CMHS data highlights on: availability of psychiatric beds, United States: selected years, 1970-1990.
Despite the decrease from 474,190 to 250,541 between 1970 and 1990 in the overall number of non-Federal psychiatric beds (excluding "scatter" beds in non-Federal general hospitals), the trend was by no means constant over time. Between 1970 and 1982, a period of rapid deinstitutionalization of State mental hospitals, the number of beds in all organizations combined dropped precipitously from 474,190 to 222,666, led by State mental hospitals which decreased from 413,066 to 140,140 beds. This was the height of the community mental health center movement and the prevailing view of mental health administrators was that persons with mental illness could be cared for better in the community, rather than at State mental hospitals, far from their homes. Thus, some hospitals closed altogether, and many others closed wards and units as part of the downsizing process. Contrary to a decrease in the number of beds in State mental hospitals during the 1970-82 period, the number of beds in other organization types, in particular private psychiatric hospitals and separate psychiatric services of non-Federal general hospitals, remained relatively constant. The net result was a substantial decrease in the overall number of non-Federal psychiatric beds. In the 1982-90 period, a different phenomenon occurred. The number of beds in State mental hospitals was continuing to decline, but at a slower rate from 140,140 to 98,789, while the number of beds in other types of mental health organizations, particularly private psychiatric hospitals and separate psychiatric inpatient services of non-Federal general hospitals, expanded somewhat.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessment of learning by emergency medicine residents and pharmacy students participating in a poison center clerkship.
An AAPCC-designated poison center developed and validated an objective testing instrument to evaluate learning during a poison center clinical rotation for 2nd-year emergency medicine residents and 5th-year pharmacy students. The examination contained multiple-choice, true-false, and fill-in questions pertaining to basic clinical toxicology. A pretest was administered prior to the rotation and a post-test was administered upon completion of the rotation. Overall pre-test mean was 56.2%; physician pre-test mean was 73.8%, and student pre-test mean was 43.9%. Overall post-test mean was 78.7%; physician post-test mean was 85.7%, and student post-test mean was 81%. Pre-test scores ranged from 21 to 86% for the group, and post-test scores ranged from 68 to 96%. The mean difference in pre-test to post-test score was 26.9%. These data suggest that a poison center rotation can result in significant increases in post-test scores in comparison to pre-test scores.


An Orbital Shaking Culture of Mammalian Cells in O-shaped Vessels to Produce Uniform Aggregates.
Suspension cultures of mammalian cell aggregates are required for various applications in medical and biotechnological fields. The disposable bag-based method is one of the simplest techniques for the mass production of cellular aggregates, but it does not protect the cultures against over-aggregation, which occurs when they gather at the bottom center of the culture vessel. To solve this problem, we developed an O-shaped dish and an O-shaped bag, neither of which contains a central region. Aggregates grown in either O-shaped culture vessel were noticeably more uniform in size than aggregates grown in conventional vessels. Histological analyses showed that aggregates in conventional culture dishes contained necrotic cores most likely caused by a poor oxygen supply. In contrast, aggregates that were grown in the O-shaped bag, even those with similar diameters to aggregates in conventional culture dishes, did not show necrotic cores. These results suggest that the O-shaped bag provides sufficient oxygen to the aggregates due to the oxygen permeability of the bag material. We, therefore, propose that this novel gas-permeable O-shaped culture bag is suitable for the mass production of uniform aggregates that are necessary in various biotechnological fields.


Surfing with the tunicates into the post-genome era.
This year is the centenary of Edward G. Conklin's signal findings in embryology: the elucidation of complete cell lineages and the discovery of localized maternal determinants. Conklin used ascidian embryos to elucidate universal principles in embryology. A century later, ascidians, or sea squirts, have not only entered the post-genome era, but in many ways are leading the way to the promise of a "systems-level" understanding of complex processes such as notochord formation, neurogenesis, and even behavior.


Abdominal paracentesis drainage attenuates intestinal inflammation in rats with severe acute pancreatitis by inhibiting the HMGB1-mediated TLR4 signaling pathway.
Our previous studies confirmed that abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury in rats with severe acute pancreatitis (SAP), and improves administration of enteral nutrition in patients with acute pancreatitis (AP). However, the underlying mechanisms of the beneficial effects of APD remain poorly understood. To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats, and its potential mechanisms. SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild AP was induced by intraperitoneal injections of cerulein (20 μg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD. Morphological changes, serum inflammatory mediators, serum and ascites high mobility group box protein 1 (HMGB1), intestinal barrier function indices, apoptosis and associated proteins, and toll-like receptor 4 (TLR4) signaling molecules in intestinal tissue were assessed. APD significantly alleviated intestinal mucosal injury induced by SAP, as demonstrated by decreased pathological scores, serum levels of D-lactate, diamine oxidase and endotoxin. APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells, and normalized the expression of apoptosis-associated proteins in intestinal tissues. APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1, thus exerting protective effects against SAP-associated intestinal injury. APD improved intestinal barrier function, intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats. The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.


Preparing and writing an undergraduate dissertation.
Nurses studying for undergraduate degrees are often required to produce a dissertation. Usually, this will be a piece of work of around 10,000 words in length. In this paper, we discuss the characteristics of a good dissertation, and discuss a range of s trategies which students might find useful as they work towards dissertation submission. Particular areas that we concentrate on include: getting started, working with supervisors, defining aclear topic area, planning work and timetabling, locating and critiquing literature, writing up the literature review, linking theory and practice, and knitting the dissertation together.


Synthesis of poly(biphenylene ruthenacyclopentatrienylene), a new organometallic conducting polymer with ferromagnetic interaction in its reduced state.
A ruthenacyclopentatriene polymer 2 was synthesized by metallacycling polymerization (MCP). Polymer 2 with Mn = 3400 and Mw = 5800 consisted of identical ruthenacyclopentatriene units. The UV-vis spectra of 2 showed a shift of the pi-pi* band to a longer wavelength due to the enlargement of the pi-conjugation. Polymer 2 underwent reversible reduction due to the ruthenacycle moiety at -1.01 V versus ferrocenium/ferrocene. The EPR spectrum of the reduced form of 2 in frozen THF indicated ferromagnetic interaction of spins at ruthenacyclopentatriene units.


The occurrence of the herbicide dalapon (2,2-dichloropropionate) in potable water as a disinfection by-product.
Salts of 2,2-dichloropropionic acid, such as dalapon, are well known as herbicides and are regulated as such in potable water in Australia and elsewhere. It is also an identified disinfection by-product (DBP), but little is known about the compound's formation and typical levels from this source. This work presents results from a sampling campaign where 2,2-dichloropropionate was found at levels between 0.1 and 0.5 µg l(-1) in potable water samples from a major treatment plant in South East Queensland, Australia. However, levels were below the reporting limit (0.01 µg l(-1)) in the immediate source water for the plant. Also, temporal trends in 2,2-dichloropropionate observed in treated water during sampling mirrored those of trihalomethanes albeit at much lower concentrations, suggesting that the occurrence is due to in situ formation as a DBP. This could present a regulatory dilemma in some jurisdictions.


Aminoterminal propeptide of type III procollagen in cord blood and amniotic fluid of high-risk pregnancies: a biochemical approach to the dynamic assessment of deviant fetal growth.
N-terminal propeptide of type III procollagen (PIIINP) concentration was measured in cord serum, amniotic fluid, and maternal serum from high-risk pregnancies. The fetal PIIINP variability was shown to be independent of the maternal serum PIIINP values. Although a highly significant negative correlation was found between the fetal propeptide level and gestational age in both appropriate-for-gestational-age neonates (n = 504) and small-for-gestational-age infants (n = 98), the PIIINP concentration in cord serum or amniotic fluid of small-for-gestational-age infants was significantly lower compared with that of appropriate-for-gestational-age infants matched for postconceptional age. PIIINP assay may thus serve as a dynamic biochemical indicator of deviant fetal growth. The PIIINP results were also related to the severity or duration of intrauterine growth retardation, as indicated by significantly lower propeptide cord serum values in nonmalformed small-for-gestational-age infants with small head circumference, known as an index for the chronicity of fetal nutritional deprivation. Preeclampsia, maternal diabetes or smoking, and congenital anomalies appeared not to be associated with any alteration of fetal propeptide concentration, provided they did not cause fetal growth deceleration. The finding of extremely high cord serum PIIINP values in six newborn infants with the Potter malformation sequence led to the speculation that large amounts of propeptides or their fragments usually are excreted by the fetal kidneys into the amniotic fluid. We suggest that determination of the PIIINP level in amniotic fluid or cord serum, obtained by amniocentesis and percutaneous umbilical sampling, may be a helpful adjunctive biochemical parameter in future research protocols assessing fetuses at risk for intrauterine growth retardation.


Coronary flow reserve, insulin resistance and blood pressure response to standing in patients with normoglycaemia: is there a relationship?
To establish the relationships between coronary flow reserve, cardiovascular autonomic function, and insulin resistance characterized by the homeostasis model assessment insulin resistance score in patients with normal carbohydrate metabolism according to the World Health Organization (WHO) and American Diabetes Association (ADA) criteria, and with morphologically normal epicardial coronary arteries. Twenty-five patients [12 women and 13 men, mean (sd) age: 53 +/- 11 years] with normal coronary angiography were enrolled into the study. Coronary flow reserve was measured during stress transoesophageal echocardiography. Autonomic dysfunction was assessed by means of five standard cardiovascular reflex tests. The fasting serum glucose and insulin levels were determined and the homeostasis assessment model insulin resistance score was calculated. In patients with normal carbohydrate metabolism, negative correlations were observed between the coronary flow reserve and both the serum insulin level (r = -0.445, P = 0.026) and the homeostasis assessment model insulin resistance score (r = -0.449, P = 0.024). The systolic blood pressure response to standing also correlated with the coronary flow reserve (r = -0.519, P = 0.011). The heart rate response to deep breathing, the Valsalva ratio, the 30/15 ratio and the sustained handgrip test results were not correlated with the coronary flow reserve. Our data suggest the possible role of insulin resistance and early sympathetic nerve dysfunction in the development of decreased coronary flow reserve in patients without diabetes mellitus or impaired glucose tolerance.


GC-MS-Based Endometabolome Analysis Differentiates Prostate Cancer from Normal Prostate Cells.
Prostate cancer (PCa) is an important health problem worldwide. Diagnosis and management of PCa is very complex because the detection of serum prostate specific antigen (PSA) has several drawbacks. Metabolomics brings promise for cancer biomarker discovery and for better understanding PCa biochemistry. In this study, a gas chromatography-mass spectrometry (GC-MS) based metabolomic profiling of PCa cell lines was performed. The cell lines include 22RV1 and LNCaP from PCa with androgen receptor (AR) expression, DU145 and PC3 (which lack AR expression), and one normal prostate cell line (PNT2). Regarding the metastatic potential, PC3 is from an adenocarcinoma grade IV with high metastatic potential, DU145 has a moderate metastatic potential, and LNCaP has a low metastatic potential. Using multivariate analysis, alterations in levels of several intracellular metabolites were detected, disclosing the capability of the endometabolome to discriminate all PCa cell lines from the normal prostate cell line. Discriminant metabolites included amino acids, fatty acids, steroids, and sugars. Six stood out for the separation of all the studied PCa cell lines from the normal prostate cell line: ethanolamine, lactic acid, β-Alanine, L-valine, L-leucine, and L-tyrosine.


Study on the Pulmonary Delivery System of Apigenin-Loaded Albumin Nanocarriers with Antioxidant Activity.
Respiratory diseases are mainly derived from acute and chronic inflammation of the alveoli and bronchi. The pathophysiological mechanisms of pulmonary inflammation mainly arise from oxidative damage that could ultimately lead to acute lung injury. Apigenin (Api) is a natural polyphenol with prominent antioxidant and anti-inflammatory properties in the lung. Inhalable formulations that consist of nanoparticles (NPs) have several advantages over other administration routes, and therefore, this study investigated the application of apigenin-loaded bovine serum albumin nanoparticles (BSA-Api-NPs) for pulmonary delivery. Dry powder formulations of BSA-Api-NPs were prepared by spray drying and characterized by laser diffraction particle sizing, scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. The influence of dispersibility enhancers (lactose monohydrate and l-leucine) on the in vitro aerosol deposition using a next-generation impactor was investigated in comparison to excipient-free formulation. The dissolution of Api was determined in simulated lung fluid by using the Franz cell apparatus. The antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH⋅) free radical scavenging assay. The encapsulation efficiency and the drug loading were measured to be 82.61% ± 4.56% and 7.51% ± 0.415%. The optimized spray drying conditions were suitable to produce particles with low residual moisture content. The spray-dried BSA-Api-NPs possessed good aerodynamic properties due to small and wrinkled particles with low mass median aerodynamic diameter, high emitted dose, and fine particle fraction. The aerodynamic properties were enhanced by leucine and decreased by lactose, however, the dissolution was reversely affected. The DPPH⋅ assay confirmed that the antioxidant activity of encapsulated Api was preserved. This study provides evidence to support that albumin nanoparticles are suitable carriers of Api and the use of traditional or novel excipients should be taken into consideration. The developed BSA-Api-NPs are a novel delivery system against lung injury with potential antioxidant activity.


Management of metastatic castration-resistant prostate cancer: Insights from urology experts in Thailand.
Treatment options for castration-resistant prostate cancer (CRPC) are available, but clear instructions for the selection of appropriate treatment are lacking. A meeting of urology experts based in Thailand was convened with the following objectives: (1) to reach a consensus and share real-life experiences about how to identify CRPC; (2) to choose the appropriate treatment for CRPC patients; (3) to evaluate disease progression using novel inhibitors of the androgen receptor pathway; (4) to identify the frequency of monitoring disease; and (5) to promote rational use of corticosteroids in CRPC patients. This consensus document can provide guidance to other urologists in Thailand to provide appropriate treatment to metastatic CRPC patients in a timely manner.


Triterpenoid saponins from Spergularia ramosa.
Six new oleanene glycosides were isolated from the MeOH extract of the aerial parts of Spergularia ramosa. They possess gypsogenin or quillaic acid as the aglycons. The disaccharide moiety linked to C-3 of the aglycons is made up of galactose (or glucose) and glucuronic acid (or glucose); the pentasaccharide moiety linked to C-28 is made up of glucose (or galactose), xylose, rhamnose, fucose, and arabinose. Their structures were elucidated by 1D and 2D NMR experiments including 1H-1H (DQF-COSY, 1D TOCSY, 2D HOHAHA, ROESY) and 1H-13C (HSQC, HMBC) spectroscopy.


Triplet combination with irinotecan plus oxaliplatin plus continuous-infusion fluorouracil and leucovorin as first-line treatment in metastatic colorectal cancer: a multicenter phase II trial.
To evaluate the efficacy and tolerance of irinotecan (CPT-11) in combination with oxaliplatin (L-OHP) plus fluorouracil (5-FU)/leucovorin (LV) (de Gramont regimen) as first-line treatment of metastatic colorectal cancer (MCC). Thirty-one patients with MCC who had not received prior therapy for metastatic disease were enrolled. Their median age was 60 years; performance status (World Health Organization) was 0 in 12, 1 in 14, and 2 in five patients; 19 patients (61%) had prior surgery, and 14 (45%) had adjuvant chemotherapy. CPT-11 was administered on day 1 at 150 mg/m(2) as a 90-minute intravenous (IV) infusion; L-OHP was administered on day 2 at 65 mg/m(2) as a 2-hour IV infusion; and on days 2 and 3, LV 200 mg/m(2) preceded 5-FU administration of 400 mg/m(2)/d initial IV bolus dose followed by 600 mg/m(2)/d 22-hour IV continuous infusion. The regimen was repeated every 2 weeks. All patients were assessable for toxicity and 30 for response to treatment. Complete response was achieved in two patients (6.5%) and partial response in 16 (51.6%) (overall response rate, 58.1%; 95% confidence interval, 40.7% to 75.4%); eight patients (25.8%) had stable disease, and five (16.1%) had disease progression. The median duration of response was 9 months, and the median time to disease progression was 13 months. Neutropenia grade 3 to 4 occurred in 14 patients (45%) and febrile neutropenia in two (6%). Diarrhea grade 3 to 4 was observed in 10 patients (32%), neurotoxicity grade 3 to 4 in three (9%), and asthenia grade 3 in two (10%). No treatment-related death has occurred. The triplet combination of 5-FU/LV + CPT-11 + L-OHP is a highly active regimen with manageable toxicity as front-line treatment in MCC.


3,5-Bis(4-chloro-benzyl-idene)-1-methyl-piperidin-4-one.
In the title mol-ecule, C(20)H(17)Cl(2)NO, the central heterocyclic ring adopts a flattened boat conformation. The dihedral angles between the planar part of this central heterocyclic ring [maximum deviation = 0.004 (1) Å] and the two almost planar side-chain fragments [maximum deviations = 0.015 (1) and 0.019 (1) Å], that include the aromatic ring and bridging atoms, are 18.1 (1) and 18.0 (1)°. In the crystal, pairs of weak inter-molecular C-H⋯O hydrogen bonds link mol-ecules into inversion dimers that form stacks along the a axis. The structure is further stabilized by weak inter-molecular C-H⋯π inter-actions involving the benzene rings.


Business law. Fundamentals for the occupational health nurse.
1. A basic understanding of the judicial system will enable occupational health nurses to read court opinions and have a better understanding of whether or how they or their companies are affected by the decision. With this knowledge, occupational health nurses can help their organization avoid legal liability by ensuring that the company does not act contrary to the decisions of the controlling courts. 2. As they are often involved in the process of contracting for goods and services, occupational health nurses need to be aware of general contract terminology and negotiating techniques so they will be better able to protect their companies. In addition, occupational health nurses can also assist in the actual contract drafting process with knowledge of a few concepts, such as the description, caption, operative language of the agreement, and definitions, of a contract. 3. Occupational health nurses are often called upon to be expert witnesses and can play an integral part in the litigation process. Because of the importance of expert witnesses, occupational health nurses must have an understanding of how to effectively provide expert witness testimony.


Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopists and Endoscopists in Training: A Joint NASPGHAN/ESPGHAN Guideline.
High-quality pediatric endoscopy requires reliable performance of procedures by competent individual providers who consistently uphold all standards determined to assure optimal patient outcomes. Establishing consensus expectations for ongoing monitoring and assessment of individual pediatric endoscopists is a method for confirming the highest possible quality of care for such procedures worldwide. We aim to provide guidance to define and measure quality of endoscopic care for children. With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopists. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. The PEnQuIN working group achieved consensus on 6 standards that all providers who perform pediatric endoscopy should uphold and 2 standards for pediatric endoscopists in training, with 7 corresponding indicators that can be used to identify high-quality endoscopists. Additionally, these can inform continuous quality improvement at the provider level. Minimum targets for defining high-quality pediatric ileocolonoscopy were set for 2 key indicators: cecal intubation rate (≥90%) and terminal ileal intubation rate (≥85%). It is recommended that all individual providers performing or training to perform pediatric endoscopy initiate and engage with these international endoscopist-related standards and indicators developed by PEnQuIN.


Additional value of computed tomography angiography in multiple coronary artery aneurysms--a case report.
Though invasive coronary angiography is the gold standard for the diagnosis of coronary artery aneurysms, computed tomography angiography may be just as useful in providing details of their morphology, size, location and associated stenosis or ectasia. Besides, it has the advantage of being a non-invasive modality.We present a case in which an aneurysm, which was not identified by conventional angiography due to the presence of thrombus, was correctly identified by computed tomography angiography.


Synthesis and biological evaluation of S-glycosylated pyridines.
The formation of thioglycosides 7a-j and 10a-j via the reaction of sodium salts of thiopyridines 3a-e with glycosyl bromides 6a,b has been studied. Comparison with the products obtained from silylated thiopyridines 8a-e and peracetylated sugars 9a,b is made. 13C NMR was utilized to elucidate the proposed structures of the products.


CRY1 and CRY2 genetic variants in seasonality: A longitudinal and cross-sectional study.
Cryptochromes are key components of the circadian clocks that generate and maintain seasonal variations. The aim of our study was to analyze the associations of CRY1 and CRY2 genetic variants with the problematicity of seasonal variations, and whether the problematicity of seasonal variations changed during the follow-up of 11 years. Altogether 21 CRY1 and 16 CRY2 single-nucleotide polymorphisms (SNPs) were genotyped and analyzed in 5910 individuals from a Finnish nationwide population-based sample who had filled in the self-report on the seasonal variations in mood and behavior in the year 2000. In the year 2011, 3356 of these individuals filled in the same self-report on the seasonal variations in mood and behavior. Regression models were used to test whether any of the SNPs associated with the problematicity of seasonal variations or with a change in the problematicity from 2000 to 2011. In the longitudinal analysis, CRY2 SNP rs61884508 was protective from worsening of problematicity of seasonal variations. In the cross-sectional analysis, CRY2 SNP rs72902437 showed evidence of association with problematicity of seasonal variations, as did SNP rs1554338 (in the MAPK8IP1 and downstream of CRY2).


[Exogenous PTEN gene induces apoptosis in breast cancer cells].
To investigate the effects of exogenous PTEN gene on apoptosis of breast cancer cells. Human breast cancer cells of the line MDA468 were cultured. Recombinant plasmid pcDNA3.1-PTEN was constructed and transfected into the breast cancer cells with the lipofectAMINE 2000 transfection technique. Parental MDA468 cells and parental MDA468 cells transfected with blank vector pcDNA3.1(-) were used as control groups. RT-PCR was used to detect the expression of the PTEN mRNA and Western blotting was used to determine the expression of PTEN protein. Epithelial growth factor (EGF) was added into the cultures of MDA468 cells transfected with pcDNA3.1-PTEN or blank vector. Then Western blotting was used to detect the expression of phosphospecific protein kinase B (PKB/Akt) and focal adhesion kinase (FAK) protein stimulated by EGF. The aapoptosis of the MDA468 cells was determined by flow cytometry with the double-staining method using FITC-conjugated annexin V and PI. Expressions of PTEN mRNA and protein were shown in the MDA468 cells transfected with pcDNA3.1-PTEN by RT-PCR and Western blotting. Both the expression of p-AKT and that of p-FAK were down-regulated in the MDA468 cells transfected with pcDNA3.1-PTEN in comparison with those in the control cells. The apoptotic rate of the MDA468 cells transfected with PCDNA3.1-PTEN was 21.68%, significantly higher than those of the blank control cells (1.17%) and pcDNA3.1(-)-transfected cells (3.55%, both P < 0.01). Exogenous PTEN suppress the growth of human breast cancer cell and induces apoptosis by phosphatase activity, which provides a new clue to gene therapy for breast cancer.


Regulation of Runx2 by microRNA-9 and microRNA-10 modulates the osteogenic differentiation of mesenchymal stem cells.
Currently, the use of stem cell transplantation for the treatment of osteoporosis is a popular research topic. In general, promotion of the osteogenic differentiation of stem cells is the goal of researchers. MicroRNAs (miRNAs of miRs) are critical regulatory factors of osteogenic induction, and miR‑9 and miR‑10 have been substantiated to be involved in the osteogenic process, yet the underlying mechanisms remain unclear. The present study investigated the role of miR‑9 and miR‑10 in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and aimed to elucidate the mechanism of osteogenic differentiation. Using MTT assay and RT-PCR, we found that miR‑9 expression was upregulated and miR-10 expression was downregulated during osteogenic differentiation. Moreover, as shown by the results of mineralization analysis and western blot analysis, the overexpression of miR‑9 enhanced the osteogenic abilities and overexpression of miR‑9 inhibited these abilities. Furthermore, miR‑9 and miR‑10 also affected the expression of Runt‑related transcription factor 2 (Runx2) and extracellular signal-regulated kinase (ERK) pathway by western blot analysis. Based on these results, we conclude that miR‑9 and miR‑10 play key roles in regulating the differentiation of BMSCs.


Strain-Level Variation and Diverse Host Bacterial Responses in Episymbiotic Saccharibacteria.
Saccharibacteria (TM7), which are obligate episymbionts growing on the surface of host bacteria, may play an important role in oral disease, such as periodontitis (1, 2). As TM7 is a newly cultured lineage of bacteria, its research is limited by the small number of isolated representatives relative to the number of TM7 genomes assembled from culture-independent studies (3-5). A comprehensive view of both TM7 taxa and TM7 strain-level variations remains opaque. In this study, we expanded our previously developed TM7 baiting method into using many host bacteria in parallel, which allowed us to obtain 37 TM7 strains from the human oral cavity. These strains were further classified into low-enrichment (LE, n = 24) and high-enrichment (HE, n = 13) groups based on their proficiency at propagating on host bacteria. Of the 13 HE strains, 10 belong to "Candidatus Nanosynbacter sp." strain HMT-352 (human microbial taxon) (6), enabling us to explore both the phenotypic and genomic strain variations within a single TM7 species. We show that TM7 HMT-352 strains exhibit a diverse host range and varied growth dynamics during the establishment of their episymbiotic relationship with host bacteria. Furthermore, despite HMT-352 strains sharing a majority of their genes, we identified several gene clusters that may play a pivotal role in host affinity. More importantly, our comparative analyses also provide TM7 gene candidates associated with strain-level phenotypic variation that may be important for episymbiotic interactions with host bacteria. IMPORTANCE Candidate phylum radiation (CPR) bacteria comprise a poorly understood phylum that is estimated to encompass ∼26% of all diversity of domain bacteria. Among CPR bacteria, the Saccharibacteria lineage (TM7) is of particular interest, as it is found in high abundance in the mammal microbiome and has been associated with oral disease. While many CPR genomes, TM7 included, have been acquired through culture-independent methods, only a small number of representatives have been isolated. Such isolated representatives, however, shed light on the physiology, pathogenesis, and episymbiotic interactions of TM7. Combined with genomic analyses, experiments involving isolated representatives can distinguish phylogenetic to phenotypic discrepancies and better identify genes of importance. In this study, we utilized multiple host bacteria in parallel to isolate TM7 bacteria and examined strain-level variation in TM7 to reveal key genes that may drive TM7-host interactions. Our findings accentuate that broad phylogenetic characterization of CPR is the next step in understanding these bacteria.


Inhibition by 1-aminocyclobutane-1-carboxylate of the activity of 1-aminocyclopropane-1-carboxylate oxidase obtained from senescing petals of carnation (Dianthus caryophyllus L.) flowers.
We partially purified 1-aminocyclopropane-1-carboxylate (ACC) oxidase from senescing petals of carnation (Dianthus caryophyllus L. cv. Nora) flowers and investigated its general characteristics, and, in particular, the inhibition of its activity by ACC analogs. The enzyme had an optimum pH at 7-7.5 and required Fe2+, ascorbate and NaHCO3 for its maximal activity. The Km for ACC was calculated as 111-125 microM in the presence of NaHCO3. Its M(r) was estimated to be 35 and 36 kDa by gel-filtration chromatography on HPLC and SDS-PAGE, respectively, indicating that the enzyme exists in a monomeric form. These properties were in agreement with those reported previously with ACC oxidases from different plant tissues including senescing carnation petals. Among six ACC analogs tested, 1-aminocyclobutane-1-carboxylate (ACBC) inhibited most severely the activity of ACC oxidase from carnation petals. ACBC acted as a competitive inhibitor with the Ki of 20-30 microM. The comparison between the Km for ACC and the Ki for ACBC indicated that ACBC had an affinity which was ca. 5-fold higher than that of ACC. Whereas ACC inactivated carnation ACC oxidase in a time-dependent manner during incubation, ACBC did not cause the inactivation of the enzyme. Preliminary experiments showed that ACBC and its N-substituted derivatives delayed the onset of senescence in cut carnation flowers.


The loudness of sounds whose spectra differ at the two ears.
Moore and Glasberg [(2007). J. Acoust. Soc. Am. 121, 1604-1612] developed a model for predicting the loudness of dichotic sounds. The model gave accurate predictions of data in the literature, except for an experiment of Zwicker and Zwicker [(1991). J. Acoust. Soc. Am. 89, 756-764], in which sounds with non-overlapping spectra were presented to the two ears. The input signal was noise with the same intensity in each critical band (bark). This noise was filtered into 24 bands each 1 bark wide. The bands were then grouped into wider composite bands (consisting of 1, 2, 4, or 12 successive sub-bands) and each composite band was presented either to one ear or the other. Loudness estimates obtained using a scaling procedure decreased somewhat as the number of composite bands increased (and their width decreased), but the predictions of the model showed the opposite pattern. This experiment was similar to that of Zwicker and Zwicker, except that the widths of the bands were based on the ERB(N)-number scale, and a loudness-matching procedure was used. The pattern of the results was consistent with the predictions of the model, showing an increase in loudness as the number of composite bands increased and their spacing decreased.


Low-dose aspirin desensitization in individuals with aspirin-exacerbated respiratory disease.
Nasal polyposis frequently occurs within the clinical picture of aspirin-exacerbated respiratory disease (AERD). A derailed arachidonic acid metabolism is regarded to be part of the pathophysiology of AERD, and aspirin desensitization is the only causal therapeutic option, so far. The optimal maintenance dose of aspirin desensitization to prevent nasal polyp recurrence on the one hand and to minimize aspirin-related side-effects, on the other hand, is still a matter of debate. The aim of this trial was to investigate the efficacy and safety of a low-dose aspirin desensitization protocol. After sinus surgery, 70 individuals with AERD were randomly allocated to a prospective double-blind placebo-controlled aspirin desensitization protocol with a maintenance dose of 100 mg daily. The primary outcome was polyp relapse after 36 months. Nasal endoscopy status, quality of life, and patients' symptom score as well as aspirin-related side-effects were monitored. Due to the high dropout rate, only 31 individuals were evaluated. After 36 months, nasal polyp relapse was less frequent (P = 0.0785) and the polyposis score was lower (P = 0.0702) in the therapy group. Quality of life obviously improved (P = 0.0324), clinical complaints (P = 0.0083) were significantly reduced, and no severe aspirin-related side-effects were observed. Aspirin desensitization with a maintenance dose of 100 mg daily has a positive impact on nasal polyp relapse and seems to be a safe and suitable therapy to improve clinical complaints and the quality of life of individuals with AERD.


Study of crystalline defect induced optical scattering loss inside photonic waveguides in UV-visible spectral wavelengths using volume current method.
In this work, we study the crystalline defect induced optical scattering loss inside photonic waveguide. Volume current method is implemented with a close form of dyadic Green's function derived. More specifically, threading dislocation induced scattering loss inside AlN waveguides in UV-visible spectrum wavelengths are studied since this material is intrinsically accompanied with high densities of dislocations (typically on order of 108-1010cm-2). The results from this study reveal that threading dislocations contribute significant amount of scattering loss when material is not MOCVD grown. Additionally, the scattering loss is strongly dependent on polarization and waveguide geometries: TM modes exhibit higher scattering loss compared with TE modes, and the multimode large core waveguides are more susceptible to threading dislocations compared with single mode waveguides and high-aspect-ratio waveguides. Conclusions from this work can be supported by several recently published investigations on III-N based photonic devices. The model derived from this work can also be easily altered to fit other material systems with other types of crystalline defects.


Synthesis of mono- and dinucleotide photoaffinity probes of ribonucleic acid polymerase.
The abortive initiation reaction of RNA polymerase has been used to prepare adenylyl-(3'--5')-uridine 5'-phosphate (pApU) in 74% yield from AMP and UTP. The reactive intermediate p-azidophenyl phosphorimidazolidate has been prepared by starting from p-nitrophenyl phosphate. Reaction of this compound with the terminal phosphates of adenosine 5'-phosphate and adenylyl-(3'--5')-uridine 5'-phosphate gives the corresponding beta-substituted 5'-diphosphates. These products are incorporated into the 5' (leading) end of RNA by RNA polymerase (Escherichia coli) and can be photoactivated at a specific stage of RNA elongation. The dinucleotide photoaffinity label beta-(4-azidophenyl) adenylyl-(3'--5')-uridine 5'-diphosphate stimulates RNA synthesis more strongly than adenylyl-(3'--5')-uridine.


Impact of endoscopic enucleation of the prostate with thulium fiber laser on the erectile function.
The impact of number of endoscopic enucleation of the prostate techniques (holmium laser enucleation - HoLEP for example) on erectile function have already been investigated. However, the thulium-fiber laser, in this setting remains unstudied. In this study, we compared sexual function outcomes in patients with benign prostatic hyperplasia (BPH) treated with transurethral resection of the prostate (TURP) or thulium-fiber laser enucleation (ThuFLEP). We performed a retrospective analysis of patients who underwent transurethral resection and endoscopic enucleation of the prostate for BPH; inclusion criteria was the presence of infravesical obstruction (IPSS > 20, Qmax < 10 mL/s). Erectile function (EF) was assessed using the International Index of Erectile Function (IIEF-5) both prior to endoscopic examination, and six months after. A total of 469 patients with BPH were included in the study; of these, 211 underwent to ThuFLEP, and 258 TURP. Preoperative IIEF-5 in TURP and ThuFLEP groups were 11.7 (±4.5) and 11.1 (±5.0), respectively (p = 0.17). At six month the IIEF-5 score was unchanged (p = 0.26 and p = 0.08) and comparable in both groups (p = 0.49). However, mean IIEF-5 score shown significant increase of 0.72 in ThuFLEP group, comparing to decrease of 0.24 in TURP patients (p < 0.001). Both TURP and ThuFLEP are effective modalities in the management of infravesical obstruction due to BPH. At six months follow-up after surgery, both techniques lead to comparable IIEF-5 score. However, our results demonstrated that the ThuFLEP is more likely to preserve the erectile function leading to increase of IIEF-5 at six months in contrast to TURP which lead to slight drop in IIEF-5 score.


Scholarship During a Pandemic: Secondary Data Analysis.
The COVID-19 pandemic has disrupted nearly every aspect of life in the United States and around the globe, including significant impacts to higher education, both in its teaching-learning and research missions. With the physical closure of so many college and university campuses, a looming challenge is how nurse researchers can continue to generate new knowledge during a temporary but extended period of social distancing where conducting research requiring physical interaction with participants is impossible. In this Methodology Corner installment, a brief overview of secondary data analysis is provided, and resources for locating potentially useful data are described. Although secondary data analysis will not replace the dominant approaches used in nursing education research, current circumstances require it to take a much more prominent place in the toolbox of nursing education researchers. [J Nurs Educ. 2020;59(5):245-247.].


General Guidelines for Quality Assurance of Immunohistochemistry in a Mohs Lab.
The adoption of recently created protocols introduces Mohs laboratories to the principles of immunohistochemistry (IHC) performance validation and clinical laboratory regulations that are unique to these evolving technologies. To review Food and Drug Administration (FDA) IHC reagent classifications, IHC validation protocols, and quality assurance (QA) procedures and documentation needed in conjunction with IHC test guidelines. A focused review of IHC reagent classifications and guidelines in clinical testing laboratories was conducted using PubMed and FDA source documents. The IHC regulation requirements are determined by the 3 FDA classifications of reagents: in vitro diagnostic reagents, analyte-specific reagents, and research use only reagents. To account for performance variability, IHC reagents benefit from routine validation and QA programs. We present our IHC adoption procedures for QA and documentation of IHC tests in a Mohs laboratory. Incorporating a well-organized IHC validation and QA program into Mohs laboratories can increase regulatory compliance and reagent performance.


A cross-cultural study of personality: egyptian and english children.
679 Egyptian boys and 696 girls completed the Junior Eysenck Personality Questionnaire, translated into Arabic. Factor comparisons were moderately high for extraversion and social desirability but weak for neuroticism and psychoticism. Suitable item substitution produced a scoring key resulting in adequate reliabilities with the exception of a somewhat low reliability for the boys on extraversion and low reliabilities on psychoticism for both sexes. Sex differences on means of the dimensions were as usual, boys scoring higher than girls on extraversion and psychoticism, but lower on neuroticism and social desirability. Moreover, on comparing Egyptian with English means, using scales of items in common only, the English boys and girls scored higher than their Egyptian counterparts on extraversion but significantly lower on social desirability. British boys scored higher on psychoticism than did Egyptian boys but British girls scored lower than Egyptian girls.


How effective are simulated molecular-level experiments for teaching diffusion and osmosis?
Diffusion and osmosis are central concepts in biology, both at the cellular and organ levels. They are presented several times throughout most introductory biology textbooks (e.g., Freeman, 2002), yet both processes are often difficult for students to understand (Odom, 1995; Zuckerman, 1994; Sanger et al., 2001; and results herein). Students have deep-rooted misconceptions about how diffusion and osmosis work, especially at the molecular level. We hypothesized that this might be in part due to the inability to see and explore these processes at the molecular level. In order to investigate this, we developed new software, OsmoBeaker, which allows students to perform inquiry-based experiments at the molecular level. Here we show that these simulated laboratories do indeed teach diffusion and osmosis and help overcome some, but not all, student misconceptions.


Rotational Molding of Linear Low-Density Polyethylene Composites Filled with Wheat Bran.
Application of lignocellulosic fillers in the manufacturing of wood polymer composites (WPCs) is a very popular trend of research, however it is still rarely observed in the case of rotational molding. The present study aimed to analyze the impact of wheat bran content (from 2.5 wt.% to 20 wt.%) on the performance of rotationally-molded composites based on a linear low-density polyethylene (LLDPE) matrix. Microscopic structure (scanning electron microscopy), as well as physico-mechanical (density, porosity, tensile performance, hardness, rebound resilience, dynamic mechanical analysis), rheological (oscillatory rheometry) and thermo-mechanical (Vicat softening temperature) properties of composites were investigated. Incorporation of 2.5 wt.% and 5 wt.% of wheat bran did not cause significant deterioration of the mechanical performance of the material, despite the presence of 'pin-holes' at the surface. Values of tensile strength and rebound resilience were maintained at a very similar level, while hardness was slightly decreased, which was associated with the porosity of the structure. Higher loadings resulted in the deterioration of mechanical performance, which was also expressed by the noticeable rise of the adhesion factor. For lower loadings of filler did not affect the rheological properties. However, composites with 10wt.% and 20 wt.% also showed behavior suitable for rotational molding. The presented results indicate that the manufacturing of thin-walled products based on wood polymer composites via rotational molding should be considered a very interesting direction of research.


The first-row transition-metal series of tris(ethylenediamine) diacetate complexes [M(en)3](OAc)2 (M is Mn, Fe, Co, Ni, Cu, and Zn).
The crystal structures of the first-row transition-metal series of tris(ethylenediamine-κ2N,N')metal(II) diacetate, [M(C2H8N2)3](CH3CO2)2, with M = Mn, Fe, Co, Ni, Cu, and Zn, are reported. The complexes are all isostructural, crystallizing in a centrosymmetric triclinic cell and possessing an asymmetric unit composed of one [M(en)3]2+ cation and two symmetrically independent acetate anions. In the unit cell, the two complex cations are inversion-generated enantiomers, possessing the energetically favoured Δ(λλλ) and Λ(δδδ) configurations. The complex cations and acetate anions combine through a series of N-H...O hydrogen bonds to generate a three-dimensional network in the crystals. The other notable feature of the series is a significant Jahn-Teller distortion for the d9 Cu2+ complex.


Basic life support in a diving bell and deck decompression chamber.
Basic life support (BLS) in a diving bell (DB) or deck decompression chamber (DDC) is difficult due to the confined space and limited equipment. Retrieval of the unconscious diver into the DB requires the use of a pulley system. Once inside the bell, space limitations dictate that any resuscitative efforts are attempted with the victim (diver) either suspended in the upright position by the pulley system or lying against the DB's curved side in a semi-supine position. BLS at best achieves a carotid artery systolic blood pressure of 40 mmHg or 30% of cardiac output in the supine position and, therefore, would be ineffective for a diver suspended on a pulley due to inadequate cerebral perfusion. Compression-only cardiopulmonary resuscitation (CPR) may be the only option with the victim lying against the bell's side due to an inability to perform rescue breathing. However, compression ventilation CPR is possible in a DDC provided space limitations do not deny the rescuers access to the patient. The use of an automatic external defibrillator in a hyperbaric chamber has not been studied and therefore cannot be recommended in a DB or DDC. The laryngeal mask airway has been recommended by the Diving Medical Advisory Committee, but an accompanying study suggests that a new device, the i-gel™ without an inflatable cuff, may be a more suitable airway option for the future.


Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis.
To evaluate the contribution of metabolites (methotrexate [MTX] and folate polyglutamate [PG] levels) and pharmacogenetic biomarkers in the folate pathway to the effects of MTX in patients with rheumatoid arthritis not previously treated with this antifolate. Forty-eight MTX-naive adult patients were enrolled in a prospective longitudinal study. MTX therapy was initiated at 7.5 mg/week and was increased every 4-6 weeks until a therapeutic response was achieved. Response was assessed using the Disease Activity Score in 28 joints (DAS28). Red blood cell (RBC) MTX and folate PG levels were measured with 9 common polymorphisms in the folate pathway. Statistical analyses consisted of generalized linear models and multivariate regressions. After 6 months of therapy, the median weekly MTX dosage was 17.5 mg and the median decrease in the DAS28 was 2.0. There was a large interpatient variability in RBC MTXPG levels (median 35 nmoles/liter [interquartile range 28-51] at month 6). Patients with a lesser decrease in the DAS28 (fewer improvements) had lower RBC MTXPG levels (P < 0.05) despite the higher MTX dose administered (P < 0.05). RBC folate PG levels decreased significantly during treatment, and a lesser decrease in RBC folate PGs was associated with a lesser decrease in the DAS28 (P < 0.05). Primary side effects were gastrointestinal and neurologic in nature. Risk genotypes associated with toxicity were in gamma-glutamyl hydrolase (-401CC), 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (347GG), methylenetetrahydrofolate reductase (1298AC/CC), methionine synthase (2756AA), and methionine synthase reductase (66GG). RBC MTXPG levels are a useful means by which to monitor therapy. The genetic associations presented generate hypotheses, and confirmation in independent cohorts is warranted.


SOX2 in squamous cell carcinoma: amplifying a pleiotropic oncogene along carcinogenesis.
SOX2 is a master pluripotency controller that was recently identified as a novel major oncogene, recurrently amplified and activated in Squamous Cell Carcinoma (SCC). These studies have used a similar strategy of chromosomal aberrations screening to identify the SOX2 locus as one of the most frequently amplified site over the SCC genome. They have further highlighted the recurrent SOX2 activation and its necessary role for squamous cell survival. Finally, they showed that SOX2 is also involved in the early steps of lung SCC, as participating to transform human bronchial epithelial cells. Furthermore, SOX2 overexpression can induce the expression of the squamous markers p63 and keratin 6, supporting the idea that SOX2 might be implicated in SCC differentiation. In addition, SOX2 overexpression stimulates lung squamous cell migration. However, neither study assessed the impact of the recurrent activation of SOX2 in advanced primary tumors nor how SOX2 may mechanistically participate to tumor progression and aggressiveness. Here we present these studies and additional data from integrative transcriptomic analyses of primary lung SCC that altogether shed new light and open new exciting perspectives on the multiples roles that SOX2 exerts all along SCC carcinogenesis.


The ultrastructure of kidney renal corpuscles of experimental animals after Cladribine (2-CdA) administration.
The renal glomeruli of the kidney of white Wistar rats were examined. The animals were given Cladribine (2-CdA) subcutaneously at dosages of 0.07 mg/kg b.m./24 h for 7 days and 0.1 mg/kg b.m./24 h for 6 days in 3 courses with 5 weeks' break between each. The animals were killed in each instance, 24 hours after the last dose of the drug or 4 weeks after the last dose. The kidney samples were taken for ultrastructural examination. In all of the groups, changes were observed but the intensity differed: widening or narrowing of the urinary space, thickening of the basement membrane of the parietal layer of the Bowman's capsule and the basement membrane of capillaries, and density changes in capillary vessels as well as infiltrations around the renal glomeruli. Most changes were observed in experimental group IV: the picnotic nuclei of epithelium, widening and fusion of the foot processes of podocytes (the narrowing of the filtration spaces) and numerous invaginations of the nuclear envelope of damaged podocytes.


Robust Control of a Cable-Driven Soft Exoskeleton Joint for Intrinsic Human-Robot Interaction.
A novel, cable-driven soft joint is presented for use in robotic rehabilitation exoskeletons to provide intrinsic, comfortable human-robot interaction. The torque-displacement characteristics of the soft elastomeric core contained within the joint are modeled. This knowledge is used in conjunction with a dynamic system model to derive a sliding mode controller (SMC) to implement low-level torque control of the joint. The SMC controller is experimentally compared with a baseline feedback-linearised proportional-derivative controller across a range of conditions and shown to be robust to un-modeled disturbances. The torque controller is then tested with six healthy subjects while they perform a selection of activities of daily living, which has validated its range of performance. Finally, a case study with a participant with spastic cerebral palsy is presented to illustrate the potential of both the joint and controller to be used in a physiotherapy setting to assist clinical populations.


Predictive Value of Combination of D-dimer and Fibrinogen in Diagnosing Acute CVST.
Cerebral venous sinus thrombosis (CVST) is an uncommon subtype of stroke, and the role of D-dimer and fibrinogen in early diagnosis of CVST has been studied with varying results. The present study aims to study the role of the combination of D-dimer and fibrinogen in early diagnosis of acute CVST. Forty consecutive confirmed acute CVST cases admitted at a tertiary care center were recruited for the study. D-dimer and fibrinogen were assessed by a rapid semiquantitative latex agglutination assay. Out of the 40 CVST patients, 21 (52.50%) were females. The mean age of the patients was 37.58 years ± 19.17 years. Common clinical features were headache (N = 38 [95%]), papilloedema (N = 15 [37.5%]), and seizures (N = 12 [30%]). Although the sensitivity (75%) of the combination of D-dimer and fibrinogen assay was lower than that of D-dimer or fibrinogen alone, the specificity and positive predictive value (75% each) was higher. The combination of D-dimer and fibrinogen testing may aid in an early diagnosis of acute CVST and in better management.


[Awake Nasotracheal Intubation for a 4-Year-old Boy with an Oral Penetrating Toothbrush Injury].
We report a case of an oral penetrating injury caused by a toothbrush in a 4-year-old 17-kg boy. The toothbrush was lodged in the right cervical region through the oral cavity, and emergency surgery for removal was planned under general anesthesia. Although mask ventilation was not possible because of the protruding toothbrush handle, awake nasotracheal intubation was successfully performed with a fiber-scope and intravenous fentanyl 25 μg. We conclude that appropriate analgesics could facilitate awake intubation in pediatric patients.


Activation of peroxisome proliferator-activated receptor-gamma by troglitazone (TGZ) inhibits human lung cell growth.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and a crucial regulator of cellular differentiation. PPAR-gamma ligands have been demonstrated to inhibit growth of several cancer cells. In this study, two human lung cancer cells (NCI-H23 and CRL-2066) and one human lung normal cell (CRL-202) were used for the experiments. The results showed that in consistence with the loss of viability, troglitazone (TGZ) induced apoptosis of CRL-2066 and NCI-H23 cells but not CCL-202 cells. TGZ upregulated PPAR-gamma expression in all the three lung cell lines, especially in the cancer cells. In association of the time-dependent inhibition of the cell proliferation, TGZ downregulated the expression of Bcl-w and Bcl-2 but activated extracellular signal-regulated kinase (ERK)1/2 and p38, suggesting that the growth-inhibitory effect of TGZ is associated with the reduction of Bcl-w and Bcl-2 and the increase of ERK1/2 and p38 activation. SAPK/JNK activation assay showed a decreased activity in all the three cell lines tested after TGZ treatment. It was also demonstrated that TGZ could activate PPAR-gamma transcriptionally. We conclude that TGZ inhibits growth of human lung cancer cells via the induction of apoptosis and the inhibition of cell growth, at least in part, in a PPAR-gamma-relevant manner. The mechanism of TGZ is associated with the activation of ERK and p38, the reduction of SAPK/JNK activity, and the alteration of Bcl-w and Bcl-2.


High dose chemotherapy with cisplatin, VP16 and carboplatin with stem cell support in patients with advanced ovarian cancer.
Authors treated 4 patients suffering from advanced ovarian cancer with high-dose chemotherapy and autologous peripheral blood stem cell (APBSC) or autologous bone marrow stem cell (ABM) as hematopoietic support. In three patients were collected peripheral blood stem cells using a fully automated blood cell separator during hematopoietic recovery following aplasia induced by non-intensive chemotherapy (cisplatin 200 mg/m2 and cyclophosphamide 1,500 mg/m2). Hemopoietic reconstitution of the four patients submitted to APBSC or ABM support after high-dose chemotherapy (cisplatin 100 mg/m2, VP16 650 mg/m2 and carboplatin 1,800 mg/m2) showed the low hematological toxicity of our treatment with APBSC support. Moreover, the drug combination of cisplatin and cyclophosphamide has clinical activity in ovarian cancer and it is an optimal association to mobilize and harvest large number of PBSC.


Circulating nucleic acids in plasma and serum: past, present and future.
Circulating nucleic acids have been detected in plasma/serum from cancer patients with a variety of tumor types. Polymerase chain reaction techniques provide a ubiquitous and facile approach for the identification of these tumor-associated genetic alterations from a minimal amount of tissue and body fluids. Increased levels of free DNA and RNA during malignancy, as well as in various medical conditions and infectious states, offers potential clinical utility for disease screening, diagnosis, prognosis, assessing occult disease progression, identifying potential therapeutic targets and monitoring treatment response. Additionally, elevated fetal DNA and RNA circulate in maternal blood and may serve as a diagnostic aide for assessing chromosomal abnormalities, fetal sexing and monitoring complications associated with pregnancy. Issues persist regarding the characteristics, etiology and potential pathological consequences of circulating cell-free DNA and RNA. Regardless, disease surveillance using nucleic acid-based assays for the evaluation of plasma/serum and body fluids provides a non-invasive and highly practical method for assessing patients.


Simultaneous hemodialysis during coronary angiography fails to prevent radiocontrast-induced nephropathy in chronic renal failure.
Radiocontrast medium- (RM) associated nephrotoxicity continues to be a common cause of acute renal failure and may lead in patients with pre-existing chronic renal insufficiency even to end-stage renal failure requiring chronic dialysis. Since extracorporeal removal of RM after RM administration has been shown to be effective but does not prevent radiocontrast-induced nephropathy, the effect of a simultaneous dialysis during RM administration on renal function is not clear. In a prospective, randomized and controlled trial, we studied the effect of a 4-hour online dialysis during RM (iomeprol) application in patients with advanced chronic renal failure (serum creatinine > or = 3 mg/dl) undergoing coronary angiography. All patients received hydration with saline before and after standardized coronary angiography and were randomized to receive a simultaneous high-flux hemodialysis (7 patients, HD group) or to control group (10 patients). 24-hour creatinine clearance (CrCl) was measured in all patients before, 1 week and 8 weeks after coronary angiography. The clinical follow-up comprised 8 weeks after RM application. RM plasma levels were measured in both groups 15, 30, 60 minutes, 2, 4, 12, 24, 48 and 72 hours after application by high-pressure liquid chromatography. At baseline, CrCl (19 +/- 10 vs 17 +/- 7 ml/min), percentage of diabetics (57 vs 70%) and dose of RM (77 +/- 27 vs 86 +/- 21 ml) were similar in both groups. Pharmacokinetics: Total clearance of iomeprol was significantly higher (54 +/- 15 vs 20 +/- 12 ml/min, p < 0.001) and the area under curve (AUC) was significantly lower (23 +/- 10 g x h/l vs 94 +/- 57 g x h/l, p < 0.001) in the HD group compared to control group. RM peak plasma levels 15 min after application were not different in both groups (3.0 +/- 1.1 vs 4.2 +/- 1.7 mmol/l, NS), however, significantly lower 60 min (1.6 +/- 0.4 vs 3.7 +/- 1.5 mmol/l, p < 0.01) and 240 min (0.7 +/- 0.3 vs 2.3 +/- 0.7 p < 0.001) after angiography. CrCl showed no difference 1 week (24 +/- 11 vs 19 +/- 9 ml/min, ns) and 8 weeks (24 +/- 5 vs 20 +/- 9 ml/min, NS) after angiography from baseline or between the groups. In each group, 2 patients developed end-stage renal disease and requested permanent dialysis during the 8-week follow-up. Simultaneous dialysis reduces AUC of iomeprol significantly, however, does not influence plasma peak concentration after angiography. Renal function and incidence of end-stage renal failure were not influenced by online-dialysis.


Changes in cell-to-cell electrical coupling associated with left ventricular hypertrophy.
The impedance to current flow in the intracellular compartment of guinea pig left ventricular myocardium was measured at 20 degrees C and 37 degrees C using tissue from hypertrophied hearts subjected to aortic constriction. Alternating current of varying frequency was passed longitudinally along myocardial preparations, which revealed two time constants: one attributed to the surface membrane at the ends of the preparation and a second lying in the intracellular pathway. The longitudinal impedance was quantitatively analyzed in terms of a parallel intracellular and extracellular pathway; the former had two series components, one attributable to the sarcoplasm and the other to the low-resistance junctions between adjacent cells. This interpretation was consistent (1) with control experiments using n-heptanol, which increased the component attributed to intercellular junctions but not sarcoplasmic resistivity, and (2) with suspensions of isolated myocytes, which yielded a similar value for the sarcoplasmic resistivity. Aortic constriction increased the heart weight-to-body weight ratio of experimental animals from a mean value of 3.10 +/- 0.28 to 5.05 +/- 0.83 g/kg after 50 days of constriction and 5.60 +/- 0.95 g/kg after 150 days of constriction. An increase of heart weight-to-body weight ratio at 150 days of constriction was associated with an increased intracellular resistivity, which could be attributed solely to an increase of the junctional resistance between adjacent cells by approximately 44% at 20 degrees C and 140% at 37 degrees C; the sarcoplasmic resistivity was unchanged. The results are discussed in terms of altered conduction in hypertrophied myocardium as a possible basis for arrhythmias in this tissue.


Inguinal hernia as a rare manifestation of meconium peritonitis: report of a case.
The usual manifestations of meconium peritonitis confined to the inguinoscrotal region are soft hydroceles, hard nodules in the scrotum, and, occasionally, calcified nodules in the wall of a hernia sac, with or without calcification on abdominal X-ray. Inguinal hernia is an extremely rare manifestation of healed meconium peritonitis. An unusual presentation of meconium peritonitis encountered during hernia repair is described herein to alert the pediatric surgeon of this possibility to avoid unnecessary abdominal exploration.


Draft Genome Sequence of the Animal and Human Pathogen Malassezia pachydermatis Strain CBS 1879.
Malassezia pachydermatis is a basidiomycetous yeast that causes infections in humans and animals. Here, we report the genome sequence of Malassezia pachydermatis strain CBS 1879, which will facilitate the study of mechanisms underlying pathogenicity of the only non-lipid-dependent Malasezzia species.


The effects of tonicity on tension and stiffness of tetanized skeletal muscle fibres of the frog.
Tension and stiffness of tetanically activated skeletal muscle fibres of the frog were studied at varied tonicity of the extracellular medium (1.7-3.2 degrees C; sarcomere length, 2.13-2.22 microns). The stiffness was measured from the change in peak tension in response to fast (0.2 ms) stretches and releases of small amplitude (0.11-0.15% of the fibre length). The bathing solution was made hypotonic by reduction of NaCl and hypertonic by addition of sucrose. The osmotic strength of the solutions tested varied from 81 to 168% of the isotonic value. Maximum tetanic tension decreased markedly with increased tonicity. The active stiffness, on the other hand, increased as the tonicity was raised, and the tension/stiffness ratio (the total extension of the undamped fibre elasticity) was thus greatly reduced under these conditions. Evidence is presented to show that the change in the tension/stiffness ratio is due neither to the development of rigor cross-bridges nor to the recruitment of passive parallel-elastic elements in response to increased tonicity. Neither are viscous-like components important for explaining the effect. A change in the tension/stiffness ratio, similar to that seen in response to increased tonicity, did not occur as fibre width was reduced by increasing the sarcomere length. This suggests that the changes in the fibre volume affect this ratio mainly by mechanisms that are unrelated to changes in lateral spacing between the myofilaments.


Internet-Based Survivorship Care Plans for Adult Survivors of Childhood Cancer: A Pilot Study.
Survivorship care plans (SCPs) provide health information to survivors and providers. An existing internet-based SCP generator was adapted to incorporate guidelines for adult survivors of pediatric leukemia and lymphoma. Survivors created an SCP online and completed a survey. Survivors (N = 30) took an average of 10 minutes to complete the SCP. The majority (95%) found the platform easy to use, would recommend it to others (85%), and intended to share SCP with their healthcare team (90%). Thus, a patient-generated internet-based SCP for adult survivors of childhood cancer may be a feasible tool to improve consistency of information for survivors and their providers.


Cell Penetrating Peptide-Based Redox-Sensitive Vaccine Delivery System for Subcutaneous Vaccination.
In immunotherapy, induction of potent cellular immunity by vaccination is essential to treat intracellular infectious diseases and tumors. In this work, we designed a new synthetic peptide carrier, Cys-Trp-Trp-Arg8-Cys-Arg8-Cys-Arg8-Cys, for vaccine delivery by integrating a redox-responsive disulfide bond cross-linking and cell-penetrating peptide arginine octamer. The carrier peptide bound to the antigen protein ovalbumin (OVA) via electrostatic self-assembly to form peptide/OVA nanocomposites. Then, the spontaneous oxidization of the thiols of the cysteine residues induced interpeptide disulfide bond cross-linking to construct denser peptide/OVA condensates. The cell-penetrating peptides incorporated in the carrier peptide could increase antigen uptake by antigen presenting cells. After being internalized by antigen presenting cells, the antigen could be rapidly released in cytoplasm along with degradation of the disulfide bonds by intracellular glutathione, which could promote potent CD8+ T cell immunity. The cross-linked peptide/OVA condensates were used for subcutaneous vaccination. The results showed that the peptide carrier mediated potent antigen-specific immune response by significantly increasing IgG titer; splenocyte proliferation; the secretion level of cytokines INF-γ, IL-12, IL-4, and IL-10; immune memory function, and the activation and maturation of dendritic cells. From the results, the low-molecular weight vaccine-condensing peptide with definite chemical composition could be developed as a novel class of vaccine delivery systems.


Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis.
Autoimmune pancreatitis (AIP) has been divided into subtypes 1 (lymphoplasmacytic sclerosing pancreatitis) and 2 (idiopathic duct centric pancreatitis). We compared clinical profiles and long-term outcomes of types 1 and 2 AIP. We compared clinical presentation, relapse, and vital status of 78 patients with type 1 AIP who met the original HISORt criteria and 19 patients with histologically confirmed type 2 AIP. At presentation, patients with type 1 AIP were older than those with type 2 AIP (62 +/- 14 vs 48 +/- 19 years; P < .0001) and had a greater prevalence of increased serum levels of immunoglobulin G4 (47/59 [80%] vs 1/6 [17%]; P = .004). Patients with type 1 were more likely than those with type 2 to have proximal biliary, retroperitoneal, renal, or salivary disease (60% vs 0; P < .0001). Inflammatory bowel disease was associated with types 1 and 2 (6% vs 16%; P = .37). During median clinical follow-up periods of 42 and 29 months, respectively, 47% of patients with type 1 and none of those with type 2 experienced a relapse. In type 1 AIP, proximal biliary involvement (hazard ratio [HR], 2.12; P = .038) and diffuse pancreatic swelling (HR, 2.00; P = .049) were predictive of relapse, whereas pancreaticoduodenectomy reduced the relapse rate (vs the corticosteroid-treated group; HR, 0.15; P = .0001). After median follow-up periods of 58 and 89 months (types 1 and 2, respectively), the 5-year survival rates for both groups were similar to those of the age- and sex-matched US population. Types 1 and 2 AIP have distinct clinical profiles. Patients with type 1 AIP have a high relapse rate, but patients with type 2 AIP do not experience relapse. AIP does not affect long-term survival.


The expression of Toll-like receptor 5 in preterm histologic chorioamnionitis.
Spontaneous preterm birth is often caused by chorioamnionitis. Toll-like receptors (TLRs) have a role in the response of the innate immune system. The role of TLR5 in chorioamnionitis remains unclear: however, TLR5 was reported to have a significantly stronger effect on the induction of interleukin (IL)-6 when compared with other TLRs in amniotic epithelial cells. The aim of this study was to investigate TLR5 expression in placentas with preterm histologic chorioamnionitis (HCA). The expression levels of TLR5 were evaluated in the amnions, chorions, deciduae and villi with and without HCA using immunohistochemistry. The co-localization of IL-6 or IL-8 with TLR5 was examined by immunofluorescence. The production of IL-6 was examined in primary tissue cultured fetal membranes treated with and without the TLR5 agonist. The protein expression of TLR5 was significantly increased in amnions with HCA (p<0.05) and showed a trend toward an increase in chorions with HCA, whereas no significant difference was detected in the villi and decidua. TLR5 co-localized with IL-6 and IL-8 in amnions and chorions. IL-6 showed a significant increase (p<0.05) with the TLR5 agonist. These results suggest that TLR5 plays a role in the pathogenesis of preterm HCA and IL-6 production.


[Disease profiles and therapy effects of patients in mother-child rehabilitation centres].
Within the setting of external quality management of mother-child rehabilitation centres the short-term and medium-term therapy effects as well as the disease profiles of patients were analysed. This paper is focused on the changing of the main symptoms among the mothers. The patients' state of health is essentially characterized by physical and psychological exhaustion as well as by multimorbidity. It is strongly associated with the mothers' current situation of living. Before intervention the patients' health status was significantly impaired. Directly after the treatment high or very high therapy effects were found. All indicators are still higher after 6 months than they were at the beginning of the treatment. The results of a quasi-control population give evidence that these effects are caused by the treatment. First trends about the children treated show that behaviour problems can be reduced and the quality of life enhanced.


Engineering of the spinosyn PKS: directing starter unit incorporation.
The spinosyns are a family of potent and highly selective insect control agents that display a favorable environmental profile. As some regions of the spinosyn molecule are recalcitrant to chemical modification, a targeted genetic approach was carried out to generate new analogues. The polyketide synthase (PKS) loading modules from the avermectin PKS of Streptomyces avermitilis and the erythromcyin PKS of Saccharopolyspora erythraea were each used to replace the spinosyn PKS loading module. Both of the resulting strains containing hybrid PKS pathways produced the anticipated spinosyn analogues. Supplementation of the culture media with a range of exogenous carboxylic acids led to the successful incorporation of these novel elements to yield further novel spinosyn molecules, some of which demonstrated potent and new insecticidal activities. Furthermore, it has been demonstrated that semisynthesis of such novel metabolites can then be used to generate active analogues, demonstrating the effectiveness of utilizing these complementary methods to search the chemical space around this template.


The alymphoplasia (aly) mutation co-segregates with the intercellular adhesion molecule-2 (lcam-2) on mouse chromosome 11.
A new spontaneous autosomal recessive mutation alymphoplasia (aly), which causes a systemic defect of lymph nodes and Peyer's patches, was mapped on mouse chromosome 11 by linkage analysis using (ALY x MSM)F1 x ALY backcross progeny (155 mice). The gene order and map distances on the chromosome were as follows (cM +/- SD); D11Mit14 (AntP91a), Krt-1 -(0.7 +/- 0.6)--D11Mit59--(1.9 +/- 1.1)--D11Mit52, D11Nds7 (Gfap)--(0.7 +/- 0.6)--aly, D11Mit10, D11Mit13 (Ace), D11Mit58 (Myla), lcam-2--(8.4 +/- 2.2)--D11Mit12. No recombinant was found among aly, D11Mit10, D11Mit13, D11Mit58 and lcam-2, suggesting the possible involvement of lcam-2 in the aly mutation. However, the nucleotide sequence of the lcam-2 gene of aly/aly mouse was identical to that of the control mouse. No difference was detected between aly/aly and the control mouse for expression of the gene by both Northern blot and reverse transcriptase polymerase chain reaction analyses. Furthermore, immunohistochemical analysis using a mAb revealed that the ICAM-2 protein was normally distributed in various tissues. These findings indicate that aly/aly mice do not suffer from defects of lcam-2. The four polymorphic microsatellite markers tightly linked with the aly gene will serve as admirable guideposts for a chromosomal walk to the aly gene.


Irf5-deficient mice are protected from pristane-induced lupus via increased Th2 cytokines and altered IgG class switching.
Polymorphisms in the transcription factor interferon (IFN) regulatory factor 5 (IRF5) have been identified that show a strong association with an increased risk of developing the autoimmune disease systemic lupus erythematosus (SLE). A potential pathological role for IRF5 in SLE development is supported by the fact that increased IRF5 mRNA and protein are observed in primary blood cells of SLE patients and this correlates with an increased risk of developing the disease. Here, we demonstrate that IRF5 is required for pristane-induced SLE via its ability to control multiple facets of autoimmunity. We show that IRF5 is required for pathological hypergammaglobulinemia and, in the absence of IRF5, IgG class switching is reduced. Examination of in vivo cytokine expression (and autoantibody production) identified an increase in Irf5(-/-) mice of Th2 cytokines. In addition, we provide clear evidence that loss of Irf5 significantly weakens the in vivo type I IFN signature critical for disease pathogenesis in this model of murine lupus. Together, these findings demonstrate the importance of IRF5 for autoimmunity and provide a significant new insight into how overexpression of IRF5 in blood cells of SLE patients may contribute to disease pathogenesis.


Top-ranked cycle flux network analysis of molecular photocells.
We introduce a top-ranked cycle flux ranking scheme of network analysis to assess the performance of molecular junction solar cells. By mapping the Lindblad master equation to the quantum-transition network, we propose a microscopic Hamiltonian description underpinning the rate equations commonly used to characterize molecular photocells. Our approach elucidates the paramount significance of edge flux and unveils two pertinent electron transfer pathways that play equally important roles in robust photocurrent generation. Furthermore, we demonstrate that nonradiative loss processes impede the maximum power efficiency of photocells, which may otherwise be above the Curzon-Ahlborn limit. These findings shed light on the intricate functionalities that govern molecular photovoltaics and offer a comprehensive approach to address them in a systematic way.


Kinetic theory analysis of laser ablation of carbon.
The paper presents a model of ablation of carbon by a nanosecond laser pulse that considers the kinetics of the process. The model approximates the process as sublimation and combines conduction heat transfer in the target with the gas dynamics of the ablated plume which are coupled through the boundary conditions at the interface. The ablated mass flux and the temperature of the ablating material are obtained from the conservation relations at the interface derived from the momentum solution of the Boltzmann equation for arbitrary strong evaporation. The effects of laser intensity and ambient pressure on the ablated mass flux and parameters of vapor plume are studied. It is shown that most of the time the ablation rate is restricted by the kinetic theory limitation on the maximum mass flux that can be attained in a phase-change process. This fact makes the model tolerant of possible inaccuracies in calculating the saturation pressure of carbon vapor.


The gendered widowhood effect and social mortality gap.
With few exceptions, greater disparities in mortality risk by socio-economic status (SES) have been found among men than among women. Most research has also shown that the higher mortality risk after widowhood (the widowhood effect) is greater for men. However, a different picture appears when examining these associations jointly. Based on Swedish register data, this study shows that widowhood weakens, or even reverses, the sex differences in socio-economic disparities in mortality. The overall findings also indicate that higher SES elevates the widowhood effect for men but diminishes it for women, and that the widowhood effect is greater for women than men in the lowest SES categories. These results imply that men with higher SES are more vulnerable after widowhood, perhaps because of their previous relatively privileged situation. The disadvantage of widows in lower SES categories may reflect exposure to financial strains after spousal loss and inequalities in the healthcare system.


Is smoking an extra hazard in pregnant MS women? Findings from a population-based registry in Norway.
Multiple sclerosis (MS) in women leads to increased risk of operative delivery and reduced birth weight, which are presumably related to the neurological dysfunction in this patient group. Lifestyle factors may also contribute, and we therefore investigated smoking habits and relevant social factors in pregnant MS women. In total, 372,128 births were registered in the compulsory Medical Birth Registry of Norway from December 1, 1998 to October 6, 2005, and of them 250 by MS mothers. The MS births were compared with all the non-MS births. Smoking during pregnancy was not increased in the MS group compared with the non-MS references. From 1998 to 2005 the MS group had a larger reduction in smoking rate during pregnancy than the reference group. The differences in pregnancy and birth outcome between smokers and non-smokers were similar in the MS and the reference group. Those in the smoking MS group had no increase in birth complications, operative interventions or negative birth outcome compared with those in the smoking reference group. Smoking during pregnancy did not explain the birth weight reduction found for newborns of MS mothers.


S(1)<--S(0) transition of 2,3-benzofluorene at low temperatures in the gas phase.
The S(1)((1)A('))<--S(0)((1)A(')) absorption spectrum of jet-cooled 2,3-benzofluorene (Bzf) has been measured by cavity ring-down spectroscopy. The potential energy surfaces of the S(n=0,1,2) states of Bzf have been investigated with calculations based on the time-dependent density functional theory (TD-DFT). At the B3LYP/TZ level of theory, TD-DFT does not deliver a realistic difference between the excited S(1) and S(2) potential energy surfaces, a problem which can be avoided by introducing a reference geometry where this difference coincides with the observation. In this geometry, an expression for the Herzberg-Teller corrected intensities of the vibronic bands is proposed, allowing a straightforward assignment of the observed a(') modes below 900 cm(-1), including realistic calculated intensities. For vibronic bands at higher energies, the agreement between calculated and observed modes is deteriorated by substantial Dushinsky rotations and nonparabolicities of the potential energy surface S(1).


An Ultra-Violet Tolerant Wild-Type Strain of Melanin-Producing Bacillus thuringiensis.
Bacillus thuringiensis is the most successful biological control agent used in agriculture, forestry and mosquito control. However, the insecticidal activity of the B. thuringiensis formulation is not very stable and rapidly loses its biological activity under field conditions, due to the ultraviolet radiation in sunlight. Melanin is known to absorb radiation therefore photo protection of B. thuringiensis based on melanin has been extensively studied. The aim of this study was to find a wild type strain of naturally melanin-producing B. thuringiensis to avoid any mutation or manipulation that can affect the Cry protein content. Bacillus thuringiensis strains were isolated from soils of different States of Mexico and pigment extraction was followed by lowering the pH to 2 using 1N HCl. Pigment was characterized by some chemical tests based on its solubility, bleaching by H2O2 and flocculation with FeCl3, and using an Infrared (IR) spectrum. Ultraviolet (UV) irradiation experiment was performed to probe the melanin efficacy. ELI52 strain of B. thuringiensis was confirmed to naturally produce melanin. The Cry protein analysis suggested that ELI52 is probably a B. thuringiensis subsp. israelensis strain with toxic activity against the Diptera order of insects. Ultra Violet protection efficacy of melanin was probed counting total viable colonies after UV radiation and comparing the results with the non-producing melanin strain L-DOPA (L-3, 4-dihydroxyphenylalanine) was also detected in the culture. ELI52 strain showed an antagonistic effect over some common bacteria from the environment. ELI52 wild-type strain of B. thuringiensis is a good bio-insecticide that produces melanin with UV-resistance that is probably toxic against the Diptera order of insects and can inhibit the growth of other environmental bacteria.


Titanium oxide-based optoelectronic synapses with visual memory synergistically adjusted by internal emotions and ambient illumination.
Brain-inspired neuromorphic computing has become one of the critical technologies to overcome the bottleneck of von Neumann architecture. It is a vital step to construct a brain-like neuromorphic computing system at the hardware level by utilizing artificial synaptic devices. Compared with electronic synaptic devices, optoelectronic synaptic devices have the advantages of low power consumption, low crosstalk, and high bandwidth. Artificial optoelectronic synapses, analogous to retinal structure, can directly respond to and process light signal information to mimic the neuromorphic visual system. As high-level nerve impulses, both generated and regulated, emotions affect the strength and persistence of memory. Ambient illumination can provide visual perception to distinguish the size, color, and other characteristics of objects as well as affect the nonvisual functions of individuals, such as emotional states, thereby affecting learning and memory function. Herein, an artificial optoelectronic synapse composed of ITO/TiO2-x /p-Si was proposed. A variety of biologically dependent synaptic plasticity relating to learning and memory, including short-term synaptic plasticity, long-term synaptic plasticity, and learning-forgetting-relearning multifunctional advanced synaptic activity, was successfully simulated. A 3 × 3 artificial optoelectronic synapse array based on 9 devices was constructed to mimic the functions of visual learning and memory affected by internal emotion and ambient illumination. The proposed artificial optoelectronic synapse will exhibit great potential in visual and image information perception and memory.


[EPIDEMIOLOGY OF OVER-ACTIVE BLADDER (OAB) SYNDROME].
An over-active bladder is a common disorder which influences women's health and quality of life. There is difficulty defining the exact prevalence of the disorder since there are various definitions in the literature. The ICS definition from 2002 on the over-active bladder (OAB) syndrome enables more uniformity, by declaring that OAB syndrome is a symptomatic syndrome defined as presence of urgency with or without urinary incontinence, mostly accompanied by frequency and nocturia. In this article we reviewed the current medical literature on the prevalence of the OAB syndrome by focusing on relevant crosssectional and longitudinal studies, the trend changes during life, co-morbidities, the influence of quality of life and the economic burden following the disorder and its treatment. The authors' hope is that elevating awareness of the OAB syndrome will help improve its diagnosis and treatment.


Substituted Ortho-Benzynes: Properties of the Triple Bond.
Ortho-benzyne has been well studied by both experiment and theory. Its substituted variants, however, have been less carefully examined. Benchmark data are computed for unsubstituted ortho-benzyne using several density functional theory functionals and basis sets, up to cc-pVQZ. Optimized geometries for the substituted ortho-benzyne as well as harmonic vibrational frequencies and singlet-triplet splittings are computed using the benchmarked functionals. A proximal (syn)OH substitution causes a mean θ1 distortion of +8.1 ± 1.4° from ortho-benzyne. Substituting in the proximal position with F shifts the singlet-triplet splitting by +4.5 ± 0.4 kcal mol-1 from ortho-benzyne. Natural bond orbital analysis, including natural Coulomb electrostatics, elucidates the presence of three influences from the selected substituents: hyperconjugative, resonance, and electrostatic effects.


Reflective practice and experiential learning: tools for continuing professional development.
The models of reflective practice and experiential learning, described within this article, provide the dental practitioner and his/her team with realistic methods by which they can improve their skills and working atmosphere, and also reduce occupational stress. The reflective dentist is one who engages his/her team in a process of discussion regarding a variety of clinical situations, and who learns from both positive and negative clinical experience. This article offers a detailed analysis of reflective practice and experiential learning, and the ways in which application of these procedures can contribute significantly to the continuing professional development of dentists and dental teams.


Direct Observation of Inherent Atomic-Scale Defect Disorders responsible for High-Performance Ti1-x Hfx NiSn1-y Sby Half-Heusler Thermoelectric Alloys.
Structural defects often dominate the electronic- and thermal-transport properties of thermoelectric (TE) materials and are thus a central ingredient for improving their performance. However, understanding the relationship between TE performance and the disordered atomic defects that are generally inherent in nanostructured alloys remains a challenge. Herein, the use of scanning transmission electron microscopy to visualize atomic defects directly is described and disordered atomic-scale defects are demonstrated to be responsible for the enhancement of TE performance in nanostructured Ti1-x Hfx NiSn1-y Sby half-Heusler alloys. The disordered defects at all atomic sites induce a local composition fluctuation, effectively scattering phonons and improving the power factor. It is observed that the Ni interstitial and Ti,Hf/Sn antisite defects are collectively formed, leading to significant atomic disorder that causes the additional reduction of lattice thermal conductivity. The Ti1-x Hfx NiSn1-y Sby alloys containing inherent atomic-scale defect disorders are produced in one hour by a newly developed process of temperature-regulated rapid solidification followed by sintering. The collective atomic-scale defect disorder improves the zT to 1.09 ± 0.12 at 800 K for the Ti0.5 Hf0.5 NiSn0.98 Sb0.02 alloy. These results provide a promising avenue for improving the TE performance of state-of-the-art materials.


Intestinal current measurement versus nasal potential difference measurements for diagnosis of cystic fibrosis: a case-control study.
Nasal potential difference (NPD) and intestinal current measurement (ICM) are functional CFTR tests that are used as adjunctive diagnostic tools for cystic fibrosis (CF). Smoking has a systemic negative impact on CFTR function. A diagnostic comparison between NPD and ICM and the impact of smoking on both CFTR tests has not been done. The sweat chloride test, NPD, and ICM were performed in 18 patients with CF (sweat chloride >60 mmol/l), including 6 pancreatic sufficient (PS) patients, and 13 healthy controls, including 8 smokers. The NPD CFTR response to Cl-free and isoproterenol perfusion (Δ0Cl- + Iso) was compared to the ICM CFTR response to forskolin/IBMX, carbachol, and histamine (ΔIsc, forskolin/IBMX+ carbachol+histamine). The mean NPD CFTR response and ICM CFTR response between patients with CF and healthy controls was significantly different (p <0.001), but not between patients with CF who were PS and those who were pancreatic insufficient (PI). Smokers have a decreased CFTR response measured by NPD (p = 0.049). For ICM there is a trend towards decreased CFTR response (NS). Three healthy control smokers had NPD responses within the CF-range. In contrast to NPD, there was no overlap of the ICM response between patients with CF and controls. ICM is superior to NPD in distinguishing between patients with CF who have a sweat chloride > 60 mmol/l and healthy controls, including smokers. Neither NPD nor ICM differentiated between patients with CF who were PS from those who were PI. Smoking has a negative impact on CFTR function in healthy controls measured by NPD and challenges the diagnostic interpretation of NPD, but not ICM.


Differential response of estrogen receptor subtypes to 1,3-diarylindene and 2,3-diarylindene ligands.
Estrogen receptors (ERs) control transcription of genes important for normal human development and reproduction. The signaling networks are complex, and there is a need for a molecular level understanding of the roles of receptor subtypes ERalpha and ERbeta in normal physiology and as therapeutic targets. We synthesized two series of ER ligands, based on a common indene scaffold, in an attempt to develop compounds that can selectively modulate ER-mediated transcription. The 3-ethyl-1,2-diarylindenes, utilizing an amide linker for the 1-aryl extension, bind weakly to the ERs. The 2,3-diarylindenes bind with high affinity to the ER subtypes and demonstrate a range of different biological activities, both in transcriptional reporter gene assays and inhibition of estradiol-stimulated proliferation of MCF-7 cells. Several ligands differentiate between ERalpha and ERbeta subtypes at an estrogen response element (ERE), displaying various levels of partial to full agonist activity at ERalpha, while antagonizing estradiol action at ERbeta.


Radiopharmaceutical treatment of malignant pheochromocytoma.
Apart from relieving effects of secreted catecholamines, treatments of malignant pheochromocytoma have achieved little success. When the radiopharmaceutical, meta-[131I] iodobenzylguanidine (I-131 MIBG ), was found to concentrate in some malignant pheochromocytomas, we calculated that this agent could impart therapeutic doses of radiation to these tumors. We therefore treated five patients with two to four doses of I-131 MIBG prepared in high specific activity, 8-11 Ci/mmol. Individual doses were given at 3- to 10-mo intervals and in 97- to 197-mCi amounts. Two patients exhibited subjective and objective benefits. Their tumors declined in size (to 28% and 30% of original volumes) and in hormone secretion (to 50% or less of baseline rates). The other three patients manifested few symptoms before treatment and showed few or no objective improvement afterward. The tumors of the patients who responded to I-131 MIBG (a) appeared to be more rapidly growing, (b) received more cumulative rads, and (c) were more predominantly in soft tissues (in contrast to bone) than those in the patients who obtained little benefit. No toxic effects were encountered during the treatments, and only minor and temporary untoward responses were seen later.


Nonmonotonic field-dependent magnetic permeability of a paramagnetic ferrofluid emulsion.
The ferrofluid emulsion, made of kerosene-based ferrofluid droplets suspended in nonmiscible aviation oil, demonstrates experimentally the nonmonotonic dependence of the effective magnetic permeability as a function of the uniform static magnetic field. In weak fields the emulsion permeability rapidly grows; it reaches its maximum at fields on the order of 1 kA/m; after that, it decays to zero. The theoretical explanation of the effect, as we show here, could be based on the following idea: In a weak magnetic field the growth of the induced droplet magnetic moment is faster than the linear one due to the droplet elongation accompanied by the reduction of the demagnetizing field. Further increase of the external magnetic field strength cannot lead to a significant decrease of the demagnetizing field, as the droplets are already highly elongated. On the other hand, the magnetic susceptibility of the ferrofluid reduces with the field strength. Thus, the effective magnetic permeability of the ferrofluid suspension starts decreasing. The developed theoretical model describes well the experimental observations.


Novel features of the respiratory tract T-cell response to influenza virus infection: lung T cells increase expression of gamma interferon mRNA in vivo and maintain high levels of mRNA expression for interleukin-5 (IL-5) and IL-10.
Analysis of the respiratory tract before and after primary influenza virus infection revealed a virus-induced preferential accumulation of a CD8+ T-cell population that coexpresses mRNA for interleukin-5 (IL-5) and IL-10 with virus dose-dependent high levels of gamma interferon. However, cytokine production in lung tissues was not restricted to the T-cell population, since CD3- cells were found to express mRNA for various cytokines, including IL-4 and particularly IL-6 and granulocyte-macrophage colony-stimulating factor. These data provide in vivo evidence for a local respiratory tract immune response to influenza virus infection dominated by cytokine-producing CD8+ T cells.


A Concept Map of What Helps People with HD Live with their Condition.
The complex effects of Huntington's disease (HD) negatively impact on every area of independent living. The perspectives of people impacted by HD on how to best manage the disease are not clearly understood. To identify what is most helpful for living with HD from the perspectives of people with HD, family caregivers and health professionals. A cross-sectional, mixed methods concept mapping methodology was used. Participants generated statements during brainstorming in response to the question 'what helps people with HD live with their condition'. Participants then prioritised statements for importance and they grouped together statements that were related into clusters. Concept mapping software ('Ariadne' ®) used multi-dimensional scaling and hierarchical cluster analysis to produce a conceptual framework of participants views about what is helpful for people living with HD. Thirty nine people at various stages of HD disease progression, 48 family caregivers and 39 health professionals with experience of HD care (n = 126) participated. The most helpful factors for living with HD were identified as access to expert assessment and treatment for co-morbid mental health problems, integrated specialist multi-disciplinary HD expertise, and the provision of flexible care. HD requires specialist, expert, multidisciplinary care teams to manage it well. Specialists need to focus on the mental health aspects, and the provision must be flexible and responsive to current needs. Patients may have impaired insight into their abilities (e.g. driving) or the need for interventions, so carers' opinions should also be respected.