A new class of plants for a biofuel feedstock energy crop.
Directly burnable biomass to be used primarily in steam boilers for power production has been researched and demonstrated in a variety of projects in the United states. The biomass typically comes from wood wastes, such as tree trimmings or the byproducts of lumber production, or from a cash crop, grown by farmers. Of this latter group, the main emphasis has been utilizing corn stover, or a prairie grass called switchgrass, or using tree seedlings such as willow. In this article, I propose an alternative to these energy crops that consists of several different herbaceous plants with the one consistent property that they annually generate an appreciable bulk of dried-down burnable mass. The fact that they are a set of plants (nine are offered as candidates) gives this energy crop a great deal of flexibility as far as growing conditions and annual harvest time line. Their predicted yield is impressive and leads to speculation that they can be economically feasible.


Risk factors for primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease of unknown cause, but strongly associated with inflammatory bowel disease (IBD). Potential risk factors triggering PSC have never been studied on a population level. The aim of this study was to evaluate smoking, appendectomy, family history and geographical distribution in a population-based cohort of PSC patients, as compared to IBD control patients and healthy controls (HC). For this case-control study 343 PSC patients, 370 IBD controls and 232 HC's living in a geographically defined area in the Netherlands filled-out a questionnaire concerning smoking, appendectomy and family history of IBD and autoimmune liver diseases. Smoking was associated with a lower risk of developing PSC in PSC-ulcerative colitis (UC) patients (adjusted OR 0.21; 95% CI 0.12-0.34; P < 0.001). Comparable results were found for PSC-Crohn's disease (CD) patients (16% former smokers) compared to CD patients (55% former smokers) (adjusted OR 0.17; 95% CI 0.08-0.39; P < 0.001). Frequency of appendectomy did not differ between PSC and HC, but PSC-UC patients had undergone appendectomy more often than UC patients (13% vs. 6%) (adjusted OR 2.51; 95%CI 1.04-6.07; P = 0.041). We found no association between family history of IBD or autoimmune liver disease and risk of PSC. Degree of urbanization was not associated with PSC incidence. In this large population-based case-control study we confirm that smoking is associated with a lower risk of developing PSC, independent of its protective effect for developing UC. Appendectomy is not associated with the risk of developing PSC.


Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial.
Ivacaftor has been previously assessed in patients with cystic fibrosis with Gly551Asp-CFTR or other gating mutations. We assessed ivacaftor in patients with Arg117His-CFTR, a residual function mutation. We did a 24-week, placebo-controlled, double-blind, randomised clinical trial, which enrolled 69 patients with cystic fibrosis aged 6 years and older with Arg117His-CFTR and percentage of predicted forced expiratory volume in 1 s (% predicted FEV1) of at least 40. We randomly assigned eligible patients (1:1) to receive placebo or ivacaftor 150 mg every 12 h for 24 weeks. Randomisation was stratified by age (6-11, 12-17, and ≥18 years) and % predicted FEV1 (<70, ≥70 to ≤90, and >90). The primary outcome was the absolute change from baseline in % predicted FEV1 through week 24. Secondary outcomes included safety and changes in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain scores. An open-label extension enrolled 65 of the patients after washout; after 12 weeks, we did an interim analysis. After 24 weeks, the treatment difference in mean absolute change in % predicted FEV1 between ivacaftor (n=34) and placebo (n=35) was 2·1 percentage points (95% CI -1·13 to 5·35; p=0·20). Ivacaftor treatment resulted in significant treatment differences in sweat chloride (-24·0 mmol/L, 95% CI -28·01 to -19·93; p<0·0001) and CFQ-R respiratory domain (8·4, 2·17 to 14·61; p=0·009). In prespecified subgroup analyses, % predicted FEV1 significantly improved with ivacaftor in patients aged 18 years or older (treatment difference vs placebo: 5·0 percentage points, 95% CI 1·15 to 8·78; p=0·01), but not in patients aged 6-11 years (-6·3 percentage points, -11·96 to -0·71; p=0·03). In the extension study, both placebo-to-ivacaftor and ivacaftor-to-ivacaftor groups showed % predicted FEV1 improvement (absolute change from post-washout baseline at week 12: placebo-to-ivacaftor, 5·0 percentage points [p=0·0005]; ivacaftor-to-ivacaftor, 6·0 percentage points [p=0·006]). We did not identify any new safety concerns. The studies are registered with ClinicalTrials.gov (the randomised, placebo-controlled study, number NCT01614457; the open-label extension study, number NCT01707290). Although this study did not show a significant improvement in % predicted FEV1, ivacaftor did significantly improve sweat chloride and CFQ-R respiratory domain scores and lung function in adult patients with Arg117His-CFTR, indicating that ivacaftor might benefit patients with Arg117His-CFTR who have established disease. Vertex Pharmaceuticals Incorporated.


eV-TEM: Transmission electron microscopy in a low energy cathode lens instrument.
We are developing a transmission electron microscope that operates at extremely low electron energies, 0-40 eV. We call this technique eV-TEM. Its feasibility is based on the fact that at very low electron energies the number of energy loss pathways decreases. Hence, the electron inelastic mean free path increases dramatically. eV-TEM will enable us to study elastic and inelastic interactions of electrons with thin samples. With the recent development of aberration correction in cathode lens instruments, a spatial resolution of a few nm appears within range, even for these very low electron energies. Such resolution will be highly relevant to study biological samples such as proteins and cell membranes. The low electron energies minimize adverse effects due to radiation damage.


[Discovery and its significance of spawning grounds of Jinshaiasinensis from upper and middle Jinshajiang River].
During April, July to August and November of 2012,three surveys were conducted to estimate the early-stage fish resources in the area of Liyuan power station on Jinshajiang River of Yunnan Province. During the survey conducted at the crossing of Daju Town, Yulong County, Yunnan Province, from July to August, 2012, two egg-tides of Jinshaia sinensis were detected. One was from 8:00 of August 1(st) to 10:00 of August 4(th) and the other one was from 23:00 of August 9(th) to 6:00 of August 13(th). The average egg diameter was 3.89 mm, ranging from 3.37 to 4.41 mm. Natural fertilization and hatching rate as well as abnormality rate in mimic wild environment were 91.5%, 97.1% and 2.2%, respectively. Meanwhile, three spawning grounds had been conjectured, which were Longpan Town, Liming Town and Judian Town of Yulong County, Yunnan Province. Moreover, the total number of eggs from those three spawning grounds during the two egg-tides was approximately 1.49×10(7) ind.. The discovery of the three spawing grounds is of importance in fullfilling the study of Jinshaia sinensis, and in protecting fish resources under the influences of power stations.


Pro: Individualized Optimal Perfusion Pressure- Maximizing Patient Care During Cardiopulmonary Bypass.
Cardiopulmonary bypass (CPB) has revolutionized cardiac surgery but poses challenges such as hemodynamic instability and adverse clinical outcomes. Achieving optimal perfusion during CPB ensures adequate oxygen delivery to vital organs. Although mean arterial pressure is a key determinant of perfusion pressure, clear guidelines for optimal perfusion have yet to be established. Autoregulation, the organ's ability to maintain consistent blood flow, plays a vital role in perfusion. Individual variability in autoregulation responses and intraoperative factors necessitate an individualized approach to determining the autoregulation range. Continuous assessment of autoregulation during surgery allows for personalized perfusion targets, optimizing organ perfusion. Exploring techniques like multimodal intravenous anesthesia guided by electroencephalogram can enhance perfusion maintenance within the auto-regulatory range. By adopting an individualized approach to perfusion targets on CPB, we can improve outcomes and enhance patient care.


Reproductive parameters of Mangalarga Marchador mares in a commercial embryo transfer programme.
The objective of this study is to evaluate the reproductive efficiency in donors and recipient Mangalarga Marchador mares in commercial programmes of embryo transfer (ET) and the effects of some reproductive characteristics and ET methodology on conception rates in the recipient mares. A total of 1140 flushing procedures were performed and 830 embryos (72.8%) were recovered. There were no differences between the rates of embryonic recovery in the different breeding seasons (p > 0.05) and 92.8% of the recovered embryos were 8-9 days old. There was no difference in the embryonic recovery regarding the collection order from the first to the ninth embryo collection along the breeding season, as well as among mares inseminated during the foal heat or subsequent cycles (p > 0.05). Pregnancy rates observed in the total period of all reproductive seasons at 15, 30, 45 and 60 days of pregnancy were 73.4, 69.9, 66.7 and 64.5%, respectively. Differences in pregnancy rate and early embryonic loss rates were not observed between embryos transferred immediately after collection (66.8% and 13.5%) and embryos transported at room temperature for periods of < 1 h (62.9% and 14.4%; p > 0.05). Pregnancy rates were higher when the interval between ovulations of donor and recipient mares remained between -3 and -2 days (p < 0.05), and the lowest rates were observed for intervals of -6 days (p < 0.05) with intermediary values for intervals of -1, 0 and +1 (p > 0.05). Embryonic loss rates, however, did not differ between intervals of ovulation's synchronism between donor and recipient mares (p > 0.05). This flexibilization in the ovulatory synchronism between donor and recipient mares optimizes the use of recipient mares, thus reducing costs and facilitating management of horse breeding farms.


Thirty-three myths and misconceptions about population data: from data capture and processing to linkage.
Databases covering all individuals of a population are increasingly used for research and decision-making. The massive size of such databases is often mistaken as a guarantee for valid inferences. However, population data have characteristics that make them challenging to use. Various assumptions on population coverage and data quality are commonly made, including how such data were captured and what types of processing have been applied to them. Furthermore, the full potential of population data can often only be unlocked when such data are linked to other databases. Record linkage often implies subtle technical problems, which are easily missed. We discuss a diverse range of myths and misconceptions relevant for anybody capturing, processing, linking, or analysing population data. Remarkably, many of these myths and misconceptions are due to the social nature of data collections and are therefore missed by purely technical accounts of data processing. Many are also not well documented in scientific publications. We conclude with a set of recommendations for using population data.


[Paradoxical thromboembolism (based on data from the Latvian Republic's Pathologico-anatomy Bureau for 1976 to 1983)].
Combined thromboembolism of both the greater and the lesser circulation was found in 164 cases (1.8%) among 8926 autopsies; in 9 observations (0.1%) paradoxical thromboembolism was detected. The factors responsible for this complication were as follows: advanced age, the increase of weight and thickness of the right ventricle, the increase of the ventricular index, the presence of chronic respiratory diseases with the development of pulmonary-cardiac decompensation.


Production of extracellular matrix by Candida albicans biofilms.
Growth of Candida albicans biofilms and production of extracellular matrix were monitored by dry weight, colorimetric and radioisotope assays, and by scanning electron microscopy. Under static incubation conditions synthesis of matrix material was minimal, but increased dramatically when developing biofilms were subjected to a liquid flow with the result that the cells were enveloped in extracellular polymer. These findings suggest that production of matrix material could contribute to the resistance of biofilm cells to antifungal agents in vivo.


Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study.
We conducted a multi-institutional randomized study to determine whether high-dose daunorubicin would be as effective as standard-dose idarubicin in remission-induction therapy for newly diagnosed adult patients younger than 65 years of age with acute myeloid leukemia. Of 1064 patients registered, 1057 were evaluable. They were randomly assigned to receive either daunorubicin (50 mg/m(2) daily for 5 days) or idarubicin (12 mg/m(2) daily for 3 days) in combination with 100 mg/m(2) of cytarabine by continuous infusion daily for 7 days as induction therapy. Complete remission was achieved in 407 (77.5%) of 525 patients in the daunorubicin group and 416 (78.2%) of 532 in the idarubicin group (P = .79). Patients achieving complete remission received intensive postremission therapy that consisted of either 3 courses of high-dose cytarabine or 4 courses of standard-dose therapy. Overall survival rates at 5 years were 48% for the daunorubicin group and 48% for the idarubicin group (P = .54), and relapse-free survival rates at 5 years were 41% and 41% (P = .97), respectively. Thus, high-dose daunorubicin and standard-dose idarubicin were equally effective for the treatment of adult acute myeloid leukemia, achieving a high rate of complete remission and good long-term efficacy. This study is registered at http://www.umin.ac.jp/ctrj/ as C000000157.


Stimulation of secretion in permeabilized PC12 cells by adenosine 5'-[gamma-thio]triphosphate: possible involvement of nucleoside diphosphate kinase.
The addition of Ca2+, adenosine 5'-[gamma-thio]triphosphate (ATP[S]) or guanosine 5'-[gamma-thio]triphosphate (GTP[S]) to digitonin-permeabilized PC12 cells stimulates noradrenaline secretion. Both ATP[S] and GTP[S] stimulate release in the absence of Ca2+. Whereas ADP and adenosine 5'-[beta gamma-imido]triphosphate inhibited ATP[S]-stimulated release, they did not inhibit Ca(2+)-stimulated release even in the absence of added ATP. This suggests that the kinase which uses ATP[S] to induce secretion may not play an essential role in Ca(2+)-stimulated release. As GTP[S]-stimulated and ATP[S]-stimulated secretions were not additive, it seemed possible that stimulation by ATP[S] might in part result from the thiophosphorylation of GDP by nucleoside-diphosphate (NDP) kinase to form GTP[S]. The following results are consistent with this possibility. (1) A low concentration of GDP increased ATP[S]-stimulated secretion, but not GTP[S]-stimulated or Ca(2+)-stimulated secretion. (2) A variety of ribo- and deoxyribo-nucleoside di- and tri-phosphates inhibited ATP[S]-stimulated secretion, but not GTP[S]-stimulated or Ca(2+)-stimulated secretion. Thus, like NDP kinase, the kinase which uses ATP[S] to cause noradrenaline release appears to have a very low specificity for ATP. (3) Incubation of permeabilized cells in a sucrose-containing buffer resulted in the preferential loss of ATP[S]-stimulated secretion and a decrease in the level of NDP kinase. The addition of rat liver NDP kinase to those depleted cells partially restored ATP[S]-stimulated secretion.


[Endocopic fetal surgery].
At present, the fetus is already considered a "patient" and as such, can develop diseases with fatal outcome in which the only therapeutic option can be fetal surgery. Currently, fetal surgery is limited almost exclusively to endoscopic surgery. Different techniques have gained clinical acceptance for improving the prognosis of various lethal fetal pathologies. Laser therapy for twin to twin transfusion syndrome and cord occlusion in monochorionic twins with selective intrauterine growth restriction are the procedures of choice for the management of monochorionic twins complications, and are associated with survival rates of up to 80-90% for at least one fetus. In fetuses with isolated congenital diaphragmatic hernia and severe pulmonary hypoplasia, fetal endoscopic tracheal occlusion has shown to improve the survival probabilities from 5% to 55% and from 1% to 33% in left and right congenital diaphragmatic hernia, respectively, and a decrease in the rate of pulmonary hypertension and neonatal morbidity. In selected cases with low urinary tract obstruction (megacystis) and without renal failure; fetal cystoscopy is a diagnostic method that excludes the possibility of urethral stenosis or atresia and may be used to ablate posterior urethral valves by laser, restoring urethral patency and potentially preserving respiratory and bladder function. In fetuses with pulmonary masses, either primary or due to airway obstruction, there is high risk of fetal death due to cardiac compression and contralateral pulmonary hypoplasia. In such cases fetal bronchoscopy can provide a successful therapeutic option to release airway obstruction.


Cerebrospinal fluid lysosomal enzymes and alpha-synuclein in Parkinson's disease.
To assess the discriminating power of multiple cerebrospinal fluid (CSF) biomarkers for Parkinson's disease (PD), we measured several proteins playing an important role in the disease pathogenesis. The activities of β-glucocerebrosidase and other lysosomal enzymes, together with total and oligomeric α-synuclein, and total and phosphorylated tau, were thus assessed in CSF of 71 PD patients and compared to 45 neurological controls. Activities of β-glucocerebrosidase, β-mannosidase, β-hexosaminidase, and β-galactosidase were measured with established enzymatic assays, while α-synuclein and tau biomarkers were evaluated with immunoassays. A subset of PD patients (n = 44) was also screened for mutations in the β-glucocerebrosidase-encoding gene (GBA1). In the PD group, β-glucocerebrosidase activity was reduced (P < 0.05) and patients at earlier stages showed lower enzymatic activity (P < 0.05); conversely, β-hexosaminidase activity was significantly increased (P < 0.05). Eight PD patients (18%) presented GBA1 sequence variations; 3 of them were heterozygous for the N370S mutation. Levels of total α-synuclein were significantly reduced (P < 0.05) in PD, in contrast to increased levels of α-synuclein oligomers, with a higher oligomeric/total α-synuclein ratio in PD patients when compared with controls (P < 0.001). A combination of β-glucocerebrosidase activity, oligomeric/total α-synuclein ratio, and age gave the best performance in discriminating PD from neurological controls (sensitivity 82%; specificity 71%, area under the receiver operating characteristic curve = 0.87). These results demonstrate the possibility of detecting lysosomal dysfunction in CSF and further support the need to combine different biomarkers for improving the diagnostic accuracy of PD.


Functional activation of PPARγ in human upper aerodigestive cancer cell lines.
Upper aerodigestive cancer is an aggressive malignancy with relatively stagnant long-term survival rates over 20 yr. Recent studies have demonstrated that exploitation of PPARγ pathways may be a novel therapy for cancer and its prevention. We tested whether PPARγ is expressed and inducible in aerodigestive carcinoma cells and whether it is present in human upper aerodigestive tumors. Human oral cancer CA-9-22 and NA cell lines were treated with the PPAR activators eicosatetraynoic acid (ETYA), 15-deoxy-δ- 12,14-prostaglandin J2 (PG-J2), and the thiazolidinedione, ciglitazone, and evaluated for their ability to functionally activate PPARγ luciferase reporter gene constructs. Cellular proliferation and clonogenic potential after PPARγ ligand treatment were also evaluated. Aerodigestive cancer specimens and normal tissues were evaluated for PPARγ expression on gene expression profiling and immunoblotting. Functional activation of PPARγ reporter gene constructs and increases in PPARγ protein were confirmed in the nuclear compartment after PPARγ ligand treatment. Significant decreases in cell proliferation and clonogenic potential resulted from treatment. Lipid accumulation was induced by PPARγ activator treatment. 75% of tumor specimens and 100% of normal control tissues expressed PPARγ RNA, and PPARγ protein was confirmed in 66% of tumor specimens analyzed by immunoblotting. We conclude PPARγ can be functionally activated in upper aerodigestive cancer and that its activation downregulates several features of the neoplastic phenotype. PPARγ expression in human upper aerodigestive tract tumors and normal cells potentially legitimizes it as a novel intervention target in this disease. © 2016 Wiley Periodicals, Inc.


Radiation dose associated with unenhanced CT for suspected renal colic: impact of repetitive studies.
The purpose of our study was to assess the dose of ionizing radiation delivered through the use of unenhanced CT for suspected renal colic by determining the incidence of repeated unenhanced CT examinations and the cumulative radiation dose delivered. All unenhanced CT examinations for suspected renal colic performed at our institution over a 6-year period were included, and patient age, sex, and multiplicity of examinations were determined. For the adult patient, this protocol prescribes a fixed tube current of 200 mA, 140 kVp, and a nominal slice width of 5 mm. The dose-length product (DLP) was estimated for 15 randomly chosen single-detector CT (SDCT) and MDCT adult flank pain examinations using manufacturer's software. The mean DLPs for SDCT and MDCT were computed and converted to effective doses. Total effective doses were calculated for patients who underwent more than three examinations, and values were compared with established standards. A total of 5,564 examinations were performed on 4,562 patients. Of these patients, 2,795 (61%) were women (mean age, 45.5 +/- 16.2 [SD] years) and 1,731 (38%) were men (mean age, 44.7 +/- 16.4 years), with 144 patients (3%) of pediatric age. The mean effective doses for a single study were 6.5 mSv for SDCT and 8.5 mSv for MDCT. A subset of 176 patients (4%) had three or more examinations, with estimated effective doses ranging from 19.5 to 153.7 mSv. All patients with multiple examinations had a known history of nephrolithiasis. Patients with a history of nephrolithiasis and flank pain are at increased risk for serial CT with potentially high cumulative effective doses.


Descendo-bifemoral bypass grafting and renal artery revascularization to treat complex obliterative arteriopathy.
Our goal was to describe a new standardized approach in patients with extensive obliterative arteriopathy aimed at distal revascularization and surgical kidney recruitment via descendo-bifemoral bypass grafting and renal artery revascularization. Three patients with Leriche's syndrome and either a compromised single kidney or unilateral significant renal artery stenosis were treated with a standardized surgical approach, restoration of distal perfusion via descendo-bifemoral bypass with synchronous ( n = 2) left-sided renal artery revascularization or metachronous ( n = 1) right-sided renal artery revascularization. The intended surgical aim was achieved successfully in all 3 cases. All patients showed a decline in serum creatinine levels. One patient who needed substitution therapy was free from dialysis 3 months after surgery. Additionally, blood pressure management was substantially reduced because uncontrolled peak systolic episodes were no longer observed and pharmacotherapeutic agents could be partially withdrawn. Distal revascularization and surgical kidney recruitment via descendo-bifemoral bypass and renal artery revascularization is a promising option to treat complex obliterative arteriopathy.


Subcutaneous to intravenous prostacyclin analog transition in pulmonary hypertension.
Prostacyclin analogs are Food and Drug Administration-approved therapies for the treatment of pulmonary arterial hypertension and can be administered by inhalational, intravenous (IV), or subcutaneous (SQ) routes. Because there are limited data to guide the transition between SQ to IV prostacyclin analogs, we describe our experience. We performed a retrospective review of patients with pulmonary hypertension diagnosed by right heart catheterization, who underwent transition from SQ to IV prostacyclin analogs. We included 7 patients with pulmonary arterial hypertension and 2 with chronic thromboembolic pulmonary hypertension in this retrospective study. Median (interquartile range) age was 54 (39-63) years, and 67% were women. The reasons for the SQ to IV switch were site pain (n = 6, 67%), major surgery (n = 2, 22%), and septic shock (n = 1, 11%). SQ treprostinil was converted to IV treprostinil (n = 5, 56%) or IV epoprostenol (n = 4, 44%). When SQ treprostinil was converted to IV treprostinil, the initial mean (range) dose decreased from 84.9 (36.5-167) to 70.8 (24-114) ng·kg⁻¹·min⁻¹. When SQ treprostinil was converted to IV epoprostenol, the dose decreased from 24.5 (17.5-30) to 13.3 (9-20) ng·kg⁻¹·min⁻¹. The patient transitioned from SQ to IV treprostinil in the context of septic shock died a month after hospitalization. No deteriorations were observed in the remaining patients during the first year. Under careful monitoring, SQ treprostinil was transitioned to IV treprostinil or epoprostenol without complications. Dosing downadjustment was needed in some patients who were switched over from SQ to IV prostacyclin analogs.


Spontaneous adverse event reports associated with zolpidem in Australia 2001-2008.
A prominent media publicity cluster during 2007-2008 in Australia linked the common hypnotic zolpidem to adverse drug reaction reports of parasomnias, amnesia, hallucinations and suicidality. The collection of adverse drug reaction data through spontaneous reporting systems is a mainstay of drug safety monitoring, but a stimulated reporting event such as this often renders such data uninterpretable. As such, we aimed to investigate whether these associations were present before the media cluster and then to quantify the effect of stimulated reporting on those four specific outcomes. Using disproportionality analyses we compared zolpidem to all other drugs in the database, and then separately to each of all hypnotics, then all benzodiazepines, and then temazepam alone, and did so in every year from 2001 to 2008. Year-by-year analyses of Reporting odds ratios for zolpidem exposure and adverse events of interest, adjusted for a number of covariates, revealed an association between zolpidem exposure and parasomnias, amnesia and hallucination both before and after the cluster of media publicity beginning in early 2007. The odds ratios increased significantly after the media publicity for only parasomnias and amnesia. Suicidality was increased in some analyses, but limited data make this outcome difficult to interpret. We conclude that zolpidem adverse drug reaction reports have higher odds for parasomnia, amnesia, hallucination and perhaps suicidality compared to either all other drugs or hypnotics, even before the media publicity cluster. However, the extant literature and the limitations of these spontaneously reported adverse drug reaction data do not allow us to conclude that these events are related causally to zolpidem.


Host-bacterial interactions in inflammatory bowel disease.
Large numbers of different bacterial species are resident in the lumen of the distal gastrointestinal tract. The normal intestinal host-microbial interactions are not well understood, but the relationship is generally believed to be either mutually beneficial or beneficial to one without disadvantage to the other. Animal model and clinical studies suggest that IBD (inflammatory bowel disease) may develop in a susceptible individual when the normal host-bacterial relationship is dysregulated. In addition to rodent models, this article reviews studies that have investigated the cellular and molecular mechanisms of interactions between intestinal mucosal cells and the resident luminal bacteria in healthy individuals and patients with ulcerative colitis and Crohn's disease. Mechanisms by which the intestinal mucosa is able to avoid pro-inflammatory responses to commensal bacteria (and their products) but able to respond appropriately to luminal pathogens is currently an area of active investigation. Such studies are beginning to provide important clues regarding possible alterations in the mucosa that lead to the development of pro-inflammatory responses to resident bacteria in patients with IBD. Approaches to alter the intestinal microflora for therapeutic purposes and their potential mechanisms of action are also discussed.


Global and local synchrony of coupled neurons in small-world networks.
Synchronous firing of neurons is thought to play important functional roles such as feature binding and switching of cognitive states. Although synchronization has mainly been investigated so far using model neurons with simple connection topology, real neural networks have more complex structures. Here we examine the behavior of pulse-coupled leaky integrate-and-fire neurons with various network structures. We first show that the dispersion of the number of connections for neurons influences dynamical behavior even if other major topological statistics are kept fixed. The rewiring probability parameter representing the randomness of networks bridges two spatially opposite frameworks: precise local synchrony and rough global synchrony. Finally, cooperation of the global connections and the local clustering property, which is prominent in small-world networks, forces synchrony of distant neuronal groups receiving coherent inputs.


Effects of hyperoxic gas mixtures on exercise tolerance in man.
This study was undertaken to determine the effects of O2-enriched gases on performance. Nine trained subjects ran to exhaustion on the treadmill on five different occasions breathing one of a range of hyperoxic gas mixtures--20%, 40%, 60%, 80%, or 100% O2. Each subject worked at a workload determined to be 110% of that necessary to elicit his maximum O2 uptake. The exercise bouts were scheduled one week apart to minimize the effects of training and fatigue. The subjects were given no cues as to the mixtures being breathed or to their running times. The parameters measured included running time, minute ventilation, and heart rate. The results indicate that the maximum performance time increases significantly as the O2 fraction of the gas is increased. Contrary to other published literature, 100% O2 increases performance significantly over 60% O2. Ventilation at any point in time is decreased when breathing hyperoxic mixtures. This decrease appears to be more a function of breathing frequency than of tidal volume. Terminal heart rates are not significantly different regardless of the O2 fraction of the inspired gas.


Influence of study population definition on the effect of age on outcomes after blunt head trauma.
The purpose of this study was to assess whether study population definition influences the effect of age on outcomes after blunt head trauma. We hypothesized that examining 'all comers' receiving head computerized tomography after blunt head trauma, fewer older individuals would meet Veterans Administration and Department of Defense (VA/DoD) criteria for traumatic brain injury (TBI), and would, therefore, display better outcomes than younger cohorts. However, restricting to participants meeting VA/DoD criteria for TBI, we hypothesized that older individuals would have worse outcomes. Data from a recently completed prospective cohort study were analysed with age dichotomized at 65 years. Logistic regression modelling, controlled for potential confounders including head trauma severity, was estimated to measure the effect of age on functional recovery, post-concussion symptoms (PCS), and depressive symptoms at 1-month post-TBI. Fewer older than younger individuals met VA/DoD criteria for TBI. Older individuals had better functional, PCS, and depressive outcomes at 1 month. Restricting to those meeting VA/DoD criteria for TBI, older individuals continued to have better functional and PCS outcomes but had outcomes comparable to younger on depressive symptoms. Contrary to our hypothesis, there was a tendency for older adults to have better outcomes than younger, independent of the diagnostic criteria applied.


Investing in Physicians Is Investing in Patients: Enhancing Patient Safety Through Physician Health and Well-Being Research.
Keeping medical practitioners healthy is an important consideration for workforce satisfaction and retention, as well as public safety. However, there is limited evidence demonstrating how to best care for this group. The absence of data is related to the lack of available funding in this area of research. Supporting investigations that examine physician health often "fall through the cracks" of traditional funding opportunities, landing somewhere between patient safety and workforce development priorities. To address this, funders must extend the scope of current grant opportunities by broadening the scope of patient safety and its relationship to physician health. Other considerations are allocating a portion of doctors' licensing fees to support physician health research and encourage researchers to collaborate with interested stakeholders who can underwrite the costs of studies. Ultimately, funding studies of physician health benefits not only the community of doctors but also the millions of patients receiving care each year.


Migration inhibitory factor mediates angiogenesis via mitogen-activated protein kinase and phosphatidylinositol kinase.
In this study, we investigated the effects of migration inhibitory factor (rhMIF) on angiogenesis-related signaling cascades and apoptosis in human endothelial cells (ECs). We show that in vitro rhMIF induces migration and tube formation in Matrigel of human dermal microvascular endothelial cells (HMVECs), with potency comparable to that of basic fibroblast growth factor. In vivo, rhMIF induces angiogenesis in Matrigel plugs and in the corneal bioassay. Using panels of relatively specific kinase inhibitors, antisense oligonucleotides, and dominant-negative mutants, we show that mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) are critical for MIF-dependent HMVEC migration, whereas Src and p38 kinases are nonessential. Moreover, we demonstrate that rhMIF induces time-dependent increases in phosphorylation levels of MEK1/2, Erk1/2, and Elk-1, as well as PI3K, and its effector kinase, Akt, in HMVECs. Studies with dominant-negative mutants and antisense oligonucleotides corroborate these effects in HMVECs. Furthermore, we demonstrate that rhMIF-induced angiogenesis in the rat cornea in vivo and in the ex vivo endothelial cell morphogenesis assay is also MAPK- and PI3K-dependent. Our findings support a role for MIF as an angiogenic factor and provide a rationale for the use of MIF as a therapeutic inducer of neovascularization in the development of collateral circulation in coronary artery disease.


Interplay between alkyl chain asymmetry and cholesterol addition in the rigid ion pair amphiphile bilayer systems.
Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic surfactants, has been proposed as a novel phospholipid substitute. Controlling the physical stability of IPA vesicles is important for its application developments such as cosmetic and drug deliveries. To investigate the effects of IPA alkyl chain combinations and the cholesterol additive on the structural and mechanical properties of IPA vesicular bilayers, we conducted a series of molecular dynamics studies on the hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium-hexadecylsulfate (DTMA-HS) IPA bilayers with cholesterol. We found that both IPA bilayers are in the gel phase at 298 K, consistent with experimental observations. Compared with the HTMA-DS system, the DTMA-HS bilayer has more disordered alkyl chains in the hydrophobic region. When adding cholesterol, it induces alkyl chain ordering around its rigid sterol ring. Yet, cholesterol increases the molecular areas for all species and disturbs the molecular packing near the hydrophilic region and the bilayer core. Cholesterol also promotes the alkyl chain mismatch between the IPA moieties, especially for the DTMA-HS bilayer. The combined effects lead to non-monotonically enhancement of the membrane mechanical moduli for both IPA-cholesterol systems. Furthermore, cholesterol can form H-bonds with the alkylsulfate and thus enhance the contribution of alkylsulfate to the overall mechanical moduli. Combined results provide valuable molecular insights into the roles of each IPA component and the cholesterol on modulating the IPA bilayer properties.


Beta-turn formation by a six-residue linear peptide in solution.
A model peptide AAGDYY-NH2 (B1), which is found to adopt a beta-turn conformation in the TEM-1 beta-lactamase inhibitor protein (BLIP) in the TEM-1/BLIP co-crystal, was synthesized to elucidate the mechanism of its beta-turn formation and stability. Its structural preferences in solution were comprehensively characterized using CD, FT-IR and 1H NMR spectroscopy, respectively. The set of observed diagnostic NOEs, the restrained molecular dynamics simulation, CD and FT-IR spectroscopy confirmed the formation of a beta-turn in solution by the model peptide. The dihedral angles [(phi3, phi3) (phi4, phi4)] of [(-52 degrees, -32 degrees ) (-38 degrees, -44 degrees )] of Gly-Asp fragment in the model peptide are consistent with those of a type III beta-turn. In a conclusion, the conformational preference of the linear hexapeptide B1 in solution was determined, and it would provide a simple template to study the mechanism of beta-turn formation and stability.


External validation and diagnostic value of the Elderly Functional Index version 2.0 for assessing functional status and frailty in older Danish patients with gastrointestinal cancer receiving chemotherapy: A prospective, clinical study.
Patient perspectives on functioning are often overlooked in oncology practice. This study externally validates the ELderly Functional Index (ELFI), a patient-reported measure for assessing multidimensional functioning, in older patients with gastrointestinal cancer receiving chemotherapy. The study compares ELFI scoring methods, evaluates its diagnostic value with geriatric oncology tools, and proposes a cut-off point for clinical use. Danish patients aged ≥70 years with gastrointestinal cancer undergoing chemotherapy from a prospective, observational study were included. Two ELFI scoring methods, item-based and domain-based, were compared. Internal consistency reliability, validity, and correlations between ELFI, its component scales, and measures of functioning/frailty (including Eastern Cooperative Oncology Group Performance Status [ECOG-PS], Geriatric-8 [G8], Vulnerable Elders Survey-13 [VES-13], Timed-Up-and-Go [TUG], and 30-s chair stand test [30CST]) were investigated. Sensitivity and specificity analyses evaluated the ability of ELFI to predict frailty outcomes and identified frailty thresholds. Receiver operating characteristic analyses assessed the diagnostic ability of ELFI, alongside other measures, for oncological outcomes and frailty differentiation. Equipercentile equating methods enabled ECOG-PS, ELFI, and G8 mapping. One hundred fifty-four patients (median age 73.5 years, range 70-85) undergoing curative- or palliative-intent chemotherapy (49%) were included. ELFI demonstrated good internal consistency (Cronbach's alpha = 0.82) and acceptable convergent, structural, and discriminant validity. ELFI showed moderate to very strong correlations with its component scales (r = 0.40-0.93), and weaker correlations with frailty measures (r = 0.02-0.60). ELFI score < 80 indicated frailty risk, with almost fivefold risk of ECOG-PS 2 at follow-up (odds ratio[OR] = 4.8, 95% confidence interval [CI] 1.4-15.9), and predicted G8, VES-13, TUG, and 30CST frailty at follow-up, not completing planned chemotherapy (OR = 3.1; 95%CI 1.5-6.2), mono-therapy (OR = 3.5; 95%CI 1.5-8.1), initial dose reduction (OR = 4.9; 95%CI 2.0-12.1), and shorter overall survival (hazard ratio = 2.0, 95%CI 1.4-3.0). A preliminary crosswalk between ECOG-PS, ELFI, and G8 was established. ELFI was validated as a concise patient-reported measure of functional status in older patients with cancer and its relationship to frailty. ELFI demonstrated comparable predictive ability to other tools for oncological outcomes. Both scoring methods yielded similar results, with the domain-based method (ELFI v2.0) endorsed for consistency. ELFI v2.0 score of 80 was suggested as the frailty threshold in this population, supporting its clinical utility.


Evidence for delayed parafoveal-on-foveal effects from word n+2 in reading.
During reading information is acquired from word(s) beyond the word that is currently looked at. It is still an open question whether such parafoveal information can influence the current viewing of a word, and if so, whether such parafoveal-on-foveal effects are attributable to distributed processing or to mislocated fixations which occur when the eyes are directed at a parafoveal word but land on another word instead. In two display-change experiments, we orthogonally manipulated the preview and target difficulty of word n+2 to investigate the role of mislocated fixations on the previous word n+1. When the eyes left word n, an easy or difficult word n+2 preview was replaced by an easy or difficult n+2 target word. In Experiment 1, n+2 processing difficulty was manipulated by means of word frequency (i.e., easy high-frequency vs. difficult low-frequency word n+2). In Experiment 2, we varied the visual familiarity of word n+2 (i.e., easy lower-case vs. difficult alternating-case writing). Fixations on the short word n+1, which were likely to be mislocated, were nevertheless not influenced by the difficulty of the adjacent word n+2, the hypothesized target of the mislocated fixation. Instead word n+1 was influenced by the preview difficulty of word n+2, representing a delayed parafoveal-on-foveal effect. The results challenge the mislocated-fixation hypothesis as an explanation of parafoveal-on-foveal effects and provide new insight into the complex spatial and temporal effect structure of processing inside the perceptual span during reading.


Rating the methodological quality of single-subject designs and n-of-1 trials: introducing the Single-Case Experimental Design (SCED) Scale.
Rating scales that assess methodological quality of clinical trials provide a means to critically appraise the literature. Scales are currently available to rate randomised and non-randomised controlled trials, but there are none that assess single-subject designs. The Single-Case Experimental Design (SCED) Scale was developed for this purpose and evaluated for reliability. Six clinical researchers who were trained and experienced in rating methodological quality of clinical trials developed the scale and participated in reliability studies. The SCED Scale is an 11-item rating scale for single-subject designs, of which 10 items are used to assess methodological quality and use of statistical analysis. The scale was developed and refined over a 3-year period. Content validity was addressed by identifying items to reduce the main sources of bias in single-case methodology as stipulated by authorities in the field, which were empirically tested against 85 published reports. Inter-rater reliability was assessed using a random sample of 20/312 single-subject reports archived in the Psychological Database of Brain Impairment Treatment Efficacy (PsycBITE). Inter-rater reliability for the total score was excellent, both for individual raters (overall ICC = 0.84; 95% confidence interval 0.73-0.92) and for consensus ratings between pairs of raters (overall ICC = 0.88; 95% confidence interval 0.78-0.95). Item reliability was fair to excellent for consensus ratings between pairs of raters (range k = 0.48 to 1.00). The results were replicated with two independent novice raters who were trained in the use of the scale (ICC = 0.88, 95% confidence interval 0.73-0.95). The SCED Scale thus provides a brief and valid evaluation of methodological quality of single-subject designs, with the total score demonstrating excellent inter-rater reliability using both individual and consensus ratings. Items from the scale can also be used as a checklist in the design, reporting and critical appraisal of single-subject designs, thereby assisting to improve standards of single-case methodology.


Cabozantinib prevents AGEs-induced degradation of type 2 collagen and aggrecan in human chondrocytes.
Osteoarthritis (OA) is a joint degenerative disease commonly observed in the old population, lacks effective therapeutic methods, and markedly impacts the normal lives of patients. Degradation of extracellular matrix (ECM) is reported to participate in OA development, which is a potential target for treating OA. Cabozantinib is an inhibitor of tyrosine kinases and is recently claimed with suppressive properties against inflammation. Herein, the protective function of Cabozantinib on advanced glycation end products (AGEs)-induced damages to chondrocytes was tested. SW1353 chondrocytes were stimulated with 100 μg/ml AGEs with or without 10 and 20 μM Cabozantinib for 24 h. Signally increased reactive oxygen species (ROS) levels, declined reduced glutathione (GSH) levels, and elevated release of inflammatory cytokines were observed in AGEs-stimulated SW1353 chondrocytes, which were markedly reversed by Cabozantinib. Moreover, the notably reduced type II collagen and aggrecan levels, and increased matrix metalloproteinase-13 (MMP-13) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs-5 (ADAMTS-5) levels in AGEs-stimulated SW1353 chondrocytes were largely rescued by Cabozantinib. The downregulated Sry-type high-mobility-group box 9 (SOX-9) observed in AGEs-stimulated SW1353 chondrocytes was abolished by Cabozantinib. Furthermore, the impact of Cabozantinib on type II collagen and aggrecan levels in AGEs-treated SW1353 chondrocytes was abrogated by silencing SOX-9. Collectively, Cabozantinib prevented AGEs-induced degradation of type 2 collagen and aggrecan in human chondrocytes by mediating SOX-9.


Plasmon enabled Claisen rearrangement with sunlight.
Plasmonic-heat generated from the solar irradiation of gold nanoparticles is used as the thermal energy source for the Claisen rearrangement of allyl phenyl ether to 2-allylphenol, which is conventionally performed with electrical heating at 250 °C. The use of a closed reactor enables the physical separation of the reactants from the source of plasmonic-heat, thereby preventing the interference of the hot-charge carriers in the plasmon-driven Claisen rearrangement. In this way, the sole effect of plasmonic-heat in driving a high temperature organic transformation is demonstrated. Our study reveals the prospects of plasmonic nanostructures in conducting energy intensive chemical synthesis in a sustainable fashion.


Aging and forgetting: Forgotten information is perceived as less important than is remembered information.
Recently, researchers have evaluated the mechanisms that contribute to younger adults' metacognitive monitoring. According to analytic-processing theory, people's beliefs about their memory are central to their monitoring judgments. Although this theory has received ample support with younger adults, it has yet to be evaluated with older adults. We aimed to address this gap in the literature. Specifically, we evaluated younger and older adults' beliefs about forgetting, and the role of these beliefs in their judgments about forgotten information. Younger adults tend to recall forgotten information as being less important than remembered information (dubbed the forgetting bias). Moreover, this bias is largely driven by their beliefs about forgotten information. In the present research, we evaluated (a) whether older adults also show a forgetting bias and (b) the contribution of their beliefs to this bias. In Studies 1 and 2, participants completed a value-directed remembering task. Next, participants took a surprise cued-recall test for the values. In Study 2, we evaluated participants' beliefs by having them make a memory-for-past-test judgment prior to recalling the values. In Study 3, we directly probed participants' beliefs about the value of forgotten information with a survey. Older and younger adults demonstrated a forgetting bias. Moreover, and consistent with analytic-processing theory, people's beliefs about forgotten information contributed to this bias. Thus, beliefs are an important mechanism that contribute to both older and younger adults' metacognitive monitoring. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


A clinicopathologic analysis of AIDS-related cryptosporidiosis.
To characterize the histology of AIDS-associated cryptosporidiosis and identify features that explain the clinical variability. A retrospective analysis of HIV-positive individuals with cryptosporidiosis who underwent endoscopy at the Johns Hopkins Hospital between 1985 and 1996. The histologic features (intensity of Cryptosporidium infection, inflammation, mucosal damage, copathogens) of gastrointestinal biopsies from 37 HIV-positive individuals with cryptosporidiosis were systematically graded. These histologic features were correlated with the severity of the diarrheal illness obtained from a patient chart review. Histologic features associated with Cryptosporidium infection include a neutrophilic infiltrate in the stomach, villus blunting in the duodenum, cryptitis and epithelial apoptosis in the colon, and reactive epithelial changes in the stomach and duodenum. The nature and intensity of the inflammatory response varied widely; however, duodenal biopsies from a subset of patients (37%) revealed marked acute inflammation that was associated with concomitant cytomegalovirus infection. Although duodenal infection was common (93% of individuals), infection of other sites was variable (gastric cryptosporidiosis in 40% and colonic cryptosporidiosis in 74%). Widespread infection of the intestinal tract, which included both the large and small intestine, was associated with the most severe diarrheal illness. Cryptosporidium infection produces histologic evidence of gastrointestinal mucosal injury. The inflammatory response to the infection is variable, and may be modified by copathogens such as cytomegalovirus. The clinical manifestations are influenced, in part, by the anatomic distribution of the infection, with extensive infections involving both small and large intestines producing the most severe illness.


On the design and analysis of protein folding potentials.
Pairwise interaction models to recognize native folds are designed and analyzed. Different sets of parameters are considered but the focus was on 20 x 20 contact matrices. Simultaneous solution of inequalities and minimization of the variance of the energy find matrices that recognize exactly the native folds of 572 sequences and structures from the protein data bank (PDB). The set includes many homologous pairs, which present a difficult recognition problem. Significant recognition ability is recovered with a small number of parameters (e.g., the H/P model). However, full recognition requires a complete set of amino acids. In addition to structures from the PDB, a folding program (MONSSTER) was used to generate decoy structures for 75 proteins. It is impossible to recognize all the native structures of the extended set by contact potentials. We therefore searched for a new functional form. An energy function U, which is based on a sum of general pairwise interactions limited to a resolution of 1 angstrom, is considered. This set was infeasible too. We therefore conjecture that it is not possible to find a folding potential, resolved to 1 angstrom, which is a sum of pair interactions.


[Interaction of alveolar macrophages with fibronectin during sensitization and anaphylactic shock].
Interaction of rabbit alveolar macrophages (AM) with homologous fibronectin bound to gelatin-sepharose granules was studied. Macrophages obtained at the height of anaphylactic shock and cells from sensitized animals after preincubation with antigen or histamine failed to adhere to the fibronectin-coated surface. AM from intact and sensitized animals were capable of adhering to the fibronectin-coated granules in a Ca2+, Mg2+-dependent manner. Pretreatment of intact cells with trypsin inhibited AM-fibronectin interaction. The data indicate that the surface of AM bears protein receptors, capable of interacting with fibronectin, which change their affinity during anaphylactic shock and under the effect of histamine. It may be thus concluded that fibronectin is involved in the function of mononuclear phagocytes in health, evidence that complements the idea of the role played by macrophages in the pathogenesis of the immediate type hypersensitivity.


EARLY EFFECTS OF STREPTOMYCIN ON BACILLUS MEGATERIUM.
Hancock, R. (Harvard Medical School, Boston, Mass.). Early effects of streptomycin on Bacillus megaterium. J. Bacteriol. 88:633-639. 1964.-The sequence of some early effects of streptomycin on Bacillus megaterium was investigated. An increase in the rate of efflux of cellular K ions preceded loss of viability, but efflux of Mg ions remained normal. Loss of viability was closely coincident with reduction in rate of protein synthesis. Nucleic acid synthesis continued after protein synthesis ceased in low-phosphate medium, but ceased simultaneously with protein synthesis in normal minimal medium. Later, after viability had begun to decrease, the respiration rate began to fall and the cellular adenosine triphosphate (ATP) content decreased slowly. No leakage of ultraviolet-absorbing materials into the medium occurred, although uracil was slowly released from nucleic acid after killing had begun. It is concluded that in this organism, as previously observed with Escherichia coli, the actions of streptomycin which led to an increased rate of efflux of K and specific inhibition of protein synthesis are the only ones early enough to be of significance in its bactericidal action, the other effects being later secondary changes.


Glucocorticoids reverse leptin effects on food intake and body fat in mice without increasing NPY mRNA.
Glucocorticoid stimulation of appetite and leptin expression conflicts with leptin inhibition of food intake and suggests that glucocorticoids reduce sensitivity to leptin. To determine if glucocorticoids impair feeding and metabolic responses to leptin, we measured leptin-induced changes in food intake, body weight, hormones, carcass fat, and hypothalamic neuropeptide Y (NPY) mRNA in adrenalectomized mice with and without corticosterone replacement. Leptin infusion (0.5 microgram/h) significantly decreased food intake and body weight in adrenalectomized mice. Corticosterone replacement approximating normal 24-h mean levels restored food intake but did not permit weight gain equivalent to PBS-infused controls. Corticosterone levels comparable to stress-induced production completely reversed leptin-induced reductions in weight gain and body fat, despite significant attenuation by leptin of corticosterone-induced increases in plasma insulin levels. Glucocorticoid replacement increased food intake without reversing leptin inhibition of hypothalamic NPY mRNA levels. We conclude that glucocorticoid levels within the physiological range can interfere with leptin action and that glucocorticoid effects are at least partly independent of NPY.


IL 33 Correlates With COVID-19 Severity, Radiographic and Clinical Finding.
Objective: The increased level of interleukin (IL)-33 is considered as a predictor of severe coronavirus disease 2019 (COVID-19) infection, but its role at different stages of the disease is still unclear. Our goal was to analyze the correlation of IL-33 and other innate immunity cytokines with disease severity. Methods: In this study, 220 patients with COVID-19 were included and divided into two groups, mild/moderate and severe/critical. The value of the cytokines, clinical, biochemical, radiographic data was collected and their correlation with disease severity was analyzed. Results: Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (p < 0.05) in these two groups between clinical features (dyspnea, dry cough, fatigue, and auscultatory findings); laboratory [(neutrophil count, lymphocyte count, monocyte count, hemoglobin, plasma glucose, urea, creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), albumin (ALB), lactate dehydrogenase (LDH), creatinine kinase (CK), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), Fe, and Ferritin)], arterial blood gases (oxygen saturation-Sa02, partial pressure of oxygen -p02), and chest X-rays (CXR) lung findings (p = 0.000). We found a significantly higher serum concentration (p < 0.05) of TNF-α, IL-1β, IL-6, IL-12, IL-23, and IL-33 in patients with COVID-19 with severe disease. In the milder stage of COVID-19, a positive correlation was detected between IL-33 and IL-1β, IL-12 and IL-23, while a stronger positive correlation between the serum values of IL-33 and TNF-α, IL-1β, IL-6, and IL-12 and IL-23 was detected in patients with COVID-19 with severe disease. A weak negative correlation (p < 0.05) between pO2 and serum IL-1β, IL-12, and IL-33 and between SaO2 and serum IL-33 was noted. The positive relation (p < 0.05) between the serum values of IL-33 and IL-12, IL-33 and IL-6, and IL-6 and IL-12 is proven. Conclusion: In a more progressive stage of COVID-19, increased IL-33 facilitates lung inflammation by inducing the production of various innate proinflammatory cytokines (IL-1β, IL-6, TNF-α, IL-12, and IL-23) in several target cells leading to the most severe forms of the disease. IL-33 correlates with clinical parameters of COVID-19 and might represent a promising marker as well as a therapeutic target in COVID-19.


From hydroxychloroquine to ivermectin: what are the anti-viral properties of anti-parasitic drugs to combat SARS-CoV-2?
Nearly a year into the COVID-19 pandemic, we still lack effective anti-SARS-CoV-2 drugs with substantial impact on mortality rates except for dexamethasone. As the search for effective antiviral agents continues, we aimed to review data on the potential of repurposing antiparasitic drugs against viruses in general, with an emphasis on coronaviruses. We performed a review by screening in vitro and in vivo studies that assessed the antiviral activity of several antiparasitic agents: chloroquine, hydroxychloroquine (HCQ), mefloquine, artemisinins, ivermectin, nitazoxanide (NTZ), niclosamide, atovaquone and albendazole. For HCQ and chloroquine we found ample in vitro evidence of antiviral activity. Cohort studies that assessed the use of HCQ for COVID-19 reported conflicting results, but randomized controlled trials (RCTs) demonstrated no effect on mortality rates and no substantial clinical benefits of HCQ used either for prevention or treatment of COVID-19. We found two clinical studies of artemisinins and two studies of NTZ for treatment of viruses other than COVID-19, all of which showed mixed results. Ivermectin was evaluated in one RCT and few observational studies, demonstrating conflicting results. As the level of evidence of these data is low, the efficacy of ivermectin against COVID-19 remains to be proven. For chloroquine, HCQ, mefloquine, artemisinins, ivermectin, NTZ and niclosamide, we found in vitro studies showing some effects against a wide array of viruses. We found no relevant studies for atovaquone and albendazole. As the search for an effective drug active against SARS-CoV-2 continues, we argue that pre-clinical research of possible antiviral effects of compounds that could have antiviral activity should be conducted. Clinical studies should be conducted when sufficient in vitro evidence exists, and drugs should be introduced into widespread clinical use only after being rigorously tested in RCTs. Such a search may prove beneficial in this pandemic or in outbreaks yet to come.


Obesity and systolic blood pressure in young adult men born small for gestational age.
Individuals born small for gestational age (SGA) are supposed to be at higher risk to develop cardiovascular disorders, and recent report showed that concurrent obesity influences blood pressure (BP) in SGA children. Our aim was to investigate the impact of obesity and birth weight on blood pressure values in young adult men born SGA and controls born after normal pregnancy, Normotensive, non-treated adult men were enrolled (N = 185; mean age 21.29 +/- 0.9 years). Birth parameters were obtained from medical records and SGA was defined as birth weight (BW) under 10th percentile for gestational age and obesity as BMI > 25 kg/m2. According to the presence or absence of obesity and BW the subjects were divided into four groups: (1) non-obese with normal BW (N = 50), (2) non-obese SGA (N = 67), (3) obese with normal BW (N = 40), (4) obese SGA (N = 28). BP was measured using Omron M6 and Spacelab 90207 device following the ESH/ESC guidelines. Systolic BP, 24-hour BP variability and pulse pressure were significantly higher in SGA subjects than in those with normal BW (p < 0.05). The highest 24-hour and daytime systolic BP values as well as 24-hour pulse pressure were found in the subgroup of obese SGA subjects (p < 0.001). Significant differences for the above parameters were observed between obese SGA group and non-obese SGA group (p < 0.05). Obese SGA subjects had higher 24-hour and daytime systolic BP values compared to obese normal BW group. No difference was found in BP between non-obese SGA and non-obese group with normal BW (p > 0.05). In addition to BW and shorter pregnancy duration, obesity concurrently and significantly determines systolic BP in young normotensive men and point to a need for more aggressive implementation of healthy lifestyle as early as possible.


Dynamical modeling of microRNA action on the protein translation process.
Protein translation is a multistep process which can be represented as a cascade of biochemical reactions (initiation, ribosome assembly, elongation, etc.), the rate of which can be regulated by small non-coding microRNAs through multiple mechanisms. It remains unclear what mechanisms of microRNA action are the most dominant: moreover, many experimental reports deliver controversial messages on what is the concrete mechanism actually observed in the experiment. Nissan and Parker have recently demonstrated that it might be impossible to distinguish alternative biological hypotheses using the steady state data on the rate of protein synthesis. For their analysis they used two simple kinetic models of protein translation. In contrary to the study by Nissan and Parker, we show that dynamical data allow discriminating some of the mechanisms of microRNA action. We demonstrate this using the same models as developed by Nissan and Parker for the sake of comparison but the methods developed (asymptotology of biochemical networks) can be used for other models. We formulate a hypothesis that the effect of microRNA action is measurable and observable only if it affects the dominant system (generalization of the limiting step notion for complex networks) of the protein translation machinery. The dominant system can vary in different experimental conditions that can partially explain the existing controversy of some of the experimental data. Our analysis of the transient protein translation dynamics shows that it gives enough information to verify or reject a hypothesis about a particular molecular mechanism of microRNA action on protein translation. For multiscale systems only that action of microRNA is distinguishable which affects the parameters of dominant system (critical parameters), or changes the dominant system itself. Dominant systems generalize and further develop the old and very popular idea of limiting step. Algorithms for identifying dominant systems in multiscale kinetic models are straightforward but not trivial and depend only on the ordering of the model parameters but not on their concrete values. Asymptotic approach to kinetic models allows putting in order diverse experimental observations in complex situations when many alternative hypotheses co-exist.


Catheter-associated urinary tract infections in intensive care units can be reduced by prompting physicians to remove unnecessary catheters.
Indwelling urinary catheters are the most common source of infections in intensive care units (ICUs). The aim of this study was to evaluate the efficacy of nurse-generated daily reminders to physicians to remove unnecessary urinary catheters 5 days after insertion. A time-sequence nonrandomized intervention study. Adult ICUs (medical, surgical, cardiovascular surgical, neurosurgical, and coronary care) of a tertiary-care university medical center. All patients admitted to the adult ICUs during a 2-year period. The study consisted of a 12-month observational phase (15,960 patient-days) followed by a 12-month intervention phase (15,525 patient-days). Daily reminders to physicians from the nursing staff to remove unnecessary urinary catheters 5 days after insertion. The duration of urinary catheterization was significantly reduced during the intervention phase (from 7.0 + 1.1 days to 4.6 +/- 0.7 days; P < .001). The rate of catheter-associated urinary tract infection (CAUTI) was also significantly reduced (from 11.5 +/- 3.1 to 8.3 +/- 2.5 patients with CAUTI per 1,000 catheter-days; P = .009). There was a linear relationship between the monthly average duration of catheterization and the rate of CAUTI (r = 0.50; P = .01). The excess monthly cost of antibiotics for CAUTI was reduced by 69% (from 4021 dollars +/- 1800 dollars to 1220 dollars +/- 941 dollars; P = .004). This study demonstrated that a simple measure instituted as part of a continuous quality improvement program significantly reduced the duration of urinary catheterization, rate of CAUTI, and additional costs of antibiotics to manage CAUTI.


[Secretory meningioma. Report of two cases].
Two surgically removed meningotheliomatous meningiomas with hyaline inclusions or pseudopsammoma bodies were studied. Both meningiomas showed expression of carcinoembryonic antigen and cytokeratin in the cells surrounding the hyaline bodies. There was widespread vimentin and epithelial membrane antigen except in the cells with hyaline inclusions. Clinically both had a severe cerebral edema. One of the cases showed multiple tumors, probably meningiomas. It is important not to misinterpret this variant of meningioma as metastatic neoplasm which may result in palliative treatment of a potentially curable tumor.


Mitochondria regulate the Ca(2+)-exocytosis relationship of bovine adrenal chromaffin cells.
The present study expands the contemporary view of mitochondria as important participants in cellular Ca(2+) dynamics and provides evidence that mitochondria regulate the supply of release-competent secretory granules. Using pharmacological probes to inhibit mitochondrial Ca(2+) import, the ability of mitochondria to modulate secretory activity in single, patch-clamped bovine chromaffin cells was examined by simultaneously monitoring rapid changes in membrane surface area (DeltaC(m)) and cytosolic Ca(2+) levels ([Ca(2+)](c)). Repetitive step depolarizations or action potential waveforms were found to raise the [Ca(2+)](c) of chromaffin cells into the 1 microM to tens of micromolar range. Inhibiting mitochondria by treatment with carbonyl cyanide p-(trifuoro-methoxy)phenylhydrazone, antimycin-oligomycin, or ruthenium red revealed that mitochondria are a prominent component for the clearance of Ca(2+) that entered via voltage-activated Ca(2+) channels. Disruption of cellular Ca(2+) homeostasis by poisoning mitochondria enhanced the secretory responsiveness of chromaffin cells by increasing the amplitude of the transient rise and the time course of recovery to baseline of the evoked Delta[Ca(2+)](c). The enhancement of the secretory response was represented by significant deviation of the Ca(2+)-exocytosis relationship from a standard relationship that equates Ca(2+) influx and DeltaC(m). Thus, mitochondria would play a critical role in the control of secretory activity in chromaffin cells that undergo tonic or repetitive depolarizing activity, likely by limiting the Ca(2+)-dependent activation of specific proteins that recruit or prime secretory granules for exocytosis.


System justification: Experimental evidence, its contextual nature, and implications for social change.
We review conceptual and empirical contributions to system justification theory over the last fifteen years, emphasizing the importance of an experimental approach and consideration of context. First, we review the indirect evidence of the system justification motive via complimentary stereotyping. Second, we describe injunctification as direct evidence of a tendency to view the extant status quo (the way things are) as the way things should be. Third, we elaborate on system justification's contextual nature and the circumstances, such as threat, dependence, inescapability, and system confidence, which are likely to elicit defensive bolstering of the status quo and motivated ignorance of critical social issues. Fourth, we describe how system justification theory can increase our understanding of both resistance to and acceptance of social change, as a change moves from proposed, to imminent, to established. Finally, we discuss how threatened systems shore up their authority by co-opting legitimacy from other sources, such as governments that draw on religious concepts, and the role of institutional-level factors in perpetuating the status quo.


Mitochondria in health, aging and diseases: the epigenetic perspective.
The rate/quality of human aging and the development/progression of diseases depend on a complex interplay among genetics, epigenetics and environment. In this scenario, mitochondrial function (or dysfunction) and mitochondrial DNA have emerged as major players. This is mainly due to their crucial role in energetic balance, in modulating epigenetic programs and in influencing cell stress response. Moreover, it is also emerging the existence of epigenetic changes in mitochondrial DNA and of non coding mitochondrial RNAs which, together with the nuclear ones, play regulatory roles in numerous human phenotypes. In this review we will provide an overview on "mitochondrial epigenetics" state of the art, by summarizing the involvement of mitochondrial function and of mitochondria-nucleus communication in regulating nuclear epigenome, as well as the key aspects of the epigenetic marks related to mitochondrial DNA. Despite the limited data available in the literature to date, mainly due to the novelty of the topic, the intriguing interplay of the mitochondrial epigenetic changes in both physiological and pathological conditions will also be presented.


Timing of symptomatic vasospasm in aneurysmal subarachnoid hemorrhage: the effect of treatment modality and clinical implications.
A better prediction of the time course of symptomatic vasospasm (SVSP) might have a significant impact on the management and prevention of delayed neurologic ischemic deficit (DIND). We studied the influence of the treatment for ruptured aneurysm on SVSP timing. We retrospectively analyzed data of consecutive patients with aneurysmal subarachnoid hemorrhage (aSAH) admitted in our center between 1999 and 2005, treated within 72 hours of the rupture by surgical clipping or endovascular coiling and in accordance with our neuroscience unit protocol. We analyzed the presence of SVSP and recorded the timing of occurrence after the aneurysmal repair intervention. Data on demographics, premorbid conditions, time elapsed from the subarachnoid hemorrhage onset and intervention, and clinical and radiologic characteristics at admission were collected. The first occurrence of postintervention SVSP was recorded and compared between the 2 treatment groups using a proportional hazards regression model, including significant covariates. Of the 67 patients analyzed, 21 (31%) underwent endovascular coiling and 46 (69%) underwent surgical clipping. The baseline variables were similar in the 2 groups. The median time from the procedure to clinical vasospasm was 4 days in the coiled patients and 7 days in the clipped patients. In a proportional hazards model regression analysis including age, sex, Fisher and Hunt-Hess grades, time between onset to procedure, and intervention type, only intervention type emerged as a significant predictor of time to SVSP after intervention (likelihood ratio chi2 = 16.8; P < .00). Treatment modality of ruptured intracranial aneurysm may influence the timing of SVSP occurrence.


Why do mothers encourage their children to control their weight? A cross-sectional study of possible contributing factors.
Mothers encouraging their children to control their weight is problematic as it is associated with children's body dissatisfaction and weight concerns as well as further weight gain. The aim of this study was to identify factors in children and mothers associated with mothers encouraging their children to control their weight and possible gender differences therein. Cross-sectional questionnaire data was available from 1658 mothers of primary school children (mean age 7.1 ±0.6 years, 50.4% boys) participating in the Baden-Württemberg Study. Children's body weight and height were measured in a standardised manner. Logistic regressions were computed separately for boys and girls, adjusted odds ratios (OR) and 95% confidence intervals (CI) from the final model are reported. 29% of children were encouraged by their mothers, girls (32.4%) significantly more often than boys (25.6%). Child BMI (girls OR 1.77, CI 1.57 to 1.99; boys OR 1.88, CI 1.66 to 2.13), and child migration background (girls OR 2.14, CI 1.45 to 3.16; boys OR 1.60, CI 1.07 to 2.37) were significantly associated with encouragement by mothers. For girls, maternal body dissatisfaction (OR 1.59, CI 1.10 to 2.30) and maternal perception of a low influence on health (OR 0.51, CI 0.29 to 0.89) were also significantly associated with maternal encouragement. For boys, this was true of mothers self-efficacy to influence their children's physical activity (OR 0.58, CI 0.40 to 0.85). Different factors are associated with mothers encouraging boys and girls to control their weight. Identifying correlates and underlying processes of maternal encouragement can inform preventive measures targeting weight and eating related problems in children.


Jupiter's atmospheric jet streams extend thousands of kilometres deep.
The depth to which Jupiter's observed east-west jet streams extend has been a long-standing question. Resolving this puzzle has been a primary goal for the Juno spacecraft, which has been in orbit around the gas giant since July 2016. Juno's gravitational measurements have revealed that Jupiter's gravitational field is north-south asymmetric, which is a signature of the planet's atmospheric and interior flows. Here we report that the measured odd gravitational harmonics J3, J5, J7 and J9 indicate that the observed jet streams, as they appear at the cloud level, extend down to depths of thousands of kilometres beneath the cloud level, probably to the region of magnetic dissipation at a depth of about 3,000 kilometres. By inverting the measured gravity values into a wind field, we calculate the most likely vertical profile of the deep atmospheric and interior flow, and the latitudinal dependence of its depth. Furthermore, the even gravity harmonics J8 and J10 resulting from this flow profile also match the measurements, when taking into account the contribution of the interior structure. These results indicate that the mass of the dynamical atmosphere is about one per cent of Jupiter's total mass.


Effects of pyridoxine deficiency and DL-p-chlorophenylalanine administration to rats on 5-hydroxytryptamine and noradrenaline concentrations in brain and 5-hydroxytryptamine concentration in blood.
Pyridoxine deficiency in post-weanling rats caused a marked decrease in body weight and a small but significant decrease in brain weight. Although the concentration of circulating 5-hydroxytryptamine was markedly decreased, the concentrations of 5-hydroxytryptamine and noradrenaline in the brain were not affected. p-Chlorophenylalanine, an inhibitor of 5-hydroxytryptamine synthesis, decreased the 5-hydroxytryptamine content of brain to very low values in both the deficient and control animals, whereas the noradrenaline contents were not appreciably affected. The concentration of 5-hydroxytryptamine in blood, the origin of which is primarily gastrointestinal, was decreased only in the controls but not in the deficient animals after p-chlorophenylalanine treatment. These results suggest that whereas l-tryptophan hydroxylase (EC 184.108.40.206) is rate-limiting in the brain as has been reported by others, the pyridoxal 5'-phosphate-dependent enzyme 5-hydroxytryptophan decarboxylase (EC 18.104.22.168) may be more important in the gastrointestinal tract in the regulation of 5-hydroxytryptamine synthesis.


Management of diastasis of the rectus abdominis muscles: recommendations for swedish national guidelines.
Diastasis of the rectus abdominis muscle is a common condition. There are no generally accepted criteria for diagnosis or treatment of diastasis of the rectus abdominis muscle, which causes uncertainty for the patient and healthcare providers alike. The consensus document was created by a group of Swedish surgeons and based on a structured literature review and practical experience. The proposed criteria for diagnosis and treatment of diastasis of the rectus abdominis muscle are as follows: (1) Diastasis diagnosed at clinical examination using a caliper or ruler for measurement. Diagnostic imaging by ultrasound or other imaging modality, should be performed when concurrent umbilical or epigastric hernia or other cause of the patient's symptoms cannot be excluded. (2) Physiotherapy is the firsthand treatment for diastasis of the rectus abdominis muscle. Surgery should only be considered in diastasis of the rectus abdominis muscle patients with functional impairment, and not until the patient has undergone a standardized 6-month abdominal core training program. (3) The largest width of the diastasis should be at least 5 cm before surgical treatment is considered. In case of pronounced abdominal bulging or concomitant ventral hernia, surgery may be considered in patients with a smaller diastasis. (4) When surgery is undertaken, at least 2 years should have elapsed since last childbirth and future pregnancy should not be planned. (5) Plication of the linea alba is the firsthand surgical technique. Other techniques may be used but have not been found superior. The level of evidence behind these statements varies, but they are intended to lay down a standard strategy for treatment of diastasis of the rectus abdominis muscle and to enable uniformity of management.


Measures of American Indian traditionality and its relationship to cervical cancer screening.
The goal of this study was to evaluate the relationship between culture and attitudes about cervical cancer screening among young American Indian women living and working in northeast Oklahoma. A cohort of 199 American Indian women, ages 18-40, were surveyed to determine their blood quantum, self-identification, and beliefs and practices regarding traditional behavior in order to develop a traditional behavior scale (the degree to which an individual maintained traditional tribal ways or behaviors). The use of this scale indicated that the degree of American Indian blood quantum, blood quantum for primary tribe, and self-identification are correlated to the traditional behavior scale. The scale, however, was unable to predict intention to get a Pap test. Results indicate that it is useful to understand the variation of traditional behavior within the specific population group to be served when planning and implementing culturally appropriate interventions for American Indian women. It is also useful to evaluate which segments of the population current programs are reaching.


Caspase-3 gene silencing for inhibiting apoptosis in insulinoma cells and human islets.
Although islet transplantation has great potential to treat type I diabetes, most islet grafts do not function due to the host immune rejection, nonspecific inflammatory response and poor revascularization. Since caspase-3 plays a crucial role in apoptosis of transplanted islet cells, we used chemically synthesized small interfering RNAs (siRNAs) to silence caspase-3 in insulinoma (INS-1E) cells and human islets, and then determined whether caspase-3 gene silencing can prevent these cells from cytokine-induced apoptosis. Transfection of INS-1E cells and islets with siRNAs reduced caspase-3 transcripts by 50-67% and 50%, respectively. Additionally, apoptosis in transfected insulinoma cells was markedly inhibited. Since gene silencing did not last beyond two days, we converted potent siRNA into shRNA and constructed replication deficient adenoviral (Adv) vectors encoding these shRNAs driven by a U6 or H1 promoter. Compared to chemically synthesized siRNA, Adv-caspase-3-shRNA efficiently transduced islets, showed relatively higher and prolonged levels of gene silencing beyond five days, with higher gene silencing with a U6 promoter, and protected islets from cytokine-induced apoptosis. Finally, return to normoglycemia was achieved at 1 day post-transplantation of Adv-caspase-3-shRNA transduced islets under the kidney capsules of streptozotocin induced nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice and maintained beyond two weeks. Blood glucose levels returned to > or = 325 mg/dL upon removal of the islet graft-bearing kidney at 32 days after transplantation, confirming that transplanted islets were functional.


Analysis of glial acidic fibrillary protein in the human entorhinal cortex during aging and in Alzheimer's disease.
Glial fibrillary acidic protein, GFAP, is a major intermediate filament protein of glial cells and major cytoskeletal structure in astrocytes. The entorhinal cortex has a key role in memory function and is one of the first brain areas to reveal hallmark structures of Alzheimer's disease and therefore provides an ideal tissue to investigate incipient neurodegenerative changes. Here we have analyzed age- and disease-related occurrence and composition of GFAP in the human entorhinal cortex by using one- and two-dimensional electrophoresis, Western blots and immunocytochemistry combined with confocal microscopy. A novel monoclonal antibody, GF-02, was characterized that mainly reacted with intact GFAP molecules and indicated that more acidic and soluble GFAP forms were also more susceptible to degradation. GFAP and vimentin increased with aging and in Alzheimer's disease (AD). Two-dimensional electrophoresis and Western blots revealed a complex GFAP pattern, both in aging and AD with different modification and degradation forms. Immunohistochemistry indicated that reactive astrocytes mainly accumulated in relation to neurofibrillary tangles and senile plaques in deeper entorhinal cortex layers. GFAP may be used as an additional but not exclusive diagnostic tool in the evaluation of neurodegenerative diseases because its levels change with age and respond to senile plaque and tangle formation.


Prior autoimmune disease and risk of monoclonal gammopathy of undetermined significance and multiple myeloma: a systematic review.
Several observational studies have investigated autoimmune disease and subsequent risk of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Findings have been largely inconsistent and hindered by the rarity and heterogeneity of the autoimmune disorders investigated. A systematic review of the literature was undertaken to evaluate the strength of the evidence linking prior autoimmune disease and risk of MGUS/multiple myeloma. A broad search strategy using key terms for MGUS, multiple myeloma, and 50 autoimmune diseases was used to search four electronic databases (PubMed, Medline, Embase, and Web of Science) from inception through November 2011. A total of 52 studies met the inclusion criteria, of which 32 were suitably comparable to perform a meta-analysis. "Any autoimmune disorder" was associated with an increased risk of both MGUS [n = 760 patients; pooled relative risk (RR) 1.42; 95% confidence interval (CI), 1.14-1.75] and multiple myeloma (n>2,530 patients; RR 1.13, 95% CI, 1.04-1.22). This risk was disease dependent with only pernicious anemia showing an increased risk of both MGUS (RR 1.67; 95% CI, 1.21-2.31) and multiple myeloma (RR 1.50; 95% CI, 1.25-1.80). Our findings, based on the largest number of autoimmune disorders and patients with MGUS/multiple myeloma reported to date, suggest that autoimmune diseases and/or their treatment may be important in the etiology of MGUS/multiple myeloma. The strong associations observed for pernicious anemia suggest that anemia seen in plasma cell dyscrasias may be of autoimmune origin. Underlying mechanisms of autoimmune diseases, general immune dysfunction, and/or treatment of autoimmune diseases may be important in the pathogenesis of MGUS/multiple myeloma.


Processing of dielectric oxynitride perovskites for powders, ceramics, compacts and thin films.
Oxynitride perovskites, having oxide and nitride anions together in a compound, are a new class of dielectric material. The shaping process in either bulk ceramics or thin films is an essential factor for investigating and utilizing the dielectric properties of these materials. In this perspective, recent studies on the shaping of dielectric oxynitride perovskites are reviewed with a consideration of the powder preparation and thermal stability for sintering, several sintering methods, ultra-high pressure compaction, and thin-film formation.


Electroosmotic and pressure-driven flow in open and packed capillaries: velocity distributions and fluid dispersion
The flow field dynamics in open and packed segments of capillary columns has been studied by a direct motion encoding of the fluid molecules using pulsed magnetic field gradient nuclear magnetic resonance. This noninvasive method operates within a time window that allows a quantitative discrimination of electroosmotic against pressure-driven flow behavior. The inherent axial fluid flow field dispersion and characteristic length scales of either transport mode are addressed, and the results demonstrate a significant performance advantage of an electrokinetically driven mobile phase in both open-tubular and packed-bed geometries. In contrast to the parabolic velocity profile and its impact on axial dispersion characterizing laminar flow through an open cylindrical capillary, a pluglike velocity distribution of the electroosmotic flow field is revealed in capillary electrophoresis. Here, the variance of the radially averaged, axial displacement probability distributions is quantitatively explained by longitudinal molecular diffusion at the actual buffer temperature, while for Poiseuille flow, the preasymptotic regime to Taylor-Aris dispersion can be shown. Compared to creeping laminar flow through a packed bed, the increased efficiency observed in capillary electrochromatography is related to the superior characteristics of the electroosmotic flow profile over any length scale in the interstitial pore space and to the origin, spatial dimension, and hydrodynamics of the stagnant fluid on the support particles' external surface. Using the Knox equation to analyze the axial plate height data, an eddy dispersion term smaller by a factor of almost 2.5 than in capillary high-performance liquid chromatography is revealed for the electroosmotic flow field in the same column.


A risk score to predict type 2 diabetes mellitus in an elderly Spanish Mediterranean population at high cardiovascular risk.
To develop and test a diabetes risk score to predict incident diabetes in an elderly Spanish Mediterranean population at high cardiovascular risk. A diabetes risk score was derived from a subset of 1381 nondiabetic individuals from three centres of the PREDIMED study (derivation sample). Multivariate Cox regression model ß-coefficients were used to weigh each risk factor. PREDIMED-personal Score included body-mass-index, smoking status, family history of type 2 diabetes, alcohol consumption and hypertension as categorical variables; PREDIMED-clinical Score included also high blood glucose. We tested the predictive capability of these scores in the DE-PLAN-CAT cohort (validation sample). The discrimination of Finnish Diabetes Risk Score (FINDRISC), German Diabetes Risk Score (GDRS) and our scores was assessed with the area under curve (AUC). The PREDIMED-clinical Score varied from 0 to 14 points. In the subset of the PREDIMED study, 155 individuals developed diabetes during the 4.75-years follow-up. The PREDIMED-clinical score at a cutoff of ≥6 had sensitivity of 72.2%, and specificity of 72.5%, whereas AUC was 0.78. The AUC of the PREDIMED-clinical Score was 0.66 in the validation sample (sensitivity = 85.4%; specificity = 26.6%), and was significantly higher than the FINDRISC and the GDRS in both the derivation and validation samples. We identified classical risk factors for diabetes and developed the PREDIMED-clinical Score to determine those individuals at high risk of developing diabetes in elderly individuals at high cardiovascular risk. The predictive capability of the PREDIMED-clinical Score was significantly higher than the FINDRISC and GDRS, and also used fewer items in the questionnaire.


Metallothioneins in terrestrial invertebrates: structural aspects, biological significance and implications for their use as biomarkers.
During the last few years the subject of metallothioneins (MTs) in terrestrial invertebrates has gained increasing attention. One reason for this may be that terrestrial invertebrates provide new insights into the biological diversity of MTs, with the potential of discovering alternative models of structural and functional relationships. Four groups of terrestrial invertebrates have been studied in detail, namely nematodes, insects, snails and earthworms, with the present article focusing on MTs from the latter two groups. Snails are interesting because they possess distinct MT isoforms involved in different metal-specific tasks. In the Roman snail (Helix pomatia), for example, one isoform is predominantly expressed in the midgut gland, accounting for the accumulation, binding and detoxification of cadmium. The second isoform, which is present in the snail's mantle, is substantially different regarding its primary structure. Furthermore, it binds nearly exclusively copper, and thus is probably involved in the homeostatic regulation of essential trace elements. Earthworm MTs merit our attention because of another peculiarity: they seem to be much more unstable than snail MTs, particularly under conventional conditions of preparation. The cDNA of the brandling worm (Eisenia foetida), for instance, codes for a putative MT, which is about twice the size of the actual protein. The isolated MT peptide binds four Cd2+ ions and represents a one-domain MT entity that is stable and functional in vitro. This strongly suggests that earthworm MTs are either posttranslationally modified, or subjected to enzymatic cleavage during preparation. Both snail and earthworm MTs are inducible by metal exposure, especially by cadmium, thus supporting the idea of using them as potential biomarkers for environmental metal pollution. Whilst snail MTs have already been tested in this respect with some success, the use of earthworm MTs as biomarkers still remains to be evaluated, especially in the light of the unknown significance of their posttranslational instability.


Infrared reflection-absorption spectra of metal-effect coatings.
The results of studies of infrared reflection-absorption spectra of metal-effect coatings are presented in this paper. Such coatings consist of metallic flakes that are dispersed in a polymer binder. The spectra show two distinct phenomena. One is due to the polymer matrix. The other is due to metallic flakes that are dispersed inside the layer. The polymer binder causes narrow spectral lines that give a thickness-dependent intensity and position. Metallic flakes change the average baseline of this spectrum over the entire infrared spectral region. This particular effect was evaluated using a simple rough-surface model. Two parameters of the model, the root-mean-square roughness and the correlation length of the rough surface, described the reflection of the partial beams on the metal flake surfaces and scattering on flakes boundaries. The other two parameters are the specular reflectance and the diffuse reflectance of the plane untextured interface between the polymer matrix and the metal flake surface. Various metal-effect coatings within the same polymer binder were analyzed. The effect of each metal flake dispersion was evaluated by the parameters within the rough-surface model. The results were analyzed in terms of the size and the loadings of flakes that were used in the coatings.


Hemispheric and sex-linked differences in Sylvian fissure morphology: a quantitative approach using volumetric magnetic resonance imaging.
In a sample of right-handed adults, volumetric magnetic resonance imaging (MRI) was used to reinvestigate hemispheric and sex-linked differences in Sylvian fissure (SF) morphology. Asymmetries of the SF exist with a predominant leftward asymmetry consistently reported in postmortem studies. These anatomic asymmetries may reflect asymmetric allocation of adjacent opercula, with some investigators positing a relationship with planum temporale asymmetries, as the postcentral SF is more asymmetric than the anterior segment. Sex-related differences have also been reported with reduced asymmetries in women relative to men. Using in vivo MRI surface renderings, SF asymmetries were studied in a group of consistently right-handed men (n = 12) and women (n = 12). Anterior and postcentral SF lengths were measured. Overall, there was a significant leftward asymmetry of the horizontal SF (anterior and postcentral) in men and women. Whereas there was a significant leftward asymmetry of the postcentral SF, there was no significant asymmetry of the anterior SF. There was an increase in the parietal operculum anterior to the posterior ascending ramus (PAR) in the left hemisphere and posterior to the PAR in the right hemisphere when SF asymmetries were leftward, with the length of the anterior parietal operculum positively correlated with postcentral SF length. These findings demonstrate that the SF is asymmetric but that clear sex-related effects do not exist in consistently right-handed subjects.


[Melancholia, psychomotor disturbance or depressed mood?].
Melancholia is a historical concept according to which the clinical condition is characterised by gloom, apprehension and psychomotor disturbance, vital symptoms and psychotic phenomena. The condition needs to be accurately diagnosed if treatment is to be appropriate. If a patient shows no clear signs of depression, psychomotor disturbance is often not recognised as a feature of severe depression and as a result treatment is delayed. On the basis of two case studies we show that psychomotor symptoms can be extremely important for an accurate clinical evaluation.


Association of Vitamin D Receptor Polymorphism with Susceptibility to Symptomatic Pertussis.
Pertussis, caused by infection with the gram negative B. pertussis bacterium, is a serious respiratory illness that can last for months. While B. pertussis infection rates are estimated between 1-10% in the general population, notifications of symptomatic pertussis only comprise 0.01-0.1% indicating that most individuals clear B. pertussis infections without developing (severe) clinical symptoms. In this study we investigated whether genetic risk factors are involved in the development of symptomatic pertussis upon B. pertussis infection. Single-nucleotide polymorphisms (SNPs) in candidate genes, MBL2, IL17A, TNFα, VDR, and IL10 were genotyped in a unique Dutch cohort of symptomatic clinically confirmed (ex-)pertussis patients and in a Dutch population cohort. Of the seven investigated SNPs in five genes, a polymorphism in the Vitamin D receptor (VDR) gene (rs10735810) was associated with pertussis. The VDR major allele and its homozygous genotype were more present in the symptomatic pertussis patient cohort compared to the control population cohort. Interestingly, the VDR major allele correlated also with the duration of reported pertussis symptoms. Vitamin D3 (VD3) and VDR are important regulators of immune activation. Altogether, these findings suggest that polymorphisms in the VDR gene may affect immune activation and the clinical outcome of B. pertussis infection.