Search

Background: In many cancers, specific subtypes are more prevalent in specific racial backgrounds. However, little is known about the racial distribution of specific molecular types of brain tumors. Public data repositories lack data on many brain tumor subtypes as well as diagnostic annotation using the current World Health Organization classification. A better understanding of the prevalence of brain tumors in different racial backgrounds may provide insight into tumor predisposition and development, and improve prevention., Methods: We retrospectively analyzed the racial distribution of 1709 primary brain tumors classified by their methylation profiles using clinically validated whole genome DNA methylation. Self-reported race was obtained from medical records. Our cohort included 82% White, 10% Black, and 8% Asian patients with 74% of patients reporting their race., Results: There was a significant difference in the racial distribution of specific types of brain tumors. Blacks were overrepresented in pituitary adenomas (35%, P < .001), with the largest proportion of FSH/LH subtype. Whites were underrepresented at 47% of all pituitary adenoma patients ( P < .001). Glioblastoma (GBM) IDH wild-type showed an enrichment of Whites, at 90% ( P  < .001), and a significantly smaller percentage of Blacks, at 3% ( P  < .001)., Conclusions: Molecularly classified brain tumor groups and subgroups show different distributions among the three main racial backgrounds suggesting the contribution of race to brain tumor development., Competing Interests: M.S. is scientific advisor and shareholder of Heidelberg Epignostix and Halo Dx, and a scientific advisor of Arima Genomics, and InnoSIGN, and received research funding from Lilly USA. Other authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Aim: This study aimed to compare the effect of inhaled aromatherapy using various essential oils on the sleep quality of critically ill patients., Background: Inhalation of essential oils significantly promotes the physiological and psychological health of patients in intensive care units (ICUs). However, research identifying and ranking the effects of different essential oils on the sleep quality of critically ill patients is lacking., Design: This study followed the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions (PRISMA-NMA) guidelines., Methods: A comprehensive search of five databases (Embase, MEDLINE, the Cochrane Library, CINAHL and PsycINFO) was conducted from their inception to March 15, 2023 (with an additional eligible study included dated August 14, 2023). Google Scholar was used as a supplementary method. Frequentist NMA was used to determine the effects of various essential oils. Certainty of evidence (CoE) was assessed using Confidence in Network Meta-Analysis (CINeMA)., Results: A total of 11 trials involving 690 critically ill patients were included in the analysis. The NMA of inhaled aromatherapy revealed that the combination of lavender, Matricaria recutita, and neroli essential oils (ratio 6:2:0.5) resulted in the most significant improvement in sleep quality compared to usual care, followed by Rosa damascene, peppermint, Citrus aurantium, pure sunflower oil and lavender oil alone. The overall CoE for the results was rated as low., Conclusions: The results of this study indicate that a combination of lavender, Matricaria recutita and neroli essential oils significantly positively affected sleep quality among critically ill patients. Despite the low quality of evidence, inhaled aromatherapy is non-invasive and easy to use., Relevance to Clinical Practice: Inhaled aromatherapy can effectively improve sleep quality among critically ill patients., Patient or Public Contribution: No patient or public contribution applies to this work., Study Registration: The study protocol was registered to the PROSPERO International Prospective Register of Systematic Reviews (protocol number CRD42023433194)., (© 2024 John Wiley & Sons Ltd.)

Aim: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM)., Methods: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually., Results: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually., Conclusion: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Noise and lighting are prime factors of poor sleep quality in critically ill patients, which impair recovery and increase the risk of delirium or complications., Aim: To identify and rank the effectiveness of sound and darkness interventions on the sleep quality of critically ill patients., Study Design: This systematic review and component network meta-analysis was based on the Preferred Reporting Items for Systematic Reviews incorporating the Network Meta-Analyses (PRISMA-NMA) Statement. The Embase, MEDLINE, Cochrane CENTRAL, CINAHL, Airiti Library, and Google Scholar databases were searched from inception to August 10, 2021, for randomized controlled trials (RCTs) on sound and darkness interventions targeting critically ill patients' sleep quality. We applied standard and component NMA to determine the effects of interventions. The certainty of evidence was evaluated using the Cochrane risk-of-bias tool (V.2.0) and the online Confidence in Network Meta-Analysis (CINeMA) application., Results: Twenty-four RCTs with 1507 participants who used combined interventions constituting seven competing interventions were included in the standard NMA. The combination of earplugs, eye masks, and music; eye masks alone; earplugs combined with eye masks; and music alone had beneficial intervention effects. The combination of earplugs, eye masks, and music was the best intervention, and these components had no interaction effect. An eye mask had the best relative effect, followed by music, quiet time, and earplugs., Conclusions: This study provides clinical evidence of the effectiveness of using eye masks, music, and earplugs to improve sleep quality in critically ill patients. We also recommend future research using bedtime music, nocturnal eye masks, and quiet time, which had the best relative effects on sleep quality., Relevance to Clinical Practice: This study provides recommendations for interventions that nurses can use to improve critically ill patients' sleep quality., (© 2022 British Association of Critical Care Nurses.)

Aim: The aim of the study was to compare the effects of massage interventions on sleep quality among patients in the adult critical care unit., Background: Massage interventions have positive effects when applied to manage sleep quality in critical care units. However, research identifying the effect of massage intervention is limited., Design: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Methods: Five databases were searched from their inception to 15 April 2022 (the last search was conducted on 15 November 2022, but it yielded no additional eligible studies). The literature search was conducted using Embase, MEDLINE, the Cochrane Library, CINAHL, PsycINFO and additional sources such as Google Scholar. The Cochrane risk of bias tool for randomised trials (RoB 2.0) was used to assess the risk of bias. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessed the certainty of evidence and recommendations., Results: In total, ten randomised controlled trials comprising 569 participants were used in the systematic review, and eight trials were included in the meta-analysis. Subgroup analysis revealed significant effects of foot reflexology massage on subjective sleep quality. Massage therapy for a two-night duration in cardiac care unit patients exhibited a significant effect on subjective sleep quality. The overall GRADE certainty of evidence was low., Conclusion: Massage intervention, particularly foot reflexology massage, with a two-night duration showed improvement in subjective sleep quality among critically ill patients. Although evidence quality was low, the results suggest that massage interventions provide a non-invasive, low-cost and effective way to promote sleep quality in critically ill adult patients., Relevance to Clinical Practice: Massage interventions can enable nurses to recommend and implement strategies promoting and improving sleep quality among critically ill patients., Study Registration: The review protocol was registered a priori and published online in the PROSPERO database of systematic reviews (www.crd.York.ac.uk/Prospero with the registration number # CRD42022332371)., Patient or Public Contribution: No patient or public contribution if such details are not necessary or do not apply to your work and state why., (© 2023 John Wiley & Sons Ltd.)

The large gap between the demand for, and the supply of organs worldwide makes promoting organ donation an important global social issue. Even after someone has signed a consent form or registered for organ donation, ethically, the hospital still requires a family member's written permission before organ donation can proceed. As a result, a family member rather than the patient makes the final decision. This study investigated the willingness of the family members of hypothetical patients in intensive care units (ICUs) suffering from an irreversible condition to sign an organ donation consent form. A cross-sectional survey was conducted among family members of ICU patients recruited from one medical center in southern Taiwan from April to October 2014, which followed the STROBE guidelines. Of 110 ICU family members, 71 (64.5%) were willing to donate the organs of hypothetical patients with irreversible conditions. Based on logistic regression, family support, attitude, and knowledge of organ donation significantly predicted 34% of the variance in willingness to sign consent. Attitude toward organ donation and behavioral knowledge of organ donation correlated significantly with a willingness to sign a consent form. This study found that family support and organ donation attitudes were important factors in predicting the willingness to sign a consent form for the organ donation of hypothetical patients. The study provides evidence that nurses and healthcare staff need to consider family support and educate families on organ donation to encourage potential donors to accept and agree to organ donation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD., (© 2023 S. Karger AG, Basel.)

Aims: To evaluate the effect of earplugs and eye masks on the sleep quality of patients in intensive care unit (ICU)., Design: Systematic review and meta-analysis., Data Sources: Randomized controlled trial studies conducted before May 5, 2020 were searched for in Embase, MEDLINE, Cochrane Library, CINAHL and Index to Taiwan Periodical Literature System databases., Review Methods: Analyses in this study were according to the PRISMA statement. The heterogeneity of the data was investigated through sub-group analysis while a meta-analysis was performed using the Review Manager 5.3 software., Results: A total of 797 patients from 13 studies were included in this study. Without considering alone or combined use of earplugs and eye masks, the meta-analysis supported that there was a significant effect on self-reported sleep quality. The overall standardized mean difference of the effect size was 1.44 (95% confidence interval [CI]: [0.80, 2.09]). Sub-group analysis indicated that the use of earplugs alone had no significant effect on sleep quality (effect size: 0.07, 95% [CI]: [-0.50, 0.64]). The use of eye masks alone had a significant effect on sleep quality (effect size: 1.56, 95% [CI]: [1.08, 2.05]). The use of both earplugs and eye masks proved to have the largest effect size on sleep quality (effect size: 2.08, 95% [CI]: [0.95, 3.21])., Conclusion: The combined use of earplugs and eye masks or the standalone use of eye masks is a non-invasive, economical and effective way to promote sleep quality in adult ICU patients., Impact: Clinical nurses could use this meta-analysis as it recommends that nurses provide adult ICU patients with either one or both earplugs and eye masks to improve the patients' sleep quality., Study Registration: The review protocol was registered a priori and published online in the PROSPERO database of systematic reviews (www.crd.York.ac.uk/Prospero with the registration number # CRD42021221185)., (© 2021 John Wiley & Sons Ltd.)

Recombinase polymerase amplification (RPA) is considered one of the best amplification methods for realizing a miniaturized diagnostic instrument; however, it is notably challenging to obtain low detection limits in solid-phase RPA. To overcome these difficulties, we combined solid-phase RPA with electrochemical detection and used a new concentration combination of three primers (surface-bound forward primer, solution reverse primer, and an extremely low concentration of solution forward primer). When solid-phase RPA was performed on an indium tin oxide (ITO) electrode modified with a surface-bound forward primer in a solution containing a biotin-terminated solution reverse primer, an extremely low concentration of a solution forward primer, and a template DNA or genomic DNA for a target gene of hepatitis B virus (HBV), amplification occurred mainly in solution until all the solution forward primers were consumed. Subsequently, DNA amplicons produced in solution participated in solid-phase amplification involving surface-bound forward primer and solution reverse primer. Afterward, neutravidin-conjugated DT-diaphorase (DT-D) was attached to a biotin-terminated DNA amplicon on the ITO electrode. Finally, chronocoulometric charges were measured using electrochemical-enzymatic redox cycling involving the ITO electrode, 1,4-naphthoquinone, DT-D, and reduced β-nicotinamide adenine dinucleotide. The detection limit for HBV was measured using microfabricated electrodes and was found to be approximately 0.1 fM. This proposed method demonstrated better amplification efficiency for HBV genomic DNA than solid-phase RPA without using additional solution primer and asymmetric solid-phase RPA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

SERPINE1 protein is one important member of the serine proteinase inhibitor E superfamily that plays a crucial role in the fibrinolytic system. It has been identified which is related to chronic inflammatory lung diseases like allergic asthma and lung fibrosis. Recently, researchers have focused on the impact of SERPINE1 and its genetic polymorphisms on inflammatory diseases of the upper respiratory tract. In this review, we conclude that SERPINE1 is widely involved in the pathological process of chronic rhinosinusitis and allergic rhinitis (AR) and may play a pivotal role in tissue remodelling in chronic rhinosinusitis without nasal polyps. It is also found that the 4G allele of SERPINE1 gene is associated with the risk of upper respiratory diseases. More studies are needed to further clarify how SERPINE1 influences chronic rhinosinusitis and AR, which would be conducive to improving the therapeutic efficacy of treatments for upper respiratory diseases., (© 2021 S. Karger AG, Basel.)

Recent evidence has linked the dysregulation of the Hippo pathway to tumorigenesis and cancer progression due to its pivotal role in regulating the stability of the oncoprotein YAP. Based on an unexpected finding from the SAR study of a recently reported oxadiazole-based EGFR/c-Met dual inhibitor (compound 1 ), we identified a closely related derivative, compound 2 , which exhibited cogent antitumor activities while devoid of compound 1 's ability to promote EGFR/c-Met degradation. Compound 2 acted, in part, by facilitating YAP degradation through activation of its upstream kinase LATS1. However, it did not alter the phosphorylation status of MST1/2, a LATS1 kinase, suggesting an alternative mechanism for LATS1 activation. Orally administered compound 2 was effective in suppressing MDA-MB-231 xenograft tumor growth while exhibiting a satisfactory safety profile. From a therapeutic perspective, compound 2 might help foster new therapeutic strategies for cancer treatment by restoring the Hippo pathway regulatory function to facilitate YAP degradation., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Development of small-molecule agents with the ability to facilitate oncoprotein degradation has emerged as a promising strategy for cancer therapy. Since EGFR and c-Met are both implicated in oncogenesis and tumor progression, we initiated a screening program by using an in-house library to identify agents capable of inducing the concomitant suppression of EGFR and c-Met expression, which led to the identification of compound 1, a 1,2,4-oxadiazole derivative. Based on the scaffold of 1, we developed a series of derivatives to assess their efficacies in facilitating the downregulation of EGFR and c-Met, among which compound 48 represented the optimal agent. 48 showed equipotent antiproliferative activity against a panel of five NSCLC cell lines with different EGFR mutational status (IC 50  = 0.2-0.6 μM), while the same panel exhibited differential sensitivity to different EGFR kinase inhibitors tested. Cell cycle analysis indicated that the antiproliferative activity of 48 was associated with its ability to cause G2/M arrest and, to a lesser extent, apoptosis. Western blot and RT-PCR analyses revealed that 48 facilitated the downregulation of EGFR and c-Met at the protein level. In vivo data showed that oral administration of 48 was effective in suppressing gefitinib-resistant H1975 xenograft tumor growth in nude mice, and at a suboptimal dose, could sensitize H1975 tumors to gefitinib. Based on these findings, 48 represents a promising candidate for further development to target EGFR TKI-resistant NSCLC via dual inhibition of EGFR and c-Met oncoproteins., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: The emergence of multiple-antibiotic-resistant (MAR) Salmonella has been a serious threat worldwide. Salmonella can invade into host cells and evade the attacks of host humoral defenses and antibiotics. Thus, a new antibacterial agent capable of inhibiting intracellular Salmonella is highly needed., Methods: The anti-intracellular activity and cytotoxicity of drugs on intracellular bacteria and macrophages were assayed using intracellular CFU assay and MTT cell viability assay, respectively. The uptake of gentamicin into macrophage and the effect of autophagy inhibitor on loxapine's anti-intracellular Salmonella activity were assessed by using image-based high-content system. The expression of bacterial genes was measured by real-time PCR. The efflux pump activity of bacteria was measured by Hoechst accumulation assays., Results: With our efforts, an antipsychotic drug, loxapine, was identified to exhibit high potency in suppressing intracellular MAR S. Typhimurium, Staphylococcus aureus, Shigella flexneri or Yersinia enterocolitica. Subsequent investigations indicated that loxapine's anti-intracellular bacteria activity was not associated with increased penetration of gentamicin into bacteria and macrophages. Loxapine didn't inhibit bacterial growth in broth at concentration up to 500 μM and has no effect on Salmonella's type III secretion system genes' expression. Blockage of autophagy also didn't reverse loxapine's anti-intracellular activity. Lastly, loxapine suppressed bacterial efflux pump activity in all bacteria tested., Conclusion: Altogether, our data suggested that loxapine might suppress intracellular bacteria through inhibiting of bacterial efflux pumps. In light of its unique activity, loxapine represents a promising lead compound with translational potential for the development of a new antibacterial agent against intracellular bacteria., (Copyright © 2019. Published by Elsevier B.V.)

Objective: The study examined the association between acculturation level, dietary nutrient intake, and psychological health of Asian students at the University of Delaware. Participants: A total of 172 students completed the study. Methods: Data were collected, using questionnaires, through Qualtrics®. Linear regression models were used to examine the association between normally distributed diet and acculturation and demographic data. Results: As length of residence in the United States increased, acculturation level and maintenance of original culture both increased. There was no significant association between acculturation and nutrient intake. Chinese students were more likely than other Asian students to have nonspecific psychological distress. Conclusion: There was no significant association between diet and acculturation level. A larger sample population with longer US residence is needed to further investigate this association. In an effort to improve psychological health of Asian students, challenges specific to this population, such as the language barrier, should be addressed.

To explore famous veteran traditional Chinese medicine( TCM) doctors' medication rules in treating spermatorrhea based on the medical cases about spermatorrhea collected from Hundred TCM Clinical Doctors of Hundred Years in China and Proven Cases and National Medical Master Test Case. Researchers extracted such data as medicinal and therapies from these cases according to the inclusion and exclusion criteria. Then,Excle 2010,SPSS Clementine 12. 0 and SPSS 22. 0 were adopted respectively for frequency analysis,association rules analysis,cluster analysis and factor analysis. Cluster analysis was carried out by Ochiai algorithm of binary variable data,one of the systematic clustering methods. And principal component analysis was used for factor analysis. Finally,27 medical cases and 41 prescriptions were included in total. The frequency analysis showed that the most common therapy was the astringent therapy( n = 28),which was followed by the tonifying method,tranquilizing method,heat-clearing method,damp-dispelling method and Qiregulating method. The top three kinds of high-frequency traditional Chinese medicines were Poria,Ostreae Concha and Dioscoreae Rhizoma. The association rules analysis found out 11 association rules of medicine pairs,23 association rules of medicine combinations of the three kinds of herbs and 6 association rules of medicine combinations of five kinds of herbs. Among them,the representatives were Rubi Fructus→Fossilia Ossis Mastodi,Rehmanniae Radix Praeparata + Corni Fructus→Dioscoreae Rhizoma,and Pinelliae Rhizoma→Citri Reticulatae Pericarpium,which showed the therapeutic characteristics of astringing,tonifying the kidney and replenishing essence,fortifying the spleen and dispelling dampness. Moreover,7 medicine groups with relevance were extracted from the tree map generated by cluster analysis,including " Phellodendri Chinensis Cortex and Anemarrhenae Rhizoma" and " Angelicae Sinensis Radix,Rehmanniae Radix,Bupleuri Radix and Glycyrrhizae Radix et Rhizoma",which demonstrated the effects of nourishing Yin and purging fire,tonifying and soothing the liver. Besides,totally 12 common factors were obtained according to factor analysis,including 14 drug combinations,like " Amomi Fructus,Anemarrhenae Rhizoma and Phellodendri Chinensis Cortex" and " Nelumbinis Stamen,Moutan Cortex,Poria and Scrophulariae Radix",which indicated the compatibility characteristics of tonifying the spleen and purging fire,dispelling dampness and clearing heat. In conclusion,data mining techniques( including frequency analysis,association rules analysis,cluster analysis and factor analysis) were used to comprehensively analyze the famous veteran TCM doctors' medication rules in treating spermatorrhea,which was helpful for guiding the clinical practice of treating spermatorrhea in TCM.

Recombinase polymerase amplification (RPA) has been combined with electrochemical detection for simple and rapid point-of-care testing. However, there are two major hindrances to this simple and rapid testing: (i) washing or purification steps are required to remove unbound labeled probes and interfering species in the sample; (ii) it is difficult to quantify double-stranded DNA (dsDNA) electrochemically by using biospecific affinity binding without dsDNA denaturation. In the present study, we describe a wash-free and rapid electrochemical method to detect RPA-amplified dsDNAs using a zinc finger protein, Zif268. Electrochemical detection is achieved using proximity-dependent electron mediation of ferrocenemethanol between a glucose-oxidase (GOx) label and an electrode, which differentiates the specifically electrode-bound and -unbound labels without a washing or purification step. RPA-amplified dsDNA containing a biotin-terminated forward primer is specifically bound to a neutravidin-modified electrode, and GOx-conjugated Zif268 is specifically bound to the dsDNA. The whole detection is performed within 17 min (15 min for the RPA reaction and <2 min for the electrochemical measurement). Electrochemical detection is carried out without an additional incubation period, because the specific binding between Zif268 and the dsDNA occurs during the RPA reaction. The detection method could discriminate between target template DNA of Piscirickettsia salmonis and nontarget DNAs (random sequence and calf thymus DNA). The detection limit for the target DNA is approximately 300 copies in 13.2 μL, indicating that the detection method is ultrasensitive. We believe that the method could offer a promising solution for simple and rapid point-of-care testing.

Both high sensitivity and high specificity are crucial for detection of miRNAs that have emerged as important clinical biomarkers. Just Another Zinc finger proteins (JAZ, ZNF346) bind preferably (but nonsequence-specifically) to DNA-RNA hybrids over single-stranded RNAs, single-stranded DNAs, and double-stranded DNAs. We present an ultrasensitive and highly specific electrochemical method for miRNA-21 detection based on the selective binding of JAZ to the DNA-RNA hybrid formed between a DNA capture probe and a target miRNA-21. This enables us to use chemically stable DNA as a capture probe instead of RNA as well as to apply a standard sandwich-type assay format to miRNA detection. High signal amplification is obtained by (i) enzymatic amplification by alkaline phosphatase (ALP) coupled with (ii) electrochemical-chemical-chemical (ECC) redox cycling involving an ALP product (hydroquinone). Low nonspecific adsorption of ALP-conjugated JAZ is obtained using a polymeric self-assembled-monolayer-modified and casein-treated indium-tin oxide electrode. The detection method can discriminate between target miRNA-21 and nontarget nucleic acids (DNA-DNA hybrid, single-stranded DNA, miRNA-125b, miRNA-155, single-base mismatched miRNA, and three-base mismatched miRNA). The detection limits for miRNA-21 in buffer and 10-fold diluted serum are approximately 2 and 30 fM, respectively, indicating that the detection method is ultrasensitive. This detection method can be readily extended to multiplex detection of miRNAs with only one ALP-conjugated JAZ probe due to its nonsequence-specific binding character. We also believe that the method could offer a promising solution for point-of-care testing of miRNAs in body fluids.

Integrin-linked kinase (ILK) is a mediator of aggressive phenotype in pancreatic cancer. On the basis of our finding that knockdown of either KRAS or ILK has a reciprocal effect on the other's expression, we hypothesized the presence of an ILK-KRAS regulatory loop that enables pancreatic cancer cells to regulate KRAS expression. This study aimed to elucidate the mechanism by which this regulatory circuitry is regulated and to investigate the translational potential of targeting ILK to suppress oncogenic KRAS signaling in pancreatic cancer. Interplay between KRAS and ILK and the roles of E2F1, c-Myc and heterogeneous nuclear ribonucleoprotein as intermediary effectors in this feedback loop was interrogated by genetic manipulations through small interfering RNA/short hairpin RNA knockdown and ectopic expression, western blotting, PCR, promoter-luciferase reporter assays, chromatin immunoprecipitation and pull-down analyses. In vivo efficacy of ILK inhibition was evaluated in two murine xenograft models. Our data show that KRAS regulated the expression of ILK through E2F1-mediated transcriptional activation, which, in turn, controlled KRAS gene expression via hnRNPA1-mediated destabilization of the G-quadruplex on the KRAS promoter. Moreover, ILK inhibition blocked KRAS-driven epithelial-mesenchymal transition and growth factor-stimulated KRAS expression. The knockdown or pharmacological inhibition of ILK suppressed pancreatic tumor growth, in part, by suppressing KRAS signaling. These studies suggest that this KRAS-E2F1-ILK-hnRNPA1 regulatory loop enables pancreatic cancer cells to promote oncogenic KRAS signaling and to interact with the tumor microenvironment to promote aggressive phenotypes. This regulatory loop provides a mechanistic rationale for targeting ILK to suppress oncogenic KRAS signaling, which might foster new therapeutic strategies for pancreatic cancer.

This communication reports a new nanocatalytic scheme based on the facts that the redox reaction between a highly outer-sphere-reaction-philic (OSR-philic) species and a highly inner-sphere-reaction-philic (ISR-philic) species is slow and that an OSR- and ISR-philic Au-nanocatalyst label can mediate the two different types of redox species. This scheme allows highly sensitive and incubation free detection of creatine kinase-MB.

Previously, we reported the identification of a thiazolidinedione-based adenosine monophosphate activated protein kinase (AMPK) activator, compound 1 (N-[4-({3-[(1-methylcyclohexyl)methyl]-2,4-dioxothiazolidin-5-ylidene}methyl)phenyl]-4-nitro-3-(trifluoromethyl)benzenesulfonamide), which provided a proof of concept to delineate the intricate role of AMPK in regulating oncogenic signaling pathways associated with cell proliferation and epithelial-mesenchymal transition (EMT) in cancer cells. In this study, we used 1 as a scaffold to conduct lead optimization, which generated a series of derivatives. Analysis of the antiproliferative and AMPK-activating activities of individual derivatives revealed a distinct structure-activity relationship and identified 59 (N-(3-nitrophenyl)-N'-{4-[(3-{[3,5-bis(trifluoromethyl)phenyl]methyl}-2,4-dioxothiazolidin-5-ylidene)methyl]phenyl}urea) as the optimal agent. Relative to 1, compound 59 exhibits multifold higher potency in upregulating AMPK phosphorylation in various cell lines irrespective of their liver kinase B1 (LKB1) functional status, accompanied by parallel changes in the phosphorylation/expression levels of p70S6K, Akt, Foxo3a, and EMT-associated markers. Consistent with its predicted activity against tumors with activated Akt status, orally administered 59 was efficacious in suppressing the growth of phosphatase and tensin homologue (PTEN)-null PC-3 xenograft tumors in nude mice. Together, these findings suggest that 59 has clinical value in therapeutic strategies for PTEN-negative cancer and warrants continued investigation in this regard., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To study the protective effects of ginkgolide N against glutamte-induced injury in PC12 cells and its mechanisms., Methods: The injury model was established by treating PC12 cells with glutamate, and PC12 cells were treated with different concentrations of ginkgolide N with ginkgolide B as control. The cells activity was analyzed by MTT assay. The apoptosis of PC12 cells were examined by acridine orange( AO) staining, the reactive oxygen species and mitochondrial membrane potential of PC12 cells were examined by flow cytometry. Western blot method was used to examine the expression of Cleaved Caspase-3 protein., Results: Ginkgolides N of 2-8 µgmol/L inhibited PC12 cells apoptosis and ROS accumulation induced by glutamate,stabilized membrane potential of damaged PC12, and reduced the expression of Cleaved Caspase-3 protein., Conclusion: Ginkgolide N has a protective effect on PC12 cells injury induced by glutamate, and the mechanism may be associated with reducing ROS generation, stabilizing membrane potential and inhibiting the expression of Cleaved Caspase-3 protein.

Gemcitabine resistance remains a significant clinical challenge. Here, we used a novel glucose transporter (Glut) inhibitor, CG-5, as a proof-of-concept compound to investigate the therapeutic utility of targeting the Warburg effect to overcome gemcitabine resistance in pancreatic cancer. The effects of gemcitabine and/or CG-5 on viability, survival, glucose uptake and DNA damage were evaluated in gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cell lines. Mechanistic studies were conducted to determine the molecular basis of gemcitabine resistance and the mechanism of CG-5-induced sensitization to gemcitabine. The effects of CG-5 on gemcitabine sensitivity were investigated in a xenograft tumor model of gemcitabine-resistant pancreatic cancer. In contrast to gemcitabine-sensitive pancreatic cancer cells, the resistant Panc-1 and Panc-1(GemR) cells responded to gemcitabine by increasing the expression of ribonucleotide reductase M2 catalytic subunit (RRM2) through E2F1-mediated transcriptional activation. Acting as a pan-Glut inhibitor, CG-5 abrogated this gemcitabine-induced upregulation of RRM2 through decreased E2F1 expression, thereby enhancing gemcitabine-induced DNA damage and inhibition of cell survival. This CG-5-induced inhibition of E2F1 expression was mediated by the induction of a previously unreported E2F1-targeted microRNA, miR-520f. The addition of oral CG-5 to gemcitabine therapy caused greater suppression of Panc-1(GemR) xenograft tumor growth in vivo than either drug alone. Glut inhibition may be an effective strategy to enhance gemcitabine activity for the treatment of pancreatic cancer., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We report on a Ag5 coordination polymer and discrete Ag8 and Ag10 dithiophosphate clusters. The cluster formation and structures were affected by the stoichiometric control of the M : L molar ratios used. The cluster [Ag5{S2P(O(i)Pr)2}4]n(PF6)n, , is a monomeric unit within a coordination polymer formed through the reaction between [Ag(CH3CN)4]PF6 and the dithiophosphate ligand, [S2P(O(i)Pr)2](-), used in a M : L molar ratio of 5 : 4. All other clusters formed in the study are discrete units with encapsulated anions within the metal framework. The clusters [Ag8(X){S2P(O(i)Pr)2}6](PF6) (X = F, , Cl, , Br, ) are all cationic and contain monoanionic halogens. The related cluster [Ag8(H/D){S2P(O(i)Pr)2}6](PF6) contains either a hydride or a deuteride ion, and , respectively. The cluster [Ag8(S){S2P(O(i)Pr)2}6], , is neutral due to the di-anionic nature of the encapsulated sulfide anion. Clusters were all formed by reacting [Ag(CH3CN)4]PF6 and [S2P(O(i)Pr)2](-) in a M : L molar ratio of 8 : 6 and stirring for 1 h in THF; thereafter the respective anions (one equiv.) were added in situ. The cluster [Ag10(I)4{S2P(O(i)Pr)2}6], , is also neutral due to the charge balancing of the additional metal and halogen. In this case the M : L : X molar ratio was 10 : 6 : 4. All new clusters were characterized by (1)H and (31)P NMR, and elemental analysis, and , , were characterized by single crystal X-ray diffraction.

M8L6 clusters (M = Cu(I), Ag(I); L = dichalcogeno ligand) are known for their ability to encapsulate various kinds of saturated atomic anions. Calculations on the models [M8(E2PH2)6](2+) (M = Cu(I), Ag(I); E = S, Se) and the ionic or neutral [M8(X)(E2PH2)6](q) (X = H, F, Cl, Br, O, S, Se, N, P, C) indicate that the cubic M8L6 cage adapts its shape for maximizing the host-guest bonding interaction. The interplay between size, covalent and ionic bonding favors either a cubic, tetracapped tetrahedral, or bicapped octahedral structure of the metal framework. Whereas the large third- and fourth-row main group anions maintain the cubic shape, a distortion toward a tetracapped tetrahedral arrangement of the metals occurs in the case of hydride, fluoride, and oxide. The distortion is strong in the case of hydride, weak in the case of fluoride, and intermediate in the case of oxide. Density functional theory (DFT) calculations predict a bicapped octahedral architecture in the case of nitride and carbide. These computational results are supported by X-ray structures, including those of new fluorine- and oxygen-containing compounds. It is suggested that other oxygen-containing as well as so far unknown nitride-containing clusters should be feasible. For the first time, the dynamical behavior of the encapsulated hydride has been investigated by metadynamics simulations. Our results clearly demonstrate that the interconversion mechanism between two identical tetracapped tetrahedral configurations occurs through a succession of M-H bonds breaking and forming which present very low activation energies and which involve a rather large number of intermediate structures. This mechanism is full in accordance with (109)Ag and (1)H state NMR measurements.

Reactions of Ag(I) salt, NH(4)(E(2)P(OR)(2)) (R = (i)Pr, Et; E = Se, S), and NaBH(4) in a 7:6:1 ratio in CH(2)Cl(2) at room temperature, led to the formation of hydride-centered heptanuclear silver clusters, [Ag(7)(H){E(2)P(OR)(2)}(6)] (R = (i)Pr, E = Se (3): R = Et; E = S(4). The reaction of [Ag(10)(E){E(2)P(OR)(2)}(8)] with NaBH(4) in CH(2)Cl(2) produced [Ag(8)(H){E(2)P(OR)(2)}(6)](PF(6)) (R = (i)Pr, E = Se (1): R = Et; E = S(2)), which can be converted to clusters 3 and 4, respectively, via the addition of 1 equiv of borohydride. Intriguingly clusters 1 and 2 can be regenerated via adding 1 equiv of Ag(CH(3)CN)(4)PF(6) to the solution of compounds 3 and 4, respectively. All complexes have been fully characterized by NMR ((1)H, (77)Se, (109)Ag) spectroscopy, UV-vis, electrospray ionization mass spectrometry (ESI-MS), FT-IR, thermogravimetric analysis (TGA), and elemental analysis, and molecular structures of 3(H) and 4(H) were clearly established by single crystal X-ray diffraction. Both 3(H) and 4(H) exhibit a tricapped tetrahedral Ag(7) skeleton, which is inscribed within an E(12) icosahedron constituted by six dialkyl dichalcogenophosphate ligands in a tetrametallic-tetraconnective (μ(2), μ(2)) bonding mode. Density functional theory (DFT) calculations on the models [Ag(7)(H)(E(2)PH(2))(6)] (E = Se: 3'; E = S: 4') yielded to a tricapped, slightly elongated tetrahedral silver skeleton, and time-dependent DFT (TDDFT) calculations reproduce satisfyingly the UV-vis spectrum with computed transitions at 452 and 423 nm for 3' and 378 nm for 4'. Intriguingly further reactions of [Ag(7)(H){E(2)P(OR)(2)}(6)] with 8-fold excess amounts of NaBH(4) produced monodisperse silver nanoparticles with an averaged particle size of 30 nm, which are characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD), and UV-vis absorption spectrum.

Reactions of Cu(I) salts with Na(S(2)CR) (R = N(n)Pr(2), NEt(2), aza-15-crown-5), and (Bu(4)N)(BH(4)) in an 8:6:1 ratio in CH(3)CN solution at room temperature yield the monocationic hydride-centered octanuclear Cu(I) clusters, [Cu(8)(H){S(2)CR}(6)](PF(6)) (R = N(n)Pr(2), 1(H); NEt(2), 2(H); aza-15-crown-5, 3(H)). Further reactions of [Cu(8)(H){S(2)CR}(6)](PF(6)) with 1 equiv of (Bu(4)N)(BH(4)) produced neutral heptanuclear copper clusters, [Cu(7)(H){S(2)CR}(6)] (R = N(n)Pr(2), 4(H); NEt(2), 5(H); aza-15-crown-5, 6(H)) and clusters 4-6 can also be generated from the reaction of Cu(BF(4))(2), Na(S(2)CR), and (Bu(4)N)(BH(4)) in a 7:6:8 molar ratio in CH(3)CN. Reformation of cationic Cu(I)(8) clusters by adding 1 equiv of Cu(I) salt to the neutral Cu(7) clusters in solution is observed. Intriguingly, the central hydride in [Cu(8)(H){S(2)CN(n)Pr(2)}(6)](PF(6)) can be oxidatively removed as H(2) by Ce(NO(3))(6)(2-) to yield [Cu(II)(S(2)CN(n)Pr(2))(2)] exploiting the redox-tolerant nature of dithiocarbamates. Regeneration of hydride-centered octanuclear copper clusters from the [Cu(II)(S(2)CN(n)Pr(2))(2)] can be achieved by reaction with Cu(I) ions and borohydride. The hydride release and regeneration of Cu(I)(8) was monitored by UV-visible titration experiments. To our knowledge, this is the first time that hydride encapsulated within a copper cluster can be released as H(2) via chemical means. All complexes have been fully characterized by (1)H NMR, FT-IR, UV-vis, and elemental analysis, and molecular structures of 1(H), 2(H), and 6(H) were clearly established by single-crystal X-ray diffraction. Both 1(H) and 2(H) exhibit a tetracapped tetrahedral Cu(8) skeleton, which is inscribed within a S(12) icosahedron constituted by six dialkyl dithiocarbamate ligands in a tetrametallic-tetraconnective (μ(2), μ(2)) bonding mode. The copper framework of 6(H) is a tricapped distorted tetrahedron in which the four-coordinate hydride is demonstrated to occupy the central site by single crystal neutron diffraction. Compounds 1-3 exhibit a yellow emission in both the solid state and in solution under UV irradiation at 77 K, and the structureless emission is assigned as a (3)metal to ligand charge transfer (MLCT) excited state. Density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations on model compounds match the experimental structures and provide rationalization of their bonding and optical properties.

Background: It is well known that pulmonary alveolar proteinosis(PAP) is characterised by accumulation of surfactant lipids and proteins within airspaces. However, few previous data describe the serum lipid levels associated with PAP., Materials and Methods: We retrospectively reviewed 25 patients with idiopathic PAP(iPAP). The serum lipid levels of patients with idiopathic PAP were compared with those of the healthy volunteers. In patients and healthy subjects, the LDL-C/HDL-C ratios were 2.94 ± 1.21 and 1.60 ± 0.70, respectively (p < 0.001), HDL-C were 1.11 ± 0.27 and 1.71 ± 0.71 respectively (p < 0.001). The values of LDL-C correlated significantly with those of PaO2 and PA-aO2 (r = -0.685, p = 0.003, and r = 0.688, p = 0.003, respectively). The values of LDL-C/HDL-C ratios also correlated with PaO2 levels and PA-aO2 levels (r = -0.698, p = 0.003, and r = 0.653, p = 0.006, respectively). 11 and 13 patients experienced respectively a decline in TC and LDL-C levels following whole lung lavage(WLL), the median decline was 0.71 mmol/L(p < 0.009) and 0.47 mmol/L(p < 0.003), respectively., Conclusions: the serum lipid levels, especially the levels of LDL-C and LDL-C/HDL-C, may reflect the severity of the disease in PAP patients, and predict the therapeutic effect of WLL.

The hydrido copper(I) and silver(I) clusters incorporating 1,1-dicyanoethylene-2,2-dithiolate (i-MNT) ligands are presented in this paper. Reactions of M(I) (M = Cu, Ag) salts, [Bu(4)N](2)[S(2)CC(CN)(2)], with the anion sources ([Bu(4)N][BH(4)] for H(-), [Bu(4)N][BD(4)] for D(-)) in an 8:6:1 molar ratio in THF produce octanuclear penta-anionic Cu(I)/Ag(I) clusters, [Bu(4)N](5)[M(8)(X){S(2)CC(CN)(2)}(6)] (M = Cu, X = H, 1(H); X = D, 1(D); M = Ag, X = H, 2(H); X = D, 2(D)). They can also be produced from the stoichiometric reaction of M(8)(i-MNT)(6)(4-) with the ammonium borohydride. All four compounds have been fully characterized spectroscopically ((1)H and (13)C NMR, IR, UV-vis) and by elemental analyses. The deuteride-encapsulated Cu(8)/Ag(8) clusters of 1(D) and 2(D) are also characterized by (2)H NMR. X-ray crystal structures of 1(H) and 2(H) reveal a hydride-centered tetracapped tetrahedral Cu(8)/Ag(8) core, which is inscribed within an S(12) icosahedron formed by six i-MNT ligands, each in a tetrametallic-tetraconnective (μ(2), μ(2)) bonding mode. The encapsulated hydride in 2(H) is unequivocally characterized by both (1)H and (109)Ag NMR spectroscopies, and the results strongly suggest that the hydride is coupled to eight magnetically equivalent silver nuclei on the NMR time scale. Therefore, a fast interchange between the vertex and capping silver atoms in solution gives a plausible explanation for the perceived structural differences between the Ag(8) geometry deduced from the X-ray structure and the NMR spectra.

The first elemental cluster with hexacapped trigonal bipyramidal geometry is revealed in the luminescent undecanuclear silver complex which is stabilized by nine dithiocarbamate ligands and has an interstitial hydride. The hydride position within the Ag(11) cage is confirmed by a DFT investigation., (© The Royal Society of Chemistry 2011)

Novel Ag(32) clusters, [Ag(16)(EO(4)){S(2)P(OEt)(2)}(12)](2) (PF(6))(4) (E = S, 1; Se, 2) and [Ag(16)(MO(4)){S(2)P(OEt)(2)}(12)](2)(PF(6))(4) (M = Cr, 3; Mo, 4), were prepared in situ from the addition of a tetrahedral-shaped anion as a template to the pentanuclear extended chain [Ag(5){S(2)P(OEt)(2)}(4)](n)(PF(6))(n).

The alternative transcription factor σ(B) is responsible for transcription in Staphylococcus aureus during the stress response. Many virulence-associated genes are directly or indirectly regulated by σ(B). We hypothesized that treatment with antibiotics may act as an environmental stressor that induces σ(B) activity in antibiotic-resistant strains. Several antibiotics with distinct modes of action, including ampicillin (12 µg/ml), vancomycin (16 or 32 µg/ml), chloramphenicol (15 µg/ml), ciprofloxacin (0.25 µg/ml), and sulfamethoxazole/trimethoprim (SXT, 0.8 µg/ml), were investigated for their ability to activate this transcription factor. We were especially interested in the stress response in vancomycin-resistant S. aureus (VRSA) strains treated with vancomycin. The transcription levels of selected genes associated with virulence were also measured. Real-time quantitative reverse transcription PCR was employed to evaluate gene transcription levels. Contact hemolytic and cytotoxicity assays were used to evaluate cell damage following antibiotic treatment. Antibiotics that target the cell wall (vancomycin and ampicillin) and SXT induced σ(B) activity in VRSA strains. Expression of σ(B)-regulated virulence genes, including hla and fnbA, was associated with the vancomycin-induced σ(B) activity in VRSA strains and the increase in cytotoxicity upon vancomycin treatment. These effects were not observed in the sigB-deficient strain but were observed in the complemented strain. We demonstrate that sub-minimum inhibitory concentration (sub-MIC) levels of antibiotics act as environmental stressors and activate the stress response sigma factor, σ(B). The improper use of antibiotics may alter the expression of virulence factors through the activation of σ(B) in drug-resistant strains of S. aureus and lead to worse clinical outcomes.

Structures of [AuSe(2)P(OR)(2)](2) (R = (i)Pr, 1; Et, 2), the first homoleptic dinuclear gold(I) bridged by phosphorodiselenoates, are reported along with their intriguing photoluminescent properties, which display multiple emissions as well as thermochromism.

Extended chain polymers [Ag(5){S(2)P(OEt)(2)}(4)(PF(6))](n), (1) could be converted to clusters of the type, [Ag(8)(X){S(2)P(OEt)(2)}(6)](PF(6)) [X = F (2); Cl (3); H (4)], by the addition of appropriate anions, of which [Ag(8)(H){S(2)P(OEt)(2)}(6)](+) showed a unique tetracapped-tetrahedral Ag(8) core and contained Ag-mu-H-Ag linkages.

Herniation of the spinal cord is a rare condition that causes non specific neurological deficits that are often a diagnostic challenge to clinicians. Despite several reports in the neurosurgical literature, it is only recently that the imaging appearances of this condition have come to be recognised, due mainly to the widespread adoption of spinal MRI. It is important for radiologists to recognise the telltale MRI features of this condition, as several cases have undergone initial misdiagnosis, resulting in delayed treatment We present a case with typical imaging features to familiarise radiologists with this condition, as it is likely that more cases will come to the fore, with more spinal MRIs being performed.

Purpose: To investigate the characteristics and outcomes of surgical patients who were readmitted to the intensive care unit (ICU)., Methods: The data were collected for all readmissions to the surgical ICUs in a tertiary hospital in the year 2003., Results: Of all the 945 ICU discharges, 110 patients (11.6%) were readmitted. They had a longer initial ICU stay (8.05 +/- 7.17 vs 5.22 +/- 4.95, P < 0.001) and were older and in a more severe condition than those not readmitted, but with a longer hospital stay and higher mortality rate (40% vs 3.6%, P < 0.001). A total of 26.4% of the readmission patients had an early readmission (<48 h), with a lower mortality rate than those with a late readmission (24.1% vs 45.7%, P = 0.049). A total of 46.4% of the patients were readmitted with the same diagnosis while the rest were readmitted with a new complication. Respiratory disease was the most common diagnosis for patients readmitted with a new complication (66.1%). The nonsurvivors had a significantly higher second Acute Physiology and Chronic Health Evaluation (APACHE II) score (22.1 +/- 8.8 vs.14.6 +/- 7.4, P < 0.001) and second Therapeutic Intervention Scoring System (TISS) score (30.1 +/- 8.7 vs 24.7 +/- 7.6, P = 0.001) and a longer stay in the first ICU admission (10.4 +/- 9 days vs 6.4 +/- 5 days, P = 0.010). A multivariate analysis showed that the first ICU length of stay and the APACHE II score at the time of readmission were the two risk factors for mortality., Conclusion: The mortality of surgical patients with ICU readmission was high with respiratory complications being the most important issue.

Introduction: Resurfacing metal-on-metal hip arthroplasty is increasing in popularity, especially in younger patients. To date, studies indicate that the procedure is associated with a good outcome in the medium-term. Formation of a peri-articuar mass is a rarely reported complication. In this study we analyse the imaging findings in patients with resurfacing implants presenting to our institution with peri-articular masses identified on cross sectional imaging., Materials and Methods: All patients with documented peri-articular masses following resurfacing arthroplasty were included. The available imaging related to the masses was reviewed and the findings documented along with the patient's demographics., Results: There were 10 patients (13 joints). All patients were female. Patients presented with periprosthetic anterior or posterolateral solid and cystic masses. The anterior masses involved psoas muscle and were predominately solid. The posterolateral masses were predominately cystic. In the three cases with bilateral arthroplasties, masses were detected in both hips. Histology in six cases showed features compatible with a type IV hypersensitivity reaction., Conclusions: The preponderance of females, the bilateral nature of the masses and the histological features suggest that peri-articular masses following resurfacing arthroplasty is due to the metal hypersensitivity.

Treatment of [Zn(tmeda)Cl2] (tmeda = N, N, N', N'-tetramethylethylenediamine) with a phosphonate-substituted 2-cyanoethylene-1,1-dithiolato ligand in air yields a tetranuclear zinc-carbonate complex 1 having the formula of [Zn4(tmeda)3(mu3-CO3){S2CC(CN)P(O)(OEt)2}3] in which four zinc atoms form a trigonal pyramid with the apical zinc atom in a hitherto unknown S3O3 coordination sphere. It is the first example of aerial CO2 fixation to afford a metal-carbonato compound incorporating 1,1-ethenedithiolate ligands. In sharp contrast, reaction with an isobutyl ester-substituted 2-cyanoethylene-1,1-dithiolate forms a trimeric zinc complex [Zn(tmeda){S2CC(CN)(CO2(i)Bu)}]3, 2, which does not contain the metal-bound carbonate. Compound 2 is the first example of a trinuclear zinc complex composed of four-, five-, and six-coordinated Zn atoms. The unsymmetrical ligand orientation around three zinc centers in 2 suggests that the other structural isomer, which would have an idealized C3 axis, may exist. The reaction of the ethyl ester derivative of 2-cyanoethylene-1,1-dithiolate with [Zn(tmeda)Cl2] affords [{Zn(tmeda)Cl}2{S2CC(CN)(CO2Et)}], 3. The ester-functionalized 1,1-dithiolate ligands in compounds 2 and 3 display a bimetallic, triconnective coordination mode, which is rare for these types of ligands. Some probable intermediates generated from the formation of compound 1 have also been proposed.

There has been interest in the use of exogenous creatine (Cr) as an adjunct treatment for neurological disorders. Creatine enhances bouts of activity through augmenting phosphocreatine for increased synthesis of ATP; however, multiple sclerosis (MS) individuals suffering from muscle weakness have not been shown to improve muscle work after 5 days of Cr supplementation. This study's purpose was to determine whether the extended duration would increase muscle capacity. In a double-blind, crossover trial, with a 3-week washout period, eleven MS subjects were randomly assigned to either Cr (5 g 4/day, day 1-7: 2.5 g 2/day, day 8-14) or placebo groups for two 14-day periods. Biodex Dynamometer recorded total work and power over three bouts of 30 maximal knee extensions and flexions. Total work was nonsignificant with Cr for knee extension (pretest 1277.7 ± 214.9 J vs. posttest = 1313.14 ± 200.5 J; p = 0.81) and flexion (pretest = 1220.7 ± 200.5 J vs. posttest = 1302.10 J ± 189.64 J; p = 0.93). Creatine did not enhance muscle power in knee extension (p = 0.31; pretest = 82.1 ± 12.7 W vs. posttest = 87.7 ± 12.6 W) or flexion (p = 0.29; pretest = 75.3 ± 12.1 W vs. posttest = 81.2 ± 11.1 W). Therefore, 14 days of Cr supplementation did not improve muscle capacity or habitual fatigue in MS individuals.

Aim: To explore the effect of Triptolide on airway remodeling and the expression of Phosphoinositide 3-Kinases in asthmatic rats., Methods: 40 rats were randomly divided into 5 groups (n = 8): (1) Control group; (2) Asthmatic 4 weeks group; (3) Asthmatic 6 weeks group; (4) Therapeutic 4 weeks group; (5) Therapeutic 6 weeks group. The airway resistance and eosinophilic inflammation of airway wall were observed. The airway wall thickness (WA/Pi), the bronchial smooth muscle thickness (smooth muscle area/Pi) and the number of bronchial smooth muscle nucleus (N/Pi) were measured by image analysis system. The expression of PI3K protein and mRNA were determined by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR)., Results: (1) The expression of PI3K p85alpha protein and mRNA in asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01, P < 0.01 P < 0.05). (2) The WA/Pi, the smooth muscle area/Pi and the N/Pi of asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01). (3) The airway resistance of asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than the control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01, P < 0.01, P < 0.05)., Conclusion: The proliferation of airway smooth muscle is a remarkable character of airway remodeling in asthma. The PI3K signal pathway may be involved in the process. Triptolide may reduce AHR and decrease the proliferation of ASMCs by inhibiting the expression of PI3K. It may have potential therapeutic effects in the asthmatic airway remodeling.

In this paper a new electroporation (EP) system is developed, which includes an EP microchip and a logic circuit, which combined with electrophoresis (ES), can provide site-specific enhancement of gene concentration. In this ES-EP microchip, an arc planar electrode provides the ES function for DNA attraction, and interdigitated array electrodes provide appropriate electric fields for the EP on the chip surface. In addition, the adherent cells can be manipulated in situ without detachment of the ES-EP microchip, which performs the "Lab on a chip". Experimental results have shown that the efficiency of gene transfection with an attracting-electric field (35.89%) becomes much higher than that without an attracting-electric field (16.62%). Cell numbers as low as 10(4) cells, and DNA as little as 4 microg are sufficient for evaluating the phenotypic effects following the over-expression of the introduced genes on the ES-EP microchip. The proposed system has the advantages of portability, cost-effectiveness, a high transfection rate and ease of operation.

This case report concerns the nursing experience of applying back massage to a patient in an intensive care unit (ICU) from 10 May, 2005, in order to improve the patient's quality of sleep. In order to collect information about his quality of sleep of the patient, the author used observation, interview and a Richards-Campbell sleep questionnaire (RCSQ). It was observed that, before massage, the patient's sleep quality was poor, which wa why the protocol with back massage was proposed. The results after back massage was applied that heart beat, respiration. oxygen saturation and blood pressure were not significantly improved. This was probably related to the patient's worry about having his endotracheal tube removed. The patient's perception of sleep, indeed, was obviously improved, a result which may have been related to his/her perception of comfort and care from the nurse. Applying back massage to an ICU patient may therefore be regarded as helpful improving the patient's sleep quality. It is hoped that this case report may serve as a positive reference for health care providers so that it may help patients to recover fully through rest and sleep. Since this report concerned only one patient, however, to understand the real outcome of how back massage could improve the quality of sleep of ICU patients, research is planned on the use of back massage protocol on a large number os such patients.

We developed a new electroporation system, including a microchip and a logic circuit, and combining with the function of electrophoresis, which can site-specific enhancement of the gene concentration. We have demonstrated that the electroporation microchip could enhance and target in vitro gene transfection for cell lines. In this micro-device, the outer electrodes could provide the electrophoresis function for DNA attraction, and the inner electrodes could provide appropriate electric fields for the electroporation on the chip surface. The electrostatic force can be designed into specific regions, where the DNA plasmids are attracted to provide the region-targeting function. This study successfully demonstrates that the electrostatic force can attract DNA plasmids to the cell surface and highly enhance the gene delivery. Experimental results showed that the efficiency of gene transfection with an attracting-electric field become much higher than that without an attracting-electric field. Furthermore, the adherent cells could be manipulated in situ without detachment by this EP microchip. The system has several advantages of portable, cost-effective, high transfection rate and easy operation.

Baker's cysts are fluid distensions of the gastrocnemius-semimembranosus bursa and are the most common cystic lesion around the knee. Typically cysts enlarge along intermuscular planes around the knee. We report three cases in which the expanding cyst did not respect these planes and dissected along an intramuscular route as confirmed by MR imaging. Such behaviour by Baker's cysts is hitherto unreported in the literature. Possible mechanisms to account for this phenomenon are discussed., (Copyright 2004 ISS)