Systemic lupus erythematosus in American Indian/Alaska natives: Incorporating our new understanding of the biology of trauma.
To review the literature regarding systemic lupus erythematosus (SLE) in American Indian/Alaska Native (AI/AN) people and relate prevalence and/or disease severity to our emerging understanding of the biology of trauma and toxic stress. We conducted a search and review of the literature using search terms "lupus and American Indians" "ACEs and disease outcome" "Biology of Adversity" "lupus and ACE scores," " lupus and childhood abuse." These search criteria were entered into Google Scholar and articles retrieved from PubMed, NBCI. This approach yielded a small numbers of papers used throughout this review. We excluded articles that were not published in a peer reviewed journals, as well as editorial commentaries. In the AI/AN population, SLE shows high prevalence rates and severe disease manifestations, comparable to the African American population. AI/AN populations also have high rates of childhood trauma. Toxic stress and trauma such as those catalogued in the Adverse Childhood Experiences (ACE) study have broad-reaching immunologic and epigenetic effects that are likely to be relevant to our understanding of SLE in AI/AN people. AI/AN people have high rates of SLE. These high rates are likely to be driven by many complex factors, not all of which are genetic. Future research is needed to establish (or refute) a causal connection between the biology of adversity and SLE in socially marginalized and historically traumatized populations.


Hydrostatic pressure effect on charge transport properties of phenacene organic semiconductors.
We investigate the charge transport properties of phenacene organic semiconductors including phenanthrene, chrysene and picene using density functional theory (DFT) calculations under hydrostatic pressure. Under compression, the crystal structures of the three materials are altered and thus, a decrease in the intermolecular distances gives changes in charge transport properties while the molecular structures remain stable. As a result of the applied pressure, the mobilities of these materials increase dramatically. Chrysene shows a transition from a p-type semiconductor to an ambipolar semiconductor at around 2.0 GPa. Interestingly, chrysene favors electron transport at above 3.0 GPa. On the other hand, both phenanthrene and picene exhibit hole transport characteristics under high pressure. Between 3.1 and 4.3 GPa, the picene crystal is found to transform from an anisotropic mobility to an isotropic mobility in the ab plane. We also found that, the bulk modulus representing the resistance of the material under pressure compression follows a linear relationship with molecular length.


Extranodal NK/T-cell lymphoma, nasal type: study of clinicopathologic and prognosis factors in a series of 78 cases from Peru.
It is well known that extranodal NK/T-cell lymphoma (NK/TCL) nasal type clusters in Asian countries. A large series of 78 cases of nasal NK/TCL from Peru is analyzed in the present study. Two histologic groups 1 (monomorphic) and 2 (polymorphic), were segregated according to the proportion of large cells (above and below 30%, respectively). Catalyzed signal amplification technique was performed for enhancement of immunohistochemistry reactivities. Epstein-Barr virus (EBV) sequences and types were investigated using polymerase chain reaction. Clinical characteristics, stage, outcome, and response to treatment were evaluated in both groups. Fourteen cases (18%) and 64 cases (82%) corresponded to groups 1 and 2, respectively. Except for nasal obstruction, more common in group 2, all other symptoms were similar in both groups. Local extension and staging were also comparable. Both groups showed CD3c+ CD2+ CD56+ CD3s- CD20- immunophenotype. All cases were positive for EBV. In this series type-2 EBV was found more frequent than type-1 EBV, contrarily to that observed in Asian series. However, about one-third of cases simultaneously harbored both viral types. Both groups received an average of 50-Gy dose of radiation therapy (RT), with or without chemotherapy. Complete therapeutic response was achieved in 89% of group 1 and in 74% of group 2, but this difference was not statistically significant. There were no significant differences between the groups regarding disease-free survival, failure-free survival, relapse, and overall survival. The overall survival, in both groups, was longer for patients treated with RT alone compared with those treated with combined RT therapy and chemotherapy. The present study has shown that dividing nasal NK/TCL in monomorphic and polymorphic variants, according to frequency of large cells, does not correlate with clinical and prognostic factors.


Fiber-optic electron-spin-resonance thermometry of single laser-activated neurons.
Optically detected electron spin resonance in fiber-coupled nitrogen-vacancy (NV) centers of diamond is used to demonstrate a fiber-optic quantum thermometry of individual thermogenetically activated neurons. Laser-induced temperature variations read out from single neurons with the NV-diamond fiber sensor are shown to strongly correlate with the fluorescence of calcium-ion sensors, serving as online indicators of the inward Ca2+ current across the cell membrane of neurons expressing transient receptor potential (TRP) cation channels. Local laser heating above the TRP-channel activation threshold is shown to reproducibly evoke robust action potentials, visualized by calcium-ion-sensor-aided fluorescence imaging and detected as prominent characteristic waveforms in the time-resolved response of fluorescence Ca2+ sensors.


An ultrastructural study of the effect of treatment with atovaquone in brains of mice chronically infected with the ME49 strain of Toxoplasma gondii.
The morphological effects of drug treatment with atovaquone in the brains of mice chronically infected with Toxoplasma gondii was examined by light and electron microscopy. As early as 1 and 2 weeks of treatment there appeared to be fewer tissue cysts compared to untreated controls and this reduction was more significant after 4 weeks treatment. There also appeared to be a decrease in the number of inflammatory nodules and the severity of the meningitis. Ultrastructurally, the cysts of both treated and control animals were located within host cells. There was a marked increase in both the number of cysts with lysed bradyzoites and the number of degenerate bradyzoites after 4 weeks treatment. It is probable that the drug is more active against the metabolically active immature bradyzoites than the mature organisms. Drug treatment does not appear to result in rupture of tissue cysts or release of Toxoplasma antigens since there is a reduction rather than an increase in the inflammatory response. This drug may be useful in treating chronic toxoplasmosis since it appears to be active against the bradyzoites reducing the parasite burden (cyst number) without initiating a destructive inflammatory response.


Patients' insight of interpreting prescriptions and drug labels--a cross sectional study.
Errors in consuming drugs are associated with significant morbidity and mortality, besides an impact on the already overburdened health-care system. Misunderstanding drug labels and prescriptions plays an important role in contributing to adverse drug events. To evaluate abilities to understand prescriptions and drug labels among patients attending tertiary care hospital in Karachi. A cross sectional study was conducted at the Aga Khan University Hospital (AKUH), from January to March 2009. After informed consent, 181 adult patients and their healthy attendants were interviewed at AKUH using a standardized questionnaire, which ascertained patient demographics, factors that might increase exposure to health-care personnel as well as the basic knowledge and understanding of prescriptions and drug labels. Out of 181, majority 137(76%) had received graduate or post-graduate degrees. 16 (9%) had received no formal education; of which all were females and 89(84%) of the total females were housewives. Overall, 130(72%) followed only a single doctor's prescription. Majority failed to understand various medical terminologies related to dosage. In the high literacy group, 45(33%) understood once daily OD (p = 0.003), 27(20%) thrice daily TID (p = 0.05), 29(21%) twice daily BD (p = 0.01), 31(23%) thrice daily TDS (p = 0.002) and 43(31%) as needed SOS (p = 0.003) as compared to the group with no formal education, who were unable to comprehend the terms. The most common reason for using more than one prescription was decreased satisfaction with the doctor in 19(39%) and multiple co-morbids as responded by 17(35%) of patients. Knowledge regarding various medical terminologies used for dosage and routes of drug administration were also understood more frequently among the English medium respondents. The elderly identified medicine through color (47%, p<0.001), and were less likely to understand drug indications (p = 0.05) compared to younger subjects. Understanding of drug prescriptions is alarmingly low in the community, even amongst the educated. Care givers need to revisit this often ignored aspect of patient care.


Retinal periphlebitis in ulcerative colitis.
A man presented with unilateral visual blurring associated with bilateral retinal periphlebitis which was felt to be a complication of his biopsy-proven active ulcerative colitis. Retinal periphlebitis has been associated rarely with some forms of colitis but we can find no report of its occurrence in association with ulcerative colitis although other ocular inflammatory disorders are well recognized.


3D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell Retention.
The development of continuous bioprocesses-which require cell retention systems in order to enable longer cultivation durations-is a primary focus in the field of modern process development. The flow environment of microfluidic systems enables the granular manipulation of particles (to allow for greater focusing in specific channel regions), which in turn facilitates the development of small continuous cell separation systems. However, previously published systems did not allow for separation control. Additionally, the focusing effect of these systems requires constant, pulsation-free flow for optimal operation, which cannot be achieved using ordinary peristaltic pumps. As described in this paper, a 3D printed cell separation spiral for CHO-K1 (Chinese hamster ovary) cells was developed and evaluated optically and with cell experiments. It demonstrated a high separation efficiency of over 95% at up to 20 × 106 cells mL-1. Control over inlet and outlet flow rates allowed the operator to adjust the separation efficiency of the device while in use-thereby enabling fine control over cell concentration in the attached bioreactors. In addition, miniaturized 3D printed buffer devices were developed that can be easily attached directly to the separation unit for usage with peristaltic pumps while simultaneously almost eradicating pump pulsations. These custom pulsation dampeners were closely integrated with the separator spiral lowering the overall dead volume of the system. The entire device can be flexibly connected directly to bioreactors, allowing continuous, pulsation-free cell retention and process operation.


Red Cell Distribution Width with CHADS2 and CHA2DS2-VASc score is associated with Post-operative Atrial Fibrillation after Coronary Artery Bypass Grafting.
The use of the CHA2DS2-VASc scoring system and red cell distribution width (RDW) as post-op Atrial Fibrillation (POAF) predictors may be promising for the identification of patients that are at a higher risk of POAF. A total of 358 patients (57 patients with POAF, and 301 patients with non-POAF ) with sinus rhythm undergoing a coronary artery bypass graft (CABG) operation were included in the study retrospectively. Preoperative RDW levels and electrocardiograms with sinus rhythm were recorded. Patients with at least one 12-lead electrocardiogram with atrial fibrillation in the postoperative period, with or without medical or electrical cardioversion, were considered to have postoperative atrial fibrillation. A CHADS2 and CHA2DS2-VASc score was calculated for all of the patients. RDW levels were significantly higher in POAF group. RDW levels were significantly correlated with CHADS2 ( r = 0.15, P = .007) and CHA2DS2-VASc (r = 0.19 P = .0001) scores. CHA2DS2-VASc scores were significantly higher in patients with POAF, whereas CHADS2 scores did not differ between groups. In multivariate analysis, left atrial diameter (LAD) (OR:2.44 [95% CI 1.16 - 5.1], P = .018), age (OR:1.04 [95% CI 1.01 - 1.08], P = .01), and RDW (OR:1.16 [95% CI 1.0 - 1.36], P = .05) were found to be predictive for POAF. The area under the receiver-operating characteristic curve of RDW was 0.65 (0.57 - 0.72, P = .0001) with 68.4% sensitivity and 51.2 % specificity to predict POAF. Our study showed that age, LAD, and the reduced probability of RDW are predictors of POAF, and that RDW is strongly associated with the thromboembolic risk as determined by CHADS2 and CHA2DS2-VASc scores.


Ethnic and regional differences in STI clinic use: a Dutch epidemiological study using aggregated STI clinic data combined with population numbers.
Ethnic minorities (EM) from STI-endemic countries are at increased risk to acquire an STI. The objectives of this study were to investigate the difference in STI clinic consultation and positivity rates between ethnic groups, and compare findings between Dutch cities. Aggregated population numbers from 2011 to 2013 of 15-44 year-old citizens of Amsterdam, Rotterdam, The Hague and Utrecht extracted from the population register (N=3 129 941 person-years) were combined with aggregated STI clinic consultation data in these cities from the national STI surveillance database (N=113 536). Using negative binomial regression analyses (adjusted for age and gender), we compared STI consultation and positivity rates between ethnic groups and cities. Compared with ethnic Dutch (consultation rate: 40.3/1000 person-years), EM from Eastern Europe, Sub-Sahara Africa, Suriname, the Netherlands Antilles/Aruba and Latin America had higher consultation rates (range relative risk (RR): 1.27-2.26), whereas EM from Turkey, North Africa, Asia and Western countries had lower consultation rates (range RR: 0.29-0.82). Of the consultations among ethnic Dutch, 12.2% was STI positive. Positivity rates were higher among all EM groups (range RR: 1.14-1.81). Consultation rates were highest in Amsterdam and lowest in Utrecht independent of ethnic background (range RR Amsterdam vs Utrecht: 4.30-10.30). Positivity rates differed less between cities. There were substantial differences in STI clinic use between ethnic groups and cities in the Netherlands. Although higher positivity rates among EM suggest that these high-risk individuals reach STI clinics, it remains unknown whether their reach is optimal. Special attention should be given to EM with comparatively low consultation rates.


Post-operative pain management practices in patients with dementia - the current situation in Finland.
The aim of this study is to describe current post-operative pain management practices for patients with dementia and hip fracture in Finland. Older adults with hip fracture are at high risk of under treatment for pain, especially if they also have a cognitive disorder at the stage of dementia. Previous studies have provided limited information about the quality of acute pain treatment for persons with dementia. In this study data concerning current pain management practices was collected by questionnaire from 333 nursing staff. They worked in surgical wards of seven universities and ten city-centre hospitals. The response rate to the questionnaire was 53%. The data was analysed using factor analysis and parametric methods. Half the respondents (53%) considered that post-operative pain management was sufficient for patients with dementia. Less than one third of respondent nurses reported that pain scales were in use on their unit: the most commonly used scale was VAS. The use of pain scales was significantly related to the respondents' opinion of the sufficiency of post-operative pain management in this patient group (p<0.001). The findings can be utilised in nursing practice and research when planning suitable complementary educational interventions for nursing staff of surgical wards. Further research is needed to explain the current situation of pain management practices from the viewpoint of patients with dementia.


Synergistic antitumor activity with IFN and monoclonal anti-idiotype for murine B cell lymphoma. Mechanism of action.
Combination therapy with syngeneic anti-idiotype antibody and human hybrid rIFN-alpha A/D synergistically increase survival in C3H/HeN mice challenged with a lethal dose of tumor cells. C3H/HeJ mice, which have previously been described to be LPS hyporesponsive and have a defect in Fc gamma R function, did not respond to anti-idiotype therapy as well as C3H/HeN normal mice. This defect was completely corrected in animals treated simultaneously with IFN. Anti-idiotype mAb that was cleaved into F(ab')2 fragments no longer had any antitumor activity alone and could not be enhanced by IFN therapy. These results suggest that antibody is functioning through Fc gamma R-bearing effector cells that are enhanced by IFN therapy. Synergy between IFN and anti-idiotype mAb was maintained in nude mice lacking classical T cells but was reduced in C3H beige mice lacking classical NK/killer cells. IFN did not increase idiotype expression on the tumor cells but did increase H-2 expression. Although we have previously shown that rIFN-alpha A/D can directly kill 38C13 in vitro, an IFN-resistant subclone derived from 38C13, SIR-1, was equally or more responsive to human rIFN-alpha A/D in vivo and had a synergistic antitumor response to combination IFN and anti-idiotype therapy, indicating that IFN acts primarily through host mediated effects rather than direct effects.


[Compliance of film-coated praziquantel tablets in schistosomiasis transmission-controlled areas].
To observe the compliance of film-coated praziquantel tablets in the schistosomiasis transmission controlled areas, so as to provide the evidence for the establishment of chemotherapy intervention measures in these areas. In the areas of schistosomiasis transmission controlled in Sichuan Province, 234 people were selected as film-coated praziquantel group (FCPG), and 203 people were selected as praziquantel group (PG). A questionnaire survey was implemented and the compliance of chemotherapy of the 2 groups was compared. In PG, all the people indicated that the praziquantel tablets has bad smell, 98.0% of the people had side-effects, such as nausea, headache, 69.5% thought the medicine was harmful to health subjectively, and 99.5% thought that it was too much dose of tablets for taking one time. In FCPG, all the people indicated that the film-coated praziquantel tablets had no bad smell, 18.8% of the people had side-effects, and 74.4% would like to choose film-coated praziquantel tablets. The rates of knowledge of praziquantel of PG and FCPG were 50.7% and 29.1%, respectively ( chi2 = 21.449, P = 0.01). The film-coated praziquantel tablets have no bad smell and lighter side-effects. The compliance of the film-coated praziquantel tablets is high in the areas of schistosomiasis transmission controlled, so the film-coated praziquantel tablets are worth to popularize and apply.


'It's been a long haul, a big haul, but we've made it': hepatitis C virus treatment in post-transplant patients with virus recurrence: An interpretative phenomenological analysis.
The lived experience of both interferon-based and new interferon-free treatments in patients with hepatitis C virus remains understudied. To explore their journey through hepatitis C virus treatment, we interviewed seven post-transplant patients with recurrent hepatitis C virus. Three themes were identified using interpretative phenomenological analysis. Participants reported an ongoing sense of ontological uncertainty characterized by lack of control over their condition and treatment. Furthermore, an apposition of scepticism and hope accompanying each stage of hepatitis C virus treatment was described. A staged approach to psychological intervention tailored to the needs of the patient and their associated 'stage' of hepatitis C virus treatment was recommended.


TMC207: the first compound of a new class of potent anti-tuberculosis drugs.
Disease caused by Mycobacterium tuberculosis continues as a global epidemic: over 2 billion people harbor latent TB infection, and more than 9 million new TB cases, of whom 500,000 are multidrug-resistant (MDR), and nearly 2 million deaths are estimated to occur each year. New drugs are required to shorten treatment duration of drug-sensitive TB and for the treatment of MDR-TB. TMC207 is a first-in-class diarylquinoline compound with a novel mechanism of action, the inhibition of bacterial ATP synthase, and potent activity against drug-sensitive and drug-resistant TB. It has bactericidal and sterilizing activity against M. tuberculosis and other mycobacterial species, but little activity against other bacteria. In a Phase II efficacy study conducted in patients with MDR-TB taking TMC207 plus a standard background regimen, the drug appeared to be safe and well tolerated, and showed significant efficacy after 2 months of treatment with conversion rates of sputum culture of 48% (vs 9% in the placebo group). Given the product development partnership between Tibotec and the TB Alliance, the strategies of using TMC207 in shorter first-line regimens or using it in second-line regimens for drug-resistant M. tuberculosis infections are both being pursued. No clinical data of TMC207 in TB patients with HIV coinfection have been published; drug-drug interaction studies with antiretrovirals are being conducted. Finally, the remarkable sterilizing capacity of TMC207 also makes it an attractive drug in the strategy of TB elimination. Current and future studies will determine the role of TMC207 in a shortened treatment regimen for drug-sensitive TB, a more effective and better-tolerated regimen for MDR-TB, the treatment of latent TB infection, and intermittent-TB treatment regimens.


WRKY70 modulates the selection of signaling pathways in plant defense.
Cross-talk between signal transduction pathways is a central feature of the tightly regulated plant defense signaling network. The potential synergism or antagonism between defense pathways is determined by recognition of the type of pathogen or pathogen-derived elicitor. Our studies have identified WRKY70 as a node of convergence for integrating salicylic acid (SA)- and jasmonic acid (JA)-mediated signaling events during plant response to bacterial pathogens. Here, we challenged transgenic plants altered in WRKY70 expression as well as WRKY70 knockout mutants of Arabidopsis with the fungal pathogens Alternaria brassicicola and Erysiphe cichoracearum to elucidate the role of WRKY70 in modulating the balance between distinct defense responses. Gain or loss of WRKY70 function causes opposite effects on JA-mediated resistance to A. brassicicola and the SA-mediated resistance to E. cichoracearum. While the up-regulation of WRKY70 caused enhanced resistance to E. cichoracearum, it compromised plant resistance to A. brassicicola. Conversely, down-regulation or insertional inactivation of WRKY70 impaired plant resistance to E. cichoracearum. Over-expression of WRKY70 resulted in the suppression of several JA responses including expression of a subset of JA- and A. brassicicola-responsive genes. We show that this WRKY70-controlled suppression of JA-signaling is partly executed by NPR1. The results indicate that WRKY70 has a pivotal role in determining the balance between SA-dependent and JA-dependent defense pathways.


Type III metacaspases: calcium-dependent activity proposes new function for the p10 domain.
Metacaspases are a subgroup of caspase homologues represented in bacteria, algae and plants. Although type I and type II metacaspases are present in plants, recently discovered and uncharacterized type III metacaspases can only be found in algae which have undergone secondary endosymbiosis. We analysed the expression levels of all 13 caspase homologues in the cryptophyte Guillardia theta in vivo and biochemically characterized its only type III metacaspase, GtMC2, in vitro. Type III metacaspase GtMC2 was shown to be an endopeptidase with a preference for basic amino acids in the P1 position, which exhibited specific N-terminal proteolytic cleavage for full catalytic efficiency. Autolytic processing, as well as the activity of the mature enzyme, required the presence of calcium ions in low millimolar concentrations. In GtMC2, two calcium-binding sites were identified, one with a dissociation constant at low and the other at high micromolar concentrations. We show high functional relatedness of type III metacaspases to type I metacaspases. Moreover, our data suggest that the low-affinity calcium-binding site is located in the p10 domain, which contains a well-conserved N-terminal region. This region can only be found in type I/II/III metacaspases, but is absent in calcium-independent caspase homologues.


Support of a bi-faceted role of estrogen receptor β (ERβ) in ERα-positive breast cancer cells.
The expression of estrogen receptor α (ERα) in breast cancer identifies patients most likely to respond to endocrine treatment. The second ER, ERβ, is also expressed in breast tumors, but its function and therapeutic potential need further study. Although in vitro studies have established that ERβ opposes transcriptional and proliferative functions of ERα, several clinical studies report its correlation with proliferative markers and poorer prognosis. The data demonstrate that ERβ opposes ERα are primarily based on transient expression of ERβ. Here, we explored the functions of constitutively expressed ERβ in ERα-positive breast cancer lines MCF7 and T47D. We found that ERβ, under these conditions heterodimerized with ERα in the presence and absence of 17β-estradiol, and induced genome-wide transcriptional changes. Widespread anti-ERα signaling was, however, not observed and ERβ was not antiproliferative. Tamoxifen antagonized proliferation and ER-mediated gene regulation both in the presence and absence of ERβ. In conclusion, ERβ's role in cells adapted to its expression appears to differ from its role in cells with transient expression. Our study is important because it provides a deeper understanding of ERβ's role in breast tumors that coexpress both receptors and supports an emerging bi-faceted role of ERβ.


Cytoprotective effect of methanolic extract of Nardostachys jatamansi against hydrogen peroxide induced oxidative damage in C6 glioma cells.
Oxidative stress has been implicated as an important factor in the process of neurodegeneration and hydrogen peroxide (H₂O₂) is one of the most important precursors of reactive oxygen species (ROS), responsible for many neurodegenerative diseases. This study used extracts from Nardostachys jatamansi rhizomes, known for nerve relaxing properties in Ayurvedic medicine, to ascertain their protective role in H₂O₂-induced oxidative stress in C6 glioma cells. The protective effect of methanolic, ethanolic and water extracts of N. jatamansi (NJ-MEx, NJ-EEx and NJ-WEx respectively) was determined by MTT assay. NJ-MEx significantly protected against H₂O₂ cytotoxicity when cells were pretreated for 24 h. The level of antioxidant enzymes, catalase, superoxide dismutase (Cu-ZnSOD), glutathione peroxidase (GPx), and a direct scavenger of free radicals, glutathione (GSH), significantly increased following pre-treatment with NJ-MEx. Lipid peroxidation (LPx) significantly decreased in NJ-MEx-pretreated cultures. The expression of a C6 differentiation marker, GFAP (glial fibrillary acidic protein), stress markers HSP70 (heat shock protein) and mortalin (also called glucose regulated protein 75, Grp75) significantly decreased when cells were pre-treated with NJ-MEx before being subjected to H₂O₂ treatment as shown by immunofluorescence, western blotting and RT-PCR results. The present study suggests that NJ-MEx could serve as a potential treatment and/or preventive measure against neurodegenerative diseases.


[Autopsy of count Jakob 3d of Baden. The earliest forensic medicine case of the Freiburg University in 1590].
In 1590 Markgrave Jakob III. of Baden died, 28 years old, after a sudden disease which had lasted nine days. A necropsy was performed by two professors of the Freiburg University faculty of medicine. A written report amazingly accurate for the time, exists. It points at poisoning by arsenic powder. This is the first existing written protocol of a forensic autopsy, performed by professors of the faculty of medicine of Freiburg in 1590, 26 years after Vesalius' death.


An 11-year longitudinal study of the occupational dust exposure and lung function of polyvinyl chloride, cement and asbestos cement factory workers.
Standardized questionnaires and lung function tests were administered in 1973, 1980, and 1984 to 126 workers occupationally exposed to polyvinyl chloride (PVC) dust, to cement dust, or to asbestos cement dust until 1974-1978 and to PVC thereafter. The workers in the last group were assigned to two asbestos exposure categories (heavy and slight). The decline in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1.0) was analyzed with regard to the length of time since the data of first employment. After adjustment for age, height, and smoking status at the date of first employment, the decline in FVC and FEV1.0 among the nonsmokers-light smokers was slightly accelerated with length of employment in the PVC and slight asbestos exposure groups and markedly accelerated with time since first employment in the heavy asbestos exposure group. The heavy smokers in all the exposure groups had FVC and FEV1.0 predicted values that were lower than those of the nonsmokers-light smokers; these differences remained constant with length of employment. Cessation of asbestos exposure for about 10 years did not seem to change lung function decline.


Cryptochrome antagonizes synchronization of Drosophila's circadian clock to temperature cycles.
In nature, both daily light:dark cycles and temperature fluctuations are used by organisms to synchronize their endogenous time with the daily cycles of light and temperature. Proper synchronization is important for the overall fitness and wellbeing of animals and humans, and although we know a lot about light synchronization, this is not the case for temperature inputs to the circadian clock. In Drosophila, light and temperature cues can act as synchronization signals (Zeitgeber), but it is not known how they are integrated. We investigated whether different groups of the Drosophila clock neurons that regulate behavioral rhythmicity contribute to temperature synchronization at different absolute temperatures. Using spatially restricted expression of the clock gene period, we show that dorsally located clock neurons mainly mediate synchronization to higher (20°C:29°C) and ventral clock neurons to lower (16°C:25°C) temperature cycles. Molecularly, the blue-light photoreceptor CRYPTOCHROME (CRY) dampens temperature-induced PERIOD (PER)-LUCIFERASE oscillations in dorsal clock neurons. Consistent with this finding, we show that in the absence of CRY very limited expression of PER in a few dorsal clock neurons is able to mediate behavioral temperature synchronization to high and low temperature cycles independent of light. We show that different subsets of clock neurons operate at high and low temperatures to mediate clock synchronization to temperature cycles, suggesting that temperature entrainment is not restricted to measuring the amplitude of such cycles. CRY dampens temperature input to the clock and thereby contributes to the integration of different Zeitgebers.


High sensitivity to gamma-hydroxybutyric acid in ethanol-preferring sP rats.
Sensitivity to the sedative effect of gamma-hydroxybutyric acid (GHB), an endogenous constituent of mammalian brain as well as an effective drug in the pharmacotherapy of alcoholism, was evaluated in rats of the selectively bred, ethanol-preferring sP and non-preferring sNP lines. GHB (0.75 and 1.0 g/kg) was administered i.p. to ethanol-naive sP and sNP rats. Times to lose (onset) and recover (sleep time) the righting reflex following GHB injection were measured. At both doses, sP rats showed a greater sensitivity to the effects of GHB than did sNP rats, as evidenced by significantly shorter onset and longer sleep time. The results of the present study indicate that genetically controlled sensitivity to the sedative effect of GHB is positively correlated to ethanol preference in sP and sNP rats and suggest a possible involvement of the brain GHB system in predisposition to ethanol preference.


The necrotrophic pathogen Parastagonospora nodorum is a master manipulator of wheat defense.
Parastagonospora nodorum is a necrotrophic pathogen of wheat that is particularly destructive in major wheat growing regions of the United States, Northern Europe, Australia, and South America. P. nodorum secretes necrotrophic effectors that target wheat susceptibility genes to induce programmed cell death (PCD), resulting in increased colonization of host tissue and ultimately sporulation to complete its pathogenic life cycle. Intensive research over the last two decades has led to the functional characterization of five proteinaceous necrotrophic effectors including SnTox1, SnToxA, SnTox267, SnTox3, SnTox5 and three wheat susceptibility genes Tsn1, Snn1, and Snn3D-1. Functional characterization has revealed that these effectors, in addition to inducing PCD, have additional roles in pathogenesis including chitin binding that results in protection from wheat chitinases, blocking defense response signaling, and facilitating plant colonization. There are still large gaps in our understanding of how this necrotrophic pathogen is successfully manipulating wheat defense to complete its life cycle. This review summarizes our current knowledge, identifies knowledge gaps, and provides a summary of well-developed tools and resources currently available to study the P. nodorum - wheat interaction. The P. nodorum-wheat interaction has become a model for necrotrophic specialist interactions. Further functional characterization of the effectors involved in this interaction and work toward a complete understanding of how P. nodorum manipulates wheat defense will provide fundamental knowledge about this and other necrotrophic interactions. Additionally, a broader understanding of this interaction will contribute to the successful management of septoria nodorum blotch disease on wheat.


Effect of aging on human mesenchymal stem cell therapy in ischemic cardiomyopathy patients.
The role of patient age in the efficacy of mesenchymal stem cell (MSC) therapy in ischemic cardiomyopathy (ICM) is controversial. This study sought to determine whether the therapeutic effect of culture-expanded MSCs persists, even in older subjects. Patients with ICM who received MSCs via transendocardial stem cell injection (TESI) as part of the TAC-HFT (Transendocardial Autologous Cells in Ischemic Heart Failure) (n = 19) and POSEIDON (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis) (n = 30) clinical trials were divided into 2 age groups: younger than 60 and 60 years of age and older. Functional capacity was measured by 6-min walk distance (6MWD) and quality of life using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) score, measured at baseline, 6 months, and 1 year post-TESI. Various cardiac imaging parameters, including absolute scar size, were compared at baseline and 1 year post-TESI. The mean 6MWD was similar at baseline and increased at 1 year post-TESI in both groups: 48.5 ± 14.6 m (p = 0.001) for the younger and 35.9 ± 18.3 m (p = 0.038) for the older participants (p = NS between groups). The older group exhibited a significant reduction in MLHFQ score (-7.04 ± 3.54; p = 0.022), whereas the younger than 60 age group had a borderline significant reduction (-11.22 ± 5.24; p = 0.058) from baseline (p = NS between groups). Although there were significant reductions in absolute scar size from baseline to 1 year post-TESI, the effect did not differ by age. MSC therapy with TESI in ICM patients improves 6MWD and MLHFQ score and reduces myocardial infarction size. Importantly, older individuals did not have an impaired response to MSC therapy.


[The nature of and the interrelations between the concepts of "life","disease" and "aging"].
An attempt is made to consider disease and aging following from the concepts of the essence of life. The proposed definition of life represents a modified Engels' (1878) definition. Proceeding from the analysis of possible mechanisms of different disturbances in the life process leading to a decreased probability of the organism existence it is concluded that disease develops either as a result of hereditary changes in the genome or due-to disorders in its realization under certain unfavorable conditions. Aging is determined by the properties of the genome itself and develops in connection with age increase.


Population density estimated from locations of individuals on a passive detector array.
The density of a closed population of animals occupying stable home ranges may be estimated from detections of individuals on an array of detectors, using newly developed methods for spatially explicit capture-recapture. Likelihood-based methods provide estimates for data from multi-catch traps or from devices that record presence without restricting animal movement ("proximity" detectors such as camera traps and hair snags). As originally proposed, these methods require multiple sampling intervals. We show that equally precise and unbiased estimates may be obtained from a single sampling interval, using only the spatial pattern of detections. This considerably extends the range of possible applications, and we illustrate the potential by estimating density from simulated detections of bird vocalizations on a microphone array. Acoustic detection can be defined as occurring when received signal strength exceeds a threshold. We suggest detection models for binary acoustic data, and for continuous data comprising measurements of all signals above the threshold. While binary data are often sufficient for density estimation, modeling signal strength improves precision when the microphone array is small.


Identification of myeloproliferative neoplasm drug agents via predictive simulation modeling: assessing responsiveness with micro-environment derived cytokines.
Previous studies have shown that the bone marrow micro-environment supports the myeloproliferative neoplasms (MPN) phenotype including via the production of cytokines that can induce resistance to frontline MPN therapies. However, the mechanisms by which this occurs are poorly understood. Moreover, the ability to rapidly identify drug agents that can act as adjuvants to existing MPN frontline therapies is virtually non-existent. Here, using a novel predictive simulation approach, we sought to determine the effect of various drug agents on MPN cell lines, both with and without the micro-environment derived inflammatory cytokines. We first created individual simulation models for two representative MPN cell lines; HEL and SET-2, based on their genomic mutation and copy number variation (CNV) data. Running computational simulations on these virtual cell line models, we identified a synergistic effect of two drug agents on cell proliferation and viability; namely, the Jak2 kinase inhibitor, G6, and the Bcl-2 inhibitor, ABT737. IL-6 did not show any impact on the cells due to the predicted lack of IL-6 signaling within these cells. Interestingly, TNFα increased the sensitivity of the single drug agents and their use in combination while IFNγ decreased the sensitivity. In summary, this study predictively identified two drug agents that reduce MPN cell viability via independent mechanisms that was prospectively validated. Moreover, their efficacy is either potentiated or inhibited, by some of the micro-environment derived cytokines. Lastly, this study has validated the use of this simulation based technology to prospectively determine such responses.


Promiscuity of clinical Plasmodium falciparum isolates for multiple adhesion molecules under flow conditions.
The central pathologic process in severe Plasmodium falciparum malaria is the cytoadherence of parasitized erythrocytes to capillary and postcapillary venular endothelium, with resultant tissue hypoxia, metabolic disturbances, and multiorgan dysfunction. The molecular basis of this process has been studied extensively using static adhesion assays. In the present study, we determined whether infected red blood cells (IRBC) from clinical parasite isolates would roll and adhere on CD36, ICAM-1, E-selectin, P-selectin, and VCAM-1 using a laminar flow system that allowed for the direct visualization of IRBC-substratum interactions. The results indicate that IRBC could tether and roll on CD36, ICAM-1, P-selectin, and VCAM-1 in a shear-dependent fashion, but significant adhesion was restricted to CD36. There was no interaction with E-selectin. When both CD36 and ICAM-1 were expressed on the same cellular substratum such as C32 melanoma cells, adhesion was significantly greater than when CD36 was present alone. The adhesive interactions were different from those between leukocytes and the same adhesion molecules. Furthermore, IRBC rolling on P-selectin and VCAM-1 was not inhibitable by Abs that entirely prevented leukocyte-receptor interactions. These findings suggest that cytoadherence under physiologic conditions may be a multistep process similar to that involved in the recruitment of a number of different cell types. Further elucidation of the molecular basis of these novel interactions is crucial for the development of therapeutic interventions aimed at inhibiting or reversing the process.


Transforming doctor-patient relationships to promote patient-centered care: lessons from palliative care.
Palliative care was studied for its potential to yield lessons for transforming doctor-patient relationships to promote patient-centered care. Examination of patient and provider experiences of the transition from curative to palliative care promises valuable insights about establishing and maintaining trust as the goals of care shift and about addressing a broad spectrum of patient needs. The study was guided by a conceptual framework grounded in existing models to address five dimensions of doctor-patient relationships: range of needs addressed, source of authority, maintenance of trust, emotional involvement, and expression of authenticity. Data collection included observation of the care of 40 patients in the inpatient hospice unit and at home, interviews with patients and family members, and in-depth interviews with 22 physicians and two nurses providing end-of-life care. Standard qualitative procedures were used to analyze the data, incorporating techniques for maximizing the validity of the results and broadening their relevance to other contexts. Findings provide evidence for challenging prominent assumptions about possibilities for doctor-patient relationships: questioning the merits of the prohibition on emotional involvement, dependence on protocols for handling difficult communication issues, unqualified reliance on consumer empowerment to assure that care is responsive to patients' needs, and adoption of narrowly defined boundaries between medical and social service systems in caring for patients. Medical education can play a role in preparing doctors to assume new roles by openly addressing management of emotions in routine clinical work, incorporating personal awareness training, facilitating reflection on interactions with patients through use of standardized patients and videotapes, and expanding capacity to effectively address a broad range of needs through teamwork training.


Adsorption of uranium (VI) complexes with polymer-based spherical activated carbon.
Adsorption processes with carbon-based adsorbents have received substantial attention as a solution to remove uranium from drinking water. This study investigated uranium adsorption by a polymer-based spherical activated carbon (PBSAC) characterised by a uniformly smooth exterior and an extended surface of internal cavities accessible via mesopores. The static adsorption of uranium was investigated applying varying PBSAC properties and relevant solution chemistry. Spatial time-of-flight secondary ion mass spectrometry (ToF-SIMS) was employed to visualise the distribution of the different uranium species in the PBSAC. The isotherms and thermodynamics calculations revealed monolayer adsorption capacities of 28-667 mg/g and physical adsorption energies of 13-21 kJ/mol. Increasing the surface oxygen content of the PBSAC to 10 % enhanced the adsorption and reduced the equilibrium time to 2 h, while the WHO drinking water guideline of 30 µgU/L could be achieved for an initial concentration of 250 µgU/L. Uranium adsorption with PBSAC was favourable at the pH 6-8. At this pH range, uranyl carbonate complexes (UO2CO3(aq), UO2(CO3)22-, (UO2)2CO3(OH)3-) predominated in the solution, and the ToF-SIMS analysis revealed that the adsorption of these complexes occurred on the surface and inside the PBSAC due to intra-particle diffusion. For the uranyl cations (UO22+, UO2OH+) at pH 2-4, only shallow adsorption in the outermost PBSAC layers was observed. The work demonstrated the effective removal of uranium from contaminated natural water (67 µgU/L) and meeting both German (10 µgU/L) and WHO guideline concentrations. These findings also open opportunities to consider PBSAC in hybrid treatment technologies for uranium removal, for instance, from high-level radioactive waste.


[Role of biochemical and radiological study methods in the evaluation of prognosis in acute ischemia of the limbs].
Examined were 47 patients with acute ischemia of the extremities: 29--with favourable outcome, and 18-with the development of gangrene. Scintigraphy of the extremity with 99mTc-Sn-pyrophosphate was performed; urinary excretion of epinephrine and norepinephrine, DOPA and dopamine, and vanillylmandelic acid as well was studied; the content of ACTH, cortisol and cyclic adenosine monophosphate in the blood was defined. The use of radionuclide and biochemical methods of investigation permits to assess the degree of severity of the ischemic injury to the tissues of the extremities.


α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling.
The ageing suppressor α-klotho binds to the fibroblast growth factor receptor (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that consists of the shed extracellular domain of α-klotho, the FGFR1c ligand-binding domain, and FGF23. In this complex, α-klotho simultaneously tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability. Dimerization of the stabilized ternary complexes and receptor activation remain dependent on the binding of heparan sulfate, a mandatory cofactor of paracrine FGF signalling. The structure of α-klotho is incompatible with its purported glycosidase activity. Thus, shed α-klotho functions as an on-demand non-enzymatic scaffold protein that promotes FGF23 signalling.


[A comparative study of serotonin metabolism in helminths and their hosts].
Studies have been made on the content of the main metabolite of serotonin, namely 5-hydroxyindoleacetic acid in parasitic worms from various classes. It was shown that 5-hydroxyindoleacetic acid level is lower than that of serotonin, which is taken as an indication of low catabolism of serotonin in worms. This tendency was observed in helminths from different taxonomic, ecological and age groups invading media with both low and high levels of serotonin metabolism.


EEG correlates of time-varying BOLD functional connectivity.
Recent resting-state fMRI studies have shown that the apparent functional connectivity (FC) between brain regions may undergo changes on time-scales of seconds to minutes, the basis and importance of which are largely unknown. Here, we examine the electrophysiological correlates of within-scan FC variations during a condition of eyes-closed rest. A sliding window analysis of simultaneous EEG-fMRI data was performed to examine whether temporal variations in coupling between three major networks (default mode; DMN, dorsal attention; DAN, and salience network; SN) are associated with temporal variations in mental state, as assessed from the amplitude of alpha and theta oscillations in the EEG. In our dataset, alpha power showed a significant inverse relationship with the strength of connectivity between DMN and DAN. In addition, alpha power covaried with the spatial extent of anticorrelation between DMN and DAN, with higher alpha power associated with larger anticorrelation extent. Results suggest an electrical signature of the time-varying FC between the DAN and DMN, potentially reflecting neural and state-dependent variations.


Elucidating the crosstalk mechanism between IFN-gamma and IL-6 via mathematical modelling.
Interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) are multifunctional cytokines that regulate immune responses, cell proliferation, and tumour development and progression, which frequently have functionally opposing roles. The cellular responses to both cytokines are activated via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. During the past 10 years, the crosstalk mechanism between the IFN-gamma and IL-6 pathways has been studied widely and several biological hypotheses have been proposed, but the kinetics and detailed crosstalk mechanism remain unclear. Using established mathematical models and new experimental observations of the crosstalk between the IFN-gamma and IL-6 pathways, we constructed a new crosstalk model that considers three possible crosstalk levels: (1) the competition between STAT1 and STAT3 for common receptor docking sites; (2) the mutual negative regulation between SOCS1 and SOCS3; and (3) the negative regulatory effects of the formation of STAT1/3 heterodimers. A number of simulations were tested to explore the consequences of cross-regulation between the two pathways. The simulation results agreed well with the experimental data, thereby demonstrating the effectiveness and correctness of the model. In this study, we developed a crosstalk model of the IFN-gamma and IL-6 pathways to theoretically investigate their cross-regulation mechanism. The simulation experiments showed the importance of the three crosstalk levels between the two pathways. In particular, the unbalanced competition between STAT1 and STAT3 for IFNR and gp130 led to preferential activation of IFN-gamma and IL-6, while at the same time the formation of STAT1/3 heterodimers enhanced preferential signal transduction by sequestering a fraction of the activated STATs. The model provided a good explanation of the experimental observations and provided insights that may inform further research to facilitate a better understanding of the cross-regulation mechanism between the two pathways.


Impact of Glabellar Injection Technique With DaxibotulinumtoxinA for Injection on Brow Position.
Precise injection technique is vital for avoiding suboptimal eyebrow position when treating glabellar lines with botulinum toxin type A. The aim of this study was to evaluate the impact of glabellar injection technique on eyebrow position in patients treated with DaxibotulinumtoxinA for Injection (DAXI). This retrospective post hoc analysis involved 60 adults who received a single treatment with DAXI 40 U to the glabella and had standardized facial photography. Median vertical and horizontal displacement of the brows (at rest) at baseline and 2 weeks after glabellar injection were measured. Brow position outcomes were evaluated by an oculoplastic surgeon and expert anatomist. Investigators were interviewed to ascertain individual injection techniques. Precise injection location and depth, and median resting brow position following treatment varied between investigators. Positive brow outcomes were achieved with deep DAXI injections into the medial corrugator, superficial lateral corrugator injections placed between the midpupil and lateral limbus, and deep midline procerus injections. Glabellar injection technique that more precisely targeted the corrugator muscles resulted in longer glabellar line treatment duration compared to a less targeted technique. Medial corrugator injections above the medial brow; lateral corrugator injections administered deeply or more medially, toward the medial third of the brow; and procerus injections superior to the inferomedial brow tended to be associated with suboptimal outcomes that were more apparent during dynamic expression. Aesthetically pleasing brow outcomes and greater duration of efficacy can be achieved with an injection pattern that precisely treats the anatomic location of the corrugator supercilii and procerus muscles, avoiding the frontalis.


Exogenous induction of the iron dicitrate transport system of Escherichia coli K-12.
Streptonigrin was used to select mutants impaired in the citrate-dependent iron transport system of Escherichia coli K-12. Mutants in fecA and fecB could not transport iron via citrate. fecA-lac and fecB-lac operon fusions were constructed with the aid of phage Mu dl(Ap lac). Strains deficient in ferric dicitrate transport which were mutated in fecB were as inducible as transport-active strains. They expressed the FecA outer membrane protein and beta-galactosidase of the fecB-lac operon fusions. In contrast, all fecA::lac mutants and fecA mutants induced with N-methyl-N'-nitro-N-nitrosoguanidine did not respond to ferric dicitrate supplied in the growth medium. tonB fecB mutants which were lacking all tonB-related functions were not inducible. We conclude that binding of iron in the presence of citrate to the outer membrane receptor protein is required for induction of the transport system. In addition, the tonB gene has to be active. However, iron and citrate must not be transported into the cytoplasm for the induction process. These data support our previous conclusion of an exogenous induction mechanism. Mutants in fur expressed the transport system nearly constitutively. In wild-type cells limiting the iron concentration in the medium enhanced the expression of the transport system. Thus, the citrate-dependent iron transport system shares regulatory devices with the other iron transport systems in E. coli and, in addition, requires ferric dicitrate for induction.


Phosphorus balance and mineral metabolism with 3 h daily hemodialysis.
Poor control of mineral metabolism is independently associated with mortality in patients receiving hemodialysis. We analyzed data from a 12-month, prospective, non-randomized, controlled study of daily hemodialysis (DHD) (six sessions/week 3 h each) (n=26) vs conventional hemodialysis (CHD) (three sessions/week 4 h each) (n=51) for achievement of mineral metabolism goals and we performed a substudy of weekly dialytic phosphorus removal in DHD vs CHD. Phosphorus control was superior in the DHD group (% change from baseline to end-of-study -27+/-30% vs +7%+/-35% in the CHD group, P=0.0001). Percentage of patients using phosphate binders decreased from 77 to 40% among subjects on DHD, whereas these parameters did not change (76 vs 77%) in the CHD group (P=0.03 by Breslow-Day test for homogeneity of the odds ratios). Weekly mean phosphorus removal was higher in the DHD group (2452+/-720 mg/week vs 1572+/-366 mg/week, P=0.04). Mean normalized protein catabolic rate increased (0.90+/-0.43-1.22+/-0.26 g/kg/day, P=0.0013). DHD was also associated with an increase in the percent of subjects achieving three or more mineral metabolism goals (for phosphorus, calcium x phosphorus and parathyroid hormone) (15 vs 46%, P=0.046). In conclusion, DHD improves phosphorus control by increasing dialytic phosphorus removal while maintaining nutritional status and reducing the use of phosphate binders. The net effect allows for improved achievement of mineral metabolism goals.


Diagnosis of cutaneous leishmaniasis and species discrimination of parasites by PCR and hybridization.
The aim of this study was to assess the efficacy of PCR methodology in establishing the diagnosis of cutaneous leishmaniasis in patients from areas of endemicity in Venezuela. Biopsies from 233 patients with cutaneous ulcers suggestive of leishmaniasis were analyzed by PCR, employing oligonucleotides directed against conserved regions of kinetoplast DNA (kDNA), and the PCR products were then hybridized to nonradioactively labeled, species-specific, cloned kDNA fragments. The ability of PCR to detect Leishmania cells was compared with those of the conventional methodologies: skin testing with killed promastigotes (Montenegro test), examination of Giemsa-stained biopsy smears, and in vitro culture of biopsy tissue. The PCR-hybridization technique detected the presence of Leishmania cells in 98% of patients clinically diagnosed as having leishmaniasis and also positive by the Montenegro skin test. In comparison, leishmania positivity was found in only 42% of cultures and 64% of biopsy smears. By hybridizing the PCR product to new kDNA probes specific for either Leishmania mexicana or Leishmania braziliensis, we found that both species are major causes of cutaneous leishmaniasis in Venezuela, and the species identification was confirmed by restriction enzyme analysis of kDNA from biopsy cultures. This work demonstrates that PCR coupled with hybridization is useful not only for the diagnosis of cutaneous leishmaniasis but also for the taxonomic discrimination essential for both epidemiology and therapy. This technique can be used to diagnose leishmaniasis in a country in which the disease is endemic and can perhaps be adapted for use in a rural clinic.


Experience with laparoscopic sleeve gastrectomy for morbid versus super morbid obesity.
We evaluated the safety and efficacy of laparoscopic sleeve gastrectomy (LSG) for super morbid obesity in patients with an initial body mass index (BMI) of <50 or > or =50. Between October 2005 and January 2008, we performed LSG in 30 patients. There were 20 males and 10 females with a mean age of 38 years. Mean initial body weight and BMI were 139 kg and 49.1 kg/m(2), respectively. Sleeve gastrectomy was carried out using a linear stapler from the greater curvature of the antrum 5 cm proximal from the pyloric ring up to the angle of His alongside a 45-Fr. bougie. Laparoscopic procedures were performed successfully in all patients. The mean operation time was 92 min, and blood loss was minimal. The BMI change and weight loss at the 1-, 3-, 6-, 9-, 12-, and 18-month follow-up points of patients with an initial BMI of <50 and > or =50 were 34.2 and 57.4, 32.1 and 53.7, 29.6 and 50.8, 29.5 and 51.2, 27.8 and 52.2, and 29.7 and 45.5 kg/m(2) and 96.8 and 172.2, 89.5 and 157.0, 83.4 and 144.8, 84.0 and 145.4, 78.0 and 153.4, and 84.5 and 119.5 kg, respectively. The patients with a BMI of <50 obtained good outcomes, but weight loss reached a plateau at 9 months after surgery in patients with a BMI of > or =50. Postoperative complications included leakage, bleeding, stricture, and peritonitis in one patient each. There was no surgical mortality. Most of the co-morbidities improved after surgery. Sleeve gastrectomy is a feasible and safe treatment for super morbid obesity, but evaluation of long-term outcome is necessary to determine whether it is a durable procedure in terms of effectiveness. We expect that patients with a BMI of <50 are good candidates for LSG as a definitive treatment, and, if those with a BMI of > or =50 hope for further weight loss, a second-step procedure may be required.


[Ultrasonics in the diagnosis of stomach tumors].
Proceeding from analysis of over 2000 ultrasound investigations (USI) the role of this method in the diagnosis of stomach tumors was defined (employed during routine investigation of the abdominal cavity and as a procedure with liquid filling of the stomach cavity). Ultrasound semiotics of a neoplastic process of the stomach was described. USI can be used for screening and specification. Various methodological approaches were proposed with regard to purposes to be achieved. Routine methods (x-ray and endoscopy) were shown to remain the chief methods. USI can be used in doubtful cases or for obtaining detailed information. The most valuable are its potentialities in showing details of intraparietal changes in endophytic stomach carcinomas which are difficult for diagnosis.


Physiological response to seawater pH of the bivalve Abra alba, a benthic ecosystem engineer, is modulated by low pH.
The presence and behaviour of bivalves can affect the functioning of seafloor sediments through the irrigation of deeper strata by feeding and respiring through siphonal channels. Here, we investigated the physiological response and consecutive impact on functioning and body condition of the white furrow shell Abra alba in three pH treatments (pH = 8.2, pH = 7.9 and pH = 7.7). Although no pH effect on survival was found, lowered respiration and calcification rates, decreased energy intake (lower absorption rate) and increased metabolic losses (increased excretion rates) occurred at pH ∼ 7.7. These physiological responses resulted in a negative Scope for Growth and a decreased condition index at this pH. This suggests that the physiological changes may not be sufficient to sustain survival in the long term, which would undoubtedly translate into consequences for ecosystem functioning.


The tobacco wars: back to the states.
With the United States Senate's failure to pass comprehensive tobacco legislation, the fight to recover public health costs from big tobacco shifts back to the states. The question for those working to reduce youth smoking rates is whether that battle can be accomplished at the state level.


Retinal vascular occlussion induced by oral contraceptives.
A case of unilateral retinal vascular occlusion secondary to the use of oral contraceptives is presented. The vision was only slightly affected. Fundus examination revealed tortuosity of venules around the macular area and alteration of the pigment epithelium indicating low-grade retinal vein occlusion. Periodic ophthalmologic examination is suggested to women on oral contraceptives to prevent serious thromboembolic complications.


[Vestibular compensation. Rehabilitation of a patient with vertigo].
Vestibular compensation is the association of neurological reorganization events that allow to recover the balance after peripheral vestibular damage. The aim of rehabilitation of the patient with vertigo is to maximize these events to achieve an earlier return of the patients to active life. An individualized vestibular rehabilitation program is used on the basis of a general protocol that includes the following four elements: a) stabilization of vision and coordination of head and eye movements; b) vestibular habituation exercises adapted on an individual basis; c) postural control exercises via biofeedback techniques; and d) a program to improve general patient conditions. It is concluded that rehabilitation therapy of vertigo should always be taken into account, both in balance alterations caused by peripheral vestibular lesions and in central nervous damage and mixed pathology.


Right ventricular hypertrophy long after reversal of severe pressure overload in cats.
To test the hypothesis that alterations in ventricular size and function may persist long after reversal of a severe pressure overload, right ventricular (RV) hypertrophy was produced in cats by abrupt, severe constriction of the pulmonary artery (PA) for 8 wk, after which pressure overload was completely reversed by surgical removal of the PA band (group III). Despite debanding and recovery from pressure overload (RV peak systolic pressure = 22 +/- 4 vs. 66 +/- 20 mmHg before debanding and 25 +/- 4 mmHg in controls), parameters of hypertrophy 8-10 mo later remained substantially increased: e.g., RV/LV (left ventricular) mass ratio was 0.36 +/- 0.06 in group III vs. 0.24 +/- 0.03 in controls (group I) and 0.43 +/- 0.07 in a separate cohort (group II) studied after 8 wk of banding. Maximum RV stroke work during volume loading was computed from RV micromanometry and PA electromagnetic flow: 20 +/- 8 g-cm/g for group III vs. 51 +/- 14 for group I, P less than 0.05, and 21 +/- 7 for group II. Thus severe pressure overload of the RV may produce changes in size and function that are not fully reversed by complete removal of the overload.


Synthesis of Chlorophyllide b from Protochlorophyllide in Chlamydomonas reinhardtii y-1.
In cells of Chlamydomonas reinhardtii y-1 kept in the dark, 1,7-phenanthroline stimulated the conversion of protochlorophyllide to chlorophyllide b. A membrane fraction was obtained from degreened cells that was active in this conversion only when phenanthroline was present. Untreated cells excreted protochlorophyllide, which was used as substrate for this in vitro reaction. This system may provide a clue to how chlorophyllide b is synthesized in plant cells.


Modification of store-operated channel coupling and inositol trisphosphate receptor function by 2-aminoethoxydiphenyl borate in DT40 lymphocytes.
Store-operated channels (SOCs) provide an important means for mediating longer-term Ca(2+) signals and replenishment of Ca(2+) stores in a multitude of cell types. However, the coupling mechanism between endoplasmic reticulum stores to activate plasma membrane SOCs remains unknown. In DT40 chicken B lymphocytes, the permeant inositol trisphosphate receptor (InsP(3)R) modifier, 2-aminoethoxydiphenyl borate (2-APB), was a powerful activator of store-operated Ca(2+) entry between 1-10 microm. 2-APB activated authentic SOCs because the entry was totally selective for Ca(2+) (no detectable entry of Ba(2+) or Sr(2+) ions), and highly sensitive to La(3+) ions (IC(50) 30-100 nm). To assess the role of InsP(3)Rs in this response, we used the DT40 triple InsP(3)R-knockout (ko) cell line, DT40InsP(3)R-ko, in which the absence of full-length InsP(3)Rs or InsP(3)R fragments was verified by Western analysis using antibodies cross-reacting with N-terminal epitopes of all three chicken InsP(3)R subtypes. The 2-APB-induced activation of SOCs was identical in the DT40InsP(3)R-ko, cells indicating InsP(3)Rs were not involved. With both wild type (wt) and ko DT40 cells, 2-APB had no effect on Ca(2+) entry in store-replete cells, indicating that its action was restricted to SOCs in a store-coupled state. 2-APB induced a robust activation of Ca(2+) release from stores in intact DT40wt cells but not in DT40InsP(3)R-ko cells, indicating an InsP(3)R-mediated effect. In contrast, 2-APB blocked InsP(3)Rs in permeabilized DT40wt cells, suggesting that the stimulatory action of 2-APB was restricted to functionally coupled InsP(3)Rs in intact cells. Uncoupling of ER/PM interactions in intact cells by calyculin A-induced cytoskeletal rearrangement prevented SOC activation by store-emptying and 2-APB; this treatment completely prevented 2-APB-induced InsP(3)R activation but did not alter InsP(3)R activation mediated by phospholipase C-coupled receptor stimulation. The results indicate that the robust bifunctional actions of 2-APB on both SOCs and InsP(3)Rs are dependent on the coupled state of these channels and suggest that 2-APB may target the coupling machinery involved in mediating store-operated Ca(2+) entry.


Inhaled mannitol identifies methacholine-responsive children with active asthma.
Inhaled mannitol has been developed for bronchial challenge testing in adults. This study determined if mannitol could identify children with active asthma and responsive to methacholine, and whether mannitol challenge was faster to complete than methacholine challenge. Twenty-five children (aged 6-13 years) responsive to methacholine and 10 nonasthmatic children unresponsive to methacholine were studied. The methacholine challenge (Cockcroft protocol) was followed by a mannitol challenge on separate days. Twenty-one asthmatic children were positive to mannitol. Three taking inhaled corticosteroids with borderline methacholine responsiveness did not respond to mannitol, and one could not complete the mannitol challenge due to cough. The geometric mean (GM) and 95% confidence interval (CI) for PD(15) for mannitol was 39 mg (19, 78), and PC(20) for methacholine was 0.6 mg/mL (0.35-1.02) (r(p) = 0.75, p < 0.001, n = 21). Responses to mannitol were repeatable: GM PD(15) for the first challenge was 29 mg (CI: 17,50), and for the second challenge, 33 mg (CI: 20, 55) (P = 0.44, n = 9). Mannitol was faster to administer than methacholine (median (range)) 14 min (5-32) vs. 29 min (19-49), respectively (P < 0.001). Time to recover to baseline FEV(1) spontaneously and after bronchodilator administration was similar for both challenges. There were no significant falls in arterial oxygen saturations. During mannitol challenge, the mean (SD) fall in FEV(1) in nonasthmatic children was 3.1% (2.9). We conclude that mannitol identifies children with airway hyperresponsiveness and is faster to perform than the methacholine challenge.


The Alteration of Plasma Matrix Metalloproteinase-9 Level after the Addition of Bromelin 500 mg to Standard Therapy of Acute Ischemic Stroke and Its Correlation with Outcome.
Matrix metalloproteinase-9 (MMP9) expression due to ischemic cause spreading of brain damage. Previous studies have reported that Bromelin was beneficial as anti-inflammation and prevent brain tissue damage. This study aimed to determine the alteration of plasma MMP9 level after addition of Bromelin 500 mg to Standard therapy and its correlation with outcome in acute ischemic stroke. This was a preliminary report of a prospective randomised, double-blind study with pre and post-test design, forty-six acute ischemic stroke patients were randomly allocated with Bromelin and Standard groups. Measurement of MMP9 and outcome were performed before and after 14-days treatment. The Bromelin group showed a significant decrement of MMP9 level, from 6.02 ± 0.32 ng/ml before treatment to 5.50 ± 0.94 ng/ml after treatment (p = 0.028). There was a negative correlation between MMP9 level and mRS (r= -0.03; p = 0.905) and a positive correlation toward BI (r = 0.039; p = 0.859), while the Standard group showed increased MMP9 level from 5.82 ± 0.71 ng/ml to 5.91 ± 0.83 ng/ml (p = 0.616) which was correlated insignificantly to outcome. We concluded that the addition of 500 mg Bromelin to standard ischemic stroke therapy reduced MMP9 level significantly and correlated to outcome improvement. However, there is a tight statistical correlation.


Antimicrobials increase travelers' risk of colonization by extended-spectrum betalactamase-producing Enterobacteriaceae.
More than 300 million travelers visit regions with poor hygiene annually. A significant percentage of them become colonized by resistant intestinal bacteria such as extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) and may transmit the strains to others and to medical care settings when they return home. Despite the threats to global healthcare caused by an upsurge in antimicrobial resistance, no effort has been centered on prevention of colonization while traveling. Stool samples were collected from 430 Finns before and after traveling outside Scandinavia. All specimens were analyzed for ESBL- and carbapenemase-producing Enterobacteriaceae (CPE). Questionnaires were used to survey volunteers about use of antimicrobials as well as other potential risk factors. The results were subjected to multivariable analysis. Twenty-one percent (90/430) of the travelers became colonized by ESBL-PE and none by CPE. Geographic region, occurrence of travelers' diarrhea (TD), age, and use of antimicrobial (AB) for TD were identified as independent risk factors predisposing to contracting ESBL-PE. Eleven percent of those in subgroup TD-AB-, 21% in TD+AB-, and 37% in TD+AB+ acquired ESBL-PE. The risk proved to be highest in South Asia (46%); 23% became colonized in subgroup TD-AB-, 47% in TD+AB-, and 80% in TD+AB+. In Southeast Asia, the rates were 14%, 37%, and 69%, respectively. TD and antimicrobials for TD proved to be independent risk factors, with up to 80% of TD+AB+ travelers contracting ESBL-PE. In modern pre-travel counseling for those visiting high-risk regions, travelers should be advised against taking antibiotics for mild or moderate TD.


Interview with Jeffrey Bronfman, representative mestre for the União do Vegetal Church in the United States. Interview by Marlene Dobkin de Rios and Charles S Grob.
A telephone interview was held in November of 2004 with Mr. Jeffrey Bronfman, representative mestre for the União do Vegetal Church in the United States, which utilizes ayahuasca as a religious sacrament. At the time of this writing, the U.S. Supreme Court has agreed to hear a case in which a large quantity of the ayahuasca tea was seized in the U.S. destined for sacramental use in church ritual. Mr. Bronfman discusses his church's attempt to seek remediation in the courts on this freedom of religion issue, in conflict with current drug legislation outlawing the ayahuasca tea as a scheduled drug.


Tramadol Use in United States Emergency Departments 2007-2018.
Amidst the opioid epidemic, there has been an increasing focus on opioid utilization in U.S. emergency departments (EDs). Compared with other opioids, little is known about the use of tramadol over the past decade. Tramadol has uncertain efficacy and a concerning adverse effect profile compared with traditional opioids. Our aim was to describe trends in tramadol use in U.S. EDs between 2007 and 2018. We analyzed the National Hospital Ambulatory Medical Care Survey from 2007 to 2018 to examine ED visits by patients 18 years or older in which tramadol was administered or prescribed. We examined trends in demographics and resource utilization and compared these trends with those of traditional opioids. Survey-weighted analyses were conducted to provide national-level estimates. Between 2007 and 2018, ED visits in which tramadol was used increased 70.6%, from 1.7% of all ED visits in 2007 to 2.9% in 2018. The largest increases were noted among patients aged 55 through 64 years and 65 years and older. Diagnostic resource utilization increased across the study period. Overall opioid utilization during the study period decreased from 28.4% in 2007 to 17.9% in 2018 (p < 0.001). The use of other specific opioids declined or remained stable between 2007 and 2018. Although the use of traditional opioids decreased from 2007 to 2018, the use of tramadol increased. Increases were largest among older patients, who may be more susceptible to the adverse effects associated with this medication. Further research in the appropriate use of tramadol in the ED setting is warranted.


Changes in Emotional-Behavioral Functioning Among Pre-school Children Following the Initial Stage Danish COVID-19 Lockdown and Home Confinement.
Unintended negative outcomes on child behavior due to lockdown and home confinement following the corona virus disease (COVID-19) pandemic needs highlighting to effectively address these issues in the current and future health crises. In this sub-study of the ODIN-study, the objectives were to determine whether the Danish lockdown and home confinement following the COVID-19 pandemic affected changes in emotional-behavioral functioning of pre-school-aged children using the validated Strength and Difficulties Questionnaire (SDQ) answered by parents shortly before lockdown and 3 weeks into lockdown, and moreover, to examine whether baseline family and social characteristics could predict change in child emotional-behavioral functioning during lockdown. Parents of 40 (82%) children with a mean(SD) age of 5.0(0.7) completed the baseline questionnaire and the lockdown follow-up questionnaire. The SDQ-Total difficulties score (SDQ-TD) and Prosocial Behavioral score (PSB) changed significantly from pre- to lockdown [SDQ-TD mean(SD): 6.0(3.8) and 7.9(5.2); P = 0.02, respectively and PSB mean(SD): 8.5(1.4) and 7.9(1.5); P = 0.03, respectively]. Attending leisure time activities before lockdown was a predicting factor of changes to the worse in the children's SDQ-TD scores, with a mean difference in SDQ-TD between those with and without activities of 3.16 (95%CI 0.27-6.12); P = 0.03. In conclusion, the study showed a modest decrease in child-emotional behavioral functioning during the COVID-19 lockdown, potentially due to parental stress. Although these results might not be generalizable due to small sample size and selected population, the results point to a need of a greater awareness of child mental wellbeing during a lockdown situation.


The radioguided 111In-pentetreotide surgery in the management of ACTH-secreting bronchial carcinoid.
A correct intra-operative detection of the tumour and, therefore, the complete surgical resection is critical to success in ACTH-secreting bronchial carcinoids. To date, all available preoperative and intra-operative procedures remain not entirely satisfactory. The use of intra-operative 111In-pentetreotide detection could offer a potentially reliable and rapid tool of real time assessment to achieve a radical resection. In two cases of ACTH-secreting bronchial carcinoids, after a preliminary 111In-pentetreotide scan, radio-guided surgery was performed using a hand-held gamma probe 24 h after i.v. administration of the tracer. The 111n-pentetreotide radioguided surgery with hand-held gamma probe, if compared with pre-operative 111In-pentetreotide, significantly improved the intra-operative surgical management by detecting a millimetric nodule in one case; detecting mediastinal lymph node metastasis in both cases and ruling out any other disease localization. Intra-operative 111In-pentetreotide detection appears to be safe and easy to perform. This technique allowed to achieve a complete resection of all the tumor locations, that would have been impossible to detect with conventional surgical approach. On the basis of these results we advocate for a wider investigation of the potentialities connected with the radioguided surgery coupled with pre-operative 111In-pentetreotide scan as a promising procedure in the management of ACTH-secreting bronchial carcinoids.


Inflammatory fibroid polyp or Vanek's tumour.
We report a case of a 65-year-old woman who presented with recurrent episodes of severe, postprandial abdominal pain followed by projectile vomiting. Gastroscopy revealed a large polyp in the prepyloric region. During peristalsis, the polyp was repeatedly 'passing' through the pylorus into the duodenal bulb, hence obstructing the lumen. The polyp was eventually removed in a piecemeal fashion. Histopathologic examination revealed an inflammatory fibroid polyp (known also as Vanek's tumour). A brief review on inflammatory fibroid polyps follows.


[Skin prick test of immediate hypersensitivity in a selected Chilean pediatric population sample].
Skin prick test (SPT) of immediate hypersensitivity is a main instrument in the diagnosis of allergy. To demonstrate the applicability of skin prick test in different age groups. We studied children and adolescents with the diagnosis of allergy in the Pediatric Respiratory Laboratory of the Catholic University of Chile, from January 2001 to March 2002. The SPT was performed using a standardized technique. The allergens were applied on the volar surface of the forearm in children older than 4 years of age and in younger children it was applied on their back. For study purposes we separated them into three age groups: GI < or =2 years and 11 months, GII from 3 to 4 years and 11 months, GIII > or =5 years. We studied 408 children, aged between 8 months and 15 years. The SPT was applied to all patients with no adverse effects of any kind. There was a positive reaction in 57.7% of children. The reaction was positive in 37% in G1, 39% in GII and 65% in GIII (p <0.001). The predominant allergens for each group were dust mites (Dermatophagoides pteronissinus and farinae). SPT was useful when used on a selected pediatric population. The frequency of sensitization increased significantly with age. However, more than one third of children between 2 and 4 years of age tested positive to one or more allergen, demonstrating its applicability in this age group.


Neutral alpha-glucosidase activity in mouse: a marker of epididymal function?
Neutral alpha-glucosidase (NAG) activity is considered a functional epididymal marker in several species. Unlike the rat, no NAG activity has been detected in mice. The aims of the present study were to evaluate NAG secretory activity (the supernatant of the incubated tissue) in mouse epididymis and to determine whether it could be used as a functional epididymal marker. Epididymides (whole or in parts) were incubated in the presence or absence of testosterone (10(-5) m) and secretory NAG activity was compared with known positive controls. Furthermore, we compared enzyme activity in epididymides from well-fed and undernourished mice (50% food restriction for 21 days), a model that alters the epididymal maturation processes. Spectrophotometric analysis revealed NAG activity in mouse epididymis (22.6 +/- 3.7 mU g(-1) tissue; n = 4), being higher in the caput. NAG activity was statistically higher in the caput than in the corpus and in the cauda. No significant differences existed between the caput NAG activity and complete epididymis NAG activity. In undernourished mice, we confirmed changes in epididymal maturation observed previously (i.e. increased number of immature spermatozoa and diminution of the sperm concentration). Concordantly, the epididymides of undernourished mice exhibited decreased enzyme secretory activity, which increased to values similar to those seen in controls following incubation in the presence of testosterone (22.5 +/- 2.6, 12.5 +/- 1.0 and 22.4 +/- 3.7 mU g(-1) tissue, n = 9 in control (n = 7), undernourished (n = 9) and undernourished + testosterone groups (n = 9), respectively). In conclusion, NAG activity was detected in mouse epididymis. Although the present study supports the possibility of using NAG as an epididymal marker, more studies are necessary to effectively prove that NAG activity can be used as an epididymal marker.


Quantitative cytochemical evidence for local increases in bone turnover at the acromial enthesis of the human coracoacromial ligament.
Enthesophytic bone outgrowths are found at many ligament attachment sites, and while their incidence is associated with many pathologies, the mechanism by which they form remains controversial. We hypothesized that changes in local cell behavior, provoked by mechanical alterations within the coracoacromial ligament (CAL), lead to acromial enthesophyte formation. We investigated whether cell behavior at acromial entheses is consistent with this. We used quantitative enzyme cytochemistry to measure glucose 6-phosphate dehydrogenase (G6PD), alkaline phosphatase (ALP; osteoblastic activity), and tartrate-resistant acid phosphatase (TRAP; osteoclastic phenotype) activities in cells of the acromial attachment into the CAL in patients with rotator cuff tears. (1) Resident osteoblasts on the acromion's inferior aspect express elevated activity of G6PD and ALP, indicative of increases in osteogenic potential. (2) These activities are selectively raised at the "leading edge" of acromial bone CAL enthesis. (3) In contrast, distribution of TRAP-positive cells does not exhibit a spatial correlation with enthesis architecture. We also found that cells situated close to the CAL attachment into the acromion exhibited elevated levels of G6PD and ALP activity, but intriguingly, also showed higher TRAP activity than neighboring cells distant from entheses. These results suggest that the acromion in these patients undergoes bone accretion at the inferior attachment of the CAL, and that enthesial ligament cells close to the bone express characteristics consistent with enthesophyte formation at the leading edge of this bony spur's extension into the ligament.


Finding the optimal dose reduction and iterative reconstruction level for coronary calcium scoring.
To assess the maximally achievable computed tomography (CT) dose reduction for coronary artery calcium (CAC) scoring with iterative reconstruction (IR) by using phantom-experiments and a systematical within-patient study. Our local institutional review-board approved this study and informed consent was obtained from all participants. A phantom and patient study were conducted with 30 patients (23 men, median age 55.0 (52.0-56.0) years) who underwent 256-slice electrocardiogram-triggered CAC-scoring at four dose levels (routine, 60%, 40%, and 20%-dose) in a single session. Tube-voltage was 120 kVp, tube-current was lowered to achieve stated dose levels. Data were reconstructed with filtered back-projection (FBP) and three IR levels. Agatston, volume and mass scores were determined with validated software and compared using Wilcoxon signed ranks-tests. Subsequently, patient reclassification was analyzed. The phantom study showed that Agatston scores remained nearly stable with FBP between routine-dose and 40%-dose and increased substantially at lower dose. Twenty-three patients (77%) had coronary calcifications. For Agatston scoring, one 40%-dose and six 20%-dose FBP reconstructions were not interpretable due to noise. In contrast, with IR all reconstructions were interpretable. Median Agatston scores increased with FBP from 26.1 (5.2-192.2) at routine-dose to 60.5 (11.6-251.7) at 20% dose. However, IR lowered Agatston scores to 22.9 (5.9-195.5) at 20%-dose and strong IR (level 7) with Agatston reclassifications in 15%. IR allows for CAC-scoring radiation dose reductions of up to 80% resulting in effective doses between 0.15 and 0.18 mSv. At these dose-levels, reclassification-rates remain within 15% if the highest IR-level is applied.


Measurement of condom use self-efficacy and outcome expectancies in a geographically diverse group of STD patients.
The aim of this project was to conduct an initial evaluation among sexually transmitted disease (STD) patients of the psychometric properties of two instruments: the National Institute of Mental Health (NIMH) multisite condom use self-efficacy scale and the NIMH multisite condom use outcome expectancy scale. The condom use self-efficacy scale was designed to measure one's degree of confidence in various aspects of condom use, whereas the outcome expectancy scale was designed to measure one's belief about the consequences of using condoms. Using a sample of 641 patients from five geographically diverse STD clinics in the eastern United States, initial reliability coefficients were computed. The alpha coefficient for the self-efficacy scale was .91 and for the outcome expectancy scale .88, indicating high internal consistency for both scales. Both scales were analyzed using common factor analytic procedures. Five factors emerged from the analysis of the self-efficacy scale and six factors from the analysis of the outcome expectancy scale. Reliability coefficients for the individual factors ranged from .76 to .86. Construct validity of each scale was assessed by hypothesis testing. As predicted, participants with higher levels of self-efficacy and more positive outcome expectancies were more likely to use condoms.


LncRNA Riken Attenuated Sevoflurane-Induced Neuroinflammation by Regulating the MicroRNA-101a/MKP-1/JNK Pathway.
The induction of anesthesia in children makes its safety one of the most important global health problems. Neuroinflammation contributes to anesthesia-induced neurotoxicity in young individuals. However, the mechanisms underlying anesthesia-induced neurotoxicity have not been established. In this study, the level of interleukin (IL)-6 in the hippocampus of mice and N2A cells treated with sevoflurane was increased, and long noncoding RNA (LncRNA) Riken was sufficient to decrease sevoflurane-induced neurotoxicity, and the level of inflammatory cytokine IL-6. The RNA pull-down assay verified that miR-101a was bound to lncRNA Riken in N2A cells. In addition, miR-101a blocked the protective effect of lncRNA Riken on anesthesia-induced neuroinflammation. These data suggest that lncRNA Riken attenuated anesthesia-induced neuroinflammation by interacting with microRNA-101a. Finally, we also demonstrated that MAPK phosphatase 1 (MKP-1) was a downstream target of miR-101a, and lncRNA Riken can regulate the expression of MKP-1; the JNK signal transduction pathway has been implicated in sevoflurane-induced IL-6 secretion. Our findings demonstrated that lncRNA Riken alleviated the sevoflurane-induced neurotoxic effects, and the lncRNA Riken/miR-101a/MKP-1/JNK axis plays an important role in the cognitive disorder.


Macrophages, monocyte chemoattractant peptide-1, and TGF-beta 1 in experimental hydronephrosis.
Early cellular and molecular derangements have been evaluated as potential pivotal factors for the late development of interstitial fibrosis after experimental hydronephrosis. In this study, we delineated the kinetics of renal cortical macrophage infiltration as well as the cortical expression of transforming growth factor-beta 1 (TGF-beta 1) and monocyte chemoattractant peptide-1 (MCP-1) at 12, 48, and 96 h after unilateral ureteral obstruction (UUO). Interstitial macrophage number in the obstructed kidney versus the contralateral unobstructed kidney (CUK) significantly increased by 12 (11.1 +/- 0.9 vs. 4.5 +/- 0.6), 48 (27.5 +/- 0.9 vs. 4.0 +/- 0.8), and 96 h (71.4 +/- 4.6 vs. 3.2 +/- 0.4) after UUO. MCP-1 mRNA was detected from 12 to 96 h in the obstructed kidney but was absent in the CUK specimens at all time points. Apical tubular MCP-1 expression, on immunolabeling, was present from 12 through 96 h after UUO in the obstructed kidney but not the CUK specimen. On Northern analysis, there were highly significant 2.6-, 5.8-, and 7.0-fold increments in renal cortical TGF-beta 1 mRNA levels at 12, 48, and 96 h, respectively, in the obstructed kidney versus the CUK specimen. Intracellular TGF-beta 1, on immunolabeling, was detected only in the obstructed kidneys of UUO rats at all three time points and was confined to peritubular cells of the renal interstitium. A significant (P < 0.005) correlation (r = 0.95) between interstitial macrophage number and cortical TGF-beta 1 mRNA levels was noted.(ABSTRACT TRUNCATED AT 250 WORDS)


Risk factors for contamination of catheterized urine specimens in febrile children.
Urinary tract infections are the most common serious bacterial infection in febrile infants. Bladder catheterization is the preferred method of obtaining urine for culture in young children. Contamination of urine can be recognized when nonpathogens or multiple pathogens are isolated; preliminary culture results may lead to unnecessary antibiotics pending final identification. Some low-colony count (<50,000 colony-forming units per milliliter) cultures may represent contamination or asymptomatic bacteriuria. Identify clinical factors that lead to contamination of catheterized urine specimens. Physicians and nurses in an urban pediatric emergency department completed a survey after performing bladder catheterization of febrile children 36 months or younger. Contamination was defined by multiple pathogens, nonpathogens, or colony counts less than 10,000 colony-forming units per milliliter. : One hundred eighty-five children were studied. The median age was 8.4 months (interquartile range, 2.4-14.4 months). Sixty-eight percent were girls. Forty-six percent of boys were circumcised. Of the 185 children, 18 (10%) had true UTI. Fourteen percent of cultures were contaminated. Univariate analysis of potential predictors identified age younger than 6 months (odds ratio [OR], 6.8; 95% confidence interval [CI], 2.6-17.9), difficult catheterization (OR, 3.6; 95% CI, 1.5-8.6), and uncircumcised boys (OR, 5.7; 95% CI, 1.2-29.4). The contamination rate in uncircumcised boys younger than 6 months was 43% (95% CI, 26-66). Volume of urine, sex, and catheter size were not predictive of contamination. Children younger than 6 months and uncircumcised boys are at increased risk of contaminated specimens from bladder catheterization. Suprapubic aspiration or use of a fresh, sterile catheter with each repeated attempt at catheterization may lead to less contamination in these patients.


Avoidant Coping Is Associated with Quality of Life in Persons with Multiple Sclerosis with High Cognitive Reserve.
The goal of this study was to determine the impact of the relationship between cognitive reserve and coping strategy on quality of life (QoL) outcomes in persons with MS (PwMS) across multiple domains. We examined the effect of the interactions between coping style and cognitive reserve on QoL and disease burden in 97 persons with MS (PwMS). Coping strategy, either active or avoidant, was measured using the COPE inventory. We defined cognitive reserve as a composite measure of years of education and scores on the Shipley-2 Vocabulary subtest. QoL and disease burden were assessed using the Functional Assessment of MS (FAMS) scale and the Expanded Disability Status Scale, respectively. We examined both the FAMS individual subscales and the overall QoL score. For those with higher cognitive reserve, greater avoidant coping was associated with lower QoL for the thinking and fatigue subscale (p < 0.001) and poorer overall QoL (p = 0.03); greater active coping was associated with poorer QoL for mobility (p = 0.001). However, these associations did not hold for those with lower cognitive reserve. Furthermore, there were no associations between coping strategy and cognitive reserve with disease burden. This study extends previous findings by demonstrating that avoidant coping, rather than active coping, is associated with poorer thinking and fatigue and overall QoL only for PwMS with greater cognitive reserve. Counseling PwMS on the impact of coping strategies on QoL outcomes, especially for those with greater cognitive reserve, may improve quality of life outcomes in this population.


Characterization of type 2 quorum sensing in Klebsiella pneumoniae and relationship with biofilm formation.
Quorum sensing is a process by which bacteria communicate by using secreted chemical signaling molecules called autoinducers. Many bacterial species modulate the expression of a wide variety of physiological functions in response to changes in population density by this mechanism. In this study, the opportunistic pathogen Klebsiella pneumoniae was observed to secrete type 2 signaling molecules. A homologue of luxS, the gene required for AI-2 synthesis in Vibrio harveyi, was isolated from the K. pneumoniae genome. A V. harveyi bioassay showed the luxS functionality in K. pneumoniae and its ability to complement the luxS-negative phenotype of Escherichia coli DH5alpha. Autoinducer activity was detected in the supernatant, and maximum expression of specific messengers detected by quantitative reverse transcription-PCR analysis occurred during the late exponential phase. The highest levels of AI-2 were observed in minimal medium supplemented with glycerol. To determine the potential role of luxS in colonization processes, a K. pneumoniae luxS isogenic mutant was constructed and tested for its capacity to form biofilms in vitro on an abiotic surface and to colonize the intestinal tract in a murine model. No difference was observed in the level of intestinal colonization between the wild-type strain and the luxS mutant. Microscopic analysis of biofilm structures revealed that the luxS mutant was able to form a mature biofilm but with reduced capacities in the development of microcolonies, mostly in the early steps of biofilm formation. These data suggest that a LuxS-dependent signal plays a role in the early stages of biofilm formation by K. pneumoniae.


Strongly spin-orbit coupled two-dimensional electron gas emerging near the surface of polar semiconductors.
We investigate the two-dimensional highly spin-polarized electron accumulation layers commonly appearing near the surface of n-type polar semiconductors BiTeX (X=I, Br, and Cl) by angular-resolved photoemission spectroscopy. Because of the polarity and the strong spin-orbit interaction built in the bulk atomic configurations, the quantized conduction-band subbands show giant Rashba-type spin splitting. The characteristic 2D confinement effect is clearly observed also in the valence bands down to the binding energy of 4 eV. The X-dependent Rashba spin-orbit coupling is directly estimated from the observed spin-split subbands, which roughly scales with the inverse of the band-gap size in BiTeX.