Characterisation of the 11 Kb DNA region adjacent to the gene encoding Desulfovibrio gigas flavoredoxin.
Flavoredoxin is an FMN binding protein that functions as an electron carrier in the sulphate metabolism of Desulfovibrio gigas. The neighbouring DNA regions of the gene encoding flavoredoxin were sequenced and characterised. Transcript analysis of the flavoredoxin gene resulted in a positive band corresponding to the size of the coding region, suggesting that flavoredoxin is encoded by a monocystronic unit, as previously suggested by sequence analysis. Analysis of the adjacent DNA regions revealed several interesting genes. The sequenced DNA regions contain nine open reading frames (ORFs) organised in two polycystronic and two monocystronic units. These genes encode proteins involved in different metabolic pathways, namely in DNA methylation, tRNA and rRNA modification, mRNA metabolism, cell division, CoA synthesis and lipoprotein transport across the membrane.


[Teaching in higher education in nursing: an integrative literature review].
To analyze the knowledge produced about teaching in higher education in nursing. Integrative literature review of full articles available on the LILACS, SciELO, BDENF and ERIC databases, through the descriptors "nursing faculty"and "practices of nursing faculty" and keywords "Teaching in nursing" or "Education in nursing"and "Nursing professors" and "Teaching knowledge" in Portuguese, English or Spanish, published from January 2008 to November 2013. 31 articles were identified. The data led to the following thematic categories: Training for faculty, Conflict of roles: being a nurse and being a teacher and Organization of the teaching work. It was found that there are numerous gaps in understanding the teaching activity in nursing. The concerns identified may offer help for understanding the teaching world and conceptions about being a teacher in nursing.


Immediate decrease in antigen-presenting function and delayed enhancement of interleukin-1 production in human epidermal cells after in vivo UVB irradiation.
Human skin was irradiated in vivo with a single UVB dose (100 mJ/cm2 or 200 mJ/cm2) to examine simultaneously the antigen-presenting function and interleukin-1 (IL-1) production capacity of irradiated epidermal cells (EC). Suction blisters were produced on irradiated areas on days 0, 3 and 7 after UVB. Irradiated EC were harvested and co-cultured with autologous T lymphocytes in the presence of antigens (PPD, HSV) or mitogen (ConA). Culture supernatants were tested for IL-1 activity using the thymocyte comitogenity assay. We found that a single 200 mJ/cm2 dose of UVB caused an immediate suppression of the antigen-presenting function of EC, but no alteration in their IL-1 production capacity or surface marker expression (ATPase, CDI). PPD- and HSV-induced lymphocyte proliferation was decreased 70-80% and ConA-driven proliferation 30% when compared to non-irradiated EC. However, this suppression was restored on days 3 and 7 after UVB irradiation, this being coexistent with an increased capacity of EC to produce IL-1. It remains to be elucidated whether the immediate UVB-induced photoimmunosuppression observed in the present study is due to inhibitory mediators or impaired membrane function of EC or both.


[Abdominal ectopic pregnancy. A case report and literature review].
Abdominal ectopic pregnancy is an extremely rare entity, which represents 1% of all ectopic pregnancies and is associated with high maternal and fetal morbidity and mortality. The maternal mortality risk of an abdominal ectopic pregnancy is seven to eight times greater than the risk of a tubal ectopic pregnancy and is 90 times greater than the risk of intrauterine pregnancy. This is a disease of difficult diagnosis that often takes place late. We report the case of a patient with an abdominal ectopic pregnancy, which was diagnosed by abdominal ultrasound in the second trimester; the patient was suc- cessfully treated with exploratory laparotomy with complete removal of the fetus and placenta. We provide a review of the literature on the risk factors for abdominal ectopic pregnancy, diagnostic tests and therapeutic options.


Identification and Funtional Characterization of Three Postsynaptic Short-chain Neurotoxins from Hydrophiinae, Lapemis hardwickii Gray.
Three cDNA clones, sn12, sn36 and sn160, encoding isoforms of postsynaptic short-chain neurotoxins, were cloned by screening a cDNA library of the venom from Hydrophiinae, Lapemis hardwickii Gray. The sequences of three cDNA clones encoded proteins consisting of 60 amino acid residues. There was only one amino acid substitution among the three isoforms SN12, SN36 and SN160 at the position 46 of mature proteins, and they were Pro(46), His(46) and Arg(46), respectively. The three molecules were expressed in Escherichia coli and the recombinant proteins were characterized. Different LD(50) were obtained, namely 0.0956 mg/kg, 0.3467 mg/kg and 0.2192 mg/kg, when the SN12, SN36 and SN160 were injected into Kunming mice(i.p.). In analgesic effect assayed by the acetic acid-induced writhing method, SN12 and SN160 showed similar analgesic effect, but SN36 had effects significantly different with the other two. Our studies suggested that the amino acid residues on position 46 could affect the combination between the postsynaptic short-chain neurotoxins and the nicotinic acetylchoine receptor, since different amino acid substitution resulted in different biological activities.


Network Coded Cooperative Communication in a Real-Time Wireless Hospital Sensor Network.
The paper presents a network coded cooperative communication (NC-CC) enabled wireless hospital sensor network architecture for monitoring health as well as postural activities of a patient. A wearable device, referred as a smartband is interfaced with pulse rate, body temperature sensors and an accelerometer along with wireless protocol services, such as Bluetooth and Radio-Frequency transceiver and Wi-Fi. The energy efficiency of wearable device is improved by embedding a linear acceleration based transmission duty cycling algorithm (NC-DRDC). The real-time demonstration is carried-out in a hospital environment to evaluate the performance characteristics, such as power spectral density, energy consumption, signal to noise ratio, packet delivery ratio and transmission offset. The resource sharing and energy efficiency features of network coding technique are improved by proposing an algorithm referred as network coding based dynamic retransmit/rebroadcast decision control (LA-TDC). From the experimental results, it is observed that the proposed LA-TDC algorithm reduces network traffic and end-to-end delay by an average of 27.8% and 21.6%, respectively than traditional network coded wireless transmission. The wireless architecture is deployed in a hospital environment and results are then successfully validated.


The happy personality revisited: Re-examining associations between Big Five personality traits and subjective well-being using meta-analytic structural equation modeling.
Using meta-analytic structural equation modeling (MASEM), we examined the link between Big Five personality traits and subjective well-being (SWB), operationalized as three separate components and as a latent factor indicated by life satisfaction (LS), positive affect (PA), and negative affect (NA). PA and NA were assessed based on frequency of a broad range of affective experiences, rather than intensity of high arousal affective experiences, thus excluding studies using the Positive and Negative Affect Schedule. 35 samples were included, encompassing 22,135 participants from 14 countries, in which all eight variables were assessed. Correlations among personality traits were moderate, on average, and the latent SWB factor had strong loadings from all three components. Personality traits together explained substantial variance in LS, PA, and NA, and in the latent SWB factor, with unique predictive effects on the latent factor from each personality trait except openness. Associations between personality traits and SWB components were fully accounted for by a latent SWB factor, with one exception: A specific association was found between neuroticism and unique variance in NA. The present findings provide new insights concerning the notion of a 'happy personality' in showing that Big Five personality traits have unique associations with an underlying sense of SWB.


Shape of the lateral mandibular outline in Lemuridae: a quantitative analysis of variability using elliptical Fourier analysis.
While several morphometric analyses in lemurids have focused on the craniofacial complex, the characterization of their mandibular morphology has received less attention. The mandibular outline, in lateral perspective, was quantified using elliptical Fourier analysis, in an osteological sample encompassing 189 lemurid mandibles (66 Eulemur, 51 Hapalemur, 22 Lemur and 50 Varecia), and compared using multivariate statistical techniques. The taxonomic value of this outline in Lemuridae was demonstrated by the existence of significant separations between the four genera studied. In particular, the mandibular morphology of Hapalemur was markedly different from that in the group Eulemur-Lemur-Varecia. Excluding Hapalemur from analysis, the distinctions between Eulemur, Lemur and Varecia were enhanced suggesting the existence of more subtle intergeneric differences in mandibular morphology. Variation in mandibular form was greatest in Hapalemur and smallest in Eulemur and Varecia (as demonstrated by the mean values of interindividual distances); variation was higher in Lemur than in Eulemur and Varecia, but not higher than in Hapalemur. This morphological diversity may be related to functional adaptation in response to particular dietary habits. The patterns of intergeneric and intrageneric shape variations of the mandible in Lemuridae presented here provide a valuable resource for the analysis of variation among living and fossil lemurids.


NBI cystoscopy in routine urological practice - from better vision to improve therapeutic management.
A single centre, retrospective trial was performed trying to assess the impact of NBI cystoscopy in cases of non-muscle invasive bladder tumors (NMIBT) by comparison to the standard approach. Our goal was to determine the superiority of the new method in terms of detection rates and subsequent postoperative treatment changes. A total of 320 NMIBT suspected consecutive cases were enrolled in the study. The inclusion criteria were represented by hematuria, positive urinary cytology and/or ultrasound suspicion of bladder tumors. All patients underwent WLC and NBI cystoscopy. Standard transurethral resection of bladder tumors (TURBT) was performed for all lesions visible in WL and NBI guided resection for solely NBI observed tumors. The overall NMIBT and CIS patients' detection rates were significantly improved for the NBI evaluation ((94.9% versus 88.1% and 95.7% versus 65.2%). Also, on a lesions' related basis, NBI cystoscopy emphasized a significantly superior diagnostic accuracy concerning the CIS, pTa and overall NMIBT formations ((95.2% versus 60.3%, 92.8% versus 83.9% and 94.1% versus 82%). Additional tumors were diagnosed by NBI in a significantly higher proportion of CIS, pTa, pT1 and NMIBT patients (56.6% versus 8.7%, 28% versus 10.3%, 30.3% versus 10.6% and 31.6% versus 9.4%). As a result of these supplementary findings, the postoperative treatment was significantly improved in a substantial proportion of cases (15.4% versus 5.1%). NBI cystoscopy represents a valuable diagnostic alternative in NMIBT patients, with significant improvement of tumor visual accuracy as well as detection rates. This approach provided a substantial amelioration to the risk category stratification and subsequent bladder cancer therapeutic management.


A Novel Oxidovanadium (IV)-Orotate Complex as an Alternative Antidiabetic Agent: Synthesis, Characterization, and Biological Assessments.
Diabetes is an increasingly common metabolic disorder with high comorbidity and societal and personal costs. Insulin replacement therapy is limited by a lack of oral bioavailability. Recent studies suggest vanadium has therapeutic potential. A newly synthesized complex between oxidovanadium (IV) and orotic acid (OAH3), [(OAH1)(VO)(NH3)2].3H2O, was characterized using spectroscopic and thermogravimetric techniques. In vivo potential was assessed in a streptozocin-induced rat model of diabetes. OAH3 acts as a bidentate ligand in the formation of the dark green, crystalline oxidovanadium (IV) complex in a square pyramidal configuration. Treatment with oxidovanadium (IV)-orotate in vivo significantly improved many biochemical parameters with minimal toxicity and restored pancreatic and hepatic histology. The results of the present work describe a safe, new compound for the treatment of diabetes.


Indonesian students' participation in an interprofessional learning workshop.
Interprofessional learning activities, such as workshops allow students to learn from, with and about each other. This study assessed the impact on Indonesian health students' attitudes towards interprofessional education (IPE) from participating in a workshop on medication safety. The students attended a two-day IPE workshop on medication safety. Thirty-five (48.6%) students completed pre-/post-workshop surveys using a modified Readiness for Interprofessional Learning Scale (RIPLS) survey. The post-workshop survey also had a series of open-ended questions. Students' responses to each RIPLS statement pre-/post-workshop were compared, whilst their responses to open-ended questions in post-workshop survey were thematically analysed. Students reported positive attitudinal changes on statements of shared learning and teamwork sub-scale (Wilcoxon p value <0.05). Analysis of the open-ended questions indicated that students perceived the workshop as having improved their understanding on the importance of teamwork and communication skills. This study found that learning with other health students through an IPE workshop improved medical, nursing and pharmacy students' attitudes towards the importance of shared learning, teamwork and communication in healthcare service.


The role of propagule pressure, genetic diversity and microsite availability for Senecio vernalis invasion.
Genetic diversity is supposed to support the colonization success of expanding species, in particular in situations where microsite availability is constrained. Addressing the role of genetic diversity in plant invasion experimentally requires its manipulation independent of propagule pressure. To assess the relative importance of these components for the invasion of Senecio vernalis, we created propagule mixtures of four levels of genotype diversity by combining seeds across remote populations, across proximate populations, within single populations and within seed families. In a first container experiment with constant Festuca rupicola density as matrix, genotype diversity was crossed with three levels of seed density. In a second experiment, we tested for effects of establishment limitation and genotype diversity by manipulating Festuca densities. Increasing genetic diversity had no effects on abundance and biomass of S. vernalis but positively affected the proportion of large individuals to small individuals. Mixtures composed from proximate populations had a significantly higher proportion of large individuals than mixtures composed from within seed families only. High propagule pressure increased emergence and establishment of S. vernalis but had no effect on individual growth performance. Establishment was favoured in containers with Festuca, but performance of surviving seedlings was higher in open soil treatments. For S. vernalis invasion, we found a shift in driving factors from density dependence to effects of genetic diversity across life stages. While initial abundance was mostly linked to the amount of seed input, genetic diversity, in contrast, affected later stages of colonization probably via sampling effects and seemed to contribute to filtering the genotypes that finally grew up. In consequence, when disentangling the mechanistic relationships of genetic diversity, seed density and microsite limitation in colonization of invasive plants, a clear differentiation between initial emergence and subsequent survival to juvenile and adult stages is required.


Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma.
Immunogenic cell death (ICD) is considered a particular cell death modality of regulated cell death (RCD) and plays a significant role in various cancers. The connection between kidney renal clear cell carcinoma (KIRC) and ICD remains to be thoroughly explored. We conducted a variety of bioinformatics analyses using R software, including cluster analysis, prognostic analysis, enrichment analysis and immune infiltration analysis. In addition, we performed Quantitative Real-time PCR to evaluate RNA levels of specific ICD genes. The proliferation was measured through Cell Counting Kit-8 (CCK-8) assay and colony-formation assay in RCC cell lines. We determined two ICD subtypes through consensus clustering analysis. The two subtypes showed significantly different clinical outcomes, genomic alterations and tumor immune microenvironment. Moreover, we constructed the ICD prognostic signature based on TF, FOXP3, LY96, SLC7A11, HSP90AA1, UCN, IFNB1 and TLR3 and calculated the risk score for each patient. Kaplan-Meier survival analysis and ROC curve demonstrated that patients in the high-risk group had significantly poorer prognosis compared with the low-risk group. We then validated the signature through external cohort and further evaluated the relation between the signature and clinical features, tumor immune microenvironment and immunotherapy response. Given its critical role in ICD, we conducted further analysis on LY96. Our results indicated that downregulation of LY96 inhibited the proliferation ability of RCC cells. Our research revealed the underlying function of ICD in KIRC and screened out a potential biomarker, which provided a novel insight into individualized immunotherapy in KIRC.


Asbestos-related disease in upholsterers.
Before its use was banned in developed countries, asbestos was widely applied in upholstery. However, the risk of asbestos diseases among upholsterers has only rarely been reported. In this case series, we present a first series of 6 workers employed in small workshops who developed several asbestos-related diseases, including pleural plaques, pleural fibrosis, and asbestosis. Exposures were intermittent and difficult to quantify, but lung asbestos content assessed by bronchoalveolar lavage was high in the 3 patients evaluated. In conclusion, upholstery work should be considered an at-risk occupation for developing asbestos-related diseases during the 20th century.


Satisfaction with the access to the health services of the people with chronic conditions in Estonia.
After the implementation of the primary health care reform in Estonia, most of chronic conditions are managed by family doctors (FD) in collaboration with specialists. Although the general population has demonstrated the increase in satisfaction with health care after the reform, it has been questioned if people with chronic diseases have been left on a more disadvantaged position in the new system with some restrictions in the access to specialists. To investigate the satisfaction of people with chronic conditions with the access to the health services and compare them to those who did not have a chronic illness. In November 2005, a random sample of Estonian residents aged 15-74 were personally interviewed using structured questionnaires (n=1446), 29% of them reported to have a chronic illness. The people with chronic conditions were less satisfied with the access to the health services. They were more satisfied with their family doctors, but less with the health insurance system and they often reported their problems in seeing the specialist. Compared to other respondents, the people with chronic conditions visited their FDs and specialists more often, but no significant differences were found between their waiting times to see the FD or a specialist. In Estonia, the people with chronic conditions do not have organisational barriers in their access to the health services. As frequent users of health services, they perceive the shortages of the health system more obviously than the rest of the population and it may reflect their satisfaction with the different aspects of the health system as well as the access to the health services.


[Hyperlipidaemia associated to inaugurated diabetic ketoacidosis].
Severe hyperlipidaemia in presenting diabetic ketoacidosis was rarely reported in child. We report the case of a three-year-old girl with presenting diabetic ketoacidosis. Family history was negative for hyperlipidaemia. Serum was creamy pink in gross appearance. The child has a hyperlipidaemia with serum triglycerides 18.5 mmol/l and serum cholesterol 13.8 mmol/l. The hyperlipidaemia disappeared with insulin therapy within seven days. We study the clinical, laboratory, pathogenic and evolution features of this uncommon trouble in diabetic children.


A Randomized Controlled Pilot Trial of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Children.
The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Children (UP-C) is an intervention for children aged 7 to 13 targeting high negative emotion, emotional reactivity, and emotion regulation deficits common across emotional disorders. Our objective was to collect pilot randomized controlled trial (RCT) data on the efficacy of the UP-C, comparing UP-C with an active, anxiety-focused intervention. Participants were 47 children with at least one primary anxiety disorder; approximately one half had elevated depression symptoms. Participants received either UP-C or the anxiety-focused control treatment. No condition-related differences were found with respect to diagnostic remission and anxiety symptoms. However, differences in favor of UP-C were observed with respect to treatment response at follow-up, depression symptoms, sadness dysregulation, and cognitive reappraisal. Results provide preliminary evidence that the UP-C may be at least as efficacious in treating anxiety as well-supported anxiety-specific treatment protocols and may produce greater gains in certain emotion reactivity and regulation variables.


Epigenetics of Cardiovascular Disease - A New "Beat" in Coronary Artery Disease.
Genome-wide association studies (GWAS) have become a powerful tool in the identification of disease-associated variants. Unfortunately, many of these studies have found that the estimated variability in cardiovascular disease risk cannot be fully explained by traditional paradigms of genetic variation in protein coding genes. Moreover, traditional views do not sufficiently explain the well-known link between cardiovascular disease and environmental influence. We posit that epigenetics, defined as chromatin-based mechanisms important in the regulation of gene expression that do not involve changes in the DNA sequence per se, represents the missing link. The nuclear-based mechanisms that contribute to epigenetic gene regulation can be broadly separated into three unique but highly interrelated processes: DNA methylation and hydroxymethylation; histone density and post-translational modifications; and RNA-based mechanisms. Together they complement the cis/trans perspective on transcriptional control paradigms in blood vessels. Moreover, it provides a molecular basis for understanding how the environment impacts the genome to modify cardiovascular disease risk over the lifetime of a cell and its offspring. This review provides an introduction to epigenetic function and cardiovascular disease, with a focus on endothelial cell biology. Additionally, we highlight emerging concepts on epigenetic gene regulation that are highly relevant to atherosclerosis and coronary artery disease.


MiR-193b, downregulated in Ewing Sarcoma, targets the ErbB4 oncogene to inhibit anchorage-independent growth.
Ewing Sarcoma is an aggressive, oncofusion-driven, malignant neoplasm of bone and soft tissue affecting predominantly children and young adults. Seeking to identify potential novel therapeutic targets/agents for this disease, our previous studies uncovered microRNAs regulated by EWS/Fli1, the most common oncofusion, with growth modulatory properties. In the present study, we sought to identify EWS/Fli1-repressed, growth suppressive, microRNAs potentially amenable to replacement in Ewing Sarcoma cells. Eight microRNAs (143, 153, 184, 193b, 195, 203, 206 and 223) were selected for evaluation as EWS/Fli1-repressed and underexpressed in Ewing Sarcoma cells, and reported to be growth suppressive in other pediatric or/and adult cancers. The selected miRs, and appropriate non-targeting controls, were introduced into two different Ewing Sarcoma cell lines (A673 and SK-ES-1), and effects on growth were examined using a high and low-density growth assay. MiR-193b was growth inhibitory in both assays and cell lines. In subsequent analyses, we found that stable overexpression of miR-193b also inhibits anchorage-independent growth in both A673 and SK-ES-1 cells. We further show that miR-193b negatively regulates expression of the ErbB4 oncogene in A673 and SK-ES-1 cells, and that depletion of ErbB4 is itself inhibitory to anchorage-independent growth in the same cell lines. Together, our studies show that the EWS/Fli1-repressed miR-193b is growth suppressive in Ewing Sarcoma, and identify ErbB4 as a target gene and candidate mediator of this growth suppression.


GLISTRboost: Combining Multimodal MRI Segmentation, Registration, and Biophysical Tumor Growth Modeling with Gradient Boosting Machines for Glioma Segmentation.
We present an approach for segmenting low- and high-grade gliomas in multimodal magnetic resonance imaging volumes. The proposed approach is based on a hybrid generative-discriminative model. Firstly, a generative approach based on an Expectation-Maximization framework that incorporates a glioma growth model is used to segment the brain scans into tumor, as well as healthy tissue labels. Secondly, a gradient boosting multi-class classification scheme is used to refine tumor labels based on information from multiple patients. Lastly, a probabilistic Bayesian strategy is employed to further refine and finalize the tumor segmentation based on patient-specific intensity statistics from the multiple modalities. We evaluated our approach in 186 cases during the training phase of the BRAin Tumor Segmentation (BRATS) 2015 challenge and report promising results. During the testing phase, the algorithm was additionally evaluated in 53 unseen cases, achieving the best performance among the competing methods.


Hospital effects of maternity early discharge.
Although the programs are of increasing popularity, little has been published on the effects of discharging maternity patients early from the hospital. In particular, there is almost no evidence to date to prove that these programs actually achieve two objectives for which they were designed; to reduce occupancy pressure on maternity beds and to lower hospital costs. Evaluation of the early stages of a relatively small and flexible maternity early discharge program in Alberta, Canada suggests that the program is effective in reducing length of stay in the hospital and hospital costs, but there is little evidence that it is actually used to reduce pressure on bed space in the maternity unit.


ChatGPT and the Future of Digital Health: A Study on Healthcare Workers' Perceptions and Expectations.
This study aimed to assess the knowledge, attitudes, and intended practices of healthcare workers (HCWs) in Saudi Arabia towards ChatGPT, an artificial intelligence (AI) Chatbot, within the first three months after its launch. We also aimed to identify potential barriers to AI Chatbot adoption among healthcare professionals. A cross-sectional survey was conducted among 1057 HCWs in Saudi Arabia, distributed electronically via social media channels from 21 February to 6 March 2023. The survey evaluated HCWs' familiarity with ChatGPT-3.5, their satisfaction, intended future use, and perceived usefulness in healthcare practice. Of the respondents, 18.4% had used ChatGPT for healthcare purposes, while 84.1% of non-users expressed interest in utilizing AI Chatbots in the future. Most participants (75.1%) were comfortable with incorporating ChatGPT into their healthcare practice. HCWs perceived the Chatbot to be useful in various aspects of healthcare, such as medical decision-making (39.5%), patient and family support (44.7%), medical literature appraisal (48.5%), and medical research assistance (65.9%). A majority (76.7%) believed ChatGPT could positively impact the future of healthcare systems. Nevertheless, concerns about credibility and the source of information provided by AI Chatbots (46.9%) were identified as the main barriers. Although HCWs recognize ChatGPT as a valuable addition to digital health in the early stages of adoption, addressing concerns regarding accuracy, reliability, and medicolegal implications is crucial. Therefore, due to their unreliability, the current forms of ChatGPT and other Chatbots should not be used for diagnostic or treatment purposes without human expert oversight. Ensuring the trustworthiness and dependability of AI Chatbots is essential for successful implementation in healthcare settings. Future research should focus on evaluating the clinical outcomes of ChatGPT and benchmarking its performance against other AI Chatbots.


[Further contribution to the occurrence of black flies (Diptera, Simuliidae) in East Germany].
A further contribution to the occurrence of Simuliidae (Diptera) in the GDR. The cause of the damage to grazing cattle in the area of Waldheim - Heiligenborn in May 1971 was Boophthora erythrocephala. In the area 6 species of Simuliidae were proved. The history of the occurrence of Simuliidae in the GDR has been completed.


Lyme Borreliosis in Finland, 1995-2014.
We investigated the epidemiology of Lyme borreliosis (LB) in Finland for the period 1995-2014 by using data from 3 different healthcare registers. We reviewed data on disseminated LB cases from the National Infectious Diseases Register (21,051 cases) and the National Hospital Discharge Register (10,402 cases) and data on primary LB (erythema migrans) cases from the Register for Primary Health Care Visits (11,793 cases). Incidence of microbiologically confirmed disseminated LB cases increased from 7/100,000 population in 1995 to 31/100,000 in 2014. Incidence of primary LB cases increased from 44/100,000 in 2011 to 61/100,000 in 2014. Overall, cases occurred predominantly in women, and we observed a bimodal age distribution in all 3 registers. Our results clearly demonstrate that the geographic distribution of LB has expanded in Finland and underscore the importance of LB as an increasing public health concern in Finland and in northern Europe in general.


Cloning and analysis of mRNAs expressed specifically in the human epididymis.
Differential cDNA screening identified four new genes that are expressed specifically in the human epididymis. Their corresponding mRNAs are relatively short, ranging from 0.7 to 1.0 kb, and belong to a class of abundant or moderately abundant transcripts. Tissue-specific expression was pronounced for all four sequences, which showed no hybridization signals with RNA from eight different human tissues. Cross-hybridization with epididymal RNAs from some non-rodent mammalian species was observed with two cDNAs; the remaining two transcripts failed to cross-hybridize with any of the animal epididymal RNAs tested.


[Contribution to neglecting of power analysis in experimental medicine studies].
The work provides basic information about what is being understood under the term "statistical analysis of power of test" from the viewpoint of correct use of mathematical statistics in medicine. The detail rules of statistical decision-making are described. Furthermore, the work contains an illustration of power analysis of test application when using unpaired t-test.


Anterior cruciate ligament tears and associated meniscal lesions: assessment at dual-detector spiral CT arthrography.
To assess dual-detector spiral computed tomographic (CT) arthrography of the knee in the evaluation of anterior cruciate ligament (ACL) tears and associated meniscal lesions. ACL and meniscal abnormalities in 125 consecutive patients who underwent dual-detector spiral CT arthrography of the knee were evaluated on the basis of both initial interpretations and retrospective review of CT images and were compared with arthroscopic findings. The sensitivity and specificity of CT arthrography for the detection of ACL tears and meniscal lesions in knees with abnormal ACLs were determined. The sensitivities and specificities for the detection of ACL tears were 90% and 96%, respectively, at initial interpretation and 95% and 99%, respectively, at retrospective interpretation. The sensitivities and specificities for the detection of meniscal tears in knees with abnormal ACLs were 92% and 88%, respectively, at initial interpretation and 96% and 94%, respectively, at retrospective interpretation. Dual-detector spiral CT arthrography of the knee is an accurate method for detecting ACL tears and associated meniscal lesions.


Use of the peritoneal equilibration test in pediatric dialysis patients.
The peritoneal equilibration test (PET) has been used in adult peritoneal dialysis (PD) patients to determine PD efficiency and optimal dialysis prescription. To investigate its usefulness in pediatric PD patients, we performed the PET in 10 patients divided into 2 groups: 3 patients less than 2 years of age (group 1) and 7 patients aged 5 to 17 years (group 2). The PET was performed after an overnight dwell by standard protocol with an overnight dialysate sample and 6 dialysate samples during the 4 hour test. Dialysate to plasma (D/P) ratios were calculated for creatinine (Cr), urea, and protein. D/PCr over time was similar in both pediatric groups compared to adults. D/P urea over time was lower in both pediatric groups compared to published adult data. D/P protein over time was markedly increased in both pediatric groups and was highest in the smallest patients. D/P ratios are different in pediatric PD patients compared to adults. In order to be used to assess dialysis efficiency, normal values for the PET test in children need to be established.


Effects of bottom water dissolved oxygen variability on copper and lead fractionation in the sediments across the oxygen minimum zone, western continental margin of India.
This study describes the effect of varying bottom-water oxygen concentration on geochemical fractionation (operational speciation) of Cu and Pb in the underneath sediments across the oxygen minimum zone (Arabian Sea) in the west coast of India. Both, Cu and Pb were redistributed among the different binding phases of the sediments with changing dissolved oxygen level (from oxic to hypoxic and close to suboxic) in the bottom water. The average lability of Cu-sediment complexes gradually decreased (i.e., stability increased) with the decreasing dissolved oxygen concentrations of the bottom water. Decreasing bottom-water oxygen concentration increased Cu association with sedimentary organic matter. However, Pb association with Fe/Mn-oxyhydroxide phases in the sediments gradually decreased with the decreasing dissolved oxygen concentration of the overlying bottom water (due to dissolution of Fe/Mn oxyhydroxide phase). The lability of Pb-sediment complexes increased with the decreasing bottom-water oxygen concentration. This study suggests that bottom-water oxygen concentration is one of the key factors governing stability and lability of Cu and Pb complexes in the underneath sediment. Sedimentary organic matter and Fe/Mn oxyhydroxide binding phases were the major hosting phases for Cu and Pb respectively in the study area. Increasing lability of Pb-complexes in bottom sediments may lead to positive benthic fluxes of Pb at low oxygen environment.


Digital subtraction angiography (DSA): a neurosurgical perspective.
The purpose of this article is to review the contribution of DSA to neurosurgical practice and to outline its advantages and limitations compared to conventional film-screen angiography. DSA is a technique whereby electronic subtraction allows the near instantaneous demonstration of vascular anatomy essentially free of bony detail. Because DSA possesses a high degree of contrast sensitivity, arterial images can be produced after an intravenous injection of contrast medium as well as by selective arterial catheterisation.


In-house 3D-printed custom splints for non-operative treatment of distal radial fractures: a randomized controlled trial.
We compared patient satisfaction and clinical effectiveness of 3D-printed splints made of photopolymer resin to conventional fibre glass casts in treating distal radial fractures. A total of 39 patients with minimally displaced distal radius fractures were included and randomized. Of them, 20 were immobilized in a fibre glass cast and 19 in a 3D-printed forearm splint. The 3D-printed splints were custom-designed based on forearm surface scanning with a handheld device and printed in-house using digital light processing printing technology. Patient satisfaction and clinical effectiveness were assessed with questionnaires 1 and 6 weeks after the initiation of immobilization. Fracture healing, pain, range of motion, grip strength and the DASH and PRWE scores were assessed up to 1-year follow-up. 3D-printed splints proved to be equally well tolerated by the patients and equally clinically effective as conventional fibre glass casts although there was a higher rate of minor complications. 3D-printed splints present a safe alternative, especially in young, active patients, for non-operative treatment of distal radial fractures.Level of evidence: I.


Prevalence and antifungal susceptibility of Sporothrix species in Jiangxi, central China.
Sporotrichosis is a subcutaneous mycosis caused by traumatic inoculation of pathogenic Sporothrix species. Until recently, Sporothrix globosa was considered as the unique Chinese species causing this disorder. In the present study, 33 clinical Sporothrix strains isolated from Jiangxi, China, were classified and antifungal susceptibility for each strain was determined. Thirteen S. globosa strains and 20 S. schenckii strains were identified by morphology and by multilocus analysis using rDNA ITS, CAL, and EF1α (i.e., internal transcribed spacer, calmodulin and elongation factor-1α). In vitro antifungal susceptibility testing of yeast phases indicated that itraconazole, terbinafine, and posaconazole were most effective against both species, followed by amphotericin B and voriconazole, while fluconazole, 5-fluorocytosine had low efficacy with high MICs. Co-occurrence of S. schenckii and S. globosa in central China may indicate different routes of transmission in this area.


Myelodysplastic Syndrome Clinically Presenting with the "Classic TTP Pentad".
The clinical presentation of myelodysplastic syndrome (MDS) is not specific. Many patients can be asymptomatic and can be detected only due to an abnormal complete blood cell count (CBC) on routine exam or for other reasons while others can be symptomatic as a consequence of underlying cytopenias. Thrombotic thrombocytopenic purpura (TTP) usually is suspected under the evidence of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia and because it is a life-threatening condition (medical emergency) immediate initiation of plasmapheresis could be life-saving. The following case illustrates an unusual presentation of MDS in a patient who came in to the emergency room with the classic TTP "pentad" of fever, renal involvement, MAHA, mental status changes, and thrombocytopenia. We will focus our discussion in the clinical presentation of this case.


Human monkeypox: An updated appraisal on epidemiology, evolution, pathogenesis, clinical manifestations, and treatment strategies.
Monkeypox (Mpox) is a zoonotic viral disease caused by the monkeypox virus (MPXV), a member of the Orthopoxvirus genus. The recent occurrence of Mpox infections has become a significant global issue in recent months. Despite being an old disease with a low mortality rate, the ongoing multicountry outbreak is atypical due to its occurrence in nonendemic countries. The current review encompasses a comprehensive analysis of the literature pertaining to MPXV, with the aim of consolidating the existing data on the virus's epidemiological, biological, and clinical characteristics, as well as vaccination and treatment regimens against the virus.


A Practical Quantum Mechanics Molecular Mechanics Method for the Dynamical Study of Reactions in Biomolecules.
Quantum mechanics/molecular mechanics (QM/MM) methods are excellent tools for the modeling of biomolecular reactions. Recently, we have implemented a new QM/MM method (Fireball/Amber), which combines an efficient density functional theory method (Fireball) and a well-recognized molecular dynamics package (Amber), offering an excellent balance between accuracy and sampling capabilities. Here, we present a detailed explanation of the Fireball method and Fireball/Amber implementation. We also discuss how this tool can be used to analyze reactions in biomolecules using steered molecular dynamics simulations. The potential of this approach is shown by the analysis of a reaction catalyzed by the enzyme triose-phosphate isomerase (TIM). The conformational space and energetic landscape for this reaction are analyzed without a priori assumptions about the protonation states of the different residues during the reaction. The results offer a detailed description of the reaction and reveal some new features of the catalytic mechanism. In particular, we find a new reaction mechanism that is characterized by the intramolecular proton transfer from O1 to O2 and the simultaneous proton transfer from Glu 165 to C2.


Characterization of Leukocyte-platelet Rich Fibrin, A Novel Biomaterial.
Autologous platelet concentrates represent promising innovative tools in the field of regenerative medicine and have been extensively used in oral surgery. Unlike platelet rich plasma (PRP) that is a gel or a suspension, Leukocyte-Platelet Rich Fibrin (L-PRF) is a solid 3D fibrin membrane generated chair-side from whole blood containing no anti-coagulant. The membrane has a dense three dimensional fibrin matrix with enriched platelets and abundant growth factors. L-PRF is a popular adjunct in surgeries because of its superior handling characteristics as well as its suturability to the wound bed. The goal of the study is to demonstrate generation as well as provide detailed characterization of relevant properties of L-PRF that underlie its clinical success.


Testing Causal Effects of Empathy on Children's Prosociality in Politeness Dilemmas - An Intervention Study.
Empathy is commonly considered a driver of prosociality in child ontogeny, but causal assumptions regarding this effect mostly rely on correlational research designs. Here, 96 urban German children (5-8 years; 48 girls; predominantly White; from mid-to-high socioeconomic backgrounds) participated in an empathy intervention or a control condition before prosocial behaviors (polite lie-telling: rating the drawing as good; prosocial encouragement: utterances interpreted as cheering up the artist) were assessed in an art-rating task. Contrasting children's empathy at baseline with their empathy after the intervention indicated promoted empathy compared to the control group. Despite the intervention's effect on children's empathy, there were no simultaneous changes in prosocial behaviors. At the same time, children's empathy at baseline was associated with their prosocial encouragement. These results indicate conceptual associations between children's empathy and prosociality. However, they do not support strict causal claims regarding this association in middle childhood. Further applications of the novel short-time intervention to address causal effects of empathy on prosociality and other developmental outcomes are discussed.


Transcription factor AP-2 controls transcription of the human transforming growth factor-alpha gene.
The epidermal growth factor receptor is vital for normal development and plays a role in oncogenesis. The level of activation of this receptor by transforming growth factor-alpha (TGF-alpha) is controlled, in part, by the rate of transcription of the TGF-alpha gene. In the characterization of the proximal TGF-alpha promoter by DNase I footprinting, a 43-base pair element (-88 to -130 relative to the transcription start site), designated TalphaRE I, was found that was specifically protected by nuclear proteins from human mammary carcinoma MDA468 cells. TalphaRE I was essential for the maximal expression of the TGF-alpha gene as indicated by deletion and mutagenesis analyses. TalphaRE I consists of two cis-acting elements, a proximal regulatory element (PRE, -89 to -103) and a distal regulatory element (DRE, -121 to -128). Both elements were able to form specific complexes with protein from MDA468 cell nuclear extracts and are necessary for the full activity of the entire 1.1-kilobase pair TGF-alpha promoter. Competition and antibody studies determined that the DRE contains a binding site for the transcription factor AP-2, while the protein that binds to the PRE has yet to be identified. When linked upstream to the heterologous herpes simplex thymidine kinase promoter, the TalphaRE I enhanced transcription up to 11-fold in MDA468 cells. Cotransfection of an AP-2 expression vector was able to activate transcription from the TalphaREI-TK construct in a DRE-dependent manner. These results further our understanding of how TGF-alpha transcription is regulated.


Angiotensin System Autoantibodies Correlate With Routine Prognostic Indicators for COVID-19 Severity.
We previously showed that angiotensin type-1 receptor and ACE2 autoantibodies (AT1-AA, ACE2-AA) are associated with COVID-19 severity. Our aim is to find correlations of these autoantibodies with routine biochemical parameters that allow an initial classification of patients. In an initial cohort of 119 COVID-19 patients, serum AT1-AA and ACE2-AA concentrations were obtained within 24 h after diagnosis. In 50 patients with a complete set of routine biochemical parameters, clinical data and disease outcome information, a Random Forest algorithm was used to select prognostic indicators, and the Spearman coefficient was used to analyze correlations with AT1-AA, ACE2-AA. Hemoglobin, lactate dehydrogenase and procalcitonin were selected. A decrease in one unit of hemoglobin, an increase in 0.25 units of procalcitonin, or an increase in 100 units of lactate dehydrogenase increased the severity of the disease by 35.27, 69.25, and 3.2%, respectively. Our binary logistic regression model had a predictive capability to differentiate between mild and moderate/severe disease of 84%, and between mild/moderate and severe disease of 76%. Furthermore, the selected parameters showed strong correlations with AT1-AA or ACE2-AA, particularly in men. Hemoglobin, lactate dehydrogenase and procalcitonin can be used for initial classification of COVID-19 patients in the admission day. Subsequent determination of more complex or late arrival biomarkers may provide further data on severity, mechanisms, and therapeutic options.


Attenuation of protein adsorption on static and oscillating magnetostrictive nanowires.
The research described here investigates the hypothesis that nanoarchitecture contained in a nanowire array is capable of attenuating the adverse host response generated when medical devices are implanted in the body. This adverse host response, or biofouling, generates an avascular fibrous mass transfer barrier between the device and the analyte of interest, disabling the implant if it is a sensor. Numerous studies have indicated that surface chemistry and architecture modulate the host response. These findings led us to hypothesize that nanostructured surfaces will inhibit the formation of an avascular fibrous capsule significantly. We are investigating whether arrays of oscillating magnetostrictive nanowires can prevent protein adsorption. Magnetostrictive nanowires were fabricated by electroplating a ferromagnetic metal alloy into the pores of a nanoporous alumina template. The ferromagnetic nanowires are made to oscillate by oscillating the magnetic field surrounding the wires. Radiolabeled bovine serum albumin, enzyme-linked immunosorbent assay (ELISA), and other protein assays were used to study protein adhesion on the nanowire arrays. These results display a reduced protein adsorption per surface area of static nanowires. Comparing the surfaces, 14-30% of the protein that absorbed on the flat surface adsorbed on the nanowires. Our contact angle measurements indicate that the attenuation of protein on the nanowire surface might be due to the increased hydrophilicity of the nanostructured surface compared to a flat surface of the same material. We oscillated the magnetostrictive wires by placing them in a 38 G 10 Hz oscillating magnetic field. The oscillating nanowires show a further reduction in protein adhesion where only 7-67% of the protein on the static wires was measured on the oscillating nanowires. By varying the viscosity of the fluid the nanowires are oscillated in, we determined that protein detachment is shear-stress modulated. We created a high shearing fluid with dextran, which reduced protein adsorption on the oscillating nanowires by 70% over nanowires oscillating in baseline viscosity fluid. Our preliminary studies strongly suggest that the architecture in the static nanowire arrays and the shear created by oscillating the nanowire arrays would attenuate the biofouling response in vivo.


Spherex (degradable starch microspheres) chemo-occlusion--enhancement of tumor drug concentration and therapeutic efficacy: an overview.
The efficacy of systemic chemotherapy in the treatment of primary and secondary liver cancer is poor. Intra-arterial delivery of fluoropyrimidines resulted in a significantly higher tumor response, but survival was prolonged by only a few months. Obviously, there is still a great need for improved therapeutic strategies. As the regional blood flow is of importance for the advantage of intra-arterial administration of cytotoxic drugs, degradable starch microspheres (DSMs) have been developed specifically to achieve temporary vascular occlusion during coadministration of cytotoxic drugs. Peak plasma concentrations, as well as the area under the concentration-time curve (AUC) of mitomycin C in plasma have been found to be significantly reduced following intra-arterial coadministration with DSMs. Similar results were also obtained with other drugs, such as nitrosoureas, doxorubicin, and 5-fluorouracil. The temporary vascular occlusion induced by DSMs enables a coadministered drug to be lodged in the target area for a prolonged period of time, resulting in a selectively increased uptake of labeled low molecular weight markers and several cytotoxic drugs into liver tumors compared with normal liver tissue. Vascular occlusion induced by DSMs has been demonstrated to redistribute the blood flow to hypovascular areas, which might be of particular importance for improving the efficacy of intra-arterial chemotherapy of hypovascular liver tumors. Passage through arteriovenous shunts was generally increased after DSM injection. However, this was without clinical significance as respiratory distress symptoms were found in only 1% of the sessions and were not considered to be serious in any of these patients. To take advantage of the pharmacokinetic modulation of coinjected drugs and, in addition, the redistribution of blood flow to hypovascular tumor areas, the goal is to achieve an almost complete vascular occlusion by injection of DSMs. Therefore, due to the wide variation between patients in the size and vascularity of liver tumors, the dose of DSMs has to be individualized. Degradable starch microspheres have been shown to enhance the antitumor efficacy of several cytotoxic drugs in animal experimental models and in noncomparative and randomized clinical studies.


Antiviral, antioxidant, and anti-inflammatory activities of rhein against white spot syndrome virus infection in red swamp crayfish (Procambarus clarkii).
Infection caused by white spot syndrome virus (WSSV) leads to massive mortality and huge economic losses in the crustacean aquaculture industry; however, to date, no effective control means are available to control the disease. Thus, to better understand the pathological aspects of WSSV and to find effective compounds that have the potential to be developed as anti-WSSV agents are imperative. Herein, based on screening of plants with antiviral activity, we found that rhein, an anthraquinone compound in Rheum palmatum L., exhibited strong activity against WSSV infection in a red swamp crayfish (Procambarus clarkii) model. The results showed that rhein could dose dependently inhibit transcription of WSSV ie1, DNApol, and Vp28 genes, reduce viral load in vivo, and significantly improve the survival rate of WSSV-infected crayfish. Through investigation of the mechanisms of action, we found that rhein did not affect the infectivity of viral particles in vitro as well as the entry and release process in vivo. Alternatively, rhein could activate JAK/STAT and NF-κB pathways, significantly decrease the expression of crustin-1 and BAF but increase the expression of C-type lectin and proPO to arrest WSSV replication. Moreover, rhein also attenuated WSSV-induced oxidative and inflammatory stresses by regulating the expression of antioxidant and anti-inflammatory-related genes and enhanced innate immunity by reducing total protein levels while increasing the phosphatase activity. Taken together, our study shows rhein as a potent WSSV inhibitor, which provides great potential for the development of prophylaxis and therapy agents for controlling WSSV infection in crustacean aquaculture.IMPORTANCEAquaculture is essential for ensuring global food security by providing a significant source of animal protein. However, the spread of the white spot syndrome virus (WSSV) has resulted in considerable economic losses in crustacean industries. In this study, we evaluated the antiviral activity of rhein, the primary bioactive component of Rheum palmatum L., against WSSV infection, and many pathological aspects of WSSV were also described for the first time. Our mechanistic studies indicated that rhein effectively arrested the replication of WSSV in crayfish by modulating innate immunity to inhibit viral gene transcription. Furthermore, we observed that rhein attenuated WSSV-induced oxidative and inflammatory stresses by regulating the expression of antioxidant and anti-inflammatory-related genes while enhancing innate immunity by reducing total protein levels and increasing phosphatase activity. Our findings suggest that rhein holds great promise as a potent antiviral agent for the prevention and treatment of WSSV in aquaculture.


Paraurethral Endometriosis as a Common Pathology in an Uncommon Location: A Case Report and a Review of the Literature.
Paraurethral endometriosis is an extremely rare condition. To the best of our knowledge, only seven cases with details on variable risk factors have been reported in the English literature. Herein, we present the case of a third nulliparous patient described in the literature at the time of diagnosis. A 30-year-old woman presented with mild urinary symptoms. A well-defined 2.3 cm paraurethral cystic lesion was found on clinical examination, and MRI findings were suggestive of hemorrhagic content, with no evidence of pelvic endometriosis. Complete surgical excision was performed, and the patient's symptoms improved. The patient experienced no recurrence for 10 months postoperatively. The histopathological findings were suggestive of endometriosis. These findings might indicate that embryonic remnants are possible causes of the pathogenesis of paraurethral endometriosis.


[New generation of androgen receptor antagonist in castration resistant prostate cancer].
Androgen ablation therapy is performed for prostate cancer patients especially with advanced stage. Nevertheless, outgrowth of hormone independent cancer cells occurs within several years and leads to a lethal condition, so-called castration resistant prostate cancer (CRPC). Even in CRPC cells under low levels of serum androgens, androgen receptor (AR) signaling still functions and is engaged in the establishment of CRPC. Recently, novel AR antagonists have been developed such as enzalutamide or ARN-509. This review focuses on these AR antagonists that have some features including high affinity to AR compared with bicalutamide, preventing nuclear translocation and DNA binding. These new hormonal agents have changed the landscape of CRPC treatment with a promising outcome.


Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture.
Phenotypic modulation of vascular myocytes is important for vascular development and adaptation. A characteristic feature of this process is alteration in intracellular Ca(2+) handling, which is not completely understood. We studied mechanisms involved in functional changes of inositol 1,4,5-trisphosphate (IP(3))- and ryanodine (Ry)-sensitive Ca(2+) stores, store-operated Ca(2+) entry (SOCE), and receptor-operated Ca(2+) entry (ROCE) associated with arterial myocyte modulation from a contractile to a proliferative phenotype in culture. Proliferating, cultured myocytes from rat mesenteric artery have elevated resting cytosolic Ca(2+) levels and increased IP(3)-sensitive Ca(2+) store content. ATP- and cyclopiazonic acid [CPA; a sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor]-induced Ca(2+) transients in Ca(2+)-free medium are significantly larger in proliferating arterial smooth muscle cells (ASMCs) than in freshly dissociated myocytes, whereas caffeine (Caf)-induced Ca(2+) release is much smaller. Moreover, the Caf/Ry-sensitive store gradually loses sensitivity to Caf activation during cell culture. These changes can be explained by increased expression of all three IP(3) receptors and a switch from Ry receptor type II to type III expression during proliferation. SOCE, activated by depletion of the IP(3)/CPA-sensitive store, is greatly increased in proliferating ASMCs. Augmented SOCE and ROCE (activated by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol) in proliferating myocytes can be attributed to upregulated expression of, respectively, transient receptor potential proteins TRPC1/4/5 and TRPC3/6. Moreover, stromal interacting molecule 1 (STIM1) and Orai proteins are upregulated in proliferating cells. Increased expression of IP(3) receptors, SERCA2b, TRPCs, Orai(s), and STIM1 in proliferating ASMCs suggests that these proteins play a critical role in an altered Ca(2+) handling that occurs during vascular growth and remodeling.


The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure.
MiDAC is one of seven distinct, large multi-protein complexes that recruit class I histone deacetylases to the genome to regulate gene expression. Despite implications of involvement in cell cycle regulation and in several cancers, surprisingly little is known about the function or structure of MiDAC. Here we show that MiDAC is important for chromosome alignment during mitosis in cancer cell lines. Mice lacking the MiDAC proteins, DNTTIP1 or MIDEAS, die with identical phenotypes during late embryogenesis due to perturbations in gene expression that result in heart malformation and haematopoietic failure. This suggests that MiDAC has an essential and unique function that cannot be compensated by other HDAC complexes. Consistent with this, the cryoEM structure of MiDAC reveals a unique and distinctive mode of assembly. Four copies of HDAC1 are positioned at the periphery with outward-facing active sites suggesting that the complex may target multiple nucleosomes implying a processive deacetylase function.


1,2,4-Triazole: A Privileged Scaffold for the Development of Potent Antifungal Agents - A Brief Review.
Over the past decades, a tremendous rise in invasive fungal infection diseases attributed to the yeast Candida albicans in immunocompromised individuals poses a seriously challenging issue. Another concern is the emergence of multi-drug resistant pathogens to the existing medicines due to their overuse and misuse. It was recently reported that 25-55% of the mortality rate is caused by invasive infection. Despite a large variety of drugs being available to treat invasive candidiasis, only two of them contain a 1,2,4-triazole core, namely Fluconazole and itraconazole, which are efficient in treating infection induced by fungal Candida species. Moreover, long-term therapy associated with azole medications has led to an increase in azole resistance as well as a high risk of toxicity. Despite numerous outstanding achievements in antifungal drug discovery, development of novel, safer and potent antifungal agents while overcoming the resistance problem associated with the current drugs is becoming the main focus of medicinal chemists. Therefore, this review outlines the breakthroughs in medicinal chemistry research regarding 1,2,4- triazole-based derivatives as potential antifungal agents in the past decade. In addition, the structureactivity relationship of these compounds is also discussed.


A Brief Review of Facial Emotion Recognition Based on Visual Information.
Facial emotion recognition (FER) is an important topic in the fields of computer vision and artificial intelligence owing to its significant academic and commercial potential. Although FER can be conducted using multiple sensors, this review focuses on studies that exclusively use facial images, because visual expressions are one of the main information channels in interpersonal communication. This paper provides a brief review of researches in the field of FER conducted over the past decades. First, conventional FER approaches are described along with a summary of the representative categories of FER systems and their main algorithms. Deep-learning-based FER approaches using deep networks enabling "end-to-end" learning are then presented. This review also focuses on an up-to-date hybrid deep-learning approach combining a convolutional neural network (CNN) for the spatial features of an individual frame and long short-term memory (LSTM) for temporal features of consecutive frames. In the later part of this paper, a brief review of publicly available evaluation metrics is given, and a comparison with benchmark results, which are a standard for a quantitative comparison of FER researches, is described. This review can serve as a brief guidebook to newcomers in the field of FER, providing basic knowledge and a general understanding of the latest state-of-the-art studies, as well as to experienced researchers looking for productive directions for future work.


An Electrode Configuration for Recording Muscle Motor Evoked Potentials in the Upper Extremities during Intraoperative Neurophysiological Monitoring.
The main aim of the present study is to examine the electrode configurations used to record the muscle motor evoked potential (mMEP) in the upper extremities during surgery with the goal of producing a high and stable mMEP signal, in particular among the abductor pollicis brevis (APB), abductor digiti minimi (ADM), and across the APB-ADM muscles, which have been widely used for the mMEP in the upper extremities. Thirty right-handed patients were recruited in this prospective study. No patients showed any adverse events in their mMEP signals of the upper extremities during surgery. The mMEPs were recorded independently from the signals for the APB and ADM and for those across the APB-ADM. The mMEP amplitude from across the APB-ADM was statistically higher than those recorded from the APB and ADM muscles. Moreover, the coefficient of variation of the mMEP amplitude from across the APB-ADM was smaller than those of mMEP amplitude recorded from the APB and ADM muscles. The mMEP from across the APB-ADM muscles showed a high yield with high stability compared to those in each case from the APB and ADM muscles. The configuration across the APB-ADM muscles would be best for mMEP recordings from the upper extremities for intraoperative neurophysiological monitoring purposes.


Nursing values: exploring the clichés.
Many fundamental values underpin the practice of nursing and, in an inaugural address to nurses and those in other disciplines, it seemed appropriate to explore values which have special relevance to nursing. If future research and practice are to exploit these values, they must be explained and understood. To that end the concept of holistic care, individualized care and practical care are discussed. Nursing research, which demonstrates their relevance to patients' needs during recovery, is then briefly reviewed. Throughout this paper differences in focus between nursing and medicine are highlighted in order to promote complementarity between the professions.


The validity of predicted body fat percent in Chinese children with Caucasian prediction formulas.
Body composition was measured by underwater weighing and by anthropometry and bio-electrical impedance in 165 Chinese boys and 150 Chinese girls, aged 7 to 17 years and living in Beijing. Until age 12 years there were no differences in body weight, body height and body mass index (kg/m2) between boys and girls, but body fat from density was slightly higher in girls. After age 12 boys had higher body weights, body heights and body mass index but lower body fat as calculated from body density. Predicted body fat from body mass index, body impedance and skinfold thickness was generally slightly lower compared to body fat from body density, except for body fat from impedance, which was both in boys and in girls slightly higher compared to body fat from body density. However, the mean differences were small and maximally reached 2.7% body fat in boys (impedance) and 1.7% in girls (skinfolds). The standard deviations of the differences were within the estimation error of the used methodology and comparable with values obtained in other studies. The differences between measured and predicted values were slightly higher in the youngest and the oldest children, probably indicating invalid assumptions in the used methodologies at these ages. At the lower level of body fatness all prediction formulas systematically overestimated body fat, and at higher fat levels body fat was systematically underestimated. It is concluded that prediction formulas developed in Caucasian subjects are generally valid in Chinese (Beijing) children.


Smartphone-based photoplethysmographic imaging for heart rate monitoring.
The purpose of this study is to make use of visible light reflected mode photoplethysmographic (PPG) imaging for heart rate (HR) monitoring via smartphones. The system uses the built-in camera feature in mobile phones to capture video from the subject's index fingertip. The video is processed, and then the PPG signal resulting from the video stream processing is used to calculate the subject's heart rate. Records from 19 subjects were used to evaluate the system's performance. The HR values obtained by the proposed method were compared with the actual HR. The obtained results show an accuracy of 99.7% and a maximum absolute error of 0.4 beats/min where most of the absolute errors lay in the range of 0.04-0.3 beats/min. Given the encouraging results, this type of HR measurement can be adopted with great benefit, especially in the conditions of personal use or home-based care. The proposed method represents an efficient portable solution for HR accurate detection and recording.


Developing High-Power-Density Electromagnetic Devices with Nanocrystalline and Amorphous Magnetic Materials.
With the increasing demand for smaller, lighter, and more affordable electromagnetic devices, there is a growing trend toward developing high-power-density transformers and electrical machines. While increasing the operating frequency is a straightforward approach to achieving high power density, it can lead to significant power loss within a limited volume, resulting in excessive temperature rise and device degradation. Therefore, it is crucial to design high-power-density electromagnetic devices that exhibit low power loss and efficient thermal dissipation to address these challenges. Advanced techniques, such as the utilization of novel and advanced electromagnetic materials, hold great promise for overcoming these issues. Specifically, nanocrystalline and amorphous magnetic materials have emerged as highly effective solutions for reducing power loss and increasing efficiency in electromagnetic devices. This paper aims to provide an overview of the application of nanocrystalline and amorphous magnetic materials in transformers and electrical machines, along with key technologies and the major challenges involved.


Diffusion of electronic health records--six years of empirical data.
The Danish EHR-Observatory has monitored Danish EHR projects since 2000 with respect to a number of parameters such as diffusion, diffusion rate and the hospital owners expectations. On the basis of the data and a model for technology diffusion three scenarios for future diffusion are built. The results show that the national goal to have EHRs fully implemented in hospitals by 2008 will not be reached. The scenarios built from empirical data provide a useful benchmarking tool for planning and evaluating the EHR implementation programs in hospitals.


Interleukin-18 Amplifies Macrophage Polarization and Morphological Alteration, Leading to Excessive Angiogenesis.
M2 macrophage (Mφ) promotes pathologic angiogenesis through a release of pro-angiogenic mediators or the direct cell-cell interaction with endothelium in the micromilieu of several chronic inflammatory diseases, including rheumatoid arthritis and cancer, where interleukin (IL)-18 also contributes to excessive angiogenesis. However, the detailed mechanism remains unclear. The aim of this study is to investigate the mechanism by which M2 Mφs in the micromilieu containing IL-18 induce excessive angiogenesis in the in vitro experimental model using mouse Mφ-like cell line, RAW264.7 cells, and mouse endothelial cell line, b.End5 cells. We discovered that IL-18 acts synergistically with IL-10 to amplify the production of Mφ-derived mediators like osteopontin (OPN) and thrombin, yielding thrombin-cleaved form of OPN generation, which acts through integrins α4/α9, thereby augmenting M2 polarization of Mφ with characteristics of increasing surface CD163 expression in association with morphological alteration. Furthermore, the results of visualizing temporal behavior and morphological alteration of Mφs during angiogenesis demonstrated that M2-like Mφs induced excessive angiogenesis through the direct cell-cell interaction with endothelial cells, possibly mediated by CD163.


Palliative and end-of-life care in pediatric solid organ transplantation.
End-of-life care is a component of palliative care and takes a holistic, individualized approach to patients, focusing on the assessment of quality of life and its maintenance until the end of life, and beyond, for the patient's family. Transplant teams do not always make timely referrals to palliative care teams due to various clinician and perceived family barriers, an important one being the simultaneous, active care plan each patient would have alongside an end-of-life plan. Application of findings and further research specific to the pediatric solid organ population would be of significant benefit to guide transplant teams as to the most effective time to introduce end-of-life care, who to involve in ongoing discussions, and important ethical and cultural considerations to include in care planning. Attention must also be paid to clinician training and support in this challenging area of health care.


Effect of Dietary Exposure to Acrylamide on Diabetes-Associated Cognitive Dysfunction from the Perspectives of Oxidative Damage, Neuroinflammation, and Metabolic Disorders.
Acrylamide is a toxic compound that is produced widely during food processing, but whether the daily dietary consumption of acrylamide can impair the cognitive dysfunction in diabetic individuals and the potential underlying mechanisms are unknown. The aim of the present study was to observe the changes in cognitive and memory performance caused by chronic acrylamide exposure and to evaluate its influence on the brain morphology, oxidative damage, neuroinflammation, and brain metabolic disturbance. Goto-Kakizaki (GK) rats, a rat model of diabetes, were orally administered acrylamide at 1 mg/kg body weight for 8 weeks. The results of the novel object recognition and Y-maze tests showed that the consumption of acrylamide significantly aggravated diabetes-associated cognitive dysfunction in GK rats. Acrylamide increased reactive oxygen species and malondialdehyde formation and reduced glutathione levels, catalase, and total antioxidant capacity activity, which caused a succession of events associated with oxidative damage, including glial cell activation. After the activation of astrocytes and microglia, related cytokines, including interleukin-1β, interleukin-6, tumor necrosis factor-α, and lipopolysaccharide, were released, amyloid β-protein was accumulated, brain-derived neurotrophic factor was decreased, and the expression of caspase-3 and caspase-9 was increased, which aggravated neuroinflammation. Furthermore, there was perturbation of some important metabolites, including glutamic acid, citric acid, pyruvic acid, lactate, and sphinganine, and their related glucose, amino acid, and energy metabolism pathways in the brain. This work helps to demonstrate the effect of consumption of acrylamide in the daily diet on diabetes-associated cognitive dysfunction and its underlying mechanisms.


Tyr-51 is the proton donor-acceptor for NAD(H)-dependent interconversion of xylose and xylitol by Candida tenuis xylose reductase (AKR2B5).
Substitution of active-site Tyr-51 by Ala (Y51A) disrupted the activity of Candida tenuis xylose reductase by six orders of magnitude. External bromide brought about unidirectional rate enhancement ( approximately 2x10(3)-fold at 300mM) for NAD(+)-dependent xylitol oxidation by Y51A. Activity of the wild-type reductase was dependent on a single ionizable protein group exhibiting a pK of 9.2+/-0.1 and 7.3+/-0.3 in the holo-enzyme bound with NADH and NAD(+), respectively. This group which had to be protonated for xylose reduction and unprotonated for xylitol oxidation was eliminated in Y51A, consistent with a catalytic acid-base function of Tyr-51. Bromide may complement the xylitol dehydrogenase activity of Y51A by partly restoring the original hydrogen bond between the reactive alcohol and the phenolate of Tyr-51.


Improving the Stability of Metal Halide Perovskite Materials and Light-Emitting Diodes.
Metal halide perovskites (MHPs) have numerous advantages as light emitters such as high photoluminescence quantum efficiency with a direct bandgap, very narrow emission linewidth, high charge-carrier mobility, low energetic disorder, solution processability, simple color tuning, and low material cost. Based on these advantages, MHPs have recently shown unprecedented radical progress (maximum current efficiency from 0.3 to 42.9 cd A-1 ) in the field of light-emitting diodes. However, perovskite light-emitting diodes (PeLEDs) suffer from intrinsic instability of MHP materials and instability arising from the operation of the PeLEDs. Recently, many researchers have devoted efforts to overcome these instabilities. Here, the origins of the instability in PeLEDs are reviewed by categorizing it into two types: instability of (i) the MHP materials and (ii) the constituent layers and interfaces in PeLED devices. Then, the strategies to improve the stability of MHP materials and PeLEDs are critically reviewed, such as A-site cation engineering, Ruddlesden-Popper phase, suppression of ion migration with additives and blocking layers, fabrication of uniform bulk polycrystalline MHP layers, and fabrication of stable MHP nanoparticles. Based on this review of recent advances, future research directions and an outlook of PeLEDs for display applications are suggested.


Metal allergy and systemic contact dermatitis: an overview.
Contact dermatitis is produced by external skin exposure to an allergen, but sometimes a systemically administered allergen may reach the skin and remain concentrated there with the aid of the circulatory system, leading to the production of systemic contact dermatitis (SCD). Metals such as nickel, cobalt, chromium, and zinc are ubiquitous in our environment. Metal allergy may result in allergic contact dermatitis and also SCD. Systemic reactions, such as hand dermatitis or generalized eczematous reactions, can occur due to dietary nickel or cobalt ingestion. Zinc-containing dental fillings can induce oral lichen planus, palmoplantar pustulosis, and maculopapular rash. A diagnosis of sensitivity to metal is established by epicutaneous patch testing and oral metal challenge with metals such as nickel, cobalt, chromium, and zinc. In vitro tests, such as the lymphocyte stimulating test (LST), have some advantages over patch testing to diagnose allergic contact dermatitis. Additionally, the determination of the production of several cytokines by primary peripheral blood mononuclear cell cultures is a potentially promising in vitro method for the discrimination of metal allergies, including SCD, as compared with the LST.


Bu-zhong-yi-qi pill alleviate the chemotherapy-related fatigue in 4 T1 murine breast cancer model.
Paclitaxel induced fatigue still remains underrecognized and undertreated, partly because of limited understanding of its pathophysiology and lack of effective treatments. This study is aim to evaluate the anti-fatigue effects and mechanism of Bu-Zhong-Yi-Qi pill in murine 4 T1 breast cancer mice were treated with paclitaxel. Breast cancer mice established with murine 4 T1 cells were randomly and repectively divided into five groups: negative control group (NC), tumor control group (TC), paclitaxel group (PTX), Bu-Zhong-Yi-Qi pill group (BZYQ) and Bu-Zhong-Yi-Qi pill plus paclitaxel group (BZYQ + PTX). The mice were administered for 21 days. During this period, the tumor volume, body weight and the weight-loaded swimming time were measured. After the last administration, all mice were sacrificed, weighted the tumor, measured immune cell cytokines and oxidative stress indicator. The remaining 10 mice in each group were observed for survival analysis. Treatments with BZYQ + PTX and PTX significantly reduced the rates of tumor volume in comparison with TC starting on the 9th day and the 18th day respectively (P < 0.05-0.01), and presented decreased tumor weight compared to TC (P < 0.05-0.01). Compared with mice in TC group, the median survival time and the average survival time in BZYQ + PTX group, BZYQ group and PTX group were significantly prolonged (P < 0.05-0.01). The swimming time of the BZYQ + PTX group gradually increased, which is longer than the PTX group on Day 14 and Day 21 (P < 0.01). The level of TNF-α was lower in BZYQ + PTX group than PTX group (P < 0.01). The level of SOD activity in BZYQ + PTX group was lower than the NC group (P <0.01), but much higher than the PTX group (P < 0.01). The level of MDA of BZYQ + PTX group was higher than the NC group (P < 0.01), but significant lower than the PTX group (P < 0.01). BZYQ has the potential of alleviating paclitaxel chemotherapy-related fatigue in 4 T1 breast cancer mice by reducing the serum levels of TNF-α and modulating the level of MDA and the SOD activity.


Preparation and evaluation of o-phenanthroline immobilized on a hybrid silica monolith modified with ionic liquids for reversed-phase pressurized capillary electrochromatography.
A novel o-phenanthroline-immobilized ionic-liquid-modified hybrid monolith for capillary electrochromatography was synthesized based on chloropropyl-silica, which was prepared by the in situ polymerization of tetramethoxysilane and 3-chloropropyltrimethoxysilane via a sol-gel process. The morphology of the hybrid monolith was characterized by scanning electron microscopy, and relatively stable anodic electroosmotic flow was observed under a broad pH ranged from pH 3.0 to 9.0. The separation mechanism was investigated by separating four neutral molecules (toluene, dimethylformamide, formamide, and thiourea). The obtained hybrid monolith possessed an obviously reversed-phase retention mechanism, but when the acetonitrile content in the mobile phase was >90% v/v, a weak hydrophilic mechanism was observed on the resultant o-phenanthroline-modified chloropropyl-silica hybrid monolith. The reproducibility of the column was also investigated by measuring relative standard deviations of the migration time for four neutral molecules. Relative standard deviations of run to run (n = 3), day to day (n = 3), and column to column (n = 3) were in the range of 0.4-0.7, 0.9-2.1, and 1.4-3.3%, respectively. Basic separations of various polar analytes including phenols and aromatic amines were successfully achieved.


Orthotopic liver transplantation with preservation of the caval and portal flows. Technique and results in 62 cases.
Sixty-two OLTs in 61 patients were performed using a technical modification reported recently, including total hepatectomy with preservation of the inferior vena cava, partial clamping of the native vena cava, and side-to-side cavacaval anastomosis. We further modified the technique by adding the early construction of a temporary end-to-side portacaval shunt, and, more recently, by using an end-to-side caval reconstruction. With this technique, the caval and portal flows were maintained throughout the procedure. Hemodynamic parameters were analyzed prospectively during the operative period and remained stable at all stages of the procedure. Venous bypass was avoided in all cases without need for increased fluid infusion. Operative time and transfusion requirements were 6.8 +/- 1.6 hr and 9.8 +/- 4.3 U of packed RBC, respectively. There were no specific complications or deaths due to the technique used and hospital mortality was 10% (6/61). The technique used in this study is a safe adjunct to the technical armamentarium of clinical liver transplantation. Its main advantage seems to be hemodynamic stability throughout the procedure, obviating the need for venous bypass or fluid overload.


Nonenzymatic modification of Ubiquitin under high-pressure and -temperature treatment: mass spectrometric studies.
The effect of high-pressure and/or high-temperature on the glycation of a model protein (ubiquitin) was investigated by mass spectrometry. This paper reports the impact of high pressure (up to 1200 MPa) on the modification of a ubiquitin using ESI-MS measurements. The application of glucose labeled with stable isotope allows a quantitative assessment of modification under the conditions of high-pressure (HPG) and high-temperature (HTG) glycation. A higher degree of modification was observed for the sample heated at 80 °C for 25 min under atmospheric pressure than for sample treated under high pressure. In samples treated at pressure below 400 MPa an insignificant increase of glycation level was observed, whereas high pressure (>600 MPa) has only a minor effect on the number of hexose moieties (Fru) attached to the lysine residue side chain.


Angiodysplastic syndrome with capillary and venous malformation associated with soft tissue hypotrophy.
Angiodysplastic syndromes include a vascular malformation which may often be associated with secondary changes such as further vascular abnormalities, soft tissue and bone hypertrophy. One of the best known is the syndrome triad originally described by Klippel and Trenaunay, which includes a unilateral capillary malformation, ectatic veins and osseous and soft tissue hypertrophy. A female patient is reported who had an extensive capillary malformation, discrete ectatic veins overlying an extensive venous malformation and soft tissue hypotrophy without bone involvement. Our patient and cases from the literature illustrate the occurrence of 'atypical', hypotrophic variants of angiodysplastic syndromes. Discrete superficial angiodysplasias may overlie deep, extensive malformations, and identification of such cases is important with regard to management and prognosis. The current classification of angiodysplasias is based on the primary vascular malformation. The use of eponyms should be avoided, because they do not contribute to the diagnosis and management of such cases.


Bedside charts: how to introduce change.
This article describes the efforts of an orthopaedic nursing team to scrutinize and reform the charts used at bedside. A review of the process revealed a ritualistic system that was ill-defined and centered around nurses' work patterns. A new chart was designed incorporating features of the old, and adding new information that was considered useful. The author reports that staff preferred the new design and argues that nurses can initiate change at ward level.


Comparative Evaluation of Small Molecular Additives and Their Effects on Peptide/Protein Identification.
Detergents and salts are widely used in lysis buffers to enhance protein extraction from biological samples, facilitating in-depth proteomic analysis. However, these detergents and salt additives must be efficiently removed from the digested samples prior to LC-MS/MS analysis to obtain high-quality mass spectra. Although filter-aided sample preparation (FASP), acetone precipitation (AP), followed by in-solution digestion, and strong cation exchange-based centrifugal proteomic reactors (CPRs) are commonly used for proteomic sample processing, little is known about their efficiencies at removing detergents and salt additives. In this study, we (i) developed an integrative workflow for the quantification of small molecular additives in proteomic samples, developing a multiple reaction monitoring (MRM)-based LC-MS approach for the quantification of six additives (i.e., Tris, urea, CHAPS, SDS, SDC, and Triton X-100) and (ii) systematically evaluated the relationships between the level of additive remaining in samples following sample processing and the number of peptides/proteins identified by mass spectrometry. Although FASP outperformed the other two methods, the results were complementary in terms of peptide/protein identification, as well as the GRAVY index and amino acid distributions. This is the first systematic and quantitative study of the effect of detergents and salt additives on protein identification. This MRM-based approach can be used for an unbiased evaluation of the performance of new sample preparation methods. Data are available via ProteomeXchange under identifier PXD005405.


Co-localization of caldesmon and calponin with cortical afferents, metabotropic glutamate and neurotrophic receptors in the lateral and central nuclei of the amygdala.
Caldesmon (Cd) and calponin (Cp) are two actin/calmodulin-binding proteins involved in 'actin-linked' regulation of smooth muscle and non-muscle Mg(2+) actin-activated myosin II ATPase activity. However, in the brain, Cd and Cp are associated with the regulation of the neuronal cytoskeleton. In this study we investigated the subcellular distribution of Cd and Cp in the amygdala and their possible relationship to metabotropic glutamate (mGluR1 alpha and 5) and TrkB receptors which interact with inputs from the cortex and are involved in associative learning. Cd and Cp immunoreactivity (IR) was mainly found in dendritic spines, along dendritic microtubules, and in neuronal perikarya but never in axon terminals. Punctate labeling representing spine labeling was restricted to small patches in the lateral nucleus of amygdala, intercalated cell masses (ICM), and the lateral subdivision of central nucleus. This restricted distribution may reflect local afferent activation. In addition, Cd, Cp, mGluR1 alpha and cortical afferents are co-distributed in the ICM distributed in the lateral nucleus and lateral capsular division of the central nucleus, and the lateral division of the central nucleus itself. Consistent with our previous studies, TrkB IR in the central nucleus was associated with Cd and Cp-immunoreactive spines whereas mGluR1 alpha IR and mGluR5 IR were almost exclusively associated with the PSDs of asymmetric synapses, in most cases apposed by cortical terminals. mGluR1 alpha and TrkB immunoreactivities were invariably associated with each other. Overall, these findings suggest that caldesmon and calponin in the amygdala are closely associated with afferents and receptors that have been strongly implicated in associative learning.


Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease.
Circulating levels of four adipokines (adiponectin, TNF-alpha, leptin, and resistin) and the postprandial lipid and adiponectin responses to an oral fat load were assessed in 25 non-obese, non-diabetic patients with biopsy-proven nonalcoholic steatohepatitis (NASH) and correlated with metabolic indices and liver histology. Circulating adiponectin was lower in NASH compared with controls (5,476 +/- 344 vs. 11,548 +/- 836 ng/mL; P = .00001) and on multiple regression analysis correlated negatively with liver steatosis, necroinflammation (OR = 5.0; P = .009), and fibrosis (OR = 8.0; P = .003). The magnitude of postprandial lipemia was significantly higher in NASH than in controls and was related to fasting adiponectin (beta = -0.78; P = .00003). Controls showed a significant increase in serum adiponectin in response to the fat load, whereas patients with NASH showed a slight decrease. Postprandial free fatty acids response correlated inversely with adiponectin response in both groups and independently predicted the severity of liver steatosis in NASH (beta = 0.51; P = .031). In conclusion, hypoadiponectinemia is present before overt diabetes and obesity appear and correlates with the severity of liver histology in NASH. Impaired postprandial lipid metabolism may be an additional mechanism linking hypoadiponectinemia and NASH and posing a higher cardiovascular risk to these subjects. The mechanism(s) underlying these differences are unknown, but the type of dietary fat seems to play a role. These findings may have important pathogenetic and therapeutic implications in both liver and metabolic disease.


Different effect of the pure Na+ channel-blocker pilsicainide on the ST-segment response in the right precordial leads in patients with normal left ventricular function.
The response of the ST-segment in the right precordial leads to Na+ channel blockers in patients without structural heart disease and a typical Brugada-type ECG has not been fully elucidated. A pilsicainide challenge test was performed in 161 patients and according to recently established ECG criteria and an organized computer algorithm, the ST morphology was classified and the maximum increase in the J wave amplitude (maxDeltaJ) from the standard and high right precordial leads V1-3 was examined. Before the test, subjects exhibiting type 1 ECG in the standard leads were excluded. After administering pilsicainide, type 1 ECGs in the standard leads were observed in 31 cases and a maxDeltaJ of >or=200 microV was observed in 29 cases (23 type 1, 2 type 2/3 and 4 normal ECGs). In the additional higher right precordial leads, type 1 ECGs were observed in 55 cases and a maxDeltaJ of >or=200 microV was observed in 45 cases (42 type 1 and 3 type 2/3 ECGs). A maxDeltaJ>or=200 microV induced by pilsicainide, including that measured in the high right precordial leads, was associated with a change mainly to a type 1 ECG.


The advanced helical generator.
A high explosive pulsed power generator called the advanced helical generator (AHG) has been designed, built, and successfully tested. The AHG incorporates design principles of voltage and current management to obtain a high current and energy gain. Its design was facilitated by the use of modern modeling tools as well as high precision manufacture. The result was a first-shot success. The AHG delivered 16 MA of current and 11 MJ of energy to a quasistatic 80 nH inductive load. A current gain of 160 times was obtained with a peak exponential rise time of 20 micros. We will describe in detail the design and testing of the AHG.


Ultrasonic-assisted synthesis of Au nanobelts and nanowires.
Au one-dimensional (1D) nanostructures, including nanobelts and nanowires, have been synthesized in an ethylene glycol (EG)/polyvinylpyrrolidone (PVP) system by a simple and convenient seed-mediated growth method. The nanobelts and nanowires have aspect ratios up to 600, a length distribution ranging from several to tens of microns, and an average width of 100 nm. In this method, we used an ultrasonic process to promote the formation of Au seeds, which largely determines the morphology of final product. Additionally, we have found that the ultrasonic process significantly increases the fabrication yield of 1D nanostructures. Further experimental results show strong polarization dependence of Surface-Enhanced Raman Scattering (SERS) on a single Au 1D nanostructure. This convenient, versatile and low-cost synthesis method can be applied to 1D nanostructures composed from a range of materials, making it widely applicable to many areas of modern science and technology.


Reducing Length of Stay, Direct Cost, and Readmissions in Total Joint Arthroplasty Patients With an Outcomes Manager-Led Interprofessional Team.
The purpose of this quality improvement project was to determine whether an outcomes manager-led interprofessional team could reduce length of stay and direct cost without increasing 30-day readmission rates in the total joint arthroplasty patient population. The goal was to promote interprofessional relationships combined with collaborative practice to promote coordinated care with improved outcomes. Results from this project showed that length of stay (total hip arthroplasty [THA] reduced by 0.4 days and total knee arthroplasty [TKA] reduced by 0.6 days) and direct cost (THA reduced by $1,020 per case and TKA reduced by $539 per case) were significantly decreased whereas 30-day readmission rates of both populations were not significantly increased.


Genetic Analysis of Iranian Patients with Familial Hypercholesterolemia
Familial hypercholesterolemia (FH) is a frequent autosomal dominant disorder of lipoprotein metabolism. This disorder is generally caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B 100 (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. In the present study, we aimed at identifying the common LDLR and APOB gene mutations in an Iranian population. Eighty unrelated Iranian patients with FH entered the study, based on Simon Broome diagnostic criteria. All samples were screened for two common APOB gene mutations, including R3500Q and R3500W, by the means of ARMS-PCR and PCR- RFLP assays, respectively. In addition, exons 3, 4, 9, and 10 of LDLR gene were sequenced in all patients. A novel mutation in exon 3 (C95W) and a previously described mutation in exon 4 (D139H) of LDLR gene were found. Three previously reported polymorphisms in LDLR gene as well as three novel polymorphisms were detected in the patients. However, in the studied population, no common mutations were observed in APOB gene. The results of our study imply that the genetic basis of FH in Iranian patients is different from other populations.


[Discovery of exogenous ligands for orphan receptor BRS-3 from Chinese herbs].
Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,β-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 μmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.