Misoprostol accelerates colonic mucosal repair in acetic acid-induced colitis.
The objectives of this study were 1) to determine whether misoprostol (MISO) (prostaglandin E1 analog) pretreatment protects the colonic mucosa from the injurious effects of acetic acid by attenuating the initial injury or by enhancing the rate of repair and 2) to assess the relationship between the protective effect of MISO pretreatment and mucosal ornithine decarboxylase activity in the inflamed colon. We found that the intrarectal administration of acetic acid caused rapid and extensive injury to the colonic mucosa, such that mucosal permeability increased 88-, 75-, 26-, 7.5- and 9.3-fold at 1, 2, 6, 24 and 48 hr after the enema, respectively. Intrarectal pretreatment with 50 micrograms of MISO for 30 min did not attenuate the increase in mucosal permeability at 1 hr after enema; however, it did significantly reduce mucosal permeability by 50 to 60% at 2, 6 and 48 hr after enema. We also demonstrated that acetic acid produced an 8.4-fold increase in colonic myeloperoxidase activity and a 1.8-fold increase in colonic weight at 48 hr after enema. MISO significantly reduced the increases in both myeloperoxidase activity and colon weight. Ornithine decarboxylase activity in the descending colon of vehicle-pretreated animals increased significantly only at 24 hr after the acetic acid enema. In addition, MISO pretreatment followed by acetic acid enema resulted in significantly higher ornithine decarboxylase activities in the descending colon at 2 and 6 hr, compared with the vehicle plus acetic acid and MISO plus saline groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Parental autonomy support and future-oriented coping among high school students: Serial mediation of future time perspective and meaning in life.
Guided by the ecosystem theory, this study aimed to explore the association between parental autonomy support and future-oriented coping of high school students, as well as the mediating effects of future time perspective and meaning in life in this relationship. A total of 707 Chinese high school students were involved in a paper questionnaire survey and data analysis. It was found that (1) parental autonomy support was significantly positively related to future-oriented coping. (2) Mediation analyses demonstrated that parental autonomy support directly affects future-oriented coping; parental autonomy support indirectly affects future-oriented coping through separate mediation and serial mediation of future time perspective and meaning in life. These findings have important implications for the improvement of future-oriented coping abilities of high school students.


Arteriovenous fistulas for hemodialysis: application of high-frequency US to assess vein wall morphology for cannulation readiness.
To determine whether venous wall thickness and hoop (circumferential) stress, as determined with high-frequency ultrasonography (US), can predict cannulation readiness in arteriovenous fistulas (AVFs). Institutional review board approval and informed consent were obtained for this prospective study. To determine the US appearance of the venous wall, an AVF specimen was excised and scanned in a bath of degassed lactated Ringer solution with a 55-MHz probe. The appearance of the wall at high-frequency US was correlated with histologic findings. High-frequency (40-55-MHz) US was used to image the near-field AVF venous wall of 14 men (mean age, 59 years ± 11 [standard deviation]) and six women (mean age, 55 years ± 14) with newly created AVFs within 1 week of cannulation between January 2008 and December 2009. Measurements of the intima-media thickness (IMT) were generated by three independent observers who were blinded to outcomes. Intraclass correlation analysis was performed. Cannulation readiness was defined as no extravasation during the first dialysis treatment. By using high-frequency US, the IMT was defined as the sum of a thin echogenic blood-intima interface and a uniform hypoechoic media. The mean IMT of the no extravasation group (0.16 mm ± 0.03) was greater than that of the extravasation group (0.10 mm ± 0.02) (P < .001). A minimum threshold IMT of 0.13 mm (P < .001) was associated with successful cannulation. The mean hoop stress of the no extravasation group (246 kPa ± 57) was lower than that of the extravasation group (530 kPa ± 199) (P < .001). A maximum hoop stress threshold of 248 kPa was associated with successful cannulation (P = .009). Venous IMT and hoop stress assessed with high-frequency US can predict cannulation readiness in AVFs that are clinically deemed mature.


[A case of pleomorphic liposarcoma in a patient with Crohn's disease taking azathioprine].
Azathioprine is frequently used for the treatment of inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. Lymphomas, squamous cell carcinomas, and undifferentiated pleomorphic sarcomas have been reported among patients receiving azathioprine therapy. Herein, we report a case of pleomorphic liposarcoma of chest wall which occurred in a 44-year-old man with Crohn's disease taking azathioprine. He was diagnosed with Crohn's disease 3 years ago after suffering from abdominal pain and hematochezia for 12 years. He had been taking 50 mg of azathioprine per day for 23 months when he visited the thoracic and cardiovascular surgery clinic due to right chest palpable mass that had rapidly grown during the past 2 months. Excisional biopsy was performed and the mass was diagnosed as pleomorphic liposarcoma. Therefore, he underwent radical excision of the right chest wall mass, which measured 11.0 × 6.5 cm in size. He is scheduled to receive radiation therapy and chemotherapy.


Genetic differentiation and connectivity of morphological types of the broadcast-spawning coral Galaxea fascicularis in the Nansei Islands, Japan.
Population connectivity resulting from larval dispersal is essential for the maintenance or recovery of populations in marine ecosystems, including coral reefs. Studies of species diversity and genetic connectivity within species are essential for the conservation of corals and coral reef ecosystems. We analyzed mitochondrial DNA sequence types and microsatellite genotypes of the broadcast-spawning coral, Galaxea fascicularis, from four regions in the subtropical Nansei Islands in the northwestern Pacific Ocean. Two types (soft and hard types) of nematocyst morphology are known in G. fascicularis and are significantly correlated with the length of a mitochondrial DNA noncoding sequence (soft type: mt-L; hard type: mt-S type). Using microsatellites, significant genetic differentiation was detected between the mitochondrial DNA sequence types in all regions. We also found a third genetic cluster (mt-L+), and this unexpected type may be a cryptic species of Galaxea. High clonal diversity was detected in both mt-L and mt-S types. Significant genetic differentiation, which was found among regions within a given type (F ST = 0.009-0.024, all Ps ≤ 0.005 in mt-L; 0.009-0.032, all Ps ≤ 0.01 in mt-S), may result from the shorter larval development than in other broadcast-spawning corals, such as the genus Acropora. Nevertheless, intraspecific genetic diversity and connectivity have been maintained, and with both sexual and asexual reproduction, this species appears to have a potential for the recovery of populations after disturbance.


Young Adult Unemployment and Later Depression and Anxiety: Does Childhood Neighborhood Matter?
Young adulthood represents a developmental period with disproportionately heightened risk of losing a job. Young adult unemployment has been linked to increased mental health problems, at least in the short term. However, their possible long-term impacts, often referred as "scarring effects," have been understudied, possibly underestimating the magnitude of mental health burden that young adult unemployment generates. This longitudinal study examined whether duration of unemployment during young adulthood is associated with later mental health disorders, after accounting for mental and behavioral health problems in childhood. Furthermore, the current study investigated whether childhood neighborhood characteristics affect this association and if so, in what specific functional ways. Data were drawn from a longitudinal study of developmental outcomes in a community sample in Seattle. Data collection began in 1985 when study participants were elementary students and involved yearly assessments in childhood and adolescence (ages 10-16) and then biennial or triennial assessments (ages 18-39; N = 677 at age 39; 47% European American, 26% African American, 22% Asian American, and 5% Native American; 49% female). The current study findings suggest that duration of unemployment across young adulthood increased mental health problems at age 39, regardless of gender. Childhood neighborhood characteristics, particularly their positive aspect, exerted independent impacts on adult mental health problems beyond unemployment experiences across young adulthood. The current findings indicate a needed shift in service profiles for unemployed young adults-a comprehensive approach that not only facilitates reemployment but also addresses mental health needs to help them to cope with job loss. Further, the present study findings suggest that childhood neighborhoods, particularly positive features such as positive neighborhood involvement, may represent concrete and malleable prevention targets that can curb mental health problems early in life.


Agriculture Development, Pesticide Application and Its Impact on the Environment.
Pesticides are indispensable in agricultural production. They have been used by farmers to control weeds and insects, and their remarkable increases in agricultural products have been reported. The increase in the world's population in the 20th century could not have been possible without a parallel increase in food production. About one-third of agricultural products are produced depending on the application of pesticides. Without the use of pesticides, there would be a 78% loss of fruit production, a 54% loss of vegetable production, and a 32% loss of cereal production. Therefore, pesticides play a critical role in reducing diseases and increasing crop yields worldwide. Thus, it is essential to discuss the agricultural development process; the historical perspective, types and specific uses of pesticides; and pesticide behavior, its contamination, and adverse effects on the natural environment. The review study indicates that agricultural development has a long history in many places around the world. The history of pesticide use can be divided into three periods of time. Pesticides are classified by different classification terms such as chemical classes, functional groups, modes of action, and toxicity. Pesticides are used to kill pests and control weeds using chemical ingredients; hence, they can also be toxic to other organisms, including birds, fish, beneficial insects, and non-target plants, as well as air, water, soil, and crops. Moreover, pesticide contamination moves away from the target plants, resulting in environmental pollution. Such chemical residues impact human health through environmental and food contamination. In addition, climate change-related factors also impact on pesticide application and result in increased pesticide usage and pesticide pollution. Therefore, this review will provide the scientific information necessary for pesticide application and management in the future.


A DNA Nanodevice Simultaneously Activating the EGFR and Integrin for Enhancing Cytoskeletal Activity and Cancer Cell Treatment.
Cell-surface receptors (e.g., EGFR and integrin) and their interactions play determining roles in signal transduction and cytoskeletal activation, which affect cell attachment/detachment, invasion, motility, metastasis (intracellular), and cell-cell signaling. For instance, the interactions between the EGFR and integrin (α6β4) may cause increased mechanical force and shear stress via enhanced cytoskeleton activation. Here, we design a DNA nanodevice (DNA-ND) that can simultaneously target the EGFR and integrin receptors on the caveolae. The piconewton (pN) forces in response to the EGFR-integrin coactivation can be sensed upon the unfolding of the DNA hairpin structure on the side arm of the device via changes of the fluorescence and plasmonic signals. We find that simultaneous activation of EGFR-integrin receptors causes enhanced signal transduction, contractions of the cells, and initiation of the biochemical pathways, thus resulting in a change of the cell division and endocytosis/exocytosis processes that affect the cell proliferation/apoptosis. The DNA-ND further enables us to visualize the cointernalization and degradation of the receptors by lysosomes, providing a novel approach toward bioimaging and mechano-pharmacology.


Late Recurrence of Hepatocellular Carcinoma in a Patient 10 Years after Liver Transplantation Unrelated to Transplanted Organ.
Liver transplantation (LTx) is an accepted method of hepatocellular carcinoma (HCC) treatment in cirrhotic patients; however, it has many limitations, and there is a substantial risk of recurrence. Most relapses occur within the first 2 posttransplant years. We aimed to present a late extrahepatic recurrence of HCC 10 years after LTx, and we discuss the possible risk factors and ways to improve transplantation results. A 68-year-old patient with liver cirrhosis and HCC on the background of chronic HCV and past HBV infection was transplanted urgently due to the rapid decompensation. Anti-HCV treatment before surgery was unsuccessful. Pretransplant computed tomography showed 1 focal 4.5 cm lesion consistent with HCC. Histopathology of the explanted organ showed 2 nodules outside the Milan criteria. Angioinvasion was not found. The patient achieved a sustained viral response to pegylated interferon and ribavirin 2 years post-LTx. Eight years were uneventful. CT of the abdomen performed occasionally was normal. Ten years after LTx, the patient unexpectedly presented with shortness of breath, fatigue, and weight loss. Two metastatic nodules of HCC in the lungs and pelvis were found. Although late HCC recurrence post-LTx is rare, it should be always considered, especially when risk factors such as viral infections and underestimation of tumor advancement were identified. We advocate that oncological surveillance of HCC relapse has to be continued during the whole posttransplant period. High AFP levels, the unfavorable neutrophil to lymphocyte ratio, and better estimation of primary tumor size seem to be useful in the identification of good candidates for transplantation.


Operational and resource management of an RCT: some of the pitfalls and lessons learned.
Nurses frequently fulfil important functions within a research team involved in clinical trials. This paper describes the challenges inherent in developing and managing a large clinical trial involving the evaluation of homoeopathy and asthma. Teamwork, a clear and comprehensive understanding of the research protocol, marketing the project, and the ability to manage human resources within both a primary and secondary care environment are all essential aspects of clinical research. Our experience in establishing and managing this project has suggested to us that a high standard of clinical research demands an open approach to problem-solving as well as the realization that efficient research is as much about the management of people as it is about scientific rigour.


Advanced Technology Evolution Pathways of Nanogenerators: A Novel Framework Based on Multi-Source Data and Knowledge Graph.
As an emerging nano energy technology, nanogenerators have been developed rapidly, which makes it crucial to analyze the evolutionary pathways of advanced technology in this field to help estimate the development trend and direction. However, some limitations existed in previous studies. On the one hand, previous studies generally made use of the explicit correlation of data such as citation and cooperation between patents and papers, which ignored the rich semantic information contained in them. On the other hand, the progressive evolutionary process from scientific grants to academic papers and then to patents was not considered. Therefore, this paper proposes a novel framework based on a separated three-layer knowledge graph with several time slices using grant data, paper data, and patent data. Firstly, by the representation learning method and clustering algorithm, several clusters representing specific technologies in different layers and different time slices can be obtained. Then, by calculating the similarity between clusters of different layers, the evolutionary pathways of advanced technology from grants to papers and then to patents is drawn. Finally, this paper monitors the pathways of some developed technologies, which evolve from grants to papers and then to patents, and finds some emerging technologies under research.


An improved molecular inversion probe based targeted sequencing approach for low variant allele frequency.
Deep targeted sequencing technologies are still not widely used in clinical practice due to the complexity of the methods and their cost. The Molecular Inversion Probes (MIP) technology is cost effective and scalable in the number of targets, however, suffers from low overall performance especially in GC rich regions. In order to improve the MIP performance, we sequenced a large cohort of healthy individuals (n = 4417), with a panel of 616 MIPs, at high depth in duplicates. To improve the previous state-of-the-art statistical model for low variant allele frequency, we selected 4635 potentially positive variants and validated them using amplicon sequencing. Using machine learning prediction tools, we significantly improved precision of 10-56.25% (P < 0.0004) to detect variants with VAF > 0.005. We further developed biochemically modified MIP protocol and improved its turn-around-time to ∼4 h. Our new biochemistry significantly improved uniformity, GC-Rich regions coverage, and enabled 95% on target reads in a large MIP panel of 8349 genomic targets. Overall, we demonstrate an enhancement of the MIP targeted sequencing approach in both detection of low frequency variants and in other key parameters, paving its way to become an ultrafast cost-effective research and clinical diagnostic tool.


The Anti-Inflammatory Effect of KS23, A Novel Peptide Derived From Globular Adiponectin, on Endotoxin-Induced Uveitis in Rats.
Purpose: Adiponectin has been shown to exert potent anti-inflammatory activities in a range of systemic inflammatory diseases. This study aimed to investigate the potential therapeutic effects of KS23, a globular adiponectin-derived peptide, on endotoxin-induced uveitis (EIU) in rats and lipopolysaccharide (LPS)-stimulated mouse macrophage-like RAW 264.7 cells. Methods: EIU was induced in Lewis rats by subcutaneous injection of LPS into a single footpad. KS23 or phosphate-buffered saline (PBS) was administered immediately after LPS induction via intravitreal injection. Twenty-four hours later, clinical and histopathological scores were evaluated, and the aqueous humor (AqH) was collected to determine the infiltrating cells, protein concentration, and levels of inflammatory cytokines. In vitro, cultured RAW 264.7 cells were stimulated with LPS in the presence or absence of KS23, inflammatory cytokine levels in the supernatant, nuclear translocation of nuclear factor kappa B (NF-κB) subunit p65, and the expression of NF-kB signaling pathway components were analyzed. Results: KS23 treatment significantly ameliorated the clinical and histopathological scores of EIU rats and reduced the levels of infiltration cells, protein, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the aqueous humor. Consistently, KS23 decreased the expression of TNF-α and IL-6 in the supernatant of LPS-stimulated RAW 264.7 cells and inhibited the LPS-induced nuclear translocation of NF-κB p65 and the phosphorylation of IKKα/β/IκBα/NF-κB. Conclusion: The in vivo and in vitro results demonstrated the anti-inflammatory effects of the peptide KS23 and suggested that KS23 is a compelling, novel therapeutic candidate for the treatment of ocular inflammation.


Pseudotyped Vesicular Stomatitis Virus-Severe Acute Respiratory Syndrome-Coronavirus-2 Spike for the Study of Variants, Vaccines, and Therapeutics Against Coronavirus Disease 2019.
World Health Organization (WHO) has prioritized the infectious emerging diseases such as Coronavirus Disease (COVID-19) in terms of research and development of effective tests, vaccines, antivirals, and other treatments. Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), the etiological causative agent of COVID-19, is a virus belonging to risk group 3 that requires Biosafety Level (BSL)-3 laboratories and the corresponding facilities for handling. An alternative to these BSL-3/-4 laboratories is to use a pseudotyped virus that can be handled in a BSL-2 laboratory for study purposes. Recombinant Vesicular Stomatitis Virus (VSV) can be generated with complementary DNA from complete negative-stranded genomic RNA, with deleted G glycoprotein and, instead, incorporation of other fusion protein, like SARS-CoV-2 Spike (S protein). Accordingly, it is called pseudotyped VSV-SARS-CoV-2 S. In this review, we have described the generation of pseudotyped VSV with a focus on the optimization and application of pseudotyped VSV-SARS-CoV-2 S. The application of this pseudovirus has been addressed by its use in neutralizing antibody assays in order to evaluate a new vaccine, emergent SARS-CoV-2 variants (delta and omicron), and approved vaccine efficacy against variants of concern as well as in viral fusion-focused treatment analysis that can be performed under BSL-2 conditions.


Asymmetric catalysis with peptides.
Over the past decade several peptides have been developed as effective asymmetric catalysts for a range of synthetically useful reactions. Many have properties that are difficult to achieve with other catalysts. The article highlights features that render peptidic organocatalysts unique and attractive for future applications. Challenges such as the design of peptidic catalysts are discussed.


Closing the gap: data-based decisions in food, nutrition and health systems: proceedings of the Fifth International Summit on Medical and Public Health Nutrition Education and Research.
Like many of the biological sciences, nutrition has rapidly become a science which relies heavily on data collection, analysis and presentation. Knowledge gaps exist where data does not, and so the fifth annual International Summit on Medical and Public Health Nutrition Education and Research was held to address the theme of 'Closing the Gap: Data-based Decisions in Food, Nutrition and Health Systems'. Homerton College, University of Cambridge, Cambridge in July 2019. Data-driven decision making is more likely to lead to positive change in areas such as malnutrition, food insecurity and food production. These decisions must be informed by multiple stakeholders from various backgrounds in multisectorial collaboration. Case examples presented at the Summit contribute to the International Knowledge Application Network in Nutrition 2025, which aims to help identify and close gaps in nutrition and healthcare. Formation of international networks are required to advance nutrition research, identify gaps and generate high-quality data. These data can be used to adequately train healthcare professionals resulting in positive impact on clinical and public health. Strengthening collaboration between existing networks will be essential in sharing data for better health outcomes.


A systematic review of the epidemiology, disease characteristics and management of systemic sclerosis in Australian adults.
Australia has one of the highest prevalence rates of systemic sclerosis (SSc) worldwide. In order to highlight management deficiencies and key areas for further research, it is essential to understand its local epidemiological patterns, natural history, prognosis and mortality trends over time. To identify Australian SSc-specific information through a systematic review focusing on areas of epidemiology, disease characteristics, treatment, functional ability, disease burden and health-related quality of life (HRQoL). MEDLINE, EMBASE and the Cochrane Library were searched on 14 September, 2016. All original full text articles on SSc in Australia were included. Of the 54 articles included in this review, the majority of studies recruited from South Australia, Victoria and New South Wales. The prevalence of SSc in Australia is increasing and is similar among the general population and the Aboriginal population. Despite improvements in care over the last three decades, morbidity and mortality remain high, with an overall standardized mortality ratio of 3.4 and a 10-year survival of 84% in a newly diagnosed patient. Cardiorespiratory manifestations are the leading cause of SSc-related death. Malignancy is the leading cause of non-SSc-related death. The role of autoantibodies in predicting disease subtype, visceral involvement and their use as a prognostic marker is becoming increasingly recognized. Information on SSc in Australia, particularly unmet healthcare needs, HRQoL and economic burden, is limited. As a heterogenous condition, SSc requires a multi-disciplinary approach to care. Research aimed at quantifying HRQoL and burden of disease in Australia is essential for advocacy and resource allocation.


Phospholipase C Isoforms, Cytoskeletal Organization, and Vascular Smooth Muscle Differentiation.
The function of differentiated vascular smooth muscle cells (VSMC) in vivo is the regulation of contractility. Following injury or disease, however, VSMC lose their contractile function and take on a synthetic, proliferative phenotype. This dedifferentiation is generally accompanied by a change in the expression profile of phospholipase C isoforms.


Telepathology and imaging spectroscopy as a new modality in histopathology.
Telemedicine started in the late 1950's by transmitting data on patients' pulse and heart rates. In the 1980's it expanded to radiology and orthopedics. The technology is now expanding to other specialties that can digitally gather patient data. Telepathology comprises the transmission of microscopic images via telecommunication network. Image compression and multiplexing technologies enabled high-resolution telepathology as well as real-time video consultations over international telephone lines. Organ transplantation has become a viable treatment and offers new life to an increasing number of patients suffering from chronic end stage diseases and from irreversible organ failure. Rejection is still a major problem in kidney, liver, and heart transplantation. To gain further insight into the complex interactions within the components of the immune system, it has become increasingly necessary to develop rapid and simple methods to monitor the status of the immune system in patients. Clinical signs suggest organ rejection and abnormal laboratory test results, but only histological signs on biopsy specimens are adequately specific. The financial cost of organ transplant makes it imperative to develop tools for the early identification and treatment of organ rejection. An increasingly sensitive and accurate way of localizing key structures and abnormalities is through spectroscopy of either H&E stained samples or with a fluorescent tag (fluorophore) or by relying on natural fluorescence. The system is based on a unique Prism and Mirror Imaging Spectroscopy System ("PARISS), spectrometer originally designed and implemented for remote Earth monitoring from space and aircraft and astronomical imaging spectroscopy. Compact and lightweight both the mirror and prism are presently constructed in inexpensive glass but can also be injection molded in plastic. Any number of vendors anywhere in the world can produce all parts of the assembly. This greatly enhances the chances of future commercial viability. The Interactive Histopathology Consultation Network INTERPATH (PL961121) project integrated of remote control imaging microscopy system, imaging spectroscopy, and communication networks called SPECTROMIC. This telepethology unit will be a useful tool in the Regional and International Integrated Telemedicine Network for Medical Assistance in End Stage Diseases and Organ Transplant, RETRANSPLANT HC 4028 (HC) & IN 4028 (HC).


Daily Life Physical Activity Modulates the Effects of an Exercise Program on Lower-Extremity Physical Function in Japanese Older Adults.
Decreasing daily life physical activity (PA) outside an exercise program might hinder the benefit of that program on lower-extremity physical function (LEPF) in older adults. The purpose of this study was to investigate how daily life PA modulates the effects of an exercise program on LEPF. The participants were 46 community-dwelling older adults (mean age, 70.1 ± 3.5 years) in Kasama City, a rural area in Japan. All participated in a fall-prevention program called square-stepping exercise once a week for 11 weeks. We evaluated their daily life PA outside the exercise program with pedometers and calculated the average daily step counts during the early and late periods of the program. We divided participants into 2 groups on the basis of whether or not they decreased PA by more than 1000 steps per day between the early and late periods. To ascertain the LEPF benefits induced by participating in the exercise program, we measured 5 physical performance tests before and after the intervention: 1-leg stand, 5-time sit-to-stand, Timed Up and Go (TUG), habitual walking speed, and choice-stepping reaction time (CSRT). We used a 2-way analysis of variance to confirm the interaction between the 2 groups and the time effect before and after the intervention. During the exercise program, 8 participants decreased their daily life PA (early period, 6971 ± 2771; late period, 5175 ± 2132) and 38 participants maintained PA (early period, 6326 ± 2477; late period, 6628 ± 2636). Both groups significantly improved their performance in TUG and CSRT at the posttest compared with the baseline. A significant group-by-time interaction on the walking speed (P = .038) was observed: participants who maintained PA improved their performance more than those who decreased their PA. Square-stepping exercise requires and strengthens dynamic balance and agility, which contributed to the improved time effects that occurred in TUG and CSRT. On the contrary, because PA is positively associated with walking speed, maintaining daily life PA outside an exercise program may have a stronger influence on walking speed. To enhance the effectiveness of an exercise program for young-old adults, researchers and instructors should try to maintain the participant's daily life PA outside the program. Regardless of decreasing or maintaining daily life PA, the square-stepping exercise program could improve aspects of LEPF that require complex physical performance. However, a greater effect can be expected when participants maintain their daily life PA outside the exercise program.


Accelerated Recovery of Endothelium Function after Stent Implantation with the Use of a Novel Systemic Nanoparticle Curcumin.
Curcumin was reported to exhibit a wide range of pharmacological effects including antioxidant, anti-inflammatory, and antiproliferative activities and significantly prevent smooth muscle cells migration. In the present study, a novel kind of curcumin loaded nanoparticles (Cur-NP) has been prepared and characterized with the aim of inhibiting inflammation formation and accelerating the healing process of the stented arteries. Cur-NP was administrated intravenously after stent implantation twice a week and detailed tissue responses were evaluated. The results demonstrated that intravenous administration of Cur-NP after stent implantation accelerated endothelial cells restoration and endothelium function recovery and may potentially be an effective therapeutic alternative to reduce adverse events for currently available drug eluting stents.


Regioselectivity and reversibility of the glutathione conjugation of quercetin quinone methide.
The chemical reactivity, isomerization, and glutathione conjugation of quercetin o-quinone were investigated. Tyrosinase was used to generate the unstable quercetin o-quinone derivative which could be observed upon its subsequent scavenging by glutathione. Identification of the products revealed formation of 6-glutathionyl-quercetin and 8-glutathionyl-quercetin adducts. Thus, in particular, glutathione adducts in the A ring of quercetin were formed, a result which was not expected a priori. Quantum mechanical calculations support the possibility that the formation of these glutathione adducts can be explained by an isomerization of quercetin o-quinone to p-quinone methides. Surprisingly, additional experiments of this study reveal the adduct formation to be reversible, leading to interconversion between the two quercetin glutathione adducts and possibilities for release and further electrophilic reactions of the quercetin quinone methide at cellular sites different from those of its generation.


Applying the balanced scorecard in healthcare provider organizations.
Several innovative healthcare executives have recently introduced a new business strategy implementation tool: the Balanced Scorecard. The scorecard's measurement and management system provides the following potential benefits to healthcare organizations: It aligns the organization around a more market-oriented, customer-focused strategy It facilitates, monitors, and assesses the implementation of the strategy It provides a communication and collaboration mechanism It assigns accountability for performance at all levels of the organization It provides continual feedback on the strategy and promotes adjustments to marketplace and regulatory changes. We surveyed executives in nine provider organizations that were implementing the Balanced Scorecard. We asked about the following issues relating to its implementation and effect: 1. The role of the Balanced Scorecard in relation to a well-defined vision, mission, and strategy 2. The motivation for adopting the Balanced Scorecard 3. The difference between the Balanced Scorecard and other measurement systems 4. The process followed to develop and implement the Balanced Scorecard 5. The challenges and barriers during the development and implementation process 6. The benefits gained by the organization from adoption and use. The executives reported that the Balanced Scorecard strategy implementation and performance management tool could be successfully applied in the healthcare sector, enabling organizations to improve their competitive market positioning, financial results, and customer satisfaction. This article concludes with guidelines for other healthcare provider organizations to capture the benefits of the Balanced Scorecard performance management system.


Neuroleptic Malignant Syndrome: A Primary Care Perspective.
In recent years, there has been an increased use of neuroleptic agents in the primary care setting. Neuroleptic malignant syndrome (NMS) is a rare complication of neuroleptic therapy that can be missed if not suspected. This manuscript reviews the diagnosis and management of NMS in the primary care setting. There is a lack of prospective data, and most of the information is obtained from case series. Physicians need to have a high index of suspicion with regard to excluding NMS in patients taking neuroleptics and presenting with hyperthermia.


Statin Modulation of Human T-Cell Proliferation, IL-1β and IL-17 Production, and IFN-γ T Cell Expression: Synergy with Conventional Immunosuppressive Agents.
HMG-CoA reductase inhibitors (statins) have been demonstrated to be immunomodulatory for human immune-mediated disease and in experimental models. The aim of this study was to compare statin-mediated immunosuppressive effects on human T-cell responses in vitro with those of conventional immunosuppressives (dexamethasone, cyclosporin A (CsA), mycophenolate, and rapamycin). Statins (atorvastatin, lovastatin, and simvastatin) were investigated for their modulatory effects on human PBMC viability, cytokine profiles, and T-cell proliferation. At concentrations that inhibited anti-CD3/28-stimulated T-cell proliferation (P < 0.01), simvastatin significantly decreased intracellular CD4(+) T-cell expression of IFN-γ (P < 0.01) to levels similar to those induced by conventional immunosuppressives. Atorvastatin and lovastatin also decreased IFN-γ expression, although to a lesser degree (P < 0.05). All three statins reduced levels of IL-17 production (P < 0.01). However, in response to anti-CD3/28 stimulation, simvastatin significantly upregulated IL-1β production (P < 0.05). The profile of cytokines produced in response to anti-CD3/28 stimulation was similar when both atorvastatin and dexamethasone were added as compared with dexamethasone alone, suggesting that atorvastatin can synergise with dexamethasone with respect to immunomodulation of cytokines. This data supports the hypothesis of selective statin-mediated immunomodulatory effects on human immune cells.


Postoperative function after implant insertion in vascularized bone grafts in maxilla and mandible.
Between 1988 and 1992, 80 Brånemark-type implants were inserted in 18 patients during reconstruction of the mandible or maxilla with vascularized iliac crest or scapula grafts with or without additional soft tissue pedicles. In these procedures, nine vascularized bone grafts were combined with a primary insertion of 32 implants and a secondary insertion of 48 implants. Twelve patients are currently wearing the implant-borne dentures. From 32 implants inserted primarily, eight could not be used for prosthodontic rehabilitation because three were lost with a graft, three were left as sleepers, and two demonstrated a lack of osseointegration. None of the implants inserted secondarily in grafts were lost. Primary implant insertion should be performed only in close cooperation with the prosthodontist and in selected cases, for example, in free-end reconstruction of the mandible with a straight graft and where a limited number of implants is needed. Although restoration of masticatory function in patients with head and neck cancer can be achieved, compared with a healthy control group, functional impairments remain. Patients subjectively favor the nonreconstructed side of the mandible or maxilla for chewing. These findings can be correlated with a postoperative follow-up investigation using a miniature force transducer and the T-scan system.


Undiagnosed prehypertension/hypertension in Canadian adolescents: The critical role of the public health nurse.
To investigate the prevalence of undiagnosed prehypertension/hypertension and other associated comorbidities in adolescents living in rural and urban settings in a mid-Western Canadian province. Data reported herein were derived from two cross-sectional studies, whereby adolescents attending either a rural (N = 143) or urban (N = 253) school were screened for blood pressure, anthropometric measures, and blood glucose measurements. Data analysis included descriptive and inferential statistics in addition to chi-square analyses. Notable prevalence of undiagnosed prehypertension/hypertension was found. Adolescents living in urban settings (49%, N = 123) were significantly more likely to have prehypertension/hypertension than rural (23%, N = 33) living adolescents. With regard to other comorbidities, the prevalence of elevated HbA1c in the urban group (32%) was significantly higher than the rural adolescents (19%); however, there was similar prevalence of overweight/obese adolescents between the urban (37%) and rural (36%) groups. The prevalence of adolescent undiagnosed prehypertension/hypertension, elevated blood glucose measurements, and overweight/obesity is concerning in both urban and rural settings. Public health nurses are uniquely positioned in health care to facilitate interventions focused on preventing and managing adolescent prehypertension/hypertension and its associated comorbidities.


A computational model of intracellular calcium oscillations in urinary bladder smooth muscle cells.
This paper presents a computational model for calcium (Ca2+) oscillations in detrusor smooth muscle (DSM) cells. The proposed model simulates the temporal profile of oscillations by incorporating various cellular and subcellular components. The cellular components include calcium influx via membrane and the plasma membrane calcium ATPase (PMCA) pump. The subcellular components include ryanodine receptors (RyRs), inositol 1, 4, 5 trisphosphate receptors (IP3Rs) and the sarco/endoplasmic reticulum calcium ATPase (SERCA) pump. The use of both cellular and subcellular components provides a better estimation of the origin and factors affecting these oscillations. Moreover, our work correlates these computational findings with associated physiology of the smooth muscle cell that aids our understanding of intracellular calcium oscillations and its inception in DSM. A deeper insight into calcium signalling in DSM cells is expected to provide a firmer basis for understanding the mechanical contractile activity.


High-performance flexible graphene field effect transistors with ion gel gate dielectrics.
A high-performance low-voltage graphene field-effect transistor (FET) array was fabricated on a flexible polymer substrate using solution-processable, high-capacitance ion gel gate dielectrics. The high capacitance of the ion gel, which originated from the formation of an electric double layer under the application of a gate voltage, yielded a high on-current and low voltage operation below 3 V. The graphene FETs fabricated on the plastic substrates showed a hole and electron mobility of 203 +/- 57 and 91 +/- 50 cm(2)/(V x s), respectively, at a drain bias of -1 V. Moreover, ion gel gated graphene FETs on the plastic substrates exhibited remarkably good mechanical flexibility. This method represents a significant step in the application of graphene to flexible and stretchable electronics.


The polypeptide antibiotic polymyxin B acts as a pro-inflammatory irritant by preferentially targeting macrophages.
Polymyxin B (PMB) is an essential antibiotic active against multidrug-resistant bacteria, such as multidrug-resistant Pseudomonas aeruginosa (MDRP). However, the clinical use of PMB is limited, because PMB causes serious side effects, such as nephrotoxicity and neurotoxicity, probably due to its cytotoxic activity. However, cytotoxic mechanisms of PMB are poorly understood. In this study, we found that macrophages are particularly sensitive to PMB, when compared with other types of cells, including fibroblasts and proximal tubule (PT) cells. Of note, PMB-induced necrosis of macrophages allowed passive release of high mobility group box 1 (HMGB1). Moreover, upon exposure of PMB to macrophages, the innate immune system mediated by the NLR family pyrin domain containing 3 (NLRP3) inflammasome that promotes the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) was stimulated. Interestingly, PMB-induced IL-1β release occurred in the absence of the pore-forming protein gasdermin D (GSDMD), which supports the idea that PMB causes plasma membrane rupture accompanying necrosis. Emerging evidence has suggested that both HMGB1 and IL-1β released from macrophages contribute to excessive inflammation that promote pathogenesis of various diseases, including nephrotoxicity and neurotoxicity. Therefore, these biochemical properties of PMB in macrophages may be associated with the induction of the adverse organ toxicity, which provides novel insights into the mechanisms of PMB-related side effects.


The difference in embryo quality between Belclare and Suffolk ewes is not due to differences in oocyte quality.
We have previously reported that the percentage of fertilized oocytes which reached the blastocyst stage by Day 6 after AI with frozen-thawed semen was higher for Belclare (94%) than Suffolk (59%) ewes. This may reflect differences in the timing of fertilization (Experiment 1) or differences in oocyte quality (Experiments 2 and 3). In Experiment 1, oocytes recovered from slaughterhouse ovaries were matured in vitro for 18, 20, 24, 28 or 30 h prior to fertilization and were then cultured in vitro. In Experiment 2, Belclare (n = 69) and Suffolk (n = 71) ewes were laparoscopically inseminated using frozen-thawed semen. Presumptive zygotes were recovered between 23 and 47 h post-insemination and cultured in vitro (grouped by breed). In Experiment 3, immature oocytes from Suffolk and Belclare ewes, were matured, fertilized and cultured in vitro (grouped by breed). Cleavage rate and blastocyst development was assessed. There was no effect of time of fertilization on cleavage rate, however, a lower proportion of cleaved oocytes reached the blastocyst stage after insemination at 30h compared to 24 h (P < 0.001). Ewe breed did not affect cleavage rate of oocytes matured and fertilized in vivo (41+/-9.6 and 47+/-10.1) or in vitro (47+/-9.4 and 52+/-9.4) for Belclare and Suffolk ewes, respectively (P > 0.05; %+/-S.E.). Likewise, ewe breed had no effect on the percentage (+/-S.E.) of cleaved oocytes developing to the blastocyst stage for in vivo (29+/-7.2 and 25+/-7.9) or in vitro matured and fertilized oocytes (29+/-6.1 and 36+/-5.9) from Belclare and Suffolk ewes, respectively (P>0.05). Based on this study oocyte quality does not differ between the breeds and in addition a 4h difference in the timing of fertilization, reflective of the breed difference in the timing of the LH surge in vivo, would not affect early embryo development.


A framework for the design, implementation, and evaluation of interprofessional education.
The growing emphasis on teamwork and care coordination within health care delivery is sparking interest in interprofessional education (IPE) among nursing and health profession faculty. Faculty often lack firsthand IPE experience, which hinders pedagogical reform. This article proposes a theoretically grounded framework for the design, implementation, and evaluation of IPE. Supporting literature and practical advice are interwoven. The proposed framework guides faculty in the successful creation and evaluation of collaborative learning experiences.


Paracetamol exerts a spinal, tropisetron-reversible, antinociceptive effect in an inflammatory pain model in rats.
Experiments were performed in carrageenin-treated rats to study, the antinociceptive and anti-inflammatory effects of paracetamol intravenously (i.v.) or intrathecally (i.t.) injected on rats submitted to a mechanical noxious stimulus. The influence of intrathecal tropisetron, a 5 hydroxytryptamine(3) (5-HT(3)) receptor antagonist, on the antinociceptive effects of paracetamol, was also studied. Paracetamol induced a significant antinociceptive effect after (100, 200 and 300 mg/kg) i.v. and (50, 100 and 200 microg/rat) i.t. injection, but no change occurred on edema volume. The effect of paracetamol was totally inhibited by tropisetron (10 microg/rat, i.t.). The foregoing results demonstrate that, in conditions of inflammatory pain, paracetamol exerts a central antinociceptive effect involving spinal 5-HT(3) receptors, without inducing any anti-inflammatory action. These data, give further arguments to consider paracetamol as a central analgesic drug which must be distinguished from non-steroidal anti-inflammatory drugs (NSAIDs), which justifies the usual combination of paracetamol in post-operative pain.


Mirror, mirror, on the wall, is that even my hand at all? Changes in the afterimage of one's reflection in a mirror in response to bodily movement.
Successful mirror self-recognition has often been considered a correlate of self-awareness in human development and phylogeny (Gallup, 1982). Studies have also shown that vision and touch interact such that objects viewed in a mirror's reflection are recoded as originating from a location within reachable, or peripersonal, space (Maravita et al. 2002). However, the association of mirror self-recognition and self-awareness is controversial, and the mechanism that underlies the recoding of visual information into peripersonal space remains an open question. In the present study, we address these issues through the novel use of an old paradigm: positive afterimages. It has been shown that when a positive afterimage is induced, and a limb is displaced from its apparent location in the afterimage, the afterimage of the limb fades or "crumbles" (Davies, 1973). We reproduced this effect in conditions where subjects viewed the afterimage of their arms' reflection using a frontally placed mirror and mirror box (Ramachandran & Rogers-Ramachandran, 1996). Our results suggest that the explicit knowledge that one is looking at a mirror as well as online visual feedback from bodily movement are unlikely to be responsible for previously observed interactions between vision and touch. Instead, we propose that a sense of ownership, and (bodily) self-awareness, might in part explain these interactions between vision and proprioception, which provides a partial vindication of the inference from successful mirror self-recognition to self-awareness.


Retinoic acid enhances the T helper 2 cell development that is essential for robust antibody responses through its action on antigen-presenting cells.
Previously we reported that vitamin A-deficient (-A) mice had a profound reduction in T helper 2 (Th2) cells, accounting for their depressed T-dependent antibody responses. Providing vitamin A or its active metabolites reversed this defect. The current experiments utilized splenocytes from T cell receptor transgenic mice to investigate how all-trans retinoic acid (atRA) augments Th2 development. These cells were stimulated in vitro in the presence or absence of atRA, with or without exogenous cytokines driving Th1 or Th2 development. Without exogenous cytokines, atRA addition significantly inhibited the interferon (IFN)-gamma response but did not alter the interleukin (IL)-4 response. With Th1 polarizing cytokines, atRA enhanced the IFN-gamma response, with no effect on the IL-4 response. Most importantly, with the Th2 polarizing cytokine IL-4, atRA significantly increased the IL-4 secretion (fivefold) and also increased the Th2 cell frequency twofold. The striking Th2 enhancement was also observed when only antigen-presenting cells were treated with atRA before stimulation of untreated CD4(+) transgenic T cells, but not vice versa. Thus, atRA maximized Th2 cell development in an IL-4-dependent manner, through an effect on antigen-presenting cell function.


Theory of Half-Space Light Absorption Enhancement for Leaky Mode Resonant Nanowires.
Semiconductor nanowires supporting leaky mode resonances have been used to increase light absorption in optoelectronic applications from solar cell to photodetector and sensor. The light conventionally illuminates these devices with a wide range of different incident angles from half space. Currently, most of the investigated nanowires have centrosymmetric geometry cross section, such as circle, hexagon, and rectangle. Here we show that the absorption capability of these symmetrical nanowires has an upper limit under the half-space illumination. Based on the temporal coupled-mode equation, we develop a reciprocity theory for leaky mode resonances in order to connect the angle-dependent absorption cross section and the radiation pattern. We show that in order to exceed such a half-space limit the radiation pattern should be noncentrosymmetric and dominate in the direction reciprocal to the illumination. As an example, we design a metal trough structure to achieve the desired radiation pattern for an embedded nanowire. In comparison to a single nanowire case the trough structure indeed overcomes the half-space limit and leads to 39% and 64% absorption enhancement in TM and TE polarizations, respectively. Also the trough structure enables the enhancement over a broad wavelength range.


Role of apoptosis, apoptosis-related factors and 17beta-hydroxysteroid dehydrogenases in human corpus luteum regression.
The human corpus luteum (CL) is a transient endocrine organ with a life span of 14-16 days. Apoptosis has been suggested to be the mechanism of CL regression and the possible regulatory role of the bcl-2 family in this process has been studied in animals and, to some extent, in humans. In the present study, apoptosis was studied in the human CL and in luteinised granulosa cells by in situ 3'-end labelling and gel electrophoretic DNA fragmentation analysis. The apoptosis-regulating factors Bcl-2, Bax and TNF-alpha, transcription factor NF-kappaB and Caspase-3, a key executioner protein in apoptotic cell death, were studied by immunohistochemistry and in situ hybridisation. Furthermore, we analysed expression of 17beta hydroxysteroid dehydrogenase (17HSD) type 1 and 2, key enzymes in the estrogen metabolism. Apoptosis was found in the CL throughout the luteal phase, but a marked increase of apoptotic luteal cells was observed during the late luteal phase (CL day 11-14). This was preceded by a clear increase of 17HSD type 1 expression. The apoptosis-regulating proteins Bcl-2 and Bax were expressed constantly in the CL throughout the luteal phase. TNF-alpha expression was constant during the early and mid-luteal phases, but in the late luteal phase, some specimens showed increased immunostaining. NF-kappaB and Caspase-3 were present in the CL throughout the luteal phase and in individual specimens, the expression of Caspase-3 was associated with a high rate of apoptosis in the late luteal phase. In conclusion, apoptosis is involved in human luteal regression and estradiol (E(2)) may function as a trigger for this process. The expression of the pro- and anti-apoptotic factors studied in the CL suggest their part in this process, but the conclusive evidence for the exact molecular mechanisms remains open.


An evaluation of the GlideScope, a new video laryngoscope for difficult airways: a manikin study.
The GlideScope is a new video laryngoscope. The aim of our study was to assess its use compared to a Macintosh blade in airway scenarios on the Airman airway simulator. The scenarios were: 'normal' or resting state of the manikin, pharyngeal obstruction, cervical rigidity and tongue oedema. Thirty anaesthetists from the Christchurch Anaesthetic Department attempted to pass a bougie or stylet through the vocal cords of the manikin with a size 3 Macintosh blade, then the GlideScope. View at laryngoscopy, ease of 'intubation' and whether they thought the GlideScope would be useful in clinical practice were recorded. Forty three percent (P = 0.02) found an improved view with the GlideScope in the pharyngeal obstruction scenario. In the other scenarios there was no significant difference in view. Reportage of ease of intubation showed no statistical difference in any scenarios. However, 93% of anaesthetists considered having the GlideScope would be useful if faced clinically with one or more of the studied scenarios. The GlideScope improved the view in one of three difficult airway situations when used by anaesthetists with no formal training in its use. No single airway device offers a solution to all scenarios, however, we consider that the GlideScope is a useful addition to the range of difficult airway devices available.


Long-Range Corrected DFT Calculations of First Hyperpolarizabilities and Excitation Energies of Metal Alkynyl Complexes.
The performance of the CAM-B3LYP, ωB97X and LC-BLYP long-range corrected density functional theory methods in the calculation of molecular first hyperpolarizabilities (β) and low-lying charge transfer (CT) excitation energies of the metal alkynyl complexes M(C≡C-4-C6 H4 -1-NO2 )(κ2 -dppe)(η5 -C5 H5 ) [M=Fe (1), Ru (2), Os (3)] and trans-[Ru{C≡C-(1,4-C6 H4 C≡C)n -4-C6 H4 -1-NO2 }Cl(κ2 -dppm)2 ] [n=0 (4), 1 (5), 2 (6)] was assessed. The BLYP, B3LYP and PBE0 standard exchange-correlation functionals and the Hartree-Fock method were also examined. The BLYP functional was shown to perform poorly in the calculation of β and low-energy CT transitions. The hybrid functionals (B3LYP and PBE0) showed significant improvement over the pure functional BLYP, but overestimated the hyperpolarizability ratios and the wavelengths of the lowest energy metal-to-ligand CT transitions for 5 and 6. The effect of long-range corrections is noteworthy, particularly for the larger complexes, improving the calculation of β ratios for 4-6. However, CAM-B3LYP, ωB97X, and LC-BLYP considerably overestimated the low-lying CT energies. PBE0 was found to give the best transition energy match for 4. The influence of the phenylene ring orientation in the alkynyl ligand on the calculated properties is substantial, particularly for the larger complexes. For these types of calculations, a basis set with diffuse functions (at least 6-31+G(d)) for the heavy elements is recommended.


Predictors of Relapse in Patients with Organizing Pneumonia.
Although organizing pneumonia (OP) responds well to corticosteroid therapy, relapse is common during dose reduction or follow-up. Predictors of relapse in OP patients remain to be established. The aim of the present study was to identify factors related to relapse in OP patients. This study was retrospectively performed in a tertiary referral center. Of 66 OP patients who were improved with or without treatment, 20 (30%) experienced relapse. The clinical and radiologic parameters in the relapse patient group (n=20) were compared to that in the non-relapse group (n=46). Multivariate analysis demonstrated that percent predicted forced vital capacity (FVC), PaO2/FiO2, and serum protein level were significant predictors of relapse in OP patients (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.97; p=0.018; OR, 1.02; 95% CI, 1.00-1.04; p=0.042; and OR, 0.06; 95% CI, 0.01-0.87; p=0.039, respectively). This study shows that FVC, PaO2/FiO2 and serum protein level at presentation can significantly predict relapse in OP patients.


Interaction of Chloroplasts with Inhibitors: Location of Carotenoid Synthesis and Inhibition during Chloroplast Development.
The inhibitor SAN 6706 [4-chloro-5-(dimethylamino)-2-(alpha,alpha,alpha,-trifluoro- m-tolyl-3(2H)-pyridazinone] has been used to study the synthesis of carotenes and xanthophylls during the conversion of etioplasts to chloroplasts in developing barley (Hordeum vulgare) shoots. SAN 6706 inhibits carotenoid synthesis and causes an accumulation of phytoene, but it is also a potent inhibitor of chloroplast electron transport. When developing barley is treated with SAN 6706, carotenoid synthesis is inhibited but total photosynthesis is unaffected. The ability of SAN 6706 to inhibit carotenoid synthesis becomes progressively less if etiolated shoots are illuminated for increasing lengths of time before treatment. During the greening of treated barley shoots only light-induced beta-carotene synthesis is immediately inhibited; xanthophyll synthesis is not affected until after about 8 hours. The hypothesis that SAN 6706 cannot enter the chloroplast but inhibits carotenoid synthesis from the cytoplasm is discussed, and the question as to whether there are not two separate groups of enzymes for the synthesis of carotenes and xanthophylls is considered.


Nonlinear acoustic propagation in bubbly liquids: Multiple scattering, softening and hardening phenomena.
The weakly nonlinear propagation of acoustic waves in monodisperse bubbly liquids is investigated numerically. A hydrodynamic model based on the averaged two-phase fluid equations is coupled with the Rayleigh-Plesset equation to model the dynamics of bubbles at the local scale. The present model is validated in the linear regime by comparing with the Foldy approximation. The analysis of the pressure signals in the linear regime highlights two resonance frequencies: the Minnaert frequency and a multiple scattering resonance that strongly depends on the bubble concentration. For weakly nonlinear regimes, the generation of higher harmonics is observed only for the Minnaert frequency. Linear combinations between the Minnaert harmonics and the multiple scattering resonance are also observed. However, the most significant effect observed is the appearance of softening-hardening effects that share some similarities with those observed for sandstones or cracked materials. These effects are related to the multiple scattering resonance. Downward or upward resonance frequency shifts can be observed depending on the characteristic of the incident wave when increasing the excitation amplitude. It is shown that the frequency shift can be explained assuming that the acoustic wave velocity depends on a law different from those usually encountered for sandstones or cracked materials.


The effectiveness of mindfulness-based cognitive therapy combined with medication therapy in preventing recurrence of major depressive disorder in convalescent patients.
This study aims to investigate the effectiveness of mindfulness-based cognitive therapy (MBCT) combined with medication therapy in preventing the recurrence of major depressive disorder (MDD) in convalescent patients. A total of 130 patients with convalescent MDD were enrolled in this prospective study. Sixty-five patients were assigned to the experimental group and received medication therapy combined with MBCT, and 65 patients were assigned to the control group and treated with medication alone. The recurrence rate and related hormonal changes were compared between the two groups. After 1 year of MBCT intervention, eight patients experienced recurrence in the experimental group, a recurrence rate of 12.31%, and 19 patients experienced recurrence in the control group, a recurrence rate of 29.23%. The Hamilton Depression Rating Scale (HAM-D) and the World Health Organization Quality of Life Scale (WHOQOL-BREF) scores in both the experimental and the control groups were significantly improved after treatment (P < 0.05). The difference in the HAM-D scores before and after treatment in the experimental group was 16.74 ± 4.54; this was significantly higher than that of the control group (8 ± 3.89, P < 0.0001). The WHOQOL-BREF scores in the experimental group were significantly improved compared with those of the control group (P < 0.0001). The differences in the levels of corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone, and cortisol before and after treatment in the experimental group and the control group were statistically significant (P < 0.05). The difference in CRH before and after treatment in the experimental group was 16.8 ± 7.2, which was higher than that of the control group (2.75 ± 9.27, P < 0.0001). The intervention with MBCT had a significant impact on the recurrence of MDD [β = 1.206, P = 0.039, 95% (confidence interval) CI = 0.0790-1.229]. The difference in the HAM-D scores also had a significant impact on the recurrence of MDD (β = 1.121, P = 0.0014, 95% CI = 0.805-0.976). Compared with medication therapy alone, the use of MBCT combined with medication therapy can effectively prevent the recurrence of MDD in convalescent patients.


Possible expression of a sigma 1 site in rat pheochromocytoma (PC12) cells.
To examine the functional interaction between the sigma binding sites and nicotinic acetylcholine receptors, we investigated the effects of various sigma receptor ligands on nicotine-evoked Ca2+ uptake in differentiated PC12 cells. The IC50 values of sigma receptor ligands tested in this uptake study did not correlate with their Ki values in the [3H]1, 3-di(2-tolyl) guanidine ([3H]DTG) binding to guinea pig brain reported by Rothman et al. (1991). To clarify further the binding characteristics of the sigma binding sites on PC12 cells, we examined the effects of sigma receptor ligands on [3H]N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine HCl ([3H]NE-100) binding to PC12 membranes. The Ki values of the various drugs tested for [3H]NE-100 binding site closely correlated with their Ki values for the DTG site-1 reported by Rothman et al. (1991). This study showed that PC12 cells express sigma 1-like sites and the inhibitory effect of sigma receptor ligands on the nicotine-evoked Ca2+ uptake was not directly coupled with either the sigma 1 or sigma 2 sites.


Integrative genomic characterization and a genomic staging system for gastrointestinal stromal tumors.
Gastrointestinal stromal tumors (GISTs) historically were grouped with leiomyosarcomas (LMSs) based on their morphologic similarities; however, recently, GIST was established unequivocally as a distinct type of sarcoma based on its molecular features and response to imatinib treatment. To gain further insight into the genomic differences between GISTs and LMSs, the authors mapped gene copy number aberrations (CNAs) in 42 GISTs and 30 LMSs and integrated the results with gene expression profiles. Distinct patterns of CNAs were revealed between GISTs and LMSs. Losses in 1p, 14q, 15q, and 22q were significantly more frequent in GISTs than in LMSs (P < .001); whereas losses in chromosomes 10 and 16 and gains in 1q, 14q, and 15q (P < .001) were more common in LMSs. By integrating CNAs with gene expression data and clinical information, the authors identified several clinically relevant CNAs that were prognostic of survival in patients with GIST. Furthermore, GISTs were categorized into 4 groups according to an accumulating pattern of genetic alterations. Many key cellular pathways were expressed differently in the 4 groups, and the patients in each group had increasingly worse prognoses as the extent of genomic alterations increased. Based on the current findings, the authors proposed a new tumor-progression genetic staging system termed genomic instability stage to complement the current prognostic predictive system based on tumor size, mitotic index, and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation.


Force characteristics of the rat sternomastoid muscle reinnervated with end-to-end nerve repair.
The goal of this study was to establish force data for the rat sternomastoid (SM) muscle after reinnervation with nerve end-to-end anastomosis (EEA), which could be used as a baseline for evaluating the efficacy of new reinnervation techniques. The SM muscle on one side was paralyzed by transecting its nerve and then EEA was performed at different time points: immediate EEA, 1-month and 3-month delay EEA. At the end of 3-month recovery period, the magnitude of functional recovery of the reinnervated SM muscle was evaluated by measuring muscle force and comparing with the force of the contralateral control muscle. Our results demonstrated that the immediately reinnervated SM produced approximately 60% of the maximal tetanic force of the control. The SM with delayed nerve repair yielded approximately 40% of the maximal force. Suboptimal recovery of muscle force after EEA demonstrates the importance of developing alternative surgical techniques to treat muscle paralysis.


Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.
Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.


Use of [3H]-clozapine as a ligand of the dopamine D4 receptor subtype in peripheral tissues.
1. Molecular biology studies have documented the presence of peripheral dopamine D4 receptors. This site has not been characterized yet with classical radioligand binding assay techniques because of the lack of selective radioligands. 2. The atypical neuroleptic clozapine labelled with tritium ([3H]-clozapine) has been proposed and sold as a radioligand for brain dopamine D4 receptors. However, the selectivity of [3H]-clozapine for D4 receptor subtypes, and its specificity for brain dopamine receptors, have been questioned. 3. In this study dopamine D4 receptors were assayed in peripheral organs known to express them, such as rat atria and kidney, by using a radioligand binding assay technique with [3H]-clozapine as the radioligand. Parallel experiments were performed using Chinese hamster ovary (CHO) cells transfected with the D4 receptor clone (variant D4.2). 4. [3H]-Clozapine was bound to sections of rat atria and kidney. After appropriate blockade of sites other than dopamine receptors to which it can bind (i.e. muscarinic cholinergic, serotonergic and alpha-adrenergic receptors), the radioligand was bound to a site displaying a pharmacological profile similar to that expressed by CHO cells transfected with the D4 receptor. 5. The above findings indicate that with appropriate protocols, [3H]-clozapine may represent a radioligand for peripheral dopamine D4 receptors.


Coherence enhancement in nonlinear systems subject to multiplicative Ornstein-Uhlenbeck noise.
We show that for two biologically relevant models with self-sustained oscillations under the action of a multiplicative Ornstein-Uhlenbeck process, their coherence response behaves nonmonotonically with the process correlation time. There is a correlation time for which the quality factor is optimized. This phenomenon is a consequence of the interplay between the correlation time and the system's periodicity. This relation is evidenced through a power law relation with an exponent close to -1 / 2.


Thymoquinone Protects Neurons in the Cerebellum of Rats through Mitigating Oxidative Stress and Inflammation Following High-Fat Diet Supplementation.
High-fat diet (HFD) is a major problem causing neuronal damage. Thymoquinone (TQ) could regulate oxidative stress and the inflammatory process. Hence, the present study elucidated the significant role of TQ on oxidative stress, inflammation, as well as morphological changes in the cerebellum of rats with HFD. Rats were divided into three groups as (1) control, (2) saturated HFD for eight weeks and (3) HFD supplementation (four weeks) followed by TQ 300 mg/kg/day treated (four weeks). After treatment, blood samples were collected to measure oxidative stress markers glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and inflammatory cytokines. Furthermore, neuronal morphological changes were also observed in the cerebellum of the rats. HFD rats show higher body weight (286.5 ± 7.4 g) as compared with the control group (224.67 ± 1.78 g). TQ treatment significantly (p < 0.05) lowered the body weight (225.83 ± 13.15 g). TQ produced a significant (p < 0.05) reduction in cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The antioxidative enzymes significantly reduced in HFD rats (GSH, 1.46 ± 0.36 mol/L and SOD, 99.13 ± 5.41 µmol/mL) as compared with the control group (GSH, 6.25 ± 0.36 mol/L and SOD, 159.67 ± 10.67 µmol/mL). MDA was increased significantly in HFD rats (2.05 ± 0.25 nmol/L) compared to the control group (0.695 ± 0.11 nmol/L). Surprisingly, treatment with TQ could improve the level of GSH, MDA, and SOD. TQ treatment significantly (p < 0.05) reduced the inflammatory markers as compared with HFD alone. TQ treatment minimizes neuronal damage as well as reduces inflammation and improves antioxidant enzymes. TQ can be considered as a promising agent in preventing the neuronal morphological changes in the cerebellum of obese populations.


Electrical Stun Gun and Modern Implantable Cardiac Stimulators: Update for a New Stun Gun Model.
In 2017, the Italian National Institute of Health conducted a study to evaluate the potential risks of Conducted Electrical Weapons (CEW, AKA "stun guns") for users bearing a pacemaker (PM) or an implantable cardioverter defibrillator (ICD). The study addressed two specific models of stun guns: the TASER model X2 and AXON model X26P. In 2019, the same experimental protocol and testing procedure was adopted to evaluate the risk for another model of stun gun, the MAGEN model 5 (MAGEN, Israel). The MAGEN 5 differs from the previous stun guns tested in terms of peak voltage generated, duration of the shock, and trigger modality for repeated shocks. This note is an update of the previous study results, including the measurements on the MAGEN 5 stun gun. Despite the differences between the stun gun models, the effects on the PM/ICD behavior were the same as previously observed for the TASER stun guns.


Simulating intervertebral disc cell behaviour within 3D multifactorial environments.
Low back pain is responsible for more global disability than any other condition. Its incidence is closely related to intervertebral disc (IVD) failure, which is likely caused by an accumulation of microtrauma within the IVD. Crucial factors in microtrauma development are not entirely known yet, probably because their exploration in vivo or in vitro remains tremendously challenging. In silico modelling is, therefore, definitively appealing, and shall include approaches to integrate influences of multiple cell stimuli at the microscale. Accordingly, this study introduces a hybrid Agent-based (AB) model in IVD research and exploits network modelling solutions in systems biology to mimic the cellular behaviour of Nucleus Pulposus cells exposed to a 3D multifactorial biochemical environment, based on mathematical integrations of existing experimental knowledge. Cellular activity reflected by mRNA expression of Aggrecan, Collagen type I, Collagen type II, MMP-3 and ADAMTS were calculated for inflamed and non-inflamed cells. mRNA expression over long periods of time is additionally determined including cell viability estimations. Model predictions were eventually validated with independent experimental data. As it combines experimental data to simulate cell behaviour exposed to a multifactorial environment, the present methodology was able to reproduce cell death within 3 days under glucose deprivation and a 50% decrease in cell viability after 7 days in an acidic environment. Cellular mRNA expression under non-inflamed conditions simulated a quantifiable catabolic shift under an adverse cell environment, and model predictions of mRNA expression of inflamed cells provide new explanation possibilities for unexpected results achieved in experimental research. The AB model as well as used mathematical functions were built with open source software. Final functions implemented in the AB model and complete AB model parameters are provided as Supplementary Material. Experimental input and validation data were provided through referenced, published papers. The code corresponding to the model can be shared upon request and shall be reused after proper training. Supplementary data are available at Bioinformatics online.


Cleavage of double-stranded DNA by 'metalloporphyrin-linker-oligonucleotide' molecules: influence of the linker.
Manganese porphyrin-linker-triple-helix-forming oligonucleotide molecules were prepared and their ability to cleave in vitro a double-stranded DNA target present in the HIV-1 genome was studied. The nature of the linker is a determining factor of the cleavage efficiency. Cleavage yields as high as 80% were observed when the linker was a spermine residue and in the absence of a large excess of free spermine known to stabilize triplex structures. The hydrophobic nature of aliphatic diamine linker modified the cleaver-DNA interactions and reduced the efficiency of DNA cleavage.


Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo.
Rhenium-186 (tin) hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that simultaneously localizes in multiple skeletal metastases in patients with advanced cancer. A single intravenous administration of 30-35 mCi (1110-1295 MBq) is associated with a prompt, significant relief of osseous pain in about 80% of such patients. The efficacy of this new compound was evaluated further by utilizing a double-blind crossover comparison with 99mTc-methylene diphosphonate (MDP) as a radioactive placebo. The new rhenium compound resulted in a significantly (p less than 0.05) greater decrease in pain than did treatment with the radioactive placebo. Rhenium-186(Sn)HEDP appears to be a useful new compound for the palliation of painful skeletal metastases.


Filter Cassette Method for Analyzing Man-Made Vitreous Fibers Settled on Surfaces.
A new method was developed to analyze the surface count of fibers in a variety of environments. The method entails sampling surfaces with the help of suction to a filter cassette holder containing a cellulose filter. The filters were collapsed using microwave digestion in dilute acid, and the fibers filtered to polycarbonate filters, gilded, and analyzed by scanning electron microscopy (SEM). The method was compared to traditional gel tape sampling as described in International Standards Organization (ISO) standard 16000-27, following analysis with phase contrast microscopy. The methods were compared in industrial environments and in office-type environments, with the concentration range studied spanning from 0.1 to 100,000 fibers/cm². The methods yielded similar results (p < 0.05) in concentrations from 100 to 10,000 cfu/cm², while the filter cassette method gave systematically higher results in high concentrations (>10,000 cfu/cm²) as well as in all office-type environments studied, where the fiber count ranged from 0.1 to 20 fibers/cm². Consequently, we recommend using the new method in working environments where the surface count is more than 100 fibers/cm², as well as in office-type environments where the fiber count is below 10 fibers/cm². It should be noted, however, that a similar limit of quantitation as with the gel tape method (0.1 fibers/cm²) requires sampling a minimum area of 100 × 100 cm² with the fiber cassette method. Using the filter cassette method will require new guide values to be formed for office-type environments, since the results are higher than with the gel tape method. Alternatively, if present guide values or limit values are to be used with the filter cassette method, conventions as to which fiber sizes to count should be set, since SEM analysis in any case will allow for including a larger size range than phase contrast microscopy (PM). We, however, recommend against such an approach, since fibers less than 1 µm in width may not be less harmful by inhalation than larger fibers.


Immediate effects of a very brief planning intervention on fruit and vegetable consumption: A randomized controlled trial.
Action planning interventions can effectively promote fruit and vegetable (FV) consumption, but not much is known about the day-to-day translation of intervention planning into action. In this randomized controlled trial, immediate intervention effects of a very brief planning intervention on FV consumption during the following 13 days were investigated. After a 13-day pre-intervention diary, N = 206 participants (aged 19-66 years) were randomly allocated to a waiting-list control condition or a planning condition, where they formed one FV plan. Participants from both conditions completed a 13-day post-intervention diary. Self-reported daily FV consumption, FV-specific self-efficacy, and action control were assessed. Segmented linear mixed models estimating a discrete change (i.e. "jump") between diary phases showed a positive "jump" of FV intake and self-efficacy in the planning condition when compared to the control condition. For action control, such effects were not observed. Changes in study variables throughout the post-intervention phase did not differ between both conditions. Present findings extend previous evidence on action planning interventions by showing that increases in self-regulatory (i.e. self-efficacy) and behavioral (i.e. FV intake) outcomes can occur very rapidly and already on the first day for which behavioral increases were planned.


Prospective randomized trial comparing endovenous laser ablation and surgery for treatment of primary great saphenous varicose veins with a 2-year follow-up.
Endovenous laser therapy (EVLT) for ablation of the great saphenous vein (GSV) is thought to minimize postoperative morbidity compared with high ligation and stripping (HL/S). Only a few randomized trials have reported early results. This prospective randomized trial compared EVLT (980 nm) and HL/S results at 1 and 2 years after the intervention. Patients with symptomatic varicose veins due to GSV insufficiency were randomized to HL/S (100 limbs) or EVLT (104 limbs). Four EVLT procedures failed primarily and were excluded. Phlebectomy and ligature of incompetent perforators were performed whenever indicated in both groups. Patients were re-examined clinically and by duplex ultrasound imaging preoperatively and at 12 days and at 1 and 2 years after treatment. Closure rate, complication rate, time to return to normal activity, the Aberdeen Varicose Vein Symptom Severity Score (AVVSS), the Varicose Venous Clinical Severity Score (VVCSS), and the Medical Outcome Study Short Form-36 scores were also recorded. There were no differences in patient demographics, CEAP class, Widmer class, or severity scores between the groups. Simultaneous interventions did not differ between the groups. Similar times for the return to normal activity and scores for postoperative pain were reported. No major complications after treatment were recorded. HL/S limbs had significantly more postoperative hematomas than EVLT limbs, and EVLT patients reported more bruising. Follow-up at 1 year was 100% for HL/S and 99% for EVLT. Two GSVs in the EVLT group reopened and three partially reopened. No open GSVs occurred in HL/S limbs. Ninety-eight percent of the limbs in both groups were free of symptoms. VCSS, AVVSS, and Short Form-36 scores did not reveal any group differences. At 2 years, no differences compared with 1-year results were observed, except that two more GSVs in the EVLT group were partially reopened. Abolition of GSV reflux and improvement in quality of life was similar after HL/S and EVLT. After EVLT, however, two GSVs were found completely reopened and five were partially reopened, which was significantly higher than after HL/S. A prolonged follow-up is ongoing.


Safety of tirofiban for patients with acute ischemic stroke in routine clinical practice.
The aim of the present study was to investigate the safety of tirofiban alone and in combination with various treatments in acute ischemic stroke (AIS). A total of 120 patients with AIS were included in the study, and these patients were divided into three treatment groups: Group A (tirofiban alone, n=68), group B (tirofiban plus thrombolytic therapy, n=26), and group C (tirofiban as a 'bridging therapy', n=26). Risk factors, stroke severity, initial imaging, treatment regimens, complications and long-term outcomes were analyzed. In total, eight patients (6.7%) [six patients (23.1%) in group B and two patients (7.7%) in group C] had hemorrhage during or subsequent to treatment. Sixteen patients (six in group A, eight in group B and two in group C) succumbed during the hospital admission period. The mortality rate was 13.3% (8.8% for group A, 30.7% for group B and 7.7% for group C) in the acute phase. A favorable outcome (modified Rankin Scale score, 0-2) in the first three months after stroke was only observed in 43.3% of patients (44.1% in group A, 46.7% in group B and 36.4% in group C). The mean Barthel index was 72.3 in group A, 84.4 in group B and 56.8 in group C (total patient population, 71.0). The results of the present study have shown that stroke treatment with tirofiban is safe in AIS. A large randomized controlled trial in the future is required to decrease the incidence of the minor bleeding complications associated with tirofiban therapy.


Determination of platinum complexes in clinical samples by a rapid flameless atomic absorption spectrometry assay.
The frequent use of platinum (Pt) complexes in cancer chemotherapy and the application of new therapeutic options and dosing strategies have increased the need for rapid analytic procedures to determine Pt concentrations in the biologic fluids of patients. Therefore a flameless atomic absorption spectrometry method for the quantification of Pt in plasma and ultrafiltrate was developed and validated. A simple sample preparation of only one dilution step was established. Only 400 microL of whole blood was required for duplicate analysis of Pt in both matrices. The matrix-specific temperature programs took less than 75 seconds. The lower limit of quantification was 40 ng Pt/mL and 20 ng Pt/mL for plasma and ultrafiltrate, respectively. Suitable linearity could be reached using separate calibration curves for the high and low Pt concentration ranges. Recovery of Pt was complete, and there were no major stability problems. The accuracy and precision of the new method met the international criteria for the validation of bioanalytic methods. In addition, the use of different anticoagulants for clinical sampling, ultrafiltration systems, and ultrafiltration conditions were investigated. The assay has already been extensively applied to pharmacokinetic studies. In conclusion, the new Pt assay proved to be rapid, simple, sensitive, and suitable for clinical use.


Management of febrile neutropenia in solid organ malignancies following chemotherapy.
Febrile neutropenia is a medical emergency and it requires immediate hospitalization for evaluation and administration of empiric broad-spectrum antibiotics. The present study was undertaken to analyze the infectious agents, choice of empiric antibiotics, and outcome in high-risk febrile neutropenia in the solid organ malignancies. In this study, 92 high risk febrile neutropenic episodes were analyzed in 72 patients with solid organ malignancies. We used cefoperazone-sulbactum as an initial empiric antibiotic. Piperacillin/tazobactum or carbapenems were added to the patients who did not respond to initial antibiotic. Among the 92 episodes treated, most patients received first-line chemotherapy for locally advanced disease. Microbes were isolated in 25% of febrile neutropenic episodes. Gram-negative organism (61.70%) constituted the most common isolates. The most common microbes identified were E. coli and Staphylococcus aureus in blood, Klebsiella pneumonia in sputum and E. coli in urine culture. Patients who had been treated with cefoperazone-sulbactum improved clinically in 70.6% of febrile neutropenic episodes. Second- line antibiotics (piperacillin-tazobactum with amikacin) were required in 24% episodes, while another 5.4% episodes required third-line antibiotics (carbapenems). In this study, mortality was seen in 12% of febrile neutropenic episodes. Staphylococcus aureus was 100% sensitive to linezolid, teicoplanin, and vancomycin, whereas Gram-negative organisms were 100% sensitive to imepenem and meropenem. Cephaperazone-sulbactum is a reasonable initial choice for empirical therapy in high risk febrile neutropenic patients in solid organ malignancies.


Management of the patient with advanced complications, functional decline, and persistent hyperglycemia.
Current management of hypoglycemic risk among seniors with type 2 diabetes mellitus (T2DM) is frequently not very effective. Treatment guidelines with target glycosylated hemoglobin (A1C) levels provide important standards for T2DM management, but target goals must be determined on an individual basis in conjunction with individual factors, including risk of hypoglycemia. This clinical review will help pharmacists develop optimal therapeutic regimens for elderly diabetic patients that carefully balance risks and benefits of therapy, better assess their elderly patients' risk of hypoglycemia, and determine appropriate blood glucose testing schedules for the long-term care patient. Live symposium presentation based on clinical practice and research, medical literature, and studies published between January 1998 and April 2009 on managing diabetes in older adults, government statistics, and medical society guidelines. When treating seniors with T2DM, it is critical that hypoglycemia be identified and avoided. Hypoglycemia, whether undiagnosed, recurring, or brought about with the use of traditional insulin or other antihyperglycemic agents with higher hypoglycemic risk, can lead to the risk of falls and injuries related to that. Certain therapeutic measures, including alterations to blood glucose testing schedules, less stringent A1C goals, and insulin analog therapies, facilitate effective glycemic control and decrease the risk of hypoglycemia.


Anticoagulation for atrial fibrillation in active cancer.
Atrial fibrillation (AF) may often pre-exist in patients with newly diagnosed cancer or occur with increased frequency shortly after cancer diagnosis. Patients with active cancer and AF have a particularly high risk of thromboembolic complications, as both conditions carry a risk of thrombosis. Thromboembolic risk is determined by several factors, including advanced age, sex (females), cancer histology (adenocarcinomas), location (e.g., pancreas, stomach), advanced stage, anticancer regimens (e.g., platinum compounds, anti-angiogenic therapies, immune modulators), comorbidities (e.g., obesity, kidney disease) and concurrent therapies (e.g., surgery, central catheters). Physicians are often reluctant to prescribe anticoagulants to patients with active cancer and AF, mainly due to fear of bleeding complications, which is partly related to the paucity of evidence in the field. Decision making regarding anticoagulation for the prevention of ischemic stroke and systemic embolism in patients with active cancer and AF may be challenging and should not simply rely on the risk prediction scores used in the general AF population. By contrast, the administration and choice of anticoagulants should be based on the comprehensive, individualized and periodic evaluation of thromboembolic and bleeding risk, drug-drug interactions, patient preferences and access to therapies.


[African Tick Bite Fever upon game hunting in South Africa].
The incident of spotted fever imported to Denmark is unknown. We present a classic case of African Tick Bite Fever (ATBF) to highlight a disease, which frequently infects wildlife enthusiasts and hunters on vacation in South Africa. ATBF has a good prognosis and is easily treated with doxycycline. The treatment should be given upon the clinical picture alone, since antibodies only reveal half of infected cases.


Improving chromatin immunoprecipitation (ChIP) by suppression of method-induced DNA-damage signaling.
Genomic DNA is always associated with proteins that modulate the accessibility of the genetic information. This chromatin is the essential structure in which all nuclear activity from regulation to replication, transcription, and repair takes place. This dynamic structure can be most efficiently analyzed by using the method of chromatin immunoprecipitation (ChIP), where application of cell-permeable cross-linkers to living cells induces covalent bridging between proteins and adjacent DNA in the nucleus. After fragmentation of the DNA, the complexed proteins are isolated by binding to specific antibodies. The attached DNA is isolated and can be analyzed. This method has been improved multiple times and adjusted to different experimental needs. This chapter describes a further advance based on the observation that the current standard method itself induces alterations in the chromatin.


Sun safety: what are the health messages?
Solar ultraviolet radiation (UVR) is a human carcinogen. The UK and the worldwide incidence of cutaneous (skin) melanoma are rising. It is now the second most common cancer in 15-34 year-olds in the UK, increasing by 49% in 1991-2000. The UK government prioritized skin cancer in 1992 in their public health strategy The Health of the Nation, and set the target for reducing the yearly rise in skin cancer incidence by 2005. In 1998 in the Saving Lives: Our Healthier Nation strategy, targets were set to reduce the death rate from cancer, including skin cancer, by 20% by 2010. As a consequence of these targets, since the mid-1990s public health campaigns to reduce sun exposure and skin cancer incidence in the UK have used specific interventions for at-risk groups and the mass media to reach the general population. Evidence indicates a shift in knowledge, with further work required to increase change in behaviour and attitudes. An associate health problem is vitamin D deficiency, which is prevalent across certain UK population groups. The main childhood health problem associated with vitamin D deficiency is the development of rickets, with evidence indicating those at high risk are exclusively breastfed dark-skinned infants, the elderly, those with dark skin pigmentation, and certain cultural groups that cover their bodies in clothing. Adolescents are the group with the highest incidence of low vitamin D status in the UK, with children of Asian descent at higher risk than Caucasian children. Increasing the outdoor activity levels of children in winter and during the cooler hours in summer is one way of increasing safe sun exposure. It is imperative to educate the general public on the risk of vitamin D deficiency, and offer advice on safe sun exposure, dietary sources of vitamin D, and dietary supplements. More research is required on recommendations for daily vitamin D supplements to determine optimal vitamin D levels in different population groups. There also needs to be reliable and accessible evidence on the links between vitamin D deficiency and lack of sun exposure, with sun safe messages adjusted accordingly.


Rebamipide promotes healing of colonic ulceration through enhanced epithelial restitution.
To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro. Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration. The distal colon was removed to evaluate the various parameters of inflammation. Moreover, wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with rebamipide. Intracolonic administration of rebamipide accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide. The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signal-regulated kinase (ERK) and activation of Rho kinase. Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells, via ERK activation. Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.


How do microbiology consultants undertake their jobs? A survey of consultant time and tasks in South West England.
To measure the total consultant medical microbiologist (CMM) weekly workload, to identify time spent on different activities, and to differentiate those tasks that were viewed by a consensus of consultants as core activities from those that could be accorded a lower priority. A self administered questionnaire completed by consultant medical microbiologists in the Public Health Laboratory Service South West Group. Reported hours worked by respondents ranged from 41 to 65 hours each week, excluding on call activities. Eleven of 20 respondents reported working in excess of 48 hours each week. There was no correlation between hours worked and laboratory workload as measured by numbers of specimens. Clinical liaison, result authorisation, infection control, and management activities took up most time. Working practices varied widely between individuals, partly reflecting their differing roles in the laboratory. A consensus was reached regarding the relative importance and priority of many regular CMM activities. Consultant microbiologists can identify, with consensus, both high and lower priority activities in their daily practice. If such clinical priorities can be more widely agreed across the profession, this would provide a rational approach to workload control.


Preventive Transhepatic Tract Embolisation after Percutaneous Biliary Interventions: A Systematic Review.
Preventive transhepatic tract embolisation (PTTE) after percutaneous biliary intervention (PBI) may reduce adverse events. The aim of this systematic review was to analyse feasibility, safety, and efficacy of PTTE with different embolic agents. A systematic literature research was performed according to the PRISMA guidelines. The identified studies were analysed concerning study quality, number of cases, indication, embolic agent, embolisation technique, success, and embolisation-related adverse events. Out of 62 identified records, 7 studies of mainly moderate study quality published through 2019 were included for further analysis. Cyanoacrylate (n = 4), gelatin sponge (n = 2), and coils (n = 1) were used as embolic agents in a total number of 314 patients. Technical success was 96-100%. Embolisation-related adverse events (glue migration, pain) occurred in 10/314 (3.2%) patients. Reduction of PBI-related pain was approved by one controlled study; haemorrhage events were reduced but not clearly significant. Overall, biliary leak, transhepatic bleeding, and PBI-related pain occurred in 7/201 (3.5%), 1/293 (0.3%), and 17/46 (36.9%) documented patients after PTTE. Adverse events which likely could not have been prevented by PTTE occurred in 23/180 (12.8%) patients. Embolic agents were not compared. In conclusion, PTTE is feasible and safe. It is effective concerning the prevention of PBI-related pain, and it may be effective concerning haemorrhage. Prevention of biliary leak is not proven. It remains unclear which embolic agent should be preferred. A prospective randomised trial including all preventable adverse events is lacking.