Prostaglandin E1 Increases Microcirculation in Random Pattern Flaps on Rats Measured with Laser Doppler Perfusion Imaging.
Reconstructive procedures with pedicled and free flaps are associated with a risk of ischemia. Prostaglandin E1 (PGE1) is a hormone-like substance with known antiischemic and tissue-protective effects. The aim of this study was to evaluate the effect of PGE1 on the microcirculation in random pattern skin flaps on rats. Twenty-four rats were divided into 2 groups: an intervention group given PGE1 for 6 hours and a control group given saline. The flap (2 × 10 cm) was created on the back of the rats, and the microcirculation was monitored with laser Doppler perfusion imaging in 5 different zones (1, proximal; 5, distal) before surgery and after 60, 180, and 360 minutes postoperatively. Before surgery, there was no difference in the perfusion in any zones between the intervention group and the control group. The mean perfusion values in zone 1 in the intervention group were significantly higher than those in the control group at 60, 180, and 360 minutes postoperatively (P = 0.02, P = 0.05, and P = 0.04, respectively). At 360 minutes, we also found significantly higher levels of perfusion in the intervention group in zones 4 and 5 (P = 0.05 and P = 0.03, respectively) compared with the controls. Comparing the perfusion at 360 to 60 minutes in the intervention group, we found a significant increase in microcirculation in all zones, which were not seen in the control group. PGE1 increased perfusion in the dermal random pattern flaps on rats.


A comparison of 3 methods for assessing insulin sensitivity in subjects with normal and abnormal glucose tolerance.
The euglycaemic clamp, insulin sensitivity test with somatostatin, and insulin sensitivity test without somatostatin, were compared as in vivo methods of assessing insulin sensitivity. Fifteen subjects with varying degrees of glucose tolerance were studied. Somatostatin was not found to influence the assessment of insulin sensitivity by the insulin sensitivity test. When glucose disposal was expressed as metabolic clearance rate significant strong correlations were found between the euglycaemic clamp technique and the insulin sensitivity test with (r = 0.90) and without (r = 0.83) somatostatin. The effects of the tests on intermediary metabolism were also similar, and all 3 tests showed a similar impairment of insulin sensitivity in subjects with abnormal glucose tolerance. The insulin sensitivity test without somatostatin thus provides a simple and economical tool for studying insulin sensitivity.


Application of iTRAQ-Based Quantitative Proteomics Approach to Identify Deregulated Proteins Associated with Liver Toxicity Induced by Polygonum Multiflorum in Rats.
Clinical reports on adverse reactions that result from Polygonum multiflorum (PM) and its preparations, especially regarding liver injury, have recently received widespread attention. This study aimed to investigate the mechanism of hepatotoxicity induced by different PM extracts through iTRAQ quantitative proteomics. The different PM extracts were orally administrated for 90 days to rats, and the hepatotoxicity effect was evaluated through measurement of biochemical indexes, oxidative damage indexes and hematoxylin-eosin (HE) staining. Then, the hepatotoxicity mechanism was investigated by iTRAQ quantitative proteomics. The results of biochemical and histopathological analyses showed that liver injury occurred in all groups of rats given by various PM extracts, which proved all of the PM extracts could induce hepatotoxicity. The hepatotoxicity mechanism may differ between the total extract group and the other groups through the results of biochemical indicators. The iTRAQ proteomics study showed that hepatotoxicity resulting from PM was mainly related to the abnormal activity of mitochondrion function-related oxidative phosphorylation pathways. This iTRAQ proteomics study revealed that the hepatotoxicity induced by PM is primarily related to the oxidative phosphorylation pathways. NADH dehydrogenase family proteins and Slc16a2 could be potential biomarkers of hepatotoxicity resulting from PM.


Induction of CD69 expression by cagPAI-positive Helicobacter pylori infection.
To investigate and elucidate the molecular mechanism that regulates inducible expression of CD69 by Helicobacter pylori (H. pylori) infection. The expression levels of CD69 in a T-cell line, Jurkat, primary human peripheral blood mononuclear cells (PBMCs), and CD4+ T cells, were assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and flow cytometry. Activation of CD69 promoter was detected by reporter gene. Nuclear factor (NF)-κB activation in Jurkat cells infected with H. pylori was evaluated by electrophoretic mobility shift assay. The role of NF-κB signaling in H. pylori-induced CD69 expression was analyzed using inhibitors of NF-κB and dominant-negative mutants. The isogenic mutants with disrupted cag pathogenicity island (cagPAI) and virD4 were used to elucidate the role of cagPAI-encoding type IV secretion system and CagA in CD69 expression. CD69 staining was detected in mucosal lymphocytes and macrophages in specimens of patients with H. pylori-positive gastritis. Although cagPAI-positive H. pylori and an isogenic mutant of virD4 induced CD69 expression, an isogenic mutant of cagPAI failed to induce this in Jurkat cells. H. pylori also induced CD69 expression in PBMCs and CD4+ T cells. The activation of the CD69 promoter by H. pylori was mediated through NF-κB. Transfection of dominant-negative mutants of IκBs, IκB kinases, and NF-κB-inducing kinase inhibited H. pylori-induced CD69 activation. Inhibitors of NF-κB suppressed H. pylori-induced CD69 mRNA expression. The results suggest that H. pylori induces CD69 expression through the activation of NF-κB. cagPAI might be relevant in the induction of CD69 expression in T cells. CD69 in T cells may play a role in H. pylori-induced gastritis.


Suppressor cell activity in tumor-bearing mice. III. Co-purification of a factor inhibiting cellular DNA synthesis and DNA polymerase activity.
The factor(s) derived from fibrosarcoma-induced suppressor T cells was sensitive to pronase and neuraminidase, but not to trypsin, beta-galactosidase, DNase, or RNase. Protein and RNA, but not DNA, synthesis were required to mediate suppression. Suppressor T cell-derived factor(s) could be precipitated by a 50% saturated ammonium sulfate (SAS) solution. The 50% SAS fraction inhibited both in vitro and in vivo spleen cell blastogenesis, whereas the 80% and unprecipitated fractions had no inhibitory activity. Using Sephadex G-200 chromatography, the 2nd protein fraction (fraction II) contained an inhibitor of both DNA polymerases (IDP) and DNA synthesis (IDS) activity, which possessed no cytotoxic activity. In vitro DNA polymerase alpha activity was suppressed by fraction II, whereas DNA polymerase beta and gamma activities remained unchanged. Molecular weight of IDP/IDS, as determined by Sephadex G-200 gel filtration chromatography, was approximately 14,500. Attempts to separate IDP/IDS activities found in fraction II by anion-exchange chromatography and slab gel electrophoresis were not successful, which suggested that the 2 activities were the same or very similar molecules.


Safety of an Escherichia coli-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine: an open-label phase I clinical trial.
An Escherichia coli-expressed recombinant bivalent human papillomavirus (types 16 and 18) vaccine candidate has been shown to be safe and immunogenic in preclinical trials. The safety of this vaccine was analyzed in an open-label phase I clinical trial in Jiangsu province, China. Thirty-eight healthy women from 18 to 55 y of age were enrolled and vaccinated at 0, 1, and 6 mo. Adverse events that occurred within 30 d after each injection and serious adverse events that occurred throughout the study were recorded. In addition, blood parameters were tested before and after each injection. All but one woman received all 3 doses. Thirty-two (84.2%) of the participants reported adverse events, all adverse events of which were mild, of short duration and resolved spontaneously. No serious adverse events occurred during the study. Changes in blood parameters after each injection were random, mild, and not clinically significant. These preliminary results show that a new Escherichia coli-expressed recombinant HPV 16/18 bivalent vaccine is well tolerated in healthy women and support further immunogenicity and efficacy studies for this HPV vaccine candidate.


Effects of pulsed electric field treatment on enhancing lipid recovery from the microalga, Scenedesmus.
Chloroform and methanol are superior solvents for lipid extraction from photosynthetic microorganisms, because they can overcome the resistance offered by the cell walls and membranes, but they are too toxic and expensive to use for large-scale fuel production. Biomass from the photosynthetic microalga Scenedesmus, subjected to a commercially available pre-treatment technology called Focused-Pulsed® (FP), yielded 3.1-fold more crude lipid and fatty acid methyl ester (FAME) after extraction with a range of solvents. FP treatment increased the FAME-to-crude-lipid ratio for all solvents, which means that the extraction of non-lipid materials was minimized, while the FAME profile itself was unchanged compared to the control. FP treatment also made it possible to use only a small proportion of chloroform and methanol, along with isopropanol, to obtain equivalent yields of lipid and FAME as with 100% chloroform plus methanol.


Auxin and growth regulation of rice coleoptile segments : molecular analysis.
Auxin-stimulated elongation of apical segments of rice (Oryza sativa L. cv Arborio) coleoptiles occurring in the first 4 hours of treatment has been studied. Cell extension promoted in the first 2 hours by 10 micromolar indole-3-acetic acid (IAA) is specifically auxin-dependent, whereas after 4 hours, elongation also depends on endogenous production of ethylene. Similar to other systems, rice coleoptile cell elongation stimulated by auxin requires continuous synthesis of RNA and protein. Two-dimensional gel analysis of the in vitro translation products obtained from polyadenylated RNAs extracted from treated and untreated segments after 1 or 4 hours from the initial addition of IAA shows few transcriptional differences. At 60 minutes of treatment, the level of three mRNAs coding for proteins of 22.5, 25, and 33 kilodaltons was moderately enhanced while the disappearance of a 38 kilodalton translation product was observed. Additional repression of another mRNA coding for a 28 kilodalton product begins to show by this time, but becomes more evident after 4 hours treatment. At 4 hours, four IAA-specific mRNA enhancements coding for proteins with molecular masses ranging between 35 to 40 kilodaltons were also observed. We discuss these data in relation to the possible involvement of IAA-mediated transcriptional regulation in growth promotion of rice coleoptiles and, more widely, in control of cell elongation.


Flavonoid-matrix cluster ions in MALDI mass spectrometry.
The behaviour of 2,5-dihydroxybenzoic acid (2,5-DHB) matrix under matrix-assisted laser desorption/ionisation (MALDI) conditions was investigated, and the formation of 2,5-DHB cluster ions, mainly dehydrated 2,5-DHB ions, is reported. Interestingly, in the mass spectra of this compound, besides dimers and trimers, protonated tetramers, pentamers, hexamers and heptamers were also found with significant abundance.The MALDI behaviour of four flavonoids, quercetin, myricetin, luteolin and kaempferol, using 2,5-DHB as matrix, was also investigated. The mass spectra of the flavonoids studied revealed a number of flavonoid-2,5-DHB cluster ions (mainly with the dehydrated 2,5-DHB). The number of clusters formed is dependent on the structure of the analyte. For luteolin and kaempferol, in particular, evidence was found for the formation of cluster ions involving retro Diels Alder fragments and intact flavonoids molecules, as well as the corresponding protonated retro Diels Alder fragments with dehydrated DHB molecules. All ion compositions were attributed taking into account high accuracy mass measurements and tandem mass spectrometry experiments.


Cultural adaptation and validation of the Persian version of the Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure.
To translate and validate the Persian version of the Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure (Persian DASH). Cultural translation and psychometric testing. Outpatient departments of orthopaedics surgery, primary care settings, rehabilitation medicine and physical therapy. Two hundred and seventy-one consecutive Persian-speaking patients with upper extremity disorders including subacromial impingement syndrome, rotator cuff disease, epicondylitis, ulnar nerve entrapment, bursitis, instability, carpal tunnel syndrome, tenosynovitis and adhesive capsulitis. The translation and cultural adaptation of the original questionnaire was carried out in accordance with published guidelines. The participants were asked to complete a questionnaire booklet including the Persian DASH, the Short Form General Health Survey (SF-36) and a visual analogue scale (VAS) of pain. In addition, 31 randomly selected patients were asked to complete the questionnaire 48 hours later for the second time. Cronbach's alpha coefficient for the Persian DASH was 0.96. The Persian DASH showed excellent test-retest reliability with intraclass correlation coefficient equal to 0.82 (P<0.01). The correlation between the Persian DASH and the functional scales of the Iranian SF-36 showed desirable results indicating a good convergent validity (Pearson's coefficients ranged from -0.25 to -0.72; P<0.001). The correlation between the Persian DASH and the visual analogue scale was 0.52 (P<0.01). The Persian DASH is a reliable and valid instrument to measure functional status in Persian-speaking patients with upper extremity disorders in Iran. It is simple and easy to use and now can be applied in clinical settings and future outcome studies in Iran and other Persian-speaking communities.


Flourishing and academic engagement among adolescents with overweight and obesity.
Overweight and obesity in adolescence are associated with several negative health indicators; the association with flourishing, an indicator of overall well-being, is less clear. To examine associations between weight status and indicators of flourishing and academic engagement in adolescents. Analyses included 22,078 adolescents (10-17 years) from the 2016 National Survey of Children's Health. Adolescents were grouped according to body mass index (BMI) classification; outcomes included indicators of flourishing and academic engagement. Logistic regression models assessed the odds of each outcome comparing adolescents with overweight and adolescents with obesity to healthy weight adolescents. For flourishing, adolescents with overweight and adolescents with obesity were less likely to stay calm during a challenge (17% and 30%, respectively; p < 0.01); adolescents with obesity were 30% less likely to finish a task they started (p < 0.001), and 34% less likely to show interest in new things (p < 0.001) in comparison to healthy weight peers. Adolescents with obesity were 26% less likely to care about doing well in school (p < 0.001), and adolescents with overweight and adolescents with obesity were significantly less likely to complete all required homework (19% and 34%, respectively) (p < 0.001), in comparison to healthy weight peers. A comprehensive approach to addressing overweight and obesity in adolescence should target improving academic engagement and flourishing to promote overall well-being.


Lactose intolerance: myths and facts. An update.
Lactose is the main carbohydrate present in human milk. It is a disaccharide made up of glucose and galactose. It is produced in the mammary glands, regardless of maternal diet. In addition to providing energy, it is the only source of dietary galactose, necessary for macromolecule synthesis, including oligosaccharides, glycoproteins, and glycolipids. It favors calcium, magnesium, and zinc absorption and retention. Its digestion by lactase and subsequent absorption occurs in the small intestine. Lactase deficiency may be classified into congenital primary (very rare), late-onset primary or secondary due to an injury of the intestine; it may cause intolerance with pain, abdominal distension, abdominal gas, and diarrhea. In the colon, it may be hydrolyzed by bifidobacteria and lactobacilli. The nutritional management of intolerance should always preserve breastfeeding. Lactose reduction or elimination should be transient, and eliminated food should be replaced with other similar in calorie, protein, mineral, and vitamin content.


Emergency department information: does it effect patients' perception and satisfaction about the care given in an emergency department?
The aim of this study was to find out if informing the patients about the facts of an emergency department (ED) on arrival influences their behaviour and satisfaction about the care given in the ED. For 5 days an information form was distributed on arrival to all patients visiting the ED and a questionnaire directed at all patients when leaving the ED. For a former 3 days the same questionnaire directed at the patients was distributed without giving them the information form. This form contained information about how the ED functions, how long and why the patients wait, and which patients are taken care of first. The patients who were not given the information form served as the control group; the patients who were given an information form but did not read it were also included in the same control group. Questionnaires of the informed group and the control group were compared. A total of 397 patients were given a questionnaire; 288 of them were given an information form and 109 did not receive a form. The number of the patients who read the information form was 178 and the rest (219 patients) served as controls. The informed group was more satisfied about the care given to them (p = 0.1), the total time spent in the ED (p = 0.3), and the information given to them (p = 0.1). More patients in the informed group stated that they would prefer this ED next time or recommend it to others (p = 0.02). The overall degree in satisfaction of the informed patients was better (p = 0.03). The differences in the overall satisfaction and preference of this ED's parameters were statistically significant, the other parameters were not so significant. These results proved that giving general information to patients visiting the ED can influence the degree of their satisfaction.


A comparative study of RNA and DNA as internal gene expression controls early in the developmental cycle of Chlamydia pneumoniae.
Many microbial pathogens invade and proliferate within host cells and the molecular mechanism underlying this behavior is currently being revealed for several bacterial species. Testing clinically relevant antibacterial compounds and elucidating their effects on gene expression requires adequate controls, especially when studying genetically intractable organisms such as Chlamydia spp., for which various gene fusions cannot be constructed. Until now, relative mRNA levels in Chlamydia have been measured using different internal gene expression controls, including 16S rRNA, mRNAs, and DNA. Here, we compared the advantages and disadvantages of various internal expression controls during the early phase of Chlamydia pneumoniae development. The relative abundance of target mRNAs varied using the different internal control RNAs. This was partly due to variation in the transcript stability of the RNA species. Also, seven out of nine of the analyzed RNAs increased fivefold or more between 2 and 14 h postinfection, while the amount of DNA and number of cells remained essentially unaltered. Our results suggest that RNA should not be used as a gene expression control during the early phase of Chlamydia development, and that intrinsic bacterial DNA is preferable for that purpose because it is stable, abundant, and its relative amount is generally correlated with bacterial numbers.


The impact of heat waves on transport volumes in an urban emergency medical services system: a retrospective review.
Heat waves pose a serious public health risk to particular patient populations, especially in urban areas. Emergency Medical Services (EMS) in many urban areas constitute the first line of regional preparation and response to major heat wave events; however, little is known on heat wave operational impact to the EMS system, such as call volume or demand. To examine the effect of heat wave periods on overall urban EMS system call volume and transport volume as well as the nature of the call types. Retrospective review of all emergency medical calls to an urban, two-tiered EMS system performed over a 5-year period from 2006-2010. Heat wave days (HWD) defined as two or more consecutive days of hot weather >32.2°C (90°F) were compared with similar non-heat wave days (nHWD) of the previous year to also include two calendar days prior to and after the heat wave. National Weather Service (NWS) temperature data, daily EMS call volume data, and call type codes were collected and underwent descriptive analysis. Thirty-one HWD were identified and compared with 93 nHWD. The mean maximum temperature for HWD was 34°C (93.2°F) compared with 25.3°C (77.6°F) for nHWD (P < .001). Average daily medical emergency calls (318.4 vs 296.3, P < .001) and actual patients transported per day (247.5 vs 198.3, P < .001) were significantly higher during HWD. There was no difference in daily medical emergency call volume or EMS transports between weekdays or weekend days. No significant differences on various call types were observed between HWD and nHWD except for "heat" related calls (7.7 vs 0.5, P < .001). Emergency Medical Services call volumes were significantly increased during heat waves, however there was minimal change in the types of calls received.


Molecular analyses confirm Brevicellicium in Trechisporales.
The genus Brevicellicium encompasses wood-inhabiting corticioid fungi characterized by isodiametric subhymenial hyphae, short basidia, and smooth, often subangular spores with a distinct apiculus. Eight new LSU nrDNA sequences and 13 new ITS nrDNA of this genus, including the type species, were aligned with 47 and 42 accessions respectively of species of Trechisporales obtained from GenBank, and phylogenetic analyses were performed. The order Trechisporales was confirmed as a monophyletic group; the genera Porpomyces, Sistotremastrum, Subulicystidium and Trechispora form a highly supported clade where all Brevicellicium sequences are included. Our analyses also support that this genus belongs to Hydnodontaceae. A new species, Brevicellicium atlanticum from the Azores Archipelago, is described.


[Three years experience of using mycosyst].
The aim of this study was to estimate therapeutical potentialities of the Mycosyst (Fluconazole) preparation, of the Gedeon-Richter company (Budapest, Hungary), in women with data for mycotic colpitis. 157 patients for three years period (April 2001-2004) were included in this study. Two groups of patients were formed. In 104 patients mycotic colpitis was diagnosed during curettage for feticide or missed abortion. Another 53 women were treated for mycotic colpitis unrelated to pregnancy. Complains of the patients disappear by the 48-th hour and in almost all women there were not complaints by the 4-th day. The most quickly were influenced itching, discomfort, erythema and dyspareunia and slowly and hardly discharge had been influenced. Mycosyst is a broad spectrum antimycotic agent of bistriazol type. It has good absorption and tissue saturation. 1-2 hours after oral administration maximal plasma concentration is achieved. Plasma half life is about 30 hours. This gave us opportunity for single or two doses Mycosyst for vaginal candidosis treatment. Use of two doses of 150 mg. was enough for acute forms treatment in almost 95% of cases. Mycosyst is sure, easy for use broad spectrum antimycotic from the azole group. This preparation is comparatively cheep and in the average Bulgarian income possibilities.


Associations of dietary fiber intake with long-term predicted cardiovascular disease risk and C-reactive protein levels (from the National Health and Nutrition Examination Survey Data [2005-2010]).
Dietary fiber intake might reduce cardiovascular risk factor levels and, in turn, might lower the long-term risk of cardiovascular disease (CVD). A total of 11,113 subjects, aged 20 to 79 years with no history of CVD, from the 2005 to 2010 National Health and Nutrition Examination Survey were included in the present study to examine associations of dietary fiber intake with predicted lifetime CVD risk and C-reactive protein levels. Dietary fiber intake showed a significant gradient association with the likelihood of having a low or an intermediate predicted lifetime CVD risk among young and middle-age adults. In fully adjusted multinomial logistic models, dietary fiber intake was related to a low lifetime CVD risk with an odds ratio of 2.71 (95% confidence interval 2.05 to 3.59) in the young adults and 2.13 (95% confidence interval 1.42 to 3.20) in the middle-age adults and was related to an intermediate lifetime risk of 2.65 (95% confidence interval 1.79 to 3.92) in the young and 1.98 (95% confidence interval 1.32 to 2.98) in the middle-age adults compared with a high lifetime risk. A significant inverse linear association was seen between dietary fiber intake and log-transformed C-reactive protein levels with a regression coefficient ± standard error of -0.18 ± 0.04 in the highest quartile of fiber intake compared with the lowest fiber intake. In conclusion, these data suggest that dietary fiber intake is independently associated with the predicted lifetime CVD risk, especially in young and middle-age adults. A greater amount of dietary fiber intake might be associated with lower C-reactive protein levels.


Self/nonself recognition in ascidian fertilization: vitelline coat protein HrVC70 is a candidate allorecognition molecule.
Ascidians are hermaphrodites releasing sperm and eggs simultaneously, but many species are self-sterile because of a self/nonself-recognition system in spermegg interaction. Here, we show that a 70-kDa vitelline coat protein, HrVC70, consisting of 12 epidermal growth factor-like repeats, plays a key role in self/nonself recognition during ascidian fertilization. We discovered that the amount of HrVC70 of the self-sterile mature oocytes is markedly higher than that of the self-fertile immature oocytes and that the selfsterile mature oocytes become self-fertile by acid treatment, which is able to release the HrVC70 from isolated vitelline coats. In addition, fertilization is strongly inhibited by the pretreatment of sperm with HrVC70 from a different individual, but not from the same individual, and the number of nonself sperm bound to HrVC70-agarose was significantly higher than that of self-sperm. A sequence analysis of HrVC70 disclosed that several amino acid residues in a restricted region are substituted at an individual level, with no identical sequences among the 10 individuals tested. Furthermore, genomic DNA analysis revealed that the epidermal growth factor-like domains correspond to the exons, and each intron is highly conserved among even- and odd-numbered introns, suggesting that multiple gene duplications or amplification of this region might have taken place during evolution. It was also found that diversity in cDNA sequences is derived from genomic DNA polymorphism probably elicited by crossing over and specific nucleotide substitutions. These results indicate that HrVC70 is a candidate allogeneic recognition molecule in the gamete interaction of the ascidian Halocynthia roretzi.


groE genes affect SOS repair in Escherichia coli.
Repair of UV-irradiated bacteriophage in Escherichia coli by Weigle reactivation requires functional recA+ and umuD+C+ genes. When the cells were UV irradiated, the groE heat shock gene products, GroES and GroEL, were needed for at least 50% of the Weigle reactivation of the single-stranded DNA phage S13. Because of repression of the umuDC and recA genes, Weigle reactivation is normally blocked by the lexA3(Ind-) mutation (which creates a noncleavable LexA protein), but it was restored by a combination of a high-copy-number umuD+C+ plasmid and a UV dose that increases groE expression. Maximal reactivation was achieved by elevated amounts of the Umu proteins, which was accomplished in part by UV-induced expression of the groE genes. By increasing the number of copies of the umuD+C+ genes, up to 50% of the normal amount of reactivation of S13 was achieved in an unirradiated recA+ host.


Health insurance in the United States.
About two-thirds of Americans under the age of 65 have health insurance coverage. This leaves 43 million without. Sixteen million people with insurance are underinsured. Lack of insurance and inadequate insurance have serious consequences for individuals, families, and the country. This article provides facts about the current system of health insurance in the United States and government reform efforts.


[Evaluation of induction of drug-metabolizing enzyme mRNAs in primary cultures of cryopreserved human and cynomolgus monkey hepatocytes].
We introduce a method for measuring drug-metabolizing enzymes and transporters using real-time one-step RT-PCR with TaqMan probes. This method has the advantages of high sensitivity, simplicity, and linearity of quantification over a wide range of mRNA concentrations, making it particularly suitable for evaluating large numbers of samples, as required in expression profile determinations. We also introduce the use of primary cultures of cryopreserved human and cynomolgus monkey hepatocytes as an enzyme induction model. Furthermore, we introduce the combination of real-time one-step RT-PCR and hepatocytes for evaluating the potency of various drugs in inducing drug-metabolizing enzymes and transporters. We discuss the usefulness of evaluating the gene induction of drug-metabolizing enzymes and transporters following exposure to drugs in human and cynomolgus monkey hepatocytes. The combination of real-time one-step RT-PCR and primary cultures of cryopreserved hepatocytes is useful for preclinical drug evaluation and for screening to evaluate the induction potency of new drug candidates.


Prosthetic hip infection due to Campylobacter jejuni.
A woman in her 60s with a left hip prosthesis was presented with left hip pain and fever. She had an elevated white blood cell count and inflammatory markers. Synovial fluid Gram stain demonstrated curved Gram-negative rods identified as Campylobacter jejuni The patient initially refused surgery and after 3 months underwent one-stage exchange after which she was treated with 12 weeks of levofloxacin. Her inflammatory markers normalised and she was clinically doing well at her 6-month follow-up. C. jejuni is a rare cause of prosthetic joint infection and should be included in the differential diagnosis when a patient has risk factors even without significant preceding gastrointestinal symptoms. Per most recent Infectious Diseases Society of America guidelines, treatment after one-stage revision includes 4-6 weeks of intravenous antimicrobials followed by possible oral suppression therapy, while the European guidelines recommend 12 weeks of orally bioavailable antibiotics.


Expression of immunomodulating genes in prostate cancer and benign prostatic tissue.
To investigate the expression of immunomodulating genes in prostate cancer and benign prostatic tissue. We investigated by quantitative real-time polymerase chain reaction the expression of indoleamine 2,3-dioxygenase, arginase 1, arginase 2, inducible form of nitric oxide synthase, cyclooxygenase 2 (COX-2), programmed death ligand 1 and interleukin 10 in 36 matched pairs of samples from prostate cancer and benign prostatic tissue. Among the genes analyzed, arginase 2 and COX-2 showed statistically significant up-regulation and down-regulation, respectively, in malignant compared to benign prostate tissue. In addition, arginase 1 was more often present in cancer than benign samples. No significant modulation was detected for the other genes under investigation. Our data suggest that arginine metabolism may be involved in prostate cancer immune response evasion, whereas COX-2 may play a role in pathogenesis. We provide a snapshot of immunosuppressive gene expression at the transcriptional level in the prostate tumor microenvironment.


Near-field THz imaging of free induction decay from a tyrosine crystal.
We demonstrate images of free induction decay (FID) signals from a grain of tyrosine in the near-field of the THz frequency region. By combining electro-optic sampling with a charge-coupled-device (CCD) camera, our near-field THz microscope allows us to visualize the electric field blinking with the FID signal with spatial resolution of better than 70 microm. The oscillating frequency of the FID signal centered at approximately 1 THz corresponds to the vibrational mode of the tyrosine crystal. These results confirm that the THz near-field microscope can take spectroscopic images with subwavelength spatial resolution (approximately lambda/4).


Association of long-term SBP with clinical outcomes and quality of life in heart failure with preserved ejection fraction: an analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial.
To determine the associations of long-term SBP (LT-SBP) levels with clinical outcomes and health-related quality of life in heart failure with preserved ejection fraction (HFpEF). We analyzed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study with available different SBP measurements from different follow-ups (n = 3310). LT-SBP was the mean SBP value from 4-week measurement to the last one. The outcome measures are all-cause mortality and a composite of heart failure readmission or all-cause mortality and the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score. To determine the associations of LT-SBP and outcomes, we used adjusted Cox proportional hazards models and restricted cubic spline models. After multivariable adjustment, LT-SBP of 120-129 and 130-139 mmHg were associated with a lower risk of mortality (hazard ratio 0.66, 95% CI 0.51-0.87, P = 0.003; hazard ratio 0.68, 95% CI 0.51-0.90, P = 0.007, respectively); LT-SBP of 100-119 mmHg had similar risk of mortality (hazard ratio 0.96, 95% CI 0.72-1.28, P = 0.778) compared with LT-SBP of at least 140 mmHg. There was U-shaped relationship between LT-SBP and all-cause mortality (P < 0.001) with nadir risk occurring around 123 mmHg. Similar relationships were observed between LT-SBP and composite end point of heart failure readmission or all-cause mortality. The adjusted mean improvement in KCCQ score was significantly higher in the 120-129 mmHg group than in the at least 140 mmHg group beginning from the 12-month follow-up visit without significant differences in other groups. Among patients with HFpEF, long-term control of SBP level at 120-129 mmHg is independently associated with the highest risk reduction of all-cause mortality and improvement of KCCQ score. Future randomized clinical trials need to specifically evaluate optimal SBP treatment goals in patients with HFpEF.


An Open-Cage Fullerene That Mimics the C60 H10 (5,5)-Carbon Nanotube Endcap to Host Acetylene and Hydrogen Cyanide Molecules.
Treatment of the open-cage fullerene C63 H4 NO2 (Ph)2 (Py)(N2 C6 H4 ) (1) with methanol at 150 °C results in an orifice-enlargement reaction to give C69 H8 NO(CO2 Me)(Ph)(Py)(N2 C6 H4 ) (2). The overall yield from C60 to isolated 2 is 6.1 % (four steps). Compound 2 contains a 24-membered elliptic orifice that spans 8.45 Å along the major axis and 6.37 Å along the minor axis. The skeleton of 2 resembles the hypothetic C60 H10 (5,5)-carbon nanotube endcap. The cup-shaped structure of 2 is able to include water, hydrogen cyanide, and acetylene, forming H2 O@2, HCN@2, and C2 H2 @2, respectively. The molecular structures of H2 O@2 and HCN@2 have been determined by X-ray crystallography. The 1 H NMR spectra reveal substantial upfield shifts for the endohedral species, such as δ=-10.30 (for H2 O), -2.74 and -14.26 (for C2 H2 ), and -1.22 ppm (for HCN), owing to the strong shielding effects of the fullerene cage.


Pre-embolization study of ruptured cerebral aneurysms with helical CT.
Sixteen ruptured aneurysms in 16 patients considered endovascular embolizations were examined. The findings of axial source images (axial images) and reconstructed three-dimensional CT angiography (3D-CTA) of helical CT were compared to those of rotational digital subtraction angiography (DSA). The aneurysmal neck and arterial branches adjacent to the neck were closely investigated. In seven out of 16 cases (43.8%), information provided by axial images and/or 3D-CTA was more useful than that of rotational DSA in evaluating the aneurysmal neck and arterial branches. Helical CT can provide valuable information on ruptured aneurysms that cannot be obtained by rotational DSA in some patients. This technique is useful to obtain anatomical information about aneurysms and to select the best therapeutic method.


Cerebrovascular Function, Vascular Risk, and Lifestyle Patterns in Resistant Hypertension.
Impaired cerebrovascular reactivity (CVR) and blunted cerebral hemodynamic recruitment are thought to be important mechanisms linking hypertension to cerebrovascular and cognitive outcomes. Few studies have examined cardiovascular or dietary correlates of CVR among hypertensives. To delineate associations between cardiometabolic risk, diet, and cerebrovascular functioning among individuals with resistant hypertension from the TRIUMPH trial (n = 140). CVR was assessed by examining changes in tissue oxygenation (tissue oxygenation index [TOI] and oxygenated hemoglobin [HBO2]) using functional near-infrared spectroscopy (fNIRS) during a breath holding test, a standardized CVR assessment to elicit a hypercapnic response. Participants also underwent fNIRS during three cognitive challenge tasks. Vascular function was assessed by measurement of brachial artery flow-mediated dilation and hyperemic flow response. Cardiometabolic fitness was assessed from peak VO2 on an exercise treadmill test and body mass index. Dietary patterns were quantified using the DASH eating score. Cognitive function was assessed using a 45-minute test battery assessing Executive Function, Processing Speed, and Memory. Greater levels fitness (B = 0.30, p = 0.011), DASH compliance (B = 0.19, p = 0.045), and lower obesity (B = -0.30, p = 0.004), associated with greater changes in TOI, whereas greater flow-mediated dilation (B = 0.19, p = 0.031) and lower stroke risk (B = -0.19, p = 0.049) associated with greater HBO2. Similar associations were found for cerebral hemodynamic recruitment, and associations between CVR and cognition were moderated by duration of hypertension. Impaired CVR elevated cardiometabolic risk, obesity, vascular function, and fitness among hypertensives.


Complement C4 null alleles as a marker of gold or D-penicillamine toxicity in the treatment of rheumatoid arthritis.
C4 null alleles and HLA-DR antigens were defined in 48 rheumatoid arthritis (RA) subjects who had developed renal or heamatological side effects to gold or penicillamine, as compared to 33 RA subjects who had received the drugs for similar time periods without developing side effects. A C4A null allele was found in 56% of subjects with and 31% of those without side effects (P = 0.027, relative risk 2.8). A similar but statistically non-significant trend was observed with the C4B null allele (P = 0.64) resulting in a higher risk of drug toxicity in rheumatoid patients bearing either a C4A or C4B null allele (relative risk 5.7). Frequencies of DR3 and DR4 were similar in the two groups.


Delocalized Davydov D1 Ansatz for the Holstein polaron.
An efficient, yet very accurate trial wave function, constructed from projecting the well-known Davydov D1 Ansatz onto momentum eigenstates, is employed to study the ground state properties of the generalized Holstein Hamiltonian with simultaneous diagonal and off-diagonal coupling. Ground-state energies have been obtained with a precision matching that of the computationally much more demanding density-matrix renormalization group method. The delocalized D1 Ansatz lowers the ground-state energies at the Brillouin zone boundary significantly compared with the Toyozawa and Global-Local Ansätze in the weak coupling regime, while considerable improvement is demonstrated to have been achieved over the entire Brillouin zone in the strong coupling regime. Unique solutions are obtained with the delocalized D1 for different initial conditions when the transfer integral is 20 times the phonon frequency at the zone center, implying the absence of any self-trapping discontinuity. The scaled correlation variance is found to fit satisfactorily well with the predictions of the perturbation theories.


A prospective study of lung disease caused by Mycobacterium avium/Mycobacterium intracellulare.
This is a prospective study of 36 patients with lung infections caused by M. avium/M. intracellulare. The division of the patients into 2 prognostic groups ("good"/"others"), and the guidelines for their treatment are based on a previous report (3). The criteria for the division were co-existing lung disease and dyspnoea on admittance. The patients in group "good" were treated with isoniazid, rifampicin and ethambutol, in group "others" these were supplemented with one or more drugs. As in the previous study (3), the prognosis was far better for group "good" than for group "others". The patients in group "good" should be treated with isoniazid, rifampicin and ethambutol, unless the course of disease is unsatisfactory. The mortality was high in group "others" and half of the deaths were related to mycobacteriosis. Some patients became culture negative and others showed decreasing numbers of bacteria, but the value of the supplementary drugs could not be proven.


The Quality of Object Relations Scale.
The Quality of Object Relations Scale (QORS) provides a methodological and theoretical framework for personality classification based on relative level and quality of object relations. The authors believe that many available clinical assessment systems have little heuristic value, and propose that the QORS yields more meaningful descriptions of people. They discuss its theoretical basis in psychoanalytic object relations theory, and how its construction and rationale represent an attempt to incorporate recent thought relevant to the classification of personality. They include criteria for its organizational levels, prototypical vignettes, and a case demonstration. They also explore methodological issues relevant to clinical use and present reliability and validity data derived from empirical studies.


RAS and RHO family GTPase mutations in cancer: twin sons of different mothers?
The RAS and RHO family comprise two major branches of the RAS superfamily of small GTPases. These proteins function as regulated molecular switches and control cytoplasmic signaling networks that regulate a diversity of cellular processes, including cell proliferation and cell migration. In the early 1980s, mutationally activated RAS genes encoding KRAS, HRAS and NRAS were discovered in human cancer and now comprise the most frequently mutated oncogene family in cancer. Only recently, exome sequencing studies identified cancer-associated alterations in two RHO family GTPases, RAC1 and RHOA. RAS and RHO proteins share significant identity in their amino acid sequences, protein structure and biochemistry. Cancer-associated RAS mutant proteins harbor missense mutations that are found primarily at one of three mutational hotspots (G12, G13 and Q61) and have been identified as gain-of-function oncogenic alterations. Although these residues are conserved in RHO family proteins, the gain-of-function mutations found in RAC1 are found primarily at a distinct hotspot. Unexpectedly, the cancer-associated mutations found with RHOA are located at different hotspots than those found with RAS. Furthermore, since the RHOA mutations suggested a loss-of-function phenotype, it has been unclear whether RHOA functions as an oncogene or tumor suppressor in cancer development. Finally, whereas RAS mutations are found in a broad spectrum of cancer types, RHOA and RAC1 mutations occur in a highly restricted range of cancer types. In this review, we focus on RHOA missense mutations found in cancer and their role in driving tumorigenesis, with comparisons to cancer-associated mutations in RAC1 and RAS GTPases.


Merkel cell carcinoma diagnosed by fine-needle aspiration.
Merkel cell carcinoma is a relatively rare neoplasm of the skin. The present study describes three cases of Merkel cell carcinoma diagnosed by fine-needle aspiration cytology and reviews their histologic, cytologic, and ultrastructural features. The advantages of using fine-needle aspiration to diagnose Merkel cell carcinoma (and other cutaneous neoplasms) are emphasized.


Immune synapse instructs epigenomic and transcriptomic functional reprogramming in dendritic cells.
Understanding the fate of dendritic cells (DCs) after productive immune synapses (postsynaptic DCs) with T cells during antigen presentation has been largely neglected in favor of deciphering the nuances of T cell activation and memory generation. Here, we describe that postsynaptic DCs switch their transcriptomic signature, correlating with epigenomic changes including DNA accessibility and histone methylation. We focus on the chemokine receptor Ccr7 as a proof-of-concept gene that is increased in postsynaptic DCs. Consistent with our epigenomic observations, postsynaptic DCs migrate more efficiently toward CCL19 in vitro and display enhanced homing to draining lymph nodes in vivo. This work describes a previously unknown DC population whose transcriptomics, epigenomics, and migratory capacity change in response to their cognate contact with T cells.


Development of a Shortened Version of the Adolescent Stress Questionnaire (ASQ-S): construct validity and sex invariance in a large sample of Swedish adolescents.
Stressor experience is an important topic of research concerning adolescent health and ill-health. For this, valid and reliable measures of adolescent stress are needed. The Adolescent Stress Questionnaire 2 was developed to tap into stressor domains specific for adolescence. Psychometric evaluations in Australian and European samples have indicated adequate psychometric properties. However, the ASQ-2 is quite extensive, which may render its use in large cohort studies, where several aspects of adolescent health are investigated, inconvenient and problematic. To evaluate the psychometric properties of a short version of the ASQ-2 (ASQ-S) in terms of construct validity and factorial invariance across gender. The ASQ-2 was translated into Swedish and items were retained from nine of the ten scales based on factor loadings. One scale (stress of emerging adult responsibilities) was removed entirely due to low internal consistency and variance explained. The remaining 27 items were piloted and then included in an ongoing 5-year longitudinal study involving the participation of all students in the 7th and 8th grade in public schools from three Swedish municipalities (N = 2768, 47.5 % girls, mean age 13.64 years). For this study data from the first and second wave was used. A nine factor Confirmatory Factor Analysis (CFA) showed a good fit to the data and invariance across sexes was supported. The nine scales correlated positively with depressive symptoms, anxiety and worry and negatively with self-esteem. Girls reported higher stress levels than boys in eight of the nine scales. Stressors related to peer pressure predicted reported levels of anxiety and worry one year later, whereas stressors related to romantic relationships predicted depressive symptoms. Overall this study suggests that the ASQ-S could be a valid measure of adolescent stressor experience and psychometrically equivalent to the full ASQ-2.


A promotor directing alpha-amanitin-sensitive transcription of GARP, the major surface antigen of insect stage Trypanosoma congolense.
The major surface antigen of procyclic and epimastigote forms of Trypanosoma congolense in the tsetse fly is GARP (glutamic acid/alanine-rich protein), which is thought to be the analogue of procyclin/PARP in Trypanosoma brucei. We have studied two T.congolense GARP loci (the 4.3 and 4.4 loci) whose transcription is alpha-amanitin sensitive. Whilst a transcriptional gap 5' of the first GARP gene in the cloned region of the 4.4 locus could not be detected, such a gap was present in the 5' flank of the first GARP gene in the 4.3 locus. We have located a GARP transcription start site and, using reporter gene constructs containing a putative GARP promoter region in transient transfection studies, we have demonstrated promoter activity for the test region in T.congolense. There are species-specific differences in sequences regulating expression of the two major surface antigens, GARP and procyclin/PARP: the GARP promoter is inactive in T.brucei while the procyclin/PARP promoter is inactive in T.congolense. We have defined the splice acceptor site for the 4.3 GARP gene by sequencing and by 5' RT-PCR and demonstrated microheterogeneity in GARP polyadenylation by 3' RT-PCR. It appears that some GARP and procyclin/PARP RNA processing signals, although similar, are also species-specific.


A non-destructive sampling protocol for field studies of seed dispersal by fishes.
This paper presents a standardized protocol for the non-lethal capture of fishes, sampling of stomach contents and quantification of seed dispersal efficiency by frugivorous fishes. Neotropical pacu Piaractus mesopotamicus individuals were collected with fruit-baited hooks. The diets of 110 fish were sampled using a lavage method, which retrieved >90% of stomach contents of both juveniles and adults and allowed individuals to recover within 5 min of treatment. The proportional volume of six food categories was similar for stomachs and whole digestive tracts retrieved by dissection. Fruit pulp was proportionally lower in the stomach. The abundance and species richness of intact seeds increased with fish size independent of whether only stomachs or whole digestive tracts were analysed. The analysis of stomach contents accounted for 62·5% of the total species richness of seeds dispersed by P. mesopotamicus and 96% of common seeds (seed species retrieved from more than one fish). Germination trials revealed that seed viability was similar for seeds collected from the stomach via lavage and seeds that passed through the entire digestive tract. Therefore, stomach contents provide an unbiased representation of the dietary patterns and seed dispersal of frugivorous fishes.


Effects of prenatal bisphenol-A exposure and postnatal overfeeding on cardiovascular function in female sheep.
Bisphenol-A (BPA) is a widely used endocrine-disrupting chemical. Prenatal exposure to BPA is known to affect birth weight, but its impact on the cardiovascular system has not been studied in detail. In this study, we investigated the effects of prenatal BPA treatment and its interaction with postnatal overfeeding on the cardiovascular system. Pregnant sheep were given daily subcutaneous injections of corn oil (control) or BPA (0.5 mg/kg/day in corn oil) from day 30 to day 90 of gestation. A subset of female offspring of these dams were overfed to increase body weight to ~30% over that of normal fed controls. Cardiovascular function was assessed using non-invasive echocardiography and cuff blood pressure (BP) monitoring at 21 months of age. Ventricular tissue was analyzed for gene expression of cardiac markers of hypertrophy and collagen at the end of the observation period. Prenatal BPA exposure had no significant effect on BP or morphometric measures. However, it increased atrial natriuretic peptide gene expression in the ventricles and reduced collagen expression in the right ventricle. Overfeeding produced a marked increase in body weight and BP. There were compensatory increases in left ventricular area and internal diameter. Prenatal BPA treatment produced a significant increase in interventricular septal thickness when animals were overfed. However, it appeared to block the increase in BP and left ventricular area caused by overfeeding. Taken together, these results suggest that prenatal BPA produces intrinsic changes in the heart that are capable of modulating morphological and functional parameters when animals become obese in later life.


Combination IK1 and IKr channel blockade: no additive lowering of the defibrillation threshold.
Selective blockade of the inward rectifier potassium channel I(K1) by barium, or of the rapidly activating delayed rectifier potassium channel I(Kr) by D,L-sotalol, prolongs repolarization and reduces the defibrillation threshold (DFT). This study hypothesized that combination I(K1) and I(Kr) channel block would produce concentration-dependent additive effects on DFT and ventricular refractoriness. A range of barium and D,L-sotalol concentrations, alone and in combination, were examined with respect to DFT, ventricular effective refractory period (VERP), and ventricular fibrillation cycle length (VFCL) in 133 Langendorff-perfused rabbit hearts. Barium produced a concentration-dependent reduction of DFT (-49+/-4%), with concentration-dependent increases in VERP (26+/-6%) and VFCL (42+/-18%). D,L-Sotalol produced a concentration-dependent lowering of DFT (-53+/-6%) with a concentration-dependent increase in VFCL (34+/-8%) but not VERP. Low (1.6 microM), intermediate (3.1 microM), and high (12.5 microM) barium concentrations combined with varying D,L-sotalol concentrations produced equal or smaller decreases in DFT compared with corresponding doses of barium or D,L-sotalol alone. Except at the lowest concentrations of barium (1.6 and 3.1 microM) (p < 0.05), there was no significant additive interaction between barium and D,L-sotalol on VERP or VFCL. Combination I(K1) and I(Kr) channel block by barium and D,L-sotalol does not produce additive reduction of DFT.


Effect of ketorolac tromethamine on atracurium-induced neuromuscular blockade in anesthetized dogs.
The purpose of this study was to determine the effect of ketorolac tromethamine or placebo on the neuromuscular blockade induced by an infusion of atracurium in isoflurane-anesthetized dogs. Randomized, controlled trial. Six healthy, adult mixed-breed dogs (five female, one male) weighing 24.8 +/- 2.8 kg. Dogs were studied on two occasions with a minimum of 7 days between studies. Dogs were induced with 5% isoflurane in oxygen and maintained with 1.6 x minimum alveolar concentration (MAC) end-tidal isoflurane. Neuromuscular blockade was assessed using the train-of-four response. Once 50% depression of the first twitch (T1) was achieved, the atracurium infusion rate was held constant for 30 minutes. Then ketorolac, 0.5 mg/kg, or the same volume of placebo (0.9% sodium chloride solution) was administered intravenously and the atracurium infusion maintained for an additional 60 minutes. Before and at 2, 5, 10, 15, 30, and 60 minutes after ketorolac or placebo, the percent depression of T1 and the fourth twitch to the first twitch (T4/T1) ratio were recorded. The atracurium infusion was discontinued and the time for T1 to recover from 50% to 75% of its original value was recorded. At 75% T1, edrophonium, 0.5 mg/kg intravenously, was administered to antagonize the residual blockade. There was no significant difference in T1%, T4/T1 ratio, or recovery time after ketorolac administration compared with placebo. Ketorolac, 0.5 mg/kg intravenously, has no significant effect on either atracurium-induced neuromuscular blockade or recovery time for T1 in isoflurane-anesthetized dogs. The concurrent use of atracurium should not be a contraindication for the administration of ketorolac for intraoperative or postoperative analgesia.


Differential gene expression in human conducting airway surface epithelia and submucosal glands.
Human conducting airways contain two anatomically distinct epithelial cell compartments: surface epithelium and submucosal glands (SMG). Surface epithelial cells interface directly with the environment and function in pathogen detection, fluid and electrolyte transport, and mucus elevation. SMG secrete antimicrobial molecules and most of the airway surface fluid. Despite the unique functional roles of surface epithelia and SMG, little is known about the differences in gene expression and cellular metabolism that orchestrate the specialized functions of these epithelial compartments. To approach this problem, we performed large-scale transcript profiling using epithelial cell samples obtained by laser capture microdissection (LCM) of human bronchus specimens. We found that SMG expressed high levels of many transcripts encoding known or putative innate immune factors, including lactoferrin, zinc alpha-2 glycoprotein, and proline-rich protein 4. By contrast, surface epithelial cells expressed high levels of genes involved in basic nutrient catabolism, xenobiotic clearance, and ciliated structure assembly. Selected confirmation of differentially expressed genes in surface and SMG epithelia demonstrated the predictive power of this approach in identifying genes with localized tissue expression. To characterize metabolic differences between surface epithelial cells and SMG, immunostaining for a mitochondrial marker (isocitrate dehydrogenase) was performed. Because greater staining was observed in the surface compartment, we predict that these cells use significantly more energy than SMG cells. This study illustrates the power of LCM in defining the roles of specific anatomic features in airway biology and may be useful in examining how disease states alter transcriptional programs in the conducting airways.


Rates and predictors of relapse following discontinuation of antipsychotic medication after a first episode of psychosis.
There is uncertainty about the required duration of long-term antipsychotic maintenance medication after a first episode of psychosis. Robust predictors of relapse after discontinuation are yet to be identified. The present study aimed to determine the proportion of young people who discontinue their antipsychotic medication after a first episode of psychosis, the proportion who experience relapse, and predictors of relapse. A retrospective study of all individuals presenting to the Early Psychosis Prevention and Intervention Centre between 01/01/11 and 31/12/13 was conducted. A Cox regression analysis was conducted to identify predictors of relapse. A total of 544 young people with a FEP were included. A trial of discontinuation was undertaken by 61% of the cohort. Median duration of antipsychotic medication prior to first trial of discontinuation was 174.50days. Amongst those trialing discontinuation, 149 (45.8%) experienced relapse in a median follow-up time post discontinuation of 372days. On multivariate analysis, predictors of relapse were a diagnosis of cannabis abuse disorder (HR: 1.40), and longer duration of antipsychotic medication (HR: 1.05). Antipsychotic discontinuation frequently occurs earlier than guidelines recommend. Individuals with a diagnosis of cannabis abuse are more likely to experience relapse and addressing this substance abuse prior to discontinuation could possibly reduce relapse rates.


Biotransformation of neuropeptides.
The ability of neuropeptides to act as precursors for smaller, biologically active fragments is discussed in terms of their biotransformation. This process may involve cleavage of the parent peptide by peptidase enzymes to produce shorter polypeptides with defined biological activity, though other enzymic processes such as sulphation and acetylation may be implicated. Detection of the specific fragments in vivo, their release, receptor-binding and biological actions may confirm biotransformation of the parent peptide. Control of biotransformation will depend upon the localization, both regional and subcellular, and the specificity of the enzymes involved. This process may give an additional degree of flexibility to the biological effects of neuropeptides.


Conflict Management Education in the Intensive Care Unit.
Conflicts in medical settings affect both team function and patient care, yet a standardized curriculum for conflict management in clinical teams does not exist. To evaluate the effects of an educational intervention for conflict management on knowledge and perceptions and to identify trends in preferred conflict management style among intensive care unit workers. A conflict management education intervention was created for an intensive care team. The intervention was 1 hour long and incorporated the Thomas-Kilmann Conflict Mode Instrument as well as conflict management concepts, self-reflection, and active learning through discussion and reviewing clinical cases. Descriptive statistics were prepared on the participants' preferred conflict management modes. A pretest/posttest was analyzed to evaluate knowledge and perceptions of conflict before and after the intervention, and 3 open-ended questions on the posttest were reviewed for categories. Forty-nine intensive care providers participated in the intervention. The largest portion of participants had an avoiding conflict management mode (32%), followed by compromising (30%), accommodating (25%), collaborating (9%), and competing (5%). Pretest/posttest data were collected for 31 participants and showed that knowledge (P < .001) and perception (P = .004) scores increased significantly after the conflict management intervention. The conflict management educational intervention improved the participants' knowledge and affected perceptions. Categorization of open-ended questions suggested that intensive care providers are interested in concrete information that will help with conflict resolution, and some participants understood that mindfulness and awareness would improve professional interactions or reduce conflict.


Role of the testa in preventing cellular rupture during imbibition of legume seeds.
Studies with the seeds of soybean, navy bean, pea, and peanut were made to determine the extent of leakage of intracellular enzymes during imbition. Embryos with intact testae from all four species were found to leak detectable activities of either intracellular enzymes of the cytosol (glucose-6-phosphate dehydrogenase) or enzymes found in both the cytosol and organelles (malate dehydrogenase, glutamate dehydrogenase, glutamate oxaloacetate transaminase, and NADP-isocitrate dehydrogenase) after 6 hours imbition at 25 C. Pea and peanut embryos with testae leaked considerably lower levels of activity for these enzymes than did those of soybean and bean. Leakage of mitochondrial marker enzymes (fumarase, cytochrome c oxidase, and adenylate kinase) was not detected from embryos with testae, suggesting that a differential diffusion of intracellular components out of cells occurred. Soybean and bean embryos without testae leaked high, and proportionally (per cent dry seed basis) similar, levels of all cytosol, cytosol-organelle, and mitochondrial marker enzymes and protein during imbibition, indicating that cell membranes were not differential to leakage and that they had ruptured. Pea and peanut embryos without testae leaked detectable activities of all cytosol and cytosol-organelle enzymes, although fumarase was the only detectable mitochondrial marker enzyme leaked, suggesting that some degree of differential leakage may have occurred in these species. The outermost layers of embryo cells of seeds without testae of all four species absorbed and sequestered the nonpermeating pigment Evan's blue after 5 to 15 minutes imbibition, indicating that membranes had ruptured. This occurred to a much lesser extent in seeds with intact testae. Both soybean and bean embryos without testae were observed to disintegrate during imbibition, whereas those of pea and peanut did not. These data indicate that seeds of certain legumes are susceptible to cellular rupture during imbibition when seed coats are damaged or missing.


Copy number variation in the Framingham Heart Study.
In this paper we test for association between copy number variation and diabetes in a subset of individuals from the Framingham Heart Study. We used the 500 k SNP data and called copy number variation using two algorithms: the genome alteration detection algorithm of Pique-Regi et al. and the software Golden Helix. We then tested for association between copy number and diabetes using a gene-based analysis. Our results show little evidence of association between copy number and diabetes status. Furthermore, our results indicate a relatively poor level of agreement between copy number calls resulting from the two programs. We then examined potential causes for this difference in results and the implications for future studies.


Pervasive Radio Mapping of Industrial Environments Using a Virtual Reality Approach.
Wireless communications in industrial environments are seriously affected by reliability and performance issues, due to the multipath nature of obstacles within such environments. Special attention needs to be given to planning a wireless industrial network, so as to find the optimum spatial position for each of the nodes within the network, and especially for key nodes such as gateways or cluster heads. The aim of this paper is to present a pervasive radio mapping system which captures (senses) data regarding the radio spectrum, using low-cost wireless sensor nodes. This data is the input of radio mapping algorithms that generate electromagnetic propagation profiles. Such profiles are used for identifying obstacles within the environment and optimum propagation pathways. With the purpose of further optimizing the radio planning process, the authors propose a novel human-network interaction (HNI) paradigm that uses 3D virtual environments in order to display the radio maps in a natural, easy-to-perceive manner. The results of this approach illustrate its added value to the field of radio resource planning of industrial communication systems.


Characterizing allelic proteins for genome mapping in maize.
Mapping cDNA probes in order to construct genetic linkage maps is becoming a widespread strategy for genome analysis and gene isolation, particularly in cultivated plant species. Nevertheless, almost all cDNAs reveal two or more unlinked loci, making it difficult to identify the gene(s) actually expressed. In a highly polymorphic species, such as maize, two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) of proteins may circumvent this limitation. With the analysis of various segregating populations, we previously showed that the apparent position shifts of proteins on the 2-D gels are monogenic and codominant. In this paper we compared allelic proteins on the basis of their high performance liquid chromatography (HPLC) profile and partial amino acid sequences. In a sample of 20 position shifts, the allelic proteins appeared to be similar in all but one case, strongly suggesting that polymorphism of structural genes is involved. Thus 2-D PAGE could prove to be a useful tool for genome mapping: when a cDNA probe detects several loci, a position shift of the encoded protein will allow the identification of the gene translated in the organ considered.


Equilibrium states of a test particle coupled to finite-size heat baths.
We report on numerical simulations of the dynamics of a test particle coupled to competing Boltzmann heat baths of finite size. After discussing some features of the single bath case, we show that the presence of two heat baths further constrains the conditions necessary for the test particle to thermalize with the heat baths. We find that thermalization is a spectral property in which the oscillators of the bath with frequencies in the range of the test particle characteristic frequency determine its degree of thermalization. We also find an unexpected frequency shift of the test particle response with respect to the spectra of the two heat baths. Finally, we discuss implications of our results for the study of high-frequency nanomechanical resonators through cold damping cooling techniques and for engineering reservoirs capable of mitigating the back action on a mechanical system.


Tunneled internal jugular hemodialysis catheters: impact of laterality and tip position on catheter dysfunction and infection rates.
To determine rates of dysfunction and infection for tunneled internal jugular vein hemodialysis catheters based on laterality of insertion and catheter tip position. Retrospective review of a procedural database for tunneled internal jugular vein hemodialysis catheter placements between January 2008 and December 2009 revealed 532 catheter insertions in 409 patients (234 male; mean age, 54.9 y). Of these, 398 catheters were placed on the right and 134 on the left. The catheter tip location was categorized as superior vena cava (SVC), pericavoatrial junction, or mid- to deep right atrium based on review of the final intraprocedural radiograph. The rates of catheter dysfunction and catheter-related infection (reported as events per 100 catheter-days) were analyzed. Catheters terminating in the SVC or pericavoatrial junction inserted from the left showed significantly higher rates of infection (0.50 vs 0.27; P = .005) and dysfunction (0.25 vs 0.11; P = .036) compared with those inserted from the right. No difference was identified based on laterality for catheter tip position in the mid- to deep right atrium. Left-sided catheters terminating in the SVC or pericavoatrial junction had significantly more episodes of catheter dysfunction or infection than catheters terminating in the mid- to deep right atrium (0.84 vs 0.35; P = .006), whereas no significant difference was identified for right-sided catheters based on tip position. When inserted from the left internal jugular vein, catheter tip position demonstrated a significant impact on catheter-related dysfunction and infection; this relationship was not demonstrated for right-sided catheters.


Evaluation of the Thermo Scientific RapidFinder™ Salmonella Species, Typhimurium, and Enteritidis Multiplex PCR Kit.
The Thermo Scientific RapidFinder™ Salmonella Species, Typhimurium, and Enteritidis Multiplex PCR Kit (candidate method) is a real-time PCR assay for the detection and differentiation of Salmonella spp., and the serovars S. Typhimurium, and S. Enteritidis from poultry, pork, and environmental samples. The method was validated in comparison to the U.S. Department of Agriculture Food Safety and Inspection Service and the U.S. Food and Drug Administration reference methods. Thermo Fisher Scientific (Basingstoke, United Kingdom) tested all matrixes. In addition, two matrixes were analyzed independently by Q Laboratories, Inc. (Cincinnati, OH). Few statistically significant differences were found between the candidate and reference methods when analyzed by probability of detection. When differences were observed, these were in favor of the candidate method. All 200 inclusivity strains and none of the 45 exclusivity strains were detected, which demonstrated that the RapidFinder Salmonella Species, Typhimurium, and Enteritidis Multiplex PCR Kit was able to detect all the major groups of Salmonella, the less common subspecies of S. enterica, and the rarely encountered S. bongori. None of the exclusivity isolates analyzed were detected. Robustness testing demonstrated that the assay gave reliable performance, with specific method deviations outside the recommended parameters. Accelerated stability testing was conducted, validating the assay shelf life.


Comprehensive assessment of the regulons controlled by the FixLJ-FixK2-FixK1 cascade in Bradyrhizobium japonicum.
Symbiotic N(2) fixation in Bradyrhizobium japonicum is controlled by a complex transcription factor network. Part of it is a hierarchically arranged cascade in which the two-component regulatory system FixLJ, in response to a moderate decrease in oxygen concentration, activates the fixK(2) gene. The FixK(2) protein then activates not only a number of genes essential for microoxic respiration in symbiosis (fixNOQP and fixGHIS) but also further regulatory genes (rpoN(1), nnrR, and fixK(1)). The results of transcriptome analyses described here have led to a comprehensive and expanded definition of the FixJ, FixK(2), and FixK(1) regulons, which, respectively, consist of 26, 204, and 29 genes specifically regulated in microoxically grown cells. Most of these genes are subject to positive control. Particular attention was addressed to the FixK(2)-dependent genes, which included a bioinformatics search for putative FixK(2) binding sites on DNA (FixK(2) boxes). Using an in vitro transcription assay with RNA polymerase holoenzyme and purified FixK(2) as the activator, we validated as direct targets eight new genes. Interestingly, the adjacent but divergently oriented fixK(1) and cycS genes shared the same FixK(2) box for the activation of transcription in both directions. This recognition site may also be a direct target for the FixK(1) protein, because activation of the cycS promoter required an intact fixK(1) gene and either microoxic or anoxic, denitrifying conditions. We present evidence that cycS codes for a c-type cytochrome which is important, but not essential, for nitrate respiration. Two other, unexpected results emerged from this study: (i) specifically FixK(1) seemed to exert a negative control on genes that are normally activated by the N(2) fixation-specific transcription factor NifA, and (ii) a larger number of genes are expressed in a FixK(2)-dependent manner in endosymbiotic bacteroids than in culture-grown cells, pointing to a possible symbiosis-specific control.


Inhibiting cell division in Escherichia coli has little if any effect on gene expression.
DNA microarrays were used to compare gene expression in dividing and nondividing (filamentous) cultures of Escherichia coli. Although cells from these cultures differed profoundly in morphology, their gene expression profiles were nearly identical. These results extend previous evidence that there is no division checkpoint in E. coli, and progression through the cell cycle is not regulated by the transcription of different genes during different parts of the cell cycle.


Differential leaf stress responses in young and senescent plants.
Responses to low temperature, mechanical wounding and salicylic acid (SA) treatments were studied in 3-week-old (young) and 6-week-old (senescent) Arabidopsis thaliana (L.) Heynh. plants by analyzing increases in Pal1 and Pr1 expression and superoxide dismutase (SOD; EC 126.96.36.199) and peroxidase (POX; EC 188.8.131.52) activities. Young plants showed higher Pal1 transcript accumulation after low temperature and wounding. In contrast, senescent plants presented higher accumulation of Pr1 transcripts after SA treatments. Similar results were obtained with the ethylene-insensitive etr1 mutant, suggesting that these differences are not related to increased ethylene content in senescent tissues. SOD activity and inducibility were lower, whereas POX activity and inducibility were higher in senescent plants. A possible relationship between senescence-associated changes in responses to stress and in the metabolism of active oxygen species is discussed.


Palaeobiology of red and white blood cell-like structures, collagen and cholesterol in an ichthyosaur bone.
Carbonate concretions are known to contain well-preserved fossils and soft tissues. Recently, biomolecules (e.g. cholesterol) and molecular fossils (biomarkers) were also discovered in a 380 million-year-old concretion, revealing their importance in exceptional preservation of biosignatures. Here, we used a range of microanalytical techniques, biomarkers and compound specific isotope analyses to report the presence of red and white blood cell-like structures as well as platelet-like structures, collagen and cholesterol in an ichthyosaur bone encapsulated in a carbonate concretion from the Early Jurassic (~182.7 Ma). The red blood cell-like structures are four to five times smaller than those identified in modern organisms. Transmission electron microscopy (TEM) analysis revealed that the red blood cell-like structures are organic in composition. We propose that the small size of the blood cell-like structures results from an evolutionary adaptation to the prolonged low oxygen atmospheric levels prevailing during the 70 Ma when ichthyosaurs thrived. The δ13C of the ichthyosaur bone cholesterol indicates that it largely derives from a higher level in the food chain and is consistent with a fish and cephalopod diet. The combined findings above demonstrate that carbonate concretions create isolated environments that promote exceptional preservation of fragile tissues and biomolecules.


Paclitaxel Promotes Oxidative Stress-Mediated Human Laryngeal Squamous Tumor Cell Death through the Stimulation of Calcium and Zinc Signaling Pathways: No Synergic Action of Melatonin.
The paclitaxel (PAX) and melatonin (MLT)-mediated mitochondria reactive free oxygen radical (miROS) generations via the influx of excessive Ca2+ and Zn2+ induce tumor cell death and apoptosis. However, a presence of resistance was demonstrated against the PAX treatment in the tumor cells. The stimulation of TRPM2 may increase the anticancer action of PAX after the treatment of MLT. We investigated the stimulating role of PAX with/without MLT on the excessive Ca2+ influx and miROS generation-mediated human laryngeal squamous cancer (Hep2) cell death through the stimulation of TRPM2. The Hep2 cells were divided into four groups as control, MLT (1 mM for 2 h), PAX (50 μM for 24 h), and PAX + MLT. In some experiments, we induced additional subgroups such as PAX+ACA and PAX+2APB. The stimulation of TRPM2 induced the increase of TRPM2 current densities, lipid peroxidation, cytosolic ROS, miROS, cytosolic Ca2+, and Zn2+ values in the Hep2 cells after the treatment of PAX, although their values were decreased by the treatment of MLT and TRPM2 antagonists (ACA and 2APB). In addition, the PAX induced apoptosis and cell death via upregulation of caspases and downregulation of antioxidant glutathione peroxidase and glutathione in the cells. The treatment of PAX increased protein band expression values of TRPM2, PARP-1, and caspase 3 and 9 in the Hep2. The increased expression, apoptotic, and cell death values were not affected by the treatment of MLT. In conclusion, PAX induced the increase of Hep2 cell death via upregulations of TRPM2 and Zn2+, although its downregulation via the treatment of MLT did not change the antitumor action of PAX.


Saturn's Rings: Identification of Water Frost.
A recently published infrared spectrum of Saturn's rings resembles our laboratory spectra of water frosts. Furthermore, there are discrepancies between the ring spectrum and ammonia frost spectra in the 2- to 2.5-micro region. These discrepancies render unlikely a reported ideti tification of ammonia frost in the ring spectrum.


Identification of DNA nucleotides by conductance and tunnelling current variation through borophene nanogaps.
Rapid and inexpensive DNA sequencing is critical to biomedical research and healthcare for the accomplishment of personalized medicine. Solid-state nanopores and nanogaps have marshalled themselves in the fascinating paradigm of nano-research since the advent of its application in DNA sequencing by analyzing the quantum conductance and electric current signals. In this study, the feasibility of the considered borophene nanogaps for DNA sequencing purposes via the electronic tunnelling current approach was investigated by utilizing combined density functional theory with non-equilibrium Green's function (DFT-NEGF) techniques. The interaction energy (Ei) and the charge density difference (CDD) plots exploit the charge modulation around the nanogap edges due to the presence of each nucleotide. Our results revealed a distinct variation in the tunnelling conductance, as a characteristic fingerprint of each nucleotide at the Fermi level. The calculated tunnelling current variation across the nanogap under an applied bias voltage was also significant due to the effective coupling of nucleotides with the electrode edges. The current was in the picoampere (pA) range, which was fairly higher than the electrical background noise and also experimentally detectable by the canning tunnelling microscopy (STM) technique. Our findings demonstrated that in the borophene nanopore vs. nanogap scenario, the nanogap has several advantages and is a more promising nanobiosensor. Moreover, we also compared our results with various previous experimental and theoretical reports on nanogaps as well as nanopores for gaining better insights.


Clinical analysis of 22 infants with afebrile cluster seizures.
The inclusion criteria for afebrile cluster seizures in infancy are defined as follows: (1) frequency of afebrile seizures at least 2 episodes within 72 hours; (2) seizure onset between 2 months and 3 years of age; (3) excluding febrile convulsion, central nervous system infections, status epilepticus, well-known epileptic syndromes in infancy (e.g. early myoclonic encephalopathy, early infantile epileptic encephalopathy, benign myoclonic epilepsy, infantile spasms. Lennox-Gastaut syndrome), electrolyte imbalance, watery diarrhea, head injury and intoxication. From 1986 to 1996, retrospectively and prospectively 22 patients were collected who fulfilled the above criteria. Based on whether or not a strong family history was present and a history of mild diarrhea was associated with seizure onset, they were divided into three groups: Group I, benign infantile familial convulsions (4 patients); Group II, cluster seizures with mild diarrhea in infancy (5 patients); Group III, cluster seizures without diarrhea in infancy (13 patients). Before seizure onset and during follow-up, all of the patients had normal development. The seizure pattern in all was generalized, most tonic type with duration of seizure less than five minutes in the majority. Recurrence rate was 100% in Group I and no recurrence in Group II. In 16 patients who were seizure-free over 12 months, the duration of persistence varied from 1 day to 8 months, and was shortest in Group II (range, 1 to 3 days). It was concluded that the vast majority of afebrile cluster seizures in infancy are benign in nature. Whether anticonvulsant therapy is justified must be individualized.


Utilizing multimodal analgesia to evaluate postoperative analgesic requirements in kidney transplant recipients.
The use of non-opioid analgesics following surgery has proven beneficial in managing pain and decreasing adverse outcomes following surgery. Data assessing outcomes related to opioid use is limited in kidney transplant recipients (KTRs). We evaluated the effectiveness of implementing a reduced to no opioid use protocol in KTRs. This retrospective cohort study included adult KTRs between January 2017 and July 2019 with a multimodal analgesic protocol (MAP), focused on limiting opioids, implemented in August 2018. We compared analgesic requirements in morphine milligram equivalents (MME) during transplant admissions between the MAP cohort and traditional cohort. There were 217 KTRs who met the criteria. Inpatient opioid use was significantly reduced in the MAP cohort (16.5 ± 19.2 MME/day vs 24.7 ± 19.7 MME/day; P <.05) with no significant difference in pain scores. No use of opioids within six months of discharge was significantly increased in the MAP cohort (50% vs 7%; P <.001), and there were no reported deaths at six months in either cohort. The use of multimodal analgesia is beneficial in KTRs to provide adequate pain control with limited to no exposure of opioids during admission or at discharge.


Maternal and fetal prostaglandin concentrations during late gestation in dairy cattle.
A study was conducted to measure the blood plasma concentrations of prostaglandin F2 alpha (PGF2 alpha), 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM), prostaglandin E2 (PGE2) and 13,14-dihydro-15-keto-prostaglandin E2 (PGEM) in the jugular vein, umbilical vein and artery and uterine vein of 18 Holstein Friesian cows during late gestation. A caesarean section was performed on all cows before term in order to obtain blood samples from the different sources. Plasma PG concentrations in the uterine or fetal circulation were significantly higher than in jugular vein plasma. Correlations between peripheral PG metabolite concentrations and primary PG concentrations in the various sources of the uterus or fetus were not significant (r = .17-.47) and demonstrated that prostaglandin values based upon peripheral blood alone are of limited value.


Schizophrenia in Surinamese and Dutch Antillean immigrants to The Netherlands: evidence of an increased incidence.
Reports of an increased incidence of schizophrenia in Afro-Caribbean immigrants to the UK are a matter of much debate. It is of interest, therefore, that in the 1970s and 1980s many immigrants from Surinam and The Netherlands Antilles have settled in The Netherlands. The purpose of our study was to compare the risk of a first admission for schizophrenia for Surinamese- and Antillean-born persons aged 15-39 years to that for their Dutch-born peers in the period 1983-1992. We used data from the Dutch psychiatric registry. Age-adjusted relative risks were calculated using Poisson regression analysis. The risk for the immigrants was found to be three to four times higher than that for the Dutch-born. Age-adjusted relative risks were significantly higher for male than for female immigrants. The results provide evidence of an increased incidence in these immigrant groups and support similar findings on Afro-Caribbeans in the UK. Migration from Surinam was on such a large scale that selective migration of persons at risk for the disorder is unlikely to account entirely for these findings.


Senescent cells in growing tumors: population dynamics and cancer stem cells.
Tumors are defined by their intense proliferation, but sometimes cancer cells turn senescent and stop replicating. In the stochastic cancer model in which all cells are tumorigenic, senescence is seen as the result of random mutations, suggesting that it could represent a barrier to tumor growth. In the hierarchical cancer model a subset of the cells, the cancer stem cells, divide indefinitely while other cells eventually turn senescent. Here we formulate cancer growth in mathematical terms and obtain predictions for the evolution of senescence. We perform experiments in human melanoma cells which are compatible with the hierarchical model and show that senescence is a reversible process controlled by survivin. We conclude that enhancing senescence is unlikely to provide a useful therapeutic strategy to fight cancer, unless the cancer stem cells are specifically targeted.


Anti-Inflammatory Effects of Magnetically Targeted Mesenchymal Stem Cells on Laser-Induced Skin Injuries in Rats.
Mesenchymal stem cells (MSCs) are a promising resource for tissue regeneration and repair. However, their clinical application is hindered by technical limitations related to MSC enrichment at the target sites. MSCs were labeled with magnetic Fe3O4 nanoparticles (NPs). We analyzed the effects of NP on cell proliferation, stem cell characteristics, and cytokine secretion. Furthermore, we induced NP-labeled MSC migration with an external magnetic field toward laser-induced skin wounds in rats and evaluated the associated anti-inflammatory effects. Fe3O4 NP application did not adversely affect MSC characteristics. Moreover, Fe3O4 NP-labeled MSCs presented increased anti-inflammatory cytokine and chemokine production compared with unlabeled MSCs. Furthermore, MSCs accumulated at the injury site and magnetic targeting promoted NP-labeled MSC migration toward burn injury sites in vivo. On day 7 following MSC injection, reduced inflammation and promoted angiogenesis were observed in the magnetically targeted MSC group. In addition, anti-inflammatory factors were upregulated, whereas pro-inflammatory factors were downregulated within the magnetically targeted MSC group compared with those in the PBS group. This study demonstrates that magnetically targeted MSCs contribute to cell migration to the site of skin injury, improve anti-inflammatory effects and enhance angiogenesis compared with MSC injection alone. Therefore, magnetically targeted MSC therapy may be an effective treatment approach for epithelial tissue injuries.


Two polymorphs of lysozyme nitrate: temperature dependence of their solubility.
Two crystallographic forms of lysozyme nitrate are known, namely monoclinic and triclinic. Having previously determined the temperature dependence of the solubility of the monoclinic form (0.2 M NaNO (3) solutions at pH = 4.5) [Legrand et al. (2001). J. Crystal Growth 232, 244-249], we focus here on the solubility of the triclinic form. The temperature dependence of the solubility of this crystallographic form has been measured with a static light device developed in our laboratory. This device allows to observe of the dissolution of one phase and/or the occurrence of a new one by varying the temperature with a sweep rate as low as 0.6 degree/hour. The new solubility data are complemented with crystallographic data of the triclinic form for the sake of completeness. The faces of a triclinic crystal are indexed. The crystallisation enthalpy of the triclinic form is deduced from these new results. These new solubility data allow us now to discuss (1). the published protocols used to obtain the monoclinic and triclinic forms of lysozyme nitrate and (2). the phase transformation.


Assessment of vaccination timeliness and associated factors among children in Toke Kutaye district, central Ethiopia: A Mixed study.
Age inappropriate vaccination of children increases the rate of mortality and morbidity. All studies conducted in some areas of Ethiopia were only quantitative in nature and focused on the main cities ignoring rural communities. The objective of this study is to assess vaccination timeliness and associated factors among children in Toke Kutaye district, central Ethiopia. A community-based cross-sectional study with quantitative and qualitative data collection methods was used, for which simple random sampling was used to select 602 mothers/caregivers who have vaccinated children aged 12 to 23 months in the district. The collected data were entered into Epi-data version 3.1 and exported to SPSS version 23 for analysis. Bivariate analysis with a P-value of < 0.25 was used to select candidate variables for multivariate logistic regression. Adjusted odds ratio (AOR) with 95% CI and p-value < 0.05 were used to declare a significant association. Qualitative data responses were classified and then organized by content with thematic analysis. A total of 590 respondents responded to the interviews, making a response rate of 98%. In this study, 23.9% (95% CI: 20.4-27.7) of children aged 12-23 months had received all vaccines in the recommended time intervals. Urban residence (AOR: 3.15, 95% CI: 1.56-6.4), participation of pregnant women in conferences (AOR: 2.35, 95% CI: 1.2-4.57), institutional delivery (AOR: 2.5: 95% CI: 1.32-4.20), and sufficient knowledge of mothers (AOR: 3, 95% CI: 1.82-5.10) were significantly associated with the timeliness of childhood vaccination. Qualitative findings revealed that lack of knowledge and lack of information from mothers or caregivers, and inadequate communication with health workers hindered timely vaccination. The overall timeliness of the child's vaccination was low in this study. Residence, participation in a conference, place of delivery, and knowledge of the mothers were predictors of vaccination timeliness. Hence, promoting institutional delivery and increasing pregnant mothers awreness on vaccination timeliness through conference participation is compulsory.


Psychopathic traits and preattentive threat processing in children: a novel test of the fearlessness hypothesis.
We tested the fearlessness hypothesis of psychopathy in an at-risk sample of 88 preadolescent children. Psychopathy was measured using combined child- and parent-reported scores on the Antisocial Process Screening Device (APSD). Using a continuous-flash-suppression paradigm, we evaluated threat processing at the preattentive level for the first time in a study of psychopathy. Scores for the APSD Callous/Unemotional factor, which assesses the core affective deficits of psychopathy, predicted preattentive face-recognition deficits for fearful faces and, to a lesser extent, for disgusted faces. This finding contradicts recent suggestions that the fearlessness associated with psychopathy is solely a consequence of overt attentional artifacts. Future research should focus on preattentive processing of fear in individuals with callous-unemotional traits, and on the implications of preattentive-processing deficits for treatment and theory development.


Nanospheric [M20(OH)12(maleate)12(Me2NH)12]4+ clusters (M = Co, Ni) with O(h) symmetry.
Nanospheric hydroxo-bridged clusters of [M(20)(OH)(12)(maleate)(12)(Me(2)NH)(12)](BF(4))(3)(OH)·nH(2)O (M = Co (1), Ni (2)) with O(h) symmetry were afforded under hydrothermal condition with Co(BF(4))(2)·6H(2)O/Ni(BF(4))(2)·6H(2)O and fumaric acid in a DMF/EtOH mixed solvent. They are characterized by elemental analysis, IR, and X-ray diffraction. X-ray single crystal diffraction analyses show that these two complexes are isostructural containing an ideally cubic M(8) core in that each two M atoms are doubly bridged at the edges by one OH(-) and one maleate, while these OH(-) and maleate groups are coordinated further by exterior identical 12 M atoms which construct a perfect M(12) icosahedron to encapsulate the cubic core. To our knowledge, such large clusters with O(h) symmetry are seldom. The variable-temperature magnetic susceptibility studies reveal that these two isostructures exhibit antiferromagnetic interactions.


Mental health nursing and the promotion of physical activity.
Evidence and recent policy initiatives support the promotion of physical activity and exercise within acute inpatient settings. Mental health nurses may perform an important role in encouraging physical activity and legitimizing its incorporation within care planning. This exploratory study aimed to investigate perceptions of the role of exercise and physical activity as a therapeutic strategy within inpatient settings. Given the exploratory nature of the study, a qualitative design using semistructured interviews was considered most appropriate. As part of a larger study regarding the promotion of physical activity within one United Kingdom (UK) Mental Health Trust, 12 mental health nurses were interviewed. All participants identified a need for increasing opportunities for physical activity on inpatient wards. Three interrelated themes emerged that related to how physical activity and exercise was conceptualized by the participants. First, exercise and physical activity was seen as a potentially beneficial distracting strategy rather than an adjunctive strategy in its own right. Secondly, exercise was considered as a lifestyle choice and an individual responsibility. Thirdly, a difficulty in articulating a possible relationship between the 'physical' and the 'mental' was predominant. The implications of these perceptions are discussed in relation to developing a greater profile for physical activity and exercise on acute wards.


Absence of Connexin 43 Results in Smaller Retinas and Arrested, Depolarized Retinal Progenitor Cells in Human Retinal Organoids.
The development of the vertebrate retina relies on complex regulatory mechanisms to achieve its characteristic layered morphology containing multiple neuronal cell types. While connexin 43 (CX43) is not expressed by mature retinal neurons, mutations in its gene GJA1 are associated with microphthalmia and low vision in patients. To delineate how lack of CX43 affects retinal development, GJA1 was disrupted in human induced pluripotent stem cells (hiPSCs) (GJA1-/-) using CRISPR/Cas9 editing, and these were subsequently differentiated into retinal organoids. GJA1-/- hiPSCs do not display defects in self-renewal and pluripotency, but the resulting organoids are smaller with a thinner neural retina and decreased abundance of many retinal cell types. CX43-deficient organoids express lower levels of the neural marker PAX6 and the retinal progenitor cell (RPC) markers PAX6, SIX3, and SIX6. Conversely, expression of the early neuroectoderm markers SOX1 and SOX2 remains high in GJA1-/- organoids throughout their development. The lack of CX43 results in an increased population of CHX10-positive RPCs that are smaller, disorganized, do not become polarized, and possess a limited ability to commit to retinal fate specification. Our data indicate that lack of CX43 causes a developmental arrest in RPCs that subsequently leads to pan-retinal defects and stunted ocular growth.