Governance education for nurses: Preparing nurses for the future.
The complexities of today's health care environment require organizational governing boards to have deeper understanding of health needs, influences, and outcomes with diverse board leadership. Nurses understand the complexities and demands of health care, but few nurses are engaged on boards of directors and many nurses feel unprepared for the governance leadership role. The nurse of the future requires governance knowledge and competencies to influence organizational policies that will improve health care outcomes and advance health promotion. Governance education is a necessary component of preparing the nurse of the future to influence health care transformation. Until nurses can confidently embrace governance leadership as a part of their professional identity, convincing and expecting non-nurse board leaders to appoint nurses to boards will continue to be a challenge. This paper describes a strategy for incorporating governance competencies into nursing curricula across all education levels by leveraging the American Hospital Association Governance Core Competencies (2009) and the Massachusetts Nurse of the Future Core Competencies©-RN (Massachusetts Department of Higher Education Nursing Initiative, 2016).


Systematics and biogeography of the Gondwanan Orthocladiinae (Diptera: Chironomidae).
Restrictions to effective dispersal and gene flow caused by the fragmentation of ancient supercontinents are considered to have driven diversification and speciation on disjunct landmasses globally. Investigating the role that these processes have played in the development of diversity within and among taxa is crucial to understanding the origins and evolution of regional biotas. Within the chironomid (non-biting midge) subfamily Orthocladiinae (Diptera: Chironomidae), a group of genera that are distributed across the austral continents (Australia, New Zealand, South America) have been proposed to represent a relict Gondwanan clade. We used a molecular approach to resolve relationships among taxa with the aim to determine the relative roles that vicariance and dispersal may have played in the evolution of this group. Continental biotas did not form monophyletic groups, in accordance with expectations given existing morphological evidence. Patterns of phylogenetic relationships among taxa did not accord with expected patterns based on the geological sequence of break-up of the Gondwanan supercontinent. Likewise, divergence time estimates, particularly for New Zealand taxa, largely post-dated continental fragmentation and implied instead that several transoceanic dispersal events may have occurred post-vicariance. Passive dispersal of gravid female chironomid adults is the most likely mechanism for transoceanic movement, potentially facilitated by West Wind Drift or anti-cyclone fronts. Estimated timings of divergence among Australian and South American Botryocladius, on the other hand, were congruent with the proposed ages of separation of the two continents from Antarctica. Taken together, these data suggest that a complex relationship between both vicariance and dispersal may explain the evolution of this group. The sampling regime we implemented here was the most intensive yet performed for austral members of the Orthocladiinae and unsurprisingly revealed several novel taxa that will require formal description.


Spatial subdivision of populations and estimates of genetic variation.
Measures of variation in space are strongly affected by correlations between subdivisions used for sampling. Here we consider variation in gene frequencies across populations. Usually the variance of gene frequencies is standardized by dividing it by the mean gene frequency times one minus the mean (FST). Under the model of isolation by distance (usually called the "stepping stone" model), at the stationary state the correlation between the gene frequencies of two populations falls exponentially with the geographic distance between them. Using this model, we derive formulas for variances of blocks of populations of different sizes in one- and two-dimensional space and suggest that the theoretical results may be useful for understanding real observations, some examples of which are presented. We demonstrate how FST increases with the degree of subdivision among populations. We also show the effect of gaps between the sampled populations. Our results are valid, however, for traits other than gene frequencies, as long as their correlation with geographic distance falls exponentially. In the extension to 2-dimensional spaces, we present in closed form the distributions of distances between nodes of a lattice or of two lattices. These distributions might have applications in ecology.


Copper-catalyzed direct amination of electron-deficient arenes with hydroxylamines.
The C-H amination of electron-deficient arenes such as polyfluoroarenes and azole compounds with O-acylated hydroxylamines effectively proceeds in the presence of a copper catalyst even at room temperature to provide the corresponding anilines and aminoazoles in good yields.


Polylactide-polyglycolide resorbable plates stimulates adipose tissue-derived stem cells towards osteoblasts differentiation.
Polylactide, polyglycolide materials or devices have been utilized routinely during maxillofacial, craniofacial, and orthopaedic reconstructive surgical procedures.(1) These materials combine the benefits of rigid fixation with the advantages of biodegradation, avoiding the need for implant removal and minimizing the risk of other complications.(2) To study how polylactide, polyglycolide acids plates (PLPG plates) can induce osteoblast differentiation and proliferation in mesenchymal stem cells, the expression levels of bone related genes (RUNX2, SP7, ALPL, SPP1, COL1A1, COL3A1 and FOSL1) and mesenchymal stem cells marker (ENG) were measured in adipose derived stem cells (ADSCs) and normal osteoblast (NO) cultivated on PLPG plates after 15 and 30 days of treatment using real time Reverse Transcription-Polymerase Chain Reaction. Significantly differentially expressed genes among ADSCs and NO were SP7, ENG, FOSL1, RUNX, ALPL and SPP1 in the first 15 days of treatment and SP7, ENG FOSL1, COL3A1 COL1A1, SPP1 and ALPL after 30 days. The present study demonstrated that PLPG plates strongly influences the behavior of ADSCs in vitro by enhancing proliferation, differentiation and deposition of matrix.


Combined Laparoscopic Treatment of Polycystic Ovary Disease and Gallstones
Laparoscopic surgery has largely replaced laparotomy in the management of both polycystic ovary disease (PCOD) and gallstones. The number of patients with a combination of these disorders has increased. From 1991 to 1996, 908 patients underwent laparoscopic cholecystectomy. In 29 women of reproductive age (18-41 yrs) with PCOD and gallstones, we performed combined laparoscopic cholecystectomy and various procedures on the ovaries (15 wedge resections, 8 multiple ovariotomies by thermocoagulation incisions, 5 electrosurgical coagulations of the ovaries). All operations were performed by the usual approach for laparoscopic cholecystectomy, and in only four women did we place a supplemental cannula. The diagnosis of PCOD was established preoperatively in 22 women, but in 6 it was an incidental finding during laparoscopic inspection of abdominal cavity. We suggest that one-stage laparoscopic cholecystectomy and procedures on the ovaries may be performed with single-puncture technique. Performing the procedures simultaneously has the advantages of minor surgical trauma, much less adhesion formation, and ability to treat hormonal disorders and infertility. For best results in women with combined PCOD and gallstones, the joint participation of abdominal surgeon and gynecologist is preferred.


Localized surface plasmon resonance induced assembly of bimetal nanochains.
Bimetal nanochains (NCs) are attracting increasing attention in the fields of catalysis and electrocatalysis due to the synergistic effects in electronic and optical properties, but the fabrication of bimetal NCs remains challenging. Here, we report a general strategy named "nucleation in the irradiation then growth in the dark" for the preparation of Au/M (second metal) NCs. In the irradiation stage, the localized surface plasmon resonance (LSPR) effect of Au NPs is excited to overcome the nucleation energy barrier for the deposition of second metals (Pt, Ag and Pd). In the followed dark process, the preferential growth of second metals on the existed nucleus leads to the formation of nanochain rather than the core/shell nanostructure. In the model reaction of electrocatalytic hydrogen evolution, the optimized Au/Pt NCs showed much better performance compared with the commercial Pt/C.


Ethical, anticipatory genomics research on human behavior means celebrating disagreement.
Despite the many social and ethical considerations in human genetics, researchers and communities remain largely siloed as for-profit, direct-to-consumer genetic testing and the application of polygenic scores to in vitro fertilization services become increasingly prevalent. The multifaceted challenges facing genomics, both empirical and ethical, require collaborations that foster critical dialogue and honest debate between communities inside and outside the research enterprise. This piece argues that in order to respond to the premature or inappropriate use of genomic data in industry, the scientific community needs to first embrace, understand, and be in dialogue about its disagreements. We introduce the research framework of adversarial collaboration as a way to celebrate disagreement and productively work toward policy-informed, ethical, and anticipatory genomics research.


Preparation and characterization of novel crown ether functionalized ionic liquid-based solid-phase microextraction coatings by sol-gel technology.
A novel crown ether functionalized ionic liquid (IL), 1-allyl-3-(6'-oxo-benzo-15-crown-5 hexyl) imidazolium hexafluorophosphate was synthesized and used as selective stationary phase to prepare task-specific IL-based solid phase microextraction (SPME) fibers by sol-gel method and free radical cross-linking technology. The underlying mechanism of the sol-gel reaction was proposed and the successful chemical bonding of the crown ether functionalized IL to the formed hybrid organic-inorganic copolymer coating was confirmed by FT-IR spectroscopy. The performance of this in situ created crown ether functionalized IL-based SPME fibers, was investigated in detail. The coating has porous surface structure, stable performance in high temperature (to 340 °C) and in different solutions (water, organic solvent, acid and alkali), and good coating preparation reproducibility. In contrast to the sol-gel derived 1-allyl-3-methyl imidazolium hexafluorophosphate-based coating prepared in our previous work with the identical procedure, the extraction performance of this newly developed sol-gel crown ether functionalized IL-based coating was superior for alcohols, phthalate esters, phenolic environmental estrogens, fatty acids and aromatic amines due to the introduction of benzo-15-crown-5 functional group in IL structure. Moreover, it was shown to provide higher or comparable extraction efficiencies for most analytes studied than did the commercial PDMS, PDMS/DVB and PA fibers.


Respiratory gases, air pollution and epilepsy.
A growing number of studies have shown that exposure to air pollutants such as particulate matter and gases can cause cardiovascular, neurodegenerative and psychiatric diseases. The severity of the changes depends on several factors such as exposure time, age and gender. Inflammation has been considered as one of the main factors associated with the generation of these diseases. Here we present some cellular mechanisms activated by air pollution that may represent risk factors for epilepsy and drug resistance associated to epilepsy.


Cognition in circadian rhythm sleep disorders.
Circadian rhythms in physiology and behavior exist in all living organisms, from cells to humans. The most evident rhythms are the recurrent cycles of sleep and wake as well as changes in alertness and cognitive performance across the 24h. Clearly, sleep pressure can exert a strong influence on cognitive performance, but the influence of circadian modulation of alertness and cognitive function is evident even when the pressure for sleep is high. Circadian rhythms also influence more complex cognitive tasks, such as selective attention and executive function, which are important for work performance and safety. The circadian timekeeping system also ensures that circadian rhythms are appropriately synchronized to the external physical environment and work and social schedules. Circadian misalignment is the basis for all circadian rhythm sleep disorders. These disorders are often associated with impairments of cognitive performance that can have adverse effects on school and work performance, overall quality of life, and safety.


Genetic factors involved in fosfomycin resistance of multidrug-resistant Acinetobacter baumannii.
The treatment of infections caused by A. baumannii is a challenge and fosfomycin has been used as a combination therapy. Moreover, data regarding the fosfomycin resistance mechanism is scarce. The goals of this study were to evaluate fosfomycin susceptibility in polyclonal multi-resistant A. baumannii isolates and characterize the fosfomycin resistance. We analyzed 32 A. baumannii isolates from a Brazilian bacterial collection, followed by their minimum inhibitory concentration (MIC), and whole-genome sequence to detect fosfomycin resistance genes. The isolates showed a fosfomycin MIC ranging from 32 to ≥256 mg/L. All isolates were negative for fosA and fosB genes, and four isolates carried the fosX gene. Two different metabolic pathways that form peptidoglycan precursors were identified. Mutations were observed in the adenylate cyclase gene. All A. baumannii isolates studied showed Val132Ala substitutions in MurA. The analysis showed different ways that may lead to the intrinsic fosfomycin-resistance of A. baumannii, such as alterations on the glycerol-3-phosphate transporter system caused by adenylate cyclase mutations; and a possible connection of cell wall recycling by different metabolic pathways.


Computer-Assisted Planning, Simulation, and Navigation System for Periacetabular Osteotomy.
Periacetabular osteotomy (PAO) is an effective approach for surgical treatment of hip dysplasia in young adults. However, achieving an optimal acetabular reorientation during PAO is the most critical and challenging step. Routinely, the correct positioning of the acetabular fragment largely depends on the surgeon's experience and is done under fluoroscopy to provide the surgeon with continuous live x-ray guidance. Our developed system starts with a fully automatic detection of the acetabular rim, which allows for quantifying the acetabular 3D morphology with parameters such as acetabular orientation, femoral head extrusion index (EI), lateral center-edge (LCE) angle, and total and regional femoral head coverage (FHC) ratio for computer-assisted diagnosis, planning, and simulation of PAO. Intraoperative navigation is conducted to implement the preoperative plan. Two validation studies were conducted on four sawbone models to evaluate the efficacy of the system intraoperatively and postoperatively. By comparing the preoperatively planned situation with the intraoperatively achieved situation, average errors of 0.6° ± 0.3°, 0.3° ± 0.2°, and 1.1° ± 1.1° were found, respectively, along three motion directions (flexion/extension, abduction/adduction, and external rotation/internal rotation). In addition, by comparing the preoperatively planned situation with the postoperative results, average errors of 0.9° ± 0.3° and 0.9° ± 0.7° were found for inclination and anteversion, respectively.


CHAMP: A cluster randomized-control trial to prevent obesity in child care centers.
Foundational elements of lifelong health are formed during the preschool years. Child care attendance has nearly doubled in the past 5 years making child care centers an ideal setting to establish healthy habits that prevent pediatric obesity. Despite the promising evidence of efficacy of child care-based obesity prevention interventions, limited attention has been directed to criteria needed for implementation at scale. There is potential to improve children's dietary and physical activity behaviors in diverse communities through theory-based, culturally appropriate, manualized interventions, delivered by child care staff. CHAMP (Creating Healthy Habits Among Maryland Preschoolers) is a 3-arm cluster randomized controlled childhood obesity prevention trial, aiming to improve motor skills, physical activity and willingness to try new foods among 864 preschoolers (age 3-5 years) enrolled in 54 child care centers in 10 Maryland counties. CHAMP is informed by social-cognitive and bioecological theories and based on an evidence-based program, The Food Friends®. The two intervention arms include: 1) child care-center based lessons (18-week gross motor and 12-week nutrition) administered by trained child care staff, and 2) a web-based intervention for caregivers in addition to center-based lessons. Evaluations are conducted among children, caregivers, and child care staff at fall enrollment, midline, and spring, following intervention completion. Analyses include linear mixed-models, accounting for clustering and repeated measures, incorporating center-arms as moderators. CHAMP will provide evidence-based information to inform wellness guidelines and policies that can be disseminated broadly, to ensure that child care centers provide opportunities for children to develop healthy eating, and physical activity habits. Trial Registration: NCT03111264; https://clinicaltrials.gov/ct2/show/NCT03111264.


Effects of platelet rich plasma on experimentally induced diabetic heart injury.
Diabetic heart is one of the common complications of diabetes mellitus. Platelet-rich plasma (PRP) is an autologous product rich in growth factors that can enhance tissue regeneration. This work was conducted to study the PRP ability to improve diabetes-inducing cardiac changes. Also, it sheds more light on the possible mechanisms through which PRP induces its effects. Rats were divided into; control, PRP, diabetic, and PRP-diabetic groups. Cardiac specimens were obtained and processed for biochemical, histological, and immunohistochemical study. The diabetic group exhibited a significant increase in cardiac oxidative stress, inflammation, and cardiac injury markers if compared with the control group. Additionally, the cardiac tissue showed variable morphological changes in the form of focal distortion and loss of cardiac myocytes. Distorted mitochondria and heterochromatic nuclei were observed in the cardiac muscle fibers. The mean number of charcoal-stained macrophages, and mean area fraction for collagen fibers, mean number of PCNA-immune positive cardiac muscle were significantly decrease in PRP- diabetic group. Collectively, the results showed that PRP treatment ameliorated most of all these previous changes. CONCLUSION: PRP ameliorated the diabetic cardiac injury via inhibition of oxidative stress and inflammation. It was confirmed by biochemical, histological, and immunohistochemical study. It could be concluded that PRP could be used as a potential therapy for diabetic heart.


Bis{μ-2-[(N,N-diisopropyl-carbamothio-yl)sulfan-yl]acetato-κO:O'}bis-(bis-(4-chloro-benz-yl){2-[(N,N-diisopropyl-carbamothio-yl)sulfan-yl]acetato-κO,O'}tin(IV)).
The dinuclear title complex, [Sn(2)(C(7)H(6)Cl)(4)(C(9)H(16)NO(2)S(2))(4)], lies on a center of inversion. The Sn(IV) atoms are chelated by one of the two carboxyl-ate ions; the other carboxyl-ate ion bridges two metal atoms. The geometry of the six-coordinate Sn(IV) atom is a distorted trans-C(2)SnO(4) octa-hedron [C-Sn-C = 155.32 (8)°].


Recasting the whale's wonderful net.
Modification of cerebral vasculature helps to cushion the brains of whales and dolphins against injury.


Control of immunity and allergy by steroid hormones.
Steroid hormones, especially glucocorticoids, androgens, and estrogens, have profound influence on immunity. Recent studies using cell-type specific steroid hormone receptor-deficient mice have revealed the precise roles of some of these hormones in the immune system. Glucocorticoids are known to have strong anti-inflammatory and immunosuppressive effects and pleiotropic effects on innate and adaptive immune responses. They suppress the production of inflammatory cytokines by macrophages and DCs and the production of IFN-γ by NK cells, thus inhibiting innate immunity. By contrast, glucocorticoids enhance the immune response by inducing the expression of IL-7R and CXCR4 in T cells and the accumulation of T cells in lymphoid organs in accordance with the diurnal change of the glucocorticoid concentration. Thus, glucocorticoids suppress innate immunity but enhance adaptive immunity. Androgens suppress the homeostasis and activation of ILC2s and the differentiation of Th2 and Th17 cells and enhance the suppressive function of Tregs, thereby alleviating allergic airway inflammation. Thus, these steroid hormones have pleiotropic functions in the immune system. Further investigations are awaited on the regulation of immunity and allergy by estrogens using cell-specific steroid hormone receptor-deficient mice.


The effect of sevoflurane on ciliary motility in rat cultured tracheal epithelial cells: a comparison with isoflurane and halothane.
Halothane and isoflurane potently depress airway ciliary motility. We compared the effect of sevoflurane on ciliary beat frequency (CBF) with that of halothane and isoflurane using purified and cultured rat tracheal epithelial cells. Rat tracheal epithelial cells were isolated from adult male Sprague-Dawley rats to establish an air-liquid interface culture. Apical surfaces of the cells were exposed to a fresh gas containing humidified and warmed (25 degrees C) air (vehicle) with or without sevoflurane (0%-4%), halothane (0%-2%), or isoflurane (0%-2%). The images of motile cilia were videotaped and CBF was analyzed using a computer. Baseline CBF (= 100%) and CBF 30 min after the exposure were measured. CBF 30 min after vehicle exposure was 101% +/- 4% (mean +/- sd). Exposures to 0.25%-2% sevoflurane did not change CBF significantly, although exposures to 0.25%-2% halothane or isoflurane decreased CBF dose-dependently. CBFs 30 min after exposures to 2% of sevoflurane, halothane, and isoflurane were 97% +/- 9%, 56% +/- 14%, and 47% +/- 6%, respectively (n = 5 each). Sevoflurane 4% reduced CBF significantly but slightly (84% +/- 2%, n = 5). These results show that sevoflurane has a direct cilioinhibitory action but its action is much weaker than that of halothane and isoflurane in isolated rat tracheal epithelial cells.


Isolation and structure determination of a new cytotoxic peptide, curacozole, from Streptomyces curacoi based on genome mining.
Using genome mining, a new cytotoxic peptide named curacozole was isolated from Streptomyces curacoi. Through ESI-MS and NMR analyses, curacozole was determined to be a macrocyclic peptide containing two isoleucine, two thiazole and three oxazole moieties. Curacozole exhibited potent cytotoxic activity against HCT116 and HOS cancer cells. The proposed biosynthetic gene cluster of curacozole was identified and compared with that of the related compound YM-216391.


Effects of air pollutant emission on the prevalence of respiratory and circulatory system diseases in Linyi, China.
As a typical industrial city, Linyi has suffered severe atmospheric pollution in recent years. Meanwhile, a high incidence of respiratory and circulatory diseases has been observed in Linyi. The relationship between air pollutants and the prevalence of respiratory and circulatory system diseases in Linyi is still unclear, and therefore, there is an urgent need to assess the human health risks associated with air pollutants. In this study, the number of outpatient visits and spatial distribution of respiratory and circulatory diseases were first investigated. To clarify the correlation between diseases and air pollutant emissions, the residential intake fraction (IF) of air pollutants was calculated. The results showed that circulatory and respiratory diseases accounted for 62.32% of the total causes of death in 2015. The incidence of respiratory diseases was high in the winter, and outpatient visits were observed for more males (60.9%) than females (39.1%). The spatial distribution suggested that outpatient visits for respiratory and circulatory diseases were concentrated in the main urban area of Linyi, including the Hedong District, Lanshan District, and Luozhuang District, and especially at the junction of these three areas. After calculating the IF combined with the characteristics of pollution sources, meteorological conditions, and population data, a high IF value was concentrated in urban and suburban areas, which was consistent with the high incidence of diseases. Moreover, high R values and a significant correlation (R > 0.6, p < 0.05) between outpatient visits and residential IF of air pollutants imply similar spatial distributions of outpatient visits and IF value of residents. The spatial similarity of air pollution and outpatient visits suggested that future air pollution control policies should better reflect the health risks of spatial hotspots. This study can provide a potentially important reference for environmental management and air pollution-related health interventions.


Prognosis and Treatment of Metastatic Breast Cancer From A Real-World Scenario in China: A Retrospective Cohort Study.
Although metastatic breast cancer (MBC) is considered incurable, a specific subset of patients exhibits prolonged survival and even achieve a "cure". We retrospectively identified predictive prognostic factors and systemic therapy models to find this group of potentially cured patients. Consecutive patients diagnosed with MBC from 1991-2016 in West China Hospital were included. Univariate and multivariate analyses were conducted to assess the association of clinical factors and systemic therapy models with overall survival (OS), breast cancer-specific survival (BCSS) and progression-free survival (PFS). The median OS was 63.4 months. Age, tumor size, lymph node metastasis, histologic grade, molecular subtype, site and number of metastases and metastasis-free interval (MFI) were related to the prognosis of MBC (P < .05). Patients with T1, N0-1, luminal A, bone metastasis, OMBC (oligometastatic breast cancer) or metastasis-free interval (MFI) ≥ 3 years showed the median OS more than 10 years (P < .001). Independent prognostic factors that correlated with OS and BCSS were residence, lymph node metastasis, histologic grade, molecular subtype, and site of metastasis (P < .05). The group of sequential chemo-endocrine therapy (ST) in hormone receptor (HR)-positive MBC patients showed the highest overall response rate (ORR) (P < .05). However, patients who received endocrine therapy (ET) showed the best OS, BCSS and PFS in the first two-line treatment, followed by ST and chemotherapy (CT) (P < .05). Our study shows the predictive prognostic factors and systemic therapy models to facilitate patients likely to achieve long-term survival.


Validating a guidelines based asthma decision support system: step one.
Purpose. To quantify the accuracy of a computerized decision support system in discerning severe asthma in a clinical setting. Design. A total of 69 consecutive asthmatics examined in an asthma clinic were classified as "severe" or "mild" by the computerized decision support system and expert asthma clinicians. The expert asthma clinicians were the reference standard. Results. The accuracy was 91%, the sensitivity 96%, the specificity 73%, the positive predictive value 93%, and the negative predictive value 85%. Conclusions. The asthma decision support system was able to discern "mild" from "severe" asthma in a similar fashion to expert asthma clinicians.


The Role of Radiation Therapy for Pancreatic Cancer in the Adjuvant and Neoadjuvant Settings.
Pancreatic cancer is the third leading cause of cancer-related death in the United States. Although surgery remains the only curative treatment, chemotherapy and radiation therapy are frequently used. In the adjuvant setting, radiation is usually delivered with chemotherapy to eradicate residual microscopic or macroscopic disease in the resection bed. Neoadjuvant radiation therapy has become more frequently utilized. This article reviews the historical and modern literature regarding radiation therapy in the neoadjuvant and adjuvant settings, focusing on the evolution of radiation therapy techniques and clinical trials in an attempt to identify patients best suited to receiving radiation therapy.


Spontaneously reported adverse reactions after diphtheria-tetanus revaccination at 4-6 years of age--a comparison of two vaccines with different amounts of diphtheria toxoid.
On 1 January 1996, diphtheria-tetanus revaccination at the age of 5 years was implemented in the Danish Childhood Vaccination Programme. Initially, a combined DT vaccine containing 25 Lf diphtheria toxoid was used. Due to a high frequency of spontaneously reported adverse reactions, however, concerns were raised that the diphtheria dose was too high, and it was reduced to 6.25 Lf. This survey presents the rates of spontaneously reported adverse reactions following diphtheria-tetanus revaccinations of 4-6-year-old from 1996 to 2002. The change to the lower dose of diphtheria toxoid resulted in a remarkable reduction in the yearly rates of injection site reactions: in 1996, the rate was 180 injection site reactions per 100,000 vaccinations; from 1998 to 2002, this changed to between 12 and 24 reactions per 100,000 vaccinations. Furthermore, the rates of systemic reactions such as fever were reduced.


Burden and risk factors for inappropriate Clostridioides Difficile infection testing among hospitalized patients.
The purpose of this study was to identify the burden and risk factors for inappropriate Clostridioides difficile infection (CDI) testing. This was a retrospective cohort study among adults hospitalized between 2010 and 2019. Inappropriate CDI testing was defined as a formed stool specimen, an order within 7 days of a previously negative test, or an order within 24 hours of laxative administration. A total of 51,302 CDI orders were placed for 29,840 unique patients. 59% were appropriate and 41% were inappropriate. An additional 24% of the appropriate orders never resulted. Risk factors for inappropriate testing included orders placed by a nurse practitioner, orders placed by high-ordering providers, specific hospital units, fever, and leukocytosis. Nearly half of all CDI orders were inappropriate among hospitalized patients, and an additional 24% of test results never returned. Provider- and patient-level risk factors included type of provider, specific hospital units, and signs of sepsis.


Glutamate dependent dendritic outgrowth in developing neuronal networks of rat hippocampal cells in vitro.
The present study was undertaken to determine whether release of glutamate is capable of influencing dendritic morphology in a developing network of rat hippocampal neurons in vitro. Control cultures developed a dense network of fibers and evinced spontaneous electrical activity from the third day in vitro. Dendrites were examined in cultures maintained for 2 weeks in vitro: the experimental group grown in medium containing the glutamate receptor antagonists AP-5 and DNQX. Dendritic extensions were analyzed as a function of time (days in vitro) using a number of morphometric parameters, vis. the number of processes, the number and length of intermediate and terminal segments, as well as the total length of all segments. We found that the effect of age and treatment was most prominently reflected in the length of the terminal segments. Chronic addition of ionotropic glutamate receptor antagonists from day 2 in culture arrested all dendrite parameters at the prefunctional level. The results suggest that glutamate release is crucial for the onset of dendritic morphological development in hippocampal neurons.


Risk Factors for the Mortality of Pneumocystis jirovecii Pneumonia in Non-HIV Patients Who Required Mechanical Ventilation: A Retrospective Case Series Study.
The risk factors for the mortality rate of Pneumocystis jirovecii pneumonia (PCP) who required mechanical ventilation (MV) remained unknown. A retrospective chart review was performed of all PCP patients admitted to our intensive care unit and treated for acute hypoxemic respiratory failure to assess the risk factors for the high mortality. Twenty patients without human immunodeficiency virus infection required mechanical ventilation; 19 received noninvasive ventilation; and 11 were intubated. PEEP was incrementally increased and titrated to maintain FIO2 as low as possible. No mandatory ventilation was used. Sixteen patients (80%) survived. Pneumothorax developed in one patient with rheumatoid arthritis (RA). Median PEEP level in the first 5 days was 10.0 cmH2O and not associated with death. Multivariate analysis showed the association of incidence of interstitial lung disease and increase in serum KL-6 with 90-day mortality. We found MV strategies to prevent pneumothorax including liberal use of noninvasive ventilation, and PEEP titration and disuse of mandatory ventilation may improve mortality in this setting. Underlying disease of interstitial lung disease was a risk factor and KL-6 may be a useful predictor associated with mortality in patients with RA. These findings will need to be validated in larger studies.


Psychological, behavioral and biochemical risk factors for coronary artery disease among American and Italian male corporate managers.
Differences in psychological, behavioral and biochemical risk factors for coronary artery disease (CAD) among male corporate managers of 2 countries (United States and Italy), with very different age-specific rates of mortality for CAD were evaluated. In all, 129 American (mean age 43 +/- 7 years) and 80 Italian (mean age 45 +/- 7 years) managers volunteered to participate in this study. Each subject was administered several questionnaires assessing various psychological and behavioral risk factors for CAD, and all 129 Americans and 55 of 80 Italians had their blood drawn between 8:00 and 9:30 AM after overnight fasting for the measurement of plasma levels of dehydroepiandrosterone-sulfate (DHEA-S), total cholesterol, triglycerides, and apolipoproteins A-I and B. Italian managers reported significantly more cynicism and hostility, and less enjoyment in leisure activities than did American ones. Furthermore, 40 Italian (51%) and only 18 American (14%) managers were smokers (this difference being statistically significant). Although no significant differences were found in factors positively related with CAD (cholesterol, triglycerides and apolipoprotein B), there were clear differences in parameters inversely correlated with the incidence of CAD. Italian managers had significantly lower levels of plasma DHEA-S and apolipoprotein A-I than did American ones. In conclusion, this study found that Italian managers had a significantly more unhealthy psychological and behavioral profile than did American ones, and had lower levels of those biochemical parameters (apolipoprotein A-I and DHEA-S) thought to have a protective role against development of CAD.


Expression Profiles of circRNAs and Identification of hsa_circ_0007608 and hsa_circ_0064656 as Potential Biomarkers for COPD-PH Patients.
Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), which can worsen the prognosis and increase the mortality of COPD patients. Circular RNA (circRNA) has been discovered to participate in the occurrence and progression of PH in COPD and may have significant prospects for advanced diagnostics and prognosis evaluation. However, the expression profile of circRNAs in human lung tissues with definite diagnosis of COPD-PH remains to be further explored and validated. Twelve human lung tissue samples (6 each from COPD-PH and control groups) were collected and subjected to high-throughput sequencing. QRT-PCR was performed to validate the differential expression levels of the top 10 dysregulated circRNAs in patients' plasma samples, HPAECs and HPASMCs. Functional and pathway enrichment analysis on target genes was performed to explore the potential functions and pathways of those circRNAs. Hub genes obtained after conducting bioinformatics analysis on the predicted target mRNAs were verified by qRT-PCR in HPAECs and HPASMCs, and then we selected VCAN as a potential key gene involved in the pathogenesis of COPD-PH for immunohistochemistry validation in lung tissue. A total of 136 circRNAs (39 up-regulated and 97 down-regulated) were differentially expressed between the two groups. Following qRT-PCR validation, two circRNAs (hsa_circ_0007608 and hsa_circ_0064656) were believed to be involved in the pathogenesis. GO and KEGG pathway analysis suggested that these two DECs were mainly related to the celluar proliferation, migration and EndMT. PPI network revealed 11 pairs of key mRNAs. VCAM1, VCAN and THBS1, three hub mRNAs with the highest reliability among all, were validated and proven to be up-regulated in COPD-PH. We innovatively found that VCAN may be involved in COPD-PH. This study identified the functional circRNAs, providing insights into the molecular mechanisms and predictions of COPD-PH, and may provide potential diagnostic biomarkers or therapeutic targets for COPD-PH.


Impact of PTRIA (Patient Test Result Information Act) on patient follow up management.
We aim to study if direct patient notification in accordance with the Patient Test Results Information Act (Act 112) in Pennsylvania leads to decreased loss to follow up and prompt management of actionable imaging findings. For this IRB-approved study, radiology reports were randomly identified using the Nuance mPower™ search engine. The actionable finding group (prior to Act-112) contained 300 patients for which a voice notification was sent by radiologists to alert ordering physicians about significant imaging findings. The PTRIA group (after Act-112) contained 300 patients who were mailed a standardized letter one day after the final report was issued. The electronic medical records were reviewed to evaluate how patients were managed. There was no difference in loss to follow up rates and time to follow up completion between the two groups. In both groups, 34% of patients were lost to follow up in transition of care from generalists to specialists; 24% cases were lost to follow up when imaging findings were not in the area of the initial ordering provider expertise. The goal of Act 112 is to increase patients' role in the timely management of their significant medical conditions and prevent medical errors, specifically loss to follow up. Our study suggests that presumed patients' awareness does not contribute to improved follow up rates or decreased time to a follow up visit. 13% of patients are lost to follow up in both groups. A tracking system is required to prevent delayed management of the significant findings.


Microdosimetry in low energy proton beam at therapeutic-equivalent fluence rate with silicon 3D-cylindrical microdetectors.
In this work we show the first microdosimetry measurements on a low energy proton beam with therapeutic-equivalent fluence rates by using the second generation of 3D-cylindrical microdetectors. The sensors belong to an improved version of a novel silicon-based 3D-microdetector design with electrodes etched inside silicon, which were manufactured at the National Microelectronics Centre (IMB-CNM, CSIC) in Spain. A new microtechnology has been employed using quasi-toroid electrodes of 25μm diameter and a depth of 20μm within the silicon bulk, resulting in a well-defined cylindrical radiation sensitive volume. These detectors were tested at the 18 MeV proton beamline of the cyclotron at the National Accelerator Centre (CNA, Spain). They were assembled into an in-house low-noise readout electronics to assess their performance at a therapeutic-equivalent fluence rate. Microdosimetry spectra of lineal energy were recorded at several proton energies starting from 18 MeV by adding 50μm thick tungsten foils gradually at the exit-window of the cyclotron external beamline, which corresponds to different depths along the Bragg curve. The experimentalyF¯values in silicon cover from (5.7 ± 0.9) to (8.5 ± 0.4) keV μm-1in the entrance to (27.4 ± 2.3) keV μm-1in the distal edge. Pulse height energy spectra were crosschecked with Monte Carlo simulations and an excellent agreement was obtained. This work demonstrates the capability of the second generation 3D-microdetectors to assess accurate microdosimetric distributions at fluence rates as high as those used in clinical centers in proton therapy.


Changes in the incidence and overall survival of patients with myeloproliferative neoplasms between 2002 and 2016 in the United States.
This analysis examined trends in incidence and survival among US adults with myeloproliferative neoplasms, including essential thrombocythemia (ET; n = 14,676), polycythemia vera (PV; n = 15,141), and primary myelofibrosis (PMF; n = 4214), using Surveillance, Epidemiology, and End User Results (SEER) data (SEER 18; 2002-2016). Incidence and survival rates over the study period and by diagnosis year (per 5-year time frames: 2002-2006; 2007-2011; 2012-2016) were assessed. The overall incidence rates (95% CI) were 1.55 (1.52-1.57) for ET, 1.57 (1.55-1.60) for PV, and 0.44 (0.43-0.45) per 100,000 person-years for PMF, with rising ET incidence. Five-year mortality over the study period was 19.2%, 19.0%, and 51.0% for ET, PV, and PMF, respectively. Improved survival over time was observed for PV and PMF, but not for ET. These findings highlight the need for effective ET therapies, as ET incidence has risen without concurrent improvements in survival over the past 2 decades.


An analysis of patients that underwent computed tomography pulmonary angiography with the prediagnosis of pulmonary embolism in the emergency department.
The purpose of this study is to analyze the frequency of other diagnoses and findings in patients that were diagnosed with or not diagnosed with PE following the CTPA in the ED and to analyze the relationship between diagnosis and D-dimer. INSTRUMENT AND METHOD: This study involves all patients that presented to the ED that underwent CTPA with the prediagnosis of PE. The items considered in this study were their reason for presenting to the ED and pretest clinical risks for PE, D-dimer, and CTPA results. Of the 696 cases, the most common cause was shortness of breath (59.3%). The CTPA showed that 145 (20.83%) patients were suffering from PE. Among the remaining cases, 464 (66.66%) patients had pathological findings other than PE and 87 (12.5%) patients were reported as normal. The most common pathological results other than PE found in CTPA were atelectasis in 244 (39.9%) and ground glass in 165 (23.7%), as well as nonpulmonary results in 70 (10.05%) patients. The differences in D-dimer results of patients diagnosed with PE, patients diagnosed with another pathology, and patients with normal CTPA results were statistically significant (P < 0.001). CTPA scanning, performed on the basis of assessment scoring, helps in discovering other fatal pathologies in addition to PE.


Actual vs. best practices for young children with cerebral palsy: a survey of paediatric occupational therapists and physical therapists in Quebec, Canada.
Cerebral palsy (CP) constitutes a substantial portion of paediatric rehabilitation, yet little is known regarding actual occupational therapy (OT) and physical therapy (PT) practices. This study describes OT and PT practices for young children with CP in Quebec, Canada. This was a cross-sectional survey. All eligible, consenting paediatric occupational therapists (OTs) and physical therapists (PTs) were interviewed using a structured telephone interview based on vignettes of two typical children with CP at two age points--18 months and 4 years. Reported practices were grouped according to the International Classification of Functioning, Disability and Health (ICF). 91.9% of PTs (n=62; 83.8% participation rate) and 67.1% of OTs (n=85; 91.4% participation rate) reported using at least one standardized paediatric assessment. OT and PT interventions focused primarily on impairments and primary function (such as gait function and activities of daily living). Both professions gave little attention to interventions related to play and recreation/leisure. Clinicians reported the need for more training and education specific to CP and to the use of research findings in clinical practice. Wide variations and gaps were identified in clinicians' responses suggesting the need for a basic standard of OT and PT management as well as strategies to encourage knowledge dissemination regarding current best practice.


Chemical ionization mass spectrometry for rapid assay of drugs in serum.
A rapid procedure has been devised for analyzing anti-epileptic drugs in serum by chemical ionization mass spectrometry. An internal standard, 5-(p-methylphenyl)-5-phenylhydantoin (MPPH), is added to serum diluted in buffer at pH 12. The mixture is washed with diethyl ether to remove neutral lipids, acidified, extracted with chloroform and the chloroform extract evaporated to dryness. The residue is then dissolved in methanol and an aliquot, corresponding to approximately 2% of the original mixture, is deposited in the glass capillary sample cup of the solid probe inlet of the mass spectrometer. The sample is then volatilized by heat into the ion source of the mass spectrometer, where it reacts with ionized methane reagent gas. As the temperature of the probe is increased, quasimolecular ion peaks of the protonated anticonvulsants appear, rise and fall on the oscilloscope tracing, indicating similar but not identical rates of volatilization. We recorded these peaks photographically by opening the shutter of the oscilloscope camera for the entire heating cycle. The concentrations of the anticonvulsants were estimated from the ratio of the height of the peaks of the drug to that of the internal standard on the photograph. The peak-height ratios were proportional to concentration within, above and below the therapeutic range. Other drugs, including barbiturates, carbamazepine, nicotine and caffeine, were readily identified when present. With one solid probe inlet, an assay could be performed every 2 min.


Subsidized Households and Wildfire Hazards in California.
As deadly and destructive wildfires become increasingly common in the western United States due to climate change, low-income households face particular difficulties recovering from these disasters. Despite this threat, surprisingly little empirical evidence exists about the exposure and vulnerability to wildfire hazards of residents of subsidized housing. This study focuses on the subsidized housing population for several reasons: residents generally have less adaptive capacity to respond to wildfires; the locations of subsidized housing units reflect relatively stable locations of low-income households for decades; and policymakers can intervene to retrofit existing housing as well as shape future housing siting and design. The dataset created for this study includes all Census tracts in California with housing units by type, wildland-urban interface (WUI) coverage, and an index of social vulnerability. Using a combination of descriptive statistics and spatial regression models, the analysis focuses on the intersection of subsidized housing and wildfire hazards. Results show that subsidized housing is disproportionately located outside the WUI in California's metropolitan and nonmetropolitan areas. However, policy interventions are necessary because many vulnerable households-including those residing in the 140,000 subsidized units in the WUI-live in harm's way.


Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial.
The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.


Survival analysis of one-stage exchange of infected unicompartmental knee arthroplasty: a single-center study with minimum 3 years follow-up.
The rates of unicompartmental knee arthroplasty (UKA) are increasing yet little data exists regarding management of periprosthetic joint infections (PJI) after UKA, particularly utilizing one-stage revision. The aim of this study was to determine the septic and all-cause revision-free survival of UKA PJIs treated with one-stage revision, as well as functional outcomes and risk factors for failure. A retrospective review of one-stage septic revisions with a hinged or rotating hinged implant between 2000 and 2015 at a single institution was performed. Results of 15 patients with a minimum of 3-year follow-up (mean = 93 months; range 37-217) were evaluated by means of infection control, survivorship, patient reported functional score and possible causal factors for a re-revision. Kaplan-Meier curves and Cox regression analysis were used. After a mean of 8 years of follow-up infection control rate was 93.3%, the survivorship free of any reoperation, including both septic and aseptic causes, was 80% at 5 years and 64.2% at ten years and average Lysholm score was 72.7 ± 21.3 (33-100). One-stage revision for PJI of UKA using a hinged knee design has excellent infection-free survival at mid to long-term follow-up. Likewise, patient reported functional outcomes are promising. However, one-third of patients required aseptic reoperation and aseptic loosening was the dominant etiology.


Percutaneous renal biopsies: accuracy, safety, and indications.
Fifty-one percutaneous renal needle biopsies were performed on 46 patients. Initial biopsy was adequate for diagnosis in 89% of patients. When a second biopsy was performed, this accuracy increased to 98%. Thirty-four of 51 (67%) biopsies were for renal masses and 17 (33%) for medical indications. Computed tomographic guidance was utilized in 94% of cases. Biopsies of renal masses were performed with 18-21-gauge needles, while biopsies for medical indications were performed with an 18-gauge cutting needle or 14-gauge Trucut. A rate of serious complications of 6% was noted.


Evaluation of pharyngeal airway volume for different dentofacial skeletal patterns using cone-beam computed tomography.
Understanding of the three-dimensional airway space in three skeletal patterns is important in orthodontic treatment. This study investigated differences between the volume of pharyngeal airway sections and the smallest cross-sectional area in three skeletal patterns by using cone-beam computed tomography (CBCT). The 90 patients were collected to measure total pharyngeal airway volume (TP), velopharyngeal airway volume (VP), glossopharyngeal airway volume (GP), oropharyngeal airway volume (OP), hypopharyngeal airway volume (HP), and the smallest cross-sectional areas (SCA) of the upper respiratory tract as well as other relevant anatomical structures. The mean values differences between classes were analyzed using ANOVA. Pearson's test was used to compare classes in terms of the correlations between different factors. Patients in skeletal classes I and III exhibited significantly higher SCA values (322.6 mm2and 344.5 mm2 respectively) than those in skeletal class II (240.8 mm2). Subjects from skeletal classes I and III exhibited significantly higher values of VP, HP, and OP than those in skeletal class II. Skeletal classes I and III exhibited significantly higher TP values (31190.1 mm3 and 30696.2 mm3, respectively) than those in skeletal class II (22386.0 mm3). Non-significant relationships were discovered between pharyngeal airway and skeletal pattern. Conversely, significant relationships were found between TP and gender, ANB, SNB, hyoid and pogonion positions. The skeletal class II has smaller airway volume than those in skeletal class I and III. The pharyngeal airway volumes could serve as a guide in differentiating the different skeletal classes in clinical settings.


Evaluation of Gianturco coils for closure of large (> or = 3.5 mm) patent ductus arteriosus.
This report evaluates the use of Gianturco coils to close large patent ductus arteriosus (PDAs) (> or = 3.5 mm) and describes transvenous delivery of 0.052-in. (0.132-cm) Gianturco coils. Coil closure of PDAs has become increasingly popular. However, the technique has significant limitations when used to close large PDAs. This report evaluates patient characteristics, PDA anatomy, hemodynamic variables, delivery technique and coil geometry to determine predictors of success. Between January 1995 and January 1997, 16 of 118 patients undergoing catheterization for PDA closure were found to have large PDAs. Their median age and weight were 14 months (range 3 months to 43 years) and 8.5 kg (range 3.5 to 73), respectively. The mean PDA diameter was 4.3 mm (range 3.5 to 5.9). Closure of PDAs was attempted using transcatheter delivery of 0.038-in. (0.096-cm) and 0.052-in. coils. Differences in clinical, anatomic, hemodynamic and technical variables between successes and failures were compared. Eleven (69%) of 16 patients had successful closure of their PDA. Failures occurred only in patients < 8 months of age with an indexed PDA diameter > 7 mm/m and a pulmonary/systemic flow ratio > or = 2.8:1. Use of 0.052-in. coils tended to reduce the incidence of embolization and the number of coils needed for closure. Patients > 8 months of age can have successful closure of large PDAs with currently available Gianturco coils. The 0.052-in. Gianturco coils can be used safely to close large PDAs in infants as small as 6 kg. Increased experience and improved coil design may improve closure rates of large PDAs in infants.


Heterotrophic and mixotrophic cultivation of microalgae to simultaneously achieve furfural wastewater treatment and lipid production.
Furfural wastewater (FWW) treatment is important in modern chemical production. However, traditional wastewater treatment methods are inappropriate for the treatment of FWW. In this work, Chlorella pyrenoidosa was employed to study the growth and pollutants removal with both heterotrophic and mixotrophic cultures. The results show that the biomass and removal efficiency for COD and TN were the highest under 10-fold dilution. However, TP removal were inconsistent when the algae were cultivated in both mixotrophic and heterotrophic modes. Compared to high nitrogen (0.75 g/L NaNO3), the algal cells grew faster when adding 0.25 g/L NaNO3 to the FWW, whether in mixotrophic or heterotrophic conditions. The total lipid content in heterotrophic conditions was 18.53%, which was higher than the values in mixotrophy when the concentration of NaNO3 was 0.75 g/L. Different carbon assimilation mechanisms of the algal cells result in a discrepancy in cell growth and pollutant removal, under different culture modes.


SYNTAX score II in patients with coronary artery disease undergoing percutaneous mitral repair with the MitraClip.
Percutaneous mitral valve repair (PMVR) using the MitraClip™ system has become a valuable alternative in patients with severe mitral regurgitation (MR) and high surgical risk. We sought to evaluate the prognostic value of the SYNTAX II score (SSII) in patients with concomitant coronary artery disease (CAD) undergoing a Mitraclip procedure. In seventy-five consecutive patients who underwent PMVR at the University Heart Center Zürich and the Cardiocentro Ticino, the SSSII was calculated at baseline. Clinical endpoints comprised of all-cause mortality, mitral valve surgery due to failure of PMVR or reoperation, hospitalization for congestive heart failure, heart transplantation and the composite of all four endpoints. Patients were followed for a median of 271days. And were divided in tertiles of SSII: SSII low ≤46.5 (n=25), SSII mid 46.6-54.4 (n=25) and SSII high ≥54.5 (n=25). Patients in the highest SSII tertile had a lower left ventricular ejection fraction (33% vs. 40% vs. 53%) with a higher log-BNP (3.6 vs. 3.45 vs. 3.16) when compared to SSII mid and SSII low, respectively. However, the anatomical syntax score (SS) did not differ significantly within the tertiles (9.1±6.3 (SSII Low) vs 9.5±7.6 (SSII Mid) vs 10.2±6.7(SSII High), p=0.837). The primary endpoint occurred in 33% of patients (n=25). By multivariate analysis patients in the high SSII tertile (OR=6.12, 95% confidence interval, [CI] 1.45-25.86, p=0.014) and patients with a history of MI (OR=3.57, 95% confidence interval, [CI] 1.17-10.88, p=0.025) were at significantly higher risk of experiencing adverse events. Furthermore, in a combined outcome ROC curve analysis, the SSII showed good discrimination with an AUC of 0.73, p=0.001. A cutoff SSII >49 has been identified to have a sensitivity of 83% and specificity of 53% with approximately 45% of the patients experiencing an event during follow-up. Using SSII in CAD patients undergoing PMVR is feasible and of prognostic significance hence widening its clinical utility in valvular heart disease.


Adiponectin receptor 1 interacts with both subunits of protein kinase CK2.
Adiponectin is an adipose tissue-derived hormone that is involved in the inhibition of metabolic syndrome, protection of hypertension, and suppression of atherosclerosis. Since these effects are not understood in detail, adiponectin signaling has to be clarified for therapeutic applications. Adiponectin activities are mediated by its two receptors adiponectin receptor 1 and adiponectin receptor 2, which consist of seven transmembrane helices. Previous studies revealed the beta subunit of protein kinase CK2 as an interaction partner of the adiponectin receptor 1 N-terminus using a yeast-two-hybrid screen, co-immunoprecipitation, ELISA experiments, and co-localization studies. Inhibition of CK2 activity by 2-dimethylamino-4,5,6,7-tetrabromo-1H-benz-imidazole led to a decrease of ACC phosphorylation and indicates an important role of CK2 in adiponectin signaling. CK2 is characterized as a heterotetramer that consists of two regulatory beta and two catalytic alpha subunits, but a holoenzyme-independent role for both subunits is described as well. Therefore, we analyzed the role of the catalytic subunit in this interaction by co-immunoprecipitation and bimolecular fluorescence complementation studies and found CK2 alpha as an interaction partner of the receptor. Treatment with full-length adiponectin resulted in no dissociation of the catalytic alpha subunit. Consequently, our data suggest an interaction of the adiponectin receptor 1 with the tetrameric complex and identified protein kinase CK2 as a key player in adiponectin signaling.


Comparison of two sample collection devices for anal cytology in HIV-positive men who have sex with men: Cytology brush and Dacron swab.
HIV-positive men who have sex with men (MSM) are a vulnerable group for anal cancer (AC), a cancer with a well-described precursor lesion, which can be detected early in screening programs using anal liquid-based cytology (aLBC). We aim to compare two aLBC sample collection devices: cytology brush (CB) and Dacron swab (DS). Retrospective analysis of two consecutive study periods, the first using CB and the second DS. Participants underwent an aLBC, a human papillomavirus (HPV) DNA test and a high-resolution anoscopy (HRA), and a biopsy was performed for suspicious lesions. The sensitivity and specificity of aLBC, area under the receiver operating characteristic (ROC) curve (AUC), and concordance between cytology and HRA were assessed using Cohen's kappa coefficient. A total of 239 participants were enrolled (CB group, 120; DS group, 119). aLBC was benign in 46% of samples, and high-grade squamous intraepithelial lesion (HSIL) was detected in 11.7%. Prevalence of biopsy-proven HSIL was 15.3%. No differences in cytological and histological results were observed between the groups. aLBC-HRA concordance was weak for benign results (CB group, k = 0.309; DS group, k = 0.350) as well as for HSIL (k = 0.321 and 0.387, respectively). Sensitivity and specificity were 100% and 51.4%, respectively, in the CB group and 88% and 54.3% in the DS group (AUC = 0.711 and 0.759, respectively, P-value = .514). Representation of the transformation zone (TZ) was adequate in 83.3% of samples in the CB group and 50.4% in the DS group (P-value <.001). Our data suggest that both devices had similar accuracy to detect anal HSIL, although samples collected with CB are more likely to have an adequate TZ representation, the presence of which could be an indicator of sample quality.


Evaluation of cough peak expiratory flow as a predictor of successful mechanical ventilation discontinuation: a narrative review of the literature.
A crucial step in the transition from mechanical ventilation to extubation is the successful performance of a spontaneous breathing trial (SBT). The American College of Chest Physicians (ACCP) Guidelines recommend removal of the endotracheal tube upon successful completion of a SBT. However, this does not guarantee successful extubation as there remains a risk of re-intubation. Guidelines have outlined ventilator liberation protocols, selected use of non-invasive ventilation on extubation, early mobilization, and dynamic ventilator metrics to prevent and better predict extubation failure. However, a significant percentage of patients still fail mechanical ventilation discontinuation. A common reason for re-intubation is having a weak cough strength, which reflects the inability to protect the airway. Evaluation of cough strength via objective measures using peak expiratory flow rate is a non-invasive and easily reproducible assessment which can predict extubation failure. We conducted a narrative review of the literature regarding use of cough strength as a predictive index for extubation failure risk. Results of our review show that cough strength, quantified objectively with a cough peak expiratory flow measurement (CPEF), is strongly associated with extubation success. Furthermore, various cutoff thresholds have been identified and can provide reasonable diagnostic accuracy and predictive power for extubation failure. These results demonstrate that measurement of the CPEF can be a useful tool to predict extubation failure in patients on MV who have passed a SBT. In addition, the data suggest that this diagnostic modality may reduce ICU length of stay, ICU expenditures, and morbidity and mortality.


[Sports injuries and overuse syndromes].
The benefit of regularly performed physical activity as a fundamental component of a healthy lifestyle is uncontradicted. The number of persons who participate in sports in Germany is approximately more than 40 million people, whereof 27.5 million are organised in sport associations. Every year 1.5-2 million sports injuries occur in Germany, which represent 25-30% of all accidents. The costs for treatment amount to a total of 1.5 billion euros. It is estimated that 80% of all sports injuries could be prevented if training and competition were performed correctly. The patterns and risk of injuries differ between particular sport disciplines and are therefore difficult to estimate. Knowledge of specific injury risks is indispensable for prevention of sports injuries. Furthermore this knowledge facilitates both sports physicians' diagnosis and therapy and guidance of the patient. In this review epidemiological data of sport traumatology are surveyed, patterns of injuries of particular sports are described in detail and prevention strategies are given. In a separate section specifics of sports injuries in children are discussed.


Screen exposure exacerbates ADHD symptoms indirectly through increased sleep disturbance.
The aim of this study was twofold. First, to confirm the deleterious aspect of evening screen exposure in school-aged children, in particular the effect of screens in the bedroom. Second, to explore the three-way association between degree of screen exposure, sleep disturbance, and ADHD symptoms. Solid evidence exists on the link between sleep disturbance and ADHD symptoms, and screen exposure and sleep disturbance. However, no studies have formally assessed the impact of screen exposure on ADHD symptoms in children, as a function of sleep disturbance. Parents of 374 French children (201 girls, 173 boys, mean age of 10.8 ± 2.8 years old) completed the Sleep Disturbance Scale for Children (SDSC), the Attention-Deficit/Hyperactivity Disorder (ADHD) Rating Scale, and a questionnaire about their children's screen habits (total hours in the morning, afternoon, and evening per day). Correlational analyses between evening screen exposure, sleep quality and behavioral problems were conducted. Then, formal mediation analyses were run in order to quantify the relationship between variables. School-aged children with screens in their bedrooms demonstrated more sleep and behavioral problems. Evening TV exposure was associated with higher SDSC and ADHD scores. Furthermore, the Structural Equation Modelling approach confirmed that evening screen exposure is directly associated with more disrupted sleep, which in turn is directly associated with behavioral problems. These findings encourage families to avoid putting screens in their children's bedrooms, and limit evening screen exposure. They furthermore demonstrate the importance of taking into account screen exposure time (morning, afternoon, evening) and location (bedroom or elsewhere) in future studies.


Factors influencing successful Agrobacterium-mediated genetic transformation of wheat.
The development of a robust Agrobacterium-mediated transformation protocol for a recalcitrant species like bread wheat requires the identification and optimisation of the factors affecting T-DNA delivery and plant regeneration. We have used immature embryos from range of wheat varieties and the Agrobacterium strain AGL1 harbouring the pGreen-based plasmid pAL156, which contains a T-DNA incorporating the bar gene and a modified uidA (beta-glucuronidase) gene, to investigate and optimise major T-DNA delivery and tissue culture variables. Factors that produced significant differences in T-DNA delivery and regeneration included embryo size, duration of pre-culture, inoculation and co-cultivation, and the presence of acetosyringone and Silwet-L77 in the media. We fully describe a protocol that allowed efficient T-DNA delivery and gave rise to 44 morphologically normal, and fully fertile, stable transgenic plants in two wheat varieties. The transformation frequency ranged from 0.3% to 3.3%. Marker-gene expression and molecular analysis demonstrated that transgenes were integrated into the wheat genome and subsequently transmitted into progeny at Mendelian ratios.


Health program for VIP's.
The question about special health program for VIP's has been discussed several times. A definition of VIP is a key person either in top management or a person with unique competence in an organization. In small companies you find 5-10 VIP's, in bigger companies up to 50. Our customers indicated a positive interest in a new type of program. They were not satisfied with just a standard screening. They wanted more from screening than just dealing with symptoms of not wellbeing. Most of them had earlier joined different personal development programs. They find those programs useful with well-motivated reasons for change in life patterns. Therefore as a top management consultant, but also certified to work with lifestyle, stress and axiological profile, I was at that time training top management both as individuals and as a team. It was therefore easy for me to combine a personal development program with lifestyle-health screening. In our new program for VIP's we therefore work with both individuals and teams and with both health and personal development.


Magnetic resonance biomarkers of neuroprotective effects in infants with hypoxic ischemic encephalopathy.
Evaluation of infants with hypoxic ischemic encephalopathy by magnetic resonance spectroscopy and imaging is useful to direct clinical care, and may assist the evaluation of candidate neuroprotective therapies. Cerebral metabolites measured by magnetic resonance spectroscopy, and visual analysis of magnetic resonance images during the first 30 days after birth accurately predict later neurological outcome and are valid biomarkers of the key physiological processes underlying brain injury in neonatal hypoxic ischemic encephalopathy. Visual assessment of magnetic resonance images may also be a suitable surrogate outcome in studies of neuroprotective therapies but current magnetic resonance methods are relatively inefficient for use in early phase, first in human infant studies of novel neuroprotective therapies. However, diffusion tensor imaging and analysis of fractional anisotropy with tract-based spatial statistics promises to be a highly efficient biomarker and surrogate outcome for rapid preliminary evaluation of promising therapies for neonatal hypoxic ischemic injury. Standardisation of scanning protocols and data analysis between different scanners is essential.


Role of melatonin in mediating seasonal energetic and immunologic adaptations.
Winter is energetically demanding and stressful; thermoregulatory demands increase when food availability usually decreases. Physiological and behavioral adaptations, including termination of breeding, have evolved among nontropical animals to cope with the energy shortages during winter. Presumably, selection for the mechanisms that permit physiological and behavioral anticipation of seasonal ambient changes have led to current seasonal breeding patterns for many populations. In addition to the well-studied seasonal cycles of mating and birth, there are also significant seasonal cycles of illness and death among field populations of mammals and birds. Energetically challenging winter conditions can directly induce death via hypothermia, starvation, or shock; surviving these demanding conditions likely puts individuals under great physiological stress. The stress of coping with energetically demanding conditions may increase adrenocortical steroid levels that could indirectly cause illness and death by compromising immune function. Individuals would enjoy a survival advantage if seasonally recurring stressors could be anticipated and countered by bolstering immune function. The primary environmental cue that permits physiological anticipation of season is daily photoperiod, a cue that is mediated by melatonin. However, other environmental factors may interact with photoperiod to affect immune function and disease processes. Immune function is compromised during the winter in field studies of birds and mammals. However, laboratory studies of seasonal changes in mammalian immunity consistently report that immune function is enhanced in short day lengths. To resolve this apparent discrepancy, we hypothesize that winter stressors present in field studies counteract short-day enhancement of immune function. Prolonged melatonin treatment mimics short days, and also enhances rodent immune function. Reproductive responsiveness to melatonin appears to affect immune function. In sum, melatonin may be part of an integrative system to coordinate reproductive, immunologic, and other physiological processes to cope successfully with energetic stressors during winter.


Bidirectional measurement of hydrogenase activity by the pH-stat method.
The protons produced by the catalytic activity of hydrogenase in H2 evolution from dithionite-reduced methyl viologen or through benzyl viologen reduction by H2 gas are automatically titrated by a pH-stat device. This approach allows the measurement of hydrogenase activity and ensures the constancy of pH during the reaction in absence of buffers. Kinetic assays and pH and temperature-dependence experiments with Desulfovibrio gigas hydrogenase performed by this method basically confirm the results obtained with customary manometric assay.


Genome-wide identification and characterization of Toll-like receptors (TLR) genes in Haliotis discus hannai, H. rufescens, and H. laevigata.
Toll-like receptors (TLRs) play essential roles in the innate immune system and have been extensively studied in mollusks. In this study, through a genome-wide search, TLR genes were identified as 29 in Haliotis discus hannai, 33 in H. rufescens, and 16 in H. laevigata. Domain analysis indicated that these TLR genes contain leucine-rich repeat (LRR) and Toll/IL-1 receptor (TIR) domains and exons ranging from 1 to 5. Polymorphism analysis showed that the TLRs in abalones did not have high diversities with 143 SNPs and no Indel in H. discus hannai, 92 SNPs and 3 Indels together with 6 missense mutations in H. rufescens, and no SNP or Indel in H. laevigata. The expression of 8 TLR genes in H. discus hannai was confirmed in the hepatopancreas, gill, hemolymph, gonads, intestine, muscle, and mantle. The expression of five TLR genes (out of 8) in gills (p < 0.05), three in hepatopancreas (p < 0.05), and three in hemolymph (p < 0.05) was upregulated separately in response to the infection caused by Vibrio parahaemolyticus. The findings in this study would contribute to a better understanding of the molecular immune mechanism of H. discus hannai against stimulation by V. parahaemolyticus and provide a basis for the study of TLRs in abalones.


APAF1-Binding Long Noncoding RNA Promotes Tumor Growth and Multidrug Resistance in Gastric Cancer by Blocking Apoptosome Assembly.
Chemotherapeutics remain the first choice for advanced gastric cancers (GCs). However, drug resistance and unavoidable severe toxicity lead to chemotherapy failure and poor prognosis. Long noncoding RNAs (lncRNAs) play critical roles in tumor progression in many cancers, including GC. Here, through RNA screening, an apoptotic protease-activating factor 1 (APAF1)-binding lncRNA (ABL) that is significantly elevated in cancerous GC tissues and an independent prognostic factor for GC patients is identified. Moreover, ABL overexpression inhibits GC cell apoptosis and promotes GC cell survival and multidrug resistance in GC xenograft and organoid models. Mechanistically, ABL directly binds to the RNA-binding protein IGF2BP1 via its KH1/2 domain, and then IGF2BP1 further recognizes the METTL3-mediated m6A modification on ABL, which maintains ABL stability. In addition, ABL can bind to the WD1/WD2 domain of APAF1, which competitively prevent cytochrome c from interacting with APAF1, blocking apoptosome assembly and caspase-9/3 activation; these events lead to resistance to cell death in GC cells. Intriguingly, targeting ABL using encapsulated liposomal siRNA can significantly enhance the sensitivity of GC cells to chemotherapy. Collectively, the results suggest that ABL can be a potential prognostic biomarker and therapeutic target in GC.


Phenytoin suppresses spontaneous ectopic discharge in rat sciatic nerve neuromas.
Afferent fibers ending in nerve-end neuromas generate spontaneous impulse discharge which has been implicated as a cause of paraesthesias and pain following peripheral nerve injury in man. We now show in rats that the anticonvulsant drug phenytoin (PT), applied systemically or topically onto desheathed neuromas, suppresses the generation of neuroma discharge without blocking impulse conduction. The effect is dose-dependent and reversible upon drug washout. Since PT is known to provide effective pain relief in some kinds of neuralgia, the data suggest that the clinical analgesic action of PT in these conditions may, at least in part, involve a direct suppression of ectopic impulses generated in the region of the nerve damage.


Flow, Liver, Flow: A Retrospective Analysis of the Interplay of Liver Disease and Coagulopathy in Chronic Subdural Hematoma.
Chronic subdural hematoma (cSDH) is a common neurosurgical ailment, particularly in elderly patients. A recent study uncovered an association between liver disease and recurrence in patients with cSDH. Here, we explored that relationship to identify recurrence predictors in at-risk patients. We hypothesized that the association between liver disease and recurrence was attributable to coagulopathy secondary to liver disease. We retrospectively reviewed all patients with cSDH treated with burr-hole drainage by 2 surgeons between 2007 and 2015. Comorbidities and laboratory findings for each patient were examined by Pearson χ2 analysis or Mann-Whitney U tests. We identified 261 cSDH in 215 patients. Patients were a mean age of 65.6 years, and 72% were male. Sixteen patients with cSDH required repeat surgery (6.1%). There were 123 coagulopathic patients (47.1%), and 14 with liver disease (5.4%), all of whom were coagulopathic (P < 0.001). Coagulopathic patients with liver disease were more likely to experience recurrence than patients with coagulopathy alone (relative risk = 4.09, P = 0.019). Patients with liver disease had significantly elevated prothrombin time (P = 0.013) and reduced platelet counts (P < 0.001). Platelets also were reduced in coagulopathic patients with liver disease, as compared with those with coagulopathy alone (P = 0.002). Thrombocytopenia remained significant in a multivariate analysis (P < 0.001). Liver disease is significantly associated with the recurrence of cSDH. Although coagulopathy alone does not predict recurrence, patients with coagulopathy and liver disease are at greater risk for recurrence than those with coagulopathy alone. Liver disease effects are reflected in certain hematologic laboratory values.


Characterization of the glycine-dependent redox-cycling activity in animal fluids and tissues using specific inhibitors and activators: evidence for presence of PQQ.
Pyrroloquinoline quinone, a redox cofactor first isolated from bacteria, efficiently catalyzes the nonenzymatic oxidation of glycine in the presence of nitroblue tetrazolium. We report that certain metallic cations and heterocyclic aromatic cations, like the N-methyl phenazonium cation and aryl-iodonium compounds, strongly and specifically inhibit this redoxcycling activity. The inhibition by metal cations is reversed by Tiron and that of the aromatic cations by Tiron and thyroxine. These inhibitors and activators affect authentic PQQ and the redox-activity of putative PQQ isolated from biological sources in a similar manner. This indicates that pyrroloquinoline quinone occurs naturally in animal tissues and fluids.


Pulmonary embolism and intracardiac shunt: a unique indication for operation.
Pulmonary embolism with right-to-left intracardiac shunt presents a special problem for the clinician. A review of the literature and 4 personal cases, all diagnosed antemortem, are presented. On the basis of this information certain conclusions are drawn, and we suggest the problem to be a unique indication for the consideration of surgical intervention.


Association of vitamin D receptor gene polymorphisms and risk of urolithiasis: results of a genetic epidemiology study and comprehensive meta-analysis.
Polymorphisms of vitamin D receptor (VDR) gene have been associated with risk of urolithiasis, but, with inconsistent results and lack data from Pakistani population. Therefore, after including our indigenous study data, a comprehensive meta-analysis was performed to provide an evidence-based estimate of any association between VDR polymorphisms and urolithiasis risk. A total of 483 Pakistani subjects, comprising 235 urolithiasis patients and 248 healthy controls, were genotyped for 6 VDR polymorphisms. Additionally, a systematic literature search with subsequent meta-analysis was conducted and pooled odds ratios (ORs) were used to determine the strength of any existent associations. Trial sequential analysis (TSA) was also performed. Results revealed no significant association of any VDR polymorphism and urolithiasis risk in indigenous Pakistani patients. However, meta-analysis of 29 relevant studies indicated that VDR FokI polymorphism significantly increased the risk of urolithiasis in allelic (f vs. F: OR = 1.13; 95% CI = 1.05-1.22; p ≤ 0.01) and recessive (ff vs. FF + Ff: OR = 1.20; 95% CI = 1.05-1.38; p = 0.01) models with no significant heterogeneity. No associations were evident for VDR ApaI, BsmI and TaqI polymorphic variants and urolithiasis risk after correction for multiple testing. Subgroup analysis by ethnicity suggested significant association for FokI variant among Asians. The TSA results demonstrated that the evidence reflecting association of FokI polymorphism and urolithiasis risk was sufficient and conclusive. In conclusion, this meta-analysis suggests that VDR FokI polymorphism is significantly associated with urolithiasis risk, especially in Asians, whereas ApaI, BsmI and TaqI polymorphisms are not associated.


Absorption of calcium, zinc, and iron from breast milk by five- to seven-month-old infants.
Data are scarce regarding mineral bioavailability from human milk in older infants who may also be receiving solid foods (beikost). We measured the absorption of Ca, Zn, and Fe in 14 healthy, nonanemic 5-7-mo-old breast-fed infants whose mothers milk was extrinsically labeled with stable isotopes (44Ca, 70Zn, and 58Fe) of these minerals. In addition, Ca and Zn stable isotopes (46Ca and 67Zn) were administered i.v., and a second isotope of Fe (57Fe) was given orally without food as a non-meal dose. Subjects were not receiving any artificial infant formula or cow's milk, but most (10/14) were receiving beikost. Ca and Zn absorption was calculated using the urinary excretion of the isotopes during the 24 h after dosing (Ca) or their urinary ratio 72 h after dosing (Zn). Fe absorption was calculated using the red blood cell incorporation at 14 d. Fe absorption averaged 20.7 +/- 14.8% from the 58Fe given with human milk (geometric mean, 14.8%) and 17.7 +/- 15.1% (geometric mean, 11.0%) from the 57Fe non-meal dose. Ca absorption averaged 61.3 +/- 22.7% and Zn absorption (n = 10) averaged 49.5 +/- 18.5%. Absorption of Fe (natural logarithm) from the non-meal Fe dose (57Fe) but not from the human milk (58Fe) was significantly negatively correlated to serum ferritin (r = -0.70, p = 0.007 versus r = -0.35, p = 0.24). At the intake levels in this study, total daily Fe, Ca, and Zn intakes from beikost were not significantly correlated to their fractional absorption from breast milk, but Fe intake from beikost was significantly negatively correlated to absorption of Fe from the non-meal dose (r = -0.61, p = 0.021). We conclude that minerals are well absorbed from human milk in older infants after the introduction of beikost to the diet.


Changes in bone mineral density following laparoscopic sleeve gastrectomy: 2-year outcomes.
Emerging evidence suggests that sleeve gastrectomy (SG) leads to significant bone mineral density (BMD) losses, but there is a paucity of studies evaluating skeletal consequences beyond 12-months post-operatively. To evaluate BMD changes 2 years postoperatively. A university hospital. Thirty-three women (mean age: 34.4 ± 12.3 years) who underwent SG and completed 24 months of follow-up were evaluated prospectively at baseline and at 3 (M3), 6 (M6), 12 (M12), and 24 (M24) months postoperatively. Data collected included BMD at the total hip, femoral neck, and lumbar spine measured by dual-energy x-ray absorptiometry and anthropometrics, biochemical, nutritional, and physical activity parameters. At M24, patients achieved a mean body mass index and excess weight loss of 32.4 ± 5.1 kg/m2 and 64.5 ± 21.4%, respectively; however, weight stabilized at M12. Femoral neck BMD decreased significantly from baseline to M24 (.924 ± .124 versus .870 ± .129 g/cm2, P < .001), with no change between M12 and M24 (P = .273). Total hip BMD decreased significantly from baseline to M24 (1.004 ± .105 versus .965 ± .132 g/cm2, P < .001) but increased between M12 and M24 (P = .001). No significant changes were noted in lumbar spine BMD. The percentage of changes in the femoral neck and the total hip BMD from baseline to M24 positively correlated with postoperative excess weight loss (r = .352, P = .045, and r = .416, P = .018, respectively). Despite notable weight loss, women who underwent SG experienced significant bone loss at the total hip and femoral neck more than 2 years postoperatively. Future studies should investigate intervention strategies to attenuate skeletal deterioration after SG.


Variations of metal distribution in sewage sludge composting.
In the study, the variations of heavy metal distributions (of Cu, Mn, Pb, and Zn) during the sewage sludge composting process were investigated by sequential extraction procedures. The total content of Cu and Zn in the composted mixture increased after the composting process. Mn and Zn were mainly found in mobile fractions (exchangeable fraction (F1), carbonate fraction (F2), and Fe/Mn oxide fraction (F3)). Cu and Pb were strongly associated with the stable fractions (organic matter/sulfides fraction (F4) and residual fraction (F5)). These five metal fractions were used to calculate the metal mobility (bioavailability) in the sewage sludge and composted mixture. The mobility (bioavailability) of Mn, Pb, and Zn (but not Cu) increased during the composting process. The metal mobility in the composted mixture ranked in the following order: Mn>Zn>Pb>Cu.


Amelioration of Combination of Paclitaxel and Di Allyl Sulfide on the Alterations of Bcl2, P53 and Apoptosis Changes Against 7,12 Di Methyl Benz (A) Anthracene Induced Skin Cancer in Experimental Animals.
The purpose of this study was to investigate the Bcl2, P53 and apoptosis changes against skin cancer in experimental animals. Skin cancer is the most common form of human cancer. It is estimated that over 1 million new cases occur annually. The annual rates of all forms of skin cancer are increasing each year, representing a growing public concern. It has also been estimated that nearly half of all Americans who live to age 65 are likely to develop skin cancer at least once. Skin cancer was induced in rats by Di Methyl Benz (a) Anthracene at the dosage of DMBA (5 µg) per animal, three times a week for 28 weeks after conformation of skin cancer treated with Paclitaxel and Di allyl sulfide for 30 days. The levels of Bcl2 gene expression were significantly decreased and P53gene expression were markedly increased in Paclitaxel and Di allyl sulfide treated animals when compared with cancer bearing animals. The treatment with combination of Paclitaxel and Di allyl sulfide effectively reduced Bcl2 protein expression and also increased P53gene expression. Moreover, the levels of Bcl2 and P53 a good indicators of restoring the skin architecture, were also reversed in skin damage subjects after treatment with the herbal compounds preparation. So, from the obtained results it is concluded that a combination of Paclitaxel and Di allyl sulfide is capable of restoring the skin architecture and can also increase the apoptosis activities in skin cancer rats.


Comparison Between Manual and Automated Analyses in Multichannel Intraluminal Impedance: pH Monitoring for Laryngopharyngeal Reflux.
To evaluate differences between manual and automated analyses of 24-hour multichannel intraluminal impedance-pH monitoring for diagnosis of laryngopharyngeal reflux. Case series with planned data collection. Academic center outpatient clinic. The study group comprised 127 patients with symptoms suspicious of laryngopharyngeal reflux, who underwent 24-hour multichannel intraluminal impedance-pH monitoring. Automated and manual analyses were performed for each patient. The following parameters were compared between analyses: number of proximal reflux episodes, proximal exposure time, symptom index, and symptom association probability. The number of proximal reflux episodes detected by manual analysis was significantly lower than that detected by automated analysis, except in acid reflux cases. The false positive of automated analysis was 39.8%. In addition, the proximal exposure time for manual analysis was significantly lower than that for automated analysis, except in cases of acid reflux. Symptom index and symptom association probability values based on manual analysis were significantly lower than in automated analysis, except in heartburn cases. Automated analysis demonstrated a tendency of excessive reflux measurement when compared with manual analysis. It is necessary to increase the accuracy of laryngopharyngeal reflux diagnosis through manual analysis.


Reduced graphene oxide nanosheets modified with nickel disulfide and curcumin nanoparticles for non-enzymatic electrochemical sensing of methyl parathion and 4-nitrophenol.
A method was designed for simultaneous voltammetric determination of methyl parathion pesticide (MP) and 4-nitrophenol (4-NP). Curcumin nanoparticles were deposited on reduced graphene oxide nanosheets that were modified with nickel disulfide. The material was placed on a screen-printed carbon electrode and then displayed high electrocatalytic activities toward MP and 4-NP, with a peak potential near -0.9 and - 0.7 V (vs. pseudo Ag/AgCl), respectively. Figures of merit include (a) good electrochemical sensitivities (7.165 and 6.252 μA·μM-1·cm-2), (b) wide linear ranges (from 0.25 to 80 μM), (c) low limits of detection (8.7 and 6.9 nM at S/N = 3) for MP and 4-NP, respectively, and (d) good selectivity, repeatability, reproducibility, and storage stability. The method was applied in the determination of MP and 4-NP in tomato and apple juices and spiked river water. Graphical abstract A novel electrocatalysis platform based on reduced graphene oxide-nickel disulfide nanosheets decorated with curcumin nanoparticles for simultaneous quantification of methyl parathion and 4-nitrophenol in various vegetarian juices and water samples.


In Vitro Efficacy of Moxidectin versus Ivermectin against Sarcoptes scabiei.
Moxidectin is under consideration for development as a treatment for human scabies. As some arthropods show decreased sensitivity to moxidectin relative to ivermectin, it was important to assess this for Sarcoptes scabieiIn vitro assays showed that the concentration of moxidectin required to kill 50% of mites was lower than that of ivermectin (0.5 μM versus 1.8 μM at 24 h; P < 0.0001). This finding provides further support for moxidectin as a candidate for the treatment of human scabies.


Hepatic Arterial Infusion Chemotherapy of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Sorafenib as Initial Treatment for Advanced Hepatocellular Carcinoma.
Our previous study showed that hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin (FOLFOX) plus sorafenib provided a significant survival benefit over sorafenib for advanced hepatocellular carcinoma. However, it is unclear whether the survival benefit should be attributed to the synergism between HAIC and sorafenib or just HAIC alone. We aim to compare HAIC using FOLFOX plus sorafenib with HAIC alone in patients with advanced hepatocellular carcinoma. This was a retrospective study including 225 eligible patients treated with HAIC using FOLFOX (HAIC alone group, n=126, oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil bolus 400 mg/m² and 2400 mg/m² for 46 hours, every 3 weeks) alone or HAIC plus sorafenib (soraHAIC group, n=99, sorafenib 400 mg twice daily). Survival curves were calculated by the Kaplan-Meier method, and propensity-score matching was used to reduce bias. The soraHAIC group showed a longer overall survival (12.9 [95% CI, 10.4-15.4] vs. 10.5 [95% CI, 9.5-11.5] months, HR=0.71 [95% CI, 0.53-0.96]; P=0.025), a better progression free survival (7.0 [95% CI, 5.3-8.8] vs. 5.3 [95% CI, 3.5-7.1] months, HR=0.76 [95% CI, 0.58-0.99]; P=0.046), and a higher disease control rate (RECIST 1.1: 74.8% vs. 61.1%, P=0.030) than the HAIC alone group. In multivariate analysis, soraHAIC was an independent favor factor for survival. In terms of the grade 3/4 adverse event, hand-foot skin reaction was more frequent in the soraHAIC group than the HAIC alone group. In the propensity-score matched cohorts (93 pairs), the overall survival, the progression free survival and disease control rates in the soraHAIC group were also better than those in the HAIC group (P<0.05). HAIC plus sorafenib may improve overall survival and progression free survival compared with HAIC alone as initial treatment for advanced hepatocellular carcinoma.


Causal Indicators for Assessing the Truthfulness of Child Speech in Forensic Interviews.
When interviewing a child who may have witnessed a crime, the interviewer must ask carefully directed questions in order to elicit a truthful statement from the child. The presented work uses Granger causal analysis to examine and represent child-interviewer interaction dynamics over such an interview. Our work demonstrates that Granger Causal analysis of psycholinguistic and acoustic signals from speech yields significant predictors of whether a child is telling the truth, as well as whether a child will disclose witnessing a transgression later in the interview. By incorporating cross-modal Granger causal features extracted from audio and transcripts of forensic interviews, we are able to substantially outperform conventional deception detection methods and a number of simulated baselines. Our results suggest that a child's use of concreteness and imageability in their language are strong psycholinguistic indicators of truth-telling and that the coordination of child and interviewer speech signals is much more informative than the specific language used throughout the interview.


[Evolution of nutritional status in physical education students, associated with the level of cardiovascular risk, food consumption and the level of physical activity].
The prevalence of overweight and obesity increases in university students as a consequence of the modification of their eating habits and their level of physical activity. The general objective of this work was to analyze the relationship between the nutritional status of Physical Education students and the level of physical activity, cardiovascular risk and eating habits, during the first three years of the degree. Observational, descriptive and longitudinal section study. 67 students were studied. To assess nutritional status and cardiovascular risk, body mass index (BMI) and waist circumference (CC) were measured, respectively. To inquire about eating habits, a survey was used based on the recommendations of the dietary guidelines for the Argentine population. To estimate the level of physical activity, the IPAQ International Physical Activity Questionnaire, short format, Spanish version was used. Students with obesity, obesity, and elevated cardiovascular risk increased during the course of the study. For their part, healthy eating behaviors and a high level of physical activity in women decreased. BMI showed a positive correlation with CC. Healthy food selection in males was correlated with BMI. The evolution of the course in Physical Education indicated a progressive increase in the factors associated with obesity. These results would allow directing and promoting legislative actions that update the curriculum of the Physical Education career, according to the social and health needs of this population.


Solving the α-helix correspondence problem at medium-resolution Cryo-EM maps through modeling and 3D matching.
Cryo-electron microscopy (cryo-EM) has recently emerged as a prominent biophysical method for macromolecular structure determination. Many research efforts have been devoted to produce cryo-EM images, density maps, at near-atomic resolution. Despite many advances in technology, the resolution of the generated density maps may not be sufficiently adequate and informative to directly construct the atomic structure of proteins. At medium-resolution (∼4-10 Å), secondary structure elements (α-helices and β-sheets) are discernible, whereas finding the correspondence of secondary structure elements detected in the density map with those on the sequence remains a challenging problem. In this paper, an automatic framework is proposed to solve α-helix correspondence problem in three-dimensional space. Through modeling of the sequence with the aid of a novel strategy, the α-helix correspondence problem is initially transformed into a complete weighted bipartite graph matching problem. An innovative correlation-based scoring function based on a well-known and robust statistical method is proposed for weighting the graph. Moreover, two local optimization algorithms, which are Greedy and Improved Greedy algorithms, have been presented to find α-helix correspondence. A widely used data set including 16 reconstructed and 4 experimental cryo-EM maps were chosen to verify the accuracy and reliability of the proposed automatic method. The experimental results demonstrate that the automatic method is highly efficient (86.25% accuracy), robust (11.3% error rate), fast (∼1.4 s), and works independently from cryo-EM skeleton.