Unfavorable neonatal outcome after intraamniotic injection of methylene blue.
A case is presented in which methylene blue dye was injected intraamniotically to confirm rupture of the membranes. Significant neonatal morbidity occurred as a direct result of the methylene blue dye injection. A syndrome of toxic side effects is described including hemolytic anemia, hyperbilirubinemia, and methemoglobinemia. The metabolic process is discussed. The authors suggest discontinuing the intraamniotic injection of methylene blue dye as a diagnostic aid.


Quality of life index: development and psychometric properties.
The purpose of the study on which this article is based was to assess the validity and reliability of an instrument designed to measure quality of life. Sixty-four items applicable to both healthy subjects and dialysis patients were tested with graduate students (n = 88); six items relative to dialysis were added, and the instrument was administered to dialysis patients (n = 37). Items were based on literature review, which supported content validity. Correlations between the instrument and an overall satisfaction with life question of 0.75 (graduate students) and 0.65 (dialysis patients) supported criterion-related validity. Support for reliability was provided by test-retest correlations of 0.87 (graduate students) and 0.81 (dialysis patients) and Cronbach's alphas of 0.93 (graduate students) and 0.90 (dialysis patients).


Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction.
It is not known whether prehospital fibrinolysis, coupled with timely coronary angiography, provides a clinical outcome similar to that with primary percutaneous coronary intervention (PCI) early after acute ST-segment elevation myocardial infarction (STEMI). Among 1892 patients with STEMI who presented within 3 hours after symptom onset and who were unable to undergo primary PCI within 1 hour, patients were randomly assigned to undergo either primary PCI or fibrinolytic therapy with bolus tenecteplase (amended to half dose in patients ≥75 years of age), clopidogrel, and enoxaparin before transport to a PCI-capable hospital. Emergency coronary angiography was performed if fibrinolysis failed; otherwise, angiography was performed 6 to 24 hours after randomization. The primary end point was a composite of death, shock, congestive heart failure, or reinfarction up to 30 days. The primary end point occurred in 116 of 939 patients (12.4%) in the fibrinolysis group and in 135 of 943 patients (14.3%) in the primary PCI group (relative risk in the fibrinolysis group, 0.86; 95% confidence interval, 0.68 to 1.09; P=0.21). Emergency angiography was required in 36.3% of patients in the fibrinolysis group, whereas the remainder of patients underwent angiography at a median of 17 hours after randomization. More intracranial hemorrhages occurred in the fibrinolysis group than in the primary PCI group (1.0% vs. 0.2%, P=0.04; after protocol amendment, 0.5% vs. 0.3%, P=0.45). The rates of nonintracranial bleeding were similar in the two groups. Prehospital fibrinolysis with timely coronary angiography resulted in effective reperfusion in patients with early STEMI who could not undergo primary PCI within 1 hour after the first medical contact. However, fibrinolysis was associated with a slightly increased risk of intracranial bleeding. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00623623.).


Interfacial icelike water local doping of graphene.
Charge transfer at interfaces plays a critical role in the performance of graphene based electronic devices. However, separate control of the charge transfer process in the graphene/SiO2 system is still challenging. Herein, we investigate the effects of the trapped interfacial icelike water layer on the charge transfer between graphene and the SiO2/Si substrate through recording the surface potential changes induced by partial removal of the interfacial icelike water layer upon in situ heating. The scanning Kelvin probe microscopy surface potential mapping shows that the graphene is electronically modified by the icelike water layer as the electron density transfers from graphene to the icelike water layer, resulting in hole-doping of graphene, which was also confirmed by the graphene field effect transistor electrical transport measurements. In addition, the density functional calculations provide in-depth insight into the electronic contributions of the icelike water layer to graphene and the charge transfer mechanism. This research will improve our ability to manipulate graphene's electronic properties for diverse applications, such as humidity sensing.


Narrow-band UV-B phototherapy: an effective and reliable treatment alternative for extensive and recurrent pityriasis versicolor.
In the previous studies, positive effect of sunlight on seborrheic dermatitis may well be explained by the direct influence of UV-light on the yeasts. Narrow-band ultraviolet-B phototherapy appears to be a very effective and safe treatment option for patients with severe seborrheic dermatitis. We aimed to investigate the efficacy of narrow-band ultraviolet-B phototherapy as an alternative treatment for pityriasis versicolor. A total of 38 patients diagnosed with disseminated pityriasis versicolor having more than four relapsing episodes within 12 months were treated with narrow-band ultraviolet-B phototherapy given three times weekly. Clinical assessment on the basis of the severity of pruritus, erythema/hyperpigmentation and scaling and mycological examination were made at Weeks 0, 4, 8, 12 and 16. Of the remaining 30 patients, 20 (66.7%) achieved excellent results and four patients (14%) had mild residual disease. The decrease in the clinical scores calculated at 4th week, 8th week, 12th week and 16th week were statistically significant. Narrow-band ultraviolet-B presumably may have an immunomodulatory and inhibitory effect on Malassezia growth. Narrowband ultraviolet-B is an effective and safe alternative tool for the management of extensive and recurrent pityriasis versicolor for patients who are unresponsive to conventional treatments.


Improving knowledge management through the support of image examination and data annotation using DICOM structured reporting.
An important effort has been invested on improving the image diagnosis process in different medical areas using information technologies. The field of medical imaging involves two main data types: medical imaging and reports. Developments based on the DICOM standard have demonstrated to be a convenient and widespread solution among the medical community. The main objective of this work is to design a Web application prototype that will be able to improve diagnosis and follow-on of breast cancer patients. It is based on TRENCADIS middleware, which provides a knowledge-oriented storage model composed by federated repositories of DICOM image studies and DICOM-SR medical reports. The full structure and contents of the diagnosis reports are used as metadata for indexing images. The TRENCADIS infrastructure takes full advantage of Grid technologies by deploying multi-resource grid services that enable multiple views (reports schemes) of the knowledge database. The paper presents a real deployment of such Web application prototype in the Dr. Peset Hospital providing radiologists with a tool to create, store and search diagnostic reports based on breast cancer explorations (mammography, magnetic resonance, ultrasound, pre-surgery biopsy and post-surgery biopsy), improving support for diagnostics decisions. A technical details for use cases (outlining enhanced multi-resource grid services communication and processing steps) and interactions between actors and the deployed prototype are described. As a result, information is more structured, the logic is clearer, network messages have been reduced and, in general, the system is more resistant to failures.


Cigarette smoking and KRAS oncogene mutations in sporadic colorectal cancer: results from the Netherlands Cohort Study.
Since a KRAS oncogene mutation is an early event in colorectal cancer development and cigarette smoking is thought to have an effect on early stages of colorectal tumorigenesis, smoking, especially long-term smoking, may be associated with the risk for colorectal cancer with KRAS oncogene mutations. In the Netherlands Cohort Study on diet and cancer (n=120,852 men and women), using a case-cohort design, adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed for colorectal tumors with wild-type and with mutated KRAS gene, and with specific G:C-->T:A or G:C-->A:T point mutations in KRAS, according to cigarette smoking status, frequency, duration, pack years, age at first exposure, years since cessation, inhalation and filter usage. After 7.3 years and excluding the first 2.3 years, 648 cases and 4083 sub-cohort members were included in the analyses. Ex-smokers, but not current smokers, were at increased risk for colorectal cancer with wild-type KRAS gene tumors when compared with never smokers, albeit not statistically significant (RR 1.26, 95% CI 0.96-1.66). This was not observed for KRAS mutated tumors when comparing ex-smokers with never smokers (RR 1.15, 95% CI 0.79-1.66). The highest category of smoking frequency (>20 cigarettes/day) and inhalation of smoke were associated with an increased risk for colorectal cancer with wild-type KRAS gene tumors, though not statistically significant, when compared with never smoking (frequency: RR 1.24, 95% CI 0.90-1.71 and inhalation: RR 1.25, 95% CI 0.94-1.67). These associations were strongest in men (ex-smokers: RR 1.79, 95% CI 1.00-3.20; frequency: RR 1.91, 95% CI 1.03-3.52; inhalation: RR 1.69, 95% CI 0.94-3.04). No associations were observed between any of the smoking characteristics and the risk for colorectal cancer with mutated KRAS gene tumors, nor where there any clear associations with tumors with specific G:C-->A:T transitions or G:C-->T:A transversions. These results suggest that, in contrast to the hypothesis, smoking does not increase the risk for colorectal tumors with a mutated KRAS gene. Some smoking characteristics, i.e. being an ex-smoker, frequency and inhalation, may be associated with risk for colorectal cancer characterized by the wild-type KRAS gene, especially in men.


Antidepressant-like Effect of Bacopaside I in Mice Exposed to Chronic Unpredictable Mild Stress by Modulating the Hypothalamic-Pituitary-Adrenal Axis Function and Activating BDNF Signaling Pathway.
Preliminary studies conducted in our laboratory have confirmed that Bacopaside I (BS-I), a saponin compound isolated from Bacopa monnieri, displayed antidepressant-like activity in the mouse behavioral despair model. The present investigation aimed to verify the antidepressant-like action of BS-I using a mouse model of behavioral deficits induced by chronic unpredictable mild stress (CUMS) and further probe its underlying mechanism of action. Mice were exposed to CUMS for a period of 5 consecutive weeks to induce depression-like behavior. Then, oral gavage administrations with vehicle (model group), fluoxetine (12 mg/kg, positive group) or BS-I (5, 15, 45 mg/kg, treated group) once daily were started during the last two weeks of CUMS procedure. The results showed that BS-I significantly ameliorated CUMS-induced depression-like behaviors in mice, as characterized by an elevated sucrose consumption in the sucrose preference test and reduced immobility time without affecting spontaneous locomotor activity in the forced swimming test, tail suspension test and open field test. It was also found that BS-I treatment reversed the increased level of plasma corticosterone and decreased mRNA and protein expressions of glucocorticoid receptor induced by CUMS exposure, indicating that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity of CUMS-exposed mice was restored by BS-I treatment. Furthermore, chronic administration of BS-I elevated expression levels of brain-derived neurotrophic factor (BDNF) (mRNA and protein) and activated the phosphorylation of extracellular signal-regulated kinase and cAMP response element-binding protein in the hippocampus and prefrontal cortex in mice subjected to CUMS procedure. Taken together, these results indicated that BS-I exhibited an obvious antidepressant-like effect in mouse model of CUMS-induced depression that was mediated, at least in part, by modulating HPA hyperactivity and activating BDNF signaling pathway.


Polymorphous low-grade adenocarcinoma of the palate: report of cases.
Polymorphous low-grade adenocarcinoma (PLGA) is a rare tumor that mostly affects minor salivary glands. The purpose of this study is to report six new cases followed-up during a long period. We also review the literature concerning clinical, histological and immunohistochemical features, as well as the proper management. Malignant tumors of the salivary glands diagnosed in our department from 1990 to 1999 were reviewed. A total of 66 cases were registered. Six of these cases were diagnosed as PLGA. All cases satisfied the histopathological criteria for this entity, and at least 3 years follow-up was available. In the six cases the primary location was the mucosa of the palate. Hard palate was affected in 83.3% of the cases. There were no cases of extraoral PLGA in our series. Tumors were ulcerated in a 16.6% of the cases, and exofitic in the other 86.4%. Histologically, it was observed a tumoral proliferation of round clusters of uniform cells with round-to-oval clear nuclei and small nucleoli. All the cases underwent surgical management with local excision with surgical margins, five of them with bone extirpation associated. No recurrence was observed in four cases, whereas the remaining two cases showed recurrence in the follow-up. In one of the patients, lococervical recurrence appeared 12 months after the surgery, and this patient died after a few months. The remaining patients have been followed-up for 11, 7, 4 and 3 years postoperatively, with no evidence of recurrence. Our results for a long follow-up period support the idea for a low grade of malignancy and good prognosis of this tumor, but the appearance of recurrences many years after the surgery must induce us to be very careful and systematic with the follow-up.


Loop-mediated amplification of the Clavibacter michiganensis subsp. michiganensis micA gene is highly specific.
Loop-mediated amplification (LAMP) was used to specifically identify Clavibacter michiganensis subsp. michiganensis, causal agent of bacterial canker of tomato. LAMP primers were developed to detect micA, a chromosomally stable gene that encodes a type II lantibiotic, michiganin A, which inhibits growth of other C. michiganensis subspecies. In all, 409 bacterial strains (351 C. michiganensis subsp. michiganensis and 58 non-C. michiganensis subsp. michiganensis) from a worldwide collection were tested with LAMP to determine its specificity. LAMP results were compared with genetic profiles established using polymerase chain reaction (PCR) amplification of seven genes (dnaA, ppaJ, pat-1, chpC, tomA, ppaA, and ppaC). C. michiganensis subsp. michiganensis strains produced eight distinct profiles. The LAMP reaction identified all C. michiganensis subsp. michiganensis strains and discriminated them from other C. michiganensis subspecies and non-Clavibacter bacteria. LAMP has advantages over immunodiagnostic and other molecular detection methods because of its specificity and isothermal nature, which allows for easy field application. The LAMP reaction is also not affected by as many inhibitors as PCR. This diagnostic tool has potential to provide an easy, one-step test for rapid identification of C. michiganensis subsp. michiganensis.


MAOA-L carriers are better at making optimal financial decisions under risk.
Genes can affect behaviour towards risks through at least two distinct neurocomputational mechanisms: they may affect the value assigned to different risky options, or they may affect the way in which the brain adjudicates between options based on their value. We combined methods from neuroeconomics and behavioural genetics to investigate the impact that the genes encoding for monoamine oxidase-A (MAOA), the serotonin transporter (5-HTT) and the dopamine D4 receptor (DRD4) have on these two computations. Consistent with previous literature, we found that carriers of the MAOA-L polymorphism were more likely to take financial risks. Our computational choice model, rooted in established decision theory, showed that MAOA-L carriers exhibited such behaviour because they are able to make better financial decisions under risk, and not because they are more impulsive. In contrast, we found no behavioural or computational differences among the 5-HTT and DRD4 polymorphisms.


Oncologic Efficacy of Radio Frequency Ablation for Small Renal Masses: Clear Cell vs Papillary Subtype.
Current radio frequency ablation series do not distinguish renal cell carcinoma subtypes when reporting oncologic efficacy. Papillary neoplasms may be more amenable to radio frequency ablation than clear cell carcinoma because they are less vascular, which may limit heat energy loss. We report the long-term outcomes of patients treated with radio frequency ablation for small renal masses by renal cell carcinoma subtype. The records of patients undergoing radio frequency ablation for small renal masses (cT1a) at 2 institutions from March 2007 to July 2012 were retrospectively reviewed. Patients were included in analysis if they had biopsy confirmed clear cell or papillary renal cell carcinoma histology. Patients had at least 1 contrast enhanced cross-sectional image following radio frequency ablation. Demographic data between tumor subtypes were compared using the paired t-test. Oncologic outcomes were determined by Kaplan-Meier survival analysis and survivor curves were compared with the log rank test. A total of 229 patients met study inclusion criteria. There were 181 clear cell tumors and 48 papillary tumors. Median followup was 33.2 months. There was no difference between tumor groups based on patient age, tumor size or grade, or months of followup. Five-year disease-free survival was 89.7% for clear cell tumors and 100% for papillary tumors (p = 0.041). There was no significant difference in overall survival (88.4% vs 89.6%, p = 0.764). Radio frequency ablation outcomes seem to be determined in part by renal cell carcinoma subtype with clear cell renal tumors having less favorable outcomes. We hypothesize that this is due to differences in tumor vascularity. Our experience suggests that future tumor ablation studies should consider reporting outcomes based on tumor cell types.


Functional and morphological correlates of mandibular symphyseal form in a living human sample.
Variation in recent human mandibular form is often thought to reflect differences in masticatory behavior associated with variation in food preparation and subsistence strategies. Nevertheless, while mandibular variation in some human comparisons appear to reflect differences in functional loading, other comparisons indicate that this relationship is not universal. This suggests that morphological variation in the mandible is influenced by other factors that may obscure the effects of loading on mandibular form. It is likely that highly strained mandibular regions, including the corpus, are influenced by well-established patterns of lower facial skeletal integration. As such, it is unclear to what degree mandibular form reflects localized stresses incurred during mastication vs. a larger set of correlated features that may influence bone distribution patterns. In this study, we examine the relationship between mandibular symphyseal bone distribution (i.e., second moments of area, cortical bone area) and masticatory force production (i.e., in vivo maximal bite force magnitude and estimated symphyseal bending forces) along with lower facial shape variation in a sample of n = 20 living human male subjects. Our results indicate that while some aspects of symphyseal form (e.g., wishboning resistance) are significantly correlated with estimates of symphyseal bending force magnitude, others (i.e., vertical bending resistance) are more closely tied to variation in lower facial shape. This suggests that while the symphysis reflects variation in some variables related to functional loading, the complex and multifactorial influences on symphyseal form underscores the importance of exercising caution when inferring function from the mandible especially in narrow taxonomic comparisons.


Magnesium, calcium and zinc [N2N'] heteroscorpionate complexes.
A new family of sterically demanding N2N' heteroscorpionate pro-ligands (HC(tBu2pz)2SiMe2N(H)R (R = iPr, tBu, Ph, Xyl)) has been prepared via a straightforward modular synthetic route. An extensive study into the synthesis and characterisation of lithium, magnesium, calcium and zinc complexes supported by both 3,5-tBu and 3,5-Me substituted N2N' ligand families has been conducted. Attempted deprotonation of the pro-ligands with nBuLi afforded the corresponding lithium salts Li{HC(tBu2pz)2SiMe2NR} (R = iPr (1), tBu (2), Ph (3) and Xyl (4)) but air- and thermal-sensitivity limited the yields of these potentially useful precursors; only the sterically encumbered ligand system allowed clean reactivity. Magnesium methyl complexes Mg{HC(tBu2pz)2SiMe2NR}Me (R = iPr (5) and R = Ph (6)) were prepared using an excess of the Grignard reagent MeMgCl. Magnesium butyl complexes were synthesised in good yields using the dialkyl precursor MgnBu2 to afford Mg{HC(R'2pz)2SiMe2NR}nBu (R' = Me; R = iPr (7), tBu (8), Ad (9), Ph (10). R' = tBu; R = iPr (11), Ph (12)). Protonolylsis reactions were used to synthesise magnesium and calcium amide complexes Mg{HC(R'2pz)2SiMe2NR}{N(SiHMe2)2} (R' = Me; R = iPr (13), tBu (14), Ph (15). R' = tBu; R = Ph (16)) or Mg{HC(R'2pz)2SiMe2NR}{N(SiMe3)2} (R' = Me; R = iPr (17), tBu (18), Ph (19). R' = tBu; R = Ph (20)), and Ca{HC(R'2pz)2SiMe2NR}{N(SiMe2)2} (L) (R' = Me; L = thf; R = iPr (21), tBu (22), Ph (23). R' = tBu; L = none; R = Ph (24). Zinc methyl complexes Zn{HC(R'2pz)2SiMe2NR}Me (R' = Me; R = iPr (25), tBu (26), Ph (27). R' = tBu; R = Ph (28)) were prepared by reaction of the N2N' heteroscorpionate pro-ligands with ZnMe2. In preliminary studies, magnesium amide complexes 16 and 20 were evaluated as initiators for the ring-opening polymerisation (ROP) of ε-caprolactone (ε-CL) and rac-lactide (rac-LA). Although the overall polymerisation control was poor, 16 and 20 were found to be active initiators.


Epidermal and dermal dendritic cells display differential activation and migratory behavior while sharing the ability to stimulate CD4+ T cell proliferation in vivo.
Migrated Langerhans cells (m-LCs) have recently been shown to comprise only a minority of skin-derived dendritic cells (DCs) expressing Langerin in cutaneous lymph nodes. We have used BM chimeric mice that differ in CD45 and MHC class II alleles to unequivocally distinguish between radioresistant m-LCs and radiosensitive migrated dermal DCs (m-dDCs), to determine their phenotype, response to contact sensitization, and ability to activate naive CD4+ T cells in vivo. We have also characterized three subsets of dDCs and their migratory counterparts, as distinguished by expression of CD11b and Langerin. Each of the four subsets of skin DCs showed differential migration to draining LN in response to contact sensitizing agents. Migration of Langerin-CD11b+ and Langerin+CD11blow dDCs peaked after 1 day, followed by Langerin-CD11blow dDCs at 2 days and Langerin+ LCs at 4 days. Moreover, while m-LCs and m-dDCs had similar surface phenotypes in the steady state, they displayed unexpectedly different activation responses to contact sensitization: m-dDCs markedly up-regulated CD80 and CD86 at day 1, whereas only m-LCs up-regulated CD40, with delayed kinetics. Thus, m-dDCs are likely to be responsible for the initial response to skin immunization. However, when expression of cognate MHC class II was restricted to LCs and m-LCs, they were also capable of processing and presenting protein Ag to drive naive CD4 T cell proliferation in vivo. Thus, m-dDCs and m-LCs display distinct behavior in cutaneous lymph nodes while sharing the ability to interact specifically with T cells to control the immune response.


Insights into the HER-2 receptor tyrosine kinase mechanism and substrate specificity using a transient kinetic analysis.
The HER-2/erbB-2/c-neu proto-oncogene encodes for an EGF receptor-like protein which has been implicated in the pathogenesis of several human malignancies. Although much has been learned about the physiological significance of this receptor tyrosine kinase, its catalytic mechanism remains poorly understood. We have expressed, purified, and characterized two recombinant proteins corresponding to a full-length (HCD) and truncated (HKD) construct of the HER-2 intracellular tyrosine kinase domain and have identified an optimal substrate (GGMEDIYFEFMGGKKK; HER2Peptide) through screening of a degenerate peptide library. We have conducted a transient kinetic analysis of the HER-2 proteins (HCD and HKD) to illuminate mechanistic details of the HER-2 pathway. In particular, stopped-flow fluorescence studies with mant (N-methylanthraniloyl)-nucleotide derivatives provided direct measurements of the association and dissociation rate constants for these nucleotide interactions with the HER-2 recombinant proteins, thereby enabling the determination of nucleotide K(d) values. Moreover, the actual step of chemical catalysis was isolated using rapid chemical quench techniques and shown to occur approximately 3-fold faster than the steady-state rate which corresponds to product release. Evidence is also provided that suggests a conformational change that is partially rate-limiting at least in HCD. Furthermore, the role that the phosphorylation state of the protein may play on catalysis was examined. Studies carried out with pre-phosphorylated recombinant HER-2 proteins suggest that while autophosphorylation is not a prerequisite for enzymatic activity, this protein modification actually directly affects the catalytic mechanism by enhancing the rate of ADP release and that of the rate-limiting step. While a pre-steady-state kinetic analysis has been carried out on the catalytic subunit of cAMP-dependent serine/threonine kinase, to our knowledge, this study represents the first reported transient kinetic investigation of a receptor tyrosine kinase. This work serves as a basis for comparison of these two important protein kinase families and in this report we highlight these similarities and differences.


Tension-type headache or migraine? Adolescents' pain descriptions are of little help.
The aim of this study was to investigate the utility of pain descriptors (pain quality, pain intensity) assessed in a questionnaire to discriminate tension-type headache (TTH) from TTH plus migraine in a sample of adolescents. Epidemiological studies assess pain characteristics via questionnaire and estimate prevalence rates based on these pain descriptions. According to International Headache Society criteria, the subjective pain quality and intensity for TTH and migraine differs and therefore should be able to discriminate the 2 diagnoses. The discriminative ability between TTH and TTH plus migraine may be a special challenge. One hundred twenty-two adolescents with pure TTH and 110 adolescents with TTH plus migraine aged 11-18 years presenting to a tertiary pediatric pain clinic were included in the study. Questionnaire reports of pain intensity and quality were compared with physician's diagnosis as the gold standard. Mean differences as well as receiver operating characteristics were analyzed. Adolescents with TTH plus migraine reported more pulsating and less intense pain compared with pure TTH. Receiver operating characteristic analysis indicated that pain descriptors did not discriminate between groups. Diagnostic utility of descriptors was similarly low for older adolescents and parental proxy reports. Pain intensity and quality assessed by questionnaires are not suitable to discriminate TTH from TTH plus migraine. This may lead to inaccurate prevalence estimates in epidemiological studies and may mislead practitioners in forming diagnostic hypotheses. The exclusion of these pain descriptors in questionnaires should be considered. More research systematically assessing the diagnostic utility of verbal pain descriptors in primary care and epidemiological samples is needed.


Orally administered apple procyanidins protect against experimental inflammatory bowel disease in mice.
Apple procyanidins (ACT) is a natural biologically active compound extracted from apple. Our recent studies have shown that ACT ameliorates the symptoms of atopic dermatitis and inhibits food-allergen-induced oral sensitization. The aim of this study was to investigate the potential protective effect and mechanism of action of ACT in a murine model of inflammatory bowel disease. We investigated the preventive effects of ACT in experimental models of colitis induced by dextran sulfate sodium (DSS) or oxazolone. Oral administration of ACT before DSS treatment attenuated the DSS-induced mortality rate and decreased body weight loss. ACT also prevented the body weight loss associated with oxazolone-induced colitis. Next we examined the effect of ACT on intraepithelial lymphocytes (IEL), which is a major T cell population in the intestine. Oral administration of ACT increased the proportions of TCRgammadelta and TCRalphabeta-CD8alphaalpha T cells in IEL and suppressed interferon gamma synthesis in stimulated IEL. In addition, ACT inhibited phorbol 12-myristate 13-acetate-induced secretion of interleukin 8 (IL-8) in intestinal epithelial cells. The combined anti-inflammatory and immunomodulatory effects of ACT on intestinal epithelial cells and IEL suggest that it may be an effective oral preventive agent for inflammatory bowel diseases.


Preventing dialysis hypotension: a comparison of usual protective maneuvers.
Intradialytic hypotension (IH) is a common adverse event. Currently, there are several commonly utilized therapies of IH, but they have not been compared directly in the same group of patients. We performed the present study in order to learn which of these techniques is most effective so that a rational approach to treating IH could then be formulated. A single-blinded, crossover study design of five different protocols was undertaken in 10 hemodialysis patients with a prior history of IH. Each patient first underwent one week (three dialyses) of standard dialysis (dialysate sodium 138 mEq/L). Then each patient was subjected to one week each (three dialyses) of the four test protocols, performed in random order in a blinded fashion. The specific protocols were as follows: high sodium dialysate, in which the patient was dialyzed using a dialysate sodium of 144 mEq/L; sodium modeling, during which the dialysate sodium declined from 152 to 140 mEq/L in the last half hour of dialysis; one hour of isolated ultrafiltration followed by three hours of isovolemic dialysis; and cool temperature dialysis in which the dialysate was cooled to 35 degrees C. Weight loss in each of the five protocols was essentially identical, varying between 2.9 and 3 kg. There were significantly fewer hypotensive episodes per treatment in the sodium modeling, high sodium, and cool temperature protocols as compared with the standard protocol (P < 0.05). Ultrafiltration followed by dialysis was associated with a significantly greater number of hypotensive episodes per treatment than any of the three test protocols (P < 0.05). Similarly, the number of nursing interventions required for IH per treatment was significantly greater in the standard dialysis and in the isolated ultrafiltration protocols compared with sodium modeling and cool temperature protocols (P < 0.05). The number of hypotensive signs and symptoms per treatment was also significantly reduced during the sodium modeling and cool temperature protocols compared with the standard protocol (P < 0.004 and P < 0.02, respectively). Again, the isolated ultrafiltration protocol resulted in significantly more hypotensive symptoms and signs than the three test protocols (P < 0.005). Finally, the nadir mean arterial pressures were significantly lower in the standard and isolated ultrafiltration protocols when compared with the three test protocols (P < 0.05). The upright postdialysis blood pressure was best preserved in the sodium modeling and cool temperature protocols compared with the standard and isolated ultrafiltration protocols (P < 0.05). This study supports the use of sodium modeling as a first step in combating IH. Also effective were the use of cool-temperature dialysate and a high-sodium dialysate. All three test protocols were well tolerated. As applied in this study, isolated ultrafiltration followed by isovolemic dialysis was notably less effective in reducing IH.


Identification of candidate proteins for the diagnosis of Bartonella henselae infections using an immunoproteomic approach.
Bartonella henselae is an emerging gram-negative facultative intracellular pathogen transmitted via Ctenocephalides felis (cat fleas) or cat scratches. Bartonellosis is present mainly in the form of cat scratch disease (CSD), bacillary angiomatosis and infective endocarditis (IE). The methods used to diagnose B. henselae rely on culturing, immunofluorescent assays and molecular techniques. The objective of the present study was to identify candidate proteins for the serodiagnosis of bartonellosis with the differential discrimination of both clinical scenarios: CSD and IE. For this, an immunoproteomic approach combined with 2-DE, immunoblotting and matrix-assisted laser desorption/ionization time-of-flight MS has been developed. Immunoproteomic profiles of sera collected from patients with CSD and IE were compared with those of blood donors. We identified several candidate proteins as phage-encoding Pap31 protein and an outer membrane protein of BH11510 that, in our view, might be useful for the serodiagnosis of bartonellosis.


Mayo Clinic experience with epithelial ovarian cancer.
Clinical investigation of epithelial ovarian cancer must involve the precise definition of the lesion, careful application of new techniques, the objective evaluation of such techniques, the comparison of results in a randomized fashion with prior forms of therapy, careful pathological evaluation of the tumour, and the evaluation of toxicity to the patient. The interdisciplinary team approach to the treatment of epithelial ovarian cancer and the development of randomized, prospective trials are essential. Utilizing these two elements, a better integration of surgery, chemotherapy and radiation therapy can be accomplished. Of great importance is the evaluation of response patterns by an observer who is skilled in pelvic examinations and familiar with the natural history of epithelial ovarian cancer. The increasingly important role of surgery in the treatment of this cancer is now more clearly defined. The psychological effects of chemotherapy as well as the response patterns to chemotherapy must be evaluated. During the past 20 years, considerable progress has been made in prolonging the useful, functional life of the patient. The ultimate cure is still a matter for the future and is predicated on more effective combinations of potent chemotherapeutic combinations and a clearer definition of the role of radiation therapy.


Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells.
Pluripotent stem cells, both embryonic stem cells and induced pluripotent stem cells, are undifferentiated cells that can self-renew and potentially differentiate into all hematopoietic lineages, such as hematopoietic stem cells (HSCs), hematopoietic progenitor cells and mature hematopoietic cells in the presence of a suitable culture system. Establishment of pluripotent stem cells provides a comprehensive model to study early hematopoietic development and has emerged as a powerful research tool to explore regenerative medicine. Nowadays, HSC transplantation and hematopoietic cell transfusion have successfully cured some patients, especially in malignant hematological diseases. Owing to a shortage of donors and a limited number of the cells, hematopoietic cell induction from pluripotent stem cells has been regarded as an alternative source of HSCs and mature hematopoietic cells for intended therapeutic purposes. Pluripotent stem cells are therefore extensively utilized to facilitate better understanding in hematopoietic development by recapitulating embryonic development in vivo, in which efficient strategies can be easily designed and deployed for the generation of hematopoietic lineages in vitro. We hereby review the current progress of hematopoietic cell induction from embryonic stem/induced pluripotent stem cells.


[Asthma and cost of illness].
The basic aim of the activities concerning health is to implement the initiatives for people to attain the best health status and sustain it. That's why these initiatives have to be chosen from the ones that consume minimum resource and affect life quality and duration in most beneficial way. Asthma is one of the most prevalent chronic disorders. Asthma brings significant direct and indirect costs to societies. To decrease the burden of asthma, it is necessary to emphasize its effects related to morbidity, mortality and material losses. Therefore, countries should give priority to cost of illness studies.


Choosing vs. allocating: discrete choice experiments and constant-sum paired comparisons for the elicitation of societal preferences.
There is growing evidence of a reluctance to allocate health care solely on the basis of maximizing quality-adjusted life years (QALYs). Stated preference methods can be used to elicit preferences for efficiency vs. equity in the allocation of health-care resources. To compare discrete choice experiment (DCE) and constant-sum paired comparison (CSPC) methods for eliciting societal preferences. Over a series of choice pairs, DCE respondents allocated a fixed budget to one preferred group and CSPC respondents allocated budget percentages between the groups. Questionnaires were compared in terms of completion rates, preference consistency, dominant preferences and derived attribute importance. There was no significant difference in the proportions that rated the questionnaires somewhat or extremely difficult, but a significantly greater proportion completed the DCE compared to the CSPC. Preference consistency was also higher in the DCE. The incidence of dominant preferences, including for aggregate QALYs, was low and not significantly different between questionnaires. Similarly, no CSCP respondents equalized budgets or outcomes in every task. Final health state was the most important attribute in both questionnaires, but the rankings diverged for the other attributes. Notably, the total patients' treated attribute was important in the CSPC but insignificant in the DCE, perhaps reflecting a 'prominence effect'. Despite lower completion rates and preference consistency, CSPC may offer advantages over DCE in eliciting preferences over the distribution of resources and/or outcomes as well as attribute levels, avoiding extreme 'all-or-nothing' distributions and possibly aligning respondent attention more closely with a societal perspective.


Similarity boosted quantitative structure-activity relationship--a systematic study of enhancing structural descriptors by molecular similarity.
The concept of molecular similarity is one of the most central in the fields of predictive toxicology and quantitative structure-activity relationship (QSAR) research. Many toxicological responses result from a multimechanistic process and, consequently, structural diversity among the active compounds is likely. Combining this knowledge, we introduce similarity boosted QSAR modeling, where we calculate molecular descriptors using similarities with respect to representative reference compounds to aid a statistical learning algorithm in distinguishing between different structural classes. We present three approaches for the selection of reference compounds, one by literature search and two by clustering. Our experimental evaluation on seven publicly available data sets shows that the similarity descriptors used on their own perform quite well compared to structural descriptors. We show that the combination of similarity and structural descriptors enhances the performance and that a simple stacking approach is able to use the complementary information encoded by the different descriptor sets to further improve predictive results. All software necessary for our experiments is available within the cheminformatics software framework AZOrange.


Instituting a New Central Line Policy to Decrease Central Line-associated Blood Stream Infection Rates During Induction Therapy in Pediatric Acute Lymphoblastic Leukemia Patients.
Children with acute lymphoblastic leukemia (ALL) require central lines to facilitate their care. Peripherally inserted central catheters (PICCs) may have lower rates of central line-associated bloodstream infections (CLABSIs) versus other central lines. The objective of this study was to compare the CLABSI rate in the first month of therapy after initiating a policy to place PICCs in new patients with severe neutropenia (SN) and Mediports in those with moderate-to-no neutropenia. We also examined thrombosis rates. We prospectively gathered data on new patients for 2.5 years following the policy change and retrospectively for the 2 years prior and compared rates of CLABSIs and thrombosis. CLABSIs decreased in SN patients from 7.52/1000 to 3.11/1000 line days (P=0.33). The CLABSI rate for all patients with SN who had a Mediport was 13.39/1000 versus 4.08/1000 line days for those that received PICCs (P=0.15). The thrombosis rate for Mediport patients was 3.13 clots/1000 versus 7.65/1000 line days for PICC patients, but the difference was not significant (P= 0.11). The differences observed suggest that placing PICCs versus Mediports in new ALL patients with SN may result in a lower incidence of CLABSIs in the first month of therapy without a significant increase in thrombosis.


Adolescent girls with asthma have worse asthma control and health-related quality of life than boys-A population based study.
Population-based studies investigating health-related quality of life (HRQoL) among asthmatic adolescents are rare. Further, among subjects with asthma, HRQoL may be affected by asthma control and severity. To investigate HRQoL in relation to asthma control and asthma severity among adolescents. As a part of the population-based OLIN pediatric study, 266 adolescents with current asthma (14-15 yr) were identified. N = 247 completed the DISABKIDS HRQoL asthma module, including the domains impact and worry. The Asthma Control Test (ACT) was used and a disease severity score was calculated based on symptoms and medicine use. The prevalence of current asthma was 11%. Well-controlled asthma was reported by 15% of the adolescents, and 53% had partly controlled asthma. The prevalence of uncontrolled asthma was significantly higher among girls than boys (38% vs 25%), and girls also reported lower HRQoL scores. There was a fairly strong correlation between the ACT and DISABKIDS scores. Independent risk factors for low HRQoL impact (a score <67) were female sex (OR 4.66, 95%CI 1.82-9.54) and decreased ACT scores (1.38, 1.18-1.62). Risk factors for low HRQoL worry (a score <70) were female sex (3.33, 1.41-7.86), decreased ACT scores (1.35, 1.16-1.57), severe asthma (6.23, 1.46-16.50), and having current eczema (2.68, 1.00-7.24). Only a minority of the asthmatic adolescents reported well-controlled asthma, and poor asthma control and female sex were risk factors for low HRQoL. Our results demonstrate that evaluation of asthma control is of great importance for asthma management.


[Prevalence and natural course of chronic high-altitude cor pulmonale].
Short-term and prospective epidemiological surveys conducted in Highlanders of the Tien Shan and Pamirs (2800-4200 m above the sea level) have shown that the chronic high-altitude pulmonary heart (CHAPH) is a common type of pathology, with growing age of the examinees the frequency of CHAPH being considerably on a decrease. CHAPH is characterized by a progressive course and is frequently complicated by various types of cardiac arrhythmia. With a growing degree of marked right ventricular hypertrophy the number of lethal outcomes among Highlanders increases.


The New Face of Preadolescent and Adolescent Acne: Beyond the Guidelines.
Acne is a highly prevalent condition, affecting the majority of people at some point in their lifetimes, most often during adolescence. Acne has also become increasingly common among preadolescents (aged ≥7 to ≤12 years old).Acne is often treated in primary care settings by nondermatologists. The most recent acne guidelines were published in 2016; since then, there have been important developments in the acne treatment landscape. Familiarity with these options is important for physicians who manage patients with acne.The Preadolescent Acne Roundtable group of dermatologists was convened in July 2019 to support discussion around modernizing the approach to treatment and evaluation of preadolescent acne. During a face-to-face meeting, 5 key areas requiring careful communication emerged: acne pathophysiology, specifically the role of hormones; psychological aspects of acne; management of acne in younger patients; acne in skin of color; and evaluation of clinical success.This roundtable report describes these 5 focus areas, with the aim of empowering primary care physicians to refine the care they provide for patients with acne. This report can help bridge the information gap until new acne treatment guidelines are published.


Differential detergent resistance of the apical and basolateral NPPases: relationship with polarized targeting.
Targeting of glycosylphosphatidylinositol-anchored proteins to the apical surface of epithelial cells involves clustering in Triton X-100-resistant membrane microdomains or rafts. The role of these microdomains in sorting transmembrane proteins is more questionable because, unlike glycosylphosphatidylinositol-anchored proteins, apical transmembrane proteins are rather soluble in Triton X-100. They are, however, resistant to milder detergents such as Lubrol WX or Tween 20. It has been proposed that specific membrane microdomains, defined by resistance to these detergents, would carry transmembrane proteins to the apical surface. We have used MDCK cells stably transfected with the apical and basolateral pyrophosphatases/phosphodiesterases, NPP3 and NPP1, to examine the relationship between detergent resistance and apical targeting. The apically expressed wild-type NPP3 was insoluble in Lubrol WX whereas wild-type NPP1, which is expressed basolaterally, was essentially soluble. By using tail mutants and chimeric constructs that combine the cytoplasmic, transmembrane and extracellular domains of NPP1 and NPP3, we show that there is not a strict correlation between detergent resistance and apical targeting. Lubrol resistance is an intrinsic property of NPP3, which is acquired early during the biosynthetic process irrespective of its final destination, and depends on positively charged residues in its cytoplasmic tail.


Prostaglandin E(2) decreases allergen-stimulated release of prostaglandin D(2) in airways of subjects with asthma.
Prostaglandin E(2) (PGE(2)) inhibits the early and late bronchoconstrictor response to inhaled allergen. The mechanisms of action, however, are not understood. We investigated the effect of inhaled PGE(2) on the release of prostaglandin D(2) (PGD(2)), preformed mast cell mediators, and other products of arachidonic acid metabolism. We compared inhaled PGE(2) (100 microgram) to placebo in a randomized double-blind crossover study. Ten atopic asthmatics underwent bronchoscopy immediately after inhalation of PGE(2) or placebo. Bronchoalveolar lavage (BAL) was performed at baseline, and in a separate segment 4 min after allergen instillation. Nebulized PGE(2) was well tolerated. PGE(2) concentrations in baseline lavage fluid were significantly greater after PGE(2) inhalation than after placebo. PGD(2) concentrations after allergen challenge were significantly reduced in those subjects receiving nebulized PGE(2) compared with control subjects. We conclude that PGE(2) can be safely delivered by inhalation. Nebulized PGE(2) administered before to segmental allergen challenge reduced PGD(2) in BAL fluid (BALF). PGE(2) also decreased the production of other mediators of the arachidonic acid pathway, although not significantly. The reduction of PGD(2) may be part of the mechanism by which PGE(2) blocks the early asthmatic response.


Optimizing spinal cord injury in zebrafish larvae: effects of age on the injury response.
Zebrafish are an increasingly popular model to study spinal cord injury (SCI) regeneration. The transparency of larval zebrafish makes them ideal to study cellular processes in real time. Standardized approaches, including age of injury, are not readily available making comparisons of the results with other models challenging. In this study, we systematically examined the response to spinal cord transection of larval zebrafish at three different ages (3-7 days post fertilization or dpf) to determine whether the developmental complexity of the central nervous system affects the overall response to SCI. We then used imaging and behavioral analysis to evaluate whether differences existed based on the age of injury. All ages of larval zebrafish upregulated the required genes for glial bridge formation, ctgfa and gfap, at the site of injury, consistent with studies from adult zebrafish. Though all larval ages upregulated factors required to promote glial bridging, young larval zebrafish (3 dpf) were better able to regenerate axons independent of the glial bridge, unlike older zebrafish (7 dpf). Consistent with this data, locomotor experiments demonstrated that some swimming behavior occurs independent of glial bridge formation, further highlighting the need for standardization of this model and recovery assays. Overall, we found subtle cellular differences based on the age of transection in zebrafish, underlining the importance of considering age when designing experiments aimed at understanding regeneration.


Metabolic surgery for non-obese type 2 diabetes: incretins, adipocytokines, and insulin secretion/resistance changes in a 1-year interventional clinical controlled study.
To compare duodenal-jejunal bypass (DJB) with standard medical care in nonobese patients with type 2 diabetes and evaluate surgically induced endocrine and metabolic changes. Eighteen patients submitted to a DJB procedure met the following criteria: overweight, diabetes diagnosis less than 15 years, current insulin treatment, residual β-cell function, and absence of autoimmunity. Patients who refused surgical treatment received standard medical care (control group). At baseline, 3, 6, and 12 months after surgery, insulin sensitivity and production of glucagon-like peptide-1 and glucose-insulinotropic polypeptide were assessed during a meal tolerance test. Fasting adipocytokines and dipeptidyl-peptidase-4 concentrations were measured. The mean age of the patients was 50 (5) years, time of diagnosis: 9 (2) years, time of insulin usage: 6 (5) months, fasting glucose: 9.9 (2.5) mmol/dL, and HbA1c (glycosylated hemoglobin) level: 8.9% (1.2%). Duodenal-jejunal bypass group showed greater reductions in fasting glucose (22% vs 6% in control group, P < 0.05) and daily insulin requirement (93% vs 15%, P < 0.01). Twelve patients from DJB group stopped using insulin and showed improvements in insulin sensitivity and β-cell function (P < 0.01), and reductions in glucose-insulinotropic polypeptide levels (P < 0.001), glucagon during the first 30 minutes after meal (P < 0.05), and leptin levels (P < 0.05). Dipeptidyl-peptidase-4 levels increased after surgery (P < 0.01), but glucagon-like peptide-1 levels did not change. Duodenal-jejunal bypass improved insulin sensitivity and β-cell function and reduced glucose-insulinotropic polypeptide, leptin, and glucagon production. Hence, DJB resulted in better glycemic control and reduction in insulin requirement but DJB did not result in remission of diabetes.


Two-stage tuberculosis diagnostics: combining centrifugal microfluidics to detect TB infection and Inh and Rif resistance at the point of care with subsequent antibiotic resistance profiling by targeted NGS.
Globally, tuberculosis (TB) remains the deadliest bacterial infectious disease, and spreading antibiotic resistances is the biggest challenge for combatting the disease. Rapid and comprehensive diagnostics including drug susceptibility testing (DST) would assure early treatment, reduction of morbidity and the interruption of transmission chains. To date, rapid genetic resistance testing addresses only one to four drug groups while complete DST is done phenotypically and takes several weeks. To overcome these limitations, we developed a two-stage workflow for rapid TB diagnostics including DST from a single sputum sample that can be completed within three days. The first stage is qPCR detection of M. tuberculosis complex (MTBC) including antibiotic resistance testing against the first-line antibiotics, isoniazid (Inh) and rifampicin (Rif). The test is automated by centrifugal microfluidics and designed for point of care (PoC). Furthermore, enriched MTBC DNA is provided in a detachable sample tube to enable the second stage: if the PCR detects MTBC and resistance to either Inh or Rif, the MTBC DNA is shipped to specialized facilities and analyzed by targeted next generation sequencing (tNGS) to assess the complete resistance profile. Proof-of-concept testing of the PoC test revealed an analytical sensitivity of 44.2 CFU ml-1, a diagnostic sensitivity of 96%, and a diagnostic specificity of 100% for MTBC detection. Coupled tNGS successfully provided resistance profiles, demonstrated for samples from 17 patients. To the best of our knowledge, the presented combination of PoC qPCR with tNGS allows for the fastest comprehensive TB diagnostics comprising decentralized pathogen detection with subsequent resistance profiling in a facility specialized in tNGS.


Ceftaroline in severe community-acquired pneumonia.
Severe community-acquired pneumonia (SCAP) is associated with high mortality. Factor such as early adequate antibiotic therapy, delay in intensive care unit (ICU) care and pneumonia caused by resistant pathogens are associated with worse outcomes in SCAP patients. Ceftaroline is a fifth-generation cephalosporin with bactericidal activity against Gram-positive pathogens (including methicillin-resistant Staphylococcus aureus [MRSA] and multidrug-resistant Streptococcus pneumoniae) and common Gram-negative organisms. The efficacy and safety for the treatment of pneumonia was evaluated in three randomized control trials were ceftaroline demonstrated superiority against ceftriaxone for the treatment of pneumonia in hospitalized patients with Pneumonia Severity Index (PSI) III - IV.


Accredited Cardiac Arrest Centers Facilitate eCPR and Improve Neurological Outcome.
Out-of-hospital cardiac arrest (OHCA) remains a frequent medical emergency with low survival rates even after a return of spontaneous circulation (ROSC). Growing evidence supports formation of dedicated teams in scenarios like cardiogenic shock to improve prognosis. Thus, the European Resuscitation Council (ERC) recommended introduction of Cardiac Arrest Centers (CAC) in their 2015 guidelines. Here, we aimed to elucidate the effects of newly introduced CACs in Germany regarding survival rate and neurological outcome. A multicenter retrospective observational cohort study was performed at three university hospitals and outcomes after OHCA were compared before and after CAC accreditation. Primary outcomes were survival until discharge and favorable neurological status (CPC 1 or 2) at discharge. In total 784 patients (368 before and 416 after CAC accreditation) were analyzed. Rates of immediate percutaneous coronary intervention (40 vs. 52%, p= 0.01) and implementation of extracorporeal CPR (8 vs. 13%, p< 0.05) increased after CAC accreditation. Likelyhood of favorable neurological status at discharge was higher after CAC accreditation (71 vs. 87%, p< 0.01), whereas overall survival remained similar (35 vs. 35%, p> 0.99). CAC accreditation is linked to higher rates of favorable neurological outcome and unchanged overall survival.


Sex differences in mapping and rhythm outcomes of a repeat atrial fibrillation ablation.
The risk of procedure-related complications and rhythm outcomes differ between men and women after atrial fibrillation catheter ablation (AFCA). We evaluated whether consistent sex differences existed in mapping and rhythm outcomes in repeat ablation procedures. Among 3282 patients in the registry, we analysed 443 consecutive patients (24.6% female, 58.5±10.3 years old, 61.5% with paroxysmal atrial fibrillation) who underwent a second AFCA. We compared the clinical factors, mapping, left atrial (LA) pressure, complications and long-term clinical recurrences after propensity score matching. LA volume index (43.1±18.6 vs 35.8±11.6 mL/m2, p<0.001) was higher, but LA dimension (40.0±6.8 vs 41.6±6.3 mm, p=0.018), LA voltage (0.94±0.55 vs 1.20±0.68 mV, p=0.002) and pericardial fat volume (89.5±43.1 vs 122.1±53.9 cm3, p<0.001) were lower in women with repeat ablation than in their male counterparts. Pulmonary vein (PV) reconnections were lower (58.7% vs 74.9%, p=0.001), but the proportion of extra-PV triggers (27.5% vs 17.0%, p=0.026) and elevated LA pulse pressures (79.7% vs 63.7%, p=0.019) was significantly higher in women than in men. There was no significant sex difference in the rate of procedure-related complications (4.6% vs 4.2%, p=0.791). During a 31-month (8-60) median follow-up, clinical recurrences were significantly higher in women after both the de novo procedure (log-rank p=0.039, antiarrhythmic drug (AAD)-free log-rank p<0.001) and the second procedure (log-rank p=0.006, AAD-free log-rank p=0.093). Female sex (HR 1.51, 95% CI 1.06 to 2.15, p=0.023), non-paroxysmal atrial fibrillation (HR 1.78, 95% CI 1.30 to 2.34, p<0.010) and extra-PV triggers (HR 1.88, 95% CI 1.28 to 2.75, p=0.001) were independently associated with clinical recurrences after repeat procedures. During repeat AFCA procedures, PV reconnections were lower in women than in men, and the existence of extra-PV triggers and an LA pressure elevation were more significant, which resulted in poor rhythm outcomes. NCT02138695.


Barriers and facilitators to participation, and key components of sleep health programmes: perspectives for the corporate work environment.
To explore the barriers and facilitators of participation and key components for sleep health programmes designed for corporate work environments. Semi-structured interviews with corporate executives and occupational medicine specialists in the decision-making and management of workplace health promotion programmes (WHPP) within their companies were held before and during COVID-19. Interviews were transcribed verbatim and analysed using thematic content analysis to identify themes. Barrier and facilitator themes emerging from the data include sleep health awareness; work culture; work-family balance and confidentiality. Key components for sleep health programmes included: identifying the need for a programme; incorporating sleep health risk screening to WHPP and promoting sleep health by raising awareness thereof. The identified barriers and facilitators to employee participation and key components of an ideal sleep health programme provide guidance for further WHPP.


Assessing drug safety by identifying the axis of arrhythmia in cardiomyocyte electrophysiology.
Many classes of drugs can induce fatal cardiac arrhythmias by disrupting the electrophysiology of cardiomyocytes. Safety guidelines thus require all new drugs to be assessed for pro-arrhythmic risk prior to conducting human trials. The standard safety protocols primarily focus on drug blockade of the delayed-rectifier potassium current (IKr). Yet the risk is better assessed using four key ion currents (IKr, ICaL, INaL, IKs). We simulated 100,000 phenotypically diverse cardiomyocytes to identify the underlying relationship between the blockade of those currents and the emergence of ectopic beats in the action potential. We call that relationship the axis of arrhythmia. It serves as a yardstick for quantifying the arrhythmogenic risk of any drug from its profile of multi-channel block alone. We tested it on 109 drugs and found that it predicted the clinical risk labels with an accuracy of 88.1-90.8%. Pharmacologists can use our method to assess the safety of novel drugs without resorting to animal testing or unwieldy computer simulations.


Allograft rejection, autograft fusion and inflammatory responses to injury in Callyspongia diffusa (Porifera; Demospongia).
Sponges exhibit a variety of swift, cellular defence responses to protect self integrity. The sponge Callyspongia diffusa has been used to characterize the cytological changes that occur during allograft rejection, autograft fusion, and inflammation. Allogeneic contact results in fusion of the two exopinacoderms followed by an infiltration of mesohyl cells into the graft zone. As mesohyl cells accumulate, they form tissue bridges that span the graft interface. After a few days, the tissue bridges and the nearby cellular infiltrate become necrotic and slough off, which separates the allogeneic tissues. Autograft fusion begins similarly but cellular infiltration does not follow exopinacoderm fusion. Contacted exopinacocytes are redistributed, the endopinacoderms and choanosomes come into contact, and the grafted sponge tissues merge. Tissue damage exposes internal regions of the sponge to the external environment. In many areas of injury, exposed choanosome is sealed by infiltrating mesohyl cells. In other areas, exposed endopinacoderm appears to serve as new exopinacoderm. Cellular debris is removed by phagocytic archaeocytes and new exopinacoderm is regenerated over the damaged choanosome. No scars remain once the inflammatory infiltrate has dispersed. In general, mesohyl cells are involved in defence responses without an observed enrichment of any specific cell type. However, archaeocytes from rejecting sponges appear to line both sides of the allogeneic interface.


Identification and characterization of circRNAs in the skin during wool follicle development in Aohan fine wool sheep.
Aohan fine wool sheep (AFWS) is a historically bred fine wool sheep, cultivated in China. The wool has excellent quality and good textile performance. Investigating the molecular mechanisms that regulate wool growth is important to improve wool quality and yield. Circular RNAs (circRNAs) are widely expressed non-coding RNAs that can act as competitive endogenous RNAs (ceRNAs) to bind to miRNAs. Although circRNAs have been studied in many fields, research on their activity in sheep wool follicles is limited. To understand the regulation of circRNAs in the growth of fine wool in sheep, we used RNA-Seq to identify circRNAs in sheep shoulder skin samples at three developmental stages: embryonic day 90 (E90d), embryonic day 120 (E120d), and at birth (Birth). We identified 8753 circRNAs and found that 918 were differentially-expressed. We then analyzed the classification and characteristic of the circRNAs in sheep shoulder skin. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we identified the source genes of circRNAs, which were mainly enriched in cellular component organization, regulation of primary metabolic processes, tight junctions, and the cGMP-PKG and AMPK signaling pathways. In addition, we predicted interactions between 17 circRNAs and eight miRNAs, using miRanda software. Based on the significant pathways, we speculate that circ_0005720, circ_0001754, circ_0008036, circ_0004032, circ_0005174, circ_0005519, and circ_0007826 might play an important role in regulating wool follicle growth in AFWS. Seven circRNAs were randomly selected to validate the RNA-Seq results, using qRT-PCR. Our results provide more information about circRNAs regulation of wool follicle development in AFWS, and establish a solid foundation for future research.


A review on emerging contaminants in wastewaters and the environment: current knowledge, understudied areas and recommendations for future monitoring.
This review identifies understudied areas of emerging contaminant (EC) research in wastewaters and the environment, and recommends direction for future monitoring. Non-regulated trace organic ECs including pharmaceuticals, illicit drugs and personal care products are focused on due to ongoing policy initiatives and the expectant broadening of environmental legislation. These ECs are ubiquitous in the aquatic environment, mainly derived from the discharge of municipal wastewater effluents. Their presence is of concern due to the possible ecological impact (e.g., endocrine disruption) to biota within the environment. To better understand their fate in wastewaters and in the environment, a standardised approach to sampling is needed. This ensures representative data is attained and facilitates a better understanding of spatial and temporal trends of EC occurrence. During wastewater treatment, there is a lack of suspended particulate matter analysis due to further preparation requirements and a lack of good analytical approaches. This results in the under-reporting of several ECs entering wastewater treatment works (WwTWs) and the aquatic environment. Also, sludge can act as a concentrating medium for some chemicals during wastewater treatment. The majority of treated sludge is applied directly to agricultural land without analysis for ECs. As a result there is a paucity of information on the fate of ECs in soils and consequently, there has been no driver to investigate the toxicity to exposed terrestrial organisms. Therefore a more holistic approach to environmental monitoring is required, such that the fate and impact of ECs in all exposed environmental compartments are studied. The traditional analytical approach of applying targeted screening with low resolution mass spectrometry (e.g., triple quadrupoles) results in numerous chemicals such as transformation products going undetected. These can exhibit similar toxicity to the parent EC, demonstrating the necessity of using an integrated analytical approach which compliments targeted and non-targeted screening with biological assays to measure ecological impact. With respect to current toxicity testing protocols, failure to consider the enantiomeric distribution of chiral compounds found in the environment, and the possible toxicological differences between enantiomers is concerning. Such information is essential for the development of more accurate environmental risk assessment.


Treatment of congestive heart failure with coenzyme Q10 illuminated by meta-analyses of clinical trials.
The purpose of this was to investigate the effect of coenzyme Q10 (CoQ10) in patients with congestive heart failure (CHF) by measuring the possible improvement of certain relevant hemodynamic heart parameters. A statistic aggregation method know as a meta-analysis was used to measure the changes in the cardiac parameters. To begin with we collected the total number of randomized controlled trials and from a total of 14 studies published in the period of 1984-1994, eight studies met our inclusion criteria. The rest were excluded because of a lack of data which made a meta-analysis impossible. The relevant effect parameters investigated were stroke volume (SV), cardiac output (CO), ejection fraction (EF), cardiac index (CI), end diastolic volume index (EDVI), systolic time intervals (PEP/LVET) and total work capacity (Wmax). Seven meta-analyses were performed, one for each of the parameters, and the calculated effect sizes were all positive. Statistical significance could be demonstrated for all of the parameters except the PEP/LVET and Wmax thereby indicating an improvement of greater or lesser magnitude in the CoQ10 group as opposed to the placebo group. Accordingly, the average patient in the CoQ10 group had a better score with regard to SV and CO than 76 and 73% respectively of the patients in the placebo group. In conclusion, supplemental treatment of CHF with CoQ10 is consistent with an improvement of SV, EF, CO, CI and EDVI. Homogeneity could be established for SV and CO. Additional clinical trials of the effect of CoQ10 on CHF are necessary, but, on the basis of the evidence currently available, the possibility remains that CoQ10 will receive a well-documented role as an adjunctive treatment of CHF.


INO-1001 a novel poly(ADP-ribose) polymerase (PARP) inhibitor improves cardiac and pulmonary function after crystalloid cardioplegia and extracorporal circulation.
Poly(ADP-ribose) polymerase (PARP) activation plays a key role in free radical-induced injury in the context of systemic inflammation and ischemia/reperfusion. In the present preclinical study, we investigated the effects of INO-1001, a novel PARP inhibitor, on cardiac and pulmonary function during reperfusion in an experimental model of cardioplegic arrest and extracorporal circulation. Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or INO-1001 (1 mg/kg), a potent PARP inhibitor (n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow and vasodilative responses to acetylcholine and sodium nitroprusside as well as pulmonary gas exchange were also determined. The administration of INO-1001 led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 min of reperfusion. Coronary blood flow was also significantly higher in the INO-1001 group (P < 0.05). Although the vasodilative response to sodium nitroprusside was similar in both groups, acetylcholine resulted in a significantly greater increase in coronary and pulmonary blood flow in the INO-1001 group (P < 0.05). Pulmonary function in terms of alveolar arterial oxygen difference was better preserved in the INO-1001-treated group (P < 0.05). Thus, PARP inhibition improves the recovery of myocardial and endothelial function after hypothermic cardiac arrest and reduces pulmonary injury associated with extracorporal circulation.


Melatonin content in plasma and large intestine of patients with colorectal carcinoma before and after surgery.
The distinct melatonin rhythm with higher concentrations during the darktime was found in plasma of both control patients and patients with colorectal carcinoma. Moderate surgery did not induce any changes in plasma melatonin levels, but a pronounced increase in both the day- and nighttime melatonin concentrations was found after surgical treatment for colon cancer. The melatonin content in the tumor tissue did not differ from that in the proximal and the distal parts of the resected gut, which were without signs of malignant changes. Neither concentrations of serotonin nor 5-hydroxyindole acetic acid differed among analyzed parts of the gut. Daytime melatonin concentrations in gut tissue (314.7 +/- 87.8 pg/g of wet tissue) were more than ten times higher than the daytime levels in circulation. It was hypothesized that increased levels of this hormone in the gastrointestinal tract may play an important protective role against the development of colorectal cancer via stimulation of the immune system, protection against free radicals, and interaction with fatty acid uptake and metabolism.


Changes in alveolar bone morphology after traction of buccally vs palatally unilateral maxillary impacted canines: A cone-beam computed tomography study.
The objective of this study was to evaluate the 3-dimensional changes in alveolar bone morphology after traction of buccally vs palatally unilateral maxillary impacted canines (MIC). Following a split-mouth model, 27 cone-beam computed tomography images of unilaterally MIC (14 palatally and 13 buccally) and 27 contralateral unimpacted controls were obtained before and after traction using nickel-titanium closed-coil springs and a rigid anchorage appliance. Alveolar bone height and width were measured in the axial, coronal, and sagittal slides by 3 calibrated orthodontists, taking into account the impaction characteristics. A t test was used to compare the 2 groups, and a paired t test was applied for intragroup comparisons (both sides). A multiple linear regression model was used to evaluate the influence of the predictor variables on alveolar bone dimensional changes. The alveolar height showed a significantly greater decrease in palatally MIC (2.09 to 2.79 mm) than buccally MIC (0.28 to 0.57 mm) (P <0.05) for all surfaces. However, the alveolar width increased similarly in both groups up to 1.36 mm. In general, the affected side had a more significant height loss and greater increases in alveolar width than the nonaffected side. Regression analysis indicated that buccally MIC and age decreased alveolar changes, whereas female sex increased alveolar changes (P <0.05). MIC traction with nickel-titanium closed-coil springs and heavy anchorage induces significant 3-dimensional changes in alveolar bone characterized by alveolar bone height decreases and cervical alveolar bone width increases. The height decrease is greater in palatally than in buccally MIC.


Quantitative electrocardiographic measures and long-term mortality in exercise test patients with clinically normal resting electrocardiograms.
Currently, the only function of the resting electrocardiogram (ECG) in patients referred for exercise testing is to determine whether imaging is mandated. It is unknown if subtle ECG findings in those patients with clinically normal resting ECGs have prognostic significance. We performed a single-center cohort study of 18,964 patients without known cardiovascular disease who had a clinically normal resting ECG and who underwent treadmill exercise testing for evaluation of suspected coronary artery disease. Eleven quantitative ECG measures relating to heart rate, conduction, left ventricular mass, or repolarization were collected digitally. The primary outcome was all-cause mortality. The prognostic importance of a composite ECG score was assessed by measuring its impact on the c-index (analogous to area under receiver operating characteristic curve) and by measures of reclassification. During a median follow-up of 10.7 years, 1,585 patients died. The 4 most predictive digital ECG variables were higher ventricular rate, more leftward QRS axis, more downward ST-segment deviation, and longer QT interval. The ECG score was independently associated with mortality (75th vs 25th percentile hazard ratio 1.36, 95% confidence interval 1.25-1.49, P < .0001). The ECG score had modest impact on discrimination (change in c-index 0.04) and reclassification of risk (3.0% decrease of relative integrated discrimination improvement, P < .001). Subtle ECG findings relating to heart rate, conduction, left ventricular mass, or repolarization in patients with clinically normal ECGs referred for exercise testing may provide modest additional prognostic information over and above clinical and exercise measures.


Scale Dependence of Land-Atmosphere Interactions in Wet and Dry Regions as Simulated with NU-WRF over the Southwestern and South-Central United States.
Large-scale forcing and land-atmosphere interactions on precipitation are investigated with NASA-Unified WRF (NU-WRF) simulations during fast transitions of ENSO phases from spring to early summer of 2010 and 2011. The model is found to capture major precipitation episodes in the 3-month simulations without resorting to nudging. However, the mean intensity of the simulated precipitation is underestimated by 46% and 57% compared with the observations in dry and wet regions in the southwestern and south-central United States, respectively. Sensitivity studies show that large-scale atmospheric forcing plays a major role in producing regional precipitation. A methodology to account for moisture contributions to individual precipitation events, as well as total precipitation, is presented under the same moisture budget framework. The analysis shows that the relative contributions of local evaporation and large-scale moisture convergence depend on the dry/wet regions and are a function of temporal and spatial scales. While the ratio of local and large-scale moisture contributions vary with domain size and weather system, evaporation provides a major moisture source in the dry region and during light rain events, which leads to greater sensitivity to soil moisture in the dry region and during light rain events. The feedback of land surface processes to large-scale forcing is well simulated, as indicated by changes in atmospheric circulation and moisture convergence. Overall, the results reveal an asymmetrical response of precipitation events to soil moisture, with higher sensitivity under dry than wet conditions. Drier soil moisture tends to suppress further existing below-normal precipitation conditions via a positive soil moisture-land surface flux feedback that could worsen drought conditions in the southwestern United States.


Effect of omega-3 fatty acids on lipid peroxidation and antioxidant enzyme status in type 2 diabetic patients.
This study was conducted to investigate the effect of omega-3 fatty acids on lipid peroxidation and antioxidant enzyme activities in non-insulin dependent diabetic patients. Thirty-four non-insulin dependent diabetic patients were selected for this study and they were initially treated with antidiabetic drugs alone for one month. This was followed by supplementation with omega-3 fatty acids (1,080 mg of EPA and 720 mg of DHA per day) along with the antidiabetic drugs for a period of two months. No change in glycaemic control was observed in diabetic patients at the end of two months of omega-3 fatty acids therapy along with antidiabetic drugs. The combined treatment significantly reduced serum triglycerides (2.07 +/- 0.94 mmol/l, before combined therapy vs 1.54 +/- 0.49 mmol/l after combined therapy, P<0.05) and increased HDL-cholesterol levels (0.93 +/- 0.099 mmol/l, before combined therapy vs 1.04 +/- 0.098 mmol/l after therapy, P<0.01). The raised lipid peroxide levels (5.14 +/- 0.61 micromol MDA/l in controls vs 6.36 +/- 1.56 micromol MDA/l in diabetic patients, P<0.001) were significantly decreased in these patients after the combined therapy (6.36 +/- 1.56 micromol MDA/l, before combined therapy vs 5.16 +/- 0.7 micromol MDA/l, after combined therapy, P<0.01). Among the erythrocyte antioxidant enzymes, the Glutathione peroxidase activity was increased (32.5 +/- 9.9 U/g Hb/min, before combined therapy vs 42.25 +/- 4.6 U/g Hb/min, after combined therapy, P<0.01) while no change was observed in Catalase (99.7 +/- 30.4 KU/g Hb before combined therapy vs 85.35 +/- 23.41 KU/g Hb, after combined therapy) and Superoxide dismutase activities (2.6 +/- 1.04 U/mg Hb/min, before therapy vs 3.01 +/- 1.08 U/mg Hb/min, after combined therapy) after the 2 months of combined treatment with antidiabetic agents and omega-3 fatty acids. Supplementation with omega-3 fatty acids has beneficial effects on serum triglycerides, HDL-cholesterol, lipid peroxidation and antioxidant enzymes, which may lead to decreased rate of occurrence of vascular complications in diabetes.


Linear versus Quadratic Detrending in Analyzing Simultaneous Changes in DC-EEG and Transcutaneous pCO2.
Physiological direct current (DC) potential shifts in electroencephalography (EEG) can be masked by artifacts such as slow electrode drifts. To reduce the influence of these artifacts, linear detrending has been proposed as a pre-processing step. We considered quadratic detrending, which has hardly been addressed for ultralow frequency components in EEG. We compared the performance of linear and quadratic detrending in simultaneously acquired DC-EEG and transcutaneous partial pressure of carbon dioxide during two activation methods: hyperventilation (HV) and apnea (AP). Quadratic detrending performed significantly better than linear detrending in HV, while for AP, our analysis was inconclusive with no statistical significance. We conclude that quadratic detrending should be considered for DC-EEG preprocessing.


Pseudomonas aeruginosa infection in cancer patients.
Pseudomonas aeruginosa is an important cause of infection in immunosuppressed patients, particularly those with cancer. However, it is being recognized with greater frequency in patients who appear to be immunocompetent. Changes in modern lifestyles have led to the appearance of some new manifestations of pseudomonas infection including corneal ulceration and keratitis associated with contact lenses, and hot-tub- or whirlpool-associated folliculitis. These represent additional hazards to patients with cancer. Many studies, both in animals and humans, have contributed to our knowledge of the pathogenesis, immunology, treatment, and prevention of pseudomonas infections. Although the aminoglycosides represented a significant step forward in the treatment of these infections, of greater importance was the discovery of the antipseudomonal penicillins. These antibiotics are more effective than the aminoglycosides in neutropenic patients, who are especially susceptible to pseudomonal infections. The older antipseudomonal penicillins (carbenicillin, tircarcillin) have largely been replaced by newer ones (mezlocillin, azlocillin, pipercillin) which are more potent in vitro against P. aeruginosa. Although the accepted therapeutic practice has been to utilize a penicillin in combination with an aminoglycoside, the introduction of newer beta lactam agents and fluoroquinolones with antipseudomonal properties offers the possibility of other approaches to combination therapy. These include the combination of a penicillin or a cephalosporin or the combination of a quinolone with an aminoglycoside or a betalactam antibiotic. However, the development of newer antimicrobial agents is not likely to be a lasting solution to the problem of pseudomonas infections. Since pseudomonas infection often progresses rapidly, optimal results will always depend upon the prompt initiation of appropriate therapy in febrile patients, particularly those who are at high risk. The use of granulocyte transfusions has proved to be of limited benefit. Early data with the use of monoclonal antibodies is promising, and the results of large-scale trials are eagerly awaited. It is hoped that continuing investigation of pseudomonas vaccines will lead to the discovery of effective prophylaxis for highly susceptible patients. It is also hoped that with the availability of GM-CSF it will become possible to reduce the period of risk for serious infections. Finally, a reduction in the frequency of microbiologically proven P. aeruginosa infections in cancer patients should not lead to the assumption that these organisms do not constitute a problem in such patients anymore. The use of prophylactic antibiotics and prompt empiric antibiotic coverage for therapy has resulted in this decline. Cultures are therefore unlikely to be positive with the same frequency as they were before antimicrobial prophylaxis and empiric antibiotic therapy became standard practice.(ABSTRACT TRUNCATED AT 400 WORDS)


Heparin in the prevention of deep vein thrombosis after myocardial infarction.
A trial of continuous intravenous heparin in the prevention of deep vein thrombosis was undertaken in 48 patients who had suffered a myocardial infarction. Of the 24 control patients who did not receive heparin seven (29%) developed calf vein thrombosis as detected by the radioactive fibrinogen technique. None of the 24 heparinized patients had any evidence of venous thrombosis. This difference is significant at the 1% level.


Electroceutical Residue-Free Graphene Device for Dopamine Monitoring and Neural Stimulation.
The simultaneous neural signal monitoring and stimulation can allow accurate neurotransmitter regulation for patients in various degrees of neural degeneration disorders. Here, we developed a residue-free graphene device as an effective electrical neural interface for dopamine sensing and secretion. We demonstrated the ultrasensitive dopamine sensing of residue-free graphene devices cultured with PC12 cells and the on-demand functional electrical stimulation for electroceutical applications. The doping effect of graphene by the released dopamine from living cells was confirmed from the electrical current change. The dopamine release could be also quantitatively analyzed by ELISA. Then, Ca2+ ion-dependent dopamine release was optically observed by fluorescence microscopy during the stimulation. Taken together, this study confirms the feasibility of graphene surface as a neural interface for electroceutical applications to various central nerve system disorders.


Long-term sequelae of childhood bacterial meningitis: an underappreciated problem.
Numerous sequelae have been noted in survivors of bacterial meningitis; however, few studies document sequelae for several years following a childhood episode of bacterial meningitis. In addition, studies generally focus on the more commonly found sequelae. To review the known information and highlight this gap, this article presents a comprehensive literature review of the long-term (≥ 5 years of follow-up) sequelae of childhood bacterial meningitis. A systematic literature search was conducted between December 2009 and February 2010. English-language articles published between January 1970 and January 2010 were selected for screening. Articles were included if the subjects were between the ages of 1 month and <18 years at the time of diagnoses of meningitis. A total of 1433 children who were survivors of childhood bacterial meningitis were evaluated for sequelae after the time of discharge. Of these children, 705 (49.2%) were reported to have 1 or more long-term sequelae. A majority of reported sequelae were behavioral and/or intellectual disorders (n 455, 45.0%). Hearing changes accounted for 6.7% (n 68) of sequelae and gross neurologic deficits accounted for 14.3% (n 145). A majority of childhood bacterial meningitis survivors with long-term sequelae that are documented in the literature have academic and behavioral limitations. While neurologic deficits may resolve over time, subtle behavioral deficits may not be appreciated initially and may continue to affect survivors for many years. Further studies are needed to quantify the true societal and economic burden of long-term sequelae as well as fully understand the breadth of types of sequelae that survivors experience.


Physical and psychological symptoms and learning difficulties in children of women exposed and non-exposed to violence: a population-based study.
To analyse the association between violence against mothers and the health of their children as reported by the mothers. The data originate from a multistage sampling health-questionnaire survey, distributed to a representative sample of women in Sweden. The health of 283 children (aged 0-18 years), as reported by women who had been exposed to violence at home or outside home during the past 12 months, was compared with that of 4,664 children of non-exposed mothers. Odds ratios regarding most registered physical symptoms showed that children of violence-exposed mothers had a significant higher risk of ill health than children of non-exposed mothers. Regarding psychological symptoms and learning difficulties, the odds were raised for girls for most symptoms, but not for boys. A twofold increase in health-care utilisation and an overall general increase in the risk of pharmaceutical consumption were shown for both girls and boys of exposed mothers. This population-based study shows an increased risk of poorer health amongst boys and girls aged 0-18 years, as reported by mothers exposed to violence.


Maternal reactions to children's negative emotions: Relations to children's socio-emotional development among European American and Chinese immigrant children.
This study examined the relations between maternal reactions to children's negative emotions and children's socio-emotional outcomes, including psychological adjustment, emotion knowledge, and coping strategies. European American and Chinese immigrant mothers reported on their reactions to children's (N = 117, M = 7.14 years) negative emotions and on children's psychological adjustment. One year later, children were interviewed for emotion knowledge and mothers reported on children's use of coping strategies. Mothers from the two cultural groups reported the same level of supportive reactions to their children's negative emotions, whereas Chinese immigrant mothers more often adopted what are commonly considered to be non-supportive strategies than did European American mothers. Whereas supportive maternal reactions were associated with better child outcomes in both cultures, maternal non-supportive reactions were negatively associated with children's functioning for European American children but not for Chinese immigrant children. The findings shed critical light on the functional meaning of parenting practices in specific cultural contexts in shaping developmental outcomes.


MicroRNA and AU-rich element regulation of prostaglandin synthesis.
Many lines of evidence demonstrate that prostaglandins play an important role in cancer, and enhanced synthesis of prostaglandin E(2) (PGE(2)) is often observed in various human malignancies often associated with poor prognosis. PGE(2) synthesis is initiated with the release of arachidonic acid by phospholipase enzymes, where it is then converted into the intermediate prostaglandin prostaglandin H(2) (PGH(2)) by members of the cyclooxygenase family. The synthesis of PGE(2) from PGH(2) is facilitated by three different PGE synthases, and functional PGE(2) can promote tumor growth by binding to four EP receptors to activate signaling pathways that control cell proliferation, migration, apoptosis, and angiogenesis. An integral method of controlling gene expression is by posttranscriptional mechanisms that regulate mRNA stability and protein translation. Messenger RNA regulatory elements typically reside within the 3' untranslated region (3'UTR) of the transcript and play a critical role in targeting specific mRNAs for posttranscriptional regulation through microRNA (miRNA) binding and adenylate- and uridylate-rich element RNA-binding proteins. In this review, we highlight the current advances in our understanding of the impact these RNA sequence elements have upon regulating PGE(2) levels. We also identify various RNA sequence elements consistently observed within the 3'UTRs of the genes involved in the PGE(2) pathway, indicating these binding sites for miRNAs and RNA-binding proteins to be central regulators of PGE(2) synthesis and function. These findings may provide a rationale for the development of new therapeutic approaches to control tumor growth and metastasis promoted by elevated PGE(2) levels.


The use of dendrograms to describe the electrical activity of motoneurons underlying behaviors in leeches.
The present manuscript aims at identifying patterns of electrical activity recorded from neurons of the leech nervous system, characterizing specific behaviors. When leeches are at rest, the electrical activity of neurons and motoneurons is poorly correlated. When leeches move their head and/or tail, in contrast, action potential (AP) firing becomes highly correlated. When the head or tail suckers detach, specific patterns of electrical activity are detected. During elongation and contraction the electrical activity of motoneurons in the Medial Anterior and Dorsal Posterior nerves increase, respectively, and several motoneurons are activated both during elongation and contraction. During crawling, swimming, and pseudo-swimming patterns of electrical activity are better described by the dendrograms of cross-correlations of motoneurons pairs. Dendrograms obtained from different animals exhibiting the same behavior are similar and by averaging these dendrograms we obtained a template underlying a given behavior. By using this template, the corresponding behavior is reliably identified from the recorded electrical activity. The analysis of dendrograms during different leech behavior reveals the fine orchestration of motoneurons firing specific to each stereotyped behavior. Therefore, dendrograms capture the subtle changes in the correlation pattern of neuronal networks when they become involved in different tasks or functions.


Kinetics of Au-Ga Droplet Mediated Decomposition of GaAs Nanowires.
Particle-assisted III-V semiconductor nanowire growth and applications thereof have been studied extensively. However, the stability of nanowires in contact with the particle and the particle chemical composition as a function of temperature remain largely unknown. In this work, we use in situ transmission electron microscopy to investigate the interface between a Au-Ga particle and the top facet of an ⟨1̅1̅1̅⟩-oriented GaAs nanowire grown via the vapor-liquid-solid process. We observed a thermally activated bilayer-by-bilayer removal of the GaAs facet in contact with the liquid particle during annealing between 300 and 420 °C in vacuum. Interestingly, the GaAs-removal rates initially depend on the thermal history of the sample and are time-invariant at later times. In situ X-ray energy dispersive spectroscopy was also used to determine that the Ga content in the particle at any given temperature remains constant over extended periods of time and increases with increasing temperature from 300 to 400 °C. We attribute the observed phenomena to droplet-assisted decomposition of GaAs at a rate that is controlled by the amount of Ga in the droplet. We suggest that the observed transients in removal rates are a direct consequence of time-dependent changes in the Ga content. Our results provide new insights into the role of droplet composition on the thermal stability of GaAs nanowires and complement the existing knowledge on the factors influencing nanowire growth. Moreover, understanding the nanowire stability and decomposition is important for improving processing protocols for the successful fabrication and sustained operation of nanowire-based devices.


Ionized calcium concentrations in squid axons.
Values for ionized [Ca] in squid axons were obtained by measuring the light emission from a 0.1-mul drop of aequorin confined to a plastic dialysis tube of 140-mum diameter located axially. Ionized Ca had a mean value of 20 x 10(-9) M as judged by the subsequent introduction of CaEGTA/EGTA buffer (ratio ca. 0.1) into the axoplasm, and light measurement on a second aequorin drop. Ionized Ca in axoplasma was also measured by introducing arsenazo dye into an axon by injection and measuring the Ca complex of such a dye by multichannel spectrophotometry. Values so obtained were ca. 50 x 10(-9) M as calibrated against CaEGTA/EGTA buffer mixtures. Wth a freshly isolated axon in 10 mM Ca seawater, the aequorin glow invariably increased with time; a seawater [Ca] of 2-3 mM allowed a steady state with respect to [Ca]. Replacement of Na+ in seawater with choline led to a large increase in light emission from aequorin. Li seawater partially reversed this change and the reintroduction of Na+ brought light levels back to their initial value. Stimulation at 60/s for 2-5 min produced an increase in aequorin glow about 0.1% of that represented by the known Ca influx, suggesting operationally the presence of substantial Ca buffering. Treatment of an axon with CN produced a very large increase in aequorin glow and in Ca arsenazo formation only if the external seawater contained Ca.


Inflammatory modulation of exercise salience: using hormesis to return to a healthy lifestyle.
Most of the human population in the western world has access to unlimited calories and leads an increasingly sedentary lifestyle. The propensity to undertake voluntary exercise or indulge in spontaneous physical exercise, which might be termed "exercise salience", is drawing increased scientific attention. Despite its genetic aspects, this complex behaviour is clearly modulated by the environment and influenced by physiological states. Inflammation is often overlooked as one of these conditions even though it is known to induce a state of reduced mobility. Chronic subclinical inflammation is associated with the metabolic syndrome; a largely lifestyle-induced disease which can lead to decreased exercise salience. The result is a vicious cycle that increases oxidative stress and reduces metabolic flexibility and perpetuates the disease state. In contrast, hormetic stimuli can induce an anti-inflammatory phenotype, thereby enhancing exercise salience, leading to greater biological fitness and improved functional longevity. One general consequence of hormesis is upregulation of mitochondrial function and resistance to oxidative stress. Examples of hormetic factors include calorie restriction, extreme environmental temperatures, physical activity and polyphenols. The hormetic modulation of inflammation, and thus, exercise salience, may help to explain the highly heterogeneous expression of voluntary exercise behaviour and therefore body composition phenotypes of humans living in similar obesogenic environments.