] from a stressed word. Contact quotient (CQ) was calculated. Maximum velocity of increase in contact area inferred from derivative (MDEGG) was examined. Fundamental frequency was calculated from the EGG signal. From the acoustic signal sound pressure level (SPL) was computed and pressedness in voice quality was evaluated perceptually. Self-evaluation was made with Voice Activity and Participation Profile (VAPP). Indirect laryngoscopy was also performed. Pressedness in voice correlated with EGG results only for the sustained vowel, and better with MDEGG than CQ values. VAPP and laryngeal evaluation did not correlate with the acoustic or EGG parameters or with perception. MDEGG is worth testing as an indicator of impact stress. Sustained vowel at a controlled SPL is more suitable for voice quality evaluation than a long stressed vowel from connected speech.


Magnetic properties of hole-doped SCGO, SrCr(8)Ga(4-x)M(x)O(19) (M = Zn, Mg, Cu).
We report changes in the magnetic properties of hole-doped SCGO, SrCr8Ga4O19, induced by replacing non-magnetic Ga3+ with both non-magnetic (Mg2+ and Zn2+) and magnetic (Cu2+) cations. The resulting solid solutions, SrCr(8)Ga(4-x)M(x)O(19) (M = Zn, Mg, Cu) have been studied by x-ray diffraction and magnetic susceptibility measurements. For all cases, at least 10% of Ga can be replaced by divalent cations resulting in oxidation of ≥5% of the Cr3+ d3 to Cr4+ (d2). The hole doping results in an increase in ferromagnetic interactions and reduces the magnetic frustration. In the SrCr(8)Ga(4-x)Cu(x)O(19) series an enhancement of the spin-glass-like transition is observed, T(f)∼ 6 K, which we ascribe to the magnetic nature of the Cu2+ (d9) dopant.


Perceived Fatigue Interference and Depressed Mood: Comparison of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients with Fatigued Breast Cancer Survivors.
Persistent fatigue and depressive symptoms are both highly prevalent among patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) as well as breast cancer survivors. This study aimed to assess and directly compare perceptions of fatigue as highly interfering in one's daily functioning in both patient populations to better understand their relationships with depressed mood. Participants were 95 female CFS/ME patients and 67 females who were approximately 5 years post-treatment for stage 0-III breast cancer presenting with clinically elevated fatigue severity. Self-report measures were obtained on participants' fatigue-related interference in daily functioning and fatigue severity as well as depressed mood. Hierarchical regression was used to test effects controlling for relevant demographic, psychosocial, and medical covariates. CFS/ME patients endorsed greater depressed mood and fatigue interference than did fatigued breast cancer survivors, p's<.001. These factors were significantly positively correlated among CFS/ME patients (β=.36, p<.001), but not the fatigued breast cancer survivors (β=.18, p=.19). CFS/ME patients reported elevated fatigue symptoms and depression relative to fatigued breast cancer survivors. In the former group, greater depressed mood was highly and significantly associated with greater fatigue-related inference in daily activities. Potential targets for cognitive behavioral interventions are discussed.


Brazilian Amazon Traditional Medicine and the Treatment of Difficult to Heal Leishmaniasis Wounds with Copaifera.
The present study describes the use of the traditional species Copaifera for treating wounds, such as ulcers scarring and antileishmanial wounds. It also relates phytochemical studies, evaluation of the leishmanicidal activity, and toxicity. The species of Copaifera with a higher incidence in the Amazon region are Copaifera officinalis, Copaifera reticulata, Copaifera multijuga Hayne. The copaiba oil is used in the Amazon's traditional medicine, especially as anti-inflammatory ingredient, in ulcers healing, and in scarring and for leishmaniasis. Chemical studies have shown that these oils contain diterpenes and sesquiterpenes. The copaiba oil and terpenes isolated have antiparasitic activity, more promising in the amastigote form of L. amazonensis. This activity is probably related to changes in the cell membrane and mitochondria. The oil showed low cytotoxicity and genotoxicity. Furthermore, it may interfere with immune response to infection and also has a healing effect. In summary, the copaiba oil is promising as leishmanicidal agent.


Atherosclerotic arterial remodeling in the superficial femoral artery. Individual variation in local compensatory enlargement response.
In previous studies on atherosclerotic arterial remodeling, compensatory enlargement of the artery in response to plaque accumulation was inferred from pooled data based on one cross section per artery. We assessed local arterial remodeling individually by analyzing 45 artery segments at 0.5-cm intervals over a length of 10 to 15 cm. Twenty patients were studied by 30-MHz intravascular ultrasound (IVUS) before balloon angioplasty of the superficial femoral artery (370 cross sections), and 25 femoral artery segments were studied postmortem (551 cross sections). In each cross section, the area surrounded by the internal elastic lamina (IEL area) and the plaque area were measured. The IEL area was larger in the cross section with the largest plaque area than in the cross section with the smallest plaque area (32.5+/-13.0 and 32.0+/-11.5 mm2 versus 28.9+/-9.7 [P=NS] and 26.7+/-10.1 [P<.05] mm2 for IVUS and histology, respectively [mean+/-SD]). A significant positive correlation was found between plaque area and IEL area for the pooled data (r=.61 and r=.47 and slope=1.07 and 0.90 for IVUS and histology, respectively; both P<.001). In 12 of 20 and 16 of 25 individual arterial segments, however, no significant correlation was observed between plaque area and IEL area for IVUS and histology, respectively. A large variation was found in the correlation of the regression of plaque to IEL area (IVUS, r=-.40 to .89; histology, r=-.13 to .91) and slope (IVUS, -0.28 to 1.29; histology, -0.18 to 1.32). In the majority of atherosclerotic femoral arteries, significant compensatory enlargement could not be determined. It is inferred that arterial remodeling in response to plaque formation may vary among individuals.


Simultaneous determination of serotonin and creatinine in urine by combining two ultrasound-assisted emulsification microextractions with on-column stacking in capillary electrophoresis.
This article describes the development of a rapid, simple, and sensitive analytical approach for the simultaneous determination of serotonin (5-hydroxytryptamine) and creatinine in urine samples by combining two ultrasound-assisted emulsification microextractions (USAEMEs) in series with on-column stacking in CE. This serial USAEME procedure comprises analytes extraction from the donor solution (urine with K(2) CO(3) additive) to an organic solvent followed by a back-extraction from the organic phase into a small volume of hydrochloric acid. After 15 min of sample pretreatment, the acidic acceptor solution was analyzed directly on CE in the mode of capillary zone electrophoresis. The adoption of HCl as the acceptor phase not only provided effective back-extraction but also facilitated pH-mediated on-column stacking in CE analysis. About 360-fold sensitivity enhancement was achieved for serotonin detection. The limits of detection were 7.9 nM for serotonin and 13.3 μM for creatinine, respectively. Satisfactory results were obtained with respect to precision and recovery. The proposed method has been demonstrated to be convenient and effective for the analysis of real urine samples. We believe that two USAEMEs in series will find wide applications in simplified sample pretreatment prior to CE analysis.


The challenges and future of oral drug delivery: An interview with David Brayden.
David Brayden speaks to Hannah Makin, Commissioning Editor: David Brayden is a Full Professor (Advanced Drug Delivery) at the School of Veterinary Medicine, University College Dublin (UCD) and also a Fellow of the UCD Conway Institute. Following a PhD in Pharmacology at the University of Cambridge, UK (1989), and a postdoctoral research fellowship at Stanford University, CA, USA, he set up Elan Biotechnology Research's in vitro pharmacology laboratory in Dublin (1991). At Elan, he became a senior scientist and project manager of several of Elan's joint-venture drug delivery research collaborations with US biotech companies. In 2001, he joined UCD as a lecturer in veterinary pharmacology and was appointed Associate Professor in 2006 and Full Professor in 2014. He was a Director of the Science Foundation Ireland Research Cluster (The Irish Drug Delivery Research Network) from 2007 to 2013, is a Deputy Coordinator of an FP7 Consortium on oral peptides in nanoparticles ('TRANS-INT', 2012-2017), and is a Co-Principal Investigator in 'CURAM', Science Foundation Ireland's new Centre for Medical Devices (2014-2020 [ 1 ]). He was made a Fellow of the Controlled Release Society in 2012. He is the author or co-author of >200 research publications and patents. D Brayden serves on the Editorial Advisory Boards of Drug Discovery Today, European Journal of Pharmaceutical Sciences, Advanced Drug Delivery Reviews and the Journal of Veterinary Pharmacology and Therapeutics, and is an Associate Editor of Therapeutic Delivery. D Brayden works as an independent consultant for drug delivery companies.